Georgia fishery study: implications for dose calculations. Revision 1

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

Turcotte, M.D.S.

Fish consumption will contribute a major portion of the estimated individual and population doses from L-Reactor liquid releases and Cs-137 remobilization in Steel Creek. It is therefore important that the values for fish consumption used in dose calculations be as realistic as possible. Since publication of the L-Reactor Environmental Information Document (EID), data have become available on sport fishing in the Savannah River. These data provide SRP with a site-specific sport fish harvest and consumption values for use in dose calculations. The Georgia fishery data support the total population fish consumption and calculated dose reported in the EID. The datamore » indicate, however, that both the EID average and maximum individual fish consumption have been underestimated, although each to a different degree. The average fish consumption value used in the EID is approximately 3% below the lower limit of the fish consumption range calculated using the Georgia data. Maximum fish consumption in the EID has been underestimated by approximately 60%, and doses to the maximum individual should also be recalculated. Future dose calculations should utilize an average adult fish consumption value of 11.3 kg/yr, and a maximum adult fish consumption value of 34 kg/yr. Consumption values for the teen and child age groups should be increased proportionally: (1) teen average = 8.5; maximum = 25.9 kg/yr; and (2) child average = 3.6; maximum = 11.2 kg/yr. 8 refs.« less

MEASUREMENT OF RADIATION DOSES TO THE EYE LENS DURING ORTHOPEDIC SURGERY USING AN C-ARM X-RAY SYSTEM.

PubMed

Suzuki, Akira; Matsubara, Kosuke; Sasa, Yuko

2018-04-01

The present study aimed to determine doses delivered to the eye lenses of surgeons while using the inverted-C-arm technique and the protective effect of leaded spectacles during orthopedic surgery. The kerma in air was measured at five positions on leaded glasses positioned near the eye lens and on the neck using small optically stimulated luminescence (OSL) dosemeters. The lens equivalent dose was also measured at the neck using an OSL dosemeter. The maximum equivalent dose to the eye lens and the maximum kerma were 0.8 mSv/month and 0.66 mGy/month, respectively. The leaded glasses reduced the exposure by ~60%. Even if the surgeons are exposed to the maximum dose of X-ray radiation for 5 years, the equivalent doses to the eye lens will not exceed the present limit recommended by the ICRP.

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

A retrospective analysis of rectal and bladder dose for gynecological brachytherapy treatments with GZP6 HDR afterloading system.

PubMed

Bahreyni Toossi, Mohammad Taghi; Ghorbani, Mahdi; Makhdoumi, Yasha; Taheri, Mojtaba; Homaee Shandiz, Fatemeh; Zahed Anaraki, Siavash; Soleimani Meigooni, Ali

2012-01-01

The aim of this work is to evaluate rectal and bladder dose for the patients treated for gynecological cancers. The GZP6 high dose rate brachytherapy system has been recently introduced to a number of radiation therapy departments in Iran, for treatment of various tumor sites such as cervix and vagina. Our analysis was based on dose measurements for 40 insertions in 28 patients, treated by a GZP6 unit between June 2009 and November 2010. Treatments consisted of combined teletherapy and intracavitary brachytherapy. In vivo dosimetry was performed with TLD-400 chips and TLD-100 microcubes in the rectum and bladder. The average of maximum rectal and bladder dose values were found to be 7.62 Gy (range 1.72-18.55 Gy) and 5.17 Gy (range 0.72-15.85 Gy), respectively. It has been recommended by the ICRU that the maximum dose to the rectum and bladder in intracavitary treatment of vaginal or cervical cancer should be lower than 80% of the prescribed dose to point A in the Manchester system. In this study, of the total number of 40 insertions, maximum rectal dose in 29 insertions (72.5% of treatment sessions) and maximum bladder dose in 18 insertions (45% of treatments sessions) were higher than 80% of the prescribed dose to the point of dose prescription. In vivo dosimetry for patients undergoing treatment by GZP6 brachytherapy system can be used for evaluation of the quality of brachytherapy treatments by this system. This information could be used as a base for developing the strategy for treatment of patients treated with GZP6 system.

A retrospective analysis of rectal and bladder dose for gynecological brachytherapy treatments with GZP6 HDR afterloading system

PubMed Central

Bahreyni Toossi, Mohammad Taghi; Ghorbani, Mahdi; Makhdoumi, Yasha; Taheri, Mojtaba; Homaee Shandiz, Fatemeh; Zahed Anaraki, Siavash; Soleimani Meigooni, Ali

2012-01-01

Aim The aim of this work is to evaluate rectal and bladder dose for the patients treated for gynecological cancers. Background The GZP6 high dose rate brachytherapy system has been recently introduced to a number of radiation therapy departments in Iran, for treatment of various tumor sites such as cervix and vagina. Materials and methods Our analysis was based on dose measurements for 40 insertions in 28 patients, treated by a GZP6 unit between June 2009 and November 2010. Treatments consisted of combined teletherapy and intracavitary brachytherapy. In vivo dosimetry was performed with TLD-400 chips and TLD-100 microcubes in the rectum and bladder. Results The average of maximum rectal and bladder dose values were found to be 7.62 Gy (range 1.72–18.55 Gy) and 5.17 Gy (range 0.72–15.85 Gy), respectively. It has been recommended by the ICRU that the maximum dose to the rectum and bladder in intracavitary treatment of vaginal or cervical cancer should be lower than 80% of the prescribed dose to point A in the Manchester system. In this study, of the total number of 40 insertions, maximum rectal dose in 29 insertions (72.5% of treatment sessions) and maximum bladder dose in 18 insertions (45% of treatments sessions) were higher than 80% of the prescribed dose to the point of dose prescription. Conclusion In vivo dosimetry for patients undergoing treatment by GZP6 brachytherapy system can be used for evaluation of the quality of brachytherapy treatments by this system. This information could be used as a base for developing the strategy for treatment of patients treated with GZP6 system. PMID:24377037

Cosmic radiation exposure of biological test systems during the EXPOSE-E mission.

PubMed

Berger, Thomas; Hajek, Michael; Bilski, Pawel; Körner, Christine; Vanhavere, Filip; Reitz, Günther

2012-05-01

In the frame of the EXPOSE-E mission on the Columbus external payload facility EuTEF on board the International Space Station, passive thermoluminescence dosimeters were applied to measure the radiation exposure of biological samples. The detectors were located either as stacks next to biological specimens to determine the depth dose distribution or beneath the sample carriers to determine the dose levels for maximum shielding. The maximum mission dose measured in the upper layer of the depth dose part of the experiment amounted to 238±10 mGy, which relates to an average dose rate of 408±16 μGy/d. In these stacks of about 8 mm height, the dose decreased by 5-12% with depth. The maximum dose measured beneath the sample carriers was 215±16 mGy, which amounts to an average dose rate of 368±27 μGy/d. These values are close to those assessed for the interior of the Columbus module and demonstrate the high shielding of the biological experiments within the EXPOSE-E facility. Besides the shielding by the EXPOSE-E hardware itself, additional shielding was experienced by the external structures adjacent to EXPOSE-E, such as EuTEF and Columbus. This led to a dose gradient over the entire exposure area, from 215±16 mGy for the lowest to 121±6 mGy for maximum shielding. Hence, the doses perceived by the biological samples inside EXPOSE-E varied by 70% (from lowest to highest dose). As a consequence of the high shielding, the biological samples were predominantly exposed to galactic cosmic heavy ions, while electrons and a significant fraction of protons of the radiation belts and solar wind did not reach the samples.

“Hallucinations” Following Acute Cannabis Dosing: A Case Report and Comparison to Other Hallucinogenic Drugs

PubMed Central

Barrett, Frederick S.; Schlienz, Nicolas J.; Lembeck, Natalie; Waqas, Muhammad; Vandrey, Ryan

2018-01-01

Abstract Introduction: Cannabis has been historically classified as a hallucinogen. However, subjective cannabis effects do not typically include hallucinogen-like effects. Empirical reports of hallucinogen-like effects produced by cannabis in controlled settings, particularly among healthy research volunteers, are rare and have mostly occurred after administration of purified Δ-9 tetrahydrocannabinol (THC) rather than whole plant cannabis. Methods: The case of a healthy 30-year-old male who experienced auditory and visual hallucinations in a controlled laboratory study after inhaling vaporized cannabis that contained 25 mg THC (case dose) is presented. Ratings on the Hallucinogen Rating Scale (HRS) following the case dose are compared with HRS ratings obtained from the participant after other doses of cannabis and with archival HRS data from laboratory studies involving acute doses of cannabis, psilocybin, dextromethorphan (DXM), and salvinorin A. Results: Scores on the Volition subscale of the HRS were greater for the case dose than for the maximum dose administered in any other comparison study. Scores on the Intensity and Perception subscales were greater for the case dose than for the maximum dose of cannabis, psilocybin, or salvinorin A. Scores on the Somaesthesia subscale were greater for the case dose than for the maximum dose of DXM, salvinorin A, or cannabis. Scores on the Affect and Cognition subscales for the case dose were significantly lower than for the maximum doses of psilocybin and DXM. Conclusion: Acute cannabis exposure in a healthy adult male resulted in self-reported hallucinations that rated high in magnitude on several subscales of the HRS. However, the hallucinatory experience in this case was qualitatively different than that typically experienced by participants receiving classic and atypical hallucinogens, suggesting that the hallucinatory effects of cannabis may have a unique pharmacological mechanism of action. This type of adverse event needs to be considered in the clinical use of cannabis. PMID:29682608

Evaluation of the dependence of the exposure dose on the attenuation correction in brain PET/CT scans using 18F-FDG

NASA Astrophysics Data System (ADS)

Choi, Eun-Jin; Jeong, Moon-Taeg; Jang, Seong-Joo; Choi, Nam-Gil; Han, Jae-Bok; Yang, Nam-Hee; Dong, Kyung-Rae; Chung, Woon-Kwan; Lee, Yun-Jong; Ryu, Young-Hwan; Choi, Sung-Hyun; Seong, Kyeong-Jeong

2014-01-01

This study examined whether scanning could be performed with minimum dose and minimum exposure to the patient after an attenuation correction. A Hoffman 3D Brain Phantom was used in BIO_40 and D_690 PET/CT scanners, and the CT dose for the equipment was classified as a low dose (minimum dose), medium dose (general dose for scanning) and high dose (dose with use of contrast medium) before obtaining the image at a fixed kilo-voltage-peak (kVp) and milliampere (mA) that were adjusted gradually in 17-20 stages. A PET image was then obtained to perform an attenuation correction based on an attenuation map before analyzing the dose difference. Depending on tube current in the range of 33-190 milliampere-second (mAs) when BIO_40 was used, a significant difference in the effective dose was observed between the minimum and the maximum mAs (p < 0.05). According to a Scheffe post-hoc test, the ratio of the minimum to the maximum of the effective dose was increased by approximately 5.26-fold. Depending on the change in the tube current in the range of 10-200 mA when D_690 was used, a significant difference in the effective dose was observed between the minimum and the maximum of mA (p < 0.05). The Scheffe posthoc test revealed a 20.5-fold difference. In conclusion, because effective exposure dose increases with increasing operating current, it is possible to reduce the exposure limit in a brain scan can be reduced if the CT dose can be minimized for a transmission scan.

Influence of intravenous opioid dose on postoperative ileus.

PubMed

Barletta, Jeffrey F; Asgeirsson, Theodor; Senagore, Anthony J

2011-07-01

Intravenous opioids represent a major component in the pathophysiology of postoperative ileus (POI). However, the most appropriate measure and threshold to quantify the association between opioid dose (eg, average daily, cumulative, maximum daily) and POI remains unknown. To evaluate the relationship between opioid dose, POI, and length of stay (LOS) and identify the opioid measure that was most strongly associated with POI. Consecutive patients admitted to a community teaching hospital who underwent elective colorectal surgery by any technique with an enhanced-recovery protocol postoperatively were retrospectively identified. Patients were excluded if they received epidural analgesia, developed a major intraabdominal complication or medical complication, or had a prolonged workup prior to surgery. Intravenous opioid doses were quantified and converted to hydromorphone equivalents. Classification and regression tree (CART) analysis was used to determine the dosing threshold for the opioid measure most associated with POI and define high versus low use of opioids. Risk factors for POI and prolonged LOS were determined through multivariate analysis. The incidence of POI in 279 patients was 8.6%. CART analysis identified a maximum daily intravenous hydromorphone dose of 2 mg or more as the opioid measure most associated with POI. Multivariate analysis revealed maximum daily hydromorphone dose of 2 mg or more (p = 0.034), open surgical technique (p = 0.045), and days of intravenous narcotic therapy (p = 0.003) as significant risk factors for POI. Variables associated with increased LOS were POI (p < 0.001), maximum daily hydromorphone dose of 2 mg or more (p < 0.001), and age (p = 0.005); laparoscopy (p < 0.001) was associated with a decreased LOS. Intravenous opioid therapy is significantly associated with POI and prolonged LOS, particularly when the maximum hydromorphone dose per day exceeds 2 mg. Clinicians should consider alternative, nonopioid-based pain management options when this occurs.

Electron fluence correction factors for various materials in clinical electron beams.

PubMed

Olivares, M; DeBlois, F; Podgorsak, E B; Seuntjens, J P

2001-08-01

Relative to solid water, electron fluence correction factors at the depth of dose maximum in bone, lung, aluminum, and copper for nominal electron beam energies of 9 MeV and 15 MeV of the Clinac 18 accelerator have been determined experimentally and by Monte Carlo calculation. Thermoluminescent dosimeters were used to measure depth doses in these materials. The measured relative dose at dmax in the various materials versus that of solid water, when irradiated with the same number of monitor units, has been used to calculate the ratio of electron fluence for the various materials to that of solid water. The beams of the Clinac 18 were fully characterized using the EGS4/BEAM system. EGSnrc with the relativistic spin option turned on was used to optimize the primary electron energy at the exit window, and to calculate depth doses in the five phantom materials using the optimized phase-space data. Normalizing all depth doses to the dose maximum in solid water stopping power ratio corrected, measured depth doses and calculated depth doses differ by less than +/- 1% at the depth of dose maximum and by less than 4% elsewhere. Monte Carlo calculated ratios of doses in each material to dose in LiF were used to convert the TLD measurements at the dose maximum into dose at the center of the TLD in the phantom material. Fluence perturbation correction factors for a LiF TLD at the depth of dose maximum deduced from these calculations amount to less than 1% for 0.15 mm thick TLDs in low Z materials and are between 1% and 3% for TLDs in Al and Cu phantoms. Electron fluence ratios of the studied materials relative to solid water vary between 0.83+/-0.01 and 1.55+/-0.02 for materials varying in density from 0.27 g/cm3 (lung) to 8.96 g/cm3 (Cu). The difference in electron fluence ratios derived from measurements and calculations ranges from -1.6% to +0.2% at 9 MeV and from -1.9% to +0.2% at 15 MeV and is not significant at the 1sigma level. Excluding the data for Cu, electron fluence correction factors for open electron beams are approximately proportional to the electron density of the phantom material and only weakly dependent on electron beam energy.

Dexmedetomidine inhibits activation of the MAPK pathway and protects PC12 and NG108-15 cells from lidocaine-induced cytotoxicity at its maximum safe dose.

PubMed

Wang, Qiong; Tan, Yonghong; Zhang, Na; Xu, Yingyi; Wei, Wei; She, Yingjun; Bi, Xiaobao; Zhao, Baisong; Ruan, Xiangcai

2017-07-01

The developing brains of pediatric patients are highly vulnerable to anesthetic regimen (e.g., lidocaine), potentially causing neurological impairment. Recently, dexmedetomidine (DEX) has been used as an adjunct for sedation, and was shown to exert dose-dependent neuroprotective effects during brain injury. However, the maximum safe dose of DEX is unclear, and its protective effects against lidocaine-related neurotoxicity need to be confirmed. In this study, PC12 and NG108-15 cells were used to estimate safe, non-cytotoxic doses of DEX. We found that 100 and 60μM are the maximum safe dose of DEX for PC12 and NG108-15 cells, respectively, with no significant cytotoxicity. Lidocaine was found to remarkably inhibit cell vitality, but could be reversed by different doses of DEX, especially its maximum safe dose. Furthermore, the apoptosis induced by lidocaine was also assessed, and 100 and 60μM DEX showed optimal protective effects in PC12 and NG108-15 cells, respectively. Mechanistically, DEX activated the mitogen-activated protein kinase (MAPK) pathway, impaired caspase-3 expression, and enhanced anti-apoptotic factor Bcl-2 to resist lidocaine-induced apoptosis, indicating that the optimal dose of DEX alleviates lidocaine-induced cytotoxicity and should be considered in clinical application. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Dosimetric verification of IMRT treatment planning using Monte Carlo simulations for prostate cancer

NASA Astrophysics Data System (ADS)

Yang, J.; Li, J.; Chen, L.; Price, R.; McNeeley, S.; Qin, L.; Wang, L.; Xiong, W.; Ma, C.-M.

2005-03-01

The purpose of this work is to investigate the accuracy of dose calculation of a commercial treatment planning system (Corvus, Normos Corp., Sewickley, PA). In this study, 30 prostate intensity-modulated radiotherapy (IMRT) treatment plans from the commercial treatment planning system were recalculated using the Monte Carlo method. Dose-volume histograms and isodose distributions were compared. Other quantities such as minimum dose to the target (Dmin), the dose received by 98% of the target volume (D98), dose at the isocentre (Diso), mean target dose (Dmean) and the maximum critical structure dose (Dmax) were also evaluated based on our clinical criteria. For coplanar plans, the dose differences between Monte Carlo and the commercial treatment planning system with and without heterogeneity correction were not significant. The differences in the isocentre dose between the commercial treatment planning system and Monte Carlo simulations were less than 3% for all coplanar cases. The differences on D98 were less than 2% on average. The differences in the mean dose to the target between the commercial system and Monte Carlo results were within 3%. The differences in the maximum bladder dose were within 3% for most cases. The maximum dose differences for the rectum were less than 4% for all the cases. For non-coplanar plans, the difference in the minimum target dose between the treatment planning system and Monte Carlo calculations was up to 9% if the heterogeneity correction was not applied in Corvus. This was caused by the excessive attenuation of the non-coplanar beams by the femurs. When the heterogeneity correction was applied in Corvus, the differences were reduced significantly. These results suggest that heterogeneity correction should be used in dose calculation for prostate cancer with non-coplanar beam arrangements.

SU-E-T-169: Characterization of Pacemaker/ICD Dose in SAVI HDR Brachytherapy

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

Kalavagunta, C; Lasio, G; Yi, B

2015-06-15

Purpose: It is important to estimate dose to pacemaker (PM)/Implantable Cardioverter Defibrillator (ICD) before undertaking Accelerated Partial Breast Treatment using High Dose Rate (HDR) brachytherapy. Kim et al. have reported HDR PM/ICD dose using a single-source balloon applicator. To the authors knowledge, there have so far not been any published PM/ICD dosimetry literature for the Strut Adjusted Volume Implant (SAVI, Cianna Medical, Aliso Viejo, CA). This study aims to fill this gap by generating a dose look up table (LUT) to predict maximum dose to the PM/ICD in SAVI HDR brachytherapy. Methods: CT scans for 3D dosimetric planning were acquiredmore » for four SAVI applicators (6−1-mini, 6−1, 8−1 and 10−1) expanded to their maximum diameter in air. The CT datasets were imported into the Elekta Oncentra TPS for planning and each applicator was digitized in a multiplanar reconstruction window. A dose of 340 cGy was prescribed to the surface of a 1 cm expansion of the SAVI applicator cavity. Cartesian coordinates of the digitized applicator were determined in the treatment leading to the generation of a dose distribution and corresponding distance-dose prediction look up table (LUT) for distances from 2 to 15 cm (6-mini) and 2 to 20 cm (10–1).The deviation between the LUT doses and the dose to the cardiac device in a clinical case was evaluated. Results: Distance-dose look up table were compared to clinical SAVI plan and the discrepancy between the max dose predicted by the LUT and the clinical plan was found to be in the range (−0.44%, 0.74%) of the prescription dose. Conclusion: The distance-dose look up tables for SAVI applicators can be used to estimate the maximum dose to the ICD/PM, with a potential usefulness for quick assessment of dose to the cardiac device prior to applicator placement.« 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.

Reconstruction of Absorbed Doses to Fibroglandular Tissue of the Breast of Women undergoing Mammography (1960 to the Present)

PubMed Central

Thierry-Chef, Isabelle; Simon, Steven L.; Weinstock, Robert M.; Kwon, Deukwoo; Linet, Martha S.

2013-01-01

The assessment of potential benefits versus harms from mammographic examinations as described in the controversial breast cancer screening recommendations of the U.S. Preventive Task Force included limited consideration of absorbed dose to the fibroglandular tissue of the breast (glandular tissue dose), the tissue at risk for breast cancer. Epidemiological studies on cancer risks associated with diagnostic radiological examinations often lack accurate information on glandular tissue dose, and there is a clear need for better estimates of these doses. Our objective was to develop a quantitative summary of glandular tissue doses from mammography by considering sources of variation over time in key parameters including imaging protocols, x-ray target materials, voltage, filtration, incident air kerma, compressed breast thickness, and breast composition. We estimated the minimum, maximum, and mean values for glandular tissue dose for populations of exposed women within 5-year periods from 1960 to the present, with the minimum to maximum range likely including 90% to 95% of the entirety of the dose range from mammography in North America and Europe. Glandular tissue dose from a single view in mammography is presently about 2 mGy, about one-sixth the dose in the 1960s. The ratio of our estimates of maximum to minimum glandular tissue doses for average-size breasts was about 100 in the 1960s compared to a ratio of about 5 in recent years. Findings from our analysis provide quantitative information on glandular tissue doses from mammographic examinations which can be used in epidemiologic studies of breast cancer. PMID:21988547

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

Direct measurement of a patient's entrance skin dose during pediatric cardiac catheterization

PubMed Central

Sun, Lue; Mizuno, Yusuke; Iwamoto, Mari; Goto, Takahisa; Koguchi, Yasuhiro; Miyamoto, Yuka; Tsuboi, Koji; Chida, Koichi; Moritake, Takashi

2014-01-01

Children with complex congenital heart diseases often require repeated cardiac catheterization; however, children are more radiosensitive than adults. Therefore, radiation-induced carcinogenesis is an important consideration for children who undergo those procedures. We measured entrance skin doses (ESDs) using radio-photoluminescence dosimeter (RPLD) chips during cardiac catheterization for 15 pediatric patients (median age, 1.92 years; males, n = 9; females, n = 6) with cardiac diseases. Four RPLD chips were placed on the patient's posterior and right side of the chest. Correlations between maximum ESD and dose–area products (DAP), total number of frames, total fluoroscopic time, number of cine runs, cumulative dose at the interventional reference point (IRP), body weight, chest thickness, and height were analyzed. The maximum ESD was 80 ± 59 (mean ± standard deviation) mGy. Maximum ESD closely correlated with both DAP (r = 0.78) and cumulative dose at the IRP (r = 0.82). Maximum ESD for coiling and ballooning tended to be higher than that for ablation, balloon atrial septostomy, and diagnostic procedures. In conclusion, we directly measured ESD using RPLD chips and found that maximum ESD could be estimated in real-time using angiographic parameters, such as DAP and cumulative dose at the IRP. Children requiring repeated catheterizations would be exposed to high radiation levels throughout their lives, although treatment influences radiation dose. Therefore, the radiation dose associated with individual cardiac catheterizations should be analyzed, and the effects of radiation throughout the lives of such patients should be followed. PMID:24968708

Estimation of eye lens doses received by pediatric interventional cardiologists.

PubMed

Alejo, L; Koren, C; Ferrer, C; Corredoira, E; Serrada, A

2015-09-01

Maximum Hp(0.07) dose to the eye lens received in a year by the pediatric interventional cardiologists has been estimated. Optically stimulated luminescence dosimeters were placed on the eyes of an anthropomorphic phantom, whose position in the room simulates the most common irradiation conditions. Maximum workload was considered with data collected from procedures performed in the Hospital. None of the maximum values obtained exceed the dose limit of 20 mSv recommended by ICRP. Copyright © 2015 Elsevier Ltd. All rights reserved.

Dose and Dose Risk Caused by Natural Phenomena - Proposed Powder Metallurgy Core Manufacturing Facility

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

Holmes, W.G.

2001-08-16

The offsite radiological effects from high velocity straight winds, tornadoes, and earthquakes have been estimated for a proposed facility for manufacturing enriched uranium fuel cores by powder metallurgy. Projected doses range up to 30 mrem/event to the maximum offsite individual for high winds and up to 85 mrem/event for very severe earthquakes. Even under conservative assumptions on meteorological conditions, the maximum offsite dose would be about 20 per cent of the DOE limit for accidents involving enriched uranium storage facilities. The total dose risk is low and is dominated by the risk from earthquakes. This report discusses this test.

Dosimetric Evaluation Between Megavoltage Cone-Beam Computed Tomography and Body Mass Index for Intracranial, Thoracic, and Pelvic Localization

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

VanAntwerp, April E.; Raymond, Sarah M., E-mail: raymons9@ccf.org; Addington, Mark C.

2011-10-01

The aim of this study was to evaluate radiation dose for organs at risk (OAR) within the cranium, thorax, and pelvis from megavoltage cone-beam computed tomography (MV-CBCT). Using a clinical treatment planning system, CBCT doses were calculated from 60 patient datasets using 27.4 x 27.4 cm{sup 2} field size and 200{sup o} arc length. The body mass indices (BMIs) for these patients range from 17.2-48.4 kg/m{sup 2}. A total of 60 CBCT plans were created and calculated with heterogeneity corrections, with monitor units (MU) that varied from 8, 4, and 2 MU per plan. The isocenters of these plans weremore » placed at defined anatomical structures. The maximum dose, dose to the isocenter, and mean dose to the selected critical organs were analyzed. The study found that maximum and isocenter doses were weakly associated with BMI, but linearly associated with the total MU. Average maximum/isocenter doses in the cranium were 10.0 ({+-} 0.18)/7.0 ({+-} 0.08) cGy, 5.0 ({+-} 0.09)/3.5 ({+-} 0.05) cGy, and 2.5 ({+-} .04)/1.8 ({+-} 0.05) cGy for 8, 4, and 2 MU, respectively. Similar trends but slightly larger maximum/isocenter doses were found in the thoracic and pelvic regions. For the cranial region, the average mean doses with a total of 8 MU to the eye, lens, and brain were 9.7 ({+-} 0.12) cGy, 9.1 ({+-} 0.16) cGy, and 7.2 ({+-} 0.10) cGy, respectively. For the thoracic region, the average mean doses to the lung, heart, and spinal cord were 6.6 ({+-} 0.05) cGy, 6.9 ({+-} 1.2) cGy, and 4.7 ({+-} 0.8) cGy, respectively. For the pelvic region, the average mean dose to the femoral heads was 6.4 ({+-} 1.1) cGy. The MV-CBCT doses were linearly associated with the total MU but weakly dependent on patients' BMIs. Daily MV-CBCT has a cumulative effect on the total body dose and critical organs, which should be carefully considered for clinical impacts.« less

Dependence of normal brain integral dose and normal tissue complication probability on the prescription isodose values for γ-knife radiosurgery

NASA Astrophysics Data System (ADS)

Ma, Lijun

2001-11-01

A recent multi-institutional clinical study suggested possible benefits of lowering the prescription isodose lines for stereotactic radiosurgery procedures. In this study, we investigate the dependence of the normal brain integral dose and the normal tissue complication probability (NTCP) on the prescription isodose values for γ-knife radiosurgery. An analytical dose model was developed for γ-knife treatment planning. The dose model was commissioned by fitting the measured dose profiles for each helmet size. The dose model was validated by comparing its results with the Leksell gamma plan (LGP, version 5.30) calculations. The normal brain integral dose and the NTCP were computed and analysed for an ensemble of treatment cases. The functional dependence of the normal brain integral dose and the NCTP versus the prescribing isodose values was studied for these cases. We found that the normal brain integral dose and the NTCP increase significantly when lowering the prescription isodose lines from 50% to 35% of the maximum tumour dose. Alternatively, the normal brain integral dose and the NTCP decrease significantly when raising the prescribing isodose lines from 50% to 65% of the maximum tumour dose. The results may be used as a guideline for designing future dose escalation studies for γ-knife applications.

Quantifying the impact of immediate reconstruction in postmastectomy radiation: a large, dose-volume histogram-based analysis.

PubMed

Ohri, Nisha; Cordeiro, Peter G; Keam, Jennifer; Ballangrud, Ase; Shi, Weiji; Zhang, Zhigang; Nerbun, Claire T; Woch, Katherine M; Stein, Nicholas F; Zhou, Ying; McCormick, Beryl; Powell, Simon N; Ho, Alice Y

2012-10-01

To assess the impact of immediate breast reconstruction on postmastectomy radiation (PMRT) using dose-volume histogram (DVH) data. Two hundred forty-seven women underwent PMRT at our center, 196 with implant reconstruction and 51 without reconstruction. Patients with reconstruction were treated with tangential photons, and patients without reconstruction were treated with en-face electron fields and customized bolus. Twenty percent of patients received internal mammary node (IMN) treatment. The DVH data were compared between groups. Ipsilateral lung parameters included V20 (% volume receiving 20 Gy), V40 (% volume receiving 40 Gy), mean dose, and maximum dose. Heart parameters included V25 (% volume receiving 25 Gy), mean dose, and maximum dose. IMN coverage was assessed when applicable. Chest wall coverage was assessed in patients with reconstruction. Propensity-matched analysis adjusted for potential confounders of laterality and IMN treatment. Reconstruction was associated with lower lung V20, mean dose, and maximum dose compared with no reconstruction (all P<.0001). These associations persisted on propensity-matched analysis (all P<.0001). Heart doses were similar between groups (P=NS). Ninety percent of patients with reconstruction had excellent chest wall coverage (D95 >98%). IMN coverage was superior in patients with reconstruction (D95 >92.0 vs 75.7%, P<.001). IMN treatment significantly increased lung and heart parameters in patients with reconstruction (all P<.05) but minimally affected those without reconstruction (all P>.05). Among IMN-treated patients, only lower lung V20 in those without reconstruction persisted (P=.022), and mean and maximum heart doses were higher than in patients without reconstruction (P=.006, P=.015, respectively). Implant reconstruction does not compromise the technical quality of PMRT when the IMNs are untreated. Treatment technique, not reconstruction, is the primary determinant of target coverage and normal tissue doses. Published by Elsevier Inc.

Cosmic Radiation Exposure of Biological Test Systems During the EXPOSE-E Mission

PubMed Central

Hajek, Michael; Bilski, Pawel; Körner, Christine; Vanhavere, Filip; Reitz, Günther

2012-01-01

Abstract In the frame of the EXPOSE-E mission on the Columbus external payload facility EuTEF on board the International Space Station, passive thermoluminescence dosimeters were applied to measure the radiation exposure of biological samples. The detectors were located either as stacks next to biological specimens to determine the depth dose distribution or beneath the sample carriers to determine the dose levels for maximum shielding. The maximum mission dose measured in the upper layer of the depth dose part of the experiment amounted to 238±10 mGy, which relates to an average dose rate of 408±16 μGy/d. In these stacks of about 8 mm height, the dose decreased by 5–12% with depth. The maximum dose measured beneath the sample carriers was 215±16 mGy, which amounts to an average dose rate of 368±27 μGy/d. These values are close to those assessed for the interior of the Columbus module and demonstrate the high shielding of the biological experiments within the EXPOSE-E facility. Besides the shielding by the EXPOSE-E hardware itself, additional shielding was experienced by the external structures adjacent to EXPOSE-E, such as EuTEF and Columbus. This led to a dose gradient over the entire exposure area, from 215±16 mGy for the lowest to 121±6 mGy for maximum shielding. Hence, the doses perceived by the biological samples inside EXPOSE-E varied by 70% (from lowest to highest dose). As a consequence of the high shielding, the biological samples were predominantly exposed to galactic cosmic heavy ions, while electrons and a significant fraction of protons of the radiation belts and solar wind did not reach the samples. Key Words: Space radiation—Dosimetry—Passive radiation detectors—Thermoluminescence—EXPOSE-E. Astrobiology 12, 387–392. PMID:22680685

IDEAL-CRT: A Phase 1/2 Trial of Isotoxic Dose-Escalated Radiation Therapy and Concurrent Chemotherapy in Patients With Stage II/III Non-Small Cell Lung Cancer

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

Landau, David B., E-mail: david.landau@kcl.ac.uk; Hughes, Laura; Baker, Angela

2016-08-01

Purpose: To report toxicity and early survival data for IDEAL-CRT, a trial of dose-escalated concurrent chemoradiotherapy (CRT) for non-small cell lung cancer. Patients and Methods: Patients received tumor doses of 63 to 73 Gy in 30 once-daily fractions over 6 weeks with 2 concurrent cycles of cisplatin and vinorelbine. They were assigned to 1 of 2 groups according to esophageal dose. In group 1, tumor doses were determined by an experimental constraint on maximum esophageal dose, which was escalated following a 6 + 6 design from 65 Gy through 68 Gy to 71 Gy, allowing an esophageal maximum tolerated dose to be determined from early and late toxicities. Tumormore » doses for group 2 patients were determined by other tissue constraints, often lung. Overall survival, progression-free survival, tumor response, and toxicity were evaluated for both groups combined. Results: Eight centers recruited 84 patients: 13, 12, and 10, respectively, in the 65-Gy, 68-Gy, and 71-Gy cohorts of group 1; and 49 in group 2. The mean prescribed tumor dose was 67.7 Gy. Five grade 3 esophagitis and 3 grade 3 pneumonitis events were observed across both groups. After 1 fatal esophageal perforation in the 71-Gy cohort, 68 Gy was declared the esophageal maximum tolerated dose. With a median follow-up of 35 months, median overall survival was 36.9 months, and overall survival and progression-free survival were 87.8% and 72.0%, respectively, at 1 year and 68.0% and 48.5% at 2 years. Conclusions: IDEAL-CRT achieved significant treatment intensification with acceptable toxicity and promising survival. The isotoxic design allowed the esophageal maximum tolerated dose to be identified from relatively few patients.« less

A Phase I Study of the Safety and Pharmacokinetics of Higher-Dose Icotinib in Patients With Advanced Non-Small Cell Lung Cancer

PubMed Central

Liu, Jian; Wu, Lihua; Wu, Guolan; Hu, Xingjiang; Zhou, Huili; Chen, Junchun; Zhu, Meixiang; Xu, Wei; Tan, Fenlai; Ding, Lieming; Wang, Yinxiang

2016-01-01

Lessons Learned This phase I study evaluated the maximum tolerated dose, dose-limiting toxicities, safety, pharmacokinetics, and efficacy of icotinib with a starting dose of 250 mg in pretreated, advanced non-small cell lung cancer patients. We observed a maximum tolerated dose of 500 mg with a favorable pharmacokinetics profile and antitumor activity. These findings provide clinicians with evidence for application of higher-dose icotinib. Background. Icotinib, an oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, has shown favorable tolerability and antitumor activity at 100–200 mg in previous studies without reaching the maximum tolerated dose (MTD). In July 2011, icotinib was approved by the China Food and Drug Administration at a dose of 125 mg three times daily for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) after failure of at least one platinum-based chemotherapy regimen. This study investigated the MTD, tolerability, and pharmacokinetics of higher-dose icotinib in patients with advanced NSCLC. Methods. Twenty-six patients with advanced NSCLC were treated at doses of 250–625 mg three times daily The EGFR mutation test was not mandatory in this study. Results. Twenty-four (92.3%) of 26 patients experienced at least one adverse event (AE); rash (61.5%), diarrhea (23.1%), and oral ulceration (11.5%) were most frequent AEs. Dose-limiting toxicities were seen in 2 of 6 patients in the 625-mg group, and the MTD was established at 500 mg. Icotinib was rapidly absorbed and eliminated. The amount of time that the drug was present at the maximum concentration in serum (Tmax) ranged from 1 to 3 hours (1.5–4 hours) after multiple doses. The t1/2 was similar after single- and multiple-dose administration (7.11 and 6.39 hours, respectively). A nonlinear relationship was observed between dose and drug exposure. Responses were seen in 6 (23.1%) patients, and 8 (30.8%) patients had stable disease. Conclusion. This study demonstrated that higher-dose icotinib was well-tolerated, with a MTD of 500 mg. Favorable antitumor activity and pharmacokinetic profile were observed in patients with heavily pretreated, advanced NSCLC. PMID:27789778

A Phase I Study of the Safety and Pharmacokinetics of Higher-Dose Icotinib in Patients With Advanced Non-Small Cell Lung Cancer.

PubMed

Liu, Jian; Wu, Lihua; Wu, Guolan; Hu, Xingjiang; Zhou, Huili; Chen, Junchun; Zhu, Meixiang; Xu, Wei; Tan, Fenlai; Ding, Lieming; Wang, Yinxiang; Shentu, Jianzhong

2016-11-01

This phase I study evaluated the maximum tolerated dose, dose-limiting toxicities, safety, pharmacokinetics, and efficacy of icotinib with a starting dose of 250 mg in pretreated, advanced non-small cell lung cancer patients. We observed a maximum tolerated dose of 500 mg with a favorable pharmacokinetics profile and antitumor activity.These findings provide clinicians with evidence for application of higher-dose icotinib. Icotinib, an oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, has shown favorable tolerability and antitumor activity at 100-200 mg in previous studies without reaching the maximum tolerated dose (MTD). In July 2011, icotinib was approved by the China Food and Drug Administration at a dose of 125 mg three times daily for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) after failure of at least one platinum-based chemotherapy regimen. This study investigated the MTD, tolerability, and pharmacokinetics of higher-dose icotinib in patients with advanced NSCLC. Twenty-six patients with advanced NSCLC were treated at doses of 250-625 mg three times daily The EGFR mutation test was not mandatory in this study. Twenty-four (92.3%) of 26 patients experienced at least one adverse event (AE); rash (61.5%), diarrhea (23.1%), and oral ulceration (11.5%) were most frequent AEs. Dose-limiting toxicities were seen in 2 of 6 patients in the 625-mg group, and the MTD was established at 500 mg. Icotinib was rapidly absorbed and eliminated. The amount of time that the drug was present at the maximum concentration in serum (T max ) ranged from 1 to 3 hours (1.5-4 hours) after multiple doses. The t 1/2 was similar after single- and multiple-dose administration (7.11 and 6.39 hours, respectively). A nonlinear relationship was observed between dose and drug exposure. Responses were seen in 6 (23.1%) patients, and 8 (30.8%) patients had stable disease. This study demonstrated that higher-dose icotinib was well-tolerated, with a MTD of 500 mg. Favorable antitumor activity and pharmacokinetic profile were observed in patients with heavily pretreated, advanced NSCLC. ©AlphaMed Press; the data published online to support this summary is the property of the authors.

Safety and tolerability of the first-in-class agent CPI-613 in combination with modified FOLFIRINOX in patients with metastatic pancreatic cancer: a single-centre, open-label, dose-escalation, phase 1 trial.

PubMed

Alistar, Angela; Morris, Bonny B; Desnoyer, Rodwige; Klepin, Heidi D; Hosseinzadeh, Keyanoosh; Clark, Clancy; Cameron, Amy; Leyendecker, John; D'Agostino, Ralph; Topaloglu, Umit; Boteju, Lakmal W; Boteju, Asela R; Shorr, Rob; Zachar, Zuzana; Bingham, Paul M; Ahmed, Tamjeed; Crane, Sandrine; Shah, Riddhishkumar; Migliano, John J; Pardee, Timothy S; Miller, Lance; Hawkins, Gregory; Jin, Guangxu; Zhang, Wei; Pasche, Boris

2017-06-01

Pancreatic cancer statistics are dismal, with a 5-year survival of less than 10%, and more than 50% of patients presenting with metastatic disease. Metabolic reprogramming is an emerging hallmark of pancreatic adenocarcinoma. CPI-613 is a novel anticancer agent that selectively targets the altered form of mitochondrial energy metabolism in tumour cells, causing changes in mitochondrial enzyme activities and redox status that lead to apoptosis, necrosis, and autophagy of tumour cells. We aimed to establish the maximum tolerated dose of CPI-613 when used in combination with modified FOLFIRINOX chemotherapy (comprising oxaliplatin, leucovorin, irinotecan, and fluorouracil) in patients with metastatic pancreatic cancer. In this single-centre, open-label, dose-escalation phase 1 trial, we recruited adult patients (aged ≥18 years) with newly diagnosed metastatic pancreatic adenocarcinoma from the Comprehensive Cancer Center of Wake Forest Baptist Medical Center (Winston-Salem, NC, USA). Patients had good bone marrow, liver and kidney function, and good performance status (Eastern Cooperative Oncology Group [ECOG] performance status 0-1). We studied CPI-613 in combination with modified FOLFIRINOX (oxaliplatin at 65 mg/m 2 , leucovorin at 400 mg/m 2 , irinotecan at 140 mg/m 2 , and fluorouracil 400 mg/m 2 bolus followed by 2400 mg/m 2 over 46 h). We applied a two-stage dose-escalation scheme (single patient and traditional 3+3 design). In the single-patient stage, one patient was accrued per dose level. The starting dose of CPI-613 was 500 mg/m 2 per day; the dose level was then escalated by doubling the previous dose if there were no adverse events worse than grade 2 within 4 weeks attributed as probably or definitely related to CPI-613. The traditional 3+3 dose-escalation stage was triggered if toxic effects attributed as probably or definitely related to CPI-613 were grade 2 or worse. The dose level for CPI-613 for the first cohort in the traditional dose-escalation stage was the same as that used in the last cohort of the single-patient dose-escalation stage. The primary objective was to establish the maximum tolerated dose of CPI-613 (as assessed by dose-limiting toxicities). This trial is registered with ClinicalTrials.gov, number NCT01835041, and is closed to recruitment. Between April 22, 2013, and Jan 8, 2016, we enrolled 20 patients. The maximum tolerated dose of CPI-613 was 500 mg/m 2 . The median number of treatment cycles given at the maximum tolerated dose was 11 (IQR 4-19). Median follow-up of the 18 patients treated at the maximum tolerated dose was 378 days (IQR 250-602). Two patients enrolled at a higher dose of 1000 mg/m 2 , and both had a dose-limiting toxicity. Two unexpected serious adverse events occurred, both for the first patient enrolled. Expected serious adverse events were: thrombocytopenia, anaemia, and lymphopenia (all for patient number 2; anaemia and lymphopenia were dose-limiting toxicities); hyperglycaemia (in patient number 7); hypokalaemia, hypoalbuminaemia, and sepsis (patient number 11); and neutropenia (patient number 20). No deaths due to adverse events were reported. For the 18 patients given the maximum tolerated dose, the most common grade 3-4 non-haematological adverse events were hyperglycaemia (ten [55%] patients), hypokalaemia (six [33%]), peripheral sensory neuropathy (five [28%]), diarrhoea (five [28%]), and abdominal pain (four [22%]). The most common grade 3-4 haematological adverse events were neutropenia (five [28%] of 18 patients), lymphopenia (five [28%]), anaemia (four [22%], and thrombocytopenia in three [17%]). Sensory neuropathy (all grade 1-3) was recorded in 17 (94%) of the 18 patients and was managed with dose de-escalation or discontinuation per standard of care. No patients died while on active treatment; 11 study participants died, with cause of death as terminal pancreatic cancer. Of the 18 patients given the maximum tolerated dose, 11 (61%) achieved an objective (complete or partial) response. A maximum tolerated dose of CPI-613 was established at 500 mg/m 2 when used in combination with modified FOLFIRINOX in patients with metastatic pancreatic cancer. The findings of clinical activity will require validation in a phase 2 trial. Comprehensive Cancer Center of Wake Forest Baptist Medical Center. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effect of the Maximum Dose on White Matter Fiber Bundles Using Longitudinal Diffusion Tensor Imaging

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

Zhu, Tong; Chapman, Christopher H.; Tsien, Christina

2016-11-01

Purpose: Previous efforts to decrease neurocognitive effects of radiation focused on sparing isolated cortical structures. We hypothesize that understanding temporal, spatial, and dosimetric patterns of radiation damage to whole-brain white matter (WM) after partial-brain irradiation might also be important. Therefore, we carried out a study to develop the methodology to assess radiation therapy (RT)–induced damage to whole-brain WM bundles. Methods and Materials: An atlas-based, automated WM tractography analysis was implemented to quantify longitudinal changes in indices of diffusion tensor imaging (DTI) of 22 major WM fibers in 33 patients with predominantly low-grade or benign brain tumors treated by RT. Sixmore » DTI scans per patient were performed from before RT to 18 months after RT. The DTI indices and planned doses (maximum and mean doses) were mapped onto profiles of each of 22 WM bundles. A multivariate linear regression was performed to determine the main dose effect as well as the influence of other clinical factors on longitudinal percentage changes in axial diffusivity (AD) and radial diffusivity (RD) from before RT. Results: Among 22 fiber bundles, AD or RD changes in 12 bundles were affected significantly by doses (P<.05), as the effect was progressive over time. In 9 elongated tracts, decreased AD or RD was significantly related to maximum doses received, consistent with a serial structure. In individual bundles, AD changes were up to 11.5% at the maximum dose locations 18 months after RT. The dose effect on WM was greater in older female patients than younger male patients. Conclusions: Our study demonstrates for the first time that the maximum dose to the elongated WM bundles causes post-RT damage in WM. Validation and correlative studies are necessary to determine the ability and impact of sparing these bundles on preserving neurocognitive function after RT.« less

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

Small, Katherine; Kelly, Chris; Beldham-Collins, Rachael

A comparative study was conducted comparing the difference between (1) conformal radiotherapy (CRT) to the whole breast with sequential boost excision cavity plans and (2) intensity-modulated radiation therapy (IMRT) to the whole breast with simultaneously integrated boost to the excision cavity. The computed tomography (CT) data sets of 25 breast cancer patients were used and the results analysed to determine if either planning method produced superior plans. CT data sets from 25 past breast cancer patients were planned using (1) CRT prescribed to 50 Gy in 25 fractions (Fx) to the whole-breast planning target volume (PTV) and 10 Gy inmore » 5Fx to the excision cavity and (2) IMRT prescribed to 60 Gy in 25Fx, with 60 Gy delivered to the excision cavity PTV and 50 Gy delivered to the whole-breast PTV, treated simultaneously. In total, 50 plans were created, with each plan evaluated by PTV coverage using conformity indices, plan maximum dose, lung dose, and heart maximum dose for patients with left-side lesions. CRT plans delivered the lowest plan maximum doses in 56% of cases (average CRT = 6314.34 cGy, IMRT = 6371.52 cGy). They also delivered the lowest mean lung dose in 68% of cases (average CRT = 1206.64 cGy, IMRT = 1288.37 cGy) and V20 in 88% of cases (average CRT = 20.03%, IMRT = 21.73%) and V30 doses in 92% of cases (average CRT = 16.82%, IMRT = 17.97%). IMRT created more conformal plans, using both conformity index and conformation number, in every instance, and lower heart maximum doses in 78.6% of cases (average CRT = 5295.26 cGy, IMRT = 5209.87 cGy). IMRT plans produced superior dose conformity and shorter treatment duration, but a slightly higher planning maximum and increased lung doses. IMRT plans are also faster to treat on a daily basis, with shorter fractionation.« less

FDA-sunlamp recommended Maximum Timer Interval And Exposure Schedule: consensus ISO/CIE dose equivalence.

PubMed

Dowdy, John C; Czako, Eugene A; Stepp, Michael E; Schlitt, Steven C; Bender, Gregory R; Khan, Lateef U; Shinneman, Kenneth D; Karos, Manuel G; Shepherd, James G; Sayre, Robert M

2011-09-01

The authors compared calculations of sunlamp maximum exposure times following current USFDA Guidance Policy on the Maximum Timer Interval and Exposure Schedule, with USFDA/CDRH proposals revising these to equivalent erythemal exposures of ISO/CIE Standard Erythema Dose (SED). In 2003, [USFDA/CDRH proposed replacing their unique CDRH/Lytle] erythema action spectrum with the ISO/CIE erythema action spectrum and revising the sunlamp maximum exposure timer to 600 J m(-2) ISO/CIE effective dose, presented as being biologically equivalent. Preliminary analysis failed to confirm said equivalence, indicating instead ∼38% increased exposure when applying these proposed revisions. To confirm and refine this finding, a collaboration of tanning bed and UV lamp manufacturers compiled 89 UV spectra representing a broad sampling of U.S. indoor tanning equipment. USFDA maximum recommended exposure time (Te) per current sunlamp guidance and CIE erythemal effectiveness per ISO/CIE standard were calculated. The CIE effective dose delivered per Te averaged 456 J(CIE) m(-2) (SD = 0.17) or ∼4.5 SED. The authors found that CDRH's proposed 600 J(CIE) m(-2) recommended maximum sunlamp exposure exceeds current Te erythemal dose by ∼33%. The current USFDA 0.75 MED initial exposure was ∼0.9 SED, consistent with 1.0 SED initial dose in existing international sunlamp standards. As no sunlamps analyzed exceeded 5 SED, a revised maximum exposure of 500 J(CIE) m(-2) (∼80% of CDRH's proposal) should be compatible with existing tanning equipment. A tanning acclimatization schedule is proposed beginning at 1 SED thrice-weekly, increasing uniformly stepwise over 4 wk to a 5 SED maximum exposure in conjunction with a tan maintenance schedule of twice-weekly 5 SED sessions, as biologically equivalent to current USFDA sunlamp policy.

Regulatory Forum Opinion Piece*: Retrospective Evaluation of Doses in the 26-week Tg.rasH2 Mice Carcinogenicity Studies: Recommendation to Eliminate High Doses at Maximum Tolerated Dose in Future Studies. A Response to the Counterpoints.

PubMed

Paranjpe, Madhav G; Denton, Melissa D; Vidmar, Tom J; Elbekai, Reem H

2016-01-01

We recently conducted a retrospective analysis of data collected from 29 Tg.rasH2 carcinogenicity studies conducted at our facility to determine how successful was the strategy of choosing the high dose of the 26-week studies based on an estimated maximum tolerated dose (MTD). As a result of our publication, 2 counterviews were expressed. Both counterviews illustrate very valid points in their interpretation of our data. In this article, we would like to highlight clarifications based on several points and issues they have raised in their papers, namely, the dose-level selection, determining if MTD was exceeded in 26-week studies, and a discussion on the number of dose groups to be used in the studies. © The Author(s) 2015.

Multileaf collimator tongue-and-groove effect on depth and off-axis doses: A comparison of treatment planning data with measurements and Monte Carlo calculations

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

Kim, Hee Jung; Department of Biomedical Engineering, Seoul National University, Seoul; Department of Radiation Oncology, Soonchunhyang University Hospital, Seoul

2015-01-01

To investigate how accurately treatment planning systems (TPSs) account for the tongue-and-groove (TG) effect, Monte Carlo (MC) simulations and radiochromic film (RCF) measurements were performed for comparison with TPS results. Two commercial TPSs computed the TG effect for Varian Millennium 120 multileaf collimator (MLC). The TG effect on off-axis dose profile at 3 depths of solid water was estimated as the maximum depth and the full width at half maximum (FWHM) of the dose dip at an interleaf position. When compared with the off-axis dose of open field, the maximum depth of the dose dip for MC and RCF rangedmore » from 10.1% to 20.6%; the maximum depth of the dose dip gradually decreased by up to 8.7% with increasing depths of 1.5 to 10 cm and also by up to 4.1% with increasing off-axis distances of 0 to 13 cm. However, TPS results showed at most a 2.7% decrease for the same depth range and a negligible variation for the same off-axis distances. The FWHM of the dose dip was approximately 0.19 cm for MC and 0.17 cm for RCF, but 0.30 cm for Eclipse TPS and 0.45 cm for Pinnacle TPS. Accordingly, the integrated value of TG dose dip for TPS was larger than that for MC and RCF and almost invariant along the depths and off-axis distances. We concluded that the TG dependence on depth and off-axis doses shown in the MC and RCF results could not be appropriately modeled by the TPS versions in this study.« less

Confusion: acetaminophen dosing changes based on NO evidence in adults.

PubMed

Krenzelok, Edward P; Royal, Mike A

2012-06-01

Acetaminophen (paracetamol) plays a vital role in American health care, with in excess of 25 billion doses being used annually as a nonprescription medication. Over 200 million acetaminophen-containing prescriptions, usually in combination with an opioid, are dispensed annually. While acetaminophen is recognized as a safe and effective analgesic and antipyretic, it is also associated with significant morbidity and mortality (hepatotoxicity) if doses in excess of the therapeutic amount are ingested inappropriately. The maximum daily therapeutic dose of 3900-4000 mg was established in separate actions in 1977 and 1988, respectively, via the Food and Drug Administration (FDA) monograph process for nonprescription medications. The FDA has conducted multiple advisory committee meetings to evaluate acetaminophen and its safety profile, and has suggested (but not mandated) a reduction in the maximum daily dosage from 3900-4000 mg to 3000-3250 mg. In 2011, McNeil, the producer of the Tylenol® brand of acetaminophen, voluntarily reduced the maximum daily dose of its 500 mg tablet product to 3000 mg/day, and it has pledged to change the labeling of its 325 mg/tablet product to reflect a maximum of 3250 mg/day. Generic manufacturers have not changed their dosing regimens and they have remained consistent with the established monograph dose. Therefore, confusion will be inevitable as both consumers and health care professionals try to determine the proper therapeutic dose of acetaminophen. Which is the correct dose of acetaminophen: 3000 mg if 500 mg tablets are used, 3250 mg with 325 mg tablets, or 3900 mg when 650 mg arthritis-strength products are used?

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

Li, Heng, E-mail: hengli@mdanderson.org; Zhu, X. Ronald; Zhang, Xiaodong

Purpose: To develop and validate a novel delivery strategy for reducing the respiratory motion–induced dose uncertainty of spot-scanning proton therapy. Methods and Materials: The spot delivery sequence was optimized to reduce dose uncertainty. The effectiveness of the delivery sequence optimization was evaluated using measurements and patient simulation. One hundred ninety-one 2-dimensional measurements using different delivery sequences of a single-layer uniform pattern were obtained with a detector array on a 1-dimensional moving platform. Intensity modulated proton therapy plans were generated for 10 lung cancer patients, and dose uncertainties for different delivery sequences were evaluated by simulation. Results: Without delivery sequence optimization,more » the maximum absolute dose error can be up to 97.2% in a single measurement, whereas the optimized delivery sequence results in a maximum absolute dose error of ≤11.8%. In patient simulation, the optimized delivery sequence reduces the mean of fractional maximum absolute dose error compared with the regular delivery sequence by 3.3% to 10.6% (32.5-68.0% relative reduction) for different patients. Conclusions: Optimizing the delivery sequence can reduce dose uncertainty due to respiratory motion in spot-scanning proton therapy, assuming the 4-dimensional CT is a true representation of the patients' breathing patterns.« less

Organ dose measurement using Optically Stimulated Luminescence Detector (OSLD) during CT examination

NASA Astrophysics Data System (ADS)

Yusuf, Muhammad; Alothmany, Nazeeh; Abdulrahman Kinsara, Abdulraheem

2017-10-01

This study provides detailed information regarding the imaging doses to patient radiosensitive organs from a kilovoltage computed tomography (CT) scan procedure using OSLD. The study reports discrepancies between the measured dose and the calculated dose from the ImPACT scan, as well as a comparison with the dose from a chest X-ray radiography procedure. OSLDs were inserted in several organs, including the brain, eyes, thyroid, lung, heart, spinal cord, breast, spleen, stomach, liver and ovaries, of the RANDO phantom. Standard clinical scanning protocols were used for each individual site, including the brain, thyroid, lung, breast, stomach, liver and ovaries. The measured absorbed doses were then compared with the simulated dose obtained from the ImPACT scan. Additionally, the equivalent doses for each organ were calculated and compared with the dose from a chest X-ray radiography procedure. Absorbed organ doses measured by OSLD in the RANDO phantom of up to 17 mGy depend on the organ scanned and the scanning protocols used. A maximum 9.82% difference was observed between the target organ dose measured by OSLD and the results from the ImPACT scan. The maximum equivalent organ dose measured during this experiment was equal to 99.899 times the equivalent dose from a chest X-ray radiography procedure. The discrepancies between the measured dose with the OSLD and the calculated dose from the ImPACT scan were within 10%. This report recommends the use of OSLD for measuring the absorbed organ dose during CT examination.

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.

The use of paracetamol (acetaminophen) among a community sample of people with chronic non-cancer pain prescribed opioids.

PubMed

Hoban, B; Larance, B; Gisev, N; Nielsen, S; Cohen, M; Bruno, R; Shand, F; Lintzeris, N; Hall, W; Farrell, M; Degenhardt, L

2015-11-01

The regular use of simple analgesics in addition to opioids such as paracetamol (or acetaminophen) is recommended for persistent pain to enhance analgesia. Few studies have examined the frequency and doses of paracetamol among people with chronic non-cancer pain including use above the recommended maximum daily dose. To assess (i) the prevalence of paracetamol use among people with chronic non-cancer pain prescribed opioids, (ii) assess the prevalence of paracetamol use above the recommended maximum daily dose and (iii) assess correlates of people who used paracetamol above the recommended maximum daily dose including: age, gender, income, education, pain severity and interference, use of paracetamol/opioid combination analgesics, total opioid dose, depression, anxiety, pain self-efficacy or comorbid substance use, among people prescribed opioids for chronic non-cancer pain. This study draws on baseline data collected for the Pain and Opioids IN Treatment (POINT) study and utilises data from 962 interviews and medication diaries. The POINT study is national prospective cohort of people with chronic non-cancer pain prescribed opioids. Participants were recruited from randomly selected pharmacies across Australia. Sixty-three per cent of the participants had used paracetamol in the past week (95% CI = 59.7-65.8). Among the paracetamol users 22% (95% CI = 19.3-24.6) had used paracetamol/opioid combination analgesics and 4.8% (95% CI = 3.6-6.3) had used paracetamol above the recommended maximum daily dose (i.e. > 4000 mg/day). Following binomial logistic regression (χ(2) = 25.98, df = 10, p = 0.004), people who had taken above the recommended maximum daily dose were less likely to have low income (AOR = 0.52, 95% CI = 0.27-0.99), more likely to use paracetamol/opioid combination analgesics (AOR = 2.01, 95% CI = 1.02-3.98) and more likely to take a higher opioid dose (AOR = 1.00, 95% CI = 1.00-1.01). The majority of people with chronic non-cancer pain prescribed opioids report using paracetamol appropriately. High income, use of paracetamol/opioid combination analgesics and higher opioid dose were independently associated with paracetamol use above the recommended maximum daily dose. © 2015 John Wiley & Sons Ltd.

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

Pokhrel, D; Sood, S; Badkul, R

Purpose: To evaluate XVMC computed rib doses for peripherally located non-small-cell-lung tumors treated with SBRT following RTOG-0915 guidelines. Methods: Twenty patients with solitary peripherally located non-small-cell-lung tumors were treated using XVMC-based SBRT to 50–54Gy in 5−3 fractions, respectively, for PTV(V100%)=95%. Based on 4D-CT, ITV was delineated on MaximumIP images and organs-at-risk(OARs) including ribs were contoured on MeanIP images. Mean PTV(ITV+5mm uniform margin) was 46.1±38.7cc (range, 11.1–163.0cc). XVMC SBRT treatment plans were generated with a combination of non-coplanar 3D-conformal arcs/beams, and were delivered by Novalis-TX consisting of HD-MLCs and a 6MV-SRS(1000MU/min) beam, following RTOG-0915 criteria. XVMC rib maximum dose and dosemore » to <1cc, <5cc, <10cc were evaluated as a function of PTV, prescription dose and 3D-distance from tumor isocenter to the most proximal rib contour. Plans were re-computed using heterogeneity-corrected pencil-beam (PB-hete) algorithm utilizing identical beam geometry/MLC positions and MUs and subsequently compared to XVMC. Results: XVMC average maximum rib dose was 50.9±6.4Gy (range, 35.1–59.3Gy). XVMC mean rib dose to <1cc was 41.6±5.6Gy (range, 27.9–47.9Gy), <5cc was 31.2±7.3Gy (range, 10.6–43.1Gy), and <10cc was 21.2±8.7Gy (range, 1.1–36Gy), respectively. For the given prescription, correlation between PTV and rib doses to <5cc (p=0.005) and <10cc (p=0.018) was observed. 3D-distance from the tumor isocenter to the proximal rib contour strongly correlated with maximum rib dose (p=0.0001). PB-hete algorithm overestimated maximum rib dose and dose to <1cc, <5cc, and <10cc of ribs by 5%, 3%, 3%, and 3%, respectively. Conclusion: PB-hete overestimates ribs dose relative to XVMC. Since all the clinical XVMC plans were generated without compromising the target coverage (per RTOG-0915), almost all patient’s ribs doses were higher than the protocol guidelines. As expected, larger tumor size and proximity to ribs received higher absolute dose to ribs. Prospective observation is needed to determine if XVMC delivered rib doses correlates with patient symptoms including chest wall pain and/or rib fractures.« less

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

Loupot, S; Han, T; Salehpour, M

Purpose: To quantify the difference in dose to PTV-EVAL and OARs (skin and rib) as calculated by (TG43) and heterogeneous calculations (CCC). Methods: 25 patient plans (5 Contura and 20 SAVI) were selected for analysis. Clinical dose distributions were computed with a commercially available treatment planning algorithm (TG43-D-(w,w)) and then recomputed with a pre-clinical collapsed cone convolution algorithm (CCCD-( m,m)). PTV-EVAL coverage (V90%, V95%), and rib and skin maximum dose were compared via percent difference. Differences in dose to normal tissue (V150cc, V200cc of PTV-EVAL) were also compared. Changes in coverage and maximum dose to organs at risk are reportedmore » in percent change, (100*(TG43 − CCC) / TG43)), and changes in maximum dose to normal tissue are absolute change in cc (TG43 − CCC). Results: Mean differences in V90, V95, V150, and V200 for the SAVI cases were −0.2%, −0.4%, −0.03cc, and −0.14cc, respectively, with maximum differences of −0.78%, −1.7%, 1.28cc, and 1.01cc, respectively. Mean differences in the 0.1cc dose to the rib and skin were −1.4% and −0.22%, respectively, with maximum differences of −4.5% and 16%, respectively. Mean differences in V90, V95, V150, and V200 for the Contura cases were −1.2%, −2.1%, −1.8cc, and −0.59cc, respectively, with maximum differences of −2.0%, −3.16%, −2.9cc, and −0.76cc, respectively. Mean differences in the 0.1cc dose to the rib and skin were −2.6% and −3.9%, respectively, with maximum differences of −3.2% and −5.7%, respectively. Conclusion: The effects of translating clinical knowledge based on D-(w,w) to plans reported in D-(m,m) are minimal (2% or less) on average, but vary based on the type and placement of the device, source, and heterogeneity information.« less

[Value of early application of different doses of amino acids in parenteral nutrition among preterm infants].

PubMed

Liu, Zhi-Juan; Liu, Guo-Sheng; Chen, Yong-Ge; Zhang, Hui-Li; Wu, Xue-Fen

2015-01-01

To study the short-term response and tolerance of different doses of amino acids in parenteral nutrition among preterm infants. This study included 86 preterm infants who had a birth weight between 1 000 to 2 000 g and were admitted to the hospital within 24 hours of birth between March 2013 and June 2014. According to the early application of different doses of amino acids, they were randomized into low-dose group (n=29, 1.0 g/kg per day with an increase of 1.0 g/kg daily and a maximum of 3.5 g/kg per day), medium-dose group (n=28, 2.0 g/kg per day with an increase of 1.0 g/kg daily and a maximum of 3.7 g/kg per day), and high-dose group (n=29, 3.0 g/kg per day with an increase of 0.5-1.0 g/kg daily and a maximum of 4.0 g/kg per day). Other routine parenteral nutrition and enteral nutrition support were also applied. The maximum weight loss was lower and the growth rate of head circumference was greater in the high-dose group than in the low-dose group (P<0.05). The infants in the medium- and high-dose groups had faster recovery of birth weight, earlier attainment of 100 kcal/(kg·d) of enteral nutrition, shorter duration of hospital stay, and less hospital cost than those in the low-dose group (P<0.05). Blood urea nitrogen (BUN) levels in the high-dose group increased compared with the other two groups 7 days after birth (P<0.05). The levels of creatinine, pH, bicarbonate, bilirubin, and transaminase and the incidence of complications showed no significant differences between groups (P>0.05). Parenteral administration of high-dose amino acids in preterm infants within 24 hours after birth can improve the short-term nutritional status of preterm infants, but there is a transient increase in BUN level.

Regulatory Forum Opinion Piece*: Retrospective Evaluation of Doses in the 26-week Tg.rasH2 Mice Carcinogenicity Studies: Recommendation to Eliminate High Doses at Maximum Tolerated Dose (MTD) in Future Studies.

PubMed

Paranjpe, Madhav G; Denton, Melissa D; Vidmar, Tom J; Elbekai, Reem H

2015-07-01

High doses in Tg.rasH2 carcinogenicity studies are usually set at the maximum tolerated dose (MTD), although this dose selection strategy has not been critically evaluated. We analyzed the body weight gains (BWGs), mortality, and tumor response in control and treated groups of 29 Tg.rasH2 studies conducted at BioReliance. Based on our analysis, it is evident that the MTD was exceeded at the high and/or mid-doses in several studies. The incidence of tumors in high doses was lower when compared to the low and mid-doses of both sexes. Thus, we recommend that the high dose in male mice should not exceed one-half of the estimated MTD (EMTD), as it is currently chosen, and the next dose should be one-fourth of the EMTD. Because females were less sensitive to decrements in BWG, the high dose in female mice should not exceed two-third of EMTD and the next dose group should be one-third of EMTD. If needed, a third dose group should be set at one-eighth EMTD in males and one-sixth EMTD in females. In addition, for compounds that do not show toxicity in the range finding studies, a limit dose should be applied for the 26-week carcinogenicity studies. © 2014 by The Author(s).

Bolus-dependent dosimetric effect of positioning errors for tangential scalp radiotherapy with helical tomotherapy

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

Lobb, Eric, E-mail: eclobb2@gmail.com

2014-04-01

The dosimetric effect of errors in patient position is studied on-phantom as a function of simulated bolus thickness to assess the need for bolus utilization in scalp radiotherapy with tomotherapy. A treatment plan is generated on a cylindrical phantom, mimicking a radiotherapy technique for the scalp utilizing primarily tangential beamlets. A planning target volume with embedded scalplike clinical target volumes (CTVs) is planned to a uniform dose of 200 cGy. Translational errors in phantom position are introduced in 1-mm increments and dose is recomputed from the original sinogram. For each error the maximum dose, minimum dose, clinical target dose homogeneitymore » index (HI), and dose-volume histogram (DVH) are presented for simulated bolus thicknesses from 0 to 10 mm. Baseline HI values for all bolus thicknesses were in the 5.5 to 7.0 range, increasing to a maximum of 18.0 to 30.5 for the largest positioning errors when 0 to 2 mm of bolus is used. Utilizing 5 mm of bolus resulted in a maximum HI value of 9.5 for the largest positioning errors. Using 0 to 2 mm of bolus resulted in minimum and maximum dose values of 85% to 94% and 118% to 125% of the prescription dose, respectively. When using 5 mm of bolus these values were 98.5% and 109.5%. DVHs showed minimal changes in CTV dose coverage when using 5 mm of bolus, even for the largest positioning errors. CTV dose homogeneity becomes increasingly sensitive to errors in patient position as bolus thickness decreases when treating the scalp with primarily tangential beamlets. Performing a radial expansion of the scalp CTV into 5 mm of bolus material minimizes dosimetric sensitivity to errors in patient position as large as 5 mm and is therefore recommended.« less

Impact of head and neck cancer adaptive radiotherapy to spare the parotid glands and decrease the risk of xerostomia.

PubMed

Castelli, Joel; Simon, Antoine; Louvel, Guillaume; Henry, Olivier; Chajon, Enrique; Nassef, Mohamed; Haigron, Pascal; Cazoulat, Guillaume; Ospina, Juan David; Jegoux, Franck; Benezery, Karen; de Crevoisier, Renaud

2015-01-09

Large anatomical variations occur during the course of intensity-modulated radiation therapy (IMRT) for locally advanced head and neck cancer (LAHNC). The risks are therefore a parotid glands (PG) overdose and a xerostomia increase. The purposes of the study were to estimate: - the PG overdose and the xerostomia risk increase during a "standard" IMRT (IMRTstd); - the benefits of an adaptive IMRT (ART) with weekly replanning to spare the PGs and limit the risk of xerostomia. Fifteen patients received radical IMRT (70 Gy) for LAHNC. Weekly CTs were used to estimate the dose distributions delivered during the treatment, corresponding either to the initial planning (IMRTstd) or to weekly replanning (ART). PGs dose were recalculated at the fraction, from the weekly CTs. PG cumulated doses were then estimated using deformable image registration. The following PG doses were compared: pre-treatment planned dose, per-treatment IMRTstd and ART. The corresponding estimated risks of xerostomia were also compared. Correlations between anatomical markers and dose differences were searched. Compared to the initial planning, a PG overdose was observed during IMRTstd for 59% of the PGs, with an average increase of 3.7 Gy (10.0 Gy maximum) for the mean dose, and of 8.2% (23.9% maximum) for the risk of xerostomia. Compared to the initial planning, weekly replanning reduced the PG mean dose for all the patients (p<0.05). In the overirradiated PG group, weekly replanning reduced the mean dose by 5.1 Gy (12.2 Gy maximum) and the absolute risk of xerostomia by 11% (p<0.01) (30% maximum). The PG overdose and the dosimetric benefit of replanning increased with the tumor shrinkage and the neck thickness reduction (p<0.001). During the course of LAHNC IMRT, around 60% of the PGs are overdosed of 4 Gy. Weekly replanning decreased the PG mean dose by 5 Gy, and therefore by 11% the xerostomia risk.

Is it possible to avoid hypopituitarism after irradiation of pituitary adenomas by the Leksell gamma knife?

PubMed

Marek, Josef; Jezková, Jana; Hána, Václav; Krsek, Michal; Bandúrová, L'ubomíra; Pecen, Ladislav; Vladyka, Vilibald; Liscák, Roman

2011-02-01

Radiation therapy is one of the treatment options for pituitary adenomas. The most common side effect associated with Leksell gamma knife (LGK) irradiation is the development of hypopituitarism. The aim of this study was to verify that hypopituitarism does not develop if the maximum mean dose to pituitary is kept under 15 Gy and to evaluate the influence of maximum distal infundibulum dose on the development of hypopituitarism. We followed the incidence of hypopituitarism in 85 patients irradiated with LGK in 1993-2003. The patients were divided in two subgroups: the first subgroup followed prospectively (45 patients), irradiated with a mean dose to pituitary <15 Gy; the second subgroup followed retrospectively 1993-2001 and prospectively 2001-2009 (40 patients), irradiated with a mean dose to pituitary >15 Gy. Serum TSH, free thyroxine, testosterone or 17β-oestradiol, IGF1, prolactin and cortisol levels were evaluated before and every 6 months after LGK irradiation. Hypopituitarism after LGK irradiation developed only in 1 out of 45 (2.2%) patients irradiated with a mean dose to pituitary <15 Gy, in contrast to 72.5% patients irradiated with a mean dose to pituitary >15 Gy. The radiation dose to the distal infundibulum was found as an independent factor of hypopituitarism with calculated maximum safe dose of 17 Gy. Keeping the mean radiation dose to pituitary under 15 Gy and the dose to the distal infundibulum under 17 Gy prevents the development of hypopituitarism following LGK irradiation.

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

Stereotactic body radiation therapy of early-stage non-small-cell lung carcinoma: Phase I study

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

McGarry, Ronald C.; Papiez, Lech; Williams, Mark

Purpose: A Phase I dose escalation study of stereotactic body radiation therapy to assess toxicity and local control rates for patients with medically inoperable Stage I lung cancer. Methods and Materials: All patients had non-small-cell lung carcinoma, Stage T1a or T1b N0, M0. Patients were immobilized in a stereotactic body frame and treated in escalating doses of radiotherapy beginning at 24 Gy total (3 x 8 Gy fractions) using 7-10 beams. Cohorts were dose escalated by 6.0 Gy total with appropriate observation periods. Results: The maximum tolerated dose was not achieved in the T1 stratum (maximum dose = 60 Gy),more » but within the T2 stratum, the maximum tolerated dose was realized at 72 Gy for tumors larger than 5 cm. Dose-limiting toxicity included predominantly bronchitis, pericardial effusion, hypoxia, and pneumonitis. Local failure occurred in 4/19 T1 and 6/28 T2 patients. Nine local failures occurred at doses {<=}16 Gy and only 1 at higher doses. Local failures occurred between 3 and 31 months from treatment. Within the T1 group, 5 patients had distant or regional recurrence as an isolated event, whereas 3 patients had both distant and regional recurrence. Within the T2 group, 2 patients had solitary regional recurrences, and the 4 patients who failed distantly also failed regionally. Conclusions: Stereotactic body radiation therapy seems to be a safe, effective means of treating early-stage lung cancer in medically inoperable patients. Excellent local control was achieved at higher dose cohorts with apparent dose-limiting toxicities in patients with larger tumors.« less

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

SU-F-T-117: A Pilot Study of Organ Dose Reconstruction for Wilms Tumor Patients Treated with Radiation Therapy

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

Makkia, R; Pelletier, C; Jung, J

Purpose: To reconstruct major organ doses for the Wilms tumor pediatric patients treated with radiation therapy using pediatric computational phantoms, treatment planning system (TPS), and Monte Carlo (MC) dose calculation methods. Methods: A total of ten female and male pediatric patients (15–88 months old) were selected from the National Wilms Tumor Study cohort and ten pediatric computational phantoms corresponding to the patient’s height and weight were selected for the organ dose reconstruction. Treatment plans were reconstructed on the computational phantoms in a Pinnacle TPS (v9.10) referring to treatment records and exported into DICOM-RT files, which were then used to generatemore » the input files for XVMC MC code. The mean doses to major organs and the dose received by 50% of the heart were calculated and compared between TPS and MC calculations. The same calculations were conducted by replacing the computational human phantoms with a series of diagnostic patient CT images selected by matching the height and weight of the patients to validate the anatomical accuracy of the computational phantoms. Results: Dose to organs located within the treatment fields from the computational phantoms and the diagnostic patient CT images agreed within 2% for all cases for both TPS and MC calculations. The maximum difference of organ doses was 55.9 % (thyroid), but the absolute dose difference in this case was 0.33 Gy which was 0.96% of the prescription dose. The doses to ovaries and testes from MC in out-of-field provided more discrepancy (the maximum difference of 13.2% and 50.8%, respectively). The maximum difference of the 50% heart volume dose between the phantoms and the patient CT images was 40.0%. Conclusion: This study showed the pediatric computational phantoms are applicable to organ doses reconstruction for the radiotherapy patients whose three-dimensional radiological images are not available.« less

Direct plan comparison of RapidArc and CyberKnife for spine stereotactic body radiation therapy

NASA Astrophysics Data System (ADS)

Choi, Young Eun; Kwak, Jungwon; Song, Si Yeol; Choi, Eun Kyung; Ahn, Seung Do; Cho, Byungchul

2015-07-01

We compared the treatment planning performance of RapidArc (RA) vs. CyberKnife (CK) for spinal stereotactic body radiation therapy (SBRT). Ten patients with spinal lesions who had been treated with CK were re-planned with RA, which consisted of two complete arcs. Computed tomography (CT) and volumetric dose data of CK, generated using the Multiplan (Accuray) treatment planning system (TPS) and the Ray-trace algorithm, were imported to Varian Eclipse TPS in Dicom format, and the data were compared with the RA plan by using an analytical anisotropic algorithm (AAA) dose calculation. The optimized dose priorities for both the CK and the RA plans were similar for all patients. The highest priority was to provide enough dose coverage to the planned target volume (PTV) while limiting the maximum dose to the spinal cord. Plan quality was evaluated with respect to PTV coverage, conformity index (CI), high-dose spillage, intermediate-dose spillage (R50% and D2cm), and maximum dose to the spinal cord, which are criteria recommended by the RTOG 0631 spine and 0915 lung SBRT protocols. The mean CI' SD values of the PTV were 1.11' 0.03 and 1.17' 0.10 for RA and CK ( p = 0.02), respectively. On average, the maximum dose delivered to the spinal cord in CK plans was approximately 11.6% higher than that in RA plans, and this difference was statistically significant ( p < 0.001). High-dose spillages were 0.86% and 2.26% for RA and CK ( p = 0.203), respectively. Intermediate-dose spillage characterized by D2cm was lower for RA than for CK; however, R50% was not statistically different. Even though both systems can create highly conformal volumetric dose distributions, the current study shows that RA demonstrates lower high- and intermediate-dose spillages than CK. Therefore, RA plans for spinal SBRT may be superior to CK plans.

Comprehensive evaluations of cone-beam CT dose in image-guided radiation therapy via GPU-based Monte Carlo simulations

NASA Astrophysics Data System (ADS)

Montanari, Davide; Scolari, Enrica; Silvestri, Chiara; Jiang Graves, Yan; Yan, Hao; Cervino, Laura; Rice, Roger; Jiang, Steve B.; Jia, Xun

2014-03-01

Cone beam CT (CBCT) has been widely used for patient setup in image-guided radiation therapy (IGRT). Radiation dose from CBCT scans has become a clinical concern. The purposes of this study are (1) to commission a graphics processing unit (GPU)-based Monte Carlo (MC) dose calculation package gCTD for Varian On-Board Imaging (OBI) system and test the calculation accuracy, and (2) to quantitatively evaluate CBCT dose from the OBI system in typical IGRT scan protocols. We first conducted dose measurements in a water phantom. X-ray source model parameters used in gCTD are obtained through a commissioning process. gCTD accuracy is demonstrated by comparing calculations with measurements in water and in CTDI phantoms. Twenty-five brain cancer patients are used to study dose in a standard-dose head protocol, and 25 prostate cancer patients are used to study dose in pelvis protocol and pelvis spotlight protocol. Mean dose to each organ is calculated. Mean dose to 2% voxels that have the highest dose is also computed to quantify the maximum dose. It is found that the mean dose value to an organ varies largely among patients. Moreover, dose distribution is highly non-homogeneous inside an organ. The maximum dose is found to be 1-3 times higher than the mean dose depending on the organ, and is up to eight times higher for the entire body due to the very high dose region in bony structures. High computational efficiency has also been observed in our studies, such that MC dose calculation time is less than 5 min for a typical case.

SU-E-T-365: Dosimetric Impact of Dental Amalgam CT Image Artifacts On IMRT and VMAT Head and Neck Plans

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

Cao, N; Young, L; Parvathaneni, U

Purpose: The presence of high density dental amalgam in patient CT image data sets causes dose calculation errors for head and neck (HN) treatment planning. This study assesses and compares dosimetric variations in IMRT and VMAT treatment plans due to dental artifacts. Methods: Sixteen HN patients with similar treatment sites (oropharynx), tumor volume and extensive dental artifacts were divided into two groups: IMRT (n=8, 6 to 9 beams) and VMAT (n=8, 2 arcs with 352° rotation). All cases were planned with the Pinnacle 9.2 treatment planning software using the collapsed cone convolution superposition algorithm and a range of prescription dosemore » from 60 to 72Gy. Two different treatment plans were produced, each based on one of two image sets: (a)uncorrected; (b)dental artifacts density overridden (set to 1.0g/cm{sup 3}). Differences between the two treatment plans for each of the IMRT and VMAT techniques were quantified by the following dosimetric parameters: maximum point dose, maximum spinal cord and brainstem dose, mean left and right parotid dose, and PTV coverage (V95%Rx). Average differences generated for these dosimetric parameters were compared between IMRT and VMAT plans. Results: The average absolute dose differences (plan a minus plan b) for the VMAT and IMRT techniques, respectively, caused by dental artifacts were: 2.2±3.3cGy vs. 37.6±57.5cGy (maximum point dose, P=0.15); 1.2±0.9cGy vs. 7.9±6.7cGy (maximum spinal cord dose, P=0.026); 2.2±2.4cGy vs. 12.1±13.0cGy (maximum brainstem dose, P=0.077); 0.9±1.1cGy vs. 4.1±3.5cGy (mean left parotid dose, P=0.038); 0.9±0.8cGy vs. 7.8±11.9cGy (mean right parotid dose, P=0.136); 0.021%±0.014% vs. 0.803%±1.44% (PTV coverage, P=0.17). Conclusion: For the HN plans studied, dental artifacts demonstrated a greater dose calculation error for IMRT plans compared to VMAT plans. Rotational arcs appear on the average to compensate dose calculation errors induced by dental artifacts. Thus, compared to VMAT, density overrides for dental artifacts are more important when planning IMRT of HN.« less

Effective chemotherapy of heterogeneous and drug-resistant early colon cancers by intermittent dose schedules: a computer simulation study.

PubMed

Axelrod, David E; Vedula, Sudeepti; Obaniyi, James

2017-05-01

The effectiveness of cancer chemotherapy is limited by intra-tumor heterogeneity, the emergence of spontaneous and induced drug-resistant mutant subclones, and the maximum dose to which normal tissues can be exposed without adverse side effects. The goal of this project was to determine if intermittent schedules of the maximum dose that allows colon crypt maintenance could overcome these limitations, specifically by eliminating mixtures of drug-resistant mutants from heterogeneous early colon adenomas while maintaining colon crypt function. A computer model of cell dynamics in human colon crypts was calibrated with measurements of human biopsy specimens. The model allowed simulation of continuous and intermittent dose schedules of a cytotoxic chemotherapeutic drug, as well as the drug's effect on the elimination of mutant cells and the maintenance of crypt function. Colon crypts can tolerate a tenfold greater intermittent dose than constant dose. This allows elimination of a mixture of relatively drug-sensitive and drug-resistant mutant subclones from heterogeneous colon crypts. Mutants can be eliminated whether they arise spontaneously or are induced by the cytotoxic drug. An intermittent dose, at the maximum that allows colon crypt maintenance, can be effective in eliminating a heterogeneous mixture of mutant subclones before they fill the crypt and form an adenoma.

Fetal radiation dose estimates for I-131 sodium iodide in cases where conception occurs after administration

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

Sparks, R.B.; Stabin, M.G.

1999-01-01

After administration of I-131 to the female patient, the possibility of radiation exposure of the embryo/fetus exists if the patient becomes pregnant while radioiodine remains in the body. Fetal radiation dose estimates for such cases were calculated. Doses were calculated for various maternal thyroid uptakes and time intervals between administration and conception, including euthyroid and hyperthyroid cases. The maximum fetal dose calculating was about 9.8E-03 mGy/MBq, which occurred with 100% maternal thyroid uptake and a 1 week interval between administration and conception. Placental crossover of the small amount of radioiodine remaining 90 days after conception was also considered. Such crossovermore » could result in an additional fetal dose of 9.8E-05 mGy/MBq and a maximum fetal thyroid self dose of 3.5E-04 mGy/MBq.« less

In vivo dosimetry for external photon treatments of head and neck cancers by diodes and TLDS.

PubMed

Tung, C J; Wang, H C; Lo, S H; Wu, J M; Wang, C J

2004-01-01

In vivo dosimetry was implemented for treatments of head and neck cancers in the large fields. Diode and thermoluminescence dosemeter (TLD) measurements were carried out for the linear accelerators of 6 MV photon beams. ESTRO in vivo dosimetry protocols were followed in the determination of midline doses from measurements of entrance and exit doses. Of the fields monitored by diodes, the maximum absolute deviation of measured midline doses from planned target doses was 8%, with the mean value and the standard deviation of -1.0 and 2.7%. If planned target doses were calculated using radiological water equivalent thicknesses rather than patient geometric thicknesses, the maximum absolute deviation dropped to 4%, with the mean and the standard deviation of 0.7 and 1.8%. For in vivo dosimetry monitored by TLDs, the shift in mean dose remained small but the statistical precision became poor.

Contura Multi-Lumen Balloon breast brachytherapy catheter: comparative dosimetric findings of a phase 4 trial.

PubMed

Arthur, Douglas W; Vicini, Frank A; Todor, Dorin A; Julian, Thomas B; Cuttino, Laurie W; Mukhopadhyay, Nitai D

2013-06-01

Final dosimetric findings of a completed, multi-institutional phase 4 registry trial using the Contura Multi-Lumen Balloon (MLB) breast brachytherapy catheter to deliver accelerated partial breast irradiation (APBI) in patients with early-stage breast cancer are presented. Three dosimetric plans with identical target coverage were generated for each patient for comparison: multilumen multidwell (MLMD); central-lumen multidwell (CLMD); and central-lumen single-dwell (CLSD) loading of the Contura catheter. For this study, a successful treatment plan achieved ideal dosimetric goals and included the following: ≥ 95% of the prescribed dose (PD) covering ≥ 95% of the target volume (TV); maximum skin dose ≤ 125% of the PD; maximum rib dose ≤ 145% of the PD; and V150 ≤50 cc and V200 ≤ 10 cc. Between January 2008 and February 2011, 23 institutions participated. A total of 318 patients were available for dosimetric review. Using the Contura MLB, all dosimetric criteria were met in 78.93% of cases planned with MLMD versus 55.38% with the CLMD versus 37.66% with the CLSD (P ≤.0001). Evaluating all patients with the full range of skin to balloon distance represented, median maximum skin dose was reduced by 12% and median maximum rib dose by 13.9% when using MLMD-based dosimetric plans compared to CLSD. The dosimetric benefit of MLMD was further demonstrated in the subgroup of patients where skin thickness was <5 mm, where MLMD use allowed a 38% reduction in median maximum skin dose over CLSD. For patients with rib distance <5 mm, the median maximum rib dose reduction was 27%. Use of the Contura MLB catheter produced statistically significant improvements in dosimetric capabilities between CLSD and CLMD treatments. This device approach demonstrates the ability not only to overcome the barriers of limited skin thickness and close rib proximity, but to consistently achieve a higher standard of dosimetric planning goals. Copyright © 2013 Elsevier Inc. All rights reserved.

Contura Multi-Lumen Balloon Breast Brachytherapy Catheter: Comparative Dosimetric Findings of a Phase 4 Trial

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

Arthur, Douglas W., E-mail: darthur@mcvh-vcu.edu; Vicini, Frank A.; Todor, Dorin A.

2013-06-01

Purpose: Final dosimetric findings of a completed, multi-institutional phase 4 registry trial using the Contura Multi-Lumen Balloon (MLB) breast brachytherapy catheter to deliver accelerated partial breast irradiation (APBI) in patients with early-stage breast cancer are presented. Methods and Materials: Three dosimetric plans with identical target coverage were generated for each patient for comparison: multilumen multidwell (MLMD); central-lumen multidwell (CLMD); and central-lumen single-dwell (CLSD) loading of the Contura catheter. For this study, a successful treatment plan achieved ideal dosimetric goals and included the following: ≥95% of the prescribed dose (PD) covering ≥95% of the target volume (TV); maximum skin dose ≤125%more » of the PD; maximum rib dose ≤145% of the PD; and V150 ≤50 cc and V200 ≤10 cc. Results: Between January 2008 and February 2011, 23 institutions participated. A total of 318 patients were available for dosimetric review. Using the Contura MLB, all dosimetric criteria were met in 78.93% of cases planned with MLMD versus 55.38% with the CLMD versus 37.66% with the CLSD (P≤.0001). Evaluating all patients with the full range of skin to balloon distance represented, median maximum skin dose was reduced by 12% and median maximum rib dose by 13.9% when using MLMD-based dosimetric plans compared to CLSD. The dosimetric benefit of MLMD was further demonstrated in the subgroup of patients where skin thickness was <5 mm, where MLMD use allowed a 38% reduction in median maximum skin dose over CLSD. For patients with rib distance <5 mm, the median maximum rib dose reduction was 27%. Conclusions: Use of the Contura MLB catheter produced statistically significant improvements in dosimetric capabilities between CLSD and CLMD treatments. This device approach demonstrates the ability not only to overcome the barriers of limited skin thickness and close rib proximity, but to consistently achieve a higher standard of dosimetric planning goals.« less

A phase I dose escalation study of TTI-237 in patients with advanced malignant solid tumors.

PubMed

Wang-Gillam, Andrea; Arnold, Susanne M; Bukowski, Ronald M; Rothenberg, Mace L; Cooper, Wendy; Wang, Kenneth K; Gauthier, Eric; Lockhart, A Craig

2012-02-01

This study was to determine the maximum tolerated dose, dose-limiting toxicities, and pharmacokinetic profile of TTI-237, a novel anti-tubulin drug, administered weekly in patients with refractory solid tumors. Using an accelerated dose escalation design, patients with refractory solid tumors were enrolled in this study and treated with TTI-237 intravenously on days 1, 8 and 15 of a 28-day cycle. The starting dose was 4.5 mg/m(2). Pharmacokinetic studies were performed in patients at all dose levels. Twenty-eight patients were enrolled and treated with TTI-237 at dose of 4.5, 9, 15, 22.5 and 31.5 mg/m(2). One dose-limiting toxicity neutropenia fever was observed at 31.5 mg/m(2), and all seven patients developed grade 3 or 4 neutropenia at that dose level. TTI-237 dosage was de-escalated to 22.5 and 18 mg/m(2). Six patients were treated at the 18 mg/m(2) dose level without dose-limiting toxicity prior to trial termination. The mean terminal-phase elimination half-life (t(1/2)) for TTI-237 was 25-29 h, and the mean area under the concentration time curve at 31.5 mg/m(2) was 2,768 ng•h/mL. A protocol defined maximum tolerated dose was not determined because of early termination of the TTI-237 trial by the sponsor. 18 mg/m(2) may be a tolerable dose of TTI-237.

A phase I study with neratinib (HKI-272), an irreversible pan ErbB receptor tyrosine kinase inhibitor, in patients with solid tumors.

PubMed

Wong, Kwok-K; Fracasso, Paula M; Bukowski, Ronald M; Lynch, Thomas J; Munster, Pamela N; Shapiro, Geoffrey I; Jänne, Pasi A; Eder, Joseph P; Naughton, Michael J; Ellis, Matthew J; Jones, Suzanne F; Mekhail, Tarek; Zacharchuk, Charles; Vermette, Jennifer; Abbas, Richat; Quinn, Susan; Powell, Christine; Burris, Howard A

2009-04-01

The dose-limiting toxicities, maximum tolerated dose, pharmacokinetic profile, and preliminary antitumor activity of neratinib (HKI-272), an irreversible pan ErbB inhibitor, were determined in patients with advanced solid tumors. Neratinib was administered orally as a single dose, followed by a 1-week observation period, and then once daily continuously. Planned dose escalation was 40, 80, 120, 180, 240, 320, 400, and 500 mg. For pharmacokinetic analysis, timed blood samples were collected after administration of the single dose and after the first 14 days of continuous daily administration. Dose-limiting toxicity was grade 3 diarrhea, which occurred in one patient treated with 180 mg and in four patients treated with 400 mg neratinib; hence, the maximum tolerated dose was determined to be 320 mg. Other common neratinib-related toxicities included nausea, vomiting, fatigue, and anorexia. Exposure to neratinib was dose dependent, and the pharmacokinetic profile of neratinib supports a once-a-day dosing regimen. Partial response was observed for 8 (32%) of the 25 evaluable patients with breast cancer. Stable disease >or=24 weeks was observed in one evaluable breast cancer patient and 6 (43%) of the 14 evaluable non-small cell lung cancer patients. The maximum tolerated dose of once-daily oral neratinib is 320 mg. The most common neratinib-related toxicity was diarrhea. Antitumor activity was observed in patients with breast cancer who had previous treatment with trastuzumab, anthracyclines, and taxanes, and tumors with a baseline ErbB-2 immunohistochemical staining intensity of 2+ or 3+. The antitumor activity, tolerable toxicity profile, and pharmacokinetic properties of neratinib warrant its further evaluation.

Implementation of a dose gradient method into optimization of dose distribution in prostate cancer 3D-CRT plans

PubMed Central

Giżyńska, Marta K.; Kukołowicz, Paweł F.; Kordowski, Paweł

2014-01-01

Aim The aim of this work is to present a method of beam weight and wedge angle optimization for patients with prostate cancer. Background 3D-CRT is usually realized with forward planning based on a trial and error method. Several authors have published a few methods of beam weight optimization applicable to the 3D-CRT. Still, none on these methods is in common use. Materials and methods Optimization is based on the assumption that the best plan is achieved if dose gradient at ICRU point is equal to zero. Our optimization algorithm requires beam quality index, depth of maximum dose, profiles of wedged fields and maximum dose to femoral heads. The method was tested for 10 patients with prostate cancer, treated with the 3-field technique. Optimized plans were compared with plans prepared by 12 experienced planners. Dose standard deviation in target volume, and minimum and maximum doses were analyzed. Results The quality of plans obtained with the proposed optimization algorithms was comparable to that prepared by experienced planners. Mean difference in target dose standard deviation was 0.1% in favor of the plans prepared by planners for optimization of beam weights and wedge angles. Introducing a correction factor for patient body outline for dose gradient at ICRU point improved dose distribution homogeneity. On average, a 0.1% lower standard deviation was achieved with the optimization algorithm. No significant difference in mean dose–volume histogram for the rectum was observed. Conclusions Optimization shortens very much time planning. The average planning time was 5 min and less than a minute for forward and computer optimization, respectively. PMID:25337411

Factors Associated With Chest Wall Toxicity After Accelerated Partial Breast Irradiation Using High-Dose-Rate Brachytherapy

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

Brown, Sheree, E-mail: shereedst32@hotmail.com; Vicini, Frank; Vanapalli, Jyotsna R.

2012-07-01

Purpose: The purpose of this analysis was to evaluate dose-volume relationships associated with a higher probability for developing chest wall toxicity (pain) after accelerated partial breast irradiation (APBI) by using both single-lumen and multilumen brachytherapy. Methods and Materials: Rib dose data were available for 89 patients treated with APBI and were correlated with the development of chest wall/rib pain at any point after treatment. Ribs were contoured on computed tomography planning scans, and rib dose-volume histograms (DVH) along with histograms for other structures were constructed. Rib DVH data for all patients were sampled at all volumes {>=}0.008 cubic centimeter (cc)more » (for maximum dose related to pain) and at volumes of 0.5, 1, 2, and 3 cc for analysis. Rib pain was evaluated at each follow-up visit. Patient responses were marked as yes or no. No attempt was made to grade responses. Eighty-nine responses were available for this analysis. Results: Nineteen patients (21.3%) complained of transient chest wall/rib pain at any point in follow-up. Analysis showed a direct correlation between total dose received and volume of rib irradiated with the probability of developing rib/chest wall pain at any point after follow-up. The median maximum dose at volumes {>=}0.008 cc of rib in patients who experienced chest wall pain was 132% of the prescribed dose versus 95% of the prescribed dose in those patients who did not experience pain (p = 0.0035). Conclusions: Although the incidence of chest wall/rib pain is quite low with APBI brachytherapy, attempts should be made to keep the volume of rib irradiated at a minimum and the maximum dose received by the chest wall as low as reasonably achievable.« less

Doses of external exposure in Jordan house due to gamma-emitting natural radionuclides in building materials.

PubMed

Al-Jundi, J; Ulanovsky, A; Pröhl, G

2009-10-01

The use of building materials containing naturally occurring radionuclides as (40)K, (232)Th, and (238)U and their progeny results in external exposures of the residents of such buildings. In the present study, indoor dose rates for a typical Jordan concrete room are calculated using Monte Carlo method. Uniform chemical composition of the walls, floor and ceiling as well as uniform mass concentrations of the radionuclides in walls, floor and ceiling are assumed. Using activity concentrations of natural radionuclides typical for the Jordan houses and assuming them to be in secular equilibrium with their progeny, the maximum annual effective doses are estimated to be 0.16, 0.12 and 0.22 mSv a(-1) for (40)K, (232)Th- and (238)U-series, respectively. In a total, the maximum annual effective indoor dose due to external gamma-radiation is 0.50 mSv a(-1). Additionally, organ dose coefficients are calculated for all organs considered in ICRP Publication 74. Breast, skin and eye lenses have the maximum equivalent dose rate values due to indoor exposures caused by the natural radionuclides, while equivalent dose rates for uterus, colon (LLI) and small intestine are found to be the smallest. More specifically, organ dose rates (nSv a(-1)per Bq kg(-1)) vary from 0.044 to 0.060 for (40)K, from 0.44 to 0.60 for radionuclides from (238)U-series and from 0.60 to 0.81 for radionuclides from (232)Th-series. The obtained organ and effective dose conversion coefficients can be conveniently used in practical dose assessment tasks for the rooms of similar geometry and varying activity concentrations and local-specific occupancy factors.

Survey of Occupational Noise Exposure in CF Personnel in Selected High-Risk Trades

DTIC Science & Technology

2003-11-01

peak, maximum level , minimum level , average sound level , time weighted average, dose, projected 8-hour dose, and upper limit time were measured for...10 4.4.2 Maximum Sound Level ...11 4.4.3 Minimum Sound Level

VMAT testing for an Elekta accelerator

PubMed Central

Sweeney, Larry E.; Marshall, Edward I.; Mahendra, Saikanth

2012-01-01

Volumetric‐modulated arc therapy (VMAT) has been shown to be able to deliver plans equivalent to intensity‐modulated radiation therapy (IMRT) in a fraction of the treatment time. This improvement is important for patient immobilization/ localization compliance due to comfort and treatment duration, as well as patient throughput. Previous authors have suggested commissioning methods for this modality. Here, we extend the methods reported for the Varian RapidArc system (which tested individual system components) to the Elekta linear accelerator, using custom files built using the Elekta iComCAT software. We also extend the method reported for VMAT commissioning of the Elekta accelerator by verifying maximum values of parameters (gantry speed, multileaf collimator (MLC) speed, and backup jaw speed), investigating: 1) beam profiles as a function of dose rate during an arc, 2) over/under dosing due to MLC reversals, and 3) over/under dosing at changing dose rate junctions. Equations for construction of the iComCAT files are given. Results indicate that the beam profile for lower dose rates varies less than 3% from that of the maximum dose rate, with no difference during an arc. The gantry, MLC, and backup jaw maximum speed are internally consistent. The monitor unit chamber is stable over the MUs and gantry movement conditions expected. MLC movement and position during VMAT delivery are within IMRT tolerances. Dose rate, gantry speed, and MLC speed are accurately controlled. Over/under dosing at junctions of MLC reversals or dose rate changes are within clinical acceptability. PACS numbers: 87.55.de, 87.55.Qr, 87.56.bd PMID:22402389

Dose Titration Algorithm Tuning (DTAT) should supersede 'the' Maximum Tolerated Dose (MTD) in oncology dose-finding trials.

PubMed

Norris, David C

2017-01-01

Background . Absent adaptive, individualized dose-finding in early-phase oncology trials, subsequent 'confirmatory' Phase III trials risk suboptimal dosing, with resulting loss of statistical power and reduced probability of technical success for the investigational therapy. While progress has been made toward explicitly adaptive dose-finding and quantitative modeling of dose-response relationships, most such work continues to be organized around a concept of 'the' maximum tolerated dose (MTD). The purpose of this paper is to demonstrate concretely how the aim of early-phase trials might be conceived, not as 'dose-finding', but as dose titration algorithm (DTA) -finding. Methods. A Phase I dosing study is simulated, for a notional cytotoxic chemotherapy drug, with neutropenia constituting the critical dose-limiting toxicity. The drug's population pharmacokinetics and myelosuppression dynamics are simulated using published parameter estimates for docetaxel. The amenability of this model to linearization is explored empirically. The properties of a simple DTA targeting neutrophil nadir of 500 cells/mm 3 using a Newton-Raphson heuristic are explored through simulation in 25 simulated study subjects. Results. Individual-level myelosuppression dynamics in the simulation model approximately linearize under simple transformations of neutrophil concentration and drug dose. The simulated dose titration exhibits largely satisfactory convergence, with great variance in individualized optimal dosing. Some titration courses exhibit overshooting. Conclusions. The large inter-individual variability in simulated optimal dosing underscores the need to replace 'the' MTD with an individualized concept of MTD i . To illustrate this principle, the simplest possible DTA capable of realizing such a concept is demonstrated. Qualitative phenomena observed in this demonstration support discussion of the notion of tuning such algorithms. Although here illustrated specifically in relation to cytotoxic chemotherapy, the DTAT principle appears similarly applicable to Phase I studies of cancer immunotherapy and molecularly targeted agents.

Monte Carlo and Phantom Study of the Radiation Dose to the Body from Dedicated Computed Tomography of the Breast

PubMed Central

Sechopoulos, Ioannis; Vedantham, Srinivasan; Suryanarayanan, Sankararaman; D’Orsi, Carl J.; Karellas, Andrew

2008-01-01

Purpose To prospectively determine the radiation dose absorbed by the organs and tissues of the body during a dedicated computed tomography of the breast (DBCT) study using Monte Carlo methods and a phantom. Materials and Methods Using the Geant4 Monte Carlo toolkit, the Cristy anthropomorphic phantom and the geometry of a prototype DBCT was simulated. The simulation was used to track x-rays emitted from the source until their complete absorption or exit from the simulation limits. The interactions of the x-rays with the 65 different volumes representing organs, bones and other tissues of the anthropomorphic phantom that resulted in energy deposition were recorded. These data were used to compute the radiation dose to the organs and tissues during a complete DBCT acquisition relative to the average glandular dose to the imaged breast (ROD, relative organ dose), using the x-ray spectra proposed for DBCT imaging. The effectiveness of a lead shield for reducing the dose to the organs was investigated. Results The maximum ROD among the organs was for the ipsilateral lung with a maximum of 3.25%, followed by the heart and the thymus. Of the skeletal tissues, the sternum received the highest dose with a maximum ROD to the bone marrow of 2.24%, and to the bone surface of 7.74%. The maximum ROD to the uterus, representative of that of an early-stage fetus, was 0.026%. These maxima occurred for the highest energy x-ray spectrum (80 kVp) analyzed. A lead shield does not protect substantially the organs that receive the highest dose from DBCT. Discussion Although the dose to the organs from DBCT is substantially higher than that from planar mammography, they are comparable or considerably lower than those reached by other radiographic procedures and much lower than other CT examinations. PMID:18292479

Impact of cardiosynchronous brain pulsations on Monte Carlo calculated doses for synchrotron micro- and minibeam radiation therapy.

PubMed

Manchado de Sola, Francisco; Vilches, Manuel; Prezado, Yolanda; Lallena, Antonio M

2018-05-15

The purpose of this study was to assess the effects of brain movements induced by heartbeat on dose distributions in synchrotron micro- and minibeam radiation therapy and to develop a model to help guide decisions and planning for future clinical trials. The Monte Carlo code PENELOPE was used to simulate the irradiation of a human head phantom with a variety of micro- and minibeam arrays, with beams narrower than 100 μm and above 500 μm, respectively, and with radiation fields of 1 × 2 cm and 2 × 2 cm. The dose in the phantom due to these beams was calculated by superposing the dose profiles obtained for a single beam of 1 μm × 2 cm. A parameter δ, accounting for the total displacement of the brain during the irradiation and due to the cardiosynchronous pulsation, was used to quantify the impact on peak-to-valley dose ratios and the full width at half maximum. The difference between the maximum (at the phantom entrance) and the minimum (at the phantom exit) values of the peak-to-valley dose ratio reduces when the parameter δ increases. The full width at half maximum remains almost constant with depth for any δ value. Sudden changes in the two quantities are observed at the interfaces between the various tissues (brain, skull, and skin) present in the head phantom. The peak-to-valley dose ratio at the center of the head phantom reduces when δ increases, remaining above 70% of the static value only for minibeams and δ smaller than ∼200 μm. Optimal setups for brain treatments with synchrotron radiation micro- and minibeam combs depend on the brain displacement due to cardiosynchronous pulsation. Peak-to-valley dose ratios larger than 90% of the maximum values obtained in the static case occur only for minibeams and relatively large dose rates. © 2018 American Association of Physicists in Medicine.

Dose Trends of Aripiprazole from 2004 to 2014 in Psychiatric Inpatients in Korea.

PubMed

Woo, Young Sup; Shim, In Hee; Lee, Sang-Yeol; Lee, Dae-Bo; Kim, Moon-Doo; Jung, Young-Eun; Lee, Jonghun; Won, Seunghee; Jon, Duk-In; Bahk, Won-Myong

2017-05-31

Although aripiprazole has been widely used to treat various psychiatric disorders, little is known about the adequate dosage for Asian patients in clinical practice. Hence, we evaluated the initial and maximum doses of aripiprazole from 2004 to 2014 to estimate the appropriate dosage for Korean psychiatric inpatients in clinical practice. In this retrospective study, we reviewed the medical records of patients who were hospitalized in five university hospitals in Korea from March 2004 to December 2014. The psychiatric diagnosis according to the text revision of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition during index hospitalization and the initial and maximum doses of aripiprazole were evaluated. There were 74 patients in Wave 1 (2004-2006), 201 patients in Wave 2 (2007-2010), and 353 patients in Wave 3 (2011-2014). The initial doses of aripiprazole in all diagnostic groups were significantly lower in Wave 3 than in Wave 2. The maximum doses of aripiprazole in each diagnostic group were not significantly different among Waves 1, 2, and 3. The relatively low initial doses of aripiprazole documented in our study may reflect a strategy by clinicians to minimize the side effects associated with aripiprazole use, such as akathisia.

Commissioning dosimetry and in situ dose mapping of a semi-industrial Cobalt-60 gamma-irradiation facility using Fricke and Ceric-cerous dosimetry system and comparison with Monte Carlo simulation data

NASA Astrophysics Data System (ADS)

Mortuza, Md Firoz; Lepore, Luigi; Khedkar, Kalpana; Thangam, Saravanan; Nahar, Arifatun; Jamil, Hossen Mohammad; Bandi, Laxminarayan; Alam, Md Khorshed

2018-03-01

Characterization of a 90 kCi (3330 TBq), semi-industrial, cobalt-60 gamma irradiator was performed by commissioning dosimetry and in-situ dose mapping experiments with Ceric-cerous and Fricke dosimetry systems. Commissioning dosimetry was carried out to determine dose distribution pattern of absorbed dose in the irradiation cell and products. To determine maximum and minimum absorbed dose, overdose ratio and dwell time of the tote boxes, homogeneous dummy product (rice husk) with a bulk density of 0.13 g/cm3 were used in the box positions of irradiation chamber. The regions of minimum absorbed dose of the tote boxes were observed in the lower zones of middle plane and maximum absorbed doses were found in the middle position of front plane. Moreover, as a part of dose mapping, dose rates in the wall positions and some selective strategic positions were also measured to carry out multiple irradiation program simultaneously, especially for low dose research irradiation program. In most of the cases, Monte Carlo simulation data, using Monte Carlo N-Particle eXtended code version MCNPX 2.7., were found to be in congruence with experimental values obtained from Ceric-cerous and Fricke dosimetry; however, in close proximity positions from the source, the dose rate variation between chemical dosimetry and MCNP was higher than distant positions.

Dosimetric comparison between VMAT with different dose calculation algorithms and protons for soft-tissue sarcoma radiotherapy.

PubMed

Fogliata, Antonella; Scorsetti, Marta; Navarria, Piera; Catalano, Maddalena; Clivio, Alessandro; Cozzi, Luca; Lobefalo, Francesca; Nicolini, Giorgia; Palumbo, Valentina; Pellegrini, Chiara; Reggiori, Giacomo; Roggio, Antonella; Vanetti, Eugenio; Alongi, Filippo; Pentimalli, Sara; Mancosu, Pietro

2013-04-01

To appraise the potential of volumetric modulated arc therapy (VMAT, RapidArc) and proton beams to simultaneously achieve target coverage and enhanced sparing of bone tissue in the treatment of soft-tissue sarcoma with adequate target coverage. Ten patients presenting with soft-tissue sarcoma of the leg were collected for the study. Dose was prescribed to 66.5 Gy in 25 fractions to the planning target volume (PTV) while significant maximum dose to the bone was constrained to 50 Gy. Plans were optimised according to the RapidArc technique with 6 MV photon beams or for intensity modulated protons. RapidArc photon plans were computed with: 1) AAA; 2) Acuros XB as dose to medium; and 3) Acuros XB as dose to water. All plans acceptably met the criteria of target coverage (V95% >90-95%) and bone sparing (D(1 cm3) <50 Gy). Significantly higher PTV dose homogeneity was found for proton plans. Near-to-maximum dose to bone was similar for RapidArc and protons, while volume receiving medium/low dose levels was minimised with protons. Similar results were obtained for the remaining normal tissue. Dose distributions calculated with the dose to water option resulted ~5% higher than corresponding ones computed as dose to medium. High plan quality was demonstrated for both VMAT and proton techniques when applied to soft-tissue sarcoma.

Developability assessment of clinical drug products with maximum absorbable doses.

PubMed

Ding, Xuan; Rose, John P; Van Gelder, Jan

2012-05-10

Maximum absorbable dose refers to the maximum amount of an orally administered drug that can be absorbed in the gastrointestinal tract. Maximum absorbable dose, or D(abs), has proved to be an important parameter for quantifying the absorption potential of drug candidates. The purpose of this work is to validate the use of D(abs) in a developability assessment context, and to establish appropriate protocol and interpretation criteria for this application. Three methods for calculating D(abs) were compared by assessing how well the methods predicted the absorption limit for a set of real clinical candidates. D(abs) was calculated for these clinical candidates by means of a simple equation and two computer simulation programs, GastroPlus and an program developed at Eli Lilly and Company. Results from single dose escalation studies in Phase I clinical trials were analyzed to identify the maximum absorbable doses for these compounds. Compared to the clinical results, the equation and both simulation programs provide conservative estimates of D(abs), but in general D(abs) from the computer simulations are more accurate, which may find obvious advantage for the simulations in developability assessment. Computer simulations also revealed the complex behavior associated with absorption saturation and suggested in most cases that the D(abs) limit is not likely to be achieved in a typical clinical dose range. On the basis of the validation findings, an approach is proposed for assessing absorption potential, and best practices are discussed for the use of D(abs) estimates to inform clinical formulation development strategies. Copyright © 2012 Elsevier B.V. All rights reserved.

Dose verification to cochlea during gamma knife radiosurgery of acoustic schwannoma using MOSFET dosimeter.

PubMed

Sharma, Sunil D; Kumar, Rajesh; Akhilesh, Philomina; Pendse, Anil M; Deshpande, Sudesh; Misra, Basant K

2012-01-01

Dose verification to cochlea using metal oxide semiconductor field effect transistor (MOSFET) dosimeter using a specially designed multi slice head and neck phantom during the treatment of acoustic schwannoma by Gamma Knife radiosurgery unit. A multi slice polystyrene head phantom was designed and fabricated for measurement of dose to cochlea during the treatment of the acoustic schwannoma. The phantom has provision to position the MOSFET dosimeters at the desired location precisely. MOSFET dosimeters of 0.2 mm x 0.2 mm x 0.5 μm were used to measure the dose to the cochlea. CT scans of the phantom with MOSFETs in situ were taken along with Leksell frame. The treatment plans of five patients treated earlier for acoustic schwannoma were transferred to the phantom. Dose and coordinates of maximum dose point inside the cochlea were derived. The phantom along with the MOSFET dosimeters was irradiated to deliver the planned treatment and dose received by cochlea were measured. The treatment planning system (TPS) estimated and measured dose to the cochlea were in the range of 7.4 - 8.4 Gy and 7.1 - 8 Gy, respectively. The maximum variation between TPS calculated and measured dose to cochlea was 5%. The measured dose values were found in good agreement with the dose values calculated using the TPS. The MOSFET dosimeter can be a suitable choice for routine dose verification in the Gamma Knife radiosurgery.

SU-G-201-08: Energy Response of Thermoluminescent Microcube Dosimeters in Water for Kilovoltage X-Ray Beams

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

Di Maso, L; Lawless, M; Culberson, W

Purpose: To characterize the energy dependence for TLD-100 microcubes in water at kilovoltage energies. Methods: TLD-100 microcubes with dimensions of (1 × 1 × 1) mm{sup 3} were irradiated with kilovoltage x-rays in a custom-built thin-window liquid water phantom. The TLD-100 microcubes were held in Virtual Water™ probes and aligned at a 2 cm depth in water. Irradiations were performed using the M-series x-ray beams of energies ranging from 50-250 kVp and normalized to a {sup 60}Co beam located at the UWADCL. Simulations using the EGSnrc Monte Carlo Code System were performed to model the x-ray beams, the {sup 60}Comore » beam, the water phantom and the dosimeters in the phantom. The egs-chamber user code was used to tally the dose to the TLDs and the dose to water. The measurements and calculations were used to determine the intrinsic energy dependence, absorbed-dose energy dependence, and absorbed-dose sensitivity. These values were compared to TLD-100 chips with dimensions of (3.2 × 0.9 × 0.9) mm{sup 3}. Results: The measured TLD-100 microcube response per dose to water among all investigated x-ray energies had a maximum percent difference of 61% relative to {sup 60}Co. The simulated ratio of dose to water to the dose to TLD had a maximum percent difference of 29% relative to {sup 60}Co. The ratio of dose to TLD to the TLD output had a maximum percent difference of 13% relative to {sup 60}Co. The maximum percent difference for the absorbed-dose sensitivity was 15% more than the used value of 1.41. Conclusion: These results confirm that differences in beam quality have a significant effect on TLD response when irradiated in water. These results also indicated a difference in TLD-100 response between microcube and chip geometries. The intrinsic energy dependence and the absorbed-dose energy dependence deviated up to 10% between TLD-100 microcubes and chips.« less

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

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

Park, J; Kim, J; Park, S

Purpose: To investigate exposure outside the treatment field when treating breast cancer with tri-Co-60 magnetic resonance (MR) image guided radiation therapy (IGRT) system. Methods: A total of 7 patients who treated with accelerated partial breast irradiation (APBI) technique were selected prospectively for this study (prescription dose = 38.5 Gy in 10 fractions). Every patient treated with two plans, one was an initial plan and the other was an adaptive plan generated after finishing 5 fractions (a total of 14 plans). Every plan was calculated with and without magnetic field in the treatment planning system. The EBT3 films were attached onmore » the front and the back of 1 cm bolus, and then it was placed on the patient body vertically to cover patient’s jaw and shoulder. After measurements, the maximum point dose and the mean dose of whole area of EBT3 film were acquired. Results: In the treatment plan with magnetic field, low dose stream outside the patient body was observed, almost reaching the patient’s jaw or shoulder, while it was not observed without magnetic field. The average values of the measured maximum and mean doses at the front of bolus were 30.1 ± 11.1 cGy (7.8% of the daily dose) and 14.7 ± 3.3 cGy (3.8%), respectively. At the back of bolus, those values were 6.0 ± 1.9 cGy (1.6%) and 5.1 ± 1.6 cGy (1.3%), respectively. The largest maximum dose at the front was 54.2 cGy (14.1%) while it was 20.7 cGy (5.4%) at the back. The average decrease of the maximum dose by the bolus was 24.0 ± 11.0 cGy. Conclusion: Due to magnetic field, dose stream outside the patient body can be generated during breast cancer treatment with the tri-Co-60 MR-IGRT system. Since this dose stream irradiated skin outside the treatment field, it should be shielded. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (No. 2015R1C1A1A01054192).« less

Prediction of Normal Organ Absorbed Doses for [177Lu]Lu-PSMA-617 Using [44Sc]Sc-PSMA-617 Pharmacokinetics in Patients With Metastatic Castration Resistant Prostate Carcinoma.

PubMed

Khawar, Ambreen; Eppard, Elisabeth; Sinnes, Jean Phlippe; Roesch, Frank; Ahmadzadehfar, Hojjat; Kürpig, Stefan; Meisenheimer, Michael; Gaertner, Florian C; Essler, Markus; Bundschuh, Ralph A

2018-04-23

In vivo pharmacokinetic analysis of [Sc]Sc-PSMA-617 was used to determine the normal organ-absorbed doses that may result from therapeutic activity of [Lu]Lu-PSMA-617 and to predict the maximum permissible activity of [Lu]Lu-PSMA-617 for patients with metastatic castration-resistant prostate carcinoma. Pharmacokinetics of [Sc]Sc-PSMA-617 was evaluated in 5 patients with metastatic castration-resistant prostate carcinoma using dynamic PET/CT, followed by 3 static PET/CT acquisitions and blood sample collection over 19.5 hours, as well as urine sample collection at 2 time points. Total activity measured in source organs by PET imaging, as well as counts per milliliter measured in blood and urine samples, was decay corrected back to the time of injection using the half-life of Sc. Afterward, forward decay correction using the half-life of Lu was performed, extrapolating the pharmacokinetics of [Sc]Sc-PSMA-617 to that of [Lu]Lu-PSMA-617. Source organs residence times and organ-absorbed doses for [Lu]Lu-PSMA-617 were calculated using OLINDA/EXM software. Bone marrow self-dose was determined with indirect blood-based method, and urinary bladder contents residence time was estimated by trapezoidal approximation. The maximum permissible activity of [Lu]Lu-PSMA-617 was calculated for each patient considering external beam radiotherapy toxicity limits for radiation absorbed doses to kidneys, bone marrow, salivary glands, and whole body. The predicted mean organ-absorbed doses were highest in the kidneys (0.44 mSv/MBq), followed by the salivary glands (0.23 mSv/MBq). The maximum permissible activity was highly variable among patients; limited by whole body-absorbed dose (1 patient), marrow-absorbed dose (1 patient), and kidney-absorbed dose (3 patients). [Sc]Sc-PSMA-617 PET/CT imaging is feasible and allows theoretical extrapolation of the pharmacokinetics of [Sc]Sc-PSMA-617 to that of [Lu]Lu-PSMA-617, with the intent of predicting normal organ-absorbed doses and maximum permissible activity in patients scheduled for therapy with [Lu]Lu-PSMA-617.

Kodak EDR2 film for patient skin dose assessment in cardiac catheterization procedures.

PubMed

Morrell, R E; Rogers, A T

2006-07-01

Patient skin doses were measured using Kodak EDR2 film for 20 coronary angiography (CA) and 32 percutaneous transluminal coronary angioplasty (PTCA) procedures. For CA, all skin doses were well below 1 Gy. However, 23% of PTCA patients received skin doses of 1 Gy or more. Dose-area product (DAP) was also recorded and was found to be an inadequate indicator of maximum skin dose. Practical compliance with ICRP recommendations requires a robust method for skin dosimetry that is more accurate than DAP and is applicable over a wider dose range than EDR2 film.

Reducing dose to the lungs through loosing target dose homogeneity requirement for radiotherapy of non small cell lung cancer.

PubMed

Miao, Junjie; Yan, Hui; Tian, Yuan; Ma, Pan; Liu, Zhiqiang; Li, Minghui; Ren, Wenting; Chen, Jiayun; Zhang, Ye; Dai, Jianrong

2017-11-01

It is important to minimize lung dose during intensity-modulated radiation therapy (IMRT) of nonsmall cell lung cancer (NSCLC). In this study, an approach was proposed to reduce lung dose by relaxing the constraint of target dose homogeneity during treatment planning of IMRT. Ten NSCLC patients with lung tumor on the right side were selected. The total dose for planning target volume (PTV) was 60 Gy (2 Gy/fraction). For each patient, two IMRT plans with six beams were created in Pinnacle treatment planning system. The dose homogeneity of target was controlled by constraints on the maximum and uniform doses of target volume. One IMRT plan was made with homogeneous target dose (the resulting target dose was within 95%-107% of the prescribed dose), while another IMRT plan was made with inhomogeneous target dose (the resulting target dose was more than 95% of the prescribed dose). During plan optimization, the dose of cord and heart in two types of IMRT plans were kept nearly the same. The doses of lungs, PTV and organs at risk (OARs) between two types of IMRT plans were compared and analyzed quantitatively. For all patients, the lung dose was decreased in the IMRT plans with inhomogeneous target dose. On average, the mean dose, V5, V20, and V30 of lung were reduced by 1.4 Gy, 4.8%, 3.7%, and 1.7%, respectively, and the dose to normal tissue was also reduced. These reductions in DVH values were all statistically significant (P < 0.05). There were no significant differences between the two IMRT plans on V25, V30, V40, V50 and mean dose for heart. The maximum doses of cords in two type IMRT plans were nearly the same. IMRT plans with inhomogeneous target dose could protect lungs better and may be considered as a choice for treating NSCLC. © 2017 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

CT Fluoroscopy Shielding: Decreases in Scattered Radiation for the Patient and Operator

PubMed Central

Neeman, Ziv; Dromi, Sergio A.; Sarin, Shawn; Wood, Bradford J.

2008-01-01

PURPOSE High-radiation exposure occurs during computed tomographic (CT) fluoroscopy. Patient and operator doses during thoracic and abdominal interventional procedures were studied in the present experiment, and a novel shielding device to reduce exposure to the patient and operator was evaluated. MATERIALS AND METHODS With a 16-slice CT scanner in CT fluoroscopy mode (120 kVp, 30 mA), surface dosimetry was performed on adult and pediatric phantoms. The shielding was composed of tungsten antimony in the form of a lightweight polymer sheet. Doses to the patient were measured with and without shielding for thoracic and abdominal procedures. Doses to the operator were recorded with and without phantom, gantry, and table shielding in place. Double-layer lead-free gloves were used by the operator during the procedures. RESULTS Tungsten antimony shielding adjacent to the scan plane resulted in a maximum dose reduction of 92.3% to the patient. Maximum 85.6%, 93.3%, and 85.1% dose reductions were observed for the operator’s torso, gonads, and hands, respectively. The use of double-layer lead-free gloves resulted in a maximum radiation dose reduction of 97%. CONCLUSIONS Methods to reduce exposure during CT fluoroscopy are effective and should be searched for. Significant reduction in radiation doses to the patient and operator can be accomplished with tungsten antimony shielding. PMID:17185699

SU-E-T-450: How Important Is a Reproducible Breath Hold for DIBH Breast Radiotherapy?

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

Liu, H; Wentworth, S; Sintay, B

Purpose: Deep inspiration breath hold (DIBH) for left-sided breast cancer has been shown to reduce heart dose. Surface imaging helps to ensure accurate breast positioning, but does not guarantee a reproducible breath hold (BH) at DIBH treatments. We examine the effects of variable BH positions for DIBH treatments. Methods: Twenty-Five patients with free breathing (FB) and DIBH scans were reviewed. Four plans were created for each patient: 1) FB, 2) DIBH, 3) FB-DIBH – the DIBH plans were copied to the FB images and recalculated (image registration was based on breast tissue), and 4) P-DIBH – a partial BH withmore » the heart shifted midway between the FB and DIBH positions. The FB-DIBH plans give “worst case” scenarios for surface imaging DIBH, where the breast is aligned by surface imaging but the patient is not holding their breath. Students t-tests were used to compare dose metrics. Results: The DIBH plans gave lower heart dose and comparable breast coverage versus FB in all cases. The FB-DIBH plans showed no significant difference versus FB plans for breast coverage, mean heart dose, or maximum heart dose (p >= 0.10). The mean heart dose differed between FB-DIBH and FB by < 2 Gy for all cases, the maximum heart dose differed by < 2 Gy for 21 cases. The P-DIBH plans showed significantly lower mean heart dose than FB (p = 0.01). The mean heart doses for the P-DIBH plans were < FB for 22 cases, the maximum dose < FB for 18 cases. Conclusions: A DIBH plan delivered to a FB patient set-up with surface imaging will yield similar dosimetry to a plan created and delivered FB. A DIBH plan delivered with even a partial BH can give reduced heart dose compared to FB techniques when the breast tissue is well aligned.« less

SU-F-T-428: An Optimization-Based Commissioning Tool for Finite Size Pencil Beam Dose Calculations

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

Li, Y; Tian, Z; Song, T

Purpose: Finite size pencil beam (FSPB) algorithms are commonly used to pre-calculate the beamlet dose distribution for IMRT treatment planning. FSPB commissioning, which usually requires fine tuning of the FSPB kernel parameters, is crucial to the dose calculation accuracy and hence the plan quality. Yet due to the large number of beamlets, FSPB commissioning could be very tedious. This abstract reports an optimization-based FSPB commissioning tool we have developed in MatLab to facilitate the commissioning. Methods: A FSPB dose kernel generally contains two types of parameters: the profile parameters determining the dose kernel shape, and a 2D scaling factors accountingmore » for the longitudinal and off-axis corrections. The former were fitted using the penumbra of a reference broad beam’s dose profile with Levenberg-Marquardt algorithm. Since the dose distribution of a broad beam is simply a linear superposition of the dose kernel of each beamlet calculated with the fitted profile parameters and scaled using the scaling factors, these factors could be determined by solving an optimization problem which minimizes the discrepancies between the calculated dose of broad beams and the reference dose. Results: We have commissioned a FSPB algorithm for three linac photon beams (6MV, 15MV and 6MVFFF). Dose of four field sizes (6*6cm2, 10*10cm2, 15*15cm2 and 20*20cm2) were calculated and compared with the reference dose exported from Eclipse TPS system. For depth dose curves, the differences are less than 1% of maximum dose after maximum dose depth for most cases. For lateral dose profiles, the differences are less than 2% of central dose at inner-beam regions. The differences of the output factors are within 1% for all the three beams. Conclusion: We have developed an optimization-based commissioning tool for FSPB algorithms to facilitate the commissioning, providing sufficient accuracy of beamlet dose calculation for IMRT optimization.« less

Survey of patient knowledge related to acetaminophen recognition, dosing, and toxicity.

PubMed

Hornsby, Lori B; Whitley, Heather P; Hester, E Kelly; Thompson, Melissa; Donaldson, Amy

2010-01-01

To assess patient knowledge regarding acetaminophen dosing, toxicity, and recognition of acetaminophen-containing products. Descriptive, nonexperimental, cross-sectional study. Alabama, January 2007 to February 2008. 284 patients at four outpatient medical facilities. 12-item investigator-administered questionnaire. Degree of patient knowledge regarding acetaminophen safety, dosing recommendations, toxicity, alternative names and abbreviations, and products. Two-thirds of the 284 patients completing the survey reported current or recent use of pain, cold, or allergy medication. Of these, 25% reported knowing the active ingredient. Of patients, 46% and 13% knew that "acetaminophen" and "APAP," respectively, were synonymous with "Tylenol." Several patients (12%) believed that ingesting a harmful amount of acetaminophen was difficult or impossible. One-third of patients correctly identified the maximum daily dose, 10% reported a dose greater than 4 g, 25% were unsure of the dose, and 7% were unsure whether a maximum dose existed. One-half recognized liver damage as the primary toxicity. Results were similar between acetaminophen users and nonusers. Deficiencies were found in patient knowledge regarding acetaminophen recognition, dosing, and potential for toxicity. The development of effective educational initiatives is warranted to ensure patient awareness and limit the potential for acetaminophen overdose.

Emergency department patient knowledge concerning acetaminophen (paracetamol) in over-the-counter and prescription analgesics.

PubMed

Fosnocht, D; Taylor, J R; Caravati, E M

2008-04-01

This study was designed to evaluate patient knowledge of the acetaminophen (paracetamol) content of commonly used pain medications and the maximum daily recommended dose of acetaminophen. A prospective, convenience sample of emergency department patients were enrolled. Data were recorded using a standardised questionnaire over 4 months. 1009 patients were enrolled. 492 patients (49%) did not know if Tylenol contained acetaminophen (paracetamol). The majority (66-90%) of patients did not know if Lortab, Vicodin, Percocet, non-aspirin pain reliever, ibuprofen, Motrin, or Advil contained acetaminophen. 568 patients (56%) reported not knowing the maximum daily dose of acetaminophen and only 71 patients (7%) reported the correct daily dose. Patient knowledge of the acetaminophen content of commonly used analgesic medications and its maximum recommended daily dose is limited. This may contribute to unintentional repeated supratherapeutic ingestion (RSTI) of acetaminophen, or overdose.

Pharmacokinetics and safety of the selective progesterone receptor modulator vilaprisan in healthy postmenopausal women
.

PubMed

Schultze-Mosgau, Marcus-Hillert; Schuett, Barbara; Hafner, Frank-Thorsten; Zollmann, Frank; Kaiser, Andreas; Hoechel, Joachim; Rohde, Beate

2017-01-01

Vilaprisan is a novel, potent, and highly selective progesterone receptor modulator, which might offer a promising option for the treatment of uterine fibroids. In this randomized, placebo-controlled, parallel-group phase 1 study, the pharmacokinetics and safety of vilaprisan were investigated in healthy postmenopausal women. Subjects received a single oral dose of vilaprisan (1, 5, 15, or 30 mg) or placebo and - after a wash-out period - daily doses of the same strength over 28 days. Safety assessments included vital signs, ECGs, clinical laboratory tests, and adverse events. Blood samples for pharmacokinetic (PK) profiles were collected over 14 days after single dose (sd) and multiple dose (md; day 28). Vilaprisan was well tolerated. Mild to moderate adverse events occurred with similar frequency at all dose levels. Following single dose, maximum vilaprisan concentrations were observed 1 - 2 hours post-dose. Terminal half-lives ranged from 31 to 38 hours. Maximum concentrations of vilaprisan (Cmax) and exposure to vilaprisan (AUC) increased roughly dose-proportionally from 3.74 µg/L (1 mg) to 68.6 µg/L (30 mg) and 58.5 µg×h/L to 1,590 µg×h/L, respectively. With daily dosing, accumulation consistent with the long terminal half-life was observed (AUC(0-24)md/AUC(0-24)sd ratios: 1.9 to 3.2). The ratio AUC(0-24)md/AUCsd increased with dose from ~ 1 (1 mg) to 1.5 (30 mg). Exposure to vilaprisan increased roughly dose-proportionally in the dose range studied and accumulated after multiple dosing as expected based on t1/2, indicating linear pharmacokinetics of vilaprisan in the expected therapeutic dose range.
.

Phase I Study of Preoperative Chemoradiation With S-1 and Oxaliplatin in Patients With Locally Advanced Resectable Rectal Cancer

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

Hong, Yong Sang; Lee, Jae-Lyun; Park, Jin Hong

Purpose: To perform a Phase I study of preoperative chemoradiation (CRT) with S-1, a novel oral fluoropyrimidine, plus oxaliplatin in patients with locally advanced rectal cancer, to determine the maximum tolerated dose and the recommended dose. Methods and Materials: Radiotherapy was delivered to a total of 45 Gy in 25 fractions and followed by a coned-down boost of 5.4 Gy in 3 fractions. Concurrent chemotherapy consisted of a fixed dose of oxaliplatin (50 mg/m{sup 2}/week) on Days 1, 8, 22, and 29 and escalated doses of S-1 on Days 1-14 and 22-35. The initial dose of S-1 was 50 mg/m{supmore » 2}/day, gradually increasing to 60, 70, and 80 mg/m{sup 2}/day. Surgery was performed within 6 {+-} 2 weeks. Results: Twelve patients were enrolled and tolerated up to Dose Level 4 (3 patients at each dose level) without dose-limiting toxicity. An additional 3 patients were enrolled at Dose Level 4, with 1 experiencing a dose-limiting toxicity of Grade 3 diarrhea. Although maximum tolerated dose was not attained, Dose Level 4 (S-1 80 mg/m{sup 2}/day) was chosen as the recommended dose for further Phase II studies. No Grade 4 toxicity was observed, and Grade 3 toxicities of leukopenia and diarrhea occurred in the same patient (1 of 15, 6.7%). Pathologic complete responses were observed in 2 of 15 patients (13.3%). Conclusions: The recommended dose of S-1 was determined to be 80 mg/m{sup 2}/day when combined with oxaliplatin in preoperative CRT, and a Phase II trial is now ongoing.« less

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.

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

Iwai, P; Lins, L Nadler

Purpose: There is a lack of studies with significant cohort data about patients using pacemaker (PM), implanted cardioverter defibrillator (ICD) or cardiac resynchronization therapy (CRT) device undergoing radiotherapy. There is no literature comparing the cumulative doses delivered to those cardiac implanted electronic devices (CIED) calculated by different algorithms neither studies comparing doses with heterogeneity correction or not. The aim of this study was to evaluate the influence of the algorithms Pencil Beam Convolution (PBC), Analytical Anisotropic Algorithm (AAA) and Acuros XB (AXB) as well as heterogeneity correction on risk categorization of patients. Methods: A retrospective analysis of 19 3DCRT ormore » IMRT plans of 17 patients was conducted, calculating the dose delivered to CIED using three different calculation algorithms. Doses were evaluated with and without heterogeneity correction for comparison. Risk categorization of the patients was based on their CIED dependency and cumulative dose in the devices. Results: Total estimated doses at CIED calculated by AAA or AXB were higher than those calculated by PBC in 56% of the cases. In average, the doses at CIED calculated by AAA and AXB were higher than those calculated by PBC (29% and 4% higher, respectively). The maximum difference of doses calculated by each algorithm was about 1 Gy, either using heterogeneity correction or not. Values of maximum dose calculated with heterogeneity correction showed that dose at CIED was at least equal or higher in 84% of the cases with PBC, 77% with AAA and 67% with AXB than dose obtained with no heterogeneity correction. Conclusion: The dose calculation algorithm and heterogeneity correction did not change the risk categorization. Since higher estimated doses delivered to CIED do not compromise treatment precautions to be taken, it’s recommend that the most sophisticated algorithm available should be used to predict dose at the CIED using heterogeneity correction.« less

Modification and validation of an analytical source model for external beam radiotherapy Monte Carlo dose calculations.

PubMed

Davidson, Scott E; Cui, Jing; Kry, Stephen; Deasy, Joseph O; Ibbott, Geoffrey S; Vicic, Milos; White, R Allen; Followill, David S

2016-08-01

A dose calculation tool, which combines the accuracy of the dose planning method (DPM) Monte Carlo code and the versatility of a practical analytical multisource model, which was previously reported has been improved and validated for the Varian 6 and 10 MV linear accelerators (linacs). The calculation tool can be used to calculate doses in advanced clinical application studies. One shortcoming of current clinical trials that report dose from patient plans is the lack of a standardized dose calculation methodology. Because commercial treatment planning systems (TPSs) have their own dose calculation algorithms and the clinical trial participant who uses these systems is responsible for commissioning the beam model, variation exists in the reported calculated dose distributions. Today's modern linac is manufactured to tight specifications so that variability within a linac model is quite low. The expectation is that a single dose calculation tool for a specific linac model can be used to accurately recalculate dose from patient plans that have been submitted to the clinical trial community from any institution. The calculation tool would provide for a more meaningful outcome analysis. The analytical source model was described by a primary point source, a secondary extra-focal source, and a contaminant electron source. Off-axis energy softening and fluence effects were also included. The additions of hyperbolic functions have been incorporated into the model to correct for the changes in output and in electron contamination with field size. A multileaf collimator (MLC) model is included to facilitate phantom and patient dose calculations. An offset to the MLC leaf positions was used to correct for the rudimentary assumed primary point source. Dose calculations of the depth dose and profiles for field sizes 4 × 4 to 40 × 40 cm agree with measurement within 2% of the maximum dose or 2 mm distance to agreement (DTA) for 95% of the data points tested. The model was capable of predicting the depth of the maximum dose within 1 mm. Anthropomorphic phantom benchmark testing of modulated and patterned MLCs treatment plans showed agreement to measurement within 3% in target regions using thermoluminescent dosimeters (TLD). Using radiochromic film normalized to TLD, a gamma criteria of 3% of maximum dose and 2 mm DTA was applied with a pass rate of least 85% in the high dose, high gradient, and low dose regions. Finally, recalculations of patient plans using DPM showed good agreement relative to a commercial TPS when comparing dose volume histograms and 2D dose distributions. A unique analytical source model coupled to the dose planning method Monte Carlo dose calculation code has been modified and validated using basic beam data and anthropomorphic phantom measurement. While this tool can be applied in general use for a particular linac model, specifically it was developed to provide a singular methodology to independently assess treatment plan dose distributions from those clinical institutions participating in National Cancer Institute trials.

Pharmacology of 13-cis-retinoic acid in humans.

PubMed

Kerr, I G; Lippman, M E; Jenkins, J; Myers, C E

1982-05-01

Vitamin A and its analogs (retinoids) have shown great promise for the chemoprevention of cancer as well as being a possible new class of chemotherapeutic agents. A Phase I and II trial of 13-cis-retinoic acid in advanced cancers was initiated, and the clinical pharmacology of the drug was studied. All patients received p.o. 13-cis-retinoic acid starting at 0.5 mg/kg/day, escalating over 4 weeks to a maximum dose of 8 mg/kg/day in divided doses. Although there was a linear correlation of plasma concentration with dose escalation, large inter-individual variations in peak plasma concentrations were noted. At the maximum drug dose, the mean peak plasma concentration was 4 X 10(-6) M. There was little drug accumulation on this schedule, as trough concentrations between p.o. doses often dropped below 1 X 10(-6) M. The drug was metabolized extensively to a metabolite, the concentrations of which exceeding parent 13-cis-retinoic acid concentrations with chronic dosing. Retinol concentrations were below the normal range.

Measurement of Individual Doses of Radiation by Personal Dosimeter Is Important for the Return of Residents from Evacuation Order Areas after Nuclear Disaster

PubMed Central

Orita, Makiko; Hayashida, Naomi; Taira, Yasuyuki; Fukushima, Yoshiko; Ide, Juichi; Endo, Yuuko; Kudo, Takashi; Yamashita, Shunichi; Takamura, Noboru

2015-01-01

To confirm the availability of individual dose evaluation for the return of residents after the accident at the Fukushima Dai-ichi Nuclear Power Plant (FNPP), we evaluated individual doses of radiation as measured by personal dosimeters in residents who temporarily stayed in Evacuation Order Areas in Kawauchi village, which is partially located within a 20 km radius of the FNPP. We also compared individual doses with the external radiation doses estimated from the ambient dose rates and with doses estimated from the concentrations of radionuclides in the soil around each individual’s house. Individual doses were significantly correlated with the ambient doses in front of the entrances to the houses (r = 0.90, p<0.01), in the backyards (r = 0.41, p<0.01) and in the nearby fields (r = 0.80, p<0.01). The maximum cumulative ambient doses in the backyards and fields around the houses were 6.38 and 9.27 mSv/y, respectively. The maximum cumulative individual dose was 3.28 mSv/y, and the median and minimum doses were 1.35 and 0.71 mSv/y. The estimated external effective doses from concentrations of artificial radionuclides in soil samples ranged from 0.03 to 23.42 mSv/y. The individual doses were moderately correlated with external effective doses in the backyards (r = 0.38, p<0.01) and in the fields (r = 0.36, p<0.01); however, the individual doses were not significantly correlated with the external effective doses in front of the entrances (r = 0.01, p = 0.92). Our study confirmed that individual doses are low levels even in the evacuation order area in Kawauchi village, and external effective dose levels are certainly decreasing due to the decay of artificial radionuclides and the decontamination of contaminated soil. Long-term follow-up of individual doses as well as internal-exposure doses, environmental monitoring and reconstruction of infrastructure are needed so that residents may return to their hometowns after a nuclear disaster. PMID:25806523

Measurement of individual doses of radiation by personal dosimeter is important for the return of residents from evacuation order areas after nuclear disaster.

PubMed

Orita, Makiko; Hayashida, Naomi; Taira, Yasuyuki; Fukushima, Yoshiko; Ide, Juichi; Endo, Yuuko; Kudo, Takashi; Yamashita, Shunichi; Takamura, Noboru

2015-01-01

To confirm the availability of individual dose evaluation for the return of residents after the accident at the Fukushima Dai-ichi Nuclear Power Plant (FNPP), we evaluated individual doses of radiation as measured by personal dosimeters in residents who temporarily stayed in Evacuation Order Areas in Kawauchi village, which is partially located within a 20 km radius of the FNPP. We also compared individual doses with the external radiation doses estimated from the ambient dose rates and with doses estimated from the concentrations of radionuclides in the soil around each individual's house. Individual doses were significantly correlated with the ambient doses in front of the entrances to the houses (r = 0.90, p<0.01), in the backyards (r = 0.41, p<0.01) and in the nearby fields (r = 0.80, p<0.01). The maximum cumulative ambient doses in the backyards and fields around the houses were 6.38 and 9.27 mSv/y, respectively. The maximum cumulative individual dose was 3.28 mSv/y, and the median and minimum doses were 1.35 and 0.71 mSv/y. The estimated external effective doses from concentrations of artificial radionuclides in soil samples ranged from 0.03 to 23.42 mSv/y. The individual doses were moderately correlated with external effective doses in the backyards (r = 0.38, p<0.01) and in the fields (r = 0.36, p<0.01); however, the individual doses were not significantly correlated with the external effective doses in front of the entrances (r = 0.01, p = 0.92). Our study confirmed that individual doses are low levels even in the evacuation order area in Kawauchi village, and external effective dose levels are certainly decreasing due to the decay of artificial radionuclides and the decontamination of contaminated soil. Long-term follow-up of individual doses as well as internal-exposure doses, environmental monitoring and reconstruction of infrastructure are needed so that residents may return to their hometowns after a nuclear disaster.

Gating window dependency on scanned carbon-ion beam dose distribution and imaging dose for thoracoabdominal treatment.

PubMed

Mori, Shinichiro; Karube, Masataka; Yasuda, Shigeo; Yamamoto, Naoyoshi; Tsuji, Hiroshi; Kamada, Tadashi

2017-06-01

To explore the trade-off between dose assessment and imaging dose in respiratory gating with radiographic fluoroscopic imaging, we evaluated the relationship between dose assessment and fluoroscopic imaging dose in various gating windows, retrospectively. Four-dimensional (4D) CT images acquired for 10 patients with lung and liver tumours were used for 4D treatment planning for scanned carbon ion beam. Imaging dose from two oblique directions was calculated by the number of images multiplied by the air kerma per image. Necessary beam-on time was calculated from the treatment log file. Accumulated dose distribution was calculated. The gating window was defined as tumour position not respiratory phase and changed from 0-100% duty cycle on 4DCT. These metrics were individually evaluated for every case. For lung cases, sufficient dose conformation was achieved in respective gating windows [D 95 -clinical target volume (CTV) > 99%]. V 20 -lung values for 50%- and 30%-duty cycles were 2.5% and 6.0% of that for 100%-duty cycle. Maximum doses (cord/oesophagus) for 30%-duty cycle decreased 6.8%/7.4% to those for 100%-duty cycle. For liver cases, V 10 -liver values for 50%- and 30%-duty cycles were 9.4% and 12.8% of those for 100%-duty cycle, respectively. Maximum doses (cord/oesophagus) for 50%- and 30%-duty cycles also decreased 17.2%/19.3% and 24.6%/29.8% to those for 100%-duty cycle, respectively. Total imaging doses increased 43.5% and 115.8% for 50%- and 30%-duty cycles to that for the 100%-duty cycle. When normal tissue doses are below the tolerance level, the gating window should be expanded to minimize imaging dose and treatment time. Advances in knowledge: The skin dose from imaging might not be counterbalanced to the OAR dose; however, imaging dose is a particularly important factor.

DOSIMETRIC CONSEQUENCES OF USING CONTRAST-ENHANCED COMPUTED TOMOGRAPHIC IMAGES FOR INTENSITY-MODULATED STEREOTACTIC BODY RADIOTHERAPY PLANNING.

PubMed

Yoshikawa, Hiroto; Roback, Donald M; Larue, Susan M; Nolan, Michael W

2015-01-01

Potential benefits of planning radiation therapy on a contrast-enhanced computed tomography scan (ceCT) should be weighed against the possibility that this practice may be associated with an inadvertent risk of overdosing nearby normal tissues. This study investigated the influence of ceCT on intensity-modulated stereotactic body radiotherapy (IM-SBRT) planning. Dogs with head and neck, pelvic, or appendicular tumors were included in this retrospective cross-sectional study. All IM-SBRT plans were constructed on a pre- or ceCT. Contours for tumor and organs at risk (OAR) were manually constructed and copied onto both CT's; IM-SBRT plans were calculated on each CT in a manner that resulted in equal radiation fluence. The maximum and mean doses for OAR, and minimum, maximum, and mean doses for targets were compared. Data were collected from 40 dogs per anatomic site (head and neck, pelvis, and limbs). The average dose difference between minimum, maximum, and mean doses as calculated on pre- and ceCT plans for the gross tumor volume was less than 1% for all anatomic sites. Similarly, the differences between mean and maximum doses for OAR were less than 1%. The difference in dose distribution between plans made on CTs with and without contrast enhancement was tolerable at all treatment sites. Therefore, although caution would be recommended when planning IM-SBRT for tumors near "reservoirs" for contrast media (such as the heart and urinary bladder), findings supported the use of ceCT with this dose calculation algorithm for both target delineation and IM-SBRT treatment planning. © 2015 American College of Veterinary Radiology.

SU-F-BRE-16: VMAT Commissioning and Quality Assurance (QA) of An Elekta Synergy-STM Linac Using ICOM Test HarnessTM

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

Nguyen, A; Ironwood CRC, Phoenix, AZ; Rajaguru, P

2014-06-15

Purpose: To establish a set of tests based on the iCOM software that can be used to commission and perform periodic QA of VMAT delivery on the Elekta Synergy-S, commonly known as the Beam Modulator (BM). Methods: iCOM is used to create and deliver customized treatment fields to characterize the system in terms of 1) MLC positioning accuracy under static and dynamic delivery with full gantry rotation, 2) MLC positioning with known errors, 3) Maximum dose rate, 4) Maximum MLC speed, 5) Maximum gantry speed, 6) Synchronization: gantry speed versus dose rate, and 7) Synchronization: MLC speed versus dose rate.more » The resulting images were captured on the iView GT and exported in DICOM format to Dosimetry Check™ system for visual and quantitative analysis. For the initial commissioning phase, the system tests described should be supplemented with extensive patient QAs covering all clinically relevant treatment sites. Results: The system performance test suite showed that on our Synergy-S, MLC positioning was accurate under both static and dynamic deliveries. Intentional errors of 1 mm were also easily identified on both static and dynamic picket fence tests. Maximum dose rate was verified with stop watch to be consistently between 475-480 MU/min. Maximum gantry speed and MLC speed were 5.5 degree/s and 2.5 cm/s respectively. After accounting for beam flatness, both synchronization tests, gantry versus dose rate and MLC speed versus dose rate, were successful as the fields were uniform across the strips and there were no obvious cold/hot spots. Conclusion: VMAT commissioning and quality assurance should include machine characterization tests in addition to patient QAs. Elekta iCOM is a valuable tool for the design of customized VMAT field with specific MU, MLC leaf positions, dose rate, and indirect control of MLC and gantry speed at each of its control points.« less

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

Pokharel, S; Rana, S

Purpose: purpose of this study is to evaluate the effect of grid size in Eclipse AcurosXB dose calculation algorithm for SBRT lung. Methods: Five cases of SBRT lung previously treated have been chosen for present study. Four of the plans were 5 fields conventional IMRT and one was Rapid Arc plan. All five cases have been calculated with five grid sizes (1, 1.5, 2, 2.5 and 3mm) available for AXB algorithm with same plan normalization. Dosimetric indices relevant to SBRT along with MUs and time have been recorded for different grid sizes. The maximum difference was calculated as a percentagemore » of mean of all five values. All the plans were IMRT QAed with portal dosimetry. Results: The maximum difference of MUs was within 2%. The time increased was as high as 7 times from highest 3mm to lowest 1mm grid size. The largest difference of PTV minimum, maximum and mean dose were 7.7%, 1.5% and 1.6% respectively. The highest D2-Max difference was 6.1%. The highest difference in ipsilateral lung mean, V5Gy, V10Gy and V20Gy were 2.6%, 2.4%, 1.9% and 3.8% respectively. The maximum difference of heart, cord and esophagus dose were 6.5%, 7.8% and 4.02% respectively. The IMRT Gamma passing rate at 2%/2mm remains within 1.5% with at least 98% points passing with all grid sizes. Conclusion: This work indicates the lowest grid size of 1mm available in AXB is not necessarily required for accurate dose calculation. The IMRT passing rate was insignificant or not observed with the reduction of grid size less than 2mm. Although the maximum percentage difference of some of the dosimetric indices appear large, most of them are clinically insignificant in absolute dose values. So we conclude that 2mm grid size calculation is best compromise in light of dose calculation accuracy and time it takes to calculate dose.« less

Isotretinoin kinetics after 80 to 320 mg oral doses.

PubMed

Colburn, W A; Gibson, D M

1985-04-01

Twelve healthy male subjects received 80, 160, 240, and 320 mg doses of oral isotretinoin as multiples of 40 mg capsules separated by 2-week washout periods in a randomized, crossover design. Blood samples were drawn at specific times over a 72-hour period after dosing. Blood concentrations of isotretinoin as well as its major metabolite, 4-oxo-isotretinoin, were determined by a specific HPLC method. In addition to the normal laboratory battery of tests, serum triglyceride levels were determined before the first dose and again 72 hours after each of the four doses. Mean (+/- SD) maximum concentrations after 80 to 320 mg doses were 366 +/- 159, 820 +/- 474, 1056 +/- 547, and 981 +/- 381 ng/ml, whereas the respective AUC0-infinity values were 3690 +/- 1280, 7030 +/- 4140, 9780 +/- 6080, and 9040 +/- 2900 ng X hr/ml. The observed apparent elimination t1/2 remained approximately the same (14.7 hours) for each dose. The maximum concentration and AUC values for isotretinoin appear to be dose proportional from 80 to 240 mg but plateau at the 320 mg dose level. Therefore, because isotretinoin blood concentrations may not increase with higher doses in the fasting state, single, oral doses in excess of 240 mg should be used with caution. The data also suggest that elevated triglyceride levels are not a simple function of isotretinoin blood concentrations across the entire study population and dose range studied, but that in subjects with triglyceride levels in excess of the normal range triglyceride levels were positively related to isotretinoin blood concentrations.

Experience of micromultileaf collimator linear accelerator based single fraction stereotactic radiosurgery: Tumor dose inhomogeneity, conformity, and dose fall off

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

Hong, Linda X.; Garg, Madhur; Lasala, Patrick

2011-03-15

Purpose: Sharp dose fall off outside a tumor is essential for high dose single fraction stereotactic radiosurgery (SRS) plans. This study explores the relationship among tumor dose inhomogeneity, conformity, and dose fall off in normal tissues for micromultileaf collimator (mMLC) linear accelerator (LINAC) based cranial SRS plans. Methods: Between January 2007 and July 2009, 65 patients with single cranial lesions were treated with LINAC-based SRS. Among them, tumors had maximum diameters {<=}20 mm: 31; between 20 and 30 mm: 21; and >30 mm: 13. All patients were treated with 6 MV photons on a Trilogy linear accelerator (Varian Medical Systems,more » Palo Alto, CA) with a tertiary m3 high-resolution mMLC (Brainlab, Feldkirchen, Germany), using either noncoplanar conformal fixed fields or dynamic conformal arcs. The authors also created retrospective study plans with identical beam arrangement as the treated plan but with different tumor dose inhomogeneity by varying the beam margins around the planning target volume (PTV). All retrospective study plans were normalized so that the minimum PTV dose was the prescription dose (PD). Isocenter dose, mean PTV dose, RTOG conformity index (CI), RTOG homogeneity index (HI), dose gradient index R{sub 50}-R{sub 100} (defined as the difference between equivalent sphere radius of 50% isodose volume and prescription isodose volume), and normal tissue volume (as a ratio to PTV volume) receiving 50% prescription dose (NTV{sub 50}) were calculated. Results: HI was inversely related to the beam margins around the PTV. CI had a ''V'' shaped relationship with HI, reaching a minimum when HI was approximately 1.3. Isocenter dose and mean PTV dose (as percentage of PD) increased linearly with HI. R{sub 50}-R{sub 100} and NTV{sub 50} initially declined with HI and then reached a plateau when HI was approximately 1.3. These trends also held when tumors were grouped according to their maximum diameters. The smallest tumor group (maximum diameters {<=}20 mm) had the most HI dependence for dose fall off. For treated plans, CI averaged 2.55{+-}0.79 with HI 1.23{+-}0.06; the average R{sub 50}-R{sub 100} was 0.41{+-}0.08, 0.55{+-}0.10, and 0.65{+-}0.09 cm, respectively, for tumors {<=}20 mm, between 20 and 30 mm, and >30 mm. Conclusions: Tumor dose inhomogeneity can be used as an important and convenient parameter to evaluate mMLC LINAC-based SRS plans. Sharp dose fall off in the normal tissue is achieved with sufficiently high tumor dose inhomogeneity. By adjusting beam margins, a homogeneity index of approximately 1.3 would provide best conformity for the authors' SRS system.« less

On the interplay effects with proton scanning beams in stage III lung cancer.

PubMed

Li, Yupeng; Kardar, Laleh; Li, Xiaoqiang; Li, Heng; Cao, Wenhua; Chang, Joe Y; Liao, Li; Zhu, Ronald X; Sahoo, Narayan; Gillin, Michael; Liao, Zhongxing; Komaki, Ritsuko; Cox, James D; Lim, Gino; Zhang, Xiaodong

2014-02-01

To assess the dosimetric impact of interplay between spot-scanning proton beam and respiratory motion in intensity-modulated proton therapy (IMPT) for stage III lung cancer. Eleven patients were sampled from 112 patients with stage III nonsmall cell lung cancer to well represent the distribution of 112 patients in terms of target size and motion. Clinical target volumes (CTVs) and planning target volumes (PTVs) were defined according to the authors' clinical protocol. Uniform and realistic breathing patterns were considered along with regular- and hypofractionation scenarios. The dose contributed by a spot was fully calculated on the computed tomography (CT) images corresponding to the respiratory phase that the spot is delivered, and then accumulated to the reference phase of the 4DCT to generate the dynamic dose that provides an estimation of what might be delivered under the influence of interplay effect. The dynamic dose distributions at different numbers of fractions were compared with the corresponding 4D composite dose which is the equally weighted average of the doses, respectively, computed on respiratory phases of a 4DCT image set. Under regular fractionation, the average and maximum differences in CTV coverage between the 4D composite and dynamic doses after delivery of all 35 fractions were no more than 0.2% and 0.9%, respectively. The maximum differences between the two dose distributions for the maximum dose to the spinal cord, heart V40, esophagus V55, and lung V20 were 1.2 Gy, 0.1%, 0.8%, and 0.4%, respectively. Although relatively large differences in single fraction, correlated with small CTVs relative to motions, were observed, the authors' biological response calculations suggested that this interfractional dose variation may have limited biological impact. Assuming a hypofractionation scenario, the differences between the 4D composite and dynamic doses were well confined even for single fraction. Despite the presence of interplay effect, the delivered dose may be reliably estimated using the 4D composite dose. In general the interplay effect may not be a primary concern with IMPT for lung cancers for the authors' institution. The described interplay analysis tool may be used to provide additional confidence in treatment delivery.

Systemic Delivery of Atropine Sulfate by the MicroDose Dry-Powder Inhaler

PubMed Central

Venkataramanan, R.; Hoffman, R.M.; George, M.P.; Petrov, A.; Richards, T.; Zhang, S.; Choi, J.; Gao, Y.Y.; Oakum, C.D.; Cook, R.O.; Donahoe, M.

2013-01-01

Abstract Background Inhaled atropine is being developed as a systemic and pulmonary treatment for the extended recovery period after chemical weapons exposure. We performed a pharmacokinetics study comparing inhaled atropine delivery using the MicroDose Therapeutx Dry Powder Inhaler (DPIA) with intramuscular (IM) atropine delivery via auto-injector (AUTO). Methods The MicroDose DPIA utilizes a novel piezoelectric system to aerosolize drug and excipient from a foil dosing blister. Subjects inhaled a 1.95-mg atropine sulfate dose from the dry powder inhaler on one study day [5 doses×0.4 mg per dose (nominal) delivered over 12 min] and received a 2-mg IM injection via the AtroPen® auto-injector on another. Pharmacokinetics, pharmacodynamic response, and safety were studied for 12 hr. Results A total of 17 subjects were enrolled. All subjects completed IM dosing. One subject did not perform inhaled delivery due to a skin reaction from the IM dose. Pharmacokinetic results were as follows: area under the curve concentration, DPIA=20.1±5.8, AUTO=23.7±4.9 ng hr/mL (means±SD); maximum concentration reached, DPIA=7.7±3.5, AUTO=11.0±3.8 ng/mL; time to reach maximum concentration, DPIA=0.25±0.47, AUTO=0.19±0.23 hr. Pharmacodynamic results were as follows: maximum increase in heart rate, DPIA=18±12, AUTO=23±13 beats/min; average change in 1-sec forced expiratory volume at 30 min, DPIA=0.16±0.22 L, AUTO=0.11±0.29 L. The relative bioavailability for DPIA was 87% (based on output dose). Two subjects demonstrated allergic responses: one to the first dose (AUTO), which was mild and transient, and one to the second dose (DPIA), which was moderate in severity, required treatment with oral and intravenous (IV) diphenhydramine and IV steroids, and lasted more than 7 days. Conclusions Dry powder inhalation is a highly bioavailable route for attaining rapid and consistent systemic concentrations of atropine. PMID:22691110

Systemic delivery of atropine sulfate by the MicroDose Dry-Powder Inhaler.

PubMed

Corcoran, T E; Venkataramanan, R; Hoffman, R M; George, M P; Petrov, A; Richards, T; Zhang, S; Choi, J; Gao, Y Y; Oakum, C D; Cook, R O; Donahoe, M

2013-02-01

Inhaled atropine is being developed as a systemic and pulmonary treatment for the extended recovery period after chemical weapons exposure. We performed a pharmacokinetics study comparing inhaled atropine delivery using the MicroDose Therapeutx Dry Powder Inhaler (DPIA) with intramuscular (IM) atropine delivery via auto-injector (AUTO). The MicroDose DPIA utilizes a novel piezoelectric system to aerosolize drug and excipient from a foil dosing blister. Subjects inhaled a 1.95-mg atropine sulfate dose from the dry powder inhaler on one study day [5 doses × 0.4 mg per dose (nominal) delivered over 12 min] and received a 2-mg IM injection via the AtroPen® auto-injector on another. Pharmacokinetics, pharmacodynamic response, and safety were studied for 12 hr. A total of 17 subjects were enrolled. All subjects completed IM dosing. One subject did not perform inhaled delivery due to a skin reaction from the IM dose. Pharmacokinetic results were as follows: area under the curve concentration, DPIA=20.1±5.8, AUTO=23.7±4.9 ng hr/mL (means±SD); maximum concentration reached, DPIA=7.7±3.5, AUTO=11.0±3.8 ng/mL; time to reach maximum concentration, DPIA=0.25±0.47, AUTO=0.19±0.23 hr. Pharmacodynamic results were as follows: maximum increase in heart rate, DPIA=18±12, AUTO=23±13 beats/min; average change in 1-sec forced expiratory volume at 30 min, DPIA=0.16±0.22 L, AUTO=0.11±0.29 L. The relative bioavailability for DPIA was 87% (based on output dose). Two subjects demonstrated allergic responses: one to the first dose (AUTO), which was mild and transient, and one to the second dose (DPIA), which was moderate in severity, required treatment with oral and intravenous (IV) diphenhydramine and IV steroids, and lasted more than 7 days. Dry powder inhalation is a highly bioavailable route for attaining rapid and consistent systemic concentrations of atropine.

Stereotactic Body Radiation Therapy Boost After Concurrent Chemoradiation for Locally Advanced Non-Small Cell Lung Cancer: A Phase 1 Dose Escalation Study

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

Hepel, Jaroslaw T., E-mail: jhepel@lifespan.org; Department of Radiation Oncology, Tufts Medical Center, Tufts University, Boston, Massachusetts; Leonard, Kara Lynne

Purpose: Stereotactic body radiation therapy (SBRT) boost to primary and nodal disease after chemoradiation has potential to improve outcomes for advanced non-small cell lung cancer (NSCLC). A dose escalation study was initiated to evaluate the maximum tolerated dose (MTD). Methods and Materials: Eligible patients received chemoradiation to a dose of 50.4 Gy in 28 fractions and had primary and nodal volumes appropriate for SBRT boost (<120 cc and <60 cc, respectively). SBRT was delivered in 2 fractions after chemoradiation. Dose was escalated from 16 to 28 Gy in 2 Gy/fraction increments, resulting in 4 dose cohorts. MTD was defined when ≥2 of 6 patients permore » cohort experienced any treatment-related grade 3 to 5 toxicity within 4 weeks of treatment or the maximum dose was reached. Late toxicity, disease control, and survival were also evaluated. Results: Twelve patients (3 per dose level) underwent treatment. All treatment plans met predetermined dose-volume constraints. The mean age was 64 years. Most patients had stage III disease (92%) and were medically inoperable (92%). The maximum dose level was reached with no grade 3 to 5 acute toxicities. At a median follow-up time of 16 months, 1-year local-regional control (LRC) was 78%. LRC was 50% at <24 Gy and 100% at ≥24 Gy (P=.02). Overall survival at 1 year was 67%. Late toxicity (grade 3-5) was seen in only 1 patient who experienced fatal bronchopulmonary hemorrhage (grade 5). There were no predetermined dose constraints for the proximal bronchial-vascular tree (PBV) in this study. This patient's 4-cc PBV dose was substantially higher than that received by other patients in all 4 cohorts and was associated with the toxicity observed: 20.3 Gy (P<.05) and 73.5 Gy (P=.07) for SBRT boost and total treatment, respectively. Conclusions: SBRT boost to both primary and nodal disease after chemoradiation is feasible and well tolerated. Local control rates are encouraging, especially at doses ≥24 Gy in 2 fractions. Toxicity at the PBV is a concern but potentially can be avoided with strict dose-volume constraints.« less

Pharmacokinetics of ABT-122, a TNF-α- and IL-17A-Targeted Dual-Variable Domain Immunoglobulin, in Healthy Subjects and Patients with Rheumatoid Arthritis: Results from Three Phase I Trials.

PubMed

Khatri, Amit; Goss, Sandra; Jiang, Ping; Mansikka, Heikki; Othman, Ahmed A

2018-05-01

ABT-122 is a dual-variable domain immunoglobulin that neutralizes both tumor necrosis factor-α and interleukin-17A, with the goal of achieving greater clinical efficacy than can be achieved by blocking either cytokine alone. This work characterized the pharmacokinetics of ABT-122 in healthy subjects and in patients with rheumatoid arthritis. ABT-122 pharmacokinetics was evaluated in three phase I studies. In Study 1, single intravenous (0.1, 0.3, 1, 3, and 10 mg/kg) and subcutaneous (0.3, 1, and 3 mg/kg) doses were evaluated in healthy subjects. In Studies 2 and 3, multiple subcutaneous doses (1 mg/kg every other week or 0.5-3 mg/kg every week) were evaluated for 8 weeks in patients with rheumatoid arthritis on stable methotrexate therapy. Pharmacokinetic data were available from 48 healthy subjects and 31 patients with rheumatoid arthritis. ABT-122 showed multi-exponential disposition with more than dose-proportional exposures at the 0.1-1 mg/kg doses and approximately dose-proportional exposures at doses ≥1 mg/kg. ABT-122 absolute subcutaneous bioavailability was approximately 50% with maximum serum concentrations observed 3-4 days after dosing. Steady state was achieved by week 6 of subcutaneous dosing. ABT-122 maximum serum concentration-to-trough concentration ratio was 2.6 for every other week dosing and 1.3 for every week dosing, corresponding to an effective half-life of 10-18 days. ABT-122 median area under the serum concentration-time curve accumulation ratio was 3.8-4.8 with every week dosing. Measureable antidrug antibodies were observed in all 48 subjects in Study 1 by day 15 post-dose and 19 of 31 ABT-122-treated patients in Studies 2 and 3 [median time to appearance of antidrug antibodies of 64 days (range 15-92 days)]. No dose-limiting toxicities were observed in these studies and the maximum tolerated dose was not identified. Results from these three phase I studies supported testing ABT-122 every week and every other week regimens in phase II trials in subjects with rheumatoid and psoriatic arthritis. Study 2 (EudraCT: 2012-003448-54); Study 3 (NCT01853033).

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

Bosarge, Christina L., E-mail: cbosarge@umail.iu.edu; Ewing, Marvene M.; DesRosiers, Colleen M.

To demonstrate the dosimetric advantages and disadvantages of standard anteroposterior-posteroanterior (S-AP/PA{sub AAA}), inverse-planned AP/PA (IP-AP/PA) and volumetry-modulated arc (VMAT) radiotherapies in the treatment of children undergoing whole-lung irradiation. Each technique was evaluated by means of target coverage and normal tissue sparing, including data regarding low doses. A historical approach with and without tissue heterogeneity corrections is also demonstrated. Computed tomography (CT) scans of 10 children scanned from the neck to the reproductive organs were used. For each scan, 6 plans were created: (1) S-AP/PA{sub AAA} using the anisotropic analytical algorithm (AAA), (2) IP-AP/PA, (3) VMAT, (4) S-AP/PA{sub NONE} without heterogeneitymore » corrections, (5) S-AP/PA{sub PB} using the Pencil-Beam algorithm and enforcing monitor units from technique 4, and (6) S-AP/PA{sub AAA[FM]} using AAA and forcing fixed monitor units. The first 3 plans compare modern methods and were evaluated based on target coverage and normal tissue sparing. Body maximum and lower body doses (50% and 30%) were also analyzed. Plans 4 to 6 provide a historic view on the progression of heterogeneity algorithms and elucidate what was actually delivered in the past. Averages of each comparison parameter were calculated for all techniques. The S-AP/PA{sub AAA} technique resulted in superior target coverage but had the highest maximum dose to every normal tissue structure. The IP-AP/PA technique provided the lowest dose to the esophagus, stomach, and lower body doses. VMAT excelled at body maximum dose and maximum doses to the heart, spine, and spleen, but resulted in the highest dose in the 30% body range. It was, however, superior to the S-AP/PA{sub AAA} approach in the 50% range. Each approach has strengths and weaknesses thus associated. Techniques may be selected on a case-by-case basis and by physician preference of target coverage vs normal tissue sparing.« less

Results of a multicentric in silico clinical trial (ROCOCO): comparing radiotherapy with photons and protons for non-small cell lung cancer.

PubMed

Roelofs, Erik; Engelsman, Martijn; Rasch, Coen; Persoon, Lucas; Qamhiyeh, Sima; de Ruysscher, Dirk; Verhaegen, Frank; Pijls-Johannesma, Madelon; Lambin, Philippe

2012-01-01

This multicentric in silico trial compares photon and proton radiotherapy for non-small cell lung cancer patients. The hypothesis is that proton radiotherapy decreases the dose and the volume of irradiated normal tissues even when escalating to the maximum tolerable dose of one or more of the organs at risk (OAR). Twenty-five patients, stage IA-IIIB, were prospectively included. On 4D F18-labeled fluorodeoxyglucose-positron emission tomography-computed tomography scans, the gross tumor, clinical and planning target volumes, and OAR were delineated. Three-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiotherapy (IMRT) photon and passive scattered conformal proton therapy (PSPT) plans were created to give 70 Gy to the tumor in 35 fractions. Dose (de-)escalation was performed by rescaling to the maximum tolerable dose. Protons resulted in the lowest dose to the OAR, while keeping the dose to the target at 70 Gy. The integral dose (ID) was higher for 3DCRT (59%) and IMRT (43%) than for PSPT. The mean lung dose reduced from 18.9 Gy for 3DCRT and 16.4 Gy for IMRT to 13.5 Gy for PSPT. For 10 patients, escalation to 87 Gy was possible for all 3 modalities. The mean lung dose and ID were 40 and 65% higher for photons than for protons, respectively. The treatment planning results of the Radiation Oncology Collaborative Comparison trial show a reduction of ID and the dose to the OAR when treating with protons instead of photons, even with dose escalation. This shows that PSPT is able to give a high tumor dose, while keeping the OAR dose lower than with the photon modalities.

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 Central

Issell, Brian F.; Gotay, Carolyn C.; Pagano, Ian; Franke, A. Adrian

2015-01-01

Purpose We conducted a Phase I study of noni in patients with advanced cancer. Quality of life measures were examined as an alternate way to select a Phase II dose of this popular dietary supplement. Patients and Methods Starting at two capsules twice daily (2 grams), the dose suggested for marketed products, dose levels were escalated by 2 grams daily in cohorts of at least five patients until a maximum tolerated dose was found. Patients completed QLQ-C30 Quality of Life, and the Brief Fatigue Inventory (BFI), questionnaires at baseline and at four week intervals. Scopoletin was measured in blood and urine collected at baseline and at approximately four week intervals. Results Fifty-one patients were enrolled at seven dose levels. Seven capsules four times daily (14 grams) was the maximum tolerated dose. No dose limiting toxicity was found but four of eight patients at this level withdrew from the study due to the challenges of ingesting so many capsules. There was a dose response for self reported physical functioning and the control of pain and fatigue. Patients taking four capsules four times daily experienced less fatigue than patients taking lower or higher doses. A relationship between noni dose and blood and urinary scopoletin concentrations was found. Conclusion Measuring quality of life to determine a dose for subsequent Phase II testing is feasible. A noni dose of four capsules four times daily (8 grams) is recommended for Phase II testing where controlling fatigue and maintaining physical function is the efficacy of interest. Scopoletin is a measurable noni ingredient for pharmacokinetic studies in patients with cancer. PMID:22435516

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.

Volumetric-modulated arc therapy (VMAT) for whole brain radiotherapy: not only for hippocampal sparing, but also for reduction of dose to organs at risk.

PubMed

Sood, Sumit; Pokhrel, Damodar; McClinton, Christopher; Lominska, Christopher; Badkul, Rajeev; Jiang, Hongyu; Wang, Fen

2017-01-01

A prospective clinical trial, Radiation Therapy Oncology Group (RTOG) 0933, has demonstrated that whole brain radiotherapy (WBRT) using conformal radiation delivery technique with hippocampal avoidance is associated with less memory complications. Further sparing of other organs at risk (OARs) including the scalp, ear canals, cochleae, and parotid glands could be associated with reductions in additional toxicities for patients treated with WBRT. We investigated the feasibility of WBRT using volumetric-modulated arc therapy (VMAT) to spare the hippocampi and the aforementioned OARs. Ten patients previously treated with nonconformal WBRT (NC-WBRT) using opposed lateral beams were retrospectively re-planned using VMAT with hippocampal sparing according to the RTOG 0933 protocol. The OARs (scalp, auditory canals, cochleae, and parotid glands) were considered as dose-constrained structures. VMAT plans were generated for a prescription dose of 30 Gy in 10 fractions. Comparison of the dosimetric parameters achieved by VMAT and NC-WBRT plans was performed using paired t-tests using upper bound p-value of < 0.001. Average beam on time and monitor units (MUs) delivered to the patients on VMAT were compared with those obtained with NC-WBRT. All VMAT plans met RTOG 0933 dosimetric criteria including the dose to hippocampi of 100% of the volume (D 100% ) of 8.4 ± 0.3 Gy and maximum dose of 15.6 ± 0.4 Gy, respectively. A statistically significant dose reduction (p < 0.001) to all OARs was achieved. The mean and maximum scalp doses were reduced by an average of 9 Gy (32%) and 2 Gy (6%), respectively. The mean and maximum doses to the auditory canals were reduced from 29.5 ± 0.5 Gy and 31.0 ± 0.4 Gy with NC-WBRT, to 21.8 ± 1.6 Gy (26%) and 27.4 ± 1.4 Gy (12%) with VMAT. VMAT also reduced mean and maximum doses to the cochlea by an average of 4 Gy (13%) and 2 Gy (6%), respectively. The parotid glands mean and maximum doses with VMAT were 4.4 ± 1.9 Gy and 15.7 ± 5.0 Gy, compared to 12.8 ± 4.9 Gy and 30.6 ± 0.5 Gy with NC-WBRT, respectively. The average dose reduction of mean and maximum of parotid glands from VMAT were 65% and 50%, respectively. The average beam on time and MUs were 2.3minutes and 719 on VMAT, and 0.7 minutes and 350 on NC-WBRT. This study demonstrated the feasibility of WBRT using VMAT to not only spare the hippocampi, but also significantly reduce dose to OARs. These advantages of VMAT could potentially decrease the toxicities associated with NC-WBRT and improve patients' quality of life, especially for patients with favorable prognosis receiving WBRT or patients receiving prophylactic cranial irradiation (PCI). Published by Elsevier Inc.

Dose Titration Algorithm Tuning (DTAT) should supersede ‘the’ Maximum Tolerated Dose (MTD) in oncology dose-finding trials

PubMed Central

Norris, David C.

2017-01-01

Background. Absent adaptive, individualized dose-finding in early-phase oncology trials, subsequent ‘confirmatory’ Phase III trials risk suboptimal dosing, with resulting loss of statistical power and reduced probability of technical success for the investigational therapy. While progress has been made toward explicitly adaptive dose-finding and quantitative modeling of dose-response relationships, most such work continues to be organized around a concept of ‘the’ maximum tolerated dose (MTD). The purpose of this paper is to demonstrate concretely how the aim of early-phase trials might be conceived, not as ‘dose-finding’, but as dose titration algorithm (DTA)-finding. Methods. A Phase I dosing study is simulated, for a notional cytotoxic chemotherapy drug, with neutropenia constituting the critical dose-limiting toxicity. The drug’s population pharmacokinetics and myelosuppression dynamics are simulated using published parameter estimates for docetaxel. The amenability of this model to linearization is explored empirically. The properties of a simple DTA targeting neutrophil nadir of 500 cells/mm 3 using a Newton-Raphson heuristic are explored through simulation in 25 simulated study subjects. Results. Individual-level myelosuppression dynamics in the simulation model approximately linearize under simple transformations of neutrophil concentration and drug dose. The simulated dose titration exhibits largely satisfactory convergence, with great variance in individualized optimal dosing. Some titration courses exhibit overshooting. Conclusions. The large inter-individual variability in simulated optimal dosing underscores the need to replace ‘the’ MTD with an individualized concept of MTD i . To illustrate this principle, the simplest possible DTA capable of realizing such a concept is demonstrated. Qualitative phenomena observed in this demonstration support discussion of the notion of tuning such algorithms. Although here illustrated specifically in relation to cytotoxic chemotherapy, the DTAT principle appears similarly applicable to Phase I studies of cancer immunotherapy and molecularly targeted agents. PMID:28663782

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

Vostrotin, Vadim; Birchall, Alan; Zhdanov, Alexey

The distribution of calculated internal doses was determined for 8043 Mayak Production Associate (Mayak PA) workers according to the epidemiological cohorts and groups of raw data used as well as the type of industrial compounds of inhaled aerosols. Statistical characteristics of point estimates of accumulated doses to 17 different tissues and organs and the uncertainty ranges were calculated. Under the MWDS-2013 dosimetry system, the mean accumulated lung dose was 185585 mGy, with a median value of 31 mGy and a maximum of 8980 mGy maximum. The ranges of relative standard uncertainty were: from 40 to 2200% for accumulated lung dose,more » from 25-90% to 2600-3000% for accumulated dose to different regions of respiratory tract, from 13-18% to 2300-2500% for systemic organs and tissues. The Mayak PA workers accumulated internal plutonium lung dose is shown to be close to lognormal. The accumulated internal plutonium dose to systemic organs was close to a log-triangle. The dependency of uncertainty of accumulated absorbed lung and liver doses on the dose estimates itself is also shown. The accumulated absorbed doses to lung, alveolar-interstitial region, liver, bone surface cells and red bone marrow, calculated both with MWDS-2013 and MWDS-2008 have been compared. In general, the accumulated lung doses increased by a factor of 1.8 in median value, while the accumulated doses to systemic organs decreased by factor of 1.3-1.4 in median value. For the cases with identical initial data, accumulated lung doses increased by a factor of 2.1 in median value, while accumulated doses to systemic organs decreased by 8-13% in median value. For the cases with both identical initial data and all of plutonium activity in urine measurements above the decision threshold, accumulated lung doses increased by a factor of 2.8 in median value, while accumulated doses to systemic organs increased by 6-12% in median value.« less

Effects of a prostagrandin EP4-receptor agonist ONO-AE1-329 on the left ventricular pressure-volume relationship in the halothane-anesthetized dogs.

PubMed

Honda, Atsushi; Nakamura, Yuji; Ohara, Hiroshi; Cao, Xin; Nomura, Hiroaki; Katagi, Jun; Wada, Takeshi; Izumi-Nakaseko, Hiroko; Ando, Kentaro; Sugiyama, Atsushi

2016-03-15

Cardiac effects of a prostagrandin EP4-receptor agonist ONO-AE1-329 were assessed in the halothane-anesthetized dogs under the monitoring of left ventricular pressure-volume relationship, which were compared with those of clinically recommended doses of dopamine, dobutamine and milrinone (n=4-5 for each treatment). ONO-AE1-329 was intravenously administered in doses of 0.3, 1 and 3 ng/kg/min for 10 min with a pause of 20 min. Dopamine in a dose of 3 µg/kg/min for 10 min, dobutamine in a dose of 1 µg/kg/min for 10 min and milrinone in a dose of 5 µg/kg/min for 10 min followed by 0.5 µg/kg/min for 10 min were intravenously administered. Low dose of ONO-AE1-329 increased the stroke volume. Middle dose of ONO-AE1-329 increased the cardiac output, left ventricular end-diastolic volume, ejection fraction, maximum upstroke/downstroke velocities of the left ventricular pressure and external work, but decreased the end-systolic pressure and internal work besides the change by the low dose. High dose of ONO-AE1-329 increased the heart rate and maximum elastance, but decreased the end-systolic volume besides the changes by the middle dose. Dopamine, dobutamine and milrinone exerted essentially similar cardiac effects to ONO-AE1-329, but they did not significantly change the end-diastolic volume, end-systolic volume, stroke volume, ejection fraction, end-systolic pressure, maximum elastance, external work or internal work. Thus, EP4-receptor stimulation by ONO-AE1-329 may have potential to better promote the passive ventricular filling than the conventional cardiotonic drugs, which could become a candidate of novel therapeutic strategy for the treatment of heart failure with preserved ejection fraction. Copyright © 2016 Elsevier B.V. All rights reserved.

External beam boost versus interstitial high-dose-rate brachytherapy boost in the adjuvant radiotherapy following breast-conserving therapy in early-stage breast cancer: a dosimetric comparison

PubMed Central

Melchert, Corinna; Kovács, György

2016-01-01

Purpose This study aims to compare the dosimetric data of local tumor's bed dose escalation (boost) with photon beams (external beam radiation therapy – EBRT) versus high-dose-rate interstitial brachytherapy (HDR-BT) after breast-conserving treatment in women with early-stage breast cancer. Material and methods We analyzed the treatment planning data of 136 irradiated patients, treated between 2006 and 2013, who underwent breast-conserving surgery and adjuvant whole breast irradiation (WBI; 50.4 Gy) and boost (HDR-BT: 10 Gy in one fraction [n = 36]; EBRT: 10 Gy in five fractions [n = 100]). Organs at risk (OAR; heart, ipsilateral lung, skin, most exposed rib segment) were delineated. Dosimetric parameters were calculated with the aid of dose-volume histograms (DVH). A non-parametric test was performed to compare the two different boost forms. Results There was no difference for left-sided cancers regarding the maximum dose to the heart (HDR-BT 29.8% vs. EBRT 29.95%, p = 0.34). The maximum doses to the other OAR were significantly lower for HDR-BT (Dmax lung 47.12% vs. 87.7%, p < 0.01; rib 61.17% vs. 98.5%, p < 0.01; skin 57.1% vs. 94.75%, p < 0.01; in the case of right-sided breast irradiation, dose of the heart 6.00% vs. 16.75%, p < 0.01). Conclusions Compared to EBRT, local dose escalation with HDR-BT presented a significant dose reduction to the investigated OAR. Only left-sided irradiation showed no difference regarding the maximum dose to the heart. Reducing irradiation exposure to OAR could result in a reduction of long-term side effects. Therefore, from a dosimetric point of view, an interstitial boost complementary to WBI via EBRT seems to be more advantageous in the adjuvant radiotherapy of breast cancer. PMID:27648082

Phase I Trial of Bortezomib and Concurrent External Beam Radiation in Patients With Advanced Solid Malignancies

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

Pugh, Thomas J.; Chen Changhu; Rabinovitch, Rachel

Purpose: To determine the maximal tolerated dose of bortezomib with concurrent external beam radiation therapy in patients with incurable solid malignant tumors requiring palliative therapy. Methods and Materials: An open label, dose escalation, phase I clinical trial evaluated the safety of three dose levels of bortezomib administered intravenously (1.0 mg/m{sup 2}, 1.3 mg/m{sup 2}, and 1.6 mg/m{sup 2}/ dose) once weekly with concurrent radiation in patients with histologically confirmed solid tumors and a radiographically appreciable lesion suitable for palliative radiation therapy. All patients received 40 Gy in 16 fractions to the target lesion. Dose-limiting toxicity was the primary endpoint, definedmore » as any grade 4 hematologic toxicity, any grade {>=}3 nonhematologic toxicity, or any toxicity requiring treatment to be delayed for {>=}2 weeks. Results: A total of 12 patients were enrolled. Primary sites included prostate (3 patients), head and neck (3 patients), uterus (1 patient), abdomen (1 patient), breast (1 patient), kidney (1 patient), lung (1 patient), and colon (1 patient). The maximum tolerated dose was not realized with a maximum dose of 1.6 mg/m{sup 2}. One case of dose-limiting toxicity was appreciated (grade 3 urosepsis) and felt to be unrelated to bortezomib. The most common grade 3 toxicity was lymphopenia (10 patients). Common grade 1 to 2 events included nausea (7 patients), infection without neutropenia (6 patients), diarrhea (5 patients), and fatigue (5 patients). Conclusions: The combination of palliative external beam radiation with concurrent weekly bortezomib therapy at a dose of 1.6 mg/m{sup 2} is well tolerated in patients with metastatic solid tumors. The maximum tolerated dose of once weekly bortezomib delivered concurrently with radiation therapy is greater than 1.6 mg/m{sup 2}.« less

Implied Maximum Dose Analysis of Standard Values of 25 Pesticides Based on Major Human Exposure Pathways

PubMed Central

Li, Zijian; Jennings, Aaron A.

2017-01-01

Worldwide jurisdictions are making efforts to regulate pesticide standard values in residential soil, drinking water, air, and agricultural commodity to lower the risk of pesticide impacts on human health. Because human may exposure to pesticides from many ways, such as ingestion, inhalation, and dermal contact, it is important to examine pesticide standards by considering all major exposure pathways. Analysis of implied maximum dose limits for commonly historical and current used pesticides was adopted in this study to examine whether worldwide pesticide standard values are enough to prevent human health impact or not. Studies show that only U.S. has regulated pesticides standard in the air. Only 4% of the total number of implied maximum dose limits is based on three major exposures. For Chlorpyrifos, at least 77.5% of the total implied maximum dose limits are above the acceptable daily intake. It also shows that most jurisdictions haven't provided pesticide standards in all major exposures yet, and some of the standards are not good enough to protect human health. PMID:29546224

The Effects of Dextromethorphan on Driving Performance and the Standardized Field Sobriety Test.

PubMed

Perry, Paul J; Fredriksen, Kristian; Chew, Stephanie; Ip, Eric J; Lopes, Ingrid; Doroudgar, Shadi; Thomas, Kelan

2015-09-01

Dextromethorphan (DXM) is abused most commonly among adolescents as a recreational drug to generate a dissociative experience. The objective of the study was to assess driving with and without DXM ingestion. The effects of one-time maximum daily doses of DXM 120 mg versus a guaifenesin 400 mg dose were compared among 40 healthy subjects using a crossover design. Subjects' ability to drive was assessed by their performance in a driving simulator (STISIM® Drive driving simulator software) and by conducting a standardized field sobriety test (SFST) administered 1-h postdrug administration. The one-time dose of DXM 120 mg did not demonstrate driving impairment on the STISIM® Drive driving simulator or increase SFST failures compared to guaifenesin 400 mg. Doses greater than the currently recommended maximum daily dose of 120 mg are necessary to perturb driving behavior. © 2015 American Academy of Forensic Sciences.

Model-based dose calculations for COMS eye plaque brachytherapy using an anatomically realistic eye phantom

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

Lesperance, Marielle; Inglis-Whalen, M.; Thomson, R. M., E-mail: rthomson@physics.carleton.ca

Purpose : To investigate the effects of the composition and geometry of ocular media and tissues surrounding the eye on dose distributions for COMS eye plaque brachytherapy with{sup 125}I, {sup 103}Pd, or {sup 131}Cs seeds, and to investigate doses to ocular structures. Methods : An anatomically and compositionally realistic voxelized eye model with a medial tumor is developed based on a literature review. Mass energy absorption and attenuation coefficients for ocular media are calculated. Radiation transport and dose deposition are simulated using the EGSnrc Monte Carlo user-code BrachyDose for a fully loaded COMS eye plaque within a water phantom andmore » our full eye model for the three radionuclides. A TG-43 simulation with the same seed configuration in a water phantom neglecting the plaque and interseed effects is also performed. The impact on dose distributions of varying tumor position, as well as tumor and surrounding tissue media is investigated. Each simulation and radionuclide is compared using isodose contours, dose volume histograms for the lens and tumor, maximum, minimum, and average doses to structures of interest, and doses to voxels of interest within the eye. Results : Mass energy absorption and attenuation coefficients of the ocular media differ from those of water by as much as 12% within the 20–30 keV photon energy range. For all radionuclides studied, average doses to the tumor and lens regions in the full eye model differ from those for the plaque in water by 8%–10% and 13%–14%, respectively; the average doses to the tumor and lens regions differ between the full eye model and the TG-43 simulation by 2%–17% and 29%–34%, respectively. Replacing the surrounding tissues in the eye model with water increases the maximum and average doses to the lens by 2% and 3%, respectively. Substituting the tumor medium in the eye model for water, soft tissue, or an alternate melanoma composition affects tumor dose compared to the default eye model simulation by up to 16%. In the full eye model simulations, the average dose to the lens is larger by 7%–9% than the dose to the center of the lens, and the maximum dose to the optic nerve is 17%–22% higher than the dose to the optic disk for all radionuclides. In general, when normalized to the same prescription dose at the tumor apex, doses delivered to all structures of interest in the full eye model are lowest for{sup 103}Pd and highest for {sup 131}Cs, except for the tumor where the average dose is highest for {sup 103}Pd and lowest for {sup 131}Cs. Conclusions : The eye is not radiologically water-equivalent, as doses from simulations of the plaque in the full eye model differ considerably from doses for the plaque in a water phantom and from simulated TG-43 calculated doses. This demonstrates the importance of model-based dose calculations for eye plaque brachytherapy, for which accurate elemental compositions of ocular media are necessary.« less

Radiation hardness study of semi-insulating GaAs detectors against 5 MeV electrons

NASA Astrophysics Data System (ADS)

Šagátová, A.; Zaťko, B.; Nečas, V.; Sedlačková, K.; Boháček, P.; Fülöp, M.; Pavlovič, M.

2018-01-01

A radiation hardness study of Semi-Insulating (SI) GaAs detectors against 5 MeV electrons is described in this paper. The influence of two parameters, the accumulative absorbed dose (from 1 to 200 kGy) and the applied dose rate (20, 40 or 80 kGy/h), on detector spectrometric properties were studied. The accumulative dose has influenced all evaluated spectrometric properties and also negatively affected the detector CCE (Charge Collection Efficiency). We have observed its systematic reduction from an initial 79% before irradiation down to about 51% at maximum dose of 200 kGy. Relative energy resolution was also influenced by electron irradiation. Its degradation was obvious in the range of doses from 24 up to a maximum dose of 200 kGy, where an increase from 19% up to 31% at 200 V reverse voltage was noticed. On the other hand, a global increase of detection efficiency with accumulative absorbed dose was observed for all samples. Concerning the actual detector degradation we can assume that the tested SI GaAs detectors will be able to operate up to a dose of 300 kGy at least, when irradiated by 5 MeV electrons. The second investigated parameter of irradiation, the dose rate of chosen ranges, did not greatly alter the spectrometric properties of studied detectors.

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

The energy-dependent electron loss model: backscattering and application to heterogeneous slab media.

PubMed

Lee, Tae Kyu; Sandison, George A

2003-01-21

Electron backscattering has been incorporated into the energy-dependent electron loss (EL) model and the resulting algorithm is applied to predict dose deposition in slab heterogeneous media. This algorithm utilizes a reflection coefficient from the interface that is computed on the basis of Goudsmit-Saunderson theory and an average energy for the backscattered electrons based on Everhart's theory. Predictions of dose deposition in slab heterogeneous media are compared to the Monte Carlo based dose planning method (DPM) and a numerical discrete ordinates method (DOM). The slab media studied comprised water/Pb, water/Al, water/bone, water/bone/water, and water/lung/water, and incident electron beam energies of 10 MeV and 18 MeV. The predicted dose enhancement due to backscattering is accurate to within 3% of dose maximum even for lead as the backscattering medium. Dose discrepancies at large depths beyond the interface were as high as 5% of dose maximum and we speculate that this error may be attributed to the EL model assuming a Gaussian energy distribution for the electrons at depth. The computational cost is low compared to Monte Carlo simulations making the EL model attractive as a fast dose engine for dose optimization algorithms. The predictive power of the algorithm demonstrates that the small angle scattering restriction on the EL model can be overcome while retaining dose calculation accuracy and requiring only one free variable, chi, in the algorithm to be determined in advance of calculation.

The energy-dependent electron loss model: backscattering and application to heterogeneous slab media

NASA Astrophysics Data System (ADS)

Lee, Tae Kyu; Sandison, George A.

2003-01-01

Electron backscattering has been incorporated into the energy-dependent electron loss (EL) model and the resulting algorithm is applied to predict dose deposition in slab heterogeneous media. This algorithm utilizes a reflection coefficient from the interface that is computed on the basis of Goudsmit-Saunderson theory and an average energy for the backscattered electrons based on Everhart's theory. Predictions of dose deposition in slab heterogeneous media are compared to the Monte Carlo based dose planning method (DPM) and a numerical discrete ordinates method (DOM). The slab media studied comprised water/Pb, water/Al, water/bone, water/bone/water, and water/lung/water, and incident electron beam energies of 10 MeV and 18 MeV. The predicted dose enhancement due to backscattering is accurate to within 3% of dose maximum even for lead as the backscattering medium. Dose discrepancies at large depths beyond the interface were as high as 5% of dose maximum and we speculate that this error may be attributed to the EL model assuming a Gaussian energy distribution for the electrons at depth. The computational cost is low compared to Monte Carlo simulations making the EL model attractive as a fast dose engine for dose optimization algorithms. The predictive power of the algorithm demonstrates that the small angle scattering restriction on the EL model can be overcome while retaining dose calculation accuracy and requiring only one free variable, χ, in the algorithm to be determined in advance of calculation.

Assessment of individual organ doses in a realistic human phantom from neutron and gamma stimulated spectroscopy of the breast and liver

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

Belley, Matthew D.; Segars, William Paul; Kapadia, Anuj J., E-mail: anuj.kapadia@duke.edu

2014-06-15

Purpose: Understanding the radiation dose to a patient is essential when considering the use of an ionizing diagnostic imaging test for clinical diagnosis and screening. Using Monte Carlo simulations, the authors estimated the three-dimensional organ-dose distribution from neutron and gamma irradiation of the male liver, female liver, and female breasts for neutron- and gamma-stimulated spectroscopic imaging. Methods: Monte Carlo simulations were developed using the Geant4 GATE application and a voxelized XCAT human phantom. A male and a female whole body XCAT phantom was voxelized into 256 × 256 × 600 voxels (3.125 × 3.125 × 3.125 mm{sup 3}). A monoenergeticmore » rectangular beam of 5.0 MeV neutrons or 7.0 MeV photons was made incident on a 2 cm thick slice of the phantom. The beam was rotated at eight different angles around the phantom ranging from 0° to 180°. Absorbed dose was calculated for each individual organ in the body and dose volume histograms were computed to analyze the absolute and relative doses in each organ. Results: The neutron irradiations of the liver showed the highest organ dose absorption in the liver, with appreciably lower doses in other proximal organs. The dose distribution within the irradiated slice exhibited substantial attenuation with increasing depth along the beam path, attenuating to ∼15% of the maximum value at the beam exit side. The gamma irradiation of the liver imparted the highest organ dose to the stomach wall. The dose distribution from the gammas showed a region of dose buildup at the beam entrance, followed by a relatively uniform dose distribution to all of the deep tissue structures, attenuating to ∼75% of the maximum value at the beam exit side. For the breast scans, both the neutron and gamma irradiation registered maximum organ doses in the breasts, with all other organs receiving less than 1% of the breast dose. Effective doses ranged from 0.22 to 0.37 mSv for the neutron scans and 41 to 66 mSv for the gamma scans. Conclusions: Neutron and gamma irradiation of a primary target organ was found to impart the majority of the total dose to the primary target organ (and other large organs) within the beam plane and considerably lower dose to proximal organs outside of the beam. These results also indicate that despite the use of a highly scattering particle such as a neutron, the dose from neutron stimulated emission computed tomography scans is on par with other clinical imaging techniques such as x-ray computed tomography (x-ray CT). Given the high nonuniformity in the dose across an organ during the neutron scan, care must be taken when computing average doses from neutron irradiations. The effective doses from neutron scanning were found to be comparable to x-ray CT. Further technique modifications are needed to reduce the effective dose levels from the gamma scans.« less

Modification and validation of an analytical source model for external beam radiotherapy Monte Carlo dose calculations

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

Davidson, Scott E., E-mail: sedavids@utmb.edu

Purpose: A dose calculation tool, which combines the accuracy of the dose planning method (DPM) Monte Carlo code and the versatility of a practical analytical multisource model, which was previously reported has been improved and validated for the Varian 6 and 10 MV linear accelerators (linacs). The calculation tool can be used to calculate doses in advanced clinical application studies. One shortcoming of current clinical trials that report dose from patient plans is the lack of a standardized dose calculation methodology. Because commercial treatment planning systems (TPSs) have their own dose calculation algorithms and the clinical trial participant who usesmore » these systems is responsible for commissioning the beam model, variation exists in the reported calculated dose distributions. Today’s modern linac is manufactured to tight specifications so that variability within a linac model is quite low. The expectation is that a single dose calculation tool for a specific linac model can be used to accurately recalculate dose from patient plans that have been submitted to the clinical trial community from any institution. The calculation tool would provide for a more meaningful outcome analysis. Methods: The analytical source model was described by a primary point source, a secondary extra-focal source, and a contaminant electron source. Off-axis energy softening and fluence effects were also included. The additions of hyperbolic functions have been incorporated into the model to correct for the changes in output and in electron contamination with field size. A multileaf collimator (MLC) model is included to facilitate phantom and patient dose calculations. An offset to the MLC leaf positions was used to correct for the rudimentary assumed primary point source. Results: Dose calculations of the depth dose and profiles for field sizes 4 × 4 to 40 × 40 cm agree with measurement within 2% of the maximum dose or 2 mm distance to agreement (DTA) for 95% of the data points tested. The model was capable of predicting the depth of the maximum dose within 1 mm. Anthropomorphic phantom benchmark testing of modulated and patterned MLCs treatment plans showed agreement to measurement within 3% in target regions using thermoluminescent dosimeters (TLD). Using radiochromic film normalized to TLD, a gamma criteria of 3% of maximum dose and 2 mm DTA was applied with a pass rate of least 85% in the high dose, high gradient, and low dose regions. Finally, recalculations of patient plans using DPM showed good agreement relative to a commercial TPS when comparing dose volume histograms and 2D dose distributions. Conclusions: A unique analytical source model coupled to the dose planning method Monte Carlo dose calculation code has been modified and validated using basic beam data and anthropomorphic phantom measurement. While this tool can be applied in general use for a particular linac model, specifically it was developed to provide a singular methodology to independently assess treatment plan dose distributions from those clinical institutions participating in National Cancer Institute trials.« less

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

Lesperance, Marielle; Inglis-Whalen, M.; Thomson, R. M., E-mail: rthomson@physics.carleton.ca

Purpose : To investigate the effects of the composition and geometry of ocular media and tissues surrounding the eye on dose distributions for COMS eye plaque brachytherapy with{sup 125}I, {sup 103}Pd, or {sup 131}Cs seeds, and to investigate doses to ocular structures. Methods : An anatomically and compositionally realistic voxelized eye model with a medial tumor is developed based on a literature review. Mass energy absorption and attenuation coefficients for ocular media are calculated. Radiation transport and dose deposition are simulated using the EGSnrc Monte Carlo user-code BrachyDose for a fully loaded COMS eye plaque within a water phantom andmore » our full eye model for the three radionuclides. A TG-43 simulation with the same seed configuration in a water phantom neglecting the plaque and interseed effects is also performed. The impact on dose distributions of varying tumor position, as well as tumor and surrounding tissue media is investigated. Each simulation and radionuclide is compared using isodose contours, dose volume histograms for the lens and tumor, maximum, minimum, and average doses to structures of interest, and doses to voxels of interest within the eye. Results : Mass energy absorption and attenuation coefficients of the ocular media differ from those of water by as much as 12% within the 20–30 keV photon energy range. For all radionuclides studied, average doses to the tumor and lens regions in the full eye model differ from those for the plaque in water by 8%–10% and 13%–14%, respectively; the average doses to the tumor and lens regions differ between the full eye model and the TG-43 simulation by 2%–17% and 29%–34%, respectively. Replacing the surrounding tissues in the eye model with water increases the maximum and average doses to the lens by 2% and 3%, respectively. Substituting the tumor medium in the eye model for water, soft tissue, or an alternate melanoma composition affects tumor dose compared to the default eye model simulation by up to 16%. In the full eye model simulations, the average dose to the lens is larger by 7%–9% than the dose to the center of the lens, and the maximum dose to the optic nerve is 17%–22% higher than the dose to the optic disk for all radionuclides. In general, when normalized to the same prescription dose at the tumor apex, doses delivered to all structures of interest in the full eye model are lowest for{sup 103}Pd and highest for {sup 131}Cs, except for the tumor where the average dose is highest for {sup 103}Pd and lowest for {sup 131}Cs. Conclusions : The eye is not radiologically water-equivalent, as doses from simulations of the plaque in the full eye model differ considerably from doses for the plaque in a water phantom and from simulated TG-43 calculated doses. This demonstrates the importance of model-based dose calculations for eye plaque brachytherapy, for which accurate elemental compositions of ocular media are necessary.« less

Positron Emission Tomography-Guided, Focal-Dose Escalation Using Intensity-Modulated Radiotherapy for Head and Neck Cancer

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

Madani, Indira; Duthoy, Wim; Derie, Cristina R.N.

2007-05-01

Purpose: To assess the feasibility of intensity-modulated radiotherapy (IMRT) using positron emission tomography (PET)-guided dose escalation, and to determine the maximum tolerated dose in head and neck cancer. Methods and Materials: A Phase I clinical trial was designed to escalate the dose limited to the [{sup 18}-F]fluoro-2-deoxy-D-glucose positron emission tomography ({sup 18}F-FDG-PET)-delineated subvolume within the gross tumor volume. Positron emission tomography scanning was performed in the treatment position. Intensity-modulated radiotherapy with an upfront simultaneously integrated boost was employed. Two dose levels were planned: 25 Gy (level I) and 30 Gy (level II), delivered in 10 fractions. Standard IMRT was appliedmore » for the remaining 22 fractions of 2.16 Gy. Results: Between 2003 and 2005, 41 patients were enrolled, with 23 at dose level I, and 18 at dose level II; 39 patients completed the planned therapy. The median follow-up for surviving patients was 14 months. Two cases of dose-limiting toxicity occurred at dose level I (Grade 4 dermitis and Grade 4 dysphagia). One treatment-related death at dose level II halted the study. Complete response was observed in 18 of 21 (86%) and 13 of 16 (81%) evaluated patients at dose levels I and II (p < 0.7), respectively, with actuarial 1-year local control at 85% and 87% (p n.s.), and 1-year overall survival at 82% and 54% (p = 0.06), at dose levels I and II, respectively. In 4 of 9 patients, the site of relapse was in the boosted {sup 18}F-FDG-PET-delineated region. Conclusions: For head and neck cancer, PET-guided dose escalation appears to be well-tolerated. The maximum tolerated dose was not reached at the investigated dose levels.« less

[Effectiveness of thalidomide for erythema nodosum leprosum (ENL): retrospective study of 20 Japanese cases in National Sanatrium Oku-Komyoen].

PubMed

Matsuki, Takanobu; Okano, Yoshiko; Aoki, Yoshinori; Ishida, Yutaka; Hatano, Kentaro; Kumano, Kimiko

2014-12-01

Thalidomide is a TNF-alpha inhibitor and has been administrated for erythema nodosum leprosum (ENL, Type II leprosy reaction) which is one of leprosy reactions and can cause serious illness to patients oflepromatous pole among the immune spectrum. Twenty live cases (at May, 2011) were identified to whom thalidomide had been administrated since 1978 for their ENL reactions. Data were collected from their clinical records in order to evaluate the usage and effectiveness of thalidomide in National Sanatorium Oku-Komyoen, Okayama, Setouchi-city, Japan. Individual data includes bacillary index (BI), total dose, average daily dose, maximum daily dose, minimum daily dose, methods of thalidomide administration and change of symptoms of ENL. Results: No adverse effect was found among 20 cases. Average daily dose of 20 cases was 19 mg. Regarding to the maximum daily dose, in 3 cases (15%) more than 100 mg, in 3 cases (15%) 50 mg, and in 14 cases (70%) less than 40 mg was administrated. Dose was gradually tapered in most cases. From clinical records, thalidomide was found effective for ENL in 19 cases and clinicians concerned were trying to adjust the proper dose of the drug carefully depending on the current symptoms, because there was no guideline of thalidomide administration for ENL. This data suggests that even less than 50-100 mg as the initial daily dose was still effective, though 50-100 mg daily dose is recommended in the current guideline of Japan (2011) and more dose had been administrated in USA and India.

Collective dose estimates by the marine food pathway from liquid radioactive wastes dumped in the Sea of Japan.

PubMed

Togawa, O; Povinec, P P; Pettersson, H B

1999-09-30

IAEA-MEL has been engaged in an assessment programme related to radioactive waste dumping by the former USSR and other countries in the western North Pacific Ocean and its marginal seas. This paper focuses on the Sea of Japan and on estimation of collective doses from liquid radioactive wastes. The results from the Japanese-Korean-Russian joint expeditions are summarized, and collective doses for the Japanese population by the marine food pathway are estimated from liquid radioactive wastes dumped in the Sea of Japan and compared with those from global fallout and natural radionuclides. The collective effective dose equivalents by the annual intake of marine products caught in each year show a maximum a few years after the disposals. The total dose from all radionuclides reaches a maximum of 0.8 man Sv in 1990. Approximately 90% of the dose derives from 137Cs, most of which is due to consumption of fish. The total dose from liquid radioactive wastes is approximately 5% of that from global fallout, the contribution of which is below 0.1% of that of natural 210Po.

Metabolism of isotretinoin. Biliary excretion of isotretinoin glucuronide in the rat.

PubMed

Meloche, S; Besner, J G

1986-01-01

The biliary metabolites of isotretinoin were examined after iv administration of 4-20-mg/kg doses to vitamin A-normal bile duct-cannulated rats. Analysis of bile by reverse phase high performance liquid chromatography showed that injection of isotretinoin is followed by a rapid excretion of metabolites in bile. Isotretinoin glucuronide was identified as the major metabolite in bile. A specific high performance liquid chromatography method based on the assay of generated isotretinoin in beta-glucuronidase-treated bile was developed for the determination of isotretinoin glucuronide in bile samples. The excretion rate of isotretinoin glucuronide increased rapidly to reach a maximum 55 min after dosing and then declined exponentially. After 330 min of collection, biliary excretion of isotretinoin glucuronide was almost complete, and the metabolite accounted for 34.8-37.9% of the dose. These results indicate that conjugation with glucuronic acid represents a major pathway for the metabolism of pharmacological doses of isotretinoin. The maximum excretion rate of isotretinoin glucuronide in bile increased in a linear manner with the dose of isotretinoin, and no delay was observed after the larger doses. These data suggest that glucuronidation and biliary excretion are not saturated at high pharmacological doses of isotretinoin.

Comparison of depth-dose distributions of proton therapeutic beams calculated by means of logical detectors and ionization chamber modeled in Monte Carlo codes

NASA Astrophysics Data System (ADS)

Pietrzak, Robert; Konefał, Adam; Sokół, Maria; Orlef, Andrzej

2016-08-01

The success of proton therapy depends strongly on the precision of treatment planning. Dose distribution in biological tissue may be obtained from Monte Carlo simulations using various scientific codes making it possible to perform very accurate calculations. However, there are many factors affecting the accuracy of modeling. One of them is a structure of objects called bins registering a dose. In this work the influence of bin structure on the dose distributions was examined. The MCNPX code calculations of Bragg curve for the 60 MeV proton beam were done in two ways: using simple logical detectors being the volumes determined in water, and using a precise model of ionization chamber used in clinical dosimetry. The results of the simulations were verified experimentally in the water phantom with Marcus ionization chamber. The average local dose difference between the measured relative doses in the water phantom and those calculated by means of the logical detectors was 1.4% at first 25 mm, whereas in the full depth range this difference was 1.6% for the maximum uncertainty in the calculations less than 2.4% and for the maximum measuring error of 1%. In case of the relative doses calculated with the use of the ionization chamber model this average difference was somewhat greater, being 2.3% at depths up to 25 mm and 2.4% in the full range of depths for the maximum uncertainty in the calculations of 3%. In the dose calculations the ionization chamber model does not offer any additional advantages over the logical detectors. The results provided by both models are similar and in good agreement with the measurements, however, the logical detector approach is a more time-effective method.

Phase I Study of Daily Irinotecan as a Radiation Sensitizer for Locally Advanced Pancreatic Cancer

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

Fouchardiere, Christelle de la, E-mail: delafo@lyon.fnclcc.f; Negrier, Sylvie; Labrosse, Hugues

2010-06-01

Purpose: The study aimed to determine the maximum tolerated dose of daily irinotecan given with concomitant radiotherapy in patients with locally advanced adenocarcinoma of the pancreas. Methods and Materials: Between September 2000 and March 2008, 36 patients with histologically proven unresectable pancreas adenocarcinoma were studied prospectively. Irinotecan was administered daily, 1 to 2 h before irradiation. Doses were started at 6 mg/m{sup 2} per day and then escalated by increments of 2 mg/m{sup 2} every 3 patients. Radiotherapy was administered in 2-Gy fractions, 5 fractions per week, up to a total dose of 50 Gy to the tumor volume. Inoperabilitymore » was confirmed by a surgeon involved in a multidisciplinary team. All images and responses were centrally reviewed by radiologists. Results: Thirty-six patients were enrolled over a period of 8 years through eight dose levels (6 mg/m{sup 2} to 20 mg/m{sup 2} per day). The maximum tolerated dose was determined to be 18 mg/m{sup 2} per day. The dose-limiting toxicities were nausea/vomiting, diarrhea, anorexia, dehydration, and hypokalemia. The median survival time was 12.6 months with a median follow-up of 53.8 months. The median progression-free survival time was 6.5 months, and 4 patients (11.4%) with very good responses could undergo surgery. Conclusions: The maximum tolerated dose of irinotecan is 18 mg/m{sup 2} per day for 5 weeks. Dose-limiting toxicities are mainly gastrointestinal. Even though efficacy was not the aim of this study, the results are very promising, with a median survival time of 12.6 months.« less

From total empiricism to a rational design of metronomic chemotherapy phase I dosing trials.

PubMed

Lam, Thomas; Hetherington, John W; Greenman, John; Maraveyas, Anthony

2006-02-01

'Metronomic chemotherapy' represents a novel anti-angiogenic strategy whereby low-dose chemotherapy is utilized in a continuous fashion in order to target tumor endothelium. There are many potential advantages of this strategy and clinical trials are already underway. However, although the scheduling of metronomic chemotherapy is relatively unequivocal, metronomic dosing principles are at present poorly defined. Arbitrarily, 10-33% of the maximum tolerated dose comprises 'the dose range'. We argue that this is too empirical and propose a set of phase I metronomic chemotherapy dosing strategies based on a principled approach which may help to reduce the problem of empiricism in dosing for metronomic chemotherapy trials.

Browns Ferry Nuclear Plant radiological impact assessment report, January-June 1988

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

Lee, B.E.

1988-01-01

Potential doses to maximum individuals and the population around Browns Ferry are calcuated for each quarter. Measured plant releases for the reporting period are used to estimate these doses. Dispersion of radioactive effluents in the environment is estimated in accordance with the guidance provided and measuring during the period. Using dose calculation methodologies which are described in detail in the Browns Ferry Offsite Dose Calculation Manual, the doses are calculated and used to determine compliance with the dose limits contained in Browns Ferry's Operating License. In this report, the doses resulting from releases are described and compared to quarterly andmore » annual limits established for Browns Ferry.« less

Pharmacokinetics of sarizotan after oral administration of single and repeat doses in healthy subjects.

PubMed

Krösser, S; Tillner, J; Fluck, M; Ungethüm, W; Wolna, P; Kovar, A

2007-05-01

Sarizotan is a 5-HTIA receptor agonist with high affinity for D3 and D4 receptors. Here we report the pharmacokinetic and tolerability results from four Phase 1 studies. Two single-dose (5 -25 mg, n = 25, 0.5 - 5 mg, n = 16) and two multiple-dose (10 and 20 mg b.i.d., n = 30, 5 mg b.i.d., n = 12) studies with orally administered sarizotan HCl were carried out in healthy subjects. Plasma sarizotan HCl concentrations were measured using a validated HPLC method and fluorescence or MS/MS detection. Pharmacokinetic parameters were obtained using standard non-compartmental methods. Sarizotan was rapidly absorbed, group-median times to reach maximum concentration (tmax) ranged from 0.5 -2.25 h after single doses and during steady state. Maximum plasma concentration (Cmax) and tmax were slightly dependent on formulation and food intake, whereas area under the curve (AUC) was unaffected by these factors. AUC and Cmax increased dose-proportionally over the tested dose range. Independently of dose and time, sarizotan HCl plasma concentrations declined polyexponentially with a terminal elimination half-life (t1/2) of 5 - 7 h. Accumulation factors corresponded to t1/2 values, and steady state was reached within 24 h. Plasma metabolite concentrations were considerably lower than those of the parent drug. The ratio metabolite AUC : parent drug AUC was time- and dose-independent for all three metabolites suggesting that the metabolism of sarizotan is non-saturable in the tested dose range. The pharmacokinetics of sarizotan were dose-proportional and time-independent for the dose range 0.5 -25 mg). The drug was well-tolerated by healthy subjects up to a single dose of 20 mg.

Applicability of the linear-quadratic formalism for modeling local tumor control probability in high dose per fraction stereotactic body radiotherapy for early stage non-small cell lung cancer.

PubMed

Guckenberger, Matthias; Klement, Rainer Johannes; Allgäuer, Michael; Appold, Steffen; Dieckmann, Karin; Ernst, Iris; Ganswindt, Ute; Holy, Richard; Nestle, Ursula; Nevinny-Stickel, Meinhard; Semrau, Sabine; Sterzing, Florian; Wittig, Andrea; Andratschke, Nicolaus; Flentje, Michael

2013-10-01

To compare the linear-quadratic (LQ) and the LQ-L formalism (linear cell survival curve beyond a threshold dose dT) for modeling local tumor control probability (TCP) in stereotactic body radiotherapy (SBRT) for stage I non-small cell lung cancer (NSCLC). This study is based on 395 patients from 13 German and Austrian centers treated with SBRT for stage I NSCLC. The median number of SBRT fractions was 3 (range 1-8) and median single fraction dose was 12.5 Gy (2.9-33 Gy); dose was prescribed to the median 65% PTV encompassing isodose (60-100%). Assuming an α/β-value of 10 Gy, we modeled TCP as a sigmoid-shaped function of the biologically effective dose (BED). Models were compared using maximum likelihood ratio tests as well as Bayes factors (BFs). There was strong evidence for a dose-response relationship in the total patient cohort (BFs>20), which was lacking in single-fraction SBRT (BFs<3). Using the PTV encompassing dose or maximum (isocentric) dose, our data indicated a LQ-L transition dose (dT) at 11 Gy (68% CI 8-14 Gy) or 22 Gy (14-42 Gy), respectively. However, the fit of the LQ-L models was not significantly better than a fit without the dT parameter (p=0.07, BF=2.1 and p=0.86, BF=0.8, respectively). Generally, isocentric doses resulted in much better dose-response relationships than PTV encompassing doses (BFs>20). Our data suggest accurate modeling of local tumor control in fractionated SBRT for stage I NSCLC with the traditional LQ formalism. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Phase 1 study of ombrabulin in combination with cisplatin (CDDP) in Japanese patients with advanced solid tumors.

PubMed

Takahashi, Shunji; Nakano, Kenji; Yokota, Tomoya; Shitara, Kohei; Muro, Kei; Sunaga, Yoshinori; Ecstein-Fraisse, Evelyne; Ura, Takashi

2016-08-27

In clinical studies in Western countries, the recommended dose of combination ombrabulin a vascular disrupting agent, with cisplatin is 25 mg/m 2 ombrabulin with 75 mg/m 2 cisplatin every 3 weeks. Here, we report the first Phase 1 study of this treatment regimen in Japanese patients with advanced solid tumors. This was an open-label, multicenter, sequential cohort, dose-escalation Phase 1 study of ombrabulin with cisplatin administered once every 3 weeks. The study used a 3 + 3 design without intrapatient dose escalation. The investigated dose levels of ombrabulin were 15.5 and 25 mg/m 2 combined with cisplatin 75 mg/m 2 . The latter dose level was regarded as the maximum administered dose if more than one patient experienced dose-limiting toxicities. Ten patients were treated, but no dose-limiting toxicity was observed at both dose levels. Ombrabulin 25 mg/m 2 with cisplatin 75 mg/m 2 was the maximum administered dose and regarded as the recommended dose in the combination regimen for Japanese patients with cancer. The most frequently reported drug-related adverse events were neutropenia, decreased appetite, constipation, nausea and fatigue. One partial response and five cases of stable disease were reported as the best overall responses. Pharmacokinetic parameters of ombrabulin and cisplatin were comparable with those in non-Japanese patients. Ombrabulin 25 mg/m 2 with cisplatin 75 mg/m 2 once every 3 weeks was well tolerated and established as the recommended dose in Japanese patients with advanced solid tumors. The safety and pharmacokinetic profiles were comparable between Japanese and Caucasian patients. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

SU-E-T-118: Dose Verification for Accuboost Applicators Using TLD, Ion Chamber and Gafchromic Film Measurements

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

Chisela, W; Yao, R; Dorbu, G

Purpose: To verify dose delivered with HDR Accuboost applicators using TLD, ion chamber and Gafchromic film measurements and to examine applicator leakage. Methods: A microSelectron HDR unit was used to deliver a dose of 50cGy to the mid-plane of a 62mm thick solid water phantom using dwell times from Monte Carlo pre-calculated nomograms for a 60mm, 70mm Round and 60mm Skin-Dose Optimized (SDO) applicators respectively. GafChromic EBT3+ film was embedded in the phantom midplane horizontally to measure dose distribution. Absolute dose was also measured with TLDs and an ADCL calibrated parallel-plate ion chamber placed in the film plane at fieldmore » center for each applicator. The film was calibrated using 6MV x-ray beam. TLDs were calibrated in a Cs-137 source at UW-Madison calibration laboratory. Radiation leakage through the tungsten alloy shell was measured with a film wrapped around outside surface of a 60mm Round applicator. Results: Measured maximum doses at field center are consistently lower than predicated by 5.8% for TLD, 8.8% for ion chamber, and 2.6% for EBT3+ film on average, with measurement uncertainties of 2.2%, 0.3%, and 2.9% for TLD, chamber, film respectively. The total standard uncertainties for ion chamber and Gafchromic film measurement are 4.9% and 4.6% respectively[1]. The area defined by the applicator aperture was covered by 80% of maximum dose for 62mm compression thickness. When 100cGy is delivered to mid-plane with a 60mm Round applicator, surface dose ranges from 60cGy to a maximum of 145cGy, which occurs at source entrance to the applicator. Conclusion: Measured doses by all three techniques are consistently lower than predicted in our measurements. For a compression thickness of 62 mm, the field size defined by the applicator is only covered by 80% of prescribed dose. Radiation leakage of up to 145cGy was found at the source entrance of applicators.« less

Flu Vaccine and People with Egg Allergies

MedlinePlus

... 12 through 2014–15 reported maximum amounts of ≤1 µg/0.5 mL dose for flu shots and 0.24 µg/0.2 mL dose ... reactions, including anaphylaxis. In a Vaccine Safety Datalink study, there were ... other vaccines, (rate of 1.35 per one million doses). Most of these ...

Pharmacokinetics of isotretinoin and its major blood metabolite following a single oral dose to man.

PubMed

Colburn, W A; Vane, F M; Shorter, H J

1983-01-01

A pharmacokinetic profile of isotretinoin and its major dermatologically active blood metabolite, 4-oxo-isotretinoin, was developed following a single 80 mg oral suspension dose of isotretinoin to 15 normal male subjects. Blood samples were assayed for isotretinoin and 4-oxo-isotretinoin using a newly developed reverse-phase HPLC method. Following rapid absorption from the suspension formulation, isotretinoin is distributed and eliminated with harmonic mean half-lives of 1.3 and 17.4 h, respectively. Maximum concentrations of isotretinoin in blood were observed at 1 to 4 h after dosing. Maximum concentrations of the major blood metabolite of isotretinoin, 4-oxo-isotretinoin, are approximately one-half those of isotretinoin and occur at 6 to 16 h after isotretinoin dosing. The ratio of areas under the curve for metabolite and parent drug following the single dose suggests that average steady-state ratios of metabolite to parent drug during a dosing interval will be approximately 2.5. Both isotretinoin and its metabolite can be adequately described using a single linear pharmacokinetic model.

Evaluation of lens dose from anterior electron beams: comparison of Pinnacle and Gafchromic EBT3 film.

PubMed

Sonier, Marcus; Wronski, Matt; Yeboah, Collins

2015-03-08

Lens dose is a concern during the treatment of facial lesions with anterior electron beams. Lead shielding is routinely employed to reduce lens dose and minimize late complications. The purpose of this work is twofold: 1) to measure dose pro-files under large-area lead shielding at the lens depth for clinical electron energies via film dosimetry; and 2) to assess the accuracy of the Pinnacle treatment planning system in calculating doses under lead shields. First, to simulate the clinical geometry, EBT3 film and 4 cm wide lead shields were incorporated into a Solid Water phantom. With the lead shield inside the phantom, the film was positioned at a depth of 0.7 cm below the lead, while a variable thickness of solid water, simulating bolus, was placed on top. This geometry was reproduced in Pinnacle to calculate dose profiles using the pencil beam electron algorithm. The measured and calculated dose profiles were normalized to the central-axis dose maximum in a homogeneous phantom with no lead shielding. The resulting measured profiles, functions of bolus thickness and incident electron energy, can be used to estimate the lens dose under various clinical scenarios. These profiles showed a minimum lead margin of 0.5 cm beyond the lens boundary is required to shield the lens to ≤ 10% of the dose maximum. Comparisons with Pinnacle showed a consistent overestimation of dose under the lead shield with discrepancies of ~ 25% occur-ring near the shield edge. This discrepancy was found to increase with electron energy and bolus thickness and decrease with distance from the lead edge. Thus, the Pinnacle electron algorithm is not recommended for estimating lens dose in this situation. The film measurements, however, allow for a reasonable estimate of lens dose from electron beams and for clinicians to assess the lead margin required to reduce the lens dose to an acceptable level.

Identifying a maximum tolerated contour in two-dimensional dose-finding

PubMed Central

Wages, Nolan A.

2016-01-01

The majority of Phase I methods for multi-agent trials have focused on identifying a single maximum tolerated dose combination (MTDC) among those being investigated. Some published methods in the area have been based on the notion that there is no unique MTDC, and that the set of dose combinations with acceptable toxicity forms an equivalence contour in two dimensions. Therefore, it may be of interest to find multiple MTDC's for further testing for efficacy in a Phase II setting. In this paper, we present a new dose-finding method that extends the continual reassessment method to account for the location of multiple MTDC's. Operating characteristics are demonstrated through simulation studies, and are compared to existing methodology. Some brief discussion of implementation and available software is also provided. PMID:26910586

SU-G-BRC-02: A Novel Multi-Criteria Optimization Approach to Generate Deliverable Intensity-Modulated Radiation Therapy (IMRT) Treatment Plans

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

Kirlik, G; D’Souza, W; Zhang, H

2016-06-15

Purpose: To present a novel multi-criteria optimization (MCO) solution approach that generates treatment plans with deliverable apertures using column generation. Methods: We demonstrate our method with 10 locally advanced head-and-neck cancer cases retrospectively. In our MCO formulation, we defined an objective function for each structure in the treatment volume. This resulted in 9 objective functions, including 3 distinct objectives for primary target volume, high-risk and low-risk target volumes, 5 objectives for each of the organs-at-risk (OARs) (two parotid glands, spinal cord, brain stem and oral cavity), and one for the non-target non-OAR normal tissue. Conditional value-at-risk (CVaR) constraints were utilizedmore » to ensure at least certain fraction of the target volumes receiving the prescription doses. To directly generate deliverable plans, column generation algorithm was embedded within our MCO approach for aperture shape generation. Final dose distributions for all plans were generated using a Monte Carlo kernel-superposition dose calculation. We compared the MCO plans with the clinical plans, which were created by clinicians. Results: At least 95% target coverage was achieved by both MCO plans and clinical plans. However, the average conformity indices of clinical plans and the MCO plans were 1.95 and 1.35, respectively (31% reduction, p<0.01). Compared to the conventional clinical plan, the proposed MCO method achieved average reductions in left parotid mean dose of 5% (p=0.06), right parotid mean dose of 18% (p<0.01), oral cavity mean dose of 21% (p=0.03), spinal cord maximum dose of 20% (p<0.01), brain stem maximum dose of 61% (p<0.01), and normal tissue maximum dose of 5% (p<0.01), respectively. Conclusion: We demonstrated that the proposed MCO method was able to obtain deliverable IMRT treatment plans while achieving significant improvements in dosimetric plan quality.« less

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

Liu, D; Chi, Z; Yang, H

Purpose: To investigate the performances of three commercial treatment planning systems (TPS) for intensity modulated radiotherapy (IMRT) optimization regarding cervical cancer. Methods: For twenty cervical cancer patients, three IMRT plans were retrospectively re-planned: one with Pinnacle TPS,one with Oncentra TPS and on with Eclipse TPS. The total prescribed dose was 50.4 Gy delivered for PTV and 58.8 Gy for PTVnd by simultaneous integrated boost technique. The treatments were delivered using the Varian 23EX accelerator. All optimization schemes generated clinically acceptable plans. They were evaluated based on target coverage, homogeneity (HI) and conformity (CI). The organs at risk (OARs) were analyzedmore » according to the percent volume under some doses and the maximum doses. The statistical method of the collected data of variance analysis was used to compare the difference among the quality of plans. Results: IMRT with Eclipse provided significant better HI, CI and all the parameters of PTV. However, the trend was not extension to the PTVnd, it was still significant better at mean dose, D50% and D98%, but plans with Oncentra showed significant better in the hight dosage volume, such as maximum dose and D2%. For the bladder wall, there were not notable difference among three groups, although Pinnacle and Oncentra systems provided a little lower dose sparing at V50Gy of bladder and rectal wall and V40Gy of bladder wall, respectively. V40Gy of rectal wall (p=0.037), small intestine (p=0.001 for V30Gy, p=0.010 for maximum dose) and V50Gy of right-femoral head (p=0.019) from Eclipse plans showed significant better than other groups. Conclusion: All SIB-IMRT plans were clinically acceptable which were generated by three commercial TPSs. The plans with Eclipse system showed advantages over the plans with Oncentra and Pinnacle system in the overwhelming majority of the dose coverage for targets and dose sparing of OARs in cervical cancer.« less

Impact of Uncertainties in Exposure Assessment on Thyroid Cancer Risk among Persons in Belarus Exposed as Children or Adolescents Due to the Chernobyl Accident.

PubMed

Little, Mark P; Kwon, Deukwoo; Zablotska, Lydia B; Brenner, Alina V; Cahoon, Elizabeth K; Rozhko, Alexander V; Polyanskaya, Olga N; Minenko, Victor F; Golovanov, Ivan; Bouville, André; Drozdovitch, Vladimir

2015-01-01

The excess incidence of thyroid cancer in Ukraine and Belarus observed a few years after the Chernobyl accident is considered to be largely the result of 131I released from the reactor. Although the Belarus thyroid cancer prevalence data has been previously analyzed, no account was taken of dose measurement error. We examined dose-response patterns in a thyroid screening prevalence cohort of 11,732 persons aged under 18 at the time of the accident, diagnosed during 1996-2004, who had direct thyroid 131I activity measurement, and were resident in the most radio-actively contaminated regions of Belarus. Three methods of dose-error correction (regression calibration, Monte Carlo maximum likelihood, Bayesian Markov Chain Monte Carlo) were applied. There was a statistically significant (p<0.001) increasing dose-response for prevalent thyroid cancer, irrespective of regression-adjustment method used. Without adjustment for dose errors the excess odds ratio was 1.51 Gy- (95% CI 0.53, 3.86), which was reduced by 13% when regression-calibration adjustment was used, 1.31 Gy- (95% CI 0.47, 3.31). A Monte Carlo maximum likelihood method yielded an excess odds ratio of 1.48 Gy- (95% CI 0.53, 3.87), about 2% lower than the unadjusted analysis. The Bayesian method yielded a maximum posterior excess odds ratio of 1.16 Gy- (95% BCI 0.20, 4.32), 23% lower than the unadjusted analysis. There were borderline significant (p = 0.053-0.078) indications of downward curvature in the dose response, depending on the adjustment methods used. There were also borderline significant (p = 0.102) modifying effects of gender on the radiation dose trend, but no significant modifying effects of age at time of accident, or age at screening as modifiers of dose response (p>0.2). In summary, the relatively small contribution of unshared classical dose error in the current study results in comparatively modest effects on the regression parameters.

SU-E-J-33: Cardiac Movement in Deep Inspiration Breath-Hold for Left-Breast Cancer Radiotherapy

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

Kim, M; Lee, S; Suh, T

Purpose: The present study was designed to investigate the displacement of heart using Deep Inspiration Breath Hold (DIBH) CT data compared to free-breathing (FB) CT data and radiation exposure to heart. Methods: Treatment planning was performed on the computed tomography (CT) datasets of 20 patients who had received lumpectomy treatments. Heart, lung and both breasts were outlined. The prescribed dose was 50 Gy divided into 28 fractions. The dose distributions in all the plans were required to fulfill the International Commission on Radiation Units and Measurement specifications that include 100% coverage of the CTV with ≥ 95% of the prescribedmore » dose and that the volume inside the CTV receiving > 107% of the prescribed dose should be minimized. Displacement of heart was measured by calculating the distance between center of heart and left breast. For the evaluation of radiation dose to heart, minimum, maximum and mean dose to heart were calculated. Results: The maximum and minimum left-right (LR) displacements of heart were 8.9 mm and 3 mm, respectively. The heart moved > 4 mm in the LR direction in 17 of the 20 patients. The distances between the heart and left breast ranged from 8.02–17.68 mm (mean, 12.23 mm) and 7.85–12.98 mm (mean, 8.97 mm) with DIBH CT and FB CT, respectively. The maximum doses to the heart were 3115 cGy and 4652 cGy for the DIBH and FB CT dataset, respectively. Conclusion: The present study has demonstrated that the DIBH technique could help to reduce the risk of radiation dose-induced cardiac toxicity by using movement of cardiac; away from radiation field. The DIBH technique could be used in an actual treatment room for a few minutes and could effectively reduce the cardiac dose when used with a sub-device or image acquisition standard to maintain consistent respiratory motion.« less

Comparison of two methods for minimizing the effect of delayed charge on the dose delivered with a synchrotron based discrete spot scanning proton beam.

PubMed

Whitaker, Thomas J; Beltran, Chris; Tryggestad, Erik; Bues, Martin; Kruse, Jon J; Remmes, Nicholas B; Tasson, Alexandria; Herman, Michael G

2014-08-01

Delayed charge is a small amount of charge that is delivered to the patient after the planned irradiation is halted, which may degrade the quality of the treatment by delivering unwarranted dose to the patient. This study compares two methods for minimizing the effect of delayed charge on the dose delivered with a synchrotron based discrete spot scanning proton beam. The delivery of several treatment plans was simulated by applying a normally distributed value of delayed charge, with a mean of 0.001(SD 0.00025) MU, to each spot. Two correction methods were used to account for the delayed charge. Method one (CM1), which is in active clinical use, accounts for the delayed charge by adjusting the MU of the current spot based on the cumulative MU. Method two (CM2) in addition reduces the planned MU by a predicted value. Every fraction of a treatment was simulated using each method and then recomputed in the treatment planning system. The dose difference between the original plan and the sum of the simulated fractions was evaluated. Both methods were tested in a water phantom with a single beam and simple target geometry. Two separate phantom tests were performed. In one test the dose per fraction was varied from 0.5 to 2 Gy using 25 fractions per plan. In the other test the number fractions were varied from 1 to 25, using 2 Gy per fraction. Three patient plans were used to determine the effect of delayed charge on the delivered dose under realistic clinical conditions. The order of spot delivery using CM1 was investigated by randomly selecting the starting spot for each layer, and by alternating per layer the starting spot from first to last. Only discrete spot scanning was considered in this study. Using the phantom setup and varying the dose per fraction, the maximum dose difference for each plan of 25 fractions was 0.37-0.39 Gy and 0.03-0.05 Gy for CM1 and CM2, respectively. While varying the total number of fractions, the maximum dose difference increased at a rate of 0.015 Gy and 0.0018 Gy per fraction for CM1 and CM2, respectively. For CM1, the largest dose difference was found at the location of the first spot in each energy layer, whereas for CM2 the difference in dose was small and showed no dependence on location. For CM1, all of the fields in the patient plans had an area where their excess dose overlapped. No such correlation was found when using CM2. Randomly selecting the starting spot reduces the maximum dose difference from 0.708 to 0.15 Gy. Alternating between first and last spot reduces the maximum dose difference from 0.708 to 0.37 Gy. In the patient plans the excess dose scaled linearly at 0.014 Gy per field per fraction for CM1 and standard delivery order. The predictive model CM2 is superior to a cumulative irradiation model CM1 for minimizing the effects of delayed charge, particularly when considering maximal dose discrepancies and the potential for unplanned hot-spots. This study shows that the dose discrepancy potentially scales at 0.014 Gy per field per fraction for CM1.

Annual committed effective dose from olive oil (due to 238U, 232Th, and 222Rn) estimated for members of the Moroccan public from ingestion and skin application.

PubMed

Misdaq, M A; Touti, R

2012-03-01

Olive oil is traditionally refined and widely consumed by Moroccan rural populations. Uranium (238U), thorium (232Th), radon (222Rn), and thoron (220Rn) contents were measured in various locally produced olive oil samples collected in rural areas of Morocco. These radionuclides were also measured inside various bottled virgin olive oils consumed by the Moroccan populations. CR-39 and LR-115 type II solid state nuclear track detectors (SSNTDs) were used. Annual committed effective doses due to 238U, 232Th, and 222Rn from the ingestion of olive oil by the members of the general public were determined. The maximum total committed effective dose due to 238U, 232Th, and 222Rn from the ingestion of olive oil by adult members of Moroccan rural populations was found equal to 5.9 µSv y-1. The influence of pollution due to building material dusts and phosphates on the radiation dose to workers from the ingestion of olive oil was investigated, and it was found that the maximum total committed effective dose due to 238U, 232Th, and 222Rn was on the order of 0.22 mSy y-1. Committed effective doses to skin due to 238U, 232Th, and 222Rn from the application of olive oil masks by rural women were evaluated. The maximum total committed effective dose to skin due to 238U, 232Th, and 222Rn was found equal to 0.07 mSy y-1 cm-2.

Model-Based Dose Selection for Intravaginal Ring Formulations Releasing Anastrozole and Levonorgestrel Intended for the Treatment of Endometriosis Symptoms.

PubMed

Reinecke, Isabel; Schultze-Mosgau, Marcus-Hillert; Nave, Rüdiger; Schmitz, Heinz; Ploeger, Bart A

2017-05-01

Pharmacokinetics (PK) of anastrozole (ATZ) and levonorgestrel (LNG) released from an intravaginal ring (IVR) intended to treat endometriosis symptoms were characterized, and the exposure-response relationship focusing on the development of large ovarian follicle-like structures was investigated by modeling and simulation to support dose selection for further studies. A population PK analysis and simulations were performed for ATZ and LNG based on clinical phase 1 study data from 66 healthy women. A PK/PD model was developed to predict the probability of a maximum follicle size ≥30 mm and the potential contribution of ATZ beside the known LNG effects. Population PK models for ATZ and LNG were established where the interaction of LNG with sex hormone-binding globulin (SHBG) as well as a stimulating effect of estradiol on SHBG were considered. Furthermore, simulations showed that doses of 40 μg/d LNG combined with 300, 600, or 1050 μg/d ATZ reached anticipated exposure levels for both drugs, facilitating selection of ATZ and LNG doses in the phase 2 dose-finding study. The main driver for the effect on maximum follicle size appears to be unbound LNG exposure. A 50% probability of maximum follicle size ≥30 mm was estimated for 40 μg/d LNG based on the exposure-response analysis. ATZ in the dose range investigated does not increase the risk for ovarian cysts as occurs with LNG at a dose that does not inhibit ovulation. © 2016, The American College of Clinical Pharmacology.

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.

Eye lens dosimetry in anesthesiology: a prospective study.

PubMed

Vaes, Bart; Van Keer, Karel; Struelens, Lara; Schoonjans, Werner; Nijs, Ivo; Vandevenne, Jan; Van Poucke, Sven

2017-04-01

The eye lens is one of the most sensitive organs for radiation injury and exposure might lead to radiation induced cataract. Eye lens dosimetry in anesthesiology has been published in few clinical trials and an active debate about the causality of radiation induced cataract is still ongoing. Recently, the International Commission on Radiological Protection (ICRP) recommended a reduction in the annual dose limit for occupational exposure for the lens of the eye from 150 to 20 mSv, averaged over a period of 5 years, with the dose in a single year not exceeding 50 mSv. This prospective study investigated eye lens dosimetry in anesthesiology practice during a routine year of professional activity. The radiation exposure measured represented the exposure in a normal working schedule of a random anesthesiologist during 1 month and this cumulative eye lens dose was extrapolated to 1 year. Next, eye lens doses were measured in anesthesiology during neuro-embolisation procedures, radiofrequency ablations or vertebroplasty/kyphoplasty procedures. The eye lens doses are measured in terms of the dose equivalent H p (3) with the Eye-D dosimeter (Radcard, Poland) close to the right eye (on the temple). In 16 anesthesiologists, the estimated annual eye lens doses range from a minimum of 0.4 mSv to a maximum of 3.5 mSv with an average dose of 1.33 mSv. Next, eye lens doses were measured for nine neuro-embolisation procedures, ten radiofrequency ablations and six vertebroplasty/kyphoplasty procedures. Average eye lens doses of 77 ± 76 µSv for neuro-embolisations, 38 ± 34 µSv for cardiac ablations and 40 ± 44 µSv for vertebro-/kyphoplasty procedures were recorded. The maximum doses were respectively 264, 97 and 122 µSv. This study demonstrated that the estimated annual eye lens dose is well below the revised ICRP's limit of 20 mSv/year. However, we demonstrated high maximum and average doses during neuro-embolisation, cardiac ablation and vertebro-/kyphoplasty procedures. With radiation induced cataract being explained as a possible stochastic effect, without a threshold dose, anesthesiologists who regularly work in a radiological environment should remain vigilant and maintain radiation safety standards at all times. This includes adequately protective equipment (protection shields, apron, thyroid shield and leaded eye wear), keeping distance, routine monitoring and appropriate education.

SU-E-T-493: Analysis of the Impact of Range and Setup Uncertainties On the Dose to Brain Stem and Whole Brain in the Passively Scattered Proton Therapy Plans

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

Sahoo, N; Zhu, X; Zhang, X

Purpose: To quantify the impact of range and setup uncertainties on various dosimetric indices that are used to assess normal tissue toxicities of patients receiving passive scattering proton beam therapy (PSPBT). Methods: Robust analysis of sample treatment plans of six brain cancer patients treated with PSPBT at our facility for whom the maximum brain stem dose exceeded 5800 CcGE were performed. The DVH of each plan was calculated in an Eclipse treatment planning system (TPS) version 11 applying ±3.5% range uncertainty and ±3 mm shift of the isocenter in x, y and z directions to account for setup uncertainties. Worst-casemore » dose indices for brain stem and whole brain were compared to their values in the nominal plan to determine the average change in their values. For the brain stem, maximum dose to 1 cc of volume, dose to 10%, 50%, 90% of volume (D10, D50, D90) and volume receiving 6000, 5400, 5000, 4500, 4000 CcGE (V60, V54, V50, V45, V40) were evaluated. For the whole brain, maximum dose to 1 cc of volume, and volume receiving 5400, 5000, 4500, 4000, 3000 CcGE (V54, V50, V45, V40 and V30) were assessed. Results: The average change in the values of these indices in the worst scenario cases from the nominal plan were as follows. Brain stem; Maximum dose to 1 cc of volume: 1.1%, D10: 1.4%, D50: 8.0%, D90:73.3%, V60:116.9%, V54:27.7%, V50: 21.2%, V45:16.2%, V40:13.6%,Whole brain; Maximum dose to 1 cc of volume: 0.3%, V54:11.4%, V50: 13.0%, V45:13.6%, V40:14.1%, V30:13.5%. Conclusion: Large to modest changes in the dosiemtric indices for brain stem and whole brain compared to nominal plan due to range and set up uncertainties were observed. Such potential changes should be taken into account while using any dosimetric parameters for outcome evaluation of patients receiving proton therapy.« less

On the interplay effects with proton scanning beams in stage III lung cancer

PubMed Central

Li, Yupeng; Kardar, Laleh; Li, Xiaoqiang; Li, Heng; Cao, Wenhua; Chang, Joe Y.; Liao, Li; Zhu, Ronald X.; Sahoo, Narayan; Gillin, Michael; Liao, Zhongxing; Komaki, Ritsuko; Cox, James D.; Lim, Gino; Zhang, Xiaodong

2014-01-01

Purpose: To assess the dosimetric impact of interplay between spot-scanning proton beam and respiratory motion in intensity-modulated proton therapy (IMPT) for stage III lung cancer. Methods: Eleven patients were sampled from 112 patients with stage III nonsmall cell lung cancer to well represent the distribution of 112 patients in terms of target size and motion. Clinical target volumes (CTVs) and planning target volumes (PTVs) were defined according to the authors' clinical protocol. Uniform and realistic breathing patterns were considered along with regular- and hypofractionation scenarios. The dose contributed by a spot was fully calculated on the computed tomography (CT) images corresponding to the respiratory phase that the spot is delivered, and then accumulated to the reference phase of the 4DCT to generate the dynamic dose that provides an estimation of what might be delivered under the influence of interplay effect. The dynamic dose distributions at different numbers of fractions were compared with the corresponding 4D composite dose which is the equally weighted average of the doses, respectively, computed on respiratory phases of a 4DCT image set. Results: Under regular fractionation, the average and maximum differences in CTV coverage between the 4D composite and dynamic doses after delivery of all 35 fractions were no more than 0.2% and 0.9%, respectively. The maximum differences between the two dose distributions for the maximum dose to the spinal cord, heart V40, esophagus V55, and lung V20 were 1.2 Gy, 0.1%, 0.8%, and 0.4%, respectively. Although relatively large differences in single fraction, correlated with small CTVs relative to motions, were observed, the authors' biological response calculations suggested that this interfractional dose variation may have limited biological impact. Assuming a hypofractionation scenario, the differences between the 4D composite and dynamic doses were well confined even for single fraction. Conclusions: Despite the presence of interplay effect, the delivered dose may be reliably estimated using the 4D composite dose. In general the interplay effect may not be a primary concern with IMPT for lung cancers for the authors' institution. The described interplay analysis tool may be used to provide additional confidence in treatment delivery. PMID:24506612

Occupational dose constraints for the lens of the eye for interventional radiologists and interventional cardiologists in the UK.

PubMed

Mairs, William DA

2016-06-01

The International Commission on Radiological Protection (ICRP) has recommended a 20 mSv year(-1) dose limit for the lens of the eye, which has been adopted in the European Union Basic Safety Standards. Interventional radiologists (IRs) and interventional cardiologists (ICs) are likely to be affected by this. The effects of radiation in the lens are somewhat uncertain, and the ICRP explicitly recommend optimization. Occupational dose constraints are part of the optimization process and define a level of dose which ought to be achievable in a well-managed practice. This commentary calls on the professional bodies to review a need for national constraints to guide local decisions. Consideration is given to developing such constraints using maximum expected doses in high-workload facilities with good radiation protection practices and application of a factor allowing for attenuation by lead glasses (LG). Doses are based on a Public Health England survey of eye dose in the UK. Maximum expected doses for ICs are approximately 21 mSv year(-1), neglecting LG. However, the extent of IR exposure is not yet fully known, and further evidence is required before conclusions are drawn. A Health and Safety Laboratory review of LG established a conservative dose reduction factor of 3 for models available in 2012. Application of this factor provides a dose constraint of 7 mSv year(-1) to the eye for ICs. To achieve this constraint, those employers with the most exposed ICs will have to provide and ensure the correct use of a ceiling-suspended eye shield and LG.

Radiation exposure of the radiologist's eye lens during CT-guided interventions.

PubMed

Heusch, Philipp; Kröpil, Patric; Buchbender, Christian; Aissa, Joel; Lanzman, Rotem S; Heusner, Till A; Ewen, Klaus; Antoch, Gerald; Fürst, Günther

2014-02-01

In the past decade the number of computed tomography (CT)-guided procedures performed by interventional radiologists have increased, leading to a significantly higher radiation exposure of the interventionalist's eye lens. Because of growing concern that there is a stochastic effect for the development of lens opacification, eye lens dose reduction for operators and patients should be of maximal interest. To determine the interventionalist's equivalent eye lens dose during CT-guided interventions and to relate the results to the maximum of the recommended equivalent dose limit. During 89 CT-guided interventions (e.g. biopsies, drainage procedures, etc.) measurements of eye lens' radiation doses were obtained from a dedicated dosimeter system for scattered radiation. The sensor of the personal dosimeter system was clipped onto the side of the lead glasses which was located nearest to the CT gantry. After the procedure, radiation dose (µSv), dose rate (µSv/min) and the total exposure time (s) were recorded. For all 89 interventions, the median total exposure lens dose was 3.3 µSv (range, 0.03-218.9 µSv) for a median exposure time of 26.2 s (range, 1.1-94.0 s). The median dose rate was 13.9 µSv/min (range, 1.1-335.5 µSv/min). Estimating 50-200 CT-guided interventions per year performed by one interventionalist, the median dose of the eye lens of the interventional radiologist does not exceed the maximum of the ICRP-recommended equivalent eye lens dose limit of 20 mSv per year.

Dose-Dependent Suppression of Gonadotropins and Ovarian Hormones by Elagolix in Healthy Premenopausal Women.

PubMed

Ng, Juki; Chwalisz, Kristof; Carter, David C; Klein, Cheri E

2017-05-01

Elagolix is a nonpeptide, oral gonadotropin-releasing hormone (GnRH) antagonist being developed for sex-hormone-dependent diseases in women. We evaluated the pharmacokinetics and pharmacodynamics of elagolix. This study was a randomized, double-blind, placebo-controlled, multiple-ascending dose study in 45 healthy premenopausal women at a research unit. Elagolix [150 mg once daily or 100, 200, 300, or 400 mg twice daily (BID)] or placebo was administered for 21 days. Main outcome measures were elagolix pharmacokinetics, suppression of gonadotropics [follicle-stimulating hormone (FSH), luteinizing hormone (LH)] and ovarian hormones [estradiol (E2), progesterone (P)], and adverse events. Elagolix was rapidly absorbed after oral dosing, reaching maximum concentrations at 1.0 to 1.5 hours, with a half-life of 4 to 6 hours. FSH, LH, and E2 were suppressed within hours of elagolix administration on day 1. Dose-dependent suppression of E2 was observed, with maximum suppression achieved with elagolix 200 mg BID. Dose-dependent suppression of FSH and LH was also observed, with maximal or near-maximal suppression achieved at 300 mg BID and 200 mg BID, respectively. At elagolix doses ≥100 mg BID, P concentrations remained at anovulatory levels throughout 21 days of dosing. The most frequently reported adverse events were headache and hot flush. Elagolix administration allows for modulation of gonadotropin and ovarian hormone concentrations, from partial suppression at lower doses to nearly full suppression at higher doses. The results of this study provide a rationale for elagolix dose selection for treatment of sex hormone-dependent diseases in women. Copyright © 2017 Endocrine Society

SU-E-T-113: Dose Distribution Using Respiratory Signals and Machine Parameters During Treatment

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

Imae, T; Haga, A; Saotome, N

Purpose: Volumetric modulated arc therapy (VMAT) is a rotational intensity-modulated radiotherapy (IMRT) technique capable of acquiring projection images during treatment. Treatment plans for lung tumors using stereotactic body radiotherapy (SBRT) are calculated with planning computed tomography (CT) images only exhale phase. Purpose of this study is to evaluate dose distribution by reconstructing from only the data such as respiratory signals and machine parameters acquired during treatment. Methods: Phantom and three patients with lung tumor underwent CT scans for treatment planning. They were treated by VMAT while acquiring projection images to derive their respiratory signals and machine parameters including positions ofmore » multi leaf collimators, dose rates and integrated monitor units. The respiratory signals were divided into 4 and 10 phases and machine parameters were correlated with the divided respiratory signals based on the gantry angle. Dose distributions of each respiratory phase were calculated from plans which were reconstructed from the respiratory signals and the machine parameters during treatment. The doses at isocenter, maximum point and the centroid of target were evaluated. Results and Discussion: Dose distributions during treatment were calculated using the machine parameters and the respiratory signals detected from projection images. Maximum dose difference between plan and in treatment distribution was −1.8±0.4% at centroid of target and dose differences of evaluated points between 4 and 10 phases were no significant. Conclusion: The present method successfully evaluated dose distribution using respiratory signals and machine parameters during treatment. This method is feasible to verify the actual dose for moving target.« less

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

Suzuki, Minoru; Sakurai, Yoshinori; Masunaga, Shinichiro

Purpose: To investigate the feasibility of boron neutron capture therapy (BNCT) for malignant pleural mesothelioma (MPM) from a viewpoint of dose distribution analysis using Simulation Environment for Radiotherapy Applications (SERA), a currently available BNCT treatment planning system. Methods and Materials: The BNCT treatment plans were constructed for 3 patients with MPM using the SERA system, with 2 opposed anterior-posterior beams. The {sup 1}B concentrations in the tumor and normal lung in this study were assumed to be 84 and 24 ppm, respectively, and were derived from data observed in clinical trials. The maximum, mean, and minimum doses to the tumorsmore » and the normal lung were assessed for each plan. The doses delivered to 5% and 95% of the tumor volume, D{sub 05} and D{sub 95}, were adopted as the representative dose for the maximum and minimum dose, respectively. Results: When the D{sub 05} to the normal ipsilateral lung was 5 Gy-Eq, the D{sub 95} and mean doses delivered to the normal lung were 2.2-3.6 and 3.5-4.2 Gy-Eq, respectively. The mean doses delivered to the tumors were 22.4-27.2 Gy-Eq. The D{sub 05} and D{sub 95} doses to the tumors were 9.6-15.0 and 31.5-39.5 Gy-Eq, respectively. Conclusions: From a viewpoint of the dose-distribution analysis, BNCT has the possibility to be a promising treatment for MPM patients who are inoperable because of age and other medical illnesses.« less

Evaluation of Clostridium novyi-NT spores in dogs with naturally occurring tumors.

PubMed

Krick, Erika L; Sorenmo, Karin U; Rankin, Shelley C; Cheong, Ian; Kobrin, Barry; Thornton, Katherine; Kinzler, Kenneth W; Vogelstein, Bert; Zhou, Shibin; Diaz, Luis A

2012-01-01

To establish the maximum tolerated dose of Clostridium novyi-NT spores in tumor-bearing dogs and evaluate spore germination within tumors and tumor response. 6 client-owned dogs. A standard dose-escalation study was planned, with maximum tolerated dose defined as the highest dose at which 0 or 1 of 6 dogs had dose-limiting toxicoses (DLT). Dogs received 1 dose of C. novyi-NT spores i.v.. Toxicoses were graded and interventions performed according to specific guidelines. Grade 3 or higher toxicosis or any toxicosis combination that substantially affected patient status was considered DLT. Clinical response was measured by use of response evaluation criteria in solid tumors at 28 days. The first 2 dogs had DLT. The dose was decreased. Two of the next 4 dogs had DLT; therefore, dose administration was stopped because the study endpoint had been reached. The most common toxicosis was fever (n = 6 dogs). Two dogs developed abscesses (1 within a nasal carcinoma and 1 splenic abscess) attributable to C. novyi-NT infection; both required surgical intervention. Clostridium novyi-NT was cultured from 1 of 6 tumors. Five dogs were available for response assessment (4 had stable disease; 1 had progressive disease). Results indicated that C. novyi-NT can germinate within tumors of dogs. Toxicosis, although common and sometimes severe, was manageable with treatment. Further studies in dogs with superficial tumors may allow for continued dose escalation and provide information for use in clinical trials in veterinary and human oncology.

SU-E-T-607: Performance Quantification of the Nine Detectors Used for Dosimetry Measurements in Advanced Radiation Therapy Treatments

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

Markovic, M; Stathakis, S; Jurkovic, I

2015-06-15

Purpose: The purpose of this study was to quantify performance of the nine detectors used for dosimetry measurements in advanced radiation therapy treatments. Methods: The 6 MV beam was utilized for measurements of the field sizes with the lack of lateral charge particle equilibrium. For dose fidelity aspect, energy dependence was studied by measuring PDD and profiles at different depths. The volume effect and its influence on the measured dose profiles have been observed by measuring detector’s response function. Output factor measurements with respect to change in energy spectrum have been performed and collected data has been analyzed. The linearitymore » of the measurements with the dose delivered has been evaluated and relevant comparisons were done. Results: The measured values of the output factors with respect to change in energy spectrum indicated presence of the energy dependence. The detectors with active volume size ≤ 0.3 mm3 maximum deviation from the mean is 5.6% for the field size 0.5 x 0.5 cm2 while detectors with active volume size > 0.3 mm3 have maximum deviation from the mean 7.1%. Linearity with dose at highest dose rate examined for diode detectors showed maximum deviation of 4% while ion chambers showed maximum deviation of 2.2%. Dose profiles showed energy dependence at shallow depths (surface to dmax) influenced by low energy particles with 12 % maximum deviation from the mean for 5 mm2 field size. In relation to Monte Carlo calculation, the detector’s response function σ values were between (0.42±0.25) mm and (1.2±0.25) mm. Conclusion: All the detectors are appropriate for the dosimetry measurements in advanced radiation therapy treatments. The choice of the detectors has to be determined by the application and the scope of the measurements in respect to energy dependence and ability to accurately resolve dose profiles as well as to it’s intrinsic characteristics.« less

Safety, efficacy and pharmacokinetics of neratinib (HKI-272) in Japanese patients with advanced solid tumors: a Phase 1 dose-escalation study.

PubMed

Ito, Yoshinori; Suenaga, Mitsukuni; Hatake, Kiyohiko; Takahashi, Shunji; Yokoyama, Masahiro; Onozawa, Yusuke; Yamazaki, Kentaro; Hironaka, Shuichi; Hashigami, Kiyoshi; Hasegawa, Hirotaka; Takenaka, Nobuko; Boku, Narikazu

2012-04-01

Neratinib (HKI-272), a potent, irreversible, small-molecule, orally administered, pan-ErbB inhibitor that blocks signal transduction via inhibition of three epidermal growth factor receptors [ErbB1, ErbB2 (Her2) and ErbB4], is being developed for the treatment of solid tumors, including breast cancer. This Phase 1 dose-escalation study assessed the safety, tolerability, maximum-tolerated dose, antitumor activity and pharmacokinetics of neratinib in Japanese patients with advanced solid tumors. Patients received neratinib 80, 160, 240 or 320 mg orally; each patient enrolled in only one dose cohort. Patients received a single dose in week 1, followed by daily continuous doses. Blood samples collected were on days 1 and 21 for pharmacokinetic analyses. Twenty-one patients were enrolled (3 breast cancer; 17 colorectal cancer; 1 gastric cancer). Neratinib-related adverse events (all grades) included diarrhea (20 patients), fatigue (14 patients), nausea and abdominal pain (9 patients each) and anorexia (8 patients). Grade ≥3 neratinib-related adverse events in two or more patients were diarrhea and anorexia (two patients each). Dose-limiting toxicities were diarrhea and anorexia (two patients, 320 mg dose). The maximum-tolerated dose and recommended dose was neratinib 240 mg once daily. Of 21 evaluable patients, 2 with breast cancer had partial response, 3 had stable disease ≥24 weeks, 7 had stable disease ≥16 weeks and 9 had progressive disease. Pharmacokinetic analyses indicated that neratinib exposures increased with dose. The safety, efficacy and pharmacokinetic profiles of neratinib are consistent with those reported for non-Japanese patients and warrant further investigation of neratinib in Japanese patients with solid tumors.

Phase I clinical and pharmacokinetic study of kahalalide F administered weekly as a 1-hour infusion to patients with advanced solid tumors.

PubMed

Pardo, Beatriz; Paz-Ares, Luis; Tabernero, Josep; Ciruelos, Eva; García, Margarita; Salazar, Ramón; López, Ana; Blanco, María; Nieto, Antonio; Jimeno, José; Izquierdo, Miguel Angel; Trigo, José Manuel

2008-02-15

A dose-escalation, phase I study evaluated the safety, pharmacokinetics, and efficacy of a weekly 1-h regimen of kahalalide F, a cyclic depsipeptide isolated from the marine mollusk Elysia rufescens, in adult patients with advanced solid tumors and no standard treatment available. Patients received an i.v. 1-h infusion of kahalalide F once weekly until disease progression or unacceptable toxicity. The starting kahalalide F dose was 266 microg/m(2), and dose escalation proceeded based on the worst toxicity found in the previous cohort. Thirty-eight patients were enrolled at three Spanish institutions and received once-weekly kahalalide F 1-h infusions at doses between 266 and 1,200 microg/m(2). Dose-limiting toxicities consisted of transient grade 3/4 increases in transaminase blood levels. The maximum tolerated dose for this kahalalide F schedule was 800 microg/m(2), and the recommended dose for phase II studies was 650 microg/m(2). No accumulated toxicity was found. One patient with malignant melanoma had unconfirmed partial response, one patient with metastatic lung adenocarcinoma had minor response, and six patients with different types of metastatic solid tumors had stable disease for 2.8 to 12.7 months. The noncompartmental pharmacokinetics of this kahalalide F schedule was linear and showed a narrow distribution and short body residence. The transaminitis associated with kahalalide F was dose dependent. The maximum tolerated dose was 800 microg/m(2). Dose-limiting toxicities with weekly kahalalide F 1-h i.v. infusions were transient grade 3/4 increases in blood transaminase levels, and 650 microg/m(2) was declared the recommended dose for phase II studies. This schedule showed a favorable safety profile and hints of antitumor activity.

Use of iodine for water disinfection: iodine toxicity and maximum recommended dose.

PubMed Central

Backer, H; Hollowell, J

2000-01-01

Iodine is an effective, simple, and cost-efficient means of water disinfection for people who vacation, travel, or work in areas where municipal water treatment is not reliable. However, there is considerable controversy about the maximum safe iodine dose and duration of use when iodine is ingested in excess of the recommended daily dietary amount. The major health effect of concern with excess iodine ingestion is thyroid disorders, primarily hypothyroidism with or without iodine-induced goiter. A review of the human trials on the safety of iodine ingestion indicates that neither the maximum recommended dietary dose (2 mg/day) nor the maximum recommended duration of use (3 weeks) has a firm basis. Rather than a clear threshold response level or a linear and temporal dose-response relationship between iodine intake and thyroid function, there appears to be marked individual sensitivity, often resulting from unmasking of underlying thyroid disease. The use of iodine for water disinfection requires a risk-benefit decision based on iodine's benefit as a disinfectant and the changes it induces in thyroid physiology. By using appropriate disinfection techniques and monitoring thyroid function, most people can use iodine for water treatment over a prolonged period of time. PMID:10964787

Radiation measurements and doses at SST altitudes

NASA Technical Reports Server (NTRS)

Foelsche, T.

1972-01-01

Radiation components and dose equivalents due to galactic and solar cosmic rays in the high atmosphere, especially at SST altitudes, are presented. The dose equivalent rate for the flight personnel flying 500 hours per year in cruise altitudes of 60,000-65,000 feet (18-19.5 km) in high magnetic latitudes is about 0.75-1.0 rem per year averaged over the solar cycle, or about 15-20 percent of the maximum permissible dose rate.

Using SAFRAN Software to Assess Radiological Hazards from Dismantling of Tammuz-2 Reactor Core at Al-tuwaitha Nuclear Site

NASA Astrophysics Data System (ADS)

Abed Gatea, Mezher; Ahmed, Anwar A.; jundee kadhum, Saad; Ali, Hasan Mohammed; Hussein Muheisn, Abbas

2018-05-01

The Safety Assessment Framework (SAFRAN) software has implemented here for radiological safety analysis; to verify that the dose acceptance criteria and safety goals are met with a high degree of confidence for dismantling of Tammuz-2 reactor core at Al-tuwaitha nuclear site. The activities characterizing, dismantling and packaging were practiced to manage the generated radioactive waste. Dose to the worker was considered an endpoint-scenario while dose to the public has neglected due to that Tammuz-2 facility is located in a restricted zone and 30m berm surrounded Al-tuwaitha site. Safety assessment for dismantling worker endpoint-scenario based on maximum external dose at component position level in the reactor pool and internal dose via airborne activity while, for characterizing and packaging worker endpoints scenarios have been done via external dose only because no evidence for airborne radioactivity hazards outside the reactor pool. The in-situ measurements approved that reactor core components are radiologically activated by Co-60 radioisotope. SAFRAN results showed that the maximum received dose for workers are (1.85, 0.64 and 1.3mSv/y) for activities dismantling, characterizing and packaging of reactor core components respectively. Hence, the radiological hazards remain below the low level hazard and within the acceptable annual dose for workers in radiation field

Safety and tolerability of ibrutinib monotherapy in Japanese patients with relapsed/refractory B cell malignancies.

PubMed

Tobinai, Kensei; Ogura, Michinori; Ishizawa, Kenichi; Suzuki, Tatsuya; Munakata, Wataru; Uchida, Toshiki; Aoki, Tomohiro; Morishita, Takanobu; Ushijima, Yoko; Takahara, Satoko

2016-01-01

In this phase I dose-escalation study we evaluated the safety, tolerability, pharmacokinetics, and antitumor activity of ibrutinib, an oral covalent inhibitor of Bruton's tyrosine kinase (BTK, in Japanese patients with relapsed/refractory B cell malignancies (RRBCM). Fifteen patients aged 42-78 years were enrolled to one of three cohorts. Cohort 1 (n = 3) consisted of two phases, a single-dose (140 and 280 mg) phase and a multiple-dose (420 mg) phase of ibrutinib; cohort 2 (n = 6) included multiple doses of ibrutinib 560 mg; and cohort 3 (n = 6) included only patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) dosed at ibrutinib 420 mg. One patient (CLL/SLL cohort) experienced grade 3 pneumonia and sepsis, which were considered dose-limiting toxicities. No deaths were reported. The most common (≥ 20% patients) adverse events were neutropenia, anemia, nasopharyngitis, increased bilirubin, and rash. Dose-dependent increase in maximum plasma concentration and area under the concentration from 0 to the last quantifiable time was observed, while time to reach maximum plasma concentration and elimination half-life was similar between doses. The overall response rate was 73.3% (11/15) for all cohorts combined. Overall, ibrutinib (420 and 560 mg) was tolerable with acceptable safety profiles and effective for Japanese patients with RRBCM including CLL/SLL. NCT01704963.

Preventive sparing of spinal cord and brain stem in the initial irradiation of locally advanced head and neck cancers.

PubMed

Farace, Paolo; Piras, Sara; Porru, Sergio; Massazza, Federica; Fadda, Giuseppina; Solla, Ignazio; Piras, Denise; Deidda, Maria Assunta; Amichetti, Maurizio; Possanzini, Marco

2014-01-06

Since reirradiation in recurrent head and neck patients is limited by previous treatment, a marked reduction of maximum doses to spinal cord and brain stem was investigated in the initial irradiation of stage III/IV head and neck cancers. Eighteen patients were planned by simultaneous integrated boost, prescribing 69.3 Gy to PTV1 and 56.1 Gy to PTV2. Nine 6 MV coplanar photon beams at equispaced gantry angles were chosen for each patient. Step-and-shoot IMRT was calculated by direct machine parameter optimization, with the maximum number of segments limited to 80. In the standard plan, optimization considered organs at risk (OAR), dose conformity, maximum dose < 45 Gy to spinal cord and < 50 Gy to brain stem. In the sparing plans, a marked reduction to spinal cord and brain stem were investigated, with/without changes in dose conformity. In the sparing plans, the maximum doses to spinal cord and brain stem were reduced from the initial values (43.5 ± 2.2 Gy and 36.7 ± 14.0 Gy), without significant changes on the other OARs. A marked difference (-15.9 ± 1.9 Gy and -10.1 ± 5.7 Gy) was obtained at the expense of a small difference (-1.3% ± 0.9%) from initial PTV195% coverage (96.6% ± 0.9%). Similar difference (-15.7 ± 2.2 Gy and -10.2 ± 6.1 Gy) was obtained compromising dose conformity, but unaffecting PTV195% and with negligible decrease in PTV295% (-0.3% ± 0.3% from the initial 98.3% ± 0.8%). A marked spinal cord and brain stem preventive sparing was feasible at the expense of a decrease in dose conformity or slightly compromising target coverage. A sparing should be recommended in highly recurrent tumors, to make potential reirradiation safer.

An analysis of collegiate band directors' exposure to sound pressure levels

NASA Astrophysics Data System (ADS)

Roebuck, Nikole Moore

Noise-induced hearing loss (NIHL) is a significant but unfortunate common occupational hazard. The purpose of the current study was to measure the magnitude of sound pressure levels generated within a collegiate band room and determine if those sound pressure levels are of a magnitude that exceeds the policy standards and recommendations of the Occupational Safety and Health Administration (OSHA), and the National Institute of Occupational Safety and Health (NIOSH). In addition, reverberation times were measured and analyzed in order to determine the appropriateness of acoustical conditions for the band rehearsal environment. Sound pressure measurements were taken from the rehearsal of seven collegiate marching bands. Single sample t test were conducted to compare the sound pressure levels of all bands to the noise exposure standards of OSHA and NIOSH. Multiple regression analysis were conducted and analyzed in order to determine the effect of the band room's conditions on the sound pressure levels and reverberation times. Time weighted averages (TWA), noise percentage doses, and peak levels were also collected. The mean Leq for all band directors was 90.5 dBA. The total accumulated noise percentage dose for all band directors was 77.6% of the maximum allowable daily noise dose under the OSHA standard. The total calculated TWA for all band directors was 88.2% of the maximum allowable daily noise dose under the OSHA standard. The total accumulated noise percentage dose for all band directors was 152.1% of the maximum allowable daily noise dose under the NIOSH standards, and the total calculated TWA for all band directors was 93dBA of the maximum allowable daily noise dose under the NIOSH standard. Multiple regression analysis revealed that the room volume, the level of acoustical treatment and the mean room reverberation time predicted 80% of the variance in sound pressure levels in this study.

SU-E-T-62: Cardiac Toxicity in Dynamic Conformal Arc Therapy, Intensity-Modulated Radiation Therapy and Volumetric Modulated Arc Therapy of Lung Cancers

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

Ming, X; Zhang, Y; Yale University, New Haven, CT, US

2014-06-01

Purpose: The cardiac toxicity for lung cancer patients, each treated with dynamic conformal arc therapy (DAT), intensity-modulated radiation therapy (IMRT), or volumetric modulated arc therapy (VMAT) is investigated. Methods: 120 lung patients were selected for this study: 25 treated with DAT, 50 with IMRT and 45 with VMAT. For comparison, all plans were generated in the same treatment planning system, normalized such that the 100% isodose lines encompassed 95% of planning target volume. The plan quality was evaluated in terms of homogeneity index (HI) and 95% conformity index (%95 CI) for target dose coverage and mean dose, maximum dose, V{submore » 30} Gy as well as V{sub 5} Gy for cardiac toxicity analysis. Results: When all the plans were analyzed, the VMAT plans offered the best target coverage with 95% CI = 0.992 and HI = 1.23. The DAT plans provided the best heart sparing with mean heart dose = 2.3Gy and maximum dose = 11.6Gy, as compared to 5.7 Gy and 31.1 Gy by IMRT as well as 4.6 Gy and 30.9 Gy by VMAT. The mean V30Gy and V5Gy of the heart in the DAT plans were up to 11.7% lower in comparison to the IMRT and VMAT plans. When the tumor volume was considered, the VMAT plans spared up to 70.9% more doses to the heart when the equivalent diameter of the tumor was larger than 4cm. Yet the maximum dose to the heart was reduced the most in the DAT plans with up to 139.8% less than that of the other two plans. Conclusion: Overall, the VMAT plans achieved the best target coverage among the three treatment modalities, and would spare the heart the most for the larger tumors. The DAT plans appeared advantageous in delivering the least maximum dose to the heart as compared to the IMRT and VMAT plans.« less

AREA RADIATION MONITOR

DOEpatents

Manning, F.W.; Groothuis, S.E.; Lykins, J.H.; Papke, D.M.

1962-06-12

S>An improved area radiation dose monitor is designed which is adapted to compensate continuously for background radiation below a threshold dose rate and to give warning when the dose integral of the dose rate of an above-threshold radiation excursion exceeds a selected value. This is accomplished by providing means for continuously charging an ionization chamber. The chamber provides a first current proportional to the incident radiation dose rate. Means are provided for generating a second current including means for nulling out the first current with the second current at all values of the first current corresponding to dose rates below a selected threshold dose rate value. The second current has a maximum value corresponding to that of the first current at the threshold dose rate. The excess of the first current over the second current, which occurs above the threshold, is integrated and an alarm is given at a selected integrated value of the excess corresponding to a selected radiation dose. (AEC)

Quantifying the Reproducibility of Heart Position During Treatment and Corresponding Delivered Heart Dose in Voluntary Deep Inhalation Breath Hold for Left Breast Cancer Patients Treated With External Beam Radiotherapy

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

McIntosh, Alyson; Shoushtari, Asal N.; Benedict, Stanley H.

Purpose: Voluntary deep inhalation breath hold (VDIBH) reduces heart dose during left breast irradiation. We present results of the first study performed to quantify reproducibility of breath hold using bony anatomy, heart position, and heart dose for VDIBH patients at treatment table. Methods and Materials: Data from 10 left breast cancer patients undergoing VDIBH whole-breast irradiation were analyzed. Two computed tomography (CT) scans, free breathing (FB) and VDIBH, were acquired to compare dose to critical structures. Pretreatment weekly kV orthogonal images and tangential ports were acquired. The displacement difference from spinal cord to sternum across the isocenter between coregistered planningmore » Digitally Reconstructed Radiographs (DRRs) and kV imaging of bony thorax is a measure of breath hold reproducibility. The difference between bony coregistration and heart coregistration was the measured heart shift if the patient is aligned to bony anatomy. Results: Percentage of dose reductions from FB to VDIBH: mean heart dose (48%, SD 19%, p = 0.002), mean LAD dose (43%, SD 19%, p = 0.008), and maximum left anterior descending (LAD) dose (60%, SD 22%, p = 0.008). Average breath hold reproducibility using bony anatomy across the isocenter along the anteroposterior (AP) plane from planning to treatment is 1 (range, 0-3; SD, 1) mm. Average heart shifts with respect to bony anatomy between different breath holds are 2 {+-} 3 mm inferior, 1 {+-} 2 mm right, and 1 {+-} 3 mm posterior. Percentage dose changes from planning to delivery: mean heart dose (7%, SD 6%); mean LAD dose, ((9%, SD 7%)S, and maximum LAD dose, (11%, SD 11%) SD 11%, p = 0.008). Conclusion: We observed excellent three-dimensional bony registration between planning and pretreatment imaging. Reduced delivered dose to heart and LAD is maintained throughout VDIBH treatment.« less

Probabilistic dose assessment of normal operations and accident conditions for an assured isolation facility in Texas

NASA Astrophysics Data System (ADS)

Arno, Matthew Gordon

Texas is investigating building a long-term waste storage facility, also known as an Assured Isolation Facility. This is an above-ground low-level radioactive waste storage facility that is actively maintained and from which waste may be retrieved. A preliminary, scoping-level analysis has been extended to consider more complex scenarios of radiation streaming and skyshine by using the computer code Monte Carlo N-Particle (MCNP) to model the facility in greater detail. Accidental release scenarios have been studied in more depth to better assess the potential dose to off-site individuals. Using bounding source term assumptions, the projected radiation doses and dose rates are estimated to exceed applicable limits by an order of magnitude. By altering the facility design to fill in the hollow cores of the prefabricated concrete slabs used in the roof over the "high-gamma rooms," where the waste with the highest concentration of gamma emitting radioactive material is stored, dose rates outside the facility decrease by an order of magnitude. With the modified design, the annual dose at the site fenceline is estimated at 86 mrem, below the 100 mrem annual limit for exposure of the public. Within the site perimeter, the dose rates are lowered sufficiently such that it is not necessary to categorize many workers and contractor personnel as radiation workers, saving on costs as well as being advisable under ALARA principles. A detailed analysis of bounding accidents incorporating information on the local meteorological conditions indicate that the maximum committed effective dose equivalent from the passage of a plume of material released in an accident at any of the cities near the facility is 59 :rem in the city of Eunice, NM based on the combined day and night meteorological conditions. Using the daytime meteorological conditions, the maximum dose at any city is 7 :rem, also in the city of Eunice. The maximum dose at the site boundary was determined to be 230 mrem using the combined day and night meteorological conditions and 33 mrem using the daytime conditions.

Green tea polyphenol (−)-epigallocatechin-3-gallate triggered hepatotoxicity in mice: Responses of major antioxidant enzymes and the Nrf2 rescue pathway

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

Wang, Dongxu; Wang, Yijun; Wan, Xiaochun

(−)-Epigallocatechin-3-gallate (EGCG), a constituent of green tea, has been suggested to have numerous health-promoting effects. On the other hand, high-dose EGCG is able to evoke hepatotoxicity. In the present study, we elucidated the responses of hepatic major antioxidant enzymes and nuclear factor erythroid 2-related factor 2 (Nrf2) rescue pathway to high-dose levels of EGCG in Kunming mice. At a non-lethal toxic dose (75 mg/kg, i.p.), repeated EGCG treatments markedly decreased the levels of superoxide dismutase, catalase, and glutathione peroxidase. As a rescue response, the nuclear distribution of Nrf2 was significantly increased; a battery of Nrf2-target genes, including heme oxygenase 1more » (HO1), NAD(P)H:quinone oxidoreductase 1 (NQO1), glutathione S-transferase (GST), and those involved in glutathione and thioredoxin systems, were all up-regulated. At the maximum tolerated dose (45 mg/kg, i.p.), repeated EGCG treatments did not disturb the major antioxidant defense. Among the above-mentioned genes, only HO1, NQO1, and GST genes were significantly but modestly up-regulated, suggesting a comprehensive and extensive activation of Nrf2-target genes principally occurs at toxic levels of EGCG. At a lethal dose (200 mg/kg, i.p.), a single EGCG treatment dramatically decreased not only the major antioxidant defense but also the Nrf2-target genes, demonstrating that toxic levels of EGCG are able to cause a biphasic response of Nrf2. Overall, the mechanism of EGCG-triggered hepatotoxicity involves suppression of major antioxidant enzymes, and the Nrf2 rescue pathway plays a vital role for counteracting EGCG toxicity. - Highlights: • EGCG at maximum tolerated dose does not disturb hepatic major antioxidant defense. • EGCG at maximum tolerated dose modestly upregulates hepatic Nrf2 target genes. • EGCG at toxic dose suppresses hepatic major antioxidant enzymes. • EGCG at non-lethal toxic dose pronouncedly activates hepatic Nrf2 rescue response. • EGCG at lethal dose substantially suppresses hepatic Nrf2 pathway.« less

SU-E-T-558: Assessing the Effect of Inter-Fractional Motion in Esophageal Sparing Plans.

PubMed

Williamson, R; Bluett, J; Niedzielski, J; Liao, Z; Gomez, D; Court, L

2012-06-01

To compare esophageal dose distributions in esophageal sparing IMRT plans with predicted dose distributions which include the effect of inter-fraction motion. Seven lung cancer patients were used, each with a standard and an esophageal sparing plan (74Gy, 2Gy fractions). The average max dose to esophagus was 8351cGy and 7758cGy for the standard and sparing plans, respectively. The average length of esophagus for which the total circumference was treated above 60Gy (LETT60) was 9.4cm in the standard plans and 5.8cm in the sparing plans. In order to simulate inter-fractional motion, a three-dimensional rigid shift was applied to the calculated dose field. A simulated course of treatment consisted of a single systematic shift applied throughout the treatment as well a random shift for each of the 37 fractions. Both systematic and random shifts were generated from Gaussian distributions of 3mm and 5mm standard deviation. Each treatment course was simulated 1000 times to obtain an expected distribution of the delivered dose. Simulated treatment dose received by the esophagus was less than dose seen in the treatment plan. The average reduction in maximum esophageal dose for the standard plans was 234cGy and 386cGY for the 3mm and 5mm Gaussian distributions, respectively. The average reduction in LETT60 was 0.6cm and 1.7cm, for the 3mm and 5mm distributions respectively. For the esophageal sparing plans, the average reduction in maximum esophageal dose was 94cGy and 202cGy for 3mm and 5mm Gaussian distributions, respectively. The average change in LETT60 for the esophageal sparing plans was smaller, at 0.1cm (increase) and 0.6cm (reduction), for the 3mm and 5mm distributions, respectively. Interfraction motion consistently reduced the maximum doses to the esophagus for both standard and esophageal sparing plans. © 2012 American Association of Physicists in Medicine.

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

Chau, Ricky; Teo, Peter; Kam, Michael

The aim of this study is to evaluate the deficiencies in target coverage and organ protection of 2-dimensional radiation therapy (2DRT) in the treatment of advanced T-stage (T3-4) nasopharyngeal carcinoma (NPC), and assess the extent of improvement that could be achieved with intensity modulated radiation therapy (IMRT), with special reference to of the dose to the planning organ-at-risk volume (PRV) of the brainstem and spinal cord. A dosimetric study was performed on 10 patients with advanced T-stage (T3-4 and N0-2) NPC. Computer tomography (CT) images of 2.5-mm slice thickness of the head and neck were acquired with the patient immobilizedmore » in semi-extended-head position. A 2D plan based on Ho's technique, and an IMRT plan based on a 7-coplanar portals arrangement, were established for each patient. 2DRT was planned with the field borders and shielding drawn on the simulator radiograph with reference to bony landmarks, digitized, and entered into a planning computer for reconstruction of the 3D dose distribution. The 2DRT and IMRT treatment plans were evaluated and compared with respect to the dose-volume histograms (DVHs) of the targets and the organs-at-risk (OARs), tumor control probability (TCP), and normal tissue complication probabilities (NTCPs). With IMRT, the dose coverage of the target was superior to that of 2DRT. The mean minimum dose of the GTV and PTV were increased from 33.7 Gy (2DRT) to 62.6 Gy (IMRT), and 11.9 Gy (2DRT) to 47.8 Gy (IMRT), respectively. The D{sub 95} of the GTV and PTV were also increased from 57.1 Gy (2DRT) to 67 Gy (IMRT), and 45 Gy (2DRT) to 63.6 Gy (IMRT), respectively. The TCP was substantially increased to 78.5% in IMRT. Better protection of the critical normal organs was also achieved with IMRT. The mean maximum dose delivered to the brainstem and spinal cord were reduced significantly from 61.8 Gy (2DRT) to 52.8 Gy (IMRT) and 56 Gy (2DRT) to 43.6 Gy (IMRT), respectively, which were within the conventional dose limits of 54 Gy for brainstem and of 45 Gy for spinal cord. The mean maximum doses deposited on the PRV of the brainstem and spinal cord were 60.7 Gy and 51.6 Gy respectively, which were above the conventional dose limits. For the chiasm, the mean dose maximum and the dose to 5% of its volume were reduced from 64.3 Gy (2DRT) to 53.7 Gy (IMRT) and from 62.8 Gy (2DRT) to 48.7 Gy (IMRT), respectively, and the corresponding NTCP was reduced from 18.4% to 2.1%. For the temporal lobes, the mean dose to 10% of its volume (about 4.6 cc) was reduced from 63.8 Gy (2DRT) to 55.4 Gy (IMRT) and the NTCP was decreased from 11.7% to 3.4%. The therapeutic ratio for T3-4 NPC tumors can be significantly improved with IMRT treatment technique due to improvement both in target coverage and the sparing of the critical normal organ. Although the maximum doses delivered to the brainstem and spinal cord in IMRT can be kept at or below their conventional dose limits, the maximum doses deposited on the PRV often exceed these limits due to the close proximity between the target and OARs. In other words, ideal dosimetric considerations cannot be fulfilled in IMRT planning for T3-4 NPC tumors. A compromise of the maximal dose limit to the PRV of the brainstem and spinal cord would need be accepted if dose coverage to the targets is not to be unacceptably compromised. Dosimetric comparison with 2DRT plans show that these dose limits to PRV were also frequently exceeded in 2DRT plans for locally advanced NPC. A dedicated retrospective study on the incidence of clinical injury to neurological organs in a large series of patients with T3-4 NPC treated by 2DRT may provide useful reference data in exploring how far the PRV dose constraints may be relaxed, to maximize the target coverage without compromising the normal organ function.« less

SU-E-T-578: On Definition of Minimum and Maximum Dose for Target Volume

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

Gong, Y; Yu, J; Xiao, Y

Purpose: This study aims to investigate the impact of different minimum and maximum dose definitions in radiotherapy treatment plan quality evaluation criteria by using tumor control probability (TCP) models. Methods: Dosimetric criteria used in RTOG 1308 protocol are used in the investigation. RTOG 1308 is a phase III randomized trial comparing overall survival after photon versus proton chemoradiotherapy for inoperable stage II-IIIB NSCLC. The prescription dose for planning target volume (PTV) is 70Gy. Maximum dose (Dmax) should not exceed 84Gy and minimum dose (Dmin) should not go below 59.5Gy in order for the plan to be “per protocol” (satisfactory).A mathematicalmore » model that simulates the characteristics of PTV dose volume histogram (DVH) curve with normalized volume is built. The Dmax and Dmin are noted as percentage volumes Dη% and D(100-δ)%, with η and d ranging from 0 to 3.5. The model includes three straight line sections and goes through four points: D95%= 70Gy, Dη%= 84Gy, D(100-δ)%= 59.5 Gy, and D100%= 0Gy. For each set of η and δ, the TCP value is calculated using the inhomogeneously irradiated tumor logistic model with D50= 74.5Gy and γ50=3.52. Results: TCP varies within 0.9% with η; and δ values between 0 and 1. With η and η varies between 0 and 2, TCP change was up to 2.4%. With η and δ variations from 0 to 3.5, maximum of 8.3% TCP difference is seen. Conclusion: When defined maximum and minimum volume varied more than 2%, significant TCP variations were seen. It is recommended less than 2% volume used in definition of Dmax or Dmin for target dosimetric evaluation criteria. This project was supported by NIH grants U10CA180868, U10CA180822, U24CA180803, U24CA12014 and PA CURE Grant.« less

Comparing photon and proton-based hypofractioned SBRT for prostate cancer accounting for robustness and realistic treatment deliverability.

PubMed

Goddard, Lee C; Brodin, N Patrik; Bodner, William R; Garg, Madhur K; Tomé, Wolfgang A

2018-05-01

To investigate whether photon or proton-based stereotactic body radiation therapy (SBRT is the preferred modality for high dose hypofractionation prostate cancer treatment. Achievable dose distributions were compared when uncertainties in target positioning and range uncertainties were appropriately accounted for. 10 patients with prostate cancer previously treated at our institution (Montefiore Medical Center) with photon SBRT using volumetric modulated arc therapy (VMAT) were identified. MRI images fused to the treatment planning CT allowed for accurate target and organ at risk (OAR) delineation. The clinical target volume was defined as the prostate gland plus the proximal seminal vesicles. Critical OARs include the bladder wall, bowel, femoral heads, neurovascular bundle, penile bulb, rectal wall, urethra and urogenital diaphragm. Photon plan robustness was evaluated by simulating 2 mm isotropic setup variations. Comparative proton SBRT plans employing intensity modulated proton therapy (IMPT) were generated using robust optimization. Plan robustness was evaluated by simulating 2 mm setup variations and 3% or 1% Hounsfield unit (HU) calibration uncertainties. Comparable maximum OAR doses are achievable between photon and proton SBRT, however, robust optimization results in higher maximum doses for proton SBRT. Rectal maximum doses are significantly higher for Robust proton SBRT with 1% HU uncertainty compared to photon SBRT (p = 0.03), whereas maximum doses were comparable for bladder wall (p = 0.43), urethra (p = 0.82) and urogenital diaphragm (p = 0.50). Mean doses to bladder and rectal wall are lower for proton SBRT, but higher for neurovascular bundle, urethra and urogenital diaphragm due to increased lateral scatter. Similar target conformality is achieved, albeit with slightly larger treated volume ratios for proton SBRT, >1.4 compared to 1.2 for photon SBRT. Similar treatment plans can be generated with IMPT compared to VMAT in terms of target coverage, target conformality, and OAR sparing when range and HU uncertainties are neglected. However, when accounting for these uncertainties during robust optimization, VMAT outperforms IMPT in terms of achievable target conformity and OAR sparing. Advances in knowledge: Comparison between achievable dose distributions using modern, robust optimization of IMPT for high dose per fraction SBRT regimens for the prostate has not been previously investigated.

Evaluation of various approaches for assessing dose indicators and patient organ doses resulting from radiotherapy cone-beam CT

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

Rampado, Osvaldo, E-mail: orampado@cittadellasalute.to.it; Giglioli, Francesca Romana; Rossetti, Veronica

Purpose: The aim of this study was to evaluate various approaches for assessing patient organ doses resulting from radiotherapy cone-beam CT (CBCT), by the use of thermoluminescent dosimeter (TLD) measurements in anthropomorphic phantoms, a Monte Carlo based dose calculation software, and different dose indicators as presently defined. Methods: Dose evaluations were performed on a CBCT Elekta XVI (Elekta, Crawley, UK) for different protocols and anatomical regions. The first part of the study focuses on using PCXMC software (PCXMC 2.0, STUK, Helsinki, Finland) for calculating organ doses, adapting the input parameters to simulate the exposure geometry, and beam dose distribution inmore » an appropriate way. The calculated doses were compared to readouts of TLDs placed in an anthropomorphic Rando phantom. After this validation, the software was used for analyzing organ dose variability associated with patients’ differences in size and gender. At the same time, various dose indicators were evaluated: kerma area product (KAP), cumulative air-kerma at the isocenter (K{sub air}), cone-beam dose index, and central cumulative dose. The latter was evaluated in a single phantom and in a stack of three adjacent computed tomography dose index phantoms. Based on the different dose indicators, a set of coefficients was calculated to estimate organ doses for a range of patient morphologies, using their equivalent diameters. Results: Maximum organ doses were about 1 mGy for head and neck and 25 mGy for chest and pelvis protocols. The differences between PCXMC and TLDs doses were generally below 10% for organs within the field of view and approximately 15% for organs at the boundaries of the radiation beam. When considering patient size and gender variability, differences in organ doses up to 40% were observed especially in the pelvic region; for the organs in the thorax, the maximum differences ranged between 20% and 30%. Phantom dose indexes provided better correlation with organ doses than K{sub air} and KAP, with average ratios ranging between 0.9 and 1.1 and variations for different organs and protocols below 20%. The triple phantom setup allowed us to take into account scatter dose contributions, but nonetheless, the correlation with the evaluated organ doses was not improved with this method. Conclusions: The simulation of rotational geometry and of asymmetric beam distribution by means of PCXMC 2.0 enabled us to determine patient organ doses depending on weight, height and gender. Alternatively, the measurement of an in phantom dose indicator combined with proper correction coefficients can be a useful tool for a first dose estimation of in-field organs. The data and coefficients provided in this study can be applied to any patient undergoing a scan by an Elekta XVI equipment.« less

Pharmacokinetics of multiple doses of transdermal flunixin meglumine in adult Holstein dairy cows.

PubMed

Kleinhenz, M D; Gorden, P J; Smith, J S; Schleining, J A; Kleinhenz, K E; Wulf, L L; Sidhu, P K; Rea, D; Coetzee, J F

2018-06-01

A transdermal formulation of the nonsteroidal anti-inflammatory drug, flunixin meglumine, has been approved in the United States and Canada for single-dose administration. Transdermal flunixin meglumine was administered to 10 adult Holstein cows in their second or third lactation at the label dose of 3.33 mg/kg every 24 hr for three total treatments. Plasma flunixin concentrations were determined using high-pressure liquid chromatography with mass spectroscopy (HPLC-MS). Pharmacokinetic analysis was completed on each individual animal with noncompartmental methods using computer software. The time to maximum drug concentration (Tmax) was 2.81 hr, and the maximum drug concentration was 1.08 μg/ml. The mean terminal half-life (T½) was determined to be 5.20 hr. Clearance per fraction absorbed (Cl/F) was calculated to be 0.294 L/hr kg -1 , and volume of distribution of fraction (Vz/F) absorbed was 2.20 L/kg. The mean accumulation factor was 1.10 after three doses. This indicates changes in dosing may not be required when giving multiple doses of flunixin transdermal. Further work is required to investigate the clinical efficacy of transdermal flunixin after multiple daily doses. © 2018 John Wiley & Sons Ltd.

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

Whitaker, Thomas J., E-mail: whitaker.thomas@mayo.edu; Beltran, Chris; Tryggestad, Erik

Purpose: Delayed charge is a small amount of charge that is delivered to the patient after the planned irradiation is halted, which may degrade the quality of the treatment by delivering unwarranted dose to the patient. This study compares two methods for minimizing the effect of delayed charge on the dose delivered with a synchrotron based discrete spot scanning proton beam. Methods: The delivery of several treatment plans was simulated by applying a normally distributed value of delayed charge, with a mean of 0.001(SD 0.00025) MU, to each spot. Two correction methods were used to account for the delayed charge.more » Method one (CM1), which is in active clinical use, accounts for the delayed charge by adjusting the MU of the current spot based on the cumulative MU. Method two (CM2) in addition reduces the planned MU by a predicted value. Every fraction of a treatment was simulated using each method and then recomputed in the treatment planning system. The dose difference between the original plan and the sum of the simulated fractions was evaluated. Both methods were tested in a water phantom with a single beam and simple target geometry. Two separate phantom tests were performed. In one test the dose per fraction was varied from 0.5 to 2 Gy using 25 fractions per plan. In the other test the number fractions were varied from 1 to 25, using 2 Gy per fraction. Three patient plans were used to determine the effect of delayed charge on the delivered dose under realistic clinical conditions. The order of spot delivery using CM1 was investigated by randomly selecting the starting spot for each layer, and by alternating per layer the starting spot from first to last. Only discrete spot scanning was considered in this study. Results: Using the phantom setup and varying the dose per fraction, the maximum dose difference for each plan of 25 fractions was 0.37–0.39 Gy and 0.03–0.05 Gy for CM1 and CM2, respectively. While varying the total number of fractions, the maximum dose difference increased at a rate of 0.015 Gy and 0.0018 Gy per fraction for CM1 and CM2, respectively. For CM1, the largest dose difference was found at the location of the first spot in each energy layer, whereas for CM2 the difference in dose was small and showed no dependence on location. For CM1, all of the fields in the patient plans had an area where their excess dose overlapped. No such correlation was found when using CM2. Randomly selecting the starting spot reduces the maximum dose difference from 0.708 to 0.15 Gy. Alternating between first and last spot reduces the maximum dose difference from 0.708 to 0.37 Gy. In the patient plans the excess dose scaled linearly at 0.014 Gy per field per fraction for CM1 and standard delivery order. Conclusions: The predictive model CM2 is superior to a cumulative irradiation model CM1 for minimizing the effects of delayed charge, particularly when considering maximal dose discrepancies and the potential for unplanned hot-spots. This study shows that the dose discrepancy potentially scales at 0.014 Gy per field per fraction for CM1.« less

Clinical implementation and evaluation of the Acuros dose calculation algorithm.

PubMed

Yan, Chenyu; Combine, Anthony G; Bednarz, Greg; Lalonde, Ronald J; Hu, Bin; Dickens, Kathy; Wynn, Raymond; Pavord, Daniel C; Saiful Huq, M

2017-09-01

The main aim of this study is to validate the Acuros XB dose calculation algorithm for a Varian Clinac iX linac in our clinics, and subsequently compare it with the wildely used AAA algorithm. The source models for both Acuros XB and AAA were configured by importing the same measured beam data into Eclipse treatment planning system. Both algorithms were validated by comparing calculated dose with measured dose on a homogeneous water phantom for field sizes ranging from 6 cm × 6 cm to 40 cm × 40 cm. Central axis and off-axis points with different depths were chosen for the comparison. In addition, the accuracy of Acuros was evaluated for wedge fields with wedge angles from 15 to 60°. Similarly, variable field sizes for an inhomogeneous phantom were chosen to validate the Acuros algorithm. In addition, doses calculated by Acuros and AAA at the center of lung equivalent tissue from three different VMAT plans were compared to the ion chamber measured doses in QUASAR phantom, and the calculated dose distributions by the two algorithms and their differences on patients were compared. Computation time on VMAT plans was also evaluated for Acuros and AAA. Differences between dose-to-water (calculated by AAA and Acuros XB) and dose-to-medium (calculated by Acuros XB) on patient plans were compared and evaluated. For open 6 MV photon beams on the homogeneous water phantom, both Acuros XB and AAA calculations were within 1% of measurements. For 23 MV photon beams, the calculated doses were within 1.5% of measured doses for Acuros XB and 2% for AAA. Testing on the inhomogeneous phantom demonstrated that AAA overestimated doses by up to 8.96% at a point close to lung/solid water interface, while Acuros XB reduced that to 1.64%. The test on QUASAR phantom showed that Acuros achieved better agreement in lung equivalent tissue while AAA underestimated dose for all VMAT plans by up to 2.7%. Acuros XB computation time was about three times faster than AAA for VMAT plans, and computation time for other plans will be discussed at the end. Maximum difference between dose calculated by AAA and dose-to-medium by Acuros XB (Acuros_D m,m ) was 4.3% on patient plans at the isocenter, and maximum difference between D 100 calculated by AAA and by Acuros_D m,m was 11.3%. When calculating the maximum dose to spinal cord on patient plans, differences between dose calculated by AAA and Acuros_D m,m were more than 3%. Compared with AAA, Acuros XB improves accuracy in the presence of inhomogeneity, and also significantly reduces computation time for VMAT plans. Dose differences between AAA and Acuros_D w,m were generally less than the dose differences between AAA and Acuros_D m,m . Clinical practitioners should consider making Acuros XB available in clinics, however, further investigation and clarification is needed about which dose reporting mode (dose-to-water or dose-to-medium) should be used in clinics. © 2017 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

Dose escalation of the hypoxic cell sensitizer etanidazole combined with ifosfamide, carboplatin, etoposide, and autologous hematopoietic stem cell support.

PubMed

Elias, A D; Wheeler, C; Ayash, L J; Schwartz, G; Ibrahim, J; Mills, L; McCauley, M; Coleman, N; Warren, D; Schnipper, L; Antman, K H; Teicher, B A; Frei, E

1998-06-01

Multiple mechanisms of drug resistance contribute to treatment failure. Although high-dose therapy attempts to overwhelm these defenses pharmacologically, this approach is only successful in a fraction of treated patients. Many drug resistance mechanisms are shared between malignant and normal cells, but the expression of various drug resistance mechanisms associated with hypoxia is largely confined to tumor tissue. Thus, reversal of this mechanism is likely to provide a therapeutic advantage to the host. This study was designed to define the dose-limiting toxicities and maximum tolerated dose of etanidazole when it is given concurrently with high-dose ifosfamide, carboplatin, and etoposide (ICE), with hematopoietic stem cell support. The maximum tolerated doses of high-dose ICE were administered concurrently with dose escalations of etanidazole, a hypoxic cell sensitizer. All agents were given by 96-h continuous i.v. infusion beginning on day -7. Mesna uroprotection was provided. Autologous marrow and cytokine mobilized peripheral blood progenitor cells were reinfused on day 0. Granulocyte colony-stimulating factor was administered following reinfusion until the granulocytes recovered to > 1000/microliter. Fifty-five adults with advanced malignancies were enrolled in cohorts of five to nine patients. Four dose levels of etanidazole between 3 and 5.5 g/m2/day (12, 16, 20, and 22 g/m2 total doses) and two doses of carboplatin (1600 and 1800 mg/m2 total doses) were evaluated. Seven patients died of organ toxicity (13%); two each from veno-occlusive disease of liver and sepsis; and one each from sudden death, renal failure, and refractory thrombocytopenic hemorrhage. Five deaths occurred at the top dose level. One additional patient suffered a witnessed cardiorespiratory arrest from ventricular fibrillation and was resuscitated. Dose-dependent and largely reversible peripheral neuropathy was observed consisting of two syndromes: severe cramping myalgic/neuralgic pain, predominantly in stocking glove distribution, occurring between day -3 and day 0, and a sensory peripheral neuropathy with similar distribution peaking around day +60. The maximal achievable dose of etanidazole (16 g/m2 dose level) resulted in a mean serum level of 38 micrograms/ml (25-55 micrograms/ml). Etanidazole significantly enhanced host toxicity of high-dose ICE. Effective modulatory doses of etanidazole could not be given with acceptable toxicity using this schedule.

Unenhanced low-dose versus standard-dose CT localization in patients with upper urinary calculi for minimally invasive percutaneous nephrolithotomy (MPCNL)

PubMed Central

Licheng, Jiang; Yidong, Fan; Ping, Wang; Keqiang, Yan; Xueting, Wang; Yingchen, Zhang; Lei, Gao; Jiyang, Ding; Zhonghua, Xu

2014-01-01

Background & objectives: With the ethical concern about the dose of CT scan and wide use of CT in protocol of suspected renal colic, more attention has been paid to low dose CT. The aim of the present study was to make a comparison of unenhanced low-dose spiral CT localization with unenhanced standard-dose spiral CT in patients with upper urinary tract calculi for minimally invasive percutaneous nephrolithotomy (MPCNL) treatment. Methods: Twenty eight patients with ureter and renal calculus, preparing to take MPCNL, underwent both abdominal low-dose CT (25 mAs) and standard-dose CT (100 mAs). Low-dose CT and standard-dose CT were independently evaluated for the characterization of renal/ureteral calculi, perirenal adjacent organs, blood vessels, indirect signs of renal or ureteral calculus (renal enlargement, pyeloureteral dilatation), and the indices of localization (percutaneous puncture angulation and depth) used in the MPCNL procedure. Results: In all 28 patients, low-dose CT was 100 per cent coincidence 100 per cent sensitive and 100 per cent specific for depicting the location of the renal and ureteral calculus, renal enlargement, pyeloureteral dilatation, adjacent organs, and the presumptive puncture point and a 96.3 per cent coincidence 96 per cent sensitivity and 93 per cent specificity for blood vessel signs within the renal sinus, and with an obvious lower radiation exposure for patients when compared to standard-dose CT (P<0.05). The indices of puncture depth, puncture angulation, and maximum calculus transverse diameter on the axial surface showed no significant difference between the two doses of CT scans, with a significant variation in calculus visualization slice numbers (P<0.05). Interpretation & conclusions: Our findings show that unenhanced low-dose CT achieves a sensitivity and accuracy similar to that of standard-dose CT in assessing the localization of renal ureteral calculus and adjacent organs conditions and identifying the maximum calculus transverse diameter on the axial surface, percutaneous puncture depth, and angulation in patients, with a significant lower radiation exposure, who are to be treated by MPCNL, and can be used as an alternative localization method. PMID:24820832

Unenhanced low-dose versus standard-dose CT localization in patients with upper urinary calculi for minimally invasive percutaneous nephrolithotomy (MPCNL).

PubMed

Licheng, Jiang; Yidong, Fan; Ping, Wang; Keqiang, Yan; Xueting, Wang; Yingchen, Zhang; Lei, Gao; Jiyang, Ding; Zhonghua, Xu

2014-03-01

With the ethical concern about the dose of CT scan and wide use of CT in protocol of suspected renal colic, more attention has been paid to low dose CT. The aim of the present study was to make a comparison of unenhanced low-dose spiral CT localization with unenhanced standard-dose spiral CT in patients with upper urinary tract calculi for minimally invasive percutaneous nephrolithotomy (MPCNL) treatment. Twenty eight patients with ureter and renal calculus, preparing to take MPCNL, underwent both abdominal low-dose CT (25 mAs) and standard-dose CT (100 mAs). Low-dose CT and standard-dose CT were independently evaluated for the characterization of renal/ureteral calculi, perirenal adjacent organs, blood vessels, indirect signs of renal or ureteral calculus (renal enlargement, pyeloureteral dilatation), and the indices of localization (percutaneous puncture angulation and depth) used in the MPCNL procedure. In all 28 patients, low-dose CT was 100 per cent coincidence 100 per cent sensitive and 100 per cent specific for depicting the location of the renal and ureteral calculus, renal enlargement, pyeloureteral dilatation, adjacent organs, and the presumptive puncture point and a 96.3 per cent coincidence 96 per cent sensitivity and 93 per cent specificity for blood vessel signs within the renal sinus, and with an obvious lower radiation exposure for patients when compared to standard-dose CT (P<0.05). The indices of puncture depth, puncture angulation, and maximum calculus transverse diameter on the axial surface showed no significant difference between the two doses of CT scans, with a significant variation in calculus visualization slice numbers (P<0.05). Our findings show that unenhanced low-dose CT achieves a sensitivity and accuracy similar to that of standard-dose CT in assessing the localization of renal ureteral calculus and adjacent organs conditions and identifying the maximum calculus transverse diameter on the axial surface, percutaneous puncture depth, and angulation in patients, with a significant lower radiation exposure, who are to be treated by MPCNL, and can be used as an alternative localization method.

Impact of tumour motion compensation and delineation methods on FDG PET-based dose painting plan quality for NSCLC radiation therapy.

PubMed

Thomas, Hannah Mary; Kinahan, Paul E; Samuel, James Jebaseelan E; Bowen, Stephen R

2018-02-01

To quantitatively estimate the impact of different methods for both boost volume delineation and respiratory motion compensation of [18F] FDG PET/CT images on the fidelity of planned non-uniform 'dose painting' plans to the prescribed boost dose distribution. Six locally advanced non-small cell lung cancer (NSCLC) patients were retrospectively reviewed. To assess the impact of respiratory motion, time-averaged (3D AVG), respiratory phase-gated (4D GATED) and motion-encompassing (4D MIP) PET images were used. The boost volumes were defined using manual contour (MANUAL), fixed threshold (FIXED) and gradient search algorithm (GRADIENT). The dose painting prescription of 60 Gy base dose to the planning target volume and an integral dose of 14 Gy (total 74 Gy) was discretized into seven treatment planning substructures and linearly redistributed according to the relative SUV at every voxel in the boost volume. Fifty-four dose painting plan combinations were generated and conformity was evaluated using quality index VQ0.95-1.05, which represents the sum of planned dose voxels within 5% deviation from the prescribed dose. Trends in plan quality and magnitude of achievable dose escalation were recorded. Different segmentation techniques produced statistically significant variations in maximum planned dose (P < 0.02), as well as plan quality between segmentation methods for 4D GATED and 4D MIP PET images (P < 0.05). No statistically significant differences in plan quality and maximum dose were observed between motion-compensated PET-based plans (P > 0.75). Low variability in plan quality was observed for FIXED threshold plans, while MANUAL and GRADIENT plans achieved higher dose with lower plan quality indices. The dose painting plans were more sensitive to segmentation of boost volumes than PET motion compensation in this study sample. Careful consideration of boost target delineation and motion compensation strategies should guide the design of NSCLC dose painting trials. © 2017 The Royal Australian and New Zealand College of Radiologists.

A rule of unity for human intestinal absorption 3: Application to pharmaceuticals.

PubMed

Patel, Raj B; Yalkowsky, Samuel H

2018-02-01

The rule of unity is based on a simple absorption parameter, Π, that can accurately predict whether or not an orally administered drug will be well absorbed or poorly absorbed. The intrinsic aqueous solubility and octanol-water partition coefficient, along with the drug dose are used to calculate Π. We show that a single delineator value for Π exist that can distinguish whether a drug is likely to be well absorbed (FA ≥ 0.5) or poorly absorbed (FA < 0.5) at any specified dose. The model is shown to give 82.5% correct predictions for over 938 pharmaceuticals. The maximum well-absorbed dose (i.e. the maximum dose that will be more than 50% absorbed) calculated using this model can be utilized as a guideline for drug design and synthesis. Copyright © 2017 John Wiley & Sons, Ltd.

[An investigation of ionizing radiation dose in a manufacturing enterprise of ion-absorbing type rare earth ore].

PubMed

Zhang, W F; Tang, S H; Tan, Q; Liu, Y M

2016-08-20

Objective: To investigate radioactive source term dose monitoring and estimation results in a manufacturing enterprise of ion-absorbing type rare earth ore and the possible ionizing radiation dose received by its workers. Methods: Ionizing radiation monitoring data of the posts in the control area and supervised area of workplace were collected, and the annual average effective dose directly estimated or estimated using formulas was evaluated and analyzed. Results: In the control area and supervised area of the workplace for this rare earth ore, α surface contamination activity had a maximum value of 0.35 Bq/cm 2 and a minimum value of 0.01 Bq/cm 2 ; β radioactive surface contamination activity had a maximum value of 18.8 Bq/cm 2 and a minimum value of 0.22 Bq/cm 2 . In 14 monitoring points in the workplace, the maximum value of the annual average effective dose of occupational exposure was 1.641 mSv/a, which did not exceed the authorized limit for workers (5 mSv/a) , but exceeded the authorized limit for general personnel (0.25 mSv/a) . The radionuclide specific activity of ionic mixed rare earth oxides was determined to be 0.9. Conclusion: The annual average effective dose of occupational exposure in this enterprise does not exceed the authorized limit for workers, but it exceeds the authorized limit for general personnel. We should pay attention to the focus of the radiation process, especially for public works radiation.

Relation of gastric acid and pepsin secretion to serum gastrin levels in dogs given bombesin and gastrin-17.

PubMed

Hirschowitz, B I; Molina, E

1983-05-01

To quantitate bombesin stimulation of gastric acid and pepsin via release of gastrin, five gastric fistula dogs were given graded doses (60-1,250 pmol X kg-1 X h-1) of bombesin tetradecapeptide and 40-2,000 pmol X kg-1 X h-1 of synthetic gastrin-17 (G-17). Acid and pepsin output and serum gastrin were proportional to the dose of stimulant. The half-maximal dose of bombesin for gastrin release was 200 pmol X kg-1 X h-1. Bombesin-stimulated acid secretion related to serum gastrin concentrations was congruent with the G-17 curve, but with a maximum of only 62% of the G-17 maximum before declining by 27% despite higher serum gastrin levels. This suggested that bombesin stimulates acid secretion only via gastrin release and inhibits at higher doses by releasing another inhibitory peptide, most likely somatostatin, which is also released by bombesin. The same mechanism could apply to supramaximal inhibition of acid and pepsin seen with high doses of G-17. Because the pepsin curve related to serum gastrin was to the left of the G-17 curve, we concluded that another secretagogue released by bombesin acts synergistically with gastrin on pepsin secretion. Therefore, bombesin stimulates gastric secretion through gastrin release, but its effects are modified by peptides coreleased to a) increase pepsin output at low doses and b) limit the output of acid and pepsin to 50-60% of the G-17 maximum.

Radiation exposure assessment for portsmouth naval shipyard health studies.

PubMed

Daniels, R D; Taulbee, T D; Chen, P

2004-01-01

Occupational radiation exposures of 13,475 civilian nuclear shipyard workers were investigated as part of a retrospective mortality study. Estimates of annual, cumulative and collective doses were tabulated for future dose-response analysis. Record sets were assembled and amended through range checks, examination of distributions and inspection. Methods were developed to adjust for administrative overestimates and dose from previous employment. Uncertainties from doses below the recording threshold were estimated. Low-dose protracted radiation exposures from submarine overhaul and repair predominated. Cumulative doses are best approximated by a hybrid log-normal distribution with arithmetic mean and median values of 20.59 and 3.24 mSv, respectively. The distribution is highly skewed with more than half the workers having cumulative doses <10 mSv and >95% having doses <100 mSv. The maximum cumulative dose is estimated at 649.39 mSv from 15 person-years of exposure. The collective dose was 277.42 person-Sv with 96.8% attributed to employment at Portsmouth Naval Shipyard.

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

Mayo, Charles, E-mail: charles.mayo@umassmemorial.or; Yorke, Ellen; Merchant, Thomas E.

Publications relating brainstem radiation toxicity to quantitative dose and dose-volume measures derived from three-dimensional treatment planning were reviewed. Despite the clinical importance of brainstem toxicity, most studies reporting brainstem effects after irradiation have fewer than 100 patients. There is limited evidence relating toxicity to small volumes receiving doses above 60-64 Gy using conventional fractionation and no definitive criteria regarding more subtle dose-volume effects or effects after hypofractionated treatment. On the basis of the available data, the entire brainstem may be treated to 54 Gy using conventional fractionation using photons with limited risk of severe or permanent neurological effects. Smaller volumesmore » of the brainstem (1-10 mL) may be irradiated to maximum doses of 59 Gy for dose fractions <=2 Gy; however, the risk appears to increase markedly at doses >64 Gy.« less

Current status of radiological protection at nuclear power stations in Japan.

PubMed

Suzuki, Akira; Hori, Shunsuke

2011-07-01

The radiation dose to workers at nuclear power stations (NPSs) in Japan was drastically reduced between the late-1970s and the early-1990s by continuous dose-reduction programmes. The total collective dose of radiation workers in FY 2008 was 84.04 person Sv, while the average collective dose was 1.5 person Sv per reactor. The average annual individual dose was 1.1 mSv and the maximum annual individual dose was 19.5 mSv. These values are sufficiently lower than the regulatory dose limits. Radioactive effluent released from NPSs is already so trivial that additional protective measures will not be necessary. Experience in radiation protection at NPSs has been accumulated over 40 y and will be very useful in establishing a rational radiation control system in the future.

Correlation of Osteoradionecrosis and Dental Events With Dosimetric Parameters in Intensity-Modulated Radiation Therapy for Head-and-Neck Cancer

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

Gomez, Daniel R., E-mail: dgomez@mdanderson.org; Estilo, Cherry L.; Wolden, Suzanne L.

Purpose: Osteoradionecrosis (ORN) is a known complication of radiation therapy to the head and neck. However, the incidence of this complication with intensity-modulated radiation therapy (IMRT) and dental sequelae with this technique have not been fully elucidated. Methods and Materials: From December 2000 to July 2007, 168 patients from our institution have been previously reported for IMRT of the oral cavity, nasopharynx, larynx/hypopharynx, sinus, and oropharynx. All patients underwent pretreatment dental evaluation, including panoramic radiographs, an aggressive fluoride regimen, and a mouthguard when indicated. The median maximum mandibular dose was 6,798 cGy, and the median mean mandibular dose was 3,845more » cGy. Patient visits were retrospectively reviewed for the incidence of ORN, and dental records were reviewed for the development of dental events. Univariate analysis was then used to assess the effect of mandibular and parotid gland dosimetric parameters on dental endpoints. Results: With a median clinic follow-up of 37.4 months (range, 0.8-89.6 months), 2 patients, both with oral cavity primaries, experienced ORN. Neither patient had preradiation dental extractions. The maximum mandibular dose and mean mandibular dose of the 2 patients were 7,183 and 6,828 cGy and 5812 and 5335 cGy, respectively. In all, 17% of the patients (n = 29) experienced a dental event. A mean parotid dose of >26 Gy was predictive of a subsequent dental caries, whereas a maximum mandibular dose >70 Gy and a mean mandibular dose >40 Gy were correlated with dental extractions after IMRT. Conclusions: ORN is rare after head-and-neck IMRT, but is more common with oral cavity primaries. Our results suggest different mechanisms for radiation-induced caries versus extractions.« less

Rapid Inpatient Titration of Intravenous Treprostinil for Pulmonary Arterial Hypertension: Safe and Tolerable.

PubMed

El-Kersh, Karim; Ruf, Kathryn M; Smith, J Shaun

There is no standard protocol for intravenous treprostinil dose escalation. In most cases, slow up-titration is performed in the outpatient setting. However, rapid up-titration in an inpatient setting is an alternative that provides opportunity for aggressive treatment of common side effects experienced during dose escalation. In this study, we describe our experience with inpatient rapid up-titration of intravenous treprostinil. This was a single-center, retrospective study in which we reviewed the data of subjects with pulmonary arterial hypertension treated at our center who underwent inpatient rapid up-titration of intravenous treprostinil. Our treprostinil dose escalation protocol included initiation at 2 ng·kg·min with subsequent up-titration by 1 ng·kg·min every 6 to 8 hours as tolerated by side effects. A total of 16 subjects were identified. Thirteen subjects were treprostinil naive (naive group), and 3 subjects were receiving subcutaneous treprostinil but were hospitalized for further intravenous up-titration of treprostinil dose (nonnaive group). In the naive group, the median maximum dose achieved was 20 ng·kg·min with an interquartile range (IQR) of 20-23 ng·kg·min. The median up-titration interval was 6 days (IQR: 4-9). In the nonnaive group, the median maximum dose achieved was 20 ng·kg·min (range: 17-30). The median up-titration interval was 8.5 days (range: 1.5-11). Overall, the median maximum dose achieved was 20 ng·kg·min (IQR: 20-23.5), and the median up-titration interval was 6 days (IQR: 4.6-9.25), with no reported significant adverse hemodynamic events. In patients with pulmonary arterial hypertension, rapid inpatient titration of intravenous treprostinil is safe and tolerable.

Correlation of osteoradionecrosis and dental events with dosimetric parameters in intensity-modulated radiation therapy for head-and-neck cancer.

PubMed

Gomez, Daniel R; Estilo, Cherry L; Wolden, Suzanne L; Zelefsky, Michael J; Kraus, Dennis H; Wong, Richard J; Shaha, Ashok R; Shah, Jatin P; Mechalakos, James G; Lee, Nancy Y

2011-11-15

Osteoradionecrosis (ORN) is a known complication of radiation therapy to the head and neck. However, the incidence of this complication with intensity-modulated radiation therapy (IMRT) and dental sequelae with this technique have not been fully elucidated. From December 2000 to July 2007, 168 patients from our institution have been previously reported for IMRT of the oral cavity, nasopharynx, larynx/hypopharynx, sinus, and oropharynx. All patients underwent pretreatment dental evaluation, including panoramic radiographs, an aggressive fluoride regimen, and a mouthguard when indicated. The median maximum mandibular dose was 6,798 cGy, and the median mean mandibular dose was 3,845 cGy. Patient visits were retrospectively reviewed for the incidence of ORN, and dental records were reviewed for the development of dental events. Univariate analysis was then used to assess the effect of mandibular and parotid gland dosimetric parameters on dental endpoints. With a median clinic follow-up of 37.4 months (range, 0.8-89.6 months), 2 patients, both with oral cavity primaries, experienced ORN. Neither patient had preradiation dental extractions. The maximum mandibular dose and mean mandibular dose of the 2 patients were 7,183 and 6,828 cGy and 5812 and 5335 cGy, respectively. In all, 17% of the patients (n = 29) experienced a dental event. A mean parotid dose of >26 Gy was predictive of a subsequent dental caries, whereas a maximum mandibular dose >70 Gy and a mean mandibular dose >40 Gy were correlated with dental extractions after IMRT. ORN is rare after head-and-neck IMRT, but is more common with oral cavity primaries. Our results suggest different mechanisms for radiation-induced caries versus extractions. Copyright © 2011 Elsevier Inc. All rights reserved.

SU-F-T-539: Dosimetric Comparison of Volumetric Modulated Arc Therapy and Intensity Modulated Radiation Therapy for Whole Brain Hippocampal Sparing Radiation Therapy Treatments

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

Kendall, E; Higby, C; Algan, O

2016-06-15

Purpose: To compare the treatment plan quality and dose gradient near the hippocampus between VMAT (RapidArc) and IMRT delivery techniques for whole brain radiation therapy. Methods: Fifteen patients were evaluated in this retrospective study. All treatments were planned on Varian Eclipse TPS, using 3-Arc VMAT and 9-Field IMRT, following NRG Oncology protocol NRG-CC001 guidelines evaluated by a single radiation oncologist. Prescribed doses in all plans were 30 Gy delivered over 10 fractions normalized to a minimum of 100% of the dose covering 95% of the target volume. Identical contour sets and dose-volume constraints following protocol guidelines were also applied inmore » all plans. A paired t-test analysis was used to compare VMAT and IMRT plans. Results: NRG-CC001 protocol dose-volume constraints were met for all VMAT and IMRT plans. For the planning target volume (PTV), the average values for D2% and D98% were 6% lower and 4% higher in VMAT than in IMRT, respectively. The average mean and maximum hippocampus doses in Gy for VMAT vs IMRT plans were (11.85±0.81 vs. 12.24±0.56, p=0.10) and (16.27±0.78 vs. 16.59±0.71, p=0.24), respectively. In VMAT, the average mean and maximum chiasm doses were 3% and 1% higher than in IMRT plans, respectively. For the left optic nerve, the average mean and maximum doses were 10% and 5% higher in VMAT than in IMRT plans, respectively. These values were 12% and 3% for the right optic nerve. The average percentage of dose gradient around the hippocampus in the 0–5mm and 5–10mm abutted regions for VMAT vs. IMRT were (4.42%±2.22% /mm vs. 3.95%±2.61% /mm, p=0.43) and (4.54%±1.50% /mm vs. 4.39%±1.28% /mm, p=0.73), respectively. Conclusion: VMAT plans can achieve higher hippocampus sparing with a faster dose fall-off than IMRT plans. Though statistically insignificant, VMAT offers better PTV coverage with slightly higher doses to OARs.« less

Pupillometry as an indicator of L-DOPA dosages in Parkinson's disease patients.

PubMed

Bartošová, O; Bonnet, C; Ulmanová, O; Šíma, M; Perlík, F; Růžička, E; Slanař, O

2018-04-01

Dopamine was shown to induce mydriasis by excitation of alpha-adrenergic receptors at the dilator pupillae muscle. Pupilla diameter may thus serve as an indirect measure of peripheral pharmacokinetics of L-DOPA and dopamine. The aim of this study is to evaluate the effect of L-DOPA dosage on pupillometric parameters in Parkinson's disease (PD) patients. Sixteen PD patients and 14 healthy control subjects (CS) were studied. The statistical analysis revealed significant differences between CS and PD patients for the mean maximum and minimum pupil diameters (p = 0.017, p = 0.028, respectively), with higher values found in PD. Moreover, a significant dose-response relationship was found between the maximum pupil diameter and both the morning L-DOPA dose (R 2  = 0.78) and the total daily L-DOPA dose (R 2  = 0.93). A sigmoid-shaped curve best describes the dose-response relationship, with a ceiling effect at about 400 mg L-DOPA daily dose. In conclusion, measuring pupillometric parameters represents a sensitive tool for non-invasive evaluation of the peripheral effect of L-DOPA, especially with daily doses below 400 mg L-DOPA.

Dosimetric aspects of breast radiotherapy with three-dimensional and intensity-modulated radiotherapy helical tomotherapy planning modules

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

Yadav, Poonam; Service of Radiation Therapy, University of Wisconsin Aspirus Cancer Center, Wisconsin Rapids, WI; Yan, Yue, E-mail: yyan5@mdanderson.org

In this work, we investigated the dosimetric differences between the intensity-modulated radiotherapy (IMRT) plans and the three-dimensional (3D) helical plans based on the TomoTherapy system. A total of 15 patients with supine setup were randomly selected from the data base. For patients with lumpectomy planning target volume (PTV), regional lymph nodes were also included as part of the target. For dose sparing, the significant differences between the helical IMRT and helical 3D were only found in the heart and contralateral breast. For the dose to the heart, helical IMRT reduced the maximum point dose by 6.98 Gy compared to themore » helical 3D plan (p = 0.01). For contralateral breast, the helical IMRT plans significantly reduced the maximum point dose by 5.6 Gy compared to the helical 3D plan. However, compared to the helical 3D plan, the helical IMRT plan increased the volume for lower dose (13.08% increase in V{sub 5} {sub Gy}, p = 0.01). In general, there are no significant differences in dose sparing between helical IMRT and helical 3D plans.« less

A phase I/II study of carfilzomib 2-10-min infusion in patients with advanced solid tumors.

PubMed

Papadopoulos, Kyriakos P; Burris, Howard A; Gordon, Michael; Lee, Peter; Sausville, Edward A; Rosen, Peter J; Patnaik, Amita; Cutler, Richard E; Wang, Zhengping; Lee, Susan; Jones, Suzanne F; Infante, Jeffery R

2013-10-01

Tolerability, pharmacokinetics (PK), pharmacodynamics, and antitumor activity of carfilzomib, a selective proteasome inhibitor, administered twice weekly by 2-10-min intravenous (IV) infusion on days 1, 2, 8, 9, 15, and 16 in 28-day cycles, were assessed in patients with advanced solid tumors in this phase I/II study. Adult patients with solid tumors progressing after ≥1 prior therapies were enrolled. The dose was 20 mg/m(2) in week 1 of cycle 1 and 20, 27, or 36 mg/m(2) thereafter. The maximum tolerated dose or protocol-defined maximum planned dose (MPD) identified during dose escalation was administered to an expansion cohort and to patients with small cell lung, non-small cell lung, ovarian, and renal cancer in phase II tumor-specific cohorts. Fourteen patients received carfilzomib during dose escalation. The single dose-limiting toxicity at 20/36 mg/m(2) was grade 3 fatigue, establishing the MPD as the expansion and phase II dose. Sixty-five additional patients received carfilzomib at the MPD. Adverse events included fatigue, nausea, anorexia, and dyspnea. Carfilzomib PK was dose proportional with a half-life <1 h. All doses resulted in at least 80 % proteasome inhibition in blood. Partial responses occurred in two patients in phase I, with 21.5 % stable disease after four cycles in evaluable patients in the expansion and phase II cohorts. Carfilzomib 20/36 mg/m(2) was well tolerated when administered twice weekly by 2-10-min IV infusion. At this dose and infusion rate, carfilzomib inhibited the proteasome in blood but demonstrated limited antitumor activity in patients with advanced solid tumors.

Side effects of methylphenidate in childhood cancer survivors: a randomized placebo-controlled trial.

PubMed

Conklin, Heather M; Lawford, Joanne; Jasper, Bruce W; Morris, E Brannon; Howard, Scott C; Ogg, Susan W; Wu, Shengjie; Xiong, Xiaoping; Khan, Raja B

2009-07-01

To investigate the frequency and severity of side effects of methylphenidate among childhood survivors of acute lymphoblastic leukemia and brain tumors and identify predictors of higher adverse effect levels. Childhood cancer survivors (N = 103) identified as having attention and learning problems completed a randomized, double-blind, 3-week, home-crossover trial of placebo, low-dose methylphenidate (0.3 mg/kg; 10 mg twice daily maximum) and moderate-dose methylphenidate (0.6 mg/kg; 20 mg twice daily maximum). Caregivers completed the Barkley Side Effects Rating Scale (SERS) at baseline and each week during the medication trial. Siblings of cancer survivors (N = 49) were recruited as a healthy comparison group. There was a significantly higher number and severity of symptoms endorsed on the SERS when patients were taking moderate dose compared with placebo or low dose, but not low dose compared with placebo. The number of side effects endorsed on the SERS was significantly lower during all 3 home-crossover weeks (placebo, low dose, moderate dose) when compared with baseline symptom scores. The severity of side effects was also significantly lower, compared with baseline screening, during placebo and low-dose weeks but not moderate-dose weeks. Both the number and severity of symptoms endorsed at baseline were significantly higher for patients compared with siblings. Female gender and lower IQ were associated with higher adverse effect levels. Methylphenidate is generally well tolerated by childhood cancer survivors. There is a subgroup at increased risk for side effects that may need to be closely monitored or prescribed a lower medication dose. The seemingly paradoxical findings of increased "side effects" at baseline must be considered when monitoring side effects and designing clinical trials.

Improvements in Critical Dosimetric Endpoints Using the Contura Multilumen Balloon Breast Brachytherapy Catheter to Deliver Accelerated Partial Breast Irradiation: Preliminary Dosimetric Findings of a Phase IV Trial

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

Arthur, Douglas W., E-mail: darthur@mcvh-vcu.ed; Vicini, Frank A.; Todor, Dorin A.

2011-01-01

Purpose: Dosimetric findings in patients treated with the Contura multilumen balloon (MLB) breast brachytherapy catheter to deliver accelerated partial breast irradiation (APBI) on a multi-institutional Phase IV registry trial are presented. Methods and Materials: Computed tomography-based three-dimensional planning with dose optimization was performed. For the trial, new ideal dosimetric goals included (1) {>=}95% of the prescribed dose (PD) covering {>=}90% of the target volume, (2) a maximum skin dose {<=}125% of the PD, (3) maximum rib dose {<=}145% of the PD, and (4) the V150 {<=}50 cc and V200 {<=}10 cc. The ability to concurrently achieve these dosimetric goals usingmore » the Contura MLB was analyzed. Results: 144 cases were available for review. Using the MLB, all dosimetric criteria were met in 76% of cases. Evaluating dosimetric criteria individually, 92% and 89% of cases met skin and rib dose criteria, respectively. In 93% of cases, ideal target volume coverage goals were met, and in 99%, dose homogeneity criteria (V150 and V200) were satisfied. When skin thickness was {>=}5 mm to <7 mm, the median skin dose was limited to 120.1% of the PD, and when skin thickness was <5 mm, the median skin dose was 124.2%. When rib distance was <5 mm, median rib dose was reduced to 136.5% of the PD. When skin thickness was <7 mm and distance to rib was <5 mm, median skin and rib doses were jointly limited to 120.6% and 142.1% of the PD, respectively. Conclusion: The Contura MLB catheter provided the means of achieving the imposed higher standard of dosimetric goals in the majority of clinical scenarios encountered.« less

Phase I study of the c-raf-1 antisense oligonucleotide ISIS 5132 in combination with carboplatin and paclitaxel in patients with previously untreated, advanced non-small cell lung cancer.

PubMed

Fidias, Panos; Pennell, Nathan A; Boral, Anthony L; Shapiro, Geoffrey I; Skarin, Arthur T; Eder, Joseph P; Kwoh, T Jesse; Geary, Richard S; Johnson, Bruce E; Lynch, Thomas J; Supko, Jeffrey G

2009-09-01

A phase I trial was performed to evaluate the administration of carboplatin/paclitaxel in combination with ISIS-5132, a phosphorothioate antisense oligodeoxynucleotide inhibitor of c-raf-1 kinase expression, in patients with advanced non-small cell lung cancer (NSCLC). Previously untreated patients with stage IIIB/IV NSCLC received ISIS 5132 by continuous intravenous infusion at 2.0 mg/kg/d for 14 days. Starting doses were paclitaxel 175 mg/m(2) and carboplatin targeting an area under the free platinum plasma concentration-time curve (AUC(fp)) of 5 mg . min/ml (dose level 1). The carboplatin dose was then increased to AUC(fp) 6 mg . min/ml (dose level 2) after which the paclitaxel dose was increased to 200 mg/m(2) (dose level 3). The maximum tolerated dose was established by toxicity during the first two 21-day cycles of therapy. The pharmacokinetics of all three agents was determined before and during the ISIS 5132 infusion. Thirteen patients were treated with the carboplatin/paclitaxel/ISIS 5132 combination. Dose-limiting neutropenia occurred in two patients at dose level 3. Grade 3 and 4 nonhematologic toxicities were infrequent and limited to nausea and constipation. The maximum tolerated doses were carboplatin AUC(fp) 6 mg . min/ml, paclitaxel 175 mg/m(2), and ISIS 5132 2.0 mg/kg/d for 14 days. There were no objective responses and the concurrent infusion of ISIS 5132 did not alter the plasma pharmacokinetics of paclitaxel or total platinum. ISIS 5132 can be safely combined with standard doses of carboplatin and paclitaxel. Combining cytotoxic chemotherapeutic agents with inhibitors of aberrant signal transduction mediated by Raf proteins produced no objective responses in the dose and schedule administered in this study.

A single-gradient junction technique to replace multiple-junction shifts for craniospinal irradiation treatment

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

Hadley, Austin; Ding, George X., E-mail: george.ding@vanderbilt.edu

2014-01-01

Craniospinal irradiation (CSI) requires abutting fields at the cervical spine. Junction shifts are conventionally used to prevent setup error–induced overdosage/underdosage from occurring at the same location. This study compared the dosimetric differences at the cranial-spinal junction between a single-gradient junction technique and conventional multiple-junction shifts and evaluated the effect of setup errors on the dose distributions between both techniques for a treatment course and single fraction. Conventionally, 2 lateral brain fields and a posterior spine field(s) are used for CSI with weekly 1-cm junction shifts. We retrospectively replanned 4 CSI patients using a single-gradient junction between the lateral brain fieldsmore » and the posterior spine field. The fields were extended to allow a minimum 3-cm field overlap. The dose gradient at the junction was achieved using dose painting and intensity-modulated radiation therapy planning. The effect of positioning setup errors on the dose distributions for both techniques was simulated by applying shifts of ± 3 and 5 mm. The resulting cervical spine doses across the field junction for both techniques were calculated and compared. Dose profiles were obtained for both a single fraction and entire treatment course to include the effects of the conventional weekly junction shifts. Compared with the conventional technique, the gradient-dose technique resulted in higher dose uniformity and conformity to the target volumes, lower organ at risk (OAR) mean and maximum doses, and diminished hot spots from systematic positioning errors over the course of treatment. Single-fraction hot and cold spots were improved for the gradient-dose technique. The single-gradient junction technique provides improved conformity, dose uniformity, diminished hot spots, lower OAR mean and maximum dose, and one plan for the entire treatment course, which reduces the potential human error associated with conventional 4-shifted plans.« less

Mars surface radiation exposure for solar maximum conditions and 1989 solar proton events

NASA Technical Reports Server (NTRS)

Simonsen, Lisa C.; Nealy, John E.

1992-01-01

The Langley heavy-ion/nucleon transport code, HZETRN, and the high-energy nucleon transport code, BRYNTRN, are used to predict the propagation of galactic cosmic rays (GCR's) and solar flare protons through the carbon dioxide atmosphere of Mars. Particle fluences and the resulting doses are estimated on the surface of Mars for GCR's during solar maximum conditions and the Aug., Sep., and Oct. 1989 solar proton events. These results extend previously calculated surface estimates for GCR's at solar minimum conditions and the Feb. 1956, Nov. 1960, and Aug. 1972 solar proton events. Surface doses are estimated with both a low-density and a high-density carbon dioxide model of the atmosphere for altitudes of 0, 4, 8, and 12 km above the surface. A solar modulation function is incorporated to estimate the GCR dose variation between solar minimum and maximum conditions over the 11-year solar cycle. By using current Mars mission scenarios, doses to the skin, eye, and blood-forming organs are predicted for short- and long-duration stay times on the Martian surface throughout the solar cycle.

Dosimetry of intracavitary placements for uterine and cervical carcinoma: results of orthogonal film, TLD, and CT-assisted techniques.

PubMed

Kapp, K S; Stuecklschweiger, G F; Kapp, D S; Hackl, A G

1992-07-01

A total of 720 192Ir high-dose-rate (HDR) applications in 331 patients with gynecological tumors were analyzed to evaluate the dose to normal tissues from brachytherapy. Based on the calculations of bladder base, bladder neck, and rectal doses derived from orthogonal films the planned tumor dose or fractionation was altered in 20.4% of intracavitary placements (ICP) for cervix carcinoma and 9.2% of ICP for treatment of the vaginal vault. In 13.8% of intracervical and 8.1% of intravaginal treatments calculated doses to both the bladder and rectum were greater than or equal to 140% of the initially planned dose fraction. Doses at the bladder base were significantly higher than at the bladder neck (p less than 0.001). In 17.5% of ICP the dose to the bladder base was at least twice as high as to the bladder neck. The ratio of bladder base dose to the bladder neck was 1.5 (+/- 1.19 SD) for intracervical and 1.46 (+/- 1.14 SD) for intravaginal applications. The comparison of calculated doses from orthogonal films with in-vivo readings showed a good correlation of rectal doses with a correlation coefficient factor of 0.9556. CT-assisted dosimetry, however, revealed that the maximum doses to bladder and rectum were generally higher than those obtained from films with ratios of 1-1.7 (average: 1.44) for the bladder neck, 1-5.4 (average: 2.42) for the bladder base, and 1.1-2.7 (average: 1.37) for the rectum. When doses to the specified reference points of bladder neck and rectum from orthogonal film dosimetry were compared with the corresponding points on CT scans, similar values were obtained for both methods with a maximum deviation of +/- 10%. Despite the determination of multiple reference points our study revealed that this information was inadequate to predict doses to the entire rectum and bladder. If conventional methods are used for dosimetry it is recommended that doses to the bladder base should be routinely calculated, since single point measurements at the bladder neck seriously underestimate the dose to the bladder. Also the rectal dose should be determined at several points over the length of the implant due to the wide range of anatomic variations possible.

Evaluation of Clostridium novyi–NT spores in dogs with naturally occurring tumors

PubMed Central

Krick, Erika L.; Sorenmo, Karin U.; Rankin, Shelley C.; Cheong, Ian; Kobrin, Barry; Thornton, Katherine; Kinzler, Kenneth W.; Vogelstein, Bert; Zhou, Shibin; Diaz, Luis A.

2015-01-01

Objective To establish the maximum tolerated dose of Clostridium novyi–NT spores in tumor-bearing dogs and evaluate spore germination within tumors and tumor response. Animals 6 client-owned dogs. Procedures A standard dose-escalation study was planned, with maximum tolerated dose defined as the highest dose at which 0 or 1 of 6 dogs had dose-limiting toxicoses (DLT). Dogs received 1 dose of C novyi–NT spores IV. Toxicoses were graded and interventions performed according to specific guidelines. Grade 3 or higher toxicosis or any toxicosis combination that substantially affected patient status was considered DLT. Clinical response was measured by use of response evaluation criteria in solid tumors at 28 days. Results The first 2 dogs had DLT. The dose was decreased. Two of the next 4 dogs had DLT; therefore, dose administration was stopped because the study endpoint had been reached. The most common toxicosis was fever (n = 6 dogs). Two dogs developed abscesses (1 within a nasal carcinoma and 1 splenic abscess) attributable to C novyi–NT infection; both required surgical intervention. Clostridium novyi–NT was cultured from 1 of 6 tumors. Five dogs were available for response assessment (4 had stable disease; 1 had progressive disease). Conclusions and Clinical Relevance Results indicated that C novyi–NT can germinate within tumors of dogs. Toxicosis, although common and sometimes severe, was manageable with treatment. Further studies in dogs with superficial tumors may allow for continued dose escalation and provide information for use in clinical trials in veterinary and human oncology. PMID:22204296

Phase 1 Dose Escalation Study of Accelerated Radiation Therapy With Concurrent Chemotherapy for Locally Advanced Lung Cancer

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

Kelsey, Chris R., E-mail: christopher.kelsey@duke.edu; Das, Shiva; Gu, Lin

2015-12-01

Purpose: To determine the maximum tolerated dose of radiation therapy (RT) given in an accelerated fashion with concurrent chemotherapy using intensity modulated RT. Methods and Materials: Patients with locally advanced lung cancer (non-small cell and small cell) with good performance status and minimal weight loss received concurrent cisplatin and etoposide with RT. Intensity modulated RT with daily image guidance was used to facilitate esophageal avoidance and delivered using 6 fractions per week (twice daily on Fridays with a 6-hour interval). The dose was escalated from 58 Gy to a planned maximum dose of 74 Gy in 4 Gy increments in a standardmore » 3 + 3 trial design. Dose-limiting toxicity (DLT) was defined as acute grade 3-5 nonhematologic toxicity attributed to RT. Results: A total of 24 patients were enrolled, filling all dose cohorts, all completing RT and chemotherapy as prescribed. Dose-limiting toxicity occurred in 1 patient at 58 Gy (grade 3 esophagitis) and 1 patient at 70 Gy (grade 3 esophageal fistula). Both patients with DLTs had large tumors (12 cm and 10 cm, respectively) adjacent to the esophagus. Three additional patients were enrolled at both dose cohorts without further DLT. In the final 74-Gy cohort, no DLTs were observed (0 of 6). Conclusions: Dose escalation and acceleration to 74 Gy with intensity modulated RT and concurrent chemotherapy was tolerable, with a low rate of grade ≥3 acute esophageal reactions.« less

How Important Is a Reproducible Breath Hold for Deep Inspiration Breath Hold Breast Radiation Therapy?

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

Wiant, David, E-mail: David.wiant@conehealth.com; Wentworth, Stacy; Liu, Han

Purpose: Deep inspiration breath hold (DIBH) for left-sided breast cancer has been shown to reduce heart dose. Surface imaging helps to ensure accurate breast positioning, but it does not guarantee a reproducible breath hold (BH) at DIBH treatments. We examine the effects of variable BH positions for DIBH treatments. Methods and Materials: Twenty-five patients who underwent free breathing (FB) and DIBH scans were reviewed. Four plans were created for each patient: FB, DIBH, FB-DIBH (the DIBH plans were copied to the FB images and recalculated, and image registration was based on breast tissue), and P-DIBH (a partial BH with themore » heart shifted midway between the FB and DIBH positions). The FB-DIBH plans give a “worst-case” scenario for surface imaging DIBH, where the breast is aligned by surface imaging but the patient is not holding their breath. Kolmogorov-Smirnov tests were used to compare the dose metrics. Results: The DIBH plans gave lower heart dose and comparable breast coverage versus FB in all cases. The FB-DIBH plans showed no significant difference versus FB plans for breast coverage, mean heart dose, or maximum heart dose (P≥.10). The mean heart dose differed between FB-DIBH and FB by <2 Gy for all cases, and the maximum heart dose differed by <2 Gy for 21 cases. The P-DIBH plans showed significantly lower mean heart dose than FB (P<.01). The mean heart doses for the P-DIBH plans were« less

Investigation of pulsed IMRT and VMAT for re-irradiation treatments: dosimetric and delivery feasibilities

NASA Astrophysics Data System (ADS)

Lin, Mu-Han; Price, Robert A., Jr.; Li, Jinsheng; Kang, Shengwei; Li, Jie; Ma, C.-M.

2013-11-01

Many tumor cells demonstrate hyperradiosensitivity at doses below ˜50 cGy. Together with the increased normal tissue repair under low dose rate, the pulsed low dose rate radiotherapy (PLDR), which separates a daily fractional dose of 200 cGy into 10 pulses with 3 min interval between pulses (˜20 cGy/pulse and effective dose rate 6.7 cGy min-1), potentially reduces late normal tissue toxicity while still providing significant tumor control for re-irradiation treatments. This work investigates the dosimetric and technical feasibilities of intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT)-based PLDR treatments using Varian Linacs. Twenty one cases (12 real re-irradiation cases) including treatment sites of pancreas, prostate, pelvis, lung, head-and-neck, and breast were recruited for this study. The lowest machine operation dose rate (100 MU min-1) was employed in the plan delivery. Ten-field step-and-shoot IMRT and dual-arc VMAT plans were generated using the Eclipse TPS with routine planning strategies. The dual-arc plans were delivered five times to achieve a 200 cGy daily dose (˜20 cGy arc-1). The resulting plan quality was evaluated according to the heterogeneity and conformity indexes (HI and CI) of the planning target volume (PTV). The dosimetric feasibility of retaining the hyperradiosensitivity for PLDR was assessed based on the minimum and maximum dose in the target volume from each pulse. The delivery accuracy of VMAT and IMRT at the 100 MU min-1 machine operation dose rate was verified using a 2D diode array and ion chamber measurements. The delivery reproducibility was further investigated by analyzing the Dynalog files of repeated deliveries. A comparable plan quality was achieved by the IMRT (CI 1.10-1.38 HI 1.04-1.10) and the VMAT (CI 1.08-1.26 HI 1.05-1.10) techniques. The minimum/maximum PTV dose per pulse is 7.9 ± 5.1 cGy/33.7 ± 6.9 cGy for the IMRT and 12.3 ± 4.1 cGy/29.2 ± 4.7 cGy for the VMAT. Six out of the 186 IMRT pulses (fields) were found to exceed 50 cGy maximum PTV dose per pulse while the maximum PTV dose per pulse was within 40 cGy for all the VMAT pulses (arcs). However, for VMAT plans, the dosimetric quality of the entire treatment plan was less superior for the breast cases and large irregular targets. The gamma passing rates for both techniques at the 100 MU min-1 dose rate were at least 94.1% (3%/3 mm) and the point dose measurements agreed with the planned values to within 2.2%. The average root mean square error of the leaf position was 0.93 ± 0.83 mm for IMRT and 0.53 ± 0.48 mm for VMAT based on the Dynalog file analysis. The RMS error of the leaf position was nearly identical for the repeated deliveries of the same plans. In general, both techniques are feasible for PLDR treatments. VMAT was more advantageous for PLDR with more uniform target dose per pulse, especially for centrally located tumors. However, for large, irregular and/or peripheral tumors, IMRT could produce more favorable PLDR plans. By taking the biological benefit of PLDR delivery and the dosimetric benefit of IMRT and VMAT, the proposed methods have a great potential for those previously-irradiated recurrent patients.

NIRS external dose estimation system for Fukushima residents after the Fukushima Dai-ichi NPP accident

NASA Astrophysics Data System (ADS)

Akahane, Keiichi; Yonai, Shunsuke; Fukuda, Shigekazu; Miyahara, Nobuyuki; Yasuda, Hiroshi; Iwaoka, Kazuki; Matsumoto, Masaki; Fukumura, Akifumi; Akashi, Makoto

2013-04-01

The great east Japan earthquake and subsequent tsunamis caused Fukushima Dai-ichi Nuclear Power Plant (NPP) accident. National Institute of Radiological Sciences (NIRS) developed the external dose estimation system for Fukushima residents. The system is being used in the Fukushima health management survey. The doses can be obtained by superimposing the behavior data of the residents on the dose rate maps. For grasping the doses, 18 evacuation patterns of the residents were assumed by considering the actual evacuation information before using the survey data. The doses of the residents from the deliberate evacuation area were relatively higher than those from the area within 20 km radius. The estimated doses varied from around 1 to 6 mSv for the residents evacuated from the representative places in the deliberate evacuation area. The maximum dose in 18 evacuation patterns was estimated to be 19 mSv.

NIRS external dose estimation system for Fukushima residents after the Fukushima Dai-ichi NPP accident.

PubMed

Akahane, Keiichi; Yonai, Shunsuke; Fukuda, Shigekazu; Miyahara, Nobuyuki; Yasuda, Hiroshi; Iwaoka, Kazuki; Matsumoto, Masaki; Fukumura, Akifumi; Akashi, Makoto

2013-01-01

The great east Japan earthquake and subsequent tsunamis caused Fukushima Dai-ichi Nuclear Power Plant (NPP) accident. National Institute of Radiological Sciences (NIRS) developed the external dose estimation system for Fukushima residents. The system is being used in the Fukushima health management survey. The doses can be obtained by superimposing the behavior data of the residents on the dose rate maps. For grasping the doses, 18 evacuation patterns of the residents were assumed by considering the actual evacuation information before using the survey data. The doses of the residents from the deliberate evacuation area were relatively higher than those from the area within 20 km radius. The estimated doses varied from around 1 to 6 mSv for the residents evacuated from the representative places in the deliberate evacuation area. The maximum dose in 18 evacuation patterns was estimated to be 19 mSv.

The space radiation environment

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

Robbins, D E

There are three primary sources of space radiation: galactic cosmic rays (GCR), trapped belt radiation, and solar particle events (SPE). All are composed of ions, the nuclei of atoms. Their energies range from a few MeV u{sup -1} to over a GeV u{sup -1}. These ions can fragment when they interact with spacecraft materials and produce energetic neutrons and ions of lower atomic mass. Absorbed dose rates inside a typical spacecraft (like the Space Shuttle) in a low inclination (28.5 degrees) orbit range between 0.05 and 2 mGy d{sup -1} depending on the altitude and flight inclination (angle of orbitmore » with the equator). The quality factor of radiation in orbit depends on the relative contributions of trapped belt radiation and GCR, and the dose rate varies both with orbital altitude and inclination. The corresponding equivalent dose rate ranges between 0.1 and 4 mSv d{sup -1}. In high inclination orbits, like that of the Mir Space Station and as is planned for the International Space Station, blood-forming organ (BFO) equivalent dose rates as high as 1.5 mSv d{sup -1}. Thus, on a 1 y mission, a crew member could obtain a total dose of 0.55 Sv. Maximum equivalent dose rates measured in high altitude passes through the South Atlantic Anomaly (SAA) were 10 mSv h{sup -1}. For an interplanetary space mission (e.g., to Mars) annual doses from GCR alone range between 150 mSv y{sup -1} at solar maximum and 580 mSv y{sup -1} at solar minimum. Large SPE, like the October 1989 series, are more apt to occur in the years around solar maximum. In free space, such an event could contribute another 300 mSv, assuming that a warning system and safe haven can be effectively used with operational procedures to minimize crew exposures. Thus, the total dose for a 3 y mission to Mars could exceed 2 Sv.« less

Comparison of the respiratory effects of intravenous buprenorphine and fentanyl in humans and rats.

PubMed

Dahan, A; Yassen, A; Bijl, H; Romberg, R; Sarton, E; Teppema, L; Olofsen, E; Danhof, M

2005-06-01

There is evidence from animal studies suggesting the existence of a ceiling effect for buprenorphine-induced respiratory depression. To study whether an apparent ceiling effect exists for respiratory depression induced by buprenorphine, we compared the respiratory effects of buprenorphine and fentanyl in humans and rats. In healthy volunteers, the opioids were infused i.v. over 90 s and measurements of minute ventilation at a fixed end-tidal PCO2 of 7 kPa were obtained for 7 h. Buprenorphine doses were 0.7, 1.4, 4.3 and 8.6 microg kg(-1) (n=20 subjects) and fentanyl doses 1.1, 2.1, 2.9, 4.3 and 7.1 microg kg(-1) (n=21). Seven subjects received placebo. In rats, both opioids were infused i.v. over 20 min, and arterial PCO2 was measured 5, 10, 15 and 20 min after the start of fentanyl infusion and 30, 150, 270 and 390 min after the start of buprenorphine infusion. Doses tested were buprenorphine 0, 100, 300, 1000 and 3000 microg kg(-1) and fentanyl 0, 50, 68 and 90 microg kg(-1). In humans, fentanyl produced a dose-dependent depression of minute ventilation with apnoea at doses > or = 2.9 microg kg(-1); buprenorphine caused depression of minute ventilation which levelled off at doses > or = 3.0 microg kg(-1) to about 50% of baseline. In rats, the relationship of arterial PCO2 and fentanyl dose was linear, with maximum respiratory depression at 20 min (maximum PaCO2 8.0 kPa). Irrespective of the time at which measurements were obtained, buprenorphine showed a non-linear effect on PaCO2, with a ceiling effect at doses > 1.4 microg kg(-1). The effect on PaCO2 was modest (maximum value measured, 5.5 kPa). Our data confirm a ceiling effect of buprenorphine but not fentanyl with respect to respiratory depression.

A comprehensive dose reconstruction methodology for former rocketdyne/atomics international radiation workers.

PubMed

Boice, John D; Leggett, Richard W; Ellis, Elizabeth Dupree; Wallace, Phillip W; Mumma, Michael; Cohen, Sarah S; Brill, A Bertrand; Chadda, Bandana; Boecker, Bruce B; Yoder, R Craig; Eckerman, Keith F

2006-05-01

Incomplete radiation exposure histories, inadequate treatment of internally deposited radionuclides, and failure to account for neutron exposures can be important uncertainties in epidemiologic studies of radiation workers. Organ-specific doses from lifetime occupational exposures and radionuclide intakes were estimated for an epidemiologic study of 5,801 Rocketdyne/Atomics International (AI) radiation workers engaged in nuclear technologies between 1948 and 1999. The entire workforce of 46,970 Rocketdyne/AI employees was identified from 35,042 Kardex work histories cards, 26,136 electronic personnel listings, and 14,189 radiation folders containing individual exposure histories. To obtain prior and subsequent occupational exposure information, the roster of all workers was matched against nationwide dosimetry files from the Department of Energy, the Nuclear Regulatory Commission, the Landauer dosimetry company, the U.S. Army, and the U.S. Air Force. Dosimetry files of other worker studies were also accessed. Computation of organ doses from radionuclide intakes was complicated by the diversity of bioassay data collected over a 40-y period (urine and fecal samples, lung counts, whole-body counts, nasal smears, and wound and incident reports) and the variety of radionuclides with documented intake including isotopes of uranium, plutonium, americium, calcium, cesium, cerium, zirconium, thorium, polonium, promethium, iodine, zinc, strontium, and hydrogen (tritium). Over 30,000 individual bioassay measurements, recorded on 11 different bioassay forms, were abstracted. The bioassay data were evaluated using ICRP biokinetic models recommended in current or upcoming ICRP documents (modified for one inhaled material to reflect site-specific information) to estimate annual doses for 16 organs or tissues taking into account time of exposure, type of radionuclide, and excretion patterns. Detailed internal exposure scenarios were developed and annual internal doses were derived on a case-by-case basis for workers with committed equivalent doses indicated by screening criteria to be greater than 10 mSv to the organ with the highest internal dose. Overall, 5,801 workers were monitored for radiation at Rocketdyne/AI: 5,743 for external exposure and 2,232 for internal intakes of radionuclides; 41,169 workers were not monitored for radiation. The mean cumulative external dose based on Rocketdyne/AI records alone was 10.0 mSv, and the dose distribution was highly skewed with most workers experiencing low cumulative doses and only a few with high doses (maximum 500 mSv). Only 45 workers received greater than 200 mSv while employed at Rocketdyne/AI. However, nearly 32% (or 1,833) of the Rocketdyne/AI workers had been monitored for radiation at other nuclear facilities and incorporation of these doses increased the mean dose to 13.5 mSv (maximum 1,005 mSv) and the number of workers with >200 mSv to 69. For a small number of workers (n=292), lung doses from internal radionuclide intakes were relatively high (mean 106 mSv; maximum 3,560 mSv) and increased the overall population mean dose to 19.0 mSv and the number of workers with lung dose>200 mSv to 109. Nearly 10% of the radiation workers (584) were monitored for neutron exposures (mean 1.2 mSv) at Rocketdyne/AI, and another 2% were monitored for neutron exposures elsewhere. Interestingly, 1,477 workers not monitored for radiation at Rocketdyne/AI (3.6%) were found to have worn dosimeters at other nuclear facilities (mean external dose of 2.6 mSv, maximum 188 mSv). Without considering all sources of occupational exposure, an incorrect characterization of worker exposure would have occurred with the potential to bias epidemiologic results. For these pioneering workers in the nuclear industry, 26.5% of their total occupational dose (collective dose) was received at other facilities both prior to and after employment at Rocketdyne/AI. In addition, a small number of workers monitored for internal radionuclides contributed disproportionately to the number of workers with high lung doses. Although nearly 12% of radiation workers had been monitored for neutron exposures during their career, the cumulative dose levels were small in comparison with other external and internal exposure. Risk estimates based on nuclear worker data must be interpreted cautiously if internally deposited radionuclides and occupational doses received elsewhere are not considered.

Evaluation of lens dose from anterior electron beams: comparison of Pinnacle and Gafchromic EBT3 film

PubMed Central

Wronski, Matt; Yeboah, Collins

2015-01-01

Lens dose is a concern during the treatment of facial lesions with anterior electron beams. Lead shielding is routinely employed to reduce lens dose and minimize late complications. The purpose of this work is twofold: 1) to measure dose profiles under large‐area lead shielding at the lens depth for clinical electron energies via film dosimetry; and 2) to assess the accuracy of the Pinnacle treatment planning system in calculating doses under lead shields. First, to simulate the clinical geometry, EBT3 film and 4 cm wide lead shields were incorporated into a Solid Water phantom. With the lead shield inside the phantom, the film was positioned at a depth of 0.7 cm below the lead, while a variable thickness of solid water, simulating bolus, was placed on top. This geometry was reproduced in Pinnacle to calculate dose profiles using the pencil beam electron algorithm. The measured and calculated dose profiles were normalized to the central‐axis dose maximum in a homogeneous phantom with no lead shielding. The resulting measured profiles, functions of bolus thickness and incident electron energy, can be used to estimate the lens dose under various clinical scenarios. These profiles showed a minimum lead margin of 0.5 cm beyond the lens boundary is required to shield the lens to ≤10% of the dose maximum. Comparisons with Pinnacle showed a consistent overestimation of dose under the lead shield with discrepancies of ∼25% occurring near the shield edge. This discrepancy was found to increase with electron energy and bolus thickness and decrease with distance from the lead edge. Thus, the Pinnacle electron algorithm is not recommended for estimating lens dose in this situation. The film measurements, however, allow for a reasonable estimate of lens dose from electron beams and for clinicians to assess the lead margin required to reduce the lens dose to an acceptable level. PACS number(s): 87.53.Bn, 87.53.Kn, 87.55.‐x, 87.55.D‐ PMID:27074448

T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial.

PubMed

Lee, Daniel W; Kochenderfer, James N; Stetler-Stevenson, Maryalice; Cui, Yongzhi K; Delbrook, Cindy; Feldman, Steven A; Fry, Terry J; Orentas, Rimas; Sabatino, Marianna; Shah, Nirali N; Steinberg, Seth M; Stroncek, Dave; Tschernia, Nick; Yuan, Constance; Zhang, Hua; Zhang, Ling; Rosenberg, Steven A; Wayne, Alan S; Mackall, Crystal L

2015-02-07

Chimeric antigen receptor (CAR) modified T cells targeting CD19 have shown activity in case series of patients with acute and chronic lymphocytic leukaemia and B-cell lymphomas, but feasibility, toxicity, and response rates of consecutively enrolled patients treated with a consistent regimen and assessed on an intention-to-treat basis have not been reported. We aimed to define feasibility, toxicity, maximum tolerated dose, response rate, and biological correlates of response in children and young adults with refractory B-cell malignancies treated with CD19-CAR T cells. This phase 1, dose-escalation trial consecutively enrolled children and young adults (aged 1-30 years) with relapsed or refractory acute lymphoblastic leukaemia or non-Hodgkin lymphoma. Autologous T cells were engineered via an 11-day manufacturing process to express a CD19-CAR incorporating an anti-CD19 single-chain variable fragment plus TCR zeta and CD28 signalling domains. All patients received fludarabine and cyclophosphamide before a single infusion of CD19-CAR T cells. Using a standard 3 + 3 design to establish the maximum tolerated dose, patients received either 1 × 10(6) CAR-transduced T cells per kg (dose 1), 3 × 10(6) CAR-transduced T cells per kg (dose 2), or the entire CAR T-cell product if sufficient numbers of cells to meet the assigned dose were not generated. After the dose-escalation phase, an expansion cohort was treated at the maximum tolerated dose. The trial is registered with ClinicalTrials.gov, number NCT01593696. Between July 2, 2012, and June 20, 2014, 21 patients (including eight who had previously undergone allogeneic haematopoietic stem-cell transplantation) were enrolled and infused with CD19-CAR T cells. 19 received the prescribed dose of CD19-CAR T cells, whereas the assigned dose concentration could not be generated for two patients (90% feasible). All patients enrolled were assessed for response. The maximum tolerated dose was defined as 1 × 10(6) CD19-CAR T cells per kg. All toxicities were fully reversible, with the most severe being grade 4 cytokine release syndrome that occurred in three (14%) of 21 patients (95% CI 3·0-36·3). The most common non-haematological grade 3 adverse events were fever (nine [43%] of 21 patients), hypokalaemia (nine [43%] of 21 patients), fever and neutropenia (eight [38%] of 21 patients), and cytokine release syndrome (three [14%) of 21 patients). CD19-CAR T cell therapy is feasible, safe, and mediates potent anti-leukaemic activity in children and young adults with chemotherapy-resistant B-precursor acute lymphoblastic leukaemia. All toxicities were reversible and prolonged B-cell aplasia did not occur. National Institutes of Health Intramural funds and St Baldrick's Foundation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Interplay effect on a 6-MV flattening-filter-free linear accelerator with high dose rate and fast multi-leaf collimator motion treating breast and lung phantoms.

PubMed

Netherton, Tucker; Li, Yuting; Nitsch, Paige; Shaitelman, Simona; Balter, Peter; Gao, Song; Klopp, Ann; Muruganandham, Manickam; Court, Laurence

2018-06-01

Using a new linear accelerator with high dose rate (800 MU/min), fast MLC motions (5.0 cm/s), fast gantry rotation (15 s/rotation), and 1 cm wide MLCs, we aimed to quantify the effects of complexity, arc number, and fractionation on interplay for breast and lung treatments under target motion. To study lung interplay, eight VMAT plans (1-6 arcs) and four-nine-field sliding-window IMRT plans varying in complexity were created. For the breast plans, four-four-field sliding-window IMRT plans were created. Using the Halcyon 1.0 linear accelerator, each plan was delivered five times each under sinusoidal breathing motion to a phantom with 20 implanted MOSFET detectors; MOSFET dose (cGy), delivery time, and MU/cGy values were recorded. Maximum and mean dose deviations were calculated from MOSFET data. The number of MOSFETs with at least 19 of 20 detectors agreeing with their expected dose within 5% per fraction was calculated across 10 6 iterations to model dose deviation as function of fraction number for all plan variants. To put interplay plans into clinical context, additional IMRT and VMAT plans were created and delivered for the sites of head and neck, prostate, whole brain, breast, pelvis, and lung. Average modulation and interplay effect were compared to those from conventional linear accelerators, as reported from previous studies. The mean beam modulation for plans created for the Halcyon 1.0 linear accelerator was 2.9 MU/cGy (two- to four-field IMRT breast plans), 6.2 MU/cGy (at least five-field IMRT), and 3.6 MU/cGy (four-arc VMAT). To achieve treatment plan objectives, Halcyon 1.0 VMAT plans require more arcs and modulation than VMAT on conventional linear accelerators. Maximum and mean dose deviations increased with increasing plan complexity under tumor motion for breast and lung treatments. Concerning VMAT plans under motion, maximum, and mean dose deviations were higher for one arc than for two arcs regardless of plan complexity. For plan variants with maximum dose deviations greater than 3.7%, dose deviation as a function of fraction number was protracted. For treatments on the Halcyon 1.0 linear accelerator, the convergence of dose deviation with fraction number happened more slowly than reported for conventional linear accelerators. However, if plan complexity is reduced for IMRT and if tumor motion is less than ~10-mm, interplay is greatly reduced. To minimize dose deviations across multiple fractions for dynamic targets, we recommend limiting treatment plan complexity and avoiding one-arc VMAT on the Halcyon 1.0 linear accelerator when interplay is a concern. © 2018 American Association of Physicists in Medicine.

Phase I trial and pharmacokinetic study of raltitrexed in children with recurrent or refractory leukemia: a pediatric oncology group study.

PubMed

Horton, Terzah M; Blaney, Susan M; Langevin, Anne-Marie; Kuhn, John; Kamen, Barton; Berg, Stacey L; Bernstein, Mark; Weitman, Steven

2005-03-01

To evaluate the toxicity, antileukemic activity, and pharmacology of raltitrexed administered weekly for 3 weeks to patients with refractory or recurrent leukemia. Raltitrexed was administered as a 15-minute infusion for 3 consecutive weeks every 5 weeks, at doses ranging from 1.3 to 2.8 mg/m(2). The first course was used to determine the dose-limiting toxicities and maximum tolerated dose. Correlative studies included an assessment of raltitrexed pharmacokinetics and measurement of plasma 2'-deoxyuridine concentrations, a surrogate measure of thymidylate synthase inhibition. Twenty-one children (18 evaluable) with refractory leukemia received 25 courses of raltitrexed. The dose-limiting toxicity was reversible elevation in liver transaminases at the 2.8-mg/m(2) dose level and the maximum tolerated dose was 2.1 mg/m(2) per dose. Pharmacokinetics were best characterized by a two-compartment model with a clearance of 139 mL/min/m(2) (8.3 L/h/m(2)), a 2.4-L volume of distribution, an initial half-life (t(1/2alpha)) of 6 minutes, and a terminal half-life (t(1/2beta)) of 45 minutes. There were three objective responses. Raltitrexed was well tolerated when administered as a single agent to children with recurrent or refractory leukemia. We observed preliminary evidence of antileukemia activity using this weekly dosing schedule and these observations support further evaluation of raltitrexed in this population.

An FDA oncology analysis of CD3 bispecific constructs and first-in-human dose selection.

PubMed

Saber, Haleh; Del Valle, Pedro; Ricks, Tiffany K; Leighton, John K

2017-11-01

We retrospectively examined the nonclinical studies conducted with 17 CD3 bispecific constructs in support of first-in-human (FIH) trials in oncology. We also collected information on the design of dose-finding clinical trials. Sponsors have used different MABEL approaches for FIH dose selection. To better assess acceptable approaches, FIH doses were computed from nonclinical studies and compared to the maximum tolerated doses (MTDs) in patients, to the highest human doses (HHDs) when an MTD was not identified, or to the recommended human dose (RHD) for blinatumomab. We concluded that approaches based on receptor occupancy, highest non-severely toxic dose, or no-observed adverse effect level are not acceptable for selecting the FIH dose as they resulted in doses close to or above the MTDs, HHDs, or the RHD. A FIH dose corresponding to 10%-30% pharmacologic activity (PA) was an acceptable approach. A FIH dose corresponding to 50% PA was acceptable for all except one construct, potentially due to its biological or structural properties. The most common toxicities in animals and patients were those related to cytokine release. Doses were better tolerated when intra-animal or intra-patient dose escalation was used. Exposing naïve patients to an MTD achieved with intra-patient dose escalation design may be unsafe. Published by Elsevier Inc.

Technical Note: Dosimetric evaluation of Monte Carlo algorithm in iPlan for stereotactic ablative body radiotherapy (SABR) for lung cancer patients using RTOG 0813 parameters.

PubMed

Pokhrel, Damodar; Badkul, Rajeev; Jiang, Hongyu; Kumar, Pravesh; Wang, Fen

2015-01-08

For stereotactic ablative body radiotherapy (SABR) in lung cancer patients, Radiation Therapy Oncology Group (RTOG) protocols currently require radiation dose to be calculated using tissue heterogeneity corrections. Dosimetric criteria of RTOG 0813 were established based on the results obtained from non-Monte Carlo (MC) algorithms, such as superposition/convolutions. Clinically, MC-based algorithms are now routinely used for lung SABR dose calculations. It is essential to confirm that MC calculations in lung SABR meet RTOG guidelines. This report evaluates iPlan MC plans for SABR in lung cancer patients using dose-volume histogram normalization per current RTOG 0813 compliance criteria. Eighteen Stage I-II non-small cell lung cancer (NSCLC) patients with centrally located tumors, who underwent MC-based lung SABR with heterogeneity correction using X-ray Voxel Monte Carlo (XVMC) algorithm (BrainLAB iPlan version 4.1.2), were analyzed. Total dose of 60 Gy in 5 fractions was delivered to planning target volume (PTV) with at least V100% = 95%. Internal target volumes (ITVs) were delineated on maximum intensity projection (MIP) images of 4D CT scans. PTV (ITV + 5 mm margin) volumes ranged from 10.0 to 99.9 cc (mean = 36.8 ± 20.7 cc). Organs at risk (OARs) were delineated on average images of 4D CT scans. Optimal clinical MC SABR plans were generated using a combination of non-coplanar conformal arcs and beams for the Novalis-TX consisting of high definition multileaf collimators (MLCs) and 6 MV-SRS (1000 MU/min) mode. All plans were evaluated using the RTOG 0813 high and intermediate dose spillage criteria: conformity index (R100%), ratio of 50% isodose volume to the PTV (R50%), maximum dose 2 cm away from PTV in any direction (D2 cm), and percent of normal lung receiving 20 Gy (V20) or more. Other organs-at-risk (OARs) doses were tabulated, including the volume of normal lung receiving 5 Gy (V5), maximum cord dose, dose to < 15 cc of heart, and dose to <5 cc of esophagus. Only six out of 18 patients met all RTOG 0813 compliance criteria. Eight of 18 patients had minor deviations in R100%, four in R50%, and nine in D2 cm. However, only one patient had minor deviation in V20. All other OARs doses, such as maximum cord dose, dose to < 15 cc of heart, and dose to < 5 cc of esophagus, were satisfactory for RTOG criteria, except for one patient, for whom the dose to < 15 cc of heart was higher than RTOG guidelines. The preliminary results for our limited iPlan XVMC dose calculations indicate that the majority (i.e., 2/3) of our patients had minor deviations in the dosimetric guidelines set by RTOG 0813 protocol in one way or another. When using an exclusive highly sophisticated XVMC algorithm, the RTOG 0813 dosimetric compliance criteria such as R100% and D2 cm may need to be revisited. Based on our limited number of patient datasets, in general, about 6% for R100% and 9% for D2 cm corrections could be applied to pass the RTOG 0813 compliance criteria in most of those patients. More patient plans need to be evaluated to make recommendation for R50%. No adjustment is necessary for OAR dose tolerances, including normal lung V20. In order to establish new MC specific dose parameters, further investigation with a large cohort of patients including central, as well as peripheral lung tumors, is anticipated and strongly recommended.

Whole-remnant and maximum-voxel SPECT/CT dosimetry in {sup 131}I-NaI treatments of differentiated thyroid cancer

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

Mínguez, Pablo, E-mail: pablo.minguezgabina@osakid

Purpose: To investigate the possible differences between SPECT/CT based whole-remnant and maximum-voxel dosimetry in patients receiving radio-iodine ablation treatment of differentiated thyroid cancer (DTC). Methods: Eighteen DTC patients were administered 1.11 GBq of {sup 131}I-NaI after near-total thyroidectomy and rhTSH stimulation. Two patients had two remnants, so in total dosimetry was performed for 20 sites. Three SPECT/CT scans were performed for each patient at 1, 2, and 3–7 days after administration. The activity, the remnant mass, and the maximum-voxel activity were determined from these images and from a recovery-coefficient curve derived from experimental phantom measurements. The cumulated activity was estimatedmore » using trapezoidal-exponential integration. Finally, the absorbed dose was calculated using S-values for unit-density spheres in whole-remnant dosimetry and S-values for voxels in maximum-voxel dosimetry. Results: The mean absorbed dose obtained from whole-remnant dosimetry was 40 Gy (range 2–176 Gy) and from maximum-voxel dosimetry 34 Gy (range 2–145 Gy). For any given patient, the activity concentrations for each of the three time-points were approximately the same for the two methods. The effective half-lives varied (R = 0.865), mainly due to discrepancies in estimation of the longer effective half-lives. On average, absorbed doses obtained from whole-remnant dosimetry were 1.2 ± 0.2 (1 SD) higher than for maximum-voxel dosimetry, mainly due to differences in the S-values. The method-related differences were however small in comparison to the wide range of absorbed doses obtained in patients. Conclusions: Simple and consistent procedures for SPECT/CT based whole-volume and maximum-voxel dosimetry have been described, both based on experimentally determined recovery coefficients. Generally the results from the two approaches are consistent, although there is a small, systematic difference in the absorbed dose due to differences in the S-values, and some variability due to differences in the estimated effective half-lives, especially when the effective half-life is long. Irrespective of the method used, the patient absorbed doses obtained span over two orders of magnitude.« less

Sodium phenylbutyrate in Huntington's disease: a dose-finding study.

PubMed

Hogarth, Penelope; Lovrecic, Luca; Krainc, Dimitri

2007-10-15

Transcriptional dysregulation in Huntington's disease (HD) is mediated in part by aberrant patterns of histone acetylation. We performed a dose-finding study in human HD of sodium phenylbutyrate (SPB), a histone deacetylase inhibitor that ameliorates the HD phenotype in animal models. We used a dose-escalation/de-escalation design, using prespecified toxicity criteria and standard clinical and laboratory safety measures. The maximum tolerated dose was 15 g/day. At higher doses, toxicity included vomiting, lightheadedness, confusion, and gait instability. We saw no significant laboratory or electrocardiographic abnormalities. Gene expression changes in blood suggested an inverse dose-response. In conclusion, SPB at 12 to 15 g/day appears to be safe and well-tolerated in human HD. 2007 Movement Disorder Society

Skin dosimetry of patients during interventional cardiology procedures in the Czech Republic

NASA Astrophysics Data System (ADS)

Sukupova, Lucie; Novak, Leos

2008-01-01

The aim of the study is to determine distribution of air kerma-area product, fluoro time and number of frames values for the two most frequent procedures in the interventional cardiology, to reconstruct skin dose distributions for some patients undergoing coronarography and percutaneous transluminal coronary angioplasty procedures. Patient dose data were obtained from X-ray unit dose monitoring software report from one hospital and the reconstructions were performed in MATLAB. Dependence of maximum skin dose on air kerma-area product, fluoro time and number of frames was determined to assess trigger levels of these quantities, which can indicate possible exceeding of the 2 Gy skin dose threshold.

Spatial frequency performance limitations of radiation dose optimization and beam positioning

NASA Astrophysics Data System (ADS)

Stewart, James M. P.; Stapleton, Shawn; Chaudary, Naz; Lindsay, Patricia E.; Jaffray, David A.

2018-06-01

The flexibility and sophistication of modern radiotherapy treatment planning and delivery methods have advanced techniques to improve the therapeutic ratio. Contemporary dose optimization and calculation algorithms facilitate radiotherapy plans which closely conform the three-dimensional dose distribution to the target, with beam shaping devices and image guided field targeting ensuring the fidelity and accuracy of treatment delivery. Ultimately, dose distribution conformity is limited by the maximum deliverable dose gradient; shallow dose gradients challenge techniques to deliver a tumoricidal radiation dose while minimizing dose to surrounding tissue. In this work, this ‘dose delivery resolution’ observation is rigorously formalized for a general dose delivery model based on the superposition of dose kernel primitives. It is proven that the spatial resolution of a delivered dose is bounded by the spatial frequency content of the underlying dose kernel, which in turn defines a lower bound in the minimization of a dose optimization objective function. In addition, it is shown that this optimization is penalized by a dose deposition strategy which enforces a constant relative phase (or constant spacing) between individual radiation beams. These results are further refined to provide a direct, analytic method to estimate the dose distribution arising from the minimization of such an optimization function. The efficacy of the overall framework is demonstrated on an image guided small animal microirradiator for a set of two-dimensional hypoxia guided dose prescriptions.

Engineering study comparing injection force and dose accuracy between two prefilled insulin injection pens.

PubMed

Ignaut, Debra A; Opincar, Michael R; Clark, Paula E; Palaisa, Melanie K; Lenox, Sheila M

2009-12-01

This study compared injection force (measured by glide force [GF] and glide force variability [GFV]) and dosing accuracy of the Humalog KwikPen * (prefilled insulin lispro [Humalog dagger] pen, Eli Lilly and Company, Indianapolis, IN) and the Next Generation FlexPen double dagger (prefilled insulin aspart [NovoRapid section sign] pen, Novo Nordisk A/S, Bagsvaerd, Denmark). * Humalog KwikPen is a registered trademark of Eli Lilly and Company, Indianapolis, IN, USA. dagger Humalog is a registered trademark of Eli Lilly and Company, Indianapolis, IN, USA. double dagger FlexPen is a registered trademark of Novo Nordisk A/S, Bagsvaerd, Denmark. section sign NovoRapid is a registered trademark of Novo Nordisk A/S, Bagsvaerd, Denmark. A total of 100 prefilled insulin pens (50 insulin lispro pens, 50 insulin aspart pens) were tested using two dose sizes (30 U and 60 U). In all, 50 devices (25 of each type) were tested at 10 U/s dosing speed and 50 were tested at 6.6 U/s. Devices were used per manufacturer instructions. Dose accuracy (represented as absolute dose error %), maximum and average GF, and GFV data were automatically collected by the test system for all datasets (dose size/dosing speed/device type). The test system controlled for potential dosing errors. The insulin lispro pen demonstrated a significantly lower median maximum GF at both dosing speeds: (2.83 vs. 3.92 lbs [30 U] and 3.00 vs. 4.14 lbs [60 U]) at 10 U/s; (1.85 vs. 2.93 lbs [30 U] and 2.14 vs. 3.02 lbs [60 U]) at 6.6 U/s, all p < 0.0001. For all datasets, the median GFV was significantly lower for the insulin lispro pen, p < 0.0001. Median dose error was comparable between device types when tested at 10 U/s dosing speed; however, at 6.6 U/s, the median dose error was significantly lower for insulin lispro pen compared to insulin aspart pen (0.47 vs. 0.67% [30 U] and 0.50 vs. 0.78% [60 U], both p < 0.05). The insulin lispro pen had significantly lower median GF and GFV compared with insulin aspart pen when tested at two dose sizes and two dosing speeds. Median dose error was similar between the device types at the 10 U/s dosing speed, but median dose error was significantly lower for the insulin lispro pen at the 6.6 U/s dosing speed. A limitation of this study was that it was executed as an open label study.

Environmental consequences of postulated plutonium releases from General Electric Company Vallecitos Nuclear Center, Vallecitos, California, as a result of severe natural phenomena

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

Jamison, J.D.; Watson, E.C.

1980-11-01

Potential environmental consequences in terms of radiation dose to people are presented for postulated plutonium releases caused by severe natural phenomena at the General Electric Company Vallecitos Nuclear Center, Vallecitos, California. The severe natural phenomena considered are earthquakes, tornadoes, and high straight-line winds. Maximum plutonium deposition values are given for significant locations around the site. All important potential exposure pathways are examined. The most likely 50-year committed dose equivalents are given for the maximum-exposed individual and the population within a 50-mile radius of the plant. The maximum plutonium deposition values likely to occur offsite are also given. The most likelymore » calculated 50-year collective committed dose equivalents are all much lower than the collective dose equivalent expected from 50 years of exposure to natural background radiation and medical x-rays. The most likely maximum residual plutonium contamination estimated to be deposited offsite following the earthquakes, and the 180-mph and 230-mph tornadoes are above the Environmental Protection Agency's (EPA) proposed guideline for plutonium in the general environment of 0.2 ..mu..Ci/m/sup 2/. The deposition values following the 135-mph tornado are below the EPA proposed guidelines.« less

Scattered radiation doses absorbed by technicians at different distances from X-ray exposure: Experiments on prosthesis.

PubMed

Chiang, Hsien-Wen; Liu, Ya-Ling; Chen, Tou-Rong; Chen, Chun-Lon; Chiang, Hsien-Jen; Chao, Shin-Yu

2015-01-01

This work aimed to investigate the spatial distribution of scattered radiation doses induced by exposure to the portable X-ray, the C-arm machine, and to simulate the radiologist without a shield of lead clothing, radiation doses absorbed by medical staff at 2 m from the central exposure point. With the adoption of the Rando Phantom, several frequently X-rayed body parts were exposed to X-ray radiation, and the scattered radiation doses were measured by ionization chamber dosimeters at various angles from the patient. Assuming that the central point of the X-ray was located at the belly button, five detection points were distributed in the operation room at 1 m above the ground and 1-2 m from the central point horizontally. The radiation dose measured at point B was the lowest, and the scattered radiation dose absorbed by the prosthesis from the X-ray's vertical projection was 0.07 ±0.03 μGy, which was less than the background radiation levels. The Fluke biomedical model 660-5DE (400 cc) and 660-3DE (4 cc) ion chambers were used to detect air dose at a distance of approximately two meters from the central point. The AP projection radiation doses at point B was the lowest (0.07±0.03 μGy) and the radiation doses at point D was the highest (0.26±0.08 μGy) .Only taking the vertical projection into account, the radiation doses at point B was the lowest (0.52 μGy), and the radiation doses at point E was the highest (4 μGy).The PA projection radiation at point B was the lowest (0.36 μGy) and the radiation doses at point E was the highest(2.77 μGy), occupying 10-32% of the maximum doses. The maximum dose in five directions was nine times to the minimum dose. When the PX and the C-arm machine were used, the radiation doses at a distance of 2 m were attenuated to the background radiation level. The radiologist without a lead shield should stand at point B of patient's feet. Accordingly, teaching materials on radiation safety for radiological interns and clinical technicians were formulated.

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

Dosimetric feasibility of an “off-target isocenter” technique for cranial intensity-modulated radiosurgery

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

Calvo-Ortega, Juan Francisco, E-mail: jfcdrr@yahoo.es; Moragues, Sandra; Pozo, Miquel

2015-01-01

To evaluate the dosimetric effect of placing the isocenter away from the planning target volume (PTV) on intensity-modulated radiosurgery (IMRS) plans to treat brain lesions. A total of 15 patients who received cranial IMRS at our institution were randomly selected. Each patient was treated with an IMRS plan designed with the isocenter located at the target center (plan A). A second off-target isocenter plan (plan B) was generated for each case. In all the plans,100% of the prescription dose covered 99% of the target volume. The plans A and B were compared for the target dosage (conformity index [CI] andmore » homogeneity index) and organs-at-risk (OAR) dose sparing. Peripheral dose falloff was compared by using the metrics volume of normal brain receiving more than 12-Gy dose (V12) and CI at the level of the 50% of the prescription dose (CI 50%). The values found for each metric (plan B vs plan A) were (mean ± standard deviation [SD]) as follows—CI: 1.28 ± 0.15 vs 1.28 ± 0.15, p = 0.978; homogeneity index (HI): 1.29 ± 0.14 vs 1.34 ± 0.17, p = 0.079; maximum dose to the brainstem: 2.95 ± 2.11 vs 2.89 ± 1.88 Gy, p = 0.813; maximum dose to the optical pathway: 2.65 ± 4.18 vs 2.44 ± 4.03 Gy, p = 0.195; and maximum dose to the eye lens: 0.33 ± 0.73 vs 0.33 ± 0.53 Gy, p = 0.970. The values of the peripheral dose falloff were (plan B vs plan A) as follows—V12: 5.98 ± 4.95 vs 6.06 ± 4.92 cm{sup 3}, p = 0.622, and CI 50%: 6.08 ± 2.77 vs 6.28 ± 3.01, p = 0.119. The off-target isocenter solution resulted in dosimetrically comparable plans as the center-target isocenter technique, by avoiding the risk of gantry-couch collision during the cone beam computed tomography (CBCT) acquisition.« less

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

[In vivo study of the pharmacokinetic interaction of afobazole and losartan (cytochrome CYP2C9 substrate)].

PubMed

Gribakina, O G; Kolyvanov, G B; Litvin, A A; Zherdev, V P; Seredin, S B

2013-01-01

The influence of afobazole on isoenzyme CYP2C9 production in rats was studied using losartan as the marker drug. Single dose of losartan was administered orally without afobazole in a dose of 30 mg/kg and in the same single (30 mg/kg) on the background of 3- and 4-day administration of afobazole in a dose of 5, 25, 75, 100, and 125 mg/kg. At 5 mg/kg (effective dose for anxiolytic effect), afobazole did not cause any induction/inhibition effect on CYP2C9 isoenzyme. A multiple increase in afobazole dose was manifested by a moderate induction effect. The maximum induction effect of afobazole was achieved in a dose of 75 mg/kg. At doses above 75 mg/kg, the induction effect of afobazole was less pronounced.

Absolute dose determination in high-energy electron beams: Comparison of IAEA dosimetry protocols

PubMed Central

Sathiyan, S.; Ravikumar, M.

2008-01-01

In this study, absorbed doses were measured and compared for high-energy electrons (6, 9, 12, 16, and 20 MeV) using International Atomic Energy Agency (IAEA), Technical Reports Series No. 277 (TRS), TRS 381, and TRS 398 dosimetry protocols. Absolute dose measurements were carried out using FC65-G Farmer chamber and Nordic Association of Clinical Physicists (NACP) parallel plate chamber with DOSE1 electrometer in WP1-D water phantom for reference field size of 15 × 15 cm2 at 100 cm source-to-surface distance. The results show that the difference between TRS 398 and TRS 381 was about 0.24% to 1.3% depending upon the energy, and the maximum difference between TRS 398 and TRS 277 was 1.5%. The use of cylindrical chamber in electron beam gives the maximum dose difference between the TRS 398 and TRS 277 in the order of 1.4% for energies above 10 MeV (R50 > 4 g/cm2). It was observed that the accuracy of dose estimation was better with the protocols based on the water calibration procedures, as no conversion quantities are involved for conversion of dose from air to water. The cross-calibration procedure of parallel plate chamber with high-energy electron beams is recommended as it avoids pwall correction factor entering into the determination of kQ,Qo. PMID:19893700

Nebulised fenoterol compared with metered aerosol.

PubMed Central

Melville, C; Phelan, P D; Landau, L I

1985-01-01

The effect of nebulised fenoterol was compared with that of a similar dose administered by metered aerosol in 14 children, aged 7 to 17 years with moderately severe asthma. The initial response to fenoterol delivered by metered aerosol or nebuliser was the same, but a second dose by nebuliser after a dose by metered aerosol produced maximum potential bronchodilatation which was not seen when a second dose by metered aerosol was given after that by nebuliser. Administration of a bronchodilator by nebuliser does seem advantageous in the treatment of some children. PMID:3985659

Location Modification Factors for Potential Dose Estimation

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

Snyder, Sandra F.; Barnett, J. Matthew

2017-01-01

A Department of Energy facility must comply with the National Emission Standard for Hazardous Air Pollutants for radioactive air emissions. The standard is an effective dose of less than 0.1 mSv yr-1 to the maximum public receptor. Additionally, a lower dose level may be assigned to a specific emission point in a State issued permit. A method to efficiently estimate the expected dose for future emissions is described. This method is most appropriately applied to a research facility with several emission points with generally low emission levels of numerous isotopes.

The methodology study of time accelerated irradiation of elastomers

NASA Astrophysics Data System (ADS)

Ito, Masayuki

2005-07-01

The article studied the methods how to shorten the irradiation time by increasing dose rate without changing the relationship between dose versus properties of degraded samples. The samples used were nine kinds of EPDM which have different compounding formula. The different dose of Co-γ ray was exposed to the samples. The maximum dose was 2 MGy. The reference condition to be compared with two short time test conditions is irradiation of 0.33 kGy/h at room temperature. Two methods shown below were studied as the time-accelerate irradiation conditions.

Escalation to High Dose Defibrotide in Patients with Hepatic Veno-Occlusive Disease

PubMed Central

Triplett, Brandon M.; Kuttab, Hani I.; Kang, Guolian; Leung, Wing

2015-01-01

Hepatic veno-occlusive disease (VOD) is a serious complication of high-dose chemotherapy regimens, such as those utilized in hematopoietic cell transplantation recipients. Defibrotide is considered a safe and effective treatment when dosed at 25 mg/kg/day. However, patients who develop VOD still have increased mortality despite the use of defibrotide. Data are limited on the use of doses above 60 mg/kg/day for persistent VOD. In this prospective clinical trial, 34 patients received escalating doses of defibrotide. For patients with persistent VOD despite doses of 60 mg/kg/day, doses were increased to a maximum of 110 mg/kg/day. There was no observed increase in toxicity until doses rose beyond 100 mg/kg/day. Patients receiving doses between 10–100 mg/kg/day experienced an average of 3 bleeding episodes per 100 days of treatment, while those receiving doses >100 mg/kg/day experienced 13.2 bleeding episodes per 100 days (p=0.008). Moreover, dose reductions due to toxicity were needed at doses of 110 mg/kg/day more often than at lower doses. Defibrotide may be safely escalated to doses well above the current standard without an increase in bleeding risk. However, the efficacy of this dose escalation strategy remains unclear, as outcomes were similar to published cohorts of patients receiving standard doses of defibrotide for VOD. PMID:26278046

[Characterization of a diode system for in vivo dosimetry with electron beams].

PubMed

Ragona, R; Rossetti, V; Lucio, F; Anglesio, S; Giglioli, F R

2001-10-01

Current quality assurance regulation stresses the basic role of in vivo dosimetry. Our study evaluates the usefulness and reliability of semiconductor diodes in determining the electron absorbed dose. P-type EDE semiconductor detectors were irradiated with electron beams of different energies produced by a CGR Saturn Therac 20. The diode and ionization chamber response were compared, and effect of energy value, collimator opening, source skin distance and gantry angle on diode response was studied. Measurements show a maximum increment of about 20% in diode response increasing the beam energy (6-20 MeV). The response also increases with: collimator opening, reaching 5% with field sizes larger than 10x10 cm2 (with the exception of 20 MeV energy); SSD increase (with a maximum of 8% for 20 MeV); transversal gantry incidence, compared with the diode longitudinal axis; it does not affect the response in the interval of +/- 45 degrees. Absorbed dose attenuation at dmax, due to the presence of diode on the axis of the beam as a function of electron energy was also determined : the maximum attenuation value is 15% in 6 MeV electron beams. A dose calculation algorithm, taking into account diode response dependence was outlined. In vivo dosimetry was performed in 92 fields for 80 patients, with an agreement of +/-4 % (1 SD) between prescribed and measured dose. It is possible to use the EDE semiconductor detectors on a quality control program of dose delivery for electron beam therapy, but particular attention should be paid to the beam incidence angle and diode dose attenuation.

Method of predicting the mean lung dose based on a patient's anatomy and dose-volume histograms

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

Zawadzka, Anna, E-mail: a.zawadzka@zfm.coi.pl; Nesteruk, Marta; Department of Radiation Oncology, University Hospital Zurich and University of Zurich, Zurich

The aim of this study was to propose a method to predict the minimum achievable mean lung dose (MLD) and corresponding dosimetric parameters for organs-at-risk (OAR) based on individual patient anatomy. For each patient, the dose for 36 equidistant individual multileaf collimator shaped fields in the treatment planning system (TPS) was calculated. Based on these dose matrices, the MLD for each patient was predicted by the homemade DosePredictor software in which the solution of linear equations was implemented. The software prediction results were validated based on 3D conformal radiotherapy (3D-CRT) and volumetric modulated arc therapy (VMAT) plans previously prepared formore » 16 patients with stage III non–small-cell lung cancer (NSCLC). For each patient, dosimetric parameters derived from plans and the results calculated by DosePredictor were compared. The MLD, the maximum dose to the spinal cord (D{sub max} {sub cord}) and the mean esophageal dose (MED) were analyzed. There was a strong correlation between the MLD calculated by the DosePredictor and those obtained in treatment plans regardless of the technique used. The correlation coefficient was 0.96 for both 3D-CRT and VMAT techniques. In a similar manner, MED correlations of 0.98 and 0.96 were obtained for 3D-CRT and VMAT plans, respectively. The maximum dose to the spinal cord was not predicted very well. The correlation coefficient was 0.30 and 0.61 for 3D-CRT and VMAT, respectively. The presented method allows us to predict the minimum MLD and corresponding dosimetric parameters to OARs without the necessity of plan preparation. The method can serve as a guide during the treatment planning process, for example, as initial constraints in VMAT optimization. It allows the probability of lung pneumonitis to be predicted.« less

TU-AB-201-06: Evaluation of Electromagnetically Guided High- Dose Rate Brachytherapy for Ablative Treatment of Lung Metastases

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

Pinkham, D.W.; Shultz, D.; Loo, B.W.

Purpose: The advent of electromagnetic navigation bronchoscopy has enabled minimally invasive access to peripheral lung tumors previously inaccessible by optical bronchoscopes. As an adjunct to Stereotactic Ablative Radiosurgery (SABR), implantation of HDR catheters can provide focal treatments for multiple metastases and sites of retreatments. The authors evaluate a procedure to deliver ablative doses via Electromagnetically-Guided HDR (EMG-HDR) to lung metastases, quantify the resulting dosimetry, and assess its role in the comprehensive treatment of lung cancer. Methods: A retrospective study was conducted on ten patients, who, from 2009 to 2011, received a hypo-fractionated SABR regimen with 6MV VMAT to lesions inmore » various lobes ranging from 1.5 to 20 cc in volume. A CT visible pathway was delineated for EM guided placement of an HDR applicator (catheter) and dwell times were optimized to ensure at least 98% prescription dose coverage of the GTV. Normal tissue doses were calculated using inhomogeneity corrections via a grid-based Boltzmann solver (Acuros-BV-1.5.0). Results: With EMG-HDR, an average of 83% (+/−9% standard deviation) of each patient’s GTV received over 200% of the prescription dose, as compared to SABR where the patients received an average maximum dose of 125% (+/−5%). EMG-HDR enabled a 59% (+/−12%) decrease in the aorta maximum dose, a 63% (+/−26%) decrease in the spinal cord max dose, and 57% (+/−23%) and 70% (+/−17%) decreases in the volume of the body receiving over 50% and 25% of the prescription dose, respectively. Conclusion: EMG-HDR enables delivery of higher ablative doses to the GTV, while concurrently reducing surrounding normal tissue doses. The single catheter approach shown here is limited to targets smaller than 20 cc. As such, the technique enables ablation of small lesions and a potentially safe and effective retreatment option in situations where external beam utility is limited by normal tissue constraints.« less

Prospective, open, multicentre Phase I/II trial to assess safety and efficacy of neoadjuvant radiochemotherapy with docetaxel and cisplatin for esophageal carcinoma.

PubMed

Ma, Hong-Bing; Di, Zheng-Li; Wen, Jiao; Ke, Yue; Sun, Xiaodong; Ren, Juan

2015-02-01

Esophageal squamous cell carcinoma is increasingly treated with trimodality therapy. The objective of this Phase I/II clinical study is to assess the efficacy and safety of neoadjuvant radiochemotherapy with docetaxel and cisplatin and radiotherapy in patients with esophagectomy for locally advanced squamous cell carcinoma of the esophagus with neoadjuvant chemoradiotherapy. Patients with esophageal squamous cell carcinoma received radiochemotherapy (50 Gy/25 fractions during Weeks 1-5) using a three-dimensional conformal radiation therapy or intensity-modulated radiation therapy technique together with weekly docetaxel (20 mg/m(2) at dose levels 1 and 2, 25 mg/m(2) at dose level 3 on Weeks 1-5) and cisplatin (30 mg/m(2) at dose level 1, 40 mg/m(2) at dose levels 2 and 3 on Weeks 1-5) from January 2009 to December 2011. The dose-limiting toxicities and maximum tolerated dose were the primary endpoints and overall response rate and progression-free survival were the secondary endpoints. Over this timeframe, a total of 49 patients completed trimodality therapy. Thirteen patients were treated at dose level 1, 21 patients at dose level 2 and 15 patients at dose level 3.The maximum tolerated dose for docetaxel was 20 mg/m(2) and cisplatin 40 mg/m(2). The complete response or partial response was observed in 26.5% (13/49) of patients. Thirty-four patients (69.4%) were treated with neoadjuvant radiochemotherapy followed by surgical resection. The median progression-free survival and median overall survival for all patients (n = 49) were 8 and 17.2 months, respectively. The median overall survival was 27.5 months for patients treated at dose level 2. Neoadjuvant radiochemotherapy with docetaxel 20 mg/m(2) and cisplatin 40 mg/m(2) was effective and tolerable induction regimen in patients with esophageal tumors. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

SU-E-T-202: Impact of Monte Carlo Dose Calculation Algorithm On Prostate SBRT Treatments

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

Venencia, C; Garrigo, E; Cardenas, J

2014-06-01

Purpose: The purpose of this work was to quantify the dosimetric impact of using Monte Carlo algorithm on pre calculated SBRT prostate treatment with pencil beam dose calculation algorithm. Methods: A 6MV photon beam produced by a Novalis TX (BrainLAB-Varian) linear accelerator equipped with HDMLC was used. Treatment plans were done using 9 fields with Iplanv4.5 (BrainLAB) and dynamic IMRT modality. Institutional SBRT protocol uses a total dose to the prostate of 40Gy in 5 fractions, every other day. Dose calculation is done by pencil beam (2mm dose resolution), heterogeneity correction and dose volume constraint (UCLA) for PTV D95%=40Gy andmore » D98%>39.2Gy, Rectum V20Gy<50%, V32Gy<20%, V36Gy<10% and V40Gy<5%, Bladder V20Gy<40% and V40Gy<10%, femoral heads V16Gy<5%, penile bulb V25Gy<3cc, urethra and overlap region between PTV and PRV Rectum Dmax<42Gy. 10 SBRT treatments plans were selected and recalculated using Monte Carlo with 2mm spatial resolution and mean variance of 2%. DVH comparisons between plans were done. Results: The average difference between PTV doses constraints were within 2%. However 3 plans have differences higher than 3% which does not meet the D98% criteria (>39.2Gy) and should have been renormalized. Dose volume constraint differences for rectum, bladder, femoral heads and penile bulb were les than 2% and within tolerances. Urethra region and overlapping between PTV and PRV Rectum shows increment of dose in all plans. The average difference for urethra region was 2.1% with a maximum of 7.8% and for the overlapping region 2.5% with a maximum of 8.7%. Conclusion: Monte Carlo dose calculation on dynamic IMRT treatments could affects on plan normalization. Dose increment in critical region of urethra and PTV overlapping region with PTV could have clinical consequences which need to be studied. The use of Monte Carlo dose calculation algorithm is limited because inverse planning dose optimization use only pencil beam.« less

SU-E-T-346: Effect of Jaw Position On Dose to Critical Structures in 3-D Conformal Radiotherapy Treatment of Pancreatic Cancer

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

Paudel, N; Han, E; Liang, X

Purpose: Three-dimensional conformal therapy remains a valid and widely used modality for pancreatic radiotherapy treatment. It usually meets dose constraints on critical structures. However, careful positioning of collimation jaws can reduce dose to the critical structures. Here we investigate the dosimetric effect of jaw position in MLC-based 3-D conformal treatment planning on critical structures. Methods: We retrospectively selected seven pancreatic cancer patients treated with 3-D conformal radiotherapy. We started with treatment plans (Varian Truebeam LINAC, Eclipse TPS, AAA, 18MV) having both x and y jaws aligned with the farthest extent of the block outline (8mm around PTV). Then we subsequentlymore » moved either both x-jaws or all x and y jaws outwards upto 3 cm in 1 cm increments and investigated their effect on average and maximum dose to neighboring critical structures keeping the same coverage to treatment volume. Results: Lateral displacement of both x-jaws by 1cm each increased kidney and spleen mean dose by as much as 1.7% and 1.3% respectively and superior inferior displacement increased liver, right kidney, stomach and spleen dose by as much as 2.1%, 2%, 5.2% and 1.6% respectively. Displacement of all x and y-jaws away by 1cm increased the mean dose to liver, right kidney, left kidney, bowels, cord, stomach and spleen by as much as 4.9%, 5.9%, 2.1%, 2.8%, 7.4%, 10.4% and 4.2% respectively. Percentage increase in mean dose due to 2 and 3cm jaw displacement increased almost linearly with the displaced distance. Changes in maximum dose were much smaller (mostly negligible) than the changes in mean dose. Conclusion: Collimation jaw position affects dose mostly to critical structures adjacent to it. Though treatment plans with MLCs conforming the block margin usually meet dose constraints to critical structures, keeping jaws all the way in, to the edge of the block reduces dose to the critical structures during radiation treatment.« less

An updated dose assessment for resettlement options at Bikini Atoll--a U.S. nuclear test site.

PubMed

Robison, W L; Bogen, K T; Conrado, C L

1997-07-01

On 1 March 1954, a nuclear weapon test, code-named BRAVO, conducted at Bikini Atoll in the northern Marshall Islands contaminated the major residence island. There has been a continuing effort since 1977 to refine dose assessments for resettlement options at Bikini Atoll. Here we provide a radiological dose assessment for the main residence island, Bikini, using extensive radionuclide concentration data derived from analysis of food crops, ground water, cistern water, fish and other marine species, animals, air, and soil collected at Bikini Island as part of our continuing research and monitoring program that began in 1978. The unique composition of coral soil greatly alters the relative contribution of 137Cs and 90Sr to the total estimated dose relative to expectations based on North American and European soils. Without counter measures, 137Cs produces 96% of the estimated dose for returning residents, mostly through uptake from the soil to terrestrial food crops but also from external gamma exposure. The doses are calculated assuming a resettlement date of 1999. The estimated maximum annual effective dose for current island conditions is 4.0 mSv when imported foods, which are now an established part of the diet, are available. The 30-, 50-, and 70-y integral effective doses are 91 mSv, 130 mSv, and 150 mSv, respectively. A detailed uncertainty analysis for these dose estimates is presented in a companion paper in this issue. We have evaluated various countermeasures to reduce 137Cs in food crops. Treatment with potassium reduces the uptake of 137Cs into food crops, and therefore the ingestion dose, to about 5% of pretreatment levels and has essentially no negative environmental consequences. We have calculated the dose for the rehabilitation scenario where the top 40 cm of soil is removed in the housing and village area, and the rest of the island is treated with potassium fertilizer; the maximum annual effective dose is 0.41 mSv and the 30-, 50-, and 70-y integral effective doses are 9.8 mSv, 14 mSv, and 16 mSv, respectively.

SU-E-J-228: MRI-Based Planning: Dosimetric Feasibility of Dose Painting for ADCDefined Intra-Prostatic Tumor

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

Chen, X; Dalah, E; Prior, P

Purpose: Apparent diffusion coefficient (ADC) map may help to delineate the gross tumor volume (GTV) in prostate gland. Dose painting with external beam radiotherapy for GTV might increase the local tumor control. The purpose of this study is to explore the maximum boosting dose on GTV using VMAT without sacrificing sparing of organs at risk (OARs) in MRI based planning. Methods: VMAT plans for 5 prostate patients were generated following the commonly used dose volume (DV) criteria based on structures contoured on T2 weighted MRI with bulk electron density assignment using electron densities derived from ICRU46. GTV for each patientmore » was manually delineated based on ADC maps and fused to T2-weighted image set for planning study. A research planning system with Monte Carlo dose engine (Monaco, Elekta) was used to generate the VMAT plans with boosting dose on GTV gradually increased from 85Gy to 100Gy. DV parameters, including V(boosting-dose) (volume covered by boosting dose) for GTV, V75.6Gy for PTV, V45Gy, V70Gy, V72Gy and D1cc (Maximum dose to 1cc volume) for rectum and bladder, were used to measure plan quality. Results: All cases achieve at least 99.0% coverage of V(boosting-dose) on GTV and 95% coverage of V75.6Gy to the PTV. All the DV criteria, V45Gy≤50% and V70Gy≤15% for bladder and rectum, D1cc ≤77Gy (Rectum) and ≤80Gy (Bladder), V72Gy≤5% (rectum and bladder) were maintained when boosting GTV to 95Gy for all cases studied. Except for two patients, all the criteria were also met when the boosting dose goes to 100Gy. Conclusion: It is dosimetrically feasible safe to boost the dose to at least 95Gy to ADC defined GTV in prostate cancer using MRI guided VMAT delivery. Conclusion: It is dosimetrically feasible safe to boost the dose to at least 95Gy to ADC defined GTV in prostate cancer using MRI guided VMAT delivery. This research is partially supported by Elekta Inc.« less

Real-time eye lens dose monitoring during cerebral angiography procedures.

PubMed

Safari, M J; Wong, J H D; Kadir, K A A; Thorpe, N K; Cutajar, D L; Petasecca, M; Lerch, M L F; Rosenfeld, A B; Ng, K H

2016-01-01

To develop a real-time dose-monitoring system to measure the patient's eye lens dose during neuro-interventional procedures. Radiation dose received at left outer canthus (LOC) and left eyelid (LE) were measured using Metal-Oxide-Semiconductor Field-Effect Transistor dosimeters on 35 patients who underwent diagnostic or cerebral embolization procedures. The radiation dose received at the LOC region was significantly higher than the dose received by the LE. The maximum eye lens dose of 1492 mGy was measured at LOC region for an AVM case, followed by 907 mGy for an aneurysm case and 665 mGy for a diagnostic angiography procedure. Strong correlations (shown as R(2)) were observed between kerma-area-product and measured eye doses (LOC: 0.78, LE: 0.68). Lateral and frontal air-kerma showed strong correlations with measured dose at LOC (AKL: 0.93, AKF: 0.78) and a weak correlation with measured dose at LE. A moderate correlation was observed between fluoroscopic time and dose measured at LE and LOC regions. The MOSkin dose-monitoring system represents a new tool enabling real-time monitoring of eye lens dose during neuro-interventional procedures. This system can provide interventionalists with information needed to adjust the clinical procedure to control the patient's dose. Real-time patient dose monitoring helps interventionalists to monitor doses. Strong correlation was observed between kerma-area-product and measured eye doses. Radiation dose at left outer canthus was higher than at left eyelid.

Dose-volume metrics and their relation to memory performance in pediatric brain tumor patients: A preliminary study.

PubMed

Raghubar, Kimberly P; Lamba, Michael; Cecil, Kim M; Yeates, Keith Owen; Mahone, E Mark; Limke, Christina; Grosshans, David; Beckwith, Travis J; Ris, M Douglas

2018-06-01

Advances in radiation treatment (RT), specifically volumetric planning with detailed dose and volumetric data for specific brain structures, have provided new opportunities to study neurobehavioral outcomes of RT in children treated for brain tumor. The present study examined the relationship between biophysical and physical dose metrics and neurocognitive ability, namely learning and memory, 2 years post-RT in pediatric brain tumor patients. The sample consisted of 26 pediatric patients with brain tumor, 14 of whom completed neuropsychological evaluations on average 24 months post-RT. Prescribed dose and dose-volume metrics for specific brain regions were calculated including physical metrics (i.e., mean dose and maximum dose) and biophysical metrics (i.e., integral biological effective dose and generalized equivalent uniform dose). We examined the associations between dose-volume metrics (whole brain, right and left hippocampus), and performance on measures of learning and memory (Children's Memory Scale). Biophysical dose metrics were highly correlated with the physical metric of mean dose but not with prescribed dose. Biophysical metrics and mean dose, but not prescribed dose, correlated with measures of learning and memory. These preliminary findings call into question the value of prescribed dose for characterizing treatment intensity; they also suggest that biophysical dose has only a limited advantage compared to physical dose when calculated for specific regions of the brain. We discuss the implications of the findings for evaluating and understanding the relation between RT and neurocognitive functioning. © 2018 Wiley Periodicals, Inc.

Dose in bone and tissue near bone-tissue interface from electron beam.

PubMed

Shiu, A S; Hogstrom, K R

1991-08-01

This work has quantitatively studied the variation of dose both within bone and in unit density tissue near bone-tissue interfaces. Dose upstream of a bone-tissue interface is increased because of an increase in the backscattered electrons from the bone. The magnitude of this effect was measured using a thin parallel-plate ionization chamber upstream of a polymethyl methacrylate (PMMA)-hard bone interface. The electron backscatter factor (EBF) increased rapidly with bone thickness until a full EBF was achieved. This occurred at approximately 3.5 mm at 2 MeV and 6 mm at 13.1 MeV. The full EBF at the interface ranged from approximately 1.018 at 13.1 MeV to 1.05 at 2 MeV. It was also observed that the EBF had a dependence on the energy spectrum at the interface. The penetration of the backscattered electrons in the upstream direction of PMMA was also measured. The dose penetration fell off rapidly in the upstream direction of the interface. Dose enhancement to unit density tissue in bone was measured for an electron beam by placing thermoluminescent dosimeters (TLDs) in a PMMA-bone-PMMA phantom. The maximum dose enhancement in bone was approximately 7% of the maximum dose in water. However, the pencil-beam algorithm of Hogstrom et al. predicted an increase of only 1%, primarily owing to the inverse-square correction. Film was also used to measure the dose enhancement in bone. The film plane was aligned either perpendicular or parallel to the central axis of the beam. The film data indicated that the maximum dose enhancement in bone was approximately 8% for the former film alignment (which was similarly predicted by the TLD measurements) and 13% for the latter film alignment. These results confirm that the X ray film is not suitable to be irritated "edge on" in an inhomogeneous phantom without making perturbation corrections resulting from the film acting as a long narrow inhomogeneous cavity within the bone. In addition, the results give the radiotherapist a basis for clinical judgment when electron beams are used to treat lesions behind bone or near bony structures. We feel these data enhance the ability to recognize the shortcomings of the current dose calculation algorithm used clinically.

SU-F-T-131: No Increase in Biological Effectiveness Through Collimator Scattered Low Energy Protons

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

Matsuura, T; Takao, S; Matsuzaki, Y

Purpose: To reduce the lateral penumbra of low-energy proton beams, brass collimators are often used in spot-scanning proton therapy (SSPT). This study investigates the increase in biological effectiveness through collimator scattered protons in SSPT. Methods: The SSPT system of the Hokkaido University Hospital Proton Beam Therapy Center, which consists of a scanning nozzle, a 2-cm thick brass collimator, and a 4-cm thick energy absorber, was simulated with our validated Geant4 Monte Carlo code (ver. 9.3). A water phantom was irradiated with proton pencil beams of 76, 110, and 143 MeV. The tested collimator opening areas (COA) were 5×5, 10×10, andmore » 15×15 cm{sup 2}. Comparisons were made among the dose-averaged LET values of protons that hit the collimators (LETDColl), protons that did not hit the collimators (LETDNoColl), and all protons (LETDTotal). X-ray equivalent doses (Deq) were calculated using the linear-quadratic model with LETDNoColl and LETDTotal, and their maximum difference was determined over regions where the physical dose was greater than 10% of the peak dose of 2 Gy. Results: The ratio of the dose contribution of collimator scattered protons to that of all protons, defined as λ, was large at high proton energies and large COAs. The maximum λ value ranged from 3% (76 MeV, 5×5 cm{sup 2}) to 29% (143 MeV, 15×15 cm{sup 2}). Moreover, a large difference between LETDColl and LETDNoColl was only found in regions where λ was below 20% (ΔLETD > 2 keV/µm) and 8% (ΔLETD > 5 keV/µm). Consequently, the maximum difference between LETDNoColl and LETDTotal was as small as 0.8 keV/µm in all simulated voxels, and the difference of Deq reached a maximum of 1.5% that of the peak dose obtained at the water surface with a 76 MeV beam. Conclusion: Although collimator scattered protons have high LET, they only increase the physical dose, not the biological effectiveness.« less

Preventive sparing of spinal cord and brain stem in the initial irradiation of locally advanced head and neck cancers

PubMed Central

Piras, Sara; Porru, Sergio; Massazza, Federica; Fadda, Giuseppina; Solla, Ignazio; Piras, Denise; Deidda, Maria Assunta; Amichetti, Maurizio; Possanzini, Marco

2014-01-01

Since reirradiation in recurrent head and neck patients is limited by previous treatment, a marked reduction of maximum doses to spinal cord and brain stem was investigated in the initial irradiation of stage III/IV head and neck cancers. Eighteen patients were planned by simultaneous integrated boost, prescribing 69.3 Gy to PTV1 and 56.1 Gy to PTV2. Nine 6 MV coplanar photon beams at equispaced gantry angles were chosen for each patient. Step‐and‐shoot IMRT was calculated by direct machine parameter optimization, with the maximum number of segments limited to 80. In the standard plan, optimization considered organs at risk (OAR), dose conformity, maximum dose <45 Gy to spinal cord and <50 Gy to brain stem. In the sparing plans, a marked reduction to spinal cord and brain stem were investigated, with/without changes in dose conformity. In the sparing plans, the maximum doses to spinal cord and brain stem were reduced from the initial values (43.5±2.2 Gy and 36.7±14.0 Gy), without significant changes on the other OARs. A marked difference (−15.9±1.9 Gy and −10.1±5.7 Gy) was obtained at the expense of a small difference (−1.3%±0.9%) from initial PTV195% coverage (96.6%±0.9%). Similar difference (−15.7±2.2 Gy and −10.2±6.1 Gy) was obtained compromising dose conformity, but unaffecting PTV195% and with negligible decrease in PTV295% (−0.3%±0.3% from the initial 98.3%±0.8%). A marked spinal cord and brain stem preventive sparing was feasible at the expense of a decrease in dose conformity or slightly compromising target coverage. A sparing should be recommended in highly recurrent tumors, to make potential reirradiation safer. PACS number: 87.55.D PMID:24423836

SU-F-18C-11: Diameter Dependency of the Radial Dose Distribution in a Long Polyethylene Cylinder

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

Bakalyar, D; McKenney, S; Feng, W

Purpose: The radial dose distribution in the central plane of a long cylinder following a long CT scan depends upon the diameter and composition of the cylinder. An understanding of this behavior is required for determining the spatial average of the dose in the central plane. Polyethylene, the material for construction of the TG200/ICRU phantom (30 cm in diameter) was used for this study. Size effects are germane to the principles incorporated in size specific dose estimates (SSDE); thus diameter dependency was explored as well. Method: ssuming a uniform cylinder and cylindrically symmetric conditions of irradiation, the dose distribution canmore » be described using a radial function. This function must be an even function of the radial distance due to the conditions of symmetry. Two effects are accounted for: The direct beam makes its weakest contribution at the center while the contribution due to scatter is strongest at the center and drops off abruptly at the outer radius. An analytic function incorporating these features was fit to Monte Carlo results determined for infinite polyethylene cylinders of various diameters. A further feature of this function is that it is integrable. Results: Symmetry and continuity dictate a local extremum at the center which is a minimum for the larger sizes. The competing effects described above can Resultin an absolute maximum occurring between the center and outer edge of the cylinders. For the smallest cylinders, the maximum dose may occur at the center. Conclusion: An integrable, analytic function can be used to characterize the radial dependency of dose for cylindrical CT phantoms of various sizes. One use for this is to help determine average dose distribution over the central cylinder plane when equilibrium dose has been reached.« less

Pre-operative combined 5-FU, low dose leucovorin, and sequential radiation therapy for unresectable rectal cancer

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

Minsky, B.D.; Cohen, A.M.; Kemeny, N.

1993-04-02

The authors performed a Phase 1 trial to determine the maximum tolerated dose of combined pre-operative radiation (5040 cGy) and 2 cycles (bolus daily [times] 5) of 5-FU and low dose LV (20 mg/m2), followed by surgery and 10 cycles of post-operative LV/5-FU in patients with unresectable primary or recurrent rectal cancer. Twelve patients were entered. The initial dose of 5-FU was 325 mg/m2. 5-FU was to be escalated while the LV remained constant at 20 mg/m2. Chemotherapy began on day 1 and radiation on day 8. The post-operative chemotherapy was not dose escalated; 5-FU: 425 mg/m2 and LV: 20more » mg/m2. The median follow-up was 14 months (7--16 months). Following pre-operative therapy, the resectability rate with negative margins was 91% and the pathologic complete response rate was 9%. For the combined modality segment (preoperative) the incidence of any grade 3+ toxicity was diarrhea: 17%, dysuria: 8%, mucositis: 8%, and erythema: 8%. The median nadir counts were WBC: 3.1, HGB: 8.8, and PLT: 153000. The maximum tolerated dose of 5-FU for pre-operative combined LV/5-FU/RT was 325 mg/m2 with no escalation possible. Therefore, the recommended dose was less than 325 mg/m2. Since adequate doses of 5-FU to treat systemic disease could not be delivered until at least 3 months (cycle 3) following the start of therapy, the authors do not recommend that this 5-FU, low dose LV, and sequential radiation therapy regimen be used as presently designed. However, given the 91% resectability rate they remain encouraged with this approach. 31 refs., 1 fig., 2 tabs.« less

Calculation of absorbed dose and biological effectiveness from photonuclear reactions in a bremsstrahlung beam of end point 50 MeV.

PubMed

Gudowska, I; Brahme, A; Andreo, P; Gudowski, W; Kierkegaard, J

1999-09-01

The absorbed dose due to photonuclear reactions in soft tissue, lung, breast, adipose tissue and cortical bone has been evaluated for a scanned bremsstrahlung beam of end point 50 MeV from a racetrack accelerator. The Monte Carlo code MCNP4B was used to determine the photon source spectrum from the bremsstrahlung target and to simulate the transport of photons through the treatment head and the patient. Photonuclear particle production in tissue was calculated numerically using the energy distributions of photons derived from the Monte Carlo simulations. The transport of photoneutrons in the patient and the photoneutron absorbed dose to tissue were determined using MCNP4B; the absorbed dose due to charged photonuclear particles was calculated numerically assuming total energy absorption in tissue voxels of 1 cm3. The photonuclear absorbed dose to soft tissue, lung, breast and adipose tissue is about (0.11-0.12)+/-0.05% of the maximum photon dose at a depth of 5.5 cm. The absorbed dose to cortical bone is about 45% larger than that to soft tissue. If the contributions from all photoparticles (n, p, 3He and 4He particles and recoils of the residual nuclei) produced in the soft tissue and the accelerator, and from positron radiation and gammas due to induced radioactivity and excited states of the nuclei, are taken into account the total photonuclear absorbed dose delivered to soft tissue is about 0.15+/-0.08% of the maximum photon dose. It has been estimated that the RBE of the photon beam of 50 MV acceleration potential is approximately 2% higher than that of conventional 60Co radiation.

Phase 1 trial of irinotecan plus BCNU in patients with progressive or recurrent malignant glioma1

PubMed Central

Quinn, Jennifer A.; Reardon, David A.; Friedman, Allan H.; Rich, Jeremy N.; Sampson, John H.; Vredenburgh, James; Gururangan, Sridharan; Provenzale, James M.; Walker, Amy; Schweitzer, Holly; Bigner, Darell D.; Tourt-Uhlig, Sandra; Herndon, James E.; Affronti, Mary Lou; Jackson, Susanne; Allen, Deborah; Ziegler, Karen; Bohlin, Cindy; Lentz, Christy; Friedman, Henry S.

2004-01-01

Irinotecan is a topoisomerase I inhibitor previously shown to be active in the treatment of malignant glioma. We now report the results of a phase 1 trial of irinotecan plus BCNU, or 1,3-bis(2-chloroethyl)-1-nitrosourea, for patients with recurrent or progressive MG. Irinotecan dose escalation occurred independently within 2 strata: patients receiving enzyme-inducing antiepileptic drugs (EIAEDs) and patients not receiving EIAEDs. BCNU was administered at a dose of 100 mg/m2 over 1 h every 6 weeks on the same day as the first irinotecan dose was administered. Irinotecan was administered intravenously over 90 min once weekly. Treatment cycles consisted of 4 weekly administrations of irinotecan followed by a 2-week rest with dose escalation in cohorts of 3 to 6 patients. Seventy-three patients were treated, including 49 patients who were on EIAEDs and 24 who were not on EIAEDs. The maximum tolerated dose for patients not on EIAEDs was 125 mg/m2. The maximum tolerated dose for patients on EIAEDs was 225 mg/m2. Dose-limiting toxicity was evenly distributed among the following organ systems: pulmonary, gastrointestinal, cardiovascular, neurologic, infectious, and hematologic, without a clear predominance of toxicity involving any one organ system. There was no evidence of increasing incidence of toxicity involving one organ system as irinotecan dose was escalated. On the basis of these results, we conclude that the recommended doses of irinotecan for a phase 2 clinical trial when given in combination with BCNU (100 mg/m2) are 225 mg/m2 for patients on EIAEDs and 125 mg/m2 for patients not on EIAEDs. PMID:15134629

[Decision process of Notification Value by the Dose Index Registry system in X-ray computed tomography].

PubMed

Shinozaki, Masafumi; Muramatsu, Yoshihisa; Sasaki, Toru

2014-01-01

A new technical standard for X-ray computed tomography (CT) has been published by the National Electrical Manufacturers Association (NEMA) that allows the Alert Value and Notification Value for cumulative dose to be configurable by CT systems operators in conjunction with the XR-25 (Dose check) standard. In this study, a decision method of the Notification Values for reducing the radiation dose was examined using the dose index registry (DIR) system, during 122 continuous days from August 1, 2012 to November 30, 2012. CT images were obtained using the Discovery CT 750HD (GE Healthcare) and the dose index was calculated using the DoseWatch DIR system. The CT dose index-volume (CTDIvol) and dose-length product (DLP) were output from the DIR system in comma-separated value (CSV) file format for each examination protocol. All data were shown as a schematic boxplot using statistical processing software. The CTDIvol of a routine chest examination showed the following values (maximum: 23.84 mGy; minimum: 2.55 mGy; median: 7.60 mGy; 75% tile: 10.01 mGy; 25% tile: 6.54 mGy). DLP showed the following values (maximum: 944.56 mGy·cm; minimum: 97.25 mGy·cm; median: 307.35 mGy·cm; 75% tile: 406.87 mGy·cm; 25% tile: 255.75 mGy·cm). These results indicate that the 75% tile of CTDIvol and DLP as an initial value proved to be safe and efficient for CT examination and operation. We have thus established one way of determining the Notification Value from the output of the DIR system. Transfer back to the protocol of the CT and automated processing each numeric value in the DIR system is desired.

The DOT1L inhibitor pinometostat reduces H3K79 methylation and has modest clinical activity in adult acute leukemia.

PubMed

Stein, Eytan M; Garcia-Manero, Guillermo; Rizzieri, David A; Tibes, Raoul; Berdeja, Jesus G; Savona, Michael R; Jongen-Lavrenic, Mojca; Altman, Jessica K; Thomson, Blythe; Blakemore, Stephen J; Daigle, Scott R; Waters, Nigel J; Suttle, A Benjamin; Clawson, Alicia; Pollock, Roy; Krivtsov, Andrei; Armstrong, Scott A; DiMartino, Jorge; Hedrick, Eric; Löwenberg, Bob; Tallman, Martin S

2018-05-03

Pinometostat (EPZ-5676) is a first-in-class, small-molecule inhibitor of the histone methyltransferase DOT1L. In this phase 1 study, pinometostat was evaluated for safety and efficacy in adult patients with advanced acute leukemias, particularly those involving MLL rearrangements ( MLL-r ) resulting from 11q23 translocations. Fifty-one patients were enrolled into 6 dose escalation cohorts (n=26) and 2 expansion cohorts (n=25) at pinometostat doses of 54 and 90 mg/m 2 /day by continuous intravenous infusion in 28-day cycles. As a maximum tolerated dose was not established in the dose escalation phase, the expansion doses were selected based upon safety and clinical response data combined with pharmacodynamic evidence of reduction in H3K79 methylation during dose escalation. Across all dose levels, plasma pinometostat concentrations increased in an approximately dose-proportional fashion, reaching an apparent steady state by 4-8 hours after infusion, and rapidly decreased following treatment cessation. The most common adverse events, of any cause, were fatigue (39%), nausea (39%), constipation (35%), and febrile neutropenia (35%). Overall, 2 patients, both with t(11;19), experienced complete remissions at 54 mg/m 2 /day by continuous intravenous infusion, demonstrating proof of concept for delivering clinically meaningful responses through targeting DOT1L using single agent pinometostat in MLL-r leukemia patients. Administration of pinometostat was generally safe with the maximum tolerated dose not being reached, although efficacy as a single agent was modest. This study demonstrates the therapeutic potential for targeting DOT1L in MLL-r leukemia and lays the groundwork for future combination approaches in this patient population. This clinical trial is registered at www.clinicaltrials.gov as no. NCT01684150. Copyright © 2018 American Society of Hematology.

The velocity of antihypertensive effect of losartan/hydrochlorothiazide and angiotensin II receptor blocker.

PubMed

Metoki, Hirohito; Ohkubo, Takayoshi; Kikuya, Masahiro; Asayama, Kei; Inoue, Ryusuke; Obara, Taku; Hirose, Takuo; Sato, Michihiro; Hashimoto, Takanao; Imai, Yutaka

2012-07-01

The hypotensive effect and the time to attain the maximum antihypertensive effect (stabilization time) of losartan/hydrochlorothiazide (HCTZ) combination therapy and therapy with a maximal dose of angiotensin II receptor blockers (ARBs) in patients who failed to achieve adequate blood pressure (BP) control on a medium-dose of ARBs were compared by analyzing exponential decay functions using daily serial morning home BP measurements. Essential hypertensive patients treated with a medium dose of ARB, in whom a target home SBP (135 mmHg) was not achieved, were randomized into two groups: a combination group (n = 110) and a maximal-dose ARB group (n = 111). The combination therapy provided additional reduction of 5.2 mmHg [95% confidence interval (CI) 1.8 to 8.5 mmHg, P = 0.003] in home SBP over the maximal-dose ARB therapy in 8 weeks after randomization. A greater reduction in the home SBP values was seen in the combination group than in the maximal-dose ARB group from the second day after randomization on the basis of a linear mixed model. The maximum antihypertensive effect and stabilization time for home SBP were 10.9 ± 5.0 mmHg and 7.3 ± 29.7 days, respectively, in the combination group, whereas the corresponding values in the maximal-dose ARB group were 7.9 ± 2.6  mmHg and 122.3 ± 42.7 days, respectively, on the basis of a nonlinear mixed model. Changing from a medium dose of ARB monotherapy to combination therapy was more effective in the reduction of home SBP and achieved goal BP more rapidly than increasing the ARB dose. Home BP measurement is a useful tool for characterizing the antihypertensive effects of drugs.

Cancer risk estimation caused by radiation exposure during endovascular procedure

NASA Astrophysics Data System (ADS)

Kang, Y. H.; Cho, J. H.; Yun, W. S.; Park, K. H.; Kim, H. G.; Kwon, S. M.

2014-05-01

The objective of this study was to identify the radiation exposure dose of patients, as well as staff caused by fluoroscopy for C-arm-assisted vascular surgical operation and to estimate carcinogenic risk due to such exposure dose. The study was conducted in 71 patients (53 men and 18 women) who had undergone vascular surgical intervention at the division of vascular surgery in the University Hospital from November of 2011 to April of 2012. It had used a mobile C-arm device and calculated the radiation exposure dose of patient (dose-area product, DAP). Effective dose was measured by attaching optically stimulated luminescence on the radiation protectors of staff who participates in the surgery to measure the radiation exposure dose of staff during the vascular surgical operation. From the study results, DAP value of patients was 308.7 Gy cm2 in average, and the maximum value was 3085 Gy cm2. When converted to the effective dose, the resulted mean was 6.2 m Gy and the maximum effective dose was 61.7 milliSievert (mSv). The effective dose of staff was 3.85 mSv; while the radiation technician was 1.04 mSv, the nurse was 1.31 mSv. All cancer incidences of operator are corresponding to 2355 persons per 100,000 persons, which deemed 1 of 42 persons is likely to have all cancer incidences. In conclusion, the vascular surgeons should keep the radiation protection for patient, staff, and all participants in the intervention in mind as supervisor of fluoroscopy while trying to understand the effects by radiation by themselves to prevent invisible danger during the intervention and to minimize the harm.

Safety evaluation of combination carboplatin and toceranib phosphate (Palladia) in tumour-bearing dogs: A phase I dose finding study.

PubMed

Wouda, R M; Hocker, S E; Higginbotham, M L

2018-03-01

Combining conventional cytotoxic maximum tolerated dose (MTD) chemotherapy with low-dose metronomic and/or anti-angiogenic agents is a exciting area of oncologic research. The objective of this study was to establish the MTD, safety and adverse event (AE) profile of 1 such drug combination. This prospective phase I dose-finding clinical trial assumed an open-label 3 + 3 cohort design. Client-owned dogs with 1 or more cytologically and/or histologically confirmed and macroscopically measurable, naive or recurrent, malignant tumours, were enrolled. No preference for tumour histology, grade or stage was expressed. Toceranib was administered at a dose of 2.75 mg kg -1 by mouth (PO) every other day (EOD), and carboplatin administered intravenously (IV) every 21 days at a starting dose of 200 mg m -2 . A total of 25% dose escalation was proposed for carboplatin, to a maximum of 300 mg m -2 . AEs were graded according to the Veterinary Cooperative Oncology Group's common terminology criteria for AEs (VCOG-CTCAE). Grade 3 haematologic or gastrointestinal AEs were nominated dose-limiting. Response to therapy was evaluated according to the VCOG's revised RECIST criteria. Eleven dogs were enrolled. Tumour histologies included sinonasal carcinoma, osteosarcoma, thyroid carcinoma, melanoma and apocrine gland anal sac adenocarcinoma. MTDs of carboplatin and toceranib were identified as 200 mg m -2 IV every 21 days and approximately 2.75 mg kg -1 PO EOD, respectively. The dose-limiting toxicity was neutropenia. Two dogs experienced a partial response, and 6 maintained stable disease. Combination carboplatin and toceranib chemotherapy was well-tolerated. Clinical benefit was observed in most cases. This protocol warrants further investigation in phase II/III trials. © 2017 John Wiley & Sons Ltd.

A Phase I Trial of High-Dose Lenalidomide and Melphalan as Conditioning for Autologous Stem Cell Transplantation in Relapsed or Refractory Multiple Myeloma.

PubMed

Mark, Tomer M; Guarneri, Danielle; Forsberg, Peter; Rossi, Adriana; Pearse, Roger; Perry, Arthur; Pekle, Karen; Tegnestam, Linda; Greenberg, June; Shore, Tsiporah; Gergis, Usama; Mayer, Sebastian; Van Besien, Koen; Ely, Scott; Jayabalan, David; Sherbenou, Daniel; Coleman, Morton; Niesvizky, Ruben

2017-06-01

Autologous stem cell transplantation (ASCT) conditioned with high-dose chemotherapy has long been established as the standard of care for eligible patients with newly diagnosed multiple myeloma. Despite recent therapeutic advances, high-dose melphalan (HDM) remains the chemotherapy regimen of choice in this setting. Lenalidomide (LEN) in combination with low-dose dexamethasone is recognized as a standard of care for patients with relapsed or refractory multiple myeloma (RRMM), and there is growing support for the administration of LEN as maintenance therapy post-ASCT. In view of the above, the present phase I clinical trial was designed to evaluate the safety and tolerability of high-dose LEN (HDLEN) in patients with RRMM, and to determine the maximum tolerated dose of HDLEN when added to HDM before ASCT. Despite administering HDLEN at doses of up to 350 mg/day, the maximum tolerated dose could not be determined, owing to an insufficient number of dose-limiting toxicities in the 21 patients enrolled in the trial. Conditioning with HDLEN plus HDM was associated with a favorable tolerability profile. Adverse events following ASCT were as expected with HDM. Median progression-free and overall survival were 10 months and 22 months, respectively, in this population of heavily pretreated patients. Our findings suggest that HDLEN in combination with HDM may offer significant potential as a conditioning regimen before ASCT in patients with RRMM. These preliminary findings are now being evaluated further in an ongoing phase II clinical trial. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Calculation of midplane dose for total body irradiation from entrance and exit dose MOSFET measurements.

PubMed

Satory, P R

2012-03-01

This work is the development of a MOSFET based surface in vivo dosimetry system for total body irradiation patients treated with bilateral extended SSD beams using PMMA missing tissue compensators adjacent to the patient. An empirical formula to calculate midplane dose from MOSFET measured entrance and exit doses has been derived. The dependency of surface dose on the air-gap between the spoiler and the surface was investigated by suspending a spoiler above a water phantom, and taking percentage depth dose measurements (PDD). Exit and entrances doses were measured with MOSFETs in conjunction with midplane doses measured with an ion chamber. The entrance and exit doses were combined using an exponential attenuation formula to give an estimate of midplane dose and were compared to the midplane ion chamber measurement for a range of phantom thicknesses. Having a maximum PDD at the surface simplifies the prediction of midplane dose, which is achieved by ensuring that the air gap between the compensator and the surface is less than 10 cm. The comparison of estimated midplane dose and measured midplane dose showed no dependence on phantom thickness and an average correction factor of 0.88 was found. If the missing tissue compensators are kept within 10 cm of the patient then MOSFET measurements of entrance and exit dose can predict the midplane dose for the patient.

The Comparison Study of Quadratic Infinite Beam Program on Optimization Instensity Modulated Radiation Therapy Treatment Planning (IMRTP) between Threshold and Exponential Scatter Method with CERR® In The Case of Lung Cancer

NASA Astrophysics Data System (ADS)

Hardiyanti, Y.; Haekal, M.; Waris, A.; Haryanto, F.

2016-08-01

This research compares the quadratic optimization program on Intensity Modulated Radiation Therapy Treatment Planning (IMRTP) with the Computational Environment for Radiotherapy Research (CERR) software. We assumed that the number of beams used for the treatment planner was about 9 and 13 beams. The case used the energy of 6 MV with Source Skin Distance (SSD) of 100 cm from target volume. Dose calculation used Quadratic Infinite beam (QIB) from CERR. CERR was used in the comparison study between Gauss Primary threshold method and Gauss Primary exponential method. In the case of lung cancer, the threshold variation of 0.01, and 0.004 was used. The output of the dose was distributed using an analysis in the form of DVH from CERR. The maximum dose distributions obtained were on the target volume (PTV) Planning Target Volume, (CTV) Clinical Target Volume, (GTV) Gross Tumor Volume, liver, and skin. It was obtained that if the dose calculation method used exponential and the number of beam 9. When the dose calculation method used the threshold and the number of beam 13, the maximum dose distributions obtained were on the target volume PTV, GTV, heart, and skin.

ESR dosimetry study of population in the vicinity of the Semipalatinsk Nuclear Test Site

PubMed Central

Zhumadilov, Kassym; Ivannikov, Alexander; Stepanenko, Valeriy; Zharlyganova, Dinara; Toyoda, Shin; Zhumadilov, Zhaxybay; Hoshi, Masaharu

2013-01-01

A tooth enamel electron spin resonance (ESR) dosimetry study was carried out with the purpose of obtaining the individual absorbed radiation doses of population from settlements in the Semipalatinsk region of Kazakhstan, which was exposed to radioactive fallout traces from nuclear explosions in the Semipalatinsk Nuclear Test Site and Lop Nor test base, China. Most of the settlements are located near the central axis of radioactive fallout trace from the most contaminating surface nuclear test, which was conducted on 29 August 1949, with the maximum detected excess dose being 430 ± 93 mGy. A maximum dose of 268 ± 79 mGy was determined from the settlements located close to radioactive fallout trace resulting from surface nuclear tests on 24 August 1956 (Ust-Kamenogorsk, Znamenka, Shemonaikha, Glubokoe, Tavriya and Gagarino). An accidental dose of 56 ± 42 mGy was found in Kurchatov city residents located close to fallout trace after the nuclear test on 7 August 1962. This method was applied to human tooth enamel to obtain individual absorbed doses of residents of the Makanchi, Urdzhar and Taskesken settlements located near the Kazakhstan–Chinese border due to the influence of nuclear tests (1964–1981) at Lop Nor. The highest dose was 123 ± 32 mGy. PMID:23404205

ESR dosimetry study of population in the vicinity of the Semipalatinsk Nuclear Test Site.

PubMed

Zhumadilov, Kassym; Ivannikov, Alexander; Stepanenko, Valeriy; Zharlyganova, Dinara; Toyoda, Shin; Zhumadilov, Zhaxybay; Hoshi, Masaharu

2013-07-01

A tooth enamel electron spin resonance (ESR) dosimetry study was carried out with the purpose of obtaining the individual absorbed radiation doses of population from settlements in the Semipalatinsk region of Kazakhstan, which was exposed to radioactive fallout traces from nuclear explosions in the Semipalatinsk Nuclear Test Site and Lop Nor test base, China. Most of the settlements are located near the central axis of radioactive fallout trace from the most contaminating surface nuclear test, which was conducted on 29 August 1949, with the maximum detected excess dose being 430 ± 93 mGy. A maximum dose of 268 ± 79 mGy was determined from the settlements located close to radioactive fallout trace resulting from surface nuclear tests on 24 August 1956 (Ust-Kamenogorsk, Znamenka, Shemonaikha, Glubokoe, Tavriya and Gagarino). An accidental dose of 56 ± 42 mGy was found in Kurchatov city residents located close to fallout trace after the nuclear test on 7 August 1962. This method was applied to human tooth enamel to obtain individual absorbed doses of residents of the Makanchi, Urdzhar and Taskesken settlements located near the Kazakhstan-Chinese border due to the influence of nuclear tests (1964-1981) at Lop Nor. The highest dose was 123 ± 32 mGy.

An analysis of interplanetary space radiation exposure for various solar cycles

NASA Technical Reports Server (NTRS)

Badhwar, G. D.; Cucinotta, F. A.; O'Neill, P. M.; Wilson, J. W. (Principal Investigator)

1994-01-01

The radiation dose received by crew members in interplanetary space is influenced by the stage of the solar cycle. Using the recently developed models of the galactic cosmic radiation (GCR) environment and the energy-dependent radiation transport code, we have calculated the dose at 0 and 5 cm water depth; using a computerized anatomical man (CAM) model, we have calculated the skin, eye and blood-forming organ (BFO) doses as a function of aluminum shielding for various solar minima and maxima between 1954 and 1989. These results show that the equivalent dose is within about 15% of the mean for the various solar minima (maxima). The maximum variation between solar minimum and maximum equivalent dose is about a factor of three. We have extended these calculations for the 1976-1977 solar minimum to five practical shielding geometries: Apollo Command Module, the least and most heavily shielded locations in the U.S. space shuttle mid-deck, center of the proposed Space Station Freedom cluster and sleeping compartment of the Skylab. These calculations, using the quality factor of ICRP 60, show that the average CAM BFO equivalent dose is 0.46 Sv/year. Based on an approach that takes fragmentation into account, we estimate a calculation uncertainty of 15% if the uncertainty in the quality factor is neglected.

Phase I study of afatinib combined with nintedanib in patients with advanced solid tumours.

PubMed

Bahleda, Rastislav; Hollebecque, Antoine; Varga, Andrea; Gazzah, Anas; Massard, Christophe; Deutsch, Eric; Amellal, Nadia; Farace, Françoise; Ould-Kaci, Mahmoud; Roux, Flavien; Marzin, Kristell; Soria, Jean-Charles

2015-11-17

This Phase I study evaluated continuous- and intermittent-dosing (every other week) of afatinib plus nintedanib in patients with advanced solid tumours. In the dose-escalation phase (n=45), maximum tolerated doses (MTDs) were determined for continuous/intermittent afatinib 10, 20, 30 or 40 mg once daily plus continuous nintedanib 150 or 200 mg twice daily. Secondary objectives included safety and efficacy. Clinical activity of continuous afatinib plus nintedanib at the MTD was further evaluated in an expansion phase (n=25). The most frequent dose-limiting toxicities were diarrhoea (11%) and transaminase elevations (7%). Maximum tolerated doses were afatinib 30 mg continuously plus nintedanib 150 mg, and afatinib 40 mg intermittently plus nintedanib 150 mg. Treatment-related adverse events (mostly Grade⩽3) included diarrhoea (98%), asthenia (64%), nausea (62%) and vomiting (60%). In the dose-escalation phase, two patients had partial responses (PRs) and 27 (60%) had stable disease (SD). In the expansion phase, one complete response and three PRs were observed (all non-small cell lung cancer), with SD in 13 (52%) patients. No pharmacokinetic interactions were observed. MTDs of continuous or intermittent afatinib plus nintedanib demonstrated a manageable safety profile with proactive management of diarrhoea. Antitumour activity was observed in patients with solid tumours.

Micronucleus induction in Vicia faba roots. Part 2. Biological effects of neutrons below 1 cGy.

PubMed

Marshall, I; Bianchi, M

1983-08-01

A dose-effect relationship has been established for high-energy neutrons (maximum energy 600 MeV) within a dose range of 0.2 to 80 cGy and for low-energy neutrons produced by a 252Cf source (mean energy 2.35 MeV) for doses between 0.2 and 5 cGy. The frequency of micronuclei was found to increase linearly with dose. The relative biological effectiveness (r.b.e) values calculated using 60Co radiation as a reference were, in the high-dose region, 4.7 +/- 0.4 and 11.8 +/- 1.3 for the high- and low-energy neutrons, respectively. At doses below 1 cGy constant values of 25.4 +/- 4.4 and 63.7 +/- 12 were reached for the respective neutron energies.

Multiple-dose pharmacokinetics and safety of bevirimat, a novel inhibitor of HIV maturation, in healthy volunteers.

PubMed

Martin, David E; Blum, Robert; Doto, Judy; Galbraith, Hal; Ballow, Charles

2007-01-01

Bevirimat [3-O-(3',3'-dimethylsuccinyl)-betulinic acid] is a novel inhibitor of HIV-1 maturation. This study was performed to investigate the pharmacokinetics and safety of bevirimat during repeated dosing in healthy volunteers. The study was a 10-day, randomised, double-blind, placebo-controlled, dose escalation study. A total of 48 healthy male volunteers, aged 19-54 years, took part in the study. Treatment was administered for 10 days in six escalating dose cohorts (n = 8 in each cohort; 6 bevirimat, 2 placebo). The doses of bevirimat given in each successive cohort were 25 mg, 50 mg, 75 mg (with 150 mg loading dose), 100 mg, 150 mg and 200mg. Safety follow-up was performed 28 days after the first dose. PHARMACOKINETIC AND STATISTICAL ANALYSIS: Plasma bevirimat levels were measured from blood samples collected pre-dose on days 1-10 and then at approximately 48-hour intervals until 21 days after dosing started. On days 1 and 10, further blood samples were obtained at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours after dosing. Urine samples were collected in the morning on days 1, 5 and 11 and at the end of the study for the measurement of cortisol and 6beta-hydroxycortisol. The pharmacokinetic parameters of bevirimat were estimated using non-compartmental methods. Dose proportionality of exposure to bevirimat, assessed by the maximum plasma concentration and the area under the plasma concentration-time curve. The mean terminal elimination half-life of bevirimat ranged from 56.3 to 69.5 hours, and the mean clearance ranged from 173.9 to 185.8 mL/hour. Bevirimat showed approximately 4-fold greater accumulation on day 10 compared with day 1, and the degree of accumulation was similar with all doses. Maximum plasma concentrations ranged from 8 to 58 microg/mL at day 10. Testing for dose-proportionality showed that exposure to bevirimat was proportional to the dose, both after a single dose and after repeat dosing for 10 days. Measurement of the urinary 6beta-hydroxycortisol/cortisol ratio indicated that bevirimat did not affect cytochrome P450 3A activity. Repeated dosing with bevirimat for 10 days was well tolerated. There was no increase in adverse events observed for bevirimat compared with placebo, and no serious adverse events occurred. No clinically relevant changes in vital signs, physical examination or clinical laboratory evaluations were observed. Bevirimat shows dose-proportional pharmacokinetics during repeated dosing for 10 days. Its accumulation is approximately 4-fold greater on day 10 compared with day 1. Repeated dosing with bevirimat is well tolerated. These properties make bevirimat potentially suitable for inclusion in highly active antiretroviral therapy regimens.

The Advantages of Collimator Optimization for Intensity Modulated Radiation Therapy

NASA Astrophysics Data System (ADS)

Doozan, Brian

The goal of this study was to improve dosimetry for pelvic, lung, head and neck, and other cancers sites with aspherical planning target volumes (PTV) using a new algorithm for collimator optimization for intensity modulated radiation therapy (IMRT) that minimizes the x-jaw gap (CAX) and the area of the jaws (CAA) for each treatment field. A retroactive study on the effects of collimator optimization of 20 patients was performed by comparing metric results for new collimator optimization techniques in Eclipse version 11.0. Keeping all other parameters equal, multiple plans are created using four collimator techniques: CA 0, all fields have collimators set to 0°, CAE, using the Eclipse collimator optimization, CAA, minimizing the area of the jaws around the PTV, and CAX, minimizing the x-jaw gap. The minimum area and the minimum x-jaw angles are found by evaluating each field beam's eye view of the PTV with ImageJ and finding the desired parameters with a custom script. The evaluation of the plans included the monitor units (MU), the maximum dose of the plan, the maximum dose to organs at risk (OAR), the conformity index (CI) and the number of fields that are calculated to split. Compared to the CA0 plans, the monitor units decreased on average by 6% for the CAX method with a p-value of 0.01 from an ANOVA test. The average maximum dose remained within 1.1% difference between all four methods with the lowest given by CAX. The maximum dose to the most at risk organ was best spared by the CAA method, which decreased by 0.62% compared to the CA0. Minimizing the x-jaws significantly reduced the number of split fields from 61 to 37. In every metric tested the CAX optimization produced comparable or superior results compared to the other three techniques. For aspherical PTVs, CAX on average reduced the number of split fields, lowered the maximum dose, minimized the dose to the surrounding OAR, and decreased the monitor units. This is achieved while maintaining the same control of the PTV.

SU-F-T-437: 3 Field VMAT Technique for Irradiation of Large Pelvic Tumors

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

Stakhursky, V

2016-06-15

Purpose: VMAT treatment planning for large pelvic volume irradiation could be suboptimal due to inability of Varian linac to split MLC carriage during VMAT delivery for fields larger than 14.5cm in X direction (direction of leaf motion). We compare the dosimetry between 3 VMAT planning techniques, two 2-arc field techniques and a 3-arc field technique: a) two small in X direction (less than 14.5cm) arc fields, complementing each other to cover the whole lateral extent of target during gantry rotation, b) two large arc fields, each covering the targets completely during the rotation, c) a 3 field technique with 2more » small in X direction arcs and 1 large field covering whole target. Methods: 5 GYN cancer patients were selected to evaluate the 3 VMAT planning techniques. Treatment plans were generated using Varian Eclipse (ver. 11) TPS. Dose painting technique was used to deliver 5300 cGy to primary target and 4500 cGy to pelvic/abdominal node target. All the plans were normalized so that the prescription dose of 5300 cGy covered 95% of primary target volume. PTV and critical structures DVH curves were compared to evaluate all 3 planning techniques. Results: The dosimetric differences between the two 2-arc techniques were minor. The small field 2-arc technique showed a colder hot spot (0.4% averaged), while variations in maximum doses to critical structures were statistically nonsignificant (under 1.3%). In comparison, the 3-field technique demonstrated a colder hot spot (1.1% less, 105.8% averaged), and better sparing of critical structures. The maximum doses to larger bowel, small bowel and gluteal fold were 3% less, cord/cauda sparing was 4.2% better, and bladder maximum dose was 4.6% less. The differences in maximum doses to stomach and rectum were statistically nonsignificant. Conclusion: 3-arc VMAT technique for large field irradiation of pelvis demonstrates dosimetric advantages compared to 2-arc VMAT techniques.« less

Knowledge of appropriate acetaminophen use: A survey of college-age women.

PubMed

Stumpf, Janice L; Liao, Allison C; Nguyen, Stacy; Skyles, Amy J; Alaniz, Cesar

To evaluate college-age women's knowledge of appropriate doses and potential toxicities of acetaminophen, competency in interpreting Drug Facts label dosing information, and ability to recognize products containing acetaminophen. In this cross-sectional prospective study, a 20-item written survey was provided to female college students at a University of Michigan fundraising event in March 2015. A total of 203 female college students, 18-24 years of age, participated in the study. Pain was experienced on a daily or weekly basis by 22% of the subjects over the previous 6 months, and 83% reported taking acetaminophen. The maximum 3-gram daily dose of extra-strength acetaminophen was correctly identified by 64 participants; an additional 51 subjects indicated the generally accepted 4 grams daily as the maximum dose. When provided with the Tylenol Drug Facts label, 68.5% correctly identified the maximum amount of regular-strength acetaminophen recommended for a healthy adult. Hepatotoxicity was associated with high acetaminophen doses by 63.6% of participants, significantly more than those who selected distracter responses (P < 0.001). Knowledge of liver damage as a potential toxicity was correlated with age 20 years and older (P < 0.001) but was independent from race and ethnicity and level of alcohol consumption. Although more than one-half of the subjects (58.6%) recognized that Tylenol contained acetaminophen, fewer than one-fourth correctly identified other acetaminophen-containing products. Despite ongoing educational campaigns, a large proportion of the college-age women who participated in our study did not know and could not interpret the maximum recommended daily dose from Drug Facts labeling, did not know that liver damage was a potential toxicity of acetaminophen, and could not recognize acetaminophen-containing products. These data suggest a continued role for pharmacists in educational efforts targeted to college-age women. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Radiation leakage dose from Elekta electron collimation system

PubMed Central

Hogstrom, Kenneth R.; Carver, Robert L.

2016-01-01

This study provided baseline data required for a greater project, whose objective was to design a new Elekta electron collimation system having significantly lighter electron applicators with equally low out‐of field leakage dose. Specifically, off‐axis dose profiles for the electron collimation system of our uniquely configured Elekta Infinity accelerator with the MLCi2 treatment head were measured and calculated for two primary purposes: 1) to evaluate and document the out‐of‐field leakage dose in the patient plane and 2) to validate the dose distributions calculated using a BEAMnrc Monte Carlo (MC) model for out‐of‐field dose profiles. Off‐axis dose profiles were measured in a water phantom at 100 cm SSD for 1 and 2 cm depths along the in‐plane, cross‐plane, and both diagonal axes using a cylindrical ionization chamber with the 10×10 and 20×20 cm2 applicators and 7, 13, and 20 MeV beams. Dose distributions were calculated using a previously developed BEAMnrc MC model of the Elekta Infinity accelerator for the same beam energies and applicator sizes and compared with measurements. Measured results showed that the in‐field beam flatness met our acceptance criteria (±3% on major and ±4% on diagonal axes) and that out‐of‐field mean and maximum percent leakage doses in the patient plane met acceptance criteria as specified by the International Electrotechnical Commission (IEC). Cross‐plane out‐of‐field dose profiles showed greater leakage dose than in‐plane profiles, attributed to the curved edges of the upper X‐ray jaws and multileaf collimator. Mean leakage doses increased with beam energy, being 0.93% and 0.85% of maximum central axis dose for the 10×10 and 20×20 cm2 applicators, respectively, at 20 MeV. MC calculations predicted the measured dose to within 0.1% in most profiles outside the radiation field; however, excluding modeling of nontrimmer applicator components led to calculations exceeding measured data by as much as 0.2% for some regions along the in‐plane axis. Using EGSnrc LATCH bit filtering to separately calculate out‐of‐field leakage dose components (photon dose, primary electron dose, and electron dose arising from interactions in various collimating components), MC calculations revealed that the primary electron dose in the out‐of‐field leakage region was small and decreased as beam energy increased. Also, both the photon dose component and electron dose component resulting from collimator scatter dominated the leakage dose, increasing with increasing beam energy. We concluded that our custom Elekta Infinity with the MLCi2 treatment head met IEC leakage dose criteria in the patient plane. Also, accuracy of our MC model should be sufficient for our use in the design of a new, improved electron collimation system. PACS number(s): 87.56.nk, 87.10.Rt, 87.56.J PMID:27685101

Correction for FDG PET dose extravasations: Monte Carlo validation and quantitative evaluation of patient studies.

PubMed

Silva-Rodríguez, Jesús; Aguiar, Pablo; Sánchez, Manuel; Mosquera, Javier; Luna-Vega, Víctor; Cortés, Julia; Garrido, Miguel; Pombar, Miguel; Ruibal, Alvaro

2014-05-01

Current procedure guidelines for whole body [18F]fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET) state that studies with visible dose extravasations should be rejected for quantification protocols. Our work is focused on the development and validation of methods for estimating extravasated doses in order to correct standard uptake value (SUV) values for this effect in clinical routine. One thousand three hundred sixty-seven consecutive whole body FDG-PET studies were visually inspected looking for extravasation cases. Two methods for estimating the extravasated dose were proposed and validated in different scenarios using Monte Carlo simulations. All visible extravasations were retrospectively evaluated using a manual ROI based method. In addition, the 50 patients with higher extravasated doses were also evaluated using a threshold-based method. Simulation studies showed that the proposed methods for estimating extravasated doses allow us to compensate the impact of extravasations on SUV values with an error below 5%. The quantitative evaluation of patient studies revealed that paravenous injection is a relatively frequent effect (18%) with a small fraction of patients presenting considerable extravasations ranging from 1% to a maximum of 22% of the injected dose. A criterion based on the extravasated volume and maximum concentration was established in order to identify this fraction of patients that might be corrected for paravenous injection effect. The authors propose the use of a manual ROI based method for estimating the effectively administered FDG dose and then correct SUV quantification in those patients fulfilling the proposed criterion.

Correction for FDG PET dose extravasations: Monte Carlo validation and quantitative evaluation of patient studies

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

Silva-Rodríguez, Jesús, E-mail: jesus.silva.rodriguez@sergas.es; Aguiar, Pablo, E-mail: pablo.aguiar.fernandez@sergas.es; Servicio de Medicina Nuclear, Complexo Hospitalario Universidade de Santiago de Compostela

Purpose: Current procedure guidelines for whole body [18F]fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET) state that studies with visible dose extravasations should be rejected for quantification protocols. Our work is focused on the development and validation of methods for estimating extravasated doses in order to correct standard uptake value (SUV) values for this effect in clinical routine. Methods: One thousand three hundred sixty-seven consecutive whole body FDG-PET studies were visually inspected looking for extravasation cases. Two methods for estimating the extravasated dose were proposed and validated in different scenarios using Monte Carlo simulations. All visible extravasations were retrospectively evaluated using a manualmore » ROI based method. In addition, the 50 patients with higher extravasated doses were also evaluated using a threshold-based method. Results: Simulation studies showed that the proposed methods for estimating extravasated doses allow us to compensate the impact of extravasations on SUV values with an error below 5%. The quantitative evaluation of patient studies revealed that paravenous injection is a relatively frequent effect (18%) with a small fraction of patients presenting considerable extravasations ranging from 1% to a maximum of 22% of the injected dose. A criterion based on the extravasated volume and maximum concentration was established in order to identify this fraction of patients that might be corrected for paravenous injection effect. Conclusions: The authors propose the use of a manual ROI based method for estimating the effectively administered FDG dose and then correct SUV quantification in those patients fulfilling the proposed criterion.« less

Risks of high-dose stimulants in the treatment of disorders of excessive somnolence: a case-control study.

PubMed

Auger, R Robert; Goodman, Scott H; Silber, Michael H; Krahn, Lois E; Pankratz, V Shane; Slocumb, Nancy L

2005-06-01

To ascertain complications associated with high-dose stimulant therapy in patients with narcolepsy or idiopathic hypersomnia. Case-control, retrospective chart review. Sleep center in an academic hospital. 116 patients with narcolepsy or idiopathic hypersomnia were individually matched by sex, diagnosis, age of onset, and duration of follow-up from both onset and diagnosis. Members of the high-dose group (n = 58) had received at least 1 stimulant at a dosage > or = 120% of the maximum recommended by the American Academy of Sleep Medicine Standards of Practice Committee. The standard-dose control group (n = 58) had received stimulants at a dosage < or = 100% of the American Academy of Sleep Medicine guidelines. N/A. The prevalence of psychosis (odds ratio = 12.0 [1.6-92.0]), alcohol or polysubstance misuse (odds ratio = 4.3 [1.2-15.2]), and psychiatric hospitalization (odds ratio = 3.2 [1.1-10.0]) was significantly increased in the high-dose group. More high-dose patients also experienced tachyarrhythmias (odds ratio = 3.3 [0.92-12.1] and anorexia or weight loss (odds ratio = 11.0 [1.4-85.2]). The frequency of physician-diagnosed depression, drug-seeking and suicide-related behaviors, hypertension, and cardiovascular disease did not differ significantly between the groups. This study demonstrated a significantly higher occurrence of psychosis, substance misuse, and psychiatric hospitalizations in patients using high-dose stimulants compared to those using standard doses. Tachyarrhythmias and anorexia or weight loss were also more common in this group as compared with controls. Clinicians should be very cautious in prescribing dosages that exceed maximum guidelines.

Cyclophosphamide priming reduces intestinal damage in man following high dose melphalan chemotherapy.

PubMed Central

Selby, P. J.; Lopes, N.; Mundy, J.; Crofts, M.; Millar, J. L.; McElwain, T. J.

1987-01-01

A small pre-treatment 'priming' dose of cyclophosphamide will reduce gut damage due to high dose i.v. melphalan in mice and sheep but efforts to demonstrate this effect in man have been hampered by difficulty in the measurement of gut damage. We have evaluated the 51CR EDTA absorption test, a new method for measuring intestinal permeability, as a means of assessing damage due to high dose melphalan. The test was reliable, with a narrow normal range, easy to use and well tolerated. It detected an increase in intestinal permeability after high dose melphalan with a maximum occurring between 9 and 15 days after treatment and subsequently returning to normal. It was shown in 19 patients that a pre-treatment dose of cyclophosphamide was capable of significantly reducing the abnormalities in intestinal permeability which resulted from high dose melphalan. PMID:3111515

Monte Carlo simulation and film dosimetry for electron therapy in vicinity of a titanium mesh

PubMed Central

Rostampour, Masoumeh; Roayaei, Mahnaz

2014-01-01

Titanium (Ti) mesh plates are used as a bone replacement in brain tumor surgeries. In the case of radiotherapy, these plates might interfere with the beam path. The purpose of this study is to evaluate the effect of titanium mesh on the dose distribution of electron fields. Simulations were performed using Monte Carlo BEAMnrc and DOSXYZnrc codes for 6 and 10 MeV electron beams. In Monte Carlo simulation, the shape of the titanium mesh was simulated. The simulated titanium mesh was considered as the one which is used in head and neck surgery with a thickness of 0.055 cm. First, by simulation, the percentage depth dose was obtained while the titanium mesh was present, and these values were then compared with the depth dose of homogeneous phantom with no titanium mesh. In the experimental measurements, the values of depth dose with titanium mesh and without titanium mesh in various depths were measured. The experiments were performed using a RW3 phantom with GAFCHROMIC EBT2 film. The results of experimental measurements were compared with values of depth dose obtained by simulation. In Monte Carlo simulation, as well as experimental measurements, for the voxels immediately beyond the titanium mesh, the change of the dose were evaluated. For this purpose the ratio of the dose for the case with titanium to the case without titanium was calculated as a function of titanium depth. For the voxels before the titanium mesh there was always an increase of the dose up to 13% with respect to the same voxel with no titanium mesh. This is because of the increased back scattering effect of the titanium mesh. The results also showed that for the voxel right beyond the titanium mesh, there is an increased or decreased dose to soft tissues, depending on the depth of the titanium mesh. For the regions before the depth of maximum dose, there is an increase of the dose up to 10% compared to the dose of the same depth in homogeneous phantom. Beyond the depth of maximum dose, there was a 16% decrease in dose. For both 6 and 10 MeV, before the titanium mesh, there was always an increase in dose. If titanium mesh is placed in buildup region, it causes an increase of the dose and could lead to overdose of the adjacent tissue, whereas if titanium mesh is placed beyond the buildup region, it would lead to a decrease in dose compared to the homogenous tissue. PACS number: 87.53.Bn PMID:25207397

Measurement of doses to the extremities of nuclear medicine staff

NASA Astrophysics Data System (ADS)

Shousha, Hany A.; Farag, Hamed; Hassan, Ramadan A.

2010-01-01

Medical uses of ionizing radiation now represent>95% of all man-made radiation exposure, and is the largest single radiation source after natural background radiation. Therefore, it is important to quantify the amount of radiation received by occupational individuals to optimize the working conditions for staff, and further, to compare doses in different departments to ensure compatibility with the recommended standards. For some groups working with unsealed sources in nuclear medicine units, the hands are more heavily exposed to ionizing radiation than the rest of the body. A personal dosimetry service runs extensively in Egypt. But doses to extremities have not been measured to a wide extent. The purpose of this study was to investigate the equivalent radiation doses to the fingers for five different nuclear medicine staff occupational groups for which heavy irradiation of the hands was suspected. Finger doses were measured for (1) nuclear medicine physicians, (2) technologists, (3) nurses and (4) physicists. The fifth group contains three technicians handling 131I, while the others handled 99mTc. Each staff member working with the radioactive material wore two thermoluminescent dosimeters (TLDs) during the whole testing period, which lasted from 1 to 4 weeks. Staff performed their work on a regular basis throughout the month, and mean annual doses were calculated for these groups. Results showed that the mean equivalent doses to the fingers of technologist, nurse and physicist groups were 30.24±14.5, 30.37±17.5 and 16.3±7.7 μSv/GBq, respectively. Equivalent doses for the physicians could not be calculated per unit of activity because they did not handle the radiopharmaceuticals directly. Their doses were reported in millisieverts (mSv) that accumulated in one week. Similarly, the dose to the fingers of individuals in Group 5 was estimated to be 126.13±38.2 μSv/GBq. The maximum average finger dose, in this study, was noted in the technologists who handled therapeutic 131I (2.5 mSv). In conclusion, the maximum expected annual dose to extremities is less than the annual limit (500 mSv/y).

Escalation to High-Dose Defibrotide in Patients with Hepatic Veno-Occlusive Disease.

PubMed

Triplett, Brandon M; Kuttab, Hani I; Kang, Guolian; Leung, Wing

2015-12-01

Hepatic veno-occlusive disease (VOD) is a serious complication of high-dose chemotherapy regimens, such as those used in hematopoietic cell transplantation recipients. Defibrotide is considered a safe and effective treatment when dosed at 25 mg/kg/day. However, patients who develop VOD still have increased mortality despite the use of defibrotide. Data are limited on the use of doses above 60 mg/kg/day for persistent VOD. In this prospective clinical trial 34 patients received escalating doses of defibrotide. For patients with persistent VOD despite doses of 60 mg/kg/day, doses were increased to a maximum of 110 mg/kg/day. Increased toxicity was not observed until doses rose beyond 100 mg/kg/day. Patients receiving doses between 10 and 100 mg/kg/day experienced an average of 3 bleeding episodes per 100 days of treatment, whereas those receiving doses >100 mg/kg/day experienced 13.2 bleeding episodes per 100 days (P = .008). Moreover, dose reductions due to toxicity were needed at doses of 110 mg/kg/day more often than at lower doses. Defibrotide may be safely escalated to doses well above the current standard without an increase in bleeding risk. However, the efficacy of this dose-escalation strategy remains unclear, because outcomes were similar to published cohorts of patients receiving standard doses of defibrotide for VOD. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

SU-E-T-374: Evaluation and Verification of Dose Calculation Accuracy with Different Dose Grid Sizes for Intracranial Stereotactic Radiosurgery

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

Han, C; Schultheiss, T

Purpose: In this study, we aim to evaluate the effect of dose grid size on the accuracy of calculated dose for small lesions in intracranial stereotactic radiosurgery (SRS), and to verify dose calculation accuracy with radiochromic film dosimetry. Methods: 15 intracranial lesions from previous SRS patients were retrospectively selected for this study. The planning target volume (PTV) ranged from 0.17 to 2.3 cm{sup 3}. A commercial treatment planning system was used to generate SRS plans using the volumetric modulated arc therapy (VMAT) technique using two arc fields. Two convolution-superposition-based dose calculation algorithms (Anisotropic Analytical Algorithm and Acuros XB algorithm) weremore » used to calculate volume dose distribution with dose grid size ranging from 1 mm to 3 mm with 0.5 mm step size. First, while the plan monitor units (MU) were kept constant, PTV dose variations were analyzed. Second, with 95% of the PTV covered by the prescription dose, variations of the plan MUs as a function of dose grid size were analyzed. Radiochomic films were used to compare the delivered dose and profile with the calculated dose distribution with different dose grid sizes. Results: The dose to the PTV, in terms of the mean dose, maximum, and minimum dose, showed steady decrease with increasing dose grid size using both algorithms. With 95% of the PTV covered by the prescription dose, the total MU increased with increasing dose grid size in most of the plans. Radiochromic film measurements showed better agreement with dose distributions calculated with 1-mm dose grid size. Conclusion: Dose grid size has significant impact on calculated dose distribution in intracranial SRS treatment planning with small target volumes. Using the default dose grid size could lead to under-estimation of delivered dose. A small dose grid size should be used to ensure calculation accuracy and agreement with QA measurements.« less

TOOTH (The Open study Of dental pulp stem cell Therapy in Humans): Study protocol for evaluating safety and feasibility of autologous human adult dental pulp stem cell therapy in patients with chronic disability after stroke.

PubMed

Nagpal, Anjali; Kremer, Karlea L; Hamilton-Bruce, Monica A; Kaidonis, Xenia; Milton, Austin G; Levi, Christopher; Shi, Songtao; Carey, Leeanne; Hillier, Susan; Rose, Miranda; Zacest, Andrew; Takhar, Parabjit; Koblar, Simon A

2016-07-01

Stroke represents a significant global disease burden. As of 2015, there is no chemical or biological therapy proven to actively enhance neurological recovery during the chronic phase post-stroke. Globally, cell-based therapy in stroke is at the stage of clinical translation and may improve neurological function through various mechanisms such as neural replacement, neuroprotection, angiogenesis, immuno-modulation, and neuroplasticity. Preclinical evidence in a rodent model of middle cerebral artery ischemic stroke as reported in four independent studies indicates improvement in neurobehavioral function with adult human dental pulp stem cell therapy. Human adult dental pulp stem cells present an exciting potential therapeutic option for improving post-stroke disability. TOOTH (The Open study Of dental pulp stem cell Therapy in Humans) will investigate the use of autologous stem cell therapy for stroke survivors with chronic disability, with the following objectives: (a) determine the maximum tolerable dose of autologous dental pulp stem cell therapy; (b) define that dental pulp stem cell therapy at the maximum tolerable dose is safe and feasible in chronic stroke; and (c) estimate the parameters of efficacy required to design a future Phase 2/3 clinical trial. TOOTH is a Phase 1, open-label, single-blinded clinical trial with a pragmatic design that comprises three stages: Stage 1 will involve the selection of 27 participants with middle cerebral artery ischemic stroke and the commencement of autologous dental pulp stem cell isolation, growth, and testing in sequential cohorts (n = 3). Stage 2 will involve the transplantation of dental pulp stem cell in each cohort of participants with an ascending dose and subsequent observation for a 6-month period for any dental pulp stem cell-related adverse events. Stage 3 will investigate the neurosurgical intervention of the maximum tolerable dose of autologous dental pulp stem cell followed by 9 weeks of intensive task-specific rehabilitation. Advanced magnetic resonance and positron emission tomography neuro-imaging, and clinical assessment will be employed to probe any change afforded by stem cell therapy in combination with rehabilitation. Nine participants will step-wise progress in Stage 2 to a dose of up to 10 million dental pulp stem cell, employing a cumulative 3 + 3 statistical design with low starting stem cell dose and subsequent dose escalation, assuming that an acceptable probability of dose-limiting complications is between 1 in 6 (17%) and 1 in 3 (33%) of patients. In Stage 3, another 18 participants will receive an intracranial injection with the maximum tolerable dose of dental pulp stem cell. The primary outcomes to be measured are safety and feasibility of intracranial administration of autologous human adult DPSC in patients with chronic stroke and determination of the maximum tolerable dose in human subjects. Secondary outcomes include estimation of the measures of effectiveness required to design a future Phase 2/3 clinical trial. © 2016 World Stroke Organization.

Optimisation techniques in vaginal cuff brachytherapy.

PubMed

Tuncel, N; Garipagaoglu, M; Kizildag, A U; Andic, F; Toy, A

2009-11-01

The aim of this study was to explore whether an in-house dosimetry protocol and optimisation method are able to produce a homogeneous dose distribution in the target volume, and how often optimisation is required in vaginal cuff brachytherapy. Treatment planning was carried out for 109 fractions in 33 patients who underwent high dose rate iridium-192 (Ir(192)) brachytherapy using Fletcher ovoids. Dose prescription and normalisation were performed to catheter-oriented lateral dose points (dps) within a range of 90-110% of the prescribed dose. The in-house vaginal apex point (Vk), alternative vaginal apex point (Vk'), International Commission on Radiation Units and Measurements (ICRU) rectal point (Rg) and bladder point (Bl) doses were calculated. Time-position optimisations were made considering dps, Vk and Rg doses. Keeping the Vk dose higher than 95% and the Rg dose less than 85% of the prescribed dose was intended. Target dose homogeneity, optimisation frequency and the relationship between prescribed dose, Vk, Vk', Rg and ovoid diameter were investigated. The mean target dose was 99+/-7.4% of the prescription dose. Optimisation was required in 92 out of 109 (83%) fractions. Ovoid diameter had a significant effect on Rg (p = 0.002), Vk (p = 0.018), Vk' (p = 0.034), minimum dps (p = 0.021) and maximum dps (p<0.001). Rg, Vk and Vk' doses with 2.5 cm diameter ovoids were significantly higher than with 2 cm and 1.5 cm ovoids. Catheter-oriented dose point normalisation provided a homogeneous dose distribution with a 99+/-7.4% mean dose within the target volume, requiring time-position optimisation.

Dose gradient curve: A new tool for evaluating dose gradient.

PubMed

Sung, KiHoon; Choi, Young Eun

2018-01-01

Stereotactic radiotherapy, which delivers an ablative high radiation dose to a target volume for maximum local tumor control, requires a rapid dose fall-off outside the target volume to prevent extensive damage to nearby normal tissue. Currently, there is no tool to comprehensively evaluate the dose gradient near the target volume. We propose the dose gradient curve (DGC) as a new tool to evaluate the quality of a treatment plan with respect to the dose fall-off characteristics. The average distance between two isodose surfaces was represented by the dose gradient index (DGI) estimated by a simple equation using the volume and surface area of isodose levels. The surface area was calculated by mesh generation and surface triangulation. The DGC was defined as a plot of the DGI of each dose interval as a function of the dose. Two types of DGCs, differential and cumulative, were generated. The performance of the DGC was evaluated using stereotactic radiosurgery plans for virtual targets. Over the range of dose distributions, the dose gradient of each dose interval was well-characterized by the DGC in an easily understandable graph format. Significant changes in the DGC were observed reflecting the differences in planning situations and various prescription doses. The DGC is a rational method for visualizing the dose gradient as the average distance between two isodose surfaces; the shorter the distance, the steeper the dose gradient. By combining the DGC with the dose-volume histogram (DVH) in a single plot, the DGC can be utilized to evaluate not only the dose gradient but also the target coverage in routine clinical practice.

RADIATION DOSE ASSESSMENT FOR THE BIOTA OF TERRESTRIAL ECOSYSTEMS IN THE SHORELINE ZONE OF THE CHERNOBYL NUCLEAR POWER PLANT COOLING POND

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

Farfan, E.; Jannik, T.

2011-10-01

Radiation exposure of the biota in the shoreline area of the Chernobyl Nuclear Power Plant Cooling Pond was assessed to evaluate radiological consequences from the decommissioning of the Cooling Pond. The article addresses studies of radioactive contamination of the terrestrial faunal complex and radionuclide concentration ratios in bodies of small birds, small mammals, amphibians, and reptiles living in the area. The data were used to calculate doses to biota using the ERICA Tool software. Doses from {sup 90}Sr and {sup 137}Cs were calculated using the default parameters of the ERICA Tool and were shown to be consistent with biota dosesmore » calculated from the field data. However, the ERICA dose calculations for plutonium isotopes were much higher (2-5 times for small mammals and 10-14 times for birds) than the doses calculated using the experimental data. Currently, the total doses for the terrestrial biota do not exceed maximum recommended levels. However, if the Cooling Pond is allowed to drawdown naturally and the contaminants of the bottom sediments are exposed and enter the biological cycle, the calculated doses to biota may exceed the maximum recommended values. The study is important in establishing the current exposure conditions such that a baseline exists from which changes can be documented following the lowering of the reservoir water. Additionally, the study provided useful radioecological data on biota concentration ratios for some species that are poorly represented in the literature.« less

Diurnal variation in the biliary excretion of flomoxef in patients with percutaneous transhepatic biliary drainage

PubMed Central

Hishikawa, Shuji; Kobayashi, Eiji; Sugimoto, Koh-ichi; Miyata, Michio; Fujimura, Akio

2001-01-01

Aims To examine diurnal variation in biliary excretion of flomoxef. Methods Flomoxef (1 g) was injected intravenously in eight patients with percutaneous transhepatic cholangiography with drainage at 09.00 h and 21.00 h by a cross-over design with a 36 h washout period. Drained biliary fluid was collected for 6 h after each dosing. These patients still had mild to moderate hepatic dysfunction. Results Bile flow and bile acid excretion for 6 h after dosing did not differ significantly between the 09.00 h and 21.00 h treatments. The maximum concentration of biliary flomoxef was significantly greater and its total excretion for 6 h tended to be greater after the 21.00 h dose [maximum concentration (µg ml−1): 34.2 ± 29.9 (09.00 h dose) vs 43.5 ± 28.3 (21.00 h dose) (95% confidence interval for difference: 2.6∼15.9, P = 0.013); total excretion (mg 6 h−1): 1.4 ± 1.3 (09.00 h dose) vs 1.6 ± 1.2 (21.00 h dose) (95% confidence interval for difference: −26.8, 313.7, P = 0.087)]. The period that biliary flomoxef remained above the minimal inhibitory concentration did not differ significantly between the two treatment times. Conclusions These results suggest that biliary excretion of flomoxef shows diurnal variation. However, as the difference was relatively small, flomoxef could be given at any time of day without any dosage adjustments. PMID:11453891

Diurnal variation in the biliary excretion of flomoxef in patients with percutaneous transhepatic biliary drainage.

PubMed

Hishikawa, S; Kobayashi, E; Sugimoto , K; Miyata, M; Fujimura, A

2001-07-01

To examine diurnal variation in biliary excretion of flomoxef. Flomoxef (1 g) was injected intravenously in eight patients with percutaneous transhepatic cholangiography with drainage at 09.00 h and 21.00 h by a cross-over design with a 36 h washout period. Drained biliary fluid was collected for 6 h after each dosing. These patients still had mild to moderate hepatic dysfunction. Bile flow and bile acid excretion for 6 h after dosing did not differ significantly between the 09.00 h and 21.00 h treatments. The maximum concentration of biliary flomoxef was significantly greater and its total excretion for 6 h tended to be greater after the 21.00 h dose [maximum concentration (microg ml(-1)): 34.2 +/- 29.9 (09.00 h dose) vs 43.5 +/- 28.3 (21.00 h dose) (95% confidence interval for difference: 2.6 approximately 15.9, P = 0.013); total excretion (mg 6 h(-1)): 1.4 +/- 1.3 (09.00 h dose) vs 1.6 +/- 1.2 (21.00 h dose) (95% confidence interval for difference: -26.8, 313.7, P = 0.087)]. The period that biliary flomoxef remained above the minimal inhibitory concentration did not differ significantly between the two treatment times. These results suggest that biliary excretion of flomoxef shows diurnal variation. However, as the difference was relatively small, flomoxef could be given at any time of day without any dosage adjustments.

On the use of volumetric-modulated arc therapy for single-fraction thoracic vertebral metastases stereotactic body radiosurgery

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

Pokhrel, Damodar, E-mail: damodar.pokhrel@uky.edu; Sood, Sumit; McClinton, Christopher

To retrospectively evaluate quality, efficiency, and delivery accuracy of volumetric-modulated arc therapy (VMAT) plans for single-fraction treatment of thoracic vertebral metastases using image-guided stereotactic body radiosurgery (SBRS) after RTOG 0631 dosimetric compliance criteria. After obtaining credentialing for MD Anderson spine phantom irradiation validation, 10 previously treated patients with thoracic vertebral metastases with noncoplanar hybrid arcs using 1 to 2 3D-conformal partial arcs plus 7 to 9 intensity-modulated radiation therapy beams were retrospectively re-optimized with VMAT using 3 full coplanar arcs. Tumors were located between T2 and T12. Contrast-enhanced T1/T2-weighted magnetic resonance images were coregistered with planning computed tomography and planningmore » target volumes (PTV) were between 14.4 and 230.1 cc (median = 38.0 cc). Prescription dose was 16 Gy in 1 fraction with 6 MV beams at Novalis-TX linear accelerator consisting of micro multileaf collimators. Each plan was assessed for target coverage using conformality index, the conformation number, the ratio of the volume receiving 50% of the prescription dose over PTV, R50%, homogeneity index (HI), and PTV-1600 coverage per RTOG 0631 requirements. Organs-at-risk doses were evaluated for maximum doses to spinal cord (D{sub 0.03} {sub cc}, D{sub 0.35} {sub cc}), partial spinal cord (D{sub 10%}), esophagus (D{sub 0.03} {sub cc} and D{sub 5} {sub cc}), heart (D{sub 0.03} {sub cc} and D{sub 15} {sub cc}), and lung (V{sub 5}, V{sub 10}, and maximum dose to 1000 cc of lung). Dose delivery efficiency and accuracy of each VMAT-SBRS plan were assessed using quality assurance (QA) plan on MapCHECK device. Total beam-on time was recorded during QA procedure, and a clinical gamma index (2%/2 mm and 3%/3 mm) was used to compare agreement between planned and measured doses. All 10 VMAT-SBRS plans met RTOG 0631 dosimetric requirements for PTV coverage. The plans demonstrated highly conformal and homogenous coverage of the vertebral PTV with mean HI, conformality index, conformation number, and R{sub 50%} values of 0.13 ± 0.03 (range: 0.09 to 0.18), 1.03 ± 0.04 (range: 0.98 to 1.09), 0.81 ± 0.06 (range: 0.72 to 0.89), and 4.2 ± 0.94 (range: 2.7 to 5.4), respectively. All 10 patients met protocol guidelines with maximum dose to spinal cord (average: 8.83 ± 1.9 Gy, range: 5.9 to 10.9 Gy); dose to 0.35 cc of spinal cord (average: 7.62 ± 1.7 Gy, range: 5.4 to 9.6 Gy); and dose to 10% of partial spinal cord (average 6.31 ± 1.5 Gy, range: 3.5 to 8.5 Gy) less than 14, 10, and 10 Gy, respectively. For all 10 patients, the maximum dose to esophagus (average: 9.41 ± 4.3 Gy, range: 1.5 to 14.9 Gy) and dose to 5 cc of esophagus (average: 7.43 ± 3.8 Gy, range: 1.1 to 11.8 Gy) were kept less than protocol requirements 16 Gy and 11.9 Gy, respectively. In a similar manner, all 10 patients met protocol compliance criteria with maximum dose to heart (average: 4.62 ± 3.5 Gy, range: 1.3 to 10.2 Gy) and dose to 15 cc of heart (average: 2.23 ± 1.8 Gy, range: 0.3 to 5.6 Gy) less than 22 and 16 Gy, respectively. The dose to the lung was retained much lower than protocol guidelines for all 10 patients. The total number of monitor units was, on average, 6919 ± 1187. The average beam-on time was 11.5 ± 2.0 minutes. The VMAT plans demonstrated dose delivery accuracy of 95.8 ± 0.7%, on average, for clinical gamma passing rate with 2%/2 mm criteria and 98.3 ± 0.8%, on average, with 3%/3 mm criteria. All VMAT-SBRS plans were considered clinically acceptable per RTOG 0631 dosimetric compliance criteria. VMAT planning provided highly conformal and homogenous dose distributions for the lower-dose vertebral PTV and the spinal cord as well as organs-at-risk such as esophagus, heart, and lung. Higher QA pass rates and shorter beam-on time suggest that VMAT-SBRS is a clinically feasible, fast, and effective treatment option for patients with thoracic vertebral metastases.« less

Radiation exposure in interventional radiology

NASA Astrophysics Data System (ADS)

Pinto, N. G. V.; Braz, D.; Vallim, M. A.; Filho, L. G. P.; Azevedo, F. S.; Barroso, R. C.; Lopes, R. T.

2007-09-01

The aim of this study is to evaluate dose values in patients and staff involved in some interventional radiology procedures. Doses have been measured using thermoluminescent dosemeters for single procedures (such as renal and cerebral arteriography, transjungular intrahepatic portasystemic shunt (TIPS) and chemoembolization). The magnitude of doses through the hands of interventional radiologists has been studied. Dose levels were evaluated in three points for patients (eye, thyroid and gonads). The dose-area product (DAP) was also investigated using a Diamentor (PTW-M2). The dose in extremities was estimated for a professional who generally performed one TIPS, two chemoembolizations, two cerebral arteriographies and two renal arteriographies in a week. The estimated annual radiation dose was converted to effective dose as suggested by the 453-MS/Brazil norm The annual dose values were 137.25 mSv for doctors, 40.27 mSv for nurses and 51.95 mSv for auxiliary doctors, and all these annual dose values are below the limit established. The maximum values of the dose obtained for patients were 6.91, 10.92 and 15.34 mGy close to eye, thyroid and gonads, respectively. The DAP values were evaluated for patients in the same interventional radiology procedures. The dose and DAP values obtained are in agreement with values encountered in the literature.

Combined Effects of Supersaturation Rates and Doses on the Kinetic-Solubility Profiles of Amorphous Solid Dispersions Based on Water-Insoluble Poly(2-hydroxyethyl methacrylate) Hydrogels.

PubMed

Schver, Giovanna C R M; Lee, Ping I

2018-05-07

Under nonsink dissolution conditions, the kinetic-solubility profiles of amorphous solid dispersions (ASDs) based on soluble carriers typically exhibit so-called "spring-and-parachute" concentration-time behaviors. However, the kinetic-solubility profiles of ASDs based on insoluble carriers (including hydrogels) are known to show sustained supersaturation during nonsink dissolution through a matrix-regulated diffusion mechanism by which the supersaturation of the drug is built up gradually and sustained over an extended period without any dissolved polymers acting as crystallization inhibitors. Despite previous findings demonstrating the interplay between supersaturation rates and total doses on the kinetic-solubility profiles of soluble amorphous systems (including ASDs based on dissolution-regulated releases from soluble polymer carriers), the combined effects of supersaturation rates and doses on the kinetic-solubility profiles of ASDs based on diffusion-regulated releases from water-insoluble carriers have not been investigated previously. Thus, the objective of this study is to examine the impacts of total doses and supersaturation-generation rates on the resulting kinetic-solubility profiles of ASDs based on insoluble hydrogel carriers. We employed a previously established ASD-carrier system based on water-insoluble-cross-linked-poly(2-hydroxyethyl methacrylate) (PHEMA)-hydrogel beads and two poorly water soluble model drugs: the weakly acidic indomethacin (IND) and the weakly basic posaconazole (PCZ). Our results show clearly for the first time that by using the smallest-particle-size fraction and a high dose (i.e., above the critical dose), it is indeed possible to significantly shorten the duration of sustained supersaturation in the kinetic-solubility profile of an ASD based on a water-insoluble hydrogel carrier, such that it resembles the spring-and-parachute dissolution profiles normally associated with ASDs based on soluble carriers. This generates sufficiently rapid initial supersaturation buildup above the critical supersaturation, resulting in more rapid precipitation. Above this smallest-particle-size range, the matrix-diffusion-regulated nonlinear rate of drug release gets slower, which results in a more modest rate of supersaturation buildup, leading to a maximum supersaturation below the critical-supersaturation level without appreciable precipitation. The area-under-the-curve (AUC) values of the in vitro kinetic-solubility concentration-time profiles were used to correlate the corresponding trends in dissolution enhancement. There are observed monotonic increases in AUC values with increasing particle sizes for high-dose ASDs based on water-insoluble hydrogel matrixes, as opposed to the previously reported AUC maxima at some intermediate supersaturation rates or doses in soluble amorphous systems, whereas in the case of low-dose ASDs (i.e., below the critical dose levels), crystallization would be negligible, leading to sustained supersaturation with all particle sizes (i.e., eventually reaching the same maximum supersaturation) and the smallest particle size reaching the maximum supersaturation the fastest. As a result, the smallest particle sizes yield the largest AUC values in the case of low-dose ASDs based on water-insoluble hydrogel matrixes. In addition to probing the interplay between the supersaturation-generation rates and total doses in ASDs based on insoluble hydrogel carriers, our results further support the fact that through either increasing the hydrogel-particle size or lowering the total dose to achieve maximum supersaturation still below the critical-supersaturation level, it is possible to avoid drug precipitation so as to maintain sustained supersaturation.

Improvements in critical dosimetric endpoints using the Contura multilumen balloon breast brachytherapy catheter to deliver accelerated partial breast irradiation: preliminary dosimetric findings of a phase iv trial.

PubMed

Arthur, Douglas W; Vicini, Frank A; Todor, Dorin A; Julian, Thomas B; Lyden, Maureen R

2011-01-01

Dosimetric findings in patients treated with the Contura multilumen balloon (MLB) breast brachytherapy catheter to deliver accelerated partial breast irradiation (APBI) on a multi-institutional Phase IV registry trial are presented. Computed tomography-based three-dimensional planning with dose optimization was performed. For the trial, new ideal dosimetric goals included (1) ≥95% of the prescribed dose (PD) covering ≥90% of the target volume, (2) a maximum skin dose ≤125% of the PD, (3) maximum rib dose ≤145% of the PD, and (4) the V150 ≤50 cc and V200 ≤10 cc. The ability to concurrently achieve these dosimetric goals using the Contura MLB was analyzed. 144 cases were available for review. Using the MLB, all dosimetric criteria were met in 76% of cases. Evaluating dosimetric criteria individually, 92% and 89% of cases met skin and rib dose criteria, respectively. In 93% of cases, ideal target volume coverage goals were met, and in 99%, dose homogeneity criteria (V150 and V200) were satisfied. When skin thickness was ≥5 mm to <7 mm, the median skin dose was limited to 120.1% of the PD, and when skin thickness was <5 mm, the median skin dose was 124.2%. When rib distance was <5 mm, median rib dose was reduced to 136.5% of the PD. When skin thickness was <7 mm and distance to rib was <5 mm, median skin and rib doses were jointly limited to 120.6% and 142.1% of the PD, respectively. The Contura MLB catheter provided the means of achieving the imposed higher standard of dosimetric goals in the majority of clinical scenarios encountered. Copyright © 2011 Elsevier Inc. All rights reserved.

Correlation of Clinical and Dosimetric Factors With Adverse Pulmonary Outcomes in Children After Lung Irradiation

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

Venkatramani, Rajkumar, E-mail: rvenkatramani@chla.usc.edu; Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, California; Kamath, Sunil

Purpose: To identify the incidence and the risk factors for pulmonary toxicity in children treated for cancer with contemporary lung irradiation. Methods and Materials: We analyzed clinical features, radiographic findings, pulmonary function tests, and dosimetric parameters of children receiving irradiation to the lung fields over a 10-year period. Results: We identified 109 patients (75 male patients). The median age at irradiation was 13.8 years (range, 0.04-20.9 years). The median follow-up period was 3.4 years. The median prescribed radiation dose was 21 Gy (range, 0.4-64.8 Gy). Pulmonary toxic chemotherapy included bleomycin in 58.7% of patients and cyclophosphamide in 83.5%. The followingmore » pulmonary outcomes were identified and the 5-year cumulative incidence after irradiation was determined: pneumonitis, 6%; chronic cough, 10%; pneumonia, 35%; dyspnea, 11%; supplemental oxygen requirement, 2%; radiographic interstitial lung disease, 40%; and chest wall deformity, 12%. One patient died of progressive respiratory failure. Post-irradiation pulmonary function tests available from 44 patients showed evidence of obstructive lung disease (25%), restrictive disease (11%), hyperinflation (32%), and abnormal diffusion capacity (12%). Thoracic surgery, bleomycin, age, mean lung irradiation dose (MLD), maximum lung dose, prescribed dose, and dosimetric parameters between V{sub 22} (volume of lung exposed to a radiation dose ≥22 Gy) and V{sub 30} (volume of lung exposed to a radiation dose ≥30 Gy) were significant for the development of adverse pulmonary outcomes on univariate analysis. MLD, maximum lung dose, and V{sub dose} (percentage of volume of lung receiving the threshold dose or greater) were highly correlated. On multivariate analysis, MLD was the sole significant predictor of adverse pulmonary outcome (P=.01). Conclusions: Significant pulmonary dysfunction occurs in children receiving lung irradiation by contemporary techniques. MLD rather than prescribed dose should be used to perform risk stratification of patients receiving lung irradiation.« less

SU-E-T-580: Comparison of Cervical Carcinoma IMRT Plans From Four Commercial Treatment Planning Systems (TPS)

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

Cao, Y; Li, R; Chi, Z

2014-06-01

Purpose: Different treatment planning systems (TPS) use different treatment optimization and leaf sequencing algorithms. This work compares cervical carcinoma IMRT plans optimized with four commercial TPSs to investigate the plan quality in terms of target conformity and delivery efficiency. Methods: Five cervical carcinoma cases were planned with the Corvus, Monaco, Pinnacle and Xio TPSs by experienced planners using appropriate optimization parameters and dose constraints to meet the clinical acceptance criteria. Plans were normalized for at least 95% of PTV to receive the prescription dose (Dp). Dose-volume histograms and isodose distributions were compared. Other quantities such as Dmin(the minimum dose receivedmore » by 99% of GTV/PTV), Dmax(the maximum dose received by 1% of GTV/PTV), D100, D95, D90, V110%, V105%, V100% (the volume of GTV/PTV receiving 110%, 105%, 100% of Dp), conformity index(CI), homogeneity index (HI), the volume of receiving 40Gy and 50 Gy to rectum (V40,V50) ; the volume of receiving 30Gy and 50 Gy to bladder (V30,V50) were evaluated. Total segments and MUs were also compared. Results: While all plans meet target dose specifications and normal tissue constraints, the maximum GTVCI of Pinnacle plans was up to 0.74 and the minimum of Corvus plans was only 0.21, these four TPSs PTVCI had significant difference. The GTVHI and PTVHI of Pinnacle plans are all very low and show a very good dose distribution. Corvus plans received the higer dose of normal tissue. The Monaco plans require significantly less segments and MUs to deliver than the other plans. Conclusion: To deliver on a Varian linear-accelerator, the Pinnacle plans show a very good dose distribution. Corvus plans received the higer dose of normal tissue. The Monaco plans have faster beam delivery.« less

Pharmacokinetics, Safety and Tolerability of Sacubitril/Valsartan (LCZ696) After Single-Dose Administration in Healthy Chinese Subjects.

PubMed

Han, Yi; Ayalasomayajula, Surya; Pan, Wei; Yang, Fan; Yuan, Yaozong; Langenickel, Thomas; Hinder, Markus; Kalluri, Sampath; Pal, Parasar; Sunkara, Gangadhar

2017-02-01

Sacubitril/valsartan (LCZ696) is a first-in-class angiotensin receptor neprilysin inhibitor (ARNI) and has been recently approved in several countries for the treatment of patients with heart failure and reduced ejection fraction. This was the first study conducted to characterise the pharmacokinetics of LCZ696 analytes (pro-drug sacubitril, active neprilysin inhibitor LBQ657 and valsartan) after single-dose administration of LCZ696 in healthy Chinese subjects. In this open-label, randomised, parallel-group study, following screening and baseline evaluation, eligible healthy subjects received single oral doses of LCZ696 50, 100, 200 or 400 mg. The pharmacokinetics, safety and tolerability of LCZ696 were assessed up to 72 h after dosing. A total of 40 healthy male subjects were enrolled, and all completed the study. Following oral administration, LCZ696 delivered systemic exposure to sacubitril, LBQ657 and valsartan with a median time to reach maximum plasma concentration (T max ) ranging from 0.50 to 1.25, 2.00 to 3.00 and 1.50 to 2.50 h, respectively, over the investigated dose range. The mean terminal elimination half-life (T 1/2 ) ranged from 0.89 to 1.35, 8.57 to 9.24 and 5.33 to 7.91 h for sacubitril, LBQ657 and valsartan, respectively. The area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (AUC 0-last ), and maximum plasma concentration (C max ) for LBQ657 increased dose proportionally over the entire dose range. Dose linear increase in the exposure was observed across the dose range for sacubitril and valsartan. LCZ696 was safe and well tolerated at all doses in this study. Adverse events of only mild intensity, which required no treatment, were reported in 6 (15 %) subjects. The pharmacokinetic profiles of LCZ696 analytes in Chinese subjects are similar to those reported previously in Caucasian subjects.

Maximum tolerated dose evaluation of the AMPA modulator Org 26576 in healthy volunteers and depressed patients: a summary and method analysis of bridging research in support of phase II dose selection.

PubMed

Nations, Kari R; Bursi, Roberta; Dogterom, Peter; Ereshefsky, Larry; Gertsik, Lev; Mant, Tim; Schipper, Jacques

2012-09-01

A key challenge to dose selection in early central nervous system (CNS) clinical drug development is that patient tolerability profiles often differ from those of healthy volunteers (HVs), yet HVs are the modal population for determining doses to be investigated in phase II trials. Without clear tolerability data from the target patient population, first efficacy trials may include doses that are either too high or too low, creating undue risk for study participants and the development program overall. Bridging trials address this challenge by carefully investigating safety and tolerability in the target population prior to full-scale proof-of-concept trials. Org 26576 is an alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor positive allosteric modulator that acts by modulating ionotropic AMPA-type glutamate receptors to enhance glutamatergic neurotransmission. In preparation for phase II efficacy trials in major depressive disorder (MDD), two separate phase I trials were conducted to evaluate safety, tolerability, and pharmacokinetics in HVs and in the target patient population. Both trials were randomized and placebo controlled, and included multiple rising-dose cohorts (HV range 100-400 mg bid; MDD range 100-600 mg bid). HVs (n = 36) and patients with MDD (n = 54) were dosed under similarly controlled conditions in an inpatient facility, HVs for up to 14 days and MDD patients for up to 28 days. Safety, tolerability, and pharmacokinetics were assessed frequently. Despite comparable pharmacokinetic profiles, the maximum tolerated dose (MTD) in depressed patients was 450 mg bid, twice the MTD established in HVs. No clinically relevant safety issues associated with Org 26576 were noted. This article presents safety, tolerability, and pharmacokinetic data from two different populations examined under similar dosing conditions. The important implications of such bridging work in phase II dose selection are discussed, as are study design and data interpretation challenges.

Intensity modulated operating mode of the rotating gamma system.

PubMed

Sengupta, Bishwambhar; Gulyas, Laszlo; Medlin, Donald; Koroknai, Tibor; Takacs, David; Filep, Gyorgy; Panko, Peter; Godo, Bence; Hollo, Tamas; Zheng, Xiao Ran; Fedorcsak, Imre; Dobai, Jozsef; Bognar, Laszlo; Takacs, Endre

2018-05-01

The purpose of this work was to explore two novel operation modalities of the rotating gamma systems (RGS) that could expand its clinical application to lesions in close proximity to critical organs at risk (OAR). The approach taken in this study consists of two components. First, a Geant4-based Monte Carlo (MC) simulation toolkit is used to model the dosimetric properties of the RGS Vertex 360™ for the normal, intensity modulated radiosurgery (IMRS), and speed modulated radiosurgery (SMRS) operation modalities. Second, the RGS Vertex 360™ at the Rotating Gamma Institute in Debrecen, Hungary is used to collect experimental data for the normal and IMRS operation modes. An ion chamber is used to record measurements of the absolute dose. The dose profiles are measured using Gafchromic EBT3 films positioned within a spherical water equivalent phantom. A strong dosimetric agreement between the measured and simulated dose profiles and penumbra was found for both the normal and IMRS operation modes for all collimator sizes (4, 8, 14, and 18 mm diameter). The simulated falloff and maximum dose regions agree better with the experimental results for the 4 and 8 mm diameter collimators. Although the falloff regions align well in the 14 and 18 mm collimators, the maximum dose regions have a larger difference. For the IMRS operation mode, the simulated and experimental dose distributions are ellipsoidal, where the short axis aligns with the blocked angles. Similarly, the simulated dose distributions for the SMRS operation mode also adopt an ellipsoidal shape, where the short axis aligns with the angles where the orbital speed is highest. For both modalities, the dose distribution is highly constrained with a sharper penumbra along the short axes. Dose modulation of the RGS can be achieved with the IMRS and SMRS modes. By providing a highly constrained dose distribution with a sharp penumbra, both modes could be clinically applicable for the treatment of lesions in close proximity to critical OARs. © 2018 American Association of Physicists in Medicine.

Safety and tolerability of guadecitabine (SGI-110) in patients with myelodysplastic syndrome and acute myeloid leukaemia: a multicentre, randomised, dose-escalation phase 1 study.

PubMed

Issa, Jean-Pierre J; Roboz, Gail; Rizzieri, David; Jabbour, Elias; Stock, Wendy; O'Connell, Casey; Yee, Karen; Tibes, Raoul; Griffiths, Elizabeth A; Walsh, Katherine; Daver, Naval; Chung, Woonbok; Naim, Sue; Taverna, Pietro; Oganesian, Aram; Hao, Yong; Lowder, James N; Azab, Mohammad; Kantarjian, Hagop

2015-09-01

Hypomethylating agents are used to treat cancers driven by aberrant DNA methylation, but their short half-life might limit their activity, particularly in patients with less proliferative diseases. Guadecitabine (SGI-110) is a novel hypomethylating dinucleotide of decitabine and deoxyguanosine resistant to degradation by cytidine deaminase. We aimed to assess the safety and clinical activity of subcutaneously given guadecitabine in patients with acute myeloid leukaemia or myelodysplastic syndrome. In this multicentre, open-label, phase 1 study, patients from nine North American medical centres with myelodysplastic syndrome or acute myeloid leukaemia that was refractory to or had relapsed after standard treatment were randomly assigned (1:1) to receive subcutaneous guadecitabine, either once-daily for 5 consecutive days (daily × 5), or once-weekly for 3 weeks, in a 28-day treatment cycle. Patients were stratified by disease. A 3 + 3 dose-escalation design was used in which we treated patients with guadecitabine doses of 3-125 mg/m(2) in separate dose-escalation cohorts. A twice-weekly treatment schedule was added to the study after a protocol amendment. The primary objective was to assess safety and tolerability of guadecitabine, determine the maximum tolerated and biologically effective dose, and identify the recommended phase 2 dose of guadecitabine. Safety analyses included all patients who received at least one dose of guadecitabine. Pharmacokinetic and pharmacodynamic analyses to determine the biologically effective dose included all patients for whom samples were available. This study is registered with ClinicalTrials.gov, number NCT01261312. Between Jan 4, 2011, and April 11, 2014, we enrolled and treated 93 patients: 35 patients with acute myeloid leukaemia and nine patients with myelodysplastic syndrome in the daily × 5 dose-escalation cohorts, 28 patients with acute myeloid leukaemia and six patients with myelodysplastic syndrome in the once-weekly dose-escalation cohorts, and 11 patients with acute myeloid leukaemia and four patients with myelodysplastic syndrome in the twice-weekly dose-escalation cohorts. The most common grade 3 or higher adverse events were febrile neutropenia (38 [41%] of 93 patients), pneumonia (27 [29%] of 93 patients), thrombocytopenia (23 [25%] of 93 patients), anaemia (23 [25%] of 93 patients), and sepsis (16 [17%] of 93 patients). The most common serious adverse events were febrile neutropenia (29 [31%] of 93 patients), pneumonia (26 [28%] of 93 patients), and sepsis (16 [17%] of 93 patients). Six of the 74 patients with acute myeloid leukaemia and six of the 19 patients with myelodysplastic syndrome had a clinical response to treatment. Two dose-limiting toxicities were noted in patients with myelodysplastic syndrome at 125 mg/m(2) daily × 5, thus the maximum tolerated dose in patients with myelodysplastic syndrome was 90 mg/m(2) daily × 5. The maximum tolerated dose was not reached in patients with acute myeloid leukaemia. Potent dose-related DNA demethylation occurred on the daily × 5 regimen, reaching a plateau at 60 mg/m(2) (designated as the biologically effective dose). Guadecitabine given subcutaneously at 60 mg/m(2) daily × 5 is well tolerated and is clinically and biologically active in patients with myelodysplastic syndrome and acute myeloid leukaemia. Guadecitabine 60 mg/m(2) daily × 5 is the recommended phase 2 dose, and these findings warrant further phase 2 studies. Astex Pharmaceuticals, Stand Up To Cancer. Copyright © 2015 Elsevier Ltd. All rights reserved.

SU-E-T-197: Helical Cranial-Spinal Treatments with a Linear Accelerator

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

Anderson, J; Bernard, D; Liao, Y

2014-06-01

Purpose: Craniospinal irradiation (CSI) of systemic disease requires a high level of beam intensity modulation to reduce dose to bone marrow and other critical structures. Current helical delivery machines can take 30 minutes or more of beam-on time to complete these treatments. This pilot study aims to test the feasibility of performing helical treatments with a conventional linear accelerator using longitudinal couch travel during multiple gantry revolutions. Methods: The VMAT optimization package of the Eclipse 10.0 treatment planning system was used to optimize pseudo-helical CSI plans of 5 clinical patient scans. Each gantry revolution was divided into three 120° arcsmore » with each isocenter shifted longitudinally. Treatments requiring more than the maximum 10 arcs used multiple plans with each plan after the first being optimized including the dose of the others (Figure 1). The beam pitch was varied between 0.2 and 0.9 (couch speed 5- 20cm/revolution and field width of 22cm) and dose-volume histograms of critical organs were compared to tomotherapy plans. Results: Viable pseudo-helical plans were achieved using Eclipse. Decreasing the pitch from 0.9 to 0.2 lowered the maximum lens dose by 40%, the mean bone marrow dose by 2.1% and the maximum esophagus dose by 17.5%. (Figure 2). Linac-based helical plans showed dose results comparable to tomotherapy delivery for both target coverage and critical organ sparing, with the D50 of bone marrow and esophagus respectively 12% and 31% lower in the helical linear accelerator plan (Figure 3). Total mean beam-on time for the linear accelerator plan was 8.3 minutes, 54% faster than the tomotherapy average for the same plans. Conclusions: This pilot study has demonstrated the feasibility of planning pseudo-helical treatments for CSI targets using a conventional linac and dynamic couch movement, and supports the ongoing development of true helical optimization and delivery.« less

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

Leney, M; Nalichowski, A; Patel, S

Purpose: To determine the effects of patient separation on absolute dose and dose distribution in patients undergoing pelvic radiotherapy on TomoTherapy. Methods: An Alderson RANDO phantom with 4cm of bolus was imaged on a CT simulator and the resulting scans were contoured as a whole pelvic case. Using TomoTherapy Planning Station, the plan was designed to give 45 Gy to 95% of the treatment volume in 25 fractions. TomoTherapy MVCT scans were performed on the RANDO phantom with 2cm and 4cm of bolus removed to simulate visible changes in a patient’s anatomy. The MVCT images were rigidly registered with planningmore » CT images on TomoTherapy Planned Adaptive. The original fluence was recalculated on the MVCT images and changes in dose distribution due to patient separation were quantified by the changes in DVHs for the target volume and the organs at risk. Results: Patient separation difference equivalent to 2cm and 4cm in anterior-posterior direction resulted in an increase of the PTV D50 and maximum PTV dose of 5.6%, 6.2% for 2cm and 7.7%, 10.4% for 4cm, respectively. For the 2cm change, D50 and maximum doses to organs at risk increased by 6.5%, 7.1% in the bladder, 4.9%, 4.8% in the rectum, and 5.3%, 6.6% in the bowel. For the 4cm change, D50 and maximum doses increased by 10.7%, 12.2% in the bladder, 5.9%, 6.1% in the rectum, and 7.7%, 10.1% in the bowel. Conclusion: This research indicates that, without any changes to the structures, patient separation in the anterior-posterior direction can affect the dose distribution for the PTV and organs at risk. These results can assist physicians in determining if obtaining a new CT simulation set and replanning is necessary for pelvic patients on TomoTherapy.« less

SU-E-T-399: Evaluation of Selection Criteria for Computational Human Phantoms for Use in Out-Of-Field Organ Dosimetry for Radiotherapy Patients

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

Pelletier, C; Jung, J; Lee, C

2015-06-15

Purpose: To quantify the dosimetric uncertainty due to organ position errors when using height and weight as phantom selection criteria in the UF/NCI Hybrid Phantom Library for the purpose of out-of-field organ dose reconstruction. Methods: Four diagnostic patient CT images were used to create 7-field IMRT plans. For each patient, dose to the liver, right lung, and left lung were calculated using the XVMC Monte Carlo code. These doses were taken to be the ground truth. For each patient, the phantom with the most closely matching height and weight was selected from the body size dependent phantom library. The patientmore » plans were then transferred to the computational phantoms and organ doses were recalculated. Each plan was also run on 4 additional phantoms with reference heights and or weights. Maximum and mean doses for the three organs were computed, and the DVHs were extracted and compared. One sample t-tests were performed to compare the accuracy of the height and weight matched phantoms against the additional phantoms in regards to both maximum and mean dose. Results: For one of the patients, the height and weight matched phantom yielded the most accurate results across all three organs for both maximum and mean doses. For two additional patients, the matched phantom yielded the best match for one organ only. In 13 of the 24 cases, the matched phantom yielded better results than the average of the other four phantoms, though the results were only statistically significant at the .05 level for three cases. Conclusion: Using height and weight matched phantoms does yield better results in regards to out-of-field dosimetry than using average phantoms. Height and weight appear to be moderately good selection criteria, though this selection criteria failed to yield any better results for one patient.« less

SU-F-T-18: The Importance of Immobilization Devices in Brachytherapy Treatments of Vaginal Cuff

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

Shojaei, M; Dumitru, N; Pella, S

2016-06-15

Purpose: High dose rate brachytherapy is a highly localized radiation therapy that has a very high dose gradient. Thus one of the most important parts of the treatment is the immobilization. The smallest movement of the patient or applicator can result in dose variation to the surrounding tissues as well as to the tumor to be treated. We will revise the ML Cylinder treatments and their localization challenges. Methods: A retrospective study of 25 patients with 5 treatments each looking into the applicator’s placement in regard to the organs at risk. Motion possibilities for each applicator intra and inter fractionationmore » with their dosimetric implications were covered and measured in regard with their dose variance. The localization immobilization devices used were assessed for the capability to prevent motion before and during the treatment delivery. Results: We focused on the 100% isodose on central axis and a 15 degree displacement due to possible rotation analyzing the dose variations to the bladder and rectum walls. The average dose variation for bladder was 15% of the accepted tolerance, with a minimum variance of 11.1% and a maximum one of 23.14% on the central axis. For the off axis measurements we found an average variation of 16.84% of the accepted tolerance, with a minimum variance of 11.47% and a maximum one of 27.69%. For the rectum we focused on the rectum wall closest to the 120% isodose line. The average dose variation was 19.4%, minimum 11.3% and a maximum of 34.02% from the accepted tolerance values Conclusion: Improved immobilization devices are recommended. For inter-fractionation, localization devices are recommended in place with consistent planning in regards with the initial fraction. Many of the present immobilization devices produced for external radiotherapy can be used to improve the localization of HDR applicators during transportation of the patient and during treatment.« less

Predicting Nonauditory Adverse Radiation Effects Following Radiosurgery for Vestibular Schwannoma: A Volume and Dosimetric Analysis

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

Hayhurst, Caroline; Monsalves, Eric; Bernstein, Mark

2012-04-01

Purpose: To define clinical and dosimetric predictors of nonauditory adverse radiation effects after radiosurgery for vestibular schwannoma treated with a 12 Gy prescription dose. Methods: We retrospectively reviewed our experience of vestibular schwannoma patients treated between September 2005 and December 2009. Two hundred patients were treated at a 12 Gy prescription dose; 80 had complete clinical and radiological follow-up for at least 24 months (median, 28.5 months). All treatment plans were reviewed for target volume and dosimetry characteristics; gradient index; homogeneity index, defined as the maximum dose in the treatment volume divided by the prescription dose; conformity index; brainstem; andmore » trigeminal nerve dose. All adverse radiation effects (ARE) were recorded. Because the intent of our study was to focus on the nonauditory adverse effects, hearing outcome was not evaluated in this study. Results: Twenty-seven (33.8%) patients developed ARE, 5 (6%) developed hydrocephalus, 10 (12.5%) reported new ataxia, 17 (21%) developed trigeminal dysfunction, 3 (3.75%) had facial weakness, and 1 patient developed hemifacial spasm. The development of edema within the pons was significantly associated with ARE (p = 0.001). On multivariate analysis, only target volume is a significant predictor of ARE (p = 0.001). There is a target volume threshold of 5 cm3, above which ARE are more likely. The treatment plan dosimetric characteristics are not associated with ARE, although the maximum dose to the 5th nerve is a significant predictor of trigeminal dysfunction, with a threshold of 9 Gy. The overall 2-year tumor control rate was 96%. Conclusions: Target volume is the most important predictor of adverse radiation effects, and we identified the significant treatment volume threshold to be 5 cm3. We also established through our series that the maximum tolerable dose to the 5th nerve is 9 Gy.« less

SU-F-J-57: Effectiveness of Daily CT-Based Three-Dimensional Image Guided and Adaptive Proton Therapy

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

Moriya, S; National Cancer Center, Kashiwa, Chiba; Tachibana, H

Purpose: Daily CT-based three-dimensional image-guided and adaptive (CTIGRT-ART) proton therapy system was designed and developed. We also evaluated the effectiveness of the CTIGRT-ART. Methods: Retrospective analysis was performed in three lung cancer patients: Proton treatment planning was performed using CT image datasets acquired by Toshiba Aquilion ONE. Planning target volume and surrounding organs were contoured by a well-trained radiation oncologist. Dose distribution was optimized using 180-deg. and 270-deg. two fields in passive scattering proton therapy. Well commissioned Simplified Monte Carlo algorithm was used as dose calculation engine. Daily consecutive CT image datasets was acquired by an in-room CT (Toshiba Aquilionmore » LB). In our in-house program, two image registrations for bone and tumor were performed to shift the isocenter using treatment CT image dataset. Subsequently, dose recalculation was performed after the shift of the isocenter. When the dose distribution after the tumor registration exhibits change of dosimetric parameter of CTV D90% compared to the initial plan, an additional process of was performed that the range shifter thickness was optimized. Dose distribution with CTV D90% for the bone registration, the tumor registration only and adaptive plan with the tumor registration was compared to the initial plan. Results: In the bone registration, tumor dose coverage was decreased by 16% on average (Maximum: 56%). The tumor registration shows better coverage than the bone registration, however the coverage was also decreased by 9% (Maximum: 22%) The adaptive plan shows similar dose coverage of the tumor (Average: 2%, Maximum: 7%). Conclusion: There is a high possibility that only image registration for bone and tumor may reduce tumor coverage. Thus, our proposed methodology of image guidance and adaptive planning using the range adaptation after tumor registration would be effective for proton therapy. This research is partially supported by Japan Agency for Medical Research and Development (AMED).« less

Acute administration of tramadol and tapentadol at effective analgesic and maximum tolerated doses causes hepato- and nephrotoxic effects in Wistar rats.

PubMed

Barbosa, Joana; Faria, Juliana; Leal, Sandra; Afonso, Luís Pedro; Lobo, João; Queirós, Odília; Moreira, Roxana; Carvalho, Félix; Dinis-Oliveira, Ricardo Jorge

2017-08-15

Tramadol and tapentadol are two atypical synthetic opioid analgesics, with monoamine reuptake inhibition properties. Mainly aimed at the treatment of moderate to severe pain, these drugs are extensively prescribed for multiple clinical applications. Along with the increase in their use, there has been an increment in their abuse, and consequently in the reported number of adverse reactions and intoxications. However, little is known about their mechanisms of toxicity. In this study, we have analyzed the in vivo toxicological effects in liver and kidney resulting from an acute exposure of a rodent animal model to both opioids. Male Wistar rats were intraperitoneally administered with 10, 25 and 50mg/kg tramadol and tapentadol, corresponding to a low, effective analgesic dose, an intermediate dose and the maximum recommended daily dose, respectively, for 24h. Toxicological effects were assessed in terms of oxidative stress, biochemical and metabolic parameters and histopathology, using serum and urine samples, liver and kidney homogenates and tissue specimens. The acute exposure to tapentadol caused a dose-dependent increase in protein oxidation in liver and kidney. Additionally, exposure to both opioids led to hepatic commitment, as shown by increased serum lipid levels, decreased urea concentration, increased alanine aminotransferase and decreased butyrylcholinesterase activities. It also led to renal impairment, as reflected by proteinuria and decreased glomerular filtration rate. Histopathological findings included sinusoidal dilatation, microsteatosis, vacuolization, cell infiltrates and cell degeneration, indicating metabolic changes, inflammation and cell damage. In conclusion, a single effective analgesic dose or the maximum recommended daily dose of both opioids leads to hepatotoxicity and nephrotoxicity, with tapentadol inducing comparatively more toxicity. Whether these effects reflect risks during the therapeutic use or human overdoses requires focused attention by the medical community. Copyright © 2017 Elsevier B.V. All rights reserved.

Poster — Thur Eve — 64: Preliminary investigation of arc configurations for optimal sparing of normal tissue in hypofractionated stereotactic radiotherapy (HF-SRT) of multiple brain metastases using a 5mm interdigitating micro-multileaf collimator

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

Leavens, C; Wronski, M; Lee, YK

2014-08-15

Purpose: To evaluate normal tissue sparing in intra-cranial HF-SRT, comparing various arc configurations with the Synergy Beam Modulator (SynBM) and Agility linacs, the latter incorporating leaf interdigitation and backup jaws. Methods: Five patients with multiple brain metastases (BMs), (5 BMs (n=2), 3 BMs (n=3)) treated with HF-SRT using 25 Gy (n=2) or 30 Gy (n=3) in 5 fractions, were investigated. Clinical treatment plans used the SynBM. Each patient was retrospectively re-planned on Agility, employing three planning strategies: (A) one isocenter and dedicated arc for each BM; (B) a single isocenter, centrally placed with respect to BMs; (C) the isocenter andmore » arc configuration used in the SynBM plan, where closely spaced (<5cm) BMs used a dedicated isocenter and arcs. Agility plans were normalized for PTV coverage and heterogeneity. Results and Conclusion: Strategy A obtained the greatest improvements over the SynBM plan, where the maximum OAR dose, and mean dose to normal brain (averaged for all patients) were reduced by 55cGy and 25cGy, respectively. Strategy B was limited by having a single isocenter, hence less jaw shielding and increased MLC leakage. The maximum OAR dose was reduced by 13cGy, however mean dose to normal brain increased by 84cGy. Strategy C reduced the maximum OAR dose and mean dose to normal brain by 32cGy and 9cGy, respectively. The results from this study indicate that, for intra-cranial HF-SRT of multiple BMs, Agility plans are equal or better than SynBM plans. Further planning is needed to investigate dose sparing using Strategy A and the SynBM.« less

SU-E-J-70: Evaluation of Multiple Isocentric Intensity Modulated and Volumetric Modulated Arc Therapy Techniques Using Portal Dosimetry

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

Muralidhar, K Raja; Pangam, S; Kolla, J

2015-06-15

Purpose: To develop a method for verification of dose distribution in a patient during treatment using multiple isocentric Intensity modulated and volumetric modulated arc therapy techniques with portal dosimetry. Methods: Varian True Beam accelerator, equipped with an aS1000 megavoltage electronic portal imaging device (EPID) has an integrated image mode for portal dosimetry (PD). The source-to-imager distance was taken at 150 cm to avoid collision to the table. Fourteen fractions were analyzed for this study. During shift in a single plan from one isocenter to another isocenter, EPID also shifted longitudinally for each field by taking the extent of divergence ofmore » beam into the consideration for EPID distance of 150cm. Patients were given treatment everyday with EPID placed in proper position for each field. Several parameters were obtained by comparing the dose distribution between fractions to fraction. The impact of the intra-fraction and inter-fraction of the patient in combination with isocenter shift of the beams were observed. Results: During treatment, measurements were performed by EPID and were evaluated by the gamma method. Analysis was done between fractions for multiple isocenter treatments. The pass rates of the gamma analysis with a criterion of 3% and 3 mm for the 14 fractions were over 97.8% with good consistency. Whereas maximum gamma exceeded the criteria in few fractions (in<1 cc vol). Average gamma was observed in the criteria of 0.5%. Maximum dose difference and average dose differences were less than 0.22 CU and 0.01 CU for maximum tolerance of 1.0 CU and 0.2 CU respectively. Conclusion: EPID with extended distance is ideal method to verify the multiple isocentric dose distribution in patient during treatment, especially cold and hot spots in junction dose. Verification of shifts as well as the dose differences between each fraction due to inter-fraction and intra-fraction of the patient can be derived.« less

Validation and uncertainty analysis of a pre-treatment 2D dose prediction model

NASA Astrophysics Data System (ADS)

Baeza, Jose A.; Wolfs, Cecile J. A.; Nijsten, Sebastiaan M. J. J. G.; Verhaegen, Frank

2018-02-01

Independent verification of complex treatment delivery with megavolt photon beam radiotherapy (RT) has been effectively used to detect and prevent errors. This work presents the validation and uncertainty analysis of a model that predicts 2D portal dose images (PDIs) without a patient or phantom in the beam. The prediction model is based on an exponential point dose model with separable primary and secondary photon fluence components. The model includes a scatter kernel, off-axis ratio map, transmission values and penumbra kernels for beam-delimiting components. These parameters were derived through a model fitting procedure supplied with point dose and dose profile measurements of radiation fields. The model was validated against a treatment planning system (TPS; Eclipse) and radiochromic film measurements for complex clinical scenarios, including volumetric modulated arc therapy (VMAT). Confidence limits on fitted model parameters were calculated based on simulated measurements. A sensitivity analysis was performed to evaluate the effect of the parameter uncertainties on the model output. For the maximum uncertainty, the maximum deviating measurement sets were propagated through the fitting procedure and the model. The overall uncertainty was assessed using all simulated measurements. The validation of the prediction model against the TPS and the film showed a good agreement, with on average 90.8% and 90.5% of pixels passing a (2%,2 mm) global gamma analysis respectively, with a low dose threshold of 10%. The maximum and overall uncertainty of the model is dependent on the type of clinical plan used as input. The results can be used to study the robustness of the model. A model for predicting accurate 2D pre-treatment PDIs in complex RT scenarios can be used clinically and its uncertainties can be taken into account.

A phase 1 trial of ABT-510 concurrent with standard chemoradiation for patients with newly diagnosed glioblastoma.

PubMed

Nabors, Louis B; Fiveash, John B; Markert, James M; Kekan, Manasi S; Gillespie, George Y; Huang, Zhi; Johnson, Martin J; Meleth, Sreelatha; Kuo, Huichien; Gladson, Candece L; Fathallah-Shaykh, Hassan M

2010-03-01

To determine the maximum tolerated dose of ABT-510, a thrombospondin-1 mimetic drug with antiangiogenic properties, when used concurrently with temozolomide and radiotherapy in patients with newly diagnosed glioblastoma. Phase 1 dose-escalation clinical trial. Comprehensive Cancer Center, University of Alabama at Birmingham. Patients A total of 23 patients with newly diagnosed, histologically verified glioblastoma enrolled between April 2005 and January 2007. Four cohorts of 3 patients each received subcutaneous ABT-510 injection at doses of 20, 50, 100, or 200 mg/d. The maximum cohort was expanded to 14 patients to obtain additional safety and gene expression data. The treatment plan included 10 weeks of induction phase (temozolomide and radiotherapy with ABT-510 for 6 weeks plus ABT-510 monotherapy for 4 weeks) followed by a maintenance phase of ABT-510 and monthly temozolomide. Patients were monitored with brain magnetic resonance imaging and laboratory testing for dose-limiting toxicities, defined as grades 3 or 4 nonhematological toxicities and grade 4 hematological toxicities. Therapy was discontinued if 14 maintenance cycles were completed, disease progression occurred, or if the patient requested withdrawal. Disease progression, survival statistics, and gene expression arrays were analyzed. There were no grade 3 or 4 dose-limiting toxicity events that appeared related to ABT-510 for the dose range of 20 to 200 mg/d. A maximum tolerated dose was not defined. Most adverse events were mild, and injection-site reactions. The median time to tumor progression was 45.9 weeks, and the median overall survival time was 64.4 weeks. Gene expression analysis using TaqMan low-density arrays identified angiogenic genes that were differentially expressed in the brains of controls compared with patients with newly diagnosed glioblastoma, and identified FGF-1 and TIE-1 as being downregulated in patients who had better clinical outcomes. ABT-510, at subcutaneous doses up to 200 mg/d, is tolerated well with concurrent temozolomide and radiotherapy in patients with newly diagnosed glioblastoma, and low-density arrays provide a useful method of exploring gene expression profiles.

A First-Time-In-Human Phase I Clinical Trial of Bispecific Antibody-Targeted, Paclitaxel-Packaged Bacterial Minicells

PubMed Central

Rosenthal, Mark; McArthur, Grant A.; Pattison, Scott T.; Pattison, Stacey L.; MacDiarmid, Jennifer; Brahmbhatt, Himanshu; Scott, Andrew M.

2015-01-01

Background We have harnessed a novel biological system, the bacterial minicell, to deliver cancer therapeutics to cancer cells. Preclinical studies showed that epidermal growth factor receptor (EGFR)-targeted, paclitaxel-loaded minicells (EGFRminicellsPac) have antitumor effects in xenograft models. To examine the safety of the minicell delivery system, we initiated a first-time-in-human, open-label, phase I clinical study of EGFRminicellsPac in patients with advanced solid tumors. Methodology Patients received 5 weekly infusions followed by a treatment free week. Seven dose levels (1x108, 1x109, 3x109, 1x1010, 1.5x1010, 2x1010, 5x1010) were evaluated using a 3+3 dose-escalation design. Primary objectives were safety, tolerability and determination of the maximum tolerated dose. Secondary objectives were assessment of immune/inflammatory responses and antitumor activity. Principal Findings Twenty eight patients were enrolled, 22 patients completed at least one cycle of EGFRminicellsPac; 6 patients did not complete a cycle due to rapidly progressive disease. A total of 236 doses was delivered over 42 cycles, with a maximum of 45 doses administered to a single patient. Most common treatment-related adverse events were rigors and pyrexia. No deaths resulted from treatment-related adverse events and the maximum tolerated dose was defined as 1x1010 EGFRminicellsPac. Surprisingly, only a mild self-limiting elevation in the inflammatory cytokines IL-6, IL-8 and TNFα and anti-inflammatory IL-10 was observed. Anti-LPS antibody titers peaked by dose 3 and were maintained at that level despite repeat dosing with the bacterially derived minicells. Ten patients (45%; n = 22) achieved stable disease as their best response. Conclusions/Significance This is the first study in humans of a novel biological system that can provide targeted delivery of a range of chemotherapeutic drugs to solid tumor cells. Bispecific antibody-targeted minicells, packaged with the chemotherapeutic paclitaxel, were shown to be safe in patients with advanced solid tumors with modest clinical efficacy observed. Further study in Phase II trials is planned. Trial Registration Australian New Zealand Clinical Trials Registry ACTRN12609000672257 PMID:26659127

TU-H-CAMPUS-TeP3-01: Gold Nanoparticle-Enhanced Radiation Therapy in In Vitro A549 Lung Carcinoma: Studies in Both Traditional Monolayer and Three Dimensional Cell Culture Models

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

Oumano, M; University of Massachusetts Lowell, Lowell, MA; Ngwa, W

Purpose: To measure the increase in in vitro radiosensitivity for A549 lung carcinoma cells due to gold nanoparticle (GNP) radiation dose enhancement in both traditional monolayer and three dimensional (3D) cell culture models. Methods: A γH2AX immunofluorescence assay is performed on monolayer A549 cell culture and quantitatively analyzed to measure the increase in double strand breaks (DSBs) resulting from GNP dose enhancement. A clonogenic survival assay (CSA) is then performed on monolayer A549 cell culture to assess true viability after treatment. And lastly, another γH2AX assay is performed on 3D A549 multicellular nodules overlaid on a bed of growth factormore » reduced matrigel to measure dose response in a model that better recapitulates treatment response to actual tumors in vivo. Results: The first γH2AX assay performed on the monolayer cell culture shows a significant increase in DSBs due to GNP dose enhancement. The maximum average observed increase in normalized fluorescent intensity for monolayer cell culture is 171% for the 6Gy-treatment groups incubated in 0.556 mg Au/ml solution. The CSA performed on monolayer cell culture also shows considerable GNP dose enhancement. The maximum decrease in the normalized surviving fraction is 12% for the 4Gy-treatment group incubated in 0.556 mg Au/ml. And lastly, the GNP dose enhancement is confirmed to be mitigated in three dimensional cell culture models as compared to the traditional monolayer model. The maximum average observed dose enhancement for 3D cell culture is 19% for the 6Gy-treatment groups and incubated in 0.556 mg Au/ml. Conclusion: A marked increase in radiosensitivity is observed for A549 lung carcinoma cells when treated with GNPs plus radiation as opposed to radiation alone. Traditional monolayer cell culture also shows a much more pronounced radiation dose enhancement than 3D cell culture.« less

Potential for focused beam orthovoltage therapy

NASA Astrophysics Data System (ADS)

Mahato, Dip N.; MacDonald, C. A.

2010-08-01

Radiation therapy typically employs high energy photon beams because the low absorption coefficient at these energies minimizes skin dose with a conventional, unfocused beam. At orthovoltage energies less than 150 keV, the maximum dose for a single beam occurs very close to the skin surface. However a well-focused beam of low energy x rays can provide much higher flux at the target depth while sparing dose to the skin. The measured focal spot size for the polycapillary optic was 0.2 mm and was found to remain unchanged through 50 mm of phantom thickness. The calculated depth-dose curve was found to peak several centimeters below the surface with 25-40 keV radiation. Modeling indicates that the tumor dose would remain much higher than the skin dose even after scanning to cover a 1 cm3 tumor.

Potential for reduced radiation‐induced toxicity using intensity‐modulated arc therapy for whole‐brain radiotherapy with hippocampal sparing

PubMed Central

Sood, Sumit; Lominska, Christopher; Kumar, Parvesh; Badkul, Rajeev; Jiang, Hongyu; Wang, Fen

2015-01-01

The purpose of this study was to retrospectively investigate the accuracy, plan quality, and efficiency of using intensity‐modulated arc therapy (IMAT) for whole brain radiotherapy (WBRT) patients with sparing not only the hippocampus (following RTOG 0933 compliance criteria) but also other organs at risk (OARs). A total of 10 patients previously treated with nonconformal opposed laterals whole‐brain radiotherapy (NC‐WBRT) were retrospectively replanned for hippocampal sparing using IMAT treatment planning. The hippocampus was volumetrically contoured on fused diagnostic T1‐weighted MRI with planning CT images and hippocampus avoidance zone (HAZ) was generated using a 5 mm uniform margin around the hippocampus. Both hippocampi were defined as one paired organ. Whole brain tissue minus HAZ was defined as the whole‐brain planning target volume (WB‐PTV). Highly conformal IMAT plans were generated in the Eclipse treatment planning system for Novalis TX linear accelerator consisting of high‐definition multileaf collimators (HD‐MLCs: 2.5 mm leaf width at isocenter) and 6 MV beam for a prescription dose of 30 Gy in 10 fractions following RTOG 0933 dosimetric criteria. Two full coplanar arcs with orbits avoidance sectors were used. In addition to RTOG criteria, doses to other organs at risk (OARs), such as parotid glands, cochlea, external/middle ear canals, skin, scalp, optic pathways, brainstem, and eyes/lens, were also evaluated. Subsequently, dose delivery efficiency and accuracy of each IMAT plan was assessed by delivering quality assurance (QA) plans with a MapCHECK device, recording actual beam‐on time and measuring planed vs. measured dose agreement using a gamma index. On IMAT plans, following RTOG 0933 dosimetric criteria, the maximum dose to WB‐PTV, mean WB‐PTV D2%, and mean WB‐PTV D98% were 34.9±0.3 Gy,33.2±0.4 Gy, and 26.0±0.4 Gy, respectively. Accordingly, WB‐PTV received the prescription dose of 30 Gy and mean V30 was 90.5%±0.5%. The D100%, and mean and maximum doses to hippocampus were 8.4±0.3 Gy,11.2±0.3 Gy, and 15.6±0.4 Gy, on average, respectively. The mean values of homogeneity index (HI) and conformity index (CI) were 0.23×0.02 and 0.96×0.02, respectively. The maximum point dose to WB‐PTV was 35.3 Gy, well below the optic pathway tolerance of 37.5 Gy. In addition, compared to NC‐WBRT, dose reduction of mean and maximum of parotid glands from IMAT were 65% and 50%, respectively. Ear canals mean and maximum doses were reduced by 26% and 12%, and mean and maximum scalp doses were reduced by 9 Gy (32%) and 2 Gy (6%), on average, respectively. The mean dose to skin was 9.7 Gy with IMAT plans compared to 16 Gy with conventional NC‐WBRT, demonstrating that absolute reduction of skin dose by a factor of 2. The mean values of the total number of monitor units (MUs) and actual beam on time were 719×44 and 2.34×0.14 min, respectively. The accuracy of IMAT QA plan delivery was (98.1±0.8) %, on average, with a 3%/3 mm gamma index passing rate criteria. All of these plans were considered clinically acceptable per RTOG 0933 criteria. IMAT planning provided highly conformal and homogenous plan with a fast and effective treatment option for WBRT patients, sparing not only hippocampi but also other OARs, which could potentially result in an additional improvement of the quality life (QoL). In the future, we plan to evaluate the clinical potential of IMAT planning and treatment option with hippocampal and other OARs avoidance in our patient's cohort and asses the QoL of the WBRT patients, as well as simultaneous integrated boost (SIB) for the brain metastases diseases. PACS number: 87 PMID:26699321

Long-term Evaluation of Radiation-Induced Optic Neuropathy After Single-Fraction Stereotactic Radiosurgery

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

Leavitt, Jacqueline A., E-mail: leavitt.jacqueline@mayo.edu; Stafford, Scott L.; Link, Michael J.

2013-11-01

Purpose: To determine the long-term risk of radiation-induced optic neuropathy (RION) in patients having single-fraction stereotactic radiosurgery (SRS) for benign skull base tumors. Methods and Materials: Retrospective review of 222 patients having Gamma Knife radiosurgery for benign tumors adjacent to the anterior visual pathway (AVP) between 1991 and 1999. Excluded were patients with prior or concurrent external beam radiation therapy or SRS. One hundred twenty-nine patients (58%) had undergone previous surgery. Tumor types included confirmed World Health Organization grade 1 or presumed cavernous sinus meningioma (n=143), pituitary adenoma (n=72), and craniopharyngioma (n=7). The maximum dose to the AVP was ≤8.0more » Gy (n=126), 8.1-10.0 Gy (n=39), 10.1-12.0 Gy (n=47), and >12 Gy (n=10). Results: The mean clinical and imaging follow-up periods were 83 and 123 months, respectively. One patient (0.5%) who received a maximum radiation dose of 12.8 Gy to the AVP developed unilateral blindness 18 months after SRS. The chance of RION according to the maximum radiation dose received by the AVP was 0 (95% confidence interval [CI] 0-3.6%), 0 (95% CI 0-10.7%), 0 (95% CI 0-9.0%), and 10% (95% CI 0-43.0%) for patients receiving ≤8 Gy, 8.1-10.0 Gy, 10.1-12.0 Gy, and >12 Gy, respectively. The overall risk of RION in patients receiving >8 Gy to the AVP was 1.0% (95% CI 0-6.2%). Conclusions: The risk of RION after single-fraction SRS in patients with benign skull base tumors who have no prior radiation exposure is very low if the maximum dose to the AVP is ≤12 Gy. Physicians performing single-fraction SRS should remain cautious when treating lesions adjacent to the AVP, especially when the maximum dose exceeds 10 Gy.« less

Erlotinib in African Americans with Advanced Non-Small Cell Lung Cancer: A Prospective Randomized Study with Genetic and Pharmacokinetic Analysis

PubMed Central

Phelps, Mitch A.; Stinchcombe, Thomas E.; Blachly, James S.; Zhao, Weiqiang; Schaaf, Larry J.; Starrett, Sherri L.; Wei, Lai; Poi, Ming; Wang, Danxin; Papp, Audrey; Aimiuwu, Josephine; Gao, Yue; Li, Junan; Otterson, Gregory A.; Hicks, William J.; Socinski, Mark A.; Villalona-Calero, Miguel A.

2014-01-01

Prospective studies focusing on EGFR inhibitors in African Americans with NSCLC have not been previously performed. In this phase II randomized study, 55 African Americans with NSCLC received erlotinib 150mg/day or a body weight adjusted dose with subsequent escalations to the maximum allowable, 200mg/day, to achieve rash. Erlotinib and OSI-420 exposures were lower compared to previous reports, consistent with CYP3A pharmacogenetics implying higher metabolic activity. Tumor genetics revealed only two EGFR mutations, EGFR amplification in 17/47 samples, 8 KRAS mutations and 5 EML4-ALK translocations. Although absence of rash was associated with shorter time to progression (TTP), disease control rate, TTP, and 1-year survival were not different between the two dose groups, indicating the dose-to-rash strategy failed to increase clinical benefit. Observed low incidence of toxicity and low erlotinib exposure suggest standardized and maximum allowable dosing may be suboptimal in African Americans. PMID:24781527

Estimation of external dose by car-borne survey in Kerala, India.

PubMed

Hosoda, Masahiro; Tokonami, Shinji; Omori, Yasutaka; Sahoo, Sarata Kumar; Akiba, Suminori; Sorimachi, Atsuyuki; Ishikawa, Tetsuo; Nair, Raghu Ram; Jayalekshmi, Padmavathy Amma; Sebastian, Paul; Iwaoka, Kazuki; Akata, Naofumi; Kudo, Hiromi

2015-01-01

A car-borne survey was carried out in Kerala, India to estimate external dose. Measurements were made with a 3-in × 3-in NaI(Tl) scintillation spectrometer from September 23 to 27, 2013. The routes were selected from 12 Panchayats in Karunagappally Taluk which were classified into high level, mid-level and low level high background radiation (HBR) areas. A heterogeneous distribution of air kerma rates was seen in the dose rate distribution map. The maximum air kerma rate, 2.1 μGy/h, was observed on a beach sand surface. 232Th activity concentration for the beach sand was higher than that for soil and grass surfaces, and the range of activity concentration was estimated to be 0.7-2.3 kBq/kg. The contribution of 232Th to air kerma rate was over 70% at the measurement points with values larger than 0.34 μGy/h. The maximum value of the annual effective dose in Karunagappally Taluk was observed around coastal areas, and it was estimated to be 13 mSv/y. More than 30% of all the annual effective doses obtained in this survey exceeded 1 mSv/y.

Assessment of radiation exposure from cesium-137 contaminated roads for epidemiological studies in Seoul, Korea.

PubMed

Lee, Yun-Keun; Ju, Young-Su; Lee, Won Jin; Hwang, Seung Sik; Yim, Sang-Hyuk; Yoo, Sang-Chul; Lee, Jieon; Choi, Kyung-Hwa; Burm, Eunae; Ha, Mina

2015-01-01

We aimed to assess the radiation exposure for epidemiologic investigation in residents exposed to radiation from roads that were accidentally found to be contaminated with radioactive cesium-137 ((137)Cs) in Seoul. Using information regarding the frequency and duration of passing via the (137)Cs contaminated roads or residing/working near the roads from the questionnaires that were obtained from 8875 residents and the measured radiation doses reported by the Nuclear Safety and Security Commission, we calculated the total cumulative dose of radiation exposure for each person. Sixty-three percent of the residents who responded to the questionnaire were considered as ever-exposed and 1% of them had a total cumulative dose of more than 10 mSv. The mean (minimum, maximum) duration of radiation exposure was 4.75 years (0.08, 11.98) and the geometric mean (minimum, maximum) of the total cumulative dose was 0.049 mSv (<0.001, 35.35) in the exposed. An individual exposure assessment was performed for an epidemiological study to estimate the health risk among residents living in the vicinity of (137)Cs contaminated roads. The average exposure dose in the exposed people was less than 5% of the current guideline.

Pharmacokinetics of gabapentin in a novel gastric-retentive extended-release formulation: comparison with an immediate-release formulation and effect of dose escalation and food.

PubMed

Chen, Cuiping; Cowles, Verne E; Hou, Eddie

2011-03-01

The objectives of the 3 phase I studies described herein were (1) to compare the pharmacokinetics of gabapentin delivered from a novel gastric-retentive dosage form vs an immediate-release formulation, (2) to assess the dose proportionality of the gastric-retentive extended-release formulation, and (3) to determine the effect of food on the pharmacokinetics of gabapentin delivered from this formulation. The time to reach maximum plasma concentration (t(max)) was extended for gabapentin delivered from the gastric-retentive extended-release formulation compared with the immediate-release formulation. A dose-related increase in both the maximum plasma concentration (C(max)) and the area under the plasma concentration-time curve (AUC) was observed as the gabapentin dose increased from 600 to 2400 mg. Fed status and increased fat content delayed t(max) and enhanced C(max) and AUC in proportion to the fat content. The pharmacokinetics of gabapentin delivered from this extended-release formulation allows a reduced dosing frequency while maintaining bioavailability and possibly diminishing the occurrence of adverse events attributable to a slower increase to the peak concentration compared with the immediate-release dosage form.

Electrocardiographic effects of hawthorn (Crataegus oxyacantha) in healthy volunteers: A randomized controlled trial.

PubMed

Trexler, Stephanie E; Nguyen, Elaine; Gromek, Samantha M; Balunas, Marcy J; Baker, William L

2018-04-19

The objective of this study was to evaluate the electrocardiographic effects of hawthorn in healthy adult volunteers. It was double-blind cross-over trial randomized 20 healthy adult volunteers to receive either a single oral 160-mg dose of hawthorn or matching placebo. Triplicate 12-lead electrocardiograms were taken before treatment and at 1-, 2-, 4-, and 6-hr post-dose. Following at least a 7-day washout period, participants were crossed over to the opposing treatment arm and had the measurements repeated. The primary endpoint was the change in corrected (Fridericia) QT intervals (QT c I) at 4 and 6 hr. Maximum post-dose QT c I and changes in PR and QRS intervals were measured. No significant differences in 4- or 6-hr QT c I were seen between hawthorn and placebo. Maximum post-dose QT c I in the hawthorn and placebo groups were similar (346 ± 35 vs 346 ± 40 ms; p = .979). No significant adverse events were seen. In conclusion, a single dose of oral hawthorn had no effect on electrocardiographic parameters in healthy volunteers. Copyright © 2018 John Wiley & Sons, Ltd.

Case Example of Dose Optimization Using Data From Bortezomib Dose-Finding Clinical Trials

PubMed Central

Backenroth, Daniel; Cheung, Ying Kuen Ken; Hershman, Dawn L.; Vulih, Diana; Anderson, Barry; Ivy, Percy; Minasian, Lori

2016-01-01

Purpose The current dose-finding methodology for estimating the maximum tolerated dose of investigational anticancer agents is based on the cytotoxic chemotherapy paradigm. Molecularly targeted agents (MTAs) have different toxicity profiles, which may lead to more long-lasting mild or moderate toxicities as well as to late-onset and cumulative toxicities. Several approved MTAs have been poorly tolerated during long-term administration, leading to postmarketing dose optimization studies to re-evaluate the optimal treatment dose. Using data from completed bortezomib dose-finding trials, we explore its toxicity profile, optimize its dose, and examine the appropriateness of current designs for identifying an optimal dose. Patients and Methods We classified the toxicities captured from 481 patients in 14 bortezomib dose-finding studies conducted through the National Cancer Institute Cancer Therapy Evaluation Program, computed the incidence of late-onset toxicities, and compared the incidence of dose-limiting toxicities (DLTs) among groups of patients receiving different doses of bortezomib. Results A total of 13,008 toxicities were captured: 46% of patients’ first DLTs and 88% of dose reductions or discontinuations of treatment because of toxicity were observed after the first cycle. Moreover, for the approved dose of 1.3 mg/m2, the estimated cumulative incidence of DLT was > 50%, and the estimated cumulative incidence of dose reduction or treatment discontinuation because of toxicity was nearly 40%. Conclusions When considering the entire course of treatment, the approved bortezomib dose exceeds the conventional ceiling DLT rate of 20% to 33%. Retrospective analysis of trial data provides an opportunity for dose optimization of MTAs. Future dose-finding studies of MTAs should take into account late-onset toxicities to ensure that a tolerable dose is identified for future efficacy and comparative trials. PMID:26926682

Case Example of Dose Optimization Using Data From Bortezomib Dose-Finding Clinical Trials.

PubMed

Lee, Shing M; Backenroth, Daniel; Cheung, Ying Kuen Ken; Hershman, Dawn L; Vulih, Diana; Anderson, Barry; Ivy, Percy; Minasian, Lori

2016-04-20

The current dose-finding methodology for estimating the maximum tolerated dose of investigational anticancer agents is based on the cytotoxic chemotherapy paradigm. Molecularly targeted agents (MTAs) have different toxicity profiles, which may lead to more long-lasting mild or moderate toxicities as well as to late-onset and cumulative toxicities. Several approved MTAs have been poorly tolerated during long-term administration, leading to postmarketing dose optimization studies to re-evaluate the optimal treatment dose. Using data from completed bortezomib dose-finding trials, we explore its toxicity profile, optimize its dose, and examine the appropriateness of current designs for identifying an optimal dose. We classified the toxicities captured from 481 patients in 14 bortezomib dose-finding studies conducted through the National Cancer Institute Cancer Therapy Evaluation Program, computed the incidence of late-onset toxicities, and compared the incidence of dose-limiting toxicities (DLTs) among groups of patients receiving different doses of bortezomib. A total of 13,008 toxicities were captured: 46% of patients' first DLTs and 88% of dose reductions or discontinuations of treatment because of toxicity were observed after the first cycle. Moreover, for the approved dose of 1.3 mg/m(2), the estimated cumulative incidence of DLT was > 50%, and the estimated cumulative incidence of dose reduction or treatment discontinuation because of toxicity was nearly 40%. When considering the entire course of treatment, the approved bortezomib dose exceeds the conventional ceiling DLT rate of 20% to 33%. Retrospective analysis of trial data provides an opportunity for dose optimization of MTAs. Future dose-finding studies of MTAs should take into account late-onset toxicities to ensure that a tolerable dose is identified for future efficacy and comparative trials. © 2016 by American Society of Clinical Oncology.

Radiation dose to the global flying population.

PubMed

Alvarez, Luis E; Eastham, Sebastian D; Barrett, Steven R H

2016-03-01

Civil airliner passengers and crew are exposed to elevated levels of radiation relative to being at sea level. Previous studies have assessed the radiation dose received in particular cases or for cohort studies. Here we present the first estimate of the total radiation dose received by the worldwide civilian flying population. We simulated flights globally from 2000 to 2013 using schedule data, applying a radiation propagation code to estimate the dose associated with each flight. Passengers flying in Europe and North America exceed the International Commission on Radiological Protection annual dose limits at an annual average of 510 or 420 flight hours per year, respectively. However, this falls to 160 or 120 h on specific routes under maximum exposure conditions.

Dose commitments due to radioactive releases from nuclear power plant sites: Methodology and data base. Supplement 1

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

Baker, D.A.

1996-06-01

This manual describes a dose assessment system used to estimate the population or collective dose commitments received via both airborne and waterborne pathways by persons living within a 2- to 80-kilometer region of a commercial operating power reactor for a specific year of effluent releases. Computer programs, data files, and utility routines are included which can be used in conjunction with an IBM or compatible personal computer to produce the required dose commitments and their statistical distributions. In addition, maximum individual airborne and waterborne dose commitments are estimated and compared to 10 CFR Part 50, Appendix 1, design objectives. Thismore » supplement is the last report in the NUREG/CR-2850 series.« less

LJM716 in Japanese patients with head and neck squamous cell carcinoma or HER2-overexpressing breast or gastric cancer.

PubMed

Takahashi, Shunji; Kobayashi, Takayuki; Tomomatsu, Junichi; Ito, Yoshinori; Oda, Hisanobu; Kajitani, Tatsuhiro; Kakizume, Tomoyuki; Tajima, Takeshi; Takeuchi, Hiromi; Maacke, Heiko; Esaki, Taito

2017-01-01

Human epidermal growth factor receptor 3 (HER3) has been identified as an important component of many receptor tyrosine kinase-driven cancers. LJM716 is a human IgG monoclonal antibody that binds HER3, trapping it in an inactive conformation. In this study, a phase I dose escalation was performed with a primary objective to establish the maximum tolerated dose and/or the recommended dose of LJM716 in Japanese patients with selected advanced solid tumors. Secondary objectives included the evaluation of the safety and tolerability, preliminary antitumor activity, and pharmacokinetics of LJM716 in Japanese patients. LJM716 was administered intravenously at doses of 10, 20, or 40 mg/kg once weekly, in 28-day cycles, to 12 patients with HER2-amplified breast cancer or gastric cancer, or with esophageal squamous cell carcinoma or squamous cell carcinoma of the head and neck, regardless of HER2 status. The maximum tolerated dose was not reached, and the recommended dose was established at 40 mg/kg. No dose-limiting toxicities were observed in the first cycle. The most frequently reported adverse events were diarrhea, fatigue, stomatitis, pyrexia, and paronychia. One unconfirmed partial response was observed in a patient with breast cancer, and 50% of the patients achieved stable disease as the best overall response. Exposure increased with ascending dose, and half-life was estimated to be 11-14 days. No anti-LJM716 antibodies were detected. LJM716 was well tolerated in Japanese patients, and a degree of tumor shrinkage was observed. ClinicalTrials.gov NCT01911936.

Contrast enema as a guide for senna-based laxatives in managing overflow retentive stool incontinence in pediatrics.

PubMed

Radwan, Ahmed Bassiuony; El-Debeiky, Mohammed Soliman; Abdel-Hay, Sameh

2015-08-01

Overflow retentive stool incontinence (ORSI) is secondary to constipation and fecal loading. In our study, the dose and duration of senna-based laxatives (SBL) treatment to achieve full defecatory control will be examined for possible correlation with new parameters measured from the initial contrast enema. Initially, an observational study was conducted prospectively on a group of patient with ORSI to define the optimum dose of SBL to achieve full defecatory control with measurement of six parameters in the initial contrast enema (level of colonic dilatation, recto-anal angle, ratio of maximal diameter of dilated colon to last lumbar spine, ratio of maximum diameter of dilated colon to normal descending colon, immediate and after 24-h post-evacuation residual contrast). The result was analyzed statistically to reach a correlation between the radiological data and prescribed dose. Over 2 and half years, 72 patients were included in the study; their mean age was 6.3 ± 3.33 years. The mean effective starting dose of SBL was 57 ± 18.13 mg/day and the mean effective ending dose was 75 ± 31.68 mg/day. Time lapsed till full defecatory control ranged from 1 to 16 weeks. Statistical correlation revealed that mean effective ending dose of SBL treatment significantly increased with higher levels of colonic dilatation. A weak positive correlation was found for both the mean effective starting and ending doses with the ratio of maximum colonic diameter to last lumbar spine and descending colonic diameters ratio. Senna-based laxatives are effective treatment for overflow retentive stool incontinence and their doses can be adjusted initially depending on the analysis of the radiological data.

Studies on the bronchodilator, tremorogenic, cardiovascular and hypokalaemic effects of fenoterol dry powder in asthma.

PubMed Central

Bauer, K G; Kaik, B; Sertl, K; Kaik, G A

1993-01-01

1. The airway and tremor response and cardiovascular and hypokalaemic effects of single and cumulative doses of fenoterol given by dry powder capsules (DPC) and by metered dose inhaler (MDI) were studied in asthmatics in two randomized, crossover trials. 2. Single doses of fenoterol DPC and MDI (0.2 mg, 0.4 mg), investigated in 24 subjects, produced similar, dose-dependent increases in FEV1. Fenoterol DPC caused less tremor response and less hypokalaemic effects than fenoterol MDI. 3. Cumulative doses of fenoterol DPC and MDI (0.2, 0.6, 1.4, 3.0, 6.2 mg), investigated in 12 subjects, produced a comparable bronchodilatation (mean maximum increase in FEV1 was 0.53 +/- 0.06/0.52 +/- 0.081 for DPC/MDI) and a similar, dose-dependent rise in heart rate (35 +/- 3.81/41 +/- 2.25 beats min(-1)). The rise in tremor and the fall in plasma potassium were smaller after DPC than after MDI. The mean maximum changes were 51.58 +/- 6.41/95.83 +/- 6.75 cm s(-2) for tremor and -0.68 +/- 0.09/-0.96 +/- 0.10 mmol l(-1) for potassium. 4. Our findings may result from a difference in the pharmacokinetics of the dry powder and the aerosol formulation, particularly differences in distribution and absorption. 5. In conclusion, fenoterol DPC used in low therapeutic doses (0.2,0.4 mg), is preferable to the MDI. Fenoterol DPC used as rescue medication in high cumulative doses, do not suggest a greater safety margin than the MDI and the same restrictions should be considered for the fenoterol dry powder formulation as suggested for the MDI. PMID:12959305

Absolute bioavailability and safety of a novel rivastigmine nasal spray in healthy elderly individuals.

PubMed

Morgan, Timothy M; Soh, Bob

2017-03-01

To test the feasibility of a novel rivastigmine nasal spray as prospective treatment for dementia. A single dose, crossover absolute bioavailability and safety study was conducted with rivastigmine intravenous solution (1 mg) and nasal spray (3.126 mg) in eight healthy elderly individuals, aged 58-75 years. Absolute bioavailability (F) of the nasal spray was significant at 0.62 (0.15) for F > 0 (P < 0.001, n = 8). The systemic dose absorbed was 2.0 (0.6) mg, time to maximum plasma concentration was 1.1 (0.5) h and maximum plasma concentration was 6.9 (2.0) ng ml -1 . The NAP226-90 to rivastigmine AUC 0-∞ ratio was 0.78 (0.19). The single dose safety was good with two of five mild adverse events related to the nasal spray. Nasal and throat irritation were perceived as mild and transient, and both had resolved at 20 min post-nasal dose. An estimated dose of two or three sprays twice-daily with nasal spray would deliver comparable rivastigmine exposure and efficacy as a 6-9.7 mg day -1 oral dose and a 10 cm 2 transdermal patch, respectively. The rivastigmine nasal spray had superior absolute bioavailability compared to historical values for oral capsule and transdermal patch determined by other researchers. It had rapid onset of action, low NAP226-90 to rivastigmine exposure ratio and a favourable safety and tolerability profile. The ability to achieve adjustable, individual, twice-daily dosing during waking hours has good potential to minimise undesirable cholinergic burden and sleep disturbances whilst delivering an effective dose for the treatment of dementia associated with Alzheimer's and Parkinson's disease. © 2016 The British Pharmacological Society.

Dose-related difference in progression rates of cytomegalovirus retinopathy during foscarnet maintenance therapy. AIDS Clinical Trials Group Protocol 915 Team.

PubMed

Holland, G N; Levinson, R D; Jacobson, M A

1995-05-01

A previous dose-ranging study of foscarnet maintenance therapy for cytomegalovirus retinopathy showed a positive relationship between dose and survival but could not confirm a relationship between dose and time to first progression. This retrospective analysis of data from that study was undertaken to determine whether there was a relationship between dose and progression rates, which reflects the amount of retina destroyed when progression occurs. Patients were randomly given one of two foscarnet maintenance therapy doses (90 mg/kg of body weight/day [FOS-90 group] or 120 mg/kg of body weight/day [FOS-120 group] after induction therapy. Using baseline and follow-up photographs and pre-established definitions and methodology in a masked analysis, posterior progression rates and foveal proximity rates for individual lesions, selected by prospectively defined criteria, were calculated in each patient. Rates were compared between groups. The following median rates were greater for the FOS-90 group (N = 8) than for the FOS-120 group (N = 10): greatest maximum rate at which lesions enlarged in a posterior direction (43.5 vs 12.5 microns/day; P = .002); posterior progression rate for lesions closest to the fovea (42.8 vs 5.5 microns/day; P = .010); and maximum foveal proximity rate for either eye (32.3 vs 3.4 microns/day; P = .031). Patients receiving higher doses of foscarnet have slower rates of progression and therefore less retinal tissue damage during maintenance therapy. A foscarnet maintenance therapy dose of 120 mg/kg of body weight/day instead of 90 mg/kg of body weight/day may help to preserve vision in patients with cytomegalovirus retinopathy.

Effect of aminocaproic acid on clot strength and clot lysis of canine blood determined by use of an in vitro model of hyperfibrinolysis.

PubMed

Brown, Jamie C; Brainard, Benjamin M; Fletcher, Daniel J; Nie, Ben; Arnold, Robert D; Schmiedt, Chad W

2016-11-01

OBJECTIVE To determine pharmacodynamic and pharmacokinetic profiles of aminocaproic acid (ACA) by use of a thromboelastography (TEG)-based in vitro model of hyperfibrinolysis and high-performance liquid chromatography-mass spectrometry. ANIMALS 5 healthy adult dogs. PROCEDURES A single dose of injectable ACA (20, 50, or 100 mg/kg) or an ACA tablet (approximately 100 mg/kg) was administered orally. Blood samples were collected at 0, 15, 30, 45, 60, 90, 120, and 240 minutes after ACA administration for pharmacokinetic analysis. Samples were obtained at 0, 60, and 240 minutes for pharmacodynamic analysis by use of a TEG model of hyperfibrinolysis. RESULTS No adverse effects were detected. In the hyperfibrinolysis model, after all doses, a significantly higher TEG maximum amplitude (clot strength), compared with baseline, was detected at 60 and 240 minutes. Additionally, the percentage of fibrinolysis was reduced from the baseline value at 60 and 240 minutes, with the greatest reduction at 60 minutes. At 240 minutes, there was significantly less fibrinolysis for the 100 mg/kg dose than the 20 mg/kg dose. Maximum plasma ACA concentration was dose dependent. There was no significant difference in pharmacokinetic parameters between 100 mg/kg formulations. CONCLUSIONS AND CLINICAL RELEVANCE In an in vitro model of hyperfibrinolysis, ACA inhibited fibrinolysis at all doses tested. At 240 minutes after administration, the 100 mg/kg dose inhibited fibrinolysis more effectively than did the 20 mg/kg dose. Thus, ACA may be useful for in vivo prevention of fibrinolysis in dogs. IMPACT FOR HUMAN MEDICINE These data may improve research models of hyperfibrinolytic diseases.

A phase I, pharmacokinetic, and pharmacodynamic study of two schedules of vorinostat in combination with 5-fluorouracil and leucovorin in patients with refractory solid tumors.

PubMed

Fakih, Marwan G; Fetterly, Gerald; Egorin, Merrill J; Muindi, Josephia R; Espinoza-Delgado, Igor; Zwiebel, James A; Litwin, Alan; Holleran, Julianne L; Wang, Kangsheng; Diasio, Robert B

2010-07-15

We conducted a phase I clinical trial to determine the maximum tolerated dose (MTD) of daily or twice daily vorinostat x 3 days when combined with fixed doses of 5-fluorouracil (FU) and leucovorin every 2 weeks. Vorinostat doses were escalated in a standard 3 x 3 phase I design. FU/leucovorin was started on day 2 of vorinostat and consisted of leucovorin 400 mg/m(2) i.v. over 2 hours followed by FU 400 mg/m(2) i.v. bolus and 2,400 mg/m(2) over 46 hours (sLV5FU2). Forty-three patients were enrolled. Grade 3 fatigue, and hand and foot syndrome were the dose-limiting toxicities (DLT) at the 2,000 mg vorinostat once-daily dose level. Grade 3 fatigue and mucositis were DLTs at the 800 mg vorinostat twice-daily dose level. None of six patients at the 1,700 mg once daily or six patients at the 600 mg twice daily dose levels had a DLT; those dose levels represent the MTD. Twenty-one of 38 patients with FU-refractory colorectal cancer had stable disease, and one had a partial response. Vorinostat maximum serum concentrations at the MTD exceeded concentrations associated with thymidylate synthase downregulation in vitro. No pharmacokinetic interactions were noted between vorinostat and FU. The MTD of vorinostat in combination with sLV5FU2 is 1,700 mg orally once daily x 3 or 600 mg orally twice daily x 3 days every 2 weeks. Clinical activity in refractory colorectal cancer supports further clinical development of this combination. Copyrighth 2010 AACR.

A Phase I, Pharmacokinetic, and Pharmacodynamic Study of Two Schedules of Vorinostat in Combination with 5-Fluorouracil and Leucovorin in Patients with Refractory Solid Tumors

PubMed Central

Fakih, Marwan G.; Fetterly, Gerald; Egorin, Merrill J.; Muindi, Josephia R.; Espinoza-Delgado, Igor; Zwiebel, James A.; Litwin, Alan; Holleran, Julianne L.; Wang, Kangsheng; Diasio, Robert B.

2010-01-01

Purpose We conducted a phase I clinical trial to determine the maximum tolerated dose (MTD) of daily or twice daily vorinostat × 3 days when combined with fixed doses of 5-fluorouracil (FU) and leucovorin every 2 weeks. Experimental Design Vorinostat doses were escalated in a standard 3 × 3 phase I design. FU/leucovorin was started on day 2 of vorinostat and consisted of leucovorin 400 mg/m2 i.v. over 2 hours followed by FU 400 mg/m2 i.v. bolus and 2,400 mg/m2 over 46 hours (sLV5FU2). Results Forty-three patients were enrolled. Grade 3 fatigue, and hand and foot syndrome were the dose-limiting toxicities (DLT) at the 2,000 mg vorinostat once-daily dose level. Grade 3 fatigue and mucositis were DLTs at the 800 mg vorinostat twice-daily dose level. None of six patients at the 1,700 mg once daily or six patients at the 600 mg twice daily dose levels had a DLT; those dose levels represent the MTD. Twenty-one of 38 patients with FU-refractory colorectal cancer had stable disease, and one had a partial response. Vorinostat maximum serum concentrations at the MTD exceeded concentrations associated with thymidylate synthase downregulation in vitro. No pharmacokinetic interactions were noted between vorinostat and FU. Conclusions The MTD of vorinostat in combination with sLV5FU2 is 1,700 mg orally once daily × 3 or 600 mg orally twice daily × 3 days every 2 weeks. Clinical activity in refractory colorectal cancer supports further clinical development of this combination. PMID:20463088

Assessment of diurnal systemic dose of agrochemicals in regulatory toxicity testing--an integrated approach without additional animal use.

PubMed

Saghir, Shakil A; Bartels, Michael J; Rick, David L; McCoy, Alene T; Rasoulpour, Reza J; Ellis-Hutchings, Robert G; Sue Marty, M; Terry, Claire; Bailey, Jason P; Billington, Richard; Bus, James S

2012-07-01

Integrated toxicokinetics (TK) data provide information on the rate, extent and duration of systemic exposure across doses, species, strains, gender, and life stages within a toxicology program. While routine for pharmaceuticals, TK assessments of non-pharmaceuticals are still relatively rare, and have never before been included in a full range of guideline studies for a new agrochemical. In order to better understand the relationship between diurnal systemic dose (AUC(24h)) and toxicity of agrochemicals, TK analyses in the study animals is now included in all short- (excluding acute), medium- and long-term guideline mammalian toxicity studies including reproduction/developmental tests. This paper describes a detailed procedure for the implementation of TK in short-, medium- and long-term regulatory toxicity studies, without the use of satellite animals, conducted on three agrochemicals (X11422208, 2,4-D and X574175). In these studies, kinetically-derived maximum doses (KMD) from short-term studies instead of, or along with, maximum tolerated doses (MTD) were used for the selection of the high dose in subsequent longer-term studies. In addition to leveraging TK data to guide dose level selection, the integrated program was also used to select the most appropriate method of oral administration (i.e., gavage versus dietary) of test materials for rat and rabbit developmental toxicity studies. The integrated TK data obtained across toxicity studies (without the use of additional/satellite animals) provided data critical to understanding differences in response across doses, species, strains, sexes, and life stages. Such data should also be useful in mode of action studies and to improve human risk assessments. Copyright © 2012 Elsevier Inc. All rights reserved.

A Phase I Study of Chemoradiotherapy With Use of Involved-Field Conformal Radiotherapy and Accelerated Hyperfractionation for Stage III Non-Small Cell Lung Cancer: WJTOG 3305

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

Tada, Takuhito, E-mail: tada@msic.med.osaka-cu.ac.jp; Department of Radiology, Izumi Municipal Hospital, Izumi; Chiba, Yasutaka

2012-05-01

Purpose: A Phase I study to determine a recommended dose of thoracic radiotherapy using accelerated hyperfractionation for unresectable non-small-cell lung cancer was conducted. Methods and Materials: Patients with unresectable Stage III non-small-cell lung cancer were treated intravenously with carboplatin (area under the concentration curve 2) and paclitaxel (40 mg/m{sup 2}) on Days 1, 8, 15, and 22 with concurrent twice-daily thoracic radiotherapy (1.5 Gy per fraction) beginning on Day 1 followed by two cycles of consolidation chemotherapy using carboplatin (area under the concentration curve 5) and paclitaxel (200 mg/m{sup 2}). Total doses were 54 Gy in 36 fractions, 60 Gymore » in 40 fractions, 66 Gy in 44 fractions, and 72 Gy in 48 fractions at Levels 1 to 4. The dose-limiting toxicity, defined as Grade {>=}4 esophagitis and neutropenic fever and Grade {>=}3 other nonhematologic toxicities, was monitored for 90 days. Results: Of 26 patients enrolled, 22 patients were assessable for response and toxicity. When 4 patients entered Level 4, enrollment was closed to avoid severe late toxicities. Dose-limiting toxicities occurred in 3 patients. They were Grade 3 neuropathy at Level 1 and Level 3 and Grade 3 infection at Level 1. However, the maximum tolerated dose was not reached. The median survival time was 28.6 months for all patients. Conclusions: The maximum tolerated dose was not reached, although the dose of radiation was escalated to 72 Gy in 48 fractions. However, a dose of 66 Gy in 44 fractions was adopted for this study because late toxicity data were insufficient.« less

Clinical implementation of MOSFET detectors for dosimetry in electron beams.

PubMed

Bloemen-van Gurp, Esther J; Minken, Andre W H; Mijnheer, Ben J; Dehing-Oberye, Cary J G; Lambin, Philippe

2006-09-01

To determine the factors converting the reading of a MOSFET detector placed on the patient's skin without additional build-up to the dose at the depth of dose maximum (D(max)) and investigate their feasibility for in vivo dose measurements in electron beams. Factors were determined to relate the reading of a MOSFET detector to D(max) for 4 - 15 MeV electron beams in reference conditions. The influence of variation in field size, SSD, angle and field shape on the MOSFET reading, obtained without additional build-up, was evaluated using 4, 8 and 15 MeV beams and compared to ionisation chamber data at the depth of dose maximum (z(max)). Patient entrance in vivo measurements included 40 patients, mostly treated for breast tumours. The MOSFET reading, converted to D(max), was compared to the dose prescribed at this depth. The factors to convert MOSFET reading to D(max) vary between 1.33 and 1.20 for the 4 and 15 MeV beams, respectively. The SSD correction factor is approximately 8% for a change in SSD from 95 to 100 cm, and 2% for each 5-cm increment above 100 cm SSD. A correction for fields having sides smaller than 6 cm and for irregular field shape is also recommended. For fields up to 20 x 20 cm(2) and for oblique incidence up to 45 degrees, a correction is not necessary. Patient measurements demonstrated deviations from the prescribed dose with a mean difference of -0.7% and a standard deviation of 2.9%. Performing dose measurements with MOSFET detectors placed on the patient's skin without additional build-up is a well suited technique for routine dose verification in electron beams, when applying the appropriate conversion and correction factors.

X-ray surface dose measurements using TLD extrapolation.

PubMed

Kron, T; Elliot, A; Wong, T; Showell, G; Clubb, B; Metcalfe, P

1993-01-01

Surface dose measurements in therapeutic x-ray beams are of importance in determining the dose to the skin of patients undergoing radiotherapy. Measurements were performed in the 6-MV beam of a medical linear accelerator with LiF thermoluminescence dosimeters (TLD) using a solid water phantom. TLD chips (surface area 3.17 x 3.17 cm2) of three different thicknesses (0.230, 0.099, and 0.038 g/cm2) were used to extrapolate dose readings to an infinitesimally thin layer of LiF. This surface dose was measured for field sizes ranging from 1 x 1 cm2 to 40 x 40 cm2. The surface dose relative to maximum dose was found to be 10.0% for a field size of 5 x 5 cm2, 16.3% for 10 x 10 cm2, and 26.9% for 20 x 20 cm2. Using a 6-mm Perspex block tray in the beam increased the surface dose in these fields to 10.7%, 17.7%, and 34.2% respectively. Due to the small size of the TLD chips, TLD extrapolation is applicable also for intracavity and exit dose determinations. The technique used for in vivo dosimetry could provide clinicians information about the build up of dose up to 1-mm depth in addition to an extrapolated surface dose measurement.

The influence of the dose calculation resolution of VMAT plans on the calculated dose for eye lens and optic pathway.

PubMed

Park, Jong Min; Park, So-Yeon; Kim, Jung-In; Carlson, Joel; Kim, Jin Ho

2017-03-01

To investigate the effect of dose calculation grid on calculated dose-volumetric parameters for eye lenses and optic pathways. A total of 30 patients treated using the volumetric modulated arc therapy (VMAT) technique, were retrospectively selected. For each patient, dose distributions were calculated with calculation grids ranging from 1 to 5 mm at 1 mm intervals. Identical structures were used for VMAT planning. The changes in dose-volumetric parameters according to the size of the calculation grid were investigated. Compared to dose calculation with 1 mm grid, the maximum doses to the eye lens with calculation grids of 2, 3, 4 and 5 mm increased by 0.2 ± 0.2 Gy, 0.5 ± 0.5 Gy, 0.9 ± 0.8 Gy and 1.7 ± 1.5 Gy on average, respectively. The Spearman's correlation coefficient between dose gradients near structures vs. the differences between the calculated doses with 1 mm grid and those with 5 mm grid, were 0.380 (p < 0.001). For the accurate calculation of dose distributions, as well as efficiency, using a grid size of 2 mm appears to be the most appropriate choice.

Dose measurements and radiation protection measures in gynecological radium therapy for medical-technical assistants and nursing staff (in German)

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

Schmidt, B.

Thesis. Appropriate measures to decrease radiation exposure of medical- technical assistants and nursing staff of hospitals with radiotherapy departments require personnel dose measurements during the different working operations. The measured values were in all cases below the maximum permissible doses; they are presented in tabular form for the various operations. Proposals are made for a further reduction of radiation exposure in particular fields of application. (GE)

Preliminary results on the photo-transferred thermoluminescence from Ge-doped SiO2 optical fiber

NASA Astrophysics Data System (ADS)

Zulkepely, Nurul Najua; Amin, Yusoff Mohd; Md Nor, Roslan; Bradley, D. A.; Maah, Mohd Jamil; Mat Nawi, Siti Nurasiah; Wahib, Nur Fadira

2015-12-01

A study is made of photo-transferred thermoluminescence (PTTL), the TL being induced by transferring charge carriers from deeper to more superficial traps through energetic light exposure. Potential applications include dose reassessment in radiation dosimetry and also as a useful tool for dating. With incomplete emptying of deep traps following first readout, subsequent UV exposure is shown to lead to charge transfer to more shallow traps. Using Ge-doped SiO2 optical fibers exposed to 60Co gamma rays, the PTTL from the medium has been characterized in terms of the stimulation provided by exposure to a UV lamp and duration of exposure, maximum read-out temperature and pre-gamma irradiation dose. Ge-doped SiO2 optical fibers of flat cross-sectional shape have been used in this study. The efficiency of dose reassessment was compared to that of the highly popular phosphor-based TL detector TLD-100. Results show the maximum temperature of readout to have no measurable effect on the PTTL signal. For doses from 20 to 500 cGy, the method is shown to be effective using a UV lamp of wavelength 254 nm, also being indicative of potential application for doses on either side of the range currently investigated. A study was also made of the effect of UV exposure time on PTTL, seeking to determine the greatest accessible sensitivity and lowest measurable dose.

Phase I study of afatinib combined with nintedanib in patients with advanced solid tumours

PubMed Central

Bahleda, Rastislav; Hollebecque, Antoine; Varga, Andrea; Gazzah, Anas; Massard, Christophe; Deutsch, Eric; Amellal, Nadia; Farace, Françoise; Ould-Kaci, Mahmoud; Roux, Flavien; Marzin, Kristell; Soria, Jean-Charles

2015-01-01

Background: This Phase I study evaluated continuous- and intermittent-dosing (every other week) of afatinib plus nintedanib in patients with advanced solid tumours. Methods: In the dose-escalation phase (n=45), maximum tolerated doses (MTDs) were determined for continuous/intermittent afatinib 10, 20, 30 or 40 mg once daily plus continuous nintedanib 150 or 200 mg twice daily. Secondary objectives included safety and efficacy. Clinical activity of continuous afatinib plus nintedanib at the MTD was further evaluated in an expansion phase (n=25). Results: The most frequent dose-limiting toxicities were diarrhoea (11%) and transaminase elevations (7%). Maximum tolerated doses were afatinib 30 mg continuously plus nintedanib 150 mg, and afatinib 40 mg intermittently plus nintedanib 150 mg. Treatment-related adverse events (mostly Grade ⩽3) included diarrhoea (98%), asthenia (64%), nausea (62%) and vomiting (60%). In the dose-escalation phase, two patients had partial responses (PRs) and 27 (60%) had stable disease (SD). In the expansion phase, one complete response and three PRs were observed (all non-small cell lung cancer), with SD in 13 (52%) patients. No pharmacokinetic interactions were observed. Conclusions: MTDs of continuous or intermittent afatinib plus nintedanib demonstrated a manageable safety profile with proactive management of diarrhoea. Antitumour activity was observed in patients with solid tumours. PMID:26512876

Passive dosimetry aboard the Mir Orbital Station: external measurements.

PubMed

Benton, E R; Benton, E V; Frank, A L

2002-10-01

This paper reports results from the first measurements made on the exterior of a LEO spacecraft of mean dose equivalent rate and average quality factor as functions of shielding depth for shielding less than 1 g/cm2 Al equivalent. Two sets of measurements were made on the outside of the Mir Orbital Station; one near solar maximum in June 1991 and one near solar minimum in 1997. Absorbed dose was measured using stacks of TLDs. LET spectrum from charged particles of LET infinity H2O > o r= 5keV/micrometers was measured using stacks of CR-39 PNTDs. Results from the TLD and PNTD measurements at a given shielding depth were combined to yield mean total dose rate, mean dose equivalent rate, and average quality factor. Measurements made near solar maximum tend to be greater than those made during solar minimum. Both mean dose rate and mean dose equivalent rate decrease by nearly four orders of magnitude within the first g/cm2 shielding illustrating the attenuation of both trapped electrons and low-energy trapped protons. In order to overcome problems with detector saturation after standard chemical processing, measurement of LET spectrum in the least shielded CR-39 PNTD layer (0.005 g/cm2 Al) was carried out using an atomic force microscope. c2002 Elsevier Science Ltd. All rights reserved.

Passive dosimetry aboard the Mir Orbital Station: external measurements

NASA Technical Reports Server (NTRS)

Benton, E. R.; Benton, E. V.; Frank, A. L.

2002-01-01

This paper reports results from the first measurements made on the exterior of a LEO spacecraft of mean dose equivalent rate and average quality factor as functions of shielding depth for shielding less than 1 g/cm2 Al equivalent. Two sets of measurements were made on the outside of the Mir Orbital Station; one near solar maximum in June 1991 and one near solar minimum in 1997. Absorbed dose was measured using stacks of TLDs. LET spectrum from charged particles of LET infinity H2O > o r= 5keV/micrometers was measured using stacks of CR-39 PNTDs. Results from the TLD and PNTD measurements at a given shielding depth were combined to yield mean total dose rate, mean dose equivalent rate, and average quality factor. Measurements made near solar maximum tend to be greater than those made during solar minimum. Both mean dose rate and mean dose equivalent rate decrease by nearly four orders of magnitude within the first g/cm2 shielding illustrating the attenuation of both trapped electrons and low-energy trapped protons. In order to overcome problems with detector saturation after standard chemical processing, measurement of LET spectrum in the least shielded CR-39 PNTD layer (0.005 g/cm2 Al) was carried out using an atomic force microscope. c2002 Elsevier Science Ltd. All rights reserved.

Comparison of GATE/GEANT4 with EGSnrc and MCNP for electron dose calculations at energies between 15 keV and 20 MeV.

PubMed

Maigne, L; Perrot, Y; Schaart, D R; Donnarieix, D; Breton, V

2011-02-07

The GATE Monte Carlo simulation platform based on the GEANT4 toolkit has come into widespread use for simulating positron emission tomography (PET) and single photon emission computed tomography (SPECT) imaging devices. Here, we explore its use for calculating electron dose distributions in water. Mono-energetic electron dose point kernels and pencil beam kernels in water are calculated for different energies between 15 keV and 20 MeV by means of GATE 6.0, which makes use of the GEANT4 version 9.2 Standard Electromagnetic Physics Package. The results are compared to the well-validated codes EGSnrc and MCNP4C. It is shown that recent improvements made to the GEANT4/GATE software result in significantly better agreement with the other codes. We furthermore illustrate several issues of general interest to GATE and GEANT4 users who wish to perform accurate simulations involving electrons. Provided that the electron step size is sufficiently restricted, GATE 6.0 and EGSnrc dose point kernels are shown to agree to within less than 3% of the maximum dose between 50 keV and 4 MeV, while pencil beam kernels are found to agree to within less than 4% of the maximum dose between 15 keV and 20 MeV.

A phase I dose-finding study of silybin phosphatidylcholine (milk thistle) in patients with advanced hepatocellular carcinoma.

PubMed

Siegel, Abby B; Narayan, Rupa; Rodriguez, Rosa; Goyal, Abhishek; Jacobson, Judith S; Kelly, Kara; Ladas, Elena; Lunghofer, Paul J; Hansen, Ryan J; Gustafson, Daniel L; Flaig, Thomas W; Tsai, Wei Yann; Wu, David P H; Lee, Valerie; Greenlee, Heather

2014-01-01

To determine the maximum tolerated dose per day of silybin phosphatidylcholine (Siliphos) in patients with advanced hepatocellular carcinoma (HCC) and hepatic dysfunction. Patients with advanced HCC not eligible for other therapies based on poor hepatic function were enrolled in a phase I study of silybin phosphatidylcholine. A standard phase I design was used with 4 planned cohorts, dose escalating from 2, 4, 8, to 12 g per day in divided doses for 12 weeks. Three participants enrolled in this single institution trial. All enrolled subjects consumed 2 g per day of study agent in divided doses. Serum concentrations of silibinin and silibinin glucuronide increased within 1 to 3 weeks. In all 3 patients, liver function abnormalities and tumor marker α-fetoprotein progressed, but after day 56 the third patient showed some improvement in liver function abnormalities and inflammatory biomarkers. All 3 participants died within 23 to 69 days of enrolling into the trial, likely from hepatic failure, but it could not be ruled out that deaths were possibly due to the study drug. Short-term administration of silybin phosphatidylcholine in patients with advanced HCC resulted in detectable increases in silibinin and its metabolite, silibinin glucuronide. The maximum tolerated dose could not be established. Since patients died soon after enrollment, this patient population may have been too ill to benefit from an intervention designed to improve liver function tests.

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

Dose gradient curve: A new tool for evaluating dose gradient

PubMed Central

Choi, Young Eun

2018-01-01

Purpose Stereotactic radiotherapy, which delivers an ablative high radiation dose to a target volume for maximum local tumor control, requires a rapid dose fall-off outside the target volume to prevent extensive damage to nearby normal tissue. Currently, there is no tool to comprehensively evaluate the dose gradient near the target volume. We propose the dose gradient curve (DGC) as a new tool to evaluate the quality of a treatment plan with respect to the dose fall-off characteristics. Methods The average distance between two isodose surfaces was represented by the dose gradient index (DGI) estimated by a simple equation using the volume and surface area of isodose levels. The surface area was calculated by mesh generation and surface triangulation. The DGC was defined as a plot of the DGI of each dose interval as a function of the dose. Two types of DGCs, differential and cumulative, were generated. The performance of the DGC was evaluated using stereotactic radiosurgery plans for virtual targets. Results Over the range of dose distributions, the dose gradient of each dose interval was well-characterized by the DGC in an easily understandable graph format. Significant changes in the DGC were observed reflecting the differences in planning situations and various prescription doses. Conclusions The DGC is a rational method for visualizing the dose gradient as the average distance between two isodose surfaces; the shorter the distance, the steeper the dose gradient. By combining the DGC with the dose-volume histogram (DVH) in a single plot, the DGC can be utilized to evaluate not only the dose gradient but also the target coverage in routine clinical practice. PMID:29698471

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

De Ornelas-Couto, M; Bossart, E; Elsayyad, N

Purpose: To determine the sensitivity of dose-mass-histogram (DMH) due to anatomical changes of head-and-neck squamous cell carcinoma (HNSCC) radiotherapy (RT). Methods: Eight patients undergoing RT treatment for HNSCC were scanned during the third and sixth week of RT. These second (CT2) and third (CT3) CTs were co-registered to the planning CT (CT1). Contours were propagated via deformable registration from CT1 and doses were re-calculated. DMHs were extracted for each CT set. DMH sensitivity was assessed by dose-mass indices (DMIs), which represent the dose delivered to a certain mass of and anatomical structure. DMIs included: dose to 98%, 95% and 2%more » of the target masses (PTV1, PTV2, and PTV3) and organs-at-risk (OARs): cord DMI2%, brainstem DMI2%, left- and right-parotid DMI2% and DMI50%, and mandible DMI2%. A two-tailed paired t-test was used to compare changes to DMIs in CT2 and CT3 with respect to CT1 (CT2/CT1 and CT3/CT1). Results: Changes to DMHs were found for all OARs and PTVs, but they were significant only for the PTVs. Maximum dose to PTVs increased significantly for CT2/CT1 in all three PTVs, but CT3/CT1 changes were only significantly different for PTV1 and PTV2. Dose coverage to the three PTVs was also significantly different, DMI98% was lower for both CT2/CT1 and CT3/CT1. DMI95% was significantly lower for PTV1 for CT2/CT1, PTV2 for CT2/CT1 and CT3/CT1, and PTV3 for CT3/CT1. Conclusion: Changes in anatomy significantly change dose-mass coverage for the planning targets, making it necessary to re-plan in order to maintain the therapeutic goals. Maximum dose to the PTVs increase significantly as RT progresses, which may not be problematic as long as the high dose remains in the gross tumor volume. Doses to OARs were minimally affected and the differences were not significant.« less

MO-F-CAMPUS-I-02: Occupational Conceptus Doses From Fluoroscopically-Guided Interventional Procedures

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

Damilakis, J; Perisinakis, K; Solomou, G

Purpose: The aim of this method was to provide dosimetric data on conceptus dose for the pregnant employee who participates in fluoroscopically-guided interventional procedures. Methods: Scattered air-kerma dose rates were obtained for 17 fluoroscopic projections involved in interventional procedures. These projections were simulated on an anthropomorphic phantom placed on the examination table supine. The operating theater was divided into two grids relative to the long table sides. Each grid consisted of 33 cells spaced 0.50 m apart. During the simulated exposures, at each cell, scatter air-kerma rate was measured at 110 cm from the floor i.e. at the height ofmore » the waist of the pregnant worker. Air-kerma rates were divided by the dose area product (DAP) rate of each exposure to obtain normalized data. For each projection, measurements were performed for 3 kVp and 3 filtration values i.e. for 9 different x-ray spectra. All measurements were performed by using a modern C-arm angiographic system (Siemens Axiom Artis, Siemens, Germany) and a radiation meter equipped with an ionization chamber. Results: The results consist of 153 iso-dose maps, which show the spatial distribution of DAP-normalized scattered air-kerma doses at the waist level of a pregnant worker. Conceptus dose estimation is possible using air-kerma to embryo/fetal dose conversion coefficients published in a previous study (J Cardiovasc Electrophysiol, Vol. 16, pp. 1–8, July 2005). Using these maps, occupationally exposed pregnant personnel may select a working position for a certain projection that keeps abdominal dose as low as reasonably achievable. Taking into consideration the regulatory conceptus dose limit for occupational exposure, determination of the maximum workload allowed for the pregnant personnel is also possible. Conclusion: Data produced in this work allow for the anticipation of conceptus dose and the determination of the maximum workload for a pregnant worker from any fluoroscopically-guided interventional procedure. This study was supported by the Greek Ministry of Education and Religious Affairs, General Secretariat for Research and Technology, Operational Program ‘Education and Lifelong Learning’, ARISTIA (Research project: CONCERT)« less

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

Update of a comparative analysis of cost minimization following the introduction of newly available intravenous iron therapies in hospital practice

PubMed Central

Bhandari, Sunil

2011-01-01

Background The clinical need to be able to administer high doses of intravenous iron conveniently as a rapid infusion has been addressed by the recent introduction of ferric carboxymaltose and subsequently iron isomaltoside 1000. Neither requires a test dose. The maximum dose of ferric carboxymaltose is 1000 mg. The maximum dose of iron isomaltoside 1000 is based on 20 mg/kg body weight without a specified ceiling dose, thereby increasing the scope of being able to achieve total iron repletion with a single infusion. This ability to give high doses of iron is important in the context of managing iron deficiency anemia, which is associated with a number of clinical conditions where demands for iron are high. It is also an important component of the strategy as an alternative to blood transfusion. Affordability is a key issue for health services. Recent price changes affecting iron sucrose and ferric carboxymaltose, plus modifications to the manufacturers’ prescribing information, have provoked this update. Methods This study is a comparative analysis of the costs of acquiring and administering the newly available intravenous iron formulations against standard treatments in the hospital setting. The costs include the medication, nursing costs, equipment, and patient transportation. Three dosage levels (600 mg, 1000 mg, and 1600 mg) are considered. Results and conclusion The traditional standard treatments, blood and iron sucrose, cost more than the alternative intravenous iron preparations across the dose spectrum and sensitivities. Low molecular weight iron dextran is the least expensive option at the 1600 mg dose level but has the caveat of a prolonged administration time and requirement for a test dose. At 600 mg and 1000 mg dose levels, both iron isomaltoside 1000 and ferric carboxymaltose are more economical than low molecular weight iron dextran. Iron isomaltoside 1000 is less expensive than ferric carboxymaltose at all dose levels. Newly available iron preparations appear to be clinically promising, cost effective, and practical alternatives to current standards of iron repletion. PMID:22241947

A quantitative comparison of noise reduction across five commercial (hybrid and model-based) iterative reconstruction techniques: an anthropomorphic phantom study.

PubMed

Patino, Manuel; Fuentes, Jorge M; Hayano, Koichi; Kambadakone, Avinash R; Uyeda, Jennifer W; Sahani, Dushyant V

2015-02-01

OBJECTIVE. The objective of our study was to compare the performance of three hybrid iterative reconstruction techniques (IRTs) (ASiR, iDose4, SAFIRE) and their respective strengths for image noise reduction on low-dose CT examinations using filtered back projection (FBP) as the standard reference. Also, we compared the performance of these three hybrid IRTs with two model-based IRTs (Veo and IMR) for image noise reduction on low-dose examinations. MATERIALS AND METHODS. An anthropomorphic abdomen phantom was scanned at 100 and 120 kVp and different tube current-exposure time products (25-100 mAs) on three CT systems (for ASiR and Veo, Discovery CT750 HD; for iDose4 and IMR, Brilliance iCT; and for SAFIRE, Somatom Definition Flash). Images were reconstructed using FBP and using IRTs at various strengths. Nine noise measurements (mean ROI size, 423 mm(2)) on extracolonic fat for the different strengths of IRTs were recorded and compared with FBP using ANOVA. Radiation dose, which was measured as the volume CT dose index and dose-length product, was also compared. RESULTS. There were no significant differences in radiation dose and image noise among the scanners when FBP was used (p > 0.05). Gradual image noise reduction was observed with each increasing increment of hybrid IRT strength, with a maximum noise suppression of approximately 50% (48.2-53.9%). Similar noise reduction was achieved on the scanners by applying specific hybrid IRT strengths. Maximum noise reduction was higher on model-based IRTs (68.3-81.1%) than hybrid IRTs (48.2-53.9%) (p < 0.05). CONCLUSION. When constant scanning parameters are used, radiation dose and image noise on FBP are similar for CT scanners made by different manufacturers. Significant image noise reduction is achieved on low-dose CT examinations rendered with IRTs. The image noise on various scanners can be matched by applying specific hybrid IRT strengths. Model-based IRTs attain substantially higher noise reduction than hybrid IRTs irrespective of the radiation dose.

MO-G-304-01: FEATURED PRESENTATION: Expanding the Knowledge Base for Data-Driven Treatment Planning: Incorporating Patient Outcome Models

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

Robertson, SP; Quon, H; Cheng, Z

2015-06-15

Purpose: To extend the capabilities of knowledge-based treatment planning beyond simple dose queries by incorporating validated patient outcome models. Methods: From an analytic, relational database of 684 head and neck cancer patients, 372 patients were identified having dose data for both left and right parotid glands as well as baseline and follow-up xerostomia assessments. For each existing patient, knowledge-based treatment planning was simulated for by querying the dose-volume histograms and geometric shape relationships (overlap volume histograms) for all other patients. Dose predictions were captured at normalized volume thresholds (NVT) of 0%, 10%, 20, 30%, 40%, 50%, and 85% and weremore » compared with the actual achieved doses using the Wilcoxon signed-rank test. Next, a logistic regression model was used to predict the maximum severity of xerostomia up to three months following radiotherapy. Baseline xerostomia scores were subtracted from follow-up assessments and were also included in the model. The relative risks from predicted doses and actual doses were computed and compared. Results: The predicted doses for both parotid glands were significantly less than the achieved doses (p < 0.0001), with differences ranging from 830 cGy ± 1270 cGy (0% NVT) to 1673 cGy ± 1197 cGy (30% NVT). The modelled risk of xerostomia ranged from 54% to 64% for achieved doses and from 33% to 51% for the dose predictions. Relative risks varied from 1.24 to 1.87, with maximum relative risk occurring at 85% NVT. Conclusions: Data-driven generation of treatment planning objectives without consideration of the underlying normal tissue complication probability may Result in inferior plans, even if quality metrics indicate otherwise. Inclusion of complication models in knowledge-based treatment planning is necessary in order to close the feedback loop between radiotherapy treatments and patient outcomes. Future work includes advancing and validating complication models in the context of knowledge-based treatment planning. This work is supported by Philips Radiation Oncology Systems.« less

First results of a phase I/II dose escalation trial in non-small cell lung cancer using three-dimensional conformal radiotherapy.

PubMed

Belderbos, José S A; De Jaeger, Katrien; Heemsbergen, Wilma D; Seppenwoolde, Yvette; Baas, Paul; Boersma, Liesbeth J; Lebesque, Joos V

2003-02-01

To evaluate the feasibility of dose escalation in non-small cell lung cancer (NSCLC) using three-dimensional conformal radiation therapy. The main eligibility criteria of the trial were: pathologically proven inoperable NSCLC, ECOG performance status or=grade 3 (SWOG), grade 3 early and grade 2 late esophageal toxicity or any other (RTOG) grade 3 or 4 complications). Fifty-five patients were included. Tumor stage was I/II in 47%, IIIA in 33% and IIIB in 20%. The majority of the patients received a dose of 74.3 Gy (n=17) or 81.0 Gy (n=23). Radiation pneumonitis occurred in seven patients: four patients developed a grade 2, two patients grade 3 and one patient a grade 4. Esophageal toxicity was mild. In 50 patients tumor response at 3 months follow-up was evaluable. In six patients a complete response was recorded, in 38 a partial response, five patients had stable disease and one patient experienced progressive disease. Only one patient developed an isolated failure in an uninvolved nodal area. So far the radiation dose was safely escalated to 87.8 Gy in group 1 (lowest rMLD), 81.0 Gy in groups 2 and 3 and 74.3 Gy in group 4. Three-dimensional conformal radiotherapy enables significant dose escalation in NSCLC. The maximum tolerable dose has not yet been reached in any risk group.

Range and trend of expected toxicity level (ETL) in standard A + B designs: a report from the Children's Oncology Group.

PubMed

Chen, Zhengjia; Krailo, Mark D; Sun, Junfeng; Azen, Stanley P

2009-03-01

The traditional algorithm-based 3+3 designs are most widely used for their practical simplicity in phase I clinical trials. At early stage, a common belief was that the expected toxicity level (ETL) at the maximum tolerated dose (MTD) should be 33% [Storer, B. Design and analysis of phase I clinical trials. Biometrics 1989;45;925-937, Gorden, N., Willson, J. Using toxicity grades in the design and analysis of cancer phase I clinical trials. Statistics in Medicine 1992; 11: 2063-2075, Mick, R. Phase I Clinical Trial Design. In Schilsky, R., Milano, G., Ratain, M., eds. Principles of Antineoplastic Drug Development and Pharmacology New York, NY: Marcel Dekker, 1996; 29-36]. Recently, Kang and Ahn [Kang, S., Ahn, C. The expected toxicity rate at the maximum tolerated dose in the standard phase I cancer clinical trial design. Drug Information Journal 2001; 35:1189-1199, Kang, S., Ahn, C. An investigation of the traditional algorithm-based designs for phase I cancer clinical trials. Drug Information Journal 2002; 36:865-873] found that the ETL is between 17% and 21% and He et al [He, W., Liu, J., Binkowitz, B., Quan, H. A model-based approach in the estimation of the maximum tolerated dose in phase I cancer clinical trials. Statistics in Medicine 2006; 25(12):2027-42] further reported that the ETL ranges from 19% to 24%. However they only investigated designs where the number of dose levels was at most 20. It has practical significance in designing and conducting phase I clinical trial to definitely assess the full range and trend of ETL by all possible number of tested dose levels in traditional algorithm-based A+B designs, especially 3+3 designs. In this simulation study, we originally find that the ETL decreases monotonically from about 30% to 0% as the number of dose levels increase from 3 to infinity, which will correct the inaccuracy in the common belief among phase I trial investigators. To help better design and conduct phase I trials, we create a table as a reference for the association between ETL and number of dose levels considered in a design when the exact shape of the dose-toxicity relationship is not well understood. We conclude that the number of specified dose levels is an important factor affecting substantially the ETL at MTD and recommend that fewer than 20 dose levels be designated.

Effective Dose of CT- and Fluoroscopy-Guided Perineural/Epidural Injections of the Lumbar Spine: A Comparative Study

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

Schmid, Gebhard; Schmitz, Alexander; Borchardt, Dieter

The objective of this study was to compare the effective radiation dose of perineural and epidural injections of the lumbar spine under computed tomography (CT) or fluoroscopic guidance with respect to dose-reduced protocols. We assessed the radiation dose with an Alderson Rando phantom at the lumbar segment L4/5 using 29 thermoluminescence dosimeters. Based on our clinical experience, 4-10 CT scans and 1-min fluoroscopy are appropriate. Effective doses were calculated for CT for a routine lumbar spine protocol and for maximum dose reduction; as well as for fluoroscopy in a continuous and a pulsed mode (3-15 pulses/s). Effective doses under CTmore » guidance were 1.51 mSv for 4 scans and 3.53 mSv for 10 scans using a standard protocol and 0.22 mSv and 0.43 mSv for the low-dose protocol. In continuous mode, the effective doses ranged from 0.43 to 1.25 mSv for 1-3 min of fluoroscopy. Using 1 min of pulsed fluoroscopy, the effective dose was less than 0.1 mSv for 3 pulses/s. A consequent low-dose CT protocol reduces the effective dose compared to a standard lumbar spine protocol by more than 85%. The latter dose might be expected when applying about 1 min of continuous fluoroscopy for guidance. A pulsed mode further reduces the effective dose of fluoroscopy by 80-90%.« less

Safety and tolerability of veliparib combined with capecitabine plus radiotherapy in patients with locally advanced rectal cancer: a phase 1b study.

PubMed

Czito, Brian G; Deming, Dustin A; Jameson, Gayle S; Mulcahy, Mary F; Vaghefi, Houman; Dudley, Matthew W; Holen, Kyle D; DeLuca, Angela; Mittapalli, Rajendar K; Munasinghe, Wijith; He, Lei; Zalcberg, John R; Ngan, Samuel Y; Komarnitsky, Philip; Michael, Michael

2017-06-01

Further optimisation of present standard chemoradiation is needed in patients with locally advanced rectal cancer. Veliparib, an oral poly(ADP-ribose) polymerase inhibitor, has been shown to enhance the antitumour activity of chemotherapy and radiotherapy in preclinical models. We aimed to establish the maximum tolerated dose and establish the recommended phase 2 dose of veliparib combined with neoadjuvant capecitabine and radiotherapy. This phase 1b, open-label, multicentre, dose-escalation study was done at six hospitals (one in Australia and five in the USA). Patients were eligible if they were aged 18 years or more and were newly diagnosed with stage II to III locally advanced, resectable adenocarcinoma of the rectum with a distal tumour border of less than 12 cm from anal verge. Patients were ineligible if they had received anticancer therapy or surgery (except colostomy or ileostomy) 28 days or less before the first dose of study drug, previous pelvic radiotherapy, or previous treatment with poly (ADP-ribose) polymerase inhibitors. Enrolled patients received capecitabine (825 mg/m 2 orally twice daily) with radiotherapy (50·4 Gy in 1·8 Gy fractions daily, approximately 5 days consecutively per week for about 5·5 weeks). Veliparib (20-400 mg orally twice daily) was administered daily starting on day 2 of week 1 and continuing until 2 days after radiotherapy completion. Patients underwent total mesorectal excision 5-10 weeks after radiotherapy completion. The primary objectives were to establish the maximum tolerated dose and recommended phase 2 dose of veliparib plus capecitabine and radiotherapy, with an exposure-adjusted continual reassessment methodology. Efficacy and safety analyses were done per protocol. The reported study has completed accrual and all analyses are final. This trial is registered with ClinicalTrials.gov, number NCT01589419. Between June 12, 2012, and Jan 13, 2015, 32 patients received veliparib (22 in the dose-escalation group; ten in the safety expansion group); 31 were assessable for efficacy (<400 mg, n=16; 400 mg, n=15). During dose escalation, grade 2 dose-limiting toxic effects occurred in two patients; no grade 3-4 dose-limiting toxic effects were noted. Therefore, the maximum tolerated dose was not reached; the recommended phase 2 dose was selected as 400 mg twice daily. The most common treatment-emergent adverse events in all 32 patients were nausea (17 [53%]), diarrhoea (16 [50%]), and fatigue (16 [50%]). Grade 3 diarrhoea was noted in three (9%) of 32 patients; no grade 4 events were reported. Veliparib pharmacokinetics were dose proportional, with no effect on capecitabine pharmacokinetics. Tumour downstaging after surgery was noted in 22 (71%) of 31 patients; nine (29%) of 31 patients achieved a pathological complete response. Veliparib plus capecitabine and radiotherapy had an acceptable safety profile and showed a dose-proportional pharmacokinetic profile with no effect on the pharmacokinetics of capecitabine. Preliminary antitumour activity warrants further evaluation. AbbVie Inc. Copyright © 2017 Elsevier Ltd. All rights reserved.

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.

Reconstruction of Internal Doses for the Alpha-Risk Case-Control Study of Lung Cancer and Leukaemia Among European Nuclear Workers.

PubMed

Bingham, Derek; Bérard, Philippe; Birchall, Alan; Bull, Richard; Cardis, Elisabeth; Challeton-de Vathaire, Cécile; Grellier, James; Hurtgen, Christian; Puncher, Matthew; Riddell, Anthony; Thierry-Chef, Isabelle

2017-05-01

The Alpha-Risk study required the reconstruction of doses to lung and red bone marrow for lung cancer and leukaemia cases and their matched controls from cohorts of nuclear workers in the UK, France and Belgium. The dosimetrists and epidemiologists agreed requirements regarding the bioassay data, biokinetic and dosimetric models and dose assessment software to be used and doses to be reported. The best values to use for uncertainties on the monitoring data, setting of exposure regimes and characteristics of the exposure material, including lung solubility, were the responsibility of the dosimetrist responsible for each cohort. Among 1721 subjects, the median absorbed dose to the lung from alpha radiations was 2.1 mGy, with a maximum dose of 316 mGy. The lung doses calculated reflect the higher levels of exposure seen among workers in the early years of the nuclear industry compared to today. © Crown copyright 2016.

In vivo urethral dose measurements: a method to verify high dose rate prostate treatments.

PubMed

Brezovich, I A; Duan, J; Pareek, P N; Fiveash, J; Ezekiel, M

2000-10-01

Radiation doses delivered in high dose rate (HDR) brachytherapy are susceptible to many inaccuracies and errors, including imaging, planning and delivery. Consequently, the dose delivered to the patient may deviate substantially from the treatment plan. We investigated the feasibility of using TLD measurements in the urethra to estimate the discrepancy in treatments for prostate cancer. The dose response of the 1 mm diam, 6 mm long LiF rods that we used for the in vivo measurements was calibrated with the 192Ir HDR source, as well as a 60Co teletherapy unit. A train of 20 rods contained in a sterile plastic tube was inserted into the urethral (Foley) catheter for the duration of a treatment fraction, and the measured doses were compared to the treatment plan. Initial results from a total of seven treatments in four patients show good agreement between theory and experiment. Analysis of any one treatment showed agreement within 11.7% +/- 6.2% for the highest dose encountered in the central prostatic urethra, and within 10.4% +/- 4.4% for the mean dose. Taking the average over all seven treatments shows agreement within 1.7% for the maximum urethral dose, and within 1.5% for the mean urethral dose. Based on these initial findings it seems that planned prostate doses can be accurately reproduced in the clinic.

[Estimation of dietary intake of radioactive materials by total diet methods].

PubMed

Uekusa, Yoshinori; Nabeshi, Hiromi; Tsutsumi, Tomoaki; Hachisuka, Akiko; Matsuda, Rieko; Teshima, Reiko

2014-01-01

Radioactive contamination in foods is a matter of great concern after the Tokyo Electric Power Company's Fukushima Daiichi nuclear power plant disaster caused by the Great East Japan Earthquake. In order to estimate human intake and annual committed effective dose of radioactive materials, market basket and duplicate diet samples from various areas in Japan were analyzed for cesium-134 ((134)Cs), -137 ((137)Cs), and natural radionuclide potassium-40 ((40)K) by γ-ray spectroscopy. Dietary intake of radioactive cesium around Fukushima area was somewhat higher than in other areas. However, maximum committed effective doses obtained by the market basket and duplicate diet samples were 0.0094 and 0.027 mSv/year, respectively, which are much lower than the maximum permissible dose (1 mSv/year) in foods in Japan.

Motion mitigation for lung cancer patients treated with active scanning proton therapy

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

Grassberger, Clemens, E-mail: Grassberger.Clemens@mgh.harvard.edu; Dowdell, Stephen; Sharp, Greg

2015-05-15

Purpose: Motion interplay can affect the tumor dose in scanned proton beam therapy. This study assesses the ability of rescanning and gating to mitigate interplay effects during lung treatments. Methods: The treatments of five lung cancer patients [48 Gy(RBE)/4fx] with varying tumor size (21.1–82.3 cm{sup 3}) and motion amplitude (2.9–30.6 mm) were simulated employing 4D Monte Carlo. The authors investigated two spot sizes (σ ∼ 12 and ∼3 mm), three rescanning techniques (layered, volumetric, breath-sampled volumetric) and respiratory gating with a 30% duty cycle. Results: For 4/5 patients, layered rescanning 6/2 times (for the small/large spot size) maintains equivalent uniformmore » dose within the target >98% for a single fraction. Breath sampling the timing of rescanning is ∼2 times more effective than the same number of continuous rescans. Volumetric rescanning is sensitive to synchronization effects, which was observed in 3/5 patients, though not for layered rescanning. For the large spot size, rescanning compared favorably with gating in terms of time requirements, i.e., 2x-rescanning is on average a factor ∼2.6 faster than gating for this scenario. For the small spot size however, 6x-rescanning takes on average 65% longer compared to gating. Rescanning has no effect on normal lung V{sub 20} and mean lung dose (MLD), though it reduces the maximum lung dose by on average 6.9 ± 2.4/16.7 ± 12.2 Gy(RBE) for the large and small spot sizes, respectively. Gating leads to a similar reduction in maximum dose and additionally reduces V{sub 20} and MLD. Breath-sampled rescanning is most successful in reducing the maximum dose to the normal lung. Conclusions: Both rescanning (2–6 times, depending on the beam size) as well as gating was able to mitigate interplay effects in the target for 4/5 patients studied. Layered rescanning is superior to volumetric rescanning, as the latter suffers from synchronization effects in 3/5 patients studied. Gating minimizes the irradiated volume of normal lung more efficiently, while breath-sampled rescanning is superior in reducing maximum doses to organs at risk.« less

Proton depth dose distribution: 3-D calculation of dose distributions from solar flare irradiation

NASA Astrophysics Data System (ADS)

Leavitt, Dennis D.

1990-11-01

Relative depth dose distribution to the head from 3 typical solar flare proton events were calculated for 3 different exposure geometries: (1) single directional radiation incident upon a fixed head; (2) single directional radiation incident upon head rotating axially (2-D rotation); and (3) omnidirectional radiation incident upon head (3-D rotation). Isodose distributions in the transverse plane intersecting isocenter are presented for each of the 3 solar flare events in all 3 exposure geometries. In all 3 calculation configurations the maximum predicted dose occurred on the surface of the head. The dose at the isocenter of the head relative to the surface dose for the 2-D and 3-D rotation geometries ranged from 2 to 19 percent, increasing with increasing energy of the event. The calculations suggest the superficially located organs (lens of the eye and skin) are at greatest risk for the proton events studied here.

Biphasic dose responses in biology, toxicology and medicine: accounting for their generalizability and quantitative features.

PubMed

Calabrese, Edward J

2013-11-01

The most common quantitative feature of the hormetic-biphasic dose response is its modest stimulatory response which at maximum is only 30-60% greater than control values, an observation that is consistently independent of biological model, level of organization (i.e., cell, organ or individual), endpoint measured, chemical/physical agent studied, or mechanism. This quantitative feature suggests an underlying "upstream" mechanism common across biological systems, therefore basic and general. Hormetic dose response relationships represent an estimate of the peak performance of integrative biological processes that are allometrically based. Hormetic responses reflect both direct stimulatory or overcompensation responses to damage induced by relatively low doses of chemical or physical agents. The integration of the hormetic dose response within an allometric framework provides, for the first time, an explanation for both the generality and the quantitative features of the hormetic dose response. Copyright © 2013 Elsevier Ltd. All rights reserved.

New approach to CT pixel-based photon dose calculations in heterogeneous media

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

Wong, J.W.; Henkelman, R.M.

The effects of small cavities on dose in water and the dose in a homogeneous nonunit density medium illustrate that inhomogeneities do not act independently in photon dose perturbation, and serve as two constraints which should be satisfied by approximate methods of computed tomography (CT) pixel-based dose calculations. Current methods at best satisfy only one of the two constraints and show inadequacies in some intermediate geometries. We have developed an approximate method that satisfies both these constraints and treats much of the synergistic effect of multiple inhomogeneities correctly. The method calculates primary and first-scatter doses by first-order ray tracing withmore » the first-scatter contribution augmented by a component of second scatter that behaves like first scatter. Multiple-scatter dose perturbation values extracted from small cavity experiments are used in a function which approximates the small residual multiple-scatter dose. For a wide range of geometries tested, our method agrees very well with measurements. The average deviation is less than 2% with a maximum of 3%. In comparison, calculations based on existing methods can have errors larger than 10%.« less

Application of bioassay technique to determine onduty herbicide resistance in soil

NASA Astrophysics Data System (ADS)

Bakar, F. A. A.; Ismail, B. S.; Bajrai, F. S. M.

2016-11-01

A study was conducted to determine the resistance of OnDuty herbicide in paddy soil with different concentrations by using a broadleaf plant, Brassica juncea. The herbicide was used in the Clearfield® Production System that was adopted in Malaysia to overcome problems mainly caused by weedy rice. Evaluation of herbicide half-life was based on bioassay technique with different concentrations, i.e 0% (control), 50% (half dose), 100% (recommended dose) and 200% (double dose). The study was done in three replicates and followed the Complete Randomized Block Design (CRBD). Results showed that there was a correlation between the amount of herbicide doses and degradation period. The highest half-life value was shown by root inhibition in the double dose concentration of 33 days half-life, followed by the recommended dose with 23 days half-life. Meanwhile, the half dose treatment indicated a half-life value of 17 days for root and 11 days for shoot. Therefore, application of herbicides should follow the recommended dose as the degradation period will not be too long, hence providing maximum effectiveness of the herbicide to overcome weed infestation problems.

Structural properties of H-implanted InP crystals

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

Bocchi, C.; Franzosi, P.; Lazzarini, L.

1993-07-01

H has been implanted in InP crystals at the energy E [equals] 100 keV and at different doses ranging from [sigma] [equals] 1 x 10[sup 13] to [sigma] [equals] 5 x 10[sup 16] cm[sup [minus]2]. The depth dependence of the elastic lattice strain has been investigated by high resolution X-ray diffractometry. The implantation produces a lattice dilation. The strain increases with increasing depth, reaches the maximum at about 0.75 [mu]m, and then decreases rapidly; moreover the maximum strain is proportional to the dose. No extended crystal defects have been detected by transmission electron microscopy up to [sigma] <1 x 10[supmore » 16] cm[sup [minus]2] a buried amorphous layer 28 nm in thickness has been observed at the same depth where the strain is maximum. The thickness of the amorphous layer increases by further increasing the dose and reaches a value of about 0.18 [mu]m for [sigma] [equals] 5 x 10[sup 16] cm[sup [minus]2].« less

Comparative analysis of radioecological monitoring dosimeters

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

Sobolev, A.I.; Pol`skii, O.G.; Shanin, O.B.

1995-03-01

This paper describes comparative estimates of radiation doses measured by two types of thermoluminescence dosimeters and two types of background radiation radiometers. The dosimetry systems were tested by simultaneously recording background radiation and standard radiation sources at a radioactive waste storage facility. Statistical analysis of the measurement results is summarized. The maximum recorded exposure dose rate for the experiment was 19 microrads per hour. The DTK-2 dosimeter overestimated dose rates by 6 to 43% and the DTU-2 dosimeter underestimated dose rates by 7 to 21%. Both devices are recommended for radioecological monitoring in populated areas. 4 refs., 3 figs., 5more » tabs.« less

Dose mapping using MCNP code and experiment for SVST-Co-60/B irradiator in Vietnam.

PubMed

Tran, Van Hung; Tran, Khac An

2010-06-01

By using MCNP code and ethanol-chlorobenzene (ECB) dosimeters the simulations and measurements of absorbed dose distribution in a tote-box of the Cobalt-60 irradiator, SVST-Co60/B at VINAGAMMA have been done. Based on the results Dose Uniformity Ratios (DUR), positions and values of minimum and maximum dose extremes in a tote-box, and efficiency of the irradiator for the different dummy densities have been gained. There is a good agreement between simulation and experimental results in comparison and they have valuable meanings for operation of the irradiator. Copyright 2010 Elsevier Ltd. All rights reserved.

An analytic linear accelerator source model for GPU-based Monte Carlo dose calculations.

PubMed

Tian, Zhen; Li, Yongbao; Folkerts, Michael; Shi, Feng; Jiang, Steve B; Jia, Xun

2015-10-21

Recently, there has been a lot of research interest in developing fast Monte Carlo (MC) dose calculation methods on graphics processing unit (GPU) platforms. A good linear accelerator (linac) source model is critical for both accuracy and efficiency considerations. In principle, an analytical source model should be more preferred for GPU-based MC dose engines than a phase-space file-based model, in that data loading and CPU-GPU data transfer can be avoided. In this paper, we presented an analytical field-independent source model specifically developed for GPU-based MC dose calculations, associated with a GPU-friendly sampling scheme. A key concept called phase-space-ring (PSR) was proposed. Each PSR contained a group of particles that were of the same type, close in energy and reside in a narrow ring on the phase-space plane located just above the upper jaws. The model parameterized the probability densities of particle location, direction and energy for each primary photon PSR, scattered photon PSR and electron PSR. Models of one 2D Gaussian distribution or multiple Gaussian components were employed to represent the particle direction distributions of these PSRs. A method was developed to analyze a reference phase-space file and derive corresponding model parameters. To efficiently use our model in MC dose calculations on GPU, we proposed a GPU-friendly sampling strategy, which ensured that the particles sampled and transported simultaneously are of the same type and close in energy to alleviate GPU thread divergences. To test the accuracy of our model, dose distributions of a set of open fields in a water phantom were calculated using our source model and compared to those calculated using the reference phase-space files. For the high dose gradient regions, the average distance-to-agreement (DTA) was within 1 mm and the maximum DTA within 2 mm. For relatively low dose gradient regions, the root-mean-square (RMS) dose difference was within 1.1% and the maximum dose difference within 1.7%. The maximum relative difference of output factors was within 0.5%. Over 98.5% passing rate was achieved in 3D gamma-index tests with 2%/2 mm criteria in both an IMRT prostate patient case and a head-and-neck case. These results demonstrated the efficacy of our model in terms of accurately representing a reference phase-space file. We have also tested the efficiency gain of our source model over our previously developed phase-space-let file source model. The overall efficiency of dose calculation was found to be improved by ~1.3-2.2 times in water and patient cases using our analytical model.

Dynamically accumulated dose and 4D accumulated dose for moving tumors

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

Li Heng; Li Yupeng; Zhang Xiaodong

2012-12-15

Purpose: The purpose of this work was to investigate the relationship between dynamically accumulated dose (dynamic dose) and 4D accumulated dose (4D dose) for irradiation of moving tumors, and to quantify the dose uncertainty induced by tumor motion. Methods: The authors established that regardless of treatment modality and delivery properties, the dynamic dose will converge to the 4D dose, instead of the 3D static dose, after multiple deliveries. The bounds of dynamic dose, or the maximum estimation error using 4D or static dose, were established for the 4D and static doses, respectively. Numerical simulations were performed (1) to prove themore » principle that for each phase, after multiple deliveries, the average number of deliveries for any given time converges to the total number of fractions (K) over the number of phases (N); (2) to investigate the dose difference between the 4D and dynamic doses as a function of the number of deliveries for deliveries of a 'pulsed beam'; and (3) to investigate the dose difference between 4D dose and dynamic doses as a function of delivery time for deliveries of a 'continuous beam.' A Poisson model was developed to estimate the mean dose error as a function of number of deliveries or delivered time for both pulsed beam and continuous beam. Results: The numerical simulations confirmed that the number of deliveries for each phase converges to K/N, assuming a random starting phase. Simulations for the pulsed beam and continuous beam also suggested that the dose error is a strong function of the number of deliveries and/or total deliver time and could be a function of the breathing cycle, depending on the mode of delivery. The Poisson model agrees well with the simulation. Conclusions: Dynamically accumulated dose will converge to the 4D accumulated dose after multiple deliveries, regardless of treatment modality. Bounds of the dynamic dose could be determined using quantities derived from 4D doses, and the mean dose difference between the dynamic dose and 4D dose as a function of number of deliveries and/or total deliver time was also established.« less

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

Liang, Xiaodong, E-mail: lxdctopone@sina.com; Ni, Lingqin; Hu, Wei

The objective of this study was to evaluate the dose conformity and feasibility of whole-brain radiotherapy with a simultaneous integrated boost by forward intensity-modulated radiation therapy in patients with 1 to 3 brain metastases. Forward intensity-modulated radiation therapy plans were generated for 10 patients with 1 to 3 brain metastases on Pinnacle 6.2 Treatment Planning System. The prescribed dose was 30 Gy to the whole brain (planning target volume [PTV]{sub wbrt}) and 40 Gy to individual brain metastases (PTV{sub boost}) simultaneously, and both doses were given in 10 fractions. The maximum diameters of individual brain metastases ranged from 1.6 tomore » 6 cm, and the summated PTVs per patient ranged from 1.62 to 69.81 cm{sup 3}. Conformity and feasibility were evaluated regarding conformation number and treatment delivery time. One hundred percent volume of the PTV{sub boost} received at least 95% of the prescribed dose in all cases. The maximum doses were less than 110% of the prescribed dose to the PTV{sub boost}, and all of the hot spots were within the PTV{sub boost}. The volume of the PTV{sub wbrt} that received at least 95% of the prescribed dose ranged from 99.2% to 100%. The mean values of conformation number were 0.682. The mean treatment delivery time was 2.79 minutes. Ten beams were used on an average in these plans. Whole-brain radiotherapy with a simultaneous integrated boost by forward intensity-modulated radiation therapy in 1 to 3 brain metastases is feasible, and treatment delivery time is short.« less

Environmental consequences of postulate plutonium releases from Atomics International's Nuclear Materials Development Facility (NMDF), Santa Susana, California, as a result of severe natural phenomena

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

Jamison, J.D.; Watson, E.C.

1982-02-01

Potential environmental consequences in terms of radiation dose to people are presented for postulated plutonium releases caused by severe natural phenomena at the Atomics International's Nuclear Materials Development Facility (NMDF), in the Santa Susana site, California. The severe natural phenomena considered are earthquakes, tornadoes, and high straight-line winds. Plutonium deposition values are given for significant locations around the site. All important potential exposure pathways are examined. The most likely 50-year committed dose equivalents are given for the maximum-exposed individual and the population within a 50-mile radius of the plant. The maximum plutonium deposition values likely to occur offsite are alsomore » given. The most likely calculated 50-year collective committed dose equivalents are all much lower than the collective dose equivalent expected from 50 years of exposure to natural background radiation and medical x-rays. The most likely maximum residual plutonium contamination estimated to be deposited offsite following the earthquake, and the 150-mph and 170-mph tornadoes are above the Environmental Protection Agency's (EPA) proposed guideline for plutonium in the general environment of 0.2 ..mu..Ci/m/sup 2/. The deposition values following the 110-mph and the 130-mph tornadoes are below the EPA proposed guideline.« less

Lithospheric flexure revealed by Pleistocene emerged marine terraces on the southern Hawaiian Islands

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

Jones, A.T.

1992-01-01

New field and geochronological data from emerged marine deposits in the southern Hawaiian Islands suggest uplift of the islands of Molokai, Lanai and Oahu. Corals from these islands were dated by ESR. The accumulated dose for aragonitic coral at ESR signal, g = 2.0007, was determined by the additive dose method. The environmental dose rate was estimated from the Uranium concentration in corals and by using an estimate of 2.5 rad/a for the cosmic ray dose. The ESR ages of the highest terraces on Molokai are 290 [+-] 31 ka (30 m), on Lanai 217 [+-] 19 ka (50 m)more » and on Oahu 468 [+-] 36 ka (28 m). The age and elevation of the marine terraces are interpreted to imply uplift during the Late Quaternary. Lithospheric flexure combined with horizontal plate motion is proposed as a mechanism to describe the pattern of uplifted terraces on these islands. Using two-dimensional elastic plate models, the height of maximum bulge is approximately 4% to 7% of the maximum deflection for a continuous or broken plate model. Drowned reefs off Hawaii indicate subsidence of 1 km since 340 ka. Thus, the magnitude of observed uplift (30--50 m) is consistent with theoretical maximum bulge heights derived from numerical results.« less

Peer Review for EPA’s Biologically Based Dose-Response (BBDR) Model for Perchlorate

EPA Science Inventory

EPA is developing a regulation for perchlorate in drinking water. As part the regulatory process EPA must develop a Maximum Contaminant Level Goal (MCLG). FDA and EPA scientists developed a biologically based dose-response (BBDR) model to assist in deriving the MCLG. This mode...

AIR insulin capsules of different dose strengths may be combined to yield equivalent pharmacokinetics and glucodynamics.

PubMed

de la Peña, Amparo; Seger, Mary; Rave, Klaus; Heinemann, Lutz; Silverman, Bernard; Muchmore, Douglas B

2009-09-01

In order to assess pharmacokinetic (PK) and glucodynamic (GD) attributes relevant to the end user of an inhaled insulin, this study examined the exposure and GD effect of doses of AIR inhaled insulin (Eli Lilly and Co., Indianapolis, IN) (AIR is a registered trademark of Alkermes, Inc., Cambridge, MA) by combining capsules of different strengths in healthy subjects. Fifty-nine healthy, nonsmoking, male or female subjects with normal pulmonary function were enrolled in an open-label, randomized, crossover study. Subjects underwent up to five euglycemic glucose clamp procedures, separated by 5-18 days. The five AIR insulin treatments tested included one 6 unit-equivalent (U-eq) capsule containing 2.6 mg of insulin, three 2 U-eq (0.9 mg) capsules (2.7 mg total), one 10 U-eq (3.9 mg) capsule, one 6 U-eq capsule plus two 2 U-eq capsules (4.4 mg total), and two 10 U-eq capsules (7.8 mg total). Samples for PK and GD assessments were taken up to 10 h post-dose. Based on both PK (area under the curve from time 0 to time of return to baseline and maximum concentration) and GD (total amount of glucose infused and maximum glucose infusion rate) responses, administration of a 6 U-eq capsule was equivalent to three 2 U-eq capsules; 90% confidence intervals for the ratios were contained within the interval (0.8, 1.25). Similarly, both overall exposure and glucodynamic response after administration of a 10 U-eq capsule were comparable to the 6 U-eq plus two 2 U-eq capsule combination. AIR insulin exhibited PK dose proportionality and dose-dependent increases in GD responses over the 2.6-7.8 mg dose range. AIR insulin exhibited dose strength interchangeability and dose proportionality after single-dose administration in healthy subjects.

Reduced dose to urethra and rectum with the use of variable needle spacing in prostate brachytherapy: a potential role for robotic technology

PubMed Central

Vyas, Shilpa; Le, Yi; Zhang, Zhe; Armour, Woody

2015-01-01

Purpose Several robotic delivery systems for prostate brachytherapy are under development or in pre-clinical testing. One of the features of robotic brachytherapy is the ability to vary spacing of needles at non-fixed intervals. This feature may play an important role in prostate brachytherapy, which is traditionally template-based with fixed needle spacing of 0.5 cm. We sought to quantify potential reductions in the dose to urethra and rectum by utilizing variable needle spacing, as compared to fixed needle spacing. Material and methods Transrectal ultrasound images from 10 patients were used by 3 experienced planners to create 120 treatment plans. Each planner created 4 plan variations per patient with respect to needle positions: 125I fixed spacing, 125I variable spacing, 103Pd fixed spacing, and 103Pd variable spacing. The primary planning objective was to achieve a prostate V100 of 100% while minimizing dose to urethra and rectum. Results All plans met the objective of achieving prostate V100 of 100%. Combined results for all plans show statistically significant improvements in all assessed dosimetric variables for urethra (Umax, Umean, D30, D5) and rectum (Rmax, Rmean, RV100) when using variable spacing. The dose reductions for mean and maximum urethra dose using variable spacing had p values of 0.011 and 0.024 with 103Pd, and 0.007 and 0.029 with 125I plans. Similarly dose reductions for mean and maximum rectal dose using variable spacing had p values of 0.007 and 0.052 with 103Pd, and 0.012 and 0.037 with 125I plans. Conclusions The variable needle spacing achievable by the use of robotics in prostate brachytherapy allows for reductions in both urethral and rectal planned doses while maintaining prostate dose coverage. Such dosimetric advantages have the potential in translating to significant clinical benefits with the use of robotic brachytherapy. PMID:26622227

Optimization of the temporal pattern of radiation: An IMRT based study

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

Altman, Michael B.; Chmura, Steven J.; Deasy, Joseph O.

Purpose: To investigate how the temporal pattern of dose applied during a single-intensity modulated radiation therapy (IMRT) fraction can be arranged to maximize or minimize cell kill. Methods and Materials: Using the linear-quadratic repair-time model and a simplified IMRT delivery pattern model, the surviving fraction of cells for a single fraction was calculated for all permutations of the dose delivery pattern for an array of clinically based IMRT cases. Maximization of cell kill was achieved by concentrating the highest doses in the middle of a fraction, while minimization was achieved by spreading the highest doses between the beginning and end.more » The percent difference between maximum and minimum cell kill (%Diff{sub min/max}) and the difference between maximum and minimum total doses normalized to 2 Gy/fx ({delta}NTD{sub 2Gy}) was calculated for varying fraction durations (T), {alpha}/{beta} ratios, and doses/fx. Results: %Diff{sub min/max} and {delta}NTD{sub 2Gy} both increased with increasing T and with decreasing {alpha}/{beta}. The largest increases occurred with dose/fx. With {alpha}/{beta} = 3 Gy and 30 min/fx, %Diff{sub min/max} ranged from 2.7-5.3% for 2 Gy/fx to 48.6-74.1% for 10 Gy/fx, whereas {delta}NTD{sub 2Gy} ranged from 1.2 Gy-2.4 Gy for 30 fractions of 2 Gy/fx to 2.3-4.8 Gy for 2 fractions of 10.84 Gy/fx. Using {alpha}/{beta} = 1.5 Gy, an analysis of prostate hypofractionation schemes yielded differences in clinical outcome based on the pattern of applied dose ranging from 3.2%-6.1% of the treated population. Conclusions: Rearrangement of the temporal pattern of dose for a single IMRT fraction could be used to optimize cell kill and to directly, though modestly, affect treatment outcome.« less

SU-E-T-396: Dosimetric Accuracy of Proton Therapy for Patients with Metal Implants in CT Scans Using Metal Deletion Technique (MDT) Artifacts Reduction

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

Li, X; Kantor, M; Zhu, X

2014-06-01

Purpose: To evaluate the dosimetric accuracy for proton therapy patients with metal implants in CT using metal deletion technique (MDT) artifacts reduction. Methods: Proton dose accuracies under CT metal artifacts were first evaluated using a water phantom with cylindrical inserts of different materials (titanium and steel). Ranges and dose profiles along different beam angles were calculated using treatment planning system (Eclipse version 8.9) on uncorrected CT, MDT CT, and manually-corrected CT, where true Hounsfield units (water) were assigned to the streak artifacts. In patient studies, the treatment plans were developed on manually-corrected CTs, then recalculated on MDT and uncorrected CTs.more » DVH indices were compared between the dose distributions on all the CTs. Results: For water phantom study with 1/2 inch titanium insert, the proton range differences estimated by MDT CT were with 1% for all beam angles, while the range error can be up to 2.6% for uncorrected CT. For the study with 1 inch stainless steel insert, the maximum range error calculated by MDT CT was 1.09% among all the beam angles compared with maximum range error with 4.7% for uncorrected CT. The dose profiles calculated on MDT CTs for both titanium and steel inserts showed very good agreements with the ones calculated on manually-corrected CTs, while large dose discrepancies calculated using uncorrected CTs were observed in the distal end region of the proton beam. The patient study showed similar dose distribution and DVHs for organs near the metal artifacts recalculated on MDT CT compared with the ones calculated on manually-corrected CT, while the differences between uncorrected and corrected CTs were much pronounced. Conclusion: In proton therapy, large dose error could occur due to metal artifact. The MDT CT can be used for proton dose calculation to achieve similar dose accuracy as the current clinical practice using manual correction.« less

Radiation-induced rib fracture after stereotactic body radiotherapy with a total dose of 54-56 Gy given in 9-7 fractions for patients with peripheral lung tumor: impact of maximum dose and fraction size.

PubMed

Aoki, Masahiko; Sato, Mariko; Hirose, Katsumi; Akimoto, Hiroyoshi; Kawaguchi, Hideo; Hatayama, Yoshiomi; Ono, Shuichi; Takai, Yoshihiro

2015-04-22

Radiation-induced rib fracture after stereotactic body radiotherapy (SBRT) for lung cancer has been recently reported. However, incidence of radiation-induced rib fracture after SBRT using moderate fraction sizes with a long-term follow-up time are not clarified. We examined incidence and risk factors of radiation-induced rib fracture after SBRT using moderate fraction sizes for the patients with peripherally located lung tumor. During 2003-2008, 41 patients with 42 lung tumors were treated with SBRT to 54-56 Gy in 9-7 fractions. The endpoint in the study was radiation-induced rib fracture detected by CT scan after the treatment. All ribs where the irradiated doses were more than 80% of prescribed dose were selected and contoured to build the dose-volume histograms (DVHs). Comparisons of the several factors obtained from the DVHs and the probabilities of rib fracture calculated by Kaplan-Meier method were performed in the study. Median follow-up time was 68 months. Among 75 contoured ribs, 23 rib fractures were observed in 34% of the patients during 16-48 months after SBRT, however, no patients complained of chest wall pain. The 4-year probabilities of rib fracture for maximum dose of ribs (Dmax) more than and less than 54 Gy were 47.7% and 12.9% (p = 0.0184), and for fraction size of 6, 7 and 8 Gy were 19.5%, 31.2% and 55.7% (p = 0.0458), respectively. Other factors, such as D2cc, mean dose of ribs, V10-55, age, sex, and planning target volume were not significantly different. The doses and fractionations used in this study resulted in no clinically significant rib fractures for this population, but that higher Dmax and dose per fraction treatments resulted in an increase in asymptomatic grade 1 rib fractures.

Evaluation of image-guided helical tomotherapy for the retreatment of spinal metastasis

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

Mahan, Stephen L.; Ramsey, Chester R.; Scaperoth, Daniel D.

Introduction: Patients with vertebral metastasis that receive radiation therapy are typically treated to the spinal cord tolerance dose. As such, it is difficult to successfully deliver a second course of radiation therapy for patients with overlapping treatment volumes. In this study, an image-guided helical tomotherapy system was evaluated for the retreatment of previously irradiated vertebral metastasis. Methods and Materials: Helical tomotherapy dose gradients and maximum cord doses were measured in a cylindrical phantom for geometric test cases with separations between the planning target volume (PTV) and the spinal cord organ at risk (OAR) of 2 mm, 4 mm, 6 mm,more » 8 mm, and 10 mm. Megavoltage computed tomography (CT) images were examined for their ability to localize spinal anatomy for positioning purposes by repeat imaging of the cervical spine in an anthropomorphic phantom. In addition to the phantom studies, 8 patients with cord compressions that had received previous radiation therapy were retreated to a mean dose of 28 Gy using conventional fractionation. Results and Discussion: Megavoltage CT images were capable of positioning an anthropomorphic phantom to within {+-}1.2 mm (2{sigma}) superior-inferiorly and within {+-}0.6 mm (2{sigma}) anterior-posteriorly and laterally. Dose gradients of 10% per mm were measured in phantom while PTV uniformity indices of less than 11% were maintained. The calculated maximum cord dose was 25% of the prescribed dose for a 10-mm PTV-to-OAR separation and 71% of the prescribed dose for a PTV-to-OAR separation of 2 mm. Eight patients total have been treated without radiation-induced myelopathy or any other adverse effects from treatment. Conclusions: A technique has been evaluated for the retreatment of vertebral metastasis using image-guided helical tomotherapy. Phantom and patient studies indicated that a tomotherapy system is capable of delivering dose gradients of 10% per mm and positioning the patient within 1.2 mm without the use of special stereotactic immobilization.« less

Phase I dose-escalation study to examine the safety and tolerability of LY2603618, a checkpoint 1 kinase inhibitor, administered 1 day after pemetrexed 500 mg/m2 every 21 days in patients with cancer

PubMed Central

Iyengar, Tara; Ramanathan, Ramesh K.; Lewandowski, Karen; Anthony, Stephen P.; Donehower, Ross C.; Westin, Eric; Hurt, Karla; Hynes, Scott M.; McKane, Scott

2013-01-01

Summary Purpose This phase I study aims at assessing the safety and tolerability of LY2603618, a selective inhibitor of Checkpoint Kinase 1, in combination with pemetrexed and determining the maximum tolerable dose and the pharmacokinetic parameters. Experimental design This was an open-label, multicenter, dose-escalation study in patients with advanced solid tumors. Increasing doses of LY2603618 (40–195 mg/m2) were combined with 500 mg/m2 of pemetrexed. LY2603618 was administered on Days 1 and 9 and pemetrexed on Day 8 in a 28-day cycle. For all subsequent 21-day cycles, pemetrexed was administered on Day 1 and LY2603618 on Day 2. Anti-tumor activity was evaluated as per Response Evaluation Criteria in Solid Tumors 1.0. Results A total of 31 patients were enrolled into six cohorts (three at 40 mg/m2 over 4.5-hour infusion, 1-hour infusion in subsequent cohorts: three each at 40 mg/m2, 70 mg/m2, and 195 mg/m2; 13 at 105 mg/m2; six at 150 mg/m2). Four patients experienced a dose-limiting toxicity: diarrhea (105 mg/m2); reversible infusion-related reaction (150 mg/m2); thrombocytopenia (195 mg/m2); and fatigue (195 mg/m2). The maximum tolerated dose was defined as 150 mg/m2. The pharmacokinetic data demonstrated that the exposure of LY2603618 increased in a dose-dependent manner, displayed a suitable half-life for maintaining required human exposures while minimizing the intra- and inter-cycle accumulation, and was unaffected by the pemetrexed administration. The pharmacokinetic-defined biologically efficacious dose was achieved at doses ≥105 mg/m2. Conclusion LY2603618 administered approximately 24 h after pemetrexed showed acceptable safety and pharmacokinetic profiles. PMID:22492020

Phase I dose-escalation study to examine the safety and tolerability of LY2603618, a checkpoint 1 kinase inhibitor, administered 1 day after pemetrexed 500 mg/m(2) every 21 days in patients with cancer.

PubMed

Weiss, Glen J; Donehower, Ross C; Iyengar, Tara; Ramanathan, Ramesh K; Lewandowski, Karen; Westin, Eric; Hurt, Karla; Hynes, Scott M; Anthony, Stephen P; McKane, Scott

2013-02-01

This phase I study aims at assessing the safety and tolerability of LY2603618, a selective inhibitor of Checkpoint Kinase 1, in combination with pemetrexed and determining the maximum tolerable dose and the pharmacokinetic parameters. This was an open-label, multicenter, dose-escalation study in patients with advanced solid tumors. Increasing doses of LY2603618 (40-195 mg/m(2)) were combined with 500 mg/m(2) of pemetrexed. LY2603618 was administered on Days 1 and 9 and pemetrexed on Day 8 in a 28-day cycle. For all subsequent 21-day cycles, pemetrexed was administered on Day 1 and LY2603618 on Day 2. Antitumor activity was evaluated as per Response Evaluation Criteria in Solid Tumors 1.0. A total of 31 patients were enrolled into six cohorts (three at 40 mg/m(2) over 4.5-hour infusion, 1-hour infusion in subsequent cohorts: three each at 40 mg/m(2), 70 mg/m(2), and 195 mg/m(2); 13 at 105 mg/m(2); six at 150 mg/m(2)). Four patients experienced a dose-limiting toxicity: diarrhea (105 mg/m(2)); reversible infusion-related reaction (150 mg/m(2)); thrombocytopenia (195 mg/m(2)); and fatigue (195 mg/m(2)). The maximum tolerated dose was defined as 150 mg/m(2). The pharmacokinetic data demonstrated that the exposure of LY2603618 increased in a dose-dependent manner, displayed a suitable half-life for maintaining required human exposures while minimizing the intra- and inter-cycle accumulation, and was unaffected by the pemetrexed administration. The pharmacokinetic-defined biologically efficacious dose was achieved at doses ≥105 mg/m(2). LY2603618 administered approximately 24 h after pemetrexed showed acceptable safety and pharmacokinetic profiles.

Quantifying the Combined Effect of Radiation Therapy and Hyperthermia in Terms of Equivalent Dose Distributions

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

Kok, H. Petra, E-mail: H.P.Kok@amc.uva.nl; Crezee, Johannes; Franken, Nicolaas A.P.

2014-03-01

Purpose: To develop a method to quantify the therapeutic effect of radiosensitization by hyperthermia; to this end, a numerical method was proposed to convert radiation therapy dose distributions with hyperthermia to equivalent dose distributions without hyperthermia. Methods and Materials: Clinical intensity modulated radiation therapy plans were created for 15 prostate cancer cases. To simulate a clinically relevant heterogeneous temperature distribution, hyperthermia treatment planning was performed for heating with the AMC-8 system. The temperature-dependent parameters α (Gy{sup −1}) and β (Gy{sup −2}) of the linear–quadratic model for prostate cancer were estimated from the literature. No thermal enhancement was assumed for normalmore » tissue. The intensity modulated radiation therapy plans and temperature distributions were exported to our in-house-developed radiation therapy treatment planning system, APlan, and equivalent dose distributions without hyperthermia were calculated voxel by voxel using the linear–quadratic model. Results: The planned average tumor temperatures T90, T50, and T10 in the planning target volume were 40.5°C, 41.6°C, and 42.4°C, respectively. The planned minimum, mean, and maximum radiation therapy doses were 62.9 Gy, 76.0 Gy, and 81.0 Gy, respectively. Adding hyperthermia yielded an equivalent dose distribution with an extended 95% isodose level. The equivalent minimum, mean, and maximum doses reflecting the radiosensitization by hyperthermia were 70.3 Gy, 86.3 Gy, and 93.6 Gy, respectively, for a linear increase of α with temperature. This can be considered similar to a dose escalation with a substantial increase in tumor control probability for high-risk prostate carcinoma. Conclusion: A model to quantify the effect of combined radiation therapy and hyperthermia in terms of equivalent dose distributions was presented. This model is particularly instructive to estimate the potential effects of interaction from different treatment modalities.« less

SU-E-T-609: Perturbation Effects of Pedicle Screws On Radiotherapy Dose Distributions

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

Bar-Deroma, R; Borzov, E; Nevelsky, A

2015-06-15

Purpose: Radiation therapy in conjunction with surgical implant fixation is a common combined treatment in case of bone metastases. However, metal implants generally used in orthopedic implants perturb radiation dose distributions. Carbon-Fiber Reinforced (CFR) PEEK material has been recently introduced for production of intramedullary screws and plates. Gold powder can be added to the CFR-PEEK material in order to enhance visibility of the screws during intraoperative imaging procedures. In this work, we investigated the perturbation effects of the pedicle screws made of CFR-PEEK, CFR-PEEK with added gold powder (CFR-PEEK-AU) and Titanium (Ti) on radiotherapy dose distributions. Methods: Monte Carlo (MC)more » simulations were performed using the EGSnrc code package for 6MV beams with 10×10 fields at SSD=100cm. By means of MC simulations, dose distributions around titanium, CFR- PEEK and CFR-PEEK-AU screws (manufactured by Carbo-Fix Orthopedics LTD, Israel) placed in a water phantom were calculated. The screw axis was either parallel or perpendicular to the beam axis. Dose perturbation (relative to dose in homogeneous water phantom) was assessed. Results: Maximum overdose due to backscatter was 10% for the Ti screws, 5% for the CFR-PEEK-AU screws and effectively zero for the CFR-PEEK screws. Maximum underdose due to attenuation was 25% for the Ti screws, 15% for the CFR-PEEK-AU screws and 5% for the CFR-PEEK screws. Conclusion: Titanium screws introduce the largest distortion on the radiation dose distribution. The gold powder added to the CFR-PEEK material improves visibility at the cost of increased dose perturbation. CFR-PEEK screws caused minimal alteration on the dose distribution. This can decrease possible over and underdose of adjacent tissue and thus favorably influence treatment efficiency. The use of such implants has potential clinical advantage in the treatment of neoplastic bone disease.« less

Clinical Toxicities and Dosimetric Parameters After Whole-Pelvis Versus Prostate-Only Intensity-Modulated Radiation Therapy for Prostate Cancer

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

Deville, Curtiland, E-mail: deville@uphs.upenn.ed; Both, Stefan; Hwang, Wei-Ting

2010-11-01

Purpose: To assess whether whole-pelvis (WP) intensity-modulated radiation therapy (IMRT) is associated with increased toxicity compared with prostate-only (PO) IMRT. Methods and Materials: We retrospectively analyzed all patients with prostate cancer undergoing definitive IMRT to 79.2 Gy with concurrent androgen deprivation at our institution from November 2005 to May 2007 with a minimum follow-up of 12 months. Thirty patients received initial WP IMRT to 45 Gy in 1.8-Gy fractions, and thirty patients received PO IMRT. Study patients underwent computed tomography simulation and treatment planning by use of predefined dose constraints. Bladder and rectal dose-volume histograms, maximum genitourinary (GU) and gastrointestinalmore » (GI) Radiation Therapy Oncology Group toxicity grade, and late Grade 2 or greater toxicity-free survival curves were compared between the two groups by use of the Student t test, Fisher exact test, and Kaplan-Meier curve, respectively. Results: Bladder minimum dose, mean dose, median dose, volume receiving 5 Gy, volume receiving 20 Gy, volume receiving 40 Gy, and volume receiving 45 Gy and rectal minimum dose, median dose, and volume receiving 20 Gy were significantly increased in the WP group (all p values < 0.01). Maximum acute GI toxicity was limited to Grade 2 and was significantly increased in the WP group at 50% vs. 13% the PO group (p = 0.006). With a median follow-up of 24 months (range, 12-35 months), there was no difference in late GI toxicity (p = 0.884) or in acute or late GU toxicity. Conclusions: Despite dosimetric differences in the volume of bowel, bladder, and rectum irradiated in the low-dose and median-dose regions, WP IMRT results only in a clinically significant increase in acute GI toxicity, in comparison to PO IMRT, with no difference in GU or late GI toxicity.« less

Reduced dose to urethra and rectum with the use of variable needle spacing in prostate brachytherapy: a potential role for robotic technology.

PubMed

Vyas, Shilpa; Le, Yi; Zhang, Zhe; Armour, Woody; Song, Daniel Y

2015-08-01

Several robotic delivery systems for prostate brachytherapy are under development or in pre-clinical testing. One of the features of robotic brachytherapy is the ability to vary spacing of needles at non-fixed intervals. This feature may play an important role in prostate brachytherapy, which is traditionally template-based with fixed needle spacing of 0.5 cm. We sought to quantify potential reductions in the dose to urethra and rectum by utilizing variable needle spacing, as compared to fixed needle spacing. Transrectal ultrasound images from 10 patients were used by 3 experienced planners to create 120 treatment plans. Each planner created 4 plan variations per patient with respect to needle positions: (125)I fixed spacing, (125)I variable spacing, (103)Pd fixed spacing, and (103)Pd variable spacing. The primary planning objective was to achieve a prostate V100 of 100% while minimizing dose to urethra and rectum. All plans met the objective of achieving prostate V100 of 100%. Combined results for all plans show statistically significant improvements in all assessed dosimetric variables for urethra (Umax, Umean, D30, D5) and rectum (Rmax, Rmean, RV100) when using variable spacing. The dose reductions for mean and maximum urethra dose using variable spacing had p values of 0.011 and 0.024 with (103)Pd, and 0.007 and 0.029 with (125)I plans. Similarly dose reductions for mean and maximum rectal dose using variable spacing had p values of 0.007 and 0.052 with (103)Pd, and 0.012 and 0.037 with (125)I plans. The variable needle spacing achievable by the use of robotics in prostate brachytherapy allows for reductions in both urethral and rectal planned doses while maintaining prostate dose coverage. Such dosimetric advantages have the potential in translating to significant clinical benefits with the use of robotic brachytherapy.

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

Phase I Study of Concurrent High-Dose Three-Dimensional Conformal Radiotherapy With Chemotherapy Using Cisplatin and Vinorelbine for Unresectable Stage III Non-Small-Cell Lung Cancer

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

Sekine, Ikuo, E-mail: isekine@ncc.go.jp; Sumi, Minako; Ito, Yoshinori

Purpose: To determine the maximum tolerated dose in concurrent three-dimensional conformal radiotherapy (3D-CRT) with chemotherapy for unresectable Stage III non-small-cell lung cancer (NSCLC). Patients and Methods: Eligible patients with unresectable Stage III NSCLC, age {>=}20 years, performance status 0-1, percent of volume of normal lung receiving 20 GY or more (V{sub 20}) {<=}30% received three to four cycles of cisplatin (80 mg/m{sup 2} Day 1) and vinorelbine (20 mg/m{sup 2} Days 1 and 8) repeated every 4 weeks. The doses of 3D-CRT were 66 Gy, 72 Gy, and 78 Gy at dose levels 1 to 3, respectively. Results: Of themore » 17, 16, and 24 patients assessed for eligibility, 13 (76%), 12 (75%), and 6 (25%) were enrolled at dose levels 1 to 3, respectively. The main reasons for exclusion were V{sub 20} >30% (n = 10) and overdose to the esophagus (n = 8) and brachial plexus (n = 2). There were 26 men and 5 women, with a median age of 60 years (range, 41-75). The full planned dose of radiotherapy could be administered to all the patients. Grade 3-4 neutropenia and febrile neutropenia were noted in 24 (77%) and 5 (16%) of the 31 patients, respectively. Grade 4 infection, Grade 3 esophagitis, and Grade 3 pulmonary toxicity were noted in 1 patient, 2 patients, and 1 patient, respectively. The dose-limiting toxicity was noted in 17% of the patients at each dose level. The median survival and 3-year and 4-year survival rates were 41.9 months, 72.3%, and 49.2%, respectively. Conclusions: 72 Gy was the maximum dose that could be achieved in most patients, given the predetermined normal tissue constraints.« less

Measurement and effects of MOSKIN detectors on skin dose during high energy radiotherapy treatment.

PubMed

Alnawaf, Hani; Butson, Martin; Yu, Peter K N

2012-09-01

During in vivo dosimetry for megavoltage X-ray beams, detectors such as diodes, Thermo luminescent dosimeters (TLD's) and MOSFET devices are placed on the patient's skin. This of course will affect the skin dose delivered during that fraction of the treatment. Whilst the overall impact on increasing skin dose would be minimal, little has been quantified concerning the level of increase in absorbed dose, in vivo dosimeters produce when placed in the beams path. To this extent, measurements have been made and analysis performed on dose changes caused by MOSKIN, MOSFET, skin dose detectors. Maximum increases in skin dose were measured as 15 % for 6 MV X-rays and 10 % for 10 MV X-rays at the active crystal of the MOSKIN device which is the thickest part of the detector. This is compared to 32 and 26 % for a standard 1 mm thick LiF TLD at 10 × 10 cm(2) field size for 6 and 10 MV X-rays respectively. Radiochromic film, EBT2 has been shown to provide a high resolution 2 dimensional map of skin dose from these detectors and measures the effects of in vivo dosimeters used for radiotherapy dose assessment.

MAGIC with formaldehyde applied to dosimetry of HDR brachytherapy source

NASA Astrophysics Data System (ADS)

Marques; T; Fernandes; J; Barbi; G; Nicolucci; P; Baffa; O

2009-05-01

The use of polymer gel dosimeters in brachytherapy can allow the determination of three-dimensional dose distributions in large volumes and with high spatial resolution if an adequate calibration process is performed. One of the major issues in these experiments is the polymer gel response dependence on dose rate when high dose rate sources are used and the doses in the vicinity of the sources are to be determinated. In this study, the response of a modified MAGIC polymer gel with formaldehyde around an Iridium-192 HDR brachytherapy source is presented. Experimental results obtained with this polymer gel were compared with ionization chamber measurements and with Monte Carlo simulation with PENELOPE. A maximum difference of 3.10% was found between gel dose measurements and Monte Carlo simulation at a radial distance of 18 mm from the source. The results obtained show that the gel's response is strongly influenced by dose rate and that a different calibration should be used for the vicinity of the source and for regions of lower dose rates. The results obtained in this study show that, provided the proper calibration is performed, MAGIC with formaldehyde can be successfully used to accurate determinate dose distributions form high dose rate brachytherapy sources.

Effects of Pharmacokinetic Processes and Varied Dosing Schedules on the Dynamics of Acquired Resistance to Erlotinib in EGFR-Mutant Lung Cancer

PubMed Central

Foo, Jasmine; Chmielecki, Juliann; Pao, William; Michor, Franziska

2013-01-01

Introduction Erlotinib (Tarceva) is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, which effectively targets EGFR-mutant driven non–small-cell lung cancer. However, the evolution of acquired resistance because of a second-site mutation (T790M) within EGFR remains an obstacle to successful treatment. Methods We used mathematical modeling and available clinical trial data to predict how different pharmacokinetic parameters (fast versus slow metabolism) and dosing schedules (low dose versus high dose; missed doses with and without make-up doses) might affect the evolution of T790M-mediated resistance in mixed populations of tumor cells. Results We found that high-dose pulses with low-dose continuous therapy impede the development of resistance to the maximum extent, both pre- and post-emergence of resistance. The probability of resistance is greater in fast versus slow drug metabolizers, suggesting a potential mechanism, unappreciated to date, influencing acquired resistance in patients. In case of required dose modifications because of toxicity, little difference is observed in terms of efficacy and resistance dynamics between the standard daily dose (150 mg/d) and 150 mg/d alternating with 100 mg/d. Missed doses are expected to lead to resistance faster, even if make-up doses are attempted. Conclusions For existing and new kinase inhibitors, this novel framework can be used to rationally and rapidly design optimal dosing strategies to minimize the development of acquired resistance. PMID:22982659

Dose calculation with respiration-averaged CT processed from cine CT without a respiratory surrogate

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

Riegel, Adam C.; Ahmad, Moiz; Sun Xiaojun

2008-12-15

Dose calculation for thoracic radiotherapy is commonly performed on a free-breathing helical CT despite artifacts caused by respiratory motion. Four-dimensional computed tomography (4D-CT) is one method to incorporate motion information into the treatment planning process. Some centers now use the respiration-averaged CT (RACT), the pixel-by-pixel average of the ten phases of 4D-CT, for dose calculation. This method, while sparing the tedious task of 4D dose calculation, still requires 4D-CT technology. The authors have recently developed a means to reconstruct RACT directly from unsorted cine CT data from which 4D-CT is formed, bypassing the need for a respiratory surrogate. Using RACTmore » from cine CT for dose calculation may be a means to incorporate motion information into dose calculation without performing 4D-CT. The purpose of this study was to determine if RACT from cine CT can be substituted for RACT from 4D-CT for the purposes of dose calculation, and if increasing the cine duration can decrease differences between the dose distributions. Cine CT data and corresponding 4D-CT simulations for 23 patients with at least two breathing cycles per cine duration were retrieved. RACT was generated four ways: First from ten phases of 4D-CT, second, from 1 breathing cycle of images, third, from 1.5 breathing cycles of images, and fourth, from 2 breathing cycles of images. The clinical treatment plan was transferred to each RACT and dose was recalculated. Dose planes were exported at orthogonal planes through the isocenter (coronal, sagittal, and transverse orientations). The resulting dose distributions were compared using the gamma ({gamma}) index within the planning target volume (PTV). Failure criteria were set to 2%/1 mm. A follow-up study with 50 additional lung cancer patients was performed to increase sample size. The same dose recalculation and analysis was performed. In the primary patient group, 22 of 23 patients had 100% of points within the PTV pass {gamma} criteria. The average maximum and mean {gamma} indices were very low (well below 1), indicating good agreement between dose distributions. Increasing the cine duration generally increased the dose agreement. In the follow-up study, 49 of 50 patients had 100% of points within the PTV pass the {gamma} criteria. The average maximum and mean {gamma} indices were again well below 1, indicating good agreement. Dose calculation on RACT from cine CT is negligibly different from dose calculation on RACT from 4D-CT. Differences can be decreased further by increasing the cine duration of the cine CT scan.« less

The Fukushima Health Management Survey: estimation of external doses to residents in Fukushima Prefecture

NASA Astrophysics Data System (ADS)

Ishikawa, Tetsuo; Yasumura, Seiji; Ozasa, Kotaro; Kobashi, Gen; Yasuda, Hiroshi; Miyazaki, Makoto; Akahane, Keiichi; Yonai, Shunsuke; Ohtsuru, Akira; Sakai, Akira; Sakata, Ritsu; Kamiya, Kenji; Abe, Masafumi

2015-08-01

The Fukushima Health Management Survey (including the Basic Survey for external dose estimation and four detailed surveys) was launched after the Fukushima Dai-ichi Nuclear Power Plant accident. The Basic Survey consists of a questionnaire that asks Fukushima Prefecture residents about their behavior in the first four months after the accident; and responses to the questionnaire have been returned from many residents. The individual external doses are estimated by using digitized behavior data and a computer program that included daily gamma ray dose rate maps drawn after the accident. The individual external doses of 421,394 residents for the first four months (excluding radiation workers) had a distribution as follows: 62.0%, <1 mSv 94.0%, <2 mSv 99.4%, <3 mSv. The arithmetic mean and maximum for the individual external doses were 0.8 and 25 mSv, respectively. While most dose estimation studies were based on typical scenarios of evacuation and time spent inside/outside, the Basic Survey estimated doses considering individually different personal behaviors. Thus, doses for some individuals who did not follow typical scenarios could be revealed. Even considering such extreme cases, the estimated external doses were generally low and no discernible increased incidence of radiation-related health effects is expected.

The Fukushima Health Management Survey: estimation of external doses to residents in Fukushima Prefecture

PubMed Central

Ishikawa, Tetsuo; Yasumura, Seiji; Ozasa, Kotaro; Kobashi, Gen; Yasuda, Hiroshi; Miyazaki, Makoto; Akahane, Keiichi; Yonai, Shunsuke; Ohtsuru, Akira; Sakai, Akira; Sakata, Ritsu; Kamiya, Kenji; Abe, Masafumi

2015-01-01

The Fukushima Health Management Survey (including the Basic Survey for external dose estimation and four detailed surveys) was launched after the Fukushima Dai-ichi Nuclear Power Plant accident. The Basic Survey consists of a questionnaire that asks Fukushima Prefecture residents about their behavior in the first four months after the accident; and responses to the questionnaire have been returned from many residents. The individual external doses are estimated by using digitized behavior data and a computer program that included daily gamma ray dose rate maps drawn after the accident. The individual external doses of 421,394 residents for the first four months (excluding radiation workers) had a distribution as follows: 62.0%, <1 mSv; 94.0%, <2 mSv; 99.4%, <3 mSv. The arithmetic mean and maximum for the individual external doses were 0.8 and 25 mSv, respectively. While most dose estimation studies were based on typical scenarios of evacuation and time spent inside/outside, the Basic Survey estimated doses considering individually different personal behaviors. Thus, doses for some individuals who did not follow typical scenarios could be revealed. Even considering such extreme cases, the estimated external doses were generally low and no discernible increased incidence of radiation-related health effects is expected. PMID:26239643

Safety, tolerability, pharmacokinetics and pharmacodynamics of single doses of empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, in healthy Japanese subjects.

PubMed

Sarashina, Akiko; Koiwai, Kazuki; Seman, Leo J; Yamamura, Norio; Taniguchi, Atsushi; Negishi, Takahiro; Sesoko, Shogo; Woerle, Hans J; Dugi, Klaus A

2013-01-01

This randomized, placebo-controlled within dose groups, double-blind, single rising dose study investigated the safety, tolerability, pharmacokinetics and pharmacodynamics of 1 mg to 100 mg doses of empagliflozin in 48 healthy Japanese male subjects. Empagliflozin was rapidly absorbed, reaching peak levels in 1.25 to 2.50 h; thereafter, plasma concentrations declined in a biphasic fashion, with mean terminal elimination half-life ranging from 7.76 to 11.7 h. Increase in empagliflozin exposure was proportional to dose. Oral clearance was dose independent and ranged from 140 to 172 mL/min. In the 24 h following 100 mg empagliflozin administration, the mean (%CV) amount of glucose excreted in urine was 74.3 (17.1) g. The amount and the maximum rate of glucose excreted via urine increased with dose of empagliflozin. Nine adverse events, all of mild intensity, were reported by 8 subjects (7 with empagliflozin and 1 with the placebo). No hypoglycemia was reported. In conclusion, 1 mg to 100 mg doses of empagliflozin had a good safety and tolerability profile in healthy Japanese male subjects. Exposure to empagliflozin was dose proportional. The amount and rate of urinary glucose excretion were higher with empagliflozin than with the placebo, and increased with empagliflozin dose.

Accuracy of patient-specific organ dose estimates obtained using an automated image segmentation algorithm.

PubMed

Schmidt, Taly Gilat; Wang, Adam S; Coradi, Thomas; Haas, Benjamin; Star-Lack, Josh

2016-10-01

The overall goal of this work is to develop a rapid, accurate, and automated software tool to estimate patient-specific organ doses from computed tomography (CT) scans using simulations to generate dose maps combined with automated segmentation algorithms. This work quantified the accuracy of organ dose estimates obtained by an automated segmentation algorithm. We hypothesized that the autosegmentation algorithm is sufficiently accurate to provide organ dose estimates, since small errors delineating organ boundaries will have minimal effect when computing mean organ dose. A leave-one-out validation study of the automated algorithm was performed with 20 head-neck CT scans expertly segmented into nine regions. Mean organ doses of the automatically and expertly segmented regions were computed from Monte Carlo-generated dose maps and compared. The automated segmentation algorithm estimated the mean organ dose to be within 10% of the expert segmentation for regions other than the spinal canal, with the median error for each organ region below 2%. In the spinal canal region, the median error was [Formula: see text], with a maximum absolute error of 28% for the single-atlas approach and 11% for the multiatlas approach. The results demonstrate that the automated segmentation algorithm can provide accurate organ dose estimates despite some segmentation errors.

Accuracy of patient-specific organ dose estimates obtained using an automated image segmentation algorithm

PubMed Central

Schmidt, Taly Gilat; Wang, Adam S.; Coradi, Thomas; Haas, Benjamin; Star-Lack, Josh

2016-01-01

Abstract. The overall goal of this work is to develop a rapid, accurate, and automated software tool to estimate patient-specific organ doses from computed tomography (CT) scans using simulations to generate dose maps combined with automated segmentation algorithms. This work quantified the accuracy of organ dose estimates obtained by an automated segmentation algorithm. We hypothesized that the autosegmentation algorithm is sufficiently accurate to provide organ dose estimates, since small errors delineating organ boundaries will have minimal effect when computing mean organ dose. A leave-one-out validation study of the automated algorithm was performed with 20 head-neck CT scans expertly segmented into nine regions. Mean organ doses of the automatically and expertly segmented regions were computed from Monte Carlo-generated dose maps and compared. The automated segmentation algorithm estimated the mean organ dose to be within 10% of the expert segmentation for regions other than the spinal canal, with the median error for each organ region below 2%. In the spinal canal region, the median error was −7%, with a maximum absolute error of 28% for the single-atlas approach and 11% for the multiatlas approach. The results demonstrate that the automated segmentation algorithm can provide accurate organ dose estimates despite some segmentation errors. PMID:27921070

Estimation Of Organ Doses From Solar Particle Events For Future Space Exploration Missions

NASA Technical Reports Server (NTRS)

Kim, Myung-Hee; Cucinotta, Francis A.

2006-01-01

Radiation protection practices define the effective dose as a weighted sum of equivalent dose over major organ sites for radiation cancer risks. Since a crew personnel dosimeter does not make direct measurement of the effective dose, it has been estimated with skin-dose measurements and radiation transport codes for ISS and STS missions. If sufficient protection is not provided near solar maximum, the radiation risk can be significant due to exposure to sporadic solar particle events (SPEs) as well as to the continuous galactic cosmic radiation (GCR) on future exploratory-class and long-duration missions. For accurate estimates of overall fatal cancer risks from SPEs, the specific doses at various blood forming organs (BFOs) were considered, because proton fluences and doses vary considerably across marrow regions. Previous estimates of BFO doses from SPEs have used an average body-shielding distribution for the bone marrow based on the computerized anatomical man model (CAM). With the development of an 82-point body-shielding distribution at BFOs, the mean and variance of SPE doses in the major active marrow regions (head and neck, chest, abdomen, pelvis and thighs) will be presented. Consideration of the detailed distribution of bone marrow sites is one of many requirements to improve the estimation of effective doses for radiation cancer risks.

The hormesis database: the occurrence of hormetic dose responses in the toxicological literature.

PubMed

Calabrese, Edward J; Blain, Robyn B

2011-10-01

In 2005 we published an assessment of dose responses that satisfied a priori evaluative criteria for inclusion within the relational retrieval hormesis database (Calabrese and Blain, 2005). The database included information on study characteristics (e.g., biological model, gender, age and other relevant aspects, number of doses, dose distribution/range, quantitative features of the dose response, temporal features/repeat measures, and physical/chemical properties of the agents). The 2005 article covered information for about 5000 dose responses; the present article has been expanded to cover approximately 9000 dose responses. This assessment extends and strengthens the conclusion of the 2005 paper that the hormesis concept is broadly generalizable, being independent of biological model, endpoint measured and chemical class/physical agent. It also confirmed the definable quantitative features of hormetic dose responses in which the strong majority of dose responses display maximum stimulation less than twice that of the control group and a stimulatory width that is within approximately 10-20-fold of the estimated toxicological or pharmacological threshold. The remarkable consistency of the quantitative features of the hormetic dose response suggests that hormesis may provide an estimate of biological plasticity that is broadly generalized across plant, microbial and animal (invertebrate and vertebrate) models. Copyright © 2011 Elsevier Inc. All rights reserved.

Can contrast media increase organ doses in CT examinations? A clinical study.

PubMed

Amato, Ernesto; Salamone, Ignazio; Naso, Serena; Bottari, Antonio; Gaeta, Michele; Blandino, Alfredo

2013-06-01

The purpose of this article is to quantify the CT radiation dose increment in five organs resulting from the administration of iodinated contrast medium. Forty consecutive patients who underwent both un-enhanced and contrast-enhanced thoracoabdominal CT were included in our retrospective study. The dose increase between CT before and after contrast agent administration was evaluated in the portal phase for the thyroid, liver, spleen, pancreas, and kidneys by applying a previously validated method. An increase in radiation dose was noted in all organs studied. Average dose increments were 19% for liver, 71% for kidneys, 33% for spleen and pancreas, and 41% for thyroid. Kidneys exhibited the maximum dose increment, whereas the pancreas showed the widest variance because of the differences in fibro-fatty involution. Finally, thyroids with high attenuation values on unenhanced CT showed a lower Hounsfield unit increase and, thus, a smaller increment in the dose. Our study showed an increase in radiation dose in several parenchymatous tissues on contrast-enhanced CT. Our method allowed us to evaluate the dose increase from the change in attenuation measured in Hounsfield units. Because diagnostic protocols require multiple acquisitions after the contrast agent administration, such a dose increase should be considered when optimizing these protocols.

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

Investigation of intracranial peripheral dose arising from the treatment of large lesions with Leksell GammaKnife Perfexion.

PubMed

Ruschin, Mark; Nordström, Håkan; Kjäll, Per; Cho, Young-Bin; Jaffray, David

2009-06-01

This investigation involves quantifying the extent of intracranial peripheral dose arising from simulated targets situated in the skull-base or upper-spine region using the Leksell GammaKnife Perfexion treatment unit. For each of three spherical target volumes--denoted as Vs (4 cm3), VM (18 cm3), and VL (60 cm3)--three treatment plans were manually generated, one for each of the three collimator sizes--4, 8, and 16 mm. Each of the plans was delivered to a spherical dosimetry phantom with an insert containing EBT Gafchromic film. The total dose at 70 mm from the targets' edges, %D(70 mm), was measured as a function of elevation angle and expressed as a percentage of the prescription dose. The film insert was placed centered in the median sagittal plane (Leksell X = 100) and %D(70 mm) was measured for the angular range from 0 degree (superior/along Z axis) to 90 degrees (anterior/along Y axis). For a given collimator i, the irradiation time ti to treat a spherical target of volume V using the 50% isodose line was observed to follow a power-law relationship of the form ti = Ai(V/ Vi)n where Ai was the maximum dose divided by collimator dose rate and Vi was the volume encompassed by the 50% isodose line for a single shot. The mean value of n was 0.61 (range: 0.61-0.62). Along the superior (Z) direction (angle=0 degree) and up to angles of around 30 degrees, the %D(70 mm) was always highest for the 4 mm plans, followed by the 8 mm, followed by the 16 mm. In this angular range, the maximum measured %D(70 mm) was 1.7% of the prescription dose. The intracranial peripheral dose along the superior direction (combined scatter and leakage dose) resulting from irradiation of upper-spine or base-of-skull lesions is measured to be less than 2% of the prescription dose, even for very large (60 cm3) targets. The results of this study indicate that, for a given target volume, treatment plans consisting of only 4 mm shots yield larger peripheral dose in the superior direction than 8 mm shot only plans, which in turn yield larger peripheral dose than 16 mm shot only plans.

First-in-human study of the toxicity, pharmacokinetics, and pharmacodynamics of CG200745, a pan-HDAC inhibitor, in patients with refractory solid malignancies.

PubMed

Kim, Kyu-pyo; Park, Seong Joon; Kim, Jeong-Eun; Hong, Yong Sang; Lee, Jae-Lyun; Bae, Kyun-Seop; Cha, Hyunju; Kwon, Sool-Ki; Ro, Seonggu; Cho, JoongMyung; Kim, Tae Won

2015-10-01

The aim of the present study was to assess the safety, maximum tolerated dose (MTD), pharmacokinetics, pharmacodynamics, and efficacy of single and multiple doses of intravenous CG200745, a novel histone deacetylase (HDAC) inhibitor, in patients with advanced solid malignancies. Two to six patients received intravenous CG200745 according to the 2 + 4 dose-escalating method. This first-in-human trial was comprised of two parts: Part 1 was a single ascending dose, and Part 2 was multiple ascending doses weekly for 3 weeks, and then 1 week off. For the first cycle, pharmacokinetic sampling for CG200745 and pharmacodynamic sampling for acetylated histone H4 in peripheral blood mononuclear cells (PBMCs) were performed on day 1 for Part 1 and on days 1 and 15 for Part 2. Examination of acetylated histone H4 in pre- and post-biopsy samples was performed in accessible patients. In all, 28 patients were treated at 13 dose levels (1.8-250 mg/m(2)) and received a total of 71 cycles of CG200745. Hematologic toxicities included grade 3/4 neutropenia (22.2 %) that did not last a week and non-hematologic toxicities included fatigue (22.2 %) and anorexia (16.7 %) that did not exceed grade 2. No dose-limiting toxic effects were noted. Dose proportionality was observed for both the maximum concentration and area under the curve. The elimination half-life was 5.67 ± 2.69 h (mean ± standard deviation). An increase in PBMC acetylated histone H4 was observed at dose levels up to 51 mg/m(2), which plateaued at higher dose levels. At 24 h, 75 % of patients (6/8) showed higher relative acetylation in tumor tissue compared to PBMCs. Although there was no partial or complete response, 57.1 % of patients (16/28) had stable disease that lasted at least 6 weeks. CG200745 can be safely administered at effective dose levels that inhibit HDAC in PBMCs and tumor tissue. Although MTD was not reached, further escalation was not performed because acetylated histone H4 plateaued at dose levels higher than 51 mg/m(2). Additional phase II trials are recommended at 250 mg/m(2).

SU-E-T-135: Investigation of Commercial-Grade Flatbed Scanners and a Medical- Grade Scanner for Radiochromic EBT Film Dosimetry.

PubMed

Syh, J; Patel, B; Syh, J; Wu, H; Rosen, L; Durci, M; Katz, S; Sibata, C

2012-06-01

To evaluate the characteristics of commercial-grade flatbed scanners and medical-grade scanners for radiochromic EBT film dosimetry. Performance aspects of a Vidar Dosimetry Pro Advantage (Red), Epson 750 Pro, Microtek ArtixScan 1800f, and Microtek ScanMaker 8700 scanner for EBT2 Gafchromic film were evaluated in the categories of repeatability, maximum distinguishable optical density (OD) differentiation, OD variance, and dose curve characteristics. OD step film by Stouffer Industries containing 31 steps ranging from 0.05 to 3.62 OD was used. EBT films were irradiated with dose ranging from 20 to 600 cGy in 6×6 cm 2 field sizes and analyzed 24 hours later using RIT113 and Tomotherapy Film Analyzer software. Scans were performed in transmissive mode, landscape orientation, 16-bit image. The mean and standard deviation Analog to Digital (A/D) scanner value was measured by selecting a 3×3 mm 2 uniform area in the central region of each OD step from a total of 20 scans performed over several weeks. Repeatability was determined from the variance of OD step 0.38. Maximum distinguishable OD was defined as the last OD step whose range of A/D values does not overlap with its neighboring step. Repeatability uncertainty ranged from 0.1% for Vidar to 4% for Epson. Average standard deviation of OD steps ranged from 0.21% for Vidar to 6.4% for ArtixScan 1800f. Maximum distinguishable optical density ranged from 3.38 for Vidar to 1.32 for ScanMaker 8700. A/D range of each OD step corresponds to a dose range. Dose ranges of OD steps varied from 1% for Vidar to 20% for ScanMaker 8700. The Vidar exhibited a dose curve that utilized a broader range of OD values than the other scanners. Vidar exhibited higher maximum distinguishable OD, smaller variance in repeatability, smaller A/D value deviation per OD step, and a shallower dose curve with respect to OD. © 2012 American Association of Physicists in Medicine.

Implications of free breathing motion assessed by 4D-computed tomography on the delivered dose in radiotherapy for esophageal cancer.

PubMed

Duma, Marciana Nona; Berndt, Johannes; Rondak, Ina-Christine; Devecka, Michal; Wilkens, Jan J; Geinitz, Hans; Combs, Stephanie Elisabeth; Oechsner, Markus

2015-01-01

The aim of this study was to assess the effect of breathing motion on the delivered dose in esophageal cancer 3-dimensional (3D)-conformal radiotherapy (3D-CRT), intensity-modulated radiotherapy (IMRT), and volumetric modulated arc therapy (VMAT). We assessed 16 patients with esophageal cancer. All patients underwent 4D-computed tomography (4D-CT) for treatment planning. For each of the analyzed patients, 1 3D-CRT, 1 IMRT, and 1 VMAT (RapidArc-RA) plan were calculated. Each of the 3 initial plans was recalculated on the 4D-CT (for the maximum free inspiration and maximum free expiration) to assess the effect of breathing motion. We assessed the minimum dose (Dmin) and mean dose (Dmean) to the esophagus within the planning target volume, the volume changes of the lungs, the Dmean and the total lung volume receiving at least 40Gy (V40), and the V30, V20, V10, and V5. For the heart we assessed the Dmean and the V25. Over all techniques and all patients the change in Dmean as compared with the planned Dmean (planning CT [PCT]) to the esophagus was 0.48% in maximum free inspiration (CT_insp) and 0.55% in maximum free expiration (CT_exp). The Dmin CT_insp change was 0.86% and CT_exp change was 0.89%. The Dmean change of the lungs (heart) was in CT_insp 1.95% (2.89%) and 3.88% (2.38%) in CT_exp. In all, 4 patients had a clinically relevant change of the dose (≥ 5% Dmean to the heart and the lungs) between inspiration and expiration. These patients had a very cranially or caudally situated tumor. There are no relevant differences in the delivered dose to the regions of interest among the 3 techniques. Breathing motion management could be considered to achieve a better sparing of the lungs or heart in patients with cranially or caudally situated tumors. Copyright © 2015 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

Implications of free breathing motion assessed by 4D-computed tomography on the delivered dose in radiotherapy for esophageal cancer

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

Duma, Marciana Nona, E-mail: Marciana.Duma@mri.tum.de; Berndt, Johannes; Rondak, Ina-Christine

2015-01-01

The aim of this study was to assess the effect of breathing motion on the delivered dose in esophageal cancer 3-dimensional (3D)-conformal radiotherapy (3D-CRT), intensity-modulated radiotherapy (IMRT), and volumetric modulated arc therapy (VMAT). We assessed 16 patients with esophageal cancer. All patients underwent 4D-computed tomography (4D-CT) for treatment planning. For each of the analyzed patients, 1 3D-CRT, 1 IMRT, and 1 VMAT (RapidArc—RA) plan were calculated. Each of the 3 initial plans was recalculated on the 4D-CT (for the maximum free inspiration and maximum free expiration) to assess the effect of breathing motion. We assessed the minimum dose (D{sub min})more » and mean dose (D{sub mean}) to the esophagus within the planning target volume, the volume changes of the lungs, the D{sub mean} and the total lung volume receiving at least 40 Gy (V{sub 40}), and the V{sub 30}, V{sub 20}, V{sub 10}, and V{sub 5}. For the heart we assessed the D{sub mean} and the V{sub 25}. Over all techniques and all patients the change in D{sub mean} as compared with the planned D{sub mean} (planning CT [PCT]) to the esophagus was 0.48% in maximum free inspiration (CT-insp) and 0.55% in maximum free expiration (CT-exp). The D{sub min} CT-insp change was 0.86% and CT-exp change was 0.89%. The D{sub mean} change of the lungs (heart) was in CT-insp 1.95% (2.89%) and 3.88% (2.38%) in CT-exp. In all, 4 patients had a clinically relevant change of the dose (≥ 5% D{sub mean} to the heart and the lungs) between inspiration and expiration. These patients had a very cranially or caudally situated tumor. There are no relevant differences in the delivered dose to the regions of interest among the 3 techniques. Breathing motion management could be considered to achieve a better sparing of the lungs or heart in patients with cranially or caudally situated tumors.« less

Comparison of the Efficacy and Safety of 2 Acetaminophen Dosing Regimens in Febrile Infants and Children: A Report on 3 Legacy Studies.

PubMed

Temple, Anthony R; Zimmerman, Brenda; Gelotte, Cathy; Kuffner, Edwin K

2017-01-01

Compare efficacy and safety of 10 to 15 mg/kg with 20 to 30 mg/kg acetaminophen in febrile children 6 months to ≤ 11 years from 3 double-blind, randomized, single or multiple dose studies. Doses were compared on sum of the temperature differences (SUMDIFF), maximum temperature difference (MAXDIFF), temperature differences at each time point, and dose by time interactions. Alanine aminotransferase (ALT) was evaluated in the 72-hour duration study. A single dose of acetaminophen 20 to 30 mg/kg produced a greater effect on temperature decrement and duration of antipyretic effect over 8 hours than a single dose of 10 to 15 mg/kg. When equivalent total doses (i.e., 2 doses of 10 to 15 mg/kg given at 4-hour intervals and 1 dose of 20 to 30 mg/kg) were given over the initial 8-hour period, there were no significant temperature differences. Over a 72-hour period, 10 to 15 mg/kg acetaminophen administered every 4 hours maintained a more consistent temperature decrement than 20 to 30 mg/kg acetaminophen administered every 8 hours. Following doses of 60 to 90 mg/kg/day for up to 72 hours, no child had a clinically important increase in ALT from baseline. The number of children with reported adverse events was similar between doses. Data demonstrate the antipyretic effect of acetaminophen is dependent on total dose over a given time interval. These 3 studies provide clinical evidence that the recommended standard acetaminophen dose of 10 to 15 mg/kg is a safe and effective dose for treating fever in pediatric patients when administered as a single dose or as multiple doses for up to 72 hours.

Measured and Calculated Neutron Spectra and Dose Equivalent Rates at High Altitudes; Relevance to SST Operations and Space Research

NASA Technical Reports Server (NTRS)

Foelsche, T.; Mendell, R. B.; Wilson, J. W.; Adams, R. R.

1974-01-01

Results of the NASA Langley-New York University high-altitude radiation study are presented. Measurements of the absorbed dose rate and of secondary fast neutrons (1 to 10 MeV energy) during the years 1965 to 1971 are used to determine the maximum radiation exposure from galactic and solar cosmic rays of supersonic transport (SST) and subsonic jet occupants. The maximum dose equivalent rates that the SST crews might receive turn out to be 13 to 20 percent of the maximum permissible dose rate (MPD) for radiation workers (5 rem/yr). The exposure of passengers encountering an intense giant-energy solar particle event could exceed the MPD for the general population (0.5 rem/yr), but would be within these permissible limits if in such rare cases the transport descends to subsonic altitude; it is in general less than 12 percent of the MPD. By Monte Carlo calculations of the transport and buildup of nucleons in air for incident proton energies E of 0.02 to 10 GeV, the measured neutron spectra were extrapolated to lower and higher energies and for galactic cosmic rays were found to continue with a relatively high intensity to energies greater than 400 MeV, in a wide altitude range. This condition, together with the measured intensity profiles of fast neutrons, revealed that the biologically important fast and energetic neutrons penetrate deep into the atmosphere and contribute approximately 50 percent of the dose equivalant rates at SST and present subsonic jet altitudes.

Application of a dummy eye shield for electron treatment planning

PubMed Central

Kang, Sei-Kwon; Park, Soah; Hwang, Taejin; Cheong, Kwang-Ho; Han, Taejin; Kim, Haeyoung; Lee, Me-Yeon; Kim, Kyoung Ju; Oh, Do Hoon; Bae, Hoonsik

2013-01-01

Metallic eye shields have been widely used for near-eye treatments to protect critical regions, but have never been incorporated into treatment plans because of the unwanted appearance of the metal artifacts on CT images. The purpose of this work was to test the use of an acrylic dummy eye shield as a substitute for a metallic eye shield during CT scans. An acrylic dummy shield of the same size as the tungsten eye shield was machined and CT scanned. The BEAMnrc and the DOSXYZnrc were used for the Monte Carlo (MC) simulation, with the appropriate material information and density for the aluminum cover, steel knob and tungsten body of the eye shield. The Pinnacle adopting the Hogstrom electron pencil-beam algorithm was used for the one-port 6-MeV beam plan after delineation and density override of the metallic parts. The results were confirmed with the metal oxide semiconductor field effect transistor (MOSFET) detectors and the Gafchromic EBT2 film measurements. For both the maximum eyelid dose over the shield and the maximum dose under the shield, the MC results agreed with the EBT2 measurements within 1.7%. For the Pinnacle plan, the maximum dose under the shield agreed with the MC within 0.3%; however, the eyelid dose differed by –19.3%. The adoption of the acrylic dummy eye shield was successful for the treatment plan. However, the Pinnacle pencil-beam algorithm was not sufficient to predict the eyelid dose on the tungsten shield, and more accurate algorithms like MC should be considered for a treatment plan. PMID:22915776

SU-F-T-329: Characteristic Study of a Rado-Photoluminescenct Glass Dosimeter with Accumulated Dose

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

Kim, D; Chung, W; Chung, M

Purpose: This study investigated the effect of accumulated dose on radiophotoluminescent glass dosimeter in megavoltage photon. Methods: 45 commercially-available radio-photoluminescence glass dosimeters (RPLGD; GD-302M, Asahi Techno Glass Co., Shizuoka, JAPAN) were irradiated to 10 × 10 cm{sup 2} open-field with 6, 10 and 15 MV photon beams at 100 cm of source to surface distance and dose maximum depths. Each energy has consists of five groups which is consists of three detectors. A group #1 and #2 was irradiated about 1 Gy to 100 Gy, and estimated the integral dose response with and without annealing procedure. A group #3 wasmore » read the dose after irradiated 10 Gy of dose by 10 times repeatedly to estimate the fading effect of RPLGD. A group #4 and #5 was produced same ways with different irradiation dose such as 50 Gy for group #4 and 100 Gy for group #5. Results: From the results of group #1 and #2, an annealed detector shows linear response to integral dose but other detectors without the annealing process, has supra linearity for integral dose especially close to 100 Gy dose. For group #3, #4 and #5, the dose response of repeated irradiation, the dose response was decreased about 15%, 12% and 7% for 6 MV, 10 MV and 15MV. Conclusion: It was found that RPLGD response to accumulated dose was supra linear and this respond was altered with amount of accumulated dose to the RPLGD. In addition, the fading effect need to be concern with RPLGD.« less

Comparison of intensity-modulated radiotherapy and volumetric-modulated arc therapy dose measurement for head and neck cancer using optical stimulated luminescence dosimeter

NASA Astrophysics Data System (ADS)

Lai, Lu-Han; Chuang, Keh-Shih; Lin, Hsin-Hon; Liu, Yi-Chi; Kuo, Chiung-Wen; Lin, Jao-Perng

2017-11-01

The in-vivo dose distributions of intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT), a newly developed technique, for head and neck cancer have been investigated for several years. The present study used a head-and-neck RANDO phantom to simulate the clinical conditions of nasopharyngeal carcinoma and compare the radiation doses between VMAT and IMRT. Three types of planning target volume (PTV) profiles were targeted by reducing the PTV surface margin by 0, 3, and 5 mm. An optically stimulated luminescence dosimeter was used to measure the surface doses. The results revealed that VMAT provided on average 16.8-13.8% lower surface doses within the PTV target areas than IMRT. When the PTV margin was reduced by 0 mm, the surface doses for IMRT reached their maximum value, accounting for 75.1% of its prescribed dose (Dp); however, the Dp value of VMAT was only 61.1%. When the PTV margin was reduced by 3 or 5 mm, the surface doses decreased considerably. The observed surface doses were insufficient when the tumours invaded the body surface; however, VMAT exerted larger skin-sparing effects than IMRT when the tumours away from the skin. These results suggest that the skin doses for these two techniques are insufficient for surface tumours. Notably, VMAT can provide lower skin doses for deep tumours.

Pharmacokinetics of isotretinoin during repetitive dosing to patients.

PubMed

Brazzell, R K; Vane, F M; Ehmann, C W; Colburn, W A

1983-01-01

The multiple dose pharmacokinetics of isotretinoin and its major blood metabolite, 4-oxo-isotretinoin, were studied in 10 patients with cystic acne and 11 patients with various keratinization disorders. Blood samples were obtained at predetermined times following the first dose, interim doses and the final dose. Blood concentrations of isotretinoin and 4-oxo-isotretinoin were measured by a specific and sensitive HPLC method. A lag time was usually observed prior to the onset of absorption following oral administration of the drug in a soft elastic gelatin capsule. Absorption then proceeded rapidly and maximum blood concentrations usually occurred within 4 h of drug administration. The harmonic mean half-life for the elimination of isotretinoin by the cystic acne patients was approximately 10 h after the initial dose and did not change significantly following 25 days of 40 mg b.i.d. dosing. Steady-state blood concentrations remained relatively constant after the fifth day of dosing. The harmonic mean elimination half-life in the patients with various disorders of keratinization was about 16 h. The results of the 2 studies suggest that no significant changes in the pharmacokinetics of isotretinoin occur during multiple dosing and that the multiple dose pharmacokinetic profile is predictable and can be described using a linear pharmacokinetic model. This suggests that the steady-state concentrations of isotretinoin can be predicted from single dose data.

Equivalent dose and effective dose from stray radiation during passively scattered proton radiotherapy for prostate cancer

NASA Astrophysics Data System (ADS)

Fontenot, Jonas; Taddei, Phillip; Zheng, Yuanshui; Mirkovic, Dragan; Jordan, Thomas; Newhauser, Wayne

2008-03-01

Proton therapy reduces the integral therapeutic dose required for local control in prostate patients compared to intensity-modulated radiotherapy. One proposed benefit of this reduction is an associated decrease in the incidence of radiogenic secondary cancers. However, patients are also exposed to stray radiation during the course of treatment. The purpose of this study was to quantify the stray radiation dose received by patients during proton therapy for prostate cancer. Using a Monte Carlo model of a proton therapy nozzle and a computerized anthropomorphic phantom, we determined that the effective dose from stray radiation per therapeutic dose (E/D) for a typical prostate patient was approximately 5.5 mSv Gy-1. Sensitivity analysis revealed that E/D varied by ±30% over the interval of treatment parameter values used for proton therapy of the prostate. Equivalent doses per therapeutic dose (HT/D) in specific organs at risk were found to decrease with distance from the isocenter, with a maximum of 12 mSv Gy-1 in the organ closest to the treatment volume (bladder) and 1.9 mSv Gy-1 in the furthest (esophagus). Neutrons created in the nozzle predominated effective dose, though neutrons created in the patient contributed substantially to the equivalent dose in organs near the proton field. Photons contributed less than 15% to equivalent doses.

Spline-based procedures for dose-finding studies with active control

PubMed Central

Helms, Hans-Joachim; Benda, Norbert; Zinserling, Jörg; Kneib, Thomas; Friede, Tim

2015-01-01

In a dose-finding study with an active control, several doses of a new drug are compared with an established drug (the so-called active control). One goal of such studies is to characterize the dose–response relationship and to find the smallest target dose concentration d*, which leads to the same efficacy as the active control. For this purpose, the intersection point of the mean dose–response function with the expected efficacy of the active control has to be estimated. The focus of this paper is a cubic spline-based method for deriving an estimator of the target dose without assuming a specific dose–response function. Furthermore, the construction of a spline-based bootstrap CI is described. Estimator and CI are compared with other flexible and parametric methods such as linear spline interpolation as well as maximum likelihood regression in simulation studies motivated by a real clinical trial. Also, design considerations for the cubic spline approach with focus on bias minimization are presented. Although the spline-based point estimator can be biased, designs can be chosen to minimize and reasonably limit the maximum absolute bias. Furthermore, the coverage probability of the cubic spline approach is satisfactory, especially for bias minimal designs. © 2014 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd. PMID:25319931

Pharmacokinetics of terbinafine after oral administration of a single dose to Hispaniolan Amazon parrots (Amazona ventralis).

PubMed

Evans, Erika E; Emery, Lee C; Cox, Sherry K; Souza, Marcy J

2013-06-01

To determine pharmacokinetics after oral administration of a single dose of terbinafine hydrochloride to Hispaniolan Amazon parrots (Amazona ventralis). 6 healthy adult Hispaniolan Amazon parrots. A single dose of terbinafine hydrochloride (60 mg/kg) was administered orally to each bird, which was followed immediately by administration of a commercially available gavage feeding formula. Blood samples were collected at the time of drug administration (time 0) and 0.25, 0.5, 1, 2, 4, 8, 12, and 24 hours after drug administration. Plasma concentrations of terbinafine were determined via high-performance liquid chromatography. Data from 1 bird were discarded because of a possible error in the dose of drug administered. After oral administration of terbinafine, the maximum concentration for the remaining 5 fed birds ranged from 109 to 671 ng/mL, half-life ranged from 6 to 13.5 hours, and time to the maximum concentration ranged from 2 to 8 hours. No adverse effects were observed. Analysis of the results indicated that oral administration of terbinafine at a dose of 60 mg/kg to Amazon parrots did not result in adverse effects and may be potentially of use in the treatment of aspergillosis. Additional studies are needed to determine treatment efficacy and safety.

Assessment of radiation exposure from cesium-137 contaminated roads for epidemiological studies in Seoul, Korea

PubMed Central

Lee, Yun-Keun; Ju, Young-Su; Lee, Won Jin; Hwang, Seung Sik; Yim, Sang-Hyuk; Yoo, Sang-Chul; Lee, Jieon; Choi, Kyung-Hwa; Burm, Eunae; Ha, Mina

2015-01-01

Objectives We aimed to assess the radiation exposure for epidemiologic investigation in residents exposed to radiation from roads that were accidentally found to be contaminated with radioactive cesium-137 (137Cs) in Seoul. Methods Using information regarding the frequency and duration of passing via the 137Cs contaminated roads or residing/working near the roads from the questionnaires that were obtained from 8875 residents and the measured radiation doses reported by the Nuclear Safety and Security Commission, we calculated the total cumulative dose of radiation exposure for each person. Results Sixty-three percent of the residents who responded to the questionnaire were considered as ever-exposed and 1% of them had a total cumulative dose of more than 10 mSv. The mean (minimum, maximum) duration of radiation exposure was 4.75 years (0.08, 11.98) and the geometric mean (minimum, maximum) of the total cumulative dose was 0.049 mSv (<0.001, 35.35) in the exposed. Conclusions An individual exposure assessment was performed for an epidemiological study to estimate the health risk among residents living in the vicinity of 137Cs contaminated roads. The average exposure dose in the exposed people was less than 5% of the current guideline. PMID:26184047

Conditioning of the 4 Curies Radium-226 Sealed Radiation Source in Thailand

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

Punnachaiya, M.; Sawangsri, T.; Wanabongse, P.

This paper describes the conditioning of the 4 curies Radium-226 (Ra-226) sealed radiation source using as a teletherapy unit for cancer treatment in Thailand. The conditioning was under the International Atomic Energy Agency (IAEA) supervision and budgetary supports, comprised of 6 operational steps: the surface dose rate and actual dimension of radium unit measurements, the appropriate lead shielding design with IAEA approval, confirmation of radioactive contamination before conditioning (smear test and radon gas leakage test), transfer of radium source unit into the designed shielding, confirmation of radioactive contamination and dose rate measurement after conditioning, and transportation of Ra-226 conditioning wastemore » package to OAP interim waste storage. The Ra-226 unit was taken out of OAP temporary waste storage for the surface dose rate and the actual dimension measurements behind the 12 inches thick heavy concrete shielding. The maximum measured surface dose rate was 70 R/hr. The special lead container was designed according to its surface dose rate along the source unit which the maximum permissible dose limit for surface dose rate of waste package after conditioning at 2 mSv/hr was applied. The IAEA approved container had total weight of 2.4 ton. After the confirmation of radioactive contamination, Ra-226 source unit was transferred and loaded in the designed lead shielding within 2 minutes. The results of smear test before and after conditioning including radon gas leakage test revealed that there was no radioactive contamination. After conditioning, the surface dose rate measured on the top, bottom were 15,10 mR/hr and varied from 6 - 50 mR/hr around lead container. The Ra-226 conditioning waste package was safely transported to store in OAP interim waste storage. Total working time including the time consumed for radon gas leakage test was 3.5 hours. The total radiation dose received by 16 operators, were ranged from 1 - 69.84 {mu}Sv and the operational team completed the conditioning safely within the effective dose limit for occupational exposure of 50 mSv/year (200 {mu}Sv/day). (authors)« less

SU-E-T-629: Feasibility Study of Treating Multiple Brain Tumors with Large Number of Noncoplanar IMRT Beams

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

Dong, P; Ma, L

Purpose: To study the feasibility of treating multiple brain tumors withlarge number of noncoplanar IMRT beams. Methods: Thirty beams are selected from 390 deliverable beams separated by six degree in 4pi space. Beam selection optimization is based on a column generation algorithm. MLC leaf size is 2 mm. Dose matrices are calculated with collapsed cone convolution and superposition method in a 2 mm by 2mm by 2 mm grid. Twelve brain tumors of various shapes, sizes and locations are used to generate four plans treating 3, 6, 9 and 12 tumors. The radiation dose was 20 Gy prescribed to themore » 100% isodose line. Dose Volume Histograms for tumor and brain were compared. Results: All results are based on a 2 mm by 2 mm by 2 mm CT grid. For 3, 6, 9 and 12 tumor plans, minimum tumor doses are all 20 Gy. Mean tumor dose are 20.0, 20.1, 20.1 and 20.1 Gy. Maximum tumor dose are 23.3, 23.6, 25.4 and 25.4 Gy. Mean ventricles dose are 0.7, 1.7, 2.4 and 3.1 Gy.Mean subventricular zone dose are 0.8, 1.3, 2.2 and 3.2 Gy. Average Equivalent uniform dose (gEUD) values for tumor are 20.1, 20.1, 20.2 and 20.2 Gy. The conformity index (CI) values are close to 1 for all 4 plans. The gradient index (GI) values are 2.50, 2.05, 2.09 and 2.19. Conclusion: Compared with published Gamma Knife treatment studies, noncoplanar IMRT treatment plan is superior in terms of dose conformity. Due to maximum limit of beams per plan, Gamma knife has to treat multiple tumors separately in different plans. Noncoplanar IMRT plans theoretically can be delivered in a single plan on any modern linac with an automated couch and image guidance. This warrants further study of using noncoplanar IMRT as a viable treatment solution for multiple brain tumors.« less

Pupillography as a sensitive, noninvasive biomarker in healthy volunteers: first-in-man study of BAY 63-9044, a new 5-HT1A-receptor agonist with dopamine agonistic properties.

PubMed

Wensing, Georg; Haase, Claus; Brendel, Erich; Böttcher, Michael Friedrich

2007-12-01

BAY 63-9044 is a new full 5-HT(1A)-agonist with functional dopamine agonist properties aimed for the treatment of Parkinson's disease. This first-in-man study investigated the pharmacodynamics, safety and tolerability as well as the pharmacokinetics of BAY 63-9044 in a randomized, single-blind, placebo-controlled group-comparison dose escalation study. 45 healthy men received BAY 63-9044 as an oral solution in single doses of 0.25 mg, 0.5 mg, 1.2 mg, 2.5 mg and 5.0 mg. Pupil reaction (baseline pupil diameter (DIAM), constriction amplitude (CA)), body temperature, electroencephalography (EEG) and prolactin, cortisol and adrenocorticotrophic hormone (ACTH) served as pharmacodynamic measures and were monitored up to 24 h after drug intake. Safety, tolerability and plasma samples for determination of BAY 63-9044 were followed up to 72 h. Up to a dose of 2.5 mg, BAY 63-9044 was safe and well tolerated. Dose-limiting adverse events (nausea, vomiting, and dizziness) occurred in 5 out of 6 volunteers at the 5 mg dose. Adverse events resolved spontaneously in all but one volunteers who was treated with an antihistaminergic for vomiting. Dose-dependent changes of DIAM and CA were observed at doses higher than 0.5 mg and 1.2 mg, respectively. Body temperature showed a trend for reduction starting at C(max) in the highest two doses only. No clear effect was found on prolactin, cortisol and ACTH levels. The pharmacokinetics of BAY 63-9044 showed a dose-dependent increase with maximum plasma concentrations reached within 1 h. Plasma concentrations declined in a bi-phased manner with an apparent terminal half-life of 5.2-8.1 h. Up to the maximum tolerated dose (MTD) of 2.5 mg BAY 63-9044 was safe and well tolerated and showed predictable linear pharmacokinetics. Pupil reaction may serve as a non-invasive biomarker for pharmacodynamic effects of 5-HT(1A)-compounds with DIAM being the most sensitive parameter.

Spinal Cord Tolerance to Single-Fraction Partial-Volume Irradiation: A Swine Model

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

Medin, Paul M., E-mail: Paul.medin@utsouthwestern.ed; Foster, Ryan D.; Kogel, Albert J. van der

2011-01-01

Purpose: To determine the spinal cord tolerance to single-fraction, partial-volume irradiation in swine. Methods and Materials: A 5-cm-long cervical segment was irradiated in 38-47-week-old Yucatan minipigs using a dedicated, image-guided radiosurgery linear accelerator. The radiation was delivered to a cylindrical volume approximately 5 cm in length and 2 cm in diameter that was positioned lateral to the cervical spinal cord, resulting in a dose distribution with the 90%, 50%, and 10% isodose lines traversing the ipsilateral, central, and contralateral spinal cord, respectively. The dose was prescribed to the 90% isodose line. A total of 26 pigs were stratified into eightmore » dose groups of 12-47 Gy. The mean maximum spinal cord dose was 16.9 {+-} 0.1, 18.9 {+-} 0.1, 21.0 {+-} 0.1, 23.0 {+-} 0.2, and 25.3 {+-} 0.3 Gy in the 16-, 18-, 20-, 22-, and 24-Gy dose groups, respectively. The mean percentage of spinal cord volumes receiving {>=}10 Gy for the same groups were 43% {+-} 3%, 48% {+-} 4%, 51% {+-} 2%, 57% {+-} 2%, and 59% {+-} 4%. The study endpoint was motor neurologic deficit determined by a change in gait during a 1-year follow-up period. Results: A steep dose-response curve was observed with a median effective dose for the maximum dose point of 20.0 Gy (95% confidence interval, 18.3-21.7). Excellent agreement was observed between the occurrence of neurologic change and the presence of histologic change. All the minipigs with motor deficits showed some degree of demyelination and focal white matter necrosis on the irradiated side, with relative sparing of the gray matter. The histologic findings were unremarkable in the minipigs with normal neurologic status. Conclusions: Our results have indicated that for a dose distribution with a steep lateral gradient, the pigs had a lower median effective dose for paralysis than has been observed in rats and more closely resembles that for rats, mice, and guinea pigs receiving uniform spinal cord irradiation.« less

SU-D-BRB-02: Combining a Commercial Autoplanning Engine with Database Dose Predictions to Further Improve Plan Quality

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

Robertson, SP; Moore, JA; Hui, X

Purpose: Database dose predictions and a commercial autoplanning engine both improve treatment plan quality in different but complimentary ways. The combination of these planning techniques is hypothesized to further improve plan quality. Methods: Four treatment plans were generated for each of 10 head and neck (HN) and 10 prostate cancer patients, including Plan-A: traditional IMRT optimization using clinically relevant default objectives; Plan-B: traditional IMRT optimization using database dose predictions; Plan-C: autoplanning using default objectives; and Plan-D: autoplanning using database dose predictions. One optimization was used for each planning method. Dose distributions were normalized to 95% of the planning target volumemore » (prostate: 8000 cGy; HN: 7000 cGy). Objectives used in plan optimization and analysis were the larynx (25%, 50%, 90%), left and right parotid glands (50%, 85%), spinal cord (0%, 50%), rectum and bladder (0%, 20%, 50%, 80%), and left and right femoral heads (0%, 70%). Results: All objectives except larynx 25% and 50% resulted in statistically significant differences between plans (Friedman’s χ{sup 2} ≥ 11.2; p ≤ 0.011). Maximum dose to the rectum (Plans A-D: 8328, 8395, 8489, 8537 cGy) and bladder (Plans A-D: 8403, 8448, 8527, 8569 cGy) were significantly increased. All other significant differences reflected a decrease in dose. Plans B-D were significantly different from Plan-A for 3, 17, and 19 objectives, respectively. Plans C-D were also significantly different from Plan-B for 8 and 13 objectives, respectively. In one case (cord 50%), Plan-D provided significantly lower dose than plan C (p = 0.003). Conclusion: Combining database dose predictions with a commercial autoplanning engine resulted in significant plan quality differences for the greatest number of objectives. This translated to plan quality improvements in most cases, although special care may be needed for maximum dose constraints. Further evaluation is warranted in a larger cohort across HN, prostate, and other treatment sites. This work is supported by Philips Radiation Oncology Systems.« less

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

Matney, Jason; Park, Peter C.; The University of Texas Graduate School of Biomedical Sciences, Houston, Texas

Purpose: To quantify and compare the effects of respiratory motion on paired passively scattered proton therapy (PSPT) and intensity modulated photon therapy (IMRT) plans; and to establish the relationship between the magnitude of tumor motion and the respiratory-induced dose difference for both modalities. Methods and Materials: In a randomized clinical trial comparing PSPT and IMRT, radiation therapy plans have been designed according to common planning protocols. Four-dimensional (4D) dose was computed for PSPT and IMRT plans for a patient cohort with respiratory motion ranging from 3 to 17 mm. Image registration and dose accumulation were performed using grayscale-based deformable imagemore » registration algorithms. The dose–volume histogram (DVH) differences (4D-3D [3D = 3-dimensional]) were compared for PSPT and IMRT. Changes in 4D-3D dose were correlated to the magnitude of tumor respiratory motion. Results: The average 4D-3D dose to 95% of the internal target volume was close to zero, with 19 of 20 patients within 1% of prescribed dose for both modalities. The mean 4D-3D between the 2 modalities was not statistically significant (P<.05) for all dose–volume histogram indices (mean ± SD) except the lung V5 (PSPT: +1.1% ± 0.9%; IMRT: +0.4% ± 1.2%) and maximum cord dose (PSPT: +1.5 ± 2.9 Gy; IMRT: 0.0 ± 0.2 Gy). Changes in 4D-3D dose were correlated to tumor motion for only 2 indices: dose to 95% planning target volume, and heterogeneity index. Conclusions: With our current margin formalisms, target coverage was maintained in the presence of respiratory motion up to 17 mm for both PSPT and IMRT. Only 2 of 11 4D-3D indices (lung V5 and spinal cord maximum) were statistically distinguishable between PSPT and IMRT, contrary to the notion that proton therapy will be more susceptible to respiratory motion. Because of the lack of strong correlations with 4D-3D dose differences in PSPT and IMRT, the extent of tumor motion was not an adequate predictor of potential dosimetric error caused by breathing motion.« less

Influence of image slice thickness on rectal dose-response relationships following radiotherapy of prostate cancer

NASA Astrophysics Data System (ADS)

Olsson, C.; Thor, M.; Liu, M.; Moissenko, V.; Petersen, S. E.; Høyer, M.; Apte, A.; Deasy, J. O.

2014-07-01

When pooling retrospective data from different cohorts, slice thicknesses of acquired computed tomography (CT) images used for treatment planning may vary between cohorts. It is, however, not known if varying slice thickness influences derived dose-response relationships. We investigated this for rectal bleeding using dose-volume histograms (DVHs) of the rectum and rectal wall for dose distributions superimposed on images with varying CT slice thicknesses. We used dose and endpoint data from two prostate cancer cohorts treated with three-dimensional conformal radiotherapy to either 74 Gy (N = 159) or 78 Gy (N = 159) at 2 Gy per fraction. The rectum was defined as the whole organ with content, and the morbidity cut-off was Grade ≥2 late rectal bleeding. Rectal walls were defined as 3 mm inner margins added to the rectum. DVHs for simulated slice thicknesses from 3 to 13 mm were compared to DVHs for the originally acquired slice thicknesses at 3 and 5 mm. Volumes, mean, and maximum doses were assessed from the DVHs, and generalized equivalent uniform dose (gEUD) values were calculated. For each organ and each of the simulated slice thicknesses, we performed predictive modeling of late rectal bleeding using the Lyman-Kutcher-Burman (LKB) model. For the most coarse slice thickness, rectal volumes increased (≤18%), whereas maximum and mean doses decreased (≤0.8 and ≤4.2 Gy, respectively). For all a values, the gEUD for the simulated DVHs were ≤1.9 Gy different than the gEUD for the original DVHs. The best-fitting LKB model parameter values with 95% CIs were consistent between all DVHs. In conclusion, we found that the investigated slice thickness variations had minimal impact on rectal dose-response estimations. From the perspective of predictive modeling, our results suggest that variations within 10 mm in slice thickness between cohorts are unlikely to be a limiting factor when pooling multi-institutional rectal dose data that include slice thickness variations within this range. Presented in part at the European Society for Therapeutic Radiotherapy and Oncology Annual Meeting, April 5-8, 2014, Vienna, Austria.

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

Vikraman, S; Ramu, M; Karrthick, Kp

Purpose: The purpose of this study was to validate the advent of COMPASS 3D dosimetry as a routine pre treatment verification tool with commercially available CMS Monaco and Oncentra Masterplan planning system. Methods: Twenty esophagus patients were selected for this study. All these patients underwent radical VMAT treatment in Elekta Linac and plans were generated in Monaco v5.0 with MonteCarlo(MC) dose calculation algorithm. COMPASS 3D dosimetry comprises an advanced dose calculation algorithm of collapsed cone convolution(CCC). To validate CCC algorithm in COMPASS, The DICOM RT Plans generated using Monaco MC algorithm were transferred to Oncentra Masterplan v4.3 TPS. Only finalmore » dose calculations were performed using CCC algorithm with out optimization in Masterplan planning system. It is proven that MC algorithm is an accurate algorithm and obvious that there will be a difference with MC and CCC algorithms. Hence CCC in COMPASS should be validated with other commercially available CCC algorithm. To use the CCC as pretreatment verification tool with reference to MC generated treatment plans, CCC in OMP and CCC in COMPASS were validated using dose volume based indices such as D98, D95 for target volumes and OAR doses. Results: The point doses for open beams were observed <1% with reference to Monaco MC algorithms. Comparisons of CCC(OMP) Vs CCC(COMPASS) showed a mean difference of 1.82%±1.12SD and 1.65%±0.67SD for D98 and D95 respectively for Target coverage. Maximum point dose of −2.15%±0.60SD difference was observed in target volume. The mean lung dose of −2.68%±1.67SD was noticed between OMP and COMPASS. The maximum point doses for spinal cord were −1.82%±0.287SD. Conclusion: In this study, the accuracy of CCC algorithm in COMPASS 3D dosimetry was validated by compared with CCC algorithm in OMP TPS. Dose calculation in COMPASS is feasible within < 2% in comparison with commercially available TPS algorithms.« less

Evaluating the efficacies of Maximum Tolerated Dose and metronomic chemotherapies: A mathematical approach

NASA Astrophysics Data System (ADS)

Guiraldello, Rafael T.; Martins, Marcelo L.; Mancera, Paulo F. A.

2016-08-01

We present a mathematical model based on partial differential equations that is applied to understand tumor development and its response to chemotherapy. Our primary aim is to evaluate comparatively the efficacies of two chemotherapeutic protocols, Maximum Tolerated Dose (MTD) and metronomic, as well as two methods of drug delivery. Concerning therapeutic outcomes, the metronomic protocol proves more effective in prolonging the patient's life than MTD. Moreover, a uniform drug delivery method combined with the metronomic protocol is the most efficient strategy to reduce tumor density.

Nanosuspension for the delivery of a poorly soluble anti-cancer kinase inhibitor.

PubMed

Danhier, Fabienne; Ucakar, Bernard; Vanderhaegen, Marie-Lyse; Brewster, Marcus E; Arien, Tina; Préat, Véronique

2014-09-01

We hypothesized that nanosuspensions could be promising for the delivery of the poorly water soluble anti-cancer multi-targeted kinase inhibitor, MTKi-327. Hence, the aims of this work were (i) to evaluate the MTKi-327 nanosuspension for parenteral and oral administrations and (ii) to compare this nanosuspension with other nanocarriers in terms of anti-cancer efficacy and pharmacokinetics. Therefore, four formulations of MTKi-327 were studied: (i) PEGylated PLGA-based nanoparticles, (ii) self-assembling PEG₇₅₀-p-(CL-co-TMC) polymeric micelles, (iii) nanosuspensions of MTKi-327; and (iv) Captisol solution (pH=3.5). All the nano-formulations presented a size below 200 nm. Injections of the highest possible dose of the three nano-formulations did not induce any side effects in mice. In contrast, the maximum tolerated dose of the control Captisol solution was 20-fold lower than its highest possible dose. The highest regrowth delay of A-431-tumor-bearing nude mice was obtained with MTKi-327 nanosuspension, administered intravenously, at a dose of 650 mg/kg. After intravenous and oral administration, the AUC₀₋∞ of MTKi-327 nanosuspension was 2.4-fold greater than that of the Captisol solution. Nanosuspension may be considered as an effective anti-cancer MTKi-327 delivery method due to (i) the higher MTKi-327 maximum tolerated dose, (ii) the possible intravenous injection of MTKi-327, (iii) its ability to enhance the administered dose and (iv) its higher efficacy. Copyright © 2014 Elsevier B.V. All rights reserved.

In Vivo Absorption and Disposition of Cefadroxil after Escalating Oral Doses in Wild-Type and PepT1 Knockout Mice

PubMed Central

Posada, Maria M.; Smith, David E.

2013-01-01

Purpose To determine the effect of PepT1 on the absorption and disposition of cefadroxil, including the potential for saturable intestinal uptake, after escalating oral doses of drug. Methods The absorption and disposition kinetics of [3H]cefadroxil was determined in wild-type and PepT1 knockout mice after 44.5, 89.1, 178, and 356 nmol/g oral doses of drug. The pharmacokinetics of [3H]cefadroxil was also determined in both genotypes after 44.5 nmol/g intravenous bolus doses. Results PepT1 deletion reduced the area under the plasma concentration-time profile (AUC0-120) of cefadroxil by 10-fold, the maximum plasma concentration (Cmax) by 17.5-fold, and increased the time to reach a maximum plasma concentration (Tmax) by 3-fold. There was no evidence of nonlinear intestinal absorption since AUC0-120 and Cmax values changed in a dose-proportional manner. Moreover, the pharmacokinetics of cefadroxil was not different between genotypes after intravenous bolus doses, indicating that PepT1 did not affect drug disposition. Finally, no differences were observed in the peripheral tissue distribution of cefadroxil (i.e., outside gastrointestinal tract) once these tissues were corrected for differences in perfusing blood concentrations. Conclusions The findings demonstrate convincingly the critical role of intestinal PepT1 in both the rate and extent of oral administration for cefadroxil and potentially other aminocephalosporin drugs. PMID:23959853

A Phase I Dose-Finding Study of Silybin Phosphatidylcholine (Milk Thistle) in Patients With Advanced Hepatocellular Carcinoma

PubMed Central

Siegel, Abby B.; Narayan, Rupa; Rodriguez, Rosa; Goyal, Abhishek; Jacobson, Judith S.; Kelly, Kara; Ladas, Elena; Lunghofer, Paul J.; Hansen, Ryan J.; Gustafson, Daniel L.; Flaig, Thomas W.; Tsai, Wei Yann; Wu, David P. H.; Lee, Valerie; Greenlee, Heather

2013-01-01

Purpose To determine the maximum tolerated dose per day of silybin phosphatidylcholine (Siliphos) in patients with advanced hepatocellular carcinoma (HCC) and hepatic dysfunction. Experimental Design Patients with advanced HCC not eligible for other therapies based on poor hepatic function were enrolled in a phase I study of silybin phosphatidylcholine. A standard phase I design was used with 4 planned cohorts, dose escalating from 2, 4, 8, to 12 g per day in divided doses for 12 weeks. Results Three participants enrolled in this single institution trial. All enrolled subjects consumed 2 g per day of study agent in divided doses. Serum concentrations of silibinin and silibinin glucuronide increased within 1 to 3 weeks. In all 3 patients, liver function abnormalities and tumor marker α-fetoprotein progressed, but after day 56 the third patient showed some improvement in liver function abnormalities and inflammatory biomarkers. All 3 participants died within 23 to 69 days of enrolling into the trial, likely from hepatic failure, but it could not be ruled out that deaths were possibly due to the study drug. Conclusion Short-term administration of silybin phosphatidylcholine in patients with advanced HCC resulted in detectable increases in silibinin and its metabolite, silibinin glucuronide. The maximum tolerated dose could not be established. Since patients died soon after enrollment, this patient population may have been too ill to benefit from an intervention designed to improve liver function tests. PMID:23757319

Engineering design constraints of the lunar surface environment

NASA Technical Reports Server (NTRS)

Morrison, D. A.

1992-01-01

Living and working on the lunar surface will be difficult. Design of habitats, machines, tools, and operational scenarios in order to allow maximum flexibility in human activity will require paying attention to certain constraints imposed by conditions at the surface and the characteristics of lunar material. Primary design drivers for habitat, crew health and safety, and crew equipment are: ionizing radiation, the meteoroid flux, and the thermal environment. Secondary constraints for engineering derive from: the physical and chemical properties of lunar surface materials, rock distributions and regolith thicknesses, topography, electromagnetic properties, and seismicity. Protection from ionizing radiation is essential for crew health and safety. The total dose acquired by a crew member will be the sum of the dose acquired during EVA time (when shielding will be least) plus the dose acquired during time spent in the habitat (when shielding will be maximum). Minimizing the dose acquired in the habitat extends the time allowable for EVA's before a dose limit is reached. Habitat shielding is enabling, and higher precision in predicting secondary fluxes produced in shielding material would be desirable. Means for minimizing dose during a solar flare event while on extended EVA will be essential. Early warning of the onset of flare activity (at least a half-hour is feasible) will dictate the time available to take mitigating steps. Warning capability affects design of rovers (or rover tools) and site layout. Uncertainty in solar flare timing is a design constraint that points to the need for quickly accessible or constructible safe havens.

Engineering design constraints of the lunar surface environment

NASA Astrophysics Data System (ADS)

Morrison, D. A.

1992-02-01

Living and working on the lunar surface will be difficult. Design of habitats, machines, tools, and operational scenarios in order to allow maximum flexibility in human activity will require paying attention to certain constraints imposed by conditions at the surface and the characteristics of lunar material. Primary design drivers for habitat, crew health and safety, and crew equipment are: ionizing radiation, the meteoroid flux, and the thermal environment. Secondary constraints for engineering derive from: the physical and chemical properties of lunar surface materials, rock distributions and regolith thicknesses, topography, electromagnetic properties, and seismicity. Protection from ionizing radiation is essential for crew health and safety. The total dose acquired by a crew member will be the sum of the dose acquired during EVA time (when shielding will be least) plus the dose acquired during time spent in the habitat (when shielding will be maximum). Minimizing the dose acquired in the habitat extends the time allowable for EVA's before a dose limit is reached. Habitat shielding is enabling, and higher precision in predicting secondary fluxes produced in shielding material would be desirable. Means for minimizing dose during a solar flare event while on extended EVA will be essential. Early warning of the onset of flare activity (at least a half-hour is feasible) will dictate the time available to take mitigating steps. Warning capability affects design of rovers (or rover tools) and site layout. Uncertainty in solar flare timing is a design constraint that points to the need for quickly accessible or constructible safe havens.

The dose-effect relationship of baclofen in alcohol dependence: A 1-year cohort study.

PubMed

Pignon, Baptiste; Labreuche, Julien; Auffret, Marine; Gautier, Sophie; Deheul, Sylvie; Simioni, Nicolas; Cottencin, Olivier; Bordet, Régis; Duhamel, Alain; Rolland, Benjamin

2017-07-01

Our aim is to study the relationship between dose of baclofen and effectiveness in alcohol dependence. Two hundred two patients with alcohol dependence, who received baclofen treatment for drinking reduction, were followed up for 1 year. For each patient-month of treatment, the maximum daily dose of baclofen (DDB) and average weekly alcohol consumption (AWAC) were calculated. We defined a favorable drinking outcome as an AWAC under 200 g/w for at least 2 consecutive months. We divided the DDB of each patient-month into 3 categories (low dose: <90 mg/d, medium dose: 90-150 mg/d, and high dose: >150 mg/d) and investigated the relationship between reaching a favorable outcome and the concurrent DDB category in a time-varying Cox regression analysis. Hazard ratios (HRs) were adjusted based on age, sex, and initial AWAC. One hundred forty subjects were followed during at least 1 month. Of these patients, 58 (41%) had a favorable drinking outcome. In comparison to low dose, medium dose was associated with a decreased rate of favorable drinking outcome (HR = 0.42; 95% CI [0.20, 0.88]), whereas no difference was found with high dose (HR = 1.31; 95% CI [0.65, 2.64]). The relationship between dose of baclofen and favorable drinking outcome was U-shaped, that is, was increased at low and high doses compared to medium doses. Copyright © 2017 John Wiley & Sons, Ltd.

Phase 1 first-in-human studies of the reactogenicity and immunogenicity of a recombinant meningococcal NspA vaccine in healthy adults.

PubMed

Halperin, Scott A; Langley, Joanne M; Smith, Bruce; Wunderli, Peter; Kaufman, Lisa; Kimura, Alan; Martin, Denis

2007-01-05

Neisserial surface protein A (NspA) is a highly conserved, surface-exposed outer membrane protein of Neisseria meningitidis that has been shown to induce a bactericidal immune response in animals against all pathogenic Neisserial serogroups. Healthy 18-50-year-old adults were assigned to receive, in a dose escalating manner, 3 doses of 1 of 5 formulations of an experimental, unfolded, recombinant NspA (rNspA) vaccine or placebo, or 1 dose of commercially available quadravalent (A, C, Y, W-135) meningococcal polysaccharide vaccine (Menomune((R))). Adverse events were collected during the first week post-immunization, prior to the next dose and 1 month after the last dose. Serum for measurement of hematological and biochemical parameters and antibodies by enzyme immunoassay and bactericidal assay were measured before the first dose, prior to the second dose and 1 month after the last dose of vaccine. The rNspA vaccine was well tolerated by recipients. Injection-site pain was reported more frequently by recipients of the three highest doses of rNspA compared to placebo but at similar rates to the licensed meningococcal polysaccharide vaccine. Adverse events were reported less frequently after subsequent doses in the three-dose series. An antibody rise measured by enzyme immunoassay was elicited with a dose-related increase that reached a maximum with the 125mug dose. Prolongation of the dosing interval between the second and third dose appeared to be associated with increased antibody levels. No bactericidal antibodies were detected after any of the rNspA formulations. The unfolded rNspA meningococcal vaccine was well tolerated and immunogenic in healthy adult volunteers but did not elicit bactericidal antibodies.

Verification of the grid size and angular increment effects in lung stereotactic body radiation therapy using the dynamic conformal arc technique

NASA Astrophysics Data System (ADS)

Park, Hae-Jin; Suh, Tae-Suk; Park, Ji-Yeon; Lee, Jeong-Woo; Kim, Mi-Hwa; Oh, Young-Taek; Chun, Mison; Noh, O. Kyu; Suh, Susie

2013-06-01

The dosimetric effects of variable grid size and angular increment were systematically evaluated in the measured dose distributions of dynamic conformal arc therapy (DCAT) for lung stereotactic body radiation therapy (SBRT). Dose variations with different grid sizes (2, 3, and 4 mm) and angular increments (2, 4, 6, and 10°) for spherical planning target volumes (PTVs) were verified in a thorax phantom by using EBT2 films. Although the doses for identical PTVs were predicted for the different grid sizes, the dose discrepancy was evaluated using one measured dose distribution with the gamma tool because the beam was delivered in the same set-up for DCAT. The dosimetric effect of the angular increment was verified by comparing the measured dose area histograms of organs at risk (OARs) at each angular increment. When the difference in the OAR doses is higher than the uncertainty of the film dosimetry, the error is regarded as the angular increment effect in discretely calculated doses. In the results, even when a 2-mm grid size was used with an elaborate dose calculation, 4-mm grid size led to a higher gamma pass ratio due to underdosage, a steep-dose descent gradient, and lower estimated PTV doses caused by the smoothing effect in the calculated dose distribution. An undulating dose distribution and a difference in the maximum contralateral lung dose of up to 14% were observed in dose calculation using a 10° angular increment. The DCAT can be effectively applied for an approximately spherical PTV in a relatively uniform geometry, which is less affected by inhomogeneous materials and differences in the beam path length.

RadNuc: A graphical user interface to deliver dose rate patterns encountered in nuclear medicine with a 137Cs irradiator

PubMed Central

Pasternack, Jordan B.; Howell, Roger W.

2012-01-01

The temporal variations in absorbed dose rates to organs and tissues in the body are very large in diagnostic and therapeutic nuclear medicine. The response of biological endpoints of relevance to radiation safety and therapeutic efficacy are generally modulated by dose rate. Therefore, it is important to understand how the complex dose rate patterns encountered in nuclear medicine impact relevant biological responses. Accordingly, a graphical user interface (GUI) was created to control a cesium-137 irradiator to deliver such dose rate patterns. Methods Visual Basic 6.0 was used to create a user-friendly GUI to control the dose rate by varying the thickness of a mercury attenuator. The GUI facilitates the delivery of a number of dose rate patterns including constant, exponential increase or decrease, and multi-component exponential. Extensive visual feedback is provided by the GUI during both the planning and delivery stages. Results The GUI controlled irradiator can achieve a maximum dose rate of 40 cGy/hr and a minimum dose rate of 0.01 cGy/hr. Addition of machined lead blocks can be used to further reduce the minimum dose rate to 0.0001 cGy/hr. Measured dose rate patterns differed from programmed dose rate patterns in total dose by 3.2% to 8.4%. Conclusion The GUI controlled irradiator is able to accurately create dose rate patterns encountered in nuclear medicine and other related fields. This makes it an invaluable tool for studying the effects of chronic constant and variable low dose rates on biological tissues in the contexts of both radiation protection and clinical administration of internal radionuclides. PMID:23265668

RadNuc: a graphical user interface to deliver dose rate patterns encountered in nuclear medicine with a 137Cs irradiator.

PubMed

Pasternack, Jordan B; Howell, Roger W

2013-02-01

The temporal variations in absorbed dose rates to organs and tissues in the body are very large in diagnostic and therapeutic nuclear medicine. The response of biological endpoints of relevance to radiation safety and therapeutic efficacy is generally modulated by dose rate. Therefore, it is important to understand how the complex dose rate patterns encountered in nuclear medicine impact relevant biological responses. Accordingly, a graphical user interface (GUI) was created to control a cesium-137 irradiator to deliver such dose rate patterns. Visual Basic 6.0 was used to create a user-friendly GUI to control the dose rate by varying the thickness of a mercury attenuator. The GUI facilitates the delivery of a number of dose rate patterns including constant, exponential increase or decrease, and multi-component exponential. Extensive visual feedback is provided by the GUI during both the planning and delivery stages. The GUI controlled irradiator can achieve a maximum dose rate of 40 cGy/h and a minimum dose rate of 0.01 cGy/h. Addition of machined lead blocks can be used to further reduce the minimum dose rate to 0.0001 cGy/h. Measured dose rate patterns differed from programmed dose rate patterns in total dose by 3.2% to 8.4%. The GUI controlled irradiator is able to accurately create dose rate patterns encountered in nuclear medicine and other related fields. This makes it an invaluable tool for studying the effects of chronic constant and variable low dose rates on biological tissues in the contexts of both radiation protection and clinical administration of internal radionuclides. Copyright © 2013 Elsevier Inc. All rights reserved.

Targeting MRS-Defined Dominant Intraprostatic Lesions with Inverse-Planned High Dose Rate Brachytherapy

DTIC Science & Technology

2007-02-01

bladder and the rectum are overprotected while the PTV coverage is undesirably reduced. On the other hand, if their maximum dose is increased and/or...B, the bladder and rectum were overprotected with undesirably low PTV coverage (84.54%). The reduction of their weighting factor increased PTV

75 FR 61226 - Exemption; Entergy Operations, Inc.; Arkansas Nuclear One, Units 1 and 2

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-04

... maximum potential annual radiation doses to the public resulting from effluent releases. The report must... radiation doses to the public resulting from effluent releases. This exemption does not affect the... submitted. Based on the above, no new accident precursors are created by extending the submittal date for...

Estimation of maximum tolerated dose for long-term bioassays from acute lethal dose and structure by QSAR

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

Gombar, V.K.; Enslein, K.; Hart, J.B.

1991-09-01

A quantitative structure-activity relationship (QSAR) model has been developed to estimate maximum tolerated doses (MTD) from structural features of chemicals and the corresponding oral acute lethal doses (LD50) as determined in male rats. The model is based on a set of 269 diverse chemicals which have been tested under the National Cancer Institute/National Toxicology Program (NCI/NTP) protocols. The rat oral LD50 value was the strongest predictor. Additionally, 22 structural descriptors comprising nine substructural MOLSTAC(c) keys, three molecular connectivity indices, and sigma charges on 10 molecular fragments were identified as endpoint predictors. The model explains 76% of the variance and ismore » significant (F = 35.7) at p less than 0.0001 with a standard error of the estimate of 0.40 in the log (1/mol) units used in Hansch-type equations. Cross-validation showed that the difference between the average deleted residual square (0.179) and the model residual square (0.160) was not significant (t = 0.98).« less

SU-E-T-503: Intensity Modulated Proton Therapy (IMPT) Versus Intensity Modulated X-Ray Therapy (IMRT) for Patient with Hepatocellular Carcinoma: A Dosimetric Comparison

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

Singh, H; Zhao, L; Prabhu, K

2015-06-15

Purpose This study compares the dosimetric parameters in treatment of unresectable hepatocellular carcinoma between intensity modulated proton therapy (IMPT) and intensity modulated x-ray radiation therapy (IMRT). Methods and Materials: We studied four patients treated at our institution. All patients were simulated supine with 4D-CT using a GE light speed simulator with a maximum slice thickness of 3mm. The average CT and an internal target volume to account for respiration motion were used for planning. Both IMRT and IMPT plans were created using Elekta’s CMSXiO treatment planning system (TPS). The prescription dose was 58.05 CGE in 15 fractions. The IMRT plansmore » had five beams with combination of co-planar and non-co-planar. The IMPT plans had 2 to 3 beams. Dose comparison was performed based on the averaged results of the four patients. Results The mean dose and V95% to PTV were 58.24CGE, 98.57% for IMPT, versus 57.34CGE and 96.68% for IMRT, respectively. The V10, V20, V30 and mean dose of the normal liver for IMPT were 23.10%, 18.61%, 13.75% and 9.78 CGE; and 47.19%, 37.55%, 22.73% and 17.12CGE for IMRT. The spinal cord didn’t receive any dose in IMPT technique, but received a maximum of 18.77CGE for IMRT. The IMPT gave lower maximum dose to the stomach as compared to IMRT (19.26 vs 26.35CGE). V14 for left and right kidney was 0% and 2.32% for IMPT and 3.89% and 29.54% for IMRT. The mean dose, V35, V40 and V45 for small bowl were similar in both techniques, 0.74CGE, 6.27cc, 4.85cc and 3.53 cc for IMPT, 3.47CGE, 9.73cc, 7.61cc 5.35cc for IMRT. Conclusion Based on this study, IMPT plans gave less dose to the critical structures such as normal liver, kidney, stomach and spinal cord as compared to IMRT plans, potentially leading to less toxicity and providing better quality of life for patients.« less

SU-E-T-624: Quantitative Evaluation of 2D Versus 3D Dosimetry for Stereotactic Volumetric Modulated Arc Delivery Using COMPASS

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

Vikraman, S; Karrthick, K; Rajesh, T

2014-06-15

Purpose: The purpose of this study was to evaluate quantitatively 2D versus 3D dosimetry for stereotactic volumetric modulated arc delivery using COMPASS with 2D array. Methods: Twenty-five patients CT images and RT structures of different sites like brain, head and neck, thorax, abdomen and spine were taken from Multiplan planning system for this study. All these patients underwent radical stereotactic treatment in Cyberknife. For each patient, linac based VMAT stereotactic plans were generated in Monaco TPS v 3.1 using Elekta Beam Modulator MLC. Dose prescription was in the range of 5-20Gy/fraction.TPS calculated VMAT plan delivery accuracy was quantitatively evaluated withmore » COMPASS measured dose and calculated dose based on DVH metrics. In order to ascertain the potential of COMPASS 3D dosimetry for stereotactic plan delivery, 2D fluence verification was performed with MatriXX using Multicube. Results: For each site, D{sub 9} {sub 5} was achieved with 100% of prescription dose with maximum 0.05SD. Conformity index (CI) was observed closer to 1.15 in all cases. Maximum deviation of 2.62 % was observed for D{sub 9} {sub 5} when compared TPS versus COMPASS measured. Considerable deviations were observed in head and neck cases compare to other sites. The maximum mean and standard deviation for D{sub 9} {sub 5}, average target dose and average gamma were -0.78±1.72, -1.10±1.373 and 0.39±0.086 respectively. Numbers of pixels passing 2D fluence verification were observed as a mean of 99.36% ±0.455 SD with 3% dose difference and 3mm DTA. For critical organs in head and neck cases, significant dose differences were observed in 3D dosimetry while the target doses were matched well within limit in both 2D and 3D dosimetry. Conclusion: The quantitative evaluations of 2D versus 3D dosimetry for stereotactic volumetric modulated plans showed the potential of highlighting the delivery errors. This study reveals that COMPASS 3D dosimetry is an effective tool for patient specific quality assurance compared to 2D fluence verification.« less

SU-E-T-87: Comparison Study of Dose Reconstruction From Cylindrical Diode Array Measurements, with TLD Measurements and Treatment Planning System Calculations in Anthropomorphic Head and Neck and Lung Phantoms

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

Benhabib, S; Cardan, R; Huang, M

Purpose: To assess dose calculated by the 3DVH software (Sun Nuclear Systems, Melbourne, FL) against TLD measurements and treatment planning system calculations in anthropomorphic phantoms. Methods: The IROC Houston (RPC) head and neck (HN) and lung phantoms were scanned and plans were generated using Eclipse (Varian Medical Systems, Milpitas, CA) following IROC Houston procedures. For the H and N phantom, 6 MV VMAT and 9-field dynamic MLC (DMLC) plans were created. For the lung phantom 6 MV VMAT and 15 MV 9-field dynamic MLC (DMLC) plans were created. The plans were delivered to the phantoms and to an ArcCHECK (Sunmore » Nuclear Systems, Melbourne, FL). The head and neck phantom contained 8 TLDs located at PTV1 (4), PTV2 (2), and OAR Cord (2). The lung phantom contained 4 TLDs, 2 in the PTV, 1 in the cord, and 1 in the heart. Daily outputs were recorded before each measurement for correction. 3DVH dose reconstruction software was used to project the calculated dose to patient anatomy. Results: For the HN phantom, the maximum difference between 3DVH and TLDs was -3.4% and between 3DVH and Eclipse was 1.2%. For the lung plan the maximum difference between 3DVH and TLDs was 4.3%, except for the spinal cord for which 3DVH overestimated the TLD dose by 12%. The maximum difference between 3DVH and Eclipse was 0.3%. 3DVH agreed well with Eclipse because the dose reconstruction algorithm uses the diode measurements to perturb the dose calculated by the treatment planning system; therefore, if there is a problem in the modeling or heterogeneity correction, it will be carried through to 3DVH. Conclusion: 3DVH agreed well with Eclipse and TLD measurements. Comparison of 3DVH with film measurements is ongoing. Work supported by PHS grant CA10953 and CA81647 (NCI, DHHS)« less

SU-E-T-505: Inter-Comparison of Clinical Plans Created On Truebeam with Trilogy and Clinac

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

Sharma, M; Wu, Y; Kim, S

2015-06-15

Purpose The purpose of this study is to investigate the dosimetric differences in clinical treatment plans when machine parameters are switched from Varian Truebeam to older Varian models and vice-versa. This is used to determine the clinically-safe limits to directly transfer patients from Truebeam to Trilogy or Clinac. Methods Thirty-two patients with cancer of different treatment sites such as lung, head-and-neck, prostate and breast were studied. The clinically approved IMRT, VMAT or 3D conformal treatment plans were delivered either on Truebeam or Clinac/Trilogy. Keeping the monitor units, fraction size and other machine parameters the same, the plans were recomputed onmore » a different Varian linear accelerator (e.g., Truebeam plans were recomputed on Trilogy and vice-versa). The plans comparison was done using the target D98 and normal organ D2, D10, D20, D30, D50 and D70 dose metrics. Results The perfraction dose-difference in the PTV-D98 for all 32 patients varied from 0.01 to −0.06 Gy with median being −0.04 Gy. For a 2Gy/fraction treatment course, this would be maximum PTV-D98 dose-difference of 6 cGy/fraction or 30 cGy/5fractions. For organs-at-risks the maximum per-fraction dosedifference in D2, D5, D10, D20, D30, D50 and D70 between Truebeam and Trilogy/Clinac plans varied from 0.06 to −0.07 Gy with median being with — 0.02 Gy. The 3D-CRT plans had relatively lower dose-difference in comparison to IMRT and VMAT plans. The dose computed on Truebeam was systematically lower than the dose computed on Trilogy/ Clinac. Conclusions for conventional fractionation schedules, assuming the maximum uncertainty of <2%, it is clinically safe to switch the treatment machine for 5 fractions. For hypo-fractionated treatments with higher dose per-fraction, plans may need to be revisited before switching the linear accelerator from Truebeam to Clinac/Trilogy or vice-versa.« less

SU-F-J-63: Abdominal Diameter Changes in Children During Volumetric Modulated Arc Therapy (VMAT): Is Re-Planning Needed?

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

Guerreiro, F; Janssens, G; Seravalli, E

Purpose: To investigate the dosimetric impact of daily changes in patient’s diameter, due to weight gain/loss and air in the bowel, based on CBCT information during radiotherapy treatment of pediatric abdominal tumors. Methods: 10 pediatric patients with neuroblastoma (n=6) and Wilms’ (n=4) tumors were included. Available CBCTs were affinely registered to the planning CT for daily set-up variations corrections. A density override approach assigning air-density to the random air pockets and water-density to the remaining anatomy was used to determine the CBCT and CT dose. Clinical VMAT plans, with a PTV prescribed dose ranging between (14.4- 36) Gy, were re-optimizedmore » on the density override CT and re-calculated on each CBCT. Dose-volume statistics of the PTV and kidneys, delineated on each CBCT, were used to compare the daily and cumulative CBCT dose with the reference CT dose. Results: The average patient diameter variation was (0.5 ± 0.7) cm (maximum daily difference of 2.3 cm). The average PTV mean dose difference (MDD) between the CT and the cumulative CBCT plans was (0.1 ± 1.1) % (maximum daily MDD of 2%). A reduction in target coverage up to 3% and 7% was observed for the cumulative and daily CBCT plans, respectively. The average kidneys’ cumulative MDD was (−2.7 ± 3.6) % (maximum daily MDD of −12%), corresponding to an overdosage. Conclusion: Due to patient’s diameter changes, a target underdosage was assessed. Given the high local tumor control of neuroblastoma and Wilms’ diseases, the need of re-planning might be discarded. However, the assessed kidneys overdosage could represent a problem when the normal tissue tolerance is reached. The necessity of re-planning should then be considered to reduce the risk of long-term renal complications. Due to the poor softtissue contrast on CBCT, MRI-guidance is required to obtain a better assessment of the accumulated dose on the remaining OARs.« less

Effect of oral administration of bark extracts of Pterocarpus santalinus L. on blood glucose level in experimental animals.

PubMed

Kameswara Rao, B; Giri, R; Kesavulu, M M; Apparao, C

2001-01-01

The effect of administration of different doses of Pterocarpus santalinus L. bark extracts in normal and diabetic rats, on blood glucose levels was evaluated in this study. Among the three fractions (aqueous, ethanol and hexane), ethanolic fraction at the dose of 0.25 g/kg body weight showed maximum antihyperglycemic activity. The same dose did not cause any hypoglycemic activity in normal rats. The results were compared with the diabetic rats treated with glibenclamide and the antihyperglycemic activity of ethanolic extract of PS bark at the dose of 0.25 g/kg b.w. was found to be more effective than that of glibenclamide.

SU-E-J-66: Significant Anatomical and Dosimetric Changes Observed with the Pharyngeal Constrictor During Head and Neck Radiotherapy Elicited From Daily Deformable Image Registration and Dose Accumulation

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

Kumarasiri, A; Siddiqui, F; Liu, C

2015-06-15

Purpose: To evaluate the anatomical changes and associated dosimetric consequences to the pharyngeal constrictor (PC) that occurs during head and neck radiotherapy (H&N RT). Methods: A cohort of 13 oro-pharyngeal cancer patients, who had daily CBCT’s for localization, was retrospectively studied. On every 5th CBCT, PC was manually delineated by a radiation oncologist. The anterior-posterior PC thickness was measured at the C3 level. Delivered dose to PC was estimated by calculating daily doses on CBCT’s, and accumulating to corresponding planning CT images. For accumulation, a parameter-optimized B- spline-based deformable image registration algorithm (Elastix) was used, in conjunction with an energy-massmore » mapping dose transfer algorithm. Mean and maximum dose (Dmean, Dmax) to PC was determined and compared with corresponding planned quantities. Results: The mean (±standard deviation) volume increase (ΔV) and thickness increase (Δt) over the course of 35 total fractions were 54±33% (11.9±7.6 cc), and 63±39% (2.9±1.9 mm), respectively. The resultant cumulative mean dose increase from planned dose to PC (ΔDmean) was 1.4±1.3% (0.9±0.8 Gy), while the maximum dose increase (ΔDmax) was 0.0±1.6% (0.0±1.1 Gy). Patients with adaptive replanning (n=6) showed a smaller mean dose increase than those without (n=7); 0.5±0.2% (0.3±0.1 Gy) vs. 2.2±1.4% (1.4±0.9 Gy). There was a statistically significant (p<0.0001) strong correlation between ΔDmean and Δt (Pearson coefficient r=0.78), and a moderate-to-strong correlation (r=0.52) between ΔDmean and ΔV. Correlation between ΔDmean and weight loss ΔW (r=0.1), as well as ΔV and ΔW (r=0.2) were negligible. Conclusion: Patients were found to undergo considerable anatomical changes to pharyngeal constrictor during H&N RT, resulting in non-negligible dose deviations from intended dose. Results are indicative that pharyngeal constrictor thickness, measured at C3 level, is a good predictor for the dose change to the organ. Daily deformable registration and dose accumulation provide a reliable means to assess important anatomical and dosimetric changes to pharyngeal constrictor occurring during treatment. This work was supported in part by a research grant from Varian Medical Systems, Palo Alto, CA.« less

Applications of tissue heterogeneity corrections and biologically effective dose volume histograms in assessing the doses for accelerated partial breast irradiation using an electronic brachytherapy source.

PubMed

Shi, Chengyu; Guo, Bingqi; Cheng, Chih-Yao; Eng, Tony; Papanikolaou, Nikos

2010-09-21

A low-energy electronic brachytherapy source (EBS), the model S700 Axxent x-ray device developed by Xoft Inc., has been used in high dose rate (HDR) intracavitary accelerated partial breast irradiation (APBI) as an alternative to an Ir-192 source. The prescription dose and delivery schema of the electronic brachytherapy APBI plan are the same as the Ir-192 plan. However, due to its lower mean energy than the Ir-192 source, an EBS plan has dosimetric and biological features different from an Ir-192 source plan. Current brachytherapy treatment planning methods may have large errors in treatment outcome prediction for an EBS plan. Two main factors contribute to the errors: the dosimetric influence of tissue heterogeneities and the enhancement of relative biological effectiveness (RBE) of electronic brachytherapy. This study quantified the effects of these two factors and revisited the plan quality of electronic brachytherapy APBI. The influence of tissue heterogeneities is studied by a Monte Carlo method and heterogeneous 'virtual patient' phantoms created from CT images and structure contours; the effect of RBE enhancement in the treatment outcome was estimated by biologically effective dose (BED) distribution. Ten electronic brachytherapy APBI cases were studied. The results showed that, for electronic brachytherapy cases, tissue heterogeneities and patient boundary effect decreased dose to the target and skin but increased dose to the bones. On average, the target dose coverage PTV V(100) reduced from 95.0% in water phantoms (planned) to only 66.7% in virtual patient phantoms (actual). The actual maximum dose to the ribs is 3.3 times higher than the planned dose; the actual mean dose to the ipsilateral breast and maximum dose to the skin were reduced by 22% and 17%, respectively. Combining the effect of tissue heterogeneities and RBE enhancement, BED coverage of the target was 89.9% in virtual patient phantoms with RBE enhancement (actual BED) as compared to 95.2% in water phantoms without RBE enhancement (planned BED). About 10% increase in the source output is required to raise BED PTV V(100) to 95%. As a conclusion, the composite effect of dose reduction in the target due to heterogeneities and RBE enhancement results in a net effect of 5.3% target BED coverage loss for electronic brachytherapy. Therefore, it is suggested that about 10% increase in the source output may be necessary to achieve sufficient target coverage higher than 95%.

Applications of tissue heterogeneity corrections and biologically effective dose volume histograms in assessing the doses for accelerated partial breast irradiation using an electronic brachytherapy source

NASA Astrophysics Data System (ADS)

Shi, Chengyu; Guo, Bingqi; Cheng, Chih-Yao; Eng, Tony; Papanikolaou, Nikos

2010-09-01

A low-energy electronic brachytherapy source (EBS), the model S700 Axxent™ x-ray device developed by Xoft Inc., has been used in high dose rate (HDR) intracavitary accelerated partial breast irradiation (APBI) as an alternative to an Ir-192 source. The prescription dose and delivery schema of the electronic brachytherapy APBI plan are the same as the Ir-192 plan. However, due to its lower mean energy than the Ir-192 source, an EBS plan has dosimetric and biological features different from an Ir-192 source plan. Current brachytherapy treatment planning methods may have large errors in treatment outcome prediction for an EBS plan. Two main factors contribute to the errors: the dosimetric influence of tissue heterogeneities and the enhancement of relative biological effectiveness (RBE) of electronic brachytherapy. This study quantified the effects of these two factors and revisited the plan quality of electronic brachytherapy APBI. The influence of tissue heterogeneities is studied by a Monte Carlo method and heterogeneous 'virtual patient' phantoms created from CT images and structure contours; the effect of RBE enhancement in the treatment outcome was estimated by biologically effective dose (BED) distribution. Ten electronic brachytherapy APBI cases were studied. The results showed that, for electronic brachytherapy cases, tissue heterogeneities and patient boundary effect decreased dose to the target and skin but increased dose to the bones. On average, the target dose coverage PTV V100 reduced from 95.0% in water phantoms (planned) to only 66.7% in virtual patient phantoms (actual). The actual maximum dose to the ribs is 3.3 times higher than the planned dose; the actual mean dose to the ipsilateral breast and maximum dose to the skin were reduced by 22% and 17%, respectively. Combining the effect of tissue heterogeneities and RBE enhancement, BED coverage of the target was 89.9% in virtual patient phantoms with RBE enhancement (actual BED) as compared to 95.2% in water phantoms without RBE enhancement (planned BED). About 10% increase in the source output is required to raise BED PTV V100 to 95%. As a conclusion, the composite effect of dose reduction in the target due to heterogeneities and RBE enhancement results in a net effect of 5.3% target BED coverage loss for electronic brachytherapy. Therefore, it is suggested that about 10% increase in the source output may be necessary to achieve sufficient target coverage higher than 95%.

Single-Dose and Multiple-Dose Pharmacokinetics of Nicotine 6 mg Gum.

PubMed

Hansson, Anna; Rasmussen, Thomas; Kraiczi, Holger

2017-04-01

Under-dosing is a recognized problem with current nicotine replacement therapy (NRT). Therefore, a new 6mg nicotine gum has been developed. To compare the nicotine uptake from the 6mg gum versus currently available NRT products, two pharmacokinetic studies were performed. In one randomized crossover study, 44 healthy adult smokers received single doses of 6, 4, and 2mg nicotine gum, and 4mg nicotine lozenge on separate occasions. In a separate randomized crossover multiple-dose study over 11 hours, 50 healthy adult smokers received one 6mg gum every hour and 90 minutes, respectively, one 4mg gum every hour, and one 4mg lozenge every hour. In both studies, blood samples were collected over 12 hours to determine single-dose and multiple-dose pharmacokinetic variables. In the single-dose study, the amount of nicotine released from the 2, 4, and 6mg gums (1.44, 3.36, and 4.94mg) as well as the resulting maximum concentration and area under the curve (5.9, 10.1, and 13.8ng/mL, and 17.1, 30.7, 46.2ng/mL × h, respectively) increased with dose. The maximum concentration and area under the curve of the 6mg gum were 44% and 30% greater, respectively, than those for 4mg lozenge. Upon hourly administration, the steady-state average plasma nicotine concentration with 6mg gum (37.4ng/mL) was significantly higher than those for 4mg lozenge (28.3ng/mL) and 4mg gum (27.1ng/mL). Nicotine delivery via the 6mg gum results in higher plasma nicotine concentrations after a single dose and at steady state than with currently available oral NRT. Under-dosing is a recognized problem with current NRT. Therefore, a new 6mg nicotine gum has been developed. Our studies show that upon single-dose and multiple-dose administration, the 6mg gum releases and delivers more nicotine to the systemic circulation than 2mg gum, 4mg gum, and 4mg lozenge. Thus, each 6mg nicotine gum provides a higher degree of nicotine substitution and/or lasts for a longer period of time than currently available nicotine gums and lozenges. © The Author 2016. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Fractionated Radioimmunotherapy With 90Y-Clivatuzumab Tetraxetan and Low-Dose Gemcitabine Is Active in Advanced Pancreatic Cancer

PubMed Central

Ocean, Allyson J.; Pennington, Kenneth L.; Guarino, Michael J.; Sheikh, Arif; Bekaii-Saab, Tanios; Serafini, Aldo N.; Lee, Daniel; Sung, Max W.; Gulec, Seza A.; Goldsmith, Stanley J.; Manzone, Timothy; Holt, Michael; O’Neil, Bert H.; Hall, Nathan; Montero, Alberto J.; Kauh, John; Gold, David V.; Horne, Heather; Wegener, William A.; Goldenberg, David M.

2014-01-01

BACKGROUND It has been demonstrated that the humanized clivatuzumab tetraxetan (hPAM4) antibody targets pancreatic ductal carcinoma selectively. After a trial of radioimmunotherapy that determined the maximum tolerated dose of single-dose yttrium-90-labeled hPAM4 (90Y-hPAM4) and produced objective responses in patients with advanced pancreatic ductal carcinoma, the authors studied fractionated radioimmunotherapy combined with low-dose gemcitabine in this disease. METHODS Thirty-eight previously untreated patients (33 patients with stage IV disease and 5 patients with stage III disease) received gemcitabine 200 mg/m2 weekly for 4 weeks with 90Y-hPAM4 given weekly in Weeks 2, 3, and 4 (cycle 1), and the same cycle was repeated in 13 patients (cycles 2–4). In the first part of the study, 19 patients received escalating weekly 90Y doses of 6.5 mCi/m2, 9.0 mCi/m2, 12.0 mCi/m2, and 15.0 mCi/m2. In the second portion, 19 additional patients received weekly doses of 9.0 mCi/m2 or 12.0 mCi/m2. RESULTS Grade 3/4 thrombocytopenia or neutropenia (according to version 3.0 of the National Cancer Institute’s Common Terminology Criteria for Adverse Events) developed in 28 of 38 patients after cycle 1 and in all retreated patients; no grade >3 nonhematologic toxicities occurred. Fractionated dosing of cycle 1 allowed almost twice the radiation dose compared with single-dose radioimmunotherapy. The maximum tolerated dose of 90Y-hPAM4 was 12.0 mCi/m2 weekly for 3 weeks for cycle 1, with ≤9.0 mCi/m2 weekly for 3 weeks for subsequent cycles, and that dose will be used in future trials. Six patients (16%) had partial responses according to computed tomography-based Response Evaluation Criteria in Solid Tumors, and 16 patients (42%) had stabilization as their best response (58% disease control). The median overall survival was 7.7 months for all 38 patients, including 11.8 months for those who received repeated cycles (46% [6 of 13 patients] ≥1 year), with improved efficacy at the higher radioimmunotherapy doses. CONCLUSIONS Fractionated radioimmunotherapy with 90Y-hPAM4 and low-dose gemcitabine demonstrated promising therapeutic activity and manageable myelosuppression in patients with advanced pancreatic ductal carcinoma. PMID:22569804

Monte Carlo simulation of the dose response of a novel 2D silicon diode array for use in hybrid MRI-LINAC systems.

PubMed

Gargett, Maegan; Oborn, Brad; Metcalfe, Peter; Rosenfeld, Anatoly

2015-02-01

MRI-guided radiation therapy systems (MRIgRT) are being developed to improve online imaging during treatment delivery. At present, the operation of single point dosimeters and an ionization chamber array have been characterized in such systems. This work investigates a novel 2D diode array, named "magic plate," for both single point calibration and 2D positional performance, the latter being a key element of modern radiotherapy techniques that will be delivered by these systems. geant4 Monte Carlo methods have been employed to study the dose response of a silicon diode array to 6 MV photon beams, in the presence of in-line and perpendicularly aligned uniform magnetic fields. The array consists of 121 silicon diodes (dimensions 1.5 × 1.5 × 0.38 mm(3)) embedded in kapton substrate with 1 cm pitch, spanning a 10 × 10 cm(2) area in total. A geometrically identical, water equivalent volume was simulated concurrently for comparison. The dose response of the silicon diode array was assessed for various photon beam field shapes and sizes, including an IMRT field, at 1 T. The dose response was further investigated at larger magnetic field strengths (1.5 and 3 T) for a 4 × 4 cm(2) photon field size. The magic plate diode array shows excellent correspondence (< ± 1%) to water dose in the in-line orientation, for all beam arrangements and magnetic field strengths investigated. The perpendicular orientation, however, exhibits a dose shift with respect to water at the high-dose-gradient beam edge of jaw-defined fields [maximum (4.3 ± 0.8)% over-response, maximum (1.8 ± 0.8)% under-response on opposing side for 1 T, uncertainty 1σ]. The trend is not evident in areas with in-field dose gradients typical of IMRT dose maps. A novel 121 pixel silicon diode array detector has been characterized by Monte Carlo simulation for its performance inside magnetic fields representative of current prototype and proposed MRI-linear accelerator systems. In the in-line orientation, the silicon dose is directly proportional to the water dose. In the perpendicular orientation, there is a shift in dose response relative to water in the highest dose gradient regions, at the edge of jaw-defined and single-segment MLC fields. The trend was not observed in-field for an IMRT beam. The array is expected to be a valuable tool in MRIgRT dosimetry.

Monte Carlo simulation of the dose response of a novel 2D silicon diode array for use in hybrid MRI–LINAC systems

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

Gargett, Maegan, E-mail: mg406@uowmail.edu.au; Rosenfeld, Anatoly; Oborn, Brad

2015-02-15

Purpose: MRI-guided radiation therapy systems (MRIgRT) are being developed to improve online imaging during treatment delivery. At present, the operation of single point dosimeters and an ionization chamber array have been characterized in such systems. This work investigates a novel 2D diode array, named “magic plate,” for both single point calibration and 2D positional performance, the latter being a key element of modern radiotherapy techniques that will be delivered by these systems. Methods: GEANT4 Monte Carlo methods have been employed to study the dose response of a silicon diode array to 6 MV photon beams, in the presence of in-linemore » and perpendicularly aligned uniform magnetic fields. The array consists of 121 silicon diodes (dimensions 1.5 × 1.5 × 0.38 mm{sup 3}) embedded in kapton substrate with 1 cm pitch, spanning a 10 × 10 cm{sup 2} area in total. A geometrically identical, water equivalent volume was simulated concurrently for comparison. The dose response of the silicon diode array was assessed for various photon beam field shapes and sizes, including an IMRT field, at 1 T. The dose response was further investigated at larger magnetic field strengths (1.5 and 3 T) for a 4 × 4 cm{sup 2} photon field size. Results: The magic plate diode array shows excellent correspondence (< ± 1%) to water dose in the in-line orientation, for all beam arrangements and magnetic field strengths investigated. The perpendicular orientation, however, exhibits a dose shift with respect to water at the high-dose-gradient beam edge of jaw-defined fields [maximum (4.3 ± 0.8)% over-response, maximum (1.8 ± 0.8)% under-response on opposing side for 1 T, uncertainty 1σ]. The trend is not evident in areas with in-field dose gradients typical of IMRT dose maps. Conclusions: A novel 121 pixel silicon diode array detector has been characterized by Monte Carlo simulation for its performance inside magnetic fields representative of current prototype and proposed MRI–linear accelerator systems. In the in-line orientation, the silicon dose is directly proportional to the water dose. In the perpendicular orientation, there is a shift in dose response relative to water in the highest dose gradient regions, at the edge of jaw-defined and single-segment MLC fields. The trend was not observed in-field for an IMRT beam. The array is expected to be a valuable tool in MRIgRT dosimetry.« less

Plasma cannabinoid pharmacokinetics following controlled oral delta9-tetrahydrocannabinol and oromucosal cannabis extract administration.

PubMed

Karschner, Erin L; Darwin, W David; Goodwin, Robert S; Wright, Stephen; Huestis, Marilyn A

2011-01-01

Sativex(®), a cannabis extract oromucosal spray containing Δ(9)-tetrahydrocannabinol (THC) and cannabidiol (CBD), is currently in phase III trials as an adjunct to opioids for cancer pain treatment, and recently received United Kingdom approval for treatment of spasticity. There are indications that CBD modulates THC's effects, but it is unclear if this is due to a pharmacokinetic and/or pharmacodynamic interaction. Cannabis smokers provided written informed consent to participate in this randomized, controlled, double-blind, double-dummy institutional review board-approved study. Participants received 5 and 15 mg synthetic oral THC, low-dose (5.4 mg THC and 5.0 mg CBD) and high-dose (16.2 mg THC and 15.0 mg CBD) Sativex, and placebo over 5 sessions. CBD, THC, 11-hydroxy-THC, and 11-nor- 9-carboxy-THC were quantified in plasma by 2-dimensional GC-MS. Lower limits of quantification were ≤0.25 μg/L. Nine cannabis smokers completed all 5 dosing sessions. Significant differences (P < 0.05) in maximum plasma concentrations (C(max)) and areas under the curve from 0-10.5 h postdose (AUC(0→10.5)) for all analytes were found between low and high doses of synthetic THC and Sativex. There were no statistically significant differences in C(max), time to maximum concentration or in the AUC(0→10.5) between similar oral THC and Sativex doses. Relative bioavailability was calculated to determine the relative rate and extent of THC absorption; 5 and 15 mg oral THC bioavailability was 92.6% (13.1%) and 98.8% (11.0%) of low- and high-dose Sativex, respectively. These data suggest that CBD modulation of THC's effects is not due to a pharmacokinetic interaction at these therapeutic doses.

Phase 1 dose-finding study of rebastinib (DCC-2036) in patients with relapsed chronic myeloid leukemia and acute myeloid leukemia

PubMed Central

Cortes, Jorge; Talpaz, Moshe; Smith, Hedy P.; Snyder, David S.; Khoury, Jean; Bhalla, Kapil N.; Pinilla-Ibarz, Javier; Larson, Richard; Mitchell, David; Wise, Scott C.; Rutkoski, Thomas J.; Smith, Bryan D.; Flynn, Daniel L.; Kantarjian, Hagop M.; Rosen, Oliver; Van Etten, Richard A.

2017-01-01

A vailable tyrosine kinase inhibitors for chronic myeloid leukemia bind in an adenosine 5′-triphosphate-binding pocket and are affected by evolving mutations that confer resistance. Rebastinib was identified as a switch control inhibitor of BCR-ABL1 and FLT3 and may be active against resistant mutations. A Phase 1, first-in-human, single-agent study investigated rebastinib in relapsed or refractory chronic or acute myeloid leukemia. The primary objectives were to investigate the safety of rebastinib and establish the maximum tolerated dose and recommended Phase 2 dose. Fifty-seven patients received treatment with rebastinib. Sixteen patients were treated using powder-in-capsule preparations at doses from 57 mg to 1200 mg daily, and 41 received tablet preparations at doses of 100 mg to 400 mg daily. Dose-limiting toxicities were dysarthria, muscle weakness, and peripheral neuropathy. The maximum tolerated dose was 150 mg tablets administered twice daily. Rebastinib was rapidly absorbed. Bioavailability was 3- to 4-fold greater with formulated tablets compared to unformulated capsules. Eight complete hematologic responses were achieved in 40 evaluable chronic myeloid leukemia patients, 4 of which had a T315I mutation. None of the 5 patients with acute myeloid leukemia responded. Pharmacodynamic analysis showed inhibition of phosphorylation of substrates of BCR-ABL1 or FLT3 by rebastinib. Although clinical activity was observed, clinical benefit was insufficient to justify continued development in chronic or acute myeloid leukemia. Pharmacodynamic analyses suggest that other kinases inhibited by rebastinib, such as TIE2, may be more relevant targets for the clinical development of rebastinib (clinicaltrials.gov Identifier:00827138). PMID:27927766

Phase 1 dose-finding study of rebastinib (DCC-2036) in patients with relapsed chronic myeloid leukemia and acute myeloid leukemia.

PubMed

Cortes, Jorge; Talpaz, Moshe; Smith, Hedy P; Snyder, David S; Khoury, Jean; Bhalla, Kapil N; Pinilla-Ibarz, Javier; Larson, Richard; Mitchell, David; Wise, Scott C; Rutkoski, Thomas J; Smith, Bryan D; Flynn, Daniel L; Kantarjian, Hagop M; Rosen, Oliver; Van Etten, Richard A

2017-03-01

A vailable tyrosine kinase inhibitors for chronic myeloid leukemia bind in an adenosine 5'-triphosphate-binding pocket and are affected by evolving mutations that confer resistance. Rebastinib was identified as a switch control inhibitor of BCR-ABL1 and FLT3 and may be active against resistant mutations. A Phase 1, first-in-human, single-agent study investigated rebastinib in relapsed or refractory chronic or acute myeloid leukemia. The primary objectives were to investigate the safety of rebastinib and establish the maximum tolerated dose and recommended Phase 2 dose. Fifty-seven patients received treatment with rebastinib. Sixteen patients were treated using powder-in-capsule preparations at doses from 57 mg to 1200 mg daily, and 41 received tablet preparations at doses of 100 mg to 400 mg daily. Dose-limiting toxicities were dysarthria, muscle weakness, and peripheral neuropathy. The maximum tolerated dose was 150 mg tablets administered twice daily. Rebastinib was rapidly absorbed. Bioavailability was 3- to 4-fold greater with formulated tablets compared to unformulated capsules. Eight complete hematologic responses were achieved in 40 evaluable chronic myeloid leukemia patients, 4 of which had a T315I mutation. None of the 5 patients with acute myeloid leukemia responded. Pharmacodynamic analysis showed inhibition of phosphorylation of substrates of BCR-ABL1 or FLT3 by rebastinib. Although clinical activity was observed, clinical benefit was insufficient to justify continued development in chronic or acute myeloid leukemia. Pharmacodynamic analyses suggest that other kinases inhibited by rebastinib, such as TIE2, may be more relevant targets for the clinical development of rebastinib ( clinicaltrials.gov Identifier:00827138 ). Copyright© Ferrata Storti Foundation.

Dosimetric comparison of IMRT rectal and anal canal plans generated using an anterior dose avoidance structure

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

Leicher, Brian, E-mail: bleicher@wpahs.org; Day, Ellen; Colonias, Athanasios

2014-10-01

To describe a dosimetric method using an anterior dose avoidance structure (ADAS) during the treatment planning process for intensity-modulated radiation therapy (IMRT) for patients with anal canal and rectal carcinomas. A total of 20 patients were planned on the Elekta/CMS XiO treatment planning system, version 4.5.1 (Maryland Heights MO) with a superposition algorithm. For each patient, 2 plans were created: one employing an ADAS (ADAS plan) and the other replanned without an ADAS (non-ADAS plan). The ADAS was defined to occupy the volume between the inguinal nodes and primary target providing a single organ at risk that is completely outsidemore » of the target volume. Each plan used the same beam parameters and was analyzed by comparing target coverage, overall plan dose conformity using a conformity number (CN) equation, bowel dose-volume histograms, and the number of segments, daily treatment duration, and global maximum dose. The ADAS and non-ADAS plans were equivalent in target coverage, mean global maximum dose, and sparing of small bowel in low-dose regions (5, 10, 15, and 20 Gy). The mean difference between the CN value for the non-ADAS plans and ADAS plans was 0.04 ± 0.03 (p < 0.001). The mean difference in the number of segments was 15.7 ± 12.7 (p < 0.001) in favor of ADAS plans. The ADAS plan delivery time was shorter by 2.0 ± 1.5 minutes (p < 0.001) than the non-ADAS one. The ADAS has proven to be a powerful tool when planning rectal and anal canal IMRT cases with critical structures partially contained inside the target volume.« less

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.

Shuttle radiation dose measurements in the International Space Station orbits

NASA Technical Reports Server (NTRS)

Badhwar, Gautam D.

2002-01-01

The International Space Station (ISS) is now a reality with the start of a permanent human presence on board. Radiation presents a serious risk to the health and safety of the astronauts, and there is a clear requirement for estimating their exposures prior to and after flights. Predictions of the dose rate at times other than solar minimum or solar maximum have not been possible, because there has been no method to calculate the trapped-particle spectrum at intermediate times. Over the last few years, a tissue-equivalent proportional counter (TEPC) has been flown at a fixed mid-deck location on board the Space Shuttle in 51.65 degrees inclination flights. These flights have provided data that cover the expected changes in the dose rates due to changes in altitude and changes in solar activity from the solar minimum to the solar maximum of the current 23rd solar cycle. Based on these data, a simple function of the solar deceleration potential has been derived that can be used to predict the galactic cosmic radiation (GCR) dose rates to within +/-10%. For altitudes to be covered by the ISS, the dose rate due to the trapped particles is found to be a power-law function, rho(-2/3), of the atmospheric density, rho. This relationship can be used to predict trapped dose rates inside these spacecraft to +/-10% throughout the solar cycle. Thus, given the shielding distribution for a location inside the Space Shuttle or inside an ISS module, this approach can be used to predict the combined GCR + trapped dose rate to better than +/-15% for quiet solar conditions.

Phase I trial of capecitabine rapidly disintegrating tablets and concomitant radiation therapy in children with newly diagnosed brainstem gliomas and high-grade gliomas

PubMed Central

Kilburn, Lindsay B.; Kocak, Mehmet; Schaedeli Stark, Franziska; Meneses-Lorente, Georgina; Brownstein, Carrie; Hussain, Sazzad; Chintagumpala, Murali; Thompson, Patrick A.; Gururangan, Sri; Banerjee, Anuradha; Paulino, Arnold C.; Kun, Larry; Boyett, James M.; Blaney, Susan M.

2013-01-01

Background We conducted a phase I study to estimate the maximum tolerated dose and describe the dose-limiting toxicities and pharmacokinetics of oral capecitabine rapidly disintegrating tablets given concurrently with radiation therapy to children with newly diagnosed brainstem or high-grade gliomas. Methods Children 3–21 y with newly diagnosed intrinsic brainstem or high-grade gliomas were eligible for enrollment. The starting dose was 500 mg/m2, given twice daily, with subsequent cohorts enrolled at 650 mg/m2 and 850 mg/m2 using a 3 + 3 phase I design. Children received capecitabine at the assigned dose daily for 9 wks starting from the first day of radiation therapy (RT). Following a 2-wk break, patients received 3 courses of capecitabine 1250 mg/m2 twice daily for 14 days followed by a 7-day rest. Pharmacokinetic sampling was performed in consenting patients. Six additional patients with intrinsic brainstem gliomas were enrolled at the maximum tolerated dose to further characterize the pharmacokinetic and toxicity profiles. Results Twenty-four patients were enrolled. Twenty were fully assessable for toxicity. Dose-limiting toxicities were palmar plantar erythroderma (grades 2 and 3) and elevation of alanine aminotransferase (grades 2 and 3). Systemic exposure to capecitabine and metabolites was similar to or slightly lower than predicted based on adult data. Conclusions Capecitabine with concurrent RT was generally well tolerated. The recommended phase II capecitabine dose when given with concurrent RT is 650 mg/m2, administered twice daily. A phase II study to evaluate the efficacy of this regimen in children with intrinsic brainstem gliomas is in progress (PBTC-030). PMID:23592571

Pharmacokinetics and pharmacodynamics of a human monoclonal anti‐FGF23 antibody (KRN23) in the first multiple ascending‐dose trial treating adults with X‐linked hypophosphatemia

PubMed Central

Imel, Erik A.; Ruppe, Mary D.; Weber, Thomas J.; Klausner, Mark A.; Ito, Takahiro; Vergeire, Maria; Humphrey, Jeffrey; Glorieux, Francis H.; Portale, Anthony A.; Insogna, Karl; Carpenter, Thomas O.; Peacock, Munro

2015-01-01

Abstract In X‐linked hypophosphatemia (XLH), serum fibroblast growth factor 23 (FGF23) is increased and results in reduced renal maximum threshold for phosphate reabsorption (TmP), reduced serum inorganic phosphorus (Pi), and inappropriately low normal serum 1,25 dihydroxyvitamin D (1,25[OH]2D) concentration, with subsequent development of rickets or osteomalacia. KRN23 is a recombinant human IgG1 monoclonal antibody that binds to FGF23 and blocks its activity. Up to 4 doses of KRN23 were administered subcutaneously every 28 days to 28 adults with XLH. Mean ± standard deviation KRN23 doses administered were 0.05, 0.10 ± 0.01, 0.28 ± 0.06, and 0.48 ± 0.16 mg/kg. The mean time to reach maximum serum KRN23 levels was 7.0 to 8.5 days. The mean KRN23 half‐life was 16.4 days. The mean area under the concentration–time curve (AUCn) for each dosing interval increased proportionally with increases in KRN23 dose. The mean intersubject variability in AUCn ranged from 30% to 37%. The area under the effect concentration–time curve (AUECn) for change from baseline in TmP per glomerular filtration rate, serum Pi, 1,25(OH)2D, and bone markers for each dosing interval increased linearly with increases in KRN23 AUCn. Linear correlation between serum KRN23 concentrations and increase in serum Pi support KRN23 dose adjustments based on predose serum Pi concentration. © 2015 The Authors. The Journal of Clinical Pharmacology Published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology PMID:26073451

Main clinical, therapeutic and technical factors related to patient's maximum skin dose in interventional cardiology procedures

PubMed Central

Journy, N; Sinno-Tellier, S; Maccia, C; Le Tertre, A; Pirard, P; Pagès, P; Eilstein, D; Donadieu, J; Bar, O

2012-01-01

Objective The study aimed to characterise the factors related to the X-ray dose delivered to the patient's skin during interventional cardiology procedures. Methods We studied 177 coronary angiographies (CAs) and/or percutaneous transluminal coronary angioplasties (PTCAs) carried out in a French clinic on the same radiography table. The clinical and therapeutic characteristics, and the technical parameters of the procedures, were collected. The dose area product (DAP) and the maximum skin dose (MSD) were measured by an ionisation chamber (Diamentor; Philips, Amsterdam, The Netherlands) and radiosensitive film (Gafchromic; International Specialty Products Advanced Materials Group, Wayne, NJ). Multivariate analyses were used to assess the effects of the factors of interest on dose. Results The mean MSD and DAP were respectively 389 mGy and 65 Gy cm−2 for CAs, and 916 mGy and 69 Gy cm−2 for PTCAs. For 8% of the procedures, the MSD exceeded 2 Gy. Although a linear relationship between the MSD and the DAP was observed for CAs (r=0.93), a simple extrapolation of such a model to PTCAs would lead to an inadequate assessment of the risk, especially for the highest dose values. For PTCAs, the body mass index, the therapeutic complexity, the fluoroscopy time and the number of cine frames were independent explanatory factors of the MSD, whoever the practitioner was. Moreover, the effect of technical factors such as collimation, cinematography settings and X-ray tube orientations on the DAP was shown. Conclusion Optimising the technical options for interventional procedures and training staff on radiation protection might notably reduce the dose and ultimately avoid patient skin lesions. PMID:22457404

Efficacy of robust optimization plan with partial-arc VMAT for photon volumetric-modulated arc therapy: A phantom study.

PubMed

Miura, Hideharu; Ozawa, Shuichi; Nagata, Yasushi

2017-09-01

This study investigated position dependence in planning target volume (PTV)-based and robust optimization plans using full-arc and partial-arc volumetric modulated arc therapy (VMAT). The gantry angles at the periphery, intermediate, and center CTV positions were 181°-180° (full-arc VMAT) and 181°-360° (partial-arc VMAT). A PTV-based optimization plan was defined by 5 mm margin expansion of the CTV to a PTV volume, on which the dose constraints were applied. The robust optimization plan consisted of a directly optimized dose to the CTV under a maximum-uncertainties setup of 5 mm. The prescription dose was normalized to the CTV D 99% (the minimum relative dose that covers 99% of the volume of the CTV) as an original plan. The isocenter was rigidly shifted at 1 mm intervals in the anterior-posterior (A-P), superior-inferior (S-I), and right-left (R-L) directions from the original position to the maximum-uncertainties setup of 5 mm in the original plan, yielding recalculated dose distributions. It was found that for the intermediate and center positions, the uncertainties in the D 99% doses to the CTV for all directions did not significantly differ when comparing the PTV-based and robust optimization plans (P > 0.05). For the periphery position, uncertainties in the D 99% doses to the CTV in the R-L direction for the robust optimization plan were found to be lower than those in the PTV-based optimization plan (P < 0.05). Our study demonstrated that a robust optimization plan's efficacy using partial-arc VMAT depends on the periphery CTV position. © 2017 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

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

Richter, Christian; Pawelke, Joerg; Karsch, Leonhard

Purpose: The aim of this article is to investigate the energy dependence of the radiochromic film type, Gafchromic EBT-1, when scanned with a flatbed scanner for film readout. Methods: Dose response curves were determined for 12 different beam qualities ranging from a 10 kVp x-ray beam to a 15 MVp x-ray beam and include also two high energy electron beam qualities (6 and 18 MeV). The dose responses measured as net optical density (netOD) for the different beam qualities were normalized to the response of a reference beam quality (6 MVp). Results: A strong systematic energy dependence of the filmmore » response was found. The lower the effective beam energy, the less sensitive the EBT-1 films get. The maximum decrease in dose for the same film response between the 25 kVp and 6 MVp beam qualities was 44%. Additionally, a difference in energy dependence for different doses was discovered, meaning that higher doses show a smaller dependency on energy than lower doses. The maximum decrease in the normalized netOD was found to be 25% for a dose of 0.5 Gy relative to the normalized netOD for 10 Gy. Moreover, a scaling procedure is introduced, allowing the correction of the energy dependence for the investigated beam qualities and also for comparable x-ray beam qualities within the energy range studied. Conclusions: A strong energy dependence for EBT-1 radiochromic films was found. The films were readout with a flatbed scanner. If the effective beam energy is known, the energy dependence can be corrected with the introduced scaling procedure. Further investigation of the influence of the spectral band of the readout device on energy dependence is needed to understand the reason for the different energy dependences found in this and previous works.« less

Hippocampal-Sparing Whole-Brain Radiotherapy: A 'How-To' Technique Using Helical Tomotherapy and Linear Accelerator-Based Intensity-Modulated Radiotherapy

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

Gondi, Vinai; Tolakanahalli, Ranjini; Mehta, Minesh P.

2010-11-15

Purpose: Sparing the hippocampus during cranial irradiation poses important technical challenges with respect to contouring and treatment planning. Herein we report our preliminary experience with whole-brain radiotherapy using hippocampal sparing for patients with brain metastases. Methods and Materials: Five anonymous patients previously treated with whole-brain radiotherapy with hippocampal sparing were reviewed. The hippocampus was contoured, and hippocampal avoidance regions were created using a 5-mm volumetric expansion around the hippocampus. Helical tomotherapy and linear accelerator (LINAC)-based intensity-modulated radiotherapy (IMRT) treatment plans were generated for a prescription dose of 30 Gy in 10 fractions. Results: On average, the hippocampal avoidance volume wasmore » 3.3 cm{sup 3}, occupying 2.1% of the whole-brain planned target volume. Helical tomotherapy spared the hippocampus, with a median dose of 5.5 Gy and maximum dose of 12.8 Gy. LINAC-based IMRT spared the hippocampus, with a median dose of 7.8 Gy and maximum dose of 15.3 Gy. On a per-fraction basis, mean dose to the hippocampus (normalized to 2-Gy fractions) was reduced by 87% to 0.49 Gy{sub 2} using helical tomotherapy and by 81% to 0.73 Gy{sub 2} using LINAC-based IMRT. Target coverage and homogeneity was acceptable with both IMRT modalities, with differences largely attributed to more rapid dose fall-off with helical tomotherapy. Conclusion: Modern IMRT techniques allow for sparing of the hippocampus with acceptable target coverage and homogeneity. Based on compelling preclinical evidence, a Phase II cooperative group trial has been developed to test the postulated neurocognitive benefit.« less

Plasma Cannabinoid Pharmacokinetics following Controlled Oral Δ9-Tetrahydrocannabinol and Oromucosal Cannabis Extract Administration

PubMed Central

Karschner, Erin L.; Darwin, W. David; Goodwin, Robert S.; Wright, Stephen; Huestis, Marilyn A.

2013-01-01

BACKGROUND Sativex®, a cannabis extract oromucosal spray containing Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), is currently in phase III trials as an adjunct to opioids for cancer pain treatment, and recently received United Kingdom approval for treatment of spasticity. There are indications that CBD modulates THC’s effects, but it is unclear if this is due to a pharmacokinetic and/or pharmacodynamic interaction. METHODS Cannabis smokers provided written informed consent to participate in this randomized, controlled, double-blind, double-dummy institutional review board–approved study. Participants received 5 and 15 mg synthetic oral THC, low-dose (5.4 mg THC and 5.0 mg CBD) and high-dose (16.2 mg THC and 15.0 mg CBD) Sativex, and placebo over 5 sessions. CBD, THC, 11-hydroxy-THC, and 11-nor-9-carboxy-THC were quantified in plasma by 2-dimensional GC-MS. Lower limits of quantification were ≤0.25 μg/L. RESULTS Nine cannabis smokers completed all 5 dosing sessions. Significant differences (P < 0.05) in maximum plasma concentrations (Cmax) and areas under the curve from 0–10.5 h postdose (AUC0→10.5) for all analytes were found between low and high doses of synthetic THC and Sativex. There were no statistically significant differences in Cmax, time to maximum concentration or in the AUC0→10.5 between similar oral THC and Sativex doses. Relative bioavailability was calculated to determine the relative rate and extent of THC absorption; 5 and 15 mg oral THC bioavailability was 92.6% (13.1%) and 98.8% (11.0%) of low- and high-dose Sativex, respectively. CONCLUSION These data suggest that CBD modulation of THC’s effects is not due to a pharmacokinetic interaction at these therapeutic doses. PMID:21078841

IMRT head and neck treatment planning with a commercially available Monte Carlo based planning system

NASA Astrophysics Data System (ADS)

Boudreau, C.; Heath, E.; Seuntjens, J.; Ballivy, O.; Parker, W.

2005-03-01

The PEREGRINE Monte Carlo dose-calculation system (North American Scientific, Cranberry Township, PA) is the first commercially available Monte Carlo dose-calculation code intended specifically for intensity modulated radiotherapy (IMRT) treatment planning and quality assurance. In order to assess the impact of Monte Carlo based dose calculations for IMRT clinical cases, dose distributions for 11 head and neck patients were evaluated using both PEREGRINE and the CORVUS (North American Scientific, Cranberry Township, PA) finite size pencil beam (FSPB) algorithm with equivalent path-length (EPL) inhomogeneity correction. For the target volumes, PEREGRINE calculations predict, on average, a less than 2% difference in the calculated mean and maximum doses to the gross tumour volume (GTV) and clinical target volume (CTV). An average 16% ± 4% and 12% ± 2% reduction in the volume covered by the prescription isodose line was observed for the GTV and CTV, respectively. Overall, no significant differences were noted in the doses to the mandible and spinal cord. For the parotid glands, PEREGRINE predicted a 6% ± 1% increase in the volume of tissue receiving a dose greater than 25 Gy and an increase of 4% ± 1% in the mean dose. Similar results were noted for the brainstem where PEREGRINE predicted a 6% ± 2% increase in the mean dose. The observed differences between the PEREGRINE and CORVUS calculated dose distributions are attributed to secondary electron fluence perturbations, which are not modelled by the EPL correction, issues of organ outlining, particularly in the vicinity of air cavities, and differences in dose reporting (dose to water versus dose to tissue type).

Retrospective cohort study of bronchial doses and radiation-induced atelectasis after stereotactic body radiation therapy of lung tumors located close to the bronchial tree.

PubMed

Karlsson, Kristin; Nyman, Jan; Baumann, Pia; Wersäll, Peter; Drugge, Ninni; Gagliardi, Giovanna; Johansson, Karl-Axel; Persson, Jan-Olov; Rutkowska, Eva; Tullgren, Owe; Lax, Ingmar

2013-11-01

To evaluate the dose-response relationship between radiation-induced atelectasis after stereotactic body radiation therapy (SBRT) and bronchial dose. Seventy-four patients treated with SBRT for tumors close to main, lobar, or segmental bronchi were selected. The association between incidence of atelectasis and bronchial dose parameters (maximum point-dose and minimum dose to the high-dose bronchial volume [ranging from 0.1 cm(3) up to 2.0 cm(3)]) was statistically evaluated with survival analysis models. Prescribed doses varied between 4 and 20 Gy per fraction in 2-5 fractions. Eighteen patients (24.3%) developed atelectasis considered to be radiation-induced. Statistical analysis showed a significant correlation between the incidence of radiation-induced atelectasis and minimum dose to the high-dose bronchial volumes, of which 0.1 cm(3) (D(0.1cm3)) was used for further analysis. The median value of D(0.1cm3) (α/β = 3 Gy) was EQD(2,LQ) = 147 Gy3 (range, 20-293 Gy3). For patients who developed atelectasis the median value was EQD(2,LQ) = 210 Gy3, and for patients who did not develop atelectasis, EQD(2,LQ) = 105 Gy3. Median time from treatment to development of atelectasis was 8.0 months (range, 1.1-30.1 months). In this retrospective study a significant dose-response relationship between the incidence of atelectasis and the dose to the high-dose volume of the bronchi is shown. Copyright © 2013 Elsevier Inc. All rights reserved.

Interactions of skin thickness and physicochemical properties of test compounds in percutaneous penetration studies.

PubMed

Wilkinson, Simon C; Maas, Wilfred J M; Nielsen, Jesper Bo; Greaves, Laura C; van de Sandt, Johannes J M; Williams, Faith M

2006-05-01

To determine the effect of skin thickness on the percutaneous penetration and distribution of test compounds with varying physicochemical properties using in vitro systems. Studies were carried out in accordance with OECD guidelines on skin absorption tests. Percutaneous penetration of caffeine (log P -0.01), testosterone (log P 3.32), propoxur (log P 1.52) (finite dose in ethanol to water vehicle ratio) and butoxyethanol (log P 0.83) (undiluted finite dose or as an infinite dose 50% [v/v] aqueous solution) through skin of varying thicknesses under occluded conditions was measured using flow through cells for 8-24 h. Saline (adjusted to pH 7.4) was used as receptor fluid, with BSA added for studies with testosterone and propoxur. Following exposure, the remaining surface dose was removed by swabbing and the skin digested prior to scintillation counting. The maximum flux of caffeine was increased with decreasing skin thickness, although these differences were found to be non-significant. The presence of caffeine in the skin membrane was not altered by skin thickness. Maximum flux and cumulative dose absorbed of testosterone and butoxyethanol (in both finite and infinite doses) were markedly reduced with full thickness (about 1 mm thick) skin compared with split thickness skin (about 0.5 mm). Maximum flux of propoxur (dissolved in 60% ethanol) was clearly higher through skin of 0.71 mm than through skin of 1.36 mm, but no difference was found between 0.56 and 0.71 mm. The proportion of propoxur present in the membrane after 24 h increased significantly over the complete range of thicknesses tested (0.56-1.36 mm). A complex relationship exists between skin thickness, lipophilicity and percutaneous penetration and distribution. This has implications for risk assessment studies and for the validation of models with data from different sources.

Effect of Steady-State Faldaprevir on the Pharmacokinetics of Steady-State Methadone and Buprenorphine-Naloxone in Subjects Receiving Stable Addiction Management Therapy

PubMed Central

Joseph, David; Schobelock, Michael J.; Riesenberg, Robert R.; Vince, Bradley D.; Webster, Lynn R.; Adeniji, Abidemi; Elgadi, Mabrouk

2014-01-01

The effects of steady-state faldaprevir on the safety, pharmacokinetics, and pharmacodynamics of steady-state methadone and buprenorphine-naloxone were assessed in 34 healthy male and female subjects receiving stable addiction management therapy. Subjects continued receiving a stable oral dose of either methadone (up to a maximum dose of 180 mg per day) or buprenorphine-naloxone (up to a maximum dose of 24 mg-6 mg per day) and also received oral faldaprevir (240 mg) once daily (QD) for 8 days following a 480-mg loading dose. Serial blood samples were taken for pharmacokinetic analysis. The pharmacodynamics of the opioid maintenance regimens were evaluated by the objective and subjective opioid withdrawal scales. Coadministration of faldaprevir with methadone or buprenorphine-naloxone resulted in geometric mean ratios for the steady-state area under the concentration-time curve from 0 to 24 h (AUC0–24,ss), the steady-state maximum concentration of the drug in plasma (Cmax,ss), and the steady-state concentration of the drug in plasma at 24 h (C24,ss) of 0.92 to 1.18 for (R)-methadone, (S)-methadone, buprenorphine, norbuprenorphine, and naloxone, with 90% confidence intervals including, or very close to including, 1.00 (no effect), suggesting a limited overall effect of faldaprevir. Although individual data showed moderate variability in the exposures between subjects and treatments, there was no evidence of symptoms of opiate overdose or withdrawal either during the coadministration of faldaprevir with methadone or buprenorphine-naloxone or after faldaprevir dosing was stopped. Similar faldaprevir exposures were observed in the methadone- and buprenorphine-naloxone-treated subjects. In conclusion, faldaprevir at 240 mg QD can be coadministered with methadone or buprenorphine-naloxone without dose adjustment, although given the relatively narrow therapeutic windows of these agents, monitoring for opiate overdose and withdrawal may still be appropriate. (This study has been registered at ClinicalTrials.gov under registration no. NCT01637922.) PMID:25385094

TH-EF-BRB-02: Feasibility of Optimization for Dynamic Trajectory Radiotherapy

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

Fix, MK; Frei, D; Volken, W

2016-06-15

Purpose: Over the last years, volumetric modulated arc therapy (VMAT) has been widely introduced into clinical routine using a coplanar delivery technique. However, VMAT might be improved by including dynamic couch and collimator rotations, leading to dynamic trajectory radiotherapy (DTRT). In this work the feasibility and the potential benefit of DTRT was investigated. Methods: A general framework for the optimization was developed using the Eclipse Scripting Research Application Programming Interface (ESRAPI). Based on contoured target and organs at risk (OARs), the structures are extracted using the ESRAPI. Sampling potential beam directions, regularly distributed on a sphere using a Fibanocci-lattice, themore » fractional volume-overlap of each OAR and the target is determined and used to establish dynamic gantry-couch movements. Then, for each gantry-couch track the most suitable collimator angle is determined for each control point by optimizing the area between the MLC leaves and the target contour. The resulting dynamic trajectories are used as input to perform the optimization using a research version of the VMAT optimization algorithm and the ESRAPI. The feasibility of this procedure was tested for a clinically motivated head and neck case. Resulting dose distributions for the VMAT plan and for the dynamic trajectory treatment plan were compared based on DVH-parameters. Results: While the DVH for the target is virtually preserved, improvements in maximum dose for the DTRT plan were achieved for all OARs except for the inner-ear, where maximum dose remains the same. The major improvements in maximum dose were 6.5% of the prescribed dose (66 Gy) for the parotid and 5.5% for the myelon and the eye. Conclusion: The result of this work suggests that DTRT has a great potential to reduce dose to OARs with similar target coverage when compared to conventional VMAT treatment plans. This work was supported by Varian Medical Systems. This work was supported by Varian Medical Systems.« less

[Induction of glutathione and activation of immune functions by low-dose, whole-body irradiation with gamma-rays].

PubMed

Kojima, Shuji

2006-10-01

We first examined the relation between the induction of glutathione and immune functions in mice after low-dose gamma-ray irradiation. Thereafter, inhibition of tumor growth by radiation was confirmed in Ehrlich solid tumor (EST)-bearing mice. The total glutathione level of the splenocytes transiently increased soon after irradiation and reached a maximum at around 4 h postirradiation. Thereafter, the level reverted to the 0 h value by 24 h postirradiation. A significantly high splenocyte proliferative response was also recognized 4 h postirradiation. Natural killer (NK) activity was also increased significantly in a similar manner. The time at which the response reached the maximum coincided well with that of maximum total glutathione levels of the splenocytes in the gamma-ray-irradiated mice. Reduced glutathione exogenously added to splenocytes obtained from normal mice enhanced the proliferative response and NK activity in a dose-dependent manner. The inhibitory effects of radiation on tumor growth was then examined in EST-bearing mice. Repeated low-dose irradiation (0.5 Gy, four times, before and within an early time after inoculation) significantly delayed the tumor growth. Finally, the effect of single low-dose (0.5 Gy), whole-body gamma-ray irradiation on immune balance was examined to elucidate the mechanism underlying the antitumor immunity. The percentage of B cells in blood lymphocytes was selectively decreased after radiation, concomitant with an increase in that of the helper T cell population. The IFN-gamma level in splenocyte culture prepared from EST-bearing mice was significantly increased 48 h after radiation, although the level of IL-4 was unchanged. IL-12 secretion from macrophages was also enhanced by radiation. These results suggest that low-dose gamma-rays induce Th1 polarization and enhance the activities of tumoricidal effector cells, leading to an inhibition of tumor growth.

Comparing the quality of passively-scattered proton and photon tomotherapy plans for brain and head and neck disease sites.

PubMed

Kainz, Kristofer; Firat, Selim; Wilson, J Frank; Schultz, Christopher; Siker, Malika; Wang, Andrew; Olson, Dan; Li, X Allen

2015-03-21

We compare the quality of photon IMRT (helical tomotherapy) with classic proton plans for brain, head and neck tumors, in terms of target dose uniformity and conformity along with organ-at-risk (OAR) sparing. Plans were created for twelve target volumes among eight cases. All patients were originally planned and treated using helical tomotherapy. Proton plans were generated using a passively-scattered beam model with a maximum range of 32 g cm(-2) (225 MeV), range modulation in 0.5 g cm(-2) increments and range compensators with 4.8 mm milling tool diameters. All proton plans were limited to two to four beams. Plan quality was compared using uniformity index (UI), conformation number (CN) and a EUD-based plan quality index (fEUD). For 11 of the 12 targets, UI was improved for the proton plan; on average, UI was 1.05 for protons versus 1.08 for tomotherapy. For 7 of the 12 targets, the tomotherapy plan exhibited more favorable CN. For proximal OARs, the improved dose conformity to the target volume from tomotherapy led to a lower maximum dose. For distal OARs, the maximum dose was much lower for proton plans. For 6 of the 8 cases, near-total avoidance for distal OARs provided by protons leads to improved fEUD. However, if distal OARs are excluded in the fEUD calculation, the proton plans exhibit better fEUD in only 3 of the 8 cases. The distal OAR sparing and target dose uniformity are generally better with passive-scatter proton planning than with photon tomotherapy; proton therapy may be preferred if the clinician deems those attributes critical. However, tomotherapy may serve equally as well as protons for cases where superior target dose conformity from tomotherapy leads to plan quality nearly identical to or better than protons and for cases where distal OAR sparing is not concerning.

Investigation on using high-energy proton beam for total body irradiation (TBI).

PubMed

Zhang, Miao; Qin, Nan; Jia, Xun; Zou, Wei J; Khan, Atif; Yue, Ning J

2016-09-08

This work investigated the possibility of using proton beam for total body irradia-tion (TBI). We hypothesized the broad-slow-rising entrance dose from a monoen-ergetic proton beam can deliver a uniform dose to patient with varied thickness. Comparing to photon-based TBI, it would not require any patient-specific com-pensator or beam spoiler. The hypothesis was first tested by simulating 250 MeV, 275 MeV, and 300 MeV protons irradiating a wedge-shaped water phantom in a paired opposing arrangement using Monte Carlo (MC) method. To allow ± 7.5% dose variation, the maximum water equivalent thickness (WET) of a treatable patient separation was 29 cm for 250 MeV proton, and > 40 cm for 275 MeV and 300 MeV proton. The compared 6 MV photon can only treat patients with up to 15.5 cm water-equivalent separation. In the second step, we simulated the dose deposition from the same beams on a patient's whole-body CT scan. The maximum patient separation in WET was 23 cm. The calculated whole-body dose variations were ± 8.9%, ± 9.0%, ± 9.6%, and ± 14% for 250 MeV proton, 275 MeV proton, 300 MeV proton, and 6 MV photon. At last, we tested the current machine capability to deliver a monoenergetic proton beam with a large uniform field. Experiments were performed on a compact double scattering single-gantry proton system. With its C-shaped gantry design, the source-to-surface distance (SSD) reached 7 m. The measured dose deposition curve had 22 cm relatively flat entrance region. The full width half maximum field size was measured 105 cm. The current scatter filter had to be redesigned to produce a uniform intensity at such treatment distance. In con-clusion, this work demonstrated the possibility of using proton beam for TBI. The current commercially available proton machines would soon be ready for such task. © 2016 The Authors.

Pharmacokinetics and Safety of MP-376 (Levofloxacin Inhalation Solution) in Cystic Fibrosis Subjects▿

PubMed Central

Geller, David E.; Flume, Patrick A.; Griffith, David C.; Morgan, Elizabeth; White, Dan; Loutit, Jeffery S.; Dudley, Michael N.

2011-01-01

The pharmacokinetics and tolerability of nebulized MP-376 (levofloxacin inhalation solution [Aeroquin]) were determined in cystic fibrosis (CF) subjects. Ten CF subjects received single 180-mg doses of two formulations of MP-376, followed by a multiple-dose phase of 240 mg once daily for 7 days. Serum and expectorated-sputum samples were assayed for levofloxacin content. Safety was evaluated following the single- and multiple-dose study phases. Nebulized MP-376 produced high concentrations of levofloxacin in sputum. The mean maximum plasma concentration (Cmax) ranged between 2,563 and 2,932 mg/liter for 180-mg doses of the 50- and 100-mg/ml formulations, respectively. After 7 days of dosing, the mean Cmax for the 240-mg dose was 4,691 mg/liter. The mean serum levofloxacin Cmax ranged between 0.95 and 1.28 for the 180-mg doses and was 1.71 for the 240-mg dose. MP-376 was well tolerated. Nebulized MP-376 produces high sputum and low serum levofloxacin concentrations. The pharmacokinetics, safety, and tolerability were similar for the two formulations. MP-376 240 mg (100 mg/ml) is being advanced into late-stage clinical development. PMID:21444699

A new radiotherapy surface dose detector:the MOSFET.

PubMed

Butson, M J; Rozenfeld, A; Mathur, J N; Carolan, M; Wong, T P; Metcalfe, P E

1996-05-01

Radiotherapy x-ray and electron beam surface doses are accurately measurable by use of a MOS-FET detector system. The MOSFET (Metal Oxide Semiconductor Field Effect Transistor) is approximately 200-microns in diameter and consists of a 0.5-microns Al electrode on top of a 1-microns SiO2 and 300-microns Si substrate. Results for % surface dose were within +/- 2% compared to the Attix chamber and within +/- 3% of TLD extrapolation results for normally incident beams. Detectors were compared using different energies, field size, and beam modifying devices such as block trays and wedges. Percentage surface dose for 10 x 10-cm and 40 x 40-cm field size for 6-MV x rays at 100-cm SSD using the MOSFET were 16% and 42% of maximum, respectively. Factors such as its small size, immediate retrieval of results, high accuracy attainable from low applied doses, and as the MOSFET records its dose history make it a suitable in vivo dosimeter where surface and skin doses need to be determined. This can be achieved within part of the first fraction of dose (i.e., only 10 cGy is required.)

Use Dose Bricks Concept to Implement Nasopharyngeal Carcinoma Treatment Planning

PubMed Central

Wu, Jia-Ming; Yu, Tsan-Jung; Yeh, Shyh-An; Chao, Pei-Ju; Huang, Chih-Jou

2014-01-01

Purpose. A “dose bricks” concept has been used to implement nasopharyngeal carcinoma treatment plan; this method specializes particularly in the case with bell shape nasopharyngeal carcinoma case. Materials and Methods. Five noncoplanar fields were used to accomplish the dose bricks technique treatment plan. These five fields include (a) right superior anterior oblique (RSAO), (b) left superior anterior oblique (LSAO), (c) right anterior oblique (RAO), (d) left anterior oblique (LAO), and (e) superior inferior vertex (SIV). Nondivergence collimator central axis planes were used to create different abutting field edge while normal organs were blocked by multileaf collimators in this technique. Results. The resulting 92% isodose curves encompassed the CTV, while maximum dose was about 115%. Approximately 50% volume of parotid glands obtained 10–15% of total dose and 50% volume of brain obtained less than 20% of total dose. Spinal cord receives only 5% from the scatter dose. Conclusions. Compared with IMRT, the expenditure of planning time and costing, “dose bricks” may after all be accepted as an optional implementation in nasopharyngeal carcinoma conformal treatment plan; furthermore, this method also fits the need of other nonhead and neck lesions if organ sparing and noncoplanar technique can be executed. PMID:24967395

Ranitidine Can Potentiate The Prokinetic Effect Of Itopride At Low Doses- An In Vitro Study.

PubMed

Butt, Aroosa Ishtiaq; Khan, Bushra Tayyaba; Khan, Asma; Khan, Qamar-Uz-Zaman

2017-01-01

Gastroparesis and GERD occur concomitantly in 40 percent of the cases. Prokinetic drugs and acid blockers are employed as the main treatment modality. Ranitidine is an acid blocker with additional prokinetic activity and Itopride is a known prokinetic drug. This study was designed to observe the synergistic potentiating prokinetic effect of Ranitidine on itopride on isolated duodenum of rabbits. Ranitidine (10-5-10-3) and itopride (10-6-10-5) were added in increasing concentrations to isolated duodenum of rabbits and contractions were recorded on PowerLab Data acquisition unit AHK/214. Cumulative dose response curves were constructed. The potentiating prokinetic effect of Ranitidine on itopride was seen by using a fixed dose of ranitidine and cumulatively enhancing doses of itopride on iWorx. Ranitidine and itopride produced a dose dependent reversible contraction of the isolated tissue of rabbits with ranitidine showing a max response of 0.124mV and itopride showing a maximum response of 0.131mV. Ranitidine was able to potentiate the prokinetic effect of itopride at low doses but at high dose the effect began to wane off. Ranitidine and itopride produce a statistically significant synergistic potentiating prokinetic effect at low doses in vitro.

Safety, Pharmacokinetics, and Pharmacodynamics in Healthy Volunteers Treated With GDC-0853, a Selective Reversible Bruton's Tyrosine Kinase Inhibitor.

PubMed

Herman, Ann E; Chinn, Leslie W; Kotwal, Shweta G; Murray, Elaine R; Zhao, Rui; Florero, Marilyn; Lin, Alyse; Moein, Anita; Wang, Rena; Bremer, Meire; Kokubu, Serika; Serone, Adrian P; Hanze, Eva L; Viberg, Anders; Morimoto, Alyssa M; Winter, Helen R; Katsumoto, Tamiko R

2018-06-01

GDC-0853 is a small molecule inhibitor of Bruton's tyrosine kinase (BTK) that is highly selective and noncovalent, leading to reversible binding. In double-blind, randomized, and placebo-controlled phase I healthy volunteer studies, GDC-0853 was well tolerated, with no dose-limiting adverse events (AEs) or serious AEs. The maximum tolerated dose was not reached during dose escalation (≤600 mg, single ascending dose (SAD) study; ≤250 mg twice daily (b.i.d.) and ≤500 mg once daily, 14-day multiple ascending dose (MAD) study). Plasma concentrations peaked 1-3 hours after oral administration and declined thereafter, with a steady-state half-life ranging from 4.2-9.9 hours. Independent assays demonstrated dose-dependent BTK target engagement. Based on pharmacokinetic/pharmacodynamic (PK/PD) simulations, a once-daily dosing regimen (e.g., 100 mg, q.d.) is expected to maintain a high level of BTK inhibition over the dosing interval. Taken together, the safety and PK/PD data support GDC-0853 evaluation in rheumatoid arthritis, lupus, and other autoimmune or inflammatory indications. © 2018 American Society for Clinical Pharmacology and Therapeutics.

Guaifenesin Pharmacokinetics Following Single‐Dose Oral Administration in Children Aged 2 to 17 Years

PubMed Central

Thompson, Gary A.; Solomon, Gail; Albrecht, Helmut H.; Reitberg, Donald P.

2016-01-01

Abstract This study characterized guaifenesin pharmacokinetics in children aged 2 to 17 years (n = 40) who received a single oral dose of guaifenesin (age‐based doses of 100‐400 mg) 2 hours after breakfast. Plasma samples were obtained before and for 8 hours after dosing and analyzed for guaifenesin using liquid chromatography‐tandem mass spectrometry. Pharmacokinetic parameters were estimated using noncompartmental methods, relationships with age were assessed using linear regression, and dose proportionality was assessed on 95% confidence intervals. Based on the upper dose recommended in the monograph (for both children and adolescents), area under the curve from time zero to infinity and maximum plasma concentration both increased with age. However, when comparing the upper dose for children aged 2 to 11 years with the lower dose for adolescents aged 12 to 17 years, similar systemic exposure was observed. As expected due to increasing body size, oral clearance (CLo) and terminal volume of distribution (Vz/F) increased with age. Due to a larger increase in Vz/F than CLo, an increase in terminal exponential half‐life was also observed. Allometric scaling indicated no maturation‐related changes in CLo and Vz/F. PMID:26632082

Percentage depth dose calculation accuracy of model based algorithms in high energy photon small fields through heterogeneous media and comparison with plastic scintillator dosimetry.

PubMed

Alagar, Ananda Giri Babu; Mani, Ganesh Kadirampatti; Karunakaran, Kaviarasu

2016-01-08

Small fields smaller than 4 × 4 cm2 are used in stereotactic and conformal treatments where heterogeneity is normally present. Since dose calculation accuracy in both small fields and heterogeneity often involves more discrepancy, algorithms used by treatment planning systems (TPS) should be evaluated for achieving better treatment results. This report aims at evaluating accuracy of four model-based algorithms, X-ray Voxel Monte Carlo (XVMC) from Monaco, Superposition (SP) from CMS-Xio, AcurosXB (AXB) and analytical anisotropic algorithm (AAA) from Eclipse are tested against the measurement. Measurements are done using Exradin W1 plastic scintillator in Solid Water phantom with heterogeneities like air, lung, bone, and aluminum, irradiated with 6 and 15 MV photons of square field size ranging from 1 to 4 cm2. Each heterogeneity is introduced individually at two different depths from depth-of-dose maximum (Dmax), one setup being nearer and another farther from the Dmax. The central axis percentage depth-dose (CADD) curve for each setup is measured separately and compared with the TPS algorithm calculated for the same setup. The percentage normalized root mean squared deviation (%NRMSD) is calculated, which represents the whole CADD curve's deviation against the measured. It is found that for air and lung heterogeneity, for both 6 and 15 MV, all algorithms show maximum deviation for field size 1 × 1 cm2 and gradually reduce when field size increases, except for AAA. For aluminum and bone, all algorithms' deviations are less for 15 MV irrespective of setup. In all heterogeneity setups, 1 × 1 cm2 field showed maximum deviation, except in 6MV bone setup. All algorithms in the study, irrespective of energy and field size, when any heterogeneity is nearer to Dmax, the dose deviation is higher compared to the same heterogeneity far from the Dmax. Also, all algorithms show maximum deviation in lower-density materials compared to high-density materials.

Soft-tissue allografts terminally sterilized with an electron beam are biomechanically equivalent to aseptic, nonsterilized tendons.

PubMed

Elenes, Egleide Y; Hunter, Shawn A

2014-08-20

Allograft safety is contingent on effective sterilization. However, current sterilization methods have been associated with decreased biomechanical strength and higher failure rates of soft-tissue allografts. In this study, electron beam (e-beam) sterilization was explored as an alternative sterilization method to preserve biomechanical integrity. We hypothesized that e-beam sterilization would not significantly alter the biomechanical properties of tendon allograft compared with aseptic, nonsterilized controls and gamma-irradiated grafts. Separate sets of forty fresh-frozen tibialis tendon allografts (four from each of ten donors) and forty bisected bone-patellar tendon-bone (BTB) allografts (four from each of ten donors) were randomly assigned to four study groups. One group received a 17.1 to 21.0-kGy gamma radiation dose; two other groups were sterilized with an e-beam at either a high (17.1 to 21.0-kGy) or low (9.2 to 12.2-kGy) dose. A fourth group served as nonsterilized controls. Each graft was cyclically loaded to 200 N of tension for 2000 cycles at a frequency of 2 Hz, allowed to relax for five minutes, and then tested in tension until failure at a 100%/sec strain rate. One-way analysis of variance testing was used to identify significant differences. Tibialis tendons sterilized with both e-beam treatments and with gamma irradiation exhibited values for cyclic tendon elongation, maximum load, maximum displacement, stiffness, maximum stress, maximum strain, and elastic modulus that were not significantly different from those of nonsterilized controls. BTB allografts sterilized with the high e-beam dose and with gamma irradiation were not significantly different in cyclic tendon elongation, maximum load, maximum displacement, stiffness, maximum stress, maximum strain, and elastic modulus from nonsterilized controls. BTB allografts sterilized with the e-beam at the lower dose were significantly less stiff than nonsterilized controls (p = 0.014) but did not differ from controls in any other properties. The difference in stiffness likely resulted from variations in tendon size rather than the treatments, as the elastic moduli of the groups were similar. The biomechanical properties of tibialis and BTB allografts sterilized with use of an e-beam at a dose range of 17.1 to 21.0 kGy were not different from those of aseptic, nonsterilized controls or gamma-irradiated allografts. E-beam sterilization can be a viable method to produce safe and biomechanically uncompromised soft-tissue allografts. Copyright © 2014 by The Journal of Bone and Joint Surgery, Incorporated.

Commissioning and initial acceptance tests for a commercial convolution dose calculation algorithm for radiotherapy treatment planning in comparison with Monte Carlo simulation and measurement

PubMed Central

Moradi, Farhad; Mahdavi, Seyed Rabi; Mostaar, Ahmad; Motamedi, Mohsen

2012-01-01

In this study the commissioning of a dose calculation algorithm in a currently used treatment planning system was performed and the calculation accuracy of two available methods in the treatment planning system i.e., collapsed cone convolution (CCC) and equivalent tissue air ratio (ETAR) was verified in tissue heterogeneities. For this purpose an inhomogeneous phantom (IMRT thorax phantom) was used and dose curves obtained by the TPS (treatment planning system) were compared with experimental measurements and Monte Carlo (MCNP code) simulation. Dose measurements were performed by using EDR2 radiographic films within the phantom. Dose difference (DD) between experimental results and two calculation methods was obtained. Results indicate maximum difference of 12% in the lung and 3% in the bone tissue of the phantom between two methods and the CCC algorithm shows more accurate depth dose curves in tissue heterogeneities. Simulation results show the accurate dose estimation by MCNP4C in soft tissue region of the phantom and also better results than ETAR method in bone and lung tissues. PMID:22973081

Pulmonary Nodule Volumetry at Different Low Computed Tomography Radiation Dose Levels With Hybrid and Model-Based Iterative Reconstruction: A Within Patient Analysis.

PubMed

den Harder, Annemarie M; Willemink, Martin J; van Hamersvelt, Robbert W; Vonken, Evertjan P A; Schilham, Arnold M R; Lammers, Jan-Willem J; Luijk, Bart; Budde, Ricardo P J; Leiner, Tim; de Jong, Pim A

2016-01-01

The aim of the study was to determine the effects of dose reduction and iterative reconstruction (IR) on pulmonary nodule volumetry. In this prospective study, 25 patients scheduled for follow-up of pulmonary nodules were included. Computed tomography acquisitions were acquired at 4 dose levels with a median of 2.1, 1.2, 0.8, and 0.6 mSv. Data were reconstructed with filtered back projection (FBP), hybrid IR, and model-based IR. Volumetry was performed using semiautomatic software. At the highest dose level, more than 91% (34/37) of the nodules could be segmented, and at the lowest dose level, this was more than 83%. Thirty-three nodules were included for further analysis. Filtered back projection and hybrid IR did not lead to significant differences, whereas model-based IR resulted in lower volume measurements with a maximum difference of -11% compared with FBP at routine dose. Pulmonary nodule volumetry can be accurately performed at a submillisievert dose with both FBP and hybrid IR.

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

Li, Xinhua; Zhang, Da; Liu, Bob, E-mail: bliu7@mgh.harvard.edu

Purpose: The knowledge of longitudinal dose distribution provides the most direct view of the accumulated dose in computed tomography (CT) scanning. The purpose of this work was to perform a comprehensive study of dose distribution width and energy absorption with a wide range of subject sizes and beam irradiated lengths. Methods: Cumulative dose distribution along the z-axis was calculated based on the previously published CT dose equilibration data by Li, Zhang, and Liu [Med. Phys. 40, 031903 (10pp.) (2013)] and a mechanism for computing dose on axial lines by Li, Zhang, and Liu [Med. Phys. 39, 5347–5352 (2012)]. Full widthmore » at half maximum (FWHM), full width at tenth maximum (FWTM), the total energy (E) absorbed in a small cylinder of unit mass per centimeter square about the central or peripheral axis, and the energy (E{sub in}) absorbed inside irradiated length (L) were subsequently extracted from the dose distribution. Results: Extensive results of FWHM, FWTM, and E{sub in}/E were presented on the central and peripheral axes of infinitely long PMMA (diameters 6–50 cm) and water (diameters 6–55 cm) cylinders with L < 100 cm. FWHM was greater than the primary beam width only on the central axes of large phantoms and also with L ranging from a few centimeter to about 33 cm. FWTM generally increased with phantom diameter, and could be up to 32 cm longer than irradiated length, depending on L, phantom diameter and axis, but was insensitive to phantom material (PMMA or water). E{sub in}/E increased with L and asymptotically approached unity for large L. As phantom diameter increased, E{sub in}/E generally decreased, but asymptotically approached constant levels on the peripheral axes of large phantoms. A heuristic explanation of dose distribution width results was presented. Conclusions: This study enables the reader to gain a comprehensive view of dose distribution width and energy absorption and provides useful data for estimating doses to organs inside or beyond the irradiated region. The dose length product (DLP) presented by CT scanners is equal to neither E nor E{sub in}. Both E and E{sub in} can be evaluated using the equations and results presented in this paper and are robust with both constant and variable tube current scanning techniques.« less

Commissioning of a Varian Clinac iX 6 MV photon beam using Monte Carlo simulation

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

Dirgayussa, I Gde Eka, E-mail: ekadirgayussa@gmail.com; Yani, Sitti; Haryanto, Freddy, E-mail: freddy@fi.itb.ac.id

2015-09-30

Monte Carlo modelling of a linear accelerator is the first and most important step in Monte Carlo dose calculations in radiotherapy. Monte Carlo is considered today to be the most accurate and detailed calculation method in different fields of medical physics. In this research, we developed a photon beam model for Varian Clinac iX 6 MV equipped with MilleniumMLC120 for dose calculation purposes using BEAMnrc/DOSXYZnrc Monte Carlo system based on the underlying EGSnrc particle transport code. Monte Carlo simulation for this commissioning head LINAC divided in two stages are design head Linac model using BEAMnrc, characterize this model using BEAMDPmore » and analyze the difference between simulation and measurement data using DOSXYZnrc. In the first step, to reduce simulation time, a virtual treatment head LINAC was built in two parts (patient-dependent component and patient-independent component). The incident electron energy varied 6.1 MeV, 6.2 MeV and 6.3 MeV, 6.4 MeV, and 6.6 MeV and the FWHM (full width at half maximum) of source is 1 mm. Phase-space file from the virtual model characterized using BEAMDP. The results of MC calculations using DOSXYZnrc in water phantom are percent depth doses (PDDs) and beam profiles at depths 10 cm were compared with measurements. This process has been completed if the dose difference of measured and calculated relative depth-dose data along the central-axis and dose profile at depths 10 cm is ≤ 5%. The effect of beam width on percentage depth doses and beam profiles was studied. Results of the virtual model were in close agreement with measurements in incident energy electron 6.4 MeV. Our results showed that photon beam width could be tuned using large field beam profile at the depth of maximum dose. The Monte Carlo model developed in this study accurately represents the Varian Clinac iX with millennium MLC 120 leaf and can be used for reliable patient dose calculations. In this commissioning process, the good criteria of dose difference in PDD and dose profiles were achieve using incident electron energy 6.4 MeV.« less

Variation in Prescribing Patterns and Therapeutic Drug Monitoring of Intravenous Busulfan in Pediatric Hematopoietic Cell Transplant Recipients

PubMed Central

McCune, Jeannine S.; Baker, K. Scott; Blough, David K.; Gamis, Alan; Bemer, Meagan J.; Kelton-Rehkopf, Megan C.; Winter, Laura; Barrett, Jeffrey S.

2016-01-01

Personalizing intravenous (IV) busulfan doses in children using therapeutic drug monitoring (TDM) is an integral component of hematopoietic cell transplant. The authors sought to characterize initial dosing and TDM of IV busulfan, along with factors associated with busulfan clearance, in 729 children who underwent busulfan TDM from December 2005 to December 2008. The initial IV busulfan dose in children weighing ≤12 kg ranged 4.8-fold, with only 19% prescribed the package insert dose of 1.1 mg/kg. In those children weighing >12 kg, the initial dose ranged 5.4-fold, and 79% were prescribed the package insert dose. The initial busulfan dose achieved the target exposure in only 24.3% of children. A wide range of busulfan exposures were targeted for children with the same disease (eg, 39 target busulfan exposures for the 264 children diagnosed with acute myeloid leukemia). Considerable heterogeneity exists regarding when TDM is conducted and the number of pharmacokinetic samples obtained. Busulfan clearance varied by age and dosing frequency but not by underlying disease. The authors’ group is currently evaluating how using population pharmacokinetics to optimize initial busulfan dose and TDM (eg, limited sampling schedule in conjunction with maximum a posteriori Bayesian estimation) may affect clinical outcomes in children. PMID:23444282

Population dose commitments due to radioactive releases from nuclear power plant sites in 1987

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

Baker, D.A.

Population radiation dose commitments have been estimated from reported radionuclide releases from commercial power reactors operating during 1987. Fifty-year dose commitments for a one-year exposure from both liquid and atmospheric releases were calculated for four population groups (infant, child, teen-ager and adult) residing between 2 and 80 km from each of 70 reactor sites. This report tabulates the results of these calculations, showing the dose commitments for both water and airborne pathways for each age group and organ. Also included for reach of the sites is a histogram showing the fraction of the total population within 2 to 80 kmmore » around each site receiving various average dose commitments from the airborne pathways. The site average individual dose commitment from all pathways ranged from a low of 2 {times} 10{sup {minus}6} mrem to a high of 0.009 mrem. No attempt was made in this study to determine the maximum dose commitment received by any one individual from the radionuclides released at any of the sites. However, licensee calculation of doses to the maximally exposed individual at some sites indicated values of up to approximately 100 times average individual doses (on the order of a few millirem per year). 2 refs., 2 figs., 7 tabs.« less

The Randomized CRM: An Approach to Overcoming the Long-Memory Property of the CRM

PubMed Central

Koopmeiners, Joseph S.; Wey, Andrew

2017-01-01

The primary object of a phase I clinical trial is to determine the maximum tolerated dose (MTD). Typically, the MTD is identified using a dose-escalation study, where initial subjects are treated at the lowest dose level and subsequent subjects are treated at progressively higher dose levels until the MTD is identified. The continual reassessment method (CRM) is a popular model-based dose-escalation design, which utilizes a formal model for the relationship between dose and toxicity to guide dose-finding. Recently, it was shown that the CRM has a tendency to get “stuck” on a dose-level, with little escalation or de-escalation in the late stages of the trial, due to the long-memory property of the CRM. We propose the randomized CRM (rCRM), which introduces random escalation and de-escalation into the standard CRM dose-finding algorithm, as well as a hybrid approach that incorporates escalation and de-escalation only when certain criteria are met. Our simulation results show that both the rCRM and the hybrid approach reduce the trial-to-trial variability in the number of cohorts treated at the MTD but that the hybrid approach has a more favorable trade-off with respect to the average number treated at the MTD. PMID:28340333