WE-AB-207B-07: Dose Cloud: Generating “Big Data” for Radiation Therapy Treatment Plan Optimization Research

DOE Office of Scientific and Technical Information (OSTI.GOV)

Folkerts, MM; University of California San Diego, La Jolla, California; Long, T

Purpose: To provide a tool to generate large sets of realistic virtual patient geometries and beamlet doses for treatment optimization research. This tool enables countless studies exploring the fundamental interplay between patient geometry, objective functions, weight selections, and achievable dose distributions for various algorithms and modalities. Methods: Generating realistic virtual patient geometries requires a small set of real patient data. We developed a normalized patient shape model (PSM) which captures organ and target contours in a correspondence-preserving manner. Using PSM-processed data, we perform principal component analysis (PCA) to extract major modes of variation from the population. These PCA modes canmore » be shared without exposing patient information. The modes are re-combined with different weights to produce sets of realistic virtual patient contours. Because virtual patients lack imaging information, we developed a shape-based dose calculation (SBD) relying on the assumption that the region inside the body contour is water. SBD utilizes a 2D fluence-convolved scatter kernel, derived from Monte Carlo simulations, and can compute both full dose for a given set of fluence maps, or produce a dose matrix (dose per fluence pixel) for many modalities. Combining the shape model with SBD provides the data needed for treatment plan optimization research. Results: We used PSM to capture organ and target contours for 96 prostate cases, extracted the first 20 PCA modes, and generated 2048 virtual patient shapes by randomly sampling mode scores. Nearly half of the shapes were thrown out for failing anatomical checks, the remaining 1124 were used in computing dose matrices via SBD and a standard 7-beam protocol. As a proof of concept, and to generate data for later study, we performed fluence map optimization emphasizing PTV coverage. Conclusions: We successfully developed and tested a tool for creating customizable sets of virtual patients suitable for large-scale radiation therapy optimization research.« less

General equations for optimal selection of diagnostic image acquisition parameters in clinical X-ray imaging.

PubMed

Zheng, Xiaoming

2017-12-01

The purpose of this work was to examine the effects of relationship functions between diagnostic image quality and radiation dose on the governing equations for image acquisition parameter variations in X-ray imaging. Various equations were derived for the optimal selection of peak kilovoltage (kVp) and exposure parameter (milliAmpere second, mAs) in computed tomography (CT), computed radiography (CR), and direct digital radiography. Logistic, logarithmic, and linear functions were employed to establish the relationship between radiation dose and diagnostic image quality. The radiation dose to the patient, as a function of image acquisition parameters (kVp, mAs) and patient size (d), was used in radiation dose and image quality optimization. Both logistic and logarithmic functions resulted in the same governing equation for optimal selection of image acquisition parameters using a dose efficiency index. For image quality as a linear function of radiation dose, the same governing equation was derived from the linear relationship. The general equations should be used in guiding clinical X-ray imaging through optimal selection of image acquisition parameters. The radiation dose to the patient could be reduced from current levels in medical X-ray imaging.

The effect of statistical noise on IMRT plan quality and convergence for MC-based and MC-correction-based optimized treatment plans.

PubMed

Siebers, Jeffrey V

2008-04-04

Monte Carlo (MC) is rarely used for IMRT plan optimization outside of research centres due to the extensive computational resources or long computation times required to complete the process. Time can be reduced by degrading the statistical precision of the MC dose calculation used within the optimization loop. However, this eventually introduces optimization convergence errors (OCEs). This study determines the statistical noise levels tolerated during MC-IMRT optimization under the condition that the optimized plan has OCEs <100 cGy (1.5% of the prescription dose) for MC-optimized IMRT treatment plans.Seven-field prostate IMRT treatment plans for 10 prostate patients are used in this study. Pre-optimization is performed for deliverable beams with a pencil-beam (PB) dose algorithm. Further deliverable-based optimization proceeds using: (1) MC-based optimization, where dose is recomputed with MC after each intensity update or (2) a once-corrected (OC) MC-hybrid optimization, where a MC dose computation defines beam-by-beam dose correction matrices that are used during a PB-based optimization. Optimizations are performed with nominal per beam MC statistical precisions of 2, 5, 8, 10, 15, and 20%. Following optimizer convergence, beams are re-computed with MC using 2% per beam nominal statistical precision and the 2 PTV and 10 OAR dose indices used in the optimization objective function are tallied. For both the MC-optimization and OC-optimization methods, statistical equivalence tests found that OCEs are less than 1.5% of the prescription dose for plans optimized with nominal statistical uncertainties of up to 10% per beam. The achieved statistical uncertainty in the patient for the 10% per beam simulations from the combination of the 7 beams is ~3% with respect to maximum dose for voxels with D>0.5D(max). The MC dose computation time for the OC-optimization is only 6.2 minutes on a single 3 Ghz processor with results clinically equivalent to high precision MC computations.

Anatomical robust optimization to account for nasal cavity filling variation during intensity-modulated proton therapy: a comparison with conventional and adaptive planning strategies

NASA Astrophysics Data System (ADS)

van de Water, Steven; Albertini, Francesca; Weber, Damien C.; Heijmen, Ben J. M.; Hoogeman, Mischa S.; Lomax, Antony J.

2018-01-01

The aim of this study is to develop an anatomical robust optimization method for intensity-modulated proton therapy (IMPT) that accounts for interfraction variations in nasal cavity filling, and to compare it with conventional single-field uniform dose (SFUD) optimization and online plan adaptation. We included CT data of five patients with tumors in the sinonasal region. Using the planning CT, we generated for each patient 25 ‘synthetic’ CTs with varying nasal cavity filling. The robust optimization method available in our treatment planning system ‘Erasmus-iCycle’ was extended to also account for anatomical uncertainties by including (synthetic) CTs with varying patient anatomy as error scenarios in the inverse optimization. For each patient, we generated treatment plans using anatomical robust optimization and, for benchmarking, using SFUD optimization and online plan adaptation. Clinical target volume (CTV) and organ-at-risk (OAR) doses were assessed by recalculating the treatment plans on the synthetic CTs, evaluating dose distributions individually and accumulated over an entire fractionated 50 GyRBE treatment, assuming each synthetic CT to correspond to a 2 GyRBE fraction. Treatment plans were also evaluated using actual repeat CTs. Anatomical robust optimization resulted in adequate CTV doses (V95%  ⩾  98% and V107%  ⩽  2%) if at least three synthetic CTs were included in addition to the planning CT. These CTV requirements were also fulfilled for online plan adaptation, but not for the SFUD approach, even when applying a margin of 5 mm. Compared with anatomical robust optimization, OAR dose parameters for the accumulated dose distributions were on average 5.9 GyRBE (20%) higher when using SFUD optimization and on average 3.6 GyRBE (18%) lower for online plan adaptation. In conclusion, anatomical robust optimization effectively accounted for changes in nasal cavity filling during IMPT, providing substantially improved CTV and OAR doses compared with conventional SFUD optimization. OAR doses can be further reduced by using online plan adaptation.

Comparison of dose volume parameters evaluated using three forward planning – optimization techniques in cervical cancer brachytherapy involving two applicators

PubMed Central

Basu-Roy, Somapriya; Kar, Sanjay Kumar; Das, Sounik; Lahiri, Annesha

2017-01-01

Purpose This study is intended to compare dose-volume parameters evaluated using different forward planning- optimization techniques, involving two applicator systems in intracavitary brachytherapy for cervical cancer. It looks for the best applicator-optimization combination to fulfill recommended dose-volume objectives in different high-dose-rate (HDR) fractionation schedules. Material and methods We used tandem-ring and Fletcher-style tandem-ovoid applicator in same patients in two fractions of brachytherapy. Six plans were generated for each patient utilizing 3 forward optimization techniques for each applicator used: equal dwell weight/times (‘no optimization’), ‘manual dwell weight/times’, and ‘graphical’. Plans were normalized to left point A and dose of 8 Gy was prescribed. Dose volume and dose point parameters were compared. Results Without graphical optimization, maximum width and thickness of volume enclosed by 100% isodose line, dose to 90%, and 100% of clinical target volume (CTV); minimum, maximum, median, and average dose to both rectum and bladder are significantly higher with Fletcher applicator. Even if it is done, dose to both points B, minimum dose to CTV, and treatment time; dose to 2 cc (D2cc) rectum and rectal point etc.; D2cc, minimum, maximum, median, and average dose to sigmoid colon; D2cc of bladder remain significantly higher with this applicator. Dose to bladder point is similar (p > 0.05) between two applicators, after all optimization techniques. Conclusions Fletcher applicator generates higher dose to both CTV and organs at risk (2 cc volumes) after all optimization techniques. Dose restriction to rectum is possible using graphical optimization only during selected HDR fractionation schedules. Bladder always receives dose higher than recommended, and 2 cc sigmoid colon always gets permissible dose. Contrarily, graphical optimization with ring applicators fulfills all dose volume objectives in all HDR fractionations practiced. PMID:29204164

Comprehensive optimization process of paranasal sinus radiography.

PubMed

Saarakkala, S; Nironen, K; Hermunen, H; Aarnio, J; Heikkinen, J O

2009-04-01

The optimization of radiological examinations is important in order to reduce unnecessary patient radiation exposure. To perform a comprehensive optimization process for paranasal sinus radiography at Mikkeli Central Hospital, Finland. Patients with suspicion of acute sinusitis were imaged with a Kodak computed radiography (CR) system (n=20) and with a Philips digital radiography (DR) system (n=30) using focus-detector distances (FDDs) of 110 cm, 150 cm, or 200 cm. Patients' radiation exposure was determined in terms of entrance surface dose and dose-area product. Furthermore, an anatomical phantom was used for the estimation of point doses inside the head. Clinical image quality was evaluated by an experienced radiologist, and physical image quality was evaluated from the digital radiography phantom. Patient doses were significantly lower and image quality better with the DR system compared to the CR system. The differences in patient dose and physical image quality were small with varying FDD. Clinical image quality of the DR system was lowest with FDD of 200 cm. Further, imaging with FDD of 150 cm was technically easier for the technologist to perform than with FDD of 110 cm. After optimization, it was recommended that the DR system with FDD of 150 cm should always be used at Mikkeli Central Hospital. We recommend this kind of comprehensive approach in all optimization processes of radiological examinations.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, E; Yuan, F; Templeton, A

Purpose: The ultimate goal of radiotherapy treatment planning is to find a treatment that will yield a high tumor-control-probability(TCP) with an acceptable normal-tissue-complication probability(NTCP). Yet most treatment planning today is not based upon optimization of TCPs and NTCPs, but rather upon meeting physical dose and volume constraints defined by the planner. We design treatment plans that optimize TCP directly and contrast them with the clinical dose-based plans. PET image is incorporated to evaluate gain in TCP for dose escalation. Methods: We build a nonlinear mixed integer programming optimization model that maximizes TCP directly while satisfying the dose requirements on themore » targeted organ and healthy tissues. The solution strategy first fits the TCP function with a piecewise-linear approximation, then solves the problem that maximizes the piecewise linear approximation of TCP, and finally performs a local neighborhood search to improve the TCP value. To gauge the feasibility, characteristics, and potential benefit of PET-image guided dose escalation, initial validation consists of fifteen cervical cancer HDR patient cases. These patients have all received prior 45Gy of external radiation dose. For both escalated strategies, we consider 35Gy PTV-dose, and two variations (37Gy-boost to BTV vs 40Gy-boost) to PET-image-pockets. Results: TCP for standard clinical plans range from 59.4% - 63.6%. TCP for dose-based PET-guided escalated-dose-plan ranges from 63.8%–98.6% for all patients; whereas TCP-optimized plans achieves over 91% for all patients. There is marginal difference in TCP among those with 37Gy-boosted vs 40Gy-boosted. There is no increase in rectum and bladder dose among all plans. Conclusion: Optimizing TCP directly results in highly conformed treatment plans. The TCP-optimized plan is individualized based on the biological PET-image of the patients. The TCP-optimization framework is generalizable and has been applied successfully to other external-beam delivery modalities. A clinical trial is on-going to gauge the clinical significance. Partially supported by the National Science Foundation.« less

Dose in x-ray computed tomography

NASA Astrophysics Data System (ADS)

Kalender, Willi A.

2014-02-01

Radiation dose in x-ray computed tomography (CT) has become a topic of high interest due to the increasing numbers of CT examinations performed worldwide. This review aims to present an overview of current concepts for both scanner output metrics and for patient dosimetry and will comment on their strengths and weaknesses. Controversial issues such as the appropriateness of the CT dose index (CTDI) are discussed in detail. A review of approaches to patient dose assessment presently in practice, of the dose levels encountered and options for further dose optimization are also given and discussed. Patient dose assessment remains a topic for further improvement and for international consensus. All approaches presently in use are based on Monte Carlo (MC) simulations. Estimates for effective dose are established, but they are crude and not patient-specific; organ dose estimates are rarely available. Patient- and organ-specific dose estimates can be provided with adequate accuracy and independent of CTDI phantom measurements by fast MC simulations. Such information, in particular on 3D dose distributions, is important and helpful in optimization efforts. Dose optimization has been performed very successfully in recent years and even resulted in applications with effective dose values of below 1 mSv. In general, a trend towards lower dose values based on technical innovations has to be acknowledged. Effective dose values are down to clearly below 10 mSv on average, and there are a number of applications such as cardiac and pediatric CT which are performed routinely below 1 mSv on modern equipment.

Optimal and safe standard doses of midazolam and propofol to achieve patient and doctor satisfaction with dental treatment: A prospective cohort study

PubMed Central

Nonaka, Mutsumi; Nishimura, Akiko; Gotoh, Kinuko; Oka, Shuichirou; Iijima, Takehiko

2017-01-01

Background The incidences of morbidity and mortality caused by pharmacosedation for dental treatment have not yet reached zero. Adverse events are related to inappropriate respiratory management, mostly originating from an overdose of sedatives. Since sedation is utilized for the satisfaction of both the dentist and the patient, the optimal dose should be minimized to prevent adverse events. We attempted to define the optimal doses of midazolam and propofol required to achieve high levels of patient and dentist satisfaction. Methods One thousand dental patients, including those undergoing third molar extractions, were enrolled in this study. A dose of 1 mg of midazolam was administered at 1-minute intervals until adequate sedation was achieved. Propofol was then infused continuously to maintain the sedation level. Both the patients and the dentists were subsequently interviewed and asked to complete a questionnaire. A multivariate logistic regression analysis was used to examine the factors that contributed to patient and dentist satisfaction. Results The peak midazolam dose resulting in the highest percentage of patient satisfaction was 3 mg. Both a lower dose and a higher dose reduced patient satisfaction. Patient satisfaction increased with an increasing dosage of propofol up until 4 mg/kg/hr, reaching a peak of 78.6%. The peak midazolam dose resulting in the highest percentage of dentist satisfaction (78.8%) was 2 mg. Incremental propofol doses reduced dentist satisfaction, in contrast to their effect on patient satisfaction. The strongest independent predictors of patient satisfaction and dentist satisfaction were no intraoperative memory (OR, 5.073; 95% CI, 3.532–7.287; P<0.001) and unintentional movements by the patient (OR, 0.035; 95% CI, 0.012–0.104; P<0.001), respectively. No serious adverse events were reported. Conclusion We found that 3 mg of midazolam and 3 mg/kg/hr of propofol may be the optimal doses for maximizing both patient and dentist satisfaction. Although this level of sedation is relatively light, memory loss and an absence of unintentional patient movements can be expected without adverse events. PMID:28182732

The impact of different dose response parameters on biologically optimized IMRT in breast cancer

NASA Astrophysics Data System (ADS)

Costa Ferreira, Brigida; Mavroidis, Panayiotis; Adamus-Górka, Magdalena; Svensson, Roger; Lind, Bengt K.

2008-05-01

The full potential of biologically optimized radiation therapy can only be maximized with the prediction of individual patient radiosensitivity prior to treatment. Unfortunately, the available biological parameters, derived from clinical trials, reflect an average radiosensitivity of the examined populations. In the present study, a breast cancer patient of stage I II with positive lymph nodes was chosen in order to analyse the effect of the variation of individual radiosensitivity on the optimal dose distribution. Thus, deviations from the average biological parameters, describing tumour, heart and lung response, were introduced covering the range of patient radiosensitivity reported in the literature. Two treatment configurations of three and seven biologically optimized intensity-modulated beams were employed. The different dose distributions were analysed using biological and physical parameters such as the complication-free tumour control probability (P+), the biologically effective uniform dose (\\bar{\\bar{D}} ), dose volume histograms, mean doses, standard deviations, maximum and minimum doses. In the three-beam plan, the difference in P+ between the optimal dose distribution (when the individual patient radiosensitivity is known) and the reference dose distribution, which is optimal for the average patient biology, ranges up to 13.9% when varying the radiosensitivity of the target volume, up to 0.9% when varying the radiosensitivity of the heart and up to 1.3% when varying the radiosensitivity of the lung. Similarly, in the seven-beam plan, the differences in P+ are up to 13.1% for the target, up to 1.6% for the heart and up to 0.9% for the left lung. When the radiosensitivity of the most important tissues in breast cancer radiation therapy was simultaneously changed, the maximum gain in outcome was as high as 7.7%. The impact of the dose response uncertainties on the treatment outcome was clinically insignificant for the majority of the simulated patients. However, the jump from generalized to individualized radiation therapy may significantly increase the therapeutic window for patients with extreme radio sensitivity or radioresistance, provided that these are identified. Even for radiosensitive patients a simple treatment technique is sufficient to maximize the outcome, since no significant benefits were obtained with a more complex technique using seven intensity-modulated beams portals.

SU-E-T-618: Dosimetric Comparison of Manual and Beam Angle Optimization of Gantry Angles in IMRT for Cervical Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, X; Sun, T; Liu, T

2014-06-01

Purpose: To evaluate the dosimetric characteristics of intensity-modulated radiotherapy (IMRT) treatment plan with beam angle optimization. Methods: Ten post-operation patients with cervical cancer were included in this analysis. Two IMRT plans using seven beams were designed in each patient. A standard coplanar equi-space beam angles were used in the first plan (plan 1), whereas the selection of beam angle was optimized by beam angle optimization algorithm in Varian Eclipse treatment planning system for the same number of beams in the second plan (plan 2). Two plans were designed for each patient with the same dose-volume constraints and prescription dose. Allmore » plans were normalized to the mean dose to PTV. The dose distribution in the target, the dose to the organs at risk and total MU were compared. Results: For conformity and homogeneity in PTV, no statistically differences were observed in the two plans. For the mean dose in bladder, plan 2 were significantly lower than plan 1(p<0.05). No statistically significant differences were observed between two plans for the mean doses in rectum, left and right femur heads. Compared with plan1, the average monitor units reduced 16% in plan 2. Conclusion: The IMRT plan based on beam angle optimization for cervical cancer could reduce the dose delivered to bladder and also reduce MU. Therefore there were some dosimetric advantages in the IMRT plan with beam angle optimization for cervical cancer.« less

Optimizing treatment of hypothyroidism.

PubMed

Clarke, Nick; Kabadi, Udaya M

2004-01-01

Several thyroid hormone preparations are currently available, including levothyroxine sodium (thyroxine), liothyronine (triiodothyronine), and desiccated thyroid extract, as well as a combination of levothyroxine sodium and liothyronine. Levothyroxine sodium monotherapy at an appropriate daily dose provides uniform levels of both thyroxine and triiodothyronine in the circulation without diurnal variation. Therefore, it is the preparation of choice in most patients with hypothyroidism of both the primary and central types. A normal thyrotropin (TSH) level of 1-2 mU/L is considered the determinant of optimal daily levothyroxine sodium dose in patients with primary hypothyroidism, whereas normal thyroxine and triiodothyronine levels in the mid or upper normal range may denote optimal replacement in patients with central hypothyroidism. Optimal daily levothyroxine sodium dose may be determined according to serum TSH level at the time of diagnosis of primary hypothyroidism. Initial administration of close to the full calculated dose of levothyroxine sodium is appropriate for younger patients, reducing the need for follow-up visits and repeated laboratory testing for dose titration. In the elderly and in patients with a history of coronary artery disease (CAD), the well established approach of starting with a low dose and gradually titrating to the full calculated dose is always the best option. Levothyroxine sodium can and should be continued in patients receiving treatment for CAD. Even minor over-replacement during initial titration of levothyroxine sodium should be avoided, because of the risk of cardiac events. Chronic over-replacement may induce osteoporosis, particularly in postmenopausal women, and should also be avoided.

Adaptive radiation therapy of prostate cancer

NASA Astrophysics Data System (ADS)

Wen, Ning

ART is a close-loop feedback algorithm which evaluates the organ deformation and motion right before the treatment and takes into account dose delivery variation daily to compensate for the difference between planned and delivered dose. It also has potential to allow further dose escalation and margin reduction to improve the clinical outcome. This retrospective study evaluated ART for prostate cancer treatment and radiobiological consequences. An IRB approved protocol has been used to evaluate actual dose delivery of patients with prostate cancer undergoing treatment with daily CBCT. The dose from CBCT was measured in phantom using TLD and ion chamber techniques in the pelvic scan setting. There were two major findings from the measurements of CBCT dose: (1) the lateral dose distribution was not symmetrical, with Lt Lat being ˜40% higher than Rt Lat and (2) AP skin dose varies with patient size, ranging 3.2--6.1 cGy for patient's AP separation of 20--33 cm (the larger the separation, the less the skin dose) but lateral skin doses depend little on separations. Dose was recalculated on each CBCT set under the same treatment plan. DIR was performed between SIM-CT and evaluated for each CT sets. Dose was reconstructed and accumulated to reflect the actual dose delivered to the patient. Then the adaptive plans were compared to the original plan to evaluate tumor control and normal tissue complication using radiobiological model. Different PTV margins were also studied to access margin reduction techniques. If the actual dose delivered to the PTV deviated significantly from the prescription dose for the given fractions or the OAR received higher dose than expected, the treatment plan would be re-optimized based on the previously delivered dose. The optimal schedule was compared based on the balance of PTV dose coverage and inhomogeneity, OAR dose constraints and labor involved. DIR was validated using fiducial marker position, visual comparison and UE. The mean and standard deviation of markers after rigid registration in L-R direction was 0 and 1 mm. But the mean was 2--4 mm in the A-P and S-I direction and standard deviation was about 2 mm. After DIR, the mean in all three directions became 0 and standard deviation was within sub millimeter. UE images were generated for each CT set and carefully reviewed in the prostate region. DIR provided accurate transformation matrix to be used for dose reconstruction. The delivered dose was evaluated with radiobiological models. TCP for the CTV was calculated to evaluate tumor control in different margin settings. TCP calculated from the reconstructed dose agreed within 5% of the value in the plan for all patients with three different margins. EUD and NTCP were calculated to evaluate reaction of rectum to radiation. Similar biological evaluation was performed for bladder. EUD of actual dose was 3%--9% higher than that of planned dose of patient 1--3, 11%--20% higher of patient 4--5. Smaller margins could not reduce late GU toxicity effectively since bladder complication was directly related to Dmax which was at the same magnitude in the bladder no matter which margin was applied. Re-optimization was performed at the 10th, 20th , 30th, and 40th fraction to evaluate the effectiveness to limit OAR dose while maintaining the target coverage. Reconstructed dose was added to dose from remaining fractions after optimization to show the total dose patient would receive. It showed that if the plan was re-optimized at 10th or 20th fraction, total dose to rectum and bladder were very similar to planned dose with minor deviations. If the plan was re-optimized at the 30th fraction, since there was a large deviation between reconstructed dose and planned dose to OAR, optimization could not limit the OAR dose to the original plan with only 12 fractions left. If the re-optimization was done at the 40th fraction, it was impossible to compensate in the last 2 fractions. Large deviations of total dose to bladder and rectum still existed while dose inhomogeneity to PTV was significantly increased due to hard constraints set in the optimization to reduce OAR dose. In summary, ART did not show improvements in TCP if the patient was setup with CBCT. However, EUD of rectum and bladder was increased significantly due to tissue deformation which varied daily. With the power of ART, margins added to the CTV could be further reduced to preserve critical organs surrounding the target. (Abstract shortened by UMI.)

WE-AB-303-06: Combining DAO with MV + KV Optimization to Improve Skin Dose Sparing with Real-Time Fluoroscopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grelewicz, Z; Wiersma, R

Purpose: Real-time fluoroscopy may allow for improved patient positioning and tumor tracking, particularly in the treatment of lung tumors. In order to mitigate the effects of the imaging dose, previous studies have demonstrated the effect of including both imaging dose and imaging constraints into the inverse treatment planning object function. That method of combined MV+kV optimization may Result in plans with treatment beams chosen to allow for more gentle imaging beam-on times. Direct-aperture optimization (DAO) is also known to produce treatment plans with fluence maps more conducive to lower beam-on times. Therefore, in this work we demonstrate the feasibility ofmore » a combination of DAO and MV+kV optimization for further optimized real-time kV imaging. Methods: Therapeutic and imaging beams were modeled in the EGSnrc Monte Carlo environment, and applied to a patient model for a previously treated lung patient to provide dose influence matrices from DOSXYZnrc. An MV + kV IMRT DAO treatment planning system was developed to compare DAO treatment plans with and without MV+kV optimization. The objective function was optimized using simulated annealing. In order to allow for comparisons between different cases of the stochastically optimized plans, the optimization was repeated twenty times. Results: Across twenty optimizations, combined MV+kV IMRT resulted in an average of 12.8% reduction in peak skin dose. Both non-optimized and MV+kV optimized imaging beams delivered, on average, mean dose of approximately 1 cGy per fraction to the target, with peak doses to target of approximately 6 cGy per fraction. Conclusion: When using DAO, MV+kV optimization is shown to Result in improvements to plan quality in terms of skin dose, when compared to the case of MV optimization with non-optimized kV imaging. The combination of DAO and MV+kV optimization may allow for real-time imaging without excessive imaging dose. Financial support for the work has been provided in part by NIH Grant T32 EB002103, ACS RSG-13-313-01-CCE, and NIH S10 RR021039 and P30 CA14599 grants. The contents of this submission do not necessarily represent the official views of any of the supporting organizations.« less

Simultaneously optimizing dose and schedule of a new cytotoxic agent.

PubMed

Braun, Thomas M; Thall, Peter F; Nguyen, Hoang; de Lima, Marcos

2007-01-01

Traditionally, phase I clinical trial designs are based upon one predefined course of treatment while varying among patients the dose given at each administration. In actual medical practice, patients receive a schedule comprised of several courses of treatment, and some patients may receive one or more dose reductions or delays during treatment. Consequently, the overall risk of toxicity for each patient is a function of both actual schedule of treatment and the differing doses used at each adminstration. Our goal is to provide a practical phase I clinical trial design that more accurately reflects actual medical practice by accounting for both dose per administration and schedule. We propose an outcome-adaptive Bayesian design that simultaneously optimizes both dose and schedule in terms of the overall risk of toxicity, based on time-to-toxicity outcomes. We use computer simulation as a tool to calibrate design parameters. We describe a phase I trial in allogeneic bone marrow transplantation that was designed and is currently being conducted using our new method. Our computer simulations demonstrate that our method outperforms any method that searches for an optimal dose but does not allow schedule to vary, both in terms of the probability of identifying optimal (dose, schedule) combinations, and the numbers of patients assigned to those combinations in the trial. Our design requires greater sample sizes than those seen in traditional phase I studies due to the larger number of treatment combinations examined. Our design also assumes that the effects of multiple administrations are independent of each other and that the hazard of toxicity is the same for all administrations. Our design is the first for phase I clinical trials that is sufficiently flexible and practical to truly reflect clinical practice by varying both dose and the timing and number of administrations given to each patient.

Patient Dose Management: Focus on Practical Actions

PubMed Central

2016-01-01

Medical radiation is a very important part of modern medicine, and should be only used when needed and optimized. Justification and optimization of radiation examinations must be performed. The first step of reduction of medical exposure is to know the radiation dose in currently performed examinations. This review covers radiation units, how various imaging modalities report dose, and the current status of radiation dose reports and legislation. Also, practical tips that can be applied to clinical practice are introduced. Afterwards, the importance of radiology exposure related education is emphasized and the current status of education for medical personal and the public is explained, and appropriate education strategies are suggested. Commonly asked radiation dose related example questions and answers are provided in detail to allow medical personnel to answer patients. Lastly, we talk about computerized programs that can be used in medical facilities for managing patient dose. While patient dose monitoring and management should be used to decrease and optimize overall radiation dose, it should not be used to assess individual cancer risk. One must always remember that medically justified examinations should always be performed, and unneeded examinations should be avoided in the first place. PMID:26908988

Optimal dose selection accounting for patient subpopulations in a randomized Phase II trial to maximize the success probability of a subsequent Phase III trial.

PubMed

Takahashi, Fumihiro; Morita, Satoshi

2018-02-08

Phase II clinical trials are conducted to determine the optimal dose of the study drug for use in Phase III clinical trials while also balancing efficacy and safety. In conducting these trials, it may be important to consider subpopulations of patients grouped by background factors such as drug metabolism and kidney and liver function. Determining the optimal dose, as well as maximizing the effectiveness of the study drug by analyzing patient subpopulations, requires a complex decision-making process. In extreme cases, drug development has to be terminated due to inadequate efficacy or severe toxicity. Such a decision may be based on a particular subpopulation. We propose a Bayesian utility approach (BUART) to randomized Phase II clinical trials which uses a first-order bivariate normal dynamic linear model for efficacy and safety in order to determine the optimal dose and study population in a subsequent Phase III clinical trial. We carried out a simulation study under a wide range of clinical scenarios to evaluate the performance of the proposed method in comparison with a conventional method separately analyzing efficacy and safety in each patient population. The proposed method showed more favorable operating characteristics in determining the optimal population and dose.

SCCT guidelines on radiation dose and dose-optimization strategies in cardiovascular CT

PubMed Central

Halliburton, Sandra S.; Abbara, Suhny; Chen, Marcus Y.; Gentry, Ralph; Mahesh, Mahadevappa; Raff, Gilbert L.; Shaw, Leslee J.; Hausleiter, Jörg

2012-01-01

Over the last few years, computed tomography (CT) has developed into a standard clinical test for a variety of cardiovascular conditions. The emergence of cardiovascular CT during a period of dramatic increase in radiation exposure to the population from medical procedures and heightened concern about the subsequent potential cancer risk has led to intense scrutiny of the radiation burden of this new technique. This has hastened the development and implementation of dose reduction tools and prompted closer monitoring of patient dose. In an effort to aid the cardiovascular CT community in incorporating patient-centered radiation dose optimization and monitoring strategies into standard practice, the Society of Cardiovascular Computed Tomography has produced a guideline document to review available data and provide recommendations regarding interpretation of radiation dose indices and predictors of risk, appropriate use of scanner acquisition modes and settings, development of algorithms for dose optimization, and establishment of procedures for dose monitoring. PMID:21723512

Individualized Selection of Beam Angles and Treatment Isocenter in Tangential Breast Intensity Modulated Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Penninkhof, Joan, E-mail: j.penninkhof@erasmusmc.nl; Spadola, Sara; Department of Physics and Astronomy, Alma Mater Studiorum, University of Bologna, Bologna

Purpose and Objective: Propose a novel method for individualized selection of beam angles and treatment isocenter in tangential breast intensity modulated radiation therapy (IMRT). Methods and Materials: For each patient, beam and isocenter selection starts with the fully automatic generation of a large database of IMRT plans (up to 847 in this study); each of these plans belongs to a unique combination of isocenter position, lateral beam angle, and medial beam angle. The imposed hard planning constraint on patient maximum dose may result in plans with unacceptable target dose delivery. Such plans are excluded from further analyses. Owing to differencesmore » in beam setup, database plans differ in mean doses to organs at risk (OARs). These mean doses are used to construct 2-dimensional graphs, showing relationships between: (1) contralateral breast dose and ipsilateral lung dose; and (2) contralateral breast dose and heart dose (analyzed only for left-sided). The graphs can be used for selection of the isocenter and beam angles with the optimal, patient-specific tradeoffs between the mean OAR doses. For 30 previously treated patients (15 left-sided and 15 right-sided tumors), graphs were generated considering only the clinically applied isocenter with 121 tangential beam angle pairs. For 20 of the 30 patients, 6 alternative isocenters were also investigated. Results: Computation time for automatic generation of 121 IMRT plans took on average 30 minutes. The generated graphs demonstrated large variations in tradeoffs between conflicting OAR objectives, depending on beam angles and patient anatomy. For patients with isocenter optimization, 847 IMRT plans were considered. Adding isocenter position optimization next to beam angle optimization had a small impact on the final plan quality. Conclusion: A method is proposed for individualized selection of beam angles in tangential breast IMRT. This may be especially important for patients with cardiac risk factors or an enhanced risk for the development of contralateral breast cancer.« less

Use of allopurinol with low-dose 6-mercaptopurine in inflammatory bowel disease to achieve optimal active metabolite levels: A review of four cases and the literature

PubMed Central

Witte, Todd N; Ginsberg, Allen L

2008-01-01

BACKGROUND: At least one-third of patients with inflammatory bowel disease do not respond or are intolerant to therapy with 6-mercaptopurine (6-MP). A subgroup fails to attain optimal levels of 6-thioguanine nucleotide (6-TGN) and instead shunts to 6-methylmercaptopurine nucleotide (6-MMPN). PATIENTS AND METHODS: A retrospective chart review was conducted, and four patients are described who had been previously unable to achieve optimal 6-TGN metabolite levels until allopurinol was added to their treatment. RESULTS: All four patients achieved optimal 6-TGN levels and undetectable 6-MMPN with a mean 6-MP dose of 0.49 mg/kg. Three achieved steroid-free clinical remission. Two of those three patients had normalization of liver enzymes; one patient had baseline normal liver enzymes despite an initial 6-MMPN level of 27,369 pmol/8×108 red blood cells. Two patients experienced reversible leukopenia. CONCLUSIONS: Combination allopurinol and low-dose 6-MP is an effective means to achieve optimal metabolite levels and steroid-free clinical remission in previously refractory patients. Caution is advised. PMID:18299738

TH-CD-202-08: Feasibility Study of Planning Phase Optimization Using Patient Geometry-Driven Information for Better Dose Sparing of Organ at Risks

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kang, S; Kim, D; Kim, T

2016-06-15

Purpose: To propose a simple and effective cost value function to search optimal planning phase (gating window) and demonstrated its feasibility for respiratory correlated radiation therapy. Methods: We acquired 4DCT of 10 phases for 10 lung patients who have tumor located near OARs such as esophagus, heart, and spinal cord (i.e., central lung cancer patients). A simplified mathematical optimization function was established by using overlap volume histogram (OVH) between the target and organ at risk (OAR) at each phase and the tolerance dose of selected OARs to achieve surrounding OARs dose-sparing. For all patients and all phases, delineation of themore » target volume and selected OARs (esophagus, heart, and spinal cord) was performed (by one observer to avoid inter-observer variation), then cost values were calculated for all phases. After the breathing phases were ranked according to cost value function, the relationship between score and dose distribution at highest and lowest cost value phases were evaluated by comparing the mean/max dose. Results: A simplified mathematical cost value function showed noticeable difference from phase to phase, implying it is possible to find optimal phases for gating window. The lowest cost value which may result in lower mean/max dose to OARs was distributed at various phases for all patients. The mean doses of the OARs significantly decreased about 10% with statistical significance for all 3 OARs at the phase with the lowest cost value. Also, the max doses of the OARs were decreased about 2∼5% at the phase with the lowest cost value compared to the phase with the highest cost value. Conclusion: It is demonstrated that optimal phases (in dose distribution perspective) for gating window could exist differently through each patient and the proposed cost value function can be a useful tool for determining such phases without performing dose optimization calculations. This research was supported by the Mid-career Researcher Program through NRF funded by the Ministry of Science, ICT & Future Planning of Korea (NRF-2014R1A2A1A10050270) and by the Radiation Technology R&D program through the National Research Foundation of Korea funded by the Ministry of Science, ICT & Future Planning (No. 2013M2A2A7038291)« less

4D Optimization of Scanned Ion Beam Tracking Therapy for Moving Tumors

PubMed Central

Eley, John Gordon; Newhauser, Wayne David; Lüchtenborg, Robert; Graeff, Christian; Bert, Christoph

2014-01-01

Motion mitigation strategies are needed to fully realize the theoretical advantages of scanned ion beam therapy for patients with moving tumors. The purpose of this study was to determine whether a new four-dimensional (4D) optimization approach for scanned-ion-beam tracking could reduce dose to avoidance volumes near a moving target while maintaining target dose coverage, compared to an existing 3D-optimized beam tracking approach. We tested these approaches computationally using a simple 4D geometrical phantom and a complex anatomic phantom, that is, a 4D computed tomogram of the thorax of a lung cancer patient. We also validated our findings using measurements of carbon-ion beams with a motorized film phantom. Relative to 3D-optimized beam tracking, 4D-optimized beam tracking reduced the maximum predicted dose to avoidance volumes by 53% in the simple phantom and by 13% in the thorax phantom. 4D-optimized beam tracking provided similar target dose homogeneity in the simple phantom (standard deviation of target dose was 0.4% versus 0.3%) and dramatically superior homogeneity in the thorax phantom (D5-D95 was 1.9% versus 38.7%). Measurements demonstrated that delivery of 4D-optimized beam tracking was technically feasible and confirmed a 42% decrease in maximum film exposure in the avoidance region compared with 3D-optimized beam tracking. In conclusion, we found that 4D-optimized beam tracking can reduce the maximum dose to avoidance volumes near a moving target while maintaining target dose coverage, compared with 3D-optimized beam tracking. PMID:24889215

4D optimization of scanned ion beam tracking therapy for moving tumors

NASA Astrophysics Data System (ADS)

Eley, John Gordon; Newhauser, Wayne David; Lüchtenborg, Robert; Graeff, Christian; Bert, Christoph

2014-07-01

Motion mitigation strategies are needed to fully realize the theoretical advantages of scanned ion beam therapy for patients with moving tumors. The purpose of this study was to determine whether a new four-dimensional (4D) optimization approach for scanned-ion-beam tracking could reduce dose to avoidance volumes near a moving target while maintaining target dose coverage, compared to an existing 3D-optimized beam tracking approach. We tested these approaches computationally using a simple 4D geometrical phantom and a complex anatomic phantom, that is, a 4D computed tomogram of the thorax of a lung cancer patient. We also validated our findings using measurements of carbon-ion beams with a motorized film phantom. Relative to 3D-optimized beam tracking, 4D-optimized beam tracking reduced the maximum predicted dose to avoidance volumes by 53% in the simple phantom and by 13% in the thorax phantom. 4D-optimized beam tracking provided similar target dose homogeneity in the simple phantom (standard deviation of target dose was 0.4% versus 0.3%) and dramatically superior homogeneity in the thorax phantom (D5-D95 was 1.9% versus 38.7%). Measurements demonstrated that delivery of 4D-optimized beam tracking was technically feasible and confirmed a 42% decrease in maximum film exposure in the avoidance region compared with 3D-optimized beam tracking. In conclusion, we found that 4D-optimized beam tracking can reduce the maximum dose to avoidance volumes near a moving target while maintaining target dose coverage, compared with 3D-optimized beam tracking.

Linear energy transfer incorporated intensity modulated proton therapy optimization

NASA Astrophysics Data System (ADS)

Cao, Wenhua; Khabazian, Azin; Yepes, Pablo P.; Lim, Gino; Poenisch, Falk; Grosshans, David R.; Mohan, Radhe

2018-01-01

The purpose of this study was to investigate the feasibility of incorporating linear energy transfer (LET) into the optimization of intensity modulated proton therapy (IMPT) plans. Because increased LET correlates with increased biological effectiveness of protons, high LETs in target volumes and low LETs in critical structures and normal tissues are preferred in an IMPT plan. However, if not explicitly incorporated into the optimization criteria, different IMPT plans may yield similar physical dose distributions but greatly different LET, specifically dose-averaged LET, distributions. Conventionally, the IMPT optimization criteria (or cost function) only includes dose-based objectives in which the relative biological effectiveness (RBE) is assumed to have a constant value of 1.1. In this study, we added LET-based objectives for maximizing LET in target volumes and minimizing LET in critical structures and normal tissues. Due to the fractional programming nature of the resulting model, we used a variable reformulation approach so that the optimization process is computationally equivalent to conventional IMPT optimization. In this study, five brain tumor patients who had been treated with proton therapy at our institution were selected. Two plans were created for each patient based on the proposed LET-incorporated optimization (LETOpt) and the conventional dose-based optimization (DoseOpt). The optimized plans were compared in terms of both dose (assuming a constant RBE of 1.1 as adopted in clinical practice) and LET. Both optimization approaches were able to generate comparable dose distributions. The LET-incorporated optimization achieved not only pronounced reduction of LET values in critical organs, such as brainstem and optic chiasm, but also increased LET in target volumes, compared to the conventional dose-based optimization. However, on occasion, there was a need to tradeoff the acceptability of dose and LET distributions. Our conclusion is that the inclusion of LET-dependent criteria in the IMPT optimization could lead to similar dose distributions as the conventional optimization but superior LET distributions in target volumes and normal tissues. This may have substantial advantages in improving tumor control and reducing normal tissue toxicities.

SU-E-T-280: Reconstructed Rectal Wall Dose Map-Based Verification of Rectal Dose Sparing Effect According to Rectum Definition Methods and Dose Perturbation by Air Cavity in Endo-Rectal Balloon

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, J; Research Institute of Biomedical Engineering, The Catholic University of Korea, Seoul; Park, H

Purpose: Dosimetric effect and discrepancy according to the rectum definition methods and dose perturbation by air cavity in an endo-rectal balloon (ERB) were verified using rectal-wall (Rwall) dose maps considering systematic errors in dose optimization and calculation accuracy in intensity-modulated radiation treatment (IMRT) for prostate cancer patients. Methods: When the inflated ERB having average diameter of 4.5 cm and air volume of 100 cc is used for patient, Rwall doses were predicted by pencil-beam convolution (PBC), anisotropic analytic algorithm (AAA), and AcurosXB (AXB) with material assignment function. The errors of dose optimization and calculation by separating air cavity from themore » whole rectum (Rwhole) were verified with measured rectal doses. The Rwall doses affected by the dose perturbation of air cavity were evaluated using a featured rectal phantom allowing insert of rolled-up gafchromic films and glass rod detectors placed along the rectum perimeter. Inner and outer Rwall doses were verified with reconstructed predicted rectal wall dose maps. Dose errors and extent at dose levels were evaluated with estimated rectal toxicity. Results: While AXB showed insignificant difference of target dose coverage, Rwall doses underestimated by up to 20% in dose optimization for the Rwhole than Rwall at all dose range except for the maximum dose. As dose optimization for Rwall was applied, the Rwall doses presented dose error less than 3% between dose calculation algorithm except for overestimation of maximum rectal dose up to 5% in PBC. Dose optimization for Rwhole caused dose difference of Rwall especially at intermediate doses. Conclusion: Dose optimization for Rwall could be suggested for more accurate prediction of rectal wall dose prediction and dose perturbation effect by air cavity in IMRT for prostate cancer. This research was supported by the Leading Foreign Research Institute Recruitment Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (MSIP) (Grant No. 200900420)« less

Impact of a phenytoin loading dose program in the emergency department.

PubMed

Brancaccio, Adam; Giuliano, Christopher; McNorton, Kelly; Delgado, George

2014-11-01

The use of a combined physician-and pharmacist-directed phenytoin loading dose program in an emergency department (ED) was evaluated. This single-center, observational, preimplementation-postimplementation study evaluated adult patients who received a phenytoin loading dose in the ED. The primary outcome compared the proportion of optimal phenytoin loading doses in the preimplementation and postimplementation groups. The postimplementation group was further stratified into pharmacist- and prescriber-dosing groups. Other outcomes evaluated included the numbers of appropriate serum phenytoin concentrations measured, adverse drug reactions (ADRs), and recurrence of seizures within 24 hours of loading dose administration in the preimplementation and postimplementation groups. There was no difference in the proportion of optimal phenytoin loading doses between the preimplementation and postimplementation groups (50% versus 62%, respectively; p=0.19). When stratified by individual groups, the rate of optimal phenytoin loading doses increased by 64% in the postimplementation pharmacist group (50% versus 82%, p=0.007), while the rate in the prescriber-dosing group remained relatively unchanged (50% versus 49%, p=0.91). The number of appropriate serum phenytoin concentrations significantly improved in the postimplementation versus preimplementation group (65% versus 40%, p=0.025). Rates of ADRs and recurrence of seizures did not differ across the study groups. No change in the percentage of optimal phenytoin loading doses in the ED was observed after implementation of a combined pharmacist- and physician- dosing program. When stratified into pharmacist or prescriber dosing, the pharmacist-led dosing program significantly improved the proportion of patients who received optimal phenytoin loading doses. Copyright © 2014 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Impact of database quality in knowledge-based treatment planning for prostate cancer.

PubMed

Wall, Phillip D H; Carver, Robert L; Fontenot, Jonas D

2018-03-13

This article investigates dose-volume prediction improvements in a common knowledge-based planning (KBP) method using a Pareto plan database compared with using a conventional, clinical plan database. Two plan databases were created using retrospective, anonymized data of 124 volumetric modulated arc therapy (VMAT) prostate cancer patients. The clinical plan database (CPD) contained planning data from each patient's clinically treated VMAT plan, which were manually optimized by various planners. The multicriteria optimization database (MCOD) contained Pareto-optimal plan data from VMAT plans created using a standardized multicriteria optimization protocol. Overlap volume histograms, incorporating fractional organ at risk volumes only within the treatment fields, were computed for each patient and used to match new patient anatomy to similar database patients. For each database patient, CPD and MCOD KBP predictions were generated for D 10 , D 30 , D 50 , D 65 , and D 80 of the bladder and rectum in a leave-one-out manner. Prediction achievability was evaluated through a replanning study on a subset of 31 randomly selected database patients using the best KBP predictions, regardless of plan database origin, as planning goals. MCOD predictions were significantly lower than CPD predictions for all 5 bladder dose-volumes and rectum D 50 (P = .004) and D 65 (P < .001), whereas CPD predictions for rectum D 10 (P = .005) and D 30 (P < .001) were significantly less than MCOD predictions. KBP predictions were statistically achievable in the replans for all predicted dose-volumes, excluding D 10 of bladder (P = .03) and rectum (P = .04). Compared with clinical plans, replans showed significant average reductions in D mean for bladder (7.8 Gy; P < .001) and rectum (9.4 Gy; P < .001), while maintaining statistically similar planning target volume, femoral head, and penile bulb dose. KBP dose-volume predictions derived from Pareto plans were more optimal overall than those resulting from manually optimized clinical plans, which significantly improved KBP-assisted plan quality. This work investigates how the plan quality of knowledge databases affects the performance and achievability of dose-volume predictions from a common knowledge-based planning approach for prostate cancer. Bladder and rectum dose-volume predictions derived from a database of standardized Pareto-optimal plans were compared with those derived from clinical plans manually designed by various planners. Dose-volume predictions from the Pareto plan database were significantly lower overall than those from the clinical plan database, without compromising achievability. Copyright © 2018 Elsevier Inc. All rights reserved.

MO-DE-204-02: Optimization of the Patient CT Dose in Europe

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tsapaki, V.

2016-06-15

The main topic of the session is to show how dose optimization is being implemented in various regions of the world, including Europe, Australia, North America and other regions. A multi-national study conducted under International Atomic Energy Agency (IAEA) across more than 50 less resourced countries gave insight into patient radiation doses and safety practices in CT, mammography, radiography and interventional procedures, both for children and adults. An important outcome was the capability development on dose assessment and management. An overview of recent European projects related to CT radiation dose and optimization both to adults and children will be presented.more » Existing data on DRLs together with a European methodology proposed on establishing and using DRLs for paediatric radiodiagnostic imaging and interventional radiology practices will be shown. Compared with much of Europe at least, many Australian imaging practices are relatively new to the task of diagnostic imaging dose optimisation. In 2008 the Australian Government prescribed a requirement to periodically compare patient radiation doses with diagnostic reference levels (DRLs), where DRLs have been established. Until recently, Australia had only established DRLs for computed tomography (CT). Regardless, both professional society and individual efforts to improved data collection and develop optimisation strategies across a range of modalities continues. Progress in this field, principally with respect to CT and interventional fluoroscopy will be presented. In the US, dose reduction and optimization efforts for computed tomography have been promoted and mandated by several organizations and accrediting entities. This presentation will cover the general motivation, implementation, and implications of such efforts. Learning Objectives: Understand importance of the dose optimization in Diagnostic Radiology. See how this goal is achieved in different regions of the World. Learn about the global trend in the dose optimization and future prospectives. M. Rehani, The work was a part of the work of IAEA where I was an employee and IAEA is a United Nations organization.« less

Voxel-based dose prediction with multi-patient atlas selection for automated radiotherapy treatment planning

NASA Astrophysics Data System (ADS)

McIntosh, Chris; Purdie, Thomas G.

2017-01-01

Automating the radiotherapy treatment planning process is a technically challenging problem. The majority of automated approaches have focused on customizing and inferring dose volume objectives to be used in plan optimization. In this work we outline a multi-patient atlas-based dose prediction approach that learns to predict the dose-per-voxel for a novel patient directly from the computed tomography planning scan without the requirement of specifying any objectives. Our method learns to automatically select the most effective atlases for a novel patient, and then map the dose from those atlases onto the novel patient. We extend our previous work to include a conditional random field for the optimization of a joint distribution prior that matches the complementary goals of an accurately spatially distributed dose distribution while still adhering to the desired dose volume histograms. The resulting distribution can then be used for inverse-planning with a new spatial dose objective, or to create typical dose volume objectives for the canonical optimization pipeline. We investigated six treatment sites (633 patients for training and 113 patients for testing) and evaluated the mean absolute difference in all DVHs for the clinical and predicted dose distribution. The results on average are favorable in comparison to our previous approach (1.91 versus 2.57). Comparing our method with and without atlas-selection further validates that atlas-selection improved dose prediction on average in whole breast (0.64 versus 1.59), prostate (2.13 versus 4.07), and rectum (1.46 versus 3.29) while it is less important in breast cavity (0.79 versus 0.92) and lung (1.33 versus 1.27) for which there is high conformity and minimal dose shaping. In CNS brain, atlas-selection has the potential to be impactful (3.65 versus 5.09), but selecting the ideal atlas is the most challenging.

SU-F-T-337: Accounting for Patient Motion During Volumetric Modulated Ac Therapy (VMAT) Planning for Post Mastectomy Chest Wall Irradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hernandez, M; Fontenot, J; Heins, D

2016-06-15

Purpose: To evaluate two dose optimization strategies for maintaining target volume coverage of inversely-planned post mastectomy radiotherapy (PMRT) plans during patient motion. Methods: Five patients previously treated with VMAT for PMRT at our clinical were randomly selected for this study. For each patient, two plan optimization strategies were compared. Plan 1 was optimized to a volume that included the physician’s planning target volume (PTV) plus an expansion up to 0.3 cm from the bolus surface. Plan 2 was optimized to the PTV plus an expansion up to 0.3 cm from the patient surface (i.e., not extending into the bolus). VMATmore » plans were optimized to deliver 95% of the prescription to 95% of the PTV while sparing organs at risk based on clinical dose limits. PTV coverage was then evaluated following the simulation of patient shifts by 1.0 cm in the anterior and posterior directions using the treatment planning system. Results: Posterior patient shifts produced a difference in D95% of around 11% in both planning approaches from the non-shifted dose distributions. Coverage of the medial and lateral borders of the evaluation volume was reduced in both the posteriorly shifted plans (Plan 1 and Plan 2). Anterior patient shifts affected Plan 2 more than Plan 1 with a difference in D95% of 1% for Plan 1 versus 6% for Plan 2 from the non-shifted dose distributions. The least variation in PTV dose homogeneity for both shifts was obtained with Plan 1. However, all posteriorly shifted plans failed to deliver 95% of the prescription to 95% of the PTV. Whereas, only a few anteriorly shifted plans failed this criteria. Conclusion: The results of this study suggest both planning volume methods are sensitive to patient motion, but that a PTV extended into a bolus volume is slightly more robust for anterior patient shifts.« less

Multivariable normal tissue complication probability model-based treatment plan optimization for grade 2-4 dysphagia and tube feeding dependence in head and neck radiotherapy.

PubMed

Kierkels, Roel G J; Wopken, Kim; Visser, Ruurd; Korevaar, Erik W; van der Schaaf, Arjen; Bijl, Hendrik P; Langendijk, Johannes A

2016-12-01

Radiotherapy of the head and neck is challenged by the relatively large number of organs-at-risk close to the tumor. Biologically-oriented objective functions (OF) could optimally distribute the dose among the organs-at-risk. We aimed to explore OFs based on multivariable normal tissue complication probability (NTCP) models for grade 2-4 dysphagia (DYS) and tube feeding dependence (TFD). One hundred head and neck cancer patients were studied. Additional to the clinical plan, two more plans (an OF DYS and OF TFD -plan) were optimized per patient. The NTCP models included up to four dose-volume parameters and other non-dosimetric factors. A fully automatic plan optimization framework was used to optimize the OF NTCP -based plans. All OF NTCP -based plans were reviewed and classified as clinically acceptable. On average, the Δdose and ΔNTCP were small comparing the OF DYS -plan, OF TFD -plan, and clinical plan. For 5% of patients NTCP TFD reduced >5% using OF TFD -based planning compared to the OF DYS -plans. Plan optimization using NTCP DYS - and NTCP TFD -based objective functions resulted in clinically acceptable plans. For patients with considerable risk factors of TFD, the OF TFD steered the optimizer to dose distributions which directly led to slightly lower predicted NTCP TFD values as compared to the other studied plans. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Limiting the risk of cardiac toxicity with esophageal-sparing intensity modulated radiotherapy for locally advanced lung cancers.

PubMed

Woodford, Katrina; Panettieri, Vanessa; Ruben, Jeremy D; Senthi, Sashendra

2016-05-01

Intensity modulated radiotherapy (IMRT) is routinely utilized in the treatment of locally advanced non-small cell lung cancer (NSCLC). RTOG 0617 found that overall survival was impacted by increased low (5 Gy) and intermediate (30 Gy) cardiac doses. We evaluated the impact of esophageal-sparing IMRT on cardiac doses with and without the heart considered in the planning process and predicted toxicity compared to 3D-conventional radiotherapy (3DCRT). Ten consecutive patients with N2 Stage III NSCLC treated to 60 Gy in 30 fractions, between February 2012 and September 2014, were evaluated. For each patient, 3DCRT and esophageal-sparing IMRT plans were generated. IMRT plans were then created with and without the heart considered in the optimization process. To compare plans, the dose delivered to 95% and 99% of the target (D95% and D99%), and doses to the esophagus, lung and heart were compared by determining the volume receiving X dose (VXGy) and the normal tissue complication probability (NTCP) calculated. IMRT reduced maximum esophagus dose to below 60 Gy in all patients and produced significant reductions to V50Gy, V40Gy and esophageal NTCP. The cost of this reduction was a non-statistically, non-clinically significant increase in low dose (5 Gy) lung exposure that did not worsen lung NTCP. IMRT plans produced significant cardiac sparing, with the amount of improvement correlating to the amount of heart overlapping with the target. When included in plan optimization, for selected patients further sparing of the heart and improvement in heart NTCP was possible. Esophageal-sparing IMRT can significantly spare the heart even if it is not considered in the optimization process. Further sparing can be achieved if plan optimization constrains low and intermediate heart doses, without compromising lung doses.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dogan, N; Padgett, K; Evans, J

Purpose: Adaptive Radiotherapy (ART) with frequent CT imaging has been used to improve dosimetric accuracy by accounting for anatomical variations, such as primary tumor shrinkage and/or body weight loss, in Head and Neck (H&N) patients. In most ART strategies, the difference between the planned and the delivered dose is estimated by generating new plans on repeated CT scans using dose-volume constraints used with the initial planning CT without considering already delivered dose. The aim of this study was to assess the dosimetric gains achieved by re-planning based on prior dose by comparing them to re-planning not based-on prior dose formore » H&N patients. Methods: Ten locally-advanced H&N cancer patients were selected for this study. For each patient, six weekly CT imaging were acquired during the course of radiotherapy. PTVs, parotids, cord, brainstem, and esophagus were contoured on both planning and six weekly CT images. ART with weekly re-plans were done by two strategies: 1) Generating a new optimized IMRT plan without including prior dose from previous fractions (NoPriorDose) and 2) Generating a new optimized IMRT plan based on the prior dose given from previous fractions (PriorDose). Deformable image registration was used to accumulate the dose distributions between planning and six weekly CT scans. The differences in accumulated doses for both strategies were evaluated using the DVH constraints for all structures. Results: On average, the differences in accumulated doses for PTV1, PTV2 and PTV3 for NoPriorDose and PriorDose strategies were <2%. The differences in Dmean to the cord and brainstem were within 3%. The esophagus Dmean was reduced by 2% using PriorDose. PriorDose strategy, however, reduced the left parotid D50 and Dmean by 15% and 14% respectively. Conclusion: This study demonstrated significant parotid sparing, potentially reducing xerostomia, by using ART with IMRT optimization based on prior dose for weekly re-planning of H&N cancer patients.« less

SU-F-BRD-07: Fast Monte Carlo-Based Biological Optimization of Proton Therapy Treatment Plans for Thyroid Tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wan Chan Tseung, H; Ma, J; Ma, D

2015-06-15

Purpose: To demonstrate the feasibility of fast Monte Carlo (MC) based biological planning for the treatment of thyroid tumors in spot-scanning proton therapy. Methods: Recently, we developed a fast and accurate GPU-based MC simulation of proton transport that was benchmarked against Geant4.9.6 and used as the dose calculation engine in a clinically-applicable GPU-accelerated IMPT optimizer. Besides dose, it can simultaneously score the dose-averaged LET (LETd), which makes fast biological dose (BD) estimates possible. To convert from LETd to BD, we used a linear relation based on cellular irradiation data. Given a thyroid patient with a 93cc tumor volume, we createdmore » a 2-field IMPT plan in Eclipse (Varian Medical Systems). This plan was re-calculated with our MC to obtain the BD distribution. A second 5-field plan was made with our in-house optimizer, using pre-generated MC dose and LETd maps. Constraints were placed to maintain the target dose to within 25% of the prescription, while maximizing the BD. The plan optimization and calculation of dose and LETd maps were performed on a GPU cluster. The conventional IMPT and biologically-optimized plans were compared. Results: The mean target physical and biological doses from our biologically-optimized plan were, respectively, 5% and 14% higher than those from the MC re-calculation of the IMPT plan. Dose sparing to critical structures in our plan was also improved. The biological optimization, including the initial dose and LETd map calculations, can be completed in a clinically viable time (∼30 minutes) on a cluster of 25 GPUs. Conclusion: Taking advantage of GPU acceleration, we created a MC-based, biologically optimized treatment plan for a thyroid patient. Compared to a standard IMPT plan, a 5% increase in the target’s physical dose resulted in ∼3 times as much increase in the BD. Biological planning was thus effective in escalating the target BD.« less

CT dose minimization using personalized protocol optimization and aggressive bowtie

NASA Astrophysics Data System (ADS)

Wang, Hui; Yin, Zhye; Jin, Yannan; Wu, Mingye; Yao, Yangyang; Tao, Kun; Kalra, Mannudeep K.; De Man, Bruno

2016-03-01

In this study, we propose to use patient-specific x-ray fluence control to reduce the radiation dose to sensitive organs while still achieving the desired image quality (IQ) in the region of interest (ROI). The mA modulation profile is optimized view by view, based on the sensitive organs and the ROI, which are obtained from an ultra-low-dose volumetric CT scout scan [1]. We use a clinical chest CT scan to demonstrate the feasibility of the proposed concept: the breast region is selected as the sensitive organ region while the cardiac region is selected as IQ ROI. Two groups of simulations are performed based on the clinical CT dataset: (1) a constant mA scan adjusted based on the patient attenuation (120 kVp, 300 mA), which serves as baseline; (2) an optimized scan with aggressive bowtie and ROI centering combined with patient-specific mA modulation. The results shows that the combination of the aggressive bowtie and the optimized mA modulation can result in 40% dose reduction in the breast region, while the IQ in the cardiac region is maintained. More generally, this paper demonstrates the general concept of using a 3D scout scan for optimal scan planning.

Population pharmacokinetics of phenytoin after intravenous administration of fosphenytoin sodium in pediatric patients, adult patients, and healthy volunteers.

PubMed

Tanaka, Jun; Kasai, Hidefumi; Shimizu, Kenji; Shimasaki, Shigeki; Kumagai, Yuji

2013-03-01

We performed a population pharmacokinetic analysis of phenytoin after intravenous administration of fosphenytoin sodium in healthy, neurosurgical, and epileptic subjects, including pediatric patients, and determined the optimal dose and infusion rate for achieving the therapeutic range. We used pooled data obtained from two phase I studies and one phase III study performed in Japan. The population pharmacokinetic analysis was performed using NONMEM software. The optimal dose and infusion rate were determined using simulation results obtained using the final model. The therapeutic range for total plasma phenytoin concentration is 10-20 μg/mL. We used a linear two-compartment model with conversion of fosphenytoin to phenytoin. Pharmacokinetic parameters of phenytoin, such as total clearance and central and peripheral volume of distribution were influenced by body weight. The dose simulations are as follows. In adult patients, the optimal dose and infusion rate of phenytoin for achieving the therapeutic range was 22.5 mg/kg and 3 mg/kg/min respectively. In pediatric patients, the total plasma concentration of phenytoin was within the therapeutic range for a shorter duration than that in adult patients at 22.5 mg/kg (3 mg/kg/min). However, many pediatric patients showed phenytoin concentration within the toxic range after administration of a dose of 30 mg/kg. The pharmacokinetics of phenytoin after intravenous administration of fosphenytoin sodium could be described using a linear two-compartment model. The administration of fosphenytoin sodium 22.5 mg/kg at an infusion rate of 3 mg/kg/min was optimal for achieving the desired plasma phenytoin concentration.

Model-based dose selection for phase III rivaroxaban study in Japanese patients with non-valvular atrial fibrillation.

PubMed

Tanigawa, Takahiko; Kaneko, Masato; Hashizume, Kensei; Kajikawa, Mariko; Ueda, Hitoshi; Tajiri, Masahiro; Paolini, John F; Mueck, Wolfgang

2013-01-01

The global ROCKET AF phase III trial evaluated rivaroxaban 20 mg once daily (o.d.) for stroke prevention in atrial fibrillation (AF). Based on rivaroxaban pharmacokinetics in Japanese subjects and lower anticoagulation preferences in Japan, particularly in elderly patients, the optimal dose regimen for Japanese AF patients was considered. The aim of this analysis was dose selection for Japanese patients from a pharmacokinetic aspect by comparison of simulated exposure in Japanese patients with those in Caucasian patients. As a result of population pharmacokinetics-pharmacodynamics analyses, a one-compartment pharmacokinetic model with first-order absorption and direct link pharmacokinetic-pharmacodynamic models optimally described the plasma concentration and pharmacodynamic models (Factor Xa activity, prothrombin time, activated partial thromboplastin time, and HepTest), which were also consistent with previous works. Steady-state simulations indicated 15 mg rivaroxaban o.d. doses in Japanese patients with AF would yield exposures comparable to the 20 mg o.d. dose in Caucasian patients with AF. In conclusion, in the context of the lower anticoagulation targets in Japanese practice, the population pharmacokinetic and pharmacodynamic modeling supports 15 mg o.d. as the principal rivaroxaban dose in J-ROCKET AF.

Dosimetric investigation of proton therapy on CT-based patient data using Monte Carlo simulation

NASA Astrophysics Data System (ADS)

Chongsan, T.; Liamsuwan, T.; Tangboonduangjit, P.

2016-03-01

The aim of radiotherapy is to deliver high radiation dose to the tumor with low radiation dose to healthy tissues. Protons have Bragg peaks that give high radiation dose to the tumor but low exit dose or dose tail. Therefore, proton therapy is promising for treating deep- seated tumors and tumors locating close to organs at risk. Moreover, the physical characteristic of protons is suitable for treating cancer in pediatric patients. This work developed a computational platform for calculating proton dose distribution using the Monte Carlo (MC) technique and patient's anatomical data. The studied case is a pediatric patient with a primary brain tumor. PHITS will be used for MC simulation. Therefore, patient-specific CT-DICOM files were converted to the PHITS input. A MATLAB optimization program was developed to create a beam delivery control file for this study. The optimization program requires the proton beam data. All these data were calculated in this work using analytical formulas and the calculation accuracy was tested, before the beam delivery control file is used for MC simulation. This study will be useful for researchers aiming to investigate proton dose distribution in patients but do not have access to proton therapy machines.

Optimal medication dosing from suboptimal clinical examples: a deep reinforcement learning approach.

PubMed

Nemati, Shamim; Ghassemi, Mohammad M; Clifford, Gari D

2016-08-01

Misdosing medications with sensitive therapeutic windows, such as heparin, can place patients at unnecessary risk, increase length of hospital stay, and lead to wasted hospital resources. In this work, we present a clinician-in-the-loop sequential decision making framework, which provides an individualized dosing policy adapted to each patient's evolving clinical phenotype. We employed retrospective data from the publicly available MIMIC II intensive care unit database, and developed a deep reinforcement learning algorithm that learns an optimal heparin dosing policy from sample dosing trails and their associated outcomes in large electronic medical records. Using separate training and testing datasets, our model was observed to be effective in proposing heparin doses that resulted in better expected outcomes than the clinical guidelines. Our results demonstrate that a sequential modeling approach, learned from retrospective data, could potentially be used at the bedside to derive individualized patient dosing policies.

Low-dose computed tomography scans with automatic exposure control for patients of different ages undergoing cardiac PET/CT and SPECT/CT.

PubMed

Yang, Ching-Ching; Yang, Bang-Hung; Tu, Chun-Yuan; Wu, Tung-Hsin; Liu, Shu-Hsin

2017-06-01

This study aimed to evaluate the efficacy of automatic exposure control (AEC) in order to optimize low-dose computed tomography (CT) protocols for patients of different ages undergoing cardiac PET/CT and single-photon emission computed tomography/computed tomography (SPECT/CT). One PET/CT and one SPECT/CT were used to acquire CT images for four anthropomorphic phantoms representative of 1-year-old, 5-year-old and 10-year-old children and an adult. For the hybrid systems investigated in this study, the radiation dose and image quality of cardiac CT scans performed with AEC activated depend mainly on the selection of a predefined image quality index. Multiple linear regression methods were used to analyse image data from anthropomorphic phantom studies to investigate the effects of body size and predefined image quality index on CT radiation dose in cardiac PET/CT and SPECT/CT scans. The regression relationships have a coefficient of determination larger than 0.9, indicating a good fit to the data. According to the regression models, low-dose protocols using the AEC technique were optimized for patients of different ages. In comparison with the standard protocol with AEC activated for adult cardiac examinations used in our clinical routine practice, the optimized paediatric protocols in PET/CT allow 32.2, 63.7 and 79.2% CT dose reductions for anthropomorphic phantoms simulating 10-year-old, 5-year-old and 1-year-old children, respectively. The corresponding results for cardiac SPECT/CT are 8.4, 51.5 and 72.7%. AEC is a practical way to reduce CT radiation dose in cardiac PET/CT and SPECT/CT, but the AEC settings should be determined properly for optimal effect. Our results show that AEC does not eliminate the need for paediatric protocols and CT examinations using the AEC technique should be optimized for paediatric patients to reduce the radiation dose as low as reasonably achievable.

Symptomatic pericardial effusion after chemoradiation therapy in esophageal cancer patients.

PubMed

Fukada, Junichi; Shigematsu, Naoyuki; Takeuchi, Hiroya; Ohashi, Toshio; Saikawa, Yoshiro; Takaishi, Hiromasa; Hanada, Takashi; Shiraishi, Yutaka; Kitagawa, Yuko; Fukuda, Keiichi

2013-11-01

We investigated clinical and treatment-related factors as predictors of symptomatic pericardial effusion in esophageal cancer patients after concurrent chemoradiation therapy. We reviewed 214 consecutive primary esophageal cancer patients treated with concurrent chemoradiation therapy between 2001 and 2010 in our institute. Pericardial effusion was detected on follow-up computed tomography. Symptomatic effusion was defined as effusion ≥grade 3 according to Common Terminology Criteria for Adverse Events v4.0 criteria. Percent volume irradiated with 5 to 65 Gy (V5-V65) and mean dose to the pericardium were evaluated employing dose-volume histograms. To evaluate dosimetry for patients treated with two-dimensional planning in the earlier period (2001-2005), computed tomography data at diagnosis were transferred to a treatment planning system to reconstruct three-dimensional plans without modification. Optimal dosimetric thresholds for symptomatic pericardial effusion were calculated by receiver operating characteristic curves. Associating clinical and treatment-related risk factors for symptomatic pericardial effusion were detected by univariate and multivariate analyses. The median follow-up was 29 (range, 6-121) months for eligible 167 patients. Symptomatic pericardial effusion was observed in 14 (8.4%) patients. Dosimetric analyses revealed average values of V30 to V45 for the pericardium and mean pericardial doses were significantly higher in patients with symptomatic pericardial effusion than in those with asymptomatic pericardial effusion (P<.05). Pericardial V5 to V55 and mean pericardial doses were significantly higher in patients with symptomatic pericardial effusion than in those without pericardial effusion (P<.001). Mean pericardial doses of 36.5 Gy and V45 of 58% were selected as optimal cutoff values for predicting symptomatic pericardial effusion. Multivariate analysis identified mean pericardial dose as the strongest risk factor for symptomatic pericardial effusion. Dose-volume thresholds for the pericardium facilitate predicting symptomatic pericardial effusion. Mean pericardial dose was selected based not only on the optimal dose-volume threshold but also on the most significant risk factor for symptomatic pericardial effusion. Copyright © 2013 Elsevier Inc. All rights reserved.

An FDA oncology analysis of immune activating products and first-in-human dose selection.

PubMed

Saber, Haleh; Gudi, Ramadevi; Manning, Michael; Wearne, Emily; Leighton, John K

2016-11-01

As sub-therapeutic doses are not medically justifiable in patients with cancer, we retrospectively analyzed data on immune activating products, to assess approaches used in first-in-human (FIH) dose selection, the utility of animal toxicology studies in dose selection, and the length of time to complete FIH trials. The information collected included pharmacology and toxicology data, FIH dose and rationale, and dose-finding trial design. We used the principles of the Hill equation to estimate the FIH doses for antibodies and compared them to the doses administered to patients with acceptable toxicities. For approximately half the antibodies (44%) examined, the FIH doses were at least a hundred-fold lower than the doses safely administered to patients, indicating optimization of FIH dose selection and/or optimization of dose-finding trial design is needed to minimize patient exposure to sub-therapeutic doses. However, selection of the FIH dose for antibodies based on animal toxicology studies using 1/6th the HNSTD or 1/10th the NOAEL resulted in human doses that were unsafe for several antibodies examined. We also concluded that antibodies with Fc-modifications for increased effector function may be less tolerated, resulting in toxicities at lower doses than those without such modifications. There was insufficient information to evaluate CD3 bispecific products. Published by Elsevier Inc.

Prescribing and up-titration in recently hospitalized heart failure patients attending a disease management program.

PubMed

Carroll, Robert; Mudge, Alison; Suna, Jessica; Denaro, Charles; Atherton, John

2016-08-01

Heart failure (HF) medications improve clinical outcomes, with optimal doses defined in clinical trials. Patient, provider and system barriers may limit achievement of optimal doses in real life settings, although disease management programs (HF-DMPs) can facilitate up-titration. Secondary analysis of a prospective cohort of 216 participants recently hospitalized with systolic HF, attending 5 HF-DMPs in Queensland, Australia. Medication history at baseline (6weeks after discharge) and 6months provided data to describe prescription rates, dosage and optimal titration of HF medications, and associations with patient and system factors were explored. At baseline, 94% were on an angiotensin converting enzyme inhibitor/angiotensin II receptor blocker (ACEI/ARB), 94% on a beta-blocker (BB) and 42% on a mineralocorticoid receptor antagonist (MRA). The proportion of participants on optimal doses of ACEI/ARB increased from 38% (baseline) to 52% (6months, p=0.001) and on optimal BB dose from 23% to 49% (p<0.001). Significant barriers to ACEI/ARB up-titration were body mass index (BMI)<25, female gender, polypharmacy, previously diagnosed HF, and tertiary hospital. Significant barriers for BB up-titration were BMI<25, previously diagnosed HF and non-cardiologist care. Effective up-titration in HF DMPs is influenced by patient, disease and service factors. Better understanding of barriers to effective up-titration in women, normal weight, and established HF patients may help provide targeted strategies for improving outcomes in these groups. Copyright © 2016 Elsevier Ltd. All rights reserved.

Feasibility of online IMPT adaptation using fast, automatic and robust dose restoration

NASA Astrophysics Data System (ADS)

Bernatowicz, Kinga; Geets, Xavier; Barragan, Ana; Janssens, Guillaume; Souris, Kevin; Sterpin, Edmond

2018-04-01

Intensity-modulated proton therapy (IMPT) offers excellent dose conformity and healthy tissue sparing, but it can be substantially compromised in the presence of anatomical changes. A major dosimetric effect is caused by density changes, which alter the planned proton range in the patient. Three different methods, which automatically restore an IMPT plan dose on a daily CT image were implemented and compared: (1) simple dose restoration (DR) using optimization objectives of the initial plan, (2) voxel-wise dose restoration (vDR), and (3) isodose volume dose restoration (iDR). Dose restorations were calculated for three different clinical cases, selected to test different capabilities of the restoration methods: large range adaptation, complex dose distributions and robust re-optimization. All dose restorations were obtained in less than 5 min, without manual adjustments of the optimization settings. The evaluation of initial plans on repeated CTs showed large dose distortions, which were substantially reduced after restoration. In general, all dose restoration methods improved DVH-based scores in propagated target volumes and OARs. Analysis of local dose differences showed that, although all dose restorations performed similarly in high dose regions, iDR restored the initial dose with higher precision and accuracy in the whole patient anatomy. Median dose errors decreased from 13.55 Gy in distorted plan to 9.75 Gy (vDR), 6.2 Gy (DR) and 4.3 Gy (iDR). High quality dose restoration is essential to minimize or eventually by-pass the physician approval of the restored plan, as long as dose stability can be assumed. Motion (as well as setup and range uncertainties) can be taken into account by including robust optimization in the dose restoration. Restoring clinically-approved dose distribution on repeated CTs does not require new ROI segmentation and is compatible with an online adaptive workflow.

Advanced proton beam dosimetry part II: Monte Carlo vs. pencil beam-based planning for lung cancer.

PubMed

Maes, Dominic; Saini, Jatinder; Zeng, Jing; Rengan, Ramesh; Wong, Tony; Bowen, Stephen R

2018-04-01

Proton pencil beam (PB) dose calculation algorithms have limited accuracy within heterogeneous tissues of lung cancer patients, which may be addressed by modern commercial Monte Carlo (MC) algorithms. We investigated clinical pencil beam scanning (PBS) dose differences between PB and MC-based treatment planning for lung cancer patients. With IRB approval, a comparative dosimetric analysis between RayStation MC and PB dose engines was performed on ten patient plans. PBS gantry plans were generated using single-field optimization technique to maintain target coverage under range and setup uncertainties. Dose differences between PB-optimized (PBopt), MC-recalculated (MCrecalc), and MC-optimized (MCopt) plans were recorded for the following region-of-interest metrics: clinical target volume (CTV) V95, CTV homogeneity index (HI), total lung V20, total lung V RX (relative lung volume receiving prescribed dose or higher), and global maximum dose. The impact of PB-based and MC-based planning on robustness to systematic perturbation of range (±3% density) and setup (±3 mm isotropic) was assessed. Pairwise differences in dose parameters were evaluated through non-parametric Friedman and Wilcoxon sign-rank testing. In this ten-patient sample, CTV V95 decreased significantly from 99-100% for PBopt to 77-94% for MCrecalc and recovered to 99-100% for MCopt (P<10 -5 ). The median CTV HI (D95/D5) decreased from 0.98 for PBopt to 0.91 for MCrecalc and increased to 0.95 for MCopt (P<10 -3 ). CTV D95 robustness to range and setup errors improved under MCopt (ΔD95 =-1%) compared to MCrecalc (ΔD95 =-6%, P=0.006). No changes in lung dosimetry were observed for large volumes receiving low to intermediate doses (e.g., V20), while differences between PB-based and MC-based planning were noted for small volumes receiving high doses (e.g., V RX ). Global maximum patient dose increased from 106% for PBopt to 109% for MCrecalc and 112% for MCopt (P<10 -3 ). MC dosimetry revealed a reduction in target dose coverage under PB-based planning that was regained under MC-based planning along with improved plan robustness. MC-based optimization and dose calculation should be integrated into clinical planning workflows of lung cancer patients receiving actively scanned proton therapy.

Advanced proton beam dosimetry part II: Monte Carlo vs. pencil beam-based planning for lung cancer

PubMed Central

Maes, Dominic; Saini, Jatinder; Zeng, Jing; Rengan, Ramesh; Wong, Tony

2018-01-01

Background Proton pencil beam (PB) dose calculation algorithms have limited accuracy within heterogeneous tissues of lung cancer patients, which may be addressed by modern commercial Monte Carlo (MC) algorithms. We investigated clinical pencil beam scanning (PBS) dose differences between PB and MC-based treatment planning for lung cancer patients. Methods With IRB approval, a comparative dosimetric analysis between RayStation MC and PB dose engines was performed on ten patient plans. PBS gantry plans were generated using single-field optimization technique to maintain target coverage under range and setup uncertainties. Dose differences between PB-optimized (PBopt), MC-recalculated (MCrecalc), and MC-optimized (MCopt) plans were recorded for the following region-of-interest metrics: clinical target volume (CTV) V95, CTV homogeneity index (HI), total lung V20, total lung VRX (relative lung volume receiving prescribed dose or higher), and global maximum dose. The impact of PB-based and MC-based planning on robustness to systematic perturbation of range (±3% density) and setup (±3 mm isotropic) was assessed. Pairwise differences in dose parameters were evaluated through non-parametric Friedman and Wilcoxon sign-rank testing. Results In this ten-patient sample, CTV V95 decreased significantly from 99–100% for PBopt to 77–94% for MCrecalc and recovered to 99–100% for MCopt (P<10−5). The median CTV HI (D95/D5) decreased from 0.98 for PBopt to 0.91 for MCrecalc and increased to 0.95 for MCopt (P<10−3). CTV D95 robustness to range and setup errors improved under MCopt (ΔD95 =−1%) compared to MCrecalc (ΔD95 =−6%, P=0.006). No changes in lung dosimetry were observed for large volumes receiving low to intermediate doses (e.g., V20), while differences between PB-based and MC-based planning were noted for small volumes receiving high doses (e.g., VRX). Global maximum patient dose increased from 106% for PBopt to 109% for MCrecalc and 112% for MCopt (P<10−3). Conclusions MC dosimetry revealed a reduction in target dose coverage under PB-based planning that was regained under MC-based planning along with improved plan robustness. MC-based optimization and dose calculation should be integrated into clinical planning workflows of lung cancer patients receiving actively scanned proton therapy. PMID:29876310

Single line source with and without vaginal loading and the impact on target coverage and organ at risk doses for cervix cancer Stages IB, II, and IIIB: treatment planning simulation in patients treated with MRI-guided adaptive brachytherapy in a multicentre study (EMBRACE).

PubMed

Nkiwane, Karen S; Pötter, Richard; Tanderup, Kari; Federico, Mario; Lindegaard, Jacob C; Kirisits, Christian

2013-01-01

Three-dimensional evaluation and comparison of target and organs at risk (OARs) doses from two traditional standard source loading patterns in the frame of MRI-guided cervical cancer brachytherapy for various clinical scenarios based on patient data collected in a multicenter trial setting. Two nonoptimized three-dimensional MRI-based treatment plans, Plan 1 (tandem and vaginal loading) and Plan 2 (tandem loading only), were generated for 134 patients from seven centers participating in the EMBRACE study. Both plans were normalized to point A (Pt. A). Target and OAR doses were evaluated in terms of minimum dose to 90% of the high-risk clinical target volume (HRCTV D90) grouped by tumor stage and minimum dose to the most exposed 2cm³ of the OARs volume. An HRCTV D90 ≥ Pt. A was achieved in 82% and 44% of the patients with Plans 1 and 2, respectively. Median HRCTV D90 with Plans 1 and 2 was 120% and 90% of Pt. A dose, respectively. Both plans had optimal dose coverage in 88% of Stage IB tumors; however, the tandem-only plan resulted in about 50% of dose reduction to the vagina and rectum. For Stages IIB and IIIB, Plan 1 had on average 35% better target coverage but with significant doses to OARs. Standard tandem loading alone results in good target coverage in most Stage IB tumors without violating OAR dose constraints. For Stage IIB tumors, standard vaginal loading improves the therapeutic window, however needs optimization to fulfill the dose prescription for target and OAR. In Stage IIIB, even optimized vaginal loading often does not fulfill the needs for dose prescription. The significant dose variation across various clinical scenarios for both target and OARs indicates the need for image-guided brachytherapy for optimal dose adaptation both for limited and advanced diseases. Copyright © 2013 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

MO-DE-204-00: International Symposium: Patient Dose Reduction in Diagnostic Radiology

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

2016-06-15

The main topic of the session is to show how dose optimization is being implemented in various regions of the world, including Europe, Australia, North America and other regions. A multi-national study conducted under International Atomic Energy Agency (IAEA) across more than 50 less resourced countries gave insight into patient radiation doses and safety practices in CT, mammography, radiography and interventional procedures, both for children and adults. An important outcome was the capability development on dose assessment and management. An overview of recent European projects related to CT radiation dose and optimization both to adults and children will be presented.more » Existing data on DRLs together with a European methodology proposed on establishing and using DRLs for paediatric radiodiagnostic imaging and interventional radiology practices will be shown. Compared with much of Europe at least, many Australian imaging practices are relatively new to the task of diagnostic imaging dose optimisation. In 2008 the Australian Government prescribed a requirement to periodically compare patient radiation doses with diagnostic reference levels (DRLs), where DRLs have been established. Until recently, Australia had only established DRLs for computed tomography (CT). Regardless, both professional society and individual efforts to improved data collection and develop optimisation strategies across a range of modalities continues. Progress in this field, principally with respect to CT and interventional fluoroscopy will be presented. In the US, dose reduction and optimization efforts for computed tomography have been promoted and mandated by several organizations and accrediting entities. This presentation will cover the general motivation, implementation, and implications of such efforts. Learning Objectives: Understand importance of the dose optimization in Diagnostic Radiology. See how this goal is achieved in different regions of the World. Learn about the global trend in the dose optimization and future prospectives. M. Rehani, The work was a part of the work of IAEA where I was an employee and IAEA is a United Nations organization.« less

Optimal precurarizing dose of rocuronium to decrease fasciculation and myalgia following succinylcholine administration.

PubMed

Kim, Kyu Nam; Kim, Kyo Sang; Choi, Hoon Il; Jeong, Ji Seon; Lee, Hee-Jong

2014-06-01

Succinylcholine commonly produces frequent adverse effects, including muscle fasciculation and myalgia. The current study identified the optimal dose of rocuronium to prevent succinylcholine-induced fasciculation and myalgia and evaluated the influence of rocuronium on the speed of onset produced by succinylcholine. This randomized, double-blinded study was conducted in 100 patients randomly allocated into five groups of 20 patients each. Patients were randomized to receive 0.02, 0.03, 0.04, 0.05 and 0.06 mg/kg rocuronium as a precurarizing dose. Neuromuscular monitoring after each precurarizing dose was recorded from the adductor pollicis muscle using acceleromyography with train-of-four stimulation of the ulnar nerve. All patients received succinylcholine 1.5 mg/kg at 2 minutes after the precurarization, and were assessed the incidence and severity of fasciculations, while myalgia was assessed at 24 hours after surgery. The incidence and severity of visible muscle fasciculation was significantly less with increasing the amount of precurarizing dose of rocuronium (P < 0.001). Those of myalgia tend to decrease according to increasing the amount of precurarizing dose of rocuronium, but there was no significance (P = 0.072). The onset time of succinylcholine was significantly longer with increasing the amount of precurarizing dose of rocuronium (P < 0.001). Precurarization with 0.04 mg/kg rocuronium was the optimal dose considering the reduction in the incidence and severity of fasciculation and myalgia with acceptable onset time, and the safe and effective precurarization.

SU-E-P-47: Evaluation of Improvement of Esophagus Sparing in SBRT Lung Patients with Biologically Based IMRT Optimization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liang, X; Penagaricano, J; Paudel, N

2015-06-15

Purpose: To study the potential of improving esophageal sparing for stereotactic body radiation therapy (SBRT) lung cancer patients by using biological optimization (BO) compared to conventional dose-volume based optimization (DVO) in treatment planning. Methods: Three NSCLC patients (PTV (62.3cc, 65.1cc, and 125.1cc) adjacent to the heart) previously treated with SBRT were re-planned using Varian Eclipse TPS (V11) using DVO and BO. The prescription dose was 60 Gy in 5 fractions normalized to 95% of the PTV volume. Plans were evaluated by comparing esophageal maximum doses, PTV heterogeneity (HI= D5%/D95%), and Paddick’s conformity (CI) indices. Quality of the plans was assessedmore » by clinically-used IMRT QA procedures. Results: By using BO, the maximum dose to the esophagus was decreased 1384 cGy (34.6%), 502 cGy (16.5%) and 532 cGy (16.2%) in patient 1, 2 and 3 respectively. The maximum doses to spinal cord and the doses to 1000 cc and 1500 cc of normal lung were comparable in both plans. The mean doses (Dmean-hrt) and doses to 15cc of the heart (V15-hrt) were comparable for patient 1 and 2. However for patient 3, with the largest PTV, Dmean-hrt and V15-hrt increased by 62.2 cGy (18.3%) and 549.9 cGy (24.9%) respectively for the BO plans. The mean target HI of BO plans (1.13) was inferior to the DVO plans (1.07). The same trend was also observed for mean CI in BO plans (0.77) versus DVO plans (0.83). The QA pass rates (3%, 3mm) were comparable for both plans. Conclusion: This study demonstrated that the use of biological models in treatment planning optimization can substantially improve esophageal sparing without compromising spinal cord and normal lung doses. However, for the large PTV case (125.1cc) we studied here, Dmean-hrt and V15-hrt increased substantially. The target HI and CI were inferior in the BO plans.« less

Moving Beyond Maximum Tolerated Dose for Targeted Oncology Drugs: Use of Clinical Utility Index to Optimize Venetoclax Dosage in Multiple Myeloma Patients.

PubMed

Freise, K J; Jones, A K; Verdugo, M E; Menon, R M; Maciag, P C; Salem, A H

2017-12-01

Exposure-response analyses of venetoclax in combination with bortezomib and dexamethasone in previously treated patients with multiple myeloma (MM) were performed on a phase Ib venetoclax dose-ranging study. Logistic regression models were utilized to determine relationships, identify subpopulations with different responses, and optimize the venetoclax dosage that balanced both efficacy and safety. Bortezomib refractory status and number of prior treatments were identified to impact the efficacy response to venetoclax treatment. Higher venetoclax exposures were estimated to increase the probability of achieving a very good partial response (VGPR) or better through venetoclax doses of 1,200 mg. However, the probability of neutropenia (grade ≥3) was estimated to increase at doses >800 mg. Using a clinical utility index, a venetoclax dosage of 800 mg daily was selected to optimally balance the VGPR or better rates and neutropenia rates in MM patients administered 1-3 prior lines of therapy and nonrefractory to bortezomib. © 2017 American Society for Clinical Pharmacology and Therapeutics.

Modeling adverse event counts in phase I clinical trials of a cytotoxic agent.

PubMed

Muenz, Daniel G; Braun, Thomas M; Taylor, Jeremy Mg

2018-05-01

Background/Aims The goal of phase I clinical trials for cytotoxic agents is to find the maximum dose with an acceptable risk of severe toxicity. The most common designs for these dose-finding trials use a binary outcome indicating whether a patient had a dose-limiting toxicity. However, a patient may experience multiple toxicities, with each toxicity assigned an ordinal severity score. The binary response is then obtained by dichotomizing a patient's richer set of data. We contribute to the growing literature on new models to exploit this richer toxicity data, with the goal of improving the efficiency in estimating the maximum tolerated dose. Methods We develop three new, related models that make use of the total number of dose-limiting and low-level toxicities a patient experiences. We use these models to estimate the probability of having at least one dose-limiting toxicity as a function of dose. In a simulation study, we evaluate how often our models select the true maximum tolerated dose, and we compare our models with the continual reassessment method, which uses binary data. Results Across a variety of simulation settings, we find that our models compare well against the continual reassessment method in terms of selecting the true optimal dose. In particular, one of our models which uses dose-limiting and low-level toxicity counts beats or ties the other models, including the continual reassessment method, in all scenarios except the one in which the true optimal dose is the highest dose available. We also find that our models, when not selecting the true optimal dose, tend to err by picking lower, safer doses, while the continual reassessment method errs more toward toxic doses. Conclusion Using dose-limiting and low-level toxicity counts, which are easily obtained from data already routinely collected, is a promising way to improve the efficiency in finding the true maximum tolerated dose in phase I trials.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wan Chan Tseung, Hok Seum, E-mail: wanchantseung.hok@mayo.edu; Ma, Jiasen; Kreofsky, Cole R.

Purpose: Our aim is to demonstrate the feasibility of fast Monte Carlo (MC)–based inverse biological planning for the treatment of head and neck tumors in spot-scanning proton therapy. Methods and Materials: Recently, a fast and accurate graphics processor unit (GPU)–based MC simulation of proton transport was developed and used as the dose-calculation engine in a GPU-accelerated intensity modulated proton therapy (IMPT) optimizer. Besides dose, the MC can simultaneously score the dose-averaged linear energy transfer (LET{sub d}), which makes biological dose (BD) optimization possible. To convert from LET{sub d} to BD, a simple linear relation was assumed. By use of thismore » novel optimizer, inverse biological planning was applied to 4 patients, including 2 small and 1 large thyroid tumor targets, as well as 1 glioma case. To create these plans, constraints were placed to maintain the physical dose (PD) within 1.25 times the prescription while maximizing target BD. For comparison, conventional intensity modulated radiation therapy (IMRT) and IMPT plans were also created using Eclipse (Varian Medical Systems) in each case. The same critical-structure PD constraints were used for the IMRT, IMPT, and biologically optimized plans. The BD distributions for the IMPT plans were obtained through MC recalculations. Results: Compared with standard IMPT, the biologically optimal plans for patients with small tumor targets displayed a BD escalation that was around twice the PD increase. Dose sparing to critical structures was improved compared with both IMRT and IMPT. No significant BD increase could be achieved for the large thyroid tumor case and when the presence of critical structures mitigated the contribution of additional fields. The calculation of the biologically optimized plans can be completed in a clinically viable time (<30 minutes) on a small 24-GPU system. Conclusions: By exploiting GPU acceleration, MC-based, biologically optimized plans were created for small–tumor target patients. This optimizer will be used in an upcoming feasibility trial on LET{sub d} painting for radioresistant tumors.« less

Optimized Dose Distribution of Gammamed Plus Vaginal Cylinders

DOE Office of Scientific and Technical Information (OSTI.GOV)

Supe, Sanjay S.; Bijina, T.K.; Varatharaj, C.

2009-04-01

Endometrial carcinoma is the most common malignancy arising in the female genital tract. Intracavitary vaginal cuff irradiation may be given alone or with external beam irradiation in patients determined to be at risk for locoregional recurrence. Vaginal cylinders are often used to deliver a brachytherapy dose to the vaginal apex and upper vagina or the entire vaginal surface in the management of postoperative endometrial cancer or cervical cancer. The dose distributions of HDR vaginal cylinders must be evaluated carefully, so that clinical experiences with LDR techniques can be used in guiding optimal use of HDR techniques. The aim of thismore » study was to optimize dose distribution for Gammamed plus vaginal cylinders. Placement of dose optimization points was evaluated for its effect on optimized dose distributions. Two different dose optimization point models were used in this study, namely non-apex (dose optimization points only on periphery of cylinder) and apex (dose optimization points on periphery and along the curvature including the apex points). Thirteen dwell positions were used for the HDR dosimetry to obtain a 6-cm active length. Thus 13 optimization points were available at the periphery of the cylinder. The coordinates of the points along the curvature depended on the cylinder diameters and were chosen for each cylinder so that four points were distributed evenly in the curvature portion of the cylinder. Diameter of vaginal cylinders varied from 2.0 to 4.0 cm. Iterative optimization routine was utilized for all optimizations. The effects of various optimization routines (iterative, geometric, equal times) was studied for the 3.0-cm diameter vaginal cylinder. The effect of source travel step size on the optimized dose distributions for vaginal cylinders was also evaluated. All optimizations in this study were carried for dose of 6 Gy at dose optimization points. For both non-apex and apex models of vaginal cylinders, doses for apex point and three dome points were higher for the apex model compared with the non-apex model. Mean doses to the optimization points for both the cylinder models and all the cylinder diameters were 6 Gy, matching with the prescription dose of 6 Gy. Iterative optimization routine resulted in the highest dose to apex point and dome points. The mean dose for optimization point was 6.01 Gy for iterative optimization and was much higher than 5.74 Gy for geometric and equal times routines. Step size of 1 cm gave the highest dose to the apex point. This step size was superior in terms of mean dose to optimization points. Selection of dose optimization points for the derivation of optimized dose distributions for vaginal cylinders affects the dose distributions.« less

Population Pharmacokinetics and Optimal Sampling Strategy for Model-Based Precision Dosing of Melphalan in Patients Undergoing Hematopoietic Stem Cell Transplantation.

PubMed

Mizuno, Kana; Dong, Min; Fukuda, Tsuyoshi; Chandra, Sharat; Mehta, Parinda A; McConnell, Scott; Anaissie, Elias J; Vinks, Alexander A

2018-05-01

High-dose melphalan is an important component of conditioning regimens for patients undergoing hematopoietic stem cell transplantation. The current dosing strategy based on body surface area results in a high incidence of oral mucositis and gastrointestinal and liver toxicity. Pharmacokinetically guided dosing will individualize exposure and help minimize overexposure-related toxicity. The purpose of this study was to develop a population pharmacokinetic model and optimal sampling strategy. A population pharmacokinetic model was developed with NONMEM using 98 observations collected from 15 adult patients given the standard dose of 140 or 200 mg/m 2 by intravenous infusion. The determinant-optimal sampling strategy was explored with PopED software. Individual area under the curve estimates were generated by Bayesian estimation using full and the proposed sparse sampling data. The predictive performance of the optimal sampling strategy was evaluated based on bias and precision estimates. The feasibility of the optimal sampling strategy was tested using pharmacokinetic data from five pediatric patients. A two-compartment model best described the data. The final model included body weight and creatinine clearance as predictors of clearance. The determinant-optimal sampling strategies (and windows) were identified at 0.08 (0.08-0.19), 0.61 (0.33-0.90), 2.0 (1.3-2.7), and 4.0 (3.6-4.0) h post-infusion. An excellent correlation was observed between area under the curve estimates obtained with the full and the proposed four-sample strategy (R 2  = 0.98; p < 0.01) with a mean bias of -2.2% and precision of 9.4%. A similar relationship was observed in children (R 2  = 0.99; p < 0.01). The developed pharmacokinetic model-based sparse sampling strategy promises to achieve the target area under the curve as part of precision dosing.

MO-DE-BRA-04: Hands-On Fluoroscopy Safety Training with Real-Time Patient and Staff Dosimetry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vanderhoek, M; Bevins, N

Purpose: Fluoroscopically guided interventions (FGI) are routinely performed across many different hospital departments. However, many involved staff members have minimal training regarding safe and optimal use of fluoroscopy systems. We developed and taught a hands-on fluoroscopy safety class incorporating real-time patient and staff dosimetry in order to promote safer and more optimal use of fluoroscopy during FGI. Methods: The hands-on fluoroscopy safety class is taught in an FGI suite, unique to each department. A patient equivalent phantom is set on the patient table with an ion chamber positioned at the x-ray beam entrance to the phantom. This provides a surrogatemore » measure of patient entrance dose. Multiple solid state dosimeters (RaySafe i2 dosimetry systemTM) are deployed at different distances from the phantom (0.1, 1, 3 meters), which provide surrogate measures of staff dose. Instructors direct participating clinical staff to operate the fluoroscopy system as they view live fluoroscopic images, patient entrance dose, and staff doses in real-time. During class, instructors work with clinical staff to investigate how patient entrance dose, staff doses, and image quality are affected by different parameters, including pulse rate, magnification, collimation, beam angulation, imaging mode, system geometry, distance, and shielding. Results: Real-time dose visualization enables clinical staff to directly see and learn how to optimize their use of their own fluoroscopy system to minimize patient and staff dose, yet maintain sufficient image quality for FGI. As a direct result of the class, multiple hospital departments have implemented changes to their imaging protocols, including reduction of the default fluoroscopy pulse rate and increased use of collimation and lower dose fluoroscopy modes. Conclusion: Hands-on fluoroscopy safety training substantially benefits from real-time patient and staff dosimetry incorporated into the class. Real-time dose display helps clinical staff visualize, internalize, and ultimately utilize the safety techniques learned during the training. RaySafe/Unfors/Fluke lent us a portable version of their RaySafe i2 Dosimetry System for 6 months.« less

Furosemide Prescription During the Dry State Is a Predictor of Long-Term Survival of Stable, Optimally Medicated Patients With Systolic Heart Failure.

PubMed

Sargento, Luis; Simões, Andre Vicente; Longo, Susana; Lousada, Nuno; Reis, Roberto Palma Dos

2017-05-01

Furosemide is associated with poor prognosis in patients with heart failure and reduced ejection fraction (HFrEF). To evaluate the association between daily furosemide dose prescribed during the dry state and long-term survival in stable, optimally medicated outpatients with HFrEF. Two hundred sixty-six consecutive outpatients with left ventricular ejection fraction <40%, clinically stable in the dry state and on optimal heart failure therapy, were followed up for 3 years in a heart failure unit. The end point was all-cause death. There were no changes in New York Heart Association class and therapeutics, including diuretics, and no decompensation or hospitalization during 6 months. Furosemide doses were categorized as low or none (0-40 mg/d), intermediate (41-80 mg/d), and high (>80 mg). Cox regression was adjusted for significant confounders. The 3-year mortality rate was 33.8%. Mean dose of furosemide was 57.3 ± 21.4 mg/d. A total of 47.6% of patients received the low dose, 42.1% the intermediate dose, and 2.3% the high dose. Receiver operating characteristics for death associated with furosemide dose showed an area under the curve of 0.74 (95% confidence interval [CI]: 0.68-0.79; P < .001), and the best cutoff was >40 mg/d. An increasing daily dose of furosemide was associated with worse prognosis. Those receiving the intermediate dose (hazard ratio [HR] = 4.1; 95% CI: 2.57-6.64; P < .001) or high dose (HR = 19.8; 95% CI: 7.9-49.6; P < .001) had a higher risk of mortality compared to those receiving a low dose. Patients receiving >40 mg/d, in a propensity score-matched cohort, had a greater risk of mortality than those receiving a low dose (HR = 4.02; 95% CI: 1.8-8.8; P = .001) and those not receiving furosemide (HR = 3.9; 95% CI: 0.07-14.2; P = .039). Furosemide administration during the dry state in stable, optimally medicated outpatients with HFrEF is unfavorably associated with long-term survival. The threshold dose was 40 mg/d.

Optimal iodine-131 dose for eliminating hyperthyroidism in Graves' disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nordyke, R.A.; Gilbert, F.I. Jr.

1991-03-01

Since hypothyroidism is commonplace after treatment of Graves' disease with radioiodine, the goal should be cure of hyperthyroidism rather than avoidance of hypothyroidism. To find the optimal dose to accomplish cure, we treated 605 patients with stepwise increasing doses of 3, 4, 5, 6, 8, and 10 mCi, analyzing the relationship of dose, age, sex, gland weight, and thyroidal uptake to cure. Estimates of cure at doses above 10 mCi were made from the literature. Cure was directly related to dose between 5 and 10 mCi. There was no significant relationship between cure and age (chi-square, p = 0.74), sexmore » (chi-square, p = 0.12), and 24-hr uptake if over 30% (chi-square for slope, p greater than 0.10). Cure and gland weight had an inverse relationship (chi-square for slope, 0.01 less than p less than 0.02). We concluded that the optimal 131I dose for curing hyperthyroidism is approximated by starting with 10 mCi and increasing it for unusually large glands or for special patient circumstances.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fukada, Junichi, E-mail: fukada@rad.med.keio.ac.jp; Shigematsu, Naoyuki; Takeuchi, Hiroya

Purpose: We investigated clinical and treatment-related factors as predictors of symptomatic pericardial effusion in esophageal cancer patients after concurrent chemoradiation therapy. Methods and Materials: We reviewed 214 consecutive primary esophageal cancer patients treated with concurrent chemoradiation therapy between 2001 and 2010 in our institute. Pericardial effusion was detected on follow-up computed tomography. Symptomatic effusion was defined as effusion ≥grade 3 according to Common Terminology Criteria for Adverse Events v4.0 criteria. Percent volume irradiated with 5 to 65 Gy (V5-V65) and mean dose to the pericardium were evaluated employing dose-volume histograms. To evaluate dosimetry for patients treated with two-dimensional planning inmore » the earlier period (2001-2005), computed tomography data at diagnosis were transferred to a treatment planning system to reconstruct three-dimensional plans without modification. Optimal dosimetric thresholds for symptomatic pericardial effusion were calculated by receiver operating characteristic curves. Associating clinical and treatment-related risk factors for symptomatic pericardial effusion were detected by univariate and multivariate analyses. Results: The median follow-up was 29 (range, 6-121) months for eligible 167 patients. Symptomatic pericardial effusion was observed in 14 (8.4%) patients. Dosimetric analyses revealed average values of V30 to V45 for the pericardium and mean pericardial doses were significantly higher in patients with symptomatic pericardial effusion than in those with asymptomatic pericardial effusion (P<.05). Pericardial V5 to V55 and mean pericardial doses were significantly higher in patients with symptomatic pericardial effusion than in those without pericardial effusion (P<.001). Mean pericardial doses of 36.5 Gy and V45 of 58% were selected as optimal cutoff values for predicting symptomatic pericardial effusion. Multivariate analysis identified mean pericardial dose as the strongest risk factor for symptomatic pericardial effusion. Conclusions: Dose-volume thresholds for the pericardium facilitate predicting symptomatic pericardial effusion. Mean pericardial dose was selected based not only on the optimal dose-volume threshold but also on the most significant risk factor for symptomatic pericardial effusion.« less

SU-G-BRC-13: Model Based Classification for Optimal Position Selection for Left-Sided Breast Radiotherapy: Free Breathing, DIBH, Or Prone

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, H; Liu, T; Xu, X

Purpose: There are clinical decision challenges to select optimal treatment positions for left-sided breast cancer patients—supine free breathing (FB), supine Deep Inspiration Breath Hold (DIBH) and prone free breathing (prone). Physicians often make the decision based on experiences and trials, which might not always result optimal OAR doses. We herein propose a mathematical model to predict the lowest OAR doses among these three positions, providing a quantitative tool for corresponding clinical decision. Methods: Patients were scanned in FB, DIBH, and prone positions under an IRB approved protocol. Tangential beam plans were generated for each position, and OAR doses were calculated.more » The position with least OAR doses is defined as the optimal position. The following features were extracted from each scan to build the model: heart, ipsilateral lung, breast volume, in-field heart, ipsilateral lung volume, distance between heart and target, laterality of heart, and dose to heart and ipsilateral lung. Principal Components Analysis (PCA) was applied to remove the co-linearity of the input data and also to lower the data dimensionality. Feature selection, another method to reduce dimensionality, was applied as a comparison. Support Vector Machine (SVM) was then used for classification. Thirtyseven patient data were acquired; up to now, five patient plans were available. K-fold cross validation was used to validate the accuracy of the classifier model with small training size. Results: The classification results and K-fold cross validation demonstrated the model is capable of predicting the optimal position for patients. The accuracy of K-fold cross validations has reached 80%. Compared to PCA, feature selection allows causal features of dose to be determined. This provides more clinical insights. Conclusion: The proposed classification system appeared to be feasible. We are generating plans for the rest of the 37 patient images, and more statistically significant results are to be presented.« less

Optimizing dosing of oncology drugs.

PubMed

Minasian, L; Rosen, O; Auclair, D; Rahman, A; Pazdur, R; Schilsky, R L

2014-11-01

The purpose of this article is to acknowledge the challenges in optimizing the dosing of oncology drugs and to propose potential approaches to address these challenges in order to optimize effectiveness, minimize toxicity, and promote adherence in patients. These approaches could provide better opportunities to understand the sources of variability in drug exposure and clinical outcomes during the development and premarketing evaluation of investigational new drugs.

A feasibility study: Selection of a personalized radiotherapy fractionation schedule using spatiotemporal optimization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Minsun, E-mail: mk688@uw.edu; Stewart, Robert D.; Phillips, Mark H.

2015-11-15

Purpose: To investigate the impact of using spatiotemporal optimization, i.e., intensity-modulated spatial optimization followed by fractionation schedule optimization, to select the patient-specific fractionation schedule that maximizes the tumor biologically equivalent dose (BED) under dose constraints for multiple organs-at-risk (OARs). Methods: Spatiotemporal optimization was applied to a variety of lung tumors in a phantom geometry using a range of tumor sizes and locations. The optimal fractionation schedule for a patient using the linear-quadratic cell survival model depends on the tumor and OAR sensitivity to fraction size (α/β), the effective tumor doubling time (T{sub d}), and the size and location of tumormore » target relative to one or more OARs (dose distribution). The authors used a spatiotemporal optimization method to identify the optimal number of fractions N that maximizes the 3D tumor BED distribution for 16 lung phantom cases. The selection of the optimal fractionation schedule used equivalent (30-fraction) OAR constraints for the heart (D{sub mean} ≤ 45 Gy), lungs (D{sub mean} ≤ 20 Gy), cord (D{sub max} ≤ 45 Gy), esophagus (D{sub max} ≤ 63 Gy), and unspecified tissues (D{sub 05} ≤ 60 Gy). To assess plan quality, the authors compared the minimum, mean, maximum, and D{sub 95} of tumor BED, as well as the equivalent uniform dose (EUD) for optimized plans to conventional intensity-modulated radiation therapy plans prescribing 60 Gy in 30 fractions. A sensitivity analysis was performed to assess the effects of T{sub d} (3–100 days), tumor lag-time (T{sub k} = 0–10 days), and the size of tumors on optimal fractionation schedule. Results: Using an α/β ratio of 10 Gy, the average values of tumor max, min, mean BED, and D{sub 95} were up to 19%, 21%, 20%, and 19% larger than those from conventional prescription, depending on T{sub d} and T{sub k} used. Tumor EUD was up to 17% larger than the conventional prescription. For fast proliferating tumors with T{sub d} less than 10 days, there was no significant increase in tumor BED but the treatment course could be shortened without a loss in tumor BED. The improvement in the tumor mean BED was more pronounced with smaller tumors (p-value = 0.08). Conclusions: Spatiotemporal optimization of patient plans has the potential to significantly improve local tumor control (larger BED/EUD) of patients with a favorable geometry, such as smaller tumors with larger distances between the tumor target and nearby OAR. In patients with a less favorable geometry and for fast growing tumors, plans optimized using spatiotemporal optimization and conventional (spatial-only) optimization are equivalent (negligible differences in tumor BED/EUD). However, spatiotemporal optimization yields shorter treatment courses than conventional spatial-only optimization. Personalized, spatiotemporal optimization of treatment schedules can increase patient convenience and help with the efficient allocation of clinical resources. Spatiotemporal optimization can also help identify a subset of patients that might benefit from nonconventional (large dose per fraction) treatments that are ineligible for the current practice of stereotactic body radiation therapy.« less

Conversion coefficients for determining organ doses in paediatric spine radiography.

PubMed

Seidenbusch, Michael; Schneider, Karl

2014-04-01

Knowledge of organ and effective doses achieved during paediatric x-ray examinations is an important prerequisite for assessment of radiation burden to the patient. Conversion coefficients for reconstruction of organ and effective doses from entrance doses for segmental spine radiographs of 0-, 1-, 5-, 10-, 15- and 30-year-old patients are provided regarding the Guidelines of Good Radiographic Technique of the European Commission. Using the personal computer program PCXMC developed by the Finnish Centre for Radiation and Nuclear Safety (Säteilyturvakeskus STUK), conversion coefficients for conventional segmental spine radiographs were calculated performing Monte Carlo simulations in mathematical hermaphrodite phantom models describing patients of different ages. The clinical variation of beam collimation was taken into consideration by defining optimal and suboptimal radiation field settings. Conversion coefficients for the reconstruction of organ doses in about 40 organs and tissues from measured entrance doses during cervical, thoracic and lumbar spine radiographs of 0-, 1-, 5-, 10-, 15- and 30-year-old patients were calculated for the standard sagittal and lateral beam projections and the standard focus detector distance of 115 cm. The conversion coefficients presented may be used for organ dose assessments from entrance doses measured during spine radiographs of patients of all age groups and all field settings within the optimal and suboptimal standard field settings.

A novel adaptive needle insertion sequencing for robotic, single needle MR-guided high-dose-rate prostate brachytherapy

NASA Astrophysics Data System (ADS)

Borot de Battisti, M.; de Senneville, B. Denis; Hautvast, G.; Binnekamp, D.; Lagendijk, J. J. W.; Maenhout, M.; Moerland, M. A.

2017-05-01

MR-guided high-dose-rate (HDR) brachytherapy has gained increasing interest as a treatment for patients with localized prostate cancer because of the superior value of MRI for tumor and surrounding tissues localization. To enable needle insertion into the prostate with the patient in the MR bore, a single needle MR-compatible robotic system involving needle-by-needle dose delivery has been developed at our institution. Throughout the intervention, dose delivery may be impaired by: (1) sub-optimal needle positioning caused by e.g. needle bending, (2) intra-operative internal organ motion such as prostate rotations or swelling, or intra-procedural rectum or bladder filling. This may result in failure to reach clinical constraints. To assess the first aforementioned challenge, a recent study from our research group demonstrated that the deposited dose may be greatly improved by real-time adaptive planning with feedback on the actual needle positioning. However, the needle insertion sequence is left to the doctor and therefore, this may result in sub-optimal dose delivery. In this manuscript, a new method is proposed to determine and update automatically the needle insertion sequence. This strategy is based on the determination of the most sensitive needle track. The sensitivity of a needle track is defined as its impact on the dose distribution in case of sub-optimal positioning. A stochastic criterion is thus presented to determine each needle track sensitivity based on needle insertion simulations. To assess the proposed sequencing strategy, HDR prostate brachytherapy was simulated on 11 patients with varying number of needle insertions. Sub-optimal needle positioning was simulated at each insertion (modeled by typical random angulation errors). In 91% of the scenarios, the dose distribution improved when the needle was inserted into the most compared to the least sensitive needle track. The computation time for sequencing was less than 6 s per needle track. The proposed needle insertion sequencing can therefore assist in delivering an optimal dose in HDR prostate brachytherapy.

Safety of an i.v. β-adrenergic blockade protocol for heart rate optimization before coronary CT angiography.

PubMed

Kassamali, Rahil H; Kim, Daniel H; Patel, Hiten; Raichura, Nitin; Hoey, Edward T D; Hodson, James; Hussain, Shahid

2014-10-01

The purpose of this study was to assess the safety of heart rate optimization by use of β-adrenergic blockade solely by the i.v. route before coronary CT angiography. The records of 679 patients undergoing CT coronary angiography after receiving i.v. β-adrenergic blockade were retrospectively analyzed. Health screening was completed before scanning, and heart rate was optimized by administration of i.v. metoprolol titrated to a maximum of 70 mg to achieve a heart rate less than 65 beats/min. The median i.v. dose was 20 mg (range, 5-70 mg). The 679 patients analyzed had a total of 10 complications (1.47%). Major complications, defined as not resolving with observation and analgesia alone, occurred in only three patients (0.44%). These complications included a second-degree atrioventricular block. A total of 299 patients (44.0%) needed more than 20 mg of i.v. metoprolol to achieve target heart rate. Only three patients needed the maximum i.v. dose of 70 mg metoprolol. Target heart rate was reached successfully in 666 patients (98.1%) with doses of less than 70 mg. This study did not show a statistically significant association between increasing complication frequency and increasing dose. This study showed that high doses of i.v. metoprolol can be used effectively and with a low rate of major complications to control heart rate before coronary CT angiography in correctly screened patients.

Application of Magnetic Resonance Imaging and Three-Dimensional Treatment Planning in the Treatment of Orbital Lymphoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rudoltz, Marc S.; Ayyangar, Komanduri; Mohiuddin, Mohammed

Radiotherapy for lymphoma of the orbit must be individualized for each patient and clinical setting. Most techniques focus on optimizing the dose to the tumor while sparing the lens. This study describes a technique utilizing magnetic resonance imaging (MRI) and three dimensional (3D) planning in the treatment of orbital lymphoma. A patient presented with an intermediate grade lymphoma of the right orbit. The prescribed tumor dose was 4050 cGy in 18 fractions. Three D planning was carried out and tumor volumes, retina, and lens were subsequently outlined. Dose calculations including dose volume histograms of the target, retina, and lens weremore » then performed. Part of the retina was outside of the treatment volume while 50% of the retina received 90% or more of the prescribed dose. The patient was clinically NED when last seen 2 years following therapy with no treatment-related morbidity. Patients with lymphomas of the orbit can be optimally treated using MRI based 3D treatment planning.« less

Dose-finding study of carbamylated monomeric allergoid tablets in grass-allergic rhinoconjunctivitis patients.

PubMed

Mösges, Ralph; Rohdenburg, Christina; Eichel, Andrea; Zadoyan, Gregor; Kasche, Elena-Manja; Shah-Hosseini, Kija; Lehmacher, Walter; Schmalz, Petra; Compalati, Enrico

2017-11-01

To determine the optimal effective and safe dose of sublingual immunotherapy tablets containing carbamylated monomeric allergoids in patients with grass pollen-induced allergic rhinoconjunctivitis. In this prospective, randomized, double-blind, active-controlled, multicenter, Phase II study, four different daily doses were applied preseasonally for 12 weeks. Of 158 randomized adults, 155 subjects (safety population) received 300 units of allergy (UA)/day (n = 36), 600 UA/day (n = 43), 1000 UA/day (n = 39), or 2000 UA/day (n = 37). After treatment, 54.3, 47.6, 59.0 and 51.4% of patients, respectively, ceased to react to the highest allergen concentration in a conjunctival provocation test. Furthermore, the response threshold improved in 70.4, 62.9, 76.7 and 66.7% of patients, respectively. No serious adverse events occurred. This study found 1000 UA/day to be the optimal effective and safe dose.

SU-F-T-336: A Quick Auto-Planning (QAP) Method for Patient Intensity Modulated Radiotherapy (IMRT)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peng, J; Zhang, Z; Wang, J

2016-06-15

Purpose: The aim of this study is to develop a quick auto-planning system that permits fast patient IMRT planning with conformal dose to the target without manual field alignment and time-consuming dose distribution optimization. Methods: The planning target volume (PTV) of the source and the target patient were projected to the iso-center plane in certain beameye- view directions to derive the 2D projected shapes. Assuming the target interior was isotropic for each beam direction boundary analysis under polar coordinate was performed to map the source shape boundary to the target shape boundary to derive the source-to-target shape mapping function. Themore » derived shape mapping function was used to morph the source beam aperture to the target beam aperture over all segments in each beam direction. The target beam weights were re-calculated to deliver the same dose to the reference point (iso-center) as the source beam did in the source plan. The approach was tested on two rectum patients (one source patient and one target patient). Results: The IMRT planning time by QAP was 5 seconds on a laptop computer. The dose volume histograms and the dose distribution showed the target patient had the similar PTV dose coverage and OAR dose sparing with the source patient. Conclusion: The QAP system can instantly and automatically finish the IMRT planning without dose optimization.« less

Dose to mass for evaluation and optimization of lung cancer radiation therapy.

PubMed

Tyler Watkins, William; Moore, Joseph A; Hugo, Geoffrey D; Siebers, Jeffrey V

2017-11-01

To evaluate potential organ at risk dose-sparing by using dose-mass-histogram (DMH) objective functions compared with dose-volume-histogram (DVH) objective functions. Treatment plans were retrospectively optimized for 10 locally advanced non-small cell lung cancer patients based on DVH and DMH objectives. DMH-objectives were the same as DVH objectives, but with mass replacing volume. Plans were normalized to dose to 95% of the PTV volume (PTV-D95v) or mass (PTV-D95m). For a given optimized dose, DVH and DMH were intercompared to ascertain dose-to-volume vs. dose-to-mass differences. Additionally, the optimized doses were intercompared using DVH and DMH metrics to ascertain differences in optimized plans. Mean dose to volume, D v ‾, mean dose to mass, D M ‾, and fluence maps were intercompared. For a given dose distribution, DVH and DMH differ by >5% in heterogeneous structures. In homogeneous structures including heart and spinal cord, DVH and DMH are nearly equivalent. At fixed PTV-D95v, DMH-optimization did not significantly reduce dose to OARs but reduced PTV-D v ‾ by 0.20±0.2Gy (p=0.02) and PTV-D M ‾ by 0.23±0.3Gy (p=0.02). Plans normalized to PTV-D95m also result in minor PTV dose reductions and esophageal dose sparing (D v ‾ reduced 0.45±0.5Gy, p=0.02 and D M ‾ reduced 0.44±0.5Gy, p=0.02) compared to DVH-optimized plans. Optimized fluence map comparisons indicate that DMH optimization reduces dose in the periphery of lung PTVs. DVH- and DMH-dose indices differ by >5% in lung and lung target volumes for fixed dose distributions, but optimizing DMH did not reduce dose to OARs. The primary difference observed in DVH- and DMH-optimized plans were variations in fluence to the periphery of lung target PTVs, where low density lung surrounds tumor. Copyright © 2017 Elsevier B.V. All rights reserved.

Treatment Optimization Using Computed Tomography-Delineated Targets Should be Used for Supraclavicular Irradiation for Breast Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liengsawangwong, Raweewan; Yu, T.-K.; Sun, T.-L.

2007-11-01

Background: The purpose of this study was to determine whether the use of optimized CT treatment planning offered better coverage of axillary level III (LIII)/supraclavicular (SC) targets than the empirically derived dose prescription that are commonly used. Materials/Methods: Thirty-two consecutive breast cancer patients who underwent CT treatment planning of a SC field were evaluated. Each patient was categorized according to body mass index (BMI) classes: normal, overweight, or obese. The SC and LIII nodal beds were contoured, and four treatment plans for each patient were generated. Three of the plans used empiric dose prescriptions, and these were compared with amore » CT-optimized plan. Each plan was evaluated by two criteria: whether 98% of target volume receive >90% of prescribed dose and whether < 5% of the irradiated volume received 105% of prescribed dose. Results: The mean depth of SC and LIII were 3.2 cm (range, 1.4-6.7 cm) and 3.1 (range, 1.7-5.8 cm). The depth of these targets varied according across BMI classes (p = 0.01). Among the four sets of plans, the CT-optimized plans were the most successful at achieving both of the dosimetry objectives for every BMI class (normal BMI, p = .003; overweight BMI, p < .0001; obese BMI, p < .001). Conclusions: Across all BMI classes, routine radiation prescriptions did not optimally cover intended targets for every patient. Optimized CT-based treatment planning generated the most successful plans; therefore, we recommend the use of routine CT simulation and treatment planning of SC fields in breast cancer.« less

Impact of Pharmacy Practice Model Expansion on Pharmacokinetic Services: Optimization of Vancomycin Dosing and Improved Patient Safety.

PubMed

Han, Zhe; Pettit, Natasha N; Landon, Emily M; Brielmaier, Benjamin D

2017-04-01

Background: The impact of pharmacy interventions on optimizing vancomycin therapy has been described, however interventions vary among studies and the most optimal pharmacy practice model (PPM) for pharmacokinetic (PK) services has not been established. Objective: The purpose of this study is to demonstrate the value of 24 hours a day, 7 days a week (24/7) PK services. Methods: New PK services were implemented in 2 phases with institutional PPM expansion. Phase 1 included universal monitoring by pharmacists with recommendations made to prescribers during business hours. Phase 2 expanded clinical pharmacists' coverage to 24/7 and provided an optional 24/7 pharmacist-managed PK consult service. We compared vancomycin therapeutic trough attainment, dosing, and clinical and safety outcomes between phases 1 and 2 in adult inpatients receiving therapeutic intravenous vancomycin. Results. One hundred and fifty patients were included in each phase. Phase 2 had a greater proportion of vancomycin courses with therapeutic initial trough concentrations (27.5% vs 46.1%; p = 0.002), higher initial trough concentrations (10.9 mcg/mL vs 16.4 mcg/mL; p < 0.001), and optimized initial vancomycin dosing (13.5 mg/kg vs 16.2 mg/kg; p < 0.001). Phase 2 also saw significant reduction in the incidence of vancomycin-associated nephrotoxicity (21.1% vs 11.7%; p = 0.038). Dose optimization and improvement in initial target trough attainment were most notable among intensive care unit (ICU) patients. Conclusions. Our study demonstrated that 24/7 PK services implemented with institutional PPM expansion optimized vancomycin target trough attainment and improved patient safety.

Patient-specific radiation dose and cancer risk estimation in pediatric chest CT: a study in 30 patients

NASA Astrophysics Data System (ADS)

Li, Xiang; Samei, Ehsan; Segars, W. Paul; Sturgeon, Gregory M.; Colsher, James G.; Frush, Donald P.

2010-04-01

Radiation-dose awareness and optimization in CT can greatly benefit from a dosereporting system that provides radiation dose and cancer risk estimates specific to each patient and each CT examination. Recently, we reported a method for estimating patientspecific dose from pediatric chest CT. The purpose of this study is to extend that effort to patient-specific risk estimation and to a population of pediatric CT patients. Our study included thirty pediatric CT patients (16 males and 14 females; 0-16 years old), for whom full-body computer models were recently created based on the patients' clinical CT data. Using a validated Monte Carlo program, organ dose received by the thirty patients from a chest scan protocol (LightSpeed VCT, 120 kVp, 1.375 pitch, 40-mm collimation, pediatric body scan field-of-view) was simulated and used to estimate patient-specific effective dose. Risks of cancer incidence were calculated for radiosensitive organs using gender-, age-, and tissue-specific risk coefficients and were used to derive patientspecific effective risk. The thirty patients had normalized effective dose of 3.7-10.4 mSv/100 mAs and normalized effective risk of 0.5-5.8 cases/1000 exposed persons/100 mAs. Normalized lung dose and risk of lung cancer correlated strongly with average chest diameter (correlation coefficient: r = -0.98 to -0.99). Normalized effective risk also correlated strongly with average chest diameter (r = -0.97 to -0.98). These strong correlations can be used to estimate patient-specific dose and risk prior to or after an imaging study to potentially guide healthcare providers in justifying CT examinations and to guide individualized protocol design and optimization.

Optimal design of clinical trials with biologics using dose-time-response models.

PubMed

Lange, Markus R; Schmidli, Heinz

2014-12-30

Biologics, in particular monoclonal antibodies, are important therapies in serious diseases such as cancer, psoriasis, multiple sclerosis, or rheumatoid arthritis. While most conventional drugs are given daily, the effect of monoclonal antibodies often lasts for months, and hence, these biologics require less frequent dosing. A good understanding of the time-changing effect of the biologic for different doses is needed to determine both an adequate dose and an appropriate time-interval between doses. Clinical trials provide data to estimate the dose-time-response relationship with semi-mechanistic nonlinear regression models. We investigate how to best choose the doses and corresponding sample size allocations in such clinical trials, so that the nonlinear dose-time-response model can be precisely estimated. We consider both local and conservative Bayesian D-optimality criteria for the design of clinical trials with biologics. For determining the optimal designs, computer-intensive numerical methods are needed, and we focus here on the particle swarm optimization algorithm. This metaheuristic optimizer has been successfully used in various areas but has only recently been applied in the optimal design context. The equivalence theorem is used to verify the optimality of the designs. The methodology is illustrated based on results from a clinical study in patients with gout, treated by a monoclonal antibody. Copyright © 2014 John Wiley & Sons, Ltd.

The Impact of Monte Carlo Dose Calculations on Intensity-Modulated Radiation Therapy

NASA Astrophysics Data System (ADS)

Siebers, J. V.; Keall, P. J.; Mohan, R.

The effect of dose calculation accuracy for IMRT was studied by comparing different dose calculation algorithms. A head and neck IMRT plan was optimized using a superposition dose calculation algorithm. Dose was re-computed for the optimized plan using both Monte Carlo and pencil beam dose calculation algorithms to generate patient and phantom dose distributions. Tumor control probabilities (TCP) and normal tissue complication probabilities (NTCP) were computed to estimate the plan outcome. For the treatment plan studied, Monte Carlo best reproduces phantom dose measurements, the TCP was slightly lower than the superposition and pencil beam results, and the NTCP values differed little.

Monte Carlo calculations for reporting patient organ doses from interventional radiology

NASA Astrophysics Data System (ADS)

Huo, Wanli; Feng, Mang; Pi, Yifei; Chen, Zhi; Gao, Yiming; Xu, X. George

2017-09-01

This paper describes a project to generate organ dose data for the purposes of extending VirtualDose software from CT imaging to interventional radiology (IR) applications. A library of 23 mesh-based anthropometric patient phantoms were involved in Monte Carlo simulations for database calculations. Organ doses and effective doses of IR procedures with specific beam projection, filed of view (FOV) and beam quality for all parts of body were obtained. Comparing organ doses for different beam qualities, beam projections, patients' ages and patient's body mass indexes (BMIs) which generated by VirtualDose-IR, significant discrepancies were observed. For relatively long time exposure, IR doses depend on beam quality, beam direction and patient size. Therefore, VirtualDose-IR, which is based on the latest anatomically realistic patient phantoms, can generate accurate doses for IR treatment. It is suitable to apply this software in clinical IR dose management as an effective tool to estimate patient doses and optimize IR treatment plans.

A novel method for interactive multi-objective dose-guided patient positioning

NASA Astrophysics Data System (ADS)

Haehnle, Jonas; Süss, Philipp; Landry, Guillaume; Teichert, Katrin; Hille, Lucas; Hofmaier, Jan; Nowak, Dimitri; Kamp, Florian; Reiner, Michael; Thieke, Christian; Ganswindt, Ute; Belka, Claus; Parodi, Katia; Küfer, Karl-Heinz; Kurz, Christopher

2017-01-01

In intensity-modulated radiation therapy (IMRT), 3D in-room imaging data is typically utilized for accurate patient alignment on the basis of anatomical landmarks. In the presence of non-rigid anatomical changes, it is often not obvious which patient position is most suitable. Thus, dose-guided patient alignment is an interesting approach to use available in-room imaging data for up-to-date dose calculation, aimed at finding the position that yields the optimal dose distribution. This contribution presents the first implementation of dose-guided patient alignment as multi-criteria optimization problem. User-defined clinical objectives are employed for setting up a multi-objective problem. Using pre-calculated dose distributions at a limited number of patient shifts and dose interpolation, a continuous space of Pareto-efficient patient shifts becomes accessible. Pareto sliders facilitate interactive browsing of the possible shifts with real-time dose display to the user. Dose interpolation accuracy is validated and the potential of multi-objective dose-guided positioning demonstrated for three head and neck (H&N) and three prostate cancer patients. Dose-guided positioning is compared to replanning for all cases. A delineated replanning CT served as surrogate for in-room imaging data. Dose interpolation accuracy was high. Using a 2 % dose difference criterion, a median pass-rate of 95.7% for H&N and 99.6% for prostate cases was determined in a comparison to exact dose calculations. For all patients, dose-guided positioning allowed to find a clinically preferable dose distribution compared to bony anatomy based alignment. For all H&N cases, mean dose to the spared parotid glands was below 26~\\text{Gy} (up to 27.5~\\text{Gy} with bony alignment) and clinical target volume (CTV) {{V}95 % } above 99.1% (compared to 95.1%). For all prostate patients, CTV {{V}95 % } was above 98.9% (compared to 88.5%) and {{V}50~\\text{Gy}} to the rectum below 50 % (compared to 56.1%). Replanning yielded improved results for the H&N cases. For the prostate cases, differences to dose-guided positioning were minor.

Optimizing bevacizumab dosing in glioblastoma: less is more.

PubMed

Ajlan, Abdulrazag; Thomas, Piia; Albakr, Abdulrahman; Nagpal, Seema; Recht, Lawrence

2017-10-01

Compared to traditional chemotherapies, where dose limiting toxicities represent the maximum possible dose, monoclonal antibody therapies are used at doses well below maximum tolerated dose. However, there has been little effort to ascertain whether there is a submaximal dose at which the efficacy/complication ratio is maximized. Thus, despite the general practice of using Bevacizumab (BEV) at dosages of 10 mg/kg every other week for glioma patients, there has not been much prior work examining whether the relatively high complication rates reported with this agent can be decreased by lowering the dose without impairing efficacy. We assessed charts from 80 patients who received BEV for glioblastoma to survey the incidence of complications relative to BEV dose. All patients were treated with standard upfront chemoradiation. The toxicity was graded based on the NCI CTCAE, version 4.03. The rate of BEV serious related adverse events was 12.5% (n = 10/80). There were no serious adverse events (≥grade 3) when the administered dose was (<3 mg/kg/week), compared to a 21% incidence in those who received higher doses (≥3 mg/kg/week) (P < 0.01). Importantly, the three patient deaths attributable to BEV administration occurred in patients receiving higher doses. Patients who received lower doses also had a better survival rate, although this did not reach statistical significance [median OS 39 for low dose group vs. 17.3 for high dose group (P = 0.07)]. Lower rates of serious BEV related toxicities are noted when lower dosages are used without diminishing positive clinical impact. Further work aimed at optimizing BEV dosage is justified.

Determination of Optimal Amikacin Dosing Regimens for Pediatric Patients With Burn Wound Sepsis.

PubMed

Yu, Tian; Stockmann, Chris; Healy, Daniel P; Olson, Jared; Wead, Stephanie; Neely, Alice N; Kagan, Richard J; Spigarelli, Michael G; Sherwin, Catherine M T

2015-01-01

This study aimed to develop optimal amikacin dosing regimens for the empirical treatment of Gram-negative bacterial sepsis in pediatric patients with burn injuries. A pharmacodynamic (PD) target in which the peak concentration (Cmax) is ≥8 times the minimum inhibitory concentration (MIC) (Cmax/MIC ≥ 8) is reflective of optimal bactericidal activity and has been used to predict clinical outcomes. Population pharmacokinetic modeling was performed in NONMEM 7.2 for pediatric patients with and without burn injuries. Amikacin pharmacokinetic parameters were compared between the two groups and multiple dosing regimens were simulated using MATLAB to achieve the PD target in ≥90% of patients with burn injuries. The pharmacokinetic analysis included 282 amikacin concentrations from 70 pediatric patients with burn injuries and 99 concentrations from 32 pediatric patients without burns. A one-compartment model with first-order elimination described amikacin pharmacokinetics well for both groups. Clearance (CL) was significantly higher in patients with burn injuries than in patients without (7.22 vs 5.36 L/h, P < .001). The volume of distribution (V) was also significantly increased in patients with burn injuries (22.7 vs 18.7 L, P < .01). Weight significantly influenced amikacin CL (P < .001) and V (P < .001) for both groups. Model-based simulations showed that a higher amikacin dose (≥25 mg/kg) achieved a Cmax/MIC ≥8 in ≥90% of patients with assumed infections of organisms with an MIC = 8 mg/L. Amikacin pharmacokinetics are altered in patients with burn injuries, including a significant increase in CL and V. In simulations, increased doses (≥25 mg/kg) led to improved PD target attainment rates. Further clinical evaluation of this proposed dosing regimen is warranted to assess clinical and microbiological outcomes in pediatric patients with burn wound sepsis.

Optimization of Treatment Geometry to Reduce Normal Brain Dose in Radiosurgery of Multiple Brain Metastases with Single-Isocenter Volumetric Modulated Arc Therapy.

PubMed

Wu, Qixue; Snyder, Karen Chin; Liu, Chang; Huang, Yimei; Zhao, Bo; Chetty, Indrin J; Wen, Ning

2016-09-30

Treatment of patients with multiple brain metastases using a single-isocenter volumetric modulated arc therapy (VMAT) has been shown to decrease treatment time with the tradeoff of larger low dose to the normal brain tissue. We have developed an efficient Projection Summing Optimization Algorithm to optimize the treatment geometry in order to reduce dose to normal brain tissue for radiosurgery of multiple metastases with single-isocenter VMAT. The algorithm: (a) measures coordinates of outer boundary points of each lesion to be treated using the Eclipse Scripting Application Programming Interface, (b) determines the rotations of couch, collimator, and gantry using three matrices about the cardinal axes, (c) projects the outer boundary points of the lesion on to Beam Eye View projection plane, (d) optimizes couch and collimator angles by selecting the least total unblocked area for each specific treatment arc, and (e) generates a treatment plan with the optimized angles. The results showed significant reduction in the mean dose and low dose volume to normal brain, while maintaining the similar treatment plan qualities on the thirteen patients treated previously. The algorithm has the flexibility with regard to the beam arrangements and can be integrated in the treatment planning system for clinical application directly.

Frame average optimization of cine-mode EPID images used for routine clinical in vivo patient dose verification of VMAT deliveries

DOE Office of Scientific and Technical Information (OSTI.GOV)

McCowan, P. M., E-mail: pmccowan@cancercare.mb.ca; McCurdy, B. M. C.; Medical Physics Department, CancerCare Manitoba, 675 McDermot Avenue, Winnipeg, Manitoba R3E 0V9

Purpose: The in vivo 3D dose delivered to a patient during volumetric modulated arc therapy (VMAT) delivery can be calculated using electronic portal imaging device (EPID) images. These images must be acquired in cine-mode (i.e., “movie” mode) in order to capture the time-dependent delivery information. The angle subtended by each cine-mode EPID image during an arc can be changed via the frame averaging number selected within the image acquisition software. A large frame average number will decrease the EPID’s angular resolution and will result in a decrease in the accuracy of the dose information contained within each image. Alternatively, lessmore » EPID images acquired per delivery will decrease the overall 3D patient dose calculation time, which is appealing for large-scale clinical implementation. Therefore, the purpose of this study was to determine the optimal frame average value per EPID image, defined as the highest frame averaging that can be used without an appreciable loss in 3D dose reconstruction accuracy for VMAT treatments. Methods: Six different VMAT plans and six different SBRT-VMAT plans were delivered to an anthropomorphic phantom. Delivery was carried out on a Varian 2300ix model linear accelerator (Linac) equipped with an aS1000 EPID running at a frame acquisition rate of 7.5 Hz. An additional PC was set up at the Linac console area, equipped with specialized frame-grabber hardware and software packages allowing continuous acquisition of all EPID frames during delivery. Frames were averaged into “frame-averaged” EPID images using MATLAB. Each frame-averaged data set was used to calculate the in vivo dose to the patient and then compared to the single EPID frame in vivo dose calculation (the single frame calculation represents the highest possible angular resolution per EPID image). A mean percentage dose difference of low dose (<20% prescription dose) and high dose regions (>80% prescription dose) was calculated for each frame averaged scenario for each plan. The authors defined their unacceptable loss of accuracy as no more than a ±1% mean dose difference in the high dose region. Optimal frame average numbers were then determined as a function of the Linac’s average gantry speed and the dose per fraction. Results: The authors found that 9 and 11 frame averages were suitable for all VMAT and SBRT-VMAT treatments, respectively. This resulted in no more than a 1% loss to any of the dose region’s mean percentage difference when compared to the single frame reconstruction. The optimized number was dependent on the treatment’s dose per fraction and was determined to be as high as 14 for 12 Gy/fraction (fx), 15 for 8 Gy/fx, 11 for 6 Gy/fx, and 9 for 2 Gy/fx. Conclusions: The authors have determined an optimal EPID frame averaging number for multiple VMAT-type treatments. These are given as a function of the dose per fraction and average gantry speed. These optimized values are now used in the authors’ clinical, 3D, in vivo patient dosimetry program. This provides a reduction in calculation time while maintaining the authors’ required level of accuracy in the dose reconstruction.« less

Therapeutic Drug Monitoring Guides the Management of Crohn's Patients with Secondary Loss of Response to Adalimumab.

PubMed

Restellini, Sophie; Chao, Che-Yung; Lakatos, Peter L; Aruljothy, Achuthan; Aziz, Haya; Kherad, Omar; Bitton, Alain; Wild, Gary; Afif, Waqqas; Bessissow, Talat

2018-04-13

Managing loss of response (LOR) in Crohn's disase (CD) patients remains challenging. Compelling evidence supports therapeutic drug monitoring (TDM) to guide management in patients on infliximab, but data for other biologics are less robust. We aimed to asses if empiric dose escalation led to improved clinical outcome in addition to TDM-guided optimization in CD patients with LOR to adalimumab (ADA). Retrospective chart review of patients followed between 2014 and 2016 at McGill IBD Center with index TDM for LOR to ADA was performed. Primary outcomes were composite remission at 3, 6, and 12 months in those with empiric adjustments versus TDM-guided optimization. There were 104 patients (54.8% men) who were included in the study. Of this group, 81 patients (77.9%) had serum level (SL) ≥5µg/ml at index TDM with a median value of 12µg/ml (IQR 6.1-16.5). There were 10 patients (9.6%) who had undetectable SL with high anti-ADA antibodies and 48 (46.2%) received empiric escalation. TDM led to change in treatment in 58 patients (55.8%). Among them, 28 (48.3%) had discontinued ADA, 12 (21.7%) had addition of immunomodulator or steroid, and 18 (31%) had ADA dose escalation. Empiric dose escalation before TDM-based optimization was not associated with improved outcomes at 3, 6, and 12 months, irrespective of SL levels. Clear SL cutoff associated with composite remission was not identified. Our data do not support empiric dose adjustment beyond that based on the result of the TDM in patients with LOR to ADA. TDM limits unnecessary dose escalation and provides appropriate treatment strategy without compromising clinical outcomes. 10.1093/ibd/izy044_video1izy044.video15768828880001.

Older patients with chronic myeloid leukemia (≥65 years) profit more from higher imatinib doses than younger patients: a subanalysis of the randomized CML-Study IV.

PubMed

Proetel, Ulrike; Pletsch, Nadine; Lauseker, Michael; Müller, Martin C; Hanfstein, Benjamin; Krause, Stefan W; Kalmanti, Lida; Schreiber, Annette; Heim, Dominik; Baerlocher, Gabriela M; Hofmann, Wolf-Karsten; Lange, Elisabeth; Einsele, Hermann; Wernli, Martin; Kremers, Stephan; Schlag, Rudolf; Müller, Lothar; Hänel, Mathias; Link, Hartmut; Hertenstein, Bernd; Pfirrman, Markus; Hochhaus, Andreas; Hasford, Joerg; Hehlmann, Rüdiger; Saußele, Susanne

2014-07-01

The impact of imatinib dose on response rates and survival in older patients with chronic myeloid leukemia in chronic phase has not been studied well. We analyzed data from the German CML-Study IV, a randomized five-arm treatment optimization study in newly diagnosed BCR-ABL-positive chronic myeloid leukemia in chronic phase. Patients randomized to imatinib 400 mg/day (IM400) or imatinib 800 mg/day (IM800) and stratified according to age (≥65 years vs. <65 years) were compared regarding dose, response, adverse events, rates of progression, and survival. The full 800 mg dose was given after a 6-week run-in period with imatinib 400 mg/day. The dose could then be reduced according to tolerability. A total of 828 patients were randomized to IM400 or IM800. Seven hundred eighty-four patients were evaluable (IM400, 382; IM800, 402). One hundred ten patients (29 %) on IM400 and 83 (21 %) on IM800 were ≥65 years. The median dose per day was lower for patients ≥65 years on IM800, with the highest median dose in the first year (466 mg/day for patients ≥65 years vs. 630 mg/day for patients <65 years). Older patients on IM800 achieved major molecular remission and deep molecular remission as fast as younger patients, in contrast to standard dose imatinib with which older patients achieved remissions much later than younger patients. Grades 3 and 4 adverse events were similar in both age groups. Five-year relative survival for older patients was comparable to that of younger patients. We suggest that the optimal dose for older patients is higher than 400 mg/day. ClinicalTrials.gov identifier: NCT00055874

Pharmacokinetic Dashboard-Recommended Dosing Is Different than Standard of Care Dosing in Infliximab-Treated Pediatric IBD Patients.

PubMed

Dubinsky, Marla C; Phan, Becky L; Singh, Namita; Rabizadeh, Shervin; Mould, Diane R

2017-01-01

Standard of care (SOC; combination of 5-10 mg/kg and an interval every 6-8 weeks) dosing of infliximab (IFX) is associated with significant loss of response. Dashboards using covariates that influence IFX pharmacokinetics (PK) may be a more precise way of optimizing anti-TNF dosing. We tested a prototype dashboard to compare forecasted dosing regimens with actual administered regimens and SOC. Fifty IBD patients completing IFX induction were monitored during maintenance (weeks 14-54). Clinical and laboratory data were collected at each infusion; serum was analyzed for IFX concentrations and anti-drug antibodies (ADA) at weeks 14 and 54 (Prometheus Labs, San Diego). Dosing was blinded to PK data. Dashboard-based assessments were conducted on de-identified clinical, laboratory, and PK data. Bayesian algorithms were used to forecast individualized troughs and determine optimal dosing to maintain target trough concentrations (3 μg/mL). Dashboard forecasted dosing post-week 14 was compared to actual administered dose and frequency and SOC. Using week 14 clinical data only, the dashboard recommended either a dose or an interval change (<0.5 mg/kg or <1 week difference) in 43/50 patients; only 44% recommended to have SOC dosing. When IFX14 concentration and ADA status were added to clinical data, dose and/or interval changes based on actual dosing were recommended in 48/50 (96%) patients; SOC dosing was recommended in only 11/50 (22%). Dashboard recommended SOC IFX dosing in a minority of patients. Dashboards will be an important tool to individualize IFX dosing to improve treatment durability.

Efficacy and Safety of Amphetamine Extended-Release Oral Suspension in Children with Attention-Deficit/Hyperactivity Disorder.

PubMed

Childress, Ann C; Wigal, Sharon B; Brams, Matthew N; Turnbow, John M; Pincus, Yulia; Belden, Heidi W; Berry, Sally A

2018-06-01

To determine the efficacy and safety of amphetamine extended-release oral suspension (AMPH EROS) in the treatment of attention-deficit/hyperactivity disorder (ADHD) in a dose-optimized, randomized, double-blind, parallel-group study. Boys and girls aged 6 to 12 years diagnosed with ADHD were enrolled. During a 5-week, open-label, dose-optimization phase, patients began treatment with 2.5 or 5 mg/day of AMPH EROS; doses were titrated until an optimal dose (maximum 20 mg/day) was reached. During the double-blind phase, patients were randomized to receive treatment with either their optimized dose (10-20 mg/day) of AMPH EROS or placebo for 1 week. Efficacy was assessed in a laboratory classroom setting on the final day of double-blind treatment using the Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Rating Scale and Permanent Product Measure of Performance (PERMP) test. Safety was assessed measuring adverse events (AEs) and vital signs. The study was completed by 99 patients. The primary efficacy endpoint (change from predose SKAMP-Combined score at 4 hours postdose) and secondary endpoints (change from predose SKAMP-Combined scores at 1, 2, 6, 8, 10, 12, and 13 hours postdose) were statistically significantly improved with AMPH EROS treatment versus placebo at all time points. Onset of treatment effect was present by 1 hour postdosing, the first time point measured, and duration of efficacy lasted 13 hours postdosing. PERMP data mirrored the SKAMP-Combined score data. AEs (>5%) reported during dose optimization were decreased appetite, insomnia, affect lability, upper abdominal pain, mood swings, and headache. AMPH EROS was effective in reducing symptoms of ADHD and had a rapid onset and extended duration of effect. Reported AEs were consistent with those of other extended-release amphetamine products.

Feasibility and robustness of dose painting by numbers in proton therapy with contour-driven plan optimization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barragán, A. M., E-mail: ana.barragan@uclouvain.be; Differding, S.; Lee, J. A.

Purpose: To prove the ability of protons to reproduce a dose gradient that matches a dose painting by numbers (DPBN) prescription in the presence of setup and range errors, by using contours and structure-based optimization in a commercial treatment planning system. Methods: For two patients with head and neck cancer, voxel-by-voxel prescription to the target volume (GTV{sub PET}) was calculated from {sup 18}FDG-PET images and approximated with several discrete prescription subcontours. Treatments were planned with proton pencil beam scanning. In order to determine the optimal plan parameters to approach the DPBN prescription, the effects of the scanning pattern, number ofmore » fields, number of subcontours, and use of range shifter were separately tested on each patient. Different constant scanning grids (i.e., spot spacing = Δx = Δy = 3.5, 4, and 5 mm) and uniform energy layer separation [4 and 5 mm WED (water equivalent distance)] were analyzed versus a dynamic and automatic selection of the spots grid. The number of subcontours was increased from 3 to 11 while the number of beams was set to 3, 5, or 7. Conventional PTV-based and robust clinical target volumes (CTV)-based optimization strategies were considered and their robustness against range and setup errors assessed. Because of the nonuniform prescription, ensuring robustness for coverage of GTV{sub PET} inevitably leads to overdosing, which was compared for both optimization schemes. Results: The optimal number of subcontours ranged from 5 to 7 for both patients. All considered scanning grids achieved accurate dose painting (1% average difference between the prescribed and planned doses). PTV-based plans led to nonrobust target coverage while robust-optimized plans improved it considerably (differences between worst-case CTV dose and the clinical constraint was up to 3 Gy for PTV-based plans and did not exceed 1 Gy for robust CTV-based plans). Also, only 15% of the points in the GTV{sub PET} (worst case) were above 5% of DPBN prescription for robust-optimized plans, while they were more than 50% for PTV plans. Low dose to organs at risk (OARs) could be achieved for both PTV and robust-optimized plans. Conclusions: DPBN in proton therapy is feasible with the use of a sufficient number subcontours, automatically generated scanning patterns, and no more than three beams are needed. Robust optimization ensured the required target coverage and minimal overdosing, while PTV-approach led to nonrobust plans with excessive overdose. Low dose to OARs can be achieved even in the presence of a high-dose escalation as in DPBN.« less

Proceedings of the 2016 Clinical Nutrition Week Research Workshop-The Optimal Dose of Protein Provided to Critically Ill Patients.

PubMed

Heyland, Daren K; Rooyakers, Olav; Mourtzakis, Marina; Stapleton, Renee D

2017-02-01

Recent literature has created considerable confusion about the optimal amount of protein/amino acids that should be provided to the critically ill patient. In fact, the evidentiary basis that directly tries to answer this question is relatively small. As a clinical nutrition research community, there is an urgent need to develop the optimal methods to assess the impact of exogenous protein/amino acid administration in the intensive care unit setting. That assessment can be conducted at various levels: (1) impact on stress response pathways, (2) impact on muscle synthesis and protein balance, (3) impact on muscle mass and function, and (4) impact on the patient's recovery. The objective of this research workshop was to review current literature relating to protein/amino acid administration for the critically ill patient and clinical outcomes and to discuss the key measurement and methodological features of future studies that should be done to inform the optimal protein/amino acid dose provided to critically ill patients.

Optimization of exposure parameters for pediatric chest x-ray imaging

NASA Astrophysics Data System (ADS)

Park, Hye-Suk; Kim, Ye-Seul; Kim, Hee-Joung

2012-03-01

The pediatric patients are more susceptible to the effects of ionizing radiation than adults. Pediatric patients are smaller, more radiosensitive than adult patients and many cannot stand unassisted. Their characteristics affect the method of imaging projection and how dose is optimized. The purpose of this study was to investigate the effect of various technical parameters for the dose optimization in pediatric chest radiological examinations by evaluating effective dose and effective detective quantum efficiency (eDQE) including the scatter radiation from the object, the blur caused by the focal spot, geometric magnification and detector characteristics. For the tube voltages ranging from 40 to 90 kV in 10 kV increments at the focus-to-detector distance of 100, 110, 120, 150, 180 cm, the eDQE was evaluated at same effective dose. The results showed that the eDQE was largest at 60 kVp without and with an anti-scatter grid. Especially, the eDQE was considerably higher without the use of an anti-scatter grid on equivalent effective dose. This indicates that the reducing the scatter radiation did not compensate for the loss of absorbed effective photons in the grid. When the grid is not used the eDQE increased with increasing focus-to-detector distance because of the greater effective modulation transfer function (eMTF) with the lower focal spot blurring. In conclusion, for pediatric patients, the amount of scattered radiation is less, and the amount of grid attenuation increased unnecessary radiation dose.

Allopurinol Medication Adherence as a Mediator of Optimal Outcomes in Gout Management.

PubMed

Coburn, Brian W; Bendlin, Kayli A; Sayles, Harlan; Meza, Jane; Russell, Cynthia L; Mikuls, Ted R

2017-09-01

Patient and provider factors, including allopurinol medication adherence, affect gout treatment outcomes. The aim of this study was to examine associations of patient and provider factors with optimal gout management. Linking longitudinal health and pharmacy dispensing records to questionnaire data, we assessed patient and provider factors among 612 patients with gout receiving allopurinol during a recent 1-year period. Associations of patient (medication adherence and patient activation) and provider factors (dose escalation, low-dose initiation, and anti-inflammatory prophylaxis) with serum urate (SU) goal achievement of less than 6.0 mg/dL were examined using multivariable logistic regression. Medication adherence was assessed as a mediator of these factors with goal achievement. A majority of patients (63%) were adherent, whereas a minority received dose escalation (31%). Medication adherence was associated with initiation of daily allopurinol doses of 100 mg/d or less (odds ratio [OR], 1.82; 95% confidence interval [CI], 1.20-2.76). In adjusted models, adherence (OR, 2.35; 95% CI, 1.50-3.68) and dose escalation (OR, 2.48; 95% CI, 2.48-4.25) were strongly associated with SU goal attainment. Low starting allopurinol dose was positively associated with SU goal attainment (OR, 1.11; 95% CI, 1.02-1.20) indirectly through early adherence, but also had a negative direct association with SU goal attainment (OR, 0.21; 95% CI, 0.12-0.37). Medication adherence and low starting dose combined with dose escalation represent promising targets for future gout quality improvement efforts. Low starting dose is associated with better SU goal attainment through increased medication adherence, but may be beneficial only in settings where appropriate dose escalation is implemented.

SU-F-T-451: Doses to Organs-At-Risk in the Presence and Absence of a 1.5 T Magnetic Field for NSCLC Patients Undergoing SABR

DOE Office of Scientific and Technical Information (OSTI.GOV)

Al-Ward, S; Kim, A; McCann, C

2016-06-15

Purpose: To determine whether the electron return effect (ERE) has deleterious effects on lung SABR plans optimized in the presence of an orthogonal 1.5 T magnetic field. Methods: Data from five NSCLC-SABR patients were used. The Dose was modeled with a 2.5 mm dose grid in the presence and absence of a magnetic field using the Monaco (Elekta) TPS with the Monte Carlo GPUMCD (v5.1) algorithm. For each patient, two plans were generated, one using our conventional Elekta Agility linac beam model and another using the Elekta MRI Linac (MRL) model. Both plans were generated on the average CT usingmore » similar dose constraints and a 5 mm PTV. The optimization was performed using our clinic’s planning criteria, with normalization of the targets such that their V99% was equal to 99%. The OAR DVHs were compared for each patient. Results: The DVH plots revealed that there were limited differences when optimizing plans in the presence or absence of the magnetic field. The mean of the absolute differences, between the two planning types, in the equivalent uniform doses (EUDs) for the OARs were: 0.3 Gy (range of 0.0 - 1.0 Gy) for the esophagus, 0.6 Gy (range of 0.1 – 1.9 Gy) for the heart, 0.5 Gy (range of 0.2 – 0.8 Gy) for the lungs, and 0.6 Gy (range of 0.2 – 1.5 Gy) for the spinal canal. Regarding the maximum doses to the serial organs, the mean of the differences were 3.0 Gy (esophagus) and 0.9 Gy (spinal canal). No trends in the differences were observed. Conclusion: This study has demonstrated that there were no major differences between plans optimized using a conventional linac and those optimized using an MRI linac with an orthogonal 1.5 T magnetic field. This is attributed to the consideration of the ERE in the optimization. This project was made possible with the financial support of Elekta.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Su, M; Sura, S

Purpose: To evaluate dosimetric impact of two axillary nodes (AX) boost techniques: (1) posterior-oblique optimized field boost (POB), (2) traditional posterior-anterior boost (PAB) with field optimization (O-PAB), for a postmastectomy breast patient with positive axillary lymph nodes. Methods: Five patients, 3 left and 2 right chest walls, were included in this study. All patients were simulated in 5mm CT slice thickness. Supraclavicular (SC) and level I/II/III AX were contoured based on the RTOG atlas guideline. Five treatment plans, (1) tangential chest wall, (2) oblique SC including AX, (3) PAB, O-PAB and POB, were created for each patient. Three plan sumsmore » (PS) were generated by sum one of (3) plan with plan (1) and (2). The field optimization was done through PS dose distribution, which included a field adjustment, a fractional dose, a calculation location and a gantry angle selection for POB. A dosimetric impact was evaluated by comparing a SC and AX coverage, a PS maximum dose, an irradiated area percentage volume received dose over 105% prescription dose (V105), an ipsi-laterial mean lung dose (MLD), an ipsi-laterial mean humeral head dose (MHHD), a mean heart dose (MHD) (for left case only) and their DVH amount these three technique. Results: O-PAB, POB and PAB dosimetric results showed that there was no significant different on SC and AX coverage (p>0.43) and MHD (p>0.16). The benefit of sparing lung irradiation from PAB to O-PAB to POB was significant (p<0.004). PAB showed a highest PS maximum dose (p<0.005), V105 (p<0.023) and MLD (compared with OPAB, p=0.055). MHHD showed very sensitive to the patient arm positioning and anatomy. O-PAB convinced a lower MHHD than PAB (p=0.03). Conclusion: 3D CT contouring plays main role in accuracy radiotherapy. Dosimetric advantage of POB and O-PAB was observed for a better normal tissue irradiation sparing.« less

Pharmacokinetics and Dosing of Anti-infective Drugs in Patients on Extracorporeal Membrane Oxygenation: A Review of the Current Literature.

PubMed

Sherwin, Jennifer; Heath, Travis; Watt, Kevin

2016-09-01

Extracorporeal membrane oxygenation (ECMO) is a cardiopulmonary bypass device that is used to temporarily support the most critically ill of patients with respiratory and/or cardiac failure. Infection and its sequelae may be an indication for ECMO or infections may be acquired while on ECMO and are associated with a mortality >50%. Effective therapy requires optimal dosing. However, optimal dosing can be different in patients on ECMO because the ECMO circuit can alter drug pharmacokinetics. This review assessed the current literature for pharmacokinetic data and subsequent dosing recommendations for anti-infective drugs in patients on ECMO. We searched the PubMed and Embase databases (1965 to February 2016) and included case reports, case series, or studies that provided pharmacokinetic data for anti-infective drugs including antibiotics, antifungals, and antivirals being used to treat patients of all age groups on ECMO. Pharmacokinetic parameters and dosing recommendations based on these data are presented. The majority of data on this topic comes from neonatal studies of antibiotics from the 1980s and 1990s. These studies generally demonstrate a larger volume of distribution due to ECMO and therefore higher doses are needed initially. More adult data are now emerging, but with a predominance of case reports and case series without comparison with critically ill controls. The available pharmacokinetic analyses do suggest that volume of distribution and clearance are unchanged in the adult population, and therefore dosing recommendations largely remain unchanged. There is a lack of data on children older than 1 year of age. The data support the importance of therapeutic drug monitoring when available in this population of patients. This review found reasonably robust dosing recommendations for some drugs and scant or no data for other important anti-infectives. In order to better determine optimal dosing for patients on ECMO, a systematic approach is needed. Approaches that combine ex vivo ECMO experiments, animal studies, specialized pharmacokinetic modeling, and human clinical trials are being developed. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.

Hard beta and gamma emissions of 124I. Impact on occupational dose in PET/CT.

PubMed

Kemerink, G J; Franssen, R; Visser, M G W; Urbach, C J A; Halders, S G E A; Frantzen, M J; Brans, B; Teule, G J J; Mottaghy, F M

2011-01-01

The hard beta and gamma radiation of 124I can cause high doses to PET/CT workers. In this study we tried to quantify this occupational exposure and to optimize radioprotection. Thin MCP-Ns thermoluminescent dosimeters suitable for measuring beta and gamma radiation were used for extremity dosimetry, active personal dosimeters for whole-body dosimetry. Extremity doses were determined during dispensing of 124I and oral administration of the activity to the patient, the body dose during all phases of the PET/CT procedure. In addition, dose rates of vials and syringes as used in clinical practice were measured. The procedure for dispensing 124I was optimized using newly developed shielding. Skin dose rates up to 100 mSv/min were measured when in contact with the manufacturer's vial containing 370 MBq of 124I. For an unshielded 5 ml syringe the positron skin dose was about seven times the gamma dose. Before optimization of the preparation of 124I, using an already reasonably safe technique, the highest mean skin dose caused by handling 370 MBq was 1.9 mSv (max. 4.4 mSv). After optimization the skin dose was below 0.2 mSv. The highly energetic positrons emitted by 124I can cause high skin doses if radioprotection is poor. Under optimized conditions occupational doses are acceptable. Education of workers is of paramount importance.

Efficacy and Safety of a Colistin Loading Dose, High-Dose Maintenance Regimen in Critically Ill Patients With Multidrug-Resistant Gram-Negative Pneumonia.

PubMed

Elefritz, Jessica L; Bauer, Karri A; Jones, Christian; Mangino, Julie E; Porter, Kyle; Murphy, Claire V

2017-09-01

Emergence of multidrug-resistant (MDR) gram-negative (GN) pathogens and lack of novel antibiotics have increased the use of colistin, despite unknown optimal dosing. This study aimed to evaluate the safety and efficacy of a colistin loading dose, high-dose (LDHD) maintenance regimen in patients with MDR-GN pneumonia. A retrospective cohort analysis was performed comparing critically ill patients with MDR-GN pneumonia pre- and postimplementation of a colistin LDHD guideline with a primary outcome of clinical cure. Safety was assessed using incidence of acute kidney injury (AKI) based on RIFLE (risk, injury, failure, loss, end-stage renal disease) criteria. Seventy-two patients met the inclusion criteria (42 preimplementation and 30 postimplementation). Clinical cure was achieved in 23 (55%) patients in the preimplementation group and 20 (67%) patients in the postimplementation group ( P = .31). AKI occurred in 50% of the patients during the preimplementation period and 58% during the postimplementation period ( P = .59) with no difference in initiation rates of renal replacement therapy. The increased clinical cure rate after implementation of the colistin LDHD guideline did not reach statistical significance. The LDHD guideline, however, was not associated with an increased incidence of AKI, despite higher intravenous colistin doses. Opportunity exists to optimize colistin dosage while balancing toxicity, but larger studies are warranted.

Comparison between DCA - SSO - VDR and VMAT dose delivery techniques for 15 SRS/SRT patients

NASA Astrophysics Data System (ADS)

Tas, B.; Durmus, I. F.

2018-02-01

To evaluate dose delivery between Dynamic Conformal Arc (DCA) - Segment Shape Optimization (SSO) - Variation Dose Rate (VDR) and Volumetric Modulated Arc Therapy (VMAT) techniques for fifteen SRS patients using Versa HD® lineer accelerator. Fifteen SRS / SRT patient's optimum treatment planning were performed using Monaco5.11® treatment planning system (TPS) with 1 coplanar and 3 non-coplanar fields for VMAT technique, then the plans were reoptimized with the same optimization parameters for DCA - SSO - VDR technique. The advantage of DCA - SSO - VDR technique were determined less MUs and beam on time, also larger segments decrease dosimetric uncertainities of small fields quality assurance. The advantage of VMAT technique were determined a little better GI, CI, PCI, brain V12Gy and brain mean dose. The results show that the clinical objectives and plans for both techniques satisfied all organs at risks (OARs) dose constraints. Depends on the shape and localization of target, we could choose one of these techniques for linear accelerator based SRS / SRT treatment.

Nilotinib dose-optimization in newly diagnosed chronic myeloid leukaemia in chronic phase: final results from ENESTxtnd.

PubMed

Hughes, Timothy P; Munhoz, Eduardo; Aurelio Salvino, Marco; Ong, Tee Chuan; Elhaddad, Alaa; Shortt, Jake; Quach, Hang; Pavlovsky, Carolina; Louw, Vernon J; Shih, Lee-Yung; Turkina, Anna G; Meillon, Luis; Jin, Yu; Acharya, Sandip; Dalal, Darshan; Lipton, Jeffrey H

2017-10-01

The Evaluating Nilotinib Efficacy and Safety in Clinical Trials-Extending Molecular Responses (ENESTxtnd) study was conducted to evaluate the kinetics of molecular response to nilotinib in patients with newly diagnosed chronic myeloid leukaemia in chronic phase and the impact of novel dose-optimization strategies on patient outcomes. The ENESTxtnd protocol allowed nilotinib dose escalation (from 300 to 400 mg twice daily) in the case of suboptimal response or treatment failure as well as dose re-escalation for patients with nilotinib dose reductions due to adverse events. Among 421 patients enrolled in ENESTxtnd, 70·8% (95% confidence interval, 66·2-75·1%) achieved major molecular response (BCR-ABL1 ≤ 0·1% on the International Scale) by 12 months (primary endpoint). By 24 months, 81·0% of patients achieved major molecular response, including 63·6% (56 of 88) of those with dose escalations for lack of efficacy and 74·3% (55 of 74) of those with dose reductions due to adverse events (including 43 of 54 patients with successful re-escalation). The safety profile of nilotinib was consistent with prior studies. The most common non-haematological adverse events were headache, rash, and nausea; cardiovascular events were reported in 4·5% of patients (grade 3/4, 3·1%). The study was registered at clinicaltrials.gov (NCT01254188). © 2017 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd.

Exploratory Study of 4D Versus 3D Robust Optimization in Intensity-Modulated Proton Therapy for Lung Cancer

PubMed Central

Liu, Wei; Schild, Steven E.; Chang, Joe Y.; Liao, Zhongxing; Chang, Yu-Hui; Wen, Zhifei; Shen, Jiajian; Stoker, Joshua B.; Ding, Xiaoning; Hu, Yanle; Sahoo, Narayan; Herman, Michael G.; Vargas, Carlos; Keole, Sameer; Wong, William; Bues, Martin

2015-01-01

Background To compare the impact of uncertainties and interplay effect on 3D and 4D robustly optimized intensity-modulated proton therapy (IMPT) plans for lung cancer in an exploratory methodology study. Methods IMPT plans were created for 11 non-randomly selected non-small-cell lung cancer (NSCLC) cases: 3D robustly optimized plans on average CTs with internal gross tumor volume density overridden to irradiate internal target volume, and 4D robustly optimized plans on 4D CTs to irradiate clinical target volume (CTV). Regular fractionation (66 Gy[RBE] in 33 fractions) were considered. In 4D optimization, the CTV of individual phases received non-uniform doses to achieve a uniform cumulative dose. The root-mean-square-dose volume histograms (RVH) measured the sensitivity of the dose to uncertainties, and the areas under the RVH curve (AUCs) were used to evaluate plan robustness. Dose evaluation software modeled time-dependent spot delivery to incorporate interplay effect with randomized starting phases of each field per fraction. Dose-volume histogram indices comparing CTV coverage, homogeneity, and normal tissue sparing were evaluated using Wilcoxon signed-rank test. Results 4D robust optimization plans led to smaller AUC for CTV (14.26 vs. 18.61 (p=0.001), better CTV coverage (Gy[RBE]) [D95% CTV: 60.6 vs 55.2 (p=0.001)], and better CTV homogeneity [D5%–D95% CTV: 10.3 vs 17.7 (p=0.002)] in the face of uncertainties. With interplay effect considered, 4D robust optimization produced plans with better target coverage [D95% CTV: 64.5 vs 63.8 (p=0.0068)], comparable target homogeneity, and comparable normal tissue protection. The benefits from 4D robust optimization were most obvious for the 2 typical stage III lung cancer patients. Conclusions Our exploratory methodology study showed that, compared to 3D robust optimization, 4D robust optimization produced significantly more robust and interplay-effect-resistant plans for targets with comparable dose distributions for normal tissues. A further study with a larger and more realistic patient population is warranted to generalize the conclusions. PMID:26725727

SU-F-18C-01: Minimum Detectability Analysis for Comprehensive Sized Based Optimization of Image Quality and Radiation Dose Across CT Protocols

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smitherman, C; Chen, B; Samei, E

2014-06-15

Purpose: This work involved a comprehensive modeling of task-based performance of CT across a wide range of protocols. The approach was used for optimization and consistency of dose and image quality within a large multi-vendor clinical facility. Methods: 150 adult protocols from the Duke University Medical Center were grouped into sub-protocols with similar acquisition characteristics. A size based image quality phantom (Duke Mercury Phantom) was imaged using these sub-protocols for a range of clinically relevant doses on two CT manufacturer platforms (Siemens, GE). The images were analyzed to extract task-based image quality metrics such as the Task Transfer Function (TTF),more » Noise Power Spectrum, and Az based on designer nodule task functions. The data were analyzed in terms of the detectability of a lesion size/contrast as a function of dose, patient size, and protocol. A graphical user interface (GUI) was developed to predict image quality and dose to achieve a minimum level of detectability. Results: Image quality trends with variations in dose, patient size, and lesion contrast/size were evaluated and calculated data behaved as predicted. The GUI proved effective to predict the Az values representing radiologist confidence for a targeted lesion, patient size, and dose. As an example, an abdomen pelvis exam for the GE scanner, with a task size/contrast of 5-mm/50-HU, and an Az of 0.9 requires a dose of 4.0, 8.9, and 16.9 mGy for patient diameters of 25, 30, and 35 cm, respectively. For a constant patient diameter of 30 cm, the minimum detected lesion size at those dose levels would be 8.4, 5, and 3.9 mm, respectively. Conclusion: The designed CT protocol optimization platform can be used to evaluate minimum detectability across dose levels and patient diameters. The method can be used to improve individual protocols as well as to improve protocol consistency across CT scanners.« less

SU-E-T-586: Optimal Determination of Tolerance Level for Radiation Dose Delivery Verification in An in Vivo Dosimetry System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Y; Souri, S; Gill, G

Purpose: To statistically determine the optimal tolerance level in the verification of delivery dose compared to the planned dose in an in vivo dosimetry system in radiotherapy. Methods: The LANDAUER MicroSTARii dosimetry system with screened nanoDots (optically stimulated luminescence dosimeters) was used for in vivo dose measurements. Ideally, the measured dose should match with the planned dose and falls within a normal distribution. Any deviation from the normal distribution may be redeemed as a mismatch, therefore a potential sign of the dose misadministration. Randomly mis-positioned nanoDots can yield a continuum background distribution. A percentage difference of the measured dose tomore » its corresponding planned dose (ΔD) can be used to analyze combined data sets for different patients. A model of a Gaussian plus a flat function was used to fit the ΔD distribution. Results: Total 434 nanoDot measurements for breast cancer patients were collected across a period of three months. The fit yields a Gaussian mean of 2.9% and a standard deviation (SD) of 5.3%. The observed shift of the mean from zero is attributed to the machine output bias and calibration of the dosimetry system. A pass interval of −2SD to +2SD was applied and a mismatch background was estimated to be 4.8%. With such a tolerance level, one can expect that 99.99% of patients should pass the verification and at most 0.011% might have a potential dose misadministration that may not be detected after 3 times of repeated measurements. After implementation, a number of new start breast cancer patients were monitored and the measured pass rate is consistent with the model prediction. Conclusion: It is feasible to implement an optimal tolerance level in order to maintain a low limit of potential dose misadministration while still to keep a relatively high pass rate in radiotherapy delivery verification.« less

MO-G-18A-01: Radiation Dose Reducing Strategies in CT, Fluoroscopy and Radiography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mahesh, M; Gingold, E; Jones, A

2014-06-15

Advances in medical x-ray imaging have provided significant benefits to patient care. According to NCRP 160, there are more than 400 million x-ray procedures performed annually in the United States alone that contributes to nearly half of all the radiation exposure to the US population. Similar growth trends in medical x-ray imaging are observed worldwide. Apparent increase in number of medical x-ray imaging procedures, new protocols and the associated radiation dose and risk has drawn considerable attention. This has led to a number of technological innovations such as tube current modulation, iterative reconstruction algorithms, dose alerts, dose displays, flat panelmore » digital detectors, high efficient digital detectors, storage phosphor radiography, variable filters, etc. that are enabling users to acquire medical x-ray images at a much lower radiation dose. Along with these, there are number of radiation dose optimization strategies that users can adapt to effectively lower radiation dose in medical x-ray procedures. The main objectives of this SAM course are to provide information and how to implement the various radiation dose optimization strategies in CT, Fluoroscopy and Radiography. Learning Objectives: To update impact of technological advances on dose optimization in medical imaging. To identify radiation optimization strategies in computed tomography. To describe strategies for configuring fluoroscopic equipment that yields optimal images at reasonable radiation dose. To assess ways to configure digital radiography systems and recommend ways to improve image quality at optimal dose.« less

Anticoagulation Endpoints with Clinical Implementation of Warfarin Pharmacogenetic Dosing in a Real-World Setting – A Proposal for a New Pharmacogenetic Dosing Approach

PubMed Central

Arwood, Meghan J.; Deng, Jiexin; Drozda, Katarzyna; Pugach, Oksana; Nutescu, Edith A.; Schmidt, Stephan; Duarte, Julio D.; Cavallari, Larisa H.

2016-01-01

Achieving therapeutic anticoagulation efficiently with warfarin is important to reduce thrombotic and bleeding risks and is influenced by genotype. Utilizing data from a diverse population of 257 patients who received VKORC1 and CYP2C9 genotype-guided warfarin dosing, we aimed to examine genotype-associated differences in anticoagulation endpoints and derive a novel pharmacogenetic nomogram to more optimally dose warfarin. We observed significant differences across patients with 0, 1, or ≥2 reduced-function VKORC1 or CYP2C9 alleles, respectively, in time to achieve therapeutic international normalized ratio (INR) (7.8±5.8, 7.2±4.7, and 5.4±4.6 days, P=0.0004) and mean percentage of time in therapeutic range in the first 28 days (22.2, 27.8, and 32.2%, P=0.0127) with use of existing pharmacogenetic algorithms. These data suggest that more aggressive dosing is necessary for patients with 0 to 1 VKORC1/CYP2C9 variants to more efficiently achieve therapeutic anticoagulation. Herein, we provide a novel kinetic/pharmacodynamic-derived dosing nomogram optimized for a heterogeneous patient population. PMID:28032893

Using spatial information about recurrence risk for robust optimization of dose-painting prescription functions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bender, Edward T.

Purpose: To develop a robust method for deriving dose-painting prescription functions using spatial information about the risk for disease recurrence. Methods: Spatial distributions of radiobiological model parameters are derived from distributions of recurrence risk after uniform irradiation. These model parameters are then used to derive optimal dose-painting prescription functions given a constant mean biologically effective dose. Results: An estimate for the optimal dose distribution can be derived based on spatial information about recurrence risk. Dose painting based on imaging markers that are moderately or poorly correlated with recurrence risk are predicted to potentially result in inferior disease control when comparedmore » the same mean biologically effective dose delivered uniformly. A robust optimization approach may partially mitigate this issue. Conclusions: The methods described here can be used to derive an estimate for a robust, patient-specific prescription function for use in dose painting. Two approximate scaling relationships were observed: First, the optimal choice for the maximum dose differential when using either a linear or two-compartment prescription function is proportional to R, where R is the Pearson correlation coefficient between a given imaging marker and recurrence risk after uniform irradiation. Second, the predicted maximum possible gain in tumor control probability for any robust optimization technique is nearly proportional to the square of R.« less

Inverse Planning Approach for 3-D MRI-Based Pulse-Dose Rate Intracavitary Brachytherapy in Cervix Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chajon, Enrique; Dumas, Isabelle; Touleimat, Mahmoud B.Sc.

2007-11-01

Purpose: The purpose of this study was to evaluate the inverse planning simulated annealing (IPSA) software for the optimization of dose distribution in patients with cervix carcinoma treated with MRI-based pulsed-dose rate intracavitary brachytherapy. Methods and Materials: Thirty patients treated with a technique using a customized vaginal mold were selected. Dose-volume parameters obtained using the IPSA method were compared with the classic manual optimization method (MOM). Target volumes and organs at risk were delineated according to the Gynecological Brachytherapy Group/European Society for Therapeutic Radiology and Oncology recommendations. Because the pulsed dose rate program was based on clinical experience with lowmore » dose rate, dwell time values were required to be as homogeneous as possible. To achieve this goal, different modifications of the IPSA program were applied. Results: The first dose distribution calculated by the IPSA algorithm proposed a heterogeneous distribution of dwell time positions. The mean D90, D100, and V100 calculated with both methods did not differ significantly when the constraints were applied. For the bladder, doses calculated at the ICRU reference point derived from the MOM differed significantly from the doses calculated by the IPSA method (mean, 58.4 vs. 55 Gy respectively; p = 0.0001). For the rectum, the doses calculated at the ICRU reference point were also significantly lower with the IPSA method. Conclusions: The inverse planning method provided fast and automatic solutions for the optimization of dose distribution. However, the straightforward use of IPSA generated significant heterogeneity in dwell time values. Caution is therefore recommended in the use of inverse optimization tools with clinical relevance study of new dosimetric rules.« less

Automatically-generated rectal dose constraints in intensity-modulated radiation therapy for prostate cancer

NASA Astrophysics Data System (ADS)

Hwang, Taejin; Kim, Yong Nam; Kim, Soo Kon; Kang, Sei-Kwon; Cheong, Kwang-Ho; Park, Soah; Yoon, Jai-Woong; Han, Taejin; Kim, Haeyoung; Lee, Meyeon; Kim, Kyoung-Joo; Bae, Hoonsik; Suh, Tae-Suk

2015-06-01

The dose constraint during prostate intensity-modulated radiation therapy (IMRT) optimization should be patient-specific for better rectum sparing. The aims of this study are to suggest a novel method for automatically generating a patient-specific dose constraint by using an experience-based dose volume histogram (DVH) of the rectum and to evaluate the potential of such a dose constraint qualitatively. The normal tissue complication probabilities (NTCPs) of the rectum with respect to V %ratio in our study were divided into three groups, where V %ratio was defined as the percent ratio of the rectal volume overlapping the planning target volume (PTV) to the rectal volume: (1) the rectal NTCPs in the previous study (clinical data), (2) those statistically generated by using the standard normal distribution (calculated data), and (3) those generated by combining the calculated data and the clinical data (mixed data). In the calculated data, a random number whose mean value was on the fitted curve described in the clinical data and whose standard deviation was 1% was generated by using the `randn' function in the MATLAB program and was used. For each group, we validated whether the probability density function (PDF) of the rectal NTCP could be automatically generated with the density estimation method by using a Gaussian kernel. The results revealed that the rectal NTCP probability increased in proportion to V %ratio , that the predictive rectal NTCP was patient-specific, and that the starting point of IMRT optimization for the given patient might be different. The PDF of the rectal NTCP was obtained automatically for each group except that the smoothness of the probability distribution increased with increasing number of data and with increasing window width. We showed that during the prostate IMRT optimization, the patient-specific dose constraints could be automatically generated and that our method could reduce the IMRT optimization time as well as maintain the IMRT plan quality.

Role of step size and max dwell time in anatomy based inverse optimization for prostate implants

PubMed Central

Manikandan, Arjunan; Sarkar, Biplab; Rajendran, Vivek Thirupathur; King, Paul R.; Sresty, N.V. Madhusudhana; Holla, Ragavendra; Kotur, Sachin; Nadendla, Sujatha

2013-01-01

In high dose rate (HDR) brachytherapy, the source dwell times and dwell positions are vital parameters in achieving a desirable implant dose distribution. Inverse treatment planning requires an optimal choice of these parameters to achieve the desired target coverage with the lowest achievable dose to the organs at risk (OAR). This study was designed to evaluate the optimum source step size and maximum source dwell time for prostate brachytherapy implants using an Ir-192 source. In total, one hundred inverse treatment plans were generated for the four patients included in this study. Twenty-five treatment plans were created for each patient by varying the step size and maximum source dwell time during anatomy-based, inverse-planned optimization. Other relevant treatment planning parameters were kept constant, including the dose constraints and source dwell positions. Each plan was evaluated for target coverage, urethral and rectal dose sparing, treatment time, relative target dose homogeneity, and nonuniformity ratio. The plans with 0.5 cm step size were seen to have clinically acceptable tumor coverage, minimal normal structure doses, and minimum treatment time as compared with the other step sizes. The target coverage for this step size is 87% of the prescription dose, while the urethral and maximum rectal doses were 107.3 and 68.7%, respectively. No appreciable difference in plan quality was observed with variation in maximum source dwell time. The step size plays a significant role in plan optimization for prostate implants. Our study supports use of a 0.5 cm step size for prostate implants. PMID:24049323

Haematological toxicity: a marker of adjuvant chemotherapy efficacy in stage II and III breast cancer.

PubMed Central

Saarto, T.; Blomqvist, C.; Rissanen, P.; Auvinen, A.; Elomaa, I.

1997-01-01

Two hundred and eleven patients with node-positive stage II and III breast cancer were treated with eight cycles of adjuvant chemotherapy comprising cyclophosphamide, doxorubicin and oral ftorafur (CAFt), with and without tamoxifen. All patients had undergone radical surgery, and 148 patients were treated with post-operative radiotherapy in two randomized studies. The impact of haematological toxicity of CAFt on distant disease-free (DDFS) and overall survival (OS) was recorded. Dose intensity of all given cycles (DI), dose intensity of the two initial cycles (DI2) and total dose (TD) were calculated separately for all chemotherapy drugs and were correlated with DDFS and OS. Patients with a lower leucocyte nadir during the chemotherapy had significantly better DDFS and OS (P = 0.01 and 0.04 respectively). Dose intensity of the two first cycles also correlated significantly with DDFS (P = 0.05) in univariate but not in multivariate analysis, while the leucocyte nadir retained its prognostic value. These results indicate that the leucocyte nadir during the adjuvant chemotherapy is a biological marker of chemotherapy efficacy; this presents the possibility of establishing an optimal dose intensity for each patient. The initial dose intensity of adjuvant chemotherapy also seems to be important in assuring the optimal effect of adjuvant chemotherapy. PMID:9010042

Sci-Thur PM - Colourful Interactions: Highlights 08: ARC TBI using Single-Step Optimized VMAT Fields

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hudson, Alana; Gordon, Deborah; Moore, Roseanne

Purpose: This work outlines a new TBI delivery technique to replace a lateral POP full bolus technique. The new technique is done with VMAT arc delivery, without bolus, treating the patient prone and supine. The benefits of the arc technique include: increased patient experience and safety, better dose conformity, better organ at risk sparing, decreased therapist time and reduction of therapist injuries. Methods: In this work we build on a technique developed by Jahnke et al. We use standard arc fields with gantry speeds corrected for varying distance to the patient followed by a single step VMAT optimization on amore » patient CT to increase dose inhomogeneity and to reduce dose to the lungs (vs. blocks). To compare the arc TBI technique to our full bolus technique, we produced plans on patient CTs for both techniques and evaluated several dosimetric parameters using an ANOVA test. Results and Conclusions: The arc technique is able reduce both the hot areas to the body (D2% reduced from 122.2% to 111.8% p<0.01) and the lungs (mean lung dose reduced from 107.5% to 99.1%, p<0.01), both statistically significant, while maintaining coverage (D98% = 97.8% vs. 94.6%, p=0.313, not statistically significant). We developed a more patient and therapist-friendly TBI treatment technique that utilizes single-step optimized VMAT plans. It was found that this technique was dosimetrically equivalent to our previous lateral technique in terms of coverage and statistically superior in terms of reduced lung dose.« less

SU-E-T-284: Dose Plan Optimization When Using Hydrogel Prostate-Rectum Spacer: A Single Institution Experience

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rajecki, M; Thurber, A; Catalfamo, F

2015-06-15

Purpose: To describe rectal dose reduction achieved and techniques used to take advantage of the increased peri-rectal spacing provided by injected polyethylene-glycol. Methods: Thirty prostate cancer patents were 2:1 randomized during a clinical trial to evaluate the effectiveness of injected poly-ethylene glycol hydrogel (SpaceOAR System) in creating space between the prostate and the anterior rectal wall. All patients received a baseline CT/MR scan and baseline IMRT treatment plan. Patients were randomized to receive hydrogel injection (n=20) or Control (n=10), followed by another CT/MR scan and treatment plan (single arc VMAT, 6 MV photons, 79.2 Gy, 44 fractions). Additional optimization structuresmore » were employed to constrain the dose to the rectum; specifically an avoidance structure to limit V75 <15%, and a control structure to limit the maximum relative dose <105% in the interface region of the anterior rectal wall and the prostate planning target volume. Dose volumetric data was analyzed for rectal volumes receiving 60 through 80 Gy. Results: Rectal dose reduction was observed in all patients who received the hydrogel. Volumetric analysis indicates a median rectal volume and (reduction from baseline plan) following spacer application of 4.9% (8.9%) at V60Gy, 3.8% (8.1%) at V65Gy, 2.5% (7.2%) at V70Gy, 1.6% (5.8%) at V75Gy, and 0.5% (2.5%) at V80Gy. Conclusion: Relative to planning without spacers, rectal dose constraints of 5%, 4%, 3%, 2%, 1% for V60, V65, V70, V75, and V80, should be obtainable when peri-rectal spacers are used. The combined effect of increased peri-rectal space provided by the hydrogel, with strict optimization objectives, resulted in reduced dose to the rectum. To maximize benefit, strict optimization objectives and reduced rectal dose constraints should be employed when creating plans for patients with perirectal spacers. Clinical Trial for SpaceOAR product conducted by Augmenix,Inc. The research site was paid to be a participating site.« less

Initial fluid resuscitation following adjusted body weight dosing is associated with improved mortality in obese patients with suspected septic shock.

PubMed

Taylor, Stephanie Parks; Karvetski, Colleen H; Templin, Megan A; Heffner, Alan C; Taylor, Brice T

2018-02-01

The optimal initial fluid resuscitation strategy for obese patients with septic shock is unknown. We evaluated fluid resuscitation strategies across BMI groups. Retrospective analysis of 4157 patients in a multicenter activation pathway for treatment of septic shock between 2014 and 2016. 1293 (31.3%) patients were obese (BMI≥30). Overall, higher BMI was associated with lower mortality, however this survival advantage was eliminated in adjusted analyses. Patients with higher BMI received significantly less fluid per kilogram at 3h than did patients with lower BMI (p≤0.001). In obese patients, fluid given at 3h mimicked a dosing strategy based on actual body weight (ABW) in 780 (72.2%), adjusted body weight (AdjBW) in 95 (8.8%), and ideal body weight (IBW) in 205 (19.0%). After adjusting for condition- and treatment-related variables, dosing based on AdjBW was associated with improved mortality compared to ABW (OR 0.45; 95% CI [0.19, 1.07]) and IBW (OR 0.29; 95% CI [0.11,0.74]). Using AdjBW to calculate initial fluid resuscitation volume for obese patients with suspected shock may improve outcomes compared to other weight-based dosing strategies. The optimal fluid dosing strategy for obese patients should be a focus of future prospective research. Copyright © 2017 Elsevier Inc. All rights reserved.

Toward optimization of imaging system and lymphatic tracer for near-infrared fluorescent sentinel lymph node mapping in breast cancer.

PubMed

Mieog, J Sven D; Troyan, Susan L; Hutteman, Merlijn; Donohoe, Kevin J; van der Vorst, Joost R; Stockdale, Alan; Liefers, Gerrit-Jan; Choi, Hak Soo; Gibbs-Strauss, Summer L; Putter, Hein; Gioux, Sylvain; Kuppen, Peter J K; Ashitate, Yoshitomo; Löwik, Clemens W G M; Smit, Vincent T H B M; Oketokoun, Rafiou; Ngo, Long H; van de Velde, Cornelis J H; Frangioni, John V; Vahrmeijer, Alexander L

2011-09-01

Near-infrared (NIR) fluorescent sentinel lymph node (SLN) mapping in breast cancer requires optimized imaging systems and lymphatic tracers. A small, portable version of the FLARE imaging system, termed Mini-FLARE, was developed for capturing color video and two semi-independent channels of NIR fluorescence (700 and 800 nm) in real time. Initial optimization of lymphatic tracer dose was performed using 35-kg Yorkshire pigs and a 6-patient pilot clinical trial. More refined optimization was performed in 24 consecutive breast cancer patients. All patients received the standard of care using (99m)Technetium-nanocolloid and patent blue. In addition, 1.6 ml of indocyanine green adsorbed to human serum albumin (ICG:HSA) was injected directly after patent blue at the same location. Patients were allocated to 1 of 8 escalating ICG:HSA concentration groups from 50 to 1000 μM. The Mini-FLARE system was positioned easily in the operating room and could be used up to 13 in. from the patient. Mini-FLARE enabled visualization of lymphatic channels and SLNs in all patients. A total of 35 SLNs (mean = 1.45, range 1-3) were detected: 35 radioactive (100%), 30 blue (86%), and 35 NIR fluorescent (100%). Contrast agent quenching at the injection site and dilution within lymphatic channels were major contributors to signal strength of the SLN. Optimal injection dose of ICG:HSA ranged between 400 and 800 μM. No adverse reactions were observed. We describe the clinical translation of a new NIR fluorescence imaging system and define the optimal ICG:HSA dose range for SLN mapping in breast cancer.

Effect of Low (5 mg) vs. High (20-40 mg) Rosuvastatin Dose on 24h Arterial Stiffness, Central Haemodynamics, and Non-Alcoholic Fatty Liver Disease in Patients with Optimally Controlled Arterial Hypertension.

PubMed

Mitsiou, Eudoxia; Boutari, Chrysoula; Kotsis, Vasilios; Georgianou, Eleni; Doumas, Michael; Karagiannis, Asterios; Athyros, Vasilios G

2018-01-01

Arterial Stiffness (AS) and Non-Alcoholic Fatty Liver Diseases (NAFLD) are 2 related, prevalent, risk predictors of Cardiovascular Disease (CVD). We assessed the effect of low dose (5 mg/day) vs. high dose (20-40 mg/day) rosuvastatin on aortic elasticity and central haemodynamics as well as on NAFLD in patients with Arterial Hypertension (AH). Forty patients with optimally controlled AH were randomised to 2 rosuvastatin doses and followed for 6 months. 24h AS was assessed by Mobil-O-Graph, which calculates (adjusted for age and gender) Pulse Wave Velocity (PWV), adjusted for Heart Rate (HR) augmentation index (AIx75%) and central haemodynamics. The diagnosis of NAFLD was based on >5% liver steatosis on ultrasound and moderately elevated serum levels of liver enzymes. Both doses of rosuvastatin reduced Central Pulse Pressure (cPP), PWV and AIx75% (adjusted for HR) to normal values (p = NS adjusted for age, gender and HR). Liver enzymes were reduced in those with NAFLD to normal, but steatosis was reduced more by the 20-40 mg/day rosuvastatin dose (p=0.01) compared with the 5 mg/day dose. Both doses of rosuvastatin had a beneficial effect on AS; the high dose was more efficient in reducing PWVs and central haemodynamics, and also the high dose was more effective in ameliorating NAFLD. Given that AH control was optimal and lipid values attained targets, 4 other CVD predictors were also addressed. Larger and longer term studies are needed to demonstrate the clinical benefit of such treatment preference. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Accelerating IMRT optimization by voxel sampling

NASA Astrophysics Data System (ADS)

Martin, Benjamin C.; Bortfeld, Thomas R.; Castañon, David A.

2007-12-01

This paper presents a new method for accelerating intensity-modulated radiation therapy (IMRT) optimization using voxel sampling. Rather than calculating the dose to the entire patient at each step in the optimization, the dose is only calculated for some randomly selected voxels. Those voxels are then used to calculate estimates of the objective and gradient which are used in a randomized version of a steepest descent algorithm. By selecting different voxels on each step, we are able to find an optimal solution to the full problem. We also present an algorithm to automatically choose the best sampling rate for each structure within the patient during the optimization. Seeking further improvements, we experimented with several other gradient-based optimization algorithms and found that the delta-bar-delta algorithm performs well despite the randomness. Overall, we were able to achieve approximately an order of magnitude speedup on our test case as compared to steepest descent.

Dosimetric benefit of adaptive re-planning in pancreatic cancer stereotactic body radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Yongbao; Center for Advanced Radiotherapy Technologies University of California San Diego, La Jolla, CA; Department of Radiation Oncology, University of California San Diego, La Jolla, CA

Stereotactic body radiotherapy (SBRT) shows promise in unresectable pancreatic cancer, though this treatment modality has high rates of normal tissue toxicity. This study explores the dosimetric utility of daily adaptive re-planning with pancreas SBRT. We used a previously developed supercomputing online re-planning environment (SCORE) to re-plan 10 patients with pancreas SBRT. Tumor and normal tissue contours were deformed from treatment planning computed tomographies (CTs) and transferred to daily cone-beam CT (CBCT) scans before re-optimizing each daily treatment plan. We compared the intended radiation dose, the actual radiation dose, and the optimized radiation dose for the pancreas tumor planning target volumemore » (PTV) and the duodenum. Treatment re-optimization improved coverage of the PTV and reduced dose to the duodenum. Within the PTV, the actual hot spot (volume receiving 110% of the prescription dose) decreased from 4.5% to 0.5% after daily adaptive re-planning. Within the duodenum, the volume receiving the prescription dose decreased from 0.9% to 0.3% after re-planning. It is noteworthy that variation in the amount of air within a patient's stomach substantially changed dose to the PTV. Adaptive re-planning with pancreas SBRT has the ability to improve dose to the tumor and decrease dose to the nearby duodenum, thereby reducing the risk of toxicity.« less

Dose reduction and image quality optimizations in CT of pediatric and adult patients: phantom studies

NASA Astrophysics Data System (ADS)

Jeon, P.-H.; Lee, C.-L.; Kim, D.-H.; Lee, Y.-J.; Jeon, S.-S.; Kim, H.-J.

2014-03-01

Multi-detector computed tomography (MDCT) can be used to easily and rapidly perform numerous acquisitions, possibly leading to a marked increase in the radiation dose to individual patients. Technical options dedicated to automatically adjusting the acquisition parameters according to the patient's size are of specific interest in pediatric radiology. A constant tube potential reduction can be achieved for adults and children, while maintaining a constant detector energy fluence. To evaluate radiation dose, the weighted CT dose index (CTDIw) was calculated based on the CT dose index (CTDI) measured using an ion chamber, and image noise and image contrast were measured from a scanned image to evaluate image quality. The dose-weighted contrast-to-noise ratio (CNRD) was calculated from the radiation dose, image noise, and image contrast measured from a scanned image. The noise derivative (ND) is a quality index for dose efficiency. X-ray spectra with tube voltages ranging from 80 to 140 kVp were used to compute the average photon energy. Image contrast and the corresponding contrast-to-noise ratio (CNR) were determined for lesions of soft tissue, muscle, bone, and iodine relative to a uniform water background, as the iodine contrast increases at lower energy (i.e., k-edge of iodine is 33 keV closer to the beam energy) using mixed water-iodine contrast normalization (water 0, iodine 25, 100, 200, and 1000 HU, respectively). The proposed values correspond to high quality images and can be reduced if only high-contrast organs are assessed. The potential benefit of lowering the tube voltage is an improved CNRD, resulting in a lower radiation dose and optimization of image quality. Adjusting the tube potential in abdominal CT would be useful in current pediatric radiography, where the choice of X-ray techniques generally takes into account the size of the patient as well as the need to balance the conflicting requirements of diagnostic image quality and radiation dose optimization.

SU-G-TeP3-01: A New Approach for Calculating Variable Relative Biological Effectiveness in IMPT Optimization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cao, W; Randeniya, K; Grosshans, D

2016-06-15

Purpose: To investigate the impact of a new approach for calculating relative biological effectiveness (RBE) in intensity-modulated proton therapy (IMPT) optimization on RBE-weighted dose distributions. This approach includes the nonlinear RBE for the high linear energy transfer (LET) region, which was revealed by recent experiments at our institution. In addition, this approach utilizes RBE data as a function of LET without using dose-averaged LET in calculating RBE values. Methods: We used a two-piece function for calculating RBE from LET. Within the Bragg peak, RBE is linearly correlated to LET. Beyond the Bragg peak, we use a nonlinear (quadratic) RBE functionmore » of LET based on our experimental. The IMPT optimization was devised to incorporate variable RBE by maximizing biological effect (based on the Linear Quadratic model) in tumor and minimizing biological effect in normal tissues. Three glioblastoma patients were retrospectively selected from our institution in this study. For each patient, three optimized IMPT plans were created based on three RBE resolutions, i.e., fixed RBE of 1.1 (RBE-1.1), variable RBE based on linear RBE and LET relationship (RBE-L), and variable RBE based on linear and quadratic relationship (RBE-LQ). The RBE weighted dose distributions of each optimized plan were evaluated in terms of different RBE values, i.e., RBE-1.1, RBE-L and RBE-LQ. Results: The RBE weighted doses recalculated from RBE-1.1 based optimized plans demonstrated an increasing pattern from using RBE-1.1, RBE-L to RBE-LQ consistently for all three patients. The variable RBE (RBE-L and RBE-LQ) weighted dose distributions recalculated from RBE-L and RBE-LQ based optimization were more homogenous within the targets and better spared in the critical structures than the ones recalculated from RBE-1.1 based optimization. Conclusion: We implemented a new approach for RBE calculation and optimization and demonstrated potential benefits of improving tumor coverage and normal sparing in IMPT planning.« less

MO-DE-204-01: Radiation Doses in Over 50 Developing Countries of Asia, Africa, Eastern European and Latin America

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rehani, M.

2016-06-15

The main topic of the session is to show how dose optimization is being implemented in various regions of the world, including Europe, Australia, North America and other regions. A multi-national study conducted under International Atomic Energy Agency (IAEA) across more than 50 less resourced countries gave insight into patient radiation doses and safety practices in CT, mammography, radiography and interventional procedures, both for children and adults. An important outcome was the capability development on dose assessment and management. An overview of recent European projects related to CT radiation dose and optimization both to adults and children will be presented.more » Existing data on DRLs together with a European methodology proposed on establishing and using DRLs for paediatric radiodiagnostic imaging and interventional radiology practices will be shown. Compared with much of Europe at least, many Australian imaging practices are relatively new to the task of diagnostic imaging dose optimisation. In 2008 the Australian Government prescribed a requirement to periodically compare patient radiation doses with diagnostic reference levels (DRLs), where DRLs have been established. Until recently, Australia had only established DRLs for computed tomography (CT). Regardless, both professional society and individual efforts to improved data collection and develop optimisation strategies across a range of modalities continues. Progress in this field, principally with respect to CT and interventional fluoroscopy will be presented. In the US, dose reduction and optimization efforts for computed tomography have been promoted and mandated by several organizations and accrediting entities. This presentation will cover the general motivation, implementation, and implications of such efforts. Learning Objectives: Understand importance of the dose optimization in Diagnostic Radiology. See how this goal is achieved in different regions of the World. Learn about the global trend in the dose optimization and future prospectives. M. Rehani, The work was a part of the work of IAEA where I was an employee and IAEA is a United Nations organization.« less

MO-DE-204-03: Radiology Dose Optimisation - An Australian Perspective

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schick, D.

2016-06-15

The main topic of the session is to show how dose optimization is being implemented in various regions of the world, including Europe, Australia, North America and other regions. A multi-national study conducted under International Atomic Energy Agency (IAEA) across more than 50 less resourced countries gave insight into patient radiation doses and safety practices in CT, mammography, radiography and interventional procedures, both for children and adults. An important outcome was the capability development on dose assessment and management. An overview of recent European projects related to CT radiation dose and optimization both to adults and children will be presented.more » Existing data on DRLs together with a European methodology proposed on establishing and using DRLs for paediatric radiodiagnostic imaging and interventional radiology practices will be shown. Compared with much of Europe at least, many Australian imaging practices are relatively new to the task of diagnostic imaging dose optimisation. In 2008 the Australian Government prescribed a requirement to periodically compare patient radiation doses with diagnostic reference levels (DRLs), where DRLs have been established. Until recently, Australia had only established DRLs for computed tomography (CT). Regardless, both professional society and individual efforts to improved data collection and develop optimisation strategies across a range of modalities continues. Progress in this field, principally with respect to CT and interventional fluoroscopy will be presented. In the US, dose reduction and optimization efforts for computed tomography have been promoted and mandated by several organizations and accrediting entities. This presentation will cover the general motivation, implementation, and implications of such efforts. Learning Objectives: Understand importance of the dose optimization in Diagnostic Radiology. See how this goal is achieved in different regions of the World. Learn about the global trend in the dose optimization and future prospectives. M. Rehani, The work was a part of the work of IAEA where I was an employee and IAEA is a United Nations organization.« less

TU-AB-BRC-12: Optimized Parallel MonteCarlo Dose Calculations for Secondary MU Checks

DOE Office of Scientific and Technical Information (OSTI.GOV)

French, S; Nazareth, D; Bellor, M

Purpose: Secondary MU checks are an important tool used during a physics review of a treatment plan. Commercial software packages offer varying degrees of theoretical dose calculation accuracy, depending on the modality involved. Dose calculations of VMAT plans are especially prone to error due to the large approximations involved. Monte Carlo (MC) methods are not commonly used due to their long run times. We investigated two methods to increase the computational efficiency of MC dose simulations with the BEAMnrc code. Distributed computing resources, along with optimized code compilation, will allow for accurate and efficient VMAT dose calculations. Methods: The BEAMnrcmore » package was installed on a high performance computing cluster accessible to our clinic. MATLAB and PYTHON scripts were developed to convert a clinical VMAT DICOM plan into BEAMnrc input files. The BEAMnrc installation was optimized by running the VMAT simulations through profiling tools which indicated the behavior of the constituent routines in the code, e.g. the bremsstrahlung splitting routine, and the specified random number generator. This information aided in determining the most efficient compiling parallel configuration for the specific CPU’s available on our cluster, resulting in the fastest VMAT simulation times. Our method was evaluated with calculations involving 10{sup 8} – 10{sup 9} particle histories which are sufficient to verify patient dose using VMAT. Results: Parallelization allowed the calculation of patient dose on the order of 10 – 15 hours with 100 parallel jobs. Due to the compiler optimization process, further speed increases of 23% were achieved when compared with the open-source compiler BEAMnrc packages. Conclusion: Analysis of the BEAMnrc code allowed us to optimize the compiler configuration for VMAT dose calculations. In future work, the optimized MC code, in conjunction with the parallel processing capabilities of BEAMnrc, will be applied to provide accurate and efficient secondary MU checks.« less

Advantages and limitations of navigation-based multicriteria optimization (MCO) for localized prostate cancer IMRT planning

DOE Office of Scientific and Technical Information (OSTI.GOV)

McGarry, Conor K., E-mail: conor.mcgarry@belfasttrust.hscni.net; Bokrantz, Rasmus; RaySearch Laboratories, Stockholm

2014-10-01

Efficacy of inverse planning is becoming increasingly important for advanced radiotherapy techniques. This study’s aims were to validate multicriteria optimization (MCO) in RayStation (v2.4, RaySearch Laboratories, Sweden) against standard intensity-modulated radiation therapy (IMRT) optimization in Oncentra (v4.1, Nucletron BV, the Netherlands) and characterize dose differences due to conversion of navigated MCO plans into deliverable multileaf collimator apertures. Step-and-shoot IMRT plans were created for 10 patients with localized prostate cancer using both standard optimization and MCO. Acceptable standard IMRT plans with minimal average rectal dose were chosen for comparison with deliverable MCO plans. The trade-off was, for the MCO plans, managedmore » through a user interface that permits continuous navigation between fluence-based plans. Navigated MCO plans were made deliverable at incremental steps along a trajectory between maximal target homogeneity and maximal rectal sparing. Dosimetric differences between navigated and deliverable MCO plans were also quantified. MCO plans, chosen as acceptable under navigated and deliverable conditions resulted in similar rectal sparing compared with standard optimization (33.7 ± 1.8 Gy vs 35.5 ± 4.2 Gy, p = 0.117). The dose differences between navigated and deliverable MCO plans increased as higher priority was placed on rectal avoidance. If the best possible deliverable MCO was chosen, a significant reduction in rectal dose was observed in comparison with standard optimization (30.6 ± 1.4 Gy vs 35.5 ± 4.2 Gy, p = 0.047). Improvements were, however, to some extent, at the expense of less conformal dose distributions, which resulted in significantly higher doses to the bladder for 2 of the 3 tolerance levels. In conclusion, similar IMRT plans can be created for patients with prostate cancer using MCO compared with standard optimization. Limitations exist within MCO regarding conversion of navigated plans to deliverable apertures, particularly for plans that emphasize avoidance of critical structures. Minimizing these differences would result in better quality treatments for patients with prostate cancer who were treated with radiotherapy using MCO plans.« less

Concurrent Monte Carlo transport and fluence optimization with fluence adjusting scalable transport Monte Carlo

PubMed Central

Svatos, M.; Zankowski, C.; Bednarz, B.

2016-01-01

Purpose: The future of radiation therapy will require advanced inverse planning solutions to support single-arc, multiple-arc, and “4π” delivery modes, which present unique challenges in finding an optimal treatment plan over a vast search space, while still preserving dosimetric accuracy. The successful clinical implementation of such methods would benefit from Monte Carlo (MC) based dose calculation methods, which can offer improvements in dosimetric accuracy when compared to deterministic methods. The standard method for MC based treatment planning optimization leverages the accuracy of the MC dose calculation and efficiency of well-developed optimization methods, by precalculating the fluence to dose relationship within a patient with MC methods and subsequently optimizing the fluence weights. However, the sequential nature of this implementation is computationally time consuming and memory intensive. Methods to reduce the overhead of the MC precalculation have been explored in the past, demonstrating promising reductions of computational time overhead, but with limited impact on the memory overhead due to the sequential nature of the dose calculation and fluence optimization. The authors propose an entirely new form of “concurrent” Monte Carlo treat plan optimization: a platform which optimizes the fluence during the dose calculation, reduces wasted computation time being spent on beamlets that weakly contribute to the final dose distribution, and requires only a low memory footprint to function. In this initial investigation, the authors explore the key theoretical and practical considerations of optimizing fluence in such a manner. Methods: The authors present a novel derivation and implementation of a gradient descent algorithm that allows for optimization during MC particle transport, based on highly stochastic information generated through particle transport of very few histories. A gradient rescaling and renormalization algorithm, and the concept of momentum from stochastic gradient descent were used to address obstacles unique to performing gradient descent fluence optimization during MC particle transport. The authors have applied their method to two simple geometrical phantoms, and one clinical patient geometry to examine the capability of this platform to generate conformal plans as well as assess its computational scaling and efficiency, respectively. Results: The authors obtain a reduction of at least 50% in total histories transported in their investigation compared to a theoretical unweighted beamlet calculation and subsequent fluence optimization method, and observe a roughly fixed optimization time overhead consisting of ∼10% of the total computation time in all cases. Finally, the authors demonstrate a negligible increase in memory overhead of ∼7–8 MB to allow for optimization of a clinical patient geometry surrounded by 36 beams using their platform. Conclusions: This study demonstrates a fluence optimization approach, which could significantly improve the development of next generation radiation therapy solutions while incurring minimal additional computational overhead. PMID:27277051

DOE Office of Scientific and Technical Information (OSTI.GOV)

Herschtal, Alan, E-mail: Alan.Herschtal@petermac.org; Faculty of Health, Arts and Design, Swinburne University of Technology, Melbourne; Te Marvelde, Luc

Objective: To develop a mathematical tool that can update a patient's planning target volume (PTV) partway through a course of radiation therapy to more precisely target the tumor for the remainder of treatment and reduce dose to surrounding healthy tissue. Methods and Materials: Daily on-board imaging was used to collect large datasets of displacements for patients undergoing external beam radiation therapy for solid tumors. Bayesian statistical modeling of these geometric uncertainties was used to optimally trade off between displacement data collected from previously treated patients and the progressively accumulating data from a patient currently partway through treatment, to optimally predictmore » future displacements for that patient. These predictions were used to update the PTV position and margin width for the remainder of treatment, such that the clinical target volume (CTV) was more precisely targeted. Results: Software simulation of dose to CTV and normal tissue for 2 real prostate displacement datasets consisting of 146 and 290 patients treated with a minimum of 30 fractions each showed that re-evaluating the PTV position and margin width after 8 treatment fractions reduced healthy tissue dose by 19% and 17%, respectively, while maintaining CTV dose. Conclusion: Incorporating patient-specific displacement patterns from early in a course of treatment allows PTV adaptation for the remainder of treatment. This substantially reduces the dose to healthy tissues and thus can reduce radiation therapy–induced toxicities, improving patient outcomes.« less

Evaluation of the Pharmacokinetics and Efficacy of a Busulfan Test Dose in Adult Patients Undergoing Myeloablative Hematopoietic Cell Transplantation.

PubMed

Weil, Elizabeth; Zook, Felicia; Oxencis, Carolyn; Canadeo, Angela; Urmanski, Angela; Waggoner, Mindy; Eastwood, Daniel; Pasquini, Marcelo; Hamadani, Mehdi; Hari, Parameswaran

2017-06-01

Owing to interpatient variability in busulfan exposure, therapeutic monitoring of busulfan is often used in myeloablative allogeneic transplantation to ensure that patients are near the optimal steady-state goal of 900 ng/mL. One challenge in therapeutic monitoring of busulfan is the brief course of busulfan treatment, requiring prompt analysis and dose adjustments as needed. Pharmacokinetic evaluation of a busulfan test dose before the start of the conditioning regimen would allow for all conditioning regimen doses to be given at the calculated optimized dose. An observational study was completed to evaluate the effects of a busulfan test dose of 0.9 mg/kg administered before the start of a myeloablative intravenous busulfan-based conditioning regimen. Sixty adult patients who received a busulfan conditioning regimen were reviewed, including 30 patients prior to the implementation of the busulfan test dose (pretest dose group) and 30 patients who received the busulfan test dose (posttest dose group). The primary objective was a pharmacokinetic evaluation of the percentage of patients who achieved the desired steady-state goal using the test dose strategy. The safety and efficacy of the busulfan test dose were evaluated as well. The average busulfan steady-state level after the first dose of the conditioning regimen was significantly lower in the pre-test dose group compared with the post-test dose group (660 ng/mL versus 879.9 ng/mL; P < 0.001). Compared with the post-test dose group, significantly fewer patients in the pre-test dose group were within 10% of the busulfan steady-state goal (10% versus 73.3%; P < 0.001) or within 5% of the goal (0% versus 53%; P < 0.001). Requirements for parenteral nutrition and/or patient-controlled analgesia owing to mucositis and rates of veno-occlusive disease were not significantly different between the pre-test dose group and the post-test dose group. The rates of disease relapse, mortality, and acute graft-versus-host disease were similar in the two groups. A pretransplantation busulfan test dose of 0.9 mg/kg improved the patients' ability to reach therapeutic busulfan target levels after the first conditioning dose and resulted in fewer adjustments during conditioning. The use of a busulfan test dose did not significantly increase patients' risk of mucositis or other safety outcomes. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Model-Based Individualized Treatment of Chemotherapeutics: Bayesian Population Modeling and Dose Optimization

PubMed Central

Jayachandran, Devaraj; Laínez-Aguirre, José; Rundell, Ann; Vik, Terry; Hannemann, Robert; Reklaitis, Gintaras; Ramkrishna, Doraiswami

2015-01-01

6-Mercaptopurine (6-MP) is one of the key drugs in the treatment of many pediatric cancers, auto immune diseases and inflammatory bowel disease. 6-MP is a prodrug, converted to an active metabolite 6-thioguanine nucleotide (6-TGN) through enzymatic reaction involving thiopurine methyltransferase (TPMT). Pharmacogenomic variation observed in the TPMT enzyme produces a significant variation in drug response among the patient population. Despite 6-MP’s widespread use and observed variation in treatment response, efforts at quantitative optimization of dose regimens for individual patients are limited. In addition, research efforts devoted on pharmacogenomics to predict clinical responses are proving far from ideal. In this work, we present a Bayesian population modeling approach to develop a pharmacological model for 6-MP metabolism in humans. In the face of scarcity of data in clinical settings, a global sensitivity analysis based model reduction approach is used to minimize the parameter space. For accurate estimation of sensitive parameters, robust optimal experimental design based on D-optimality criteria was exploited. With the patient-specific model, a model predictive control algorithm is used to optimize the dose scheduling with the objective of maintaining the 6-TGN concentration within its therapeutic window. More importantly, for the first time, we show how the incorporation of information from different levels of biological chain-of response (i.e. gene expression-enzyme phenotype-drug phenotype) plays a critical role in determining the uncertainty in predicting therapeutic target. The model and the control approach can be utilized in the clinical setting to individualize 6-MP dosing based on the patient’s ability to metabolize the drug instead of the traditional standard-dose-for-all approach. PMID:26226448

Impact of respiratory motion on worst-case scenario optimized intensity modulated proton therapy for lung cancers.

PubMed

Liu, Wei; Liao, Zhongxing; Schild, Steven E; Liu, Zhong; Li, Heng; Li, Yupeng; Park, Peter C; Li, Xiaoqiang; Stoker, Joshua; Shen, Jiajian; Keole, Sameer; Anand, Aman; Fatyga, Mirek; Dong, Lei; Sahoo, Narayan; Vora, Sujay; Wong, William; Zhu, X Ronald; Bues, Martin; Mohan, Radhe

2015-01-01

We compared conventionally optimized intensity modulated proton therapy (IMPT) treatment plans against worst-case scenario optimized treatment plans for lung cancer. The comparison of the 2 IMPT optimization strategies focused on the resulting plans' ability to retain dose objectives under the influence of patient setup, inherent proton range uncertainty, and dose perturbation caused by respiratory motion. For each of the 9 lung cancer cases, 2 treatment plans were created that accounted for treatment uncertainties in 2 different ways. The first used the conventional method: delivery of prescribed dose to the planning target volume that is geometrically expanded from the internal target volume (ITV). The second used a worst-case scenario optimization scheme that addressed setup and range uncertainties through beamlet optimization. The plan optimality and plan robustness were calculated and compared. Furthermore, the effects on dose distributions of changes in patient anatomy attributable to respiratory motion were investigated for both strategies by comparing the corresponding plan evaluation metrics at the end-inspiration and end-expiration phase and absolute differences between these phases. The mean plan evaluation metrics of the 2 groups were compared with 2-sided paired Student t tests. Without respiratory motion considered, we affirmed that worst-case scenario optimization is superior to planning target volume-based conventional optimization in terms of plan robustness and optimality. With respiratory motion considered, worst-case scenario optimization still achieved more robust dose distributions to respiratory motion for targets and comparable or even better plan optimality (D95% ITV, 96.6% vs 96.1% [P = .26]; D5%- D95% ITV, 10.0% vs 12.3% [P = .082]; D1% spinal cord, 31.8% vs 36.5% [P = .035]). Worst-case scenario optimization led to superior solutions for lung IMPT. Despite the fact that worst-case scenario optimization did not explicitly account for respiratory motion, it produced motion-resistant treatment plans. However, further research is needed to incorporate respiratory motion into IMPT robust optimization. Copyright © 2015 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

SU-E-T-452: Impact of Respiratory Motion On Robustly-Optimized Intensity-Modulated Proton Therapy to Treat Lung Cancers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, W; Schild, S; Bues, M

Purpose: We compared conventionally optimized intensity-modulated proton therapy (IMPT) treatment plans against the worst-case robustly optimized treatment plans for lung cancer. The comparison of the two IMPT optimization strategies focused on the resulting plans' ability to retain dose objectives under the influence of patient set-up, inherent proton range uncertainty, and dose perturbation caused by respiratory motion. Methods: For each of the 9 lung cancer cases two treatment plans were created accounting for treatment uncertainties in two different ways: the first used the conventional Method: delivery of prescribed dose to the planning target volume (PTV) that is geometrically expanded from themore » internal target volume (ITV). The second employed the worst-case robust optimization scheme that addressed set-up and range uncertainties through beamlet optimization. The plan optimality and plan robustness were calculated and compared. Furthermore, the effects on dose distributions of the changes in patient anatomy due to respiratory motion was investigated for both strategies by comparing the corresponding plan evaluation metrics at the end-inspiration and end-expiration phase and absolute differences between these phases. The mean plan evaluation metrics of the two groups were compared using two-sided paired t-tests. Results: Without respiratory motion considered, we affirmed that worst-case robust optimization is superior to PTV-based conventional optimization in terms of plan robustness and optimality. With respiratory motion considered, robust optimization still leads to more robust dose distributions to respiratory motion for targets and comparable or even better plan optimality [D95% ITV: 96.6% versus 96.1% (p=0.26), D5% - D95% ITV: 10.0% versus 12.3% (p=0.082), D1% spinal cord: 31.8% versus 36.5% (p =0.035)]. Conclusion: Worst-case robust optimization led to superior solutions for lung IMPT. Despite of the fact that robust optimization did not explicitly account for respiratory motion it produced motion-resistant treatment plans. However, further research is needed to incorporate respiratory motion into IMPT robust optimization.« less

Optimization of (131)I doses for the treatment of hyperthyroidism.

PubMed

Araujo, F; Rebelo, A M O; Pereira, A C; Moura, M B; Lucena, E A; Dantas, A L A; Dantas, B M; Corbo, R

2009-11-15

Several methods can be used to determine the activity of (131)I in the treatment of hyperthyroidism. However, many of them do not consider all the parameters necessary for optimum dose calculation. The relationship between the dose absorbed by the thyroid and the activity administered depends basically on three parameters: organ mass, iodine uptake and effective half-life of iodine in the thyroid. Such parameters should be individually determined for each patient in order to optimize the administered activity. The objective of this work is to develop a methodology for individualized treatment with (131)I in patients with hyperthyroidism of the Grave's Disease. A neck-thyroid phantom developed at the IRD was used to calibrate a scintillation camera and a uptake probe SCT-13004 at the Nuclear Medicine Center of the University Hospital of Rio de Janeiro and a uptake probe SCT-13002, available at the Nuclear Medicine Institute in Goiânia. The biokinetic parameters were determined based on measurements performed in eight voluntary patients. It is concluded that the use of the equipment available at the hospital (scintillation camera and uptake probe) has shown to be a suitable and feasible procedure for dose optimization in terms of effectiveness, simplicity and cost.

SU-F-T-344: Commissioning Constant Dose Rate VMAT in the Raystation Treatment Planning System for a Varian Clinac IX

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pursley, J; Gueorguiev, G; Prichard, H

Purpose: To demonstrate the commissioning of constant dose rate volumetric modulated arc therapy (VMAT) in the Raystation treatment planning system for a Varian Clinac iX with Exact couch. Methods: Constant dose rate (CDR) VMAT is an option in the Raystation treatment planning system, enabling VMAT delivery on Varian linacs without a RapidArc upgrade. Raystation 4.7 was used to commission CDR-VMAT for a Varian Clinac iX. Raystation arc model parameters were selected to match machine deliverability characteristics. A Varian Exact couch model was added to Raystation 4.7 and commissioned for use in VMAT optimization. CDR-VMAT commissioning checks were performed on themore » linac, including patient-specific QA measurements for 10 test patients using both the ArcCHECK from Sun Nuclear Corporation and COMPASS from IBA Dosimetry. Multi-criteria optimization (MCO) in Raystation was used for CDR-VMAT planning. Results: Raystation 4.7 generated clinically acceptable and deliverable CDR-VMAT plans for the Varian Clinac. VMAT plans were optimized including a model of the Exact couch with both rails in the out positions. CDR-VMAT plans generated with MCO in Raystation were dosimetrically comparable to Raystation MCO-generated IMRT plans. Patient-specific QA measurements with the ArcCHECK on the couch showed good agreement with the treatment planning system prediction. Patient-specific, structure-specific, multi-statistical parameter 3D QA measurements with gantry-mounted COMPASS also showed good agreement. Conclusion: Constant dose rate VMAT was successfully modeled in Raystation 4.7 for a Varian Clinac iX, and Raystation’s multicriteria optimization generated constant dose rate VMAT plans which were deliverable and dosimetrically comparable to IMRT plans.« less

CT-guided brachytherapy of prostate cancer: reduction of effective dose from X-ray examination

NASA Astrophysics Data System (ADS)

Sanin, Dmitriy B.; Biryukov, Vitaliy A.; Rusetskiy, Sergey S.; Sviridov, Pavel V.; Volodina, Tatiana V.

2014-03-01

Computed tomography (CT) is one of the most effective and informative diagnostic method. Though the number of CT scans among all radiographic procedures in the USA and European countries is 11% and 4% respectively, CT makes the highest contribution to the collective effective dose from all radiographic procedures, it is 67% in the USA and 40% in European countries [1-5]. Therefore it is necessary to understand the significance of dose value from CT imaging to a patient . Though CT dose from multiple scans and potential risk is of great concern in pediatric patients, this applies to adults as well. In this connection it is very important to develop optimal approaches to dose reduction and optimization of CT examination. International Commission on Radiological Protection (ICRP) in its publications recommends radiologists to be aware that often CT image quality is higher than it is necessary for diagnostic confidence[6], and there is a potential to reduce the dose which patient gets from CT examination [7]. In recent years many procedures, such as minimally invasive surgery, biopsy, brachytherapy and different types of ablation are carried out under guidance of computed tomography [6;7], and during a procedures multiple CT scans focusing on a specific anatomic region are performed. At the Clinics of MRRC different types of treatment for patients with prostate cancer are used, incuding conformal CT-guided brachytherapy, implantation of microsources of I into the gland under guidance of spiral CT [8]. So, the purpose of the study is to choose optimal method to reduce radiation dose from CT during CT-guided prostate brachytherapy and to obtain the image of desired quality.

Impact of Spot Size and Spacing on the Quality of Robustly Optimized Intensity Modulated Proton Therapy Plans for Lung Cancer.

PubMed

Liu, Chenbin; Schild, Steven E; Chang, Joe Y; Liao, Zhongxing; Korte, Shawn; Shen, Jiajian; Ding, Xiaoning; Hu, Yanle; Kang, Yixiu; Keole, Sameer R; Sio, Terence T; Wong, William W; Sahoo, Narayan; Bues, Martin; Liu, Wei

2018-06-01

To investigate how spot size and spacing affect plan quality, robustness, and interplay effects of robustly optimized intensity modulated proton therapy (IMPT) for lung cancer. Two robustly optimized IMPT plans were created for 10 lung cancer patients: first by a large-spot machine with in-air energy-dependent large spot size at isocenter (σ: 6-15 mm) and spacing (1.3 σ), and second by a small-spot machine with in-air energy-dependent small spot size (σ: 2-6 mm) and spacing (5 mm). Both plans were generated by optimizing radiation dose to internal target volume on averaged 4-dimensional computed tomography scans using an in-house-developed IMPT planning system. The dose-volume histograms band method was used to evaluate plan robustness. Dose evaluation software was developed to model time-dependent spot delivery to incorporate interplay effects with randomized starting phases for each field per fraction. Patient anatomy voxels were mapped phase-to-phase via deformable image registration, and doses were scored using in-house-developed software. Dose-volume histogram indices, including internal target volume dose coverage, homogeneity, and organs at risk (OARs) sparing, were compared using the Wilcoxon signed-rank test. Compared with the large-spot machine, the small-spot machine resulted in significantly lower heart and esophagus mean doses, with comparable target dose coverage, homogeneity, and protection of other OARs. Plan robustness was comparable for targets and most OARs. With interplay effects considered, significantly lower heart and esophagus mean doses with comparable target dose coverage and homogeneity were observed using smaller spots. Robust optimization with a small spot-machine significantly improves heart and esophagus sparing, with comparable plan robustness and interplay effects compared with robust optimization with a large-spot machine. A small-spot machine uses a larger number of spots to cover the same tumors compared with a large-spot machine, which gives the planning system more freedom to compensate for the higher sensitivity to uncertainties and interplay effects for lung cancer treatments. Copyright © 2018 Elsevier Inc. All rights reserved.

Geometric parameter analysis to predetermine optimal radiosurgery technique for the treatment of arteriovenous malformation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mestrovic, Ante; Clark, Brenda G.; Department of Medical Physics, British Columbia Cancer Agency, Vancouver, British Columbia

2005-11-01

Purpose: To develop a method of predicting the values of dose distribution parameters of different radiosurgery techniques for treatment of arteriovenous malformation (AVM) based on internal geometric parameters. Methods and Materials: For each of 18 previously treated AVM patients, four treatment plans were created: circular collimator arcs, dynamic conformal arcs, fixed conformal fields, and intensity-modulated radiosurgery. An algorithm was developed to characterize the target and critical structure shape complexity and the position of the critical structures with respect to the target. Multiple regression was employed to establish the correlation between the internal geometric parameters and the dose distribution for differentmore » treatment techniques. The results from the model were applied to predict the dosimetric outcomes of different radiosurgery techniques and select the optimal radiosurgery technique for a number of AVM patients. Results: Several internal geometric parameters showing statistically significant correlation (p < 0.05) with the treatment planning results for each technique were identified. The target volume and the average minimum distance between the target and the critical structures were the most effective predictors for normal tissue dose distribution. The structure overlap volume with the target and the mean distance between the target and the critical structure were the most effective predictors for critical structure dose distribution. The predicted values of dose distribution parameters of different radiosurgery techniques were in close agreement with the original data. Conclusions: A statistical model has been described that successfully predicts the values of dose distribution parameters of different radiosurgery techniques and may be used to predetermine the optimal technique on a patient-to-patient basis.« less

Tamoxifen dose and serum concentrations of tamoxifen and six of its metabolites in routine clinical outpatient care.

PubMed

Jager, N G L; Rosing, H; Schellens, J H M; Linn, S C; Beijnen, J H

2014-02-01

A sensitive and selective HPLC-MS/MS assay was used to analyze steady-state serum concentrations of tamoxifen, N-desmethyltamoxifen (E)-endoxifen, (Z)-endoxifen, N-desmethyl-4'-hydroxytamoxifen, 4-hydroxytamoxifen, and 4'-hydroxytamoxifen to support therapeutic drug monitoring (TDM) in patients treated with tamoxifen according to standard of care. When the (Z)-endoxifen serum concentration was below the predefined therapeutic threshold concentration of 5.9 ng/mL, the clinician was advised to increase the tamoxifen dose and to collect another serum sample. Paired serum samples from patients at one dose level at different time points during the tamoxifen treatment were used to assess the intra-patient variability. A total of 251 serum samples were analyzed, obtained from 205 patients. Of these patients, 197 used 20 mg tamoxifen per day and 8 patients used 10 mg/day. There was wide variability in tamoxifen and metabolite concentrations within the dosing groups. The threshold concentration for (Z)-endoxifen was reached in one patient (12 %) in the 10 mg group, in 153 patients (78 %) in the 20 mg group, and in 26 (96 %) of the patients who received a dose increase to 30 or 40 mg/day. Dose increase from 20 to 30 or 40 mg per day resulted in a significant increase in the mean serum concentrations of all analytes (p < 0.001). The mean intra-patient variability was between 10 and 20 % for all analytes. These results support the suitability of TDM for optimizing the tamoxifen treatment. It is shown that tamoxifen dose is related to (Z)-endoxifen exposure and increasing this dose leads to a higher serum concentration of tamoxifen and its metabolites. The low intra-patient variability suggests that only one serum sample is needed for TDM, making this a relatively noninvasive way to optimize the patient's treatment.

Brachytherapy optimization using radiobiological-based planning for high dose rate and permanent implants for prostate cancer treatment

NASA Astrophysics Data System (ADS)

Seeley, Kaelyn; Cunha, J. Adam; Hong, Tae Min

2017-01-01

We discuss an improvement in brachytherapy--a prostate cancer treatment method that directly places radioactive seeds inside target cancerous regions--by optimizing the current standard for delivering dose. Currently, the seeds' spatiotemporal placement is determined by optimizing the dose based on a set of physical, user-defined constraints. One particular approach is the ``inverse planning'' algorithms that allow for tightly fit isodose lines around the target volumes in order to reduce dose to the patient's organs at risk. However, these dose distributions are typically computed assuming the same biological response to radiation for different types of tissues. In our work, we consider radiobiological parameters to account for the differences in the individual sensitivities and responses to radiation for tissues surrounding the target. Among the benefits are a more accurate toxicity rate and more coverage to target regions for planning high-dose-rate treatments as well as permanent implants.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Y. M., E-mail: ymingy@gmail.com; Bednarz, B.; Svatos, M.

Purpose: The future of radiation therapy will require advanced inverse planning solutions to support single-arc, multiple-arc, and “4π” delivery modes, which present unique challenges in finding an optimal treatment plan over a vast search space, while still preserving dosimetric accuracy. The successful clinical implementation of such methods would benefit from Monte Carlo (MC) based dose calculation methods, which can offer improvements in dosimetric accuracy when compared to deterministic methods. The standard method for MC based treatment planning optimization leverages the accuracy of the MC dose calculation and efficiency of well-developed optimization methods, by precalculating the fluence to dose relationship withinmore » a patient with MC methods and subsequently optimizing the fluence weights. However, the sequential nature of this implementation is computationally time consuming and memory intensive. Methods to reduce the overhead of the MC precalculation have been explored in the past, demonstrating promising reductions of computational time overhead, but with limited impact on the memory overhead due to the sequential nature of the dose calculation and fluence optimization. The authors propose an entirely new form of “concurrent” Monte Carlo treat plan optimization: a platform which optimizes the fluence during the dose calculation, reduces wasted computation time being spent on beamlets that weakly contribute to the final dose distribution, and requires only a low memory footprint to function. In this initial investigation, the authors explore the key theoretical and practical considerations of optimizing fluence in such a manner. Methods: The authors present a novel derivation and implementation of a gradient descent algorithm that allows for optimization during MC particle transport, based on highly stochastic information generated through particle transport of very few histories. A gradient rescaling and renormalization algorithm, and the concept of momentum from stochastic gradient descent were used to address obstacles unique to performing gradient descent fluence optimization during MC particle transport. The authors have applied their method to two simple geometrical phantoms, and one clinical patient geometry to examine the capability of this platform to generate conformal plans as well as assess its computational scaling and efficiency, respectively. Results: The authors obtain a reduction of at least 50% in total histories transported in their investigation compared to a theoretical unweighted beamlet calculation and subsequent fluence optimization method, and observe a roughly fixed optimization time overhead consisting of ∼10% of the total computation time in all cases. Finally, the authors demonstrate a negligible increase in memory overhead of ∼7–8 MB to allow for optimization of a clinical patient geometry surrounded by 36 beams using their platform. Conclusions: This study demonstrates a fluence optimization approach, which could significantly improve the development of next generation radiation therapy solutions while incurring minimal additional computational overhead.« less

New approach based on tetrahedral-mesh geometry for accurate 4D Monte Carlo patient-dose calculation

NASA Astrophysics Data System (ADS)

Han, Min Cheol; Yeom, Yeon Soo; Kim, Chan Hyeong; Kim, Seonghoon; Sohn, Jason W.

2015-02-01

In the present study, to achieve accurate 4D Monte Carlo dose calculation in radiation therapy, we devised a new approach that combines (1) modeling of the patient body using tetrahedral-mesh geometry based on the patient’s 4D CT data, (2) continuous movement/deformation of the tetrahedral patient model by interpolation of deformation vector fields acquired through deformable image registration, and (3) direct transportation of radiation particles during the movement and deformation of the tetrahedral patient model. The results of our feasibility study show that it is certainly possible to construct 4D patient models (= phantoms) with sufficient accuracy using the tetrahedral-mesh geometry and to directly transport radiation particles during continuous movement and deformation of the tetrahedral patient model. This new approach not only produces more accurate dose distribution in the patient but also replaces the current practice of using multiple 3D voxel phantoms and combining multiple dose distributions after Monte Carlo simulations. For routine clinical application of our new approach, the use of fast automatic segmentation algorithms is a must. In order to achieve, simultaneously, both dose accuracy and computation speed, the number of tetrahedrons for the lungs should be optimized. Although the current computation speed of our new 4D Monte Carlo simulation approach is slow (i.e. ~40 times slower than that of the conventional dose accumulation approach), this problem is resolvable by developing, in Geant4, a dedicated navigation class optimized for particle transportation in tetrahedral-mesh geometry.

Optimization of image quality and dose for Varian aS500 electronic portal imaging devices (EPIDs).

PubMed

McGarry, C K; Grattan, M W D; Cosgrove, V P

2007-12-07

This study was carried out to investigate whether the electronic portal imaging (EPI) acquisition process could be optimized, and as a result tolerance and action levels be set for the PIPSPro QC-3V phantom image quality assessment. The aim of the optimization process was to reduce the dose delivered to the patient while maintaining a clinically acceptable image quality. This is of interest when images are acquired in addition to the planned patient treatment, rather than images being acquired using the treatment field during a patient's treatment. A series of phantoms were used to assess image quality for different acquisition settings relative to the baseline values obtained following acceptance testing. Eight Varian aS500 EPID systems on four matched Varian 600C/D linacs and four matched Varian 2100C/D linacs were compared for consistency of performance and images were acquired at the four main orthogonal gantry angles. Images were acquired using a 6 MV beam operating at 100 MU min(-1) and the low-dose acquisition mode. Doses used in the comparison were measured using a Farmer ionization chamber placed at d(max) in solid water. The results demonstrated that the number of reset frames did not have any influence on the image contrast, but the number of frame averages did. The expected increase in noise with corresponding decrease in contrast was also observed when reducing the number of frame averages. The optimal settings for the low-dose acquisition mode with respect to image quality and dose were found to be one reset frame and three frame averages. All patients at the Northern Ireland Cancer Centre are now imaged using one reset frame and three frame averages in the 6 MV 100 MU min(-1) low-dose acquisition mode. Routine EPID QC contrast tolerance (+/-10) and action (+/-20) levels using the PIPSPro phantom based around expected values of 190 (Varian 600C/D) and 225 (Varian 2100C/D) have been introduced. The dose at dmax from electronic portal imaging has been reduced by approximately 28%, and while the image quality has been reduced, the images produced are still clinically acceptable.

A technique for multi-dimensional optimization of radiation dose, contrast dose, and image quality in CT imaging

NASA Astrophysics Data System (ADS)

Sahbaee, Pooyan; Abadi, Ehsan; Sanders, Jeremiah; Becchetti, Marc; Zhang, Yakun; Agasthya, Greeshma; Segars, Paul; Samei, Ehsan

2016-03-01

The purpose of this study was to substantiate the interdependency of image quality, radiation dose, and contrast material dose in CT towards the patient-specific optimization of the imaging protocols. The study deployed two phantom platforms. First, a variable sized phantom containing an iodinated insert was imaged on a representative CT scanner at multiple CTDI values. The contrast and noise were measured from the reconstructed images for each phantom diameter. Linearly related to iodine-concentration, contrast to noise ratio (CNR), was calculated for different iodine-concentration levels. Second, the analysis was extended to a recently developed suit of 58 virtual human models (5D-XCAT) with added contrast dynamics. Emulating a contrast-enhanced abdominal image procedure and targeting a peak-enhancement in aorta, each XCAT phantom was "imaged" using a CT simulation platform. 3D surfaces for each patient/size established the relationship between iodine-concentration, dose, and CNR. The Sensitivity of Ratio (SR), defined as ratio of change in iodine-concentration versus dose to yield a constant change in CNR was calculated and compared at high and low radiation dose for both phantom platforms. The results show that sensitivity of CNR to iodine concentration is larger at high radiation dose (up to 73%). The SR results were highly affected by radiation dose metric; CTDI or organ dose. Furthermore, results showed that the presence of contrast material could have a profound impact on optimization results (up to 45%).

Image quality, threshold contrast and mean glandular dose in CR mammography

NASA Astrophysics Data System (ADS)

Jakubiak, R. R.; Gamba, H. R.; Neves, E. B.; Peixoto, J. E.

2013-09-01

In many countries, computed radiography (CR) systems represent the majority of equipment used in digital mammography. This study presents a method for optimizing image quality and dose in CR mammography of patients with breast thicknesses between 45 and 75 mm. Initially, clinical images of 67 patients (group 1) were analyzed by three experienced radiologists, reporting about anatomical structures, noise and contrast in low and high pixel value areas, and image sharpness and contrast. Exposure parameters (kV, mAs and target/filter combination) used in the examinations of these patients were reproduced to determine the contrast-to-noise ratio (CNR) and mean glandular dose (MGD). The parameters were also used to radiograph a CDMAM (version 3.4) phantom (Artinis Medical Systems, The Netherlands) for image threshold contrast evaluation. After that, different breast thicknesses were simulated with polymethylmethacrylate layers and various sets of exposure parameters were used in order to determine optimal radiographic parameters. For each simulated breast thickness, optimal beam quality was defined as giving a target CNR to reach the threshold contrast of CDMAM images for acceptable MGD. These results were used for adjustments in the automatic exposure control (AEC) by the maintenance team. Using optimized exposure parameters, clinical images of 63 patients (group 2) were evaluated as described above. Threshold contrast, CNR and MGD for such exposure parameters were also determined. Results showed that the proposed optimization method was effective for all breast thicknesses studied in phantoms. The best result was found for breasts of 75 mm. While in group 1 there was no detection of the 0.1 mm critical diameter detail with threshold contrast below 23%, after the optimization, detection occurred in 47.6% of the images. There was also an average MGD reduction of 7.5%. The clinical image quality criteria were attended in 91.7% for all breast thicknesses evaluated in both patient groups. Finally, this study also concluded that the use of the AEC of the x-ray unit based on the constant dose to the detector may bring some difficulties to CR systems to operate under optimal conditions. More studies must be performed, so that the compatibility between systems and optimization methodologies can be evaluated, as well as this optimization method. Most methods are developed for phantoms, so comparative studies including clinical images must be developed.

Quality assurance for high dose rate brachytherapy treatment planning optimization: using a simple optimization to verify a complex optimization

NASA Astrophysics Data System (ADS)

Deufel, Christopher L.; Furutani, Keith M.

2014-02-01

As dose optimization for high dose rate brachytherapy becomes more complex, it becomes increasingly important to have a means of verifying that optimization results are reasonable. A method is presented for using a simple optimization as quality assurance for the more complex optimization algorithms typically found in commercial brachytherapy treatment planning systems. Quality assurance tests may be performed during commissioning, at regular intervals, and/or on a patient specific basis. A simple optimization method is provided that optimizes conformal target coverage using an exact, variance-based, algebraic approach. Metrics such as dose volume histogram, conformality index, and total reference air kerma agree closely between simple and complex optimizations for breast, cervix, prostate, and planar applicators. The simple optimization is shown to be a sensitive measure for identifying failures in a commercial treatment planning system that are possibly due to operator error or weaknesses in planning system optimization algorithms. Results from the simple optimization are surprisingly similar to the results from a more complex, commercial optimization for several clinical applications. This suggests that there are only modest gains to be made from making brachytherapy optimization more complex. The improvements expected from sophisticated linear optimizations, such as PARETO methods, will largely be in making systems more user friendly and efficient, rather than in finding dramatically better source strength distributions.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kofler, J.

The main topic of the session is to show how dose optimization is being implemented in various regions of the world, including Europe, Australia, North America and other regions. A multi-national study conducted under International Atomic Energy Agency (IAEA) across more than 50 less resourced countries gave insight into patient radiation doses and safety practices in CT, mammography, radiography and interventional procedures, both for children and adults. An important outcome was the capability development on dose assessment and management. An overview of recent European projects related to CT radiation dose and optimization both to adults and children will be presented.more » Existing data on DRLs together with a European methodology proposed on establishing and using DRLs for paediatric radiodiagnostic imaging and interventional radiology practices will be shown. Compared with much of Europe at least, many Australian imaging practices are relatively new to the task of diagnostic imaging dose optimisation. In 2008 the Australian Government prescribed a requirement to periodically compare patient radiation doses with diagnostic reference levels (DRLs), where DRLs have been established. Until recently, Australia had only established DRLs for computed tomography (CT). Regardless, both professional society and individual efforts to improved data collection and develop optimisation strategies across a range of modalities continues. Progress in this field, principally with respect to CT and interventional fluoroscopy will be presented. In the US, dose reduction and optimization efforts for computed tomography have been promoted and mandated by several organizations and accrediting entities. This presentation will cover the general motivation, implementation, and implications of such efforts. Learning Objectives: Understand importance of the dose optimization in Diagnostic Radiology. See how this goal is achieved in different regions of the World. Learn about the global trend in the dose optimization and future prospectives. M. Rehani, The work was a part of the work of IAEA where I was an employee and IAEA is a United Nations organization.« less

Uncertainties in endocrine substitution therapy for central hypocortisolism.

PubMed

Swords, Francesca M

2014-01-01

Central hypocortisolism is common, and has multiple potential causes. However, the treatment aims remain the same whatever the cause: to maximize quality of life, while minimizing treatment-related adverse effects. The majority of patients with central hypocortisolism now receive hydrocortisone in two to three divided doses with a total daily dose of 10-20mg, or a weight-based regimen of 8.1mg/m(2)/day. However, various areas of controversy remain: how to assess the patient with suspected hypocortisolism, which is the optimal agent to use, what is the optimal total daily dose, how to administer divided daily doses, how to monitor therapy and individually tailor doses, whether to replace other adrenal androgens, how to approach the patient with adrenal suppression, and how to best educate patients with hypocortisolism and treat them in emergency situations. This chapter will discuss the evidence behind each of these controversial areas in turn. The evidence for newer agents such as prolonged- and delayed-release preparations of hydrocortisone will also be explored, with a discussion on their potential role in the future management of this major clinical problem. © 2014 Elsevier B.V. All rights reserved.

Prospective estimation of organ dose in CT under tube current modulation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tian, Xiaoyu, E-mail: xt3@duke.edu; Li, Xiang; Segars, W. Paul

Purpose: Computed tomography (CT) has been widely used worldwide as a tool for medical diagnosis and imaging. However, despite its significant clinical benefits, CT radiation dose at the population level has become a subject of public attention and concern. In this light, optimizing radiation dose has become a core responsibility for the CT community. As a fundamental step to manage and optimize dose, it may be beneficial to have accurate and prospective knowledge about the radiation dose for an individual patient. In this study, the authors developed a framework to prospectively estimate organ dose for chest and abdominopelvic CT examsmore » under tube current modulation (TCM). Methods: The organ dose is mainly dependent on two key factors: patient anatomy and irradiation field. A prediction process was developed to accurately model both factors. To model the anatomical diversity and complexity in the patient population, the authors used a previously developed library of computational phantoms with broad distributions of sizes, ages, and genders. A selected clinical patient, represented by a computational phantom in the study, was optimally matched with another computational phantom in the library to obtain a representation of the patient’s anatomy. To model the irradiation field, a previously validated Monte Carlo program was used to model CT scanner systems. The tube current profiles were modeled using a ray-tracing program as previously reported that theoretically emulated the variability of modulation profiles from major CT machine manufacturers Li et al., [Phys. Med. Biol. 59, 4525–4548 (2014)]. The prediction of organ dose was achieved using the following process: (1) CTDI{sub vol}-normalized-organ dose coefficients (h{sub organ}) for fixed tube current were first estimated as the prediction basis for the computational phantoms; (2) each computation phantom, regarded as a clinical patient, was optimally matched with one computational phantom in the library; (3) to account for the effect of the TCM scheme, a weighted organ-specific CTDI{sub vol} [denoted as (CTDI{sub vol}){sub organ,weighted}] was computed for each organ based on the TCM profile and the anatomy of the “matched” phantom; (4) the organ dose was predicted by multiplying the weighted organ-specific CTDI{sub vol} with the organ dose coefficients (h{sub organ}). To quantify the prediction accuracy, each predicted organ dose was compared with the corresponding organ dose simulated from the Monte Carlo program with the TCM profile explicitly modeled. Results: The predicted organ dose showed good agreements with the simulated organ dose across all organs and modulation profiles. The average percentage error in organ dose estimation was generally within 20% across all organs and modulation profiles, except for organs located in the pelvic and shoulder regions. For an average CTDI{sub vol} of a CT exam of 10 mGy, the average error at full modulation strength (α = 1) across all organs was 0.91 mGy for chest exams, and 0.82 mGy for abdominopelvic exams. Conclusions: This study developed a quantitative model to predict organ dose for clinical chest and abdominopelvic scans. Such information may aid in the design of optimized CT protocols in relation to a targeted level of image quality.« less

Comparison of DVH parameters and loading patterns of standard loading, manual and inverse optimization for intracavitary brachytherapy on a subset of tandem/ovoid cases.

PubMed

Jamema, Swamidas V; Kirisits, Christian; Mahantshetty, Umesh; Trnkova, Petra; Deshpande, Deepak D; Shrivastava, Shyam K; Pötter, Richard

2010-12-01

Comparison of inverse planning with the standard clinical plan and with the manually optimized plan based on dose-volume parameters and loading patterns. Twenty-eight patients who underwent MRI based HDR brachytherapy for cervix cancer were selected for this study. Three plans were calculated for each patient: (1) standard loading, (2) manual optimized, and (3) inverse optimized. Dosimetric outcomes from these plans were compared based on dose-volume parameters. The ratio of Total Reference Air Kerma of ovoid to tandem (TRAK(O/T)) was used to compare the loading patterns. The volume of HR CTV ranged from 9-68 cc with a mean of 41(±16.2) cc. Mean V100 for standard, manual optimized and inverse plans was found to be not significant (p=0.35, 0.38, 0.4). Dose to bladder (7.8±1.6 Gy) and sigmoid (5.6±1.4 Gy) was high for standard plans; Manual optimization reduced the dose to bladder (7.1±1.7 Gy p=0.006) and sigmoid (4.5±1.0 Gy p=0.005) without compromising the HR CTV coverage. The inverse plan resulted in a significant reduction to bladder dose (6.5±1.4 Gy, p=0.002). TRAK was found to be 0.49(±0.02), 0.44(±0.04) and 0.40(±0.04) cGy m(-2) for the standard loading, manual optimized and inverse plans, respectively. It was observed that TRAK(O/T) was 0.82(±0.05), 1.7(±1.04) and 1.41(±0.93) for standard loading, manual optimized and inverse plans, respectively, while this ratio was 1 for the traditional loading pattern. Inverse planning offers good sparing of critical structures without compromising the target coverage. The average loading pattern of the whole patient cohort deviates from the standard Fletcher loading pattern. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

A randomized, double-blind, active control, multicenter, dose-finding study of lipegfilgrastim (XM22) in breast cancer patients receiving myelosuppressive therapy.

PubMed

Buchner, Anton; Elsässer, Reiner; Bias, Peter

2014-11-01

This dose-ranging study was conducted to identify the optimal fixed dose of lipegfilgrastim compared with pegfilgrastim 6.0 mg for the provision of neutrophil support during myelosuppressive chemotherapy in patients with breast cancer. A phase 2 study was conducted in which 208 chemotherapy-naive patients were randomized to receive lipegfilgrastim 3.0, 4.5, or 6.0 mg or pegfilgrastim 6.0 mg. Study drugs were administered as a single subcutaneous injection on day 2 of each chemotherapy cycle (doxorubicin/docetaxel on day 1 for four 3-week cycles). The primary outcome measure was duration of severe neutropenia (DSN) in cycle 1. Patients treated with lipegfilgrastim experienced shorter DSN in cycle 1 with higher doses. The mean DSN was 0.76 days in the lipegfilgrastim 6.0-mg group and 0.87 days in the pegfilgrastim 6.0-mg group, with no significant differences between treatment groups. Treatment with lipegfilgrastim 6.0 mg was consistently associated with a higher absolute neutrophil count (ANC) at nadir, shorter ANC recovery time, and a similar safety and tolerability profile compared with pegfilgrastim. This phase 2 study demonstrated that lipegfilgrastim 6.0 mg is the optimal dose for patients with breast cancer and provides neutrophil support that is at least equivalent to the standard 6.0-mg fixed dose of pegfilgrastim.

SU-E-T-175: Clinical Evaluations of Monte Carlo-Based Inverse Treatment Plan Optimization for Intensity Modulated Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chi, Y; Li, Y; Tian, Z

2015-06-15

Purpose: Pencil-beam or superposition-convolution type dose calculation algorithms are routinely used in inverse plan optimization for intensity modulated radiation therapy (IMRT). However, due to their limited accuracy in some challenging cases, e.g. lung, the resulting dose may lose its optimality after being recomputed using an accurate algorithm, e.g. Monte Carlo (MC). It is the objective of this study to evaluate the feasibility and advantages of a new method to include MC in the treatment planning process. Methods: We developed a scheme to iteratively perform MC-based beamlet dose calculations and plan optimization. In the MC stage, a GPU-based dose engine wasmore » used and the particle number sampled from a beamlet was proportional to its optimized fluence from the previous step. We tested this scheme in four lung cancer IMRT cases. For each case, the original plan dose, plan dose re-computed by MC, and dose optimized by our scheme were obtained. Clinically relevant dosimetric quantities in these three plans were compared. Results: Although the original plan achieved a satisfactory PDV dose coverage, after re-computing doses using MC method, it was found that the PTV D95% were reduced by 4.60%–6.67%. After re-optimizing these cases with our scheme, the PTV coverage was improved to the same level as in the original plan, while the critical OAR coverages were maintained to clinically acceptable levels. Regarding the computation time, it took on average 144 sec per case using only one GPU card, including both MC-based beamlet dose calculation and treatment plan optimization. Conclusion: The achieved dosimetric gains and high computational efficiency indicate the feasibility and advantages of the proposed MC-based IMRT optimization method. Comprehensive validations in more patient cases are in progress.« less

SU-E-T-230: Creating a Large Number of Focused Beams with Variable Patient Head Tilt to Improve Dose Fall-Off for Brain Radiosurgery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chiu, J; Ma, L

2015-06-15

Purpose: To develop a treatment delivery and planning strategy by increasing the number of beams to minimize dose to brain tissue surrounding a target, while maximizing dose coverage to the target. Methods: We analyzed 14 different treatment plans via Leksell PFX and 4C. For standardization, single tumor cases were chosen. Original treatment plans were compared with two optimized plans. The number of beams was increased in treatment plans by varying tilt angles of the patient head, while maintaining original isocenter and the beam positions in the x-, y- and z-axes, collimator size, and beam blocking. PFX optimized plans increased beammore » numbers with three pre-set tilt angles, 70, 90, 110, and 4C optimized plans increased beam numbers with tilt angles increasing arbitrarily from range of 30 to 150 degrees. Optimized treatment plans were compared dosimetrically with original treatment plans. Results: Comparing total normal tissue isodose volumes between original and optimized plans, the low-level percentage isodose volumes decreased in all plans. Despite the addition of multiple beams up to a factor of 25, beam-on times for 1 tilt angle versus 3 or more tilt angles were comparable (<1 min.). In 64% (9/14) of the studied cases, the volume percentage decrease by >5%, with the highest value reaching 19%. The addition of more tilt angles correlates to a greater decrease in normal brain irradiated volume. Selectivity and coverage for original and optimized plans remained comparable. Conclusion: Adding large number of additional focused beams with variable patient head tilt shows improvement for dose fall-off for brain radiosurgery. The study demonstrates technical feasibility of adding beams to decrease target volume.« less

Population Pharmacokinetics of Doripenem in Critically Ill Patients with Sepsis in a Malaysian Intensive Care Unit.

PubMed

Abdul-Aziz, Mohd H; Abd Rahman, Azrin N; Mat-Nor, Mohd-Basri; Sulaiman, Helmi; Wallis, Steven C; Lipman, Jeffrey; Roberts, Jason A; Staatz, Christine E

2016-01-01

Doripenem has been recently introduced in Malaysia and is used for severe infections in the intensive care unit. However, limited data currently exist to guide optimal dosing in this scenario. We aimed to describe the population pharmacokinetics of doripenem in Malaysian critically ill patients with sepsis and use Monte Carlo dosing simulations to develop clinically relevant dosing guidelines for these patients. In this pharmacokinetic study, 12 critically ill adult patients with sepsis receiving 500 mg of doripenem every 8 h as a 1-hour infusion were enrolled. Serial blood samples were collected on 2 different days, and population pharmacokinetic analysis was performed using a nonlinear mixed-effects modeling approach. A two-compartment linear model with between-subject and between-occasion variability on clearance was adequate in describing the data. The typical volume of distribution and clearance of doripenem in this cohort were 0.47 liters/kg and 0.14 liters/kg/h, respectively. Doripenem clearance was significantly influenced by patients' creatinine clearance (CL(CR)), such that a 30-ml/min increase in the estimated CL(CR) would increase doripenem CL by 52%. Monte Carlo dosing simulations suggested that, for pathogens with a MIC of 8 mg/liter, a dose of 1,000 mg every 8 h as a 4-h infusion is optimal for patients with a CL(CR) of 30 to 100 ml/min, while a dose of 2,000 mg every 8 h as a 4-h infusion is best for patients manifesting a CL(CR) of >100 ml/min. Findings from this study suggest that, for doripenem usage in Malaysian critically ill patients, an alternative dosing approach may be meritorious, particularly when multidrug resistance pathogens are involved. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Population Pharmacokinetics of Doripenem in Critically Ill Patients with Sepsis in a Malaysian Intensive Care Unit

PubMed Central

Abd Rahman, Azrin N.; Mat-Nor, Mohd-Basri; Sulaiman, Helmi; Wallis, Steven C.; Lipman, Jeffrey; Roberts, Jason A.; Staatz, Christine E.

2015-01-01

Doripenem has been recently introduced in Malaysia and is used for severe infections in the intensive care unit. However, limited data currently exist to guide optimal dosing in this scenario. We aimed to describe the population pharmacokinetics of doripenem in Malaysian critically ill patients with sepsis and use Monte Carlo dosing simulations to develop clinically relevant dosing guidelines for these patients. In this pharmacokinetic study, 12 critically ill adult patients with sepsis receiving 500 mg of doripenem every 8 h as a 1-hour infusion were enrolled. Serial blood samples were collected on 2 different days, and population pharmacokinetic analysis was performed using a nonlinear mixed-effects modeling approach. A two-compartment linear model with between-subject and between-occasion variability on clearance was adequate in describing the data. The typical volume of distribution and clearance of doripenem in this cohort were 0.47 liters/kg and 0.14 liters/kg/h, respectively. Doripenem clearance was significantly influenced by patients' creatinine clearance (CLCR), such that a 30-ml/min increase in the estimated CLCR would increase doripenem CL by 52%. Monte Carlo dosing simulations suggested that, for pathogens with a MIC of 8 mg/liter, a dose of 1,000 mg every 8 h as a 4-h infusion is optimal for patients with a CLCR of 30 to 100 ml/min, while a dose of 2,000 mg every 8 h as a 4-h infusion is best for patients manifesting a CLCR of >100 ml/min. Findings from this study suggest that, for doripenem usage in Malaysian critically ill patients, an alternative dosing approach may be meritorious, particularly when multidrug resistance pathogens are involved. PMID:26482304

Low incidence of chest wall pain with a risk-adapted lung stereotactic body radiation therapy approach using three or five fractions based on chest wall dosimetry.

PubMed

Coroller, Thibaud P; Mak, Raymond H; Lewis, John H; Baldini, Elizabeth H; Chen, Aileen B; Colson, Yolonda L; Hacker, Fred L; Hermann, Gretchen; Kozono, David; Mannarino, Edward; Molodowitch, Christina; Wee, Jon O; Sher, David J; Killoran, Joseph H

2014-01-01

To examine the frequency and potential of dose-volume predictors for chest wall (CW) toxicity (pain and/or rib fracture) for patients receiving lung stereotactic body radiotherapy (SBRT) using treatment planning methods to minimize CW dose and a risk-adapted fractionation scheme. We reviewed data from 72 treatment plans, from 69 lung SBRT patients with at least one year of follow-up or CW toxicity, who were treated at our center between 2010 and 2013. Treatment plans were optimized to reduce CW dose and patients received a risk-adapted fractionation of 18 Gy×3 fractions (54 Gy total) if the CW V30 was less than 30 mL or 10-12 Gy×5 fractions (50-60 Gy total) otherwise. The association between CW toxicity and patient characteristics, treatment parameters and dose metrics, including biologically equivalent dose, were analyzed using logistic regression. With a median follow-up of 20 months, 6 (8.3%) patients developed CW pain including three (4.2%) grade 1, two (2.8%) grade 2 and one (1.4%) grade 3. Five (6.9%) patients developed rib fractures, one of which was symptomatic. No significant associations between CW toxicity and patient and dosimetric variables were identified on univariate nor multivariate analysis. Optimization of treatment plans to reduce CW dose and a risk-adapted fractionation strategy of three or five fractions based on the CW V30 resulted in a low incidence of CW toxicity. Under these conditions, none of the patient characteristics or dose metrics we examined appeared to be predictive of CW pain.

Exploratory Study of 4D versus 3D Robust Optimization in Intensity Modulated Proton Therapy for Lung Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Wei, E-mail: Liu.Wei@mayo.edu; Schild, Steven E.; Chang, Joe Y.

Purpose: The purpose of this study was to compare the impact of uncertainties and interplay on 3-dimensional (3D) and 4D robustly optimized intensity modulated proton therapy (IMPT) plans for lung cancer in an exploratory methodology study. Methods and Materials: IMPT plans were created for 11 nonrandomly selected non-small cell lung cancer (NSCLC) cases: 3D robustly optimized plans on average CTs with internal gross tumor volume density overridden to irradiate internal target volume, and 4D robustly optimized plans on 4D computed tomography (CT) to irradiate clinical target volume (CTV). Regular fractionation (66 Gy [relative biological effectiveness; RBE] in 33 fractions) was considered.more » In 4D optimization, the CTV of individual phases received nonuniform doses to achieve a uniform cumulative dose. The root-mean-square dose-volume histograms (RVH) measured the sensitivity of the dose to uncertainties, and the areas under the RVH curve (AUCs) were used to evaluate plan robustness. Dose evaluation software modeled time-dependent spot delivery to incorporate interplay effect with randomized starting phases of each field per fraction. Dose-volume histogram (DVH) indices comparing CTV coverage, homogeneity, and normal tissue sparing were evaluated using Wilcoxon signed rank test. Results: 4D robust optimization plans led to smaller AUC for CTV (14.26 vs 18.61, respectively; P=.001), better CTV coverage (Gy [RBE]) (D{sub 95%} CTV: 60.6 vs 55.2, respectively; P=.001), and better CTV homogeneity (D{sub 5%}-D{sub 95%} CTV: 10.3 vs 17.7, resspectively; P=.002) in the face of uncertainties. With interplay effect considered, 4D robust optimization produced plans with better target coverage (D{sub 95%} CTV: 64.5 vs 63.8, respectively; P=.0068), comparable target homogeneity, and comparable normal tissue protection. The benefits from 4D robust optimization were most obvious for the 2 typical stage III lung cancer patients. Conclusions: Our exploratory methodology study showed that, compared to 3D robust optimization, 4D robust optimization produced significantly more robust and interplay-effect-resistant plans for targets with comparable dose distributions for normal tissues. A further study with a larger and more realistic patient population is warranted to generalize the conclusions.« less

[Applying dose banding to the production of antineoplastic drugs: a narrative review of the literature].

PubMed

Pérez Huertas, Pablo; Cueto Sola, Margarita; Escobar Cava, Paloma; Borrell García, Carmela; Albert Marí, Asunción; López Briz, Eduardo; Poveda Andrés, José Luis

2015-07-01

The dosage of antineoplastic drugs has historically been based on individualized prescription and preparation according to body surface area or patient´s weight. Lack of resources and increased assistance workload in the areas where chemotherapy is made, are leading to the development of new systems to optimize the processing without reducing safety. One of the strategies that has been proposed is the elaboration by dose banding. This new approach standardizes the antineoplastic agents doses by making ranges or bands accepting a percentage of maximum variation. It aims to reduce processing time with the consequent reduction in waiting time for patients; to reduce errors in the manufacturing process and to promote the rational drug use. In conclusion, dose banding is a suitable method for optimizing the development of anticancer drugs, obtaining reductions in oncologic patients waiting time but without actually causing a favorable impact on direct or indirect costs. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Camingue, Pamela; Christian, Rochelle; Ng, Davin

The purpose of this study was to compare 4 different external beam radiation therapy treatment techniques for the treatment of T1-2, N0, M0 glottic cancers: traditional lateral beams with wedges (3D), 5-field intensity-modulated radiation therapy (IMRT), volumetric modulated arc therapy (VMAT), and proton therapy. Treatment plans in each technique were created for 10 patients using consistent planning parameters. The photon treatment plans were optimized using Philips Pinnacle{sub 3} v.9 and the IMRT and VMAT plans used the Direct Machine Parameter Optimization algorithm. The proton treatment plans were optimized using Varian Eclipse Proton v.8.9. The prescription used for each plan wasmore » 63 Gy in 28 fractions. The contours for spinal cord, right carotid artery, left carotid artery, and normal tissue were created with respect to the patient's bony anatomy so that proper comparisons of doses could be made with respect to volume. An example of the different isodose distributions will be shown. The data collection for comparison purposes includes: clinical treatment volume coverage, dose to spinal cord, dose to carotid arteries, and dose to normal tissue. Data comparisons will be displayed graphically showing the maximum, mean, median, and ranges of doses.« less

Universal field matching in craniospinal irradiation by a background-dose gradient-optimized method.

PubMed

Traneus, Erik; Bizzocchi, Nicola; Fellin, Francesco; Rombi, Barbara; Farace, Paolo

2018-01-01

The gradient-optimized methods are overcoming the traditional feathering methods to plan field junctions in craniospinal irradiation. In this note, a new gradient-optimized technique, based on the use of a background dose, is described. Treatment planning was performed by RayStation (RaySearch Laboratories, Stockholm, Sweden) on the CT scans of a pediatric patient. Both proton (by pencil beam scanning) and photon (by volumetric modulated arc therapy) treatments were planned with three isocenters. An 'in silico' ideal background dose was created first to cover the upper-spinal target and to produce a perfect dose gradient along the upper and lower junction regions. Using it as background, the cranial and the lower-spinal beams were planned by inverse optimization to obtain dose coverage of their relevant targets and of the junction volumes. Finally, the upper-spinal beam was inversely planned after removal of the background dose and with the previously optimized beams switched on. In both proton and photon plans, the optimized cranial and the lower-spinal beams produced a perfect linear gradient in the junction regions, complementary to that produced by the optimized upper-spinal beam. The final dose distributions showed a homogeneous coverage of the targets. Our simple technique allowed to obtain high-quality gradients in the junction region. Such technique universally works for photons as well as protons and could be applicable to the TPSs that allow to manage a background dose. © 2017 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

Optimal radiotherapy dose schedules under parametric uncertainty

NASA Astrophysics Data System (ADS)

Badri, Hamidreza; Watanabe, Yoichi; Leder, Kevin

2016-01-01

We consider the effects of parameter uncertainty on the optimal radiation schedule in the context of the linear-quadratic model. Our interest arises from the observation that if inter-patient variability in normal and tumor tissue radiosensitivity or sparing factor of the organs-at-risk (OAR) are not accounted for during radiation scheduling, the performance of the therapy may be strongly degraded or the OAR may receive a substantially larger dose than the allowable threshold. This paper proposes a stochastic radiation scheduling concept to incorporate inter-patient variability into the scheduling optimization problem. Our method is based on a probabilistic approach, where the model parameters are given by a set of random variables. Our probabilistic formulation ensures that our constraints are satisfied with a given probability, and that our objective function achieves a desired level with a stated probability. We used a variable transformation to reduce the resulting optimization problem to two dimensions. We showed that the optimal solution lies on the boundary of the feasible region and we implemented a branch and bound algorithm to find the global optimal solution. We demonstrated how the configuration of optimal schedules in the presence of uncertainty compares to optimal schedules in the absence of uncertainty (conventional schedule). We observed that in order to protect against the possibility of the model parameters falling into a region where the conventional schedule is no longer feasible, it is required to avoid extremal solutions, i.e. a single large dose or very large total dose delivered over a long period. Finally, we performed numerical experiments in the setting of head and neck tumors including several normal tissues to reveal the effect of parameter uncertainty on optimal schedules and to evaluate the sensitivity of the solutions to the choice of key model parameters.

Successful Optimization of Adalimumab Therapy in Refractory Uveitis Due to Behçet's Disease.

PubMed

Martín-Varillas, José Luis; Calvo-Río, Vanesa; Beltrán, Emma; Sánchez-Bursón, Juan; Mesquida, Marina; Adán, Alfredo; Hernandez, María Victoria; Garfella, Marisa Hernández; Pascual, Elia Valls; Martínez-Costa, Lucía; Sellas-Fernández, Agustí; Cordero-Coma, Miguel; Díaz-Llopis, Manuel; Gallego, Roberto; Salom, David; Ortego, Norberto; García-Serrano, José L; Callejas-Rubio, José-Luis; Herreras, José M; García-Aparicio, Ángel; Maíz, Olga; Blanco, Ana; Torre, Ignacio; Díaz-Valle, David; Pato, Esperanza; Aurrecoechea, Elena; Caracuel, Miguel A; Gamero, Fernando; Minguez, Enrique; Carrasco-Cubero, Carmen; Olive, Alejandro; Vázquez, Julio; Ruiz-Moreno, Oscar; Manero, Javier; Muñoz-Fernández, Santiago; Martinez, Myriam Gandía; Rubio-Romero, Esteban; Toyos-Sáenz de Miera, F Javier; López Longo, Francisco Javier; Nolla, Joan M; Revenga, Marcelino; González-Vela, Carmen; Loricera, Javier; Atienza-Mateo, Belén; Demetrio-Pablo, Rosalía; Hernández, José Luis; González-Gay, Miguel A; Blanco, Ricardo

2018-03-27

To assess efficacy, safety, and cost-effectiveness of adalimumab (ADA) therapy optimization in a large series of patients with uveitis due to Behçet disease (BD) who achieved remission after the use of this biologic agent. Open-label multicenter study of ADA-treated patients with BD uveitis refractory to conventional immunosuppressants. Sixty-five of 74 patients with uveitis due to BD, who achieved remission after a median ADA duration of 6 (range, 3-12) months. ADA was optimized in 23 (35.4%) of them. This biologic agent was maintained at a dose of 40 mg/subcutaneously/2 weeks in the remaining 42 patients. After remission, based on a shared decision between the patient and the treating physician, ADA was optimized. When agreement between patient and physician was reached, optimization was performed by prolonging the ADA dosing interval progressively. Comparison between optimized and nonoptimized patients was performed. Efficacy, safety, and cost-effectiveness in optimized and nonoptimized groups. To determine efficacy, intraocular inflammation (anterior chamber cells, vitritis, and retinal vasculitis), macular thickness, visual acuity, and the sparing effect of glucocorticoids were assessed. No demographic or ocular differences were found at the time of ADA onset between the optimized and the nonoptimized groups. Most ocular outcomes were similar after a mean ± standard deviation follow-up of 34.7±13.3 and 26±21.3 months in the optimized and nonoptimized groups, respectively. However, relevant adverse effects were only seen in the nonoptimized group (lymphoma, pneumonia, severe local reaction at the injection site, and bacteremia by Escherichia coli, 1 each). Moreover, the mean ADA treatment costs were lower in the optimized group than in the nonoptimized group (6101.25 euros/patient/year vs. 12 339.48; P < 0.01). ADA optimization in BD uveitis refractory to conventional therapy is effective, safe, and cost-effective. Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Amino acid composition in parenteral nutrition: what is the evidence?

PubMed Central

Yarandi, Shadi S.; Zhao, Vivian M.; Hebbar, Gautam; Ziegler, Thomas R.

2011-01-01

Purpose of review Complete parenteral nutrition solutions contain mixed amino acid products providing all nine essential amino acids and a varying composition of nonessential amino acids. Relatively little rigorous comparative efficacy research on altered parenteral nutrition amino acid composition has been published in recent years. Recent findings Limited data from randomized, double-blind, adequately powered clinical trials to define optimal doses of total or individual amino acids in parenteral nutrition are available. An exception is the growing number of studies on the efficacy of glutamine supplementation of parenteral nutrition or given as a single parenteral agent. Parenteral glutamine appears to confer benefit in selected patients; however, additional data to define optimal glutamine dosing and the patient subgroups who may most benefit from this amino acid are needed. Although some promising studies have been published, little data are available in the current era of nutrition support on the clinical efficacy of altered doses of arginine, branched chain amino acids, cysteine, or taurine supplementation of parenteral nutrition. Summary Despite routine use of parenteral nutrition, surprisingly little clinical efficacy data are available to guide total or specific amino acid dosing in adult and pediatric patients requiring this therapy. This warrants increased attention by the research community and funding agencies to better define optimal amino acid administration strategies in patient subgroups requiring parenteral nutrition. PMID:21076291

The Mobile Insulin Titration Intervention (MITI) for Insulin Adjustment in an Urban, Low-Income Population: Randomized Controlled Trial.

PubMed

Levy, Natalie; Moynihan, Victoria; Nilo, Annielyn; Singer, Karyn; Bernik, Lidia S; Etiebet, Mary-Ann; Fang, Yixin; Cho, James; Natarajan, Sundar

2015-07-17

Diabetes patients are usually started on a low dose of insulin and their dose is adjusted or "titrated" according to their blood glucose levels. Insulin titration administered through face-to-face visits with a clinician can be time consuming and logistically burdensome for patients, especially those of low socioeconomic status (SES). Given the wide use of mobile phones among this population, there is the potential to use short message service (SMS) text messaging and phone calls to perform insulin titration remotely. The goals of this pilot study were to (1) evaluate if our Mobile Insulin Titration Intervention (MITI) intervention using text messaging and phone calls was effective in helping patients reach their optimal insulin glargine dose within 12 weeks, (2) assess the feasibility of the intervention within our clinic setting and patient population, (3) collect data on the cost savings associated with the intervention, and (4) measure patient satisfaction with the intervention. This was a pilot study evaluating an intervention for patients requiring insulin glargine titration in the outpatient medical clinic of Bellevue Hospital Center in New York City. Patients in the intervention arm received weekday SMS text messages from a health management platform requesting their fasting blood glucose values. The clinic's diabetes nurse educator monitored the texted responses on the platform website each weekday for alarm values. Once a week, the nurse reviewed the glucose values, consulted the MITI titration algorithm, and called patients to adjust their insulin dose. Patients in the usual care arm continued to receive their standard clinic care for insulin titration. The primary outcome was whether a patient reached his/her optimal insulin glargine dose within 12 weeks. A total of 61 patients consented and were randomized into the study. A significantly greater proportion of patients in the intervention arm reached their optimal insulin glargine dose than patients in the usual care arm (88%, 29/33 vs 37%, 10/27; P<.001). Patients responded to 84.3% (420/498) of the SMS text messages requesting their blood glucose values. The nurse reached patients within 2 attempts or by voicemail 91% of the time (90/99 assigned calls). When patients traveled to the clinic, they spent a median of 45 minutes (IQR 30-60) on travel and 39 minutes (IQR 30-64) waiting prior to appointments. A total of 61% (37/61) of patients had appointment copays. After participating in the study, patients in the intervention arm reported higher treatment satisfaction than those in the usual care arm. MITI is an effective way to help low-SES patients reach their optimal insulin glargine dose using basic SMS text messaging and phone calls. The intervention was feasible and patients were highly satisfied with their treatment. The intervention was cost saving in terms of time for patients, who were able to have their insulin titrated without multiple clinic appointments. Similar interventions should be explored to improve care for low-SES patients managing chronic disease. Clinicaltrials.gov NCT01879579; https://clinicaltrials.gov/ct2/show/NCT01879579 (Archived by WebCite at http://www.webcitation.org/6YZik33L3).

Prediction of an Optimal Dose of Aripiprazole in the Treatment of Schizophrenia From Plasma Concentrations of Aripiprazole Plus Its Active Metabolite Dehydroaripiprazole at Week 1.

PubMed

Nagai, Goyo; Mihara, Kazuo; Nakamura, Akifumi; Nemoto, Kenji; Kagawa, Shoko; Suzuki, Takeshi; Kondo, Tsuyoshi

2017-02-01

It has been suggested that a plasma trough concentration of aripiprazole plus its active metabolite, dehydroaripiprazole of 225 ng/mL is a threshold for a good therapeutic response in the treatment of acutely exacerbated patients with schizophrenia. The present study investigated whether or not an optimal dose of aripiprazole could be predicted from these concentrations at week 1. The subjects were 26 inpatients with schizophrenia, who received aripiprazole once a day for 3 weeks. The daily doses were 12 mg for the first week and 24 mg for the next 2 weeks. No other drugs except biperiden and flunitrazepam were coadministered. Blood samples were taken at weeks 1 and 3 after the treatment. Plasma concentrations of aripiprazole and dehydroaripiprazole were measured using liquid chromatography with mass-spectrometric detection. There was a significant linear relationship between the plasma concentrations of aripiprazole plus dehydroaripiprazole at weeks 1 (x) and 3 (y) (P < 0.001). Regression equation was y = 2.580x + 34.86 (R = 0.698). Based on the equation, a nomogram to estimate an optimal dose of aripiprazole could be constructed. The present study suggests that an optimal dose of aripiprazole for the treatment of patients with schizophrenia can be predicted from the plasma concentrations of the sum of the 2 compounds at week 1.

Stereotactic Body Radiotherapy in the Management of Oligometastatic Disease.

PubMed

Ahmed, Kamran A; Torres-Roca, Javier F

2016-01-01

The treatment of oligometastatic disease has become common as imaging techniques have advanced and the management of systemic disease has improved. Use of highly targeted, hypofractionated regimens of stereotactic body radiotherapy (SBRT) is now a primary management option for patients with oligometastatic disease. The properties of SBRT are summarized and the results of retrospective and prospective studies of SBRT use in the management of oligometastases are reviewed. Future directions of SBRT, including optimizing dose and fractionation schedules, are also discussed. SBRT can deliver highly conformal, dosed radiation treatments for ablative tumors in a few treatment sessions. Phase 1/2 trials and retrospective institutional results support use of SBRT as a treatment option for oligometastatic disease metastasized to the lung, liver, and spine, and SBRT offers adequate toxicity profiles with good rates of local control. Future directions will involve optimizing dose and fractionation schedules for select histologies to improve rates of local control while limiting toxicity to normal structures. SBRT offers an excellent management option for patients with oligometastases. However, additional research is still needed to optimize dose and fractionation schedules.

SU-G-TeP3-11: Radiobiological-Cum-Dosimetric Quality Assurance of Complex Radiotherapy Plans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Paudel, N; Narayanasamy, G; Zhang, X

2016-06-15

Purpose: Dosimetric gamma-analysis used for QA of complex radiotherapy plans tests the dosimetric equivalence of a delivered plan with the treatment planning system (TPS) optimized plan. It does not examine whether a dosimetric difference results in any radiobiological difference. This study introduces a method to test the radiobiological and dosimetric equivalence between a delivered and the TPS optimized plan. Methods: Six head and neck and seven lung cancer VMAT or IMRT plans optimized for patient treatment were calculated and delivered to an ArcCheck phantom. ArcCheck measured dose distributions were compared with the TPS calculated dose distributions using a 2-D gamma-analysis.more » Dose volume histograms (DVHs) for various patient structures were obtained by using measured data in 3DVH software and compared against the TPS calculated DVHs using 3-D gamma analysis. DVH data were used in the Poisson model to calculate tumor control probability (TCP) for the treatment targets and in the sigmoid dose response model to calculate normal tissue complication probability (NTCP) for the normal structures. Results: Two-D and three-D gamma passing rates among six H&N patient plans differed by 0 to 2.7% and among seven lung plans by 0.1 to 4.5%. Average ± SD TCPs based on measurement and TPS were 0.665±0.018 and 0.674±0.044 for H&N, and 0.791±0.027 and 0.733±0.031 for lung plans, respectively. Differences in NTCPs were usually negligible. The differences in dosimetric results, TCPs and NTCPs were insignificant. Conclusion: The 2-D and 3-D gamma-analysis based agreement between measured and planned dose distributions may indicate their dosimetric equivalence. Small and insignificant differences in TCPs and NTCPs based on measured and planned dose distributions indicate the radiobiological equivalence between the measured and optimized plans. However, patient plans showing larger differences between 2-D and 3-D gamma-analysis can help us make a more definite conclusion through our ongoing research with a larger number of patients.« less

MO-E-18A-01: Imaging: Best Practices In Pediatric Imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Willis, C; Strauss, K; MacDougall, R

This imaging educational program will focus on solutions to common pediatric imaging challenges. The speakers will present collective knowledge on best practices in pediatric imaging from their experience at dedicated children's hospitals. Areas of focus will include general radiography, the use of manual and automatic dose management in computed tomography, and enterprise-wide radiation dose management in the pediatric practice. The educational program will begin with a discussion of the complexities of exposure factor control in pediatric projection radiography. Following this introduction will be two lectures addressing the challenges of computed tomography (CT) protocol optimization in the pediatric population. The firstmore » will address manual CT protocol design in order to establish a managed radiation dose for any pediatric exam on any CT scanner. The second CT lecture will focus on the intricacies of automatic dose modulation in pediatric imaging with an emphasis on getting reliable results in algorithmbased technique selection. The fourth and final lecture will address the key elements needed to developing a comprehensive radiation dose management program for the pediatric environment with particular attention paid to new regulations and obligations of practicing medical physicists. Learning Objectives: To understand how general radiographic techniques can be optimized using exposure indices in order to improve pediatric radiography. To learn how to establish diagnostic dose reference levels for pediatric patients as a function of the type of examination, patient size, and individual design characteristics of the CT scanner. To learn how to predict the patient's radiation dose prior to the exam and manually adjust technique factors if necessary to match the patient's dose to the department's established dose reference levels. To learn how to utilize manufacturer-provided automatic dose modulation technology to consistently achieve patient doses within the department's established size-based diagnostic reference range. To understand the key components of an enterprise-wide pediatric dose management program that integrates the expanding responsibilities of medial physicists in the new era of dose monitoring.« less

Evaluation of automatic exposure control system chamber for the dose optimization when examining pelvic in digital radiography.

PubMed

Kim, Sung-Chul; Lee, Hae-Kag; Lee, Yang-Sub; Cho, Jae-Hwan

2015-01-01

We found a way to optimize the image quality and reduce the exposure dose of patients through the proper activity combination of the automatic exposure control system chamber for the dose optimization when examining the pelvic anteroposterior side using the phantom of the human body standard model. We set 7 combinations of the chamber of automatic exposure control system. The effective dose was yielded by measuring five times for each according to the activity combination of the chamber for the dose measurement. Five radiologists with more than five years of experience evaluated the image through picture archiving and communication system using double blind test while classifying the 6 anatomical sites into 3-point level (improper, proper, perfect). When only one central chamber was activated, the effective dose was found to be the highest level, 0.287 mSv; and lowest when only the top left chamber was used, 0.165 mSv. After the subjective evaluation by five panel members on the pelvic image was completed, there was no statistically meaningful difference between the 7 chamber combinations, and all had good image quality. When testing the pelvic anteroposterior side with digital radiography, we were able to reduce the exposure dose of patients using the combination of the top right side of or the top two of the chamber.

SU-F-T-195: Systematic Constraining of Contralateral Parotid Gland Led to Improved Dosimetric Outcomes for Multi-Field Optimization with Scanning Beam Proton Therapy: Promising Results From a Pilot Study in Patients with Base of Tongue Carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, R; Liu, A; Poenisch, F

Purpose: Treatment planning for Intensity Modulated Proton Therapy (IMPT) for head and neck cancer is time-consuming due to the large number of organs-at-risk (OAR) to be considered. As there are many competing objectives and also wide range of acceptable OAR constraints, the final approved plan may not be most optimal for the given structures. We evaluated the dose reduction to the contralateral parotid by implementing standardized constraints during optimization for scanning beam proton therapy planning. Methods: Twenty-four (24) consecutive patients previously treated for base of tongue carcinoma were retrospectively selected. The doses were 70Gy, 63Gy and 57Gy (SIB in 33more » fractions) for high-, intermediate-, and standard-risk clinical target volumes (CTV), respectively; the treatment included bilateral neck. Scanning beams using MFO with standardized bilateral anterior oblique and PA fields were applied. New plans where then developed and optimized by employing additional contralateral parotid constraints at multiple defined dose levels. Using a step-wise iterative process, the volume-based constraints at each level were then further reduced until known target coverages were compromised. The newly developed plans were then compared to the original clinically approved plans using paired student t-testing. Results: All 24 newly optimized treatment plans maintained initial plan quality as compared to the approved plans, and the 98% prescription dose coverage to the CTV’s were not compromised. Representative DVH comparison is shown in FIGURE 1. The contralateral parotid doses were reduced at all levels of interest when systematic constraints were applied to V10, V20, V30 and V40Gy (All P<0.0001; TABLE 1). Overall, the mean contralateral parotid doses were reduced by 2.26 Gy on average, a ∼13% relative improvement. Conclusion: Applying systematic and volume-based contralateral parotid constraints for IMPT planning significantly reduced the dose at all dosimetric levels for patients with base of tongue cancer.« less

Clinical implementation of a knowledge based planning tool for prostate VMAT.

PubMed

Powis, Richard; Bird, Andrew; Brennan, Matthew; Hinks, Susan; Newman, Hannah; Reed, Katie; Sage, John; Webster, Gareth

2017-05-08

A knowledge based planning tool has been developed and implemented for prostate VMAT radiotherapy plans providing a target average rectum dose value based on previously achievable values for similar rectum/PTV overlap. The purpose of this planning tool is to highlight sub-optimal clinical plans and to improve plan quality and consistency. A historical cohort of 97 VMAT prostate plans was interrogated using a RayStation script and used to develop a local model for predicting optimum average rectum dose based on individual anatomy. A preliminary validation study was performed whereby historical plans identified as "optimal" and "sub-optimal" by the local model were replanned in a blinded study by four experienced planners and compared to the original clinical plan to assess whether any improvement in rectum dose was observed. The predictive model was then incorporated into a RayStation script and used as part of the clinical planning process. Planners were asked to use the script during planning to provide a patient specific prediction for optimum average rectum dose and to optimise the plan accordingly. Plans identified as "sub-optimal" in the validation study observed a statistically significant improvement in average rectum dose compared to the clinical plan when replanned whereas plans that were identified as "optimal" observed no improvement when replanned. This provided confidence that the local model can identify plans that were suboptimal in terms of rectal sparing. Clinical implementation of the knowledge based planning tool reduced the population-averaged mean rectum dose by 5.6Gy. There was a small but statistically significant increase in total MU and femoral head dose and a reduction in conformity index. These did not affect the clinical acceptability of the plans and no significant changes to other plan quality metrics were observed. The knowledge-based planning tool has enabled substantial reductions in population-averaged mean rectum dose for prostate VMAT patients. This suggests plans are improved when planners receive quantitative feedback on plan quality against historical data.

Optimal Chemotherapy for Leukemia: A Model-Based Strategy for Individualized Treatment

PubMed Central

Jayachandran, Devaraj; Rundell, Ann E.; Hannemann, Robert E.; Vik, Terry A.; Ramkrishna, Doraiswami

2014-01-01

Acute Lymphoblastic Leukemia, commonly known as ALL, is a predominant form of cancer during childhood. With the advent of modern healthcare support, the 5-year survival rate has been impressive in the recent past. However, long-term ALL survivors embattle several treatment-related medical and socio-economic complications due to excessive and inordinate chemotherapy doses received during treatment. In this work, we present a model-based approach to personalize 6-Mercaptopurine (6-MP) treatment for childhood ALL with a provision for incorporating the pharmacogenomic variations among patients. Semi-mechanistic mathematical models were developed and validated for i) 6-MP metabolism, ii) red blood cell mean corpuscular volume (MCV) dynamics, a surrogate marker for treatment efficacy, and iii) leukopenia, a major side-effect. With the constraint of getting limited data from clinics, a global sensitivity analysis based model reduction technique was employed to reduce the parameter space arising from semi-mechanistic models. The reduced, sensitive parameters were used to individualize the average patient model to a specific patient so as to minimize the model uncertainty. Models fit the data well and mimic diverse behavior observed among patients with minimum parameters. The model was validated with real patient data obtained from literature and Riley Hospital for Children in Indianapolis. Patient models were used to optimize the dose for an individual patient through nonlinear model predictive control. The implementation of our approach in clinical practice is realizable with routinely measured complete blood counts (CBC) and a few additional metabolite measurements. The proposed approach promises to achieve model-based individualized treatment to a specific patient, as opposed to a standard-dose-for-all, and to prescribe an optimal dose for a desired outcome with minimum side-effects. PMID:25310465

Reduced tyrosine kinase inhibitor dose is predicted to be as effective as standard dose in chronic myeloid leukemia: A simulation study based on phase 3 trial data.

PubMed

Fassoni, Artur C; Baldow, Christoph; Roeder, Ingo; Glauche, Ingmar

2018-06-28

Continuing tyrosine kinase inhibitor mediated targeting of the BCR-ABL1 oncoprotein is the standard therapy for chronic myeloid leukemia and allows for a sustained disease control in the majority of patients. While therapy cessation for patients appeared as a safe option for about half of the optimally responding patients, a systematic assessment of long-term tyrosine kinase inhibitor dose de-escalation is missing. We use a mathematical model to analyze and consistently describe biphasic treatment responses from tyrosine kinase inhibitor treated patients from two independent clinical phase-3 trials. Scale estimates reveal that drug efficiency determines the initial response while the long-term behavior is limited by the rare activation of leukemic stem cells. We use this mathematical framework to investigate the influence of different dosing regimens on the treatment outcome. We provide strong evidence suggesting that tyrosine kinase inhibitor dose de-escalation (at least 50%) does not lead to a reduction of long-term treatment efficiency for most patients, which have already achieved sustained remission, and maintains the secondary decline of BCR-ABL1 levels. We demonstrate that continuous BCR-ABL1 monitoring provides patient-specific predictions of an optimal reduced dose not decreasing the anti-leukemic effect on residual leukemic stem cells. Our results are consistent with the interim results of the DESTINY trial and provide clinically testable predictions. Our results suggest that dose halving should be considered as a long-term treatment option for well-responding chronic myeloid leukemia patients under continuing maintenance therapy with tyrosine kinase inhibitors. We emphasize the clinical potential of this approach to reduce treatment-related side-effects and therapy costs. Copyright © 2018, Ferrata Storti Foundation.

Radionuclide bone scan SPECT-CT: lowering the dose of CT significantly reduces radiation dose without impacting CT image quality

PubMed Central

Gupta, Sandeep Kumar; Trethewey, Scott; Brooker, Bree; Rutherford, Natalie; Diffey, Jenny; Viswanathan, Suresh; Attia, John

2017-01-01

The CT component of SPECT-CT is required for attenuation correction and anatomical localization of the uptake on SPECT but there is no guideline about the optimal CT acquisition parameters. In our department, a standard CT acquisition protocol was changed in 2013 to give lower radiation dose to the patient. In this study, we retrospectively compared the effects on patient dose as well as the CT image quality with current versus older CT protocols. Ninety nine consecutive patients [n=51 Standard dose ‘old’ protocol (SDP); n=48 lower dose ‘new’ protocol (LDP)] with lumbar spine SPECT-CT for bone scan were examined. The main differences between the two protocols were that SDP used 130 kVp tube voltage and reference current-time product of 70 mAs whereas the LDP used 110 kVp and 40 mAs respectively. Various quantitative parameters from the CT images were obtained and the images were also rated blindly by two experienced nuclear medicine physicians for bony definition and noise. The mean calculated dose length product of the LDP group (121.5±39.6 mGy.cm) was significantly lower compared to the SDP group patients (266.9±96.9 mGy.cm; P<0.0001). This translated into a significant reduction in the mean effective dose to 1.8 mSv from 4.0 mSv. The physicians reported better CT image quality for the bony structures in LDP group although for soft tissue structures, the SDP group had better image quality. The optimized new CT acquisition protocol significantly reduced the radiation dose to the patient and in-fact improved CT image quality for the assessment of bony structures. PMID:28533938

Integrated beam orientation and scanning-spot optimization in intensity-modulated proton therapy for brain and unilateral head and neck tumors.

PubMed

Gu, Wenbo; O'Connor, Daniel; Nguyen, Dan; Yu, Victoria Y; Ruan, Dan; Dong, Lei; Sheng, Ke

2018-04-01

Intensity-Modulated Proton Therapy (IMPT) is the state-of-the-art method of delivering proton radiotherapy. Previous research has been mainly focused on optimization of scanning spots with manually selected beam angles. Due to the computational complexity, the potential benefit of simultaneously optimizing beam orientations and spot pattern could not be realized. In this study, we developed a novel integrated beam orientation optimization (BOO) and scanning-spot optimization algorithm for intensity-modulated proton therapy (IMPT). A brain chordoma and three unilateral head-and-neck patients with a maximal target size of 112.49 cm 3 were included in this study. A total number of 1162 noncoplanar candidate beams evenly distributed across 4π steradians were included in the optimization. For each candidate beam, the pencil-beam doses of all scanning spots covering the PTV and a margin were calculated. The beam angle selection and spot intensity optimization problem was formulated to include three terms: a dose fidelity term to penalize the deviation of PTV and OAR doses from ideal dose distribution; an L1-norm sparsity term to reduce the number of active spots and improve delivery efficiency; a group sparsity term to control the number of active beams between 2 and 4. For the group sparsity term, convex L2,1-norm and nonconvex L2,1/2-norm were tested. For the dose fidelity term, both quadratic function and linearized equivalent uniform dose (LEUD) cost function were implemented. The optimization problem was solved using the Fast Iterative Shrinkage-Thresholding Algorithm (FISTA). The IMPT BOO method was tested on three head-and-neck patients and one skull base chordoma patient. The results were compared with IMPT plans created using column generation selected beams or manually selected beams. The L2,1-norm plan selected spatially aggregated beams, indicating potential degeneracy using this norm. L2,1/2-norm was able to select spatially separated beams and achieve smaller deviation from the ideal dose. In the L2,1/2-norm plans, the [mean dose, maximum dose] of OAR were reduced by an average of [2.38%, 4.24%] and[2.32%, 3.76%] of the prescription dose for the quadratic and LEUD cost function, respectively, compared with the IMPT plan using manual beam selection while maintaining the same PTV coverage. The L2,1/2 group sparsity plans were dosimetrically superior to the column generation plans as well. Besides beam orientation selection, spot sparsification was observed. Generally, with the quadratic cost function, 30%~60% spots in the selected beams remained active. With the LEUD cost function, the percentages of active spots were in the range of 35%~85%.The BOO-IMPT run time was approximately 20 min. This work shows the first IMPT approach integrating noncoplanar BOO and scanning-spot optimization in a single mathematical framework. This method is computationally efficient, dosimetrically superior and produces delivery-friendly IMPT plans. © 2018 American Association of Physicists in Medicine.

HEXAMETHONIUM AND HYDRALAZINE HYDROCHLORIDE—For Treatment of Hypertension

PubMed Central

Stuppy, Laurence J.

1954-01-01

Twenty-one patients have been treated for hypertension with oral doses of hexamethonium salts, Apresoline® or combinations of both. Three of 18 patients had good or excellent response to hexamethonium alone. Five of 13 treated with hexamethonium salts plus Apresoline had good or excellent results, as did 8 of 14 treated with Apresoline alone. The addition of very small doses of hexamethonium chloride to optimal doses of Apresoline improved the effect of the Apresoline in three patients. Postural hypotension and constipation due to hexamethonium were the most serious undesirable effects. PMID:13126825

Sexual Function and the use of Medical Devices or Drugs to Optimize Potency after Prostate Brachytherapy

PubMed Central

Whaley, J. Taylor; Levy, Lawrence B.; Swanson, David A.; Pugh, Thomas J.; Kudchadker, Rajat J.; Bruno, Teresa L.; Frank, Steven J.

2013-01-01

Purpose Prospective evaluation of sexual outcomes after prostate brachytherapy with iodine-125 seeds as monotherapy at a tertiary cancer care center. Methods and Materials Subjects were 129 men with prostate cancer with I-125 seed implants (prescribed dose, 145 Gy) without supplemental hormonal or external beam radiation therapy. Sexual function, potency, and bother were prospectively assessed at baseline and at 1, 4, 8, and 12 months using validated quality-of-life self-assessment surveys. Postimplant dosimetry values, including dose to 10% of the penile bulb (D10), D20, D33, D50, D75, D90, and penile-volume receiving 100% of the prescribed dose (V100) were calculated. Results At baseline, 56% of patients recorded having optimal erections; at 1 year, 62% of patients with baseline erectile function maintained optimal potency, 58% of whom with medically prescribed sexual aids or drugs. Variables associated with pretreatment-to-posttreatment decline in potency were time after implant (p=0.04) and age (p=0.01). Decline in urinary function may have been related to decline in potency. At 1 year, 69% of potent patients younger than 70 years maintained optimal potency, whereas 31% of patients over 70 maintained optimal potency (p=0.02). Diabetes was related to a decline in potency (p=0.05), but neither smoking nor hypertension were. For patients with optimal potency at baseline, mean sexual bother scores had declined significantly at 1 year (p<0.01). Sexual potency, sexual function, and sexual bother scores failed to correlate with any dosimetric variable tested. Conclusions Erections firm enough for intercourse can be achieved at 1 year after treatment, but most men will require medical aids to optimize potency. Although younger men were better able to maintain erections firm enough for intercourse than older men, there was no correlation between potency, sexual function, or sexual bother and penile bulb dosimetry. PMID:22300559

Sexual function and the use of medical devices or drugs to optimize potency after prostate brachytherapy.

PubMed

Whaley, J Taylor; Levy, Lawrence B; Swanson, David A; Pugh, Thomas J; Kudchadker, Rajat J; Bruno, Teresa L; Frank, Steven J

2012-04-01

Prospective evaluation of sexual outcomes after prostate brachytherapy with iodine-125 seeds as monotherapy at a tertiary cancer care center. Subjects were 129 men with prostate cancer with I-125 seed implants (prescribed dose, 145 Gy) without supplemental hormonal or external beam radiation therapy. Sexual function, potency, and bother were prospectively assessed at baseline and at 1, 4, 8, and 12 months using validated quality-of-life self-assessment surveys. Postimplant dosimetry values, including dose to 10% of the penile bulb (D10), D20, D33, D50, D75, D90, and penile volume receiving 100% of the prescribed dose (V100) were calculated. At baseline, 56% of patients recorded having optimal erections; at 1 year, 62% of patients with baseline erectile function maintained optimal potency, 58% of whom with medically prescribed sexual aids or drugs. Variables associated with pretreatment-to-posttreatment decline in potency were time after implant (p = 0.04) and age (p = 0.01). Decline in urinary function may have been related to decline in potency. At 1 year, 69% of potent patients younger than 70 years maintained optimal potency, whereas 31% of patients older than 70 maintained optimal potency (p = 0.02). Diabetes was related to a decline in potency (p = 0.05), but neither smoking nor hypertension were. For patients with optimal potency at baseline, mean sexual bother scores had declined significantly at 1 year (p < 0.01). Sexual potency, sexual function, and sexual bother scores failed to correlate with any dosimetric variable tested. Erections firm enough for intercourse can be achieved at 1 year after treatment, but most men will require medical aids to optimize potency. Although younger men were better able to maintain erections firm enough for intercourse than older men, there was no correlation between potency, sexual function, or sexual bother and penile bulb dosimetry. Copyright © 2012 Elsevier Inc. All rights reserved.

Sexual Function and the Use of Medical Devices or Drugs to Optimize Potency After Prostate Brachytherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Whaley, J. Taylor; Levy, Lawrence B.; Swanson, David A.

Purpose: Prospective evaluation of sexual outcomes after prostate brachytherapy with iodine-125 seeds as monotherapy at a tertiary cancer care center. Methods and Materials: Subjects were 129 men with prostate cancer with I-125 seed implants (prescribed dose, 145 Gy) without supplemental hormonal or external beam radiation therapy. Sexual function, potency, and bother were prospectively assessed at baseline and at 1, 4, 8, and 12 months using validated quality-of-life self-assessment surveys. Postimplant dosimetry values, including dose to 10% of the penile bulb (D10), D20, D33, D50, D75, D90, and penile volume receiving 100% of the prescribed dose (V100) were calculated. Results: Atmore » baseline, 56% of patients recorded having optimal erections; at 1 year, 62% of patients with baseline erectile function maintained optimal potency, 58% of whom with medically prescribed sexual aids or drugs. Variables associated with pretreatment-to-posttreatment decline in potency were time after implant (p = 0.04) and age (p = 0.01). Decline in urinary function may have been related to decline in potency. At 1 year, 69% of potent patients younger than 70 years maintained optimal potency, whereas 31% of patients older than 70 maintained optimal potency (p = 0.02). Diabetes was related to a decline in potency (p = 0.05), but neither smoking nor hypertension were. For patients with optimal potency at baseline, mean sexual bother scores had declined significantly at 1 year (p < 0.01). Sexual potency, sexual function, and sexual bother scores failed to correlate with any dosimetric variable tested. Conclusions: Erections firm enough for intercourse can be achieved at 1 year after treatment, but most men will require medical aids to optimize potency. Although younger men were better able to maintain erections firm enough for intercourse than older men, there was no correlation between potency, sexual function, or sexual bother and penile bulb dosimetry.« less

Robust optimization in lung treatment plans accounting for geometric uncertainty.

PubMed

Zhang, Xin; Rong, Yi; Morrill, Steven; Fang, Jian; Narayanasamy, Ganesh; Galhardo, Edvaldo; Maraboyina, Sanjay; Croft, Christopher; Xia, Fen; Penagaricano, Jose

2018-05-01

Robust optimization generates scenario-based plans by a minimax optimization method to find optimal scenario for the trade-off between target coverage robustness and organ-at-risk (OAR) sparing. In this study, 20 lung cancer patients with tumors located at various anatomical regions within the lungs were selected and robust optimization photon treatment plans including intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) plans were generated. The plan robustness was analyzed using perturbed doses with setup error boundary of ±3 mm in anterior/posterior (AP), ±3 mm in left/right (LR), and ±5 mm in inferior/superior (IS) directions from isocenter. Perturbed doses for D 99 , D 98 , and D 95 were computed from six shifted isocenter plans to evaluate plan robustness. Dosimetric study was performed to compare the internal target volume-based robust optimization plans (ITV-IMRT and ITV-VMAT) and conventional PTV margin-based plans (PTV-IMRT and PTV-VMAT). The dosimetric comparison parameters were: ITV target mean dose (D mean ), R 95 (D 95 /D prescription ), Paddick's conformity index (CI), homogeneity index (HI), monitor unit (MU), and OAR doses including lung (D mean , V 20 Gy and V 15 Gy ), chest wall, heart, esophagus, and maximum cord doses. A comparison of optimization results showed the robust optimization plan had better ITV dose coverage, better CI, worse HI, and lower OAR doses than conventional PTV margin-based plans. Plan robustness evaluation showed that the perturbed doses of D 99 , D 98 , and D 95 were all satisfied at least 99% of the ITV to received 95% of prescription doses. It was also observed that PTV margin-based plans had higher MU than robust optimization plans. The results also showed robust optimization can generate plans that offer increased OAR sparing, especially for normal lungs and OARs near or abutting the target. Weak correlation was found between normal lung dose and target size, and no other correlation was observed in this study. © 2018 University of Arkansas for Medical Sciences. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

Cherenkov imaging method for rapid optimization of clinical treatment geometry in total skin electron beam therapy

PubMed Central

Zhang, Rongxiao; Gladstone, David J.; Williams, Benjamin B.; Glaser, Adam K.; Pogue, Brian W.; Jarvis, Lesley A.

2016-01-01

Purpose: A method was developed utilizing Cherenkov imaging for rapid and thorough determination of the two gantry angles that produce the most uniform treatment plane during dual-field total skin electron beam therapy (TSET). Methods: Cherenkov imaging was implemented to gather 2D measurements of relative surface dose from 6 MeV electron beams on a white polyethylene sheet. An intensified charge-coupled device camera time-gated to the Linac was used for Cherenkov emission imaging at sixty-two different gantry angles (1° increments, from 239.5° to 300.5°). Following a modified Stanford TSET technique, which uses two fields per patient position for full body coverage, composite images were created as the sum of two beam images on the sheet; each angle pair was evaluated for minimum variation across the patient region of interest. Cherenkov versus dose correlation was verified with ionization chamber measurements. The process was repeated at source to surface distance (SSD) = 441, 370.5, and 300 cm to determine optimal angle spread for varying room geometries. In addition, three patients receiving TSET using a modified Stanford six-dual field technique with 6 MeV electron beams at SSD = 441 cm were imaged during treatment. Results: As in previous studies, Cherenkov intensity was shown to directly correlate with dose for homogenous flat phantoms (R2 = 0.93), making Cherenkov imaging an appropriate candidate to assess and optimize TSET setup geometry. This method provided dense 2D images allowing 1891 possible treatment geometries to be comprehensively analyzed from one data set of 62 single images. Gantry angles historically used for TSET at their institution were 255.5° and 284.5° at SSD = 441 cm; however, the angles optimized for maximum homogeneity were found to be 252.5° and 287.5° (+6° increase in angle spread). Ionization chamber measurements confirmed improvement in dose homogeneity across the treatment field from a range of 24.4% at the initial angles, to only 9.8% with the angles optimized. A linear relationship between angle spread and SSD was observed, ranging from 35° at 441 cm, to 39° at 300 cm, with no significant variation in percent-depth dose at midline (R2 = 0.998). For patient studies, factors influencing in vivo correlation between Cherenkov intensity and measured surface dose are still being investigated. Conclusions: Cherenkov intensity correlates to relative dose measured at depth of maximum dose in a uniform, flat phantom. Imaging of phantoms can thus be used to analyze and optimize TSET treatment geometry more extensively and rapidly than thermoluminescent dosimeters or ionization chambers. This work suggests that there could be an expanded role for Cherenkov imaging as a tool to efficiently improve treatment protocols and as a potential verification tool for routine monitoring of unique patient treatments. PMID:26843259

Cherenkov imaging method for rapid optimization of clinical treatment geometry in total skin electron beam therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Andreozzi, Jacqueline M., E-mail: Jacqueline.M.Andreozzi.th@dartmouth.edu, E-mail: Lesley.A.Jarvis@hitchcock.org; Glaser, Adam K.; Zhang, Rongxiao

2016-02-15

Purpose: A method was developed utilizing Cherenkov imaging for rapid and thorough determination of the two gantry angles that produce the most uniform treatment plane during dual-field total skin electron beam therapy (TSET). Methods: Cherenkov imaging was implemented to gather 2D measurements of relative surface dose from 6 MeV electron beams on a white polyethylene sheet. An intensified charge-coupled device camera time-gated to the Linac was used for Cherenkov emission imaging at sixty-two different gantry angles (1° increments, from 239.5° to 300.5°). Following a modified Stanford TSET technique, which uses two fields per patient position for full body coverage, compositemore » images were created as the sum of two beam images on the sheet; each angle pair was evaluated for minimum variation across the patient region of interest. Cherenkov versus dose correlation was verified with ionization chamber measurements. The process was repeated at source to surface distance (SSD) = 441, 370.5, and 300 cm to determine optimal angle spread for varying room geometries. In addition, three patients receiving TSET using a modified Stanford six-dual field technique with 6 MeV electron beams at SSD = 441 cm were imaged during treatment. Results: As in previous studies, Cherenkov intensity was shown to directly correlate with dose for homogenous flat phantoms (R{sup 2} = 0.93), making Cherenkov imaging an appropriate candidate to assess and optimize TSET setup geometry. This method provided dense 2D images allowing 1891 possible treatment geometries to be comprehensively analyzed from one data set of 62 single images. Gantry angles historically used for TSET at their institution were 255.5° and 284.5° at SSD = 441 cm; however, the angles optimized for maximum homogeneity were found to be 252.5° and 287.5° (+6° increase in angle spread). Ionization chamber measurements confirmed improvement in dose homogeneity across the treatment field from a range of 24.4% at the initial angles, to only 9.8% with the angles optimized. A linear relationship between angle spread and SSD was observed, ranging from 35° at 441 cm, to 39° at 300 cm, with no significant variation in percent-depth dose at midline (R{sup 2} = 0.998). For patient studies, factors influencing in vivo correlation between Cherenkov intensity and measured surface dose are still being investigated. Conclusions: Cherenkov intensity correlates to relative dose measured at depth of maximum dose in a uniform, flat phantom. Imaging of phantoms can thus be used to analyze and optimize TSET treatment geometry more extensively and rapidly than thermoluminescent dosimeters or ionization chambers. This work suggests that there could be an expanded role for Cherenkov imaging as a tool to efficiently improve treatment protocols and as a potential verification tool for routine monitoring of unique patient treatments.« less

An automated optimization tool for high-dose-rate (HDR) prostate brachytherapy with divergent needle pattern

NASA Astrophysics Data System (ADS)

Borot de Battisti, M.; Maenhout, M.; de Senneville, B. Denis; Hautvast, G.; Binnekamp, D.; Lagendijk, J. J. W.; van Vulpen, M.; Moerland, M. A.

2015-10-01

Focal high-dose-rate (HDR) for prostate cancer has gained increasing interest as an alternative to whole gland therapy as it may contribute to the reduction of treatment related toxicity. For focal treatment, optimal needle guidance and placement is warranted. This can be achieved under MR guidance. However, MR-guided needle placement is currently not possible due to space restrictions in the closed MR bore. To overcome this problem, a MR-compatible, single-divergent needle-implant robotic device is under development at the University Medical Centre, Utrecht: placed between the legs of the patient inside the MR bore, this robot will tap the needle in a divergent pattern from a single rotation point into the tissue. This rotation point is just beneath the perineal skin to have access to the focal prostate tumor lesion. Currently, there is no treatment planning system commercially available which allows optimization of the dose distribution with such needle arrangement. The aim of this work is to develop an automatic inverse dose planning optimization tool for focal HDR prostate brachytherapy with needle insertions in a divergent configuration. A complete optimizer workflow is proposed which includes the determination of (1) the position of the center of rotation, (2) the needle angulations and (3) the dwell times. Unlike most currently used optimizers, no prior selection or adjustment of input parameters such as minimum or maximum dose or weight coefficients for treatment region and organs at risk is required. To test this optimizer, a planning study was performed on ten patients (treatment volumes ranged from 8.5 cm3to 23.3 cm3) by using 2-14 needle insertions. The total computation time of the optimizer workflow was below 20 min and a clinically acceptable plan was reached on average using only four needle insertions.

Expected treatment dose construction and adaptive inverse planning optimization: Implementation for offline head and neck cancer adaptive radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yan Di; Liang Jian

Purpose: To construct expected treatment dose for adaptive inverse planning optimization, and evaluate it on head and neck (h and n) cancer adaptive treatment modification. Methods: Adaptive inverse planning engine was developed and integrated in our in-house adaptive treatment control system. The adaptive inverse planning engine includes an expected treatment dose constructed using the daily cone beam (CB) CT images in its objective and constrains. Feasibility of the adaptive inverse planning optimization was evaluated retrospectively using daily CBCT images obtained from the image guided IMRT treatment of 19 h and n cancer patients. Adaptive treatment modification strategies with respect tomore » the time and the number of adaptive inverse planning optimization during the treatment course were evaluated using the cumulative treatment dose in organs of interest constructed using all daily CBCT images. Results: Expected treatment dose was constructed to include both the delivered dose, to date, and the estimated dose for the remaining treatment during the adaptive treatment course. It was used in treatment evaluation, as well as in constructing the objective and constraints for adaptive inverse planning optimization. The optimization engine is feasible to perform planning optimization based on preassigned treatment modification schedule. Compared to the conventional IMRT, the adaptive treatment for h and n cancer illustrated clear dose-volume improvement for all critical normal organs. The dose-volume reductions of right and left parotid glands, spine cord, brain stem and mandible were (17 {+-} 6)%, (14 {+-} 6)%, (11 {+-} 6)%, (12 {+-} 8)%, and (5 {+-} 3)% respectively with the single adaptive modification performed after the second treatment week; (24 {+-} 6)%, (22 {+-} 8)%, (21 {+-} 5)%, (19 {+-} 8)%, and (10 {+-} 6)% with three weekly modifications; and (28 {+-} 5)%, (25 {+-} 9)%, (26 {+-} 5)%, (24 {+-} 8)%, and (15 {+-} 9)% with five weekly modifications. Conclusions: Adaptive treatment modification can be implemented including the expected treatment dose in the adaptive inverse planning optimization. The retrospective evaluation results demonstrate that utilizing the weekly adaptive inverse planning optimization, the dose distribution of h and n cancer treatment can be largely improved.« less

Radiotherapy Dose Fractionation under Parameter Uncertainty

NASA Astrophysics Data System (ADS)

Davison, Matt; Kim, Daero; Keller, Harald

2011-11-01

In radiotherapy, radiation is directed to damage a tumor while avoiding surrounding healthy tissue. Tradeoffs ensue because dose cannot be exactly shaped to the tumor. It is particularly important to ensure that sensitive biological structures near the tumor are not damaged more than a certain amount. Biological tissue is known to have a nonlinear response to incident radiation. The linear quadratic dose response model, which requires the specification of two clinically and experimentally observed response coefficients, is commonly used to model this effect. This model yields an optimization problem giving two different types of optimal dose sequences (fractionation schedules). Which fractionation schedule is preferred depends on the response coefficients. These coefficients are uncertainly known and may differ from patient to patient. Because of this not only the expected outcomes but also the uncertainty around these outcomes are important, and it might not be prudent to select the strategy with the best expected outcome.

Internal photon and electron dosimetry of the newborn patient—a hybrid computational phantom study

NASA Astrophysics Data System (ADS)

Wayson, Michael; Lee, Choonsik; Sgouros, George; Treves, S. Ted; Frey, Eric; Bolch, Wesley E.

2012-03-01

Estimates of radiation absorbed dose to organs of the nuclear medicine patient are a requirement for administered activity optimization and for stochastic risk assessment. Pediatric patients, and in particular the newborn child, represent that portion of the patient population where such optimization studies are most crucial owing to the enhanced tissue radiosensitivities and longer life expectancies of this patient subpopulation. In cases where whole-body CT imaging is not available, phantom-based calculations of radionuclide S values—absorbed dose to a target tissue per nuclear transformation in a source tissue—are required for dose and risk evaluation. In this study, a comprehensive model of electron and photon dosimetry of the reference newborn child is presented based on a high-resolution hybrid-voxel phantom from the University of Florida (UF) patient model series. Values of photon specific absorbed fraction (SAF) were assembled for both the reference male and female newborn using the radiation transport code MCNPX v2.6. Values of electron SAF were assembled in a unique and time-efficient manner whereby the collisional and radiative components of organ dose--for both self- and cross-dose terms—were computed separately. Dose to the newborn skeletal tissues were assessed via fluence-to-dose response functions reported for the first time in this study. Values of photon and electron SAFs were used to assemble a complete set of S values for some 16 radionuclides commonly associated with molecular imaging of the newborn. These values were then compared to those available in the OLINDA/EXM software. S value ratios for organ self-dose ranged from 0.46 to 1.42, while similar ratios for organ cross-dose varied from a low of 0.04 to a high of 3.49. These large discrepancies are due in large part to the simplistic organ modeling in the stylized newborn model used in the OLINDA/EXM software. A comprehensive model of internal dosimetry is presented in this study for the newborn nuclear medicine patient based upon the UF hybrid computational phantom. Photon dose response functions, photon and electron SAFs, and tables of radionuclide S values for the newborn child--both male and female--are given in a series of four electronic annexes available at stacks.iop.org/pmb/57/1433/mmedia. These values can be applied to optimization studies of image quality and stochastic risk for this most vulnerable class of pediatric patients.

Choosing the optimal dose in sublingual immunotherapy: Rationale for the 300 index of reactivity dose.

PubMed

Demoly, Pascal; Passalacqua, Gianni; Calderon, Moises A; Yalaoui, Tarik

2015-01-01

Sublingual immunotherapy (SLIT) is an effective and well-tolerated method of treating allergic respiratory diseases associated with seasonal and perennial allergens. In contrast to the subcutaneous route, SLIT requires a much greater amount of antigen to achieve a clinical effect. Many studies have shown that SLIT involves a dose-response relationship, and therefore it is important to use a proven clinically effective dose from the onset of treatment, because low doses are ineffective and very high doses may increase the risk of side effects. A well-defined standardization of allergen content is also crucial to ensure consistent quality, potency and appropriate immunomodulatory action of the SLIT product. Several methods of measuring antigenicity are used by manufacturers of SLIT products, including the index of reactivity (IR), standardized quality tablet unit, and bioequivalent allergy unit. A large body of evidence has established the 300 IR dose of SLIT as offering optimal efficacy and tolerability for allergic rhinitis due to grass and birch pollen and HDM, and HDM-induced moderate, persistent allergic asthma. The 300 IR dose also offers consistency of dosing across a variety of different allergens, and is associated with higher rates of adherence and patient satisfaction. Studies in patients with grass pollen allergies showed that the 300 IR dose has a rapid onset of action, is effective in both adults and children in the short term and, when administered pre-coseasonally in the long term, and maintains the clinical benefit, even after cessation of treatment. In patients with HDM-associated AR and/or asthma, the 300 IR dose also demonstrated significant improvements in symptoms and quality of life, and significantly decreased use of symptomatic medication. The 300 IR dose is well tolerated, with adverse events generally being of mild or moderate severity, declining in frequency and severity over time and in the subsequent courses. We discuss herein the most important factors that affect the selection of the optimal dose of SLIT with natural allergens, and review the rationale and evidence supporting the use of the 300 IR dose.

High Atomic Number Contrast Media Offer Potential for Radiation Dose Reduction in Contrast-Enhanced Computed Tomography.

PubMed

Roessler, Ann-Christin; Hupfer, Martin; Kolditz, Daniel; Jost, Gregor; Pietsch, Hubertus; Kalender, Willi A

2016-04-01

Spectral optimization of x-ray computed tomography (CT) has led to substantial radiation dose reduction in contrast-enhanced CT studies using standard iodinated contrast media. The purpose of this study was to analyze the potential for further dose reduction using high-atomic-number elements such as hafnium and tungsten. As in previous studies, spectra were determined for which the patient dose necessary to provide a given contrast-to-noise ratio (CNR) is minimized. We used 2 different quasi-anthropomorphic phantoms representing the liver cross-section of a normal adult and an obese adult patient with the lateral widths of 360 and 460 mm and anterior-posterior heights of 200 and 300 mm, respectively. We simulated and measured on 2 different scanners with x-ray spectra from 80 to 140 kV and from 70 to 150 kV, respectively. We determined the contrast for iodine-, hafnium-, and tungsten-based contrast media, the noise, and 3-dimensional dose distributions at all available tube voltages by measurements and by simulations. The dose-weighted CNR was determined as optimization parameter. Simulations and measurements were in good agreement regarding their dependence on energy for all parameters investigated. Hafnium provided the best performance for normal and for obese patient phantoms, indicating a dose reduction potential of 30% for normal and 50% for obese patients at 120 kV compared with iodine; this advantage increased further with higher kV values. Dose-weighted CNR values for tungsten were always slightly below the hafnium results. Iodine proved to be the superior choice at voltage values of 80 kV and below. Hafnium and tungsten both seem to be candidates for contrast-medium-enhanced CT of normal and obese adult patients with strongly reduced radiation dose at unimpaired image quality. Computed tomography examinations of obese patients will decrease in dose for higher kV values.

Restless legs syndrome augmentation among Japanese patients receiving pramipexole therapy: Rate and risk factors in a retrospective study

PubMed Central

Takahashi, Masayoshi; Nishida, Shingo; Nakamura, Masaki; Kobayashi, Mina; Matsui, Kentaro; Ito, Eiki; Usui, Akira; Inoue, Yuichi

2017-01-01

To investigate the rate of and risk factors for restless legs syndrome (RLS) augmentation in Japanese patients receiving pramipexole (PPX) treatment. Records of 231 consecutive patients with idiopathic RLS who received PPX therapy for more than one month in a single sleep disorder center were analyzed retrospectively. Augmentation was diagnosed based on the Max Planck Institute criteria; associated factors were identified by logistic regression analysis. Mean age at PPX initiation was 60.6 ± 14.9 years and mean treatment duration was 48.5 ± 26.4 months. Augmentation was diagnosed in 21 patients (9.1%). Daily PPX dose and treatment duration were significantly associated with augmentation. By analyzing the receiver operating characteristic curve, a PPX dose of 0.375 mg/day was found to be the optimal cut-off value for predicting augmentation. After stratifying patients according to PPX treatment duration, at median treatment duration of 46 months, optimal cut-off values for daily doses were 0.375 and 0.500 mg/day for <46 months and ≥46 months of treatment, respectively. The RLS augmentation with PPX treatment in Japanese patients was occurred at rate of 9.1%, being quite compatible with previously reported rates in Caucasian patients. The symptom could appear within a relatively short period after starting the treatment in possibly vulnerable cases even with a smaller drug dose. Our results support the importance of keeping doses of PPX low throughout the RLS treatment course to prevent augmentation. PMID:28264052

Clinical Implementation of a Model-Based In Vivo Dose Verification System for Stereotactic Body Radiation Therapy-Volumetric Modulated Arc Therapy Treatments Using the Electronic Portal Imaging Device.

PubMed

McCowan, Peter M; Asuni, Ganiyu; Van Uytven, Eric; VanBeek, Timothy; McCurdy, Boyd M C; Loewen, Shaun K; Ahmed, Naseer; Bashir, Bashir; Butler, James B; Chowdhury, Amitava; Dubey, Arbind; Leylek, Ahmet; Nashed, Maged

2017-04-01

To report findings from an in vivo dosimetry program implemented for all stereotactic body radiation therapy patients over a 31-month period and discuss the value and challenges of utilizing in vivo electronic portal imaging device (EPID) dosimetry clinically. From December 2013 to July 2016, 117 stereotactic body radiation therapy-volumetric modulated arc therapy patients (100 lung, 15 spine, and 2 liver) underwent 602 EPID-based in vivo dose verification events. A developed model-based dose reconstruction algorithm calculates the 3-dimensional dose distribution to the patient by back-projecting the primary fluence measured by the EPID during treatment. The EPID frame-averaging was optimized in June 2015. For each treatment, a 3%/3-mm γ comparison between our EPID-derived dose and the Eclipse AcurosXB-predicted dose to the planning target volume (PTV) and the ≥20% isodose volume were performed. Alert levels were defined as γ pass rates <85% (lung and liver) and <80% (spine). Investigations were carried out for all fractions exceeding the alert level and were classified as follows: EPID-related, algorithmic, patient setup, anatomic change, or unknown/unidentified errors. The percentages of fractions exceeding the alert levels were 22.6% for lung before frame-average optimization and 8.0% for lung, 20.0% for spine, and 10.0% for liver after frame-average optimization. Overall, mean (± standard deviation) planning target volume γ pass rates were 90.7% ± 9.2%, 87.0% ± 9.3%, and 91.2% ± 3.4% for the lung, spine, and liver patients, respectively. Results from the clinical implementation of our model-based in vivo dose verification method using on-treatment EPID images is reported. The method is demonstrated to be valuable for routine clinical use for verifying delivered dose as well as for detecting errors. Copyright © 2017 Elsevier Inc. All rights reserved.

Clinical Implementation of a Model-Based In Vivo Dose Verification System for Stereotactic Body Radiation Therapy–Volumetric Modulated Arc Therapy Treatments Using the Electronic Portal Imaging Device

DOE Office of Scientific and Technical Information (OSTI.GOV)

McCowan, Peter M., E-mail: pmccowan@cancercare.mb.ca; Asuni, Ganiyu; Van Uytven, Eric

Purpose: To report findings from an in vivo dosimetry program implemented for all stereotactic body radiation therapy patients over a 31-month period and discuss the value and challenges of utilizing in vivo electronic portal imaging device (EPID) dosimetry clinically. Methods and Materials: From December 2013 to July 2016, 117 stereotactic body radiation therapy–volumetric modulated arc therapy patients (100 lung, 15 spine, and 2 liver) underwent 602 EPID-based in vivo dose verification events. A developed model-based dose reconstruction algorithm calculates the 3-dimensional dose distribution to the patient by back-projecting the primary fluence measured by the EPID during treatment. The EPID frame-averaging was optimized in Junemore » 2015. For each treatment, a 3%/3-mm γ comparison between our EPID-derived dose and the Eclipse AcurosXB–predicted dose to the planning target volume (PTV) and the ≥20% isodose volume were performed. Alert levels were defined as γ pass rates <85% (lung and liver) and <80% (spine). Investigations were carried out for all fractions exceeding the alert level and were classified as follows: EPID-related, algorithmic, patient setup, anatomic change, or unknown/unidentified errors. Results: The percentages of fractions exceeding the alert levels were 22.6% for lung before frame-average optimization and 8.0% for lung, 20.0% for spine, and 10.0% for liver after frame-average optimization. Overall, mean (± standard deviation) planning target volume γ pass rates were 90.7% ± 9.2%, 87.0% ± 9.3%, and 91.2% ± 3.4% for the lung, spine, and liver patients, respectively. Conclusions: Results from the clinical implementation of our model-based in vivo dose verification method using on-treatment EPID images is reported. The method is demonstrated to be valuable for routine clinical use for verifying delivered dose as well as for detecting errors.« less

Emerging Techniques for Dose Optimization in Abdominal CT

PubMed Central

Platt, Joel F.; Goodsitt, Mitchell M.; Al-Hawary, Mahmoud M.; Maturen, Katherine E.; Wasnik, Ashish P.; Pandya, Amit

2014-01-01

Recent advances in computed tomographic (CT) scanning technique such as automated tube current modulation (ATCM), optimized x-ray tube voltage, and better use of iterative image reconstruction have allowed maintenance of good CT image quality with reduced radiation dose. ATCM varies the tube current during scanning to account for differences in patient attenuation, ensuring a more homogeneous image quality, although selection of the appropriate image quality parameter is essential for achieving optimal dose reduction. Reducing the x-ray tube voltage is best suited for evaluating iodinated structures, since the effective energy of the x-ray beam will be closer to the k-edge of iodine, resulting in a higher attenuation for the iodine. The optimal kilovoltage for a CT study should be chosen on the basis of imaging task and patient habitus. The aim of iterative image reconstruction is to identify factors that contribute to noise on CT images with use of statistical models of noise (statistical iterative reconstruction) and selective removal of noise to improve image quality. The degree of noise suppression achieved with statistical iterative reconstruction can be customized to minimize the effect of altered image quality on CT images. Unlike with statistical iterative reconstruction, model-based iterative reconstruction algorithms model both the statistical noise and the physical acquisition process, allowing CT to be performed with further reduction in radiation dose without an increase in image noise or loss of spatial resolution. Understanding these recently developed scanning techniques is essential for optimization of imaging protocols designed to achieve the desired image quality with a reduced dose. © RSNA, 2014 PMID:24428277

Treatment regimens of classical and newer taxanes.

PubMed

Joerger, Markus

2016-02-01

The classical taxanes (paclitaxel, docetaxel), the newer taxane cabazitaxel and the nanoparticle-bound nab-paclitaxel are among the most widely used anticancer drugs. The taxanes share the characteristics of extensive hepatic metabolism and biliary excretion, the need for dose adaptation in patients with liver dysfunction, and a substantial pharmacokinetic variability even after taking into account known covariates. Data from clinical studies suggest that optimal scheduling of the taxanes is dependent not only on the specific taxane compound, but also on the tumor type and line of treatment. Still, the optimal dosing regimen (weekly vs 3 weekly) and optimal dose of the taxanes are controversial, as is the value of pharmacological personalization of taxane dosing. In this article, an overview is given on the pharmacological properties of the taxanes, including metabolism, pharmacokinetics-pharmacodynamics and aspects in the clinical use of taxanes. The latter includes the ongoing debate on the most active and safe regimen, the recommended initial dose and the issue of therapeutic drug dosing.

Phase 2 Randomized, Dose-Ranging Study of Oxymetazoline Cream for Treatment of Persistent Facial Erythema Associated With Rosacea.

PubMed

DuBois, Janet; Dover, Jeffrey S; Jones, Terry M; Weiss, Robert A; Berk, David R; Ahluwalia, Gurpreet

2018-03-01

Rosacea is a chronic dermatologic condition with limited treatment options. This phase 2 study evaluated the optimal oxymetazoline dosing regimen in patients with moderate to severe persistent facial erythema of rosacea. Patients were randomly assigned to oxymetazoline cream, 0.5%, 1.0%, or 1.5%, or vehicle, administered once daily (QD) or twice daily (BID) for 28 consecutive days. The primary efficacy endpoint was the proportion of patients with ≥2-grade improvement from baseline on the Clinician Erythema Assessment (CEA) and the Subject Self-Assessment of erythema (SSA-1) on day 28. Safety assessments included treatment-emergent adverse events and dermal tolerability. A total of 356 patients were treated (mean age, 50.0 years; 80.1% female). The proportions of patients achieving the primary endpoint were significantly higher with oxymetazoline 0.5% QD (P=0.049), 1.0% QD (P=0.006), 1.5% QD (P=0.012), 1.0% BID (P=0.021), and 1.5% BID (P=0.006) versus their respective vehicles. For both QD and BID dosing, the efficacy of oxymetazoline 1.0% was greater than the 0.5% dose and comparable to the 1.5% dose. Safety and application-site tolerability were similar across groups. Short-term treatment period. Oxymetazoline 1.0% QD provided the optimal dosing regimen and was selected for evaluation in phase 3 clinical studies. J Drugs Dermatol. 2018;17(3):308-316.

Do Asian renal transplant patients need another mycophenolate mofetil dose compared with Caucasian or African American patients?

PubMed

Li, Pengmei; Shuker, Nauras; Hesselink, Dennis A; van Schaik, Ron H N; Zhang, Xianglin; van Gelder, Teun

2014-10-01

Mycophenolate mofetil (MMF) is used to prevent acute rejection following solid organ transplantation in transplant centers all over the world. Patients from different ethnic backgrounds are treated with this drug, for which therapeutic drug monitoring (TDM) has not become the standard of practice in most centers. Whether or not some ethnic groups require a different MMF dose has been a topic of debate in recent years. In this review, it is shown that Asian patients, compared with Caucasian patients, with a comparable MMF dose reach higher mycophenolic acid (MPA) exposure. Also clinical experience points toward more adverse events in case of treatment with 1 g MMF bid in Asian patients, and therefore, for this ethnic group, a lower maintenance dose seems justified. In contrast, African American patients reach similar drug concentrations as Caucasians patients receiving the same MMF dose, but due to immunological reasons, they require a higher MMF dose to reach comparable acute rejection incidences. When TDM is performed, clinicians can correct the dose and compensate for interethnic differences in drug exposure. Otherwise, it is important to choose the right dose. This optimal dose is 20-46% lower in Asian transplant recipients than in Caucasian or African American patients. © 2014 Steunstichting ESOT.

An Analysis of Plan Robustness for Esophageal Tumors: Comparing Volumetric Modulated Arc Therapy Plans and Spot Scanning Proton Planning.

PubMed

Warren, Samantha; Partridge, Mike; Bolsi, Alessandra; Lomax, Anthony J; Hurt, Chris; Crosby, Thomas; Hawkins, Maria A

2016-05-01

Planning studies to compare x-ray and proton techniques and to select the most suitable technique for each patient have been hampered by the nonequivalence of several aspects of treatment planning and delivery. A fair comparison should compare similarly advanced delivery techniques from current clinical practice and also assess the robustness of each technique. The present study therefore compared volumetric modulated arc therapy (VMAT) and single-field optimization (SFO) spot scanning proton therapy plans created using a simultaneous integrated boost (SIB) for dose escalation in midesophageal cancer and analyzed the effect of setup and range uncertainties on these plans. For 21 patients, SIB plans with a physical dose prescription of 2 Gy or 2.5 Gy/fraction in 25 fractions to planning target volume (PTV)50Gy or PTV62.5Gy (primary tumor with 0.5 cm margins) were created and evaluated for robustness to random setup errors and proton range errors. Dose-volume metrics were compared for the optimal and uncertainty plans, with P<.05 (Wilcoxon) considered significant. SFO reduced the mean lung dose by 51.4% (range 35.1%-76.1%) and the mean heart dose by 40.9% (range 15.0%-57.4%) compared with VMAT. Proton plan robustness to a 3.5% range error was acceptable. For all patients, the clinical target volume D98 was 95.0% to 100.4% of the prescribed dose and gross tumor volume (GTV) D98 was 98.8% to 101%. Setup error robustness was patient anatomy dependent, and the potential minimum dose per fraction was always lower with SFO than with VMAT. The clinical target volume D98 was lower by 0.6% to 7.8% of the prescribed dose, and the GTV D98 was lower by 0.3% to 2.2% of the prescribed GTV dose. The SFO plans achieved significant sparing of normal tissue compared with the VMAT plans for midesophageal cancer. The target dose coverage in the SIB proton plans was less robust to random setup errors and might be unacceptable for certain patients. Robust optimization to ensure adequate target coverage of SIB proton plans might be beneficial. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Unkelbach, Jan, E-mail: junkelbach@mgh.harvard.edu; Botas, Pablo; Faculty of Physics, Ruprecht-Karls-Universität Heidelberg, Heidelberg

Purpose: We describe a treatment plan optimization method for intensity modulated proton therapy (IMPT) that avoids high values of linear energy transfer (LET) in critical structures located within or near the target volume while limiting degradation of the best possible physical dose distribution. Methods and Materials: To allow fast optimization based on dose and LET, a GPU-based Monte Carlo code was extended to provide dose-averaged LET in addition to dose for all pencil beams. After optimizing an initial IMPT plan based on physical dose, a prioritized optimization scheme is used to modify the LET distribution while constraining the physical dosemore » objectives to values close to the initial plan. The LET optimization step is performed based on objective functions evaluated for the product of LET and physical dose (LET×D). To first approximation, LET×D represents a measure of the additional biological dose that is caused by high LET. Results: The method is effective for treatments where serial critical structures with maximum dose constraints are located within or near the target. We report on 5 patients with intracranial tumors (high-grade meningiomas, base-of-skull chordomas, ependymomas) in whom the target volume overlaps with the brainstem and optic structures. In all cases, high LET×D in critical structures could be avoided while minimally compromising physical dose planning objectives. Conclusion: LET-based reoptimization of IMPT plans represents a pragmatic approach to bridge the gap between purely physical dose-based and relative biological effectiveness (RBE)-based planning. The method makes IMPT treatments safer by mitigating a potentially increased risk of side effects resulting from elevated RBE of proton beams near the end of range.« less

Pharmacological management of anticholinergic delirium - theory, evidence and practice.

PubMed

Dawson, Andrew H; Buckley, Nicholas A

2016-03-01

The spectrum of anticholinergic delirium is a common complication following drug overdose. Patients with severe toxicity can have significant distress and behavioural problems that often require pharmacological management. Cholinesterase inhibitors, such as physostigmine, are effective but widespread use has been limited by concerns about safety, optimal dosing and variable supply. Case series support efficacy in reversal of anticholinergic delirium. However doses vary widely and higher doses commonly lead to cholinergic toxicity. Seizures are reported in up to 2.5% of patients and occasional cardiotoxic effects are also recorded. This article reviews the serendipitous path whereby physostigmine evolved into the preferred anticholinesterase antidote largely without any research to indicate the optimal dosing strategy. Adverse events observed in case series should be considered in the context of pharmacokinetic/pharmacodynamic studies of physostigmine which suggest a much longer latency before the maximal increase in brain acetylcholine than had been previously assumed. This would favour protocols that use lower doses and longer re-dosing intervals. We propose based on the evidence reviewed that the use of cholinesterase inhibitors should be considered in anticholinergic delirium that has not responded to non-pharmacological delirium management. The optimal risk/benefit would be with a titrated dose of 0.5 to 1 mg physostigmine (0.01-0.02 mg kg(-1) in children) with a minimum delay of 10-15 min before re-dosing. Slower onset and longer acting agents such as rivastigmine would also be logical but more research is needed to guide the appropriate dose in this setting. © 2015 The British Pharmacological Society.

Semiautomated head-and-neck IMRT planning using dose warping and scaling to robustly adapt plans in a knowledge database containing potentially suboptimal plans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schmidt, Matthew, E-mail: matthew.schmidt@varian.com; Grzetic, Shelby; Lo, Joseph Y.

Purpose: Prior work by the authors and other groups has studied the creation of automated intensity modulated radiotherapy (IMRT) plans of equivalent quality to those in a patient database of manually created clinical plans; those database plans provided guidance on the achievable sparing to organs-at-risk (OARs). However, in certain sites, such as head-and-neck, the clinical plans may not be sufficiently optimized because of anatomical complexity and clinical time constraints. This could lead to automated plans that suboptimally exploit OAR sparing. This work investigates a novel dose warping and scaling scheme that attempts to reduce effects of suboptimal sparing in clinicalmore » database plans, thus improving the quality of semiautomated head-and-neck cancer (HNC) plans. Methods: Knowledge-based radiotherapy (KBRT) plans for each of ten “query” patients were semiautomatically generated by identifying the most similar “match” patient in a database of 103 clinical manually created patient plans. The match patient’s plans were adapted to the query case by: (1) deforming the match beam fluences to suit the query target volume and (2) warping the match primary/boost dose distribution to suit the query geometry and using the warped distribution to generate query primary/boost optimization dose-volume constraints. Item (2) included a distance scaling factor to improve query OAR dose sparing with respect to the possibly suboptimal clinical match plan. To further compensate for a component plan of the match case (primary/boost) not optimally sparing OARs, the query dose volume constraints were reduced using a dose scaling factor to be the minimum from either (a) the warped component plan (primary or boost) dose distribution or (b) the warped total plan dose distribution (primary + boost) scaled in proportion to the ratio of component prescription dose to total prescription dose. The dose-volume constraints were used to plan the query case with no human intervention to adjust constraints during plan optimization. Results: KBRT and original clinical plans were dosimetrically equivalent for parotid glands (mean/median doses), spinal cord, and brainstem (maximum doses). KBRT plans significantly reduced larynx median doses (21.5 ± 6.6 Gy to 17.9 ± 3.9 Gy), and oral cavity mean (32.3 ± 6.2 Gy to 28.9 ± 5.4 Gy) and median (28.7 ± 5.7 Gy to 23.2 ± 5.3 Gy) doses. Doses to ipsilateral parotid gland, larynx, oral cavity, and brainstem were lower or equivalent in the KBRT plans for the majority of cases. By contrast, KBRT plans generated without the dose warping and dose scaling steps were not significantly different from the clinical plans. Conclusions: Fast, semiautomatically generated HNC IMRT plans adapted from existing plans in a clinical database can be of equivalent or better quality than manually created plans. The reductions in OAR doses in the semiautomated plans, compared to the clinical plans, indicate that the proposed dose warping and scaling method shows promise in mitigating the impact of suboptimal clinical plans.« less

Predicting Maintenance Doses of Vancomycin for Hospitalized Patients Undergoing Hemodialysis.

PubMed

El Nekidy, Wasim S; El-Masri, Maher M; Umstead, Greg S; Dehoorne-Smith, Michelle

2016-01-01

Methicillin-resistant Staphylococcus aureus is a leading cause of death in patients undergoing hemodialysis. However, controversy exists about the optimal dose of vancomycin that will yield the recommended pre-hemodialysis serum concentration of 15-20 mg/L. To develop a data-driven model to optimize the accuracy of maintenance dosing of vancomycin for patients undergoing hemodialysis. A prospective observational cohort study was performed with 164 observations obtained from a convenience sample of 63 patients undergoing hemodialysis. All vancomycin doses were given on the floor after completion of a hemodialysis session. Multivariate linear generalized estimating equation analysis was used to examine independent predictors of pre-hemodialysis serum vancomycin concentration. Pre-hemodialysis serum vancomycin concentration was independently associated with maintenance dose ( B = 0.658, p < 0.001), baseline pre-hemodialysis serum concentration of the drug ( B = 0.492, p < 0.001), and interdialytic interval ( B = -2.133, p < 0.001). According to the best of 4 models that were developed, the maintenance dose of vancomycin required to achieve a pre-hemodialysis serum concentration of 15-20 mg/L, if the baseline serum concentration of the drug was also 15-20 mg/L, was 5.9 mg/kg with interdialytic interval of 48 h and 7.1 mg/kg with interdialytic interval of 72 h. However, if the baseline pre-hemodialysis serum concentration was 10-14.99 mg/L, the required dose increased to 9.2 mg/kg with an interdialytic interval of 48 h and 10.0 mg/kg with an interdialytic interval of 72 h. The maintenance dose of vancomycin varied according to baseline pre-hemodialysis serum concentration of the drug and interdialytic interval. The current practice of targeting a pre-hemodialysis concentration of 15-20 mg/L may be difficult to achieve for the majority of patients undergoing hemodialysis.

Optimal dose and volume for postoperative radiotherapy in brain oligometastases from lung cancer: a retrospective study.

PubMed

Chung, Seung Yeun; Chang, Jong Hee; Kim, Hye Ryun; Cho, Byoung Chul; Lee, Chang Geol; Suh, Chang-Ok

2017-06-01

To evaluate intracranial control after surgical resection according to the adjuvant treatment received in order to assess the optimal radiotherapy (RT) dose and volume. Between 2003 and 2015, a total of 53 patients with brain oligometastases from non-small cell lung cancer (NSCLC) underwent metastasectomy. The patients were divided into three groups according to the adjuvant treatment received: whole brain radiotherapy (WBRT) ± boost (WBRT ± boost group, n = 26), local RT/Gamma Knife surgery (local RT group, n = 14), and the observation group (n = 13). The most commonly used dose schedule was WBRT (25 Gy in 10 fractions, equivalent dose in 2 Gy fractions [EQD2] 26.04 Gy) with tumor bed boost (15 Gy in 5 fractions, EQD2 16.25 Gy). The WBRT ± boost group showed the lowest 1-year intracranial recurrence rate of 30.4%, followed by the local RT and observation groups, at 66.7%, and 76.9%, respectively (p = 0.006). In the WBRT ± boost group, there was no significant increase in the 1-year new site recurrence rate of patients receiving a lower dose of WBRT (EQD2) <27 Gy compared to that in patients receiving a higher WBRT dose (p = 0.553). The 1-year initial tumor site recurrence rate was lower in patients receiving tumor bed dose (EQD2) of ≥42.3 Gy compared to those receiving <42.3 Gy, although the difference was not significant (p = 0.347). Adding WBRT after resection of brain oligometastases from NSCLC seems to enhance intracranial control. Furthermore, combining lower-dose WBRT with a tumor bed boost may be an attractive option.

Optimal dose and volume for postoperative radiotherapy in brain oligometastases from lung cancer: a retrospective study

PubMed Central

Chung, Seung Yeun; Chang, Jong Hee; Kim, Hye Ryun; Cho, Byoung Chul; Lee, Chang Geol; Suh, Chang-Ok

2017-01-01

Purpose To evaluate intracranial control after surgical resection according to the adjuvant treatment received in order to assess the optimal radiotherapy (RT) dose and volume. Materials and Methods Between 2003 and 2015, a total of 53 patients with brain oligometastases from non-small cell lung cancer (NSCLC) underwent metastasectomy. The patients were divided into three groups according to the adjuvant treatment received: whole brain radiotherapy (WBRT) ± boost (WBRT ± boost group, n = 26), local RT/Gamma Knife surgery (local RT group, n = 14), and the observation group (n = 13). The most commonly used dose schedule was WBRT (25 Gy in 10 fractions, equivalent dose in 2 Gy fractions [EQD2] 26.04 Gy) with tumor bed boost (15 Gy in 5 fractions, EQD2 16.25 Gy). Results The WBRT ± boost group showed the lowest 1-year intracranial recurrence rate of 30.4%, followed by the local RT and observation groups, at 66.7%, and 76.9%, respectively (p = 0.006). In the WBRT ± boost group, there was no significant increase in the 1-year new site recurrence rate of patients receiving a lower dose of WBRT (EQD2) <27 Gy compared to that in patients receiving a higher WBRT dose (p = 0.553). The 1-year initial tumor site recurrence rate was lower in patients receiving tumor bed dose (EQD2) of ≥42.3 Gy compared to those receiving <42.3 Gy, although the difference was not significant (p = 0.347). conclusions Adding WBRT after resection of brain oligometastases from NSCLC seems to enhance intracranial control. Furthermore, combining lower-dose WBRT with a tumor bed boost may be an attractive option. PMID:28712276

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gorissen, BL; Giantsoudi, D; Unkelbach, J

Purpose: Cell survival experiments suggest that the relative biological effectiveness (RBE) of proton beams depends on linear energy transfer (LET), leading to higher RBE near the end of range. With intensity-modulated proton therapy (IMPT), multiple treatment plans that differ in the dose contribution per field may yield a similar physical dose distribution, but the RBE-weighted dose distribution may be disparate. RBE models currently do not have the required predictive power to be included in an optimization model due to the variations in experimental data. We propose an LET-based planning method that guides IMPT optimization models towards plans with reduced RBE-weightedmore » dose in surrounding organs at risk (OARs) compared to inverse planning based on physical dose alone. Methods: Optimization models for physical dose are extended with a term for dose times LET (doseLET). Monte Carlo code is used to generate the physical dose and doseLET distribution of each individual pencil beam. The method is demonstrated for an atypical meningioma patient where the target volume abuts the brainstem and partially overlaps with the optic nerve. Results: A reference plan optimized based on physical dose alone yields high doseLET values in parts of the brainstem and optic nerve. Minimizing doseLET in these critical structures as an additional planning goal reduces the risk of high RBE-weighted dose. The resulting treatment plan avoids the distal fall-off of the Bragg peaks for shaping the dose distribution in front of critical stuctures. The maximum dose in the OARs evaluated with RBE models from literature is reduced by 8–14\\% with our method compared to conventional planning. Conclusion: LET-based inverse planning for IMPT offers the ability to reduce the RBE-weighted dose in OARs without sacrificing target dose. This project was in part supported by NCI - U19 CA 21239.« less

Dynamic trajectory-based couch motion for improvement of radiation therapy trajectories in cranial SRT

DOE Office of Scientific and Technical Information (OSTI.GOV)

MacDonald, R. Lee; Thomas, Christopher G., E-mail: Chris.Thomas@cdha.nshealth.ca; Department of Medical Physics, Nova Scotia Cancer Centre, Queen Elizabeth II Health Sciences Centre, Halifax, Nova Scotia B3H 1V7

2015-05-15

Purpose: To investigate potential improvement in external beam stereotactic radiation therapy plan quality for cranial cases using an optimized dynamic gantry and patient support couch motion trajectory, which could minimize exposure to sensitive healthy tissue. Methods: Anonymized patient anatomy and treatment plans of cranial cancer patients were used to quantify the geometric overlap between planning target volumes and organs-at-risk (OARs) based on their two-dimensional projection from source to a plane at isocenter as a function of gantry and couch angle. Published dose constraints were then used as weighting factors for the OARs to generate a map of couch-gantry coordinate space,more » indicating degree of overlap at each point in space. A couch-gantry collision space was generated by direct measurement on a linear accelerator and couch using an anthropomorphic solid-water phantom. A dynamic, fully customizable algorithm was written to generate a navigable ideal trajectory for the patient specific couch-gantry space. The advanced algorithm can be used to balance the implementation of absolute minimum values of overlap with the clinical practicality of large-scale couch motion and delivery time. Optimized cranial cancer treatment trajectories were compared to conventional treatment trajectories. Results: Comparison of optimized treatment trajectories with conventional treatment trajectories indicated an average decrease in mean dose to the OARs of 19% and an average decrease in maximum dose to the OARs of 12%. Degradation was seen for homogeneity index (6.14% ± 0.67%–5.48% ± 0.76%) and conformation number (0.82 ± 0.02–0.79 ± 0.02), but neither was statistically significant. Removal of OAR constraints from volumetric modulated arc therapy optimization reveals that reduction in dose to OARs is almost exclusively due to the optimized trajectory and not the OAR constraints. Conclusions: The authors’ study indicated that simultaneous couch and gantry motion during radiation therapy to minimize the geometrical overlap in the beams-eye-view of target volumes and the organs-at-risk can have an appreciable dose reduction to organs-at-risk.« less

SU-E-P-10: Establishment of Local Diagnostic Reference Levels of Routine Exam in Computed Tomography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yeh, M; Wang, Y; Weng, H

Introduction National diagnostic reference levels (NDRLs) can be used as a reference dose of radiological examination can provide radiation dose as the basis of patient dose optimization. Local diagnostic reference levels (LDRLs) by periodically view and check doses, more efficiency to improve the way of examination. Therefore, the important first step is establishing a diagnostic reference level. Computed Tomography in Taiwan had been built up the radiation dose limit value,in addition, many studies report shows that CT scan contributed most of the radiation dose in different medical. Therefore, this study was mainly to let everyone understand DRL’s international status. Formore » computed tomography in our hospital to establish diagnostic reference levels. Methods and Materials: There are two clinical CT scanners (a Toshiba Aquilion and a Siemens Sensation) were performed in this study. For CT examinations the basic recommended dosimetric quantity is the Computed Tomography Dose Index (CTDI). Each exam each different body part, we collect 10 patients at least. Carried out the routine examinations, and all exposure parameters have been collected and the corresponding CTDIv and DLP values have been determined. Results: The majority of patients (75%) were between 60–70 Kg of body weight. There are 25 examinations in this study. Table 1 shows the LDRL of each CT routine examination. Conclusions: Therefore, this study would like to let everyone know DRL’s international status, but also establishment of computed tomography of the local reference levels for our hospital, and providing radiation reference, as a basis for optimizing patient dose.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Benassi, Michaela; Di Murro, Luana; Tolu, Barbara, E-mail: barbara.tolu@gmail.com

This study aims at optimizing treatment planning in young patients affected by lymphoma (Stage II to III) by using an inclined board (IB) that allows reducing doses to the organs at risk. We evaluated 19 young patients affected by stage I to III lymphomas, referred to our Department for consolidation radiotherapy (RT) treatment on the mediastinum. Patients underwent 2 planning computed tomography (CT) scans performed in different positions: flat standard position and inclined position. A direct comparison between the different treatment plans was carried out analyzing dosimetric parameters obtained from dose-volume histograms generated for each plan. Comparison was performed tomore » evaluate the sparing obtained on breast and heart. Dosimetric evaluation was performed for the following organs at risk (OARs): mammary glands, lungs, and heart. A statistically significant advantage was reported for V{sub 5}, V{sub 20}, and V{sub 30} for the breast when using the inclined board. A similar result was obtained for V{sub 5} and V{sub 10} on the heart. No advantage was observed in lung doses. The use of a simple device, such as an inclined board, allows the optimization of treatment plan, especially in young female patients, by ensuring a significant reduction of the dose delivered to breast and heart.« less

SU-F-T-01: Optimization of the Accelerated Partial Breast Brachytherapy Fractionation with Consideration of Physical Doses to Tumor and Organ at Risk

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fu, W; Huq, M

2016-06-15

Purpose: The accelerated partial breast irradiation (APBI) with brachytherapy prescribes 34Gy to be delivered in 10 fractions over 5 consecutive working days without considering the physical dose to the target and organs at risk (OARs) for an individual patient. The purpose of this study is to optimize the fractionation scheme by evaluating the radiation effect on tumor and OARs with a modified linear-quadratic (LQ) model based on dose-volume histograms (DVHs). Methods: Five breast patients treated with multilumen balloon brachytherapy were selected. The minimum skin and rib spacing were ranged from 2.5mm to 14.3mm and from 1.0mm to 25.0mm, respectively. Themore » LQ model parameters were set as: (1) breast: α=0.08, β=0.028, doubling time Tpot=14.4 days, and starting time Tk=21days; (2) skin: acute reaction α=0.101, β=0.009; late reaction α=0.064, β=0.029; (3) rib: α=0.3, β=0.12. Boundary dose Dt was 6 Gy for both target and OARs. The relation between radiation effects on the tumor (ET) and OARs (EOAR) were plotted for fraction number from 1 to 20. Results: The value of radiation effect from routine 3.4Gyx10 fractions was used as reference, ETref and EOARref. If set ET=ETref, the fractionation that results in minimum EOAR values correspond to the optimal fractionation. For these patients, the optimal numbers are 10 fractions for skin acute reaction, 18 fractions for skin and rib late reaction while the doses per fraction are 3.4Gy and 2.05–2.10Gy, respectively. If set EOAR=EOARref, the fractionation that results in a maximum ET value corresponds to the optimal fractionation. The optimal fractionation is 3.4Gyx10 fractions for skin acute reaction, and 2.10–2.25Gyx18 fractions for skin late reaction and rib. Conclusion: For APBI brachytherapy, the routine 3.4Gyx10 fractions is optimal fractionation for skin acute reaction, while 2.05–2.25Gyx18 fractions is optimal fractionation for late reaction of skin and rib.« less

What Is the Optimal Target Convective Volume in On-Line Hemodiafiltration Therapy?

PubMed

Canaud, Bernard; Koehler, Katrin; Bowry, Sudhir; Stuard, Stefano

2017-01-01

Conventional diffusion-based dialysis modalities including high-flux hemodialysis are limited in their capacity to effectively remove large uremic toxins and to improve outcomes for end-stage chronic kidney disease (ESKD) patients. By increasing convective solute transport, hemodiafiltration (HDF) enhances solute removal capacity over a broad range of middle- and large-size uremic toxins implicated in the pathophysiology of chronic kidney disease. Furthermore, by offering flexible convection volume, on-line HDF permits customizing the treatment dose to the patient's needs. In addition, convective-based modalities have been shown to improve hemodynamic stability and to reduce patients' inflammation profile - both of which are implicated in CKD morbidity and mortality. Growing clinical evidence indicates that HDF-based modalities provide ESKD patients with a number of clinical and biological benefits, including improved outcomes. Interestingly, it has recently emerged that the clinical benefits associated with HDF are positively associated with the total ultrafiltered volume per session (and per week), namely convective dose. In this chapter, we revisit the concept of convective dose and discuss the threshold value above which an improvement in ESKD patient outcome can be expected. This particular point will be addressed by stratifying the level of efficacy of convective volumes, schematically defined as minimal, optimal, personalized, and maximal. In addition, factors and best clinical practices implicated in the achievement of an optimal convective dose are reviewed. To conclude, we show how HDF differs from standard hemodialysis and why HDF offers a paradigm shift in renal replacement therapy. © 2017 S. Karger AG, Basel.

Immuno-oncology Clinical Trial Design: Limitations, Challenges, and Opportunities

PubMed Central

Baik, Christina S.; Rubin, Eric H.; Forde, Patrick M.; Mehnert, Janice M.; Collyar, Deborah; Butler, Marcus O.; Dixon, Erica L.; Chow, Laura Q.M.

2017-01-01

Recent advances in immuno-oncology and regulatory approvals have been rapid and paradigm shifting in many difficult-to-treat malignancies. Despite immune checkpoint inhibitor therapy becoming the standard of care across multiple tumor types, there are many unanswered questions that need to be addressed before this therapeutic modality can be fully harnessed. Areas of limitations include treatment of patients not sufficiently represented in clinical trials, uncertainty of the optimal treatment dosing and duration, and lack of understanding regarding long-term immune related toxicities and atypical tumor responses. Patients such as those with autoimmune disease, chronic viral infections, limited performance status, and brain metastases were often excluded from initial trials due to concerns of safety. However, limited data suggest that some of these patients can benefit from therapy with manageable toxicities; thus, future studies should incorporate these patients to clearly define safety and efficacy. There are still controversies regarding the optimal dosing strategy that can vary from weight-based to flat dosing, with undefined treatment duration. Further elucidation of the optimal dosing approach and evaluation of predictive biomarkers should be incorporated in the design of future trials. Finally, there are long-term immune-mediated toxicities, atypical tumor responses such as pseudoprogression and endpoints unique to immuno-oncology that are not adequately captured by traditional trial designs; thus, novel study designs are needed. In this article, we discuss in detail the above challenges and propose needed areas of research for exploration and incorporation in the next generation of immuno-oncology clinical trials. PMID:28864727

A randomized controlled trial investigating the use of a predictive nomogram for the selection of the FSH starting dose in IVF/ICSI cycles.

PubMed

Allegra, Adolfo; Marino, Angelo; Volpes, Aldo; Coffaro, Francesco; Scaglione, Piero; Gullo, Salvatore; La Marca, Antonio

2017-04-01

The number of oocytes retrieved is a relevant intermediate outcome in women undergoing IVF/intracytoplasmic sperm injection (ICSI). This trial compared the efficiency of the selection of the FSH starting dose according to a nomogram based on multiple biomarkers (age, day 3 FSH, anti-Müllerian hormone) versus an age-based strategy. The primary outcome measure was the proportion of women with an optimal number of retrieved oocytes defined as 8-14. At their first IVF/ICSI cycle, 191 patients underwent a long gonadotrophin-releasing hormone agonist protocol and were randomized to receive a starting dose of recombinant (human) FSH, based on their age (150 IU if ≤35 years, 225 IU if >35 years) or based on the nomogram. Optimal response was observed in 58/92 patients (63%) in the nomogram group and in 42/99 (42%) in the control group (+21%, 95% CI = 0.07 to 0.35, P = 0.0037). No significant differences were found in the clinical pregnancy rate or the number of embryos cryopreserved per patient. The study showed that the FSH starting dose selected according to ovarian reserve is associated with an increase in the proportion of patients with an optimal response: large trials are recommended to investigate any possible effect on the live-birth rate. Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Definition of the supraclavicular and infraclavicular nodes: implications for three-dimensional CT-based conformal radiation therapy.

PubMed

Madu, C N; Quint, D J; Normolle, D P; Marsh, R B; Wang, E Y; Pierce, L J

2001-11-01

To delineate with computed tomography (CT) the anatomic regions containing the supraclavicular (SCV) and infraclavicular (IFV) nodal groups, to define the course of the brachial plexus, to estimate the actual radiation dose received by these regions in a series of patients treated in the traditional manner, and to compare these doses to those received with an optimized dosimetric technique. Twenty patients underwent contrast material-enhanced CT for the purpose of radiation therapy planning. CT scans were used to study the location of the SCV and IFV nodal regions by using outlining of readily identifiable anatomic structures that define the nodal groups. The brachial plexus was also outlined by using similar methods. Radiation therapy doses to the SCV and IFV were then estimated by using traditional dose calculations and optimized planning. A repeated measures analysis of covariance was used to compare the SCV and IFV depths and to compare the doses achieved with the traditional and optimized methods. Coverage by the 90% isodose surface was significantly decreased with traditional planning versus conformal planning as the depth to the SCV nodes increased (P < .001). Significantly decreased coverage by using the 90% isodose surface was demonstrated for traditional planning versus conformal planning with increasing IFV depth (P = .015). A linear correlation was found between brachial plexus depth and SCV depth up to 7 cm. Conformal optimized planning provided improved dosimetric coverage compared with standard techniques.

Toward endobronchial Ir-192 high-dose-rate brachytherapy therapeutic optimization

NASA Astrophysics Data System (ADS)

Gay, H. A.; Allison, R. R.; Downie, G. H.; Mota, H. C.; Austerlitz, C.; Jenkins, T.; Sibata, C. H.

2007-06-01

A number of patients with lung cancer receive either palliative or curative high-dose-rate (HDR) endobronchial brachytherapy. Up to a third of patients treated with endobronchial HDR die from hemoptysis. Rather than accept hemoptysis as an expected potential consequence of HDR, we have calculated the radial dose distribution for an Ir-192 HDR source, rigorously examined the dose and prescription points recommended by the American Brachytherapy Society (ABS), and performed a radiobiological-based analysis. The radial dose rate of a commercially available Ir-192 source was calculated with a Monte Carlo simulation. Based on the linear quadratic model, the estimated palliative, curative and blood vessel rupture radii from the center of an Ir-192 source were obtained for the ABS recommendations and a series of customized HDR prescriptions. The estimated radius at risk for blood vessel perforation for the ABS recommendations ranges from 7 to 9 mm. An optimized prescription may in some situations reduce this radius to 4 mm. The estimated blood perforation radius is generally smaller than the palliative radius. Optimized and individualized endobronchial HDR prescriptions are currently feasible based on our current understanding of tumor and normal tissue radiobiology. Individualized prescriptions could minimize complications such as fatal hemoptysis without sacrificing efficacy. Fiducial stents, HDR catheter centering or spacers and the use of CT imaging to better assess the relationship between the catheter and blood vessels promise to be useful strategies for increasing the therapeutic index of this treatment modality. Prospective trials employing treatment optimization algorithms are needed.

MO-C-18A-01: Advances in Model-Based 3D Image Reconstruction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, G; Pan, X; Stayman, J

2014-06-15

Recent years have seen the emergence of CT image reconstruction techniques that exploit physical models of the imaging system, photon statistics, and even the patient to achieve improved 3D image quality and/or reduction of radiation dose. With numerous advantages in comparison to conventional 3D filtered backprojection, such techniques bring a variety of challenges as well, including: a demanding computational load associated with sophisticated forward models and iterative optimization methods; nonlinearity and nonstationarity in image quality characteristics; a complex dependency on multiple free parameters; and the need to understand how best to incorporate prior information (including patient-specific prior images) within themore » reconstruction process. The advantages, however, are even greater – for example: improved image quality; reduced dose; robustness to noise and artifacts; task-specific reconstruction protocols; suitability to novel CT imaging platforms and noncircular orbits; and incorporation of known characteristics of the imager and patient that are conventionally discarded. This symposium features experts in 3D image reconstruction, image quality assessment, and the translation of such methods to emerging clinical applications. Dr. Chen will address novel methods for the incorporation of prior information in 3D and 4D CT reconstruction techniques. Dr. Pan will show recent advances in optimization-based reconstruction that enable potential reduction of dose and sampling requirements. Dr. Stayman will describe a “task-based imaging” approach that leverages models of the imaging system and patient in combination with a specification of the imaging task to optimize both the acquisition and reconstruction process. Dr. Samei will describe the development of methods for image quality assessment in such nonlinear reconstruction techniques and the use of these methods to characterize and optimize image quality and dose in a spectrum of clinical applications. Learning Objectives: Learn the general methodologies associated with model-based 3D image reconstruction. Learn the potential advantages in image quality and dose associated with model-based image reconstruction. Learn the challenges associated with computational load and image quality assessment for such reconstruction methods. Learn how imaging task can be incorporated as a means to drive optimal image acquisition and reconstruction techniques. Learn how model-based reconstruction methods can incorporate prior information to improve image quality, ease sampling requirements, and reduce dose.« less

Multiple anatomy optimization of accumulated dose

DOE Office of Scientific and Technical Information (OSTI.GOV)

Watkins, W. Tyler, E-mail: watkinswt@virginia.edu; Siebers, Jeffrey V.; Moore, Joseph A.

Purpose: To investigate the potential advantages of multiple anatomy optimization (MAO) for lung cancer radiation therapy compared to the internal target volume (ITV) approach. Methods: MAO aims to optimize a single fluence to be delivered under free-breathing conditions such that the accumulated dose meets the plan objectives, where accumulated dose is defined as the sum of deformably mapped doses computed on each phase of a single four dimensional computed tomography (4DCT) dataset. Phantom and patient simulation studies were carried out to investigate potential advantages of MAO compared to ITV planning. Through simulated delivery of the ITV- and MAO-plans, target dosemore » variations were also investigated. Results: By optimizing the accumulated dose, MAO shows the potential to ensure dose to the moving target meets plan objectives while simultaneously reducing dose to organs at risk (OARs) compared with ITV planning. While consistently superior to the ITV approach, MAO resulted in equivalent OAR dosimetry at planning objective dose levels to within 2% volume in 14/30 plans and to within 3% volume in 19/30 plans for each lung V20, esophagus V25, and heart V30. Despite large variations in per-fraction respiratory phase weights in simulated deliveries at high dose rates (e.g., treating 4/10 phases during single fraction beams) the cumulative clinical target volume (CTV) dose after 30 fractions and per-fraction dose were constant independent of planning technique. In one case considered, however, per-phase CTV dose varied from 74% to 117% of prescription implying the level of ITV-dose heterogeneity may not be appropriate with conventional, free-breathing delivery. Conclusions: MAO incorporates 4DCT information in an optimized dose distribution and can achieve a superior plan in terms of accumulated dose to the moving target and OAR sparing compared to ITV-plans. An appropriate level of dose heterogeneity in MAO plans must be further investigated.« less

Forcing lateral electron disequilibrium to spare lung tissue: a novel technique for stereotactic body radiation therapy of lung cancer

NASA Astrophysics Data System (ADS)

Disher, Brandon; Hajdok, George; Gaede, Stewart; Mulligan, Matthew; Battista, Jerry J.

2013-10-01

Stereotactic body radiation therapy (SBRT) has quickly become a preferred treatment option for early-stage lung cancer patients who are ineligible for surgery. This technique uses tightly conformed megavoltage (MV) x-ray beams to irradiate a tumour with ablative doses in only a few treatment fractions. Small high energy x-ray fields can cause lateral electron disequilibrium (LED) to occur within low density media, which can reduce tumour dose. These dose effects may be challenging to predict using analytic dose calculation algorithms, especially at higher beam energies. As a result, previous authors have suggested using low energy photons (<10 MV) and larger fields (>5 × 5 cm2) for lung cancer patients to avoid the negative dosimetric effects of LED. In this work, we propose a new form of SBRT, described as LED-optimized SBRT (LED-SBRT), which utilizes radiotherapy (RT) parameters designed to cause LED to advantage. It will be shown that LED-SBRT creates enhanced dose gradients at the tumour/lung interface, which can be used to manipulate tumour dose, and/or normal lung dose. To demonstrate the potential benefits of LED-SBRT, the DOSXYZnrc (National Research Council of Canada, Ottawa, ON) Monte Carlo (MC) software was used to calculate dose within a cylindrical phantom and a typical lung patient. 6 MV or 18 MV x-ray fields were focused onto a small tumour volume (diameter ˜1 cm). For the phantom, square fields of 1 × 1 cm2, 3 × 3 cm2, or 5 × 5 cm2 were applied. However, in the patient, 3 × 1 cm2, 3 × 2 cm2, 3 × 2.5 cm2, or 3 × 3 cm2 field sizes were used in simulations to assure target coverage in the superior-inferior direction. To mimic a 180° SBRT arc in the (symmetric) phantom, a single beam profile was calculated, rotated, and beams were summed at 1° segments to accumulate an arc dose distribution. For the patient, a 360° arc was modelled with 36 equally weighted (and spaced) fields focused on the tumour centre. A planning target volume (PTV) was generated by considering the extent of tumour motion over the patient's breathing cycle and set-up uncertainties. All patient dose results were normalized such that at least 95% of the PTV received at least 54 Gy (i.e. D95 = 54 Gy). Further, we introduce ‘LED maps’ as a novel clinical tool to compare the magnitude of LED resulting from the various SBRT arc plans. Results from the phantom simulation suggest that the best lung sparing occurred for RT parameters that cause severe LED. For equal tumour dose coverage, normal lung dose (2 cm outside the target region) was reduced from 92% to 23%, comparing results between the 18 MV (5 × 5 cm2) and 18 MV (1 × 1 cm2) arc simulations. In addition to reduced lung dose for the 18 MV (1 × 1 cm2) arc, maximal tumour dose increased beyond 125%. Thus, LED can create steep dose gradients to spare normal lung, while increasing tumour dose levels (if desired). In the patient simulation, a LED-optimized arc plan was designed using either 18 MV (3 × 1 cm2) or 6 MV (3 × 3cm2) beams. Both plans met the D95 dose coverage requirement for the target. However, the LED-optimized plan increased the maximum, mean, and minimum dose within the PTV by as much as 80 Gy, 11 Gy, and 3 Gy, respectively. Despite increased tumour dose levels, the 18 MV (3 × 1 cm2) arc plan improved or maintained the V20, V5, and mean lung dose metrics compared to the 6 MV (3 × 3 cm2) simulation. We conclude that LED-SBRT has the potential to increase dose gradients, and dose levels within a small lung tumour. The magnitude of tumour dose increase or lung sparing can be optimized through manipulation of RT parameters (e.g. beam energy and field size).

Optimization in Radiation Therapy: Applications in Brachytherapy and Intensity Modulated Radiation Therapy

NASA Astrophysics Data System (ADS)

McGeachy, Philip David

Over 50% of cancer patients require radiation therapy (RT). RT is an optimization problem requiring maximization of the radiation damage to the tumor while minimizing the harm to the healthy tissues. This dissertation focuses on two main RT optimization problems: 1) brachytherapy and 2) intensity modulated radiation therapy (IMRT). The brachytherapy research involved solving a non-convex optimization problem by creating an open-source genetic algorithm optimizer to determine the optimal radioactive seed distribution for a given set of patient volumes and constraints, both dosimetric- and implant-based. The optimizer was tested for a set of 45 prostate brachytherapy patients. While all solutions met the clinical standards, they also benchmarked favorably with those generated by a standard commercial solver. Compared to its compatriot, the salient features of the generated solutions were: slightly reduced prostate coverage, lower dose to the urethra and rectum, and a smaller number of needles required for an implant. Historically, IMRT requires modulation of fluence while keeping the photon beam energy fixed. The IMRT-related investigation in this thesis aimed at broadening the solution space by varying photon energy. The problem therefore involved simultaneous optimization of photon beamlet energy and fluence, denoted by XMRT. Formulating the problem as convex, linear programming was applied to obtain solutions for optimal energy-dependent fluences, while achieving all clinical objectives and constraints imposed. Dosimetric advantages of XMRT over single-energy IMRT in the improved sparing of organs at risk (OARs) was demonstrated in simplified phantom studies. The XMRT algorithm was improved to include clinical dose-volume constraints and clinical studies for prostate and head and neck cancer patients were investigated. Compared to IMRT, XMRT provided improved dosimetric benefit in the prostate case, particularly within intermediate- to low-dose regions (≤ 40 Gy) for OARs. For head and neck cases, XMRT solutions showed no significant disadvantage or advantage over IMRT. The deliverability concerns for the fluence maps generated from XMRT were addressed by incorporating smoothing constraints during the optimization and through successful generation of treatment machine files. Further research is needed to explore the full potential of the XMRT approach to RT.

Occupational dose constraints in interventional cardiology procedures: the DIMOND approach

NASA Astrophysics Data System (ADS)

Tsapaki, Virginia; Kottou, Sophia; Vano, Eliseo; Komppa, Tuomo; Padovani, Renato; Dowling, Annita; Molfetas, Michael; Neofotistou, Vassiliki

2004-03-01

Radiation fields involved in angiographic suites are most uneven with intensity and gradient varying widely with projection geometry. The European Commission DIMOND III project addressed among others, the issues regarding optimization of staff doses with an attempt to propose preliminary occupational dose constraints. Two thermoluminescent dosemeters (TLD) were used to assess operators' extremity doses (left shoulder and left foot) during 20 coronary angiographies (CAs) and 20 percutaneous transluminal coronary angioplasties (PTCAs) in five European centres. X-ray equipment, radiation protection measures used and the dose delivered to the patient in terms of dose-area product (DAP) were recorded so as to subsequently associate them with operator's dose. The range of staff doses noted for the same TLD position, centre and procedure type emphasizes the importance of protective measures and technical characteristics of x-ray equipment. Correlation of patient's DAP with staff shoulder dose is moderate whereas correlation of patient's DAP with staff foot dose is poor in both CA and PTCA. Therefore, it is difficult to predict operator's dose from patient's DAP mainly due to the different use of protective measures. A preliminary occupational dose constraint value was defined by calculating cardiologists' annual effective dose and found to be 0.6 mSv.

Correlation between radiation dose and histopathological findings in patients with gliblastoma treated with boron neutron capture therapy (BNCT).

PubMed

Kageji, T; Mizobuchi, Y; Nagahiro, S; Nakagawa, Y; Kumada, H

2014-06-01

The purpose of this study was to clarify the correlation between the radiation dose and histopathological findings in patients with glioblastoma multiforme (GBM) treated with boron neutron capture therapy (BNCT). Histopathological studies were performed on specimens from 8 patients, 3 had undergone salvage surgery and 5 were autopsied. For histopathological cure of GBM at the primary site, the optimal minimal dose to the gross tumor volume (GTV) and the clinical target volume (CTV) were 68Gy(w) and 44Gy(w), respectively. Copyright © 2014. Published by Elsevier Ltd.

A comparison between simplified and intensive dose-titration algorithms using AIR inhaled insulin for insulin-naive patients with type 2 diabetes in a randomized noninferiority trial.

PubMed

Mathieu, C; Cuddihy, R; Arakaki, R F; Belin, R M; Planquois, J-M; Lyons, J N; Heilmann, C R

2009-09-01

Insulin initiation and optimization is a challenge for patients with type 2 diabetes. Our objective was to determine whether safety and efficacy of AIR inhaled insulin (Eli Lilly and Co., Indianapolis, IN) (AIR is a registered trademark of Alkermes, Inc., Cambridge, MA) using a simplified regimen was noninferior to an intensive regimen. This was an open-label, randomized study in insulin-naive adults not optimally controlled by oral antihyperglycemic medications. Simplified titration included a 6 U per meal AIR insulin starting dose. Individual doses were adjusted at mealtime in 2-U increments from the previous day's four-point self-monitored blood glucose (SMBG) (total < or =6 U). Starting Air insulin doses for intensive titration were based on fasting blood glucose, gender, height, and weight. Patients conducted four-point SMBG daily for the study duration. Insulin doses were titrated based on the previous 3 days' mean SMBG (total < or =8 U). End point hemoglobin A1C (A1C) was 7.07 +/- 0.09% and 6.87 +/- 0.09% for simplified (n = 178) and intensive (n = 180) algorithms, respectively. Noninferiority between algorithms was not established. The fasting blood glucose (least squares mean +/- standard error) values for the simplified (137.27 +/- 3.42 mg/dL) and intensive (133.13 +/- 3.42 mg/dL) algorithms were comparable. Safety profiles were comparable. The hypoglycemic rate at 4, 8, 12, and 24 weeks was higher in patients receiving intensive titration (all P < .0001). The nocturnal hypoglycemic rate for patients receiving intensive titration was higher than for those receiving simplified titration at 8 (P < 0.015) and 12 weeks (P < 0.001). Noninferiority between the algorithms, as measured by A1C, was not demonstrated. This finding re-emphasizes the difficulty of identifying optimal, simplified insulin regimens for patients.

An Analysis of Plan Robustness for Esophageal Tumors: Comparing Volumetric Modulated Arc Therapy Plans and Spot Scanning Proton Planning

DOE Office of Scientific and Technical Information (OSTI.GOV)

Warren, Samantha, E-mail: samantha.warren@oncology.ox.ac.uk; Partridge, Mike; Bolsi, Alessandra

Purpose: Planning studies to compare x-ray and proton techniques and to select the most suitable technique for each patient have been hampered by the nonequivalence of several aspects of treatment planning and delivery. A fair comparison should compare similarly advanced delivery techniques from current clinical practice and also assess the robustness of each technique. The present study therefore compared volumetric modulated arc therapy (VMAT) and single-field optimization (SFO) spot scanning proton therapy plans created using a simultaneous integrated boost (SIB) for dose escalation in midesophageal cancer and analyzed the effect of setup and range uncertainties on these plans. Methods andmore » Materials: For 21 patients, SIB plans with a physical dose prescription of 2 Gy or 2.5 Gy/fraction in 25 fractions to planning target volume (PTV){sub 50Gy} or PTV{sub 62.5Gy} (primary tumor with 0.5 cm margins) were created and evaluated for robustness to random setup errors and proton range errors. Dose–volume metrics were compared for the optimal and uncertainty plans, with P<.05 (Wilcoxon) considered significant. Results: SFO reduced the mean lung dose by 51.4% (range 35.1%-76.1%) and the mean heart dose by 40.9% (range 15.0%-57.4%) compared with VMAT. Proton plan robustness to a 3.5% range error was acceptable. For all patients, the clinical target volume D{sub 98} was 95.0% to 100.4% of the prescribed dose and gross tumor volume (GTV) D{sub 98} was 98.8% to 101%. Setup error robustness was patient anatomy dependent, and the potential minimum dose per fraction was always lower with SFO than with VMAT. The clinical target volume D{sub 98} was lower by 0.6% to 7.8% of the prescribed dose, and the GTV D{sub 98} was lower by 0.3% to 2.2% of the prescribed GTV dose. Conclusions: The SFO plans achieved significant sparing of normal tissue compared with the VMAT plans for midesophageal cancer. The target dose coverage in the SIB proton plans was less robust to random setup errors and might be unacceptable for certain patients. Robust optimization to ensure adequate target coverage of SIB proton plans might be beneficial.« less

An Analysis of Plan Robustness for Esophageal Tumors: Comparing Volumetric Modulated Arc Therapy Plans and Spot Scanning Proton Planning

PubMed Central

Warren, Samantha; Partridge, Mike; Bolsi, Alessandra; Lomax, Anthony J.; Hurt, Chris; Crosby, Thomas; Hawkins, Maria A.

2016-01-01

Purpose Planning studies to compare x-ray and proton techniques and to select the most suitable technique for each patient have been hampered by the nonequivalence of several aspects of treatment planning and delivery. A fair comparison should compare similarly advanced delivery techniques from current clinical practice and also assess the robustness of each technique. The present study therefore compared volumetric modulated arc therapy (VMAT) and single-field optimization (SFO) spot scanning proton therapy plans created using a simultaneous integrated boost (SIB) for dose escalation in midesophageal cancer and analyzed the effect of setup and range uncertainties on these plans. Methods and Materials For 21 patients, SIB plans with a physical dose prescription of 2 Gy or 2.5 Gy/fraction in 25 fractions to planning target volume (PTV)50Gy or PTV62.5Gy (primary tumor with 0.5 cm margins) were created and evaluated for robustness to random setup errors and proton range errors. Dose–volume metrics were compared for the optimal and uncertainty plans, with P<.05 (Wilcoxon) considered significant. Results SFO reduced the mean lung dose by 51.4% (range 35.1%-76.1%) and the mean heart dose by 40.9% (range 15.0%-57.4%) compared with VMAT. Proton plan robustness to a 3.5% range error was acceptable. For all patients, the clinical target volume D98 was 95.0% to 100.4% of the prescribed dose and gross tumor volume (GTV) D98 was 98.8% to 101%. Setup error robustness was patient anatomy dependent, and the potential minimum dose per fraction was always lower with SFO than with VMAT. The clinical target volume D98 was lower by 0.6% to 7.8% of the prescribed dose, and the GTV D98 was lower by 0.3% to 2.2% of the prescribed GTV dose. Conclusions The SFO plans achieved significant sparing of normal tissue compared with the VMAT plans for midesophageal cancer. The target dose coverage in the SIB proton plans was less robust to random setup errors and might be unacceptable for certain patients. Robust optimization to ensure adequate target coverage of SIB proton plans might be beneficial. PMID:27084641

WE-AB-209-12: Quasi Constrained Multi-Criteria Optimization for Automated Radiation Therapy Treatment Planning

DOE Office of Scientific and Technical Information (OSTI.GOV)

Watkins, W.T.; Siebers, J.V.

Purpose: To introduce quasi-constrained Multi-Criteria Optimization (qcMCO) for unsupervised radiation therapy optimization which generates alternative patient-specific plans emphasizing dosimetric tradeoffs and conformance to clinical constraints for multiple delivery techniques. Methods: For N Organs At Risk (OARs) and M delivery techniques, qcMCO generates M(N+1) alternative treatment plans per patient. Objective weight variations for OARs and targets are used to generate alternative qcMCO plans. For 30 locally advanced lung cancer patients, qcMCO plans were generated for dosimetric tradeoffs to four OARs: each lung, heart, and esophagus (N=4) and 4 delivery techniques (simple 4-field arrangements, 9-field coplanar IMRT, 27-field non-coplanar IMRT, and non-coplanarmore » Arc IMRT). Quasi-constrained objectives included target prescription isodose to 95% (PTV-D95), maximum PTV dose (PTV-Dmax)< 110% of prescription, and spinal cord Dmax<45 Gy. The algorithm’s ability to meet these constraints while simultaneously revealing dosimetric tradeoffs was investigated. Statistically significant dosimetric tradeoffs were defined such that the coefficient of determination between dosimetric indices which varied by at least 5 Gy between different plans was >0.8. Results: The qcMCO plans varied mean dose by >5 Gy to ipsilateral lung for 24/30 patients, contralateral lung for 29/30 patients, esophagus for 29/30 patients, and heart for 19/30 patients. In the 600 plans computed without human interaction, average PTV-D95=67.4±3.3 Gy, PTV-Dmax=79.2±5.3 Gy, and spinal cord Dmax was >45 Gy in 93 plans (>50 Gy in 2/600 plans). Statistically significant dosimetric tradeoffs were evident in 19/30 plans, including multiple tradeoffs of at least 5 Gy between multiple OARs in 7/30 cases. The most common statistically significant tradeoff was increasing PTV-Dmax to reduce OAR dose (15/30 patients). Conclusion: The qcMCO method can conform to quasi-constrained objectives while revealing significant variations in OAR doses including mean dose reductions >5 Gy. Clinical implementation will facilitate patient-specific decision making based on achievable dosimetry as opposed to accept/reject models based on population derived objectives.« less

Clinical application of a nomogram based on age, serum FSH and AMH to select the FSH starting dose in IVF/ICSI cycles: a retrospective two-centres study.

PubMed

Papaleo, Enrico; Zaffagnini, Stefano; Munaretto, Maria; Vanni, Valeria Stella; Rebonato, Giorgia; Grisendi, Valentina; Di Paola, Rossana; La Marca, Antonio

2016-12-01

To externally validate a nomogram based on ovarian reserve markers as a tool to optimize the FSH starting dose in IVF/ICSI cycles. A two-centres retrospective study including 398 infertile women undergoing their first IVF/ICSI cycle (June 2013-June 2014). IVF data were retrieved from two independent IVF centres in Italy (San Raffaele Hospital, Centre 1; Verona Hospital, Centre 2). A central lab for the routine measurement of AMH and FSH was used for both centres. All women were treated based on physical and hormonal characteristics according to locally adopted protocols. The nomogram was then retrospectively applied to the patients comparing the calculated starting dose to the one actually given. In Centre 1, 64/131 women (48.8%) had an ovarian response below the target. While 45 of these patients were treated with a maximal FSH starting dose (≥225 IU), n=19/131 (14.5%) were treated with a submaximal dose. The vast majority of them (n=17/19) would have received a higher FSH starting dose by using the nomogram. Seventeen patients (n=17/131) had hyper response and about half of them would have been treated with a reduced FSH starting dose according to the nomogram. In Centre 2, 142/267 patients (53.2%) had an ovarian response below the target. While 136 of these were treated with a maximal FSH starting dose (≥225 IU), n=6/267 were treated with a submaximal dose. The majority of them (n=5/6) would have received a higher FSH starting dose. Thirty-two (n=32/267) patients had hyper response and more than half of them would have been treated with a reduced FSH dose. In both Centres, applying the nomogram would have resulted in more appropriate FSH starting doses compared to the the ones actually given based on clinicians choices. The use of an objective algorithm based on patient's age, serum FSH and AMH levels may thus be an effective advice on the selection of the tailored FSH starting dose. Hence, the use of this easily available nomogram could increase the proportion of patients achieving the optimal ovarian response. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Prescription of and adherence to non-steroidal anti-inflammatory drugs and gastroprotective agents in at-risk gastrointestinal patients.

PubMed

Lanas, Angel; Polo-Tomás, Mónica; Roncales, Pilar; Gonzalez, Miguel A; Zapardiel, Javier

2012-05-01

Patients with gastrointestinal (GI) risk factors who take non-steroidal anti-inflammatory drugs (NSAIDs) should also take gastroprotective agents (GPAs). No studies have evaluated adherence and reasons for non-adherence to GPA and NSAID therapies. This was a prospective, multicenter, observational, longitudinal study. Patients attending rheumatology/orthopedic clinics who were co-prescribed NSAID plus GPA for at least 15 days and had risk factors for GI complications were followed up by telephone call. Optimal adherence was defined as taking the drug for ≥ 80% of prescribed days. Multivariate logistic regression analysis was used to determine factors associated with non-adherence. Of 1,232 patients interviewed, 192 were excluded because of inaccurate data. Of the remaining 1,040 patients, 74 % were prescribed low-dose NSAIDs and 99.8 % were prescribed a standard or high-dose GPA. In all, 70 % of NSAIDs and 63.1 % of GPA prescriptions were short term (< 30 days). The majority of patients who were prescribed either an NSAID (92.5 % ) or GPA (85.9 % ) started therapy. Optimal adherence to GPA or NSAIDs was reported by 79.7 % (95 % confidence interval (CI): 76.9-82.2 % ) and 84.1 % (95 % CI: 81.7-86.3 % ) of patients, respectively. More adverse events occurred among patients who reported non-optimal adherence than among patients with optimal adherence to GPA (22.1 vs. 1.9 % , P < 0.0001). As reasons for non-adherence, patients most frequently cited infrequent/low-intensity rheumatic pain (NSAIDs) or forgetfulness (GPAs). Adverse events and short-term treatment were independent factors associated with poor adherence for both NSAIDs and GPAs. History of uncomplicated peptic ulcer and frequent dosing were additional factors associated with non-adherence to NSAIDs. Most frequent reasons for non-adherence are infrequent/low-intensity rheumatic pain (NSAIDs) or forgetfulness (GPAs). Short-term treatment and adverse events were associated with poor adherence for both therapies.

A rapid non invasive L-DOPA-¹³C breath test for optimally suppressing extracerebral AADC enzyme activity - toward individualizing carbidopa therapy in Parkinson’s disease.

PubMed

Modak, Anil; Durso, Raymon; Josephs, Ephraim; Rosen, David

2012-01-01

Peripheral carbidopa (CD) levels directly impact on central dopamine (DA) production in Parkinson disease (PD) through extracerebral inhibition of dopa decarboxylase (AADC) resulting in an increase in levodopa (LD) bioavailability. Recent data suggests that higher CD doses than those presently used in PD treatment may result in improved clinical response. Optimizing CD doses in individual patients may, therefore, result in ideal individualized treatment. A single center, randomized, double-blind study was carried out recruiting 5 Parkinson’s disease (PD) patients already on LD/CD and 1 treatment näve PD patient using stable isotope labeled LD-1-¹³C as a substrate for a noninvasive breath test to evaluate individual AADC enzyme activity. Each patient was studied five times, receiving 200 mg LD-¹³C at each visit along with one of five randomized CD doses (0, 25, 50, 100 and 200 mg). The metabolite ¹³CO₂ in breath was measured for evaluating AADC enzyme activity and plasma metabolite levels for LD-¹³C and homovanillic acid (HVA) were measured for 4 hours. HVA in plasma and ¹³CO₂ in breath are metabolic products of LD. We found a significant positive correlation of ¹³CO₂ DOB AUC0-240 with serum HVA AUC0-240 following the oral dose of LD-1-¹³C for all 5 doses of CD (r² = 0.9378). With increasing inhibition of AADC enzyme activity with CD, we observed an increase in the plasma concentration of LD.We found an inverse correlation of the 13CO2 DOB AUC with serum LD-¹³C AUC. Our studies indicate the optimal dose of CD for maximal suppression of AADC enzyme activity can be determined for each individual from ¹³CO₂ generation in breath. The LD-breath test can be a useful noninvasive diagnostic tool for evaluation of AADC enzyme activity using the biomarker ¹³CO₂ in breath, a first step in personalizing CD doses for PD patients.

SU-F-T-497: Spatiotemporally Optimal, Personalized Prescription Scheme for Glioblastoma Patients Using the Proliferation and Invasion Glioma Model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, M; Rockhill, J; Phillips, M

Purpose: To investigate a spatiotemporally optimal radiotherapy prescription scheme and its potential benefit for glioblastoma (GBM) patients using the proliferation and invasion (PI) glioma model. Methods: Standard prescription for GBM was assumed to deliver 46Gy in 23 fractions to GTV1+2cm margin and additional 14Gy in 7 fractions to GTV2+2cm margin. We simulated the tumor proliferation and invasion in 2D according to the PI glioma model with a moving velocity of 0.029(slow-move), 0.079(average-move), and 0.13(fast-move) mm/day for GTV2 with a radius of 1 and 2cm. For each tumor, the margin around GTV1 and GTV2 was varied to 0–6 cm and 1–3more » cm respectively. Total dose to GTV1 was constrained such that the equivalent uniform dose (EUD) to normal brain equals EUD with the standard prescription. A non-stationary dose policy, where the fractional dose varies, was investigated to estimate the temporal effect of the radiation dose. The efficacy of an optimal prescription scheme was evaluated by tumor cell-surviving fraction (SF), EUD, and the expected survival time. Results: Optimal prescription for the slow-move tumors was to use 3.0(small)-3.5(large) cm margins to GTV1, and 1.5cm margin to GTV2. For the average- and fast-move tumors, it was optimal to use 6.0cm margin for GTV1 suggesting that whole brain therapy is optimal, and then 1.5cm (average-move) and 1.5–3.0cm (fast-move, small-large) margins for GTV2. It was optimal to deliver the boost sequentially using a linearly decreasing fractional dose for all tumors. Optimal prescription led to 0.001–0.465% of the tumor SF resulted from using the standard prescription, and increased tumor EUD by 25.3–49.3% and the estimated survival time by 7.6–22.2 months. Conclusion: It is feasible to optimize a prescription scheme depending on the individual tumor characteristics. A personalized prescription scheme could potentially increase tumor EUD and the expected survival time significantly without increasing EUD to normal brain.« less

Efficacy of Low-Dose Corticosteroid Therapy Versus High-Dose Corticosteroid Therapy in Bell's Palsy in Children.

PubMed

Arican, Pinar; Dundar, Nihal Olgac; Gencpinar, Pinar; Cavusoglu, Dilek

2017-01-01

Bell's palsy is the most common cause of acute peripheral facial nerve paralysis, but the optimal dose of corticosteroids in pediatric patients is still unclear. This retrospective study aimed to evaluate the efficacy of low-dose corticosteroid therapy compared with high-dose corticosteroid therapy in children with Bell's palsy. Patients were divided into 2 groups based on the dose of oral prednisolone regimen initiated. The severity of idiopathic facial nerve paralysis was graded according to the House-Brackmann Grading Scale. The patients were re-assessed in terms of recovery rate at the first, third, and sixth months of treatment. There was no significant difference in complete recovery between the 2 groups after 1, 3, and 6 months of treatment. In our study, we concluded that even at a dose of 1 mg/kg/d, oral prednisolone was highly effective in the treatment of Bell's palsy in children.

Radiation Dose Estimation for Pediatric Patients Undergoing Cardiac Catheterization

NASA Astrophysics Data System (ADS)

Wang, Chu

Patients undergoing cardiac catheterization are potentially at risk of radiation-induced health effects from the interventional fluoroscopic X-ray imaging used throughout the clinical procedure. The amount of radiation exposure is highly dependent on the complexity of the procedure and the level of optimization in imaging parameters applied by the clinician. For cardiac catheterization, patient radiation dosimetry, for key organs as well as whole-body effective, is challenging due to the lack of fixed imaging protocols, unlike other common X-ray based imaging modalities. Pediatric patients are at a greater risk compared to adults due to their greater cellular radio-sensitivities as well as longer remaining life-expectancy following the radiation exposure. In terms of radiation dosimetry, they are often more challenging due to greater variation in body size, which often triggers a wider range of imaging parameters in modern imaging systems with automatic dose rate modulation. The overall objective of this dissertation was to develop a comprehensive method of radiation dose estimation for pediatric patients undergoing cardiac catheterization. In this dissertation, the research is divided into two main parts: the Physics Component and the Clinical Component. A proof-of-principle study focused on two patient age groups (Newborn and Five-year-old), one popular biplane imaging system, and the clinical practice of two pediatric cardiologists at one large academic medical center. The Physics Component includes experiments relevant to the physical measurement of patient organ dose using high-sensitivity MOSFET dosimeters placed in anthropomorphic pediatric phantoms. First, the three-dimensional angular dependence of MOSFET detectors in scatter medium under fluoroscopic irradiation was characterized. A custom-made spherical scatter phantom was used to measure response variations in three-dimensional angular orientations. The results were to be used as angular dependence correction factors for the MOSFET organ dose measurements in the following studies. Minor angular dependence (< +/-20% at all angles tested, < +/-10% at clinically relevant angles in cardiac catheterization) was observed. Second, the cardiac dose for common fluoroscopic imaging techniques for pediatric patients in the two age groups was measured. Imaging technique settings with variations of individual key imaging parameters were tested to observe the quantitative effect of imaging optimization or lack thereof. Along with each measurement, the two standard system output indices, the Air Kerma (AK) and Dose-Area Product (DAP), were also recorded and compared to the measured cardiac and skin doses -- the lack of correlation between the indices and the organ doses shed light to the substantial limitation of the indices in representing patient radiation dose, at least within the scope of this dissertation. Third, the effective dose (ED) for Posterior-Anterior and Lateral fluoroscopic imaging techniques for pediatric patients in the two age groups was determined. In addition, the dosimetric effect of removing the anti-scatter grid was studied, for which a factor-of-two ED rate reduction was observed for the imaging techniques. The Clinical Component involved analytical research to develop a validated retrospective cardiac dose reconstruction formulation and to propose the new Optimization Index which evaluates the level of optimization of the clinician's imaging usage during a procedure; and small sample group of actual procedures were used to demonstrate applicability of these formulations. In its entirety, the research represents a first-of-its-kind comprehensive approach in radiation dosimetry for pediatric cardiac catheterization; and separately, it is also modular enough that each individual section can serve as study templates for small-scale dosimetric studies of similar purposes. The data collected and algorithmic formulations developed can be of use in areas of personalized patient dosimetry, clinician training, image quality studies and radiation-associated health effect research.

A 4D-optimization concept for scanned ion beam therapy.

PubMed

Graeff, Christian; Lüchtenborg, Robert; Eley, John Gordon; Durante, Marco; Bert, Christoph

2013-12-01

Scanned carbon beam therapy offers advantageous dose distributions and an increased biological effect. Treating moving targets is complex due to sensitivity to range changes and interplay. We propose a 4D treatment planning concept that considers motion during particle number optimization. The target was subdivided into sectors, one for each motion phase of a 4D-CT. Each sector was non-rigidly transformed to its motion phase and there targeted by a dedicated raster field (RST). Therefore, the resulting 4D-RST compensated target motion and range changes. A 4D treatment control system (TCS) was needed for synchronized delivery to the measured patient motion. 4D-optimized plans were simulated for 9 NSCLC lung cancer patients and compared to static irradiation at end-exhale. A prototype TCS was implemented and successfully tested in a film experiment. The 4D-optimized treatment plan resulted in only slightly lower dose coverage of the target compared to static optimization, with V 95% of 97.9% (median, range 96.5-99.4%) vs. 99.3% (98.5-99.8%), with negligible overdose. The conformity number was comparable at 88.2% (85.1-92.5%) vs. 85.2% (79.9-91.2%) for 4D and static, respectively. We implemented and tested a 4D treatment plan optimization method resulting in highly conformal dose delivery. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

TH-AB-202-09: Direct-Aperture Optimization for Combined MV+kV Dose Planning in Fluoroscopic Real-Time Tumor-Tracking Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, X; Belcher, AH; Grelewicz, Z

Purpose: Real-time kV fluoroscopic tumor tracking has the benefit of direct tumor position monitoring. However, there is clinical concern over the excess kV imaging dose cost to the patient when imaging in continuous fluoroscopic mode. This work addresses this specific issue by proposing a combined MV+kV direct-aperture optimization (DAO) approach to integrate the kV imaging beam into a treatment planning such that the kV radiation is considered as a contributor to the overall dose delivery. Methods: The combined MV+kV DAO approach includes three algorithms. First, a projected Quasi-Newton algorithm (L-BFGS) is used to find optimized fluence with MV+kV dose formore » the best possible dose distribution. Then, Engel’s algorithm is applied to optimize the total number of monitor units and heuristically optimize the number of apertures. Finally, an aperture shape optimization (ASO) algorithm is applied to locally optimize the leaf positions of MLC. Results: Compared to conventional DAO MV plans with continuous kV fluoroscopic tracking, combined MV+kV DAO plan leads to a reduction in the total number of MV monitor units due to inclusion of kV dose as part of the PTV, and was also found to reduce the mean and maximum doses on the organs at risk (OAR). Compared to conventional DAO MV plan without kV tracking, the OAR dose in the combined MV+kV DAO plan was only slightly higher. DVH curves show that combined MV+kV DAO plan provided about the same PTV coverage as that in the conventional DAO plans without kV imaging. Conclusion: We report a combined MV+kV DAO approach that allows real time kV imager tumor tracking with only a trivial increasing on the OAR doses while providing the same coverage to PTV. The approach is suitable for clinic implementation.« less

The Optimal Dose of Nicardipine for Enhancement of Indirect Portography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Inoue, Yutaka; Nakamura, Hironobu; Akaji, Hideyo

1998-01-15

Purpose: To determine the optimal dose of nicardipine (NCR) for enhancement of indirect portography. Methods: Forty-eight patients underwent conventional film indirect portography via the superior mesenteric artery (SMA) first without and then with preinjection of 1/64-2 mg of NCR into the SMA. Results: NCR (1/8-2 mg) shortened the arterial phase to 50% and the portal appearance time to 60% of control without reflux of contrast medium into the aorta. Portal enhancement was excellent at doses of 1/32 mg or more. Blood pressures and pulse rate showed no significant change at 1/4 mg or less. Conclusion: NCR (1/8-1/4 mg) into themore » SMA is the optimal dose for achieving sufficient contrast enhancement on indirect portography while reducing the transit time of contrast medium and minimizing effects on the systemic circulation.« less

Real-World Dosing Patterns of Atomoxetine in Adults with Attention-Deficit/Hyperactivity Disorder.

PubMed

Kabul, Samaneh; Alatorre, Carlos; Montejano, Leslie B; Farr, Amanda M; Clemow, David B

2015-12-01

The aim was to investigate the dosing patterns of atomoxetine monotherapy in adult patients with attention-deficit/hyperactivity disorder (ADHD) in a retrospective analysis. Adult (≥ 18 years) patients with ADHD newly initiated on atomoxetine with ≥ 1 outpatient pharmacy claim for atomoxetine between January 2006 and December 2011 were selected from the Truven Health MarketScan(®) Commercial database. After a 30-day titration period, dosing patterns of atomoxetine monotherapy were analyzed in the 12 months following initiation. In addition, patient demographic and clinical characteristics were compared to identify characteristics associated with suboptimal versus recommended dosing. Of the 12,412 adult patients with ADHD newly initiated on atomoxetine, 4548 (36.6%) were suboptimally dosed, whereas 3323 (26.7%) were treated at recommended dose. Overall, study patients were treated at a mean (standard deviation [SD]) dose of 68.5 (44.9) mg/day. The suboptimal dosing cohort included significantly more females (54% vs. 44%, P < 0.001) and had fewer patients with pre-index use of other ADHD medications (17% vs. 20%, P < 0.001) compared with the recommended dosing cohort. Adult patients with ADHD receiving atomoxetine therapy in a real-world setting are often dosed suboptimally. Increasing the awareness on optimal dosing strategy among clinicians and patients is warranted to maximize the therapeutic benefits of atomoxetine among adult patients with ADHD. © 2015 Eli Lilly and Company. CNS Neuroscience and Therapeutics published by John Wiley & Sons Ltd.

TU-G-204-04: A Unified Strategy for Bi-Factorial Optimization of Radiation Dose and Contrast Dose in CT Imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sahbaee, P; Zhang, Y; Solomon, J

Purpose: To substantiate the interdependency of contrast dose, radiation dose, and image quality in CT towards the patient- specific optimization of the imaging protocols Methods: The study deployed two phantom platforms. A variable sized (12, 18, 23, 30, 37 cm) phantom (Mercury-3.0) containing an iodinated insert (8.5 mgI/ml) was imaged on a representative CT scanner at multiple CTDI values (0.7–22.6 mGy). The contrast and noise were measured from the reconstructed images for each phantom diameter. Linearly related to iodine-concentration, contrast-to-noise ratio (CNR), were calculated for 16 iodine-concentration levels (0–8.5 mgI/ml). The analysis was extended to a recently developed suit ofmore » 58 virtual human models (5D XCAT) with added contrast dynamics. Emulating a contrast-enhanced abdominal image procedure and targeting a peak-enhancement in aorta, each XCAT phantom was “imaged” using a simulation platform (CatSim, GE). 3D surfaces for each patient/size established the relationship between iodine-concentration, dose, and CNR. The ratios of change in iodine-concentration versus dose (IDR) to yield a constant change in CNR were calculated for each patient size. Results: Mercury phantom results show the image-quality size- dependence on CTDI and IC levels. For desired image-quality values, the iso-contour-lines reflect the trade off between contrast-material and radiation doses. For a fixed iodine-concentration (4 mgI/mL), the IDR values for low (1.4 mGy) and high (11.5 mGy) dose levels were 1.02, 1.07, 1.19, 1.65, 1.54, and 3.14, 3.12, 3.52, 3.76, 4.06, respectively across five sizes. The simulation data from XCAT models confirmed the empirical results from Mercury phantom. Conclusion: The iodine-concentration, image quality, and radiation dose are interdependent. The understanding of the relationships between iodine-concentration, image quality, and radiation dose will allow for a more comprehensive optimization of CT imaging devices and techniques, providing the methodology to balance iodine-concentration and dose based on patient’s attributes.« less

SU-F-T-194: Analyzing the Effect of Range Shifter Air Gap On TPS Dose Modeling Accuracy in Superficial PBS Proton Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shirey, R; Wu, H

2016-06-15

Purpose: Treatment planning systems (TPS) may not accurately model superficial dose distributions of range shifted proton pencil beam scanning (PBS) treatments. Numerous patient-specific QA tests performed on superficially treated PBS plans have shown a consistent overestimate of dose by the TPS. This study quantifies variations between TPS planned dose and measured dose as a function of range shifter air gap and treatment depths up to 5 cm. Methods: PBS treatment plans were created in the TPS to uniformly irradiate a volume of solid water. One plan was created for each range shifter position analyzed, and all plans utilized identical dosemore » optimization parameters. Each optimized plan was analyzed in the TPS to determine the planned dose at varying depths. A PBS proton therapy system with a 3.5 cm lucite range shifter delivered the treatment plans, and a parallel plate chamber embedded in RW3 solid water measured dose at shallow depths for each air gap. Differences between measured and planned doses were plotted and analyzed. Results: The data show that the TPS more accurately models superficial dose as the air gap between the range shifter and patient surface decreases. Air gaps less than 10 cm have an average dose difference of only 1.6%, whereas air gaps between 10 and 20 cm differ by 3.0% and gaps greater than 20 cm differ by 4.4%. Conclusion: This study has shown that the TPS is unable to accurately model superficial dose with a large range shifter air gap. Dose differences greater than 3% will likely cause QA failure, as many institutions analyze patient QA with a 3%/3mm gamma analysis. For superficial PBS therapy, range shifter positions should be chosen to keep the air gap less then 10 cm when patient setup and gantry geometry allow.« less

Research on Ratio of Dosage of Drugs in Traditional Chinese Prescriptions by Data Mining.

PubMed

Yu, Xing-Wen; Gong, Qing-Yue; Hu, Kong-Fa; Mao, Wen-Jing; Zhang, Wei-Ming

2017-01-01

Maximizing the effectiveness of prescriptions and minimizing adverse effects of drugs is a key component of the health care of patients. In the practice of traditional Chinese medicine (TCM), it is important to provide clinicians a reference for dosing of prescribed drugs. The traditional Cheng-Church biclustering algorithm (CC) is optimized and the data of TCM prescription dose is analyzed by using the optimization algorithm. Based on an analysis of 212 prescriptions related to TCM treatment of kidney diseases, the study generated 87 prescription dose quantum matrices and each sub-matrix represents the referential value of the doses of drugs in different recipes. The optimized CC algorithm can effectively eliminate the interference of zero in the original dose matrix of TCM prescriptions and avoid zero appearing in output sub-matrix. This results in the ability to effectively analyze the reference value of drugs in different prescriptions related to kidney diseases, so as to provide valuable reference for clinicians to use drugs rationally.

Dosimetric comparison between VMAT and RC3D techniques: case of prostate treatment

NASA Astrophysics Data System (ADS)

Chemingui, Fatima Zohra; Benrachi, Fatima; Bali, Mohamed Saleh; Ladjal, Hamid

2017-09-01

Considered as the second men cancer in Algeria, prostate cancer is treated in 70% by radiation. That's why radiation therapy is therapeutic weapon for prostate cancer. Conformational Radiotherapy in 3D is the most common technique [1-5]. The use of conventionally optimized treatment plans was compared at case scenario of optimized treatment plans VMAT for prostate cancer. The evaluation of the two optimizations strategies focused on the resulting plans ability to retain dose objectives under the influence of patient set up. Dose Volume Histogram in the Planning Target Volume and dose in the Organs At Risks were used to calculate the conformity index, and evaluation ratio of irradiated volume which represent the main tool of comparison [6,7]. The situation was analysed systematically. The 14% dose increase in the target leads to a decrease in the dose in adjacent organs with 39% in the bladder. Therefore, the criterion for better efficacy and less toxicity reveal that VMAT is the best choice.

A Prospective, Randomized, Open-Label, Blinded, Endpoint Study Exploring Platelet Response to Half-Dose Prasugrel and Ticagrelor in Patients with the Acute Coronary Syndrome: HOPE-TAILOR Study.

PubMed

Jin, Cai De; Kim, Moo Hyun; Bang, Junghee; Serebruany, Victor

The optimal dosing of novel oral P2Y12 receptor platelet inhibitors such as prasugrel or ticagrelor is unclear and especially challenging in East Asians. We hypothesize that half-dose prasugrel and ticagrelor may be sufficient for long-term maintenance management in Korean patients with the acute coronary syndrome (ACS) compared with conventional dosages. HOPE-TAILOR (Half Dose of Prasugrel and Ticagrelor in Platelet Response after Acute Coronary Syndromes) is a prospective, randomized, open-label, blinded, endpoint (PROBE) single-center, clinical trial. A total of 100 patients with ACS undergoing drug-eluting stent implantation will be randomly assigned to prasugrel, ticagrelor, or clopidogrel, and the patients in each treatment group will receive 1-month therapy with 100 mg q.d. aspirin plus prasugrel 10 mg q.d., ticagrelor 90 mg b.i.d., or clopidogrel 75 mg q.d., followed by half-dose prasugrel 5 mg q.d. or ticagrelor 45 mg b.i.d. for maintenance treatment but without clopidogrel dose reduction. The primary endpoint will be optimal platelet reactivity 3 months after coronary intervention, defined by VerifyNow Analyzer (PRU: 85-208) and vasodilator-stimulated phosphoprotein P2Y12 flow cytometry assay (platelet reactivity indices: 16-50%). Clinical outcomes will also be assessed, including major efficacy (composite of cardiac death, nonfatal myocardial infarction, repeat revascularization, or stroke) and safety (bleeding ≥2 according to the Bleeding Academic Research Consortium). HOPE-TAILOR is a prospective, randomized, open-label, blinded, endpoint study to explore the efficacy and safety of novel P2Y12 receptor inhibitors administered orally at half the dose in Korean patients with ACS. The results will be available late in 2017. © 2017 S. Karger AG, Basel.

A versatile multi-objective FLUKA optimization using Genetic Algorithms

NASA Astrophysics Data System (ADS)

Vlachoudis, Vasilis; Antoniucci, Guido Arnau; Mathot, Serge; Kozlowska, Wioletta Sandra; Vretenar, Maurizio

2017-09-01

Quite often Monte Carlo simulation studies require a multi phase-space optimization, a complicated task, heavily relying on the operator experience and judgment. Examples of such calculations are shielding calculations with stringent conditions in the cost, in residual dose, material properties and space available, or in the medical field optimizing the dose delivered to a patient under a hadron treatment. The present paper describes our implementation inside flair[1] the advanced user interface of FLUKA[2,3] of a multi-objective Genetic Algorithm[Erreur ! Source du renvoi introuvable.] to facilitate the search for the optimum solution.

Motion-robust intensity-modulated proton therapy for distal esophageal cancer.

PubMed

Yu, Jen; Zhang, Xiaodong; Liao, Li; Li, Heng; Zhu, Ronald; Park, Peter C; Sahoo, Narayan; Gillin, Michael; Li, Yupeng; Chang, Joe Y; Komaki, Ritsuko; Lin, Steven H

2016-03-01

To develop methods for evaluation and mitigation of dosimetric impact due to respiratory and diaphragmatic motion during free breathing in treatment of distal esophageal cancers using intensity-modulated proton therapy (IMPT). This was a retrospective study on 11 patients with distal esophageal cancer. For each patient, four-dimensional computed tomography (4D CT) data were acquired, and a nominal dose was calculated on the average phase of the 4D CT. The changes of water equivalent thickness (ΔWET) to cover the treatment volume from the peak of inspiration to the valley of expiration were calculated for a full range of beam angle rotation. Two IMPT plans were calculated: one at beam angles corresponding to small ΔWET and one at beam angles corresponding to large ΔWET. Four patients were selected for the calculation of 4D-robustness-optimized IMPT plans due to large motion-induced dose errors generated in conventional IMPT. To quantitatively evaluate motion-induced dose deviation, the authors calculated the lowest dose received by 95% (D95) of the internal clinical target volume for the nominal dose, the D95 calculated on the maximum inhale and exhale phases of 4D CT DCT0 andDCT50 , the 4D composite dose, and the 4D dynamic dose for a single fraction. The dose deviation increased with the average ΔWET of the implemented beams, ΔWETave. When ΔWETave was less than 5 mm, the dose error was less than 1 cobalt gray equivalent based on DCT0 and DCT50 . The dose deviation determined on the basis of DCT0 and DCT50 was proportionally larger than that determined on the basis of the 4D composite dose. The 4D-robustness-optimized IMPT plans notably reduced the overall dose deviation of multiple fractions and the dose deviation caused by the interplay effect in a single fraction. In IMPT for distal esophageal cancer, ΔWET analysis can be used to select the beam angles that are least affected by respiratory and diaphragmatic motion. To further reduce dose deviation, the 4D-robustness optimization can be implemented for IMPT planning. Calculation of DCT0 and DCT50 is a conservative method to estimate the motion-induced dose errors.

Impact of adherence on the outcome of antiviral therapy for chronic hepatitis C.

PubMed

Mulhall, Brian P; Younossi, Zobair

2005-01-01

Nearly 4 million people in the United States have evidence of hepatitis C infection (HCV), representing a significant cause of cirrhosis and liver cancer as well a major burden to our healthcare systems and society. Antiviral therapy can successfully eradicate HCV over the long term, potentially reducing the risk of progression and improving patients' quality of life. The currently preferred HCV treatment is a combination of pegylated interferon alfa and ribavirin, which can achieve an overall sustained viral eradication rate of 55%. The duration of this treatment is typically determined by HCV genotype and the patient's early virologic response to the antiviral regimen. Evidence has accumulated over the past few years to indicate that close adherence to the optimal antiviral regimen can enhance sustained virologic response. But optimal treatment outcomes require diligence and careful management of side effects related to combination therapy. Although reducing the dose of pegylated interferon alfa, ribavirin, or both can effectively treat side effects, suboptimal doses of this regimen, especially ribavirin, may negatively affect virologic response. An alternative strategy is to use growth factors to treat cytopenias. This strategy can obviate dose reductions while potentially improving patients' quality of life. Patient support seems especially important early after the initiation of antiviral therapy. Encouraging study findings involving the growth factors, epoetin alfa and darbepoetin alfa, suggest improved anemia and quality of life while maintaining the optimal ribavirin dose. Future work should be aimed at providing stronger evidence for the use of these "supportive products" during anti-HCV therapy. As we strive to develop better treatment options for our HCV patients, the importance of adhering to the treatment regimen continues to play a central role. Effective side effect management is crucial for the success of this treatment because adherence is negatively affected by side effects related to the antiviral regimen. By identifying and addressing the important side effects of combination therapy for HCV, adherence to treatment can be improved and optimal outcomes can be achieved.

SU-E-T-294: Dosimetric Analysis of Planning Phase Using Overlap Volume Histogram for Respiratory Gated Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kang, S; Kim, D; Kim, T

2015-06-15

Purpose: End-of-exhale (EOE) phase is generally preferred for gating window because tumor position is more reproducible. However, other gating windows might be more appropriate for dose distribution perspective. In this pilot study, we proposed to utilize overlap volume histogram (OVH) to search optimized gating window and demonstrated its feasibility. Methods: We acquired 4DCT of 10 phases for 3 lung patients (2 with a target at right middle lobe and 1 at right upper lobe). After structures were defined in every phase, the OVH of each OAR was generated to quantify the three dimensional spatial relationship between the PTV and OARsmore » (bronchus, esophagus, heart and cord etc.) at each phase. OVH tells the overlap volume of an OAR according to outward distance from the PTV. Relative overlap volume at 20 mm outward distance from the PTV (ROV-20) was also defined as a metric for measuring overlap volume and obtained. For dose calculation, 3D CRT plans were made for all phases under the same beam angles and objectives (e.g., 95% of the PTV coverage with at least 100% of the prescription dose of 50 Gy). The gating window phase was ranked according to ROV-20, and the relationship between the OVH and dose distribution at each phase was evaluated by comparing the maximum dose, mean dose, and equivalent uniform dose of OAR. Results: OVHs showed noticeable difference from phase to phase, implying it is possible to find optimal phases for gating window. For 2 out of 3 patients (both with a target at RML), maximum dose, mean dose, and EUD increased as ROV-20 increased. Conclusion: It is demonstrated that optimal phases (in dose distribution perspective) for gating window could exist and OVH can be a useful tool for determining such phases without performing dose optimization calculations in all phases. This work was supported by the Radiation Technology R&D program (No. 2013M2A2A7043498) and the Mid-career Researcher Program (2012-007883) through the National Research Foundation (NRF) funded by the Ministry of Science, ICT & Future Planning (MSIP) of Korea.« less

Current practices in the management of adverse events associated with targeted therapies for advanced renal cell carcinoma: a national survey of oncologists.

PubMed

Ruiz, Janelle Nicole; Belum, Viswanath Reddy; Creel, Patricia; Cohn, Allen; Ewer, Michael; Lacouture, Mario E

2014-10-01

Oncologists treating patients with targeted therapies encounter adverse events (AEs) that pose management challenges, lead to dosing inconsistencies, and impact patient quality of life. Oncologists' practices and attitudes in the management of targeted therapy-related AEs in patients with renal cell carcinoma (RCC) are poorly understood. We sought to identify unmet needs associated with AE management and understand oncologists' treatment optimization strategies. A 24-item online survey was administered in August 2012 to 119 US oncologists treating patients with advanced RCC. The survey solicited responses regarding demographics, practice settings, AE management practice patterns and beliefs, treatment barriers, and patient education. Respondents indicated that between 25% and 50% of patients require dose modification/discontinuation because of AEs. The greatest barrier to optimizing treatment for RCC is the unpredictability of patient responses to treatment (43%). Most respondents (78%) discuss AE management with patients, but only a minority of them proactively reach out to patients (46%). Most practitioners (70%) refer patients to nononcology specialists when faced with unfamiliar AEs, although finding interested physicians (43%) and time constraints (40%) were the most commonly cited barriers to consulting with other specialties. Results suggest that many patients require dose modification/discontinuation because of AEs and that nononcologists are a frequently utilized resource to manage these events. There is a need for predictive drug toxicity markers to establish counseling and prevention, along with opportunities for increased education on supportive care techniques to maintain health-related quality of life and consistent dosing. Copyright © 2014 Elsevier Inc. All rights reserved.

The effect of mannitol on intraoperative brain relaxation in patients undergoing supratentorial tumor surgery: study protocol for a randomized controlled trial

PubMed Central

2014-01-01

Background The risk of brain swelling after dural opening is high in patients with midline shift undergoing supratentorial tumor surgery. Brain swelling may result in increased intracranial pressure, impeded tumor exposure, and adverse outcomes. Mannitol is recommended as a first-line dehydration treatment to reduce brain edema and enable brain relaxation during neurosurgery. Research has indicated that mannitol enhanced brain relaxation in patients undergoing supratentorial tumor surgery; however, these results need further confirmation, and the optimal mannitol dose has not yet been established. We propose to examine whether different doses of 20% mannitol improve brain relaxation in a dose-dependent manner when administered at the time of incision. We will examine patients with preexisting mass effects and midline shift undergoing elective supratentorial brain tumor surgery. Methods This is a single-center, randomized controlled, parallel group trial that will be carried out at Beijing Tiantan Hospital, Capital Medical University. Randomization will be achieved using a computer-generated table. The study will include 220 patients undergoing supratentorial tumor surgery whose preoperative computed tomography/magnetic resonance imaging results indicate a brain midline shift. Patients in group A, group B, and group C will receive dehydration treatment at incision with 20% mannitol solutions of 0.7, 1.0, and 1.4 g/kg, respectively, at a rate of 600 mL/h. The patients in the control group will not receive mannitol. The primary outcome is an improvement in intraoperative brain relaxation and dura tension after dehydration with mannitol. Secondary outcomes are postoperative outcomes and the incidence of mannitol side effects. Discussion The aim of this study is to determine the optimal dose of 20% mannitol for intraoperative infusion. We will examine brain relaxation and outcome in patients undergoing supratentorial tumor surgery. If our results are positive, the study will indicate the optimal dose of mannitol to improve brain relaxation and avoid side effects during brain tumor surgery. Trial registration The study is registered with the registry website http://www.chictr.org with the registration number ChiCTRTRC13003984 (17 December 2013). PMID:24884731

SU-E-J-86: Functional Conformal Planning for Stereotactic Body Radiation Therapy with CT-Pulmonary Ventilation Imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kurosawa, T; Moriya, S; Sato, M

2015-06-15

Purpose: To evaluate the functional planning using CT-pulmonary ventilation imaging for conformal SBRT. Methods: The CT-pulmonary ventilation image was generated using the Jacobian metric in the in-house program with the NiftyReg software package. Using the ventilation image, the normal lung was split into three lung regions for functionality (high, moderate and low). The anatomical plan (AP) and functional plan (FP) were made for ten lung SBRT patients. For the AP, the beam angles were optimized with the dose-volume constraints for the normal lung sparing and the PTV coverage. For the FP, the gantry angles were also optimized with the additionalmore » constraint for high functional lung. The MLC aperture shapes were adjusted to the PTV with the additional 5 mm margin. The dosimetric parameters for PTV, the functional volumes, spinal cord and so on were compared in both plans. Results: Compared to the AP, the FP showed better dose sparing for high- and moderate-functional lungs with similar PTV coverage while not taking care of the low functional lung (High:−12.9±9.26% Moderate: −2.0±7.09%, Low: +4.1±12.2%). For the other normal organs, the FP and AP showed similar dose sparing in the eight patients. However, the FP showed that the maximum doses for spinal cord were increased with the significant increment of 16.4Gy and 21.0Gy in other two patients, respectively. Because the beam direction optimizer chose the unexpected directions passing through the spinal cord. Conclusion: Even the functional conformal SBRT can selectively reduce high- and moderatefunctional lung while keeping the PTV coverage. However, it would be careful that the optimizer would choose unexpected beam angles and the dose sparing for the other normal organs can be worse. Therefore, the planner needs to control the dose-volume constraints and also limit the beam angles in order to achieve the expected dose sparing and coverage.« less

Limited Impact of Setup and Range Uncertainties, Breathing Motion, and Interplay Effects in Robustly Optimized Intensity Modulated Proton Therapy for Stage III Non-small Cell Lung Cancer.

PubMed

Inoue, Tatsuya; Widder, Joachim; van Dijk, Lisanne V; Takegawa, Hideki; Koizumi, Masahiko; Takashina, Masaaki; Usui, Keisuke; Kurokawa, Chie; Sugimoto, Satoru; Saito, Anneyuko I; Sasai, Keisuke; Van't Veld, Aart A; Langendijk, Johannes A; Korevaar, Erik W

2016-11-01

To investigate the impact of setup and range uncertainties, breathing motion, and interplay effects using scanning pencil beams in robustly optimized intensity modulated proton therapy (IMPT) for stage III non-small cell lung cancer (NSCLC). Three-field IMPT plans were created using a minimax robust optimization technique for 10 NSCLC patients. The plans accounted for 5- or 7-mm setup errors with ±3% range uncertainties. The robustness of the IMPT nominal plans was evaluated considering (1) isotropic 5-mm setup errors with ±3% range uncertainties; (2) breathing motion; (3) interplay effects; and (4) a combination of items 1 and 2. The plans were calculated using 4-dimensional and average intensity projection computed tomography images. The target coverage (TC, volume receiving 95% of prescribed dose) and homogeneity index (D2 - D98, where D2 and D98 are the least doses received by 2% and 98% of the volume) for the internal clinical target volume, and dose indexes for lung, esophagus, heart and spinal cord were compared with that of clinical volumetric modulated arc therapy plans. The TC and homogeneity index for all plans were within clinical limits when considering the breathing motion and interplay effects independently. The setup and range uncertainties had a larger effect when considering their combined effect. The TC decreased to <98% (clinical threshold) in 3 of 10 patients for robust 5-mm evaluations. However, the TC remained >98% for robust 7-mm evaluations for all patients. The organ at risk dose parameters did not significantly vary between the respective robust 5-mm and robust 7-mm evaluations for the 4 error types. Compared with the volumetric modulated arc therapy plans, the IMPT plans showed better target homogeneity and mean lung and heart dose parameters reduced by about 40% and 60%, respectively. In robustly optimized IMPT for stage III NSCLC, the setup and range uncertainties, breathing motion, and interplay effects have limited impact on target coverage, dose homogeneity, and organ-at-risk dose parameters. Copyright © 2016 Elsevier Inc. All rights reserved.

SU-E-T-574: Novel Chance-Constrained Optimization in Intensity-Modulated Proton Therapy Planning to Account for Range and Patient Setup Uncertainties

DOE Office of Scientific and Technical Information (OSTI.GOV)

An, Y; Liang, J; Liu, W

2015-06-15

Purpose: We propose to apply a probabilistic framework, namely chanceconstrained optimization, in the intensity-modulated proton therapy (IMPT) planning subject to range and patient setup uncertainties. The purpose is to hedge against the influence of uncertainties and improve robustness of treatment plans. Methods: IMPT plans were generated for a typical prostate patient. Nine dose distributions are computed — the nominal one and one each for ±5mm setup uncertainties along three cardinal axes and for ±3.5% range uncertainty. These nine dose distributions are supplied to the solver CPLEX as chance constraints to explicitly control plan robustness under these representative uncertainty scenarios withmore » certain probability. This probability is determined by the tolerance level. We make the chance-constrained model tractable by converting it to a mixed integer optimization problem. The quality of plans derived from this method is evaluated using dose-volume histogram (DVH) indices such as tumor dose homogeneity (D5% – D95%) and coverage (D95%) and normal tissue sparing like V70 of rectum, V65, and V40 of bladder. We also compare the results from this novel method with the conventional PTV-based method to further demonstrate its effectiveness Results: Our model can yield clinically acceptable plans within 50 seconds. The chance-constrained optimization produces IMPT plans with comparable target coverage, better target dose homogeneity, and better normal tissue sparing compared to the PTV-based optimization [D95% CTV: 67.9 vs 68.7 (Gy), D5% – D95% CTV: 11.9 vs 18 (Gy), V70 rectum: 0.0 % vs 0.33%, V65 bladder: 2.17% vs 9.33%, V40 bladder: 8.83% vs 21.83%]. It also simultaneously makes the plan more robust [Width of DVH band at D50%: 2.0 vs 10.0 (Gy)]. The tolerance level may be varied to control the tradeoff between plan robustness and quality. Conclusion: The chance-constrained optimization generates superior IMPT plan compared to the PTV-based optimization with explicit control of plan robustness. NIH/NCI K25CA168984, Eagles Cancer Research Career Development, The Lawrence W. and Marilyn W. Matteson Fund for Cancer Research, Mayo ASU Seed Grant, and The Kemper Marley Foundation.« less

Determining the Optimal Dose of Adenosine for Unmasking Dormant Pulmonary Vein Conduction Following Atrial Fibrillation Ablation: Electrophysiological and Hemodynamic Assessment. DORMANT-AF Study.

PubMed

Prabhu, Sandeep; Mackin, Vincent; McLellan, Alex J A; Phan, Tuong; McGlade, Desmond; Ling, Liang-Han; Peck, Kah Y; Voskoboinik, Alexandr; Pathik, Bupesh; Nalliah, Chrishan J; Wong, Geoff R; Azzopardi, Sonia M; Lee, Geoffrey; Mariani, Justin; Taylor, Andrew J; Kalman, Jonathan M; Kistler, Peter M

2017-01-01

ELECTROPHYSIOLOGICAL AND HEMODYNAMIC ASSESSMENT. The significance of adenosine induced dormant pulmonary vein (PV) conduction in atrial fibrillation (AF) ablation remains controversial. The optimal dose of adenosine to determine dormant PV conduction is yet to be systematically explored. ELECTROPHYSIOLOGICAL AND HEMODYNAMIC ASSESSMENT. Consecutive patients undergoing index AF ablation received 3 adenosine doses (12, 18, and 24 mg) in a randomized blinded order, immediately after pulmonary vein isolation (PVI). Electrophysiological (PR prolongation, AV block (AVB) and PV reconnection) and hemodynamic (BP) parameters were measured. A total, 339 doses (113/dose) assessed 191 PVs in 50 patients (66% male, 72% PAF, 52% hypertensive). Dormant PV conduction occurred in 28% of patients (16.5% [32] of PVs). All cases were associated with AVB (AVB: PV reconnection vs. no PV reconnection 100% vs. 83%, P = 0.007). AVB occurred more frequently at 24 mg versus 12 mg (92% vs. 82%, P = 0.019) but not versus 18 mg (91%, P = 0.62). AVB duration progressed between 12 mg (12.0 ± 8.9 seconds), 18 mg (16.1 ± 9.1 seconds, P = 0.001), and 24 mg (19.0 ± 9.3 seconds, P < 0.001) doses. MBP fell further at 24 mg (ΔMBP: 27 ± 12 mmHg) and 18 mg (26 ± 13 mmHg) doses compared to 12 mg (22 ± 10 mmHg vs., P < 0.001). A significant reduction in AVB in patients >110 kg (65% vs. 91% in 70-110 kg group, P < 0.001) in response to adenosine was seen. ELECTROPHYSIOLOGICAL AND HEMODYNAMIC ASSESSMENT. An adenosine dose producing AVB is required to unmask dormant PV conduction. AVB is significantly reduced in patients >110 kg. Weight and dosing variability may in part explain the conflicting results of studies evaluating the clinical utility of adenosine in PVI. © 2016 Wiley Periodicals, Inc.

TU-D-201-07: Severity Indication in High Dose Rate Brachytherapy Emergency Response Procedure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, K; Rustad, F

Purpose: Understanding the corresponding dose to different staff during the High Dose Rate (HDR) Brachytherapy emergency response procedure could help to develop a strategy in efficiency and effective action. In this study, the variation and risk analysis methodology was developed to simulation the HDR emergency response procedure based on severity indicator. Methods: A GammaMedplus iX HDR unit from Varian Medical System was used for this simulation. The emergency response procedure was decomposed based on risk management methods. Severity indexes were used to identify the impact of a risk occurrence on the step including dose to patient and dose to operationmore » staff by varying the time, HDR source activity, distance from the source to patient and staff and the actions. These actions in 7 steps were to press the interrupt button, press emergency shutoff switch, press emergency button on the afterloader keypad, turn emergency hand-crank, remove applicator from the patient, disconnect transfer tube and move afterloader from the patient, and execute emergency surgical recovery. Results: Given the accumulated time in second at the assumed 7 steps were 15, 5, 30, 15, 180, 120, 1800, and the dose rate of HDR source is 10 Ci, the accumulated dose in cGy to patient at 1cm distance were 188, 250, 625, 813, 3063, 4563 and 27063, and the accumulated exposure in rem to operator at outside the vault, 1m and 10cm distance were 0.0, 0.0, 0.1, 0.1, 22.6, 37.6 and 262.6. The variation was determined by the operators in action at different time and distance from the HDR source. Conclusion: The time and dose were estimated for a HDR unit emergency response procedure. It provided information in making optimal decision during the emergency procedure. Further investigation would be to optimize and standardize the responses for other emergency procedure by time-spatial-dose severity function.« less

Fast online Monte Carlo-based IMRT planning for the MRI linear accelerator

NASA Astrophysics Data System (ADS)

Bol, G. H.; Hissoiny, S.; Lagendijk, J. J. W.; Raaymakers, B. W.

2012-03-01

The MRI accelerator, a combination of a 6 MV linear accelerator with a 1.5 T MRI, facilitates continuous patient anatomy updates regarding translations, rotations and deformations of targets and organs at risk. Accounting for these demands high speed, online intensity-modulated radiotherapy (IMRT) re-optimization. In this paper, a fast IMRT optimization system is described which combines a GPU-based Monte Carlo dose calculation engine for online beamlet generation and a fast inverse dose optimization algorithm. Tightly conformal IMRT plans are generated for four phantom cases and two clinical cases (cervix and kidney) in the presence of the magnetic fields of 0 and 1.5 T. We show that for the presented cases the beamlet generation and optimization routines are fast enough for online IMRT planning. Furthermore, there is no influence of the magnetic field on plan quality and complexity, and equal optimization constraints at 0 and 1.5 T lead to almost identical dose distributions.

A comparative analysis of 3D conformal deep inspiratory–breath hold and free-breathing intensity-modulated radiation therapy for left-sided breast cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reardon, Kelli A.; Read, Paul W.; Morris, Monica M.

2013-07-01

Patients undergoing radiation for left-sided breast cancer have increased rates of coronary artery disease. Free-breathing intensity-modulated radiation therapy (FB-IMRT) and 3-dimensional conformal deep inspiratory–breath hold (3D-DIBH) reduce cardiac irradiation. The purpose of this study is to compare the dose to organs at risk in FB-IMRT vs 3D-DIBH for patients with left-sided breast cancer. Ten patients with left-sided breast cancer had 2 computed tomography scans: free breathing and voluntary DIBH. Optimization of the IMRT plan was performed on the free-breathing scan using 6 noncoplanar tangential beams. The 3D-DIBH plan was optimized on the DIBH scan and used standard tangents. Mean volumesmore » of the heart, the left anterior descending coronary artery (LAD), the total lung, and the right breast receiving 5% to 95% (5% increments) of the prescription dose were calculated. Mean volumes of the heart and the LAD were lower (p<0.05) in 3D-DIBH for volumes receiving 5% to 80% of the prescription dose for the heart and 5% for the LAD. Mean dose to the LAD and heart were lower in 3D-DIBH (p≤0.01). Mean volumes of the total lung were lower in FB-IMRT for dose levels 20% to 75% (p<0.05), but mean dose was not different. Mean volumes of the right breast were not different for any dose; however, mean dose was lower for 3D-DIBH (p = 0.04). 3D-DIBH is an alternative approach to FB-IMRT that provides a clinically equivalent treatment for patients with left-sided breast cancer while sparing organs at risk with increased ease of implementation.« less

ON THE PROBLEM OF THE OPTIMAL DOSE IN THE RADIOTHERAPY OF NONMALIGNANT DISEASES

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pape, R.

1961-01-01

Dosage for the treatment of benign conditions is considered from the viewpoint of 15 yr experience with 2514 patients. It was judged that doses of 1 to 20 r are optimal for treatment of inflammatory and degenerative joint diseases, although many authors call for 30- to 50-r single doses for these conditions. Equally good subjective results were obtained in arthritis and spondylitis cases with the lower doses, but suggestion plays a large role in improvement following radiotherapy. For juvenile mastitis, surface doses of 10 to 12 r, giving depth doses of approximates 1 r at 5 cm, are recommended. Somemore » estimates were made of gonadal doses encountered in various types of nonabdominal radiotherapy. For example, 10-r doses of 90-kv x rays given in the axillary region result in ovarian doses of 0.2 mr. The effect of radiation on the brain and other neural structures is discussed. (H.H.D.)« less

Biological-based and physical-based optimization for biological evaluation of prostate patient's plans

NASA Astrophysics Data System (ADS)

Sukhikh, E.; Sheino, I.; Vertinsky, A.

2017-09-01

Modern modalities of radiation treatment therapy allow irradiation of the tumor to high dose values and irradiation of organs at risk (OARs) to low dose values at the same time. In this paper we study optimal radiation treatment plans made in Monaco system. The first aim of this study was to evaluate dosimetric features of Monaco treatment planning system using biological versus dose-based cost functions for the OARs and irradiation targets (namely tumors) when the full potential of built-in biological cost functions is utilized. The second aim was to develop criteria for the evaluation of radiation dosimetry plans for patients based on the macroscopic radiobiological criteria - TCP/NTCP. In the framework of the study four dosimetric plans were created utilizing the full extent of biological and physical cost functions using dose calculation-based treatment planning for IMRT Step-and-Shoot delivery of stereotactic body radiation therapy (SBRT) in prostate case (5 fractions per 7 Gy).

Adherence to Antiretroviral Therapy in Turkey: Results from the ACTHIV-IST Study Group.

PubMed

Yildiz Sevgi, Dilek; Gunduz, Alper; Altuntas Aydin, Ozlem; Mete, Bilgul; Sargin, Fatma; Kumbasar Karaosmanoglu, Hayat; Uzun, Nuray; Yemisen, Mucahit; Dokmetas, Ilyas; Tabak, Fehmi

2017-12-01

Maintaining optimal adherence to antiretroviral therapy (ART) is essential for optimizing the management of HIV infection. The aim of this study is to explore ART adherence rates in Turkey. Included in this study were a total of 263 HIV-infected patients followed up by the ACTHIV-IST (ACTion against HIV in Istanbul) Study Group affiliated with four tertiary hospitals. The study population included patients 18 years of age or older who were on ART for over 12 months. Adherence was assessed by the medication possession ratio (MPR) calculated for each patient using data (a list of all drugs dispensed within the previous year for that patient) obtained from pharmacy medication records. In addition, patients completed a self-report questionnaire addressing missed doses and the AIDS Clinical Trials Group (ACTG) adherence questionnaire. The study was reviewed and approved by the Ethics Committee of Cerrahpasa Medical Faculty. Patient ages ranged from 19 to 71 years. Two hundred and thirty-one patients were male (88%). Two hundred and twenty-four patients (85%) had optimal adherence (MPR ≥95%). During the course of ART, 236 patients (90%) reported no missed doses in the past 4 days of their treatment, whereas 206 patients (78%) reported no missed doses in the past month. Simply forgetting was the most common reason for nonadherence. MPR was associated with virologic rebound. Major factors affecting adherence were being female, taking antituberculosis drugs, having an opportunistic infection, being able to take all or most of the medication as directed, and being aware of the need to take medication exactly as instructed to prevent the development of drug resistance. Adherence to ART measured by MPR and self-report surveys is relatively high in Turkey when compared with other countries, which probably led to high ART success rates.

High-dose Versus Low-dose Tranexamic Acid to Reduce Transfusion Requirements in Pediatric Scoliosis Surgery.

PubMed

Johnson, Daniel J; Johnson, Christine C; Goobie, Susan M; Nami, Nina; Wetzler, Joshua A; Sponseller, Paul D; Frank, Steven M

2017-12-01

Our objective was to quantify blood loss and transfusion requirements for high-dose and low-dose tranexamic acid (TXA) dosing regimens in pediatric patients undergoing spinal fusion for correction of idiopathic scoliosis. Previous investigators have established the efficacy of TXA in pediatric scoliosis surgery; however, the dosing regimens vary widely and the optimal dose has not been established. We retrospectively analyzed electronic medical records for 116 patients who underwent spinal fusion surgery for idiopathic scoliosis by a single surgeon and were treated with TXA. In total, 72 patients received a 10 mg/kg loading dose with a 1 mg/kg/h maintenance dose (low-dose) and 44 patients received 50 mg/kg loading dose with a 5 mg/kg/h maintenance dose (high-dose). Estimated blood loss and transfusion requirements were compared between dosing groups. Patient characteristics were nearly identical between the 2 groups. Compared with the low-dose TXA group, the high-dose TXA group had decreased estimated blood loss (695 vs. 968 mL, P=0.01), and a decrease in both intraoperative (0.3 vs. 0.9 units, P=0.01) and whole hospitalization (0.4 vs. 1.0 units, P=0.04) red blood cell transfusion requirements. The higher-dose TXA was associated with decreased intraoperative (P=0.01), and whole hospital transfusion (P=0.01) requirements, even after risk-adjustment for potential confounding variables. High-dose TXA is more effective than low-dose TXA in reducing blood loss and transfusion requirements in pediatric idiopathic scoliosis patients undergoing surgery. Level-III, retrospective cohort study.

Challenges and Potential Solutions – Individualised Antibiotic Dosing at the Bedside for Critically Ill Patients: a structured review

PubMed Central

Roberts, Jason A.; Aziz, Mohd Hafiz Abdul; Lipman, Jeffrey; Mouton, Johan W.; Vinks, Alexander A.; Felton, Timothy W.; Hope, William W.; Farkas, Andras; Neely, Michael N.; Schentag, Jerome J.; Drusano, George; Frey, Otto R.; Theuretzbacher, Ursula; Kuti, Joseph L.

2014-01-01

Summary Infections in critically ill patients are associated with persistently poor clinical outcomes. These patients have severely altered and variable antibiotic pharmacokinetics and are infected by less susceptible pathogens. Antibiotic dosing that does not account for these features is likely to result in sub-optimal outcomes. In this paper, we review the patient- and pathogen-related challenges that contribute to inadequate antibiotic dosing and discuss how a process for individualised antibiotic therapy, that increases the accuracy of dosing, can be implemented to further optimise care for the critically ill patient. The process for optimised antibiotic dosing firstly requires determination of the physiological derangements in the patient that can alter antibiotic concentrations including altered fluid status, microvascular failure, serum albumin concentrations as well as altered renal and hepatic function. Secondly, knowledge of the susceptibility of the infecting pathogen should be determined through liaison with the microbiology laboratory. The patient and pathogen challenges can then be solved by combining susceptibility data with measured antibiotic concentration data (where possible) into a clinical dosing software. Such software uses pharmacokinetic-pharmacodynamic (PK/PD) models from critically ill patients to accurately predict the dosing requirements for the individual patient with the aim of optimising antibiotic exposure and maximising effectiveness. PMID:24768475

Population Pharmacokinetics of Vancomycin in Patients Undergoing Allogeneic Hematopoietic Stem-Cell Transplantation.

PubMed

Okada, Akira; Kariya, Misato; Irie, Kei; Okada, Yutaka; Hiramoto, Nobuhiro; Hashimoto, Hisako; Kajioka, Ryosuke; Maruyama, Chika; Kasai, Hidefumi; Hamori, Mami; Nishimura, Asako; Shibata, Nobuhito; Fukushima, Keizo; Sugioka, Nobuyuki

2018-05-15

Vancomycin is a commonly used antimicrobial agent for patients undergoing allogeneic hematopoietic stem-cell transplantation (allo-HSCT). Vancomycin has large inter- and intraindividual pharmacokinetic variability, which is mainly described by renal function; various studies have indicated that vancomycin pharmacokinetics are altered in special populations. However, little is known regarding vancomycin pharmacokinetics in patients undergoing allo-HSCT. Therefore, we aimed to develop a population pharmacokinetic (PopPK) model of vancomycin in patients undergoing allo-HSCT for effective and safe antimicrobial therapy and to develop a vancomycin dosing nomogram for a vancomycin optimal-dosing strategy. In total, 285 observations from 95 patients undergoing allo-HSCT were available. The final PopPK parameter estimates were central volume of distribution (V1, L), 39.2; clearance (L/h), 4.25; peripheral volume of distribution (V2, L), 56.1; and intercompartmental clearance (L/h), 1.95. The developed vancomycin model revealed an increase in V1 and V2 compared with those in the general population that consisted of patients with methicillin-resistant Staphylococcus aureus. Moreover, serum creatinine was reduced because of an increase in the plasma fraction because of destruction of hematopoietic stem cells accompanying allo-HSCT pretreatment, suggesting that the Cockcroft-Gault equation-based creatinine clearance value was overestimated. To our knowledge, this is the first PopPK study to develop a dosing nomogram for vancomycin in patients undergoing allo-HSCT and was proven to be useful in optimizing the dosage and dosing interval of vancomycin in these patients. This strategy will provide more useful information for vancomycin therapy with an evidence-based dose adjustment. © 2018, The American College of Clinical Pharmacology.

Multi-Case Knowledge-Based IMRT Treatment Planning in Head and Neck Cancer

NASA Astrophysics Data System (ADS)

Grzetic, Shelby Mariah

Head and neck cancer (HNC) IMRT treatment planning is a challenging process that relies heavily on the planner's experience. Previously, we used the single, best match from a library of manually planned cases to semi-automatically generate IMRT plans for a new patient. The current multi-case Knowledge Based Radiation Therapy (MC-KBRT) study utilized different matching cases for each of six individual organs-at-risk (OARs), then combined those six cases to create the new treatment plan. From a database of 103 patient plans created by experienced planners, MC-KBRT plans were created for 40 (17 unilateral and 23 bilateral) HNC "query" patients. For each case, 2D beam's-eye-view images were used to find similar geometric "match" patients separately for each of 6 OARs. Dose distributions for each OAR from the 6 matching cases were combined and then warped to suit the query case's geometry. The dose-volume constraints were used to create the new query treatment plan without the need for human decision-making throughout the IMRT optimization. The optimized MC-KBRT plans were compared against the clinically approved plans and Version 1 (previous KBRT using only one matching case with dose warping) using the dose metrics: mean, median, and maximum (brainstem and cord+5mm) doses. Compared to Version 1, MC-KBRT had no significant reduction of the dose to any of the OARs in either unilateral or bilateral cases. Compared to the manually planned unilateral cases, there was significant reduction of the oral cavity mean/median dose (>2Gy) at the expense of the contralateral parotid. Compared to the manually planned bilateral cases, reduction of dose was significant in the ipsilateral parotid, larynx, and oral cavity (>3Gy mean/median) while maintaining PTV coverage. MC-KBRT planning in head and neck cancer generates IMRT plans with better dose sparing than manually created plans. MC-KBRT using multiple case matches does not show significant dose reduction compared to using a single match case with dose warping.

SU-E-I-33: Establishment of CT Diagnostic Reference Levels in Province Nova Scotia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tonkopi, E; Abdolell, M; Duffy, S

2015-06-15

Purpose: To evaluate patient radiation dose from the most frequently performed CT examinations and to establish provincial diagnostic reference levels (DRLs) as a tool for protocol optimization. Methods: The study investigated the following CT examinations: head, chest, abdomen/pelvis, and chest/abdomen/pelvis (CAP). Dose data, volume CT dose index (CTDIvol) and dose-length product (DLP), were collected from 15 CT scanners installed during 2004–2014 in 11 hospital sites of Nova Scotia. All scanners had dose modulation options and multislice capability (16–128 detector rows). The sample for each protocol included 15 average size patients (70±20 kg). Provincial DRLs were calculated as the 75th percentilemore » of patient dose distributions. The differences in dose between hospitals were evaluated with a single factor ANOVA statistical test. Generalized linear modeling was used to determine the factors associated with higher radiation dose. A sample of 36 abdominal studies performed on three different scanners was blinded and randomized for an assessment by an experienced radiologist who graded the imaging quality of anatomic structures. Results: Data for 900 patients were collected. The DRLs were proposed using CTDIvol (mGy) and DLP (mGy*cm) values for CT head (67 and 1049, respectively), chest (12 and 393), abdomen/pelvis (16 and 717), and CAP (14 and 1034). These DRLs were lower than the published national data except for the head CTDIvol. The differences between the means of the dose distributions from each scanner were statistically significant (p<0.05) for all examinations. A very weak correlation was found between the dose and the scanner age or the number of slices with Pearson’s correlation coefficients of 0.011–0.315. The blinded analysis of image quality demonstrated no clinically significant difference except for the noise category. Conclusion: Provincial DRLs were established for typical CT examinations. The variations in dose between the hospitals suggested a large potential for optimization of examinations. Radiology Research Foundation grant.« less

Robust optimization based upon statistical theory.

PubMed

Sobotta, B; Söhn, M; Alber, M

2010-08-01

Organ movement is still the biggest challenge in cancer treatment despite advances in online imaging. Due to the resulting geometric uncertainties, the delivered dose cannot be predicted precisely at treatment planning time. Consequently, all associated dose metrics (e.g., EUD and maxDose) are random variables with a patient-specific probability distribution. The method that the authors propose makes these distributions the basis of the optimization and evaluation process. The authors start from a model of motion derived from patient-specific imaging. On a multitude of geometry instances sampled from this model, a dose metric is evaluated. The resulting pdf of this dose metric is termed outcome distribution. The approach optimizes the shape of the outcome distribution based on its mean and variance. This is in contrast to the conventional optimization of a nominal value (e.g., PTV EUD) computed on a single geometry instance. The mean and variance allow for an estimate of the expected treatment outcome along with the residual uncertainty. Besides being applicable to the target, the proposed method also seamlessly includes the organs at risk (OARs). The likelihood that a given value of a metric is reached in the treatment is predicted quantitatively. This information reveals potential hazards that may occur during the course of the treatment, thus helping the expert to find the right balance between the risk of insufficient normal tissue sparing and the risk of insufficient tumor control. By feeding this information to the optimizer, outcome distributions can be obtained where the probability of exceeding a given OAR maximum and that of falling short of a given target goal can be minimized simultaneously. The method is applicable to any source of residual motion uncertainty in treatment delivery. Any model that quantifies organ movement and deformation in terms of probability distributions can be used as basis for the algorithm. Thus, it can generate dose distributions that are robust against interfraction and intrafraction motion alike, effectively removing the need for indiscriminate safety margins.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lafata, K; Ren, L; Wu, Q

Purpose: To develop a data-mining methodology based on quantum clustering and machine learning to predict expected dosimetric endpoints for lung SBRT applications based on patient-specific anatomic features. Methods: Ninety-three patients who received lung SBRT at our clinic from 2011–2013 were retrospectively identified. Planning information was acquired for each patient, from which various features were extracted using in-house semi-automatic software. Anatomic features included tumor-to-OAR distances, tumor location, total-lung-volume, GTV and ITV. Dosimetric endpoints were adopted from RTOG-0195 recommendations, and consisted of various OAR-specific partial-volume doses and maximum point-doses. First, PCA analysis and unsupervised quantum-clustering was used to explore the feature-space tomore » identify potentially strong classifiers. Secondly, a multi-class logistic regression algorithm was developed and trained to predict dose-volume endpoints based on patient-specific anatomic features. Classes were defined by discretizing the dose-volume data, and the feature-space was zero-mean normalized. Fitting parameters were determined by minimizing a regularized cost function, and optimization was performed via gradient descent. As a pilot study, the model was tested on two esophageal dosimetric planning endpoints (maximum point-dose, dose-to-5cc), and its generalizability was evaluated with leave-one-out cross-validation. Results: Quantum-Clustering demonstrated a strong separation of feature-space at 15Gy across the first-and-second Principle Components of the data when the dosimetric endpoints were retrospectively identified. Maximum point dose prediction to the esophagus demonstrated a cross-validation accuracy of 87%, and the maximum dose to 5cc demonstrated a respective value of 79%. The largest optimized weighting factor was placed on GTV-to-esophagus distance (a factor of 10 greater than the second largest weighting factor), indicating an intuitively strong correlation between this feature and both endpoints. Conclusion: This pilot study shows that it is feasible to predict dose-volume endpoints based on patient-specific anatomic features. The developed methodology can potentially help to identify patients at risk for higher OAR doses, thus improving the efficiency of treatment planning. R01-184173.« less

Optimization of Craniospinal Irradiation for Pediatric Medulloblastoma Using VMAT and IMRT.

PubMed

Al-Wassia, Rolina K; Ghassal, Noor M; Naga, Adly; Awad, Nesreen A; Bahadur, Yasir A; Constantinescu, Camelia

2015-10-01

Intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) provide highly conformal target radiation doses, but also expose large volumes of healthy tissue to low-dose radiation. With improving survival, more children with medulloblastoma (MB) are at risk of late adverse effects of radiotherapy, including secondary cancers. We evaluated the characteristics of IMRT and VMAT craniospinal irradiation treatment plans in children with standard-risk MB to compare radiation dose delivery to target organs and organs at risk (OAR). Each of 10 children with standard-risk MB underwent both IMRT and VMAT treatment planning. Dose calculations used inverse planning optimization with a craniospinal dose of 23.4 Gy followed by a posterior fossa boost to 55.8 Gy. Clinical and planning target volumes were demarcated on axial computed tomography images. Dose distributions to target organs and OAR for each planning technique were measured and compared with published dose-volume toxicity data for pediatric patients. All patients completed treatment planning for both techniques. Analyses and comparisons of dose distributions and dose-volume histograms for the planned target volumes, and dose delivery to the OAR for each technique demonstrated the following: (1) VMAT had a modest, but significantly better, planning target volume-dose coverage and homogeneity compared with IMRT; (2) there were different OAR dose-sparing profiles for IMRT versus VMAT; and (3) neither IMRT nor VMAT demonstrated dose reductions to the published pediatric dose limits for the eyes, the lens, the cochlea, the pituitary, and the brain. The use of both IMRT and VMAT provides good target tissue coverage and sparing of the adjacent tissue for MB. Both techniques resulted in OAR dose delivery within published pediatric dose guidelines, except those mentioned above. Pediatric patients with standard-risk MB remain at risk for late endocrinologic, sensory (auditory and visual), and brain functional impairments.

Development, validation, and implementation of a patient-specific Monte Carlo 3D internal dosimetry platform

NASA Astrophysics Data System (ADS)

Besemer, Abigail E.

Targeted radionuclide therapy is emerging as an attractive treatment option for a broad spectrum of tumor types because it has the potential to simultaneously eradicate both the primary tumor site as well as the metastatic disease throughout the body. Patient-specific absorbed dose calculations for radionuclide therapies are important for reducing the risk of normal tissue complications and optimizing tumor response. However, the only FDA approved software for internal dosimetry calculates doses based on the MIRD methodology which estimates mean organ doses using activity-to-dose scaling factors tabulated from standard phantom geometries. Despite the improved dosimetric accuracy afforded by direct Monte Carlo dosimetry methods these methods are not widely used in routine clinical practice because of the complexity of implementation, lack of relevant standard protocols, and longer dose calculation times. The main goal of this work was to develop a Monte Carlo internal dosimetry platform in order to (1) calculate patient-specific voxelized dose distributions in a clinically feasible time frame, (2) examine and quantify the dosimetric impact of various parameters and methodologies used in 3D internal dosimetry methods, and (3) develop a multi-criteria treatment planning optimization framework for multi-radiopharmaceutical combination therapies. This platform utilizes serial PET/CT or SPECT/CT images to calculate voxelized 3D internal dose distributions with the Monte Carlo code Geant4. Dosimetry can be computed for any diagnostic or therapeutic radiopharmaceutical and for both pre-clinical and clinical applications. In this work, the platform's dosimetry calculations were successfully validated against previously published reference doses values calculated in standard phantoms for a variety of radionuclides, over a wide range of photon and electron energies, and for many different organs and tumor sizes. Retrospective dosimetry was also calculated for various pre-clinical and clinical patients and large dosimetric differences resulted when using conventional organ-level methods and the patient-specific voxelized methods described in this work. The dosimetric impact of various steps in the 3D voxelized dosimetry process were evaluated including quantitative imaging acquisition, image coregistration, voxel resampling, ROI contouring, CT-based material segmentation, and pharmacokinetic fitting. Finally, a multi-objective treatment planning optimization framework was developed for multi-radiopharmaceutical combination therapies.

A detailed dosimetric comparison between manual and inverse plans in HDR intracavitary/interstitial cervical cancer brachytherapy.

PubMed

Trnková, Petra; Baltas, Dimos; Karabis, Andreas; Stock, Markus; Dimopoulos, Johannes; Georg, Dietmar; Pötter, Richard; Kirisits, Christian

2010-12-01

The purpose of this study was to compare two inverse planning algorithms for cervical cancer brachytherapy and a conventional manual treatment planning according to the MUW (Medical University of Vienna) protocol. For 20 patients, manually optimized, and, inversely optimized treatment plans with Hybrid Inverse treatment Planning and Optimization (HIPO) and with Inverse Planning Simulated Annealing (IPSA) were created. Dosimetric parameters, absolute volumes of normal tissue receiving reference doses, absolute loading times of tandem, ring and interstitial needles, Paddick and COIN conformity indices were evaluated. HIPO was able to achieve a similar dose distribution to manual planning with the restriction of high dose regions. It reduced the loading time of needles and the overall treatment time. The values of both conformity indices were the lowest. IPSA was able to achieve acceptable dosimetric results. However, it overloaded the needles. This resulted in high dose regions located in the normal tissue. The Paddick index for the volume of two times prescribed dose was outstandingly low. HIPO can produce clinically acceptable treatment plans with the elimination of high dose regions in normal tissue. Compared to IPSA, it is an inverse optimization method which takes into account current clinical experience gained from manual treatment planning.

A detailed dosimetric comparison between manual and inverse plans in HDR intracavitary/interstitial cervical cancer brachytherapy

PubMed Central

Baltas, Dimos; Karabis, Andreas; Stock, Markus; Dimopoulos, Johannes; Georg, Dietmar; Pötter, Richard; Kirisits, Christian

2011-01-01

Purpose The purpose of this study was to compare two inverse planning algorithms for cervical cancer brachytherapy and a conventional manual treatment planning according to the MUW (Medical University of Vienna) protocol. Material and methods For 20 patients, manually optimized, and, inversely optimized treatment plans with Hybrid Inverse treatment Planning and Optimization (HIPO) and with Inverse Planning Simulated Annealing (IPSA) were created. Dosimetric parameters, absolute volumes of normal tissue receiving reference doses, absolute loading times of tandem, ring and interstitial needles, Paddick and COIN conformity indices were evaluated. Results HIPO was able to achieve a similar dose distribution to manual planning with the restriction of high dose regions. It reduced the loading time of needles and the overall treatment time. The values of both conformity indices were the lowest. IPSA was able to achieve acceptable dosimetric results. However, it overloaded the needles. This resulted in high dose regions located in the normal tissue. The Paddick index for the volume of two times prescribed dose was outstandingly low. Conclusions HIPO can produce clinically acceptable treatment plans with the elimination of high dose regions in normal tissue. Compared to IPSA, it is an inverse optimization method which takes into account current clinical experience gained from manual treatment planning. PMID:27853479

Proton-Pump Inhibitors Reduce Gastrointestinal Events Regardless of Aspirin Dose in Patients Requiring Dual Antiplatelet Therapy.

PubMed

Vaduganathan, Muthiah; Bhatt, Deepak L; Cryer, Byron L; Liu, Yuyin; Hsieh, Wen-Hua; Doros, Gheorghe; Cohen, Marc; Lanas, Angel; Schnitzer, Thomas J; Shook, Thomas L; Lapuerta, Pablo; Goldsmith, Mark A; Laine, Loren; Cannon, Christopher P

2016-04-12

The COGENT (Clopidogrel and the Optimization of Gastrointestinal Events Trial) showed that proton-pump inhibitors (PPIs) safely reduced rates of gastrointestinal (GI) events in patients requiring dual antiplatelet therapy (DAPT). However, utilization of appropriate prophylactic PPI therapy remains suboptimal, especially with low-dose aspirin. The authors investigated the safety and efficacy of PPI therapy in patients receiving DAPT in low- and high-dose aspirin subsets. Randomized patients with available aspirin dosing information in COGENT (N = 3,752) were divided into "low-dose" (≤ 100 mg) and "high-dose" (>100 mg) aspirin groups. The primary GI and cardiovascular endpoints were composite upper GI events and major adverse cardiac events, respectively. All events were adjudicated by independent, blinded gastroenterologists and cardiologists. Median duration of follow-up was 110 days. Low-dose aspirin users (n = 2,480; 66.1%) were more likely to be older, female, and have higher rates of peripheral artery disease, prior stroke, and hypertension, whereas high-dose aspirin users (n = 1,272; 33.9%) had higher rates of hyperlipidemia, smoking, a history of percutaneous coronary intervention, and were more than twice as likely to be enrolled from sites within the United States (80.4% vs. 39.8%). High-dose aspirin was associated with similar 180-day Kaplan-Meier estimates of adjudicated composite GI events (1.7% vs. 2.1%; adjusted hazard ratio: 0.88; 95% confidence interval: 0.46 to 1.66) and major adverse cardiac events (4.8% vs. 5.5%; adjusted hazard ratio: 0.73; 95% confidence interval: 0.48 to 1.11) compared with low-dose aspirin. Randomization to PPI therapy reduced 180-day Kaplan-Meier estimates of the primary GI endpoint in low-dose (1.2% vs. 3.1%) and high-dose aspirin subsets (0.9% vs. 2.6%; p for interaction = 0.80), and did not adversely affect the primary cardiovascular endpoint in either group. Gastroprotection with PPI therapy should be utilized in appropriately selected patients with coronary artery disease requiring DAPT, even if the patients are on low-dose aspirin. (Clopidogrel and the Optimization of Gastrointestinal Events Trial [COGENT]; NCT00557921). Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Canadian guideline for safe and effective use of opioids for chronic noncancer pain

PubMed Central

Kahan, Meldon; Mailis-Gagnon, Angela; Wilson, Lynn; Srivastava, Anita

2011-01-01

Abstract Objective To provide family physicians with a practical clinical summary of the Canadian Guideline for Safe and Effective Use of Opioids for Chronic Non-Cancer Pain, developed by the National Opioid Use Guideline Group. Quality of evidence Researchers for the guideline conducted a systematic review of the literature on the effectiveness and safety of opioids for chronic noncancer pain, and drafted a series of recommendations. A panel of 49 clinicians from across Canada reviewed the draft and achieved consensus on 24 recommendations. Main message Screening for addiction risk is recommended before prescribing opioids. Weak opioids (codeine and tramadol) are recommended for mild to moderate pain that has not responded to first-line treatments. Oxycodone, hydromorphone, and morphine can be tried in patients who have not responded to weaker opioids. A low initial dose and slow upward titration is recommended, with patient education and close monitoring. Physicians should watch for the development of complications such as sleep apnea. The optimal dose is one which improves function or decreases pain ratings by at least 30%. For by far most patients, the optimal dose will be well below a 200-mg morphine equivalent dose per day. Tapering is recommended for patients who have not responded to an adequate opioid trial. Conclusion Opioids play an important role in the management of chronic noncancer pain, but careful prescribing is needed to limit potential harms. The new Canadian guideline provides much-needed guidance to help physicians achieve a balance between optimal pain control and safety. PMID:22084455

Canadian guideline for safe and effective use of opioids for chronic noncancer pain: clinical summary for family physicians. Part 1: general population.

PubMed

Kahan, Meldon; Mailis-Gagnon, Angela; Wilson, Lynn; Srivastava, Anita

2011-11-01

To provide family physicians with a practical clinical summary of the Canadian Guideline for Safe and Effective Use of Opioids for Chronic Non-Cancer Pain, developed by the National Opioid Use Guideline Group. Researchers for the guideline conducted a systematic review of the literature on the effectiveness and safety of opioids for chronic noncancer pain, and drafted a series of recommendations. A panel of 49 clinicians from across Canada reviewed the draft and achieved consensus on 24 recommendations. Screening for addiction risk is recommended before prescribing opioids. Weak opioids (codeine and tramadol) are recommended for mild to moderate pain that has not responded to first-line treatments. Oxycodone, hydromorphone, and morphine can be tried in patients who have not responded to weaker opioids. A low initial dose and slow upward titration is recommended, with patient education and close monitoring. Physicians should watch for the development of complications such as sleep apnea. The optimal dose is one which improves function or decreases pain ratings by at least 30%. For by far most patients, the optimal dose will be well below a 200-mg morphine equivalent dose per day. Tapering is recommended for patients who have not responded to an adequate opioid trial. Opioids play an important role in the management of chronic noncancer pain, but careful prescribing is needed to limit potential harms. The new Canadian guideline provides much-needed guidance to help physicians achieve a balance between optimal pain control and safety.

Dosing algorithm to target a predefined AUC in patients with primary central nervous system lymphoma receiving high dose methotrexate.

PubMed

Joerger, Markus; Ferreri, Andrés J M; Krähenbühl, Stephan; Schellens, Jan H M; Cerny, Thomas; Zucca, Emanuele; Huitema, Alwin D R

2012-02-01

There is no consensus regarding optimal dosing of high dose methotrexate (HDMTX) in patients with primary CNS lymphoma. Our aim was to develop a convenient dosing algorithm to target AUC(MTX) in the range between 1000 and 1100 µmol l(-1) h. A population covariate model from a pooled dataset of 131 patients receiving HDMTX was used to simulate concentration-time curves of 10,000 patients and test the efficacy of a dosing algorithm based on 24 h MTX plasma concentrations to target the prespecified AUC(MTX) . These data simulations included interindividual, interoccasion and residual unidentified variability. Patients received a total of four simulated cycles of HDMTX and adjusted MTX dosages were given for cycles two to four. The dosing algorithm proposes MTX dose adaptations ranging from +75% in patients with MTX C(24) < 0.5 µmol l(-1) up to -35% in patients with MTX C(24) > 12 µmol l(-1). The proposed dosing algorithm resulted in a marked improvement of the proportion of patients within the AUC(MTX) target between 1000 and 1100 µmol l(-1) h (11% with standard MTX dose, 35% with the adjusted dose) and a marked reduction of the interindividual variability of MTX exposure. A simple and practical dosing algorithm for HDMTX has been developed based on MTX 24 h plasma concentrations, and its potential efficacy in improving the proportion of patients within a prespecified target AUC(MTX) and reducing the interindividual variability of MTX exposure has been shown by data simulations. The clinical benefit of this dosing algorithm should be assessed in patients with primary central nervous system lymphoma (PCNSL). © 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.

Right dose, right now: using big data to optimize antibiotic dosing in the critically ill.

PubMed

Elbers, Paul W G; Girbes, Armand; Malbrain, Manu L N G; Bosman, Rob

2015-01-01

Antibiotics save lives and are essential for the practice of intensive care medicine. Adequate antibiotic treatment is closely related to outcome. However this is challenging in the critically ill, as their pharmacokinetic profile is markedly altered. Therefore, it is surprising that critical care physicians continue to rely on standard dosing regimens for every patient, regardless of the actual clinical situation. This review outlines the pharmacokinetic and pharmacodynamic principles that underlie the need for individualized and personalized drug dosing. At present, therapeutic drug monitoring may be of help, but has major disadvantages, remains unavailable for most antibiotics and has produced mixed results. We therefore propose the AutoKinetics concept, taking decision support for antibiotic dosing back to the bedside. By direct interaction with electronic patient records, this opens the way for the use of big data for providing the right dose at the right time in each patient.

Weight changes and their associations with demographic and clinical characteristics in risperidone maintenance treatment for schizophrenia.

PubMed

Xiang, Y-T; Wang, C-Y; Ungvari, G S; Kreyenbuhl, J A; Chiu, H F K; Lai, K Y C; Lee, E H M; Bo, Q-J; Dixon, L B

2011-06-01

This study aimed to characterize weight changes in schizophrenia patients taking risperidone as part of a randomized, controlled, open-label clinical trial. A total of 374 patients with schizophrenia who had been clinically stabilized following an acute episode were randomly assigned to a 'no-dose-reduction' group (initial optimal therapeutic doses continued throughout the study), a '4-week group' (initial optimal therapeutic doses continued for 4 weeks followed by a half dose reduction that was maintained until the end of the study) or a '26-week group' (initial optimal therapeutic doses continued for 26 weeks followed by a half dose reduction until the end of the study). Participants were assessed monthly using standardized assessment instruments during the first 6 months, and then every 2 months until the last recruited patient completed the 1-year follow-up. Weight gain was defined as gaining at least 7% of initial body weight, weight loss as losing at least 7% of initial body weight. A BMI <18.5 kg m⁻² was defined as underweight, 18.5-24.9 kg m⁻² as normal range, and ≥ 25 kg m⁻² as overweight or obese. At the end of follow-up, of the patients who started within the underweight range (n=22), 77.3% gained weight, whereas 4.5% lost weight. The corresponding figures were 39.6% and 4.8% in patients who started at normal weight (n=273), respectively, and 17.7% and 17.7% in patients who started at overweight (n=79), respectively. At the same time, 59.1% of the patients who started at underweight range went into the normal weight and 13.6% into the overweight/obese range, respectively, while 24.5% of those who started at normal weight went into the overweight/obese range, and 1.1% into underweight range, respectively; 20.3% of those who started at overweight range went into normal weight at the end of the follow-up. Multiple logistic regression analyses revealed that being underweight or normal weight at study entry predicted weight gain compared to being overweight, whereas being overweight at entry was associated with a higher likelihood of weight loss compared to being normal weight. No correlation was found between weight change and dose reduction. Weight change is a common, long-term, but heterogeneous side effect in risperidone maintenance treatment for stable schizophrenia patients. Special attention should be paid to fluctuations in weight that may occur throughout the course of treatment with risperidone. © Georg Thieme Verlag KG Stuttgart · New York.

SU-E-T-625: Robustness Evaluation and Robust Optimization of IMPT Plans Based on Per-Voxel Standard Deviation of Dose Distributions.

PubMed

Liu, W; Mohan, R

2012-06-01

Proton dose distributions, IMPT in particular, are highly sensitive to setup and range uncertainties. We report a novel method, based on per-voxel standard deviation (SD) of dose distributions, to evaluate the robustness of proton plans and to robustly optimize IMPT plans to render them less sensitive to uncertainties. For each optimization iteration, nine dose distributions are computed - the nominal one, and one each for ± setup uncertainties along x, y and z axes and for ± range uncertainty. SD of dose in each voxel is used to create SD-volume histogram (SVH) for each structure. SVH may be considered a quantitative representation of the robustness of the dose distribution. For optimization, the desired robustness may be specified in terms of an SD-volume (SV) constraint on the CTV and incorporated as a term in the objective function. Results of optimization with and without this constraint were compared in terms of plan optimality and robustness using the so called'worst case' dose distributions; which are obtained by assigning the lowest among the nine doses to each voxel in the clinical target volume (CTV) and the highest to normal tissue voxels outside the CTV. The SVH curve and the area under it for each structure were used as quantitative measures of robustness. Penalty parameter of SV constraint may be varied to control the tradeoff between robustness and plan optimality. We applied these methods to one case each of H&N and lung. In both cases, we found that imposing SV constraint improved plan robustness but at the cost of normal tissue sparing. SVH-based optimization and evaluation is an effective tool for robustness evaluation and robust optimization of IMPT plans. Studies need to be conducted to test the methods for larger cohorts of patients and for other sites. This research is supported by National Cancer Institute (NCI) grant P01CA021239, the University Cancer Foundation via the Institutional Research Grant program at the University of Texas MD Anderson Cancer Center, and MD Anderson’s cancer center support grant CA016672. © 2012 American Association of Physicists in Medicine.

On the role of the optimization algorithm of RapidArc(®) volumetric modulated arc therapy on plan quality and efficiency.

PubMed

Vanetti, Eugenio; Nicolini, Giorgia; Nord, Janne; Peltola, Jarkko; Clivio, Alessandro; Fogliata, Antonella; Cozzi, Luca

2011-11-01

The RapidArc volumetric modulated arc therapy (VMAT) planning process is based on a core engine, the so-called progressive resolution optimizer (PRO). This is the optimization algorithm used to determine the combination of field shapes, segment weights (with dose rate and gantry speed variations), which best approximate the desired dose distribution in the inverse planning problem. A study was performed to assess the behavior of two versions of PRO. These two versions mostly differ in the way continuous variables describing the modulated arc are sampled into discrete control points, in the planning efficiency and in the presence of some new features. The analysis aimed to assess (i) plan quality, (ii) technical delivery aspects, (iii) agreement between delivery and calculations, and (iv) planning efficiency of the two versions. RapidArc plans were generated for four groups of patients (five patients each): anal canal, advanced lung, head and neck, and multiple brain metastases and were designed to test different levels of planning complexity and anatomical features. Plans from optimization with PRO2 (first generation of RapidArc optimizer) were compared against PRO3 (second generation of the algorithm). Additional plans were optimized with PRO3 using new features: the jaw tracking, the intermediate dose and the air cavity correction options. Results showed that (i) plan quality was generally improved with PRO3 and, although not for all parameters, some of the scored indices showed a macroscopic improvement with PRO3. (ii) PRO3 optimization leads to simpler patterns of the dynamic parameters particularly for dose rate. (iii) No differences were observed between the two algorithms in terms of pretreatment quality assurance measurements and (iv) PRO3 optimization was generally faster, with a time reduction of a factor approximately 3.5 with respect to PRO2. These results indicate that PRO3 is either clinically beneficial or neutral in terms of dosimetric quality while it showed significant advantages in speed and technical aspects.

Assessing the Dosimetric Accuracy of Magnetic Resonance-Generated Synthetic CT Images for Focal Brain VMAT Radiation Therapy.

PubMed

Paradis, Eric; Cao, Yue; Lawrence, Theodore S; Tsien, Christina; Feng, Mary; Vineberg, Karen; Balter, James M

2015-12-01

The purpose of this study was to assess the dosimetric accuracy of synthetic CT (MRCT) volumes generated from magnetic resonance imaging (MRI) data for focal brain radiation therapy. A study was conducted in 12 patients with gliomas who underwent both MR and CT imaging as part of their simulation for external beam treatment planning. MRCT volumes were generated from MR images. Patients' clinical treatment planning directives were used to create 12 individual volumetric modulated arc therapy (VMAT) plans, which were then optimized 10 times on each of their respective CT and MRCT-derived electron density maps. Dose metrics derived from optimization criteria, as well as monitor units and gamma analyses, were evaluated to quantify differences between the imaging modalities. Mean differences between planning target volume (PTV) doses on MRCT and CT plans across all patients were 0.0% (range: -0.1 to 0.2%) for D(95%); 0.0% (-0.7 to 0.6%) for D(5%); and -0.2% (-1.0 to 0.2%) for D(max). MRCT plans showed no significant changes in monitor units (-0.4%) compared to CT plans. Organs at risk (OARs) had average D(max) differences of 0.0 Gy (-2.2 to 1.9 Gy) over 85 structures across all 12 patients, with no significant differences when calculated doses approached planning constraints. Focal brain VMAT plans optimized on MRCT images show excellent dosimetric agreement with standard CT-optimized plans. PTVs show equivalent coverage, and OARs do not show any overdose. These results indicate that MRI-derived synthetic CT volumes can be used to support treatment planning of most patients treated for intracranial lesions. Copyright © 2015 Elsevier Inc. All rights reserved.

Patient-specific radiation dose and cancer risk for pediatric chest CT.

PubMed

Li, Xiang; Samei, Ehsan; Segars, W Paul; Sturgeon, Gregory M; Colsher, James G; Frush, Donald P

2011-06-01

To estimate patient-specific radiation dose and cancer risk for pediatric chest computed tomography (CT) and to evaluate factors affecting dose and risk, including patient size, patient age, and scanning parameters. The institutional review board approved this study and waived informed consent. This study was HIPAA compliant. The study included 30 patients (0-16 years old), for whom full-body computer models were recently created from clinical CT data. A validated Monte Carlo program was used to estimate organ dose from eight chest protocols, representing clinically relevant combinations of bow tie filter, collimation, pitch, and tube potential. Organ dose was used to calculate effective dose and risk index (an index of total cancer incidence risk). The dose and risk estimates before and after normalization by volume-weighted CT dose index (CTDI(vol)) or dose-length product (DLP) were correlated with patient size and age. The effect of each scanning parameter was studied. Organ dose normalized by tube current-time product or CTDI(vol) decreased exponentially with increasing average chest diameter. Effective dose normalized by tube current-time product or DLP decreased exponentially with increasing chest diameter. Chest diameter was a stronger predictor of dose than weight and total scan length. Risk index normalized by tube current-time product or DLP decreased exponentially with both chest diameter and age. When normalized by DLP, effective dose and risk index were independent of collimation, pitch, and tube potential (<10% variation). The correlations of dose and risk with patient size and age can be used to estimate patient-specific dose and risk. They can further guide the design and optimization of pediatric chest CT protocols. http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.11101900/-/DC1. RSNA, 2011

Febuxostat as a novel option to optimize thiopurines' metabolism in patients with inadequate metabolite levels.

PubMed

Doré, Maxime; Frenette, Anne Julie; Mansour, Anne-Marie; Troyanov, Yves; Bégin, Josiane

2014-05-01

To report the use of febuxostat in order to potentiate thiopurines' metabolism in a patient on azathioprine (AZA) therapy with low metabolite 6-thioguanine nucleotides (6-TGN) levels and elevated metabolite 6-methylmercaptopurine (6-MMP) levels. A 44-year-old woman with a history of anti-signal recognition particle necrotizing myopathy was treated with AZA-allopurinol combination therapy. When she developed an atypical drug-induced hypersensitivity syndrome, allopurinol was replaced by the new xanthine oxidase (XO) inhibitor febuxostat, at a daily dose of 40 mg. Febuxostat-AZA combination was successful with 6-TGN reaching therapeutic levels while 6-MMP levels remained low. After 5 months, she developed similar manifestations that she had presented on AZA-allopurinol combination. Febuxostat and AZA were then stopped. AZA and 6-MP are both inactive pro-drugs that undergo a complex metabolic transformation leading to active 6-TGN and potentially hepatotoxic 6-MMP. Some patients with unfavorable thiopurine metabolism might benefit from addition of XO inhibitor allopurinol in order to potentiate 6-TGN and reduce 6-MMP levels. It is likely that febuxostat, via its XO inhibition, would exhibit the same effect on thiopurines' metabolism. It has been shown that low dose of febuxostat was able to prevent hypermethylation and to potentiate 6-TGN levels in an AZA-treated patient. Thus, febuxostat could be useful in optimizing thiopurines' metabolism, but more data are needed before this practice can be recommended. The mechanisms by which febuxostat optimizes thiopurines' metabolism remain to be confirmed. Also, the optimal dose of febuxostat for this use remains to be determined.

Radiation Dose Optimization For Critical Organs

NASA Astrophysics Data System (ADS)

Khodadadegan, Yasaman

Ionizing radiation used in the patient diagnosis or therapy has negative effects on the patient body in short term and long term depending on the amount of exposure. More than 700,000 examinations are everyday performed on Interventional Radiology modalities, however; there is no patient-centric information available to the patient or the Quality Assurance for the amount of organ dose received. In this study, we are exploring the methodologies to systematically reduce the absorbed radiation dose in the Fluoroscopically Guided Interventional Radiology procedures. In the first part of this study, we developed a mathematical model which determines a set of geometry settings for the equipment and a level for the energy during a patient exam. The goal is to minimize the amount of absorbed dose in the critical organs while maintaining image quality required for the diagnosis. The model is a large-scale mixed integer program. We performed polyhedral analysis and derived several sets of strong inequalities to improve the computational speed and quality of the solution. Results present the amount of absorbed dose in the critical organ can be reduced up to 99% for a specific set of angles. In the second part, we apply an approximate gradient method to simultaneously optimize angle and table location while minimizing dose in the critical organs with respect to the image quality. In each iteration, we solve a sub-problem as a MIP to determine the radiation field size and corresponding X-ray tube energy. In the computational experiments, results show further reduction (up to 80%) of the absorbed dose in compare with previous method. Last, there are uncertainties in the medical procedures resulting imprecision of the absorbed dose. We propose a robust formulation to hedge from the worst case absorbed dose while ensuring feasibility. In this part, we investigate a robust approach for the organ motions within a radiology procedure. We minimize the absorbed dose for the critical organs across all input data scenarios which are corresponding to the positioning and size of the organs. The computational results indicate up to 26% increase in the absorbed dose calculated for the robust approach which ensures the feasibility across scenarios.

A pharmacodynamic comparison of prasugrel vs. high-dose clopidogrel in patients with type 2 diabetes mellitus and coronary artery disease: results of the Optimizing anti-Platelet Therapy In diabetes MellitUS (OPTIMUS)-3 Trial

PubMed Central

Angiolillo, Dominick J.; Badimon, Juan Jose; Saucedo, Jorge F.; Frelinger, Andrew L.; Michelson, Alan D.; Jakubowski, Joseph A.; Zhu, Baojin; Ojeh, Clement K.; Baker, Brian A.; Effron, Mark B.

2011-01-01

Aims Patients with diabetes mellitus (DM) have increased platelet reactivity and reduced platelet response to clopidogrel compared with patients without DM. Prasugrel, a more potent antiplatelet agent, is associated with greater reductions in ischaemic events compared with clopidogrel, particularly in patients with DM. The aim of this study was to perform serial pharmacodynamic assessments of prasugrel with high-dose clopidogrel in patients with DM. Methods and results Optimizing anti-Platelet Therapy In diabetes MellitUS (OPTIMUS)-3 was a prospective, randomized, double-blind, crossover study in patients with type 2 DM and coronary artery disease (CAD). Patients (n= 35) were randomly assigned to either prasugrel 60 mg loading dose (LD)/10 mg maintenance dose (MD) or clopidogrel 600 mg LD/150 mg MD over two 1-week treatment periods separated by a 2-week washout period. Platelet function was assessed by VerifyNow® P2Y12 assay, light transmission aggregometry, and vasodilator-stimulated phosphoprotein phosphorylation at 0, 1, 4, and 24 h and 7 days. Greater platelet inhibition by VerifyNow® P2Y12 was achieved by prasugrel compared with clopidogrel at 4 h post-LD (least squares mean, 89.3 vs. 27.7%, P< 0.0001; primary endpoint). The difference in platelet inhibition between prasugrel and clopidogrel was significant from 1 h through 7 days (P < 0.0001). Similar results were obtained using all other platelet function measures. Prasugrel resulted in fewer poor responders at all time points irrespective of definition used. Conclusion In patients with type 2 DM and CAD, standard-dose prasugrel is associated with greater platelet inhibition and better response profiles during both the loading and maintenance periods when compared with double-dose clopidogrel. Clinical trial identifier: www.clinicaltrials.gov—NCT00642174 PMID:21252171

TH-C-12A-04: Dosimetric Evaluation of a Modulated Arc Technique for Total Body Irradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tsiamas, P; Czerminska, M; Makrigiorgos, G

2014-06-15

Purpose: A simplified Total Body Irradiation (TBI) was developed to work with minimal requirements in a compact linac room without custom motorized TBI couch. Results were compared to our existing fixed-gantry double 4 MV linac TBI system with prone patient and simultaneous AP/PA irradiation. Methods: Modulated arc irradiates patient positioned in prone/supine positions along the craniocaudal axis. A simplified inverse planning method developed to optimize dose rate as a function of gantry angle for various patient sizes without the need of graphical 3D treatment planning system. This method can be easily adapted and used with minimal resources. Fixed maximum fieldmore » size (40×40 cm2) is used to decrease radiation delivery time. Dose rate as a function of gantry angle is optimized to result in uniform dose inside rectangular phantoms of various sizes and a custom VMAT DICOM plans were generated using a DICOM editor tool. Monte Carlo simulations, film and ionization chamber dosimetry for various setups were used to derive and test an extended SSD beam model based on PDD/OAR profiles for Varian 6EX/ TX. Measurements were obtained using solid water phantoms. Dose rate modulation function was determined for various size patients (100cm − 200cm). Depending on the size of the patient arc range varied from 100° to 120°. Results: A PDD/OAR based beam model for modulated arc TBI therapy was developed. Lateral dose profiles produced were similar to profiles of our existing TBI facility. Calculated delivery time and full arc depended on the size of the patient (∼8min/ 100° − 10min/ 120°, 100 cGy). Dose heterogeneity varied by about ±5% − ±10% depending on the patient size and distance to the surface (buildup region). Conclusion: TBI using simplified modulated arc along craniocaudal axis of different size patients positioned on the floor can be achieved without graphical / inverse 3D planning.« less

SU-E-J-58: Dosimetric Verification of Metal Artifact Effects: Comparison of Dose Distributions Affected by Patient Teeth and Implants

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, M; Kang, S; Lee, S

Purpose: Implant-supported dentures seem particularly appropriate for the predicament of becoming edentulous and cancer patients are no exceptions. As the number of people having dental implants increased in different ages, critical dosimetric verification of metal artifact effects are required for the more accurate head and neck radiation therapy. The purpose of this study is to verify the theoretical analysis of the metal(streak and dark) artifact, and to evaluate dosimetric effect which cause by dental implants in CT images of patients with the patient teeth and implants inserted humanoid phantom. Methods: The phantom comprises cylinder which is shaped to simulate themore » anatomical structures of a human head and neck. Through applying various clinical cases, made phantom which is closely allied to human. Developed phantom can verify two classes: (i)closed mouth (ii)opened mouth. RapidArc plans of 4 cases were created in the Eclipse planning system. Total dose of 2000 cGy in 10 fractions is prescribed to the whole planning target volume (PTV) using 6MV photon beams. Acuros XB (AXB) advanced dose calculation algorithm, Analytical Anisotropic Algorithm (AAA) and progressive resolution optimizer were used in dose optimization and calculation. Results: In closed and opened mouth phantom, because dark artifacts formed extensively around the metal implants, dose variation was relatively higher than that of streak artifacts. As the PTV was delineated on the dark regions or large streak artifact regions, maximum 7.8% dose error and average 3.2% difference was observed. The averaged minimum dose to the PTV predicted by AAA was about 5.6% higher and OARs doses are also 5.2% higher compared to AXB. Conclusion: The results of this study showed that AXB dose calculation involving high-density materials is more accurate than AAA calculation, and AXB was superior to AAA in dose predictions beyond dark artifact/air cavity portion when compared against the measurements.« less

SU-F-T-380: Comparing the Effect of Respiration On Dose Distribution Between Conventional Tangent Pair and IMRT Techniques for Adjuvant Radiotherapy in Early Stage Breast Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, M; Ramaseshan, R

2016-06-15

Purpose: In this project, we compared the conventional tangent pair technique to IMRT technique by analyzing the dose distribution. We also investigated the effect of respiration on planning target volume (PTV) dose coverage in both techniques. Methods: In order to implement IMRT technique a template based planning protocol, dose constrains and treatment process was developed. Two open fields with optimized field weights were combined with two beamlet optimization fields in IMRT plans. We compared the dose distribution between standard tangential pair and IMRT. The improvement in dose distribution was measured by parameters such as conformity index, homogeneity index and coveragemore » index. Another end point was the IMRT technique will reduce the planning time for staff. The effect of patient’s respiration on dose distribution was also estimated. The four dimensional computed tomography (4DCT) for different phase of breathing cycle was used to evaluate the effect of respiration on IMRT planned dose distribution. Results: We have accumulated 10 patients that acquired 4DCT and planned by both techniques. Based on the preliminary analysis, the dose distribution in IMRT technique was better than conventional tangent pair technique. Furthermore, the effect of respiration in IMRT plan was not significant as evident from the 95% isodose line coverage of PTV drawn on all phases of 4DCT. Conclusion: Based on the 4DCT images, the breathing effect on dose distribution was smaller than what we expected. We suspect that there are two reasons. First, the PTV movement due to respiration was not significant. It might be because we used a tilted breast board to setup patients. Second, the open fields with optimized field weights in IMRT technique might reduce the breathing effect on dose distribution. A further investigation is necessary.« less

Individual dose adjustment of riociguat in patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension.

PubMed

Hill, Nicholas S; Rahaghi, Franck F; Sood, Namita; Frey, Reiner; Ghofrani, Hossein-Ardeschir

2017-08-01

Riociguat is a soluble guanylate cyclase stimulator that has been approved for the treatment of pulmonary arterial hypertension and inoperable chronic thromboembolic pulmonary hypertension or persistent/recurrent pulmonary hypertension following pulmonary endarterectomy. Riociguat is administered using an 8-week individual dose-adjustment scheme whereby a patient initially receives riociguat 1.0 mg three times daily (tid), and the dose is then increased every 2 weeks in the absence of hypotension, indicated by systolic blood pressure measurements and symptoms, up to a maximum dose of 2.5 mg tid. The established riociguat dose-adjustment scheme allows the dose of riociguat to be individually optimized in terms of tolerability and efficacy. The majority of patients in the phase III clinical trials and their long-term extension phases achieved the maximum riociguat dose, whereas some patients remained on lower doses. There is evidence that these patients may experience benefits at riociguat doses lower than 2.5 mg tid, with improvement in exercise capacity being observed after only 2-4 weeks of treatment in the phase III studies and in the exploratory 1.5 mg-maximum patient group of PATENT-1. This review aims to provide an overview of the rationale behind the riociguat dose-adjustment scheme and examine its application to both clinical trials and real-life clinical practice. Copyright © 2017 Elsevier Ltd. All rights reserved.

Definitions and outlook targeting x-ray exposure of patients in diagnostic imaging

NASA Astrophysics Data System (ADS)

Regulla, Dieter F.

2011-03-01

Computer tomography (CT) is vital and currently irreplaceable in diagnostic radiology. But CT operates with ionizing radiation which may cause cancer or non-cancer diseases in humans. The degree of radiation impact depends on the dose administered by an investigation. And this is the core issue: Even CT exams executed lege artis, administer doses to patients which by magnitude are far beyond the level of hitherto known doses of conventional film-screen techniques. Patients undergoing one or multiple CT examinations, digital angiographies or interventions will be exposed to effective doses between roughly several mSv and several 100 mSv depending on type and frequency of the diagnostic investigations. From the radiation protection point of view, there is therefore the worldwide problem of formulating firm rules for the control of these high-dose investigations, as dose limits can not be established for reasons of the medical benefit. This makes the difference compared with radiation protection for occupationally exposed persons. What remains is "software", namely "justification" and "optimization". Justification requires balancing the interests between the health benefit and the potential harm of an exam which has to be responsibly executed by the physician himself; therefore the radiologists' associations are in the duty to prepare practicable rules for justification. Optimization again needs a cooperative solution, and that is the establishment of reference doses for diagnostic examinations, to be checked by the technical service of the producers' companies. Experts and authorities have been aware of the high-dose dilemma in diagnostic imaging since long. It is time for the reflection of active solutions and their implementation into practice.

SU-E-I-29: Care KV: Dose It Influence Radiation Dose in Non-Contrast Examination of CT Abdomen/pelvis?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, J; Ganesh, H; Weir, V

Purpose: CARE kV is a tool that automatically recommends optimal kV setting for individual patient for specific CT examination. The use of CARE kV depends on topogram and the user-selected contrast behavior. CARE kV is expected to reduce radiation dose while improving image quality. However, this may work only for certain groups of patients and/or certain CT examinations. This study is to investigate the effects of CARE kV on radiation dose of non-contrast examination of CT abdomen/pelvis. Methods: Radiation dose (CTDIvol and DLP) from patients who underwent abdomen/pelvis non-contrast examination with and without CARE kV were retrospectively reviewed. All patientsmore » were scanned in the same scanner (Siemens Somatom AS64). To mitigate any possible influences due to technologists’ unfamiliarity with the CARE kV, the data with CARE kV were retrieved 1.5 years after the start of CARE kV usage. T-test was used for significant difference in radiation dose. Results: Volume CTDIs and DLPs from 18 patients before and 24 patients after the use of CARE kV were obtained in a duration of one month. There is a slight increase in both average CTDIvol and average DLP with CARE kV compared to those without CARE kV (25.52 mGy vs. 22.65 mGy for CTDIvol; 1265.81 mGy-cm vs. 1199.19 mGy-cm). Statistically there was no significant difference. Without CARE kV, 140 kV was used in 9 of 18 patients, while with CARE KV, 140 kV was used in 15 of 24 patients. 80kV was not used in either group. Conclusion: The use of CARE kV may save time for protocol optimization and minimize variability among technologists. Radiation dose reduction was not observed in non-contrast examinations of CT abdomen/pelvis. This was partially because our CT protocols were tailored according to patient size before CARE kV and partially because of large size patients.« less

Real-time in vivo rectal wall dosimetry using plastic scintillation detectors for patients with prostate cancer

NASA Astrophysics Data System (ADS)

Wootton, Landon; Kudchadker, Rajat; Lee, Andrew; Beddar, Sam

2014-02-01

We designed and constructed an in vivo dosimetry system using plastic scintillation detectors (PSDs) to monitor dose to the rectal wall in patients undergoing intensity-modulated radiation therapy for prostate cancer. Five patients were enrolled in an Institutional Review Board-approved protocol for twice weekly in vivo dose monitoring with our system, resulting in a total of 142 in vivo dose measurements. PSDs were attached to the surface of endorectal balloons used for prostate immobilization to place the PSDs in contact with the rectal wall. Absorbed dose was measured in real time and the total measured dose was compared with the dose calculated by the treatment planning system on the daily computed tomographic image dataset. The mean difference between measured and calculated doses for the entire patient population was -0.4% (standard deviation 2.8%). The mean difference between daily measured and calculated doses for each patient ranged from -3.3% to 3.3% (standard deviation ranged from 5.6% to 7.1% for four patients and was 14.0% for the last, for whom optimal positioning of the detector was difficult owing to the patient's large size). Patients tolerated the detectors well and the treatment workflow was not compromised. Overall, PSDs performed well as in vivo dosimeters, providing excellent accuracy, real-time measurement and reusability.

Spot-Scanning Proton Arc (SPArc) Therapy: The First Robust and Delivery-Efficient Spot-Scanning Proton Arc Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ding, Xuanfeng, E-mail: Xuanfeng.ding@beaumont.org; Li, Xiaoqiang; Zhang, J. Michele

Purpose: To present a novel robust and delivery-efficient spot-scanning proton arc (SPArc) therapy technique. Methods and Materials: A SPArc optimization algorithm was developed that integrates control point resampling, energy layer redistribution, energy layer filtration, and energy layer resampling. The feasibility of such a technique was evaluated using sample patients: 1 patient with locally advanced head and neck oropharyngeal cancer with bilateral lymph node coverage, and 1 with a nonmobile lung cancer. Plan quality, robustness, and total estimated delivery time were compared with the robust optimized multifield step-and-shoot arc plan without SPArc optimization (Arc{sub multi-field}) and the standard robust optimized intensity modulatedmore » proton therapy (IMPT) plan. Dose-volume histograms of target and organs at risk were analyzed, taking into account the setup and range uncertainties. Total delivery time was calculated on the basis of a 360° gantry room with 1 revolutions per minute gantry rotation speed, 2-millisecond spot switching time, 1-nA beam current, 0.01 minimum spot monitor unit, and energy layer switching time of 0.5 to 4 seconds. Results: The SPArc plan showed potential dosimetric advantages for both clinical sample cases. Compared with IMPT, SPArc delivered 8% and 14% less integral dose for oropharyngeal and lung cancer cases, respectively. Furthermore, evaluating the lung cancer plan compared with IMPT, it was evident that the maximum skin dose, the mean lung dose, and the maximum dose to ribs were reduced by 60%, 15%, and 35%, respectively, whereas the conformity index was improved from 7.6 (IMPT) to 4.0 (SPArc). The total treatment delivery time for lung and oropharyngeal cancer patients was reduced by 55% to 60% and 56% to 67%, respectively, when compared with Arc{sub multi-field} plans. Conclusion: The SPArc plan is the first robust and delivery-efficient proton spot-scanning arc therapy technique, which could potentially be implemented into routine clinical practice.« less

Explicit optimization of plan quality measures in intensity-modulated radiation therapy treatment planning.

PubMed

Engberg, Lovisa; Forsgren, Anders; Eriksson, Kjell; Hårdemark, Björn

2017-06-01

To formulate convex planning objectives of treatment plan multicriteria optimization with explicit relationships to the dose-volume histogram (DVH) statistics used in plan quality evaluation. Conventional planning objectives are designed to minimize the violation of DVH statistics thresholds using penalty functions. Although successful in guiding the DVH curve towards these thresholds, conventional planning objectives offer limited control of the individual points on the DVH curve (doses-at-volume) used to evaluate plan quality. In this study, we abandon the usual penalty-function framework and propose planning objectives that more closely relate to DVH statistics. The proposed planning objectives are based on mean-tail-dose, resulting in convex optimization. We also demonstrate how to adapt a standard optimization method to the proposed formulation in order to obtain a substantial reduction in computational cost. We investigated the potential of the proposed planning objectives as tools for optimizing DVH statistics through juxtaposition with the conventional planning objectives on two patient cases. Sets of treatment plans with differently balanced planning objectives were generated using either the proposed or the conventional approach. Dominance in the sense of better distributed doses-at-volume was observed in plans optimized within the proposed framework. The initial computational study indicates that the DVH statistics are better optimized and more efficiently balanced using the proposed planning objectives than using the conventional approach. © 2017 American Association of Physicists in Medicine.

Patient-specific Radiation Dose and Cancer Risk for Pediatric Chest CT

PubMed Central

Samei, Ehsan; Segars, W. Paul; Sturgeon, Gregory M.; Colsher, James G.; Frush, Donald P.

2011-01-01

Purpose: To estimate patient-specific radiation dose and cancer risk for pediatric chest computed tomography (CT) and to evaluate factors affecting dose and risk, including patient size, patient age, and scanning parameters. Materials and Methods: The institutional review board approved this study and waived informed consent. This study was HIPAA compliant. The study included 30 patients (0–16 years old), for whom full-body computer models were recently created from clinical CT data. A validated Monte Carlo program was used to estimate organ dose from eight chest protocols, representing clinically relevant combinations of bow tie filter, collimation, pitch, and tube potential. Organ dose was used to calculate effective dose and risk index (an index of total cancer incidence risk). The dose and risk estimates before and after normalization by volume-weighted CT dose index (CTDIvol) or dose–length product (DLP) were correlated with patient size and age. The effect of each scanning parameter was studied. Results: Organ dose normalized by tube current–time product or CTDIvol decreased exponentially with increasing average chest diameter. Effective dose normalized by tube current–time product or DLP decreased exponentially with increasing chest diameter. Chest diameter was a stronger predictor of dose than weight and total scan length. Risk index normalized by tube current–time product or DLP decreased exponentially with both chest diameter and age. When normalized by DLP, effective dose and risk index were independent of collimation, pitch, and tube potential (<10% variation). Conclusion: The correlations of dose and risk with patient size and age can be used to estimate patient-specific dose and risk. They can further guide the design and optimization of pediatric chest CT protocols. © RSNA, 2011 Supplemental material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.11101900/-/DC1 PMID:21467251

[Diagnostic reference levels in interventional radiology].

PubMed

Vañó Carruana, E; Fernández Soto, J M; Sánchez Casanueva, R M; Ten Morón, J I

2013-12-01

This article discusses the diagnostic reference levels for radiation exposure proposed by the International Commission on Radiological Protection (ICRP) to facilitate the application of the optimization criteria in diagnostic imaging and interventional procedures. These levels are normally established as the third quartile of the dose distributions to patients in an ample sample of centers and are supposed to be representative of good practice regarding patient exposure. In determining these levels, it is important to evaluate image quality as well to ensure that it is sufficient for diagnostic purposes. When the values for the dose received by patients are systematically higher or much lower than the reference levels, an investigation should determine whether corrective measures need to be applied. The European and Spanish regulations require the use of these reference values in quality assurance programs. For interventional procedures, the dose area product (or kerma area product) values are usually used as reference values together with the time under fluoroscopy and the total number of images acquired. The most modern imaging devices allow the value of the accumulated dose at the entrance to the patient to be calculated to optimize the distribution of the dose on the skin. The ICRP recommends that the complexity of interventional procedures be taken into account when establishing reference levels. In the future, diagnostic imaging departments will have automatic systems to manage patient dosimetric data; these systems will enable continuous dosage auditing and alerts about individual procedures that might involve doses several times above the reference values. This article also discusses aspects that need to be clarified to take better advantage of the reference levels in interventional procedures. Copyright © 2013 SERAM. Published by Elsevier Espana. All rights reserved.

SU-F-T-188: A Robust Treatment Planning Technique for Proton Pencil Beam Scanning Cranial Spinal Irradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhu, M; Mehta, M; Badiyan, S

2016-06-15

Purpose: To propose a proton pencil beam scanning (PBS) cranial spinal irradiation (CSI) treatment planning technique robust against patient roll, isocenter offset and proton range uncertainty. Method: Proton PBS plans were created (Eclipse V11) for three previously treated CSI patients to 36 Gy (1.8 Gy/fractions). The target volume was separated into three regions: brain, upper spine and lower spine. One posterior-anterior (PA) beam was used for each spine region, and two posterior-oblique beams (15° apart from PA direction, denoted as 2PO-15) for the brain region. For comparison, another plan using one PA beam for the brain target (denoted as 1PA)more » was created. Using the same optimization objectives, 98% CTV was optimized to receive the prescription dose. To evaluate plan robustness against patient roll, the gantry angle was increased by 3° and dose was recalculated without changing the proton spot weights. On the re-calculated plan, doses were then calculated using 12 scenarios that are combinations of isocenter shift (±3mm in X, Y, and Z directions) and proton range variation (±3.5%). The worst-case-scenario (WCS) brain CTV dosimetric metrics were compared to the nominal plan. Results: For both beam arrangements, the brain field(s) and upper-spine field overlap in the T2–T5 region depending on patient anatomy. The maximum monitor unit per spot were 48.7%, 47.2%, and 40.0% higher for 1PA plans than 2PO-15 plans for the three patients. The 2PO-15 plans have better dose conformity. At the same level of CTV coverage, the 2PO-15 plans have lower maximum dose and higher minimum dose to the CTV. The 2PO-15 plans also showed lower WCS maximum dose to CTV, while the WCS minimum dose to CTV were comparable between the two techniques. Conclusion: Our method of using two posterior-oblique beams for brain target provides improved dose conformity and homogeneity, and plan robustness including patient roll.« less

SU-E-J-53: Dosimetric Evaluation at Volumetric Modulated Arc Therapy for Treatment of Prostate Cancer Using Single Or Double Arcs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Silva, D; Salmon, H; Pavan, G

2014-06-01

Purpose: Evaluate and compare retrospective prostate treatment plan using Volumetric Modulated Arc Therapy (RapidArc™ - Varian) technique with single or double arcs at COI Group. Methods: Ten patients with present prostate and seminal vesicle neoplasia were replanned as a target treatment volume and a prescribed dose of 78 Gy. A baseline planning, using single arc, was developed for each case reaching for the best result on PTV, in order to minimize the dose on organs at risk (OAR). Maintaining the same optimization objectives used on baseline plan, two copies for optimizing single and double arcs, have been developed. The plansmore » were performed with 10 MV photon beam energy on Eclipse software, version 11.0, making use of Trilogy linear accelerator with Millenium HD120 multileaf collimator. Comparisons on PTV have been performed, such as: maximum, minimum and mean dose, gradient dose, as well as the quantity of monitor units, treatment time and homogeneity and conformity index. OARs constrains dose have been evaluated, comparing both optimizations. Results: Regarding PTV coverage, the difference of the minimum, maximum and mean dose were 1.28%, 0.7% and 0.2% respectively higher for single arc. When analyzed the index of homogeneity found a difference of 0.99% higher when compared with double arcs. However homogeneity index was 0.97% lower on average by using single arc. The doses on the OARs, in both cases, were in compliance to the recommended limits RTOG 0415. With the use of single arc, the quantity of monitor units was 10,1% lower, as well as the Beam-On time, 41,78%, when comparing double arcs, respectively. Conclusion: Concerning the optimization of patients with present prostate and seminal vesicle neoplasia, the use of single arc reaches similar objectives, when compared to double arcs, in order to decrease the treatment time and the quantity of monitor units.« less

Booster and higher antigen doses of inactivated influenza vaccine in HIV-infected patients.

PubMed

Johnston, Jessica A; Tincher, Lindsey B; Lowe, Denise K

2013-12-01

To review the literature regarding booster or higher doses of influenza antigen for increasing immunogenicity of inactivated influenza vaccine (IIV) in HIV-infected patients. MEDLINE (1966 to September 2013) was searched using the terms immunize, influenza, vaccine, and HIV or AIDS in combination with two-dose, booster-dose, increased antigen, or high-dose. One trial of booster dosing with standard doses (SDs) of IIV, trivalent (IIV3); 2 trials of booster dosing with intermediate doses (ID) of H1N1 IIV or IIV3; and 1 trial of high-dose (HD) IIV3 were identified. Trials administering 2-dose, booster-dose, or increased antigen of influenza vaccine to patients with HIV were reviewed. Because adjuvanted IIV is not available and IIV, quadrivalent was recently approved in the United States, studies evaluating these vaccines were excluded. HIV-infected individuals are at high risk for influenza-related complications; however, vaccination with SD IIV may not confer optimal protection. It has been postulated that booster or higher doses of influenza antigen may lead to increased immunogenicity. When ID and SD or ID with boosters were evaluated in HIV-infected patients, significant increases in surrogate markers for influenza protection were not achieved. However, HD IIV3 did result in significant increases in seroprotective antibody levels, though 'clinical' influenza was not evaluated. Currently, evidence is insufficient to reach conclusions about the efficacy of booster dosing, ID, or HD influenza vaccine in HIV-infected patients. Trials evaluating booster or higher-antigen doses of IIV for 'clinical' influenza are necessary before routinely recommending for HIV-infected patients.

The treatment of extensive scalp lesions combining electrons with intensity-modulated photons.

PubMed

Chan, Maria F; Song, Yulin; Burman, Chandra; Chui, Chen S; Schupak, Karen

2006-01-01

This study was to investigate the feasibility and potential benefits of combining electrons with intensity modulated photons (IMRT+e) for patients with extensive scalp lesions. A case of a patient with an extensive scalp lesion, in which the target volume covered the entire front half of the scalp, is presented. This approach incorporated the electron dose into the inverse treatment planning optimization. The resulting doses to the planning target volume (PTV) and relevant critical structures were compared. Thermoluminescent dosimeters (TLD), diodes, and GAFCHROMIC EBT films were used to verify the accuracy of the techniques. The IMRT+e plan produced a superior dose distribution to the patient as compared to the IMRT plan in terms of reduction of the dose to the brain with the same dose conformity and homogeneity in the target volumes. This study showed that IMRT+e is a viable treatment modality for extensive scalp lesions patients. It provides a feasible alternative to existing treatment techniques, resulting in improved homogeneity of dose to the PTV compared to conventional electron techniques and a decrease in dose to the brain compared to photon IMRT alone.

Low-Dose CT of the Paranasal Sinuses: Minimizing X-Ray Exposure with Spectral Shaping.

PubMed

Wuest, Wolfgang; May, Matthias; Saake, Marc; Brand, Michael; Uder, Michael; Lell, Michael

2016-11-01

Shaping the energy spectrum of the X-ray beam has been shown to be beneficial in low-dose CT. This study's aim was to investigate dose and image quality of tin filtration at 100 kV for pre-operative planning in low-dose paranasal CT imaging in a large patient cohort. In a prospective trial, 129 patients were included. 64 patients were randomly assigned to the study protocol (100 kV with additional tin filtration, 150mAs, 192x0.6-mm slice collimation) and 65 patients to the standard low-dose protocol (100 kV, 50mAs, 128 × 0.6-mm slice collimation). To assess the image quality, subjective parameters were evaluated using a five-point scale. This scale was applied on overall image quality and contour delineation of critical anatomical structures. All scans were of diagnostic image quality. Bony structures were of good diagnostic image quality in both groups, soft tissues were of sufficient diagnostic image quality in the study group because of a high level of noise. Radiation exposure was very low in both groups, but significantly lower in the study group (CTDI vol 1.2 mGy vs. 4.4 mGy, p < 0.001). Spectral optimization (tin filtration at 100 kV) allows for visualization of the paranasal sinus with sufficient image quality at a very low radiation exposure. • Spectral optimization (tin filtration) is beneficial to low-dose parasinus CT • Tin filtration at 100 kV yields sufficient image quality for pre-operative planning • Diagnostic parasinus CT can be performed with an effective dose <0.05 mSv.

Pediatric cleft palate patients show a 3- to 5-fold increase in cumulative radiation exposure from dental radiology compared with an age- and gender-matched population: a retrospective cohort study.

PubMed

Jacobs, Reinhilde; Pauwels, Ruben; Scarfe, William C; De Cock, Carl; Dula, Karl; Willems, Guy; Verdonck, An; Politis, Constantinus

2018-05-01

The objective of the study was to compare estimates of pediatric cumulative exposure and lifetime attributable risk (LAR) of radiation-induced cancer from dental radiology between cleft palate (CP) subjects and age- and gender-matched controls (non-CP), with and without orthodontic treatment. The radiation exposure frequency of CP subjects and non-CP controls with and without orthodontic treatment was compared for two-dimensional radiography (intra-oral, panoramic and cephalometric radiography), computed tomography (CT), and cone-beam CT (CBCT) using cumulative radiation dose as an estimate. From this dose estimate, the age- and gender-dependent risk for radiation-induced stochastic effects was calculated for each patient group. CP patients received more radiographic examinations than non-CP controls, with the exception of intra-oral radiographs. The cumulative dose to CP patients was considerably higher (1963 μSv at the age of 20 years) than non-CP patients with (597 μSv) and without (383 μSv) orthodontic treatment, primarily due to the higher frequency of CT scanning. Accordingly, CP patients had a three to five times higher LAR than non-CP patients. This study suggests a significantly higher lifetime radiation exposure to CP patients than non-CP controls from dental radiographic procedures. Diagnostic benefits from the use of CT and CBCT in children must be justified and appropriate dose optimization strategies implemented. The present study indicates the need for proper justification and optimization of pediatric exposures in dentistry, with a special focus on high-risk groups.

Formulation Development and Evaluation of Fast Disintegrating Tablets of Salbutamol Sulphate for Respiratory Disorders

PubMed Central

Sharma, Deepak

2013-01-01

Recent developments in fast disintegrating tablets have brought convenience in dosing to pediatric and elderly patients who have trouble in swallowing tablets. The objective of the present study was to prepare the fast disintegrating tablet of salbutamol sulphate for respiratory disorders for pediatrics. As precision of dosing and patient's compliance become important prerequisites for a long-term treatment, there is a need to develop a formulation for this drug which overcomes problems such as difficulty in swallowing, inconvenience in administration while travelling, and patient's acceptability. Hence, the present investigation were undertaken with a view to develop a fast disintegrating tablet of salbutamol sulphate which offers a new range of products having desired characteristics and intended benefits. Superdisintegrants such as sodium starch glycolate was optimized. Different binders were optimized along with optimized superdisintegrant concentration. The tablets were prepared by direct compression technique. The tablets were evaluated for hardness, friability, weight variation, wetting time, disintegration time, and uniformity of content. Optimized formulation was evaluated by in vitro dissolution test, drug-excipient compatibility, and accelerated stability study. It was concluded that fast disintegrating tablets of salbutamol sulphate were formulated successfully with desired characteristics which disintegrated rapidly; provided rapid onset of action; and enhanced the patient convenience and compliance. PMID:23956881

[Optimization of radiological scoliosis assessment].

PubMed

Enríquez, Goya; Piqueras, Joaquim; Catalá, Ana; Oliva, Glòria; Ruiz, Agustí; Ribas, Montserrat; Duran, Carmina; Rodrigo, Carlos; Rodríguez, Eugenia; Garriga, Victoria; Maristany, Teresa; García-Fontecha, César; Baños, Joan; Muchart, Jordi; Alava, Fernando

2014-07-01

Most scoliosis are idiopathic (80%) and occur more frequently in adolescent girls. Plain radiography is the imaging method of choice, both for the initial study and follow-up studies but has the disadvantage of using ionizing radiation. The breasts are exposed to x-ray along these repeated examinations. The authors present a range of recommendations in order to optimize radiographic exam technique for both conventional and digital x-ray settings to prevent unnecessary patients' radiation exposure and to reduce the risk of breast cancer in patients with scoliosis. With analogue systems, leaded breast protectors should always be used, and with any radiographic equipment, analog or digital radiography, the examination should be performed in postero-anterior projection and optimized low-dose techniques. The ALARA (as low as reasonable achievable) rule should always be followed to achieve diagnostic quality images with the lowest feasible dose. Copyright © 2014. Published by Elsevier Espana.

Optimal sampling theory and population modelling - Application to determination of the influence of the microgravity environment on drug distribution and elimination

NASA Technical Reports Server (NTRS)

Drusano, George L.

1991-01-01

The optimal sampling theory is evaluated in applications to studies related to the distribution and elimination of several drugs (including ceftazidime, piperacillin, and ciprofloxacin), using the SAMPLE module of the ADAPT II package of programs developed by D'Argenio and Schumitzky (1979, 1988) and comparing the pharmacokinetic parameter values with results obtained by traditional ten-sample design. The impact of the use of optimal sampling was demonstrated in conjunction with NONMEM (Sheiner et al., 1977) approach, in which the population is taken as the unit of analysis, allowing even fragmentary patient data sets to contribute to population parameter estimates. It is shown that this technique is applicable in both the single-dose and the multiple-dose environments. The ability to study real patients made it possible to show that there was a bimodal distribution in ciprofloxacin nonrenal clearance.

Characterization and validation of the thorax phantom Lungman for dose assessment in chest radiography optimization studies.

PubMed

Rodríguez Pérez, Sunay; Marshall, Nicholas William; Struelens, Lara; Bosmans, Hilde

2018-01-01

This work concerns the validation of the Kyoto-Kagaku thorax anthropomorphic phantom Lungman for use in chest radiography optimization. The equivalence in terms of polymethyl methacrylate (PMMA) was established for the lung and mediastinum regions of the phantom. Patient chest examination data acquired under automatic exposure control were collated over a 2-year period for a standard x-ray room. Parameters surveyed included exposure index, air kerma area product, and exposure time, which were compared with Lungman values. Finally, a voxel model was developed by segmenting computed tomography images of the phantom and implemented in PENELOPE/penEasy Monte Carlo code to compare phantom tissue-equivalent materials with materials from ICRP Publication 89 in terms of organ dose. PMMA equivalence varied depending on tube voltage, from 9.5 to 10.0 cm and from 13.5 to 13.7 cm, for the lungs and mediastinum regions, respectively. For the survey, close agreement was found between the phantom and the patients' median values (deviations lay between 8% and 14%). Differences in lung doses, an important organ for optimization in chest radiography, were below 13% when comparing the use of phantom tissue-equivalent materials versus ICRP materials. The study confirms the value of the Lungman for chest optimization studies.

Dosing strategies to optimize currently available anti-MRSA treatment options (Part 1: IV options).

PubMed

Hall, Ronald G; Thatcher, Michael; Wei, Wei; Varghese, Shibin; Varughese, Lincy; Ndiulor, Michelle; Payne, Kenna D

2017-05-01

Methicillin-resistant Staphylococcus aureus (MRSA) continues to be a predominant pathogen resulting in significant morbidity and mortality. Optimal dosing of anti-MRSA agents is needed to help prevent the development of antimicrobial resistance and to increase the likelihood of a favorable clinical outcome. Areas covered: This review summarizes the available data for antimicrobials routinely used for MRSA infections that are not administered orally or topically. We make recommendations and highlight the current gaps in the literature. A PubMed (1966 - Present) search was performed to identify relevant literature for this review. Expert commentary: Improvements in MIC determination and therapeutic drug monitoring are needed to fully implement individualized dosing that optimizes antimicrobial pharmacodynamics.Additional data will become available for these agents in regards to effectiveness for severe MRSA infections and pharmacokinetic data for special patient populations.

Genomic tissue typing and optimal antithymocyte globuline dose using unrelated donors results in similar survival and relapse as HLA-identical siblings in haematopoietic stem-cell transplantation for leukaemia.

PubMed

Remberger, Mats; Mattsson, Jonas; Hausenberger, Dan; Schaffer, Marie; Svahn, Britt-Marie; Ringdén, Olle

2008-05-01

Sixty-one leukaemia patients treated with haematopoietic stem cell transplantation (HSCT) from a genomic human leucocyte antigen (HLA)-A, -B and -DRbeta1 matched unrelated donor (MUD) were compared with 121 patients with an HLA-identical sibling donor. All patients received conventional conditioning. We selected all patients with unrelated donors who received optimal antithymocyte globuline (ATG) dose, 6 mg/kg. One hundred and seven patients received stem cells from peripheral blood and 75 patients received bone marrow (BM) cells. The incidences of acute graft-versus-host disease (GVHD) grades II-IV were 33.4% and 34.7% in the MUD and sibling group, respectively. After year 2001, the incidence of chronic GVHD was similar in the two groups (27.8% vs. 25.8%). There was no difference in overall survival (60% vs. 60%), transplant-related mortality (18.6% vs. 16.6%) and relapse (23% vs. 26.4%) between the two groups. Haematopoietic stem cell transplantation with unrelated donors results in similar GVHD, relapse and survival as compared to using sibling donors. Reasons for this may be improved tissue-typing techniques and supportive care and optimisation of the ATG dose.

An evaluation of the impact of digital imaging on radiographic practice and patient doses

NASA Astrophysics Data System (ADS)

Horrocks, J.; Violaki, K.

2015-09-01

Direct digital imaging technology was implemented in all areas in general and mobile radiology at Barts and the Royal London Hospitals in 2012. Evidence from recent radiation incident investigations indicates optimum exposure factors are not consistently selected, with the greater dynamic range of the digital detectors allowing sub-optimal practice. To investigate further patient dose data were extracted from the Radiology Information System for adult chest X-ray examinations in 2014, covering over 50,000 studies in the Trust. Chest X-ray examinations were selected as they are low dose but frequent examinations. The patient dose data were evaluated taking into account X-ray system type and detector performance measurements, and individual cases studies were used to highlight where practice can be improved.

Influence of tumor location on the intensity-modulated radiation therapy plan of helical tomotherapy.

PubMed

Xu, Yingjie; Yan, Hui; Hu, Zhihui; Ma, Pan; Men, Kuo; Huang, Peng; Ren, Wenting; Dai, Jianrong; Li, Yexiong

2017-01-01

Given the design of the Helical TomoTherapy device, the patient's central axis is routinely aligned with the machine's rotational axis to prevent the patient's body from colliding with the machine walls. However, for treatment of tumors located away from the patient's central axis, this position may not be optimal as the adequate radiation dose may not reach the affected site. Our study aimed to investigate the influence of tumor location on dose quality and delivery efficiency of tomotherapy plans. A phantom and 15 patients were selected for this study. Two plans, A and B, were implemented for each case. In plan A, the patient's central axis was aligned with the machine's rotational axis, whereas in plan B, the center of the planning target volume (PTV) was aligned with the machine's rotational axis. Both plans were optimized with the same planning parameters, and the dose quality of the plans was evaluated using dosimetrics. The delivery efficiency was determined from delivery time and monitor units (MUs). A paired t-test or nonparametric Wilcoxon signed-rank test was performed for statistical comparison. In the phantom study, the median delivery times were 358 and 336 seconds for plans A and B, respectively, and this difference was significant (p = 0.005). In the patient study, the median delivery times were 348 and 317 seconds for plans A and B, respectively, and this difference was also significant (p = 0.001). The dose qualities of both plans for each patient were nearly identical. No significant differences were found in the conformal index, heterogeneity index, and mean dose delivered to normal tissue between the plans. Both phantom and patient studies showed that for normal-sized patients, the delivery time reduced as the distance between the PTV and the patient's central axis increased when the PTV center was aligned with the machine axis. In conclusion, aligning the PTV center with the machine's rotational axis by shifting the patient during tomotherapy reduces the delivery time without compromising the dose quality of intensity-modulated radiation therapy. Copyright © 2017 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

Optimization of light source parameters in the photodynamic therapy of heterogeneous prostate

NASA Astrophysics Data System (ADS)

Li, Jun; Altschuler, Martin D.; Hahn, Stephen M.; Zhu, Timothy C.

2008-08-01

The three-dimensional (3D) heterogeneous distributions of optical properties in a patient prostate can now be measured in vivo. Such data can be used to obtain a more accurate light-fluence kernel. (For specified sources and points, the kernel gives the fluence delivered to a point by a source of unit strength.) In turn, the kernel can be used to solve the inverse problem that determines the source strengths needed to deliver a prescribed photodynamic therapy (PDT) dose (or light-fluence) distribution within the prostate (assuming uniform drug concentration). We have developed and tested computational procedures to use the new heterogeneous data to optimize delivered light-fluence. New problems arise, however, in quickly obtaining an accurate kernel following the insertion of interstitial light sources and data acquisition. (1) The light-fluence kernel must be calculated in 3D and separately for each light source, which increases kernel size. (2) An accurate kernel for light scattering in a heterogeneous medium requires ray tracing and volume partitioning, thus significant calculation time. To address these problems, two different kernels were examined and compared for speed of creation and accuracy of dose. Kernels derived more quickly involve simpler algorithms. Our goal is to achieve optimal dose planning with patient-specific heterogeneous optical data applied through accurate kernels, all within clinical times. The optimization process is restricted to accepting the given (interstitially inserted) sources, and determining the best source strengths with which to obtain a prescribed dose. The Cimmino feasibility algorithm is used for this purpose. The dose distribution and source weights obtained for each kernel are analyzed. In clinical use, optimization will also be performed prior to source insertion to obtain initial source positions, source lengths and source weights, but with the assumption of homogeneous optical properties. For this reason, we compare the results from heterogeneous optical data with those obtained from average homogeneous optical properties. The optimized treatment plans are also compared with the reference clinical plan, defined as the plan with sources of equal strength, distributed regularly in space, which delivers a mean value of prescribed fluence at detector locations within the treatment region. The study suggests that comprehensive optimization of source parameters (i.e. strengths, lengths and locations) is feasible, thus allowing acceptable dose coverage in a heterogeneous prostate PDT within the time constraints of the PDT procedure.

Novel Approaches for Visualizing and Analyzing Dose-Timing Data from Electronic Drug Monitors, or "How the 'Broken Window' Theory Pertains to ART Adherence".

PubMed

Gill, Christopher J; DeSilva, Mary Bachman; Hamer, Davidson H; Keyi, Xu; Wilson, Ira B; Sabin, Lora

2015-11-01

Adherence to antiretroviral medications is usually expressed in terms of the proportion of doses taken. However, the timing of doses taken may also be an important dimension to overall adherence. Little is known about whether patients who mistime doses are also more likely to skip doses. Using data from the completed Adherence for Life randomized controlled trial, we created visual and statistical models to capture and analyze dose timing data collected longitudinally with electronic drug monitors (EDM). From scatter plots depicting dose time versus calendar date, we identified dominant patterns of dose taking and calculated key features [slope of line over calendar date; residual mean standard error (RMSE)]. Each was assessed for its ability to categorize subjects with 'sub-optimal' (<95 % of doses taken) using area under the receiver operating characteristic (AROC) curve analysis. Sixty eight subjects contributed EDM data, with ~300 to 400 observations/subject. While regression line slopes did not predict 'sub-optimal' adherence (AROC 0.51, 95 % CI 0.26-0.75), the variability in dose timing (RMSE) was strongly predictive (AROC 0.79, 95 % CI 0.62-0.97). Compared with the lowest quartile of RMSE (minimal dose time variability), each successive quartile roughly doubled the odds of 'sub-optimal' adherence (OR 2.1, 95 % CI 1.3-3.4). Patterns of dose timing and mistiming are strongly related to overall adherence behavior. Notably, individuals who skip doses are more likely to mistime doses, with the degree of risk positively correlated with the extent of dose timing variability.

Open-label randomized clinical trial of atropine bolus injection versus incremental boluses plus infusion for organophosphate poisoning in Bangladesh.

PubMed

Abedin, Mohammed Joynal; Sayeed, Abdullah Abu; Basher, Ariful; Maude, Richard J; Hoque, Gofranul; Faiz, M A

2012-06-01

Severe organophosphate compound (OPC) poisoning is an important clinical problem in many countries of the world. Unfortunately, little clinical research has been performed and little evidence exists with which to determine the best therapy. A study was therefore undertaken to determine the optimal dosing regimen for atropine in the treatment of OPC poisoning. An open-label randomized clinical trial was conducted in Chittagong Medical College Hospital, Chittagong, Bangladesh, on 156 hospitalized individuals with OPC poisoning from June to September 2006. The aim was to compare the efficacy and safety of conventional bolus doses with individualized incremental doses of atropine for atropinization followed by continuous atropine infusion for management of OPC poisoning. Inclusion criteria were patients with a clear history of OPC poisoning with clear clinical signs of toxicity, i.e. features of cholinergic crisis. The patients were observed for at least 96 h. Immediate outcome and complications were recorded. Out of 156 patients, 81 patients received conventional bolus dose atropine (group A) and 75 patients received rapidly incremental doses of atropine followed by infusion (group B). The mortality in group 'A' was 22.5% (18/80) and in group 'B' 8% (6/75) (p < 0.05). The mean duration of atropinization in group 'A' was 151.74 min compared to 23.90 min for group 'B' (p < 0.001). More patients in group A experienced atropine toxicity than in group 'B' (28.4% versus 12.0%, p < 0.05); intermediate syndrome was more common in group 'A' than in group 'B' (13.6% versus 4%, p < 0.05), and respiratory support was required more often for patients in group 'A' than in group 'B' (24.7% versus 8%, p < 0.05). Rapid incremental dose atropinization followed by atropine infusion reduces mortality and morbidity from OPC poisoning and shortens the length of hospital stay and recovery. Incremental atropine and infusion should become the treatment of choice for OPC poisoning. Given the paucity of existing evidence, further clinical studies should be performed to determine the optimal dosing regimen of atropine that most rapidly and safely achieves atropinization in these patients.

Real-time in vivo rectal wall dosimetry using plastic scintillation detectors for patients with prostate cancer

PubMed Central

Wootton, Landon; Kudchadker, Rajat; Lee, Andrew; Beddar, Sam

2014-01-01

We designed and constructed an in vivo dosimetry system using plastic scintillation detectors (PSDs) to monitor dose to the rectal wall in patients undergoing intensity-modulated radiation therapy for prostate cancer. Five patients were enrolled in an Institutional Review Board–approved protocol for twice weekly in vivo dose monitoring with our system, resulting in a total of 142 in vivo dose measurements. PSDs were attached to the surface of endorectal balloons used for prostate immobilization to place the PSDs in contact with the rectal wall. Absorbed dose was measured in real time and the total measured dose was compared with the dose calculated by the treatment planning system on the daily CT image dataset. The mean difference between measured and calculated doses for the entire patient population was −0.4% (standard deviation 2.8%). The mean difference between daily measured and calculated doses for each patient ranged from −3.3% to 3.3% (standard deviation ranged from 5.6% to 7.1% for 4 patients and was 14.0% for the last, for whom optimal positioning of the detector was difficult owing to the patient’s large size). Patients tolerated the detectors well and the treatment workflow was not compromised. Overall, PSDs performed well as in vivo dosimeters, providing excellent accuracy, real-time measurement, and reusability. PMID:24434775

Successful pharmacogenetics-based optimization of unboosted atazanavir plasma exposure in HIV-positive patients: a randomized, controlled, pilot study (the REYAGEN study).

PubMed

Bonora, S; Rusconi, S; Calcagno, A; Bracchi, M; Viganò, O; Cusato, J; Lanzafame, M; Trentalange, A; Marinaro, L; Siccardi, M; D'Avolio, A; Galli, M; Di Perri, G

2015-11-01

Atazanavir without ritonavir, despite efficacy and tolerability, shows low plasma concentrations that warrant optimization. In a randomized, controlled, pilot trial, stable HIV-positive patients on atazanavir/ritonavir (with tenofovir/emtricitabine) were switched to atazanavir. In the standard-dose arm, atazanavir was administered as 400 mg once daily, while according to patients' genetics (PXR, ABCB1 and SLCO1B1), in the pharmacogenetic arm: patients with unfavourable genotypes received 200 mg of atazanavir twice daily. EudraCT number: 2009-014216-35. Eighty patients were enrolled with balanced baseline characteristics. The average atazanavir exposure was 253 ng/mL (150-542) in the pharmacogenetic arm versus 111 ng/mL (64-190) in the standard-dose arm (P < 0.001); 28 patients in the pharmacogenetic arm (75.7%) had atazanavir exposure >150 ng/mL versus 14 patients (38.9%) in the standard-dose arm (P = 0.001). Immunovirological and laboratory parameters had a favourable outcome throughout the study with non-significant differences between study arms. Atazanavir plasma exposure is higher when the schedule is chosen according to the patient's genetic profile. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Randomized, Multicenter Study of Gefitinib Dose-escalation in Advanced Non-small-cell Lung Cancer Patients Achieved Stable Disease after One-month Gefitinib Treatment

PubMed Central

Xue, Cong; Hong, Shaodong; Li, Ning; Feng, Weineng; Jia, Jun; Peng, Jiewen; Lin, Daren; Cao, Xiaolong; Wang, Siyang; Zhang, Weimin; Zhang, Hongyu; Dong, Wei; Zhang, Li

2015-01-01

There is no consensus on the optimal treatment for patients with advanced non-small-cell lung cancer (NSCLC) and stable disease (SD) after gefitinib therapy. This randomized, open-label, multicenter study aimed to explore whether dose-escalation of gefitinib would improve response and survival in NSCLC patients who achieved SD after one-month of standard gefitinib dosage. Between May 2009 and January 2012, 466 patients were enrolled and 100 eligible patients were randomized (1:1) to receive either a higher dose (500 mg/d; H group) or to continue standard dose (250 mg/d; S group) of gefitinib. Objective response rate (ORR) was similar between the two groups (12.5% vs 12.5%, p = 1.000). There were no significant differences regarding progression-free survival (PFS) and overall survival (OS) between both arms (H group vs S group: median PFS, 5.30 months vs 6.23 months, p = 0.167; median OS, 13.70 months vs 18.87 months, p = 0.156). Therefore, dose-escalation of gefitinib does not confer a response or survival advantage in patients who achieve SD with one month of standard-dose gefitinib treatment. PMID:26216071

Reconstruction of paediatric organ doses from axial CT scans performed in the 1990s - range of doses as input to uncertainty estimates.

PubMed

Olerud, Hilde M; Toft, Benthe; Flatabø, Silje; Jahnen, Andreas; Lee, Choonsik; Thierry-Chef, Isabelle

2016-09-01

To assess the range of doses in paediatric CT scans conducted in the 1990s in Norway as input to an international epidemiology study: the EPI-CT study, http://epi-ct.iarc.fr/ . National Cancer Institute dosimetry system for Computed Tomography (NCICT) program based on pre-calculated organ dose conversion coefficients was used to convert CT Dose Index to organ doses in paediatric CT in the 1990s. Protocols reported from local hospitals in a previous Norwegian CT survey were used as input, presuming these were used without optimization for paediatric patients. Large variations in doses between different scanner models and local scan parameter settings are demonstrated. Small children will receive a factor of 2-3 times higher doses compared with adults if the protocols are not optimized for them. For common CT examinations, the doses to the active bone marrow, breast tissue and brain may have exceeded 30 mGy, 60 mGy and 100 mGy respectively, for the youngest children in the 1990s. The doses children received from non-optimised CT examinations during the 1990s are of such magnitude that they may provide statistically significant effects in the EPI-CT study, but probably do not reflect current practice. • Some organ doses from paediatric CT in the 1990s may have exceeded 100 mGy. • Small children may have received doses 2-3 times higher compared with adults. • Different scanner models varied by a factor of 2-3 in dose to patients. • Different local scan parameter settings gave dose variations of a factor 2-3. • Modern CTs and age-adjusted protocols will give much lower paediatric doses.


Intrathecal analgesia by bupivacaine is not enhanced by coadministration of morphine in patients with severe cancer-related pain: a randomized double-blind cross-over study.

PubMed

Reif, Ingalill; Wincent, Anders; Stiller, Carl-Olav

2017-06-01

The objective of this randomized double blind cross-over trial was to determine if patients with severe cancer-related pain and inadequate response to systemic opioids prefer intrathecal (IT) pain relief with a combination of bupivacaine and morphine or bupivacaine only. Adult patients with cancer-related pain (n = 23) scheduled for IT analgesia at the Pain Center at the Karo-linska University Hospital Solna, Stockholm, Sweden, were included. The optimal individual flow rate of IT bupivacaine (2 mg/mL) in addition to bolus doses was titrated and maintained for 4 days. Morphine (1 mg/mL) was added to bupivacaine either on day 2 or 4 according to a randomization protocol. Expression of pain relief preference for morphine instead of control (bupivacaine only) was the primary outcome. Secondary outcomes were difference in pain intensity, pain relief, total use of bupivacaine per 24 hours and number of requested bolus doses. Eight patients dropped out during the 4-day study period for reasons not related to the trial. IT bupivacaine significantly decreased median (interquartile range) pain intensity from 5 (3 - 7) at baseline (before catheter insertion) to 1 (0 - 1) (p = 0.0001; Wilcoxon test). Only 1 patient of 15 with 4-day data expressed any preference for morphine. The addition of IT morphine did not result in any significant change of pain intensity, pain relief score, total use of bupivacaine per 24 hours, or number of requested bolus doses. These results suggest that patients with cancer-related pain treated with high doses of systemic opioids, may start IT treatment with an optimal dose of IT bupivacaine without morphine.
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Impact of ibrutinib dose adherence on therapeutic efficacy in patients with previously treated CLL/SLL.

PubMed

Barr, Paul M; Brown, Jennifer R; Hillmen, Peter; O'Brien, Susan; Barrientos, Jacqueline C; Reddy, Nishitha M; Coutre, Steven; Mulligan, Stephen P; Jaeger, Ulrich; Furman, Richard R; Cymbalista, Florence; Montillo, Marco; Dearden, Claire; Robak, Tadeusz; Moreno, Carol; Pagel, John M; Burger, Jan A; Suzuki, Samuel; Sukbuntherng, Juthamas; Cole, George; James, Danelle F; Byrd, John C

2017-05-11

Ibrutinib, an oral inhibitor of Bruton's tyrosine kinase (BTK), at a once-daily dose of 420 mg achieved BTK active-site occupancy in patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) that was maintained at 24 hours. It is unknown if intermittent interruption of ibrutinib therapy contributes to altered clinical outcomes. We therefore evaluated the effect of ibrutinib dose adherence on patient outcomes in the phase 3 RESONATE trial. The overall mean dose intensity (DI) was 95% with median treatment duration of ∼9 months. Pharmacokinetic assessment of ibrutinib exposure at 420-mg dose suggested similar exposure regardless of patient weight or age. As assessed by independent review committee, patients with higher DI experienced longer median progression-free survival (PFS) compared with those with lower DI regardless of del17p and/or TP53 status. Of 79 patients requiring a drug hold, treatment was restarted at the original dose in 73 (92%) patients. Mean duration of a missed-dose event was 18.7 days (range, 8-56). Patients missing ≥8 consecutive days of ibrutinib had a shorter median PFS vs those missing <8 days (10.9 months vs not reached). These results support sustained adherence to once-daily ibrutinib dosing at 420 mg as clinically feasible to achieve optimal outcomes in patients with previously treated CLL. The trial was registered at www.clinicaltrials.gov as #NCT01578707. © 2017 by The American Society of Hematology.

System for verifiable CT radiation dose optimization based on image quality. part II. process control system.

PubMed

Larson, David B; Malarik, Remo J; Hall, Seth M; Podberesky, Daniel J

2013-10-01

To evaluate the effect of an automated computed tomography (CT) radiation dose optimization and process control system on the consistency of estimated image noise and size-specific dose estimates (SSDEs) of radiation in CT examinations of the chest, abdomen, and pelvis. This quality improvement project was determined not to constitute human subject research. An automated system was developed to analyze each examination immediately after completion, and to report individual axial-image-level and study-level summary data for patient size, image noise, and SSDE. The system acquired data for 4 months beginning October 1, 2011. Protocol changes were made by using parameters recommended by the prediction application, and 3 months of additional data were acquired. Preimplementation and postimplementation mean image noise and SSDE were compared by using unpaired t tests and F tests. Common-cause variation was differentiated from special-cause variation by using a statistical process control individual chart. A total of 817 CT examinations, 490 acquired before and 327 acquired after the initial protocol changes, were included in the study. Mean patient age and water-equivalent diameter were 12.0 years and 23.0 cm, respectively. The difference between actual and target noise increased from -1.4 to 0.3 HU (P < .01) and the standard deviation decreased from 3.9 to 1.6 HU (P < .01). Mean SSDE decreased from 11.9 to 7.5 mGy, a 37% reduction (P < .01). The process control chart identified several special causes of variation. Implementation of an automated CT radiation dose optimization system led to verifiable simultaneous decrease in image noise variation and SSDE. The automated nature of the system provides the opportunity for consistent CT radiation dose optimization on a broad scale. © RSNA, 2013.

Real-life indications to ivabradine treatment for heart rate optimization in patients with chronic systolic heart failure.

PubMed

Tondi, Lara; Fragasso, Gabriele; Spoladore, Roberto; Pinto, Giuseppe; Gemma, Marco; Slavich, Massimo; Godino, Cosmo; Salerno, Anna; Montanaro, Claudia; Margonato, Alberto

2018-05-11

: Ivabradine is a selective and specific inhibitor of If current. With its pure negative chronotropic action, it is recommended by European Society of Cardiology and American College of Cardiology/American Heart Association guidelines in symptomatic heart failure patients (NYHA ≥ 2) with ejection fraction 35% or less, sinus rhythm and heart rate (HR) at least 70 bpm, despite maximally titrated β-blocker therapy. Data supporting this indication mainly derive from the SHIFT study, in which ivabradine reduced the combined endpoint of mortality and hospitalization, despite the fact that only 26% of patients enrolled were on optimal β-blocker doses. The aim of the present analysis is to establish the real-life eligibility for ivabradine in a population of patients with systolic heart failure, regularly attending a single heart failure clinic and treated according to guideline-directed medical therapy (GDMT). The clinical cards of 308 patients with heart failure with reduced ejection fraction (HFrEF) through a 68-month period of observation were retrospectively analyzed. GDMT, including β-blocker up-titration to maximal tolerated dose, was implemented during consecutive visits at variable intervals. Demographic, clinical and echocardiographic data were collected at each visit, together with 12-leads ECG and N-terminal pro-B-type natriuretic peptide levels. Out of 308 analyzed HFrEF patients, 220 (71%) were on effective β-blocker therapy, up-titrated to effective/maximal tolerated dose (55 ± 28% of maximal dose) (HR 67 ± 10 bpm). Among the remaining 88 patients, 10 (3.2%) were on maximally tolerated β blocker and ivabradine; 21 patients (6.8%), despite being on maximal tolerated β-blocker dose, had still HR ≥70 bpm, ejection fraction 35% or less and were symptomatic NYHA ≥2, being therefore eligible for ivabradine treatment. The remaining 57 (18%) patients were not on β blocker due to either intolerance or major contraindications. Among them, 13 (4%) were taking ivabradine alone. Of the final 44 (14%) patients, 27 (9%) showed an inadequate HR control (74 ± 6 bpm). Of these, only eight (3%) patients resulted to be eligible for ivabradine introduction according to HR and ejection fraction parameters. Overall ivabradine was indicated in 52 patients (16.8%) out of 308 enrolled.In conclusion, in a carefully managed population of patients with moderate and stable HFrEF, in which optimal GDMT is properly attained, indication to ivabradine treatment is around 17%.

SU-E-T-295: Simultaneous Beam Sampling and Aperture Shape Optimization for Station Parameter Optimized Radiation Therapy (SPORT)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zarepisheh, M; Li, R; Xing, L

Purpose: Station Parameter Optimized Radiation Therapy (SPORT) was recently proposed to fully utilize the technical capability of emerging digital LINACs, in which the station parameters of a delivery system, (such as aperture shape and weight, couch position/angle, gantry/collimator angle) are optimized altogether. SPORT promises to deliver unprecedented radiation dose distributions efficiently, yet there does not exist any optimization algorithm to implement it. The purpose of this work is to propose an optimization algorithm to simultaneously optimize the beam sampling and aperture shapes. Methods: We build a mathematical model whose variables are beam angles (including non-coplanar and/or even nonisocentric beams) andmore » aperture shapes. To solve the resulting large scale optimization problem, we devise an exact, convergent and fast optimization algorithm by integrating three advanced optimization techniques named column generation, gradient method, and pattern search. Column generation is used to find a good set of aperture shapes as an initial solution by adding apertures sequentially. Then we apply the gradient method to iteratively improve the current solution by reshaping the aperture shapes and updating the beam angles toward the gradient. Algorithm continues by pattern search method to explore the part of the search space that cannot be reached by the gradient method. Results: The proposed technique is applied to a series of patient cases and significantly improves the plan quality. In a head-and-neck case, for example, the left parotid gland mean-dose, brainstem max-dose, spinal cord max-dose, and mandible mean-dose are reduced by 10%, 7%, 24% and 12% respectively, compared to the conventional VMAT plan while maintaining the same PTV coverage. Conclusion: Combined use of column generation, gradient search and pattern search algorithms provide an effective way to optimize simultaneously the large collection of station parameters and significantly improves quality of resultant treatment plans as compared with conventional VMAT or IMRT treatments.« less

VERifyNow in DIabetes high-on-treatment platelet reactivity: a pharmacodynamic study on switching from clopidogrel to prasugrel.

PubMed

Cubero Gómez, José M; Acosta Martínez, Juan; Mendias Benítez, Crsitina; Díaz De La Llera, Luis S; Fernández-Quero, Mónica; Guisado Rasco, Agustí; Villa Gil-Ortega, Manuel; Sánchez González, Ángel

2015-12-01

Diabetic patients with an acute coronary syndrome undergoing percutaneous coronary intervention frequently exhibit high platelet reactivity while on clopidogrel. We hypothesized that in diabetic patients undergoing percutaneous coronary intervention, who exhibit high-platelet-reactivity after standard treatment with clopidogrel, a 60-mg prasugrel loading dose is superior to standard treatment with clopidogrel for optimal P2Y12 inhibition within the first 24-36 h post-angioplasty. VERDI was a prospective, randomized, single-centre, single-blind, parallel-design study (NCT01684813). Consecutive diabetic patients with an non-ST-segment elevation acute coronary syndrome undergoing percutaneous coronary intervention and loaded with clopidogrel were considered for platelet reactivity assessment immediately before angioplasty with the VerifyNow assay measured in P2Y12 reaction units (PRU). Fifty of 63 screened patients (79.4%) had high platelet reactivity (PRU ≥ 208) and were randomized to receive a 60-mg prasugrel loading dose (n = 25) versus clopidogrel standard dose (n = 25). Platelet function was assessed again 24 hours post-angioplasty. Prasugrel achieved greater platelet inhibition than clopidogrel 24 hours post-angioplasty (median [interquartile range], 38 [9-72] vs 285 [240-337], respectively; P < 0.001). The non-high-platelet-reactivity rate (PRU < 208) at 24 h post-angioplasty (primary end point) was higher with prasugrel; 25 patients (100%) in the prasugrel group achieved optimal antiaggregation vs 4 patients (16%) in the clopidogrel group (P < 0.001). No significant acute bleeding was documented in either group. Among type 2 diabetic patients suffering an acute coronary syndrome with high-platelet-reactivity undergoing percutaneous coronary intervention, switching from clopidogrel to prasugrel was superior to standard treatment with clopidogrel for the achievement of optimal antiaggregation within the first 24 hours post-angioplasty.

Radiation Safety in Children With Congenital and Acquired Heart Disease: A Scientific Position Statement on Multimodality Dose Optimization From the Image Gently Alliance.

PubMed

Hill, Kevin D; Frush, Donald P; Han, B Kelly; Abbott, Brian G; Armstrong, Aimee K; DeKemp, Robert A; Glatz, Andrew C; Greenberg, S Bruce; Herbert, Alexander Sheldon; Justino, Henri; Mah, Douglas; Mahesh, Mahadevappa; Rigsby, Cynthia K; Slesnick, Timothy C; Strauss, Keith J; Trattner, Sigal; Viswanathan, Mohan N; Einstein, Andrew J

2017-07-01

There is a need for consensus recommendations for ionizing radiation dose optimization during multimodality medical imaging in children with congenital and acquired heart disease (CAHD). These children often have complex diseases and may be exposed to a relatively high cumulative burden of ionizing radiation from medical imaging procedures, including cardiac computed tomography, nuclear cardiology studies, and fluoroscopically guided diagnostic and interventional catheterization and electrophysiology procedures. Although these imaging procedures are all essential to the care of children with CAHD and have contributed to meaningfully improved outcomes in these patients, exposure to ionizing radiation is associated with potential risks, including an increased lifetime attributable risk of cancer. The goal of these recommendations is to encourage informed imaging to achieve appropriate study quality at the lowest achievable dose. Other strategies to improve care include a patient-centered approach to imaging, emphasizing education and informed decision making and programmatic approaches to ensure appropriate dose monitoring. Looking ahead, there is a need for standardization of dose metrics across imaging modalities, so as to encourage comparative effectiveness studies across the spectrum of CAHD in children. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

SU-E-T-802: Verification of Implanted Cardiac Pacemaker Doses in Intensity-Modulated Radiation Therapy: Dose Prediction Accuracy and Reduction Effect of a Lead Sheet

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, J; Chung, J

2015-06-15

Purpose: To verify delivered doses on the implanted cardiac pacemaker, predicted doses with and without dose reduction method were verified using the MOSFET detectors in terms of beam delivery and dose calculation techniques in intensity-modulated radiation therapy (IMRT). Methods: The pacemaker doses for a patient with a tongue cancer were predicted according to the beam delivery methods [step-and-shoot (SS) and sliding window (SW)], intensity levels for dose optimization, and dose calculation algorithms. Dosimetric effects on the pacemaker were calculated three dose engines: pencil-beam convolution (PBC), analytical anisotropic algorithm (AAA), and Acuros-XB. A lead shield of 2 mm thickness was designedmore » for minimizing irradiated doses to the pacemaker. Dose variations affected by the heterogeneous material properties of the pacemaker and effectiveness of the lead shield were predicted by the Acuros-XB. Dose prediction accuracy and the feasibility of the dose reduction strategy were verified based on the measured skin doses right above the pacemaker using mosfet detectors during the radiation treatment. Results: The Acuros-XB showed underestimated skin doses and overestimated doses by the lead-shield effect, even though the lower dose disagreement was observed. It led to improved dose prediction with higher intensity level of dose optimization in IMRT. The dedicated tertiary lead sheet effectively achieved reduction of pacemaker dose up to 60%. Conclusion: The current SS technique could deliver lower scattered doses than recommendation criteria, however, use of the lead sheet contributed to reduce scattered doses.Thin lead plate can be a useful tertiary shielder and it could not acuse malfunction or electrical damage of the implanted pacemaker in IMRT. It is required to estimate more accurate scattered doses of the patient with medical device to design proper dose reduction strategy.« less

Can Saliva and Plasma Methadone Concentrations Be Used for Enantioselective Pharmacokinetic and Pharmacodynamic Studies in Patients With Advanced Cancer?

PubMed

George, Rani; Haywood, Alison; Good, Phillip; Hennig, Stefanie; Khan, Sohil; Norris, Ross; Hardy, Janet

2017-09-01

Methadone is a potent analgesic used to treat refractory cancer pain. It is administered as a racemic mixture, with the l-enantiomer being primarily a μ-receptor agonist, whereas the d-enantiomer is an N-methyl-d-aspartate antagonist and inhibits serotonin and norepinephrine reuptake. Dose requirements vary greatly among patients to achieve optimal pain control and to avoid the risk of adverse effects. The relationship between plasma and saliva methadone enantiomer concentrations was investigated to determine if saliva could be a substitute for plasma in pharmacodynamic and pharmacokinetic studies for clinical monitoring and dose optimization of methadone in patients with advanced cancer. Patients with advanced cancer who were prescribed varying doses of oral methadone for pain management were recruited to obtain paired plasma and saliva samples. Pain scores were recorded at the time of sampling. The total and unbound plasma and saliva concentrations of the l- and d-enantiomers of methadone were quantified by using an HPLC-MS/MS method. The relationship between plasma (total and unbound) and saliva concentrations were compared. The saliva-to-plasma concentration ratio was compared versus the dose administered and the time after dosing for both enantiomers. The association of methadone concentrations with reported pain scores was compared by using a Mann-Whitney U test for significance. Fifty patients receiving a mean dose of 11mg/d of methadone provided 151 paired plasma and saliva samples. The median age of the population was 61 years with an interquartile range of 53-71 years with total body weight ranging from 59-88 kg. Median (interquartile) total plasma concentrations for l- and d-methadone were 50.78 ng/mL (30.6-113.0 ng/mL) and 62.0 ng/mL (28.7-116.0 ng/mL), respectively. Median (interquartile range) saliva concentrations for l- and d-methadone were 81.5 ng/mL (28.0-203.2 ng/mL) and 44.2 (16.2-149.7 ng/mL). No relationship could be established between plasma and saliva concentrations for l- and d-methadone (r 2 = 0.35 and 0.25). The saliva-to-plasma concentration analyzed with the methadone dose showed higher saliva concentrations at lower doses. Dose-normalized saliva concentrations followed a similar pattern over time compared with plasma concentrations. No correlation was found between l-methadone plasma, d-methadone plasma, l-methadone saliva, d-methadone saliva concentrations, and pain score. Saliva concentration was not a better predictor of pain control than plasma concentration for dose optimization and monitoring studies of methadone in patients with cancer. Although the saliva-to-plasma ratio of the concentration of methadone enantiomers was stable across the dosing range, due to the variability in individual saliva-to-plasma ratios, saliva sampling may not be a valid substitute in pharmacokinetic studies of methadone in cancer. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

A D-Optimal designed population pharmacokinetic study of oral itraconazole in adult cystic fibrosis patients

PubMed Central

Hennig, Stefanie; Waterhouse, Timothy H; Bell, Scott C; France, Megan; Wainwright, Claire E; Miller, Hugh; Charles, Bruce G; Duffull, Stephen B

2007-01-01

What is already known about this subject • Itraconazole is a triazole antifungal used in the treatment of allergic bronchopulmonary aspergillosis in patients with cystic fibrosis (CF). • The pharmacokinetic (PK) properties of this drug and its active metabolite have been described before, mostly in healthy volunteers. • However, only sparse information from case reports were available of the PK properties of this drug in CF patients at the start of our study. What this study adds • This study reports for the first time the population pharmacokinetic properties of itraconazole and a known active metabolite, hydroxy-itraconazole in adult patients with CF. • As a result, this study offers new dosing approaches and their pharmacoeconomic impact as well as a PK model for therapeutic drug monitoring of this drug in this patient group. • Furthermore, it is an example of a successful d-optimal design application in a clinical setting. Aim The primary objective of the study was to estimate the population pharmacokinetic parameters for itraconazole and hydroxy-itraconazole, in particular, the relative oral bioavailability of the capsule compared with solution in adult cystic fibrosis patients, in order to develop new dosing guidelines. A secondary objective was to evaluate the performance of a population optimal design. Methods The blood sampling times for the population study were optimized previously using POPT v.2.0. The design was based on the administration of solution and capsules to 30 patients in a cross-over study. Prior information suggested that itraconazole is generally well described by a two-compartment disposition model with either linear or saturable elimination. The pharmacokinetics of itraconazole and the metabolite were modelled simultaneously using NONMEM. Dosing schedules were simulated to assess their ability to achieve a trough target concentration of 0.5 mg ml−1. Results Out of 241 blood samples, 94% were taken within the defined optimal sampling windows. A two-compartment model with first order absorption and elimination best described itraconazole kinetics, with first order metabolism to the hydroxy-metabolite. For itraconazole the absorption rate constants (between-subject variability) for capsule and solution were 0.0315 h−1 (91.9%) and 0.125 h−1 (106.3%), respectively, and the relative bioavailability of the capsule was 0.82 (62.3%) (confidence interval 0.36, 1.97), compared with the solution. There was no evidence of nonlinearity. Simulations from the final model showed that a dosing schedule of 500 mg twice daily for both formulations provided the highest chance of target success. Conclusion The optimal design performed well and the pharmacokinetics of itraconazole and hydroxy-itraconazole were described adequately by the model. The relative bioavailability for itraconazole capsules was 82% compared with the solution. PMID:17073891

Robust plan optimization for electromagnetic transponder guided hypo-fractionated prostate treatment using volumetric modulated arc therapy

NASA Astrophysics Data System (ADS)

Zhang, Pengpeng; Hunt, Margie; Happersett, Laura; Yang, Jie; Zelefsky, Michael; Mageras, Gig

2013-11-01

To develop an optimization algorithm for volumetric modulated arc therapy which incorporates an electromagnetic tracking (EMT) guided gating strategy and is robust to residual intra-fractional motion uncertainties. In a computer simulation, intra-fractional motion traces from prior treatments with EMT were converted to a probability distribution function (PDF), truncated using a patient specific action volume that encloses allowed deviations from the planned position, and renormalized to yield a new PDF with EMT-gated interventions. In lieu of a conventional planning target volume (PTV), multiple instances of clinical target volume (CTV) and organs at risk (OARs) were replicated and displaced to extreme positions inside the action volume representing possible delivery scenarios. When optimizing the volumetric modulated arc therapy plan, doses to the CTV and OARs were calculated as a sum of doses to the replicas weighted by the PDF to account for motion. A treatment plan meeting the clinical constraints was produced and compared to the counterpart conventional margin (PTV) plan. EMT traces from a separate testing database served to simulate motion during gated delivery. Dosimetric end points extracted from dose accumulations for each motion trace were utilized to evaluate potential clinical benefit. Five prostate cases from a hypofractionated protocol (42.5 Gy in 5 fractions) were retrospectively investigated. The patient specific gating window resulted in tight anterior and inferior action levels (∼1 mm) to protect rectal wall and bladder wall, and resulted in an average of four beam interruptions per fraction in the simulation. The robust-optimized plans achieved the same average CTV D95 coverage of 40.5 Gy as the PTV-optimized plans, but with reduced patient-averaged rectum wall D1cc by 2.2 Gy (range 0.7 to 4.7 Gy) and bladder wall mean dose by 2.9 Gy (range 2.0 to 3.4 Gy). Integration of an intra-fractional motion management strategy into the robust optimization process is feasible and may yield improved OAR sparing compared to the standard margin approach.

Robust plan optimization for electromagnetic transponder guided hypo-fractionated prostate treatment using volumetric modulated arc therapy.

PubMed

Zhang, Pengpeng; Hunt, Margie; Happersett, Laura; Yang, Jie; Zelefsky, Michael; Mageras, Gig

2013-11-07

To develop an optimization algorithm for volumetric modulated arc therapy which incorporates an electromagnetic tracking (EMT) guided gating strategy and is robust to residual intra-fractional motion uncertainties. In a computer simulation, intra-fractional motion traces from prior treatments with EMT were converted to a probability distribution function (PDF), truncated using a patient specific action volume that encloses allowed deviations from the planned position, and renormalized to yield a new PDF with EMT-gated interventions. In lieu of a conventional planning target volume (PTV), multiple instances of clinical target volume (CTV) and organs at risk (OARs) were replicated and displaced to extreme positions inside the action volume representing possible delivery scenarios. When optimizing the volumetric modulated arc therapy plan, doses to the CTV and OARs were calculated as a sum of doses to the replicas weighted by the PDF to account for motion. A treatment plan meeting the clinical constraints was produced and compared to the counterpart conventional margin (PTV) plan. EMT traces from a separate testing database served to simulate motion during gated delivery. Dosimetric end points extracted from dose accumulations for each motion trace were utilized to evaluate potential clinical benefit. Five prostate cases from a hypofractionated protocol (42.5 Gy in 5 fractions) were retrospectively investigated. The patient specific gating window resulted in tight anterior and inferior action levels (~1 mm) to protect rectal wall and bladder wall, and resulted in an average of four beam interruptions per fraction in the simulation. The robust-optimized plans achieved the same average CTV D95 coverage of 40.5 Gy as the PTV-optimized plans, but with reduced patient-averaged rectum wall D1cc by 2.2 Gy (range 0.7 to 4.7 Gy) and bladder wall mean dose by 2.9 Gy (range 2.0 to 3.4 Gy). Integration of an intra-fractional motion management strategy into the robust optimization process is feasible and may yield improved OAR sparing compared to the standard margin approach.

CSF1R inhibition with emactuzumab in locally advanced diffuse-type tenosynovial giant cell tumours of the soft tissue: a dose-escalation and dose-expansion phase 1 study.

PubMed

Cassier, Philippe A; Italiano, Antoine; Gomez-Roca, Carlos A; Le Tourneau, Christophe; Toulmonde, Maud; Cannarile, Michael A; Ries, Carola; Brillouet, Anne; Müller, Claudia; Jegg, Anna-Maria; Bröske, Ann-Marie; Dembowski, Markus; Bray-French, Katharine; Freilinger, Christine; Meneses-Lorente, Georgina; Baehner, Monika; Harding, Ross; Ratnayake, Jayantha; Abiraj, Keelara; Gass, Nathalie; Noh, Karen; Christen, Randolph D; Ukarma, Lidia; Bompas, Emmanuelle; Delord, Jean-Pierre; Blay, Jean-Yves; Rüttinger, Dominik

2015-08-01

Diffuse-type tenosynovial giant cell tumour (dt-GCT) of the soft tissue (alternatively known as pigmented villonodular synovitis), an orphan disease with unmet medical need, is characterised by an overexpression of colony-stimulating factor 1 (CSF1), and is usually caused by a chromosomal translocation involving CSF1. CSF1 receptor (CSF1R) activation leads to the recruitment of CSF1R-expressing cells of the mononuclear phagocyte lineage that constitute the tumor mass in dt-GCT. Emactuzumab (RG7155) is a novel monoclonal antibody that inhibits CSF1R activation. We have assessed the safety, tolerability and activity of emactuzumab in patients with Dt-GCT of the soft tissue. In this phase 1, first-in-human dose-escalation and dose-expansion study, eligible patients were aged 18 years or older with dt-GCT of the soft tissue with locally advanced disease or resectable tumours requiring extensive surgery, an Eastern Cooperative Oncology Group performance status of 1 or less, measurable disease according to Response Evaluation Criteria In Solid Tumors version 1.1, and adequate end-organ function. Patients with GCT of the bone were not eligible. Patients received intravenous emactuzumab at 900 mg, 1350 mg, or 2000 mg every 2 weeks in the dose-escalation phase and at the optimal biological dose in a dose-expansion phase. The primary objective was to evaluate the safety and tolerability of emactuzumab, and to determine the maximum tolerated dose or optimal biological dose. All treated patients were included in the analyses. Expansion cohorts are currently ongoing. This study is registered with ClinicalTrials.gov, number NCT01494688. Between July 26, 2012, and Oct 21, 2013, 12 patients were enrolled in the dose-escalation phase. No dose-limiting toxicities were noted in the dose-escalation cohort; on the basis of pharmacokinetic, pharmacodynamic, and safety information, we chose a dose of 1000 mg every 2 week for the dose-expansion cohort, into which 17 patients were enrolled. Owing to different cutoff dates for safety and efficacy readouts, the safety population comprised 25 patients. Common adverse events after emactuzumab treatment were facial oedema (16 [64%] of 25 patients), asthenia (14 [56%]), and pruritus (14 [56%]). Five serious adverse events (periorbital oedema, lupus erythematosus [occurring twice], erythema, and dermohypodermitis all experienced by one [4%] patient each) were reported in five patients. Three of the five serious adverse events-periorbital oedema (one [4%]), lupus erythematosus (one [4%]), and dermohypodermitis (one [4%])-were assessed as grade 3. Two other grade 3 events were reported: mucositis (one [4%]) and fatigue (one [4%]). 24 (86%) of 28 patients achieved an objective response; two (7%) patients achieved a complete response. Further study of dt-GCT is warranted and different possibilities, such as an international collaboration with cooperative groups to assure appropriate recruitment in this rare disease, are currently being assessed. F Hoffmann-La Roche. Copyright © 2015 Elsevier Ltd. All rights reserved.

Accuracy and optimal timing of activity measurements in estimating the absorbed dose of radioiodine in the treatment of Graves' disease

NASA Astrophysics Data System (ADS)

Merrill, S.; Horowitz, J.; Traino, A. C.; Chipkin, S. R.; Hollot, C. V.; Chait, Y.

2011-02-01

Calculation of the therapeutic activity of radioiodine 131I for individualized dosimetry in the treatment of Graves' disease requires an accurate estimate of the thyroid absorbed radiation dose based on a tracer activity administration of 131I. Common approaches (Marinelli-Quimby formula, MIRD algorithm) use, respectively, the effective half-life of radioiodine in the thyroid and the time-integrated activity. Many physicians perform one, two, or at most three tracer dose activity measurements at various times and calculate the required therapeutic activity by ad hoc methods. In this paper, we study the accuracy of estimates of four 'target variables': time-integrated activity coefficient, time of maximum activity, maximum activity, and effective half-life in the gland. Clinical data from 41 patients who underwent 131I therapy for Graves' disease at the University Hospital in Pisa, Italy, are used for analysis. The radioiodine kinetics are described using a nonlinear mixed-effects model. The distributions of the target variables in the patient population are characterized. Using minimum root mean squared error as the criterion, optimal 1-, 2-, and 3-point sampling schedules are determined for estimation of the target variables, and probabilistic bounds are given for the errors under the optimal times. An algorithm is developed for computing the optimal 1-, 2-, and 3-point sampling schedules for the target variables. This algorithm is implemented in a freely available software tool. Taking into consideration 131I effective half-life in the thyroid and measurement noise, the optimal 1-point time for time-integrated activity coefficient is a measurement 1 week following the tracer dose. Additional measurements give only a slight improvement in accuracy.

Optimal blood glucose level control using dynamic programming based on minimal Bergman model

NASA Astrophysics Data System (ADS)

Rettian Anggita Sari, Maria; Hartono

2018-03-01

The purpose of this article is to simulate the glucose dynamic and the insulin kinetic of diabetic patient. The model used in this research is a non-linear Minimal Bergman model. Optimal control theory is then applied to formulate the problem in order to determine the optimal dose of insulin in the treatment of diabetes mellitus such that the glucose level is in the normal range for some specific time range. The optimization problem is solved using dynamic programming. The result shows that dynamic programming is quite reliable to represent the interaction between glucose and insulin levels in diabetes mellitus patient.

Efficacy of allopurinol and benzbromarone for the control of hyperuricaemia. A pathogenic approach to the treatment of primary chronic gout

PubMed Central

Perez-Ruiz, F; Alonso-Ruiz, A; Calabozo, M; Herrero-Beites, A; Garcia-Erauskin, G; Ruiz-Lucea, E

1998-01-01

OBJECTIVES—To study the efficacy of allopurinol and benzbromarone to reduce serum urate concentrations in patients with primary chronic gout.
METHODS—Prospective, parallel, open study of 86 consecutive male patients with primary chronic gout. Forty nine patients (26 normal excretors and 23 under excretors) were given allopurinol 300 mg/day and 37 under excretors benzbromarone 100 mg/day. After achieving steady plasma urate concentrations with such doses, treatment was then adjusted to obtain optimal plasmatic urate concentrations (under 6 mg/dl).
RESULTS—Patients receiving allopurinol 300 mg/day showed a mean reduction of plasmatic urate of 2.75 mg/dl (from 8.60 to 5.85 mg/dl) and 3.34 mg/dl (from 9.10 to 5.76 mg/dl) in normal excretors and under excretors respectively. Patients receiving benzbromarone 100 mg/day achieved a reduction of plasmatic urate of 5.04 mg/dl (from 8.58 to 3.54 mg/dl). Fifty three per cent of patients receiving allopurinol and 100% receiving benzbromarone achieved optimal plasma urate concentrations at such doses. The patients with poor results with allopurinol 300 mg/day achieved a proper plasma urate concentration with allopurinol 450 to 600 mg/day, the mean final dose being 372 mg/day. Renal fuction improved and no case of renal lithiasis was observed among benzbromarone treated patients, whose mean final dose was 76 mg/day.
CONCLUSION—Benzbromarone is very effective to control plasma urate concentrations at doses ranging from 50 to 100 mg/day. Uricosuric treatment is a suitable approach to the treatment of patients with gout who show underexcretion of urate.

 Keywords: gout; gout suppressants; allopurinol; benzbromarone PMID:9849314

Influence of beam efficiency through the patient-specific collimator on secondary neutron dose equivalent in double scattering and uniform scanning modes of proton therapy.

PubMed

Hecksel, D; Anferov, V; Fitzek, M; Shahnazi, K

2010-06-01

Conventional proton therapy facilities use double scattering nozzles, which are optimized for delivery of a few fixed field sizes. Similarly, uniform scanning nozzles are commissioned for a limited number of field sizes. However, cases invariably occur where the treatment field is significantly different from these fixed field sizes. The purpose of this work was to determine the impact of the radiation field conformity to the patient-specific collimator on the secondary neutron dose equivalent. Using a WENDI-II neutron detector, the authors experimentally investigated how the neutron dose equivalent at a particular point of interest varied with different collimator sizes, while the beam spreading was kept constant. The measurements were performed for different modes of dose delivery in proton therapy, all of which are available at the Midwest Proton Radiotherapy Institute (MPRI): Double scattering, uniform scanning delivering rectangular fields, and uniform scanning delivering circular fields. The authors also studied how the neutron dose equivalent changes when one changes the amplitudes of the scanned field for a fixed collimator size. The secondary neutron dose equivalent was found to decrease linearly with the collimator area for all methods of dose delivery. The relative values of the neutron dose equivalent for a collimator with a 5 cm diameter opening using 88 MeV protons were 1.0 for the double scattering field, 0.76 for rectangular uniform field, and 0.6 for the circular uniform field. Furthermore, when a single circle wobbling was optimized for delivery of a uniform field 5 cm in diameter, the secondary neutron dose equivalent was reduced by a factor of 6 compared to the double scattering nozzle. Additionally, when the collimator size was kept constant, the neutron dose equivalent at the given point of interest increased linearly with the area of the scanned proton beam. The results of these experiments suggest that the patient-specific collimator is a significant contributor to the secondary neutron dose equivalent to a distant organ at risk. Improving conformity of the radiation field to the patient-specific collimator can significantly reduce secondary neutron dose equivalent to the patient. Therefore, it is important to increase the number of available generic field sizes in double scattering systems as well as in uniform scanning nozzles.

Limited Impact of Setup and Range Uncertainties, Breathing Motion, and Interplay Effects in Robustly Optimized Intensity Modulated Proton Therapy for Stage III Non-small Cell Lung Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Inoue, Tatsuya; Widder, Joachim; Dijk, Lisanne V. van

2016-11-01

Purpose: To investigate the impact of setup and range uncertainties, breathing motion, and interplay effects using scanning pencil beams in robustly optimized intensity modulated proton therapy (IMPT) for stage III non-small cell lung cancer (NSCLC). Methods and Materials: Three-field IMPT plans were created using a minimax robust optimization technique for 10 NSCLC patients. The plans accounted for 5- or 7-mm setup errors with ±3% range uncertainties. The robustness of the IMPT nominal plans was evaluated considering (1) isotropic 5-mm setup errors with ±3% range uncertainties; (2) breathing motion; (3) interplay effects; and (4) a combination of items 1 and 2.more » The plans were calculated using 4-dimensional and average intensity projection computed tomography images. The target coverage (TC, volume receiving 95% of prescribed dose) and homogeneity index (D{sub 2} − D{sub 98}, where D{sub 2} and D{sub 98} are the least doses received by 2% and 98% of the volume) for the internal clinical target volume, and dose indexes for lung, esophagus, heart and spinal cord were compared with that of clinical volumetric modulated arc therapy plans. Results: The TC and homogeneity index for all plans were within clinical limits when considering the breathing motion and interplay effects independently. The setup and range uncertainties had a larger effect when considering their combined effect. The TC decreased to <98% (clinical threshold) in 3 of 10 patients for robust 5-mm evaluations. However, the TC remained >98% for robust 7-mm evaluations for all patients. The organ at risk dose parameters did not significantly vary between the respective robust 5-mm and robust 7-mm evaluations for the 4 error types. Compared with the volumetric modulated arc therapy plans, the IMPT plans showed better target homogeneity and mean lung and heart dose parameters reduced by about 40% and 60%, respectively. Conclusions: In robustly optimized IMPT for stage III NSCLC, the setup and range uncertainties, breathing motion, and interplay effects have limited impact on target coverage, dose homogeneity, and organ-at-risk dose parameters.« less

Improved plan quality with automated radiotherapy planning for whole brain with hippocampus sparing: a comparison to the RTOG 0933 trial.

PubMed

Krayenbuehl, J; Di Martino, M; Guckenberger, M; Andratschke, N

2017-10-02

Whole-brain radiation therapy (WBRT) with hippocampus sparing (HS) has been investigated by the radiation oncology working group (RTOG) 0933 trial for patients with multiple brain metastases. They showed a decrease of adverse neurocognitive effects with HS WBRT compared to WBRT alone. With the development of automated treatment planning system (aTPS) in the last years, a standardization of the plan quality at a high level was achieved. The goal of this study was to evaluate the feasibility of using an aTPS for the treatment of HS WBRT and see if the RTOG 0933 dose constraints could be achieved and improved. Ten consecutive patients treated with HS WBRT were enrolled in this study. 10 × 3 Gy was prescribed according to the RTOG 0933 protocol to 92% of the target volume (whole-brain excluding the hippocampus expanded by 5 mm in 3-dimensions). In contrast to RTOG 0933, the maximum allowed point dose to normal brain was significantly lowered and restricted to 36.5 Gy. All patients were planned with volumetric modulated arc therapy (VMAT) technique using four arcs. Plans were optimized using Auto-Planning (AP) (Philips Radiation Oncology Systems) with one single AP template and optimization. All the constraints from the RTOG 0933 trial were achieved. A significant improvement for the maximal dose to 2% of the brain with a reduction of 4 Gy was achieved (33.5 Gy vs. RTOG 37.5 Gy) and the minimum hippocampus dose was reduced by 10% (8.1 Gy vs. RTOG 9 Gy). A steep dose gradient around the hippocampus was achieved with a mean dose of 27.3 Gy at a distance between 0.5 cm and 1 cm from the hippocampus. The effective working time to optimize a plan was kept below 6'. Automated treatment planning for HS WBRT was able to fulfil all the recommendations from the RTOG 0933 study while significantly improving dose homogeneity and decreasing unnecessary hot spot in the normal brain. With this approach, a standardization of plan quality was achieved and the effective time required for plan optimization was minimized.

Effect of Admission Oral Diuretic Dose on Response to Continuous versus Bolus Intravenous Diuretics in Acute Heart Failure: An Analysis from DOSE-AHF

PubMed Central

Shah, Ravi V.; McNulty, Steven; O'Connor, Christopher M.; Felker, G. Michael; Braunwald, Eugene; Givertz, Michael M.

2014-01-01

Background Results from the Diuretic Optimization Strategies in Acute Heart Failure (DOSE-AHF) study suggest that an initial continuous infusion of loop diuretics is not superior to bolus dosing with regard to clinical endpoints in AHF. We hypothesized that outpatient furosemide dose was associated with congestion and poorer renal function, and explored the hypothesis that a continuous infusion may be more effective in patients on higher outpatient diuretic doses. Methods DOSE-AHF randomized 308 patients within 24 hours of admission to high vs. low initial intravenous diuretic dose given as either a continuous infusion or bolus. We compared baseline characteristics and assessed associations between mode of administration (bolus vs. continuous) and outcomes in patients receiving high-dose (≥120 mg furosemide equivalent, n=177) versus low-dose (<120 mg furosemide equivalent, n=131) outpatient diuretics. Results Patients on higher doses of furosemide were less frequently on renin-angiotensin system inhibitors (P=.01), and had worse renal function and more advanced symptoms. There was a significant interaction between outpatient dose and mode of therapy (P=0.01) with respect to net fluid loss at 72 hours after adjusting for creatinine and intensification strategy. Admission diuretic dose was associated with an increased risk of death or rehospitalization at 60 days (adjusted HR=1.08 per 20-mg increment in dose, 95% CI 1.01–1.16, P=.03). Conclusions In acute HF, patients on higher diuretic doses have greater disease severity, and may benefit from an initial bolus strategy. PMID:23194486

Directional interstitial brachytherapy from simulation to application

NASA Astrophysics Data System (ADS)

Lin, Liyong

Organs at risk (OAR) are sometimes adjacent to or embedded in or overlap with the clinical target volume (CTV) to be treated. The purpose of this PhD study is to develop directionally low energy gamma-emitting interstitial brachytherapy sources. These sources can be applied between OAR to selectively reduce hot spots in the OARs and normal tissues. The reduction of dose over undesired regions can expand patient eligibility or reduce toxicities for the treatment by conventional interstitial brachytherapy. This study covers the development of a directional source from design optimization to construction of the first prototype source. The Monte Carlo code MCNP was used to simulate the radiation transport for the designs of directional sources. We have made a special construction kit to assemble radioactive and gold-shield components precisely into D-shaped titanium containers of the first directional source. Directional sources have a similar dose distribution as conventional sources on the treated side but greatly reduced dose on the shielded side, with a sharp dose gradient between them. A three-dimensional dose deposition kernel for the 125I directional source has been calculated. Treatment plans can use both directional and conventional 125I sources at the same source strength for low-dose-rate (LDR) implants to optimize the dose distributions. For prostate tumors, directional 125I LDR brachytherapy can potentially reduce genitourinary and gastrointestinal toxicities and improve potency preservation for low risk patients. The combination of better dose distribution of directional implants and better therapeutic ratio between tumor response and late reactions enables a novel temporary LDR treatment, as opposed to permanent or high-dose-rate (HDR) brachytherapy for the intermediate risk T2b and high risk T2c tumors. Supplemental external-beam treatments can be shortened with a better brachytherapy boost for T3 tumors. In conclusion, we have successfully finished the design optimization and construction of the first prototype directional source. Potential clinical applications and potential benefits of directional sources have been shown for prostate and breast tumors.

Design of the heart failure endpoint evaluation of AII-antagonist losartan (HEAAL) study in patients intolerant to ACE-inhibitor.

PubMed

Konstam, Marvin A; Poole-Wilson, Philip A; Dickstein, Kenneth; Drexler, Helmut; Justice, Steven J; Komajda, Michel; Malbecq, William; Martinez, Felipe A; Neaton, James D; Riegger, Gunter A J; Guptha, Soneil

2008-09-01

In patients with heart failure and reduced left ventricular ejection fraction, angiotensin receptor blockers have been found to reduce mortality and morbidity and to prevent or reverse left ventricular remodelling, compared to optimized background treatment. In light of these data, The Heart failure Endpoint evaluation of Angiotensin II Antagonist Losartan (HEAAL) study was developed to determine whether losartan 150 mg is superior to losartan 50 mg (antihypertensive dose) in reducing morbidity and mortality among patients with symptomatic heart failure who are intolerant of angiotensin-converting enzyme (ACE)-inhibitors. To compare the effect of high and moderate doses of losartan on the primary endpoint of all-cause mortality and hospitalisation due to heart failure in patients (n = 3834) with symptomatic heart failure and an ejection fraction < or = 40% who are intolerant of ACE-inhibitor treatment. This paper presents the rationale, trial design, and baseline characteristics of the study population. The study, which completed recruitment on 31 March 2005, is event-driven and is estimated to accrue the target of 1710 adjudicated primary events during the latter half of 2008. The results of HEAAL should facilitate selection of an optimal dosing regimen for losartan in patients with symptomatic heart failure who are intolerant of ACE-inhibitors.

MO-PIS-Exhibit Hall-01: Imaging: CT Dose Optimization Technologies I

DOE Office of Scientific and Technical Information (OSTI.GOV)

Denison, K; Smith, S

Partners in Solutions is an exciting new program in which AAPM partners with our vendors to present practical “hands-on” information about the equipment and software systems that we use in our clinics. The imaging topic this year is CT scanner dose optimization capabilities. Note that the sessions are being held in a special purpose room built on the Exhibit Hall Floor, to encourage further interaction with the vendors. Dose Optimization Capabilities of GE Computed Tomography Scanners Presentation Time: 11:15 – 11:45 AM GE Healthcare is dedicated to the delivery of high quality clinical images through the development of technologies, whichmore » optimize the application of ionizing radiation. In computed tomography, dose management solutions fall into four categories: employs projection data and statistical modeling to decrease noise in the reconstructed image - creating an opportunity for mA reduction in the acquisition of diagnostic images. Veo represents true Model Based Iterative Reconstruction (MBiR). Using high-level algorithms in tandem with advanced computing power, Veo enables lower pixel noise standard deviation and improved spatial resolution within a single image. Advanced Adaptive Image Filters allow for maintenance of spatial resolution while reducing image noise. Examples of adaptive image space filters include Neuro 3-D filters and Cardiac Noise Reduction Filters. AutomA adjusts mA along the z-axis and is the CT equivalent of auto exposure control in conventional x-ray systems. Dynamic Z-axis Tracking offers an additional opportunity for dose reduction in helical acquisitions while SmartTrack Z-axis Tracking serves to ensure beam, collimator and detector alignment during tube rotation. SmartmA provides angular mA modulation. ECG Helical Modulation reduces mA during the systolic phase of the heart cycle. SmartBeam optimization uses bowtie beam-shaping hardware and software to filter off-axis x-rays - minimizing dose and reducing x-ray scatter. The DICOM Radiation Dose Structured Report (RDSR) generates a dose report at the conclusion of every examination. Dose Check preemptively notifies CT operators when scan parameters exceed user-defined dose thresholds. DoseWatch is an information technology application providing vendor-agnostic dose tracking and analysis for CT (and all other diagnostic x-ray modalities) SnapShot Pulse improves coronary CTA dose management. VolumeShuttle uses two acquisitions to increase coverage, decrease dose, and conserve on contrast administration. Color-Coding for Kids applies the Broselow-Luten Pediatric System to facilitate pediatric emergency care and reduce medical errors. FeatherLight achieves dose optimization through pediatric procedure-based protocols. Adventure Series scanners provide a child-friendly imaging environment promoting patient cooperation with resultant reduction in retakes and patient motion. Philips CT Dose Optimization Tools and Advanced Reconstruction Presentation Time: 11:45 ‘ 12:15 PM The first part of the talk will cover “Dose Reduction and Dose Optimization Technologies” present in Philips CT Scanners. The main Technologies to be presented include: DoseRight and tube current modulation (DoseRight, Z-DOM, 3D-DOM, DoseRight Cardiac) Special acquisition modes Beam filtration and beam shapers Eclipse collimator and ClearRay collimator NanoPanel detector DoseRight will cover automatic tube current selection that automatically adjusts the dose for the individual patient. The presentation will explore the modulation techniques currently employed in Philips CT scanners and will include the algorithmic concepts as well as illustrative examples. Modulation and current selection technologies to be covered include the Automatic Current Selection component of DoseRight, ZDOM longitudinal dose modulation, 3D-DOM (combination of longitudinal and rotational dose modulation), Cardiac Dose right (an ECG based dose modulation scheme), and the DoseRight Index (DRI) IQ index. The special acquisition modes covers acquisition techniques such as prospective gating that is designed to reduce exposure to the patient through the Cardiac Step and Shoot scan mode. This mode can substitute the much higher dose retrospective scan modes for certain types of cardiac imaging. The beam filtration and beam shaper portion will discuss the variety of filtration and beam shaping configurations available on Philips scanners. This topic includes the x-ray beam characteristics, tube filtration as well as dose compensator characteristics. The Eclipse collimator, ClearRay collimator and the NanoPanel detector portion will discuss additional technologies specific to wide coverage CT that address some of the unique challenges encountered and techniques employed to optimize image quality and optimize dose utilization. The Eclipse collimator reduces extraneous exposure by actively blocking the radiation tails at either end of helical scans that do not contribute to the image generation. The ClearRay collimator and the NanoPanel detector optimize the quality of the signal that reaches the detectors by addressing the increased scattered radiation present in wide coverage and the NanoPanel detector adds superior electronic noise characteristics valuable when imaging at a low dose level. The second part of the talk will present “Advanced Reconstruction Technologies” currently available on Philips CT Scanners. The talk will cover filtered back projection (FBP), iDose4 and Iterative Model Reconstruction (IMR). Each reconstruction method will include a discussion of the algorithm as well as similarities and differences between the algorithms. Examples illustrating the merits of each algorithm will be presented, and techniques and metrics to characterize the performance of each type of algorithm will be presented. The Filtered Back projection portion will discuss and provide a brief summary of relevant standard image reconstruction techniques in common use, and discuss the common tradeoffs when using the FBP algorithm. The iDose4 portion will present the algorithms used for iDose4 as well the different levels. The meaning of different levels of iDose4 available will be presented and quantified. Guidelines for selection iDose4 parameters based on the imaging need will be explained. The different image quality goals available with iDose4 and specifically how iDose4 enables noise reduction, spatial resolution improvement or both will be explained. The approaches to leveraging the benefits of iDose4 such as improved spatial resolution, decreased noise, and artifact prevention will be described and quantified; and measurements and metrics behind the improvements will be presented. The image quality benefits in specific imaging situations as well as how to best combine the technology with other dose reduction strategies to ensure the best image quality at a given dose level will be presented. Insight into the IMR algorithm as well as contrast to the iDose4 techniques and performance characteristics will be discussed. Metrics and techniques for characterizing this class of algorithm and IQ performance will be presented. The image quality benefits and the dose reduction capabilities of IMR will be explored. Illustrative examples of the noise reduction, spatial resolution improvement, and low contrast detectability improvements of the reconstruction method will be presented: clinical cases and phantom measurements demonstrating the benefits of IMR in the areas of low dose imaging, spatial resolution and low contrast resolution are discussed and the technical details behind the measurements will be presented compared to both iDose4 and traditional filtered back projection (FBP)« less

Automated construction of an intraoperative high-dose-rate treatment plan library for the Varian brachytherapy treatment planning system.

PubMed

Deufel, Christopher L; Furutani, Keith M; Dahl, Robert A; Haddock, Michael G

2016-01-01

The ability to create treatment plans for intraoperative high-dose-rate (IOHDR) brachytherapy is limited by lack of imaging and time constraints. An automated method for creation of a library of high-dose-rate brachytherapy plans that can be used with standard planar applicators in the intraoperative setting is highly desirable. Nonnegative least squares algebraic methods were used to identify dwell time values for flat, rectangular planar applicators. The planar applicators ranged in length and width from 2 cm to 25 cm. Plans were optimized to deliver an absorbed dose of 10 Gy to three different depths from the patient surface: 0 cm, 0.5 cm, and 1.0 cm. Software was written to calculate the optimized dwell times and insert dwell times and positions into a .XML plan template that can be imported into the Varian brachytherapy treatment planning system. The user may import the .XML template into the treatment planning system in the intraoperative setting to match the patient applicator size and prescribed treatment depth. A total of 1587 library plans were created for IOHDR brachytherapy. Median plan generation time was approximately 1 minute per plan. Plan dose was typically 100% ± 1% (mean, standard deviation) of the prescribed dose over the entire length and width of the applicator. Plan uniformity was best for prescription depths of 0 cm and 0.5 cm from the patient surface. An IOHDR plan library may be created using automated methods. Thousands of plan templates may be optimized and prepared in a few hours to accommodate different applicator sizes and treatment depths and reduce treatment planning time. The automated method also enforces dwell time symmetry for symmetrical applicator geometries, which simplifies quality assurance. Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

SU-F-J-16: Planar KV Imaging Dose Reduction Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gershkevitsh, E; Zolotuhhin, D

Purpose: IGRT has become an indispensable tool in modern radiotherapy with kV imaging used in many departments due to superior image quality and lower dose when compared to MV imaging. Many departments use manufacturer supplied protocols for imaging which are not always optimised between image quality and radiation dose (ALARA). Methods: Whole body phantom PBU-50 (Kyoto Kagaku ltd., Japan) for imaging in radiology has been imaged on Varian iX accelerator (Varian Medical Systems, USA) with OBI 1.5 system. Manufacturer’s default protocols were adapted by modifying kV and mAs values when imaging different anatomical regions of the phantom (head, thorax, abdomen,more » pelvis, extremities). Images with different settings were independently reviewed by two persons and their suitability for IGRT set-up correction protocols were evaluated. The suitable images with the lowest mAs were then selected. The entrance surface dose (ESD) for manufacturer’s default protocols and modified protocols were measured with RTI Black Piranha (RTI Group, Sweden) and compared. Image quality was also measured with kVQC phantom (Standard Imaging, USA) for different protocols. The modified protocols have been applied for clinical work. Results: For most cases optimized protocols reduced the ESD on average by a factor of 3(range 0.9–8.5). Further reduction in ESD has been observed by applying bow-tie filter designed for CBCT. The largest reduction in dose (12.2 times) was observed for Thorax lateral protocol. The dose was slightly increased (by 10%) for large pelvis AP protocol. Conclusion: Manufacturer’s default IGRT protocols could be optimised to reduce the ESD to the patient without losing the necessary image quality for patient set-up correction. For patient set-up with planar kV imaging the bony anatomy is mostly used and optimization should focus on this aspect. Therefore, the current approach with anthropomorphic phantom is more advantageous in optimization over standard kV quality control phantoms and SNR metrics.« less

Flucytosine Pharmacokinetics in a Critically Ill Patient Receiving Continuous Renal Replacement Therapy.

PubMed

Kunka, Megan E; Cady, Elizabeth A; Woo, Heejung C; Thompson Bastin, Melissa L

2015-01-01

Purpose. A case report evaluating flucytosine dosing in a critically ill patient receiving continuous renal replacement therapy. Summary. This case report outlines an 81-year-old male who was receiving continuous venovenous hemofiltration (CVVH) for acute renal failure and was being treated with flucytosine for the treatment of disseminated Cryptococcus neoformans infection. Due to patient specific factors, flucytosine was empirically dose adjusted approximately 50% lower than intermittent hemodialysis (iHD) recommendations and approximately 33% lower than CRRT recommendations. Peak and trough levels were obtained, which were supratherapeutic, and pharmacokinetic parameters were calculated. The patient experienced thrombocytopenia, likely due to elevated flucytosine levels, and flucytosine was ultimately discontinued. Conclusion. Despite conservative flucytosine dosing for a patient receiving CVVH, peak and trough serum flucytosine levels were supratherapeutic (120 μg/mL at 2 hours and 81 μg/mL at 11.5 hours), which increased drug-related adverse effects. The results indicate that this conservative dosing regimen utilizing the patient's actual body weight was too aggressive. This case report provides insight into flucytosine dosing in CVVH, a topic that has not been investigated previously. Further pharmacokinetic studies of flucytosine dosing in critically ill patients receiving CVVH are needed in order to optimize pharmacokinetic and pharmacodynamic parameters while avoiding toxic flucytosine exposure.

TH-CD-209-04: Fuzzy Robust Optimization in Intensity-Modulated Proton Therapy Planning to Account for Range and Patient Setup Uncertainties

DOE Office of Scientific and Technical Information (OSTI.GOV)

An, Y; Bues, M; Schild, S

Purpose: We propose to apply a robust optimization model based on fuzzy-logic constraints in the intensity-modulated proton therapy (IMPT) planning subject to range and patient setup uncertainties. The purpose is to ensure the plan robustness under uncertainty and obtain the best trade-off between tumor dose coverage and organ-at-risk(OAR) sparing. Methods: Two IMPT plans were generated for 3 head-and-neck cancer patients: one used the planning target volume(PTV) method; the other used the fuzzy robust optimization method. In the latter method, nine dose distributions were computed - the nominal one and one each for ±3mm setup uncertainties along three cardinal axes andmore » for ±3.5% range uncertainty. For tumors, these nine dose distributions were explicitly controlled by adding hard constraints with adjustable parameters. For OARs, fuzzy constraints that allow the dose to vary within a certain range were used so that the tumor dose distribution was guaranteed by minimum compromise of that of OARs. We rendered this model tractable by converting the fuzzy constraints to linear constraints. The plan quality was evaluated using dose-volume histogram(DVH) indices such as tumor dose coverage(D95%), homogeneity(D5%-D95%), plan robustness(DVH band at D95%), and OAR sparing like D1% of brain and D1% of brainstem. Results: Our model could yield clinically acceptable plans. The fuzzy-logic robust optimization method produced IMPT plans with comparable target dose coverage and homogeneity compared to the PTV method(unit: Gy[RBE]; average[min, max])(CTV D95%: 59 [52.7, 63.5] vs 53.5[46.4, 60.1], CTV D5% - D95%: 11.1[5.3, 18.6] vs 14.4[9.2, 21.5]). It also generated more robust plans(CTV DVH band at D95%: 3.8[1.2, 5.6] vs 11.5[6.2, 16.7]). The parameters of tumor constraints could be adjusted to control the tradeoff between tumor coverage and OAR sparing. Conclusion: The fuzzy-logic robust optimization generates superior IMPT with minimum compromise of OAR sparing. This research was supported by the National Cancer Institute Career Developmental Award K25CA168984, by the Fraternal Order of Eagles Cancer Research Fund Career Development Award, by The Lawrence W. and Marilyn W. Matteson Fund for Cancer Research, by Mayo Arizona State University Seed Grant, and by The Kemper Marley Foundation. eRA Person ID(s) for the Principal Investigator: 11017970 (Research Supported by National Institutes of Health)« less

SU-E-T-07: 4DCT Robust Optimization for Esophageal Cancer Using Intensity Modulated Proton Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liao, L; Department of Industrial Engineering, University of Houston, Houston, TX; Yu, J

2015-06-15

Purpose: To develop a 4DCT robust optimization method to reduce the dosimetric impact from respiratory motion in intensity modulated proton therapy (IMPT) for esophageal cancer. Methods: Four esophageal cancer patients were selected for this study. The different phases of CT from a set of 4DCT were incorporated into the worst-case dose distribution robust optimization algorithm. 4DCT robust treatment plans were designed and compared with the conventional non-robust plans. Result doses were calculated on the average and maximum inhale/exhale phases of 4DCT. Dose volume histogram (DVH) band graphic and ΔD95%, ΔD98%, ΔD5%, ΔD2% of CTV between different phases were used tomore » evaluate the robustness of the plans. Results: Compare to the IMPT plans optimized using conventional methods, the 4DCT robust IMPT plans can achieve the same quality in nominal cases, while yield a better robustness to breathing motion. The mean ΔD95%, ΔD98%, ΔD5% and ΔD2% of CTV are 6%, 3.2%, 0.9% and 1% for the robustly optimized plans vs. 16.2%, 11.8%, 1.6% and 3.3% from the conventional non-robust plans. Conclusion: A 4DCT robust optimization method was proposed for esophageal cancer using IMPT. We demonstrate that the 4DCT robust optimization can mitigate the dose deviation caused by the diaphragm motion.« less

Optimization of hybrid iterative reconstruction level in pediatric body CT.

PubMed

Karmazyn, Boaz; Liang, Yun; Ai, Huisi; Eckert, George J; Cohen, Mervyn D; Wanner, Matthew R; Jennings, S Gregory

2014-02-01

The objective of our study was to attempt to optimize the level of hybrid iterative reconstruction (HIR) in pediatric body CT. One hundred consecutive chest or abdominal CT examinations were selected. For each examination, six series were obtained: one filtered back projection (FBP) and five HIR series (iDose(4)) levels 2-6. Two pediatric radiologists, blinded to noise measurements, independently chose the optimal HIR level and then rated series quality. We measured CT number (mean in Hounsfield units) and noise (SD in Hounsfield units) changes by placing regions of interest in the liver, muscles, subcutaneous fat, and aorta. A mixed-model analysis-of-variance test was used to analyze correlation of noise reduction with the optimal HIR level compared with baseline FBP noise. One hundred CT examinations were performed of 88 patients (52 females and 36 males) with a mean age of 8.5 years (range, 19 days-18 years); 12 patients had both chest and abdominal CT studies. Radiologists agreed to within one level of HIR in 92 of 100 studies. The mean quality rating was significantly higher for HIR than FBP (3.6 vs 3.3, respectively; p < 0.01). HIR caused minimal (0-0.2%) change in CT numbers. Noise reduction varied among structures and patients. Liver noise reduction positively correlated with baseline noise when the optimal HIR level was used (p < 0.01). HIR levels were significantly correlated with body weight and effective diameter of the upper abdomen (p < 0.01). HIR, such as iDose(4), improves the quality of body CT scans of pediatric patients by decreasing noise; HIR level 3 or 4 is optimal for most studies. The optimal HIR level was less effective in reducing liver noise in children with lower baseline noise.

Modeling the economic and health consequences of managing chronic osteoarthritis pain with opioids in Germany: comparison of extended-release oxycodone and OROS hydromorphone.

PubMed

Ward, Alexandra; Bozkaya, Duygu; Fleischmann, Jochen; Dubois, Dominique; Sabatowski, Rainer; Caro, J Jaime

2007-10-01

The Osmotic controlled-Release Oral delivery System (OROS) hydromorphone ensures continuous release of hydromorphone over 24 hours. It is anticipated that this will facilitate optimal pain relief, improve quality of sleep and compliance. This simulation compared managing chronic osteoarthritis pain with once-daily OROS hydromorphone with an equianalgesic dose of extended-release (ER) oxycodone administered two or three times a day. This discrete event simulation follows patients for a year after initiating opioid treatment. Pairs of identical patients are created; one receives OROS hydromorphone the other ER oxycodone; undergo dose adjustments and after titration can be dissatisfied or satisfied, suffer adverse events, pain recurrence, or discontinue the opioid. Each is assigned an initial sleep problems score, and an improved score from a treatment dependent distribution at the end of titration; these are translated to a utility value. Utilities are assigned pre-treatment, updated until the patient reaches the optimal dose or is non-compliant or dissatisfied. The OROS hydromorphone and ER oxycodone doses are converted to equianalgesic morphine doses using the following ratios: hydromorphone to morphine ratio; 1:5, oxycodone to morphine ratio; 1:2. Sensitivity analyses explored uncertainty in the conversion ratios and other key parameters. Direct medical costs are in 2005 euros. Over 1 year on a mean daily morphine-equivalent dose of 90 mg, 14% were estimated to be dissatisfied with each opioid. OROS hydromorphone was predicted to yield 0.017 additional quality-adjusted life years (QALYs)/patient for a small additional annual cost (E141/patient), yielding an incremental cost-effectiveness ratio (ICER) of E8343/QALY gained. Changing the assumed conversion ratio for oxycodone:morphine to 1:1.5 led to lower net costs of E68 per patient, E3979/QALY, and for hydromorphone to 1:7.5 to savings. Based on these analyses, OROS hydromorphone is expected to yield health benefits at reasonable cost in Germany.

Using quality of life measures in a Phase I clinical trial of noni in patients with advanced cancer to select a Phase II dose.

PubMed

Issell, Brian F; Gotay, Carolyn C; Pagano, Ian; Franke, Adrian A

2009-01-01

ABSTRACT. The purpose of this study was to determine a maximum tolerated dose of noni in cancer patients and whether an optimal quality of life-sustaining dose could be identified as an alternative way to select a dose for subsequent Phase II efficacy trials. Dose levels started at two capsules twice daily (2 g), the suggested dose for the marketed product, and were escalated by 2 g daily in cohorts of at least five patients until a maximum tolerated dose was found. Patients completed subscales of the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 quality of life (physical functioning, pain, and fatigue) the brief fatigue inventory (BFI), questionnaires at baseline and at approximately 4-week intervals. Blood and urine were collected at baseline and at approximately 4-week intervals for measurement of scopoletin. Fifty-one patients were enrolled at seven dose levels. The maximum tolerated dose was six capsules four times daily (12 g). Although no dose-limiting toxicity was found, seven of eight patients at the next level (14 g), withdrew due to the challenges of ingesting so many capsules. There were dose-related differences in self-reported physical functioning and pain and fatigue control. Overall, patients taking three or four capsules four times daily experienced better outcomes than patients taking lower or higher doses. Blood and urinary scopoletin concentrations related to noni dose. We concluded that it is feasible to use quality of life measures to select a Phase II dose. Three or four capsules four times daily (6-8 g) is recommended when controlling fatigue, pain, and maintaining physical function are the efficacies of interest. Scopoletin, a bioactive component of noni fruit extract, is measurable in blood and urine following noni ingestion and can be used to study the pharmacokinetics of noni in cancer patients.

Volume-of-interest reconstruction from severely truncated data in dental cone-beam CT

NASA Astrophysics Data System (ADS)

Zhang, Zheng; Kusnoto, Budi; Han, Xiao; Sidky, E. Y.; Pan, Xiaochuan

2015-03-01

As cone-beam computed tomography (CBCT) has gained popularity rapidly in dental imaging applications in the past two decades, radiation dose in CBCT imaging remains a potential, health concern to the patients. It is a common practice in dental CBCT imaging that only a small volume of interest (VOI) containing the teeth of interest is illuminated, thus substantially lowering imaging radiation dose. However, this would yield data with severe truncations along both transverse and longitudinal directions. Although images within the VOI reconstructed from truncated data can be of some practical utility, they often are compromised significantly by truncation artifacts. In this work, we investigate optimization-based reconstruction algorithms for VOI image reconstruction from CBCT data of dental patients containing severe truncations. In an attempt to further reduce imaging dose, we also investigate optimization-based image reconstruction from severely truncated data collected at projection views substantially fewer than those used in clinical dental applications. Results of our study show that appropriately designed optimization-based reconstruction can yield VOI images with reduced truncation artifacts, and that, when reconstructing from only one half, or even one quarter, of clinical data, it can also produce VOI images comparable to that of clinical images.

The optimal dose of dexmedetomidine added to an sufentanil-based analgesic regimen for postoperative pain control in spine surgery

PubMed Central

Dong, Chun-Shan; Lu, Yao; Zhang, Jun; Sun, Peng; Yu, Jun-Ma; Wu, Chao; Lu, Qiang

2016-01-01

Abstract Postoperative spinal patients remain a challenge for provision of postoperative analgesia. Patient-controlled intravenous analgesia (PCIA) is a major method in reducing the severe pain after the surgery in our institution, but some adverse effects prevent the use of adequate dosage opioids. This study was determined using the probit analysis to investigate the optimal dose of dexmedetomidine (DEX) infusion for postoperative analgesia combined with sufentanil (SUF) in spine surgery. The dose of DEX needed to produce satisfactory analgesia conditions following combination of 3.0 μg/kg SUF in PCIA pump, which was diluted to 250 mL with a 4 mL/h as background infusion. Patients were recruited with age 35 to 65 years. The satisfactory criteria of postoperative analgesia were determined with a average satisfaction level of pain control, sedation, self-satisfaction, and adverse effects, among others. The dose of DEX was determined using the modified Dixon's up-and-down method (0.5 μg/kg as a step size). The first patient was test at 3.0 μg/kg DEX. The patient was assessed at 6, 12, 36 hours, and termination of PCIA following the continuous infusion of DEX-SUF mixture in PCIA after surgery. Twenty-five patients were enrolled by predetermined criteria. The optimal dose of DEX required for satisfactory analgesic was 4.33 (SD, 0.38) μg/kg combined with 3.0 μg/kg SUF via a PCIA volume of 250 mL by background infusion of 4 mL/h. Using probit analysis, the ED50 of DEX was 4.12 μg/kg (95% confidence limits 3.74–4.52 μg/kg) for satisfactory postoperative analgesic in spine surgery, the ED95 of DEX was 4.85 μg/kg (95% confidence limits 4.48–7.13 μg/kg). There was no report of somnolence or respiratory depression, relevant bradycardia or hypotension, or over sedation in this study. The optimal dose of DEX was 4.33 (0.38) μg/kg−1 combined with 3.0 μg/kg−1 SUF diluted to 250 mL with a background infusion of 4 mL/h for satisfactory analgesic after spine surgery. From probit analysis, ED50 and ED95 of DEX were 4.12 μg/kg (95% confidence limits 3.74–4.52 μg/kg) and 4.85 μg.kg−1 (95% confidence limits 4.48–7.13 μg/kg), respectively. PMID:27684802

Fully automated treatment planning for head and neck radiotherapy using a voxel-based dose prediction and dose mimicking method

NASA Astrophysics Data System (ADS)

McIntosh, Chris; Welch, Mattea; McNiven, Andrea; Jaffray, David A.; Purdie, Thomas G.

2017-08-01

Recent works in automated radiotherapy treatment planning have used machine learning based on historical treatment plans to infer the spatial dose distribution for a novel patient directly from the planning image. We present a probabilistic, atlas-based approach which predicts the dose for novel patients using a set of automatically selected most similar patients (atlases). The output is a spatial dose objective, which specifies the desired dose-per-voxel, and therefore replaces the need to specify and tune dose-volume objectives. Voxel-based dose mimicking optimization then converts the predicted dose distribution to a complete treatment plan with dose calculation using a collapsed cone convolution dose engine. In this study, we investigated automated planning for right-sided oropharaynx head and neck patients treated with IMRT and VMAT. We compare four versions of our dose prediction pipeline using a database of 54 training and 12 independent testing patients by evaluating 14 clinical dose evaluation criteria. Our preliminary results are promising and demonstrate that automated methods can generate comparable dose distributions to clinical. Overall, automated plans achieved an average of 0.6% higher dose for target coverage evaluation criteria, and 2.4% lower dose at the organs at risk criteria levels evaluated compared with clinical. There was no statistically significant difference detected in high-dose conformity between automated and clinical plans as measured by the conformation number. Automated plans achieved nine more unique criteria than clinical across the 12 patients tested and automated plans scored a significantly higher dose at the evaluation limit for two high-risk target coverage criteria and a significantly lower dose in one critical organ maximum dose. The novel dose prediction method with dose mimicking can generate complete treatment plans in 12-13 min without user interaction. It is a promising approach for fully automated treatment planning and can be readily applied to different treatment sites and modalities.

Fully automated treatment planning for head and neck radiotherapy using a voxel-based dose prediction and dose mimicking method.

PubMed

McIntosh, Chris; Welch, Mattea; McNiven, Andrea; Jaffray, David A; Purdie, Thomas G

2017-07-06

Recent works in automated radiotherapy treatment planning have used machine learning based on historical treatment plans to infer the spatial dose distribution for a novel patient directly from the planning image. We present a probabilistic, atlas-based approach which predicts the dose for novel patients using a set of automatically selected most similar patients (atlases). The output is a spatial dose objective, which specifies the desired dose-per-voxel, and therefore replaces the need to specify and tune dose-volume objectives. Voxel-based dose mimicking optimization then converts the predicted dose distribution to a complete treatment plan with dose calculation using a collapsed cone convolution dose engine. In this study, we investigated automated planning for right-sided oropharaynx head and neck patients treated with IMRT and VMAT. We compare four versions of our dose prediction pipeline using a database of 54 training and 12 independent testing patients by evaluating 14 clinical dose evaluation criteria. Our preliminary results are promising and demonstrate that automated methods can generate comparable dose distributions to clinical. Overall, automated plans achieved an average of 0.6% higher dose for target coverage evaluation criteria, and 2.4% lower dose at the organs at risk criteria levels evaluated compared with clinical. There was no statistically significant difference detected in high-dose conformity between automated and clinical plans as measured by the conformation number. Automated plans achieved nine more unique criteria than clinical across the 12 patients tested and automated plans scored a significantly higher dose at the evaluation limit for two high-risk target coverage criteria and a significantly lower dose in one critical organ maximum dose. The novel dose prediction method with dose mimicking can generate complete treatment plans in 12-13 min without user interaction. It is a promising approach for fully automated treatment planning and can be readily applied to different treatment sites and modalities.

Patient-specific dosimetric endpoints based treatment plan quality control in radiotherapy.

PubMed

Song, Ting; Staub, David; Chen, Mingli; Lu, Weiguo; Tian, Zhen; Jia, Xun; Li, Yongbao; Zhou, Linghong; Jiang, Steve B; Gu, Xuejun

2015-11-07

In intensity modulated radiotherapy (IMRT), the optimal plan for each patient is specific due to unique patient anatomy. To achieve such a plan, patient-specific dosimetric goals reflecting each patient's unique anatomy should be defined and adopted in the treatment planning procedure for plan quality control. This study is to develop such a personalized treatment plan quality control tool by predicting patient-specific dosimetric endpoints (DEs). The incorporation of patient specific DEs is realized by a multi-OAR geometry-dosimetry model, capable of predicting optimal DEs based on the individual patient's geometry. The overall quality of a treatment plan is then judged with a numerical treatment plan quality indicator and characterized as optimal or suboptimal. Taking advantage of clinically available prostate volumetric modulated arc therapy (VMAT) treatment plans, we built and evaluated our proposed plan quality control tool. Using our developed tool, six of twenty evaluated plans were identified as sub-optimal plans. After plan re-optimization, these suboptimal plans achieved better OAR dose sparing without sacrificing the PTV coverage, and the dosimetric endpoints of the re-optimized plans agreed well with the model predicted values, which validate the predictability of the proposed tool. In conclusion, the developed tool is able to accurately predict optimally achievable DEs of multiple OARs, identify suboptimal plans, and guide plan optimization. It is a useful tool for achieving patient-specific treatment plan quality control.

Breast Radiotherapy with Mixed Energy Photons; a Model for Optimal Beam Weighting.

PubMed

Birgani, Mohammadjavad Tahmasebi; Fatahiasl, Jafar; Hosseini, Seyed Mohammad; Bagheri, Ali; Behrooz, Mohammad Ali; Zabiehzadeh, Mansour; Meskani, Reza; Gomari, Maryam Talaei

2015-01-01

Utilization of high energy photons (>10 MV) with an optimal weight using a mixed energy technique is a practical way to generate a homogenous dose distribution while maintaining adequate target coverage in intact breast radiotherapy. This study represents a model for estimation of this optimal weight for day to day clinical usage. For this purpose, treatment planning computed tomography scans of thirty-three consecutive early stage breast cancer patients following breast conservation surgery were analyzed. After delineation of the breast clinical target volume (CTV) and placing opposed wedge paired isocenteric tangential portals, dosimeteric calculations were conducted and dose volume histograms (DVHs) were generated, first with pure 6 MV photons and then these calculations were repeated ten times with incorporating 18 MV photons (ten percent increase in weight per step) in each individual patient. For each calculation two indexes including maximum dose in the breast CTV (Dmax) and the volume of CTV which covered with 95% Isodose line (VCTV, 95%IDL) were measured according to the DVH data and then normalized values were plotted in a graph. The optimal weight of 18 MV photons was defined as the intersection point of Dmax and VCTV, 95%IDL graphs. For creating a model to predict this optimal weight multiple linear regression analysis was used based on some of the breast and tangential field parameters. The best fitting model for prediction of 18 MV photons optimal weight in breast radiotherapy using mixed energy technique, incorporated chest wall separation plus central lung distance (Adjusted R2=0.776). In conclusion, this study represents a model for the estimation of optimal beam weighting in breast radiotherapy using mixed photon energy technique for routine day to day clinical usage.

SU-F-T-191: 4D Dose Reconstruction of Intensity Modulated Proton Therapy (IMPT) Based On Breathing Probability Density Function (PDF) From 4D Cone Beam Projection Images: A Study for Lung Treatment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhou, J; Ding, X; Liang, J

2016-06-15

Purpose: With energy repainting in lung IMPT, the dose delivered is approximate to the convolution of dose in each phase with corresponding breathing PDF. This study is to compute breathing PDF weighted 4D dose in lung IMPT treatment and compare to its initial robust plan. Methods: Six lung patients were evaluated in this study. Amsterdam shroud image were generated from pre-treatment 4D cone-beam projections. Diaphragm motion curve was extract from the shroud image and the breathing PDF was generated. Each patient was planned to 60 Gy (12GyX5). In initial plans, ITV density on average CT was overridden with its maximummore » value for planning, using two IMPT beams with robust optimization (5mm uncertainty in patient position and 3.5% range uncertainty). The plan was applied to all 4D CT phases. The dose in each phase was deformed to a reference phase. 4D dose is reconstructed by summing all these doses based on corresponding weighting from the PDF. Plan parameters, including maximum dose (Dmax), ITV V100, homogeneity index (HI=D2/D98), R50 (50%IDL/ITV), and the lung-GTV’s V12.5 and V5 were compared between the reconstructed 4D dose to initial plans. Results: The Dmax is significantly less dose in the reconstructed 4D dose, 68.12±3.5Gy, vs. 70.1±4.3Gy in the initial plans (p=0.015). No significant difference is found for the ITV V100, HI, and R50, 92.2%±15.4% vs. 96.3%±2.5% (p=0.565), 1.033±0.016 vs. 1.038±0.017 (p=0.548), 19.2±12.1 vs. 18.1±11.6 (p=0.265), for the 4D dose and initial plans, respectively. The lung-GTV V12.5 and V5 are significantly high in the 4D dose, 13.9%±4.8% vs. 13.0%±4.6% (p=0.021) and 17.6%±5.4% vs. 16.9%±5.2% (p=0.011), respectively. Conclusion: 4D dose reconstruction based on phase PDF can be used to evaluate the dose received by the patient. A robust optimization based on the phase PDF may even further improve patient care.« less

ESTIMATION OF ADULT PATIENT DOSES FOR CHEST X-RAY EXAMINATIONS AND COMPARISON WITH DIAGNOSTIC REFERENCE LEVELS (DRLs).

PubMed

Bas Mor, H; Altinsoy, N; Söyler, I

2018-05-08

The aim of this study was to evaluate the radiation doses to patient during chest (posterior anterior/and lateral) examinations. The study was performed in three public hospitals of İstanbul province with a total of 300 adult patients. Entrance surface dose (ESD) measurements were conducted on computed radiography, digital radiography and screen film system. ESD was estimated by using International Atomic Energy Agency (IAEA) model and Davies model which are the common indirect models. Results were compared with diagnostic reference levels from the European Commission, IAEA and National Radiological Protection Board. Although the results are compatible with the international diagnostic reference levels, they present variations between the hospitals. Dose variations for the same type of X-ray examination support the idea that further optimization is possible.

TH-E-BRF-01: Exploiting Tumor Shrinkage in Split-Course Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Unkelbach, J; Craft, D; Hong, T

2014-06-15

Purpose: In split-course radiotherapy, a patient is treated in several stages separated by weeks or months. This regimen has been motivated by radiobiological considerations. However, using modern image-guidance, it also provides an approach to reduce normal tissue dose by exploiting tumor shrinkage. In this work, we consider the optimal design of split-course treatments, motivated by the clinical management of large liver tumors for which normal liver dose constraints prohibit the administration of an ablative radiation dose in a single treatment. Methods: We introduce a dynamic tumor model that incorporates three factors: radiation induced cell kill, tumor shrinkage, and tumor cellmore » repopulation. The design of splitcourse radiotherapy is formulated as a mathematical optimization problem in which the total dose to the liver is minimized, subject to delivering the prescribed dose to the tumor. Based on the model, we gain insight into the optimal administration of radiation over time, i.e. the optimal treatment gaps and dose levels. Results: We analyze treatments consisting of two stages in detail. The analysis confirms the intuition that the second stage should be delivered just before the tumor size reaches a minimum and repopulation overcompensates shrinking. Furthermore, it was found that, for a large range of model parameters, approximately one third of the dose should be delivered in the first stage. The projected benefit of split-course treatments in terms of liver sparing depends on model assumptions. However, the model predicts large liver dose reductions by more than a factor of two for plausible model parameters. Conclusion: The analysis of the tumor model suggests that substantial reduction in normal tissue dose can be achieved by exploiting tumor shrinkage via an optimal design of multi-stage treatments. This suggests taking a fresh look at split-course radiotherapy for selected disease sites where substantial tumor regression translates into reduced target volumes.« less

Transferring Patients From Methadone to Buprenorphine: The Feasibility and Evaluation of Practice Guidelines.

PubMed

Lintzeris, Nicholas; Monds, Lauren A; Rivas, Consuelo; Leung, Stefanie; Dunlop, Adrian; Newcombe, David; Walters, Carina; Galea, Susanna; White, Nancy; Montebello, Mark; Demirkol, Apo; Swanson, Nicola; Ali, Robert

Transfer from methadone to buprenorphine is problematic for many opioid-dependent patients, with limited documented evidence or practical clinical guidance, particularly for the range of methadone doses routinely prescribed for most patients (>50 mg). This study aimed to implement and evaluate recent national Australian guidelines for transferring patients from methadone to buprenorphine. A multisite prospective cohort study. Participants were patients who transferred from methadone to buprenorphine-naloxone at 1 of 4 specialist addiction centers in Australia and New Zealand. Clinicians were trained in the guidelines, and medical records were reviewed to examine process (eg, transfer setting, doses, and guideline adherence) and safety (precipitated withdrawal) measures. Participants completed research interviews before and after transfer-assessing changes in substance use, health outcomes, and side effects. In all, 33 participants underwent transfer, 9 from low methadone doses (<30 mg), 9 from medium doses (30-50 mg), and 15 from high doses (>50 mg). The majority of high-dose transfers occurred in inpatient settings. There was reasonable guideline adherence, and no complications identified in the low and medium-dose transfers. Three high-dose transfers (20%) experienced precipitated withdrawal, and 7/33 participants (21%) returned to methadone within 1 week of attempted transfer. Transfer is feasible in outpatient settings for those transferring from methadone doses below 50 mg; however, inpatient settings and specialist supervision is recommended for higher-dose transfers. The Australian clinical guidelines appear safe and feasible, although further research is required to optimize high-dose transfer procedures.

Evidence for the use PET for radiation therapy planning in patients with cervical cancer: a systematic review.

PubMed

Salem, A; Salem, A F; Al-Ibraheem, A; Lataifeh, I; Almousa, A; Jaradat, I

2011-01-01

In recent years, the role of positron emission tomography (PET) in the staging and management of gynecological cancers has been increasing. The aim of this study was to systematically review the role of PET in radiotherapy planning and brachytherapy treatment optimization in patients with cervical cancer. Systematic literature review. Systematic review of relevant literature addressing the utilization of PET and/or PET-computed tomography (CT) in external-beam radiotherapy planning and brachytherapy treatment optimization. We performed an extensive PubMed database search on 20 April 2011. Nineteen studies, including 759 patients, formed the basis of this systematic review. PET/ PET-CT is the most sensitive imaging modality for detecting nodal metastases in patients with cervical cancer and has been shown to impact external-beam radiotherapy planning by modifying the treatment field and customizing the radiation dose. This particularly applies to detection of previously uncovered para-aortic and inguinal nodal metastases. Furthermore, PET/ PET-CT guided intensity-modulated radiation therapy (IMRT) allows delivery of higher doses of radiation to the primary tumor, if brachytherapy is unsuitable, and to grossly involved nodal disease while minimizing treatment-related toxicity. PET/ PET-CT based brachytherapy optimization allows improved tumor-volume dose distribution and detailed 3D dosimetric evaluation of risk organs. Sequential PET/ PET-CT imaging performed during the course of brachytherapy form the basis of “adaptive” brachytherapy in cervical cancer. This review demonstrates the effectiveness of pretreatment PET/ PET-CT in cervical cancer patients treated by radiotherapy. Further prospective studies are required to define the group of patients who would benefit the most from this procedure.

Implementation of protocolized tight control and biological dose optimization in daily clinical practice: results of a pilot study.

PubMed

Lesuis, N; Verhoef, L M; Nieboer, L M; Bruyn, G A; Baudoin, P; van Vollenhoven, R F; Hulscher, Mejl; van den Hoogen, Fhj; den Broeder, A A

2017-03-01

To assess the effects of education, guideline development, and individualized treatment advice on rheumatologist adherence to tight control-based treatment and biological dose optimization in rheumatoid arthritis (RA), psoriatic arthritis (PsA), and spondyloarthropathy (SpA) patients. This pilot study, among two rheumatologists and two specialized nurses in a general hospital, combined education, feedback, local guideline development, and individualized treatment advice. Outcomes (baseline and 1 year post-intervention) were the percentage of patients with a Disease Activity Score in 28 joints (DAS28) or Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) measured during the visit, mean DAS28/BASDAI, and the percentage of patients using a reduced biological dose. DAS28 outcomes only applied to RA and PsA patients, BASDAI outcomes only applied to SpA patients whereas outcomes on biological dose applied to all patients. A total of 232 patients (67% RA, 15% PsA, 18% SpA; 58% female, mean age 56 ± 15 years) were included in the study. The percentage of DAS28 and BASDAI measurements performed increased after the intervention [DAS28 15-51%, odds ratio (OR) 3.3, 95% confidence interval (CI) 2.1-5.5; BASDAI 23-50%, OR 2.2, 95% CI 1.0-5.5], with mean DAS28 and BASDAI scores remaining similar (DAS28: mean difference 0.1, 95% CI -0.3 to 0.5; BASDAI: mean difference 0.03, 95% CI -1.8 to 1.9). Use of a reduced biological dose increased from 10% to 61% (OR 3.9, 95% CI 2.4-6.5). A multicomponent intervention strategy aimed at rheumatologists can lead to improved adherence to tight control-based treatment and a reduction in the use of biologicals in RA, SpA, and PsA patients.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Unkelbach, J; Perko, Z; Wolfgang, J

Purpose: Stereotactic body radiotherapy (SBRT) has become an established treatment option for liver cancer. For patients with large tumors, the prescription dose is often limited by constraints on the mean liver dose, leading to tumor recurrence. In this work, we demonstrate that spatiotemporal fractionation schemes, ie delivering distinct dose distributions in different fractions, may allow for a 10% increase in biologically effective dose (BED) in the tumor compared to current practice where each fraction delivers the same dose distribution. Methods: We consider rotation therapy delivered with x-ray beams. Treatment plan optimization is performed using objective functions evaluated for the cumulativemore » BED delivered at the end of treatment. This allows for simultaneously optimizing multiple distinct treatment plans for different fractions. Results: The treatment that optimally exploits fractionation effects is designed such that each fraction delivers a similar dose bath to the uninvolved liver while delivering high single fraction doses to complementary parts of the target volume. Thereby, partial hypofractionation in the tumor is achieved along with near uniform fractionation in the surrounding liver - leading to an improvement in the therapeutic ratio. The benefit of such spatiotemporal fractionation schemes depends on tumor geometry and location as well as the number of fractions. For 5-fraction treatments (allowing for 5 distinct dose distributions) an improvement in the order of 10% is observed. Conclusion: Delivering distinct dose distributions in different fractions, purely motivated by fractionation effects rather than geometric changes, may improve the therapeutic ratio. For treatment sites where the prescriptions dose is limited by mean dose constraints in the surrounding organ, such as liver cancer, this approach may facilitate biological dose escalation and improved cure rates.« less

Combined Inter- and Intrafractional Plan Adaptation Using Fraction Partitioning in Magnetic Resonance-guided Radiotherapy Delivery.

PubMed

Lagerwaard, Frank; Bohoudi, Omar; Tetar, Shyama; Admiraal, Marjan A; Rosario, Tezontl S; Bruynzeel, Anna

2018-04-05

Magnetic resonance-guided radiation therapy (MRgRT) not only allows for superior soft-tissue setup and online MR-guidance during delivery but also for inter-fractional plan re-optimization or adaptation. This plan adaptation involves repeat MR imaging, organs at risk (OARs) re-contouring, plan prediction (i.e., recalculating the baseline plan on the anatomy of that moment), plan re-optimization, and plan quality assurance. In contrast, intrafractional plan adaptation cannot be simply performed by pausing delivery at any given moment, adjusting contours, and re-optimization because of the complex and composite nature of deformable dose accumulation. To overcome this limitation, we applied a practical workaround by partitioning treatment fractions, each with half the original fraction dose. In between successive deliveries, the patient remained in the treatment position and all steps of the initial plan adaptation were repeated. Thus, this second re-optimization served as an intrafractional plan adaptation at 50% of the total delivery. The practical feasibility of this partitioning approach was evaluated in a patient treated with MRgRT for locally advanced pancreatic cancer (LAPC). MRgRT was delivered in 40Gy in 10 fractions, with two fractions scheduled successively on each treatment day. The contoured gross tumor volume (GTV) was expanded by 3 mm, excluding parts of the OARs within this expansion to derive the planning target volume for daily re-optimization (PTV OPT ). The baseline GTVV 95%  achieved in this patient was 80.0% to adhere to the high-dose constraints for the duodenum, stomach, and bowel (V 33 Gy <1 cc and V 36 Gy <0.1 cc). Treatment was performed on the MRIdian (ViewRay Inc, Mountain View, USA) using video-assisted breath-hold in shallow inspiration. The dual plan adaptation resulted, for each partitioned fraction, in the generation of Plan PREDICTED1 , Plan RE-OPTIMIZED1  (inter-fractional adaptation), Plan PREDICTED2 , and Plan RE-OPTIMIZED2  (intrafractional adaptation). An offline analysis was performed to evaluate the benefit of inter-fractional versus intrafractional plan adaptation with respect to GTV coverage and high-dose OARs sparing for all five partitioned fractions. Interfractional changes in adjacent OARs were substantially larger than intrafractional changes. Mean GTV V 95% was 76.8 ± 1.8% (Plan PREDICTED1 ), 83.4 ± 5.7% (Plan RE-OPTIMIZED1 ), 82.5 ± 4.3% (Plan PREDICTED2 ),and 84.4 ± 4.4% (Plan RE-OPTIMIZED2 ). Both plan re-optimizations appeared important for correcting the inappropriately high duodenal V 33 Gy values of 3.6 cc (Plan PREDICTED1 ) and 3.9 cc (Plan PREDICTED2 ) to 0.2 cc for both re-optimizations. To a smaller extent, this improvement was also observed for V 25 Gy values. For the stomach, bowel, and all other OARs, high and intermediate doses were well below preset constraints, even without re-optimization. The mean delivery time of each daily treatment was 90 minutes. This study presents the clinical application of combined inter-fractional and intrafractional plan adaptation during MRgRT for LAPC using fraction partitioning with successive re-optimization. Whereas, in this study, interfractional plan adaptation appeared to benefit both GTV coverage and OARs sparing, intrafractional adaptation was particularly useful for high-dose OARs sparing. Although all necessary steps lead to a prolonged treatment duration, this may be applied in selected cases where high doses to adjacent OARs are regarded as critical.

Combined Inter- and Intrafractional Plan Adaptation Using Fraction Partitioning in Magnetic Resonance-guided Radiotherapy Delivery

PubMed Central

Bohoudi, Omar; Tetar, Shyama; Admiraal, Marjan A; Rosario, Tezontl S; Bruynzeel, Anna

2018-01-01

Magnetic resonance-guided radiation therapy (MRgRT) not only allows for superior soft-tissue setup and online MR-guidance during delivery but also for inter-fractional plan re-optimization or adaptation. This plan adaptation involves repeat MR imaging, organs at risk (OARs) re-contouring, plan prediction (i.e., recalculating the baseline plan on the anatomy of that moment), plan re-optimization, and plan quality assurance. In contrast, intrafractional plan adaptation cannot be simply performed by pausing delivery at any given moment, adjusting contours, and re-optimization because of the complex and composite nature of deformable dose accumulation. To overcome this limitation, we applied a practical workaround by partitioning treatment fractions, each with half the original fraction dose. In between successive deliveries, the patient remained in the treatment position and all steps of the initial plan adaptation were repeated. Thus, this second re-optimization served as an intrafractional plan adaptation at 50% of the total delivery. The practical feasibility of this partitioning approach was evaluated in a patient treated with MRgRT for locally advanced pancreatic cancer (LAPC). MRgRT was delivered in 40Gy in 10 fractions, with two fractions scheduled successively on each treatment day. The contoured gross tumor volume (GTV) was expanded by 3 mm, excluding parts of the OARs within this expansion to derive the planning target volume for daily re-optimization (PTVOPT). The baseline GTVV95% achieved in this patient was 80.0% to adhere to the high-dose constraints for the duodenum, stomach, and bowel (V33 Gy <1 cc and V36 Gy <0.1 cc). Treatment was performed on the MRIdian (ViewRay Inc, Mountain View, USA) using video-assisted breath-hold in shallow inspiration. The dual plan adaptation resulted, for each partitioned fraction, in the generation of PlanPREDICTED1, PlanRE-OPTIMIZED1 (inter-fractional adaptation), PlanPREDICTED2, and PlanRE-OPTIMIZED2 (intrafractional adaptation). An offline analysis was performed to evaluate the benefit of inter-fractional versus intrafractional plan adaptation with respect to GTV coverage and high-dose OARs sparing for all five partitioned fractions. Interfractional changes in adjacent OARs were substantially larger than intrafractional changes. Mean GTV V95% was 76.8 ± 1.8% (PlanPREDICTED1), 83.4 ± 5.7% (PlanRE-OPTIMIZED1), 82.5 ± 4.3% (PlanPREDICTED2),and 84.4 ± 4.4% (PlanRE-OPTIMIZED2). Both plan re-optimizations appeared important for correcting the inappropriately high duodenal V33 Gy values of 3.6 cc (PlanPREDICTED1) and 3.9 cc (PlanPREDICTED2) to 0.2 cc for both re-optimizations. To a smaller extent, this improvement was also observed for V25 Gy values. For the stomach, bowel, and all other OARs, high and intermediate doses were well below preset constraints, even without re-optimization. The mean delivery time of each daily treatment was 90 minutes. This study presents the clinical application of combined inter-fractional and intrafractional plan adaptation during MRgRT for LAPC using fraction partitioning with successive re-optimization. Whereas, in this study, interfractional plan adaptation appeared to benefit both GTV coverage and OARs sparing, intrafractional adaptation was particularly useful for high-dose OARs sparing. Although all necessary steps lead to a prolonged treatment duration, this may be applied in selected cases where high doses to adjacent OARs are regarded as critical. PMID:29876156

Study on the quality assurance of diagnostic X-ray machines and assessment of the absorbed dose to patients

NASA Astrophysics Data System (ADS)

Hassan, G. M.; Rabie, N.; Mustafa, K. A.; Abdel-Khalik, S. S.

2012-09-01

Radiation exposure and image quality in X-ray diagnostic radiology provide a clear understanding of the relationship between the radiation dose delivered to a patient and image quality in optimizing medical diagnostic radiology. Because a certain amount of radiation is unavoidably delivered to patients, this should be as low as reasonably achievable. Several X-ray diagnostic machines were used at different medical diagnostic centers in Egypt for studying the beam quality and the dose delivered to the patient. This article studies the factors affecting the beam quality, such as the kilo-volt peak (kVp), exposure time (mSc), tube current (mAs) and the absorbed dose in (μGy) for different examinations. The maximum absorbed dose measured per mAs was 594±239 and 12.5±3.7 μGy for the abdomen and the chest, respectively, while the absorbed dose at the elbow was 18±6 μGy, which was the minimum dose recorded. The compound and expanded uncertainties accompanying these measurements were 4±0.35% and 8±0.7%, respectively. The measurements were done through quality control tests as acceptance procedures.

Rectal artemisinins for malaria: a review of efficacy and safety from individual patient data in clinical studies

PubMed Central

Gomes, Melba; Ribeiro, Isabela; Warsame, Marian; Karunajeewa, Harin; Petzold, Max

2008-01-01

Background Rectal administration of artemisinin derivatives has potential for early treatment for severe malaria in remote settings where injectable antimalarial therapy may not be feasible. Preparations available include artesunate, artemisinin, artemether and dihydroartemisinin. However each may have different pharmacokinetic properties and more information is needed to determine optimal dose and comparative efficacy with each another and with conventional parenteral treatments for severe malaria. Methods Individual patient data from 1167 patients in 15 clinical trials of rectal artemisinin derivative therapy (artesunate, artemisinin and artemether) were pooled in order to compare the rapidity of clearance of Plasmodium falciparum parasitaemia and the incidence of reported adverse events with each treatment. Data from patients who received comparator treatment (parenteral artemisinin derivative or quinine) were also included. Primary endpoints included percentage reductions in parasitaemia at 12 and 24 hours. A parasite reduction of >90% at 24 hours was defined as parasitological success. Results Artemisinin and artesunate treatment cleared parasites more rapidly than parenteral quinine during the first 24 hours of treatment. A single higher dose of rectal artesunate treatment was five times more likely to achieve >90% parasite reductions at 24 hours than were multiple lower doses of rectal artesunate, or a single lower dose administration of rectal artemether. Conclusion Artemisinin and artesunate suppositories rapidly eliminate parasites and appear to be safe. There are less data on artemether and dihydroartemisinin suppositories. The more rapid parasite clearance of single high-dose regimens suggests that achieving immediate high drug concentrations may be the optimal strategy. PMID:18373841

SU-F-T-35: Optimization of Bladder and Rectal Doses Using a Multi-Lumen Intracavitary Applicator for Gynecological Brachytherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Laoui, S; Dietrich, S; Sehgal, V

2016-06-15

Purpose: Radiation dose delivery for endometrial cancer using HDR techniques is limited by dose to bladder and rectum. A dosimetric study was performed using Varian Capri vaginal brachytherapy applicator to determine the optimal channel configuration which minimizes dose to bladder and rectum, while providing good target coverage. Methods: A total of 17 patients, 63 plans clinically delivered, and 252 simulated plans using Varian BrachyVision planning system were generated to investigate optimal channel configuration which results in minimum dose to bladder and rectum while providing adequate target coverage. The Capri applicator consists of 13 lumens arranged in two concentric rings, onemore » central lumen and six lumens per ring. Manual dose shaping is invariably required to lower the dose to critical organs. Three-dimensional plans were simulated for 4 channel arrangements, all 13 channels, channel 12 o’clock (close to bladder) and 6 o’clock (close to rectum) deactivated, central channel deactivated, and central channel in addition to 12 o’clock and 6 o’clock deactivated. A relationship between V100, the volume that receives the prescribed dose, and the amount of curie-seconds required to deliver it, was established. Results: Using all 13 channels results in maximum dose to bladder and rectum. Deactivating central channel in addition to 12 o’clock and 6 o’clock resulted in minimizing bladder and rectum doses but compromised target coverage. The relationship between V100, the volume that receives the prescribed dose, and the curie seconds was found to be linear. Conclusion: Deactivating channels 12 o’clock and 6 o’clock was shown to be the optimal configuration leading to minimum dose to bladder and rectum without compromising target coverage. The linear relationship between V100 and the curie- seconds can be used as a verification parameter.« less

A phase I, pharmacokinetic and pharmacodynamic study on vorinostat in combination with 5-fluorouracil, leucovorin, and oxaliplatin in patients with refractory colorectal cancer.

PubMed

Fakih, Marwan G; Pendyala, Lakshmi; Fetterly, Gerald; Toth, Karoli; Zwiebel, James A; Espinoza-Delgado, Igor; Litwin, Alan; Rustum, Youcef M; Ross, Mary Ellen; Holleran, Julianne L; Egorin, Merrill J

2009-05-01

We conducted a phase I study to determine the maximum tolerated dose of vorinostat in combination with fixed doses of 5-fluorouracil (FU), leucovorin, and oxaliplatin (FOLFOX). Vorinostat was given orally twice daily for 1 week every 2 weeks. FOLFOX was given on days 4 and 5 of vorinostat. The vorinostat starting dose was 100 mg twice daily. Escalation occurred in cohorts of three to six patients. Pharmacokinetics of vorinostat, FU, and oxaliplatin were studied. Twenty-one patients were enrolled. Thrombocytopenia, neutropenia, gastrointestinal toxicities, and fatigue increased in frequency and severity at higher dose levels of vorinostat. Two of 4 evaluable patients at dose level 4 (vorinostat 400 mg orally twice daily) developed dose-limiting fatigue. One of 10 evaluable patients at dose level 3 (vorinostat 300 mg orally twice daily) had dose-limiting fatigue, anorexia, and dehydration. There were significant relationships between vorinostat dose and the area under the curve on days 1 and 5 (Pearson, < 0.001). The vorinostat area under the curve increased (P = 0.005) and clearance decreased (P = 0.003) on day 5 compared with day 1. The median C(max) of FU at each dose level increased significantly with increasing doses of vorinostat, suggesting a pharmacokinetic interaction between FU and vorinostat. Vorinostat-induced thymidylate synthase (TS) modulation was not consistent; only two of six patients had a decrease in intratumoral TS expression by reverse transcription-PCR. The maximum tolerated dose of vorinostat in combination with FOLFOX is 300 mg orally twice daily x 1 week every 2 weeks. Alternative vorinostat dosing schedules may be needed for optimal down-regulation of TS expression.

Optimal blood glucose control in diabetes mellitus treatment using dynamic programming based on Ackerman’s linear model

NASA Astrophysics Data System (ADS)

Pradanti, Paskalia; Hartono

2018-03-01

Determination of insulin injection dose in diabetes mellitus treatment can be considered as an optimal control problem. This article is aimed to simulate optimal blood glucose control for patient with diabetes mellitus. The blood glucose regulation of diabetic patient is represented by Ackerman’s Linear Model. This problem is then solved using dynamic programming method. The desired blood glucose level is obtained by minimizing the performance index in Lagrange form. The results show that dynamic programming based on Ackerman’s Linear Model is quite good to solve the problem.

Planning hybrid intensity modulated radiation therapy for whole-breast irradiation.

PubMed

Farace, Paolo; Zucca, Sergio; Solla, Ignazio; Fadda, Giuseppina; Durzu, Silvia; Porru, Sergio; Meleddu, Gianfranco; Deidda, Maria Assunta; Possanzini, Marco; Orrù, Sivia; Lay, Giancarlo

2012-09-01

To test tangential and not-tangential hybrid intensity modulated radiation therapy (IMRT) for whole-breast irradiation. Seventy-eight (36 right-, 42 left-) breast patients were randomly selected. Hybrid IMRT was performed by direct aperture optimization. A semiautomated method for planning hybrid IMRT was implemented using Pinnacle scripts. A plan optimization volume (POV), defined as the portion of the planning target volume covered by the open beams, was used as the target objective during inverse planning. Treatment goals were to prescribe a minimum dose of 47.5 Gy to greater than 90% of the POV and to minimize the POV and/or normal tissue receiving a dose greater than 107%. When treatment goals were not achieved by using a 4-field technique (2 conventional open plus 2 IMRT tangents), a 6-field technique was applied, adding 2 non tangential (anterior-oblique) IMRT beams. Using scripts, manual procedures were minimized (choice of optimal beam angle, setting monitor units for open tangentials, and POV definition). Treatment goals were achieved by using the 4-field technique in 61 of 78 (78%) patients. The 6-field technique was applied in the remaining 17 of 78 (22%) patients, allowing for significantly better achievement of goals, at the expense of an increase of low-dose (∼5 Gy) distribution in the contralateral tissue, heart, and lungs but with no significant increase of higher doses (∼20 Gy) in heart and lungs. The mean monitor unit contribution to IMRT beams was significantly greater (18.7% vs 9.9%) in the group of patients who required 6-field procedure. Because hybrid IMRT can be performed semiautomatically, it can be planned for a large number of patients with little impact on human or departmental resources, promoting it as the standard practice for whole-breast irradiation. Copyright © 2012 Elsevier Inc. All rights reserved.

Taking side effects into account for HIV medication.

PubMed

Costanza, Vicente; Rivadeneira, Pablo S; Biafore, Federico L; D'Attellis, Carlos E

2010-09-01

A control-theoretic approach to the problem of designing "low-side-effects" therapies for HIV patients based on highly active drugs is substantiated here. The evolution of side effects during treatment is modeled by an extra differential equation coupled to the dynamics of virions, healthy T-cells, and infected ones. The new equation reflects the dependence of collateral damages on the amount of each dose administered to the patient and on the evolution of the viral load detected by periodical blood analysis. The cost objective accounts for recommended bounds on healthy cells and virions, and also penalizes the appearance of collateral morbidities caused by the medication. The optimization problem is solved by a hybrid dynamic programming scheme that adhere to discrete-time observation and control actions, but by maintaining the continuous-time setup for predicting states and side effects. The resulting optimal strategies employ less drugs than those prescribed by previous optimization studies, but maintaining high doses at the beginning and the end of each period of six months. If an inverse discount rate is applied to favor early actions, and under a mild penalization of the final viral load, then the optimal doses are found to be high at the beginning and decrease afterward, thus causing an apparent stabilization of the main variables. But in this case, the final viral load turns higher than acceptable.

What is the optimal radiation dose for non-operable esophageal cancer? Dissecting the evidence in a meta-analysis.

PubMed

Chen, Yong; Zhu, Hui-Ping; Wang, Tao; Sun, Chang-Jiang; Ge, Xiao-Lin; Min, Ling-Feng; Zhang, Xian-Wen; Jia, Qing-Qing; Yu, Jie; Yang, Jian-Qi; Allgayer, Heike; Abba, Mohammed L; Zhang, Xi-Zhi; Sun, Xin-Chen

2017-10-24

The standard radiation dose 50.4 Gy with concurrent chemotherapy for localized inoperable esophageal cancer as supported by INT-0123 trail is now being challenged since a radiation dose above 50 Gy has been successfully administered with an observable dose-response relationship and insignificant untoward effects. Therefore, to ascertain the treatment benefits of different radiation doses, we performed a meta-analysis with 18 relative publications. According to our findings, a dose between 50 and 70 Gy appears optimal and patients who received ≥ 60 Gy radiation had a significantly better prognosis (pooled HR = 0.78, P = 0.004) as compared with < 60 Gy, especially in Asian countries (pooled HR = 0.75, P = 0.003). However, contradictory results of treatment benefit for ≥ 60 Gy were observed in two studies from Western countries, and the pooled treatment benefit of ≥ 60 Gy radiation was inconclusive (pooled HR = 0.86, P = 0.64). There was a marginal benefit in locoregional control in those treated with high dose (> 50.4/51 Gy) radiation when compared with those treated with low dose (≤ 50.4/51 Gy) radiation (pooled OR = 0.71, P = 0.06). Patients that received ≥ 60 Gy radiation had better locoregional control (OR = 0.29, P = 0.001), and for distant metastasis control, neither the > 50.4 Gy nor the ≥ 60 Gy treated group had any treatment benefit as compared to the groups that received ≤ 50.4 Gy and < 60 Gy group respectively. Taken together, a dose range of 50 to 70 Gy radiation with CCRT is recommended for non-operable EC patients. A dose of ≥ 60 Gy appears to be better in improving overall survival and locoregional control, especially in Asian countries, while the benefit of ≥ 60 Gy radiation in Western countries still remains controversial.

SPECT-CT in routine clinical practice: increase in patient radiation dose compared with SPECT alone.

PubMed

Sharma, Punit; Sharma, Shekhar; Ballal, Sanjana; Bal, Chandrasekhar; Malhotra, Arun; Kumar, Rakesh

2012-09-01

To assess the patient radiation dose during routine clinical single-photon emission computed tomography-computed tomography (SPECT-CT) and measure the increase as compared with SPECT alone. Data pertaining to 357 consecutive patients who had undergone radioisotope imaging along with SPECT-CT of a selected volume were retrospectively evaluated. Dose of the injected radiopharmaceutical (MBq) was noted, and the effective dose (mSv) was calculated as per International Commission on Radiological Protection (ICRP) guidelines. The volume-weighted computed tomography dose index (CTDIvol) and dose length product of the CT were also assessed using standard phantoms. The effective dose (mSv) due to CT was calculated as the product of dose length product and a conversion factor depending on the region of investigation, using ICRP guidelines. The dose due to CT was compared among different investigations. The increase in effective dose was calculated as CT dose expressed as a percentage of radiopharmaceutical dose. The per-patient CT effective dose for different studies varied between 0.06 and 11.9 mSv. The mean CT effective dose was lowest for 99mTc-ethylene cysteine dimer brain SPECT-CT (0.9 ± 0.7) and highest for 99mTc-methylene diphosphonate bone SPECT-CT (4.2 ± 2.8). The increase in radiation dose (SPECT-CT vs. SPECT) varied widely (2.3-666.4% for 99mTc-tracers and 0.02-96.2% for 131I-tracers). However, the effective dose of CT in SPECT-CT was less than the values reported for conventional CT examinations of the same regions. Addition of CT to nuclear medicine imaging in the form of SPECT-CT increases the radiation dose to the patient, with the effective dose due to CT exceeding the effective dose of RP in many instances. Hence, appropriate utilization and optimization of the protocols of SPECT-CT is needed to maximize benefit to patients.

Increased Hair Cortisol Concentrations and BMI in Patients With Pituitary-Adrenal Disease on Hydrocortisone Replacement.

PubMed

Staufenbiel, Sabine M; Andela, Cornelie D; Manenschijn, Laura; Pereira, Alberto M; van Rossum, Elisabeth F C; Biermasz, Nienke R

2015-06-01

Intrinsic imperfections and lack of reliable biomarkers preclude optimal individual dosing of hydrocortisone replacement in adrenal insufficiency (AI). However, the clinical relevance of optimal dosing is exemplified by frequently occurring side effects of overreplacement and the dangers of underreplacement. Cortisol in scalp hair has been identified as a retrospective biomarker for long-term cortisol exposure. We compared hair cortisol concentrations (CORT(hair)) of patients with primary or secondary AI on replacement therapy with those of patient controls with a pituitary disease without AI (PCs) and of healthy controls (HCs). In this cross-sectional study, hair samples and anthropometric data were collected in 132 AI patients (52 males), 42 PCs (11 males), and 195 HCs (90 males). The proximal 3 cm of hair were used. CORT(hair) were measured using an ELISA. CORT(hair) were higher in AI patients than in HCs and PCs (P < .001), and hydrocortisone dose correlated with CORT(hair) (P = .04). Male AI patients demonstrated higher CORT(hair) than female patients (P < .001). AI patients had higher body mass index (BMI) than HCs (P < .001), and BMI correlated with CORT(hair) in the whole sample (P < .001). Physiological hydrocortisone replacement is associated with increased CORT(hair). The association between CORT(hair) and BMI could suggest a mild overtreatment that may lead to adverse anthropomorphic side effects, especially in males. CORT(hair) measurements may be a promising additional tool to monitor cumulative hydrocortisone replacement in AI.

Accounting for patient size in the optimization of dose and image quality of pelvis cone beam CT protocols on the Varian OBI system.

PubMed

Wood, Tim J; Moore, Craig S; Horsfield, Carl J; Saunderson, John R; Beavis, Andrew W

2015-01-01

The purpose of this study was to develop size-based radiotherapy kilovoltage cone beam CT (CBCT) protocols for the pelvis. Image noise was measured in an elliptical phantom of varying size for a range of exposure factors. Based on a previously defined "small pelvis" reference patient and CBCT protocol, appropriate exposure factors for small, medium, large and extra-large patients were derived which approximate the image noise behaviour observed on a Philips CT scanner (Philips Medical Systems, Best, Netherlands) with automatic exposure control (AEC). Selection criteria, based on maximum tube current-time product per rotation selected during the radiotherapy treatment planning scan, were derived based on an audit of patient size. It has been demonstrated that 110 kVp yields acceptable image noise for reduced patient dose in pelvic CBCT scans of small, medium and large patients, when compared with manufacturer's default settings (125 kVp). Conversely, extra-large patients require increased exposure factors to give acceptable images. 57% of patients in the local population now receive much lower radiation doses, whereas 13% require higher doses (but now yield acceptable images). The implementation of size-based exposure protocols has significantly reduced radiation dose to the majority of patients with no negative impact on image quality. Increased doses are required on the largest patients to give adequate image quality. The development of size-based CBCT protocols that use the planning CT scan (with AEC) to determine which protocol is appropriate ensures adequate image quality whilst minimizing patient radiation dose.

Rasagiline for dysexecutive symptoms during wearing-off in Parkinson's disease: a pilot study.

PubMed

Rinaldi, Domiziana; Assogna, Francesca; Sforza, Michela; Tagliente, Stefania; Pontieri, Francesco E

2018-01-01

Wearing-off refers to the predictable worsening of motor and sometimes non-motor symptoms of Parkinson's disease occurring at the end of levodopa dose that improves with the next drug dose. Here, we investigated the efficacy of rasagiline on executive functions at the end of levodopa dose in patients displaying symptoms of wearing-off. Rasagiline was well-tolerated and produced a significant improvement at the Frontal Assessment Battery, together with improvement of motor symptoms at the end of levodopa dose. These results suggest that treatment of motor symptoms of wearing-off with rasagiline may be accompanied by improvement of executive functions, and further support the need for optimizing dopamine replacement therapy in fluctuating Parkinson's disease patients.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Demirag, N

Purpose: To verify the benefits of the biological cost functions. Methods: TG166 patients were used for the test case scenarios. Patients were planned using Monaco V5.0 (CMS/Elekta, St.Louis, MO) Monaco has 3 biological and 8 physical CFs. In this study the plans were optimized using 3 different scenarios. 1- Biological CFs only 2-Physical CFs only 3- Combination of Physical and Biological CFsMonaco has 3 biological CFs. Target EUD used for the targets, derived from the poisson cell kill model, has an α value that controls the cold spots inside the target. α values used in the optimization were 0.5 andmore » 0.8. if cold spots needs to be penalized α value increased. Serial CF: it's called serial to mimic the behaviour of the serial organs, if a high k value like 12 or 14 is used it controls the maximum dose. Serial CF has a k parameter that is used to shape the whole dvh curve. K value ranges between 1–20. k:1 is used to control the mean dose, lower k value controls the mean dose, higher k value controls the higher dose, using 2 serial CFs with different k values controls the whole DVH. Paralel CF controls the percentage of the volume that tolerates higher doses than the reference dose to mimic the behaviour of the paralel organs. Results: It was possible to achive clinically accepted plans in all 3 scenarios. The benefit of the biological cost functions were to control the mean dose for target and OAR, to shape the DVH curve using one EUD value and one k value simplifies the optimization process. Using the biological CFs alone, it was hard to control the dose at a point. Conclusion: Biological CFs in Monaco doesn't require the ntcp/tcp values from the labs and useful to shape the whole dvh curve. I work as an applications support specialist for Elekta and I am a Ph.D. Student in Istanbul University for radiation therapy physics.« less

SU-E-I-60: The Correct Selection of Pitch and Rotation Time for Optimal CT Scanning : The Big Misconception

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ranallo, F; Szczykutowicz, T

2014-06-01

Purpose: To provide correct guidance in the proper selection of pitch and rotation time for optimal CT imaging with multi-slice scanners. Methods: There exists a widespread misconception concerning the role of pitch in patient dose with modern multi-slice scanners, particularly with the use of mA modulation techniques. We investigated the relationship of pitch and rotation time to image quality, dose, and scan duration, with CT scanners from different manufacturers in a way that clarifies this misconception. This source of this misconception may concern the role of pitch in single slice CT scanners. Results: We found that the image noise andmore » dose are generally independent of the selected effective mAs (mA*time/ pitch) with manual mA technique settings and are generally independent of the selected pitch and /or rotation time with automatic mA modulation techniques. However we did find that on certain scanners the use of a pitch just above 0.5 provided images of equal image noise at a lower dose compared to the use of a pitch just below 1.0. Conclusion: The misconception that the use of a lower pitch over-irradiates patients by wasting dose is clearly false. The use of a lower pitch provides images of equal or better image quality at the same patient dose, whether using manual mA or automatic mA modulation techniques. By decreasing the pitch and the rotation times by equal amounts, both helical and patient motion artifacts can be reduced without affecting the exam time. The use of lower helical pitch also allows better scanning of larger patients by allowing a greater scan effective mAs, if the exam time can be extended. The one caution with the use of low pitch is not related to patient dose, but to the length of the scan time if the rotation time is not set short enough. Partial Research funding from GE HealthCare.« less

Optimization of the intravenous glucose tolerance test in T2DM patients using optimal experimental design.

PubMed

Silber, Hanna E; Nyberg, Joakim; Hooker, Andrew C; Karlsson, Mats O

2009-06-01

Intravenous glucose tolerance test (IVGTT) provocations are informative, but complex and laborious, for studying the glucose-insulin system. The objective of this study was to evaluate, through optimal design methodology, the possibilities of more informative and/or less laborious study design of the insulin modified IVGTT in type 2 diabetic patients. A previously developed model for glucose and insulin regulation was implemented in the optimal design software PopED 2.0. The following aspects of the study design of the insulin modified IVGTT were evaluated; (1) glucose dose, (2) insulin infusion, (3) combination of (1) and (2), (4) sampling times, (5) exclusion of labeled glucose. Constraints were incorporated to avoid prolonged hyper- and/or hypoglycemia and a reduced design was used to decrease run times. Design efficiency was calculated as a measure of the improvement with an optimal design compared to the basic design. The results showed that the design of the insulin modified IVGTT could be substantially improved by the use of an optimized design compared to the standard design and that it was possible to use a reduced number of samples. Optimization of sample times gave the largest improvement followed by insulin dose. The results further showed that it was possible to reduce the total sample time with only a minor loss in efficiency. Simulations confirmed the predictions from PopED. The predicted uncertainty of parameter estimates (CV) was low in all tested cases, despite the reduction in the number of samples/subject. The best design had a predicted average CV of parameter estimates of 19.5%. We conclude that improvement can be made to the design of the insulin modified IVGTT and that the most important design factor was the placement of sample times followed by the use of an optimal insulin dose. This paper illustrates how complex provocation experiments can be improved by sequential modeling and optimal design.

Filgrastim use in patients receiving chemotherapy for early-stage breast cancer-a survey of physicians and patients.

PubMed

Hilton, John; Vandermeer, Lisa; Sienkiewicz, Marta; Mazzarello, Sasha; Hutton, Brian; Stober, Carol; Fergusson, Dean; Blanchette, Phillip; Joy, Anil A; Brianne Bota, A; Clemons, Mark

2018-07-01

Despite its widespread use as primary febrile neutropenia (FN) prophylaxis during chemotherapy for early-stage breast cancer, the optimal duration of daily filgrastim is unknown. Using the minimum effective duration may improve patient comfort and acceptability while reducing costs. Yet, suboptimal dosing may also negatively impact patient care. A survey was performed to obtain information regarding current practices for granulocyte colony-stimulating factor (G-CSF) use. Canadian oncologists involved in the treatment of breast cancer patients, as well as patients who had received neo/adjuvant chemotherapy for breast cancer, were surveyed. Standardized surveys were designed to collect information on perceived reasons for G-CSF use and current practices. The surveys were completed by 38/50 (76%) physicians and 95/97 (98%) patients. For physicians, there was variability in the choice of chemotherapy regimens that required G-CSF support, the dose of filgrastim prescribed and the number of days prescribed. The majority of physicians reported using 5 (31.6%), 7 (47.4%), or 10 (13.2%) days of therapy. Nearly half of the patients (46.3%) recalled having experienced at least one of the chemotherapy-related complications including chemotherapy delays, dose reductions, and FN. While on filgrastim, 66.3% of patients reported myalgia and bone pain. Both physicians and patients expressed interest in participating in clinical trials designed to optimize the duration of filgrastim administration. Significant variability in practice exists with respect to filgrastim administration. Definitive studies are therefore required to standardize and improve care, as this has the potential to impact treatment outcomes, patient quality of life, and cost savings.

Deferasirox for the treatment of iron overload after allogeneic hematopoietic cell transplantation: multicenter phase I study (KSGCT1302).

PubMed

Tachibana, Takayoshi; Kanda, Junya; Machida, Shinichiro; Saito, Takeshi; Tanaka, Masatsugu; Najima, Yuho; Koyama, Satoshi; Miyazaki, Takuya; Yamamoto, Eri; Takeuchi, Masahiro; Morita, Satoshi; Kanda, Yoshinobu; Kanamori, Heiwa; Okamoto, Shinichiro

2018-05-01

The aim of this study was to assess the safety and optimal dose of deferasirox for the treatment of iron overload after allogeneic hematopoietic cell transplantation (HCT). The primary endpoint was the maximum tolerated dose of deferasirox that was determined by the intrapatient dose escalation methods. A total of 16 patients with post-HCT iron overload were enrolled in the study. After excluding one case of early relapse, 15 remained evaluable. Their median age was 42 years (range 22-68). Median time from HCT to deferasirox administration was 9 months (range 6-84). Deferasirox was started at a dose of 5 mg/kg, and the dose was increased to 7.5 and 10 mg/kg every 4 weeks unless there were no grade ≥ 2 of adverse events. Achievement rates of planned medication were 80% in 5 mg/kg (12 of 15), 73% in 7.5 mg/kg (11 of 15), and 60% in 10 mg/kg (9 of 15), respectively. The reasons for discontinuation of the drug were grade 2 of adverse events (n = 4), late relapse (n = 1), and self-cessation (n = 1). None of the patients developed grade ≥ 3 of adverse events or exacerbation of GVHD. Among 11 evaluable cases, mean value of ferritin decreased from 1560 ng/ml pre-treatment to 1285 ng/ml post-treatment. These data suggested that 10 mg/kg of deferasirox may be maximum tolerated dose when given after HCT. Our dose escalating method of deferasirox is useful to identify the optimal dosage of the drug in each patient. UMIN000011251.

[Optimization of the dose of radiation in shoulder arthrography].

PubMed

Campos, P A; Redondo, M V; Berná-Serna, J D; Reus, M; Martínez, F

2009-01-01

The aim of this study was to determine whether using a film with radiopaque coordinates placed over the region of interest to guide shoulder arthrography can reduce the dose of radiation received by patients. The entrance dose was obtained in 34 patients (mean age, 44 years; range, 15 to 75 years). The dose received by organs at risk and the effective dose were estimated with Monte Carlo techniques using the following input parameters: patient anatomy, examination geometry, and air kerma at the entrance to the patient without backscattering. Arthrography was performed with a remote controlled device and images were acquired digitally without fluoroscopy. The mean thickness of the shoulders studied was 14.6+/-2.1cm (9-20 cm). Images were obtained with 80+/-10 kVp (60-85 kVp) and 6.5+/-3.5 mAs (1.4-17 mAs). The mean time of irradiation for each patient was 20+/-6 ms (6.9-47.9 ms). The calculated air kerma was 0.41+/-0.19 mGy and the effective dose was 0.79+/-0.40 muSv. The technique described in this study has enabled us to reduce the dose of radiation received by patients undergoing shoulder arthrography in comparison with other techniques described in the literature and to ensure that the radiologist performing the procedure is not irradiated.

Dashboard systems: Pharmacokinetic/pharmacodynamic mediated dose optimization for monoclonal antibodies.

PubMed

Mould, Diane R; Dubinsky, Marla C

2015-03-01

Many marketed drugs exhibit high variability in exposure and response. While these drugs are efficacious in their approved indications, finding appropriate dose regimens for individual patients is not straightforward. Similar dose adjustment problems are also seen with drugs that have a complex relationship between exposure and response and/or a narrow therapeutic window. This is particularly true for monoclonal antibodies, where prolonged dosing at a sub-therapeutic dose can also elicit anti-drug antibodies which will further compromise safety and efficacy. Thus, finding appropriate doses quickly would represent a substantial improvement in healthcare. Dashboard systems, which are decision-support tools, offer an improved, convenient means of tailoring treatment for individual patients. This article reviews the clinical need for this approach, particularly with monoclonal antibodies, the design, development, and testing of such systems, and the likely benefits of dashboard systems in clinical practice. We focus on infliximab for reference. © 2015, The American College of Clinical Pharmacology.

Discharge aspirin dose and clinical outcomes in patients with acute coronary syndromes treated with prasugrel versus clopidogrel: an analysis from the TRITON-TIMI 38 study (trial to assess improvement in therapeutic outcomes by optimizing platelet inhibition with prasugrel-thrombolysis in myocardial infarction 38).

PubMed

Kohli, Payal; Udell, Jacob A; Murphy, Sabina A; Cannon, Christopher P; Antman, Elliott M; Braunwald, Eugene; Wiviott, Stephen D

2014-01-28

The goal of this study was to determine whether there is a relationship between aspirin dose and the potent antiplatelet agent prasugrel in the TRITON-TIMI 38 (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel-Thrombolysis In Myocardial Infarction 38) study. Optimal aspirin dosing after acute coronary syndromes remains uncertain. Previous studies have raised questions regarding an interaction between high-dose aspirin and the potent antiplatelet agent ticagrelor. In TRITON-TIMI 38, we classified 12,674 patients into low-dose (<150 mg) or high-dose (≥150 mg) aspirin groups based on discharge dose. We identified independent correlates of dose selection and studied the impact of aspirin dose on the clinical effects of prasugrel. There was significant geographical variation in aspirin dosing, with North American patients receiving high-dose aspirin more frequently than other countries (66% vs. 28%; p < 0.001). Clinical factors correlating with high-dose aspirin included previous percutaneous coronary intervention and use of aspirin before randomization. Characteristics associated with the use of low-dose aspirin included age ≥75 years, white race, and use of bivalirudin or a glycoprotein IIb/IIIa inhibitor during coronary intervention. Regardless of low- or high-dose aspirin use, prasugrel had lower rates of the primary efficacy endpoint (cardiovascular death, myocardial infarction, or stroke [CVD/MI/stroke]) (hazard ratio [HR]CVD/MI/stroke = 0.78 [95% confidence interval (CI) 0.64 to 0.95] and HRCVD/MI/stroke = 0.87 [95% CI 0.69 to 1.10], respectively; p value for interaction = 0.48) and higher rates of the primary safety endpoint (HR TIMI major bleeding = 1.40 [95% CI 0.81 to 2.42] and TIMImajor bleeding = 1.30 [95% CI 0.63 to 2.68], respectively; p value for interaction = 0.84) compared with clopidogrel. In TRITON-TIMI 38, the safety and efficacy outcomes of prasugrel compared with those of clopidogrel were directionally consistent regardless of aspirin dose, although only the primary efficacy endpoint achieved statistical significance. There was no clinically meaningful interaction of aspirin with prasugrel, suggesting that previous observations with potent antiplatelet agents indicating differential results are not universal. (A Comparison of Prasugrel [CS-747] and Clopidogrel in Acute Coronary Syndrome Subjects Who Are to Undergo Percutaneous Coronary Intervention; NCT00097591). Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Comparison of a 3-D multi-group SN particle transport code with Monte Carlo for intracavitary brachytherapy of the cervix uteri.

PubMed

Gifford, Kent A; Wareing, Todd A; Failla, Gregory; Horton, John L; Eifel, Patricia J; Mourtada, Firas

2009-12-03

A patient dose distribution was calculated by a 3D multi-group S N particle transport code for intracavitary brachytherapy of the cervix uteri and compared to previously published Monte Carlo results. A Cs-137 LDR intracavitary brachytherapy CT data set was chosen from our clinical database. MCNPX version 2.5.c, was used to calculate the dose distribution. A 3D multi-group S N particle transport code, Attila version 6.1.1 was used to simulate the same patient. Each patient applicator was built in SolidWorks, a mechanical design package, and then assembled with a coordinate transformation and rotation for the patient. The SolidWorks exported applicator geometry was imported into Attila for calculation. Dose matrices were overlaid on the patient CT data set. Dose volume histograms and point doses were compared. The MCNPX calculation required 14.8 hours, whereas the Attila calculation required 22.2 minutes on a 1.8 GHz AMD Opteron CPU. Agreement between Attila and MCNPX dose calculations at the ICRU 38 points was within +/- 3%. Calculated doses to the 2 cc and 5 cc volumes of highest dose differed by not more than +/- 1.1% between the two codes. Dose and DVH overlays agreed well qualitatively. Attila can calculate dose accurately and efficiently for this Cs-137 CT-based patient geometry. Our data showed that a three-group cross-section set is adequate for Cs-137 computations. Future work is aimed at implementing an optimized version of Attila for radiotherapy calculations.

Cumulative iron dose and resistance to erythropoietin.

PubMed

Rosati, A; Tetta, C; Merello, J I; Palomares, I; Perez-Garcia, R; Maduell, F; Canaud, B; Aljama Garcia, P

2015-10-01

Optimizing anemia treatment in hemodialysis (HD) patients remains a priority worldwide as it has significant health and financial implications. Our aim was to evaluate in a large cohort of chronic HD patients in Fresenius Medical Care centers in Spain the value of cumulative iron (Fe) dose monitoring for the management of iron therapy in erythropoiesis-stimulating agent (ESA)-treated patients, and the relationship between cumulative iron dose and risk of hospitalization. Demographic, clinical and laboratory parameters from EuCliD(®) (European Clinical Dialysis Database) on 3,591 patients were recorded including ESA dose (UI/kg/week), erythropoietin resistance index (ERI) [U.I weekly/kg/gr hemoglobin (Hb)] and hospitalizations. Moreover the cumulative Fe dose (mg/kg of bodyweight) administered over the last 2 years was calculated. Univariate and multivariate analyses were performed to identify the main predictors of ESA resistance and risk of hospitalization. Patients belonging to the 4th quartile of ERI were defined as hypo-responders. The 2-year iron cumulative dose was significantly higher in the 4th quartile of ERI. In hypo-responders, 2-year cumulative iron dose was the only iron marker associated with ESA resistance. At case-mix adjusted multivariate analysis, 2-year iron cumulative dose was an independent predictor of hospitalization risk. In ESA-treated patients cumulative Fe dose could be a useful tool to monitor the appropriateness of Fe therapy and to prevent iron overload. To establish whether the associations between cumulative iron dose, ERI and hospitalization risk are causal or attributable to selection bias by indication, clinical trials are necessary.

Comparison of a 3D multi‐group SN particle transport code with Monte Carlo for intercavitary brachytherapy of the cervix uteri

PubMed Central

Wareing, Todd A.; Failla, Gregory; Horton, John L.; Eifel, Patricia J.; Mourtada, Firas

2009-01-01

A patient dose distribution was calculated by a 3D multi‐group SN particle transport code for intracavitary brachytherapy of the cervix uteri and compared to previously published Monte Carlo results. A Cs‐137 LDR intracavitary brachytherapy CT data set was chosen from our clinical database. MCNPX version 2.5.c, was used to calculate the dose distribution. A 3D multi‐group SN particle transport code, Attila version 6.1.1 was used to simulate the same patient. Each patient applicator was built in SolidWorks, a mechanical design package, and then assembled with a coordinate transformation and rotation for the patient. The SolidWorks exported applicator geometry was imported into Attila for calculation. Dose matrices were overlaid on the patient CT data set. Dose volume histograms and point doses were compared. The MCNPX calculation required 14.8 hours, whereas the Attila calculation required 22.2 minutes on a 1.8 GHz AMD Opteron CPU. Agreement between Attila and MCNPX dose calculations at the ICRU 38 points was within ±3%. Calculated doses to the 2 cc and 5 cc volumes of highest dose differed by not more than ±1.1% between the two codes. Dose and DVH overlays agreed well qualitatively. Attila can calculate dose accurately and efficiently for this Cs‐137 CT‐based patient geometry. Our data showed that a three‐group cross‐section set is adequate for Cs‐137 computations. Future work is aimed at implementing an optimized version of Attila for radiotherapy calculations. PACS number: 87.53.Jw

Repeat Gamma-Knife Radiosurgery for Refractory or Recurrent Trigeminal Neuralgia with Consideration About the Optimal Second Dose.

PubMed

Park, Seong-Cheol; Kwon, Do Hoon; Lee, Do Hee; Lee, Jung Kyo

2016-02-01

To investigate adequate radiation doses for repeat Gamma Knife radiosurgery (GKS) for trigeminal neuralgia in our series and meta-analysis. Fourteen patients treated by ipsilateral repeat GKS for trigeminal neuralgia were included. Median age of patients was 65 years (range, 28-78), the median target dose, 140-180). Patients were followed a median of 10.8 months (range, 1-151) after the second gamma-knife surgery. Brainstem dose analysis and vote-counting meta-analysis of 19 studies were performed. After the second gamma-knife radiosurgeries, pain was relieved effectively in 12 patients (86%; Barrow Neurological Institute Pain Intensity Score I-III). Post-gamma-knife radiosurgery trigeminal nerve deficits were mild in 5 patients. No serious anesthesia dolorosa was occurred. The second GKS radiation dose ≤ 60 Gy was significantly associated with worse pain control outcome (P = 0.018 in our series, permutation analysis of variance, and P = 0.009 in the meta-analysis, 2-tailed Fisher's exact test). Cumulative dose ≤ 140-150 Gy was significantly associated with poor pain control outcome (P = 0.033 in our series and P = 0.013 in the meta-analysis, 2-tailed Fisher's exact test). A cumulative brainstem edge dose >12 Gy tended to be associated with trigeminal nerve deficit (P = 0.077). Our study suggests that the second GKS dose is a potentially important factor. Copyright © 2016 Elsevier Inc. All rights reserved.

Volumetric tumor burden and its effect on brachial plexus dosimetry in head and neck intensity-modulated radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Romesser, Paul B.; Qureshi, Muhammad M.; Kovalchuk, Nataliya

2014-07-01

To determine the effect of gross tumor volume of the primary (GTV-P) and nodal (GTV-N) disease on planned radiation dose to the brachial plexus (BP) in head and neck intensity-modulated radiotherapy (IMRT). Overall, 75 patients underwent definitive IMRT to a median total dose of 69.96 Gy in 33 fractions. The right BP and left BP were prospectively contoured as separate organs at risk. The GTV was related to BP dose using the unpaired t-test. Receiver operating characteristics curves were constructed to determine optimized volumetric thresholds of GTV-P and GTV-N corresponding to a maximum BP dose cutoff of > 66 Gy.more » Multivariate analyses were performed to account for factors associated with a higher maximal BP dose. A higher maximum BP dose (> 66 vs ≤ 66 Gy) correlated with a greater mean GTV-P (79.5 vs 30.8 cc; p = 0.001) and ipsilateral GTV-N (60.6 vs 19.8 cc; p = 0.014). When dichotomized by the optimized nodal volume, patients with an ipsilateral GTV-N ≥ 4.9 vs < 4.9 cc had a significant difference in maximum BP dose (64.2 vs 59.4 Gy; p = 0.001). Multivariate analysis confirmed that an ipsilateral GTV-N ≥ 4.9 cc was an independent predictor for the BP to receive a maximal dose of > 66 Gy when adjusted individually for BP volume, GTV-P, the use of a low anterior neck field technique, total planned radiation dose, and tumor category. Although both the primary and the nodal tumor volumes affected the BP maximal dose, the ipsilateral nodal tumor volume (GTV-N ≥ 4.9 cc) was an independent predictor for high maximal BP dose constraints in head and neck IMRT.« less

Dual Inhibition of the Epidermal Growth Factor Receptor Pathway with Cetuximab and Erlotinib: A Phase I Study in Patients with Advanced Solid Malignancies

PubMed Central

Guarino, Michael J.; Schneider, Charles J.; Hosford, Martha A.; Brahmer, Julie R.; Rudin, Charles M.; Finckenstein, Friedrich Graf; Philip-Norton, Robyn E.; Lu, Haolan; Weber, Martin R.; Ettinger, David S.

2017-01-01

Purpose To determine the optimal dose of the antiepidermal growth factor receptor (EGFR) monoclonal antibody cetuximab that can be safely administered in combination with a standard daily dose of erlotinib in patients with advanced solid malignancies. Patients and Methods Patients with advanced solid malignancies who had failed standard chemotherapies received escalating doses of cetuximab without a loading dose (100, 200, 250 mg/m2 i.v. weekly) in combination with a fixed dose of erlotinib (150 mg daily orally) until disease progression or unacceptable toxicity. Results Twenty-two patients were treated, including 14 patients (64%) with non-small cell lung cancer. Twenty patients received combination treatment at the highest dose level for a median of 5.5 weeks (range, 1–31 weeks). One dose-limiting toxicity was observed: grade 3 skin rash. Overall, the most common adverse events (any grade, grade 3/4) were consistent with the safety profiles of the individual drugs: acneform rash (100%, 9%), diarrhea (77%, 5%), and hypomagnesemia (59%, 12%). Seven of 18 evaluable patients (38.9%) had stable disease lasting for a median of 16.6 weeks (range, 6.1–25.1 weeks). Conclusion Dual EGFR inhibition with cetuximab and erlotinib is feasible; the observed toxicities were manageable and consistent with the safety profiles of the individual drugs. The recommended doses for phase II studies are 250 mg/m2 i.v. weekly for cetuximab and 150 mg daily orally for erlotinib. PMID:19182243

SU-F-P-28: A Method of Maximize the Noncoplanar Beam Orientations and Assure the Beam Delivery Clearance for Stereotactic Body Radiation Therapy (SBRT)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhu, J

2016-06-15

Purpose: Develop a method to maximize the noncoplanar beam orientations and assure the beam delivery clearance for SBRT, therefore, optimize the dose conformality to the target, increase the dose sparing to the critical normal organs and reduce the hot spots in the body. Methods: A SBRT body frame (Elekta, Stockholm, Sweden) was used for patient immobilization and target localization. The SBRT body frame has CT fiducials on its side frames. After patient’s CT scan, the radiation treatment isocenter was defined and its coordinators referring to the body frame was calculated in the radiation treatment planning process. Meanwhile, initial beam orientationsmore » were designed based on the patient target and critical organ anatomy. The body frame was put on the linear accelerator couch and positioned to the calculated isocenter. Initially designed beam orientations were manually measured by tuning the body frame position on the couch, the gantry and couch angles. The finalized beam orientations were put into the treatment planning for dosimetric calculations. Results: Without patient presence, an optimal set of beam orientations were designed and validated. The radiation treatment plan was optimized and guaranteed for delivery clearance. Conclusion: The developed method is beneficial and effective in SBRT treatment planning for individual patient. It first allows maximizing the achievable noncoplanar beam orientation space, therefore, optimize the treatment plan for specific patient. It eliminates the risk that a plan needs to be modified due to the gantry and couch collision during patient setup.« less

The performance of the progressive resolution optimizer (PRO) for RapidArc planning in targets with low-density media.

PubMed

Kan, Monica W K; Leung, Lucullus H T; Yu, Peter K N

2013-11-04

A new version of progressive resolution optimizer (PRO) with an option of air cavity correction has been implemented for RapidArc volumetric-modulated arc therapy (RA). The purpose of this study was to compare the performance of this new PRO with the use of air cavity correction option (PRO10_air) against the one without the use of the air cavity correction option (PRO10_no-air) for RapidArc planning in targets with low-density media of different sizes and complexities. The performance of PRO10_no-air and PRO10_air was initially compared using single-arc plans created for four different simple heterogeneous phantoms with virtual targets and organs at risk. Multiple-arc planning of 12 real patients having nasopharyngeal carcinomas (NPC) and ten patients having non-small cell lung cancer (NSCLC) were then performed using the above two options for further comparison. Dose calculations were performed using both the Acuros XB (AXB) algorithm with the dose to medium option and the analytical anisotropic algorithm (AAA). The effect of using intermediate dose option after the first optimization cycle in PRO10_air and PRO10_no-air was also investigated and compared. Plans were evaluated and compared using target dose coverage, critical organ sparing, conformity index, and dose homogeneity index. For NSCLC cases or cases for which large volumes of low-density media were present in or adjacent to the target volume, the use of the air cavity correction option in PRO10 was shown to be beneficial. For NPC cases or cases for which small volumes of both low- and high-density media existed in the target volume, the use of air cavity correction in PRO10 did not improve the plan quality. Based on the AXB dose calculation results, the use of PRO10_air could produce up to 18% less coverage to the bony structures of the planning target volumes for NPC cases. When the intermediate dose option in PRO10 was used, there was negligible difference observed in plan quality between optimizations with and without using the air cavity correction option.

A dose optimization method for electron radiotherapy using randomized aperture beams

NASA Astrophysics Data System (ADS)

Engel, Konrad; Gauer, Tobias

2009-09-01

The present paper describes the entire optimization process of creating a radiotherapy treatment plan for advanced electron irradiation. Special emphasis is devoted to the selection of beam incidence angles and beam energies as well as to the choice of appropriate subfields generated by a refined version of intensity segmentation and a novel random aperture approach. The algorithms have been implemented in a stand-alone programme using dose calculations from a commercial treatment planning system. For this study, the treatment planning system Pinnacle from Philips has been used and connected to the optimization programme using an ASCII interface. Dose calculations in Pinnacle were performed by Monte Carlo simulations for a remote-controlled electron multileaf collimator (MLC) from Euromechanics. As a result, treatment plans for breast cancer patients could be significantly improved when using randomly generated aperture beams. The combination of beams generated through segmentation and randomization achieved the best results in terms of target coverage and sparing of critical organs. The treatment plans could be further improved by use of a field reduction algorithm. Without a relevant loss in dose distribution, the total number of MLC fields and monitor units could be reduced by up to 20%. In conclusion, using randomized aperture beams is a promising new approach in radiotherapy and exhibits potential for further improvements in dose optimization through a combination of randomized electron and photon aperture beams.

Cavitary Penetration of Levofloxacin among Patients with Multidrug-Resistant Tuberculosis

PubMed Central

Barth, Aline B.; Vashakidze, Sergo; Nikolaishvili, Ketino; Sabulua, Irina; Tukvadze, Nestani; Bablishvili, Nino; Gogishvili, Shota; Singh, Ravi Shankar P.; Guarner, Jeannette; Derendorf, Hartmut; Peloquin, Charles A.; Blumberg, Henry M.

2015-01-01

A better understanding of second-line drug (SLD) pharmacokinetics, including cavitary penetration, may help optimize SLD dosing. Patients with pulmonary multidrug-resistant tuberculosis (MDR-TB) undergoing adjunctive surgery were enrolled in Tbilisi, Georgia. Serum was obtained at 0, 1, 4, and 8 h and at the time of cavitary removal to measure levofloxacin concentrations. After surgery, microdialysis was performed using the ex vivo cavity, and levofloxacin concentrations in the collected dialysate fluid were measured. Noncompartmental analysis was performed, and a cavitary-to-serum levofloxacin concentration ratio was calculated. Twelve patients received levofloxacin for a median of 373 days before surgery (median dose, 11.8 mg/kg). The median levofloxacin concentration in serum (Cmax) was 6.5 μg/ml, and it was <2 μg/ml in 3 (25%) patients. Among 11 patients with complete data, the median cavitary concentration of levofloxacin was 4.36 μg/ml (range, 0.46 to 8.82). The median cavitary/serum levofloxacin ratio was 1.33 (range, 0.63 to 2.36), and 7 patients (64%) had a ratio of >1. There was a significant correlation between serum and cavitary concentrations (r = 0.71; P = 0.01). Levofloxacin had excellent penetration into chronic cavitary TB lesions, and there was a good correlation between serum and cavitary concentrations. Optimizing serum concentrations will help ensure optimal cavitary concentrations of levofloxacin, which may enhance treatment outcomes. PMID:25779583

SU-E-T-214: Intensity Modulated Proton Therapy (IMPT) Based On Passively Scattered Protons and Multi-Leaf Collimation: Prototype TPS and Dosimetry Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sanchez-Parcerisa, D; Carabe-Fernandez, A

2014-06-01

Purpose. Intensity-modulated proton therapy is usually implemented with multi-field optimization of pencil-beam scanning (PBS) proton fields. However, at the view of the experience with photon-IMRT, proton facilities equipped with double-scattering (DS) delivery and multi-leaf collimation (MLC) could produce highly conformal dose distributions (and possibly eliminate the need for patient-specific compensators) with a clever use of their MLC field shaping, provided that an optimal inverse TPS is developed. Methods. A prototype TPS was developed in MATLAB. The dose calculation process was based on a fluence-dose algorithm on an adaptive divergent grid. A database of dose kernels was precalculated in order tomore » allow for fast variations of the field range and modulation during optimization. The inverse planning process was based on the adaptive simulated annealing approach, with direct aperture optimization of the MLC leaves. A dosimetry study was performed on a phantom formed by three concentrical semicylinders separated by 5 mm, of which the inner-most and outer-most were regarded as organs at risk (OARs), and the middle one as the PTV. We chose a concave target (which is not treatable with conventional DS fields) to show the potential of our technique. The optimizer was configured to minimize the mean dose to the OARs while keeping a good coverage of the target. Results. The plan produced by the prototype TPS achieved a conformity index of 1.34, with the mean doses to the OARs below 78% of the prescribed dose. This Result is hardly achievable with traditional conformal DS technique with compensators, and it compares to what can be obtained with PBS. Conclusion. It is certainly feasible to produce IMPT fields with MLC passive scattering fields. With a fully developed treatment planning system, the produced plans can be superior to traditional DS plans in terms of plan conformity and dose to organs at risk.« less

GPU-based ultra-fast dose calculation using a finite size pencil beam model.

PubMed

Gu, Xuejun; Choi, Dongju; Men, Chunhua; Pan, Hubert; Majumdar, Amitava; Jiang, Steve B

2009-10-21

Online adaptive radiation therapy (ART) is an attractive concept that promises the ability to deliver an optimal treatment in response to the inter-fraction variability in patient anatomy. However, it has yet to be realized due to technical limitations. Fast dose deposit coefficient calculation is a critical component of the online planning process that is required for plan optimization of intensity-modulated radiation therapy (IMRT). Computer graphics processing units (GPUs) are well suited to provide the requisite fast performance for the data-parallel nature of dose calculation. In this work, we develop a dose calculation engine based on a finite-size pencil beam (FSPB) algorithm and a GPU parallel computing framework. The developed framework can accommodate any FSPB model. We test our implementation in the case of a water phantom and the case of a prostate cancer patient with varying beamlet and voxel sizes. All testing scenarios achieved speedup ranging from 200 to 400 times when using a NVIDIA Tesla C1060 card in comparison with a 2.27 GHz Intel Xeon CPU. The computational time for calculating dose deposition coefficients for a nine-field prostate IMRT plan with this new framework is less than 1 s. This indicates that the GPU-based FSPB algorithm is well suited for online re-planning for adaptive radiotherapy.

Favorable toxicity and biochemical control using real-time inverse optimization technique for prostate brachytherapy.

PubMed

Raben, Adam; Rusthoven, Kyle E; Sarkar, Abrihup; Glick, Andrew; Benge, Bruce; Jacobs, Dayee; Raben, David

2009-01-01

Favorable dosimetric results have been reported using intraoperative inverse optimization (IO) for permanent prostate brachytherapy. The clinical implications of these improvements in dosimetry are unclear. We review toxicity and early biochemical outcomes for patients implanted using IO technique. Between 2001 and 2007, 165 patients received permanent prostate implants using real-time IO and had >/=3 months of followup. Dose constraints for inverse planning were: the prostate volume receiving 100% of the prescription dose [prostate V(100)] was >95%; the dose received by 90% of the gland [prostate D(90)] was within the 140-180 by dose range; the volume of urethra receiving 150% of the prescription dose [urethra V(150)] was <30%; and the volume of rectal wall receiving 110% of the prescription dose [rectal V(110)] was <1.0 cc. Toxicity was prospectively scored using the Radiation Therapy Oncology Group toxicity scale and the International Prostate Symptom Score questionnaire. Biochemical control was determined using the nadir + 2 ng/mL definition. Mean followup was 30 months (range, 6-63 months). Risk classification was low risk in 89% and intermediate risk in 11%. Iodine-125 sources were used for 161 implants and palladium-103 sources for four implants. The median number of seeds and total activity implanted were 61 and 999 MBq, respectively, for a median prostate volume of 33.6 cc. Late GU and GI morbidity was uncommon. Among patients with at least 24 months followup, 16% had persistent Grade 2-3 urinary morbidity. Grade 2 rectal bleeding occurred in 1 patient (0.6%). Biochemical failure has occurred in only 4 patients at last followup. IO technique for prostate brachytherapy is associated with low rates of late morbidity and excellent early biochemical control. Additionally, the number of seeds and total implanted activity required to achieve a high-quality implant are lower compared with historical controls.

SU-F-T-356: DosimetricComparison of VMAT Vs Step and Shoot IMRT Plans for Stage III Lung CancerPatients with Mediastinal Involvement

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pearson, D; Bogue, J

Purpose: For Stage III lung cancers that entail treatment of some or all of the mediastinum, anterior-posterior focused Step and Shoot IMRT (SS-IMRT) and VMAT plans have been clinically used to deliver the prescribed dose while working to minimize lung dose and avoid other critical structures. A comparison between the two planning methods was completed to see which treatment method is superior and minimizes dose to healthy lung tissue. Methods: Ten patients who were recently treated with SS-IMRT or VMAT plans for Stage III lung cancer with mediastinal involvement were selected. All patients received a simulation CT for treatment planning,more » as well as a 4D CT and PET/CT fusion for target delineation. Plans were prescribed 6250 cGy in 25 fractions and normalized such that 100% of the prescription dose covered 95% of the PTV. Clinically approved SS-IMRT or VMAT plans were then copied and planned using the alternative modality with identical optimization criteria. SS-IMRT plans utilized seven to nine beams distributed around the patient while the VMAT plans consisted of two full 360 degree arcs. Plans were compared for the lung volume receiving 20 Gy (V20). Results: Both SS-IMRT and VMAT can be used to achieve clinical treatment plans for patients with Stage III Lung cancer with targets encompassing the mediastinum. VMAT plans produced an average V20 of 23.0+/−8.3% and SS-IMRT produced an average of 24.2+/−10.0%. Conclusion: Results indicate that either method can achieve comparable dose distributions, however, VMAT can allow the optimizer to distribute dose over paths of minimal lung tissue and reduce the V20. Therefore, creating a VMAT with constraints identical to an SS-IMRT plan could help to reduce the V20 in clinical treatment plans.« less

Image acquisition optimization of a limited-angle intrafraction verification (LIVE) system for lung radiotherapy.

PubMed

Zhang, Yawei; Deng, Xinchen; Yin, Fang-Fang; Ren, Lei

2018-01-01

Limited-angle intrafraction verification (LIVE) has been previously developed for four-dimensional (4D) intrafraction target verification either during arc delivery or between three-dimensional (3D)/IMRT beams. Preliminary studies showed that LIVE can accurately estimate the target volume using kV/MV projections acquired over orthogonal view 30° scan angles. Currently, the LIVE imaging acquisition requires slow gantry rotation and is not clinically optimized. The goal of this study is to optimize the image acquisition parameters of LIVE for different patient respiratory periods and gantry rotation speeds for the effective clinical implementation of the system. Limited-angle intrafraction verification imaging acquisition was optimized using a digital anthropomorphic phantom (XCAT) with simulated respiratory periods varying from 3 s to 6 s and gantry rotation speeds varying from 1°/s to 6°/s. LIVE scanning time was optimized by minimizing the number of respiratory cycles needed for the four-dimensional scan, and imaging dose was optimized by minimizing the number of kV and MV projections needed for four-dimensional estimation. The estimation accuracy was evaluated by calculating both the center-of-mass-shift (COMS) and three-dimensional volume-percentage-difference (VPD) between the tumor in estimated images and the ground truth images. The robustness of LIVE was evaluated with varied respiratory patterns, tumor sizes, and tumor locations in XCAT simulation. A dynamic thoracic phantom (CIRS) was used to further validate the optimized imaging schemes from XCAT study with changes of respiratory patterns, tumor sizes, and imaging scanning directions. Respiratory periods, gantry rotation speeds, number of respiratory cycles scanned and number of kV/MV projections acquired were all positively correlated with the estimation accuracy of LIVE. Faster gantry rotation speed or longer respiratory period allowed less respiratory cycles to be scanned and less kV/MV projections to be acquired to estimate the target volume accurately. Regarding the scanning time minimization, for patient respiratory periods of 3-4 s, gantry rotation speeds of 1°/s, 2°/s, 3-6°/s required scanning of five, four, and three respiratory cycles, respectively. For patient respiratory periods of 5-6 s, the corresponding respiratory cycles required in the scan changed to four, three, and two cycles, respectively. Regarding the imaging dose minimization, for patient respiratory periods of 3-4 s, gantry rotation speeds of 1°/s, 2-4°/s, 5-6°/s required acquiring of 7, 5, 4 kV and MV projections, respectively. For patient respiratory periods of 5-6 s, 5 kV and 5 MV projections are sufficient for all gantry rotation speeds. The optimized LIVE system was robust against breathing pattern, tumor size and tumor location changes. In the CIRS study, the optimized LIVE system achieved the average center-of-mass-shift (COMS)/volume-percentage-difference (VPD) of 0.3 ± 0.1 mm/7.7 ± 2.0% for the scanning time priority case, 0.2 ± 0.1 mm/6.1 ± 1.2% for the imaging dose priority case, respectively, among all gantry rotation speeds tested. LIVE was robust against different scanning directions investigated. The LIVE system has been preliminarily optimized for different patient respiratory periods and treatment gantry rotation speeds using digital and physical phantoms. The optimized imaging parameters, including number of respiratory cycles scanned and kV/MV projection numbers acquired, provide guidelines for optimizing the scanning time and imaging dose of the LIVE system for its future evaluations and clinical implementations through patient studies. © 2017 American Association of Physicists in Medicine.

SU-E-T-06: 4D Particle Swarm Optimization to Enable Lung SBRT in Patients with Central And/or Large Tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Modiri, A; Gu, X; Hagan, A

2015-06-15

Purpose: Patients presenting with large and/or centrally-located lung tumors are currently considered ineligible for highly potent regimens such as SBRT due to concerns of toxicity to normal tissues and organs-at-risk (OARs). We present a particle swarm optimization (PSO)-based 4D planning technique, designed for MLC tracking delivery, that exploits the temporal dimension as an additional degree of freedom to significantly improve OAR-sparing and reduce toxicity to levels clinically considered as acceptable for SBRT administration. Methods: Two early-stage SBRT-ineligible NSCLC patients were considered, presenting with tumors of maximum dimensions of 7.4cm (central-right lobe; 1.5cm motion) and 11.9cm (upper-right lobe; 1cm motion). Inmore » each case, the target and normal structures were manually contoured on each of the ten 4DCT phases. Corresponding ten initial 3D-conformal plans (Pt#1: 7-beams; Pt#2: 9-beams) were generated using the Eclipse planning system. Using 4D-PSO, fluence weights were optimized over all beams and all phases (70 and 90 apertures for Pt1&2, respectively). Doses to normal tissues and OARs were compared with clinicallyestablished lung SBRT guidelines based on RTOG-0236. Results: The PSO-based 4D SBRT plan yielded tumor coverage and dose—sparing for parallel and serial OARs within the SBRT guidelines for both patients. The dose-sparing compared to the clinically-delivered conventionallyfractionated plan for Patient 1 (Patient 2) was: heart Dmean = 11% (33%); lung V20 = 16% (21%); lung Dmean = 7% (20%); spinal cord Dmax = 5% (16%); spinal cord Dmean = 7% (33%); esophagus Dmax = 0% (18%). Conclusion: Truly 4D planning can significantly reduce dose to normal tissues and OARs. Such sparing opens up the possibility of using highly potent and effective regimens such as lung SBRT for patients who were conventionally considered SBRT non-eligible. Given the large, non-convex solution space, PSO represents an attractive, parallelizable tool to successfully achieve a globally optimal solution for this problem. This work was supported through funding from the National Institutes of Health and Varian Medical Systems.« less

Comparing conformal, arc radiotherapy and helical tomotherapy in craniospinal irradiation planning.

PubMed

Myers, Pamela A; Mavroidis, Panayiotis; Papanikolaou, Nikos; Stathakis, Sotirios

2014-09-08

Currently, radiotherapy treatment plan acceptance is based primarily on dosimetric performance measures. However, use of radiobiological analysis to assess benefit in terms of tumor control and harm in terms of injury to normal tissues can be advantageous. For pediatric craniospinal axis irradiation (CSI) patients, in particular, knowing the technique that will optimize the probabilities of benefit versus injury can lead to better long-term outcomes. Twenty-four CSI pediatric patients (median age 10) were retrospectively planned with three techniques: three-dimensional conformal radiation therapy (3D CRT), volumetric-modulated arc therapy (VMAT), and helical tomotherapy (HT). VMAT plans consisted of one superior and one inferior full arc, and tomotherapy plans were created using a 5.02cm field width and helical pitch of 0.287. Each plan was normalized to 95% of target volume (whole brain and spinal cord) receiving prescription dose 23.4Gy in 13 fractions. Using an in-house MATLAB code and DVH data from each plan, the three techniques were evaluated based on biologically effective uniform dose (D=), the complication-free tumor control probability (P+), and the width of the therapeutically beneficial range. Overall, 3D CRT and VMAT plans had similar values of D= (24.1 and 24.2 Gy), while HT had a D= slightly lower (23.6 Gy). The average values of the P+ index were 64.6, 67.4, and 56.6% for 3D CRT, VMAT, and HT plans, respectively, with the VMAT plans having a statistically significant increase in P+. Optimal values of D= were 28.4, 33.0, and 31.9 Gy for 3D CRT, VMAT, and HT plans, respectively. Although P+ values that correspond to the initial dose prescription were lower for HT, after optimizing the D= prescription level, the optimal P+ became 94.1, 99.5, and 99.6% for 3D CRT, VMAT, and HT, respectively, with the VMAT and HT plans having statistically significant increases in P+. If the optimal dose level is prescribed using a radiobiological evaluation method, as opposed to a purely dosimetric one, the two IMRT techniques, VMAT and HT, will yield largest overall benefit to CSI patients by maximizing tumor control and limiting normal tissue injury. Using VMAT or HT may provide these pediatric patients with better long-term outcomes after radiotherapy.

Spot Scanning Proton Therapy for Malignancies of the Base of Skull: Treatment Planning, Acute Toxicities, and Preliminary Clinical Outcomes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grosshans, David R., E-mail: dgrossha@mdanderson.org; Zhu, X. Ronald; Melancon, Adam

2014-11-01

Purpose: To describe treatment planning techniques and early clinical outcomes in patients treated with spot scanning proton therapy for chordoma or chondrosarcoma of the skull base. Methods and Materials: From June 2010 through August 2011, 15 patients were treated with spot scanning proton therapy for chordoma (n=10) or chondrosarcoma (n=5) at a single institution. Toxicity was prospectively evaluated and scored weekly and at all follow-up visits according to Common Terminology Criteria for Adverse Events, version 3.0. Treatment planning techniques and dosimetric data were recorded and compared with those of passive scattering plans created with clinically applicable dose constraints. Results: Tenmore » patients were treated with single-field-optimized scanning beam plans and 5 with multifield-optimized intensity modulated proton therapy. All but 2 patients received a simultaneous integrated boost as well. The mean prescribed radiation doses were 69.8 Gy (relative biological effectiveness [RBE]; range, 68-70 Gy [RBE]) for chordoma and 68.4 Gy (RBE) (range, 66-70) for chondrosarcoma. In comparison with passive scattering plans, spot scanning plans demonstrated improved high-dose conformality and sparing of temporal lobes and brainstem. Clinically, the most common acute toxicities included fatigue (grade 2 for 2 patients, grade 1 for 8 patients) and nausea (grade 2 for 2 patients, grade 1 for 6 patients). No toxicities of grades 3 to 5 were recorded. At a median follow-up time of 27 months (range, 13-42 months), 1 patient had experienced local recurrence and a second developed distant metastatic disease. Two patients had magnetic resonance imaging-documented temporal lobe changes, and a third patient developed facial numbness. No other subacute or late effects were recorded. Conclusions: In comparison to passive scattering, treatment plans for spot scanning proton therapy displayed improved high-dose conformality. Clinically, the treatment was well tolerated, and with short-term follow-up, disease control rates and toxicity profiles were favorable.« less

SU-E-T-424: Dosimetric Verification of Modulated Electron Radiation Therapy Delivered Using An Electron Specific Multileaf Collimator for Treatment of Scalp Cases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eldib, A; Al-Azhar University Cairo; Jin, L

2014-06-01

Purpose: Modulated electron radiotherapy (MERT) has the potential to achieve better treatment outcome for shallow tumors such as those of breast and scalp. In a separate study with scalp lesions, MERT was compared to volumetric modulated arc therapy. Our results showed a reduction in the dose reaching the brain with MERT. However dose calculation accuracy and delivery efficiency challenges remain. Thus in the current study we proceed to add more cases to demonstrate MERT beneficial outcome and its delivery accuracy using an electron specific multileaf collimator (eMLC). Methods: We have used the MCBEAM code for treatment head simulation and formore » generating phase space files to be used as radiation source input for our Monte Carlo based treatment planning system (MC TPS). MCPLAN code is used for calculation of patient specific dose deposition coefficient and for final MERT plan dose calculation. An in-house developed optimization code is used for the optimization process. MERT plans were generated for real patients and head and neck phantom. Film was used for dosimetric verification. The film was cut following the contour of the curved phantom surface and then sealed with black masking tape. In the measurement, the sealed film packet was sandwiched between two adjacent slabs of the head and neck phantom. The measured 2D dose distribution was then compared with calculations. Results: The eMLC allows effective treatment of scalps with multi-lesions spreading around the patient head, which was usually difficult to plan or very time consuming with conventional applicators. MERT continues to show better reduction in the brain dose. The dosimetric measurements showed slight discrepancy, which was attributed to the film setup. Conclusion: MERT can improve treatment plan quality for patients with scalp cancers. Our in-house MC TPS is capable of performing treatment planning and accurate dose calculation for MERT using the eMLC.« less

SU-D-BRC-05: Effects of Motion and Variable RBE in a Lung Patient Treated with Passively Scattered Protons

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mirkovic, D; Titt, U; Mohan, R

2016-06-15

Purpose: To evaluate effects of motion and variable relative biological effectiveness (RBE) in a lung cancer patient treated with passively scattered proton therapy using dose volume histograms associated with patient dose computed using three different methods. Methods: A proton treatment plan of a lung cancer patient optimized using clinical treatment planning system (TPS) was used to construct a detailed Monte Carlo (MC) model of the beam delivery system and the patient specific aperture and compensator. A phase space file containing all particles transported through the beam line was collected at the distal surface of the range compensator and subsequently transportedmore » through two different patient models. The first model was based on the average CT used by the TPS and the second model included all 10 phases of the corresponding 4DCT. The physical dose and proton linear energy transfer (LET) were computed in each voxel of two models and used to compute constant and variable RBE MC dose on average CT and 4D CT. The MC computed doses were compared to the TPS dose using dose volume histograms for relevant structures. Results: The results show significant differences in doses to the target and critical structures suggesting the need for more accurate proton dose computation methods. In particular, the 4D dose shows reduced coverage of the target and higher dose to the spinal cord, while variable RBE dose shows higher lung dose. Conclusion: The methodology developed in this pilot study is currently used for the analysis of a cohort of ∼90 lung patients from a clinical trial comparing proton and photon therapy for lung cancer. The results from this study will help us in determining the clinical significance of more accurate dose computation models in proton therapy.« less

Dose-Finding and Pharmacokinetic Study to Optimize the Dosing of Irinotecan According to the UGT1A1 Genotype of Patients With Cancer

PubMed Central

Innocenti, Federico; Schilsky, Richard L.; Ramírez, Jacqueline; Janisch, Linda; Undevia, Samir; House, Larry K.; Das, Soma; Wu, Kehua; Turcich, Michelle; Marsh, Robert; Karrison, Theodore; Maitland, Michael L.; Salgia, Ravi; Ratain, Mark J.

2014-01-01

Purpose The risk of severe neutropenia from treatment with irinotecan is related in part to UGT1A1*28, a variant that reduces the elimination of SN-38, the active metabolite of irinotecan. We aimed to identify the maximum-tolerated dose (MTD) and dose-limiting toxicity (DLT) of irinotecan in patients with advanced solid tumors stratified by the *1/*1, *1/*28, and *28/*28 genotypes. Patients and Methods Sixty-eight patients received an intravenous flat dose of irinotecan every 3 weeks. Forty-six percent of the patients had the *1/*1 genotype, 41% had the *1/*28 genotype, and 13% had the *28/*28 genotype. The starting dose of irinotecan was 700 mg in patients with the *1/*1 and *1/*28 genotypes and 500 mg in patients with the *28/*28 genotype. Pharmacokinetic evaluation was performed at cycle 1. Results In patients with the *1/*1 genotype, the MTD was 850 mg (four DLTs per 16 patients), and 1,000 mg was not tolerated (two DLTs per six patients). In patients with the *1/*28 genotype, the MTD was 700 mg (five DLTs per 22 patients), and 850 mg was not tolerated (four DLTs per six patients). In patients with the *28/*28 genotype, the MTD was 400 mg (one DLT per six patients), and 500 mg was not tolerated (three DLTs per three patients). The DLTs were mainly myelosuppression and diarrhea. Irinotecan clearance followed linear kinetics. At the MTD for each genotype, dosing by genotype resulted in similar SN-38 areas under the curve (AUCs; r2 = 0.0003; P = .97), but the irinotecan AUC was correlated with the actual dose (r2 = 0.39; P < .001). Four of 48 patients with disease known to be responsive to irinotecan achieved partial response. Conclusion The UGT1A1*28 genotype can be used to individualize dosing of irinotecan. Additional studies should evaluate the effect of genotype-guided dosing on efficacy in patients receiving irinotecan. PMID:24958824

Patient doses from CT examinations in Turkey.

PubMed

Ataç, Gökçe Kaan; Parmaksız, Aydın; İnal, Tolga; Bulur, Emine; Bulgurlu, Figen; Öncü, Tolga; Gündoğdu, Sadi

2015-01-01

We aimed to establish the first diagnostic reference levels (DRLs) for computed tomography (CT) examinations in adult and pediatric patients in Turkey and compare these with international DRLs. CT performance information and examination parameters (for head, chest, high-resolution CT of the chest [HRCT-chest], abdominal, and pelvic protocols) from 1607 hospitals were collected via a survey. Dose length products and effective doses for standard patient sizes were calculated from the reported volume CT dose index (CTDIvol). The median number of protocols reported from the 167 responding hospitals (10% response rate) was 102 across five different age groups. Third quartile CTDIvol values for adult pelvic and all pediatric body protocols were higher than the European Commission standards but were comparable to studies conducted in other countries. The radiation dose indicators for adult patients were similar to those reported in the literature, except for those associated with head protocols. CT protocol optimization is necessary for adult head and pediatric chest, HRCT-chest, abdominal, and pelvic protocols. The findings from this study are recommended for use as national DRLs in Turkey.

Clinical observation of the application of autologous peripheral blood stem cell transplantation for the treatment of diabetic foot gangrene

PubMed Central

XU, SHI-MIN; LIANG, TING

2016-01-01

The aim of the present study was to investigate the optimal mobilization plan in autologous peripheral blood stem cell transplantation for the treatment of diabetic foot and to observe its clinical curative effect. A total of 127 patients with diabetic foot were treated with different doses of granulocyte colony stimulating factor (G-CSF) to mobilize their hematopoietic stem cells. Subsequently, the extracted stem cell suspension was injected into the ischemic lower extremities along the blood vessels in the areas presenting with pathological changes. Following the treatment, the intermittent claudication distance, skin temperature, ankle brachial index and pain scores of the patients were evaluated. In addition, the associations among the mobilization time, doses and peripheral blood CD34+ level were analyzed. The collection efficiency of the stem cells was associated with the dose of G-CSF and the mobilization time. Following the injection of the autologous peripheral blood stem cell suspension, the ischemic area of the patients was improved significantly. In conclusion, autologous peripheral blood stem cell transplantation can promote the establishment of collateral circulation in patients with diabetic foot, and the optimal time for gathering stem cells is closely correlated with the peripheral blood CD34+ level. PMID:26889255

Recommendations for optimizing methotrexate treatment for patients with rheumatoid arthritis

PubMed Central

Bello, Alfonso E; Perkins, Elizabeth L; Jay, Randy; Efthimiou, Petros

2017-01-01

Methotrexate (MTX) remains the cornerstone therapy for patients with rheumatoid arthritis (RA), with well-established safety and efficacy profiles and support in international guidelines. Clinical and radiologic results indicate benefits of MTX monotherapy and combination with other agents, yet patients may not receive optimal dosing, duration, or route of administration to maximize their response to this drug. This review highlights best practices for MTX use in RA patients. First, to improve the response to oral MTX, a high initial dose should be administered followed by rapid titration. Importantly, this approach does not appear to compromise safety or tolerability for patients. Treatment with oral MTX, with appropriate dose titration, then should be continued for at least 6 months (as long as the patient experiences some response to treatment within 3 months) to achieve an accurate assessment of treatment efficacy. If oral MTX treatment fails due to intolerability or inadequate response, the patient may be “rescued” by switching to subcutaneous delivery of MTX. Consideration should also be given to starting with subcutaneous MTX given its favorable bioavailability and pharmacodynamic profile over oral delivery. Either initiation of subcutaneous MTX therapy or switching from oral to subcutaneous administration improves persistence with treatment. Upon transition from oral to subcutaneous delivery, MTX dosage should be maintained, rather than increased, and titration should be performed as needed. Similarly, if another RA treatment is necessary to control the disease, the MTX dosage and route of administration should be maintained, with titration as needed. PMID:28435338

Construction of anthropomorphic hybrid, dual-lattice voxel models for optimizing image quality and dose in radiography

NASA Astrophysics Data System (ADS)

Petoussi-Henss, Nina; Becker, Janine; Greiter, Matthias; Schlattl, Helmut; Zankl, Maria; Hoeschen, Christoph

2014-03-01

In radiography there is generally a conflict between the best image quality and the lowest possible patient dose. A proven method of dosimetry is the simulation of radiation transport in virtual human models (i.e. phantoms). However, while the resolution of these voxel models is adequate for most dosimetric purposes, they cannot provide the required organ fine structures necessary for the assessment of the imaging quality. The aim of this work is to develop hybrid/dual-lattice voxel models (called also phantoms) as well as simulation methods by which patient dose and image quality for typical radiographic procedures can be determined. The results will provide a basis to investigate by means of simulations the relationships between patient dose and image quality for various imaging parameters and develop methods for their optimization. A hybrid model, based on NURBS (Non Linear Uniform Rational B-Spline) and PM (Polygon Mesh) surfaces, was constructed from an existing voxel model of a female patient. The organs of the hybrid model can be then scaled and deformed in a non-uniform way i.e. organ by organ; they can be, thus, adapted to patient characteristics without losing their anatomical realism. Furthermore, the left lobe of the lung was substituted by a high resolution lung voxel model, resulting in a dual-lattice geometry model. "Dual lattice" means in this context the combination of voxel models with different resolution. Monte Carlo simulations of radiographic imaging were performed with the code EGS4nrc, modified such as to perform dual lattice transport. Results are presented for a thorax examination.

Automatic treatment planning facilitates fast generation of high-quality treatment plans for esophageal cancer.

PubMed

Hansen, Christian Rønn; Nielsen, Morten; Bertelsen, Anders Smedegaard; Hazell, Irene; Holtved, Eva; Zukauskaite, Ruta; Bjerregaard, Jon Kroll; Brink, Carsten; Bernchou, Uffe

2017-11-01

The quality of radiotherapy planning has improved substantially in the last decade with the introduction of intensity modulated radiotherapy. The purpose of this study was to analyze the plan quality and efficacy of automatically (AU) generated VMAT plans for inoperable esophageal cancer patients. Thirty-two consecutive inoperable patients with esophageal cancer originally treated with manually (MA) generated volumetric modulated arc therapy (VMAT) plans were retrospectively replanned using an auto-planning engine. All plans were optimized with one full 6MV VMAT arc giving 60 Gy to the primary target and 50 Gy to the elective target. The planning techniques were blinded before clinical evaluation by three specialized oncologists. To supplement the clinical evaluation, the optimization time for the AU plan was recorded along with DVH parameters for all plans. Upon clinical evaluation, the AU plan was preferred for 31/32 patients, and for one patient, there was no difference in the plans. In terms of DVH parameters, similar target coverage was obtained between the two planning methods. The mean dose for the spinal cord increased by 1.8 Gy using AU (p = .002), whereas the mean lung dose decreased by 1.9 Gy (p < .001). The AU plans were more modulated as seen by the increase of 12% in mean MUs (p = .001). The median optimization time for AU plans was 117 min. The AU plans were in general preferred and showed a lower mean dose to the lungs. The automation of the planning process generated esophageal cancer treatment plans quickly and with high quality.

Methotrexate consolidation treatment according to pharmacogenetics of MTHFR ameliorates event-free survival in childhood acute lymphoblastic leukaemia.

PubMed

Salazar, J; Altés, A; del Río, E; Estella, J; Rives, S; Tasso, M; Navajas, A; Molina, J; Villa, M; Vivanco, J L; Torrent, M; Baiget, M; Badell, I

2012-10-01

Recent advances in treatment for childhood acute lymphoblastic leukaemia (ALL) have significantly increased outcome. High-dose methotrexate (MTX) is the most commonly used regimen during the consolidation period, but the optimal dose remains to be defined. We investigated the usefulness of the MTHFR genotype to increase the MTX dosage in the consolidation phase in 141 childhood ALL patients enrolled in the ALL/SHOP-2005 protocol. We also investigated the pharmacogenetic role of polymorphisms in genes involved in MTX metabolism on therapy-related toxicity and survival. Patients with a favourable MTHFR genotype (normal enzymatic activity) treated with MTX doses of 5 g m⁻² had a significantly lower risk of suffering an event than patients with an unfavourable MTHFR genotype (reduced enzymatic activity) that were treated with the classical MTX dose of 3 g m⁻² (P=0.012). Our results indicate that analysis of the MTHFR genotype is a useful tool to optimise MTX therapy in childhood patients with ALL.

Management Strategies to Facilitate Optimal Outcomes for Patients Treated with Delayed-release Dimethyl Fumarate.

PubMed

Mayer, Lori; Fink, Mary Kay; Sammarco, Carrie; Laing, Lisa

2018-04-01

Delayed-release dimethyl fumarate is an oral disease-modifying therapy that has demonstrated significant efficacy in adults with relapsing-remitting multiple sclerosis. Incidences of flushing and gastrointestinal adverse events are common in the first month after delayed-release dimethyl fumarate initiation. Our objective was to propose mitigation strategies for adverse events related to initiation of delayed-release dimethyl fumarate in the treatment of patients with multiple sclerosis. Studies of individually developed mitigation strategies and chart reviews were evaluated. Those results, as well as mitigation protocols developed at multiple sclerosis care centers, are summarized. Key steps to optimize the effectiveness of delayed-release dimethyl fumarate treatment include education prior to and at the time of delayed-release dimethyl fumarate initiation, initiation dose protocol gradually increasing to maintenance dose, dietary suggestions for co-administration with food, gastrointestinal symptom management with over-the-counter medications, flushing symptom management with aspirin, and temporary dose reduction. Using the available evidence from clinical trials and evaluations of post-marketing studies, these strategies to manage gastrointestinal and flushing symptoms can be effective and helpful to the patient when initiating delayed-release dimethyl fumarate.

Patient radiation doses in interventional cardiology in the U.S.: Advisory data sets and possible initial values for U.S. reference levels

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miller, Donald L.; Hilohi, C. Michael; Spelic, David C.

2012-10-15

Purpose: To determine patient radiation doses from interventional cardiology procedures in the U.S and to suggest possible initial values for U.S. benchmarks for patient radiation dose from selected interventional cardiology procedures [fluoroscopically guided diagnostic cardiac catheterization and percutaneous coronary intervention (PCI)]. Methods: Patient radiation dose metrics were derived from analysis of data from the 2008 to 2009 Nationwide Evaluation of X-ray Trends (NEXT) survey of cardiac catheterization. This analysis used deidentified data and did not require review by an IRB. Data from 171 facilities in 30 states were analyzed. The distributions (percentiles) of radiation dose metrics were determined for diagnosticmore » cardiac catheterizations, PCI, and combined diagnostic and PCI procedures. Confidence intervals for these dose distributions were determined using bootstrap resampling. Results: Percentile distributions (advisory data sets) and possible preliminary U.S. reference levels (based on the 75th percentile of the dose distributions) are provided for cumulative air kerma at the reference point (K{sub a,r}), cumulative air kerma-area product (P{sub KA}), fluoroscopy time, and number of cine runs. Dose distributions are sufficiently detailed to permit dose audits as described in National Council on Radiation Protection and Measurements Report No. 168. Fluoroscopy times are consistent with those observed in European studies, but P{sub KA} is higher in the U.S. Conclusions: Sufficient data exist to suggest possible initial benchmarks for patient radiation dose for certain interventional cardiology procedures in the U.S. Our data suggest that patient radiation dose in these procedures is not optimized in U.S. practice.« less

SU-E-T-163: Evaluation of Dose Distributions Recalculated with Per-Field Measurement Data Under the Condition of Respiratory Motion During IMRT for Liver Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Song, J; Yoon, M; Nam, T

2014-06-01

Purpose: The dose distributions within the real volumes of tumor targets and critical organs during internal target volume-based intensity-modulated radiation therapy (ITV-IMRT) for liver cancer were recalculated by applying the effects of actual respiratory organ motion, and the dosimetric features were analyzed through comparison with gating IMRT (Gate-IMRT) plan results. Methods: The 4DCT data for 10 patients who had been treated with Gate-IMRT for liver cancer were selected to create ITV-IMRT plans. The ITV was created using MIM software, and a moving phantom was used to simulate respiratory motion. The period and range of respiratory motion were recorded in allmore » patients from 4DCT-generated movie data, and the same period and range were applied when operating the dynamic phantom to realize coincident respiratory conditions in each patient. The doses were recalculated with a 3 dose-volume histogram (3DVH) program based on the per-field data measured with a MapCHECK2 2-dimensional diode detector array and compared with the DVHs calculated for the Gate-IMRT plan. Results: Although a sufficient prescription dose covered the PTV during ITV-IMRT delivery, the dose homogeneity in the PTV was inferior to that with the Gate-IMRT plan. We confirmed that there were higher doses to the organs-at-risk (OARs) with ITV-IMRT, as expected when using an enlarged field, but the increased dose to the spinal cord was not significant and the increased doses to the liver and kidney could be considered as minor when the reinforced constraints were applied during IMRT plan optimization. Conclusion: Because Gate-IMRT cannot always be considered an ideal method with which to correct the respiratory motional effect, given the dosimetric variations in the gating system application and the increased treatment time, a prior analysis for optimal IMRT method selection should be performed while considering the patient's respiratory condition and IMRT plan results.« less

Dynamic simulation of motion effects in IMAT lung SBRT.

PubMed

Zou, Wei; Yin, Lingshu; Shen, Jiajian; Corradetti, Michael N; Kirk, Maura; Munbodh, Reshma; Fang, Penny; Jabbour, Salma K; Simone, Charles B; Yue, Ning J; Rengan, Ramesh; Teo, Boon-Keng Kevin

2014-11-01

Intensity modulated arc therapy (IMAT) has been widely adopted for Stereotactic Body Radiotherapy (SBRT) for lung cancer. While treatment dose is optimized and calculated on a static Computed Tomography (CT) image, the effect of the interplay between the target and linac multi-leaf collimator (MLC) motion is not well described and may result in deviations between delivered and planned dose. In this study, we investigated the dosimetric consequences of the inter-play effect on target and organs at risk (OAR) by simulating dynamic dose delivery using dynamic CT datasets. Fifteen stage I non-small cell lung cancer (NSCLC) patients with greater than 10 mm tumor motion treated with SBRT in 4 fractions to a dose of 50 Gy were retrospectively analyzed for this study. Each IMAT plan was initially optimized using two arcs. Simulated dynamic delivery was performed by associating the MLC leaf position, gantry angle and delivered beam monitor units (MUs) for each control point with different respiratory phases of the 4D-CT using machine delivery log files containing time stamps of the control points. Dose maps associated with each phase of the 4D-CT dose were calculated in the treatment planning system and accumulated using deformable image registration onto the exhale phase of the 4D-CT. The original IMAT plans were recalculated on the exhale phase of the CT for comparison with the dynamic simulation. The dose coverage of the PTV showed negligible variation between the static and dynamic simulation. There was less than 1.5% difference in PTV V95% and V90%. The average inter-fraction and cumulative dosimetric effects among all the patients were less than 0.5% for PTV V95% and V90% coverage and 0.8 Gy for the OARs. However, in patients where target is close to the organs, large variations were observed on great vessels and bronchus for as much as 4.9 Gy and 7.8 Gy. Limited variation in target dose coverage and OAR constraints were seen for each SBRT fraction as well as over all four fractions. Large dose variations were observed on critical organs in patients where these organs were closer to the target.

Managing toxicities and optimal dosing of targeted drugs in advanced kidney cancer

PubMed Central

Seruga, B.; Gan, H.K.; Knox, J.J.

2009-01-01

The toxicities of new, targeted drugs may diminish their effectiveness in advanced kidney cancer if those toxicities are not recognized and properly addressed early in patient treatment. Most of the drug-related toxicities in advanced kidney cancer are manageable with supportive care, obviating a need for long interruptions, dose reductions, or permanent discontinuation of the treatment. PMID:19478903

Optimizing global liver function in radiation therapy treatment planning

NASA Astrophysics Data System (ADS)

Wu, Victor W.; Epelman, Marina A.; Wang, Hesheng; Romeijn, H. Edwin; Feng, Mary; Cao, Yue; Ten Haken, Randall K.; Matuszak, Martha M.

2016-09-01

Liver stereotactic body radiation therapy (SBRT) patients differ in both pre-treatment liver function (e.g. due to degree of cirrhosis and/or prior treatment) and radiosensitivity, leading to high variability in potential liver toxicity with similar doses. This work investigates three treatment planning optimization models that minimize risk of toxicity: two consider both voxel-based pre-treatment liver function and local-function-based radiosensitivity with dose; one considers only dose. Each model optimizes different objective functions (varying in complexity of capturing the influence of dose on liver function) subject to the same dose constraints and are tested on 2D synthesized and 3D clinical cases. The normal-liver-based objective functions are the linearized equivalent uniform dose (\\ell \\text{EUD} ) (conventional ‘\\ell \\text{EUD} model’), the so-called perfusion-weighted \\ell \\text{EUD} (\\text{fEUD} ) (proposed ‘fEUD model’), and post-treatment global liver function (GLF) (proposed ‘GLF model’), predicted by a new liver-perfusion-based dose-response model. The resulting \\ell \\text{EUD} , fEUD, and GLF plans delivering the same target \\ell \\text{EUD} are compared with respect to their post-treatment function and various dose-based metrics. Voxel-based portal venous liver perfusion, used as a measure of local function, is computed using DCE-MRI. In cases used in our experiments, the GLF plan preserves up to 4.6 % ≤ft(7.5 % \\right) more liver function than the fEUD (\\ell \\text{EUD} ) plan does in 2D cases, and up to 4.5 % ≤ft(5.6 % \\right) in 3D cases. The GLF and fEUD plans worsen in \\ell \\text{EUD} of functional liver on average by 1.0 Gy and 0.5 Gy in 2D and 3D cases, respectively. Liver perfusion information can be used during treatment planning to minimize the risk of toxicity by improving expected GLF; the degree of benefit varies with perfusion pattern. Although fEUD model optimization is computationally inexpensive and often achieves better GLF than \\ell \\text{EUD} model optimization does, the GLF model directly optimizes a more clinically relevant metric and can further improve fEUD plan quality.

A new approach to integrate GPU-based Monte Carlo simulation into inverse treatment plan optimization for proton therapy.

PubMed

Li, Yongbao; Tian, Zhen; Song, Ting; Wu, Zhaoxia; Liu, Yaqiang; Jiang, Steve; Jia, Xun

2017-01-07

Monte Carlo (MC)-based spot dose calculation is highly desired for inverse treatment planning in proton therapy because of its accuracy. Recent studies on biological optimization have also indicated the use of MC methods to compute relevant quantities of interest, e.g. linear energy transfer. Although GPU-based MC engines have been developed to address inverse optimization problems, their efficiency still needs to be improved. Also, the use of a large number of GPUs in MC calculation is not favorable for clinical applications. The previously proposed adaptive particle sampling (APS) method can improve the efficiency of MC-based inverse optimization by using the computationally expensive MC simulation more effectively. This method is more efficient than the conventional approach that performs spot dose calculation and optimization in two sequential steps. In this paper, we propose a computational library to perform MC-based spot dose calculation on GPU with the APS scheme. The implemented APS method performs a non-uniform sampling of the particles from pencil beam spots during the optimization process, favoring those from the high intensity spots. The library also conducts two computationally intensive matrix-vector operations frequently used when solving an optimization problem. This library design allows a streamlined integration of the MC-based spot dose calculation into an existing proton therapy inverse planning process. We tested the developed library in a typical inverse optimization system with four patient cases. The library achieved the targeted functions by supporting inverse planning in various proton therapy schemes, e.g. single field uniform dose, 3D intensity modulated proton therapy, and distal edge tracking. The efficiency was 41.6  ±  15.3% higher than the use of a GPU-based MC package in a conventional calculation scheme. The total computation time ranged between 2 and 50 min on a single GPU card depending on the problem size.

A new approach to integrate GPU-based Monte Carlo simulation into inverse treatment plan optimization for proton therapy

NASA Astrophysics Data System (ADS)

Li, Yongbao; Tian, Zhen; Song, Ting; Wu, Zhaoxia; Liu, Yaqiang; Jiang, Steve; Jia, Xun

2017-01-01

Monte Carlo (MC)-based spot dose calculation is highly desired for inverse treatment planning in proton therapy because of its accuracy. Recent studies on biological optimization have also indicated the use of MC methods to compute relevant quantities of interest, e.g. linear energy transfer. Although GPU-based MC engines have been developed to address inverse optimization problems, their efficiency still needs to be improved. Also, the use of a large number of GPUs in MC calculation is not favorable for clinical applications. The previously proposed adaptive particle sampling (APS) method can improve the efficiency of MC-based inverse optimization by using the computationally expensive MC simulation more effectively. This method is more efficient than the conventional approach that performs spot dose calculation and optimization in two sequential steps. In this paper, we propose a computational library to perform MC-based spot dose calculation on GPU with the APS scheme. The implemented APS method performs a non-uniform sampling of the particles from pencil beam spots during the optimization process, favoring those from the high intensity spots. The library also conducts two computationally intensive matrix-vector operations frequently used when solving an optimization problem. This library design allows a streamlined integration of the MC-based spot dose calculation into an existing proton therapy inverse planning process. We tested the developed library in a typical inverse optimization system with four patient cases. The library achieved the targeted functions by supporting inverse planning in various proton therapy schemes, e.g. single field uniform dose, 3D intensity modulated proton therapy, and distal edge tracking. The efficiency was 41.6  ±  15.3% higher than the use of a GPU-based MC package in a conventional calculation scheme. The total computation time ranged between 2 and 50 min on a single GPU card depending on the problem size.

A New Approach to Integrate GPU-based Monte Carlo Simulation into Inverse Treatment Plan Optimization for Proton Therapy

PubMed Central

Li, Yongbao; Tian, Zhen; Song, Ting; Wu, Zhaoxia; Liu, Yaqiang; Jiang, Steve; Jia, Xun

2016-01-01

Monte Carlo (MC)-based spot dose calculation is highly desired for inverse treatment planning in proton therapy because of its accuracy. Recent studies on biological optimization have also indicated the use of MC methods to compute relevant quantities of interest, e.g. linear energy transfer. Although GPU-based MC engines have been developed to address inverse optimization problems, their efficiency still needs to be improved. Also, the use of a large number of GPUs in MC calculation is not favorable for clinical applications. The previously proposed adaptive particle sampling (APS) method can improve the efficiency of MC-based inverse optimization by using the computationally expensive MC simulation more effectively. This method is more efficient than the conventional approach that performs spot dose calculation and optimization in two sequential steps. In this paper, we propose a computational library to perform MC-based spot dose calculation on GPU with the APS scheme. The implemented APS method performs a non-uniform sampling of the particles from pencil beam spots during the optimization process, favoring those from the high intensity spots. The library also conducts two computationally intensive matrix-vector operations frequently used when solving an optimization problem. This library design allows a streamlined integration of the MC-based spot dose calculation into an existing proton therapy inverse planning process. We tested the developed library in a typical inverse optimization system with four patient cases. The library achieved the targeted functions by supporting inverse planning in various proton therapy schemes, e.g. single field uniform dose, 3D intensity modulated proton therapy, and distal edge tracking. The efficiency was 41.6±15.3% higher than the use of a GPU-based MC package in a conventional calculation scheme. The total computation time ranged between 2 and 50 min on a single GPU card depending on the problem size. PMID:27991456

A Bayesian Dose-finding Design for Oncology Clinical Trials of Combinational Biological Agents

PubMed Central

Cai, Chunyan; Yuan, Ying; Ji, Yuan

2013-01-01

Treating patients with novel biological agents is becoming a leading trend in oncology. Unlike cytotoxic agents, for which efficacy and toxicity monotonically increase with dose, biological agents may exhibit non-monotonic patterns in their dose-response relationships. Using a trial with two biological agents as an example, we propose a dose-finding design to identify the biologically optimal dose combination (BODC), which is defined as the dose combination of the two agents with the highest efficacy and tolerable toxicity. A change-point model is used to reflect the fact that the dose-toxicity surface of the combinational agents may plateau at higher dose levels, and a flexible logistic model is proposed to accommodate the possible non-monotonic pattern for the dose-efficacy relationship. During the trial, we continuously update the posterior estimates of toxicity and efficacy and assign patients to the most appropriate dose combination. We propose a novel dose-finding algorithm to encourage sufficient exploration of untried dose combinations in the two-dimensional space. Extensive simulation studies show that the proposed design has desirable operating characteristics in identifying the BODC under various patterns of dose-toxicity and dose-efficacy relationships. PMID:24511160

SU-E-J-07: IGRT Gently: Evaluating Imaging Dose in Phantoms of Different Sizes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Morris, B; Duggar, W; Stanford, J

Purpose: IGRT imaging procedures have emerged as a common method of patient position verification in radiotherapy, though imaging dose is generally neglected in the treatment plan. Consequently, evaluating and optimizing the dose from these procedures is worthwhile. This process is especially important for children, who are more radiosensitive than adults. The aim of this work was to gain some understanding of the relative doses involved with various XVI-preset parameters for an “adult” and “child” phantom set, with the hopes that imaging dose for a child can be reduced. Methods: 32 and 16cm CTDI-phantoms were used as surrogates for adult andmore » child torsos, respectively. Dose was measured in the central and peripheral chamber positions of the phantoms. CBCT scans were made for both phantoms using Elekta’s Chest-preset to establish a dose baseline. The child-phantom was then scanned using the Elekta Head and Neck (HN) preset. A modified HN-preset (named Peds Abd-pelvis) was also created with a doubled mAs to maintain a reduction in dose to the child-phantom (relative to the baseline), while providing clinically-usable image quality. Results: The baseline dose to the child-phantom from the Chest-preset was 310% that of the adult-phantom for the center chamber position and 150% at the periphery. An average dose reduction of 97% was obtained in the childphantom by switching from the Chest-preset to the HN-preset, while the Peds Abd-pelvis-preset similarly reduced the dose by an average of 92%. Conclusion: XVI-preset parameters significantly affect dose, and should be optimized to reduce dose, while ensuring clinically-usable image quality. Using a modified imaging preset (Peds Abd-pelvis-preset) greatly reduced the dose to the child-phantom compared to the dose for the Chest-preset for both the child and adult-phantoms. This outcome provides support for the development of child-specific protocols for IGRT imaging in pediatric patients.« less

Total body irradiation, toward optimal individual delivery: dose evaluation with metal oxide field effect transistors, thermoluminescence detectors, and a treatment planning system.

PubMed

Bloemen-van Gurp, Esther J; Mijnheer, Ben J; Verschueren, Tom A M; Lambin, Philippe

2007-11-15

To predict the three-dimensional dose distribution of our total body irradiation technique, using a commercial treatment planning system (TPS). In vivo dosimetry, using metal oxide field effect transistors (MOSFETs) and thermoluminescence detectors (TLDs), was used to verify the calculated dose distributions. A total body computed tomography scan was performed and loaded into our TPS, and a three-dimensional-dose distribution was generated. In vivo dosimetry was performed at five locations on the patient. Entrance and exit dose values were converted to midline doses using conversion factors, previously determined with phantom measurements. The TPS-predicted dose values were compared with the MOSFET and TLD in vivo dose values. The MOSFET and TLD dose values agreed within 3.0% and the MOSFET and TPS data within 0.5%. The convolution algorithm of the TPS, which is routinely applied in the clinic, overestimated the dose in the lung region. Using a superposition algorithm reduced the calculated lung dose by approximately 3%. The dose inhomogeneity, as predicted by the TPS, can be reduced using a simple intensity-modulated radiotherapy technique. The use of a TPS to calculate the dose distributions in individual patients during total body irradiation is strongly recommended. Using a TPS gives good insight of the over- and underdosage in a patient and the influence of patient positioning on dose homogeneity. MOSFETs are suitable for in vivo dosimetry purposes during total body irradiation, when using appropriate conversion factors. The MOSFET, TLD, and TPS results agreed within acceptable margins.

Standardization and Optimization of Computed Tomography Protocols to Achieve Low-Dose

PubMed Central

Chin, Cynthia; Cody, Dianna D.; Gupta, Rajiv; Hess, Christopher P.; Kalra, Mannudeep K.; Kofler, James M.; Krishnam, Mayil S.; Einstein, Andrew J.

2014-01-01

The increase in radiation exposure due to CT scans has been of growing concern in recent years. CT scanners differ in their capabilities and various indications require unique protocols, but there remains room for standardization and optimization. In this paper we summarize approaches to reduce dose, as discussed in lectures comprising the first session of the 2013 UCSF Virtual Symposium on Radiation Safety in Computed Tomography. The experience of scanning at low dose in different body regions, for both diagnostic and interventional CT procedures, is addressed. An essential primary step is justifying the medical need for each scan. General guiding principles for reducing dose include tailoring a scan to a patient, minimizing scan length, use of tube current modulation and minimizing tube current, minimizing-tube potential, iterative reconstruction, and periodic review of CT studies. Organized efforts for standardization have been spearheaded by professional societies such as the American Association of Physicists in Medicine. Finally, all team members should demonstrate an awareness of the importance of minimizing dose. PMID:24589403

Noncoplanar VMAT for nasopharyngeal tumors: Plan quality versus treatment time.

PubMed

Wild, Esther; Bangert, Mark; Nill, Simeon; Oelfke, Uwe

2015-05-01

The authors investigated the potential of optimized noncoplanar irradiation trajectories for volumetric modulated arc therapy (VMAT) treatments of nasopharyngeal patients and studied the trade-off between treatment plan quality and delivery time in radiation therapy. For three nasopharyngeal patients, the authors generated treatment plans for nine different delivery scenarios using dedicated optimization methods. They compared these scenarios according to dose characteristics, number of beam directions, and estimated delivery times. In particular, the authors generated the following treatment plans: (1) a 4π plan, which is a not sequenced, fluence optimized plan that uses beam directions from approximately 1400 noncoplanar directions and marks a theoretical upper limit of the treatment plan quality, (2) a coplanar 2π plan with 72 coplanar beam directions as pendant to the noncoplanar 4π plan, (3) a coplanar VMAT plan, (4) a coplanar step and shoot (SnS) plan, (5) a beam angle optimized (BAO) coplanar SnS IMRT plan, (6) a noncoplanar BAO SnS plan, (7) a VMAT plan with rotated treatment couch, (8) a noncoplanar VMAT plan with an optimized great circle around the patient, and (9) a noncoplanar BAO VMAT plan with an arbitrary trajectory around the patient. VMAT using optimized noncoplanar irradiation trajectories reduced the mean and maximum doses in organs at risk compared to coplanar VMAT plans by 19% on average while the target coverage remains constant. A coplanar BAO SnS plan was superior to coplanar SnS or VMAT; however, noncoplanar plans like a noncoplanar BAO SnS plan or noncoplanar VMAT yielded a better plan quality than the best coplanar 2π plan. The treatment plan quality of VMAT plans depended on the length of the trajectory. The delivery times of noncoplanar VMAT plans were estimated to be 6.5 min in average; 1.6 min longer than a coplanar plan but on average 2.8 min faster than a noncoplanar SnS plan with comparable treatment plan quality. The authors' study reconfirms the dosimetric benefits of noncoplanar irradiation of nasopharyngeal tumors. Both SnS using optimized noncoplanar beam ensembles and VMAT using an optimized, arbitrary, noncoplanar trajectory enabled dose reductions in organs at risk compared to coplanar SnS and VMAT. Using great circles or simple couch rotations to implement noncoplanar VMAT, however, was not sufficient to yield meaningful improvements in treatment plan quality. The authors estimate that noncoplanar VMAT using arbitrary optimized irradiation trajectories comes at an increased delivery time compared to coplanar VMAT yet at a decreased delivery time compared to noncoplanar SnS IMRT.

An in vivo investigative protocol for HDR prostate brachytherapy using urethral and rectal thermoluminescence dosimetry.

PubMed

Toye, Warren; Das, Ram; Kron, Tomas; Franich, Rick; Johnston, Peter; Duchesne, Gillian

2009-05-01

To develop an in vivo dosimetry based investigative action level relevant for a corrective protocol for HDR brachytherapy boost treatment. The dose delivered to points within the urethra and rectum was measured using TLD in vivo dosimetry in 56 patients. Comparisons between the urethral and rectal measurements and TPS calculations showed differences, which are related to the relative position of the implant and TLD trains, and allowed shifts of implant position relative to the prostate to be estimated. Analysis of rectal dose measurements is consistent with implant movement, which was previously only identified with the urethral data. Shift corrected doses were compared with results from the TPS. Comparison of peak doses to the urethra and rectum has been assessed against the proposed corrective protocol to limit overdosing these critical structures. An initial investigative level of 20% difference between measured and TPS peak dose was established, which corresponds to 1/3 of patients which was practical for the caseload. These patients were assessed resulting in corrective action being applied for one patient. Multiple triggering for selective investigative action is outlined. The use of a single in vivo measurement in the first fraction optimizes patient benefit at acceptable cost.

VMAT optimization with dynamic collimator rotation.

PubMed

Lyu, Qihui; O'Connor, Daniel; Ruan, Dan; Yu, Victoria; Nguyen, Dan; Sheng, Ke

2018-04-16

Although collimator rotation is an optimization variable that can be exploited for dosimetric advantages, existing Volumetric Modulated Arc Therapy (VMAT) optimization uses a fixed collimator angle in each arc and only rotates the collimator between arcs. In this study, we develop a novel integrated optimization method for VMAT, accounting for dynamic collimator angles during the arc motion. Direct Aperture Optimization (DAO) for Dynamic Collimator in VMAT (DC-VMAT) was achieved by adding to the existing dose fidelity objective an anisotropic total variation term for regulating the fluence smoothness, a binary variable for forming simple apertures, and a group sparsity term for controlling collimator rotation. The optimal collimator angle for each beam angle was selected using the Dijkstra's algorithm, where the node costs depend on the estimated fluence map at the current iteration and the edge costs account for the mechanical constraints of multi-leaf collimator (MLC). An alternating optimization strategy was implemented to solve the DAO and collimator angle selection (CAS). Feasibility of DC-VMAT using one full-arc with dynamic collimator rotation was tested on a phantom with two small spherical targets, a brain, a lung and a prostate cancer patient. The plan was compared against a static collimator VMAT (SC-VMAT) plan using three full arcs with 60 degrees of collimator angle separation in patient studies. With the same target coverage, DC-VMAT achieved 20.3% reduction of R50 in the phantom study, and reduced the average max and mean OAR dose by 4.49% and 2.53% of the prescription dose in patient studies, as compared with SC-VMAT. The collimator rotation co-ordinated with the gantry rotation in DC-VMAT plans for deliverability. There were 13 beam angles in the single-arc DC-VMAT plan in patient studies that requires slower gantry rotation to accommodate multiple collimator angles. The novel DC-VMAT approach utilizes the dynamic collimator rotation during arc delivery. In doing so, DC-VMAT affords more sophisticated intensity modulation, alleviating the limitation previously imposed by the square beamlet from the MLC leaf thickness and achieves higher effective modulation resolution. Consequently, DC-VMAT with a single arc manages to achieve superior dosimetry than SC-VMAT with three full arcs. © 2018 American Association of Physicists in Medicine.

American Brachytherapy Society consensus report for accelerated partial breast irradiation using interstitial multicatheter brachytherapy.

PubMed

Hepel, Jaroslaw T; Arthur, Douglas; Shaitelman, Simona; Polgár, Csaba; Todor, Dorin; Zoberi, Imran; Kamrava, Mitchell; Major, Tibor; Yashar, Catheryn; Wazer, David E

To develop a consensus report for the quality practice of accelerated partial breast irradiation (APBI) using interstitial multicatheter brachytherapy (IMB). The American Brachytherapy Society Board appointed an expert panel with clinical and research experience with breast brachytherapy to provide guidance for the current practice of IMB. This report is based on a comprehensive literature review with emphasis on randomized data and expertise of the panel. Randomized trials have demonstrated equivalent efficacy of APBI using IMB compared with whole breast irradiation for select patients with early-stage breast cancer. Several techniques for placement of interstitial catheters are described, and importance of three-dimensional planning with appropriate optimization is reviewed. Optimal target definition is outlined. Commonly used dosing schemas include 50 Gy delivered in pulses of 0.6-0.8 Gy/h using pulsed-dose-rate technique and 34 Gy in 10 fractions, 32 Gy in eight fractions, or 30 Gy in seven fractions using high-dose-rate technique. Potential toxicities and strategies for toxicity avoidance are described in detail. Dosimetric constraints include limiting whole breast volume that receives ≥50% of prescription dose to <60%, skin dose to ≤100% of prescription dose (≤60-70% preferred), chest wall dose to ≤125% of prescription dose, Dose Homogeneity Index to >0.75 (>0.85 preferred), V 150  < 45 cc, and V 200  < 14 cc. Using an optimal implant technique coupled with optimal planning and appropriate dose constraints, a low rate of toxicity and a good-to-excellent cosmetic outcome of ≥90% is expected. IMB is an effective technique to deliver APBI for appropriately selected women with early-stage breast cancer. This consensus report has been created to assist clinicians in the appropriate practice of APBI using IMB. Copyright © 2017 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Patient specific optimization-based treatment planning for catheter-based ultrasound hyperthermia and thermal ablation

NASA Astrophysics Data System (ADS)

Prakash, Punit; Chen, Xin; Wootton, Jeffery; Pouliot, Jean; Hsu, I.-Chow; Diederich, Chris J.

2009-02-01

A 3D optimization-based thermal treatment planning platform has been developed for the application of catheter-based ultrasound hyperthermia in conjunction with high dose rate (HDR) brachytherapy for treating advanced pelvic tumors. Optimal selection of applied power levels to each independently controlled transducer segment can be used to conform and maximize therapeutic heating and thermal dose coverage to the target region, providing significant advantages over current hyperthermia technology and improving treatment response. Critical anatomic structures, clinical target outlines, and implant/applicator geometries were acquired from sequential multi-slice 2D images obtained from HDR treatment planning and used to reconstruct patient specific 3D biothermal models. A constrained optimization algorithm was devised and integrated within a finite element thermal solver to determine a priori the optimal applied power levels and the resulting 3D temperature distributions such that therapeutic heating is maximized within the target, while placing constraints on maximum tissue temperature and thermal exposure of surrounding non-targeted tissue. This optimizationbased treatment planning and modeling system was applied on representative cases of clinical implants for HDR treatment of cervix and prostate to evaluate the utility of this planning approach. The planning provided significant improvement in achievable temperature distributions for all cases, with substantial increase in T90 and thermal dose (CEM43T90) coverage to the hyperthermia target volume while decreasing maximum treatment temperature and reducing thermal dose exposure to surrounding non-targeted tissues and thermally sensitive rectum and bladder. This optimization based treatment planning platform with catheter-based ultrasound applicators is a useful tool that has potential to significantly improve the delivery of hyperthermia in conjunction with HDR brachytherapy. The planning platform has been extended to model thermal ablation, including the addition of temperature dependent attenuation, perfusion, and tissue damage. Pilot point control at the target boundaries was implemented to control power delivery to each transducer section, simulating an approach feasible for MR guided procedures. The computer model of thermal ablation was evaluated on representative patient anatomies to demonstrate the feasibility of using catheter-based ultrasound thermal ablation for treatment of benign prostate hyperplasia (BPH) and prostate cancer, and to assist in designing applicators and treatment delivery strategies.

Development of light ion therapy at the Karolinska Hospital and Institute.

PubMed

Svensson, Hans; Ringborg, Ulrik; Näslund, Ingemar; Brahme, Anders

2004-12-01

Recent developments in radiation therapy have made it possible to optimize the high dose region to cover almost any target volume and shape at the same time as the dose level to adjacent organs at risk is acceptable. Further implementations of IMRT (Intensity Modulated Radiation Therapy), and inverse treatment planning using already available technologies but also foreseeable improved design of therapy accelerators delivering electron- and photon beams, will bring these advances to the benefit of a broad population of cancer patients. Protons will therefore generally not be needed since in most situations the improvement will be insignificant or moderate due to the large lateral penumbra with deep proton therapy. A further step would be to use He-ions, which have only half the penumbra width of protons and still a fairly low-LET in the spread-out Bragg peak. There is however still a group of patients that cannot be helped by these advances as the tumor might be radioresistant for the presently utilized low ionization density beam qualities. The ultimate step in the therapy development process should therefore be to optimize the beam quality for each tumor-normal tissue situation. To facilitate beam quality optimization light ions are needed. It is argued that in many radioresistant tumors a dose-mean LET of 25-50 eV/nm in the target would be optimum as then tumor cells will be lost in the highest proportion through apoptotic cell kill and the superficial tissues will still be irradiated with a fairly low LET. Light ions using Li, Be, B, and C would then be the ideal choice. In this paper a light ion facility is outlined for the Karolinska University Hospital facilitating both dose distribution and beam quality optimization.

Real-time computed tomography dosimetry during ultrasound-guided brachytherapy for prostate cancer.

PubMed

Kaplan, Irving D; Meskell, Paul; Oldenburg, Nicklas E; Saltzman, Brian; Kearney, Gary P; Holupka, Edward J

2006-01-01

Ultrasound-guided implantation of permanent radioactive seeds is a treatment option for localized prostate cancer. Several techniques have been described for the optimal placement of the seeds in the prostate during this procedure. Postimplantation dosimetric calculations are performed after the implant. Areas of underdosing can only be corrected with either an external beam boost or by performing a second implant. We demonstrate the feasibility of performing computed tomography (CT)-based postplanning during the ultrasound-guided implant and subsequently correcting for underdosed areas. Ultrasound-guided brachytherapy is performed on a modified CT table with general anesthesia. The postplanning CT scan is performed after the implant, while the patient is still under anesthesia. Additional seeds are implanted into "cold spots," and the resultant dosimetry confirmed with CT. Intraoperative postplanning was successfully performed. Dose-volume histograms demonstrated adequate dose coverage during the initial implant, but on detailed analysis, for some patients, areas of underdosing were observed either at the apex or the peripheral zone. Additional seeds were implanted to bring these areas to prescription dose. Intraoperative postplanning is feasible during ultrasound-guided brachytherapy for prostate cancer. Although the postimplant dose-volume histograms for all patients, before the implantation of additional seeds, were adequate according to the American Brachytherapy Society criteria, specific critical areas can be underdosed. Additional seeds can then be implanted to optimize the dosimetry and reduce the risk of underdosing areas of cancer.

Spatiotemporal Fractionation Schemes for Irradiating Large Cerebral Arteriovenous Malformations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Unkelbach, Jan, E-mail: junkelbach@mgh.harvard.edu; Bussière, Marc R.; Chapman, Paul H.

2016-07-01

Purpose: To optimally exploit fractionation effects in the context of radiosurgery treatments of large cerebral arteriovenous malformations (AVMs). In current practice, fractionated treatments divide the dose evenly into several fractions, which generally leads to low obliteration rates. In this work, we investigate the potential benefit of delivering distinct dose distributions in different fractions. Methods and Materials: Five patients with large cerebral AVMs were reviewed and replanned for intensity modulated arc therapy delivered with conventional photon beams. Treatment plans allowing for different dose distributions in all fractions were obtained by performing treatment plan optimization based on the cumulative biologically effective dosemore » delivered at the end of treatment. Results: We show that distinct treatment plans can be designed for different fractions, such that high single-fraction doses are delivered to complementary parts of the AVM. All plans create a similar dose bath in the surrounding normal brain and thereby exploit the fractionation effect. This partial hypofractionation in the AVM along with fractionation in normal brain achieves a net improvement of the therapeutic ratio. We show that a biological dose reduction of approximately 10% in the healthy brain can be achieved compared with reference treatment schedules that deliver the same dose distribution in all fractions. Conclusions: Boosting complementary parts of the target volume in different fractions may provide a therapeutic advantage in fractionated radiosurgery treatments of large cerebral AVMs. The strategy allows for a mean dose reduction in normal brain that may be valuable for a patient population with an otherwise normal life expectancy.« less

SU-F-J-178: A Computer Simulation Model Observer for Task-Based Image Quality Assessment in Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dolly, S; Mutic, S; Anastasio, M

Purpose: Traditionally, image quality in radiation therapy is assessed subjectively or by utilizing physically-based metrics. Some model observers exist for task-based medical image quality assessment, but almost exclusively for diagnostic imaging tasks. As opposed to disease diagnosis, the task for image observers in radiation therapy is to utilize the available images to design and deliver a radiation dose which maximizes patient disease control while minimizing normal tissue damage. The purpose of this study was to design and implement a new computer simulation model observer to enable task-based image quality assessment in radiation therapy. Methods: A modular computer simulation framework wasmore » developed to resemble the radiotherapy observer by simulating an end-to-end radiation therapy treatment. Given images and the ground-truth organ boundaries from a numerical phantom as inputs, the framework simulates an external beam radiation therapy treatment and quantifies patient treatment outcomes using the previously defined therapeutic operating characteristic (TOC) curve. As a preliminary demonstration, TOC curves were calculated for various CT acquisition and reconstruction parameters, with the goal of assessing and optimizing simulation CT image quality for radiation therapy. Sources of randomness and bias within the system were analyzed. Results: The relationship between CT imaging dose and patient treatment outcome was objectively quantified in terms of a singular value, the area under the TOC (AUTOC) curve. The AUTOC decreases more rapidly for low-dose imaging protocols. AUTOC variation introduced by the dose optimization algorithm was approximately 0.02%, at the 95% confidence interval. Conclusion: A model observer has been developed and implemented to assess image quality based on radiation therapy treatment efficacy. It enables objective determination of appropriate imaging parameter values (e.g. imaging dose). Framework flexibility allows for incorporation of additional modules to include any aspect of the treatment process, and therefore has great potential for both assessment and optimization within radiation therapy.« less

SU-F-J-214: Dose Reduction by Spatially Optimized Image Quality Via Fluence Modulated Proton CT (FMpCT)

DOE Office of Scientific and Technical Information (OSTI.GOV)

De Angelis, L; Landry, G; Dedes, G

Purpose: Proton CT (pCT) is a promising imaging modality for reducing range uncertainty in image-guided proton therapy. Range uncertainties partially originate from X-ray CT number conversion to stopping power ratio (SPR) and are limiting the exploitation of the full potential of proton therapy. In this study we explore the concept of spatially dependent fluence modulated proton CT (FMpCT), for achieving optimal image quality in a clinical region of interest (ROI), while reducing significantly the imaging dose to the patient. Methods: The study was based on simulated ideal pCT using pencil beam (PB) scanning. A set of 250 MeV protons PBsmore » was used to create 360 projections of a cylindrical water phantom and a head and neck cancer patient. The tomographic images were reconstructed using a filtered backprojection (FBP) as well as an iterative algorithm (ITR). Different fluence modulation levels were investigated and their impact on the image was quantified in terms of SPR accuracy as well as noise within and outside selected ROIs, as a function of imaging dose. The unmodulated image served as reference. Results: Both FBP reconstruction and ITR without total variation (TV) yielded image quality in the ROIs similar to the reference images, for modulation down to 0.1 of the full proton fluence. The average dose was reduced by 75% for the water phantom and by 40% for the patient. FMpCT does not improve the noise for ITR with TV and modulation 0.1. Conclusion: This is the first work proposing and investigating FMpCT for producing optimal image quality for treatment planning and image guidance, while simultaneously reducing imaging dose. Future work will address spatial resolution effects and the impact of FMpCT on the quality of proton treatment plans for a prototype pCT scanner capable of list mode data acquisition. Acknowledgement: DFG-MAP DFG - Munich-Centre for Advanced Photonics (MAP)« less

Detection of anatomical changes in lung cancer patients with 2D time-integrated, 2D time-resolved and 3D time-integrated portal dosimetry: a simulation study

NASA Astrophysics Data System (ADS)

Wolfs, Cecile J. A.; Brás, Mariana G.; Schyns, Lotte E. J. R.; Nijsten, Sebastiaan M. J. J. G.; van Elmpt, Wouter; Scheib, Stefan G.; Baltes, Christof; Podesta, Mark; Verhaegen, Frank

2017-08-01

The aim of this work is to assess the performance of 2D time-integrated (2D-TI), 2D time-resolved (2D-TR) and 3D time-integrated (3D-TI) portal dosimetry in detecting dose discrepancies between the planned and (simulated) delivered dose caused by simulated changes in the anatomy of lung cancer patients. For six lung cancer patients, tumor shift, tumor regression and pleural effusion are simulated by modifying their CT images. Based on the modified CT images, time-integrated (TI) and time-resolved (TR) portal dose images (PDIs) are simulated and 3D-TI doses are calculated. The modified and original PDIs and 3D doses are compared by a gamma analysis with various gamma criteria. Furthermore, the difference in the D 95% (ΔD 95%) of the GTV is calculated and used as a gold standard. The correlation between the gamma fail rate and the ΔD 95% is investigated, as well the sensitivity and specificity of all combinations of portal dosimetry method, gamma criteria and gamma fail rate threshold. On the individual patient level, there is a correlation between the gamma fail rate and the ΔD 95%, which cannot be found at the group level. The sensitivity and specificity analysis showed that there is not one combination of portal dosimetry method, gamma criteria and gamma fail rate threshold that can detect all simulated anatomical changes. This work shows that it will be more beneficial to relate portal dosimetry and DVH analysis on the patient level, rather than trying to quantify a relationship for a group of patients. With regards to optimizing sensitivity and specificity, different combinations of portal dosimetry method, gamma criteria and gamma fail rate should be used to optimally detect certain types of anatomical changes.

A Clinical Concept for Interfractional Adaptive Radiation Therapy in the Treatment of Head and Neck Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jensen, Alexandra D., E-mail: Alexandra.Jensen@med.uni-heidelberg.de; Nill, Simeon; Huber, Peter E.

Purpose: To present an approach to fast, interfractional adaptive RT in intensity-modulated radiation therapy (IMRT) of head and neck tumors in clinical routine. Ensuring adequate patient position throughout treatment proves challenging in high-precision RT despite elaborate immobilization. Because of weight loss, treatment plans must be adapted to account for requiring supportive therapy incl. feeding tube or parenteral nutrition without treatment breaks. Methods and Materials: In-room CT position checks are used to create adapted IMRT treatment plans by stereotactic correlation to the initial setup, and volumes are adapted to the new geometry. New IMRT treatment plans are prospectively created on themore » basis of position control scans using the initial optimization parameters in KonRad without requiring complete reoptimization and thus facilitating quick replanning in daily routine. Patients treated for squamous cell head and neck cancer (SCCHN) in 2006-2007 were evaluated as to necessity/number of replannings, weight loss, dose, and plan parameters. Results: Seventy-two patients with SCCHN received IMRT to the primary site and lymph nodes (median dose 70.4 Gy). All patients received concomitant chemotherapy requiring supportive therapy by feeding tube or parenteral nutrition. Median weight loss was 7.8 kg, median volume loss was approximately 7%. Fifteen of 72 patients required adaptation of their treatment plans at least once. Target coverage was improved by up to 10.7% (median dose). The increase of dose to spared parotid without replanning was 11.7%. Replanning including outlining and optimization was feasible within 2 hours for each patient, and treatment could be continued without any interruptions. Conclusion: To preserve high-quality dose application, treatment plans must be adapted to anatomical changes. Replanning based on position control scans therefore presents a practical approach in clinical routine. In the absence of clinically usable online correction methods, this approach allows significant improvement of target volume coverage and continuous parotid sparing without treatment delays.« less

A clinical concept for interfractional adaptive radiation therapy in the treatment of head and neck cancer.

PubMed

Jensen, Alexandra D; Nill, Simeon; Huber, Peter E; Bendl, Rolf; Debus, Jürgen; Münter, Marc W

2012-02-01

To present an approach to fast, interfractional adaptive RT in intensity-modulated radiation therapy (IMRT) of head and neck tumors in clinical routine. Ensuring adequate patient position throughout treatment proves challenging in high-precision RT despite elaborate immobilization. Because of weight loss, treatment plans must be adapted to account for requiring supportive therapy incl. feeding tube or parenteral nutrition without treatment breaks. In-room CT position checks are used to create adapted IMRT treatment plans by stereotactic correlation to the initial setup, and volumes are adapted to the new geometry. New IMRT treatment plans are prospectively created on the basis of position control scans using the initial optimization parameters in KonRad without requiring complete reoptimization and thus facilitating quick replanning in daily routine. Patients treated for squamous cell head and neck cancer (SCCHN) in 2006-2007 were evaluated as to necessity/number of replannings, weight loss, dose, and plan parameters. Seventy-two patients with SCCHN received IMRT to the primary site and lymph nodes (median dose 70.4 Gy). All patients received concomitant chemotherapy requiring supportive therapy by feeding tube or parenteral nutrition. Median weight loss was 7.8 kg, median volume loss was approximately 7%. Fifteen of 72 patients required adaptation of their treatment plans at least once. Target coverage was improved by up to 10.7% (median dose). The increase of dose to spared parotid without replanning was 11.7%. Replanning including outlining and optimization was feasible within 2 hours for each patient, and treatment could be continued without any interruptions. To preserve high-quality dose application, treatment plans must be adapted to anatomical changes. Replanning based on position control scans therefore presents a practical approach in clinical routine. In the absence of clinically usable online correction methods, this approach allows significant improvement of target volume coverage and continuous parotid sparing without treatment delays. Copyright © 2012 Elsevier Inc. All rights reserved.

Detection of anatomical changes in lung cancer patients with 2D time-integrated, 2D time-resolved and 3D time-integrated portal dosimetry: a simulation study.

PubMed

Wolfs, Cecile J A; Brás, Mariana G; Schyns, Lotte E J R; Nijsten, Sebastiaan M J J G; van Elmpt, Wouter; Scheib, Stefan G; Baltes, Christof; Podesta, Mark; Verhaegen, Frank

2017-07-12

The aim of this work is to assess the performance of 2D time-integrated (2D-TI), 2D time-resolved (2D-TR) and 3D time-integrated (3D-TI) portal dosimetry in detecting dose discrepancies between the planned and (simulated) delivered dose caused by simulated changes in the anatomy of lung cancer patients. For six lung cancer patients, tumor shift, tumor regression and pleural effusion are simulated by modifying their CT images. Based on the modified CT images, time-integrated (TI) and time-resolved (TR) portal dose images (PDIs) are simulated and 3D-TI doses are calculated. The modified and original PDIs and 3D doses are compared by a gamma analysis with various gamma criteria. Furthermore, the difference in the D 95% (ΔD 95% ) of the GTV is calculated and used as a gold standard. The correlation between the gamma fail rate and the ΔD 95% is investigated, as well the sensitivity and specificity of all combinations of portal dosimetry method, gamma criteria and gamma fail rate threshold. On the individual patient level, there is a correlation between the gamma fail rate and the ΔD 95% , which cannot be found at the group level. The sensitivity and specificity analysis showed that there is not one combination of portal dosimetry method, gamma criteria and gamma fail rate threshold that can detect all simulated anatomical changes. This work shows that it will be more beneficial to relate portal dosimetry and DVH analysis on the patient level, rather than trying to quantify a relationship for a group of patients. With regards to optimizing sensitivity and specificity, different combinations of portal dosimetry method, gamma criteria and gamma fail rate should be used to optimally detect certain types of anatomical changes.

Accounting for patient size in the optimization of dose and image quality of pelvis cone beam CT protocols on the Varian OBI system

PubMed Central

Moore, Craig S; Horsfield, Carl J; Saunderson, John R; Beavis, Andrew W

2015-01-01

Objective: The purpose of this study was to develop size-based radiotherapy kilovoltage cone beam CT (CBCT) protocols for the pelvis. Methods: Image noise was measured in an elliptical phantom of varying size for a range of exposure factors. Based on a previously defined “small pelvis” reference patient and CBCT protocol, appropriate exposure factors for small, medium, large and extra-large patients were derived which approximate the image noise behaviour observed on a Philips CT scanner (Philips Medical Systems, Best, Netherlands) with automatic exposure control (AEC). Selection criteria, based on maximum tube current–time product per rotation selected during the radiotherapy treatment planning scan, were derived based on an audit of patient size. Results: It has been demonstrated that 110 kVp yields acceptable image noise for reduced patient dose in pelvic CBCT scans of small, medium and large patients, when compared with manufacturer's default settings (125 kVp). Conversely, extra-large patients require increased exposure factors to give acceptable images. 57% of patients in the local population now receive much lower radiation doses, whereas 13% require higher doses (but now yield acceptable images). Conclusion: The implementation of size-based exposure protocols has significantly reduced radiation dose to the majority of patients with no negative impact on image quality. Increased doses are required on the largest patients to give adequate image quality. Advances in knowledge: The development of size-based CBCT protocols that use the planning CT scan (with AEC) to determine which protocol is appropriate ensures adequate image quality whilst minimizing patient radiation dose. PMID:26419892

Statistical model based iterative reconstruction in clinical CT systems. Part III. Task-based kV/mAs optimization for radiation dose reduction

PubMed Central

Li, Ke; Gomez-Cardona, Daniel; Hsieh, Jiang; Lubner, Meghan G.; Pickhardt, Perry J.; Chen, Guang-Hong

2015-01-01

Purpose: For a given imaging task and patient size, the optimal selection of x-ray tube potential (kV) and tube current-rotation time product (mAs) is pivotal in achieving the maximal radiation dose reduction while maintaining the needed diagnostic performance. Although contrast-to-noise (CNR)-based strategies can be used to optimize kV/mAs for computed tomography (CT) imaging systems employing the linear filtered backprojection (FBP) reconstruction method, a more general framework needs to be developed for systems using the nonlinear statistical model-based iterative reconstruction (MBIR) method. The purpose of this paper is to present such a unified framework for the optimization of kV/mAs selection for both FBP- and MBIR-based CT systems. Methods: The optimal selection of kV and mAs was formulated as a constrained optimization problem to minimize the objective function, Dose(kV,mAs), under the constraint that the achievable detectability index d′(kV,mAs) is not lower than the prescribed value of d℞′ for a given imaging task. Since it is difficult to analytically model the dependence of d′ on kV and mAs for the highly nonlinear MBIR method, this constrained optimization problem is solved with comprehensive measurements of Dose(kV,mAs) and d′(kV,mAs) at a variety of kV–mAs combinations, after which the overlay of the dose contours and d′ contours is used to graphically determine the optimal kV–mAs combination to achieve the lowest dose while maintaining the needed detectability for the given imaging task. As an example, d′ for a 17 mm hypoattenuating liver lesion detection task was experimentally measured with an anthropomorphic abdominal phantom at four tube potentials (80, 100, 120, and 140 kV) and fifteen mA levels (25 and 50–700) with a sampling interval of 50 mA at a fixed rotation time of 0.5 s, which corresponded to a dose (CTDIvol) range of [0.6, 70] mGy. Using the proposed method, the optimal kV and mA that minimized dose for the prescribed detectability level of d℞′=16 were determined. As another example, the optimal kV and mA for an 8 mm hyperattenuating liver lesion detection task were also measured using the developed framework. Both an in vivo animal and human subject study were used as demonstrations of how the developed framework can be applied to the clinical work flow. Results: For the first task, the optimal kV and mAs were measured to be 100 and 500, respectively, for FBP, which corresponded to a dose level of 24 mGy. In comparison, the optimal kV and mAs for MBIR were 80 and 150, respectively, which corresponded to a dose level of 4 mGy. The topographies of the iso-d′ map and the iso-CNR map were the same for FBP; thus, the use of d′- and CNR-based optimization methods generated the same results for FBP. However, the topographies of the iso-d′ and iso-CNR map were significantly different in MBIR; the CNR-based method overestimated the performance of MBIR, predicting an overly aggressive dose reduction factor. For the second task, the developed framework generated the following optimization results: for FBP, kV = 140, mA = 350, dose = 37.5 mGy; for MBIR, kV = 120, mA = 250, dose = 18.8 mGy. Again, the CNR-based method overestimated the performance of MBIR. Results of the preliminary in vivo studies were consistent with those of the phantom experiments. Conclusions: A unified and task-driven kV/mAs optimization framework has been developed in this work. The framework is applicable to both linear and nonlinear CT systems such as those using the MBIR method. As expected, the developed framework can be reduced to the conventional CNR-based kV/mAs optimization frameworks if the system is linear. For MBIR-based nonlinear CT systems, however, the developed task-based kV/mAs optimization framework is needed to achieve the maximal dose reduction while maintaining the desired diagnostic performance. PMID:26328971

SU-E-I-54: Effective Dose and Radiation Cancer Risks for Scoliosis Patients Undergoing Full Spine Radiography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, Y; Hwang, Y; Tsai, H

2015-06-15

Purpose: Scoliotic patients underwent a lot of radiologic examinations during the control and treatment periods. This study used the PCXMC program to calculate the effective dose of the patients and assess the radiation cancer risks. Methods: Seventy five scoliotic patients were examined using CR or DR systems during the control and treatment periods in Chang Gung Memorial Hospital. The technical factors were recorded for each patient during his/her control and treatment period. The entrance surface dose was measured using thermoluminence dosimeters and derived from technical factors and irradiated geometry. The effective dose of patients and relative radiation cancer risks weremore » calculated by the PCXMC program. All required information regarding patient age and sex, the x-ray spectra, and the tube voltage and current were registered. The radiation risk were estimated using the model developed by the BEIR VII committee (2006). Results: The effective doses of full spine radiography with anteroposterior and lateral projections were 0.626 mSv for patients using DR systems, and 0.483mSv for patients using CR systems, respectively. The dose using DR system was 29.6% higher than those using CR system. The maximum organ dose was observed in the breast for both projections in all the systems. The risk of exposure—induced cancer death (REID) of patients for DR and CR systems were 0.009% and 0.007%, respectively. Conclusion: The risk estimates were regarded with healthy skepticism, placed more emphasis on the magnitude of the risk. The effective doses estimated in this study could be served as a reference for radiologists and technologists and demonstrate the necessity to optimize patient protection for full spine radiography though the effective doses are not at the level to induce deterministic effects and not significant in the stochastic effect. This study was supported by the grants from the Chang Gung Memorial Hospital (CMRPD1D0421)« less

An information and communication technology-based centralized clinical trial to determine the efficacy and safety of insulin dose adjustment education based on a smartphone personal health record application: a randomized controlled trial.

PubMed

Kim, Gyuri; Bae, Ji Cheol; Yi, Byoung Kee; Hur, Kyu Yeon; Chang, Dong Kyung; Lee, Moon-Kyu; Kim, Jae Hyeon; Jin, Sang-Man

2017-07-18

A Personal Health Record (PHR) is an online application that allows patients to access, manage, and share their health data. PHRs not only enhance shared decision making with healthcare providers, but also enable remote monitoring and at-home-collection of detailed data. The benefits of PHRs can be maximized in insulin dose adjustment for patients starting or intensifying insulin regimens, as frequent self-monitoring of glucose, self-adjustment of insulin dose, and precise at-home data collection during the visit-to-visit period are important for glycemic control. The aim of this study is to examine the efficacy and safety of insulin dose adjustment based on a smartphone PHR application in patients with diabetes mellitus (DM) and to confirm the validity and stability of an information and communication technology (ICT)-based centralized clinical trial monitoring system. This is a 24-week, open-label, randomized, multi-center trial. There are three follow-up measures: baseline, post-intervention at week 12, and at week 24. Subjects diagnosed with type 1 DM, type 2 DM, and/or post-transplant DM who initiate basal insulin or intensify their insulin regimen to a basal-bolus regimen are included. After education on insulin dose titration and prevention for hypoglycemia and a 1-week acclimation period, subjects are randomized in a 1:1 ratio to either an ICT-based intervention group or a conventional intervention group. Subjects in the conventional intervention group will save and send their health information to the server via a PHR application, whereas those in ICT-based intervention group will receive additional algorithm-based feedback messages. The health information includes level of blood glucose, insulin dose, details on hypoglycemia, food diary, and step count. The primary outcome will be the proportion of patients who reach an optimal insulin dose within 12 weeks of study enrollment, without severe hypoglycemia or unscheduled clinic visits. This clinical trial will reveal whether insulin dose adjustment based on a smartphone PHR application can facilitate the optimization of insulin doses in patients with DM. In addition, the process evaluation will provide information about the validity and stability of the ICT-based centralized clinical trial monitoring system in this research field. Clinicaltrials.gov NCT 03112343 . Registered on 12 April 2017.

SU-E-T-250: New IMRT Sequencing Strategy: Towards Intra-Fraction Plan Adaptation for the MR-Linac

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kontaxis, C; Bol, G; Lagendijk, J

2014-06-01

Purpose: To develop a new sequencer for IMRT planning that during treatment makes the inclusion of external factors possible and by doing so accounts for intra-fraction anatomy changes. Given a real-time imaging modality that will provide the updated patient anatomy during delivery, this sequencer is able to take these changes into account during the calculation of subsequent segments. Methods: Pencil beams are generated for each beam angle of the treatment and a fluence optimization is performed. The pencil beams, together with the patient anatomy and the above optimal fluence form the input of our algorithm. During each iteration the followingmore » steps are performed: A fluence optimization is done and each beam's fluence is then split to discrete intensity levels. Deliverable segments are calculated for each one of these. Each segment's area multiplied by its intensity describes its efficiency. The most efficient segment among all beams is then chosen to deliver a part of the calculated fluence and the dose that will be delivered by this segment is calculated. This delivered dose is then subtracted from the remaining dose. This loop is repeated until 90% of the dose has been delivered and a final segment weight optimization is performed to reach full convergence. Results: This algorithm was tested in several prostate cases yielding results that meet all clinical constraints. Quality assurance was performed on Delta4 and film phantoms for one of these prostate cases and received clinical acceptance after passing both gamma analyses with the 3%/3mm criteria. Conclusion: A new sequencing algorithm was developed to facilitate the needs of intensity modulated treatment. The first results on static anatomy confirm that it can calculate clinical plans equivalent to those of the commercially available planning systems. We are now working towards 100% dose convergence which will allow us to handle anatomy deformations. This work is financially supported by Elekta AB, Stockholm, Sweden.« less

SU-D-BRB-04: Plan Quality Comparison of Intracranial Stereotactic Radiosurgery (SRS) for Gamma Knife and VMAT Treatments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Keeling, V; Algan, O; Ahmad, S

2015-06-15

Purpose: To compare treatment plan quality of intracranial stereotactic radiosurgery (SRS) for VMAT (RapidArc) and Gamma Knife (GK) systems. Methods: Ten patients with 24 tumors (seven with 1–2 and three with 4–6 lesions), previously treated with GK 4C (prescription doses ranging from 14–23 Gy) were re-planned for RapidArc. Identical contour sets were kept on MRI images for both plans with tissues assigned a CT number of zero. RapidArc plans were performed using 6 MV flattening-filter-free (FFF) beams with dose rate of 1400 MU/minute using two to eight arcs with the following combinations: 2 full coplanar arcs and the rest non-coplanarmore » half arcs. Beam selection was based on target depth. Areas that penetrated more than 10 cm of tissue were avoided by creating smaller arcs or using avoidance sectors in optimization. Plans were optimized with jaw tracking and a high weighting to the normal-brain-tissue and Normal-Tissue-Objective without compromising PTV coverage. Plans were calculated on a 1 mm grid size using AAA algorithm and then normalized so that 99% of each target volume received the prescription dose. Plan quality was assessed by target coverage using Paddick Conformity Index (PCI), sparing of normal-brain-tissue through analysis of V4, V8, and V12 Gy, and integral dose. Results: In all cases critical structure dose criteria were met. RapidArc had a higher PCI than GK plans for 23 out of 24 lesions. The average PCI was 0.76±0.21 for RapidArc and 0.46±0.20 for GK plans (p≤0.001), respectively. Integral dose and normal-brain-tissue doses for all criteria were lower for RapidArc in nearly all patients. The average ratio of GK to RapidArc plans was 1.28±0.27 (p=0.018), 1.31±0.25 (p=0.017), 1.81±0.43 (p=0.005), and 1.50±0.61 (p=0.006) for V4, V8, and V12 Gy, and integral dose, respectively. Conclusion: VMAT was capable of producing higher quality treatment plans than GK when using optimal beam geometries and proper optimization techniques.« less

SU-E-J-193: Feasibility of MRI-Only Based IMRT Planning for Pancreatic Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prior, P; Botros, M; Chen, X

2014-06-01

Purpose: With the increasing use of MRI simulation and the advent of MRI-guided delivery, it is desirable to use MRI only for treatment planning. In this study, we assess the dosimetric difference between MRI- and CTbased IMRT planning for pancreatic cancer. Methods: Planning CTs and MRIs acquired for a representative pancreatic cancer patient were used. MRI-based planning utilized forced relative electron density (rED) assignment of organ specific values from IRCU report 46, where rED = 1.029 for PTV and a rED = 1.036 for non-specified tissue (NST). Six IMRT plans were generated with clinical dose-volume (DV) constraints using a researchmore » Monaco planning system employing Monte Carlo dose calculation with optional perpendicular magnetic field (MF) of 1.5T. The following five plans were generated and compared with the planning CT: 1.) CT plan with MF and dose recalculation without optimization; 2.) MRI (T2) plan with target and OARs redrawn based on MRI, forced rED, no MF, and recalculation without optimization; 3.) Similar as in 2 but with MF; 4.) MRI plan with MF but without optimization; and 5.) Similar as in 4 but with optimization. Results: Generally, noticeable differences in PTV point doses and DV parameters (DVPs) between the CT-and MRI-based plans with and without the MF were observed. These differences between the optimized plans were generally small, mostly within 2%. Larger differences were observed in point doses and mean doses for certain OARs between the CT and MRI plan, mostly due to differences between image acquisition times. Conclusion: MRI only based IMRT planning for pancreatic cancer is feasible. The differences observed between the optimized CT and MRI plans with or without the MF were practically negligible if excluding the differences between MRI and CT defined structures.« less

Dosimetry during intramedullary nailing of the tibia

PubMed Central

2009-01-01

Background Intramedullary nailing under fluoroscopic guidance is a common operation. We studied the intraoperative radiation dose received by both the patient and the personnel. Patients and methods 25 intramedullary nailing procedures of the tibia were studied. All patients suffered from tibial fractures and were treated using the Grosse-Kempf intramedullary nail, with free-hand technique for fixation of the distal screws, under fluoroscopic guidance. The exposure, at selected positions, was recorded using an ion chamber, while the dose area product (DAP) was measured with a DAP meter, attached to the tube head. Thermoluminescent dosimeters (TLDs) were used to derive the occupational dose to the personnel, and also to monitor the surface dose on the gonads of some of the patients. Results The mean operation time was 101 (48–240) min, with a mean fluoroscopic time of 72 seconds and a mean DAP value of 75 cGy·cm2. The surface dose to the gonads of the patients was less than 8.8 mGy during any procedure, and thus cannot be considered to be a contraindication for the use of this technique. Occupational dose differed substantially between members of the operating personnel, the maximum dose recorded being to the operator of the fluoroscopic equipment (0.11 mSv). Interpretation Our findings underscore the care required by the primary operator not to exceed the dose constraint of 10 mSv per year. The rest of the operating personnel, although they do not receive very high doses, should focus on the dose optimization of the technique. PMID:19916691

Lens dose in routine head CT: comparison of different optimization methods with anthropomorphic phantoms.

PubMed

Nikupaavo, Ulla; Kaasalainen, Touko; Reijonen, Vappu; Ahonen, Sanna-Mari; Kortesniemi, Mika

2015-01-01

The purpose of this study was to study different optimization methods for reducing eye lens dose in head CT. Two anthropomorphic phantoms were scanned with a routine head CT protocol for evaluation of the brain that included bismuth shielding, gantry tilting, organ-based tube current modulation, or combinations of these techniques. Highsensitivity metal oxide semiconductor field effect transistor dosimeters were used to measure local equivalent doses in the head region. The relative changes in image noise and contrast were determined by ROI analysis. The mean absorbed lens doses varied from 4.9 to 19.7 mGy and from 10.8 to 16.9 mGy in the two phantoms. The most efficient method for reducing lens dose was gantry tilting, which left the lenses outside the primary radiation beam, resulting in an approximately 75% decrease in lens dose. Image noise decreased, especially in the anterior part of the brain. The use of organ-based tube current modulation resulted in an approximately 30% decrease in lens dose. However, image noise increased as much as 30% in the posterior and central parts of the brain. With bismuth shields, it was possible to reduce lens dose as much as 25%. Our results indicate that gantry tilt, when possible, is an effective method for reducing exposure of the eye lenses in CT of the brain without compromising image quality. Measurements in two different phantoms showed how patient geometry affects the optimization. When lenses can only partially be cropped outside the primary beam, organ-based tube current modulation or bismuth shields can be useful in lens dose reduction.

Estimating cancer risk from dental cone-beam CT exposures based on skin dosimetry

NASA Astrophysics Data System (ADS)

Pauwels, Ruben; Cockmartin, Lesley; Ivanauskaité, Deimante; Urbonienė, Ausra; Gavala, Sophia; Donta, Catherine; Tsiklakis, Kostas; Jacobs, Reinhilde; Bosmans, Hilde; Bogaerts, Ria; Horner, Keith; SEDENTEXCT Project Consortium, The

2014-07-01

The aim of this study was to measure entrance skin doses on patients undergoing cone-beam computed tomography (CBCT) examinations, to establish conversion factors between skin and organ doses, and to estimate cancer risk from CBCT exposures. 266 patients (age 8-83) were included, involving three imaging centres. CBCT scans were acquired using the SCANORA 3D (Soredex, Tuusula, Finland) and NewTom 9000 (QR, Verona, Italy). Eight thermoluminescent dosimeters were attached to the patient's skin at standardized locations. Using previously published organ dose estimations on various CBCTs with an anthropomorphic phantom, correlation factors to convert skin dose to organ doses were calculated and applied to estimate patient organ doses. The BEIR VII age- and gender-dependent dose-risk model was applied to estimate the lifetime attributable cancer risk. For the SCANORA 3D, average skin doses over the eight locations varied between 484 and 1788 µGy. For the NewTom 9000 the range was between 821 and 1686 µGy for Centre 1 and between 292 and 2325 µGy for Centre 2. Entrance skin dose measurements demonstrated the combined effect of exposure and patient factors on the dose. The lifetime attributable cancer risk, expressed as the probability to develop a radiation-induced cancer, varied between 2.7 per million (age >60) and 9.8 per million (age 8-11) with an average of 6.0 per million. On average, the risk for female patients was 40% higher. The estimated radiation risk was primarily influenced by the age at exposure and the gender, pointing out the continuing need for justification and optimization of CBCT exposures, with a specific focus on children.

Intensity-Modulated Radiotherapy of Head and Neck Cancer Aiming to Reduce Dysphagia: Early Dose-Effect Relationships for the Swallowing Structures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Feng, Felix Y.; Kim, Hyungjin M.; Lyden, Teresa H.

2007-08-01

Purpose: To present initial results of a clinical trial of intensity-modulated radiotherapy (IMRT) aiming to spare the swallowing structures whose dysfunction after chemoradiation is a likely cause of dysphagia and aspiration, without compromising target doses. Methods and Materials: This was a prospective, longitudinal study of 36 patients with Stage III-IV oropharyngeal (31) or nasopharyngeal (5) cancer. Definitive chemo-IMRT spared salivary glands and swallowing structures: pharyngeal constrictors (PC), glottic and supraglottic larynx (GSL), and esophagus. Lateral but not medial retropharyngeal nodes were considered at risk. Dysphagia endpoints included objective swallowing dysfunction (videofluoroscopy), and both patient-reported and observer-rated scores. Correlations between dosesmore » and changes in these endpoints from pre-therapy to 3 months after therapy were assessed. Results: Significant correlations were observed between videofluoroscopy-based aspirations and the mean doses to the PC and GSL, as well as the partial volumes of these structures receiving 50-65 Gy; the highest correlations were associated with doses to the superior PC (p = 0.005). All patients with aspirations received mean PC doses >60 Gy or PC V{sub 65} >50%, and GSL V{sub 50} >50%. Reduced laryngeal elevation and epiglottic inversion were correlated with mean PC and GSL doses (p < 0.01). All 3 patients with strictures had PC V{sub 70} >50%. Worsening patient-reported liquid swallowing was correlated with mean PC (p = 0.05) and esophageal (p 0.02) doses. Only mean PC doses were correlated with worsening patient-reported solid swallowing (p = 0.04) and observer-rated swallowing scores (p = 0.04). Conclusions: These dose-volume-effect relationships provide initial IMRT optimization goals and motivate further efforts to reduce swallowing structures doses to reduce dysphagia and aspiration.« less

[Baseline characteristics and changes in treatment after a period of optimization of the patients included in the study EFICAR].

PubMed

Gómez-Marcos, Manuel A; Agudo-Conde, Cristina; Torcal, Jesús; Echevarria, Pilar; Domingo, Mar; Arietaleanizbeascoa, María; Sanz-Guinea, Aitor; de la Torre, Maria M; Ramírez, Jose I; García-Ortiz, Luis

2016-03-01

To describe the baseline date and drugs therapy changes during treatment optimization in patients with heart failure with depressed systolic function included in the EFICAR study. Multicenter randomized clinical trial. Seven Health Centers. 150 patients (ICFSD) age 68±10 years, 77% male. Sociodemographic variables, comorbidities (Charlson index), functional capacity and quality of life. Drug therapy optimization was performed. The main etiology was ischemic heart disease (45%), with 89% in functional class II. The Charlson index was 2.03±1.05. The ejection fraction mean was 37%±8, 19% with ejection fraction <30%. With the stress test 6.3±1.6 mean was reached, with the 6 minutes test 446±78 meters and the chair test 13.7±4.4 seconds. The overall quality of life with ejection fraction was 22.8±18.7 and with the Short Form-36 Health Survey, physical health 43.3±8.4 and mental health 50.1±10.6. After optimizing the treatment, the percentage of patients on drugs therapy and the dose of angiotensin converting enzyme inhibitors, angiotensin II receptor antagonists and beta-blockers were not changed. The majority of the subjects are in functional class II, with functional capacity and quality of life decreased and comorbidity index high. A protocolized drug therapy adjustment did not increase the dose or number of patients with effective drugs for heart failure with depressed systolic function. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

Medical and occupational dose reduction in pediatric barium meal procedures

NASA Astrophysics Data System (ADS)

Filipov, D.; Schelin, H. R.; Denyak, V.; Paschuk, S. A.; Ledesma, J. A.; Legnani, A.; Bunick, A. P.; Sauzen, J.; Yagui, A.; Vosiak, P.

2017-11-01

Doses received in pediatric Barium Meal procedure can be rather high. It is possible to reduce dose values following the recommendations of the European Communities (EC) and the International Commission on Radiological Protection (ICRP). In the present work, the modifications of radiographic techniques made in a Brazilian hospital according to the EC and the ICRP recommendations and their influence on medical and occupational exposure are reported. The procedures of 49 patients before and 44 after the optimization were studied and air kerma-area product (PK,A) values and the effective doses were evaluated. The occupational equivalent doses were measured next to the eyes, under the thyroid shield and on each hand of both professionals who remained inside the examination room. The implemented modifications reduced by 70% and 60% the PK,A and the patient effective dose, respectively. The obtained dose values are lower than approximately 75% of the results from similar studies. The occupational annual equivalent doses for all studied organs became lower than the limits set by the ICRP. The equivalent doses in one examination were on average below than 75% of similar studies.

Optimal dose of hyperbaric bupivacaine 0.5% for unilateral spinal anesthesia during diagnostic knee arthroscopy

PubMed Central

Atef, HM; El-Kasaby, AM; Omera, MA; Badr, MD

2010-01-01

Objective To determine the dose of hyperbaric bupivacaine 0.5% required for unilateral spinal anesthesia during diagnostic knee arthroscopy. Patients and methods This prospective, randomized, clinical study was performed in 80 patients who were assigned to four groups to receive different doses of intrathecal hyperbaric bupivacaine (5 mg, 7.5 mg, 10 mg and 12.5 mg in Groups 1, 2, 3, and 4 respectively). Onset of sensory and motor block, hemodynamic changes, regression of motor block, and incidence of complications were recorded. Results Unilateral sensory block was reported in 90% and 85% of patients in Group 1 and Group 2, respectively, but not in any patient in Group 3 and Group 4. Unilateral motor block (modified Bromage scale 0) was reported in 95% of patients in Group 1, 90% in Group 2, and only 5% in Group 3, while no patient in Group 4 showed unilateral motor block. The time required for regression of motor block (Bromage scale 0) was prolonged with higher doses. The incidence of nausea, vomiting, and urine retention was similar in the study groups. Conclusion Unilateral sensory and motor block can be achieved with doses of 5 mg and 7.5 mg hyperbaric bupivacaine 0.5% with a stable hemodynamic state. However, 7.5 mg of hyperbaric bupivacaine 0.5% was the dose required for adequate unilateral spinal anesthesia. PMID:22915874

Determinants of amikacin first peak concentration in critically ill patients.

PubMed

Boidin, Clément; Jenck, Sophie; Bourguignon, Laurent; Torkmani, Sejad; Roussey-Jean, Aurore; Ledochowski, Stanislas; Marry, Lucie; Ammenouche, Nacim; Dupont, Hervé; Marçon, Frédéric; Allaouchiche, Bernard; Bohé, Julien; Lepape, Alain; Goutelle, Sylvain; Friggeri, Arnaud

2018-04-16

Amikacin antimicrobial effect has been correlated with the ratio of the peak concentration (C max ) to the minimum inhibitory concentration. A target C max ≥ 60-80 mg/L has been suggested. It has been shown that such target is not achieved in a large proportion of critically ill patients in intensive care units. A retrospective analysis was performed to examine the determinants of C max ≥ 80 mg/L on the first peak in 339 critically ill patients treated by amikacin. The influence of available variables on C max target attainment was analyzed using a classification and regression tree (CART) and logistic regression. Mean C max in the 339 patients was 73.0 ± 23.9 mg/L, with a target attainment rate (TAR, C max ≥ 80 mg/L) of 37.5%. In CART analysis, the strongest predictor of amikacin target peak attainment was dose per kilogram of lean body weight (dose/LBW). TAR was 60.1% in patients with dose/LBW ≥ 37.8 vs. 19.9% in patients with lower dose/LBW (OR = 6.0 (95% CI: 3.6-10.2)). Renal function was a secondary predictor of C max . Logistic regression analysis identified dose per kilogram of ideal body weight (OR = 1.13 (95% CI: 1.09-1.17)) and creatinine clearance (OR = 0.993 (95% CI: 0.988-0.998)) as predictors of target peak achievement. Based on our results, an amikacin dose ≥ 37.8 mg/kg of LBW should be used to optimize the attainment of C max ≥ 80 mg/L after the first dose in critically ill patients. An even higher dose may be necessary in patients with normal renal function. © 2018 Société Française de Pharmacologie et de Thérapeutique.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ju, N; Chen, C; Gans, S

Purpose: A fixed-beam room could be underutilized in a multi-room proton center. We investigated the use of proton pencil beam scanning (PBS) on a fixed-beam as an alternative for posterior fossa tumor bed (PF-TB) boost treatments which were usually treating on a gantry with uniform scanning. Methods: Five patients were treated with craniospinal irradiation (CSI, 23.4 or 36.0 Gy(RBE)) followed by a PF-TB boost to 54 Gy(RBE) with proton beams. Three PF-TB boost plans were generated for each patient: (1) a uniform scanning (US) gantry plan with 4–7 posterior fields shaped with apertures and compensators (2) a PBS plan usingmore » bi-lateral and vertex fields with a 3-mm planning organ-at-risk volume (PRV) expansion around the brainstem and (3) PBS fields using same beam arrangement but replacing the PRV with robust optimization considering a 3-mm setup uncertainty. Results: A concave 54-Gy(RBE) isodose line surrounding the brainstem could be achieved using all three techniques. The mean V95% of the PTV was 99.7% (range: 97.6% to 100%) while the V100% of the PTV ranged from 56.3% to 93.1% depending on the involvement of the brainstem with the PTV. The mean doses received by 0.05 cm{sup 3} of the brainstem were effectively identical: 54.0 Gy(RBE), 53.4 Gy(RBE) and 53.3 Gy(RBE) for US, PBS optimized with PRV, and PBS optimized with robustness plans respectively. The cochlea mean dose increased by 23% of the prescribed boost dose in average from the bi-lateral fields used in the PBS plan. Planning time for the PBS plan with PRV was 5–10 times less than the US plan and the robustly optimized PBS plan. Conclusion: We have demonstrated that a fixed-beam with PBS can deliver a dose distribution comparable to a gantry plan using uniform scanning. Planning time can be reduced substantially using a PRV around the brainstem instead of robust optimization.« less

A novel method for the evaluation of uncertainty in dose-volume histogram computation.

PubMed

Henríquez, Francisco Cutanda; Castrillón, Silvia Vargas

2008-03-15

Dose-volume histograms (DVHs) are a useful tool in state-of-the-art radiotherapy treatment planning, and it is essential to recognize their limitations. Even after a specific dose-calculation model is optimized, dose distributions computed by using treatment-planning systems are affected by several sources of uncertainty, such as algorithm limitations, measurement uncertainty in the data used to model the beam, and residual differences between measured and computed dose. This report presents a novel method to take them into account. To take into account the effect of associated uncertainties, a probabilistic approach using a new kind of histogram, a dose-expected volume histogram, is introduced. The expected value of the volume in the region of interest receiving an absorbed dose equal to or greater than a certain value is found by using the probability distribution of the dose at each point. A rectangular probability distribution is assumed for this point dose, and a formulation that accounts for uncertainties associated with point dose is presented for practical computations. This method is applied to a set of DVHs for different regions of interest, including 6 brain patients, 8 lung patients, 8 pelvis patients, and 6 prostate patients planned for intensity-modulated radiation therapy. Results show a greater effect on planning target volume coverage than in organs at risk. In cases of steep DVH gradients, such as planning target volumes, this new method shows the largest differences with the corresponding DVH; thus, the effect of the uncertainty is larger.

Dosimetry during intramedullary nailing of the tibia.

PubMed

Kirousis, George; Delis, Harry; Megas, Panagiotis; Lambiris, Elias; Panayiotakis, George

2009-10-01

Intramedullary nailing under fluoroscopic guidance is a common operation. We studied the intraoperative radiation dose received by both the patient and the personnel. 25 intramedullary nailing procedures of the tibia were studied. All patients suffered from tibial fractures and were treated using the Grosse-Kempf intramedullary nail, with free-hand technique for fixation of the distal screws, under fluoroscopic guidance. The exposure, at selected positions, was recorded using an ion chamber, while the dose area product (DAP) was measured with a DAP meter, attached to the tube head. Thermoluminescent dosimeters (TLDs) were used to derive the occupational dose to the personnel, and also to monitor the surface dose on the gonads of some of the patients. The mean operation time was 101 (48-240) min, with a mean fluoroscopic time of 72 seconds and a mean DAP value of 75 cGy x cm(2). The surface dose to the gonads of the patients was less than 8.8 mGy during any procedure, and thus cannot be considered to be a contraindication for the use of this technique. Occupational dose differed substantially between members of the operating personnel, the maximum dose recorded being to the operator of the fluoroscopic equipment (0.11 mSv). Our findings underscore the care required by the primary operator not to exceed the dose constraint of 10 mSv per year. The rest of the operating personnel, although they do not receive very high doses, should focus on the dose optimization of the technique.

Is It Better to Enter a Volume CT Dose Index Value before or after Scan Range Adjustment for Radiation Dose Optimization of Pediatric Cardiothoracic CT with Tube Current Modulation?

PubMed Central

2018-01-01

Objective To determine whether the body size-adapted volume computed tomography (CT) dose index (CTDvol) in pediatric cardiothoracic CT with tube current modulation is better to be entered before or after scan range adjustment for radiation dose optimization. Materials and Methods In 83 patients, cardiothoracic CT with tube current modulation was performed with the body size-adapted CTDIvol entered after (group 1, n = 42) or before (group 2, n = 41) scan range adjustment. Patient-related, radiation dose, and image quality parameters were compared and correlated between the two groups. Results The CTDIvol after the CT scan in group 1 was significantly higher than that in group 2 (1.7 ± 0.1 mGy vs. 1.4 ± 0.3 mGy; p < 0.0001). Image noise (4.6 ± 0.5 Hounsfield units [HU] vs. 4.5 ± 0.7 HU) and image quality (1.5 ± 0.6 vs. 1.5 ± 0.6) showed no significant differences between the two (p > 0.05). In both groups, all patient-related parameters, except body density, showed positive correlations (r = 0.49–0.94; p < 0.01) with the CTDIvol before and after the CT scan. The CTDIvol after CT scan showed modest positive correlation (r = 0.49; p ≤ 0.001) with image noise in group 1 but no significant correlation (p > 0.05) in group 2. Conclusion In pediatric cardiothoracic CT with tube current modulation, the CTDIvol entered before scan range adjustment provides a significant dose reduction (18%) with comparable image quality compared with that entered after scan range adjustment.

The Creating an Optimal Warfarin Nomogram (CROWN) Study

PubMed Central

Perlstein, Todd S.; Goldhaber, Samuel Z.; Nelson, Kerrie; Joshi, Victoria; Morgan, T. Vance; Lesko, Lawrence J.; Lee, Joo-Yeon; Gobburu, Jogarao; Schoenfeld, David; Kucherlapati, Raju; Freeman, Mason W.; Creager, Mark A.

2014-01-01

A significant proportion of warfarin dose variability is explained by variation in the genotypes of the cytochrome P450 CYP2C9 and the vitamin K epoxide reductase complex, VKORC1, enzymes that influence warfarin metabolism and sensitivity, respectively. We sought to develop an optimal pharmacogenetic warfarin dosing algorithm that incorporated clinical and genetic information. We enroled patients initiating warfarin therapy. Genotyping was performed of the VKORC1, –1639G>A, the CYP2C9*2, 430C>T, and the CYP2C9*3, 1075C>A genotypes. The initial warfarin dosing algorithm (Algorithm A) was based upon established clinical practice and published warfarin pharmacogenetic information. Subsequent dosing algorithms (Algorithms B and Algorithm C) were derived from pharmacokinetic / pharmacodynamic (PK/PD) modelling of warfarin dose, international normalised ratio (INR), clinical and genetic factors from patients treated by the preceding algorithm(s). The primary outcome was the time in the therapeutic range, considered an INR of 1.8 to 3.2. A total of 344 subjects are included in the study analyses. The mean percentage time within the therapeutic range for each subject increased progressively from Algorithm A to Algorithm C from 58.9 (22.0), to 59.7 (23.0), to 65.8 (16.9) percent (p = 0.04). Improvement also occurred in most secondary endpoints, which included the per-patient percentage of INRs outside of the therapeutic range (p = 0.004), the time to the first therapeutic INR (p = 0.07), and the time to achieve stable therapeutic anticoagulation (p < 0.001). In conclusion, warfarin pharmacogenetic dosing can be optimised in real time utilising observed PK/PD information in an adaptive fashion. Clinical Trial Registration ClinicalTrials.gov (NCT00401414) PMID:22116191

Simultaneous assay of multiple antibiotics in human plasma by LC-MS/MS: importance of optimizing formic acid concentration.

PubMed

Chen, Feng; Hu, Zhe-Yi; Laizure, S Casey; Hudson, Joanna Q

2017-03-01

Optimal dosing of antibiotics in critically ill patients is complicated by the development of resistant organisms requiring treatment with multiple antibiotics and alterations in systemic exposure due to diseases and extracorporeal drug removal. Developing guidelines for optimal antibiotic dosing is an important therapeutic goal requiring robust analytical methods to simultaneously measure multiple antibiotics. An LC-MS/MS assay using protein precipitation for cleanup followed by a 6-min gradient separation was developed to simultaneously determine five antibiotics in human plasma. The precision and accuracy were within the 15% acceptance range. The formic acid concentration was an important determinant of signal intensity, peak shape and matrix effects. The method was designed to be simple and successfully applied to a clinical pharmacokinetic study.

Factors associated with the immune response to hepatitis A vaccination in HIV-infected patients in the era of highly active antiretroviral therapy.

PubMed

Mena, Guillermo; García-Basteiro, Alberto L; Llupià, Anna; Díez, Consolación; Costa, Josep; Gatell, Josep-María; García, Felipe; Bayas, José-María

2013-08-12

HIV seropositivity is considered a risk factor for complications in hepatitis A virus (HAV) infection. HAV vaccination schedules are widely implemented in HIV-infected patients, but the immune response remains impaired. We analysed the response to vaccination (antiHAV titres ≥20IU/l) in 282 HIV-infected patients included in a standard (1440 Elisa Units (EU) at 0, 6 months) or rapidly accelerated schedule (720 EU at 0, 7, 21 days and 6 months) between 1997 and 2009. Factors associated with the response to vaccination were analysed using logistic regression. The overall response rate was 73.4%. Male sex (OR: 0.16, 95% CI 0.05-0.51) and hepatitis C virus co-infection (OR: 0.30, 95% CI 0.14-0.74) were associated with a lower probability of response. Protective antibody response was associated with a higher CD4/CD8 ratio (OR: 3.69, 95% CI 1.3-10.5) and having received two doses of standard schedule (compared with patients receiving only one dose of the same schedule) (OR: 2.51, 95% CI 1.22-5.15). Three doses of the rapidly accelerated schedule were not more effective than a single dose of 1440 EU (OR: 1.32, 95% CI 0.48-3.63). The low responses observed in patients receiving a single dose suggest the need to emphasize adhesion to vaccination protocols to avoid failure. The CD4/CD8 ratio may be considered as an immune status marker which could help to better choose the moment of vaccination. Our findings underscore the importance of identifying strategies that optimize the timing and effectiveness of hepatitis A vaccination in HIV-infected patients and of the need for further studies on individual factors such as sex and hepatitis C co-infection that may affect the response to vaccination. Likewise, the sub-optimal effectiveness of three doses of 720 EU in the rapidly accelerated schedule, if confirmed in future studies, might lead to a revision of the current schedule recommended for HIV-infected travellers. Copyright © 2013 Elsevier Ltd. All rights reserved.

Osimertinib Western and Asian clinical pharmacokinetics in patients and healthy volunteers: implications for formulation, dose, and dosing frequency in pivotal clinical studies.

PubMed

Planchard, David; Brown, Kathryn H; Kim, Dong-Wan; Kim, Sang-We; Ohe, Yuichiro; Felip, Enriqueta; Leese, Philip; Cantarini, Mireille; Vishwanathan, Karthick; Jänne, Pasi A; Ranson, Malcolm; Dickinson, Paul A

2016-04-01

Osimertinib (AZD9291) 80 mg once daily is approved by the US FDA for the treatment of patients with metastatic EGFR T790M-positive NSCLC whose disease has previously progressed on EGFR-TKI therapy. Osimertinib PK was evaluated to define the dose and dosing interval, whether a fixed-dosing approach can be used globally, and the impact of formulation and food on exposure. AURA (NCT01802632): single- and multiple-dose PK of osimertinib (20-240 mg daily) was determined in patients with advanced NSCLC. Bioavailability study (NCT01951599): single-dose PK of osimertinib (20 mg) was determined in healthy volunteers with administration of capsule, solution, or tablet formulations fasted, and as a tablet in the fed and fasted state. Osimertinib was slowly absorbed and displayed dose-proportional increases in exposure from 20 to 240 mg. Distribution was extensive and clearance low to moderate, resulting in a mean half-life of 48.3 h. Steady state was achieved by 15 days of dosing, consistent with single-dose PK, with a peak-to-trough ratio of 1.6. Two active metabolites circulated at ~10 % of osimertinib exposure. Ethnicity did not appear to affect exposure. Osimertinib PK profiles in healthy volunteers were similar to those in patients and were unaffected by formulation. Food caused a clinically insignificant increase in exposure. Osimertinib PK supports once-daily dosing; the same dose for Asian and non-Asian populations; a fixed-dosing approach; a minimal effect of food on exposure; and a switch to tablet formulation without alteration to dose or schedule. Osimertinib plasma concentrations are sustained throughout the dosing period, which is considered optimal for efficacy.

Evaluation of optimal parameters for using low-dose computed tomography to diagnose urolithiasis

NASA Astrophysics Data System (ADS)

Chen, Hui-Hsien; Yu, Cheng-Ching; Hsu, Fang-Yuh

2017-11-01

Urolithiasis is a common disease; patients suspected of suffering from urolithiasis will be examined by abdomen x-ray, Sono, Intraudio Videonous Urography (IVU) and Computed Tomography (CT). The detection rates for calculus in above examinations are respectively: 50-70% (x-ray), 50-60% (Sono), 70-90% (IVU) and 97% (CT). In addition, the effective doses are respectively: 0.63 mSv (x-ray), no radiation dose (Sono), 2.6 mSv (IVU) and 8-16 mSv (CT). Although CT has the highest detection rate for calculus, it also has the highest radiation dose. This research sought to lower the radiation dose by using CT scans with different dose conditions of standard dose (SD), 50% SD, 25% SD, and 15% SD to diagnose patients who suffer from urolithiasis and thus explore the feasibility of examining urolithiasis via CT with lower dose conditions. This research simulated the examination of patients with RANDO phantom, collocating PMMA slice phantom and pig's kidney. Fake calculuses made of five different materials of different sizes were put into the phantom and scanned individually. The results of the scanned images were given to two physicians who had many years of diagnostic experience to interpret the urolithiasis images. This study explored the different image qualities of CT with different dose conditions. In addition, this research used thermoluminescent dosimeters (TLD) to measure the radiation doses and compared the results with the dose values shown on the screen of the CT scanner to estimate the dose conversion factor (k). The research results showed that a low-dose CT was able to provide good image quality and thus have a lower radiation dose. Therefore, a low-dose CT is suggested the main examination method to diagnose patients with urolithiasis.

Individualized drug dosing using RBF-Galerkin method: Case of anemia management in chronic kidney disease.

PubMed

Mirinejad, Hossein; Gaweda, Adam E; Brier, Michael E; Zurada, Jacek M; Inanc, Tamer

2017-09-01

Anemia is a common comorbidity in patients with chronic kidney disease (CKD) and is frequently associated with decreased physical component of quality of life, as well as adverse cardiovascular events. Current treatment methods for renal anemia are mostly population-based approaches treating individual patients with a one-size-fits-all model. However, FDA recommendations stipulate individualized anemia treatment with precise control of the hemoglobin concentration and minimal drug utilization. In accordance with these recommendations, this work presents an individualized drug dosing approach to anemia management by leveraging the theory of optimal control. A Multiple Receding Horizon Control (MRHC) approach based on the RBF-Galerkin optimization method is proposed for individualized anemia management in CKD patients. Recently developed by the authors, the RBF-Galerkin method uses the radial basis function approximation along with the Galerkin error projection to solve constrained optimal control problems numerically. The proposed approach is applied to generate optimal dosing recommendations for individual patients. Performance of the proposed approach (MRHC) is compared in silico to that of a population-based anemia management protocol and an individualized multiple model predictive control method for two case scenarios: hemoglobin measurement with and without observational errors. In silico comparison indicates that hemoglobin concentration with MRHC method has less variation among the methods, especially in presence of measurement errors. In addition, the average achieved hemoglobin level from the MRHC is significantly closer to the target hemoglobin than that of the other two methods, according to the analysis of variance (ANOVA) statistical test. Furthermore, drug dosages recommended by the MRHC are more stable and accurate and reach the steady-state value notably faster than those generated by the other two methods. The proposed method is highly efficient for the control of hemoglobin level, yet provides accurate dosage adjustments in the treatment of CKD anemia. Copyright © 2017 Elsevier B.V. All rights reserved.

MCTP system model based on linear programming optimization of apertures obtained from sequencing patient image data maps.

PubMed

Ureba, A; Salguero, F J; Barbeiro, A R; Jimenez-Ortega, E; Baeza, J A; Miras, H; Linares, R; Perucha, M; Leal, A

2014-08-01

The authors present a hybrid direct multileaf collimator (MLC) aperture optimization model exclusively based on sequencing of patient imaging data to be implemented on a Monte Carlo treatment planning system (MC-TPS) to allow the explicit radiation transport simulation of advanced radiotherapy treatments with optimal results in efficient times for clinical practice. The planning system (called CARMEN) is a full MC-TPS, controlled through aMATLAB interface, which is based on the sequencing of a novel map, called "biophysical" map, which is generated from enhanced image data of patients to achieve a set of segments actually deliverable. In order to reduce the required computation time, the conventional fluence map has been replaced by the biophysical map which is sequenced to provide direct apertures that will later be weighted by means of an optimization algorithm based on linear programming. A ray-casting algorithm throughout the patient CT assembles information about the found structures, the mass thickness crossed, as well as PET values. Data are recorded to generate a biophysical map for each gantry angle. These maps are the input files for a home-made sequencer developed to take into account the interactions of photons and electrons with the MLC. For each linac (Axesse of Elekta and Primus of Siemens) and energy beam studied (6, 9, 12, 15 MeV and 6 MV), phase space files were simulated with the EGSnrc/BEAMnrc code. The dose calculation in patient was carried out with the BEAMDOSE code. This code is a modified version of EGSnrc/DOSXYZnrc able to calculate the beamlet dose in order to combine them with different weights during the optimization process. Three complex radiotherapy treatments were selected to check the reliability of CARMEN in situations where the MC calculation can offer an added value: A head-and-neck case (Case I) with three targets delineated on PET/CT images and a demanding dose-escalation; a partial breast irradiation case (Case II) solved with photon and electron modulated beams (IMRT + MERT); and a prostatic bed case (Case III) with a pronounced concave-shaped PTV by using volumetric modulated arc therapy. In the three cases, the required target prescription doses and constraints on organs at risk were fulfilled in a short enough time to allow routine clinical implementation. The quality assurance protocol followed to check CARMEN system showed a high agreement with the experimental measurements. A Monte Carlo treatment planning model exclusively based on maps performed from patient imaging data has been presented. The sequencing of these maps allows obtaining deliverable apertures which are weighted for modulation under a linear programming formulation. The model is able to solve complex radiotherapy treatments with high accuracy in an efficient computation time.

SU-E-T-436: Fluence-Based Trajectory Optimization for Non-Coplanar VMAT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smyth, G; Bamber, JC; Bedford, JL

2015-06-15

Purpose: To investigate a fluence-based trajectory optimization technique for non-coplanar VMAT for brain cancer. Methods: Single-arc non-coplanar VMAT trajectories were determined using a heuristic technique for five patients. Organ at risk (OAR) volume intersected during raytracing was minimized for two cases: absolute volume and the sum of relative volumes weighted by OAR importance. These trajectories and coplanar VMAT formed starting points for the fluence-based optimization method. Iterative least squares optimization was performed on control points 24° apart in gantry rotation. Optimization minimized the root-mean-square (RMS) deviation of PTV dose from the prescription (relative importance 100), maximum dose to the brainstemmore » (10), optic chiasm (5), globes (5) and optic nerves (5), plus mean dose to the lenses (5), hippocampi (3), temporal lobes (2), cochleae (1) and brain excluding other regions of interest (1). Control point couch rotations were varied in steps of up to 10° and accepted if the cost function improved. Final treatment plans were optimized with the same objectives in an in-house planning system and evaluated using a composite metric - the sum of optimization metrics weighted by importance. Results: The composite metric decreased with fluence-based optimization in 14 of the 15 plans. In the remaining case its overall value, and the PTV and OAR components, were unchanged but the balance of OAR sparing differed. PTV RMS deviation was improved in 13 cases and unchanged in two. The OAR component was reduced in 13 plans. In one case the OAR component increased but the composite metric decreased - a 4 Gy increase in OAR metrics was balanced by a reduction in PTV RMS deviation from 2.8% to 2.6%. Conclusion: Fluence-based trajectory optimization improved plan quality as defined by the composite metric. While dose differences were case specific, fluence-based optimization improved both PTV and OAR dosimetry in 80% of cases.« less

Harmony search optimization for HDR prostate brachytherapy

NASA Astrophysics Data System (ADS)

Panchal, Aditya

In high dose-rate (HDR) prostate brachytherapy, multiple catheters are inserted interstitially into the target volume. The process of treating the prostate involves calculating and determining the best dose distribution to the target and organs-at-risk by means of optimizing the time that the radioactive source dwells at specified positions within the catheters. It is the goal of this work to investigate the use of a new optimization algorithm, known as Harmony Search, in order to optimize dwell times for HDR prostate brachytherapy. The new algorithm was tested on 9 different patients and also compared with the genetic algorithm. Simulations were performed to determine the optimal value of the Harmony Search parameters. Finally, multithreading of the simulation was examined to determine potential benefits. First, a simulation environment was created using the Python programming language and the wxPython graphical interface toolkit, which was necessary to run repeated optimizations. DICOM RT data from Varian BrachyVision was parsed and used to obtain patient anatomy and HDR catheter information. Once the structures were indexed, the volume of each structure was determined and compared to the original volume calculated in BrachyVision for validation. Dose was calculated using the AAPM TG-43 point source model of the GammaMed 192Ir HDR source and was validated against Varian BrachyVision. A DVH-based objective function was created and used for the optimization simulation. Harmony Search and the genetic algorithm were implemented as optimization algorithms for the simulation and were compared against each other. The optimal values for Harmony Search parameters (Harmony Memory Size [HMS], Harmony Memory Considering Rate [HMCR], and Pitch Adjusting Rate [PAR]) were also determined. Lastly, the simulation was modified to use multiple threads of execution in order to achieve faster computational times. Experimental results show that the volume calculation that was implemented in this thesis was within 2% of the values computed by Varian BrachyVision for the prostate, within 3% for the rectum and bladder and 6% for the urethra. The calculation of dose compared to BrachyVision was determined to be different by only 0.38%. Isodose curves were also generated and were found to be similar to BrachyVision. The comparison between Harmony Search and genetic algorithm showed that Harmony Search was over 4 times faster when compared over multiple data sets. The optimal Harmony Memory Size was found to be 5 or lower; the Harmony Memory Considering Rate was determined to be 0.95, and the Pitch Adjusting Rate was found to be 0.9. Ultimately, the effect of multithreading showed that as intensive computations such as optimization and dose calculation are involved, the threads of execution scale with the number of processors, achieving a speed increase proportional to the number of processor cores. In conclusion, this work showed that Harmony Search is a viable alternative to existing algorithms for use in HDR prostate brachytherapy optimization. Coupled with the optimal parameters for the algorithm and a multithreaded simulation, this combination has the capability to significantly decrease the time spent on minimizing optimization problems in the clinic that are time intensive, such as brachytherapy, IMRT and beam angle optimization.

Integration of Functional Magnetic Resonance Imaging and Magnetoencephalography Functional Maps Into a CyberKnife Planning System: Feasibility Study for Motor Activity Localization and Dose Planning.

PubMed

De Martin, Elena; Duran, Dunja; Ghielmetti, Francesco; Visani, Elisa; Aquino, Domenico; Marchetti, Marcello; Sebastiano, Davide Rossi; Cusumano, Davide; Bruzzone, Maria Grazia; Panzica, Ferruccio; Fariselli, Laura

2017-12-01

Magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI) provide noninvasive localization of eloquent brain areas for presurgical planning. The aim of this study is the integration of MEG and fMRI maps into a CyberKnife (CK) system to optimize dose planning. Four patients with brain metastases in the motor area underwent functional imaging study of the hand motor cortex before radiosurgery. MEG data were acquired during a visually cued hand motor task. Motor activations were identified also using an fMRI block-designed paradigm. MEG and fMRI maps were then integrated into a CK system and contoured as organs at risk for treatment planning optimization. The integration of fMRI data into the CK system was achieved for all patients by means of a standardized protocol. We also implemented an ad hoc pipeline to convert the MEG signal into a DICOM standard, to make sure that it was readable by our CK treatment planning system. Inclusion of the activation areas into the optimization plan allowed the creation of treatment plans that reduced the irradiation of the motor cortex yet not affecting the brain peripheral dose. The availability of advanced neuroimaging techniques is playing an increasingly important role in radiosurgical planning strategy. We successfully imported MEG and fMRI activations into a CK system. This additional information can improve dose sparing of eloquent areas, allowing a more comprehensive investigation of the related dose-volume constraints that in theory could translate into a gain in tumor local control, and a reduction of neurological complications. Copyright © 2017 Elsevier Inc. All rights reserved.

Incorporating uncertainty and motion in Intensity Modulated Radiation Therapy treatment planning

NASA Astrophysics Data System (ADS)

Martin, Benjamin Charles

In radiation therapy, one seeks to destroy a tumor while minimizing the damage to surrounding healthy tissue. Intensity Modulated Radiation Therapy (IMRT) uses overlapping beams of x-rays that add up to a high dose within the target and a lower dose in the surrounding healthy tissue. IMRT relies on optimization techniques to create high quality treatments. Unfortunately, the possible conformality is limited by the need to ensure coverage even if there is organ movement or deformation. Currently, margins are added around the tumor to ensure coverage based on an assumed motion range. This approach does not ensure high quality treatments. In the standard IMRT optimization problem, an objective function measures the deviation of the dose from the clinical goals. The optimization then finds the beamlet intensities that minimize the objective function. When modeling uncertainty, the dose delivered from a given set of beamlet intensities is a random variable. Thus the objective function is also a random variable. In our stochastic formulation we minimize the expected value of this objective function. We developed a problem formulation that is both flexible and fast enough for use on real clinical cases. While working on accelerating the stochastic optimization, we developed a technique of voxel sampling. Voxel sampling is a randomized algorithms approach to a steepest descent problem based on estimating the gradient by only calculating the dose to a fraction of the voxels within the patient. When combined with an automatic sampling rate adaptation technique, voxel sampling produced an order of magnitude speed up in IMRT optimization. We also develop extensions of our results to Intensity Modulated Proton Therapy (IMPT). Due to the physics of proton beams the stochastic formulation yields visibly different and better plans than normal optimization. The results of our research have been incorporated into a software package OPT4D, which is an IMRT and IMPT optimization tool that we developed.

[Optimizing staff radiation protection in radiology by minimizing the effective dose].

PubMed

von Boetticher, H; Lachmund, J; Hoffmann, W; Luska, G

2006-03-01

In the present study the optimization of radiation protection devices is achieved by minimizing the effective dose of the staff members since the stochastic radiation effects correlate to the effective dose. Radiation exposure dosimetry was performed with TLD measurements using one Alderson Phantom in the patient position and a second phantom in the typical position of the personnel. Various types of protective clothing as well as fixed shields were considered in the calculations. It was shown that the doses of the unshielded organs (thyroid, parts of the active bone marrow) contribute significantly to the effective dose of the staff. Therefore, there is no linear relationship between the shielding factors for protective garments and the effective dose. An additional thyroid protection collar reduces the effective dose by a factor of 1.7 - 3.0. X-ray protective clothing with a 0.35 mm lead equivalent and an additional thyroid protection collar provides better protection against radiation than an apron with a 0.5 mm lead equivalent but no collar. The use of thyroid protection collars is an effective preventive measure against exceeding occupational organ dose limits, and a thyroid shield also considerably reduces the effective dose. Therefore, thyroid protection collars should be a required component of anti-X protection.

Model-based meta-analysis to evaluate optimal doses of direct oral factor Xa inhibitors in atrial fibrillation patients

PubMed Central

Yoshioka, Hideki; Sato, Hiromi; Hatakeyama, Hiroto

2018-01-01

The noninferiority of direct oral factor Xa (FXa) inhibitors (rivaroxaban, apixaban, and edoxaban) in treatment of atrial fibrillation were demonstrated compared with warfarin by several large clinical trials; however, subsequent meta-analyses reported a higher risk of major bleeding with rivaroxaban than with the other FXa inhibitors. In the present study, we first estimated the changes of prothrombin time (PT) in 5 randomized trials based on reported population pharmacokinetic and pharmacodynamic models and then carried out a model-based meta-analysis to obtain models describing the relationship between PT changes and the event rates of ischemic stroke/systemic embolism (SE) and of major bleeding. By using the models, we simulated the optimal therapeutic doses for each FXa inhibitor. It was suggested that dose reduction of rivaroxaban from the current 20 mg/d to 10 mg/d would decrease patient deaths from major bleeding (hazard ratio [HR], 0.69; 95% confidence interval [CI], 0.64-0.74) with little increase in those for ischemic stroke/SE (HR, 1.11; 95% CI, 1.07-1.20). The overall decrease in the mortality caused by both events was estimated as 5.81 per 10 000 patient-years (95% CI, 3.92-8.16), with an HR of 0.87 (95% CI, 0.83-0.91). For apixaban and edoxaban, no distinct change in the overall mortality was simulated by dose modification. This study suggested that the current dose of rivaroxaban might be excessive and would need to be reduced to decrease the excess risk of major bleeding. PMID:29760204

Comparative evaluation of two dose optimization methods for image-guided, highly-conformal, tandem and ovoids cervix brachytherapy planning

NASA Astrophysics Data System (ADS)

Ren, Jiyun; Menon, Geetha; Sloboda, Ron

2013-04-01

Although the Manchester system is still extensively used to prescribe dose in brachytherapy (BT) for locally advanced cervix cancer, many radiation oncology centers are transitioning to 3D image-guided BT, owing to the excellent anatomy definition offered by modern imaging modalities. As automatic dose optimization is highly desirable for 3D image-based BT, this study comparatively evaluates the performance of two optimization methods used in BT treatment planning—Nelder-Mead simplex (NMS) and simulated annealing (SA)—for a cervix BT computer simulation model incorporating a Manchester-style applicator. Eight model cases were constructed based on anatomical structure data (for high risk-clinical target volume (HR-CTV), bladder, rectum and sigmoid) obtained from measurements on fused MR-CT images for BT patients. D90 and V100 for HR-CTV, D2cc for organs at risk (OARs), dose to point A, conformation index and the sum of dwell times within the tandem and ovoids were calculated for optimized treatment plans designed to treat the HR-CTV in a highly conformal manner. Compared to the NMS algorithm, SA was found to be superior as it could perform optimization starting from a range of initial dwell times, while the performance of NMS was strongly dependent on their initial choice. SA-optimized plans also exhibited lower D2cc to OARs, especially the bladder and sigmoid, and reduced tandem dwell times. For cases with smaller HR-CTV having good separation from adjoining OARs, multiple SA-optimized solutions were found which differed markedly from each other and were associated with different choices for initial dwell times. Finally and importantly, the SA method yielded plans with lower dwell time variability compared with the NMS method.

Deformable Dose Reconstruction to Optimize the Planning and Delivery of Liver Cancer Radiotherapy

NASA Astrophysics Data System (ADS)

Velec, Michael

The precise delivery of radiation to liver cancer patients results in improved control with higher tumor doses and minimized normal tissues doses. A margin of normal tissue around the tumor requires irradiation however to account for treatment delivery uncertainties. Daily image-guidance allows targeting of the liver, a surrogate for the tumor, to reduce geometric errors. However poor direct tumor visualization, anatomical deformation and breathing motion introduce uncertainties between the planned dose, calculated on a single pre-treatment computed tomography image, and the dose that is delivered. A novel deformable image registration algorithm based on tissue biomechanics was applied to previous liver cancer patients to track targets and surrounding organs during radiotherapy. Modeling these daily anatomic variations permitted dose accumulation, thereby improving calculations of the delivered doses. The accuracy of the algorithm to track dose was validated using imaging from a deformable, 3-dimensional dosimeter able to optically track absorbed dose. Reconstructing the delivered dose revealed that 70% of patients had substantial deviations from the initial planned dose. An alternative image-guidance technique using respiratory-correlated imaging was simulated, which reduced both the residual tumor targeting errors and the magnitude of the delivered dose deviations. A planning and delivery strategy for liver radiotherapy was then developed that minimizes the impact of breathing motion, and applied a margin to account for the impact of liver deformation during treatment. This margin is 38% smaller on average than the margin used clinically, and permitted an average dose-escalation to liver tumors of 9% for the same risk of toxicity. Simulating the delivered dose with deformable dose reconstruction demonstrated the plans with smaller margins were robust as 90% of patients' tumors received the intended dose. This strategy can be readily implemented with widely available technologies and thus can potentially improve local control for liver cancer patients receiving radiotherapy.

Treatment Planning for Accelerator-Based Boron Neutron Capture Therapy

NASA Astrophysics Data System (ADS)

Herrera, María S.; González, Sara J.; Minsky, Daniel M.; Kreiner, Andrés J.

2010-08-01

Glioblastoma multiforme and metastatic melanoma are frequent brain tumors in adults and presently still incurable diseases. Boron Neutron Capture Therapy (BNCT) is a promising alternative for this kind of pathologies. Accelerators have been proposed for BNCT as a way to circumvent the problem of siting reactors in hospitals and for their relative simplicity and lower cost among other advantages. Considerable effort is going into the development of accelerator-based BNCT neutron sources in Argentina. Epithermal neutron beams will be produced through appropriate proton-induced nuclear reactions and optimized beam shaping assemblies. Using these sources, computational dose distributions were evaluated in a real patient with diagnosed glioblastoma treated with BNCT. The simulated irradiation was delivered in order to optimize dose to the tumors within the normal tissue constraints. Using Monte Carlo radiation transport calculations, dose distributions were generated for brain, skin and tumor. Also, the dosimetry was studied by computing cumulative dose-volume histograms for volumes of interest. The results suggest acceptable skin average dose and a significant dose delivered to tumor with low average whole brain dose for irradiation times less than 60 minutes, indicating a good performance of an accelerator-based BNCT treatment.

Treatment Planning for Accelerator-Based Boron Neutron Capture Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Herrera, Maria S.; Gonzalez, Sara J.; Minsky, Daniel M.

2010-08-04

Glioblastoma multiforme and metastatic melanoma are frequent brain tumors in adults and presently still incurable diseases. Boron Neutron Capture Therapy (BNCT) is a promising alternative for this kind of pathologies. Accelerators have been proposed for BNCT as a way to circumvent the problem of siting reactors in hospitals and for their relative simplicity and lower cost among other advantages. Considerable effort is going into the development of accelerator-based BNCT neutron sources in Argentina. Epithermal neutron beams will be produced through appropriate proton-induced nuclear reactions and optimized beam shaping assemblies. Using these sources, computational dose distributions were evaluated in a realmore » patient with diagnosed glioblastoma treated with BNCT. The simulated irradiation was delivered in order to optimize dose to the tumors within the normal tissue constraints. Using Monte Carlo radiation transport calculations, dose distributions were generated for brain, skin and tumor. Also, the dosimetry was studied by computing cumulative dose-volume histograms for volumes of interest. The results suggest acceptable skin average dose and a significant dose delivered to tumor with low average whole brain dose for irradiation times less than 60 minutes, indicating a good performance of an accelerator-based BNCT treatment.« less

Patient-specific dose estimation for pediatric chest CT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li Xiang; Samei, Ehsan; Segars, W. Paul

2008-12-15

Current methods for organ and effective dose estimations in pediatric CT are largely patient generic. Physical phantoms and computer models have only been developed for standard/limited patient sizes at discrete ages (e.g., 0, 1, 5, 10, 15 years old) and do not reflect the variability of patient anatomy and body habitus within the same size/age group. In this investigation, full-body computer models of seven pediatric patients in the same size/protocol group (weight: 11.9-18.2 kg) were created based on the patients' actual multi-detector array CT (MDCT) data. Organs and structures in the scan coverage were individually segmented. Other organs and structuresmore » were created by morphing existing adult models (developed from visible human data) to match the framework defined by the segmented organs, referencing the organ volume and anthropometry data in ICRP Publication 89. Organ and effective dose of these patients from a chest MDCT scan protocol (64 slice LightSpeed VCT scanner, 120 kVp, 70 or 75 mA, 0.4 s gantry rotation period, pitch of 1.375, 20 mm beam collimation, and small body scan field-of-view) was calculated using a Monte Carlo program previously developed and validated to simulate radiation transport in the same CT system. The seven patients had normalized effective dose of 3.7-5.3 mSv/100 mAs (coefficient of variation: 10.8%). Normalized lung dose and heart dose were 10.4-12.6 mGy/100 mAs and 11.2-13.3 mGy/100 mAs, respectively. Organ dose variations across the patients were generally small for large organs in the scan coverage (<7%), but large for small organs in the scan coverage (9%-18%) and for partially or indirectly exposed organs (11%-77%). Normalized effective dose correlated weakly with body weight (correlation coefficient: r=-0.80). Normalized lung dose and heart dose correlated strongly with mid-chest equivalent diameter (lung: r=-0.99, heart: r=-0.93); these strong correlation relationships can be used to estimate patient-specific organ dose for any other patient in the same size/protocol group who undergoes the chest scan. In summary, this work reported the first assessment of dose variations across pediatric CT patients in the same size/protocol group due to the variability of patient anatomy and body habitus and provided a previously unavailable method for patient-specific organ dose estimation, which will help in assessing patient risk and optimizing dose reduction strategies, including the development of scan protocols.« less

Treatment and follow-up of venous thrombosis in the neonatal intensive care unit: A retrospective study

PubMed Central

Bohnhoff, James C.; DiSilvio, Stefanie A.; Aneja, Rajesh K.; Shenk, Jennifer R.; Domnina, Yuliya A.; Brozanski, Beverly S.; Good, Misty

2016-01-01

Objective The critically ill, premature patients of neonatal intensive care units are susceptible to venous thrombosis, an adverse event associated with short- and long-term morbidity. Venous thrombosis is frequently treated with low molecular weight heparins (LMWH) such as enoxaparin, but optimal dosing of LMWH must balance the morbidity of venous thrombosis with the potential adverse affects of anticoagulation. The optimal dosing of enoxaparin for premature infants is unclear. The objective of this study was to describe enoxaparin therapy and follow-up in critically ill neonates diagnosed with venous thrombosis. Study Design Retrospective medical record review in the neonatal intensive care unit (NICU) in a single tertiary care institution. Infants with venous thrombosis diagnosed in the NICU were identified using pre-existing quality improvement lists and medical records. Results Twenty-six infants with 30 venous thromboses were identified with a median gestational age of 31 weeks at birth. Eighteen (69%) infants received enoxaparin for venous thrombosis during their hospitalization, beginning with a median dose of 1.5 mg/kg every 12h. This dose was increased to a median 2.1 mg/kg every 12h to achieve target anti-factor Xa levels. The target dose was significantly higher in patients with a postmenstrual age less than 37 weeks. Enoxaparin treatment was documented after discharge in 12 patients, continuing for a median of 99 days. Four patients died during hospitalization and their deaths were not attributable to venous thrombosis or anticoagulation complication. Follow-up documentation between 6 and 24 months after venous thrombosis diagnosis revealed no major morbidity of venous thrombosis or enoxaparin therapy. Conclusions Our data reinforces the relative safety and necessity of enoxaparin doses above 1.5 mg/kg per 12 hours in most neonates. This was particularly true for infants at lower postmenstrual age. PMID:27906197

Real-World Data Collection Regarding Titration Algorithms for Insulin Glargine in Patients With Type 2 Diabetes Mellitus

PubMed Central

Pfützner, Andreas; Stratmann, Bernd; Funke, Klaus; Pohlmeier, Harald; Rose, Ludger; Sieber, Jochen; Flacke, Frank; Tschoepe, Diethelm

2016-01-01

The primary objective of this study was to collect data regarding the effectiveness of different dose titration algorithms (TAs) for optimization or initiation of basal insulin supported oral therapy (BOT) in patients with type 2 diabetes. A total of 50 patients were enrolled in this trial (17 women, 33 men, age 63 ± 8 years, HbA1c 7.9 ± 0.8%). The investigator decided on an individual basis to apply any of 4 standard TAs: standard (S: fasting glucose target 90-130 mg/dL, n = 39), standard-fast titration (S-FT: 90-130 mg/dL, larger dose increments at FBG < 180 mg/dl, n = 1), less tight (LT: 110-150 mg/dL, n = 5), and tight (T: 70-100 mg/dL, n = 5). During the next 30 days daily contacts were used to adapt the insulin dose. The majority of all patients (70%) achieved a stable insulin glargine dose within 5 ± 6 days after initiation of the dose titration. HbA1c improved from 7.9 ± 0.8% to 7.5 ± 0.7% (P < .001). In total, 1300 dose decisions were made (1192 according to the TA and 108 by the physicians independently from the TA in 29 patients [58% of study population]). Reasons for TA-overruling dosing decisions were hypoglycemic events (14 mild/4 moderate) in 9 patients. In the majority of these cases (89.8%), the physician recommended continuation of the previous dose or a higher dose. The majority of FBG values were within the respective target range after 4 weeks. In conclusion, the insulin glargine TAs delivered safe dose recommendations with a low risk of hypoglycemia, which successfully led to a stable dose in the vast majority of patients. PMID:27325389

Cebranopadol, a novel first-in-class analgesic drug candidate: first experience in patients with chronic low back pain in a randomized clinical trial.

PubMed

Christoph, Annette; Eerdekens, Marie-Henriette; Kok, Maurits; Volkers, Gisela; Freynhagen, Rainer

2017-09-01

Chronic low back pain (LBP) is a common condition, usually with the involvement of nociceptive and neuropathic pain components, high economic burden and impact on quality of life. Cebranopadol is a potent, first-in-class drug candidate with a novel mechanistic approach, combining nociceptin/orphanin FQ peptide and opioid peptide receptor agonism. We conducted the first phase II, randomized, double-blind, placebo- and active-controlled trial, evaluating the analgesic efficacy, safety, and tolerability of cebranopadol in patients with moderate-to-severe chronic LBP with and without neuropathic pain component. Patients were treated for 14 weeks with cebranopadol 200, 400, or 600 μg once daily, tapentadol 200 mg twice daily, or placebo. The primary efficacy endpoints were the change from baseline pain to the weekly average 24-hour pain during the entire 12 weeks and during week 12 of the maintenance phase. Cebranopadol demonstrated analgesic efficacy, with statistically significant and clinically relevant improvements over placebo for all doses as did tapentadol. The responder analysis (≥30% or ≥50% pain reduction) confirmed these results. Cebranopadol and tapentadol displayed beneficial effects on sleep and functionality. Cebranopadol treatment was safe, with higher doses leading to higher treatment discontinuations because of treatment-emergent adverse events occurring mostly during titration. Those patients reaching the target doses had an acceptable tolerability profile. The incidence rate of most frequently reported treatment-emergent adverse events during maintenance phase was ≤10%. Although further optimizing the titration scheme to the optimal dose for individual patients is essential, cebranopadol is a new drug candidate with a novel mechanistic approach for potential chronic LBP treatment.

Renin angiotensin-aldosterone system (RAAS) blockers usage among type II diabetes mellitus patients-A Retrospective Study.

PubMed

Ng, Yen Ping; Balasubramanian, Ganesh Pandian; Heng, Yi Ping; Kalaiselvan, Meera; Teh, Yu Wen; Cheong, Kin Man; Hadi, Muhammad Faiz Bin Abdul; Othman, Rosmaliza Bt

2018-05-01

Recent data showed an alarming rise of new dialysis cases secondary to diabetic nephropathy despite the growing usage of RAAS blockers. Primary objective of this study is to explore the prevalence of RAAS blockers usage among type II diabetic patients, secondary objectives are to compare the prescribing pattern of RAAS blocker between primary and tertiary care center and to explore if the dose of RAAS blocker prescribed was at optimal dose as suggested by trials. This is a retrospective study conducted at one public tertiary referral hospital and one public health clinic in Sungai Petani, Kedah, Malaysia. RAAS blockers in T2DM patients was found to be 65%. In primary care, 14.3% of the RAAS blockers prescribed was ARB. Tertiary care had higher utilization of ARB, which was 42.9%. In primary care setting, the most commonly used ACEI were perindopril (92.4%) followed by enalapril (7.6%), meanwhile perindopril was the only ACEI being prescribed in tertiary care. The most prescribed ARB was irbesartan (63.6%) and telmisartan (54.2%) respectively in primary and tertiary care. Overall, 64.9% of RAAS blockers prescribed by both levels of care were found to be achieving the target dose as recommended in landmark trials. Crude odd ratio of prescribing RAAS blocker in primary care versus tertiary care was reported as 2.70 (95% CI: 1.49 to 4.91). RAAS blockers usage among T2DM patients was higher in primary care versus tertiary care settings. Majority of the patients did not receive optimal dose of RAAS blockers. Copyright © 2017 Diabetes India. Published by Elsevier Ltd. All rights reserved.

A Phase I, Pharmacokinetic, and Pharmacodynamic Study of Vorinostat in Combination with 5-Fluorouracil, Leucovorin, and Oxaliplatin in Patients with Refractory Colorectal Cancer

PubMed Central

Fakih, Marwan G.; Pendyala, Lakshmi; Fetterly, Gerald; Toth, Karoli; Zwiebel, James A; Espinoza-Delgado, Igor; Litwin, Alan; Rustum, Youcef M.; Ross, Mary Ellen; Holleran, Julianne L.; Egorin, Merrill J.

2014-01-01

Purpose We conducted a phase I study to determine the maximum tolerated dose (MTD) of vorinostat in combination with fixed doses of 5-Fluorouracil (5-FU), leucovorin, and oxaliplatin (FOLFOX). Experimental Design Vorinostat was given PO BID for 1 week every 2 weeks. FOLFOX was given on days 4 and 5 of vorinostat. The vorinostat starting dose was 100 mg BID. Escalation occurred in cohorts of 3–6 patients. Pharmacokinetics of vorinostat, 5-FU, and oxaliplatin were studied. Results Twenty-one patients were enrolled. Thrombocytopenia, neutropenia, gastrointestinal toxicities, and fatigue increased in frequency and severity at higher dose-levels (DL) of vorinostat. Two of 4 evaluable patients at DL 4 (vorinostat 400 mg PO BID) developed dose-limiting fatigue. One of 10 evaluable patients at DL3 (vorinostat 300 mg PO BID) had dose-limiting fatigue, anorexia, and dehydration. There were significant relationships between vorinostat dose and AUC on days 1 and 5 (Pearson, < 0.001). Vorinostat AUC increased (p = 0.005) and clearance decreased (p = 0.003) on day 5 compared to day 1. The median Cmax of 5-FU at each DL increased significantly with increasing doses of vorinostat, suggesting a pharmacokinetic interaction between 5-FU and vorinostat. Vorinostat-induced thymidylate synthase modulation was not consistent; only two of six patients had a decrease in intra-tumoral thymidylate synthase expression by RT-PCR. Conclusions The MTD of vorinostat in combination with FOLFOX is 300 mg PO BID x 1 week every two weeks. Alternative vorinostat dosing schedules may be needed for optimal down-regulation of thymidylate synthase expression. PMID:19383814

SU-E-J-52: Dosimetric Benefit of Adaptive Re-Planning in Lung Cancer Stereotactic Body Radiotherapy (SBRT)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jia, J; Tian, Z; Gu, X

Purpose: To investigate the dosimetric benefit of adaptive re-planning for lung stereotactic body radiotherapy(SBRT). Methods: Five lung cancer patients with SBRT treatment were retrospectively investigated. Our in-house supercomputing online re-planning environment (SCORE) was used to realize the re-planning process. First a deformable image registration was carried out to transfer contours from treatment planning CT to each treatment CBCT. Then an automatic re-planning using original plan DVH guided fluence-map optimization is performed to get a new plan for the up-to-date patient geometry. We compared the re-optimized plan to the original plan projected on the up-to-date patient geometry in critical dosimetric parameters,more » such as PTV coverage, spinal cord maximum and volumetric constraint dose, esophagus maximum and volumetric constraint dose. Results: The average volume of PTV covered by prescription dose for all patients was improved by 7.56% after the adaptive re-planning. The volume of the spinal cord receiving 14.5Gy and 23Gy (V14.5, V23) decreased by 1.48% and 0.68%, respectively. For the esophagus, the volume receiving 19.5Gy (V19.5) reduced by 1.37%. Meanwhile, the maximum dose dropped off by 2.87% for spinal cord and 4.80% for esophagus. Conclusion: Our experimental results demonstrate that adaptive re-planning for lung SBRT has the potential to minimize the dosimetric effect of inter-fraction deformation and thus improve target coverage while reducing the risk of toxicity to nearby normal tissues.« less

Recommendations for the use of methotrexate in rheumatoid arthritis: up and down scaling of the dose and administration routes.

PubMed

Tornero Molina, Jesús; Ballina García, Francisco Javier; Calvo Alén, Jaime; Caracuel Ruiz, Miguel Ángel; Carbonell Abelló, Jordi; López Meseguer, Antonio; Moreno Muelas, José Vicente; Pérez Sandoval, Trinidad; Quijada Carrera, Jesús; Trenor Larraz, Pilar; Zea Mendoza, Antonio

2015-01-01

To describe the optimal therapeutic strategy for use of methotrexate in RA patients over the initial dose, route of administration, dose increase and decrease, patient monitoring, and use of folic/folinic acid. Eleven clinical experts proposed some questions to be solved. A systematic literature search was conducted. The contents were selected in a work session and subsequently validated via email to establish the level of agreement. The initial dose of methotrexate should not be <10mg/week, preferably orally, but considering the parenteral route as an alternative due to compliance, non effectiveness of treatment or gastrointestinal side effects, polypharmacy, obesity (if required doses are >20mg/week), patient preference, very active disease or to avoid administration errors. Changing to a parenteral administration is proposed when the oral route is not effective enough, gastrointestinal toxicity appears, there is non-compliance or due to cost-effectiveness reasons before using more expensive drugs. On the contrary, due to patient preferences, intolerance to injections, dose reduction <7.5mg/week, non effectiveness of the route, poor compliance or gastrointestinal side effects. There should be a rapid dose escalation if inadequate responses occurr up to 15-20 or even 25mg/week in about 8 weeks, with increments of 2.5-5mg. The reduction will be carried out according to the dose the patient had, with decreases of 2.5-5mg every 3-6 months. Patient monitoring should be performed every 1-1.5 months until stability and then every 1-3 months. This document pretends to solve some common clinical questions and facilitate decision-making in RA patients treated with methotrexate. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

Acinetobacter Prosthetic Joint Infection Treated with Debridement and High-Dose Tigecycline.

PubMed

Vila, Andrea; Pagella, Hugo; Amadio, Claudio; Leiva, Alejandro

2016-12-01

Prosthesis retention is not recommended for multidrug-resistant Acinetobacter prosthetic joint infection due to its high failure rate. Nevertheless, replacing the prosthesis implies high morbidity and prolonged hospitalization. Although tigecycline is not approved for the treatment of prosthetic joint infection due to multidrug resistant Acinetobacter baumannii, its appropriate use may preclude prosthesis exchange. Since the area under the curve divided by the minimum inhibitory concentration is the best pharmacodynamic predictor of its efficacy, we used tigecycline at high dose, in order to optimize its efficacy and achieve implant retention in 3 patients who refused prosthesis exchange. All patients with prosthetic joint infections treated at our Institution are prospectively registered in a database. Three patients with early prosthetic joint infection of total hip arthroplasty due to multidrug resistant A. baumannii were treated with debridement, antibiotics and implant retention, using a high maintenance dose of tigecycline (100 mg every 12 hours). The cases were retrospectively reviewed. All patients signed informed consent for receiving off-label use of tigecycline. Tigecycline was well tolerated, allowing its administration at high maintenance dose for a median of 40 days (range 30-60). Two patients were then switched to minocycline at standard doses for a median of 3.3 months in order to complete treatment. Currently, none of the patients showed relapse. Increasing the dose of tigecycline could be considered as a means to better attain pharmacodynamic targets in patients with severe or difficult-to-treat infections. Tigecycline at high maintenance dose might be useful when retention of the implant is attempted for treatment for prosthetic joint infections due to multidrug resistant Acinetobacter. Although this approach might be promising, off-label use of tigecycline should be interpreted cautiously until prospective data are available. Tigecycline is probably under-dosed for the treatment of implant and biofilm associated infections.

Clinical pharmacokinetics, safety, and preliminary efficacy evaluation of icotinib in patients with advanced non-small cell lung cancer.

PubMed

Liu, Dongyang; Zhang, Li; Wu, Yiwen; Jiang, Ji; Tan, Fenlai; Wang, Yingxiang; Liu, Yong; Hu, Pei

2015-09-01

To receive pharmacokinetics, safety, and anti-tumor activity of icotinib, a novel epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), in patients with advanced non-small-cell lung cancer (NSCLC). Patients (n=40) with advanced NSCLC were enrolled to receive escalating doses of icotinib, which was administrated on Day 1 followed by 28-day continuous dosing starting from Day 4. Four dosing regimens, 100mg b.i.d., 150 mg b.i.d., 125 mg t.i.d., and 200mg b.i.d. were studied. Pharmacokinetics (PK), safety, and efficacy of icotinib were evaluated. Icotinib was well tolerated in Chinese patients with refractory NSCLC. No toxicity with >3 grades were reported in more than 2 patients under any dose levels. One complete response (3%) and 9 partial responses (23%) were received. Total disease control rate could reach at 73% and median progress-free survival (range) was 154 (17-462) days. PK exposure of icotinib increased with increase of dose in NSCLC patients. Food was suggested to increase PK exposure by ∼30%. Mean t1/2β was within 5.31-8.07 h. No major metabolite (>10% plasma exposure of icotinib) was found in NSCLC patients. Icotinib with up to 400 mg/day exhibited good tolerance and preliminary antitumor activity in Chinese NSCLC patients. Pharmacokinetics of icotinib and 5 major metabolites were fully investigated in NSCLC patients. Optimized biologic dose (OBD) was finally recommended to be 125 mg t.i.d. for the later clinical study. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Feasibility of TCP-based dose painting by numbers applied to a prostate case with (18)F-choline PET imaging.

PubMed

Dirscherl, Thomas; Rickhey, Mark; Bogner, Ludwig

2012-02-01

A biologically adaptive radiation treatment method to maximize the TCP is shown. Functional imaging is used to acquire a heterogeneous dose prescription in terms of Dose Painting by Numbers and to create a patient-specific IMRT plan. Adapted from a method for selective dose escalation under the guidance of spatial biology distribution, a model, which translates heterogeneously distributed radiobiological parameters into voxelwise dose prescriptions, was developed. At the example of a prostate case with (18)F-choline PET imaging, different sets of reported values for the parameters were examined concerning their resulting range of dose values. Furthermore, the influence of each parameter of the linear-quadratic model was investigated. A correlation between PET signal and proliferation as well as cell density was assumed. Using our in-house treatment planning software Direct Monte Carlo Optimization (DMCO), a treatment plan based on the obtained dose prescription was generated. Gafchromic EBT films were irradiated for evaluation. When a TCP of 95% was aimed at, the maximal dose in a voxel of the prescription exceeded 100Gy for most considered parameter sets. One of the parameter sets resulted in a dose range of 87.1Gy to 99.3Gy, yielding a TCP of 94.7%, and was investigated more closely. The TCP of the plan decreased to 73.5% after optimization based on that prescription. The dose difference histogram of optimized and prescribed dose revealed a mean of -1.64Gy and a standard deviation of 4.02Gy. Film verification showed a reasonable agreement of planned and delivered dose. If the distribution of radiobiological parameters within a tumor is known, this model can be used to create a dose-painting by numbers plan which maximizes the TCP. It could be shown, that such a heterogeneous dose distribution is technically feasible. Copyright © 2012. Published by Elsevier GmbH.

Application of mathematical models to metronomic chemotherapy: What can be inferred from minimal parameterized models?

PubMed

Ledzewicz, Urszula; Schättler, Heinz

2017-08-10

Metronomic chemotherapy refers to the frequent administration of chemotherapy at relatively low, minimally toxic doses without prolonged treatment interruptions. Different from conventional or maximum-tolerated-dose chemotherapy which aims at an eradication of all malignant cells, in a metronomic dosing the goal often lies in the long-term management of the disease when eradication proves elusive. Mathematical modeling and subsequent analysis (theoretical as well as numerical) have become an increasingly more valuable tool (in silico) both for determining conditions under which specific treatment strategies should be preferred and for numerically optimizing treatment regimens. While elaborate, computationally-driven patient specific schemes that would optimize the timing and drug dose levels are still a part of the future, such procedures may become instrumental in making chemotherapy effective in situations where it currently fails. Ideally, mathematical modeling and analysis will develop into an additional decision making tool in the complicated process that is the determination of efficient chemotherapy regimens. In this article, we review some of the results that have been obtained about metronomic chemotherapy from mathematical models and what they infer about the structure of optimal treatment regimens. Copyright © 2017 Elsevier B.V. All rights reserved.

Evaluation of a 15-week CHOP protocol for the treatment of canine multicentric lymphoma.

PubMed

Burton, J H; Garrett-Mayer, E; Thamm, D H

2013-12-01

Dose intense CHOP protocols have been shown to improve outcome for people with non-Hodgkin's lymphoma, but evaluation of dose intense CHOP protocols for canine lymphoma is currently limited. The hypothesis of this retrospective study was that a 15-week dose intense CHOP protocol would have shorter treatment duration with similar efficacy to other doxorubicin-based multidrug protocols. Thirty-one client owned dogs with multicentric lymphoma were treated with a 15-week CHOP chemotherapy protocol with an overall response rate of 100% and a median progression-free interval (PFI) of 140 days [95% confidence interval (CI) 91-335 days]. Dogs that had two or more treatment delays had significantly prolonged PFI and overall survival in multivariate analysis. Dose intensity did not correlate with patient outcome. Dogs experiencing multiple treatment delays secondary to adverse events may receive their individual maximally tolerated dose while dogs with no adverse events may be underdosed. Future studies should focus on individual patient dose optimization. © 2012 Blackwell Publishing Ltd.

Dose--effect relationships for femoral fractures after multimodality limb-sparing therapy of soft-tissue sarcomas of the proximal lower extremity.

PubMed

Pak, Daniel; Vineberg, Karen A; Griffith, Kent A; Sabolch, Aaron; Chugh, Rashmi; Ben-Josef, Edgar; Biermann, Janet Sybil; Feng, Mary

2012-07-15

We investigated the clinical and dosimetric predictors for radiation-associated femoral fractures in patients with proximal lower extremity soft tissue sarcomas (STS). We examined 131 patients with proximal lower extremity STS who received limb-sparing surgery and external-beam radiation therapy between 1985 and 2006. Five (4%) patients sustained pathologic femoral fractures. Dosimetric analysis was limited to 4 fracture patients with full three-dimensional dose information, who were compared with 59 nonfracture patients. The mean doses and volumes of bone (V(d)) receiving specified doses (≥30 Gy, 45 Gy, 60 Gy) at the femoral body, femoral neck, intertrochanteric region, and subtrochanteric region were compared. Clinical predictive factors were also evaluated. Of 4 fracture patients in our dosimetric series, there were three femoral neck fractures with a mean dose of 57.6 ± 8.9 Gy, V30 of 14.5 ± 2.3 cc, V45 of 11.8 ± 1.1 cc, and V60 of 7.2 ± 2.2 cc at the femoral neck compared with 22.9 ± 20.8 Gy, 4.8 ± 5.6 cc, 2.5 ± 3.9 cc, and 0.8 ± 2.7 cc, respectively, for nonfracture patients (p < 0.03 for all). The femoral neck fracture rate was higher than at the subtrochanteric region despite lower mean doses at these subregions. All fracture sites received mean doses greater than 40 Gy. Also, with our policy of prophylactic femoral intramedullary nailing for high-risk patients, there was no significant difference in fracture rates between patients with and without periosteal excision. There were no significant differences in age, sex, tumor size, timing of radiation therapy, and use of chemotherapy between fracture and nonfracture patients. These dose-volume toxicity relationships provide RT optimization goals to guide future efforts for reducing pathologic fracture rates. Prophylactic femoral intramedullary nailing may also reduce fracture risk for susceptible patients. Copyright © 2012 Elsevier Inc. All rights reserved.

Rituximab maintenance for relapsed refractory thrombotic thrombocytopenic purpura.

PubMed

Bhagirath, Vinai C; Kelton, John G; Moore, Jane; Arnold, Donald M

2012-12-01

Rituximab, an anti-CD20 chimeric monoclonal antibody, has been used successfully to treat patients with relapsed or refractory thrombotic thrombocytopenic purpura (TTP); however, the optimal dose and frequency and the role of rituximab maintenance remain uncertain. We describe a 45-year-old woman with chronic relapsing immune thrombocytopenia who responded to rituximab retreatment administered in four doses over the course of 12 months. Previously, she had received four doses of rituximab and sustained a remission for 19 months. During her latest TTP relapse, multiple treatments were administered including rituximab retreatment. After the first dose (375 mg/m2), she developed serum sickness requiring further doses to be deferred. Three subsequent doses were administered at 4-month intervals over the course of 12 months. ADAMTS13 activity was measured by von Willebrand factor (VWF) digestion. ADAMTS13 inhibition was measured by a modification of the VWF digestion assay and anti-ADAMTS13 antibodies were measured by enzyme-linked immunoassay (enzyme-linked immunosorbent assay, American Diagnostica). Clinical and laboratory remission were achieved after one dose of rituximab, with normalization of ADAMTS13 activity and disappearance of ADAMTS13 inhibitor. Three subsequent doses of rituximab were given without incident and the patient remained in remission after 3.5 years of follow-up (2.5 years since her last dose of rituximab). Maintenance dosing of rituximab should be considered in some patients with relapsing TTP. © 2012 American Association of Blood Banks.

Patient-specific dose estimation for pediatric chest CT

PubMed Central

Li, Xiang; Samei, Ehsan; Segars, W. Paul; Sturgeon, Gregory M.; Colsher, James G.; Frush, Donald P.

2008-01-01

Current methods for organ and effective dose estimations in pediatric CT are largely patient generic. Physical phantoms and computer models have only been developed for standard/limited patient sizes at discrete ages (e.g., 0, 1, 5, 10, 15years old) and do not reflect the variability of patient anatomy and body habitus within the same size/age group. In this investigation, full-body computer models of seven pediatric patients in the same size/protocol group (weight: 11.9–18.2kg) were created based on the patients’ actual multi-detector array CT (MDCT) data. Organs and structures in the scan coverage were individually segmented. Other organs and structures were created by morphing existing adult models (developed from visible human data) to match the framework defined by the segmented organs, referencing the organ volume and anthropometry data in ICRP Publication 89. Organ and effective dose of these patients from a chest MDCT scan protocol (64 slice LightSpeed VCT scanner, 120kVp, 70 or 75mA, 0.4s gantry rotation period, pitch of 1.375, 20mm beam collimation, and small body scan field-of-view) was calculated using a Monte Carlo program previously developed and validated to simulate radiation transport in the same CT system. The seven patients had normalized effective dose of 3.7–5.3mSv∕100mAs (coefficient of variation: 10.8%). Normalized lung dose and heart dose were 10.4–12.6mGy∕100mAs and 11.2–13.3mGy∕100mAs, respectively. Organ dose variations across the patients were generally small for large organs in the scan coverage (<7%), but large for small organs in the scan coverage (9%–18%) and for partially or indirectly exposed organs (11%–77%). Normalized effective dose correlated weakly with body weight (correlation coefficient:r=−0.80). Normalized lung dose and heart dose correlated strongly with mid-chest equivalent diameter (lung: r=−0.99, heart: r=−0.93); these strong correlation relationships can be used to estimate patient-specific organ dose for any other patient in the same size/protocol group who undergoes the chest scan. In summary, this work reported the first assessment of dose variations across pediatric CT patients in the same size/protocol group due to the variability of patient anatomy and body habitus and provided a previously unavailable method for patient-specific organ dose estimation, which will help in assessing patient risk and optimizing dose reduction strategies, including the development of scan protocols. PMID:19175138

SU-F-BRD-01: A Novel 4D Robust Optimization Mitigates Interplay Effect in Intensity-Modulated Proton Therapy for Lung Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, W; Shen, J; Stoker, J

2015-06-15

Purpose: To compare the impact of interplay effect on 3D and 4D robustly optimized intensity-modulated proton therapy (IMPT) plans to treat lung cancer. Methods: Two IMPT plans were created for 11 non-small-cell-lung-cancer cases with 6–14 mm spots. 3D robust optimization generated plans on average CTs with the internal gross tumor volume density overridden to deliver 66 CGyE in 33 fractions to the internal target volume (ITV). 4D robust optimization generated plans on 4D CTs with the delivery of prescribed dose to the clinical target volume (CTV). In 4D optimization, the CTV of individual 4D CT phases received non-uniform doses tomore » achieve a uniform cumulative dose. Dose evaluation software was developed to model time-dependent spot delivery to incorporate interplay effect with randomized starting phases of each field per fraction. Patient anatomy voxels were mapped from phase to phase via deformable image registration to score doses. Indices from dose-volume histograms were used to compare target coverage, dose homogeneity, and normal-tissue sparing. DVH indices were compared using Wilcoxon test. Results: Given the presence of interplay effect, 4D robust optimization produced IMPT plans with better target coverage and homogeneity, but slightly worse normal tissue sparing compared to 3D robust optimization (unit: Gy) [D95% ITV: 63.5 vs 62.0 (p=0.014), D5% - D95% ITV: 6.2 vs 7.3 (p=0.37), D1% spinal cord: 29.0 vs 29.5 (p=0.52), Dmean total lung: 14.8 vs 14.5 (p=0.12), D33% esophagus: 33.6 vs 33.1 (p=0.28)]. The improvement of target coverage (D95%,4D – D95%,3D) was related to the ratio RMA3/(TVx10−4), with RMA and TV being respiratory motion amplitude (RMA) and tumor volume (TV), respectively. Peak benefit was observed at ratios between 2 and 10. This corresponds to 125 – 625 cm3 TV with 0.5-cm RMA. Conclusion: 4D optimization produced more interplay-effect-resistant plans compared to 3D optimization. It is most effective when respiratory motion is modest compared to TV. NIH/NCI K25CA168984; Eagles Cancer Research Career Development; The Lawrence W. and Marilyn W. Matteson Fund for Cancer Research; Mayo ASU Seed Grant; The Kemper Marley Foundation.« less

Clinical implications of the HPV-16 infection & 7 beneficial effects of optimal dose of Vitamin D3 in safe, effective cancer treatment: Non-invasive rapid cancer screening using "Mouth, Hand & Foot Writing Form" of 40 participants during 150- minute workshop on the Bi-Digital 0-ring Test, in the 1st day of European Congress for Integrative Medicine, September 9-11, 2016 in Budapest.

PubMed

Omura, Yoshiaki

During the 1st day of European Congress for Integrative Medicine held September 9-11, 2016, almost the entire 1st day was scheduled for the Bi-Digital O-Ring Test, which was originally developed by this author, & consists of 2 main parts for which a U.S. patent was issued in 1993. One is a non-invasive, detection of various molecules using very strong Electromagnetic Field (EMF) Resonance Phenomenon between 2 identical molecules with identical weight. Using this strong EMF Resonance Phenomenon, most molecules & microorganisms can be detected rapidly and non-invasively without directly contacting patients. We measured the HPV-16 infection of 70 participants non-invasively in the first 30 minutes, then screened cancers for 40 volunteers who completed one page "Mouth, Hand & Foot Writing Form," which took an average of 5∼10 minutes for each person to complete. Screening of 75 common cancers was made in 2-5 minutes for each patient. Analysis of 40 volunteers revealed 32 persons had some malignancies including 5 Anaplastic Astrocytomas of the L-brain, 3 Multiple Myelomas, 7 Hodgkin's Lymphomas, 8 Non-Hodgkin's Lymphomas, 2 rectum cancers (with chief complaints of worsening Irritable Bowel Syndrome). Although everyone had HPV-16 infections between about 6,000ng & 250ng, malignancy could not be found among those who had less than 1,200ng. Our individualized safe, effective and economical treatment of various cancers consists of optimal doses of Vitamin D3 with or without Taurine and/or PQQ depending on the positive synergetic compatibility among these 3 substances as normal parts of human tissue. The most serious 2 cases of rectum cancer with multiple metastasis, we confirmed very significant anti-cancer effects of their optimal doses of vitamin D3, which is increased to 800~1,000 I.U. (due to advanced cancer with multiple metastasis instead of the usual 400 I.U. for average adults). The unique 7 beneficial effects of optimal dose of Vitamin D3 (also Taurine or PQQ) include: 1) significant Anti-cancer effects without side effects; 2) marked decrease in DNA mutation as decreases in 8-OH-dG; 3) marked urinary excretion of Viruses, Bacteria, Fungi, & Toxic substances, including Asbestos & metals; 4) marked increase in Acetylcholine in the brain & the rest of the body; 5) marked increase in DHEA; 6) marked decrease in β-Amyloid (I-42); 7) marked decrease in Cardiac Troponin I. Optimal dose of Vitamin D3 is clinically most important for cancer, ischemic heart, and memory problems. Optimal dose of Taurine is 150∼175mg and PQQ is 5-7.5mg and should be taken 3-4 times a day, depending on the patient. Medications and supplements including excessive Vitamin C (as well as multivitamins) but also inhibited optimal doses of Vitamin D3, Taurine & PQQ. Often coffee, drinks containing high Vitamin C content (e.g., some green tea & orange juice), & multivitamins as well as pain medicine (e.g., Oxycodone), strong EMF from cellular phones, and strong negative BDORT underwear often completely eliminate the above beneficial effects of Vitamin D3 and promote growth of cancer.

Comprehensive assessment of patient image quality and radiation dose in latest generation cardiac x-ray equipment for percutaneous coronary interventions

PubMed Central

Gislason-Lee, Amber J.; Keeble, Claire; Egleston, Daniel; Bexon, Josephine; Kengyelics, Stephen M.; Davies, Andrew G.

2017-01-01

Abstract. This study aimed to determine whether a reduction in radiation dose was found for percutaneous coronary interventional (PCI) patients using a cardiac interventional x-ray system with state-of-the-art image enhancement and x-ray optimization, compared to the current generation x-ray system, and to determine the corresponding impact on clinical image quality. Patient procedure dose area product (DAP) and fluoroscopy duration of 131 PCI patient cases from each x-ray system were compared using a Wilcoxon test on median values. Significant reductions in patient dose (p≪0.001) were found for the new system with no significant change in fluoroscopy duration (p=0.2); procedure DAP reduced by 64%, fluoroscopy DAP by 51%, and “cine” acquisition DAP by 76%. The image quality of 15 patient angiograms from each x-ray system (30 total) was scored by 75 clinical professionals on a continuous scale for the ability to determine the presence and severity of stenotic lesions; image quality scores were analyzed using a two-sample t-test. Image quality was reduced by 9% (p≪0.01) for the new x-ray system. This demonstrates a substantial reduction in patient dose, from acquisition more than fluoroscopy imaging, with slightly reduced image quality, for the new x-ray system compared to the current generation system. PMID:28491907

Patient safety and minimizing risk with insulin administration - role of insulin degludec.

PubMed

Aye, Myint M; Atkin, Stephen L

2014-01-01

Diabetes is a lifelong condition requiring ongoing medical care and patient self-management. Exogenous insulin therapy is essential in type 1 diabetes and becomes a necessity in patients with longstanding type 2 diabetes who fail to achieve optimal control with lifestyle modification, oral agents, and glucagon-like peptide 1-based therapy. One of the risks that hinders insulin use is hypoglycemia. Optimal insulin therapy should therefore minimize the risk of hypoglycemia while improving glycemic control. Insulin degludec (IDeg) is a novel basal insulin that, following subcutaneous injection, assembles into a depot of soluble multihexamer chains. These subsequently release IDeg monomers that are absorbed at a slow and steady rate into the circulation, with the terminal half-life of IDeg being ~25 hours. Thus, it requires only once-daily dosing unlike other basal insulin preparations that often require twice-daily dosing. Despite its long half-life, once-daily IDeg does not cause accumulation of insulin in the circulation after reaching steady state. IDeg once a day will produce a steady-state profile with a lower peak:trough ratio than other basal insulins. In clinical trials, this profile translates into a lower frequency of nocturnal hypoglycemia compared with insulin glargine, as well as an ability to allow some flexibility in dose timing without compromising efficacy and safety. Indeed, a study that tested the extremes of dosing intervals of 8 and 40 hours showed no detriment in either glycemic control or hypoglycemic frequency versus insulin glargine given at the same time each day. While extreme flexibility in dose timing is not recommended, these findings are reassuring. This may be particularly beneficial to elderly patients, patients with learning difficulties, or others who have to rely on health-care professionals for their daily insulin injections. Further studies are required to confirm whether this might benefit adherence to treatment, reduce long-term hypoglycemia or reduce diabetes-related complications.

3D conformal planning using low segment multi-criteria IMRT optimization

PubMed Central

Khan, Fazal; Craft, David

2014-01-01

Purpose To evaluate automated multicriteria optimization (MCO) – designed for intensity modulated radiation therapy (IMRT), but invoked with limited segmentation – to efficiently produce high quality 3D conformal radiation therapy (3D-CRT) plans. Methods Ten patients previously planned with 3D-CRT to various disease sites (brain, breast, lung, abdomen, pelvis), were replanned with a low-segment inverse multicriteria optimized technique. The MCO-3D plans used the same beam geometry of the original 3D plans, but were limited to an energy of 6 MV. The MCO-3D plans were optimized using fluence-based MCO IMRT and then, after MCO navigation, segmented with a low number of segments. The 3D and MCO-3D plans were compared by evaluating mean dose for all structures, D95 (dose that 95% of the structure receives) and homogeneity indexes for targets, D1 and clinically appropriate dose volume objectives for individual organs at risk (OARs), monitor units (MUs), and physician preference. Results The MCO-3D plans reduced the OAR mean doses (41 out of a total of 45 OARs had a mean dose reduction, p<<0.01) and monitor units (seven out of ten plans have reduced MUs; the average reduction is 17%, p=0.08) while maintaining clinical standards on coverage and homogeneity of target volumes. All MCO-3D plans were preferred by physicians over their corresponding 3D plans. Conclusion High quality 3D plans can be produced using MCO-IMRT optimization, resulting in automated field-in-field type plans with good monitor unit efficiency. Adopting this technology in a clinic could improve plan quality, and streamline treatment plan production by utilizing a single system applicable to both IMRT and 3D planning. PMID:25413405

Trajectory optimization for dynamic couch rotation during volumetric modulated arc radiotherapy

NASA Astrophysics Data System (ADS)

Smyth, Gregory; Bamber, Jeffrey C.; Evans, Philip M.; Bedford, James L.

2013-11-01

Non-coplanar radiation beams are often used in three-dimensional conformal and intensity modulated radiotherapy to reduce dose to organs at risk (OAR) by geometric avoidance. In volumetric modulated arc radiotherapy (VMAT) non-coplanar geometries are generally achieved by applying patient couch rotations to single or multiple full or partial arcs. This paper presents a trajectory optimization method for a non-coplanar technique, dynamic couch rotation during VMAT (DCR-VMAT), which combines ray tracing with a graph search algorithm. Four clinical test cases (partial breast, brain, prostate only, and prostate and pelvic nodes) were used to evaluate the potential OAR sparing for trajectory-optimized DCR-VMAT plans, compared with standard coplanar VMAT. In each case, ray tracing was performed and a cost map reflecting the number of OAR voxels intersected for each potential source position was generated. The least-cost path through the cost map, corresponding to an optimal DCR-VMAT trajectory, was determined using Dijkstra’s algorithm. Results show that trajectory optimization can reduce dose to specified OARs for plans otherwise comparable to conventional coplanar VMAT techniques. For the partial breast case, the mean heart dose was reduced by 53%. In the brain case, the maximum lens doses were reduced by 61% (left) and 77% (right) and the globes by 37% (left) and 40% (right). Bowel mean dose was reduced by 15% in the prostate only case. For the prostate and pelvic nodes case, the bowel V50 Gy and V60 Gy were reduced by 9% and 45% respectively. Future work will involve further development of the algorithm and assessment of its performance over a larger number of cases in site-specific cohorts.

Tranexamic Acid: From Trauma to Routine Perioperative Use

PubMed Central

Simmons, Jeff; Sikorski, Robert A.; Pittet, Jean-Francois

2015-01-01

Purpose Of Review Optimizing hemostasis with antifibrinolytics is becoming a common surgical practice. Large clinical studies have demonstrated efficacy and safety of tranexamic acid (TXA) in the trauma population to reduce blood loss and transfusions. Its use in patients without preexisting coagulopathies is debated, as thromboembolic events are a concern. In this review, perioperative administration of TXA is examined in non-trauma surgical populations. Additionally, risk of thromboembolism, dosing regimens, and timing of dosing are assessed. Recent Findings Perioperative use of tranexamic acid is associated with reduced blood loss and transfusions. Thromboembolic effects do not appear to be increased. However, optimal dosing and timing of TXA administration is still under investigation for non-trauma surgical populations. Summary As part of a perioperative blood management program, tranexamic acid can be used to help reduce blood loss and mitigate exposure to blood transfusion. PMID:25635366

DOE Office of Scientific and Technical Information (OSTI.GOV)

Widesott, Lamberto; Lomax, Antony J.; Schwarz, Marco

Purpose: To assess the quality of dose distributions in real clinical cases for different dimensions of scanned proton pencil beams. The distance between spots (i.e., the grid of delivery) is optimized for each dimension of the pencil beam. Methods: The authors vary the {sigma} of the initial Gaussian size of the spot, from {sigma}{sub x} = {sigma}{sub y} = 3 mm to {sigma}{sub x} = {sigma}{sub y} = 8 mm, to evaluate the impact of the proton beam size on the quality of intensity modulated proton therapy (IMPT) plans. The distance between spots, {Delta}x and {Delta}y, is optimized on themore » spot plane, ranging from 4 to 12 mm (i.e., each spot size is coupled with the best spot grid resolution). In our Hyperion treatment planning system (TPS), constrained optimization is applied with respect to the organs at risk (OARs), i.e., the optimization tries to satisfy the dose objectives in the planning target volume (PTV) as long as all planning objectives for the OARs are met. Three-field plans for a nasopharynx case, two-field plans for a prostate case, and two-field plans for a malignant pleural mesothelioma case are considered in our analysis. Results: For the head and neck tumor, the best grids (i.e., distance between spots) are 5, 4, 6, 6, and 8 mm for {sigma} = 3, 4, 5, 6, and 8 mm, respectively. {sigma} {<=} 5 mm is required for tumor volumes with low dose and {sigma}{<=} 4 mm for tumor volumes with high dose. For the prostate patient, the best grid is 4, 4, 5, 5, and 5 mm for {sigma} = 3, 4, 5, 6, and 8 mm, respectively. Beams with {sigma} > 3 mm did not satisfy our first clinical requirement that 95% of the prescribed dose is delivered to more than 95% of prostate and proximal seminal vesicles PTV. Our second clinical requirement, to cover the distal seminal vesicles PTV, is satisfied for beams as wide as {sigma} = 6 mm. For the mesothelioma case, the low dose PTV prescription is well respected for all values of {sigma}, while there is loss of high dose PTV coverage for {sigma} > 5 mm. The best grids have a spacing of 6, 7, 8, 9, and 12 mm for {sigma} = 3, 4, 5, 6, and 8 mm, respectively. Conclusions: The maximum acceptable proton pencil beam {sigma} depends on the volume treated, the protocol of delivery, and optimization of the plan. For the clinical cases, protocol and optimization used in this analysis, acceptable {sigma}s are {<=} 4 mm for the head and neck tumor, {<=} 3 mm for the prostate tumor and {<=} 6 mm for the malignant pleural mesothelioma. One can apply the same procedure used in this analysis when given a ''class'' of patients, a {sigma} and a clinical protocol to determine the optimal grid spacing.« less