Radiotherapy Dose Fractionation under Parameter Uncertainty
NASA Astrophysics Data System (ADS)
Davison, Matt; Kim, Daero; Keller, Harald
2011-11-01
In radiotherapy, radiation is directed to damage a tumor while avoiding surrounding healthy tissue. Tradeoffs ensue because dose cannot be exactly shaped to the tumor. It is particularly important to ensure that sensitive biological structures near the tumor are not damaged more than a certain amount. Biological tissue is known to have a nonlinear response to incident radiation. The linear quadratic dose response model, which requires the specification of two clinically and experimentally observed response coefficients, is commonly used to model this effect. This model yields an optimization problem giving two different types of optimal dose sequences (fractionation schedules). Which fractionation schedule is preferred depends on the response coefficients. These coefficients are uncertainly known and may differ from patient to patient. Because of this not only the expected outcomes but also the uncertainty around these outcomes are important, and it might not be prudent to select the strategy with the best expected outcome.
Radiotherapy Dose Fractionation under Parameter Uncertainty
Davison, Matt; Kim, Daero; Keller, Harald
2011-11-30
In radiotherapy, radiation is directed to damage a tumor while avoiding surrounding healthy tissue. Tradeoffs ensue because dose cannot be exactly shaped to the tumor. It is particularly important to ensure that sensitive biological structures near the tumor are not damaged more than a certain amount. Biological tissue is known to have a nonlinear response to incident radiation. The linear quadratic dose response model, which requires the specification of two clinically and experimentally observed response coefficients, is commonly used to model this effect. This model yields an optimization problem giving two different types of optimal dose sequences (fractionation schedules). Which fractionation schedule is preferred depends on the response coefficients. These coefficients are uncertainly known and may differ from patient to patient. Because of this not only the expected outcomes but also the uncertainty around these outcomes are important, and it might not be prudent to select the strategy with the best expected outcome.
Normal tissue dose conformality measures to guide radiotherapy fractionation decisions
Myerson, Robert J.
2011-04-15
Purpose: To determine conditions under which hypofractionation could be favorable for a normal tissue--even if tumor [{alpha}/{beta}] exceeds the normal tissue's [{alpha}/{beta}]. Methods: The hypofractionation sufficiency condition (HSC) for an organ is defined as a dose conformality constraint such that, if satisfied, a family of tumor control probability isoeffective fractionation schemes will show decreasing normal tissue complication probability with decreasing number of fractions. Results: In the extended equivalent uniform dose (EUD) model [obtained by replacing dose with linear quadratic (LQ) 2 Gy equivalent dose], the HSC for a normal organ is proven to be satisfied if a suitably weighted average of the relative dose [hypofractionation sufficiency index (HSI)] is less than the ratio of normal tissue to tumor [{alpha}/{beta}]. The HSI is determined solely by dose distribution and the normal tissue volume factor, ''a.'' If the HSC is satisfied for every normal tissue of concern, then there is a therapeutic gain with hypofractionation. The corresponding multifractionation sufficiency condition (therapeutic gain with increasing number of fractions) and multifractionation sufficiency index (MSI) are also derived. A sample clinical case is presented. Conclusions: Within the context of the LQ/EUD models, conformality measures (HSI and MSI) can be used to inform fractionation decisions.
Radiation effect in mouse skin: Dose fractionation and wound healing
Gorodetsky, R.; Mou, X.D.; Fisher, D.R.; Taylor, J.M.; Withers, H.R. )
1990-05-01
Radiation induced dermal injury was measured by the gain in the physical strength of healing wounds in mouse skin. A sigmoid dose response for the inhibition of wound healing 14 days after surgery was found for single doses of X rays. The sparing of dermal damage from fractionation of the X-ray dose was quantified in terms of the alpha/beta ratio in the linear-quadratic (LQ) model, at a wide range of doses per fraction reaching as low as about 1 Gy. The fit and the appropriateness of the LQ model for the skin wound healing assay was examined with the use of the Fe-plot in which inverse total dose is plotted versus dose per fraction for wound strength isoeffects. The alpha/beta ratio of the skin was about 2.5 Gy (95% confidence of less than +/- 1 Gy) and was appropriate over a dose range of 1 Gy to about 8 Gy. The low alpha/beta value is typical for a late responding tissue. This assay, therefore, has the advantage of measuring and forecasting late radiation responses of the dermis within a short time after irradiation.
NASA Astrophysics Data System (ADS)
Tilly, David; Ahnesjö, Anders
2015-07-01
A fast algorithm is constructed to facilitate dose calculation for a large number of randomly sampled treatment scenarios, each representing a possible realisation of a full treatment with geometric, fraction specific displacements for an arbitrary number of fractions. The algorithm is applied to construct a dose volume coverage probability map (DVCM) based on dose calculated for several hundred treatment scenarios to enable the probabilistic evaluation of a treatment plan. For each treatment scenario, the algorithm calculates the total dose by perturbing a pre-calculated dose, separately for the primary and scatter dose components, for the nominal conditions. The ratio of the scenario specific accumulated fluence, and the average fluence for an infinite number of fractions is used to perturb the pre-calculated dose. Irregularities in the accumulated fluence may cause numerical instabilities in the ratio, which is mitigated by regularisation through convolution with a dose pencil kernel. Compared to full dose calculations the algorithm demonstrates a speedup factor of ~1000. The comparisons to full calculations show a 99% gamma index (2%/2 mm) pass rate for a single highly modulated beam in a virtual water phantom subject to setup errors during five fractions. The gamma comparison shows a 100% pass rate in a moving tumour irradiated by a single beam in a lung-like virtual phantom. DVCM iso-probability lines computed with the fast algorithm, and with full dose calculation for each of the fractions, for a hypo-fractionated prostate case treated with rotational arc therapy treatment were almost indistinguishable.
Tilly, David; Ahnesjö, Anders
2015-07-21
A fast algorithm is constructed to facilitate dose calculation for a large number of randomly sampled treatment scenarios, each representing a possible realisation of a full treatment with geometric, fraction specific displacements for an arbitrary number of fractions. The algorithm is applied to construct a dose volume coverage probability map (DVCM) based on dose calculated for several hundred treatment scenarios to enable the probabilistic evaluation of a treatment plan.For each treatment scenario, the algorithm calculates the total dose by perturbing a pre-calculated dose, separately for the primary and scatter dose components, for the nominal conditions. The ratio of the scenario specific accumulated fluence, and the average fluence for an infinite number of fractions is used to perturb the pre-calculated dose. Irregularities in the accumulated fluence may cause numerical instabilities in the ratio, which is mitigated by regularisation through convolution with a dose pencil kernel.Compared to full dose calculations the algorithm demonstrates a speedup factor of ~1000. The comparisons to full calculations show a 99% gamma index (2%/2 mm) pass rate for a single highly modulated beam in a virtual water phantom subject to setup errors during five fractions. The gamma comparison shows a 100% pass rate in a moving tumour irradiated by a single beam in a lung-like virtual phantom. DVCM iso-probability lines computed with the fast algorithm, and with full dose calculation for each of the fractions, for a hypo-fractionated prostate case treated with rotational arc therapy treatment were almost indistinguishable. PMID:26118844
Impact of dose size in single fraction spatially fractionated (grid) radiotherapy for melanoma
Zhang, Hualin E-mail: hualinzhang@yahoo.com; Zhong, Hualiang; Barth, Rolf F.; Cao, Minsong; Das, Indra J.
2014-02-15
Purpose: To evaluate the impact of dose size in single fraction, spatially fractionated (grid) radiotherapy for selectively killing infiltrated melanoma cancer cells of different tumor sizes, using different radiobiological models. Methods: A Monte Carlo technique was employed to calculate the 3D dose distribution of a commercially available megavoltage grid collimator in a 6 MV beam. The linear-quadratic (LQ) and modified linear quadratic (MLQ) models were used separately to evaluate the therapeutic outcome of a series of single fraction regimens that employed grid therapy to treat both acute and late responding melanomas of varying sizes. The dose prescription point was at the center of the tumor volume. Dose sizes ranging from 1 to 30 Gy at 100% dose line were modeled. Tumors were either touching the skin surface or having their centers at a depth of 3 cm. The equivalent uniform dose (EUD) to the melanoma cells and the therapeutic ratio (TR) were defined by comparing grid therapy with the traditional open debulking field. The clinical outcomes from recent reports were used to verify the authors’ model. Results: Dose profiles at different depths and 3D dose distributions in a series of 3D melanomas treated with grid therapy were obtained. The EUDs and TRs for all sizes of 3D tumors involved at different doses were derived through the LQ and MLQ models, and a practical equation was derived. The EUD was only one fifth of the prescribed dose. The TR was dependent on the prescribed dose and on the LQ parameters of both the interspersed cancer and normal tissue cells. The results from the LQ model were consistent with those of the MLQ model. At 20 Gy, the EUD and TR by the LQ model were 2.8% higher and 1% lower than by the MLQ, while at 10 Gy, the EUD and TR as defined by the LQ model were only 1.4% higher and 0.8% lower, respectively. The dose volume histograms of grid therapy for a 10 cm tumor showed different dosimetric characteristics from those of conventional
High dose bystander effects in spatially fractionated radiation therapy
Asur, Rajalakshmi; Butterworth, Karl T.; Penagaricano, Jose A.; Prise, Kevin M.; Griffin, Robert J.
2014-01-01
Traditional radiotherapy of bulky tumors has certain limitations. Spatially fractionated radiation therapy (GRID) and intensity modulated radiotherapy (IMRT) are examples of advanced modulated beam therapies that help in significant reductions in normal tissue damage. GRID refers to the delivery of a single high dose of radiation to a large treatment area that is divided into several smaller fields, while IMRT allows improved dose conformity to the tumor target compared to conventional three-dimensional conformal radiotherapy. In this review, we consider spatially fractionated radiotherapy approaches focusing on GRID and IMRT, and present complementary evidence from different studies which support the role of radiation induced signaling effects in the overall radiobiological rationale for these treatments. PMID:24246848
Single-Dose Versus Fractionated Stereotactic Radiotherapy for Brain Metastases
Kim, Yeon-Joo; Cho, Kwan Ho; Kim, Joo-Young; Lim, Young Kyung; Min, Hye Sook; Lee, Sang Hyun; Kim, Ho Jin; Gwak, Ho Shin; Yoo, Heon; Lee, Seung Hoon
2011-10-01
Purpose: To evaluate the efficacy of stereotactic radiotherapy in patients with brain metastases by comparing two different treatment regimens, single-dose radiosurgery (SRS) and fractionated stereotactic radiotherapy (FSRT). Methods and Materials: Between November 2003 and December 2008, 98 patients with brain metastases were included. Fifty-eight patients were treated with SRS, and forty were treated with FSRT. Fractionated stereotactic radiotherapy was used for large lesions or lesions located near critical structures. The median doses were 20 Gy for the SRS group and 36 Gy in 6 fractions for the FSRT group. Results: With a median follow-up period of 7 months, the median survival was 7 months for all patients, with a median of 6 months for the SRS group and 8 months for the FSRT group (p = 0.89). Local progression-free survival (LPFS) rates at 6 months and 1 year were 81% and 71%, respectively, for the SRS group and 97% and 69%, respectively, for the FSRT group (p = 0.31). Despite the fact that FSRT was used for large lesions and lesions in adverse locations, LPFS was not inferior to SRS. Toxicity was more frequently observed in the SRS group than in the FSRT group (17% vs. 5%, p = 0.05). Conclusions: Because patients treated with FSRT exhibited similar survival times and LPFS rates with a lower risk of toxicity in comparison to those treated with SRS, despite the fact that FSRT was used for large lesions and lesions in adverse locations, we find that FSRT can particularly be beneficial for patients with large lesions or lesions located near critical structures. Further investigation is warranted to determine the optimal dose/fractionation.
Radiation-induced lung damage: dose-time-fractionation considerations.
Van Dyk, J; Mah, K; Keane, T J
1989-01-01
The comparison of different dose-time-fractionation schedules requires the use of an isoeffect formula. In recent years, the NSD isoeffect formula has been heavily criticized. In this report, we consider an isoeffect formula which is specifically developed for radiation-induced lung damage. The formula is based on the linear-quadratic model and includes a factor for overall treatment time. The proposed procedures allow for the simultaneous derivation of an alpha/beta ratio and a gamma/beta time factor. From animal data in the literature, the derived alpha/beta and gamma/beta ratios for acute lung damage are 5.0 +/- 1.0 Gy and 2.7 +/- 1.4 Gy2/day respectively, while for late damage the suggested values are 2.0 Gy and 0.0 Gy2/day. Data from two clinical studies, one prospective and the other retrospective, were also analysed and corresponding alpha/beta and gamma/beta ratios were determined. For the prospective clinical study, with a limited range of doses per fraction, the resultant alpha/beta and gamma/beta ratios were 0.9 +/- 2.6 Gy and 2.6 +/- 2.5 Gy2/day. The combination of the retrospective and prospective data yielded alpha/beta and gamma/beta ratios of 3.3 +/- 1.5 Gy and 2.4 +/- 1.5 Gy2/day, respectively. One potential advantage of this isoeffect formalism is that it might possibly be applied to both acute and late lung damage. The results of this formulation for acute lung damage indicate that time-dependent effects such as slow repair or proliferation might be more important in determining isoeffect doses than previously predicted by the estimated single dose (ED) formula. Although we present this as an alternative approach, we would caution against its clinical use until its applicability has been confirmed by additional clinical data. PMID:2928557
NASA Astrophysics Data System (ADS)
Jordan, K.; Battista, J.
2004-01-01
Investigations of the dose dependent change in optical transmission, dose response, for radiochromic ferrous-xylenol orange-gelatin gels (FXG) 3D optical CT scanning has revealed that gelation time, temperature, and dose fractionation affect the dose response (Δμ/Δdose). Correction for these factors is important for developing a reproducible dosimeter that can be reliably calibrated and used clinically. The purpose of this report is to examine trends in dose response changes for the following parameters: gelation time-temperature, concentrations of ferrous ion and xylenol orange (XO), dose range and dose fractionation.
Paul, Subhadip; Roy, Prasun Kumar
2016-02-01
Radiation therapy is one of the important treatment procedures of cancer. The day-to-day delivered dose to the tissue in radiation therapy often deviates from the planned fixed dose per fraction. This day-to-day variation of radiation dose is stochastic. Here, we have developed the mathematical formulation to represent the day-to-day stochastic dose variation effect in radiation therapy. Our analysis shows that that the fixed dose delivery approximation under-estimates the biological effective dose, even if the average delivered dose per fraction is equal to the planned dose per fraction. The magnitude of the under-estimation effect relies upon the day-to-day stochastic dose variation level, the dose fraction size and the values of the radiobiological parameters of the tissue. We have further explored the application of our mathematical formulation for adaptive dose calculation. Our analysis implies that, compared to the premise of the Linear Quadratic Linear (LQL) framework, the Linear Quadratic framework based analytical formulation under-estimates the required dose per fraction necessary to produce the same biological effective dose as originally planned. Our study provides analytical formulation to calculate iso-effect in adaptive radiation therapy considering day-to-day stochastic dose deviation from planned dose and also indicates the potential utility of LQL framework in this context. PMID:26776265
Dose fractionation theorem in 3-D reconstruction (tomography)
Glaeser, R.M.
1997-02-01
It is commonly assumed that the large number of projections for single-axis tomography precludes its application to most beam-labile specimens. However, Hegerl and Hoppe have pointed out that the total dose required to achieve statistical significance for each voxel of a computed 3-D reconstruction is the same as that required to obtain a single 2-D image of that isolated voxel, at the same level of statistical significance. Thus a statistically significant 3-D image can be computed from statistically insignificant projections, as along as the total dosage that is distributed among these projections is high enough that it would have resulted in a statistically significant projection, if applied to only one image. We have tested this critical theorem by simulating the tomographic reconstruction of a realistic 3-D model created from an electron micrograph. The simulations verify the basic conclusions of high absorption, signal-dependent noise, varying specimen contrast and missing angular range. Furthermore, the simulations demonstrate that individual projections in the series of fractionated-dose images can be aligned by cross-correlation because they contain significant information derived from the summation of features from different depths in the structure. This latter information is generally not useful for structural interpretation prior to 3-D reconstruction, owing to the complexity of most specimens investigated by single-axis tomography. These results, in combination with dose estimates for imaging single voxels and measurements of radiation damage in the electron microscope, demonstrate that it is feasible to use single-axis tomography with soft X-ray microscopy of frozen-hydrated specimens.
Effect of radiation protraction on BED in the case of large fraction dose
Kuperman, V. Y.
2013-08-15
Purpose: To investigate the effect of radiation protraction on biologically effective dose (BED) in the case when dose per fraction is significantly greater than the standard dose of 2 Gy.Methods: By using the modified linear-quadratic model with monoexponential repair, the authors investigate the effect of long treatment times combined with dose escalation.Results: The dependences of the protraction factor and the corresponding BED on fraction time were determined for different doses per fraction typical for stereotactic radiosurgery (SRS) and stereotactic body radiation therapy (SBRT). In the calculations, the authors consider changes in the BED to the normal tissue under the condition of fixed BED to the target.Conclusion: The obtained results demonstrate that simultaneous increase in fraction time and dose per fraction can be beneficial for SRS and SBRT because of the related decrease in BED to normal structures while BED to the target is fixed.
Accelerated heavy particles and the lens. III. Cataract enhancement by dose fractionation
Worgul, B.V.; Merriam, G.R. Jr.; Medvedovsky, C.; Brenner, D.J.
1989-04-01
For a number of biological end points it has been shown that, in contrast to low linear energy transfer (LET) radiation, dose fractionation of high-LET radiation does not result in a reduction in overall effectiveness. Studies were conducted to determine the effect of fractionating the exposures to heavy ion doses on the development of cataracts. Rat eyes were exposed to single doses of 1, 5, and 25 cGy of 570 MeV/amu40Ar ions and to 2, 4, and 10 Gy of 250 kVp X rays. These were compared to unirradiated controls and eyes which were exposed to the same total dose delivered in four fractions over 12 h. While in all cases fractionation of the exposure to X rays produced significant reduction in cataractogenic potential, fractionating doses of 40Ar ions caused a dose- and stage-dependent enhancement in the development of cataracts.
NASA Astrophysics Data System (ADS)
Naveen, T.; Supe, Sanjay S.; Ganesh, K. M.; Samuel, Jacob
2009-01-01
Bone metastases develop in up to 70% of newly diagnosed cancer patients and result in immobility, anxiety, and depression, severely diminishing the patients quality of life. Radiotherapy is a frequently used modality for bone metastasis and has been shown to be effective in reducing metastatic bone pain and in some instances, causing tumor shrinkage or growth inhibition. There is controversy surrounding the optimal fractionation schedule and total dose of external beam radiotherapy, despite many randomized trials and overviews addressing the issue. This study was undertaken to apply BED to clinical fractionation data of radiotherapeutic management of bone metastases in order to arrive at optimum BED values for acceptable level of response rate. A computerised literature search was conducted to identify all prospective clinical studies that addressed the issue of fractionation for the treatment of bone metastasis. The results of these studies were pooled together to form the database for the analysis. A total of 4111 number of patients received radiation dose ranging from 4 to 40.5 Gy in 1 to 15 fractions with dose per fraction ranging from 2 to 10 Gy. Single fraction treatments were delivered in 2013 patients and the dose varied from 4 to 10 Gy. Multifraction treatments were delivered in 2098 patients and the dose varied from 15 to 40.5 Gy. The biological effective dose (BED) was evaluated for each fractionation schedule using the linear quadratic model and an α/β value of 10 Gy. Response rate increased significantly beyond a BED value of 14.4 Gy (p < 0.01). Based on our analysis and indications from the literature about higher retreatment and fracture rate of single fraction treatments, minimum BED value of 14.4 Gy is recommended.
Renal damage in the mouse: the response to very small doses per fraction
Joiner, M.C.; Johns, H.
1988-05-01
Experiments were undertaken to study the effect on the mouse kidney of repeated X-ray doses in the range 0.2 to 1.6 Gy per fraction and neutron doses in the range 0.05 to 0.25 Gy per fraction. A top-up design of experiment was used, so that additional graded doses of d(4)-Be neutrons (EN = 2.3 MeV) were given to bring the subthreshold damage produced by these treatments into the measurable range. This approach avoided the necessity to use a large number of fractions to study low doses per fraction. Renal damage was assessed using three methods: 51Cr-EDTA clearance, urine output, and hematocrit at 16-50 weeks postirradiation. The dose-response curves obtained were resolved best at 29 weeks. However, the results were also examined by fitting second-order polynomials to the data for response versus time postirradiation and using interpolated values from these functions at 29 weeks to construct dose-response curves. This method reduced slightly the variation in the dose-response data, but the interrelationship between the dose-response curves remained the same. The data were used to test the linear-quadratic (LQ) description of the underlying X-ray dose-fractionation relationship. The model fits well down to X-ray doses per fraction of approximately 1 Gy, but lower X-ray doses were more effective per gray than predicted by LQ, as seen previously in skin. This increased X-ray effectiveness and deviation from LQ are reflected directly in a decrease in the RBE of d(4)-Be neutrons relative to X-rays at low doses, since the underlying response to these neutrons is linear in this low-dose region.
The effect of fractionated doses of radiation on mouse spinal cord
Lo, Y.C. Memorial Sloan-Kettering Cancer Center, New York, NY ); Taylor, J.M.G.; McBridge, W.H.; Withers, H.R. )
1993-09-20
The purpose was to determine: (a) the dose-response relationship and latent time to paralysis following fractionated doses of radiation in mice, (b) the values of parameters for isoeffect curves, and (c) whether these parameters depend on the size of dose per fraction and the severity of injury. The spinal cords (T[sub 9]-L[sub 5]) of 608 C[sub 3]Hf/Sed/Kam mice were irradiated with fractionated doses of x-radiation. Three levels of neurological damage were used to grade the spinal cord response. Animals which did not develop paralysis were observed for at least 18 months after irradiation. The fractionated schedules consisted of either 2, 3, 4, 6, 10, or 20 fractions in addition to single doses. For the fractionated regimes the daily fraction size ranged from 2 Gy to 24 Gy, and for single doses the range was 12 Gy to 52 Gy. Both the latent time to paralysis and the incidence of paralysis were considered as endpoints. For analysis of the sparing associated with fractionation, the dose points were divided into two groups: a [open quotes]low damage[close quotes] group consisting of doses of near or less than the ED[sub 50] at 450 days and a [open quotes]high damage[close quotes] group consisting of doses much larger than the ED[sub 50] at 450 days in which there was 100% incidence of paralysis. The latent time depended on the radiation dose; for each fixed fraction number the latent period became progressively shorter with higher total doses. Differences in histology in fractionation sensitivity are observed between the two groups. The low damage data in each fractionation treatment are the important data in the analysis of long-term incidence of paralysis. On the other hand, the high damage data were emphasized for the analysis of latency. Three statistical methods (mixture model, Cox model, and Fe-plot) were used to fit the linear-quadratic dose response model and the [open quotes]Nominal Standard Dose[close quotes] (NSD) model. 29 refs., 4 figs., 5 tabs.
Dose fractionation and single subject studies in PET
NASA Astrophysics Data System (ADS)
Balakrishnan, Karthikayan
Conventional positron emission tomography (PET) for cognitive brain studies typically relies on information collected from the distribution of decays following an injection of 15O-labeled water. The number of injections that can be administered to the subject are constrained by radiation dose to the subject and total length of the PET scan. The standard protocol involves 8--10 injections of H152O separated by approximately 5--7 half-lives of 15O. The number of activation conditions that can be realistically studied in a standard PET session is between 8 and 10. This work investigates the physiological response of a simulated subject to H152O injections that are administered in small doses (1--5 mCi) with short inter-injection intervals (40--180 seconds). A larger number of activation conditions are presented to the subject with a wider variation in the activation paradigm. Repeat conditions are studies. Signal averaging methods are feasible with this method of dose administration. Sinograms from scans with similar activation conditions are summed together before reconstruction. The signal in the primary activation region of the brain is shown to increase while suppressing the contribution of secondary activation regions in the brain. The contrast of the final image is similarly increased which leads to easier identification of the primary activation region. An automated H152O -production unit controlled by a PC running LabView software was developed to produce the dose required for the injection sequence by controlling the flow of H152O -vapor that diffuses across a semi-permeable membrane into saline. The unit is capable of producing H152O rapidly for both the standard and the proposed dose administration methods. The system also detects the bolus arrival time at the subject's lungs using a small external plastic detector. Activation sequence commences with the rise in radioactivity observed by the detector. The simulations indicate that inter-injection intervals
Low or High Fractionation Dose {beta}-Radiotherapy for Pterygium? A Randomized Clinical Trial
Viani, Gustavo Arruda; De Fendi, Ligia Issa; Fonseca, Ellen Carrara; Stefano, Eduardo Jose
2012-02-01
Purpose: Postoperative adjuvant treatment using {beta}-radiotherapy (RT) is a proven technique for reducing the recurrence of pterygium. A randomized trial was conducted to determine whether a low fractionation dose of 2 Gy within 10 fractions would provide local control similar to that after a high fractionation dose of 5 Gy within 7 fractions for surgically resected pterygium. Methods: A randomized trial was conducted in 200 patients (216 pterygia) between February 2006 and July 2007. Only patients with fresh pterygium resected using a bare sclera method and given RT within 3 days were included. Postoperative RT was delivered using a strontium-90 eye applicator. The pterygia were randomly treated using either 5 Gy within 7 fractions (Group 1) or 2 Gy within 10 fractions (Group 2). The local control rate was calculated from the date of surgery. Results: Of the 216 pterygia included, 112 were allocated to Group 1 and 104 to Group 2. The 3-year local control rate for Groups 1 and 2 was 93.8% and 92.3%, respectively (p = .616). A statistically significant difference for cosmetic effect (p = .034), photophobia (p = .02), irritation (p = .001), and scleromalacia (p = .017) was noted in favor of Group 2. Conclusions: No better local control rate for postoperative pterygium was obtained using high-dose fractionation vs. low-dose fractionation. However, a low-dose fractionation schedule produced better cosmetic effects and resulted in fewer symptoms than high-dose fractionation. Moreover, pterygia can be safely treated in terms of local recurrence using RT schedules with a biologic effective dose of 24-52.5 Gy{sub 10.}.
ANALYSIS OF RESPIRATORY DESPOSITION DOSE OF INHALED AMBIENT AEROSOLS FOR DIFFERENT SIZE FRACTIONS
ANALYSIS OF RESPIRATORY DEPOSITION DOSE OF INHALED AMBIENT AEROSOLS FOR DIFFERENT SIZE FRACTIONS. Chong S. Kim, SC. Hu**, PA Jaques*, US EPA, National Health and Environmental Effects Research Laboratory, Research Triangle Park, NC 27711; **IIT Research Institute, Chicago, IL; *S...
Simultaneous optimization of dose distributions and fractionation schemes in particle radiotherapy
Unkelbach, Jan; Zeng, Chuan; Engelsman, Martijn
2013-09-15
Purpose: The paper considers the fractionation problem in intensity modulated proton therapy (IMPT). Conventionally, IMPT fields are optimized independently of the fractionation scheme. In this work, we discuss the simultaneous optimization of fractionation scheme and pencil beam intensities.Methods: This is performed by allowing for distinct pencil beam intensities in each fraction, which are optimized using objective and constraint functions based on biologically equivalent dose (BED). The paper presents a model that mimics an IMPT treatment with a single incident beam direction for which the optimal fractionation scheme can be determined despite the nonconvexity of the BED-based treatment planning problem.Results: For this model, it is shown that a small α/β ratio in the tumor gives rise to a hypofractionated treatment, whereas a large α/β ratio gives rise to hyperfractionation. It is further demonstrated that, for intermediate α/β ratios in the tumor, a nonuniform fractionation scheme emerges, in which it is optimal to deliver different dose distributions in subsequent fractions. The intuitive explanation for this phenomenon is as follows: By varying the dose distribution in the tumor between fractions, the same total BED can be achieved with a lower physical dose. If it is possible to achieve this dose variation in the tumor without varying the dose in the normal tissue (which would have an adverse effect), the reduction in physical dose may lead to a net reduction of the normal tissue BED. For proton therapy, this is indeed possible to some degree because the entrance dose is mostly independent of the range of the proton pencil beam.Conclusions: The paper provides conceptual insight into the interdependence of optimal fractionation schemes and the spatial optimization of dose distributions. It demonstrates the emergence of nonuniform fractionation schemes that arise from the standard BED model when IMPT fields and fractionation scheme are optimized
Storb, R.; Raff, R.F.; Graham, T.; Appelbaum, F.R.; Deeg, H.J.; Schuening, F.G.; Shulman, H.; Pepe, M. )
1993-03-20
The authors explored in dogs the marrow toxicity of single dose total body irradiation delivered from two opposing [sup 60]Co sources at a rate of 10 cGy/min and compared results to those seen with total body irradiation administered in 100 cGy fractions with minimum interfraction intervals of 6 hr. Dogs were not given marrow transplants. They found that 200 cGy single dose total body irradiation was sublethal, with 12 of 13 dogs showing hematopoietic recovery and survival. Seven of 21 dogs given 300 cGy single dose total body irradiation survived compared to 6 of 10 dogs given 300 cGy fractionated total body irradiation. One of 28 dogs given 400 cGy single dose total body irradiation survived compared to none of six given fractionated radiation. With granulocyte colony stimulating factor (GCSF) administered from day 0-21 after 400 cGy total body irradiation, most dogs survived with hematological recovery. Because of the almost uniform success with GCSF after 400 cGy single dose total body irradiation, a study of GCSF after 400 cGy fractionated total body irradiation was deemed not to be informative and, thus, not carried out. Additional comparisons between single dose and fractionated total body irradiation were carried out with GCSF administered after 500 and 600 cGy of total body irradiation. As with lower doses of total body irradiation, no significant survival differences were seen between the two modes of total body irradiation, and only 3 of 26 dogs studied survived with complete hematological recovery. Overall, therefore, survival among dogs given single dose total body irradiation was not different from that of dogs given fractionated total body irradiation (p = .67). Similarly, the slopes of the postirradiation declines of granulocyte and platelet counts and the rates of their recovery in surviving dogs given equal total doses of single versus fractionated total body irradiation were indistinguishable. 24 refs., 3 figs., 2 tabs.
Hardcastle, Nicholas; Bayliss, Adam; Wong, Jeannie Hsiu Ding; Rosenfeld, Anatoly B.; Tome, Wolfgang A.
2012-08-15
Purpose: A recent field safety notice from TomoTherapy detailed the underdosing of small, off-axis targets when receiving high doses per fraction. This is due to angular undersampling in the dose calculation gantry angles. This study evaluates a correction method to reduce the underdosing, to be implemented in the current version (v4.1) of the TomoTherapy treatment planning software. Methods: The correction method, termed 'Super Sampling' involved the tripling of the number of gantry angles from which the dose is calculated during optimization and dose calculation. Radiochromic film was used to measure the dose to small targets at various off-axis distances receiving a minimum of 21 Gy in one fraction. Measurements were also performed for single small targets at the center of the Lucy phantom, using radiochromic film and the dose magnifying glass (DMG). Results: Without super sampling, the peak dose deficit increased from 0% to 18% for a 10 mm target and 0% to 30% for a 5 mm target as off-axis target distances increased from 0 to 16.5 cm. When super sampling was turned on, the dose deficit trend was removed and all peak doses were within 5% of the planned dose. For measurements in the Lucy phantom at 9.7 cm off-axis, the positional and dose magnitude accuracy using super sampling was verified using radiochromic film and the DMG. Conclusions: A correction method implemented in the TomoTherapy treatment planning system which triples the angular sampling of the gantry angles used during optimization and dose calculation removes the underdosing for targets as small as 5 mm diameter, up to 16.5 cm off-axis receiving up to 21 Gy.
Target point correction optimized based on the dose distribution of each fraction in daily IGRT
NASA Astrophysics Data System (ADS)
Stoll, Markus; Giske, Kristina; Stoiber, Eva M.; Schwarz, Michael; Bendl, Rolf
2014-03-01
Purpose: To use daily re-calculated dose distributions for optimization of target point corrections (TPCs) in image guided radiation therapy (IGRT). This aims to adapt fractioned intensity modulated radiation therapy (IMRT) to changes in the dose distribution induced by anatomical changes. Methods: Daily control images from an in-room on-rail spiral CT-Scanner of three head-and-neck cancer patients were analyzed. The dose distribution was re-calculated on each control CT after an initial TPC, found by a rigid image registration method. The clinical target volumes (CTVs) were transformed from the planning CT to the rigidly aligned control CTs using a deformable image registration method. If at least 95% of each transformed CTV was covered by the initially planned D95 value, the TPC was considered acceptable. Otherwise the TPC was iteratively altered to maximize the dose coverage of the CTVs. Results: In 14 (out of 59) fractions the criterion was already fulfilled after the initial TPC. In 10 fractions the TPC can be optimized to fulfill the coverage criterion. In 31 fractions the coverage can be increased but the criterion is not fulfilled. In another 4 fractions the coverage cannot be increased by the TPC optimization. Conclusions: The dose coverage criterion allows selection of patients who would benefit from replanning. Using the criterion to include daily re-calculated dose distributions in the TPC reduces the replanning rate in the analysed three patients from 76% to 59% compared to the rigid image registration TPC.
SU-E-T-511: Do Presage 3D Dosimeters Show Dose Fractionation Sensitivity?
Klawikowski, S; Alqathami, M; Ibbott, G; Adamovics, J; Benning, R
2014-06-01
Purpose: To determine whether Presage 3D polymer dosimeter dose response is sensitive to dose delivery fractionation. Bang gels have demonstrated a dose fractionation related dependence in which a single 400 cGy irradiation would produce a different detector response than four 100 cGy irradiations even if delivered closely in time to one another. Such a fractional dependent response in Presage would be detrimental for measuring multi-beam irradiations. Methods: Two separate batches of Presage were poured into cuvettes, and a third batch was molded into cuvette shaped blocks. A total of 37 cuvettes/blocks were irradiated in a Cobalt-60 irradiator to 400 cGy within solid water phantoms in either one, eight, or sixteen fractions. Another group of 15 cuvettes were also kept unirradiated and used for background subtraction between the pre-scan and post-scan results. The times between fractional deliveries were held constant at 30 seconds and the Cobalt irradiator dose rate was 49 cGy/min. Each Presage batch has a separate dose sensitivity and therefore fractionation response comparisons were only performed within the same batch. The cuvettes were first pre-scanned the day prior to irradiation and post-scanned the day after irradiation. Other than approximately 3 hours warming time prior to each irradiation and optical density measurement the cuvettes were stored in a refrigerator. All cuvettes were stored in a lightless environment throughout manufacturing and testing. The cuvettes’ optical densities were optically measured at 632 nm with a spectrophotometer. Results: No noticeable dose fractionation dependence was detected for any of the three independent batches of Presage for either the eight or sixteen fraction irradiation schemes. Conclusion: These results indicate using Presage 3D dosimeters to measure multi-beam photon irradiations common in IMRT, Gamma Knife, and Cyberknife treatment delivery schemes. Presage dosimeters are made by and trademarked by Heuris
Recalculation of dose for each fraction of treatment on TomoTherapy
Romanchikova, Marina; Harrison, Karl; Parker, Michael A; Bates, Amy M; Scaife, Jessica E; Sutcliffe, Michael PF; Burnet, Neil G
2016-01-01
Objective: The VoxTox study, linking delivered dose to toxicity requires recalculation of typically 20–37 fractions per patient, for nearly 2000 patients. This requires a non-interactive interface permitting batch calculation with multiple computers. Methods: Data are extracted from the TomoTherapy® archive and processed using the computational task-management system GANGA. Doses are calculated for each fraction of radiotherapy using the daily megavoltage (MV) CT images. The calculated dose cube is saved as a digital imaging and communications in medicine RTDOSE object, which can then be read by utilities that calculate dose–volume histograms or dose surface maps. The rectum is delineated on daily MV images using an implementation of the Chan–Vese algorithm. Results: On a cluster of up to 117 central processing units, dose cubes for all fractions of 151 patients took 12 days to calculate. Outlining the rectum on all slices and fractions on 151 patients took 7 h. We also present results of the Hounsfield unit (HU) calibration of TomoTherapy MV images, measured over an 8-year period, showing that the HU calibration has become less variable over time, with no large changes observed after 2011. Conclusion: We have developed a system for automatic dose recalculation of TomoTherapy dose distributions. This does not tie up the clinically needed planning system but can be run on a cluster of independent machines, enabling recalculation of delivered dose without user intervention. Advances in knowledge: The use of a task management system for automation of dose calculation and outlining enables work to be scaled up to the level required for large studies. PMID:26728661
Park, Shin-Hyung; Kim, Jae-Chul
2016-01-01
Purpose: The standard radiation dose for patients with locally rectal cancer treated with preoperative chemoradiotherapy is 45–50 Gy in 25–28 fractions. We aimed to assess whether a difference exists within this dose fractionation range. Materials and Methods: A retrospective analysis was performed to compare three dose fractionation schedules. Patients received 50 Gy in 25 fractions (group A), 50.4 Gy in 28 fractions (group B), or 45 Gy in 25 fractions (group C) to the whole pelvis, as well as concurrent 5-fluorouracil. Radical resection was scheduled for 8 weeks after concurrent chemoradiotherapy. Results: Between September 2010 and August 2013, 175 patients were treated with preoperative chemoradiotherapy at our institution. Among those patients, 154 were eligible for analysis (55, 50, and 49 patients in groups A, B, and C, respectively). After the median follow-up period of 29 months (range, 5 to 48 months), no differences were found between the 3 groups regarding pathologic complete remission rate, tumor regression grade, treatment-related toxicity, 2-year locoregional recurrence-free survival, distant metastasis-free survival, disease-free survival, or overall survival. The circumferential resection margin width was a prognostic factor for 2-year locoregional recurrence-free survival, whereas ypN category was associated with distant metastasis-free survival, disease-free survival, and overall survival. High tumor regression grading score was correlated with 2-year distant metastasis-free survival and disease-free survival in univariate analysis. Conclusion: Three different radiation dose fractionation schedules, within the dose range recommended by the National Comprehensive Cancer Network, had no impact on pathologic tumor regression and early clinical outcome for locally advanced rectal cancer. PMID:27306773
Comparative assessment of single-dose and fractionated boron neutron capture therapy
Coderre, J.A.; Micca, P.L.; Fisher, C.D.
1995-12-01
The effects of fractionating boron neutron capture therapy (BNCT) were evaluated in the intracerebral rat 9L gliosarcoma and rat spinal cord models using the Brookhaven Medical Research Reactor (BMRR) thermal neutron beam. The amino acid analog p-boronophenylalanine (BPA) was administered prior to each exposure to the thermal neutron beam. The total physical absorbed dose to the tumor during BNCT using BPA was 91% high-linear energy transfer (LET) radiation. Two tumor doses of 5.2 Gy spaced 48 h apart (n = 14) or three tumor doses of 5.2 Gy, each separated by 48 h (n = 10), produced 50 and 60% long-term (>1 year) survivors, respectively. The outcome of neither the two nor the three fractions of radiation was statistically different from that of the corresponding single-fraction group. In the rat spinal cord, the ED{sub 50} for radiation myelopathy (as indicated by limb paralysis within 7 months) after exposure to the thermal beam alone was 13.6 {+-} 0.4 Gy. Dividing the beam-only irradiation into two or four consecutive daily fractions increased the ED{sub 50} to 14.7 {+-} 0.2 Gy and 15.5 {+-} 0.4 Gy, respectively. Thermal neutron irradiation in the presence of BPA resulted in an ED{sub 50} for myelopathy of 13.8 {+-} 0.6 Gy after a single fraction and 14.9 {+-} 0.9 Gy after two fractions. An increase in the number of fractions to four resulted in an ED{sub 50} of 14.3 {+-} 0.6 Gy. The total physical absorbed dose to the blood in the vasculature of the spinal cord during BNCT using BPA was 80% high-LET radiation. It was observed that fractionation was of minor significance in the amelioration of damage to the normal central nervous system in the rat after boron neutron capture irradiation. 30 refs., 5 figs., 3 tabs.
Somnolence syndrome in leukemic children following reduced daily dose fractions of cranial radiation
Littman, P.; Rosenstock, J.; Gale, G.; Krisch, R.E.; Meadows, A.; Sather, H.; Coccia, P.; DeCamagro, B.
1984-10-01
A group of children with acute lymphocytic leukemia was studied to investigate if a reduction in daily dose fraction of cranial radiation would reduce the incidence of somnolence syndrome. Thirty-one evaluable patients received 100 rad x 18 cranial radiation therapy. Sixty-six similar evaluable patients were given 180 rad x 10. Both groups received the same chemotherapy including intrathecal methotrexate. Clinically detectable somnolence appeared in 58% of each group without significant differences in the overall frequency or severity of somnolence. This study failed to substantiate a radiation dose fraction size dependence for somnolence syndrome in children with acute lymphocytic leukemia.
Comparison of particle lung doses from the fine and coarse fractions of urban PM-10 aerosols.
Venkataraman, C; Kao, A S
1999-02-01
The U.S. Environmental Protection Agency (EPA) recently revised the national ambient air quality standards to include a new PM-2.5 particulate standard. We examine the contributions of fine (PM-2.5) and coarse (PM-2.5 to -10) fraction of typical urban aerosols to particle doses in different lung airways resulting from 24-h exposure to the standard concentration of 150 microg m-3. The aerosol is assumed to have a bimodal lognormal mass distribution with mass median diameters of 0.2 and 5 microm, and geometric standard deviation of 1.7 and 57% of the mass in the fine (PM-2.5) mode. The daily mass dose from exposure to 150 microg m-3 of PM-10 in the nasopharyngeal (NPL) region is 20-51 microg day-1 (1.5% of inhaled fines) and 377-687 microg day-1 (30% of inhaled coarse), respectively, of fine and coarse mass filtered in the nose. Similar daily mass doses from fine and coarse fractions, respectively, to the tracheobronchial (TBL) region are 28-38 (1.5%) and 40-52 (4%) microg day-1 and to the pulmonary (PUL) region are 18-194 (6%) and 32-55 microg day-1 (2%). The daily number dose in the NPL region is 5-15 x 10(8) (0.06% of inhaled fines) and 5-10 x 10(6) day-1 (13% of inhaled coarse) respectively, of fine and coarse particles. Similar number doses to the TBL region are 2.2-3.1 x 10(10) (2%) and 7.1-11. 1 x 10(5) (2%) day-1 and to the PUL region are 1.6-16.7 x 10(10) (9%) and 2.9-17.0 x 10(5) (3%) day-1. The daily surface mass dose (microg cm-2 day-1) from coarse fraction particles is large in generations 3-5. The daily number dose (particles day-1) and surface number dose (particles cm-2 day-1) are higher from the fine than the coarse fraction, by about 10(3) to 10(5) times in all lung airways. Fine fraction particles result in 10,000 times greater particle number dose per macrophage than coarse fraction particles. Particle number doses do not follow trends in mass doses, are much larger from fine than coarse fraction, and must be considered in assessing PM health
Uzan, J; Nahum, A E
2012-01-01
Objective Radiobiological models provide a means of evaluating treatment plans. Keeping in mind their inherent limitations, they can also be used prospectively to design new treatment strategies which maximise therapeutic ratio. We propose here a new method to customise fractionation and prescription dose. Methods To illustrate our new approach, two non-small cell lung cancer treatment plans and one prostate plan from our archive are analysed using the in-house software tool BioSuite. BioSuite computes normal tissue complication probability and tumour control probability using various radiobiological models and can suggest radiobiologically optimal prescription doses and fractionation schemes with limited toxicity. Results Dose–response curves present varied aspects depending on the nature of each case. The optimisation process suggests doses and fractionation schemes differing from the original ones. Patterns of optimisation depend on the degree of conformality, the behaviour of the normal tissue (i.e. “serial” or “parallel”), the volume of the tumour and the parameters of clonogen proliferation. Conclusion Individualising the prescription dose and number of fractions with the help of BioSuite results in improved therapeutic ratios as evaluated by radiobiological models. PMID:22457318
Dale, R G
1990-04-01
Using commonly assumed alpha/beta ratios for tumours and late-reacting tissues, the linear-quadratic (LQ) model has been used to compare low dose-rate (LDR) gynaecological treatment with high dose-rate (HDR) techniques given in small fraction numbers. Even in the absence of relatively favourable tissue recovery constants (mu values) it is shown that, provided a modest extra amount of geometrical sparing of critical tissues is available (by means of spacing or shielding), HDR treatment in a small number of fractions may be used in place of an LDR regime without loss of therapeutic ratio. This general result, although not universally true, does indicate that HDR treatment delivered in a small number of fractions may be more feasible than is sometimes thought. These findings do not contradict currently accepted radiobiological philosophy, which cautions against the use of small numbers of high-dose fractions. Primarily they serve to emphasize the importance of the recommendations of the ICRU (1985), which stress the need to consider the complete time-dose pattern of radiation delivery to all the critical tissues in an intracavitary treatment. PMID:2346867
Deeg, H.J.; Flournoy, N.; Sullivan, K.M.; Sheehan, K.; Buckner, C.D.; Sanders, J.E.; Storb, R.; Witherspoon, R.P.; Thomas, E.D.
1984-07-01
Two hundred seventy-seven patients, who have been followed for 1 to 12 years after marrow transplantation, have been examined for cataract development. In preparation for transplantation, 96 patients with aplastic anemia were conditioned with chemotherapy only, while 181 patients (two with aplastic anemia and 179 with a hematologic malignancy) were conditioned with a regimen of total body irradiation (TBI) and chemotherapy. TBI was delivered from two opposing /sup 60/Co sources at an exposure rate of 4 to 8 cGy/min, either as a single dose of 10 Gy (105 patients) or in fractions (76 patients). To date, 86 patients have developed cataracts. Kaplan-Meier product limit estimates of the incidence of cataracts for patients given chemotherapy only and no TBI, single-dose TBI, and fractionated TBI are 19, 80, 18%, respectively. On the basis of proportional hazards regression analyses, patients given single-dose TBI had a relative risk of developing cataracts that was 4.7-fold higher than in patients given fractionated TBI or chemotherapy only, suggesting a significant sparing effect with use of TBI dose fractionation.
Edmondson, Elijah F.; Hunter, Nancy R.; Weil, Michael M.; Mason, Kathryn A.
2015-01-01
Purpose To investigate differences in tumor histotype, incidence, latency, and strain susceptibility in mice exposed to single dose or clinically relevant, fractioned dose γ-ray radiation. Methods C3Hf/Kam and C57BL/6J mice were locally irradiated to the right hindlimb with either single large doses between 10 and 70 Gray (Gy) or fractionated doses totaling 40 to 80 Gy delivered at 2 Gy/day fractions, 5 days/week, for 4 to 8 weeks. The mice were closely evaluated for tumor development in the irradiated field for 800 days following irradiation and all tumors were characterized histologically. Results A total of 210 tumors were induced within the radiation field in 788 mice. An overall decrease in tumor incidence was observed following fractionated irradiation (16.4%) in comparison to single dose irradiation (36.1%). Sarcomas were the predominant post-irradiation tumor observed (n = 201) with carcinomas occurring less frequently (n = 9). The proportion of mice developing tumors increased significantly with total dose for both single dose and fractionated schedules and latencies were significantly decreased in mice exposed to larger total doses. C3Hf/Kam mice were more susceptible to tumor induction than C57BL/6J mice following single dose irradiation, however, significant differences in tumor susceptibilities following fractionated radiation were not observed. For both strains of mice, osteosarcomas and hemangiosarcomas were significantly more common following fractionated irradiation whereas fibrosarcomas and malignant fibrous histiocytomas were significantly more common following single dose irradiation. Conclusions This study investigated the tumorigenic effect of acute large doses in comparison to fractionated radiation in which both the dose and delivery schedule were similar to those used in clinical radiotherapy. Differences in tumor histotype following single dose or fractionated radiation exposures provides novel in vivo evidence for differences in tumor
Edmondson, Elijah F.; Hunter, Nancy R.; Weil, Michael M.; Mason, Kathryn A.
2015-07-15
Purpose: To investigate differences in tumor histotype, incidence, latency, and strain susceptibility in mice exposed to single-dose or clinically relevant, fractioned-dose γ-ray radiation. Methods and Materials: C3Hf/Kam and C57BL/6J mice were locally irradiated to the right hindlimb with either single large doses between 10 and 70 Gy or fractionated doses totaling 40 to 80 Gy delivered at 2-Gy/d fractions, 5 d/wk, for 4 to 8 weeks. The mice were closely evaluated for tumor development in the irradiated field for 800 days after irradiation, and all tumors were characterized histologically. Results: A total of 210 tumors were induced within the radiation field in 788 mice. An overall decrease in tumor incidence was observed after fractionated irradiation (16.4%) in comparison with single-dose irradiation (36.1%). Sarcomas were the predominant postirradiation tumor observed (n=201), with carcinomas occurring less frequently (n=9). The proportion of mice developing tumors increased significantly with total dose for both single-dose and fractionated schedules, and latencies were significantly decreased in mice exposed to larger total doses. C3Hf/Kam mice were more susceptible to tumor induction than C57BL/6J mice after single-dose irradiation; however, significant differences in tumor susceptibilities after fractionated radiation were not observed. For both strains of mice, osteosarcomas and hemangiosarcomas were significantly more common after fractionated irradiation, whereas fibrosarcomas and malignant fibrous histiocytomas were significantly more common after single-dose irradiation. Conclusions: This study investigated the tumorigenic effect of acute large doses in comparison with fractionated radiation in which both the dose and delivery schedule were similar to those used in clinical radiation therapy. Differences in tumor histotype after single-dose or fractionated radiation exposures provide novel in vivo evidence for differences in tumor
NASA Astrophysics Data System (ADS)
Popović, Jovan K.; Spasić, Dragan T.; Tošić, Jela; Kolarović, Jovanka L.; Malti, Rachid; Mitić, Igor M.; Pilipović, Stevan; Atanacković, Teodor M.
2015-05-01
The aim of this study is to promote a model based on the fractional differential calculus related to the pharmacokinetic individualization of high dose methotrexate treatment in children with acute lymphoblastic leukaemia, especially in high risk patients. We applied two-compartment fractional model on 8 selected cases with the largest number (4-19) of measured concentrations, among 43 pediatric patients received 24-h methotrexate 2-5 g/m2 infusions. The plasma concentrations were determined by fluorescence polarization immunoassay. Our mathematical procedure, designed by combining Post's and Newton's method, was coded in Mathematica 8.0 and performed on Fujicu Celsius M470-2 PC. Experimental data show that most of the measured values of methotrexate were in decreasing order. However, in certain treatments local maximums were detected. On the other hand, integer order compartmental models do not give values which fit well with the observed data. By the use of our model, we obtained better results, since it gives more accurate behavior of the transmission, as well as the local maximums which were recognized in methotrexate monitoring. It follows from our method that an additional test with a small methotrexate dose can be suggested for the fractional system parameter identification and the prediction of a possible pattern with a full dose in the case of high risk patients. A special feature of the fractional model is that it can also recognize and better fit an observed non-monotonic behavior. A new parameter determination procedure can be successfully used.
NASA Astrophysics Data System (ADS)
Kim, M.; Ghate, A.; Phillips, M. H.
2009-07-01
The current state of the art in cancer treatment by radiation optimizes beam intensity spatially such that tumors receive high dose radiation whereas damage to nearby healthy tissues is minimized. It is common practice to deliver the radiation over several weeks, where the daily dose is a small constant fraction of the total planned. Such a 'fractionation schedule' is based on traditional models of radiobiological response where normal tissue cells possess the ability to repair sublethal damage done by radiation. This capability is significantly less prominent in tumors. Recent advances in quantitative functional imaging and biological markers are providing new opportunities to measure patient response to radiation over the treatment course. This opens the door for designing fractionation schedules that take into account the patient's cumulative response to radiation up to a particular treatment day in determining the fraction on that day. We propose a novel approach that, for the first time, mathematically explores the benefits of such fractionation schemes. This is achieved by building a stylistic Markov decision process (MDP) model, which incorporates some key features of the problem through intuitive choices of state and action spaces, as well as transition probability and reward functions. The structure of optimal policies for this MDP model is explored through several simple numerical examples.
Single high-dose vs. fractionated radiotherapy: Effects on plant growth rates
Guedea, Marc; Castel, Antoni; Arnalte, Marc; Mollera, Alex; Muñoz, Victor; Guedea, Ferran
2013-01-01
Aim To evaluate the differential effects of fractionated vs. high-dose radiotherapy on plant growth. Background Interest in hypofractionated radiotherapy has increased substantially in recent years as tumours (especially of the lung, prostate, and liver) can be irradiated with ever greater accuracy due to technological improvements. The effects of low-dose ionizing radiation on plant growth have been studied extensively, yet few studies have investigated the effect of high-dose, hypofractionated radiotherapy on plant growth development. Materials and methods A total of 150 plants from the genus Capsicum annuum were randomized to receive fractionated radiotherapy (5 doses of 10 Gy each), single high-dose (SHD) radiotherapy (single 50 Gy dose), or no radiotherapy (control group). Irradiation was delivered via linear accelerator and all samples were followed daily for 26 days to assess and compare daily growth. Results On day 26, plants in the control, fractionated, and SHD groups had grown to a mean height of 7.55 cm, 4.32 cm, and 2.94 cm, respectively. These differences in overall growth were highly significant (P = 0.005). The SHD group showed the least amount of growth. Conclusions SHD effectively stunts plant growth and development. Despite the evident differences between plant and animal cells, ionizing radiation is believed to work in a similar manner in all biological cells. These findings highlight the need to continue investigating the use of hypofractionated schemes in humans to improve cancer treatment outcomes. PMID:24416565
Kaprealian, Tania; Weinberg, Vivian; Speight, Joycelyn L.; Gottschalk, Alexander R.; Roach, Mack; Shinohara, Katsuto; Hsu, I.-Chow
2012-01-01
Purpose: This is a retrospective study comparing our experience with high-dose-rate (HDR) brachytherapy boost for prostate cancer, using two different fractionation schemes, 600 cGy Multiplication-Sign 3 fractions (patient group 1) and 950 cGy Multiplication-Sign 2 fractions (patient group 2). Methods and Materials: A total of 165 patients were treated for prostate cancer using external beam radiation therapy up to a dose of 45 Gy, followed by an HDR brachytherapy prostate radiation boost. Between July 1997 and Nov 1999, 64 patients were treated with an HDR boost of 600 cGy Multiplication-Sign 3 fractions; and between June 2000 and Nov 2005, 101 patients were treated with an HDR boost of 950 cGy Multiplication-Sign 2 fractions. All but 9 patients had at least one of the following risk features: pretreatment prostate-specific antigen (PSA) level >10, a Gleason score {>=}7, and/or clinical stage T3 disease. Results: Median follow-up was 105 months for group 1 and 43 months for group 2. Patients in group 2 had a greater number of high-risk features than group 1 (p = 0.02). Adjusted for comparable follow-up, there was no difference in biochemical no-evidence-of-disease (bNED) rate between the two fractionation scheme approaches, with 5-year Kaplan-Meier estimates of 93.5% in group 1 and 87.3% in group 2 (p = 0.19). The 5-year estimates of progression-free survival were 86% for group 1 and 83% for group 2 (p = 0.53). Among high-risk patients, there were no differences in bNED or PFS rate due to fractionation. Conclusions: Results were excellent for both groups. Adjusted for comparable follow-up, no differences were found between groups.
Response of rat spinal cord to single and fractionated doses of accelerated heavy ions
Leith, J.T.; McDonald, M.; Powers-Risius, P.; Bliven, S.F.; Howard, J.
1982-01-01
The thoraco-lumbar (T12-L1) region of the spinal cord of rats was exposed to either single or fractionated (four daily exposures) doses of X rays (230 kVp) or heavy ions. The heavy ions used were carbon and neon, and the relative biological effectiveness (RBE) of both the plateau ionization region and the midpeak region of 4-cm spread-out Bragg peaks of each heavy ion were investigated. For single doses of carbon and neon ions in the plateau ionization region, RBE values of 1.45 +/- 0.25 (propagated 95% confidence limits) and 1.46 +/- 0.33, respectively, were obtained. In the spread peak regions for carbon and neon ions, the RBE values were 1.48 +/- 0.18 and 1.86 +/- 0.42, respectively. These values were obtained using the dose needed to produce 50% paralysis in a group of irradiated rats as the isoeffect comparison dose (ED/sub 50/ dose). Similarly, in groups of rats receiving four daily exposures, the RBE values for carbon and neon ions in the plateau ionization region were 1.31 +/- 0.27 and 1.80 +/- 0.24, respectively. In the spread peak regions of ionization for carbon and neon ions, the RBE values were 1.95 +/- 0.19 and 2.18 +/- 0.23, respectively. Similar values for RBE were obtained using changes in the activity of enzymes in spinal cord tissue (cyclic nucleotide phosphohydrolase and ..gamma..-glutamyl transpeptidase). Also, it was estimated that, for X irradiation, the fractional amount of dose repaired (at the ED/sub 50/ dose) was 0.64 +/- 0.10 (95% confidence limits). For carbon and neon ions in the plateau ionization region, the values for the fractional amount of dose repaired were 0.70 +/- 0.27 and 0.48 +/- 0.20, and for carbon and neon ions in the spread peak region of ionization, the fractional repair values were 0.40 +/- 0.10 and 0.52 +/- 0.17. Spinal cord tissue therefore shows a high capacity for subeffective damage repair, and even at the highest LET investigated (neon ions in
Functional and morphological changes in pig skin after single or fractionated doses in x rays
Young, C.M.A.; Hopewell, J.W.
1982-09-01
The flank skin of pigs has been treated with either single or fractionated doses of x-irradiation. A single dose (2070 cGy) was compared with treatment given as 6 fractions in 18 days (6f/18 days; 3780 cGy) or 30 fractions in 39 days (30f/39 days; 8000 cGy). The doses were selected on the basis that similar levels of late tissue damage would result. Radiation induced changes in the skin were assessed by observing the skin reactions and by the measurement of isotope clearance (functional study), relative field contraction, dermal and epidermal thickness and dermal vascular density (morphological studies). In the three treatment groups the early radiation reaction varied considerably. In the first wave reaction (3 to 6 weeks after treatment) bright red erythema was recorded in many fields but moist desquamation developed only in the 30f/39 days treatment group. The second wave (10-16 weeks) was characterized by an ischemic mauve/dusky reaction. Dermal necrosis developed in 50% of the single dose fields. In the 30f/39 days regimen persistent moist desquamation progressed to dermal necrosis. Neither desquamation nor necrosis developed after 6f/18 days. Different levels of vascular damage in the dermis were assessed using an isotope clearance technique; for example in the early reaction significant changes were recorded in the papillary dermis (faster clearance) prior to the development of moist desquamation (30f/39 days) and in the reticular dermis (slower clearance) before necrosis (single dose). Changes in clearance rates have been correlated with changes in the vascular density and thickness of the dermis. Between 26 and 52 weeks (the late reaction) relative field contraction was slightly greater in the 30f/39 days group than in the other treatment groups.
Kamen, B.A.; Moulder, J.E.; Kun, L.E.; Ring, B.J.; Adams, S.M.; Fish, B.L.; Holcenberg, J.S.
1984-11-01
The effects of single-dose and fractionated whole-brain irradiation on brain methotrexate (MTX) has been studied in a rat model. The amount of MTX present in the brain 24 hr after a single i.p. dose (100 mg/kg) was the same whether animals were sham irradiated or given a single dose of 2000 rads 6 or 48 hr prior to the drug (6.9, 8.3, and 6.8 pmol MTX/g, wet weight, respectively). Animals sham irradiated or given 2000 rads in 10 fractions over 11 days and treated with an average dose of 1.2 mg MTX/kg i.p. twice a week for 24 weeks did not differ significantly in their brain MTX concentration (7.9 and 8.3 pmol MTX/g, wet weight, respectively). Chronically MTX-treated animals became folate deficient whether they were irradiated or not (450 and 670 pmol folate/g, wet weight, brain in MTX-treated and control animals). Thus, MTX accumulates in the brain with acute or chronic administration, and this accumulation is not altered by this amount of brain irradiation.
Bedi, Meena; Firat, Selim; Semenenko, Vladimir A.; Schultz, Christopher; Tripp, Patrick; Byhardt, Roger; Wang, Dian
2012-05-01
Purpose: Intensity-modulated radiation therapy (IMRT) is the standard of care for head-and-neck cancer (HNC). We treated patients with HNC by delivering either a moderate hypofractionation (MHF) schedule (66 Gy at 2.2 Gy per fraction to the gross tumor [primary and nodal]) with standard dose fractionation (54-60 Gy at 1.8-2.0 Gy per fraction) to the elective neck lymphatics or a conventional dose and fractionation (CDF) schedule (70 Gy at 2.0 Gy per fraction) to the gross tumor (primary and nodal) with reduced dose to the elective neck lymphatics. We analyzed these two cohorts for treatment outcomes. Methods and Materials: Between November 2001 and February 2009, 89 patients with primary carcinomas of the oral cavity, larynx, oropharynx, hypopharynx, and nasopharynx received definitive IMRT with or without concurrent chemotherapy. Twenty patients were treated using the MHF schedule, while 69 patients were treated with the CDF schedule. Patient characteristics and dosimetry plans were reviewed. Patterns of failure including local recurrence (LR), regional recurrence (RR), distant metastasis (DM), disease-free survival (DFS), overall survival (OS), and toxicities, including rate of feeding tube placement and percentage of weight loss, were reviewed and analyzed. Results: Median follow-up was 31.2 months. Thirty-five percent of patients in the MHF cohort and 77% of patients in the CDF cohort received chemotherapy. No RR was observed in either cohort. OS, DFS, LR, and DM rates for the entire group at 2 years were 89.3%, 81.4%, 7.1%, and 9.4%, respectively. Subgroup analysis showed no significant differences in OS (p = 0.595), DFS (p = 0.863), LR (p = 0.833), or DM (p = 0.917) between these two cohorts. Similarly, no significant differences were observed in rates of feeding tube placement and percentages of weight loss. Conclusions: Similar treatment outcomes were observed for MHF and CDF cohorts. A dose of 50 Gy at 1.43 Gy per fraction may be sufficient to electively
Fields, Emma C.; Damek, Denise; Gaspar, Laurie E.; Liu, Arthur K.; Kavanagh, Brian D.; Waziri, Allen; Lillehei, Kevin; Chen, Changhu
2012-01-01
Purpose: To determine the maximum tolerated dose (MTD) of vandetanib with fractionated stereotactic radiosurgery (SRS) in patients with recurrent malignant gliomas. Methods and Materials: Patients with a recurrent malignant glioma and T1-enhancing recurrent tumor {<=}6 cm were eligible. Vandetanib was given orally, once per day, 7 days a week, starting at least 7 days before SRS and continued until a dose-limiting toxicity (DLT) or disease progression. The planned vandetanib daily dose was 100 mg, 200 mg, and 300 mg for the cohorts 1, 2, and 3, respectively, and was escalated using a standard 3+3 design. A total SRS dose of 36 Gy, 12 Gy per fraction, was delivered over 3 consecutive days. The MTD was defined as the dose of vandetanib at which less than 33% of patients developed DLTs, defined by the Common Terminology Criteria for Adverse Events (CTCAE) version 3 as any Grade 3 or greater nonhematologic toxicity and Grade 4 or greater hematologic toxicity. Results: Ten patients were treated, 6 on cohort 1 and 4 on cohort 2. Treatment characteristics were: 7 men, 3 women; median age, 40 years (range, 22-72); 7 GBM, 3 anaplastic astrocytoma (AA); median initial radiation (RT) dose, 60 Gy (range, 59.4-70); median interval since initial RT, 14.5 months (range, 7-123); All patients received SRS per protocol. The median follow-up time was 4 months (range, 1-10 months). Median time on vandetanib was 3 months (range 1-11). One of 6 patients in the first cohort developed a DLT of Grade 3 hemothorax while on anticoagulation. The MTD was reached when 2 of the 4 patients enrolled in the second cohort developed DLTs. Six patients had radiographic response, 2 with stable disease. Conclusion: The MTD of vandetanib, with SRS in recurrent malignant glioma, is 100 mg daily. Further evaluation of safety and efficacy is warranted.
Estimation of dose absorbed fraction for 131I-beta rays in rat thyroid.
Endo, S; Nitta, Y; Ohtaki, M; Takada, J; Stepanenko, V; Komatsu, K; Tauchi, H; Matsuura, S; Iaskova, E; Hoshi, M
1998-09-01
The dose absorbed fraction of rat thyroid by internal deposit of 131I has been calculated as a function of effective diameter of thyroid. The calculations were done using two types of Monte Carlo simulations: one was by a simple energy-loss calculation in spherical volume according to the electron stopping power, and another by a more realistic simulation using Monte Carlo N-Particle Transport code system Version 4A (MCNP). These two calculations were consistent with each other within a deviation of 5%. The absorbed fractions in spherical thyroid were drastically changed up to 5 mm diameter, and then almost all energy was deposited within 10 mm diameter. For the practical application to the animal experiment, the absorbed fractions of ellipsoid-shaped thyroids were also calculated for 1-, 4- and 9-week-old rats, where the fractions were estimated to be 0.61, 0.67 and 0.68, respectively. It was also found that the absorbed fraction of the ellipsoid with various dimensions can be simulated by a calculation for spherical volume with a comparable effective diameter. PMID:9868871
Uncertainties in electron-absorbed fractions and lung doses from inhaled beta-emitters.
Farfán, Eduardo B; Bolch, Wesley E; Huston, Thomas E; Rajon, Didier A; Huh, Chulhaeng; Bolch, W Emmett
2005-01-01
The computer code LUDUC (Lung Dose Uncertainty Code), developed at the University of Florida, was originally used to investigate the range of potential doses from the inhalation of either plutonium or uranium oxides. The code employs the ICRP Publication 66 Human Respiratory Tract model; however, rather than using simple point estimates for each of the model parameters associated with particle deposition, clearance, and lung-tissue dosimetry, probability density functions are ascribed to these parameters based upon detailed literature review. These distributions are subsequently sampled within LUDUC using Latin hypercube sampling techniques to generate multiple (e.g., approximately 1,000) sets of input vectors (i.e., trials), each yielding a unique estimate of lung dose. In the present study, the dosimetry component of the ICRP-66 model within LUDUC has been extended to explicitly consider variations in the beta particle absorbed fraction due to corresponding uncertainties and biological variabilities in both source and target tissue depths and thicknesses within the bronchi and bronchioles of the thoracic airways. Example dose distributions are given for the inhalation of absorption Type S compounds of 90Sr (Tmax = 546 keV) and 90Y (Tmax = 2,284 keV) as a function of particle size. Over the particle size range of 0.001 to 1 microm, estimates of total lung dose vary by a factor of 10 for 90Sr particles and by a factor of 4 to 10 for 90Y particles. As the particle size increases to 10 microm, dose uncertainties reach a factor of 100 for both radionuclides. In comparisons to identical exposures scenarios run by the LUDEP 2.0 code, Reference Man doses for inhaled beta-emitters were shown to provide slightly conservative estimates of lung dose compared to those in this study where uncertainties in lung airway histology are considered. PMID:15596988
Guo, Changning; Ngo, Diem; Ahadi, Shafiq; Doub, William H
2013-09-01
Abbreviated impactors have been developed recently to allow more rapid evaluation of inhalation products as alternates to the eight-stage Andersen Cascade Impactor (ACI) which has been widely used in the pharmaceutical industry for assessing aerodynamic particle size distribution. In this paper, a two-stage abbreviated impactor, Westech Fine Particle Dose Impactor (WFPD), was used to characterize the aerodynamic particle size of metered dose inhaler (MDI) products, and the results were compared with those obtained using the standard eight-stage ACI. Seven commercial MDI products, with different propellants (chlorofluorocarbon/hydrofluoroalkane) and formulation types (suspension/solution, dry/normal/wet), were tested in this study by both WFPD and ACI. Substantially equivalent measures of fine particle fraction were obtained for most of the tested MDI products, but larger coarse particle fraction and extra-fine particle fraction values were measured from WFPD relative to those measured using the ACI. Use of the WFPD also produced more wall loss than the ACI. Therefore, it is recommended that the system suitability be evaluated on a product-by-product basis to establish substantial equivalency before implementing an abbreviated impactor measurement methodology for routine use in inhaler product characterization. PMID:23780781
A framework to measure myocardial extracellular volume fraction using dual-phase low dose CT images
Liu, Yixun; Summers, Ronald M.; Yao, Jianhua; Liu, Songtao; Sibley, Christopher T.; Bluemke, David A.; Nacif, Marcelo S.
2013-10-15
Purpose: Myocardial extracellular volume fraction (ECVF) is a surrogate imaging biomarker of diffuse myocardial fibrosis, a hallmark of pathologic ventricular remodeling. Low dose cardiac CT is emerging as a promising modality to detect diffuse interstitial myocardial fibrosis due to its fast acquisition and low radiation; however, the insufficient contrast in the low dose CT images poses great challenge to measure ECVF from the image. Methods: To deal with this difficulty, the authors present a complete ECVF measurement framework including a point-guided myocardial modeling, a deformable model-based myocardium segmentation, nonrigid registration of pre- and post-CT, and ECVF calculation. Results: The proposed method was evaluated on 20 patients by two observers. Compared to the manually delineated reference segmentations, the accuracy of our segmentation in terms of true positive volume fraction (TPVF), false positive volume fraction (FPVF), and average surface distance (ASD), were 92.18% ± 3.52%, 0.31% ± 0.10%, 0.69 ± 0.14 mm, respectively. The interobserver variability measured by concordance correlation coefficient regarding TPVF, FPVF, and ASD were 0.95, 0.90, 0.94, respectively, demonstrating excellent agreement. Bland-Altman method showed 95% limits of agreement between ECVF at CT and ECVF at MR. Conclusions: The proposed framework demonstrates its efficiency, accuracy, and noninvasiveness in ECVF measurement and dramatically advances the ECVF at cardiac CT toward its clinical use.
Deeg, H.J.; Storb, R.; Shulman, H.M.; Weiden, P.L.; Graham, T.C.; Thomas, E.D.
1982-04-01
Marrow transplants were carried out between unrelated DLA-nonidentical dogs. Recipients were conditioned for transplantation by total body irradiation (TBI) given eigher as a single dose of 9 Gy (900 rad) or fractionated in three increments of 6 Gy (600 rad) each at intervals of 48 hr. All recipients received marrow, less than or equal to 4 x 10(8) cells/kg, and no buffy coat cells. No immunosuppression was given after grafting. All 10 dogs given single dose total body irradiation failed to show engraftment and died with marrow aplasia and infectious complications (median survival 12 days). In contrast, all 10 dogs given fractionated TBI had sustained engraftment and died with graft-versus-host disease (GVHD) and infectious complications (median survival 12.5 days). None of the dogs died from radiation-induced gastroenteritis. In conclusion, resistance to DLA-nonidentical unrelated marrow grafts can be abrogated by high-dose TBI. This technique may allow hemopoietic engraftment even after i vitro manipulation of the marrow such as lymphocyte depletion by cell separation or treatment with anti-T cell antisera.
Deeg, H.J.; Storb, R.; Shulman, H.M.; Weiden, P.L.; Graham, T.C.; Thomas, E.D.
1982-04-01
Marrow transplants were carried out between unrelated DLA-nonidentical dogs. Recipients were conditioned for transplantation by total body irradiation (TBI) given either as a single dose of 9 Gy (900 rad) or fractionated in three increments of 6 Gy (600 rad) each at intervals of 48 hr. All recipients received marrow, less than or equal to to 4 X 10/sup 8/ cells/kg, and no buffy coat cells. No immunosuppression was given after grafting. All 10 dogs given single-dose total body irradiation failed to show engraftment and died with marrow aplasia and infectious complications (median survival 12 days). In contrast, all 10 dogs given fractionated TBI had sustained engraftment and died with graft-versus-host disease (GVHD) and infectious complications (median survival 12.5 days). None of the dogs died from radiation-induced gastroenteritis.In conclusion, resistance to DLA-nonidentical unrelated marrow grafts can be abrogated by high-dose TBI. This technique may allow hemopoietic engraftment even after in vitro manipulation of the marrow such as lymphocyte depletion by cell separation or treatment with anti-T cell antisera.
Esophageal Toxicity From High-Dose, Single-Fraction Paraspinal Stereotactic Radiosurgery
Cox, Brett W.; Jackson, Andrew; Hunt, Margie; Bilsky, Mark; Yamada, Yoshiya
2012-08-01
Purpose: To report the esophageal toxicity from single-fraction paraspinal stereotactic radiosurgery (SRS) and identify dosimetric and clinical risk factors for toxicity. Methods and Materials: A total of 204 spinal metastases abutting the esophagus (182 patients) were treated with high-dose single-fraction SRS during 2003-2010. Toxicity was scored using the National Cancer Institute Common Toxicity Criteria for Adverse Events, version 4.0. Dose-volume histograms were combined to generate a comprehensive atlas of complication incidence that identifies risk factors for toxicity. Correlation of dose-volume factors with esophageal toxicity was assessed using Fisher's exact test and logistic regression. Clinical factors were correlated with toxicity. Results: The median dose to the planning treatment volume was 24 Gy. Median follow-up was 12 months (range, 3-81). There were 31 (15%) acute and 24 (12%) late esophageal toxicities. The rate of grade {>=}3 acute or late toxicity was 6.8% (14 patients). Fisher's exact test resulted in significant median splits for grade {>=}3 toxicity at V12 = 3.78 cm{sup 3} (relative risk [RR] 3.7, P=.05), V15 = 1.87 cm{sup 3} (RR 13, P=.0013), V20 = 0.11 cm{sup 3} (RR 6, P=0.01), and V22 = 0.0 cm{sup 3} (RR 13, P=.0013). The median split for D2.5 cm{sup 3} (14.02 Gy) was also a significant predictor of toxicity (RR 6; P=.01). A highly significant logistic regression model was generated on the basis of D2.5 cm{sup 3}. One hundred percent (n = 7) of grade {>=}4 toxicities were associated with radiation recall reactions after doxorubicin or gemcitabine chemotherapy or iatrogenic manipulation of the irradiated esophagus. Conclusions: High-dose, single-fraction paraspinal SRS has a low rate of grade {>=}3 esophageal toxicity. Severe esophageal toxicity is minimized with careful attention to esophageal doses during treatment planning. Iatrogenic manipulation of the irradiated esophagus and systemic agents classically associated with radiation
Challenges of Using High-Dose Fractionation Radiotherapy in Combination Therapy
Yang, Ying-Chieh; Chiang, Chi-Shiun
2016-01-01
Radiotherapy is crucial and substantially contributes to multimodal cancer treatment. The combination of conventional fractionation radiotherapy (CFRT) and systemic therapy has been established as the standard treatment for many cancer types. With advances in linear accelerators and image-guided techniques, high-dose fractionation radiotherapy (HFRT) is increasingly introduced in cancer centers. Clinicians are currently integrating HFRT into multimodality treatment. The shift from CFRT to HFRT reveals different effects on the tumor microenvironment and responses, particularly the immune response. Furthermore, the combination of HFRT and drugs yields different results in different types of tumors or using different treatment schemes. We have reviewed clinical trials and preclinical evidence on the combination of HFRT with drugs, such as chemotherapy, targeted therapy, and immune therapy. Notably, HFRT apparently enhances tumor cell killing and antigen presentation, thus providing opportunities and challenges in treating cancer. PMID:27446811
Spatial fractionation of the dose using neon and heavier ions: A Monte Carlo study
Peucelle, C.; Martínez-Rovira, I.; Prezado, Y.
2015-10-15
Purpose: This work explores a new radiation therapy approach which might trigger a renewed use of neon and heavier ions to treat cancers. These ions were shown to be extremely efficient in radioresistant tumor killing. Unfortunately, the efficient region also extends into the normal tissue in front of the tumor. The strategy the authors propose is to profit from the well-established sparing effect of thin spatially fractionated beams, so that the impact on normal tissues might be minimized while a high tumor control is achieved. The main goal of this work is to provide a proof of concept of this new approach. With that aim, a dosimetric study was carried out as a first step to evaluate the interest of further explorations of this avenue. Methods: The GATE/GEANT4 v.6.1 Monte Carlo simulation platform was employed to simulate arrays of rectangular minibeams (700 μm × 2 cm) of four ions (Ne, Si, Ar, and Fe). The irradiations were performed with a 2 cm-long spread-out Bragg peak centered at 7 cm-depth. Dose distributions in a water phantom were scored considering two minibeams center-to-center distances: 1400 and 3500 μm. Peak and valley doses, peak-to-valley dose ratios (PVDRs), beam penumbras, and relative contribution of nuclear fragments and electromagnetic processes were assessed as figures of merit. In addition, the type and proportion of the secondary nuclear fragments were evaluated in both peak and valley regions. Results: Extremely high PVDR values (>100) and low valley doses were obtained. The higher the atomic number (Z) of the primary ion is, the lower the valleys and the narrower the penumbras. Although the yield of secondary nuclear products increases with Z, the actual dose being deposited by the secondary nuclear fragments in the valleys starts to be the dominant contribution at deeper points, helping in the sparing of proximal normal tissues. Additionally, a wider center-to-center distance leads to a minimized contribution of heavier secondary
Five-Year Outcomes of High-Dose Single-Fraction Spinal Stereotactic Radiosurgery
Moussazadeh, Nelson; Lis, Eric; Katsoulakis, Evangelia; Kahn, Sweena; Svoboda, Marek; DiStefano, Natalie M.; McLaughlin, Lily; Bilsky, Mark H.; Yamada, Yoshiya; Laufer, Ilya
2015-10-01
Purpose: To characterize local tumor control and toxicity risk in very long-term survivors (>5 years) after high-dose spinal image guided, intensity modulated radiation therapy delivered as single-dose stereotactic radiosurgery (SRS). Previously published spinal SRS outcome analyses have included a heterogeneous population of cancer patients, mostly with short survival. This is the first study reporting the long-term tumor control and toxicity profiles after high-dose single-fraction spinal SRS. Methods and Materials: The study population included all patients treated from June 2004 to July 2009 with single-fraction spinal SRS (dose 24 Gy) who had survived at least 5 years after treatment. The endpoints examined included disease progression, surgical or radiation retreatment, in-field fracture development, and radiation-associated toxicity, scored using the Radiation Therapy Oncology Group radiation morbidity scoring criteria and the Common Terminology Criteria for Adverse Events, version 4.0. Local control and fracture development were assessed using Kaplan-Meier analysis. Results: Of 278 patients, 31 (11.1%), with 36 segments treated for spinal tumors, survived at least 5 years after treatment and were followed up radiographically and clinically for a median of 6.1 years (maximum 102 months). The histopathologic findings for the 5-year survivors included radiation-resistant metastases in 58%, radiation-sensitive metastases in 22%, and primary bone tumors in 19%. In this selected cohort, 3 treatment failures occurred at a median of 48.6 months, including 2 recurrences in the radiation field and 1 patient with demonstrated progression at the treatment margins. Ten lesions (27.8%) were associated with acute grade 1 cutaneous or gastrointestinal toxicity. Delayed toxicity ≥3 months after treatment included 8 cases (22.2%) of mild neuropathy, 2 (5.6%) of gastrointestinal discomfort, 8 (22.2%) of dermatitides, and 3 (8.3%) of myalgias/myositis. Thirteen
A plausible radiobiological model of cardiovascular disease at low or fractionated doses
NASA Astrophysics Data System (ADS)
Little, Mark; Vandoolaeghe, Wendy; Gola, Anna; Tzoulaki, Ioanna
Atherosclerosis is the main cause of coronary heart disease and stroke, the two major causes of death in developed society. There is emerging evidence of excess risk of cardiovascular disease at low radiation doses in various occupationally-exposed groups receiving small daily radia-tion doses. Assuming that they are causal, the mechanisms for effects of chronic fractionated radiation exposures on cardiovascular disease are unclear. We outline a spatial reaction-diffusion model for atherosclerosis, and perform stability analysis, based wherever possible on human data. We show that a predicted consequence of multiple small radiation doses is to cause mean chemo-attractant (MCP-1) concentration to increase linearly with cumulative dose. The main driver for the increase in MCP-1 is monocyte death, and consequent reduction in MCP-1 degradation. The radiation-induced risks predicted by the model are quantitatively consistent with those observed in a number of occupationally-exposed groups. The changes in equilibrium MCP-1 concentrations with low density lipoprotein cholesterol concentration are also consistent with experimental and epidemiologic data. This proposed mechanism would be experimentally testable. If true, it also has substantive implications for radiological protection, which at present does not take cardiovascular disease into account. The Japanese A-bomb survivor data implies that cardiovascular disease and can-cer mortality contribute similarly to radiogenic risk. The major uncertainty in assessing the low-dose risk of cardiovascular disease is the shape of the dose response relationship, which is unclear in the Japanese data. The analysis of the present paper suggests that linear extrapo-lation would be appropriate for this endpoint.
Pedicini, Piernicola; Strigari, Lidia; Benassi, Marcello; Caivano, Rocchina; Fiorentino, Alba; Nappi, Antonio; Salvatore, Marco; Storto, Giovanni
2014-04-01
To increase the efficacy of radiotherapy for non–small cell lung cancer (NSCLC), many schemes of dose fractionation were assessed by a new “toxicity index” (I), which allows one to choose the fractionation schedules that produce less toxic treatments. Thirty-two patients affected by non resectable NSCLC were treated by standard 3-dimensional conformal radiotherapy (3DCRT) with a strategy of limited treated volume. Computed tomography datasets were employed to re plan by simultaneous integrated boost intensity-modulated radiotherapy (IMRT). The dose distributions from plans were used to test various schemes of dose fractionation, in 3DCRT as well as in IMRT, by transforming the dose-volume histogram (DVH) into a biological equivalent DVH (BDVH) and by varying the overall treatment time. The BDVHs were obtained through the toxicity index, which was defined for each of the organs at risk (OAR) by a linear quadratic model keeping an equivalent radiobiological effect on the target volume. The less toxic fractionation consisted in a severe/moderate hyper fractionation for the volume including the primary tumor and lymph nodes, followed by a hypofractionation for the reduced volume of the primary tumor. The 3DCRT and IMRT resulted, respectively, in 4.7% and 4.3% of dose sparing for the spinal cord, without significant changes for the combined-lungs toxicity (p < 0.001). Schedules with reduced overall treatment time (accelerated fractionations) led to a 12.5% dose sparing for the spinal cord (7.5% in IMRT), 8.3% dose sparing for V{sub 20} in the combined lungs (5.5% in IMRT), and also significant dose sparing for all the other OARs (p < 0.001). The toxicity index allows to choose fractionation schedules with reduced toxicity for all the OARs and equivalent radiobiological effect for the tumor in 3DCRT, as well as in IMRT, treatments of NSCLC.
Grewenig, Angelika; Schuler, Nadine; Rübe, Claudia E.
2015-08-01
Purpose: Testicular spermatogenesis is extremely sensitive to radiation-induced damage, and even low scattered doses to testis from radiation therapy may pose reproductive risks with potential treatment-related infertility. Radiation-induced DNA double-strand breaks (DSBs) represent the greatest threat to the genomic integrity of spermatogonial stem cells (SSCs), which are essential to maintain spermatogenesis and prevent reproduction failure. Methods and Materials: During daily low-dose radiation with 100 mGy or 10 mGy, radiation-induced DSBs were monitored in mouse testis by quantifying 53 binding protein 1 (53BP-1) foci in SSCs within their stem cell niche. The accumulation of DSBs was correlated with proliferation, differentiation, and apoptosis of testicular germ cell populations. Results: Even very low doses of ionizing radiation arrested spermatogenesis, primarily by inducing apoptosis in spermatogonia. Eventual recovery of spermatogenesis depended on the survival of SSCs and their functional ability to proliferate and differentiate to provide adequate numbers of differentiating spermatogonia. Importantly, apoptosis-resistant SSCs resulted in increased 53BP-1 foci levels during, and even several months after, fractionated low-dose radiation, suggesting that surviving SSCs have accumulated an increased load of DNA damage. Conclusions: SSCs revealed elevated levels of DSBs for weeks after radiation, and if these DSBs persist through differentiation to spermatozoa, this may have severe consequences for the genomic integrity of the fertilizing sperm.
Glueck, S.; Van Dyk, J.; Messner, H.A. )
1994-03-01
Evaluation of radiation dose rate and fractionation effects on clonogenic myeloma cells was carried out. The radiosensitivity of clonogenic myeloma cells was evaluated for seven human myeloma cell lines. The lines were maintained in liquid suspension culture. Following radiation, cells were plated in semisolid medium using methylcellulose as viscous support. Radiation doses up to 12 Gy were delivered at dose rates of 0.05 and 0.5 Gy/min by a [sup 60]Co source. Each total dose was administered either as a single dose or in multiple fractions of 2 Gy. The data were analyzed according to the linear quadratic and multi target model of irradiation. Clonogenic progenitors of the seven myeloma cell lines differed in their radiosensitivity as measured by multiple parameters. The differences were mainly observed at low dose. The most effective cytoreduction was seen when radiation was administered in a single fraction at high dose rate. The cytoreductive effect on clonogenic myeloma cells was compared for clinically practiced total body irradiation (TBI) schedules delivered either in a single or in multiple fractions without causing significant pulmonary toxicity. The administration of 12 Gy delivered in six fractions of 2 Gy resulted in a superior reduction of clonogenic cells compared to a single fraction of 5 Gy. The preparation of bone marrow transplant recipients with multiple myeloma using fractionated radiation with a total dose of 12 Gy appears to afford better ablation than a single dose of 5 Gy while maintaining a low incidence of pulmonary toxicity. 20 refs., 4 figs., 4 tabs.
Greene-Schloesser, Dana M.; Kooshki, Mitra; Payne, Valerie; D’Agostino, Ralph B.; Wheeler, Kenneth T.; Metheny-Barlow, Linda J.; Robbins, Mike E.
2014-01-01
Purpose To determine if the brain’s response to single doses predicts its response to ‘biologically equivalent’ fractionated doses. Methods Young adult male Fischer 344 rats were whole-brain irradiated with either single 11, 14, or 16.5 Gy doses of 137Cs γ rays or their ‘biologically equivalent’ 20, 30, or 40 Gy fractionated doses (fWBI) delivered in 5 Gy fractions, twice/week for 2, 3, or 4 weeks, respectively. At 2 months post-irradiation, cellular markers of inflammation (total, activated, and newborn microglia) and neurogenesis (newborn neurons) were measured in 40 µm sections of the dentate gyrus (DG). Results Although the total number of microglia in the DG/hilus was not significantly different (p > 0.7) in unirradiated, single dose, and fWBI rats, single doses produced a significant (p < 0.003) increase in the percent-activated microglia; fWBI did not (p > 0.1). Additionally, single doses produced a significant (p < 0.002) dose-dependent increase in surviving newborn microglia; fWBI did not (p < 0.8). Although total proliferation in the DG was reduced equally by single and fWBI doses, single doses produced a significant dose-dependent (p < 0.02) decrease in surviving newborn neurons; fWBI did not (p > 0.6). Conclusions These data demonstrate that the rat brain’s cellular response to single doses often does not predict its cellular response to ‘biologically equivalent’ fWBI doses. PMID:24937374
Deeg, H.J.; Storb, R.; Weiden, P.L.; Schumacher, D.; Shulman, H.; Graham, T.; Thomas, E.D.
1981-11-01
Beagle dogs treated by total-body irradiation (TBI) were given autologous marrow grafts in order to avoid death from marrow toxicity. Acute and delayed non-marrow toxicities of high single-dose (27 dogs) and fractionated TBI (20 dogs) delivered at 0.05 or 0.1 Gy/min were compared. Fractionated TBI was given in increments of 2 Gy every 6 hr for three increments per day. Acute toxicity and early mortality (<1 month) at identical total irradiation doses were comparable for dogs given fractionated or single-dose TBI. With single-dose TBI, 14, 16, and 18 Gy, respectively, given at 0.05 Gy/min, 0/5, 5/5, and 2/2 dogs died from acute toxicity; with 10, 12, and 14 Gy, respectively, given at 0.1 Gy/min, 1/5, 4/5, and 5/5 dogs died acutely. With fractionated TBI, 14 and 16 Gy, respectively, given at 0.1 Gy/min, 1/5, 4/5, and 2/2 dogs died auctely. Early deaths were due to radiation enteritis with or without associated septicemia (29 dogs; less than or equal to Day 10). Three dogs given 10 Gy of TBI at 0.1 Gy/min died from bacterial pneumonia; one (Day 18) had been given fractionated and two (Days 14, 22) single-dose TBI. Fifteen dogs survived beyond 1 month; eight of these had single-dose TBI (10-14 Gy) and all died within 7 months of irradiation from a syndrome consisting of hepatic damage, pancreatic fibrosis, malnutrition, wasting, and anemia. Seven of the 15 had fractionated TBI, and only one (14 Gy) died on Day 33 from hepatic failure, whereas 6 (10-14 Gy) are alive and well 250 to 500 days after irradiation. In conclusion, fractionated TBI did not offer advantages over single-dose TBI with regard to acute toxicity and early mortality; rather, these were dependent upon the total dose of TBI. The total acutely tolerated dose was dependent upon the exposure rate; however, only dogs given fractionated TBI became healthy long-term survivors.
Hoffmann, Aswin L; Nahum, Alan E
2013-10-01
The simple Linear-Quadratic (LQ)-based Withers iso-effect formula (WIF) is widely used in external-beam radiotherapy to derive a new tumour dose prescription such that there is normal-tissue (NT) iso-effect when changing the fraction size and/or number. However, as conventionally applied, the WIF is invalid unless the normal-tissue response is solely determined by the tumour dose. We propose a generalized WIF (gWIF) which retains the tumour prescription dose, but replaces the intrinsic fractionation sensitivity measure (α/β) by a new concept, the normal-tissue effective fractionation sensitivity, [Formula: see text], which takes into account both the dose heterogeneity in, and the volume effect of, the late-responding normal-tissue in question. Closed-form analytical expressions for [Formula: see text] ensuring exact normal-tissue iso-effect are derived for: (i) uniform dose, and (ii) arbitrary dose distributions with volume-effect parameter n = 1 from the normal-tissue dose-volume histogram. For arbitrary dose distributions and arbitrary n, a numerical solution for [Formula: see text] exhibits a weak dependence on the number of fractions. As n is increased, [Formula: see text] increases from its intrinsic value at n = 0 (100% serial normal-tissue) to values close to or even exceeding the tumour (α/β) at n = 1 (100% parallel normal-tissue), with the highest values of [Formula: see text] corresponding to the most conformal dose distributions. Applications of this new concept to inverse planning and to highly conformal modalities are discussed, as is the effect of possible deviations from LQ behaviour at large fraction sizes. PMID:24029492
NASA Astrophysics Data System (ADS)
Hoffmann, Aswin L.; Nahum, Alan E.
2013-10-01
The simple Linear-Quadratic (LQ)-based Withers iso-effect formula (WIF) is widely used in external-beam radiotherapy to derive a new tumour dose prescription such that there is normal-tissue (NT) iso-effect when changing the fraction size and/or number. However, as conventionally applied, the WIF is invalid unless the normal-tissue response is solely determined by the tumour dose. We propose a generalized WIF (gWIF) which retains the tumour prescription dose, but replaces the intrinsic fractionation sensitivity measure (α/β) by a new concept, the normal-tissue effective fractionation sensitivity, (\\alpha /\\beta )_{eff}^{NT}, which takes into account both the dose heterogeneity in, and the volume effect of, the late-responding normal-tissue in question. Closed-form analytical expressions for (\\alpha /\\beta )_{eff}^{NT} ensuring exact normal-tissue iso-effect are derived for: (i) uniform dose, and (ii) arbitrary dose distributions with volume-effect parameter n = 1 from the normal-tissue dose-volume histogram. For arbitrary dose distributions and arbitrary n, a numerical solution for (\\alpha /\\beta )_{eff}^{NT} exhibits a weak dependence on the number of fractions. As n is increased, (\\alpha /\\beta )_{eff}^{NT} increases from its intrinsic value at n = 0 (100% serial normal-tissue) to values close to or even exceeding the tumour (α/β) at n = 1 (100% parallel normal-tissue), with the highest values of (\\alpha /\\beta )_{eff}^{NT} corresponding to the most conformal dose distributions. Applications of this new concept to inverse planning and to highly conformal modalities are discussed, as is the effect of possible deviations from LQ behaviour at large fraction sizes.
Impact of Fractionation and Dose in a Multivariate Model for Radiation-Induced Chest Wall Pain
Din, Shaun U.; Williams, Eric L.; Jackson, Andrew; Rosenzweig, Kenneth E.; Wu, Abraham J.; Foster, Amanda; Yorke, Ellen D.; Rimner, Andreas
2015-10-01
Purpose: To determine the role of patient/tumor characteristics, radiation dose, and fractionation using the linear-quadratic (LQ) model to predict stereotactic body radiation therapy–induced grade ≥2 chest wall pain (CWP2) in a larger series and develop clinically useful constraints for patients treated with different fraction numbers. Methods and Materials: A total of 316 lung tumors in 295 patients were treated with stereotactic body radiation therapy in 3 to 5 fractions to 39 to 60 Gy. Absolute dose–absolute volume chest wall (CW) histograms were acquired. The raw dose-volume histograms (α/β = ∞ Gy) were converted via the LQ model to equivalent doses in 2-Gy fractions (normalized total dose, NTD) with α/β from 0 to 25 Gy in 0.1-Gy steps. The Cox proportional hazards (CPH) model was used in univariate and multivariate models to identify and assess CWP2 exposed to a given physical and NTD. Results: The median follow-up was 15.4 months, and the median time to development of CWP2 was 7.4 months. On a univariate CPH model, prescription dose, prescription dose per fraction, number of fractions, D83cc, distance of tumor to CW, and body mass index were all statistically significant for the development of CWP2. Linear-quadratic correction improved the CPH model significance over the physical dose. The best-fit α/β was 2.1 Gy, and the physical dose (α/β = ∞ Gy) was outside the upper 95% confidence limit. With α/β = 2.1 Gy, V{sub NTD99Gy} was most significant, with median V{sub NTD99Gy} = 31.5 cm{sup 3} (hazard ratio 3.87, P<.001). Conclusion: There were several predictive factors for the development of CWP2. The LQ-adjusted doses using the best-fit α/β = 2.1 Gy is a better predictor of CWP2 than the physical dose. To aid dosimetrists, we have calculated the physical dose equivalent corresponding to V{sub NTD99Gy} = 31.5 cm{sup 3} for the 3- to 5-fraction groups.
Rynasiewicz, J.J.; Sutherland, D.E.R.; Kawahara, K.; Kim, T.; Najarian, J.S.
1981-03-01
The survival or organ allografts is prolonged in mice and rats treated with fractionated, high-dose total lymphoid irradiation (TLI). We have studied the effect of TLI, alone or in combination with donor bone marrow or pharmacologic immunosuppression (cyclosporin-A: CY-A), on the survival of heterotopic rat heart allografts. Specifically, we evaluated the generalized immunosuppressive effect of TLI as a function of accumulated dose and fractionation schedule. In addition, TLI and CY-A were used individually in schedules that by themselves gave only moderate graft prolongation and then subsequently in sequential combination.
Rischke, Hans-Christian; Meyer, Philipp Tobias; Knobe, Sven; Volgeova-Neher, Natalja; Kollefrath, Michael; Jilg, Cordula Annette; Grosu, Anca Ligia; Baltas, Dimos; Kroenig, Malte
2016-01-01
Purpose We present a novel method for treatment of locally recurrent prostate cancer (PCa) following radiation therapy: focal, multimodal image guided high-dose-rate (HDR) brachytherapy. Material and methods We treated two patients with recurrent PCa after primary (#1) or adjuvant (#2) external beam radiation therapy. Multiparametric magnetic resonance imaging (mpMRI), choline, positron emission tomography combined with computed tomography (PET/CT), or prostate-specific membrane antigen (PSMA)-PET combined with CT identified a single intraprostatic lesion. Positron emission tomography or magnetic resonance imaging – transrectal ultrasound (MRI-TRUS) fusion guided transperineal biopsy confirmed PCa within each target lesion. We defined a PET and mpMRI based gross tumor volume (GTV). A 5 mm isotropic margin was applied additionally to each lesion to generate a planning target volume (PTV), which accounts for technical fusion inaccuracies. A D90 of 18 Gy was intended in one fraction to each PTV using ultrasound guided HDR brachytherapy. Results Six month follow-up showed adequate prostate specific antygen (PSA) decline in both patients (ΔPSA 83% in patient 1 and ΔPSA 59.3% in patient 2). Follow-up 3-tesla MRI revealed regressive disease in both patients and PSMA-PET/CT showed no evidence of active disease in patient #1. No acute or late toxicities occurred. Conclusions Single fraction, focal, multimodal image guided salvage HDR brachytherapy for recurrent prostate cancer is a feasible therapy for selected patients with single lesions. This approach has to be evaluated in larger clinical trials. PMID:27504134
Pan, Jianmin; Yusuf, Mehran B; Dragun, Anthony; Dunlap, Neal; Guan, Timothy; Boling, Warren; Rai, Shesh; Woo, Shiao
2016-01-01
Background: Our aim was to identify a dose-volume response relationship for brain metastases treated with frameless stereotactic radiosurgery (SRS). Methods: We reviewed patients who underwent frameless single-fraction linear accelerator SRS for brain metastases between 2007 and 2013 from an institutional database. Proportional hazards modeling was used to identify predictors of outcome. A ratio of maximum lesion dose per mm-diameter (Gy/mm) was constructed to establish a dose-volume relationship. Results: There were 316 metastases evaluated in 121 patients (2 - 33 mm in the largest diameter). The median peripheral dose was 18.0 Gy (range: 10.0 – 24.0 Gy). Local control was 84.8% for all lesions and was affected by location, peripheral dose, maximum dose, and lesion size (p values < 0.050). A dose-volume response relationship was constructed using the maximum dose and lesion size. A unit increase in Gy/mm was associated with decreased local failure (p = 0.005). Local control of 80%, 85%, and 90% corresponded to maximum doses per millimeter of 1.67 Gy/mm, 2.86 Gy/mm, and 4.4 Gy/mm, respectively. Toxicity was uncommon and only 1.0% of lesions developed radionecrosis requiring surgery. Conclusions: For brain metastases less than 3 cm, a dose-volume response relationship exists between maximum radiosurgical dose and lesion size, which is predictive of local control. PMID:27284495
Demizu, Yusuke; Fujii, Osamu; Nagano, Fumiko; Terashima, Kazuki; Jin, Dongcun; Mima, Masayuki; Oda, Naoharu; Takeuchi, Kaoru; Takeda, Makiko; Ito, Kazuyuki; Fuwa, Nobukazu; Okimoto, Tomoaki
2015-11-01
Carbon ion therapy is a type of radiotherapy that can deliver high-dose radiation to a tumor while minimizing the dose delivered to organs at risk. Moreover, carbon ions are classified as high linear energy transfer radiation and are expected to be effective for even photon-resistant tumors. A 73-year-old man with glottic squamous cell carcinoma, T3N0M0, refused laryngectomy and received carbon ion therapy of 70 Gy (relative biological effectiveness) in 35 fractions. Three months after the therapy, the patient had an upper airway inflammation, and then laryngeal edema and pain occurred. Five months after the therapy, the airway stenosis was severe and computed tomography showed lack of the left arytenoid cartilage and exacerbation of laryngeal necrosis. Despite the treatment, 5 and a half months after the therapy, the laryngeal edema and necrosis had become even worse and the surrounding mucosa was edematous and pale. Six months after the therapy, pharyngolaryngoesophagectomy and reconstruction with free jejunal autograft were performed. The surgical specimen pathologically showed massive necrosis and no residual tumor. Three years after the carbon ion therapy, he is alive without recurrence. The first reported laryngeal squamous cell carcinoma case treated with carbon ion therapy resulted in an unexpected radiation laryngeal necrosis. Tissue damage caused by carbon ion therapy may be difficult to repair even for radioresistant cartilage; therefore, hollow organs reinforced by cartilage, such as the larynx, may be vulnerable to carbon ion therapy. Caution should be exercised when treating tumors in or adjacent to such organs with carbon ion therapy. PMID:26355161
Bahl, Sunil; Verma, Harish; Bhatnagar, Pankaj; Haldar, Pradeep; Satapathy, Asish; Kumar, K N Arun; Horton, Jennifer; Estivariz, Concepcion F; Anand, Abhijeet; Sutter, Roland
2016-01-01
Wild poliovirus type 2 was declared eradicated in September 2015 (1). In April 2016, India, switched from use of trivalent oral poliovirus vaccine (tOPV; containing types 1, 2, and 3 polio vaccine viruses), to bivalent OPV (bOPV; containing types 1 and 3), as part of a globally synchronized initiative to withdraw Sabin poliovirus type 2 vaccine. Concurrently, inactivated poliovirus vaccine (IPV) was introduced into India's routine immunization program to maintain an immunity base that would mitigate the number of paralytic cases in the event of epidemic transmission of poliovirus type 2 (2,3). After cessation of use of type 2 Sabin vaccine, any reported isolation of vaccine-derived poliovirus type 2 (VDPV2) would be treated as a public health emergency and might need outbreak response with monovalent type 2 oral vaccine, IPV, or both (4). In response to identification of a VDPV2 isolate from a sewage sample collected in the southern state of Telangana in May 2016, India conducted a mass vaccination campaign in June 2016 using an intradermal fractional dose (0.1 ml) of IPV (fIPV). Because of a global IPV supply shortage, fIPV, which uses one fifth of regular intramuscular (IM) dose administered intradermally, has been recommended as a response strategy for VDPV2 (5). Clinical trials have demonstrated that fIPV is highly immunogenic (6,7). During the 6-day campaign, 311,064 children aged 6 weeks-3 years were vaccinated, achieving an estimated coverage of 94%. With appropriate preparation, an emergency fIPV response can be promptly and successfully implemented. Lessons learned from this campaign can be applied to successful implementation of future outbreak responses using fIPV. PMID:27559683
NASA Astrophysics Data System (ADS)
Bewes, J. M.; Suchowerska, N.; Jackson, M.; Zhang, M.; McKenzie, D. R.
2008-07-01
Intensity-modulated radiation therapy (IMRT) achieves optimal dose conformity to the tumor through the use of spatially and temporally modulated radiation fields. In particular, average dose rate and instantaneous dose rate (pulse amplitude) are highly variable within a single IMRT fraction. In this study we isolate these variables and determine their impact on cell survival. Survival was assessed using a clonogenic assay. Two cell lines of differing radiosensitivity were examined: melanoma (MM576) and non-small cell lung cancer (NCI-H460). The survival fraction was observed to be independent of instantaneous dose rate. A statistically significant trend to increased survival was observed as the average dose rate was decreased, for a constant total dose. The results are relevant to IMRT practice, where average treatment times can be significantly extended to allow for movement of the multi-leaf collimator (MLC). Our in vitro study adds to the pool of theoretical evidence for the consequences of protracted treatments. We find that extended delivery times can substantially increase the cell survival. This also suggests that regional variation in the dose-rate history across a tumor, which is inherent to IMRT, will affect radiation dose efficacy.
Mizuta, Masahiro; Takao, Seishin; Date, Hiroyuki; Kishimoto, Naoki; Sutherland, Kenneth L.; Onimaru, Rikiya; Shirato, Hiroki
2012-11-01
Purpose: Hypofractionated irradiation is often used in precise radiotherapy instead of conventional multifractionated irradiation. We propose a novel mathematical method for selecting a hypofractionated or multifractionated irradiation regimen based on physical dose distribution adding to biologic consideration. Methods and Materials: The linear-quadratic model was used for the radiation effects on tumor and normal tissues, especially organs at risk (OARs). On the basis of the assumption that the OAR receives a fraction of the dose intended for the tumor, the minimization problem for the damage effect on the OAR was treated under the constraint that the radiation effect on the tumor is fixed. Results: For an N-time fractionated irradiation regimen, the constraint of tumor lethality was described by an N-dimensional hypersphere. The total dose of the fractionated irradiations was considered for minimizing the damage effect on the OAR under the hypersphere condition. It was found that the advantage of hypofractionated or multifractionated irradiation therapies depends on the magnitude of the ratio of {alpha}/{beta} parameters for the OAR and tumor in the linear-quadratic model and the ratio of the dose for the OAR and tumor. Conclusions: Our mathematical method shows that multifractionated irradiation with a constant dose is better if the ratio of {alpha}/{beta} for the OAR and tumor is less than the ratio of the dose for the OAR and tumor, whereas hypofractionated irradiation is better otherwise.
Hiniker, Susan M; Modlin, Leslie A; Choi, Clara Y; Atalar, Banu; Seiger, Kira; Binkley, Michael S; Harris, Jeremy P; Liao, Yaping Joyce; Fischbein, Nancy; Wang, Lei; Ho, Anthony; Lo, Anthony; Chang, Steven D; Harsh, Griffith R; Gibbs, Iris C; Hancock, Steven L; Li, Gordon; Adler, John R; Soltys, Scott G
2016-04-01
Patients with tumors adjacent to the optic nerves and chiasm are frequently not candidates for single-fraction stereotactic radiosurgery (SRS) due to concern for radiation-induced optic neuropathy. However, these patients have been successfully treated with hypofractionated SRS over 2-5 days, though dose constraints have not yet been well defined. We reviewed the literature on optic tolerance to radiation and constructed a dose-response model for visual pathway tolerance to SRS delivered in 1-5 fractions. We analyzed optic nerve and chiasm dose-volume histogram (DVH) data from perioptic tumors, defined as those within 3mm of the optic nerves or chiasm, treated with SRS from 2000-2013 at our institution. Tumors with subsequent local progression were excluded from the primary analysis of vision outcome. A total of 262 evaluable cases (26 with malignant and 236 with benign tumors) with visual field and clinical outcomes were analyzed. Median patient follow-up was 37 months (range: 2-142 months). The median number of fractions was 3 (1 fraction n = 47, 2 fraction n = 28, 3 fraction n = 111, 4 fraction n = 10, and 5 fraction n = 66); doses were converted to 3-fraction equivalent doses with the linear quadratic model using α/β = 2Gy prior to modeling. Optic structure dose parameters analyzed included Dmin, Dmedian, Dmean, Dmax, V30Gy, V25Gy, V20Gy, V15Gy, V10Gy, V5Gy, D50%, D10%, D5%, D1%, D1cc, D0.50cc, D0.25cc, D0.20cc, D0.10cc, D0.05cc, D0.03cc. From the plan DVHs, a maximum-likelihood parameter fitting of the probit dose-response model was performed using DVH Evaluator software. The 68% CIs, corresponding to one standard deviation, were calculated using the profile likelihood method. Of the 262 analyzed, 2 (0.8%) patients experienced common terminology criteria for adverse events grade 4 vision loss in one eye, defined as vision of 20/200 or worse in the affected eye. One of these patients had received 2 previous courses of radiotherapy to the optic structures
Effects of fractionated doses of fast neutrons or photons on the canine cervical spinal cord
Zook, B.C.; Bradley, E.W.; Casarett, G.W.
1981-10-01
The cervical spinal cords of 36 young adult male beagles were irradiated with fast neutrons with a mean energy of 15 MeV in four fractions/week/5 weeks to total doses of 1167, 1750, 2625, or 3938 rad. Nineteen beagles received 3500, 5250, or 7875 rad of photons in like manner. Sensory evoked responses recorded before and periodically after irradiations remained stable on 22 test and 6 control dogs. The cerebrospinal fluid contained excess protein and erythrocytes often before and always after the onset of neurological symptons. All dogs in the 3938-rad neutron, 6/9 dogs in the 2625-rad neutron, and 4/6 dogs in the 7875-rad photon groups developed cervical muscular spasms, incoordination, and progressive paralysis and were euthanatized. The relative biological effectiveness of fast neutrons as measured by the onset of neurological signs is approximately 3 (7875 photons/ 2625 neutrons) and is less than 4.5 (7875 photons/1750 neutrons). Gross pathological findings included hemorrhages, softening, and poliomyelomalacia, especially of the dorsal horns. Two dogs developed neoplasms in the irradiated field 1065 and 1470 days following neutron irradiation.
Sorbe, Bengt . E-mail: bengt.sorbe@orebroll.se; Straumits, Andris; Karlsson, Leif
2005-08-01
Purpose To compare two different fractionation schedules for postoperative vaginal high-dose-rate (HDR) irradiation in endometrial carcinomas. Methods and Materials In a complete geographic series of 290 low-risk endometrial carcinomas, the efficacy and side effects of two different fractionation schedules for postoperative vaginal irradiation were evaluated. The patients were treated during the years 1989-2003. The tumors were in International Federation of Gynecology and Obstetrics Stages IA-IB and Grades 1-2. The HDR MicroSelectron afterloading equipment (iridium-192) was used. Perspex vaginal applicators with diameters of 20-30 mm were used, and the dose was specified at 5 mm from the surface of the applicator. Six fractions were given, and the overall treatment time was 8 days. The size of the dose per fraction was randomly set to 2.5 Gy (total dose of 15.0 Gy) or 5.0 Gy (total dose of 30.0 Gy). One hundred forty-four patients were treated with the 2.5-Gy fraction and 146 patients with the 5.0-Gy fraction. Results The overall locoregional recurrence rate of the complete series was 1.4% and the rate of vaginal recurrences 0.7%. There was no difference between the two randomized groups. The vaginal shortening measured by colpometry was not significant (p = 0.159) in the 2.5-Gy group (mean, 0.3 cm) but was highly significant (p < 0.000001) in the 5.0-Gy group (mean 2.1 cm) after 5 years. Mucosal atrophy and bleedings were significantly more frequent in the 5.0-Gy group. Symptoms noted in the 2.5-Gy group were not different from what could be expected in a normal group of postmenopausal women. Conclusion The fractionation schedule recommended for postoperative vaginal irradiation in low-risk endometrial carcinoma is six fractions of 2.5 Gy when the HDR technique is used.
Maruyama, Y.; Wierzbicki, J. )
1990-12-01
Time-dose fractionation factors (TDF) were calculated for 252Cf (Cf) neutron therapy versus 137Cs for intracavitary use in the preoperative treatment of bulky/barrel-shaped Stage IB cervix cancers. The endpoint assessed was gross and microscopic tumor eradication from the hysterectomy specimen. We reviewed the data obtained in clinical trials between 1976-1987 at the University of Kentucky Medical Center. Preoperative photon therapy was approximately 45 Gy of whole pelvis irradiation in 5 weeks for both 137Cs and Cf treated patients. 137Cs implant was done after pelvic irradiation x1 to a mean dose of 2104 +/- 36 cGy at point A at a dose rate of 50.5 cGy/h. There were 37.5% positive specimens. Using Cf intracavitary implants, dose varied from 109 to 459 neutron cGy in 1-2 sessions. Specimens were more frequently cleared of tumor (up to 100% at appropriate dose) and showed a dose-response relationship, both by nominal dose and by TDF adjusted analysis of dose, dose-rate, number of sessions, and overall time. Limited understanding of relative biological effectiveness, schedule, effect of implants, and dose rate all made it difficult to use TDF to study neutron effects. Relative biological effectiveness (RBE) was estimated and showed that for Cf, RBE was a complex function of treatment variables. In the pilot clinical studies, a value of 6.0 had been assumed. The present findings of RBE for tumor destruction are larger than those assumed. Cf was effective for cervix tumor therapy and produced control without significant side effects due to the brachytherapy method used. The TDF model was of limited value in the present analysis and more information is still needed for RBE, dose-rate, and fractionation effects for Cf neutrons to develop a more sophisticated and relevant model.
SU-E-T-94: Daily Fraction Dose Recalculation Based On Rigid Registration Using Cone Beam CT
Bosse, C; Tuohy, R; Mavroidis, P; Shi, Z; Crownover, R; Papanikolaou, N; Stathakis, S
2014-06-01
Purpose: To calculate the daily fraction dose for a CBCT recalculation based on rigid registration and compare it to the planned CT dose. Methods: For this study, 30 patients that were previously treated (10 SBRT lung, 10 prostate and 10 abdomen) were considered. The daily CBCT images were imported into the Pinnacle treatment planning system from Mosaic. The prescribing physician contoured the regions of interest (ROI) on each CBCT and then dose was computed on each CBCT. Each CBCT dose distribution was then compared against the plan. The evaluation was based on isodose line comparison and Dose Volume Histogram comparison. Results: In the case of lung patients the dose differences between daily dose and plan dose were considered small. The PTV coverage was not compromised and the dose to the organs at risk had negligible differences. Larger differences were observed for prostate and abdomen patients. In these cases, although the PTV doses did not change on a daily basis, the doses to the organs at risk had significant differences. For a prostate patient, the bladder dose at 35% volume was 2714.444 cGy for the CT plan and 2844.747, 2801.556, 3552.37, and 2970.968 cGy for subsequent CBCTs. For the PTV on a SBRT patient, however, the CT plan had a dose at 35% volume of 6917.71 cGy and 6815.385, 6892.5, 6896.25, and 6922.9 cGy for the CBCTs. Conclusion: Daily dose validation is feasible using CBCT and treatment planning system. It provides means to evaluate the course of treatment for the patient undergoing radiation therapy and can assist in the decision of the need of adaptation of the treatment plan.
Sugano, Yasutaka; Mizuta, Masahiro; Takao, Seishin; Shirato, Hiroki; Sutherland, Kenneth L.; Date, Hiroyuki
2015-11-15
Purpose: Radiotherapy of solid tumors has been performed with various fractionation regimens such as multi- and hypofractionations. However, the ability to optimize the fractionation regimen considering the physical dose distribution remains insufficient. This study aims to optimize the fractionation regimen, in which the authors propose a graphical method for selecting the optimal number of fractions (n) and dose per fraction (d) based on dose–volume histograms for tumor and normal tissues of organs around the tumor. Methods: Modified linear-quadratic models were employed to estimate the radiation effects on the tumor and an organ at risk (OAR), where the repopulation of the tumor cells and the linearity of the dose-response curve in the high dose range of the surviving fraction were considered. The minimization problem for the damage effect on the OAR was solved under the constraint that the radiation effect on the tumor is fixed by a graphical method. Here, the damage effect on the OAR was estimated based on the dose–volume histogram. Results: It was found that the optimization of fractionation scheme incorporating the dose–volume histogram is possible by employing appropriate cell surviving models. The graphical method considering the repopulation of tumor cells and a rectilinear response in the high dose range enables them to derive the optimal number of fractions and dose per fraction. For example, in the treatment of prostate cancer, the optimal fractionation was suggested to lie in the range of 8–32 fractions with a daily dose of 2.2–6.3 Gy. Conclusions: It is possible to optimize the number of fractions and dose per fraction based on the physical dose distribution (i.e., dose–volume histogram) by the graphical method considering the effects on tumor and OARs around the tumor. This method may stipulate a new guideline to optimize the fractionation regimen for physics-guided fractionation.
Song, C.W.; Kim, T.H.; Khan, F.M.; Kersey, J.H.; Levitt, S.H.
1981-12-01
Total body irradiation (TBI) followed by bone marrow transplantation is being used in the treatment of malignant or non-malignant hemopoietic disorders. It has been believed that the ability of hemopoietic cells to repair sublethal radiation damage is negligible. Therefore, several schools of investigators suggested that TBI in a single exposure at extremely low dose rate (5 rad/min) over several hours, or in several fractions in 2-3 days, should yield a higher therapeutic gain, as compared with a single exposure at a high dose rate (26 rad/min). We reviewed the existing data in the literature, in particular, the response of hemopoietic cells to fractionated doses of irradiation and found that the repair capacity of both malignant and non-malignant hemopoietic cells might be greater than has been thought. It is concluded that we should not underestimate the ability of hemopoietic cells to repair sublethal radiation damage in using TBI.
Song, C.W.; Kim, T.H.; Khan, F.M.; Kersey, J.H.; Levitt, S.H.
1981-12-01
Total body irradiation (TBI) followed by bone marrow transplantation is being used in the treatment of malignant or non-malignant hemopoietic disorders. It has been believed that the ability of hemopoietic cells to repair sublethal radiation damage is negligible. Therefore, several schools of investigators suggested that TBI in a single exposure at extremely low dose rate (5 rad/min) over several hours, or in several fractions in 2-3 days, should yield a higher therapeutic gain, as compared with a single exposure at a high dose rate (25 rad/min). We reviewed the existing data in the literature, in particular, the response of hemopoietic cells to fractionated doses of irradiation and found that the repair capacity of both malignant and non-malignant hemopoietic cells might be greater than has been thought. It is concluded that we should not underestimate the ability of hemopoietic cells to repair sublethal radiation damage in using TBI.
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
Yamada, Yoshiya Bilsky, Mark H.; Lovelock, D. Michael; Venkatraman, Ennapadam S.; Toner, Sean; Johnson, Jared; Zatcky, Joan N.P.; Zelefsky, Michael J.; Fuks, Zvi
2008-06-01
Purpose: To report tumor control and toxicity for patients treated with image-guided intensity-modulated radiotherapy (RT) for spinal metastases with high-dose single-fraction RT. Methods and Materials: A total of 103 consecutive spinal metastases in 93 patients without high-grade epidural spinal cord compression were treated with image-guided intensity-modulated RT to doses of 18-24 Gy (median, 24 Gy) in a single fraction between 2003 and 2006. The spinal cord dose was limited to a 14-Gy maximal dose. The patients were prospectively examined every 3-4 months with clinical assessment and cross-sectional imaging. Results: The overall actuarial local control rate was 90% (local failure developed in 7 patients) at a median follow-up of 15 months (range, 2-45 months). The median time to local failure was 9 months (range, 2-15 months) from the time of treatment. Of the 93 patients, 37 died. The median overall survival was 15 months. In all cases, death was from progression of systemic disease and not local failure. The histologic type was not a statistically significant predictor of survival or local control. The radiation dose was a significant predictor of local control (p = 0.03). All patients without local failure also reported durable symptom palliation. Acute toxicity was mild (Grade 1-2). No case of radiculopathy or myelopathy has developed. Conclusion: High-dose, single-fraction image-guided intensity-modulated RT is a noninvasive intervention that appears to be safe and very effective palliation for patients with spinal metastases, with minimal negative effects on quality of life and a high probability of tumor control.
NASA Astrophysics Data System (ADS)
Curnow, Alison; Postle-Hacon, Matthew J.; MacRobert, Alexander J.; Bown, Stephen G.
1998-05-01
Preliminary clinical studies of 5-aminolaevulinic acid (ALA) induced photodynamic therapy (PDT) with the maximum tolerated oral dose (60 mg/kg), currently appear to only produce limited amounts of necrosis. We have studied ways of increasing this effect without increasing the drug dose. In normal, female, Wistar rats we have found it possible to increase the area of necrosis produced in the colon substantially by simply interrupting the light dose (25 J, 635 nm, 100 mW) for a short period of time, while all other variables are kept constant. It is possible to cause up to four times more necrosis with a dose of 200 mg/kg ALA i.v. by introducing a single 150 second interval which splits the light dose into two fractions after 5 J has been delivered. We have found these parameters to be optimal for this dose. Likewise, in the same model, the effect of the iron chelating agent, CP94, was also investigated and we have found it possible to produce three times the area of necrosis with the simultaneous administration of 100 mg/kg CP94 i.v. and 50 mg/kg ALA i.v. We have therefore shown, that it is possible to significantly increase the effects of ALA induced PDT without increasing the administered dose of ALA by utilizing these techniques.
Sudhoff, M; Lamba, M; Kumar, N; Ward, A; Elson, H
2015-06-15
Purpose: To systematically characterize inter-fraction breast variability and determine implications on delivered dose. Methods: Weekly port films were used to characterize breast setup variability. Five evenly spaced representative positions across the contour of each breast were chosen on the electronic port film in reference to graticule, and window and level was set such that the skin surface of the breast was visible. Measurements from the skin surface to treatment field edge were taken on each port film at each position and compared to the planning DRR, quantifying the variability. The systematic measurement technique was repeated for all port films for 20 recently treated breast cancer patients. Measured setup variability for each patient was modeled as a normal distribution. The distribution was randomly sampled from the model and applied as isocentric shifts in the treatment planning computer, representing setup variability for each fraction. Dose was calculated for each shifted fraction and summed to obtain DVHs and BEDs that modeled the dose with daily setup variability. Patients were categorized in to relevant groupings that were chosen to investigate the rigorousness of immobilization types, treatment techniques, and inherent anatomical difficulties. Mean position differences and dosimetric differences were evaluated between planned and delivered doses. Results: The setup variability was found to follow a normal distribution with mean position differences between the DRR and port film between − 8.6–3.5 mm with sigma range of 5.3–9.8 mm. Setup position was not found to be significantly different than zero. The mean seroma or whole breast PTV dosimetric difference, calculated as BED, ranged from a −0.23 to +1.13Gy. Conclusion: A systematic technique to quantify and model setup variability was used to calculate the dose in 20 breast cancer patients including variable setup. No statistically significant PTV or OAR BED differences were found between
Marshall, Thomas I.; Chaudhary, Pankaj; Michaelidesová, Anna; Vachelová, Jana; Davídková, Marie; Vondráček, Vladimir; Schettino, Giuseppe; Prise, Kevin M.
2016-01-01
Purpose To investigate the clinical implications of a variable relative biological effectiveness (RBE) on proton dose fractionation. Using acute exposures, the current clinical adoption of a generic, constant cell killing RBE has been shown to underestimate the effect of the sharp increase in linear energy transfer (LET) in the distal regions of the spread-out Bragg peak (SOBP). However, experimental data for the impact of dose fractionation in such scenarios are still limited. Methods and Materials Human fibroblasts (AG01522) at 4 key depth positions on a clinical SOBP of maximum energy 219.65 MeV were subjected to various fractionation regimens with an interfraction period of 24 hours at Proton Therapy Center in Prague, Czech Republic. Cell killing RBE variations were measured using standard clonogenic assays and were further validated using Monte Carlo simulations and parameterized using a linear quadratic formalism. Results Significant variations in the cell killing RBE for fractionated exposures along the proton dose profile were observed. RBE increased sharply toward the distal position, corresponding to a reduction in cell sparing effectiveness of fractionated proton exposures at higher LET. The effect was more pronounced at smaller doses per fraction. Experimental survival fractions were adequately predicted using a linear quadratic formalism assuming full repair between fractions. Data were also used to validate a parameterized variable RBE model based on linear α parameter response with LET that showed considerable deviations from clinically predicted isoeffective fractionation regimens. Conclusions The RBE-weighted absorbed dose calculated using the clinically adopted generic RBE of 1.1 significantly underestimates the biological effective dose from variable RBE, particularly in fractionation regimens with low doses per fraction. Coupled with an increase in effective range in fractionated exposures, our study provides an RBE dataset that can be used
Qureshi, Asaf A; Sami, Saeed A; Salser, Winston A; Khan, Farooq A
2002-03-01
Tocotrienols are effective in lowering serum total and LDL-cholesterol levels by inhibiting the hepatic enzymic activity of beta-hydroxy-beta-methylglutaryl coenzymeA (HMG-CoA) reductase through the post-transcriptional mechanism. alpha-Tocopherol, however, has an opposite effect (induces) on this enzyme activity. Since tocotrienols are also converted to tocopherols in vivo, it is necessary not to exceed a certain dose, as this would be counter-productive. The present study demonstrates the effects of various doses of a tocotrienol-rich fraction (TRF25) of stabilized and heated rice bran in hypercholesterolemic human subjects on serum lipid parameters. Ninety (18/group) hypercholesterolemic human subjects participated in this study, which comprised three phases of 35 days each. The subjects were initially placed on the American Heart Association (AHA) Step-1 diet and the effects noted. They were then administered 25, 50, 100, and 200 mg/day of TRF25 while on the restricted (AHA) diet. The results show that a dose of 100 mg/day of TRF25 produce maximum decreases of 20, 25, 14 (P<0.05) and 12%, respectively, in serum total cholesterol, LDL-cholesterol, apolipoprotein B and triglycerides compared with the baseline values, suggesting that a dose of 100 mg/day TRF25 plus AHA Step-1 diet may be the optimal dose for controlling the risk of coronary heart disease in hypercholesterolemic human subjects. PMID:11882333
Shin, Eunhyuk; Han, Youngyih; Park, Hee-Chul; Sung Kim, Jin; Hwan Ahn, Sung; Suk Shin, Jung; Gyu Ju, Sang; Ho Choi, Doo; Lee, Jaiki
2013-01-01
This study was conducted to evaluate the cumulative dosimetric error that occurs in both target and surrounding normal tissues when treating a moving target in multifractional treatment with tomotherapy. An experiment was devised to measure cumulative error in multifractional treatments delivered to a horseshoe-shaped clinical target volume (CTV) surrounding a cylinder shape of organ at risk (OAR). Treatments differed in jaw size (1.05 vs 2.5 cm), pitch (0.287 vs 0.660), and modulation factor (1.5 vs 2.5), and tumor motion characteristics differing in amplitude (1 to 3 cm), period (3 to 5 second), and regularity (sinusoidal vs irregular) were tested. Treatment plans were delivered to a moving phantom up to 5-times exposure. Dose distribution on central coronal plane from 1 to 5 times exposure was measured with GAFCHROMIC EBT film. Dose differences occurring across 1 to 5 times exposure of treatment and between treatment plans were evaluated by analyzing measurements of gamma index, gamma index histogram, histogram changes, and dose at the center of the OAR. The experiment showed dose distortion due to organ motion increased between multiexposure 1 to 3 times but plateaued and remained constant after 3-times exposure. In addition, although larger motion amplitude and a longer period of motion both increased dosimetric error, the dose at the OAR was more significantly affected by motion amplitude rather than motion period. Irregularity of motion did not contribute significantly to dosimetric error when compared with other motion parameters. Restriction of organ motion to have small amplitude and short motion period together with larger jaw size and small modulation factor (with small pitch) is effective in reducing dosimetric error. Pretreatment measurements for 3-times exposure of treatment to a moving phantom with patient-specific tumor motion would provide a good estimation of the delivered dose distribution.
Zakariaee, R; Brown, C J; Hamarneh, G; Parsons, C A; Spadinger, I
2014-08-15
Dosimetric parameters based on dose-volume histograms (DVH) of contoured structures are routinely used to evaluate dose delivered to target structures and organs at risk. However, the DVH provides no information on the spatial distribution of the dose in situations of repeated fractions with changes in organ shape or size. The aim of this research was to develop methods to more accurately determine geometrically localized, cumulative dose to the bladder wall in intracavitary brachytherapy for cervical cancer. The CT scans and treatment plans of 20 cervical cancer patients were used. Each patient was treated with five high-dose-rate (HDR) brachytherapy fractions of 600cGy prescribed dose. The bladder inner and outer surfaces were delineated using MIM Maestro software (MIM Software Inc.) and were imported into MATLAB (MathWorks) as 3-dimensional point clouds constituting the “bladder wall”. A point-set registration toolbox for MATLAB, Coherent Point Drift (CPD), was used to non-rigidly transform the bladder-wall points from four of the fractions to the coordinate system of the remaining (reference) fraction, which was chosen to be the emptiest bladder for each patient. The doses were accumulated on the reference fraction and new cumulative dosimetric parameters were calculated. The LENT-SOMA toxicity scores of these patients were studied against the cumulative dose parameters. Based on this study, there was no significant correlation between the toxicity scores and the determined cumulative dose parameters.
2013-01-01
Background The purpose of this study was to evaluate the impact of Cone Beam CT (CBCT) based setup correction on total dose distributions in fractionated frameless stereotactic radiation therapy of intracranial lesions. Methods Ten patients with intracranial lesions treated with 30 Gy in 6 fractions were included in this study. Treatment planning was performed with Oncentra® for a SynergyS® (Elekta Ltd, Crawley, UK) linear accelerator with XVI® Cone Beam CT, and HexaPOD™ couch top. Patients were immobilized by thermoplastic masks (BrainLab, Reuther). After initial patient setup with respect to lasers, a CBCT study was acquired and registered to the planning CT (PL-CT) study. Patient positioning was corrected according to the correction values (translational, rotational) calculated by the XVI® system. Afterwards a second CBCT study was acquired and registered to the PL-CT to confirm the accuracy of the corrections. An in-house developed software was used for rigid transformation of the PL-CT to the CBCT geometry, and dose calculations for each fraction were performed on the transformed CT. The total dose distribution was achieved by back-transformation and summation of the dose distributions of each fraction. Dose distributions based on PL-CT, CBCT (laser set-up), and final CBCT were compared to assess the influence of setup inaccuracies. Results The mean displacement vector, calculated over all treatments, was reduced from (4.3 ± 1.3) mm for laser based setup to (0.5 ± 0.2) mm if CBCT corrections were applied. The mean rotational errors around the medial-lateral, superior-inferior, anterior-posterior axis were reduced from (−0.1 ± 1.4)°, (0.1 ± 1.2)° and (−0.2 ± 1.0)°, to (0.04 ± 0.4)°, (0.01 ± 0.4)° and (0.02 ± 0.3)°. As a consequence the mean deviation between planned and delivered dose in the planning target volume (PTV) could be reduced from 12.3% to 0.4% for D95 and from 5.9% to 0.1% for Dav. Maximum
Liu, J.C.; Bacza, E.T.; Findley, D.O.; Forell, B.W.
1983-09-01
Eighty-five patients with acute myelogenous or acute lymphoblastic leukemia were treated at the Cit of Hope National Medicine Center with chemotherapy, total body irradiation, and bone marrow transplant. The average mid-line dose to these patients was 1002 rad with a uniformity of 8%.
Takeda, Atsuya; Sanuki, Naoko; Tsurugai, Yuichiro; Oku, Yohei; Aoki, Yousuke
2016-01-01
We previously reported that the local control of pulmonary metastases from colorectal cancer (CRC) following stereotactic body radiotherapy (SBRT) with moderate prescription dose was relatively worse. We investigated the treatment outcomes and toxicities of patients with oligometastases from CRC treated by SBRT using risk-adapted, very high- and convergent-dose regimens. Among patients referred for SBRT from August 2011 to January 2015, those patients were extracted who had liver or pulmonary metastases from CRC, and they were treated with a total dose of 50–60 Gy in five fractions prescribed to the 60% isodose line of the maximum dose covering the surface of the planning target volume. Concurrent administration of chemotherapy was not admitted during SBRT, while neoadjuvant or adjuvant chemotherapy was allowed. A total of 21 patients (12 liver, 9 lung) with 28 oligometastases were evaluated. The median follow-up duration was 27.5 months (range: 6.5–43.3 months). Four patients were treated with SBRT as a series of initial treatments, and 17 patients were treated after recurrent oligometastases. The local control rates at 1 and 2 years from the start of SBRT were 100%. The disease-free and actuarial overall survival rates were 62% and 55%, and 79% and 79%, respectively. No severe toxicities (≥grade 3) occurred during follow-up. The outcomes following high-dose SBRT were excellent. This treatment can provide an alternative to the surgical resection of oligometastases from CRC. Prospective studies are needed to validate the effectiveness of SBRT. PMID:26983981
Singh, Parminder; Saini, Komal; Mishra, Rosaline; Sahoo, Bijay Kumar; Bajwa, Bikramjit Singh
2016-08-01
In this study, measurements of indoor radon ((222)Rn), thoron ((220)Rn) and their equilibrium equivalent concentration (EEC) were carried out in 96 dwellings from 22 different villages situated in Hamirpur district, Himachal Pradesh, India, by using LR-115 type II-based pinhole twin cup dosimeters and deposition-based progeny sensors (DRPS/DTPS). The annual average indoor (222)Rn and (220)Rn concentrations observed in these dwellings were 63.82 and 89.59 Bq/m(3), respectively, while the average EEC (attached + unattached) for (222)Rn and (220)Rn was 29.28 and 2.74 Bq/m(3). For (222)Rn (f Rn) and (220)Rn (f Tn), the average values of unattached fraction were 0.11 and 0.09, respectively. The equilibrium factors for radon (F Rn) and thoron (F Tn) varied from 0.12 to 0.77 with an average of 0.50, and from 0.01 to 0.34 with an average of 0.05, respectively. The annual inhalation dose due to mouth and nasal breathing was calculated using dose conversion factors and unattached fractions. The indoor annual effective doses for (222)Rn (AEDR) and (220)Rn (AEDT) were found to be 1.92 and 0.83 mSv a(-1), respectively. The values of (222)Rn/(220)Rn concentrations and annual effective doses obtained in the present study are within the safe limits as recommended by the International Commission on Radiological Protection for indoor dwelling exposure conditions. PMID:27289385
McCarthy, Ian D; Brown, James
2016-07-01
The flooding dose technique of Garlick et al. (1980) has become the main method for measuring tissue and whole-animal rates of protein synthesis in ectotherms. However, single tissue samples are used to determine rates of protein synthesis and no studies have examined the pattern of flooding in large tissues such as the white muscle in fishes, which can comprise up to 55% of the wet body mass of a fish and which is poorly perfused. The present study has examined, for the first time, the patterns of flooding and measured rates of protein synthesis in five different regions of the white muscle in the Arctic charr Salvelinus alpinus ranging in size from 25g to 1.6kg following a flooding dose injection of L-[(3)H]-phenylalanine. The results indicate that the degree of flooding (i.e. free pool specific radioactivity relative to that of the injection solution) and elevation in free phenylalanine concentrations can vary between regions but the calculated fractional rates of protein synthesis were similar in four of the five regions studied. The variability in rates of protein synthesis increased with body size with greater variability observed between regions for fish >1kg in body mass. For consistency between studies, it is recommended that samples are taken from the epaxial muscle in the region below the dorsal fin when measuring fractional rates of white muscle synthesis in fishes. PMID:26970581
Denham, J.W.; Abbott, R.L. )
1991-03-01
After a preliminary dose-finding study involving 12 patients with advanced or locally recurrent head and neck cancer, 27 patients were treated on a phase II protocol, using fluorouracil 350 mg/m2/d by continuous intravenous (IV) infusion over 5 days, followed on the sixth day by a 2-hour IV infusion of cisplatin 50 mg/m2, administered during the first and fourth weeks of radiation therapy to total doses between 60 and 64 Gy, using 2 Gy daily fractions. Eight of these 27 patients had American Joint Committee on Cancer Staging (AJCC) stage III disease, and 12 had stage IV disease. Four had recurrent disease after surgery. Three-year follow-up is now available. Twenty-one (77.8%) remitted completely following treatment, and 11 remain free of local and regional relapse at 3 years. Four have developed systemic metastases. Following successful salvage treatment in two cases, estimated determinate survival at 3 years is 64%. Acute toxicity was manageable with this regime. Eleven instances of grade 3 Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC) mucositis were observed, which caused interruptions to radiotherapy in only four cases. No late sequelae have so far been recorded. It is concluded that the protocol described is tolerable but probably did not cause a greater number of locoregional cures than would have been expected following conventional radiotherapy alone in this group of patients. The use of infusional fluorouracil with concurrent conventionally fractionated radiation therapy and cisplatin infusion results in mucositis that limits the dose of fluorouracil to levels that are probably subtherapeutic.
Lee, Eun-Jung; Kim, Jun Won; Yoo, Hyun; Kwak, Woori; Choi, Won Hoon; Cho, Seoae; Choi, Yu Jeong; Lee, Yoon-Jin; Cho, Jaeho
2015-08-14
We have revealed in a porcine skin injury model that eosinophil recruitment was dose-dependently enhanced by a single high-dose irradiation. In this study, we investigated the underlying mechanism of eosinophil-associated skin fibrosis and the effect of high-dose-per-fraction radiation. The dorsal skin of a mini-pig was divided into two sections containing 4-cm(2) fields that were irradiated with 30 Gy in a single fraction or 5 fractions and biopsied regularly over 14 weeks. Eosinophil-related Th2 cytokines such as interleukin (IL)-4, IL-5, and C-C motif chemokine-11 (CCL11/eotaxin) were evaluated by quantitative real-time PCR. RNA-sequencing using 30 Gy-irradiated mouse skin and functional assays in a co-culture system of THP-1 and irradiated-human umbilical vein endothelial cells (HUVECs) were performed to investigate the mechanism of eosinophil-mediated radiation fibrosis. Single high-dose-per-fraction irradiation caused pronounced eosinophil accumulation, increased profibrotic factors collagen and transforming growth factor-β, enhanced production of eosinophil-related cytokines including IL-4, IL-5, CCL11, IL-13, and IL-33, and reduced vessels compared with 5-fraction irradiation. IL-33 notably increased in pig and mouse skin vessels after single high-dose irradiation of 30 Gy, as well as in irradiated HUVECs following 12 Gy. Blocking IL-33 suppressed the migration ability of THP-1 cells and cytokine secretion in a co-culture system of THP-1 cells and irradiated HUVECs. Hence, high-dose-per-fraction irradiation appears to enhance eosinophil-mediated fibrotic responses, and IL-33 may be a key molecule operating in eosinophil-mediated fibrosis in high-dose-per fraction irradiated skin. PMID:26047701
Lee, Eun-Jung; Kim, Jun Won; Yoo, Hyun; Kwak, Woori; Choi, Won Hoon; Cho, Seoae; Choi, Yu Jeong; Lee, Yoon-Jin; Cho, Jaeho
2015-08-14
We have revealed in a porcine skin injury model that eosinophil recruitment was dose-dependently enhanced by a single high-dose irradiation. In this study, we investigated the underlying mechanism of eosinophil-associated skin fibrosis and the effect of high-dose-per-fraction radiation. The dorsal skin of a mini-pig was divided into two sections containing 4-cm{sup 2} fields that were irradiated with 30 Gy in a single fraction or 5 fractions and biopsied regularly over 14 weeks. Eosinophil-related Th2 cytokines such as interleukin (IL)-4, IL-5, and C–C motif chemokine-11 (CCL11/eotaxin) were evaluated by quantitative real-time PCR. RNA-sequencing using 30 Gy-irradiated mouse skin and functional assays in a co-culture system of THP-1 and irradiated-human umbilical vein endothelial cells (HUVECs) were performed to investigate the mechanism of eosinophil-mediated radiation fibrosis. Single high-dose-per-fraction irradiation caused pronounced eosinophil accumulation, increased profibrotic factors collagen and transforming growth factor-β, enhanced production of eosinophil-related cytokines including IL-4, IL-5, CCL11, IL-13, and IL-33, and reduced vessels compared with 5-fraction irradiation. IL-33 notably increased in pig and mouse skin vessels after single high-dose irradiation of 30 Gy, as well as in irradiated HUVECs following 12 Gy. Blocking IL-33 suppressed the migration ability of THP-1 cells and cytokine secretion in a co-culture system of THP-1 cells and irradiated HUVECs. Hence, high-dose-per-fraction irradiation appears to enhance eosinophil-mediated fibrotic responses, and IL-33 may be a key molecule operating in eosinophil-mediated fibrosis in high-dose-per fraction irradiated skin. - Highlights: • Single high-dose irradiation aggravates eosinophil-mediated fibrosis through IL-33. • Vascular endothelial cells damaged by high-dose radiation secrete IL-33. • Blocking IL-33 suppressed migration of inflammatory cells and cytokine secretion. • IL
Yang, Hao; Cai, Bo-ning; Wang, Xiao-shen; Cong, Xiao-hu; Xu, Wei; Wang, Jin-yuan; Yang, Jun; Xu, Shou-ping; Ju, Zhong-jian; Ma, Lin
2016-01-01
Background This study investigated and quantified the dosimetric impact of the distance from the tumor to the spinal cord and fractionation schemes for patients who received stereotactic body radiation therapy (SBRT) and hypofractionated simultaneous integrated boost (HF-SIB). Material/Methods Six modified planning target volumes (PTVs) for 5 patients with spinal metastases were created by artificial uniform extension in the region of PTV adjacent spinal cord with a specified minimum tumor to cord distance (0–5 mm). The prescription dose (biologic equivalent dose, BED) was 70 Gy in different fractionation schemes (1, 3, 5, and 10 fractions). For PTV V100, Dmin, D98, D95, and D1, spinal cord dose, conformity index (CI), V30 were measured and compared. Results PTV-to-cord distance influenced PTV V100, Dmin, D98, and D95, and fractionation schemes influenced Dmin and D98, with a significant difference. Distances of ≥2 mm, ≥1 mm, ≥1 mm, and ≥0 mm from PTV to spinal cord meet dose requirements in 1, 3, 5, and 10 fractionations, respectively. Spinal cord dose, CI, and V30 were not impacted by PTV-to-cord distance and fractionation schemes. Conclusions Target volume coverage, Dmin, D98, and D95 were directly correlated with distance from the spinal cord for spine SBRT and HF-SIB. Based on our study, ≥2 mm, ≥1 mm, ≥1 mm, and ≥0 mm distance from PTV to spinal cord meets dose requirements in 1, 3, 5 and 10 fractionations, respectively. PMID:26902177
Schwer, Amanda L.; Damek, Denise M.; Kavanagh, Brian D.; Gaspar, Laurie E.; Lillehei, Kevin; Stuhr, Kelly; Chen Changhu
2008-03-15
Purpose: To determine the maximum tolerated dose (MTD) of fractionated stereotactic radiosurgery (SRS) with gefitinib in patients with recurrent malignant gliomas. Methods and Materials: A Phase I clinical trial was performed. Eligible patients had pathologically proved recurrent anaplastic astrocytoma or glioblastoma. Patients started gefitinib (250 mg/day) 7 days before SRS and continued for 1 year or until disease progression. SRS was delivered in three fractions over 3 days. The planning target volume (PTV) was the T1-weighted MRI postcontrast enhancing lesion + 2 mm. The first cohort received an SRS dose of 18 Gy, and subsequent cohorts received higher doses up to the maximum dose of 36 Gy. Dose-limiting toxicity (DLT) was any Grade 3 toxicity. The MTD was exceeded if 2 of 6 patients in a cohort experienced DLT. Results: Characteristics of the 15 patients enrolled were: 9 men, 6 women; median age, 47 years (range, 23-65 years); 11 glioblastoma, 4 AA; median prior RT dose, 60 Gy (range, 54-61.2 Gy); median interval since RT, 12 months (range, 3-57 months); median PTV, 41 cc (range, 12-151 cc). Median follow-up time was 7 months (range, 2-28 months). Median time on gefitinib was 5 months (range, 2-12 months). No patient experienced a DLT, and the SRS dose was escalated from 18 to 36 Gy. Grade 1-2 gefitinib-related dermatitis and diarrhea were common (10 and 7 patients, respectively). Conclusion: Fractionated SRS to a dose of 36 Gy in three fractions is well tolerated with gefitinib at daily dose of 250 mg. Further studies of SRS and novel molecular targeted agents are warranted in this challenging clinical setting.
Neuner, Geoffrey; Mohiuddin, Majid M.; Vander Walde, Noam; Goloubeva, Olga; Ha, Jonathan; Yu, Cedric X.; Regine, William F.
2012-04-01
Purpose: Spatially fractionated GRID radiotherapy (SFGRT) using a customized Cerrobend block has been used to improve response rates in patients with bulky tumors. The clinical efficacy of our own multileaf collimator (MLC) technique is unknown. We undertook a retrospective analysis to compare clinical response rates attained using these two techniques. Methods and Materials: Seventy-nine patients with bulky tumors (median diameter, 7.6 cm; range, 4-30 cm) treated with SFGRT were reviewed. Between 2003 and late 2005, the Cerrobend block technique (n = 39) was used. Between late 2005 and 2008, SFGRT was delivered using MLC-shaped fields (n = 40). Dose was prescribed to dmax (depth of maximum dose) and was typically 15 Gy. Eighty percent of patients in both groups received external beam radiotherapy in addition to SFGRT. The two-sided Fisher-Freeman-Halton test was used to compare pain and mass effect response rates between the two groups. Results: Sixty-one patients (77%) were treated for palliative intent and 18 (23%) for curative intent. The majority of patients had either lung or head-and-neck primaries in both groups; the most frequent site of SFGRT application was the neck. The majority of patients complained of either pain (65%) or mass effect (58%) at intake. Overall response rates for pain and mass response were no different between the Cerrobend and MLC groups: pain, 75% and 74%, respectively (p = 0.50), and mass effect, 67% and 73%, respectively (p = 0.85). The majority of toxicities were Grade 1 or 2, and only 3 patients had late Grade 3-4 toxicities. Conclusions: MLC-based and Cerrobend-based SFGRT have comparable and encouraging response rates when used either in the palliative or curative setting. MLC-based SGFRT should allow clinics to more easily adopt this novel treatment approach for the treatment of bulky tumors.
Han, Youngyih; Shin, Eun Hyuk; Huh, Seung Jae . E-mail: sjhuh@smc.samsung.co.kr; Lee, Jung Eun; Park, Won
2006-06-01
Purpose: To investigate the inter fractional dose variation of a small-bowel displacement system (SBDS)-assisted intensity-modulated radiation therapy (IMRT) for the treatment of cervical cancer. Methods: Four computed tomography (CT) scans were carried out in 10 patients who received radiotherapy for uterine cervical cancer. The initial CT was taken by use of the SBDS, before the beginning of radiotherapy, and 3 additional CT scans with the SBDS were done in subsequent weeks. IMRT was planned by use of the initial CT, and the subsequent images were fused with the initial CT set. Dose-volume histogram (DVH) changes of the targets (planning target volume [PTV] = clinical target volume [CTV] + 1.5 cm) and of the critical organs were evaluated after obtaining the volumes of each organ on 4 CT sets. Results: No significant differences were found in PTV volumes. Changes on the DVH of the CTVs were not significant, whereas DVH changes of the PTVs at 40% to 100% of the prescription dose level were significant (V{sub 90%}; 2nd week: p = 0.0091, 3rd week: p = 0.0029, 4th week: p = 0.0050). The changes in the small-bowel volume included in the treatment field were significant. These were 119.5 cm{sup 3} (range, 26.9-251.0 cm{sup 3}), 126 cm{sup 3} (range, 38.3-336 cm{sup 3}), 161.9 cm{sup 3} (range, 37.7-294.6 cm{sup 3}), and 149.1 cm{sup 3} (range, 38.6-277.8 cm{sup 3}) at the 1st, 2nd, 3rd, and 4th weeks, respectively, and were significantly correlated with the DVH change in the small bowel, which were significant at the 3rd (V{sub 80%}; p = 0.0230) and 4th (V{sub 80%}; p = 0.0263) weeks. The bladder-volume change correlated to the large volume change (>20%) of the small-bowel volume. Conclusions: Significant DVH differences for the small bowel can result because of interfractional position variations, whereas the DVH differences of the CTV were not significant. Strict bladder-filling control and an accurate margin for the PTV, as well as image-guided position verification
NASA Astrophysics Data System (ADS)
Mínguez, Pablo; Gustafsson, Johan; Flux, Glenn; Sjögreen Gleisner, Katarina
2016-03-01
In this work, the biologically effective dose (BED) is investigated for fractionated molecular radiotherapy (MRT). A formula for the Lea-Catcheside G-factor is derived which takes the possibility of combinations of sub-lethal damage due to radiation from different administrations of activity into account. In contrast to the previous formula, the new G-factor has an explicit dependence on the time interval between administrations. The BED of tumour and liver is analysed in MRT of neuroblastoma with 131I-mIBG, following a common two-administration protocol with a mass-based activity prescription. A BED analysis is also made for modified schedules, when due to local regulations there is a maximum permitted activity for each administration. Modifications include both the simplistic approach of delivering this maximum permitted activity in each of the two administrations, and also the introduction of additional administrations while maintaining the protocol-prescribed total activity. For the cases studied with additional (i.e. more than two) administrations, BED of tumour and liver decreases at most 12% and 29%, respectively. The decrease in BED of the tumour is however modest compared to the two-administration schedule using the maximum permitted activity, where the decrease compared to the original schedule is 47%.
Guerin, Philippe J.; Næss, Lisbeth M.; Fogg, Carole; Rosenqvist, Einar; Pinoges, Loretxu; Bajunirwe, Francis; Nabasumba, Carolyn; Borrow, Ray; Frøholm, Leif O.; Ghabri, Salah; Batwala, Vincent; Twesigye, Rogers; Aaberge, Ingeborg S.; Røttingen, John-Arne; Piola, Patrice; Caugant, Dominique A.
2008-01-01
Background Neisseria meningitidis serogroup A is the main causative pathogen of meningitis epidemics in sub-Saharan Africa. In recent years, serogroup W135 has also been the cause of epidemics. Mass vaccination campaigns with polysaccharide vaccines are key elements in controlling these epidemics. Facing global vaccine shortage, we explored the use of fractional doses of a licensed A/C/Y/W135 polysaccharide meningococcal vaccine. Methods and Findings We conducted a randomized, non-inferiority trial in 750 healthy volunteers 2–19 years old in Mbarara, Uganda, to compare the immune response of the full dose of the vaccine versus fractional doses (1/5 or 1/10). Safety and tolerability data were collected for all subjects during the 4 weeks following the injection. Pre- and post-vaccination sera were analyzed by measuring serum bactericidal activity (SBA) with baby rabbit complement. A responder was defined as a subject with a ≥4-fold increase in SBA against a target strain from each serogroup and SBA titer ≥128. For serogroup W135, 94% and 97% of the vaccinees in the 1/5- and 1/10-dose arms, respectively, were responders, versus 94% in the full-dose arm; for serogroup A, 92% and 88% were responders, respectively, versus 95%. Non-inferiority was demonstrated between the full dose and both fractional doses in SBA seroresponse against serogroups W135 and Y, in total population analysis. Non-inferiority was shown between the full and 1/5 doses for serogroup A in the population non-immune prior to vaccination. Non-inferiority was not shown for any of the fractionate doses for serogroup C. Safety and tolerability data were favourable, as observed in other studies. Conclusions While the advent of conjugate A vaccine is anticipated to largely contribute to control serogroup A outbreaks in Africa, the scale-up of its production will not cover the entire “Meningitis Belt” target population for at least the next 3 to 5 years. In view of the current shortage of
Crocker, James K; Ng, Jin Aun; Keall, Paul J; Booth, Jeremy T
2012-01-01
The dose for image-based motion monitoring of prostate tumours during radiotherapy delivery has not been established. This study aimed to provide quantitative analysis and optimisation of the fluoroscopic patient imaging dose during radiotherapy for IMRT and VMAT treatments using standard and hypofractionated treatment schedules. Twenty-two patients with type T1c N0/M0 prostate cancer and three implanted fiducial markers were considered. Minimum field sizes encompassing all fiducial markers plus a 7.5mm motion margin were determined for each treatment beam, each patient and the complete cohort. Imaging doses were measured for different field sizes and depths in a phantom at 75kV and 120kV. Based on these measurements, the patient imaging doses were then estimated according to beam-on time for clinical settings. The population minimum field size was 5.3 × 6.1cm2, yielding doses of 406mGy and 185mGy over the course of an IMRT treatment for 75kV (10 mAs) and 120kV (1.04 mAs) imaging, respectively at 1Hz. The imaging dose was reduced by an average of 28% and 32% by adopting patient specific and treatment-beam specific field sizes respectively. Standard fractionation VMAT imaging doses were 37% lower than IMRT doses over a complete treatment. Hypofractionated IMRT SBRT and VMAT SBRT imaging doses were 58% and 76% lower than IMRT doses respectively. The patient dose for kilovoltage intrafraction monitoring of the prostate was quantified. Tailoring imaging field sizes to specific patients yielded a significant reduction in the imaging dose, as did adoption of faster treatment modalities such as VMAT. PMID:22517054
Yu, V; Nguyen, D; Pajonk, F; Kaprealian, T; Kupelian, P; Steinberg, M; Low, D; Sheng, K
2015-06-15
Purpose: To explore the feasibility of improving GBM treatment outcome with temporal-spatial dose optimization of an ordinary differential equation (ODE) that models the differentiation and distinct radiosensitivity between cancer stem cells (CSC) and differentiated cancer cells (DCC). Methods: The ODE was formulated into a non-convex optimization problem with the objective to minimize remaining total cancer cells 500 days from the onset of radiotherapy when the total cancer cell number was 3.5×10{sup 7}, while maintaining normal tissue biological effective dose (BED) of 100Gy resulted from standard prescription of 2Gyx30. Assuming spatially separated CSC and DCC, optimization was also performed to explore the potential benefit from dose-painting the two compartments. Dose escalation to a sub-cell-population in the GTV was also examined assuming that a 2 cm margin around the GTV allows sufficient dose drop-off to 100Gy BED. The recurrence time was determined as the time at which the total cancer cell number regrows to 10{sup 9} cells. Results: The recurrence time with variable fractional doses administered once per week, bi-week and month for one year were found to be 615, 593 and 570 days, superior to the standard-prescription recurrence time of 418 days. The optimal dose-fraction size progression for both uniform and dose-painting to the tumor is low and relatively constant in the beginning and gradually increases to more aggressive fractions at end of the treatment course. Dose escalation to BED of 200Gy to the whole tumor alongside with protracted weekly treatment was found to further delay recurrence to 733 days. Dose-painting of 200 and 500Gy BED to CSC on a year-long weekly schedule further extended recurrence to 736 and 1076 days, respectively. Conclusion: GBM treatment outcome can possibly be improved with a chronic treatment approach. Further dose escalation to the entire tumor or CSC targeted killing is needed to achieve total tumor control. This work
Philippo, H; Winter, E A M; van der Kogel, A J; Huiskamp, R
2005-06-01
Previous experiments on the radiosensitivity of O-2A glial progenitors determined for single-dose fission-neutron and X irradiation showed log-linear survival curves, suggesting a lack of accumulation of recovery of sublethal damage. In the present study, we addressed this question and further characterized the radiobiological properties of these glial stem cells by investigating the recovery capacity of glial stem cells using either fractionated or protracted whole-body irradiation. Irradiations were performed on newborn, 2-week-old or 12-week-old rats. Fractionated irradiations (four fractions) were performed with 24-h intervals, followed by cell isolations 16- 24 h after the last irradiation. Single-dose irradiations were followed by cell isolation 16-24 h after irradiation or delayed cell isolation (4 days after irradiation) of the O-2A progenitor cells from either spinal cord (newborns) or optic nerve (2- and 12-week-old rats). Results for neonatal progenitor cell survival show effect ratios for both fractionated fission-neutron and X irradiation of the order of 1.8 when compared with single-dose irradiation. A similar ratio was found after single-dose irradiation combined with delayed plating. Comparable results were observed for juvenile and adult optic nerve progenitors, with effect ratios of the order of 1.2. The present investigation clearly shows that fractionated irradiation regimens using X rays or fission neutrons and CNS tissue from rats of various ages results in an increase in O-2A progenitor cell survival while repair is virtually absent. This recovery of the progenitor pool after irradiation can be observed at all ages but is greatest in the neonatal spinal cord and can probably be attributed to repopulation. PMID:15913395
NASA Astrophysics Data System (ADS)
Pervez, Nadeem
Prostate cancer is the most common cancer among Canadian men. The standard treatment in high-risk category is radical radiation, with androgen suppression treatment (AST). Significant disease progression is reported despite this approach. Radiation dose escalation has been shown to improve disease-free survival; however, it results in higher toxicities. Hypofractionated radiation schedules (larger dose each fraction in shorter overall treatment time) are expected to deliver higher biological doses. A hypofractionated scheme was used in this study to escalate radiation doses with AST. Treatment was well tolerated acutely. Early results of self-administered quality of life reported by patients shows a decrease in QOL which is comparable to other treatment schedules. Significant positional variation of the prostate was observed during treatment. Therefore, we suggest daily target verification to avoid a target miss. Initial late effects are reasonable and early treatment outcomes are promising. Longer follow-up is required for full outcomes assessments.
Effet de la dose d'irradiation sur la fraction tocophérolique d'huiles végétales
NASA Astrophysics Data System (ADS)
Chaouch, A.; El Fartah, S.; Pouliquen-Sonaglia, I.; Lesgards, G.; Raffi, J.; Trihi, M.
1999-01-01
Tocopherols, minor components of vegetable oils, are very important due to their high antioxydant power; we studied separation and quantification of tocopherol fraction with regard to the irradiation dose, using liquid chromatography combined with electrochemical detection. Dans les huiles végétales, les tocophérols sont des constituants mineurs très importants grâce à leur pouvoir antioxydant très élevé. Notre travail s'est porté sur la séparation et la quantification de la fraction tocophérolique et son évolution en fonction des différentes doses d'ionisation par la technique C.L.H.P. / détection électrochimique.
K-Ras mutant fraction in A/J mouse lung increases as a function of benzo[a]pyrene dose
K-Ras mutant fraction (MF) was measured to examine the default assumption of low dose linearity in the benzo[a]pyrene (B[a]P) mutational response. Groups of ten male A/J mice (7-9 weeks-old) received a single i.p. injection of 0, 0.05, 0.5, 5, or 50 mg/kg B[a]P, and were sacrifi...
Yoon, Sang Min; Huh, Seung Jae . E-mail: sjhuh@smc.samsung.co.kr; Park, Won; Lee, Jeung Eun; Park, Young Je; Nam, Hee Rim; Lim, Do Hoon; Ahn, Yong Chan
2006-08-01
Purpose: This study evaluated the treatment results of external beam radiotherapy administered in six fractions per week and high-dose-rate (HDR) brachytherapy for the treatment of cervical cancer. Methods and Materials: From July 2000 to July 2003, 43 patients were enrolled in this study. The patients received 45 Gy from a 10-MV photon beam using four-field box or anterior-posterior beams. Parametrial regions and the pelvic side walls were boosted with up to 50.4 Gy using a midline block. The daily fraction dose was 1.8 Gy administered in six-weekly fractions, from Monday to Saturday. HDR brachytherapy was also delivered at doses of 24 Gy to point A in six fractions twice a week. The median follow-up time was 37 months (range, 9-60 months). Results: The median overall treatment time was 51 days for all patients (range, 44-62 days). Thirty-four patients (79.1%) achieved complete remission and 8 (18.6%) achieved partial remission after radiotherapy. Locoregional recurrence occurred in 5 patients (11.6%), and a distant metastasis was encountered in 6 patients (13.9%). The 3-year overall survival, locoregional, and distant metastasis-free survival rates were 74.7%, 87.8%, and 84.7%, respectively. Grade 2 and 3 late rectal complications were encountered in 3 (6.5%) and 1 (2.2%), respectively. There were no Grade 3 late bladder complications. Conclusions: Six fractions per week of external beam radiotherapy and HDR brachytherapy is an effective treatment for patients with a carcinoma of the uterine cervix and can be used as a possible alternative to concomitant chemoradiotherapy in elderly patients or in patients with co-morbidity.
Jebsen, Nina L.; Engellau, Jacob; Engström, Katarina; Bauer, Henrik C.; Monge, Odd R.; Muren, Ludvig P.; Eide, Geir E.; Trovik, Clement S.; Bruland, Øyvind S.
2013-08-01
Purpose: To study the impact of dose fractionation of adjuvant radiation therapy (RT) on local recurrence (LR) and the relation of LR to radiation fields. Methods and Materials: LR rates were analyzed in 462 adult patients with soft tissue sarcoma who underwent surgical excision and adjuvant RT at five Scandinavian sarcoma centers from 1998 to 2009. Medical records were reviewed for dose fractionation parameters and to determine the location of the LR relative to the radiation portals. Results: Fifty-five of 462 patients developed a LR (11.9%). Negative prognostic factors included intralesional surgical margin (hazard ratio [HR]: 7.83, 95% confidence interval [CI]: 3.08-20.0), high malignancy grade (HR: 5.82, 95% CI: 1.31-25.8), age at diagnosis (HR per 10 years: 1.27, 95% CI: 1.03-1.56), and malignant peripheral nerve sheath tumor histological subtype (HR: 6.66, 95% CI: 2.56-17.3). RT dose was tailored to margin status. No correlation between RT dose and LR rate was found in multiple Cox regression analysis. The majority (65%) of LRs occurred within the primary RT volume. Conclusions: No significant dose–response effect of adjuvant RT was demonstrated. Interestingly, patients given 45-Gy accelerated RT (1.8 Gy twice daily/2.5 weeks) had the best local outcome. A total dose of 50 Gy in 25 fractions seemed adequate following wide margin surgery. The risk of LR was associated with histopathologic subtype, which should be included in the treatment algorithm of adjuvant RT in soft tissue sarcoma.
Hoving, Saske; Heeneman, Sylvia; Gijbels, Marion J.J.; Poele, Johannes A.M. te; Russell, Nicola S.; Daemen, Mat J.A.P.; Stewart, Fiona A.
2008-07-01
Purpose: Increased risk of atherosclerosis and stroke has been demonstrated in patients receiving radiotherapy for Hodgkin's lymphoma and head-and-neck cancer. We previously showed that 14 Gy to the carotid arteries of hypercholesterolemic ApoE{sup -/-} mice resulted in accelerated development of macrophage-rich, inflammatory atherosclerotic lesions. Here we investigate whether clinically relevant fractionated irradiation schedules and lower single doses also predispose to an inflammatory plaque phenotype. Methods and Materials: ApoE{sup -/-} mice were given 8 or 14 Gy, or 20 x 2.0 Gy in 4 weeks to the neck, and the carotid arteries were subsequently examinated for presence of atherosclerotic lesions, plaque size, and phenotype. Results: At 4 weeks, early atherosclerotic lesions were found in 44% of the mice after single doses of 14 Gy but not in age-matched controls. At 22 to 30 weeks after irradiation there was a twofold increase in the mean number of carotid lesions (8-14 Gy and 20 x 2.0 Gy) and total plaque burden (single doses only), compared with age-matched controls. The majority of lesions seen at 30 to 34 weeks after fractionated irradiation or 14-Gy single doses were granulocyte rich (100% and 63%, respectively), with thrombotic features (90% and 88%), whereas these phenotypes were much less common in age-matched controls or after a single dose of 8 Gy. Conclusions: We showed that fractionated irradiation accelerated the development of atherosclerosis in ApoE{sup -/-} mice and predisposed to the formation of an inflammatory, thrombotic plaque phenotype.
Deeg, H J; Sullivan, K M; Buckner, C D; Storb, R; Appelbaum, F R; Clift, R A; Doney, K; Sanders, J E; Witherspoon, R P; Thomas, E D
1986-12-01
Seventy-five patients with acute nonlymphoblastic leukemia (ANL) in first remission were treated with cyclophosphamide, 60 mg/kg on each of two consecutive days followed by total body irradiation (TBI) at an exposure rate of 4-6 cGy/min from two opposing 60Co sources. The first 22 patients were given 9.2 Gy of TBI as a single dose. Subsequently 53 patients were randomized to receive either 10 Gy single dose TBI (n = 27) or 6 x 2 Gy fractionated TBI (n = 26). All patients received marrow transplants from HLA-identical siblings and all had sustained engraftment. Patients given 10 Gy of TBI had more early toxicity, especially veno-occlusive disease of the liver, than patients given 9.2 or 6 x 2 Gy of TBI. Idiopathic interstitial pneumonitis appeared to be more frequent in patients given 9.2 or 10 Gy single-dose TBI than in patients given 6 x 2 Gy fractionated TBI. Patients have now been followed from 5 to 9 years. Survival (+/- 95% confidence limits) at 5 years is 54 +/- 31% among patients given 9.2 Gy single dose TBI, 33 +/- 31% among patients given 10 Gy single dose TBI, and 54 +/- 26% among patients given 6 x 2 Gy fractionated TBI (P = 0.04). These results indicate that about half the patients with ANL transplanted while in first chemotherapy-induced remission can be expected to become long-term survivors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3332129
Sano, Y; Hoshino, T; Barker, M; Deen, D F
1984-02-01
the overall cytotoxicity produced by fractionated BCNU protocols. Although spheroids did not shrink during or after exposure to BCNU, growth was retarded by treatment with all doses and schedules. An optimum time point for growth delay measurement could not be determined from the data. However, correlations between cell survival and growth delay were obtained with arbitrarily chosen end point volumes of four and ten times the volume at the time of treatment. PMID:6692362
Crane, Christopher H; Koay, Eugene J
2016-07-01
The emergence and success of stereotactic body radiation therapy (SBRT) for the treatment of lung cancer have led to its rapid adoption for liver cancers. SBRT can achieve excellent results for small liver tumors. However, the vast majority of physicians interpret SBRT as meaning doses of radiation (range, 4-20 Gray [Gy]) that may not be ablative but are delivered within about 1 week (ie, in 3-6 fractions). Adherence to this approach has limited the effectiveness of SBRT for large liver tumors (>7 cm) because of the need to reduce doses to meet organ constraints. The prognosis for patients who present with large liver tumors is poor, with a median survival ≤12 months, and most of these patients die from tumor-related liver failure. Herein, the authors present a comprehensive solution to achieve ablative SBRT doses for patients with large liver tumors by using a combination of classic, modern, and novel concepts of radiotherapy: fractionation, dose painting, motion management, image guidance, and simultaneous integrated protection. The authors discuss these concepts in the context of large, inoperable liver tumors and review how this approach can substantially prolong survival for patients, most of whom otherwise have a very poor prognosis and few effective treatment options. Cancer 2016;122:1974-86. © 2016 American Cancer Society. PMID:26950735
Combs, Stephanie E.; Welzel, Thomas; Schulz-Ertner, Daniela; Huber, Peter E.; Debus, Juergen
2010-01-15
Purpose: To evaluate the outcomes of patients with vestibular schwannoma (VS) treated with fractionated stereotactic radiotherapy (FSRT) vs. those treated with stereotactic radiosurgery (SRS). Methods and Materials: This study is based on an analysis of 200 patients with 202 VSs treated with FSRT (n = 172) or SRS (n = 30). Patients with tumor progression and/or progression of clinical symptoms were selected for treatment. In 165 out of 202 VSs (82%), RT was performed as the primary treatment for VS, and for 37 VSs (18%), RT was conducted for tumor progression after neurosurgical intervention. For patients receiving FSRT, a median total dose of 57.6 Gy was prescribed, with a median fractionation of 5 x 1.8 Gy per week. For patients who underwent SRS, a median single dose of 13 Gy was prescribed to the 80% isodose. Results: FSRT and SRS were well tolerated. Median follow-up time was 75 months. Local control was not statistically different for both groups. The probability of maintaining the pretreatment hearing level after SRS with doses of <=13 Gy was comparable to that of FSRT. The radiation dose for the SRS group (<=13 Gy vs. >13 Gy) significantly influenced hearing preservation rates (p = 0.03). In the group of patients treated with SRS doses of <=13 Gy, cranial nerve toxicity was comparable to that of the FSRT group. Conclusions: FSRT and SRS are both safe and effective alternatives for the treatment of VS. Local control rates are comparable in both groups. SRS with doses of <=13 Gy is a safe alternative to FSRT. While FSRT can be applied safely for the treatment of VSs of all sizes, SRS should be reserved for smaller lesions.
Yoshioka, Yasuo; Konishi, Koji; Sumida, Iori; Takahashi, Yutaka; Isohashi, Fumiaki; Ogata, Toshiyuki; Koizumi, Masahiko; Yamazaki, Hideya; Nonomura, Norio; Okuyama, Akihiko; Inoue, Takehiro
2011-06-01
Purpose: To evaluate an extreme hypofractionation regimen with 54 Gy in nine fractions provided by high-dose-rate (HDR) brachytherapy as monotherapy for prostate cancer by reporting 5-year clinical results. Methods and Materials: Between 1996 and 2005, 112 patients with localized prostate cancer were treated with HDR brachytherapy without external beam radiotherapy. Of the 112 patients, 15 were considered low risk, 29 intermediate risk, and 68 as high risk. The prescribed dose was uniformly 54 Gy in nine fractions within 5 days. Of the 112 patients, 94 also received hormonal therapy. The median follow-up time was 5.4 years. Results: All the patients safely completed the treatment regimen. The 5-year prostate-specific antigen (PSA) failure-free, local control, disease-free survival, and overall survival rate was 83%, 97%, 87%, and 96%, respectively. The 5-year PSA failure-free rate for low-, intermediate-, and high-risk patients was 85% (95% confidence interval, 66-100%), 93% (95% confidence interval, 83-100%), and 79% (95% confidence interval, 69-89%), respectively. The significant prognostic factors for PSA failure were the initial PSA level (p = .029) and younger age (p = .019). The maximal toxicities observed were Grade 3 using the Common Terminology Criteria for Adverse Events, version 3.0, for both acute and late toxicity (6 and 3 patients had acute and late Grade 3 toxicity, respectively). Late Grade 2 toxicity was observed in 13 patients. Conclusion: Monotherapeutic HDR brachytherapy with an extreme hypofractionation regimen of 54 Gy in nine fractions associated with hormonal therapy was feasible, and its toxicity was acceptable. The interim tumor control rate at a median 5.4 years was promising, even for patients with locally advanced disease. This dose-fractionation scheme might be referred to by other terms, such as stereotactic body radiotherapy. Studies with longer follow-up periods and from multiple institutions are needed to confirm the efficacy of
Van Den Bogaert, W.; Van Der Schueren, E.; Horiot, J.C.; Chaplain, G.; Arcangeli, G.; Gonzalez, D.; Svoboda, V.
1982-10-01
From 1978 to the end of 1980, 179 patients with advanced head and neck tumors were accrued in a multicenter pilot study of the EORTC Radiotherapy Group, investigating the feasibility of high dose multiple daily fractionation (MDF) and its combination with misonidazole. The irradiation scheme consisted of three daily fractions of 1.6 Gy (four hour intervals) to a total dose of 48 Gy in two weeks, followed 3 to 4 weeks later by a boost to a total of about 70 Gy in 6 to 7 weeks. Misonidazole was given in daily doses of 1 g/m/sup 2/ (total 13 or 14 g/m/sup 2/) to 53 patients, thus sensitizing every radiation session. All patients had large head and neck tumors, with poor prognosis. Acute reactions were well tolerated. Skin reactions were very moderate; mucosal reactions started at day 10 to 12. All patients had a confluent mucositis that lasted for one to two weeks. When the whole oral cavity was irradiated, reactions lasted somewhat longer. The boost caused no significant symptoms. The radiosensitizer did not modify the reaction pattern. Tumor regression was very impressive, so that palliation was obtained quickly. Nine patients died from treatment related causes. It is difficult to assess local control at this time, but at the time of analysis (August 1981), the actuarial control was 48% at 20 months, with misonidazole 57%. This difference, however, is not statistically significant. Survival of the total group is 31% at 20 months. In these patients with a heavy tumor burden the early results were considered a success by all participants. For patients with sufficient follow-up, late reactions can be evaluated. Some edema and fibrosis is seen, but did not exceed a degree which could be expected with single daily fractionation to the same dose.
Thomas, Tarita O.; Agrawal, Priya; Guitart, Joan; Rosen, Steven T.; Querfeld, Christiane; Kuzel, Timothy M.
2013-03-01
Purpose: Cutaneous T-cell lymphoma (CTCL) is a radiosensitive tumor. Presently, treatment with radiation is given in multiple fractions. The current literature lacks data that support single-fraction treatment for CTCL. This retrospective review assesses the clinical response in patients treated with a single fraction of radiation. Methods and Materials: This study reviewed the records of 58 patients with CTCL, primarily mycosis fungoides, treated with a single fraction of palliative radiation therapy (RT) between October 1991 and January 2011. Patient and tumor characteristics were reviewed. Response rates were compared using Fisher's exact test and multiple logistic regressions. Survival rates were determined using the Kaplan-Meier method. Cost-effectiveness analysis was performed to assess the cost of a single vs a multifractionated treatment regimen. Results: Two hundred seventy individual lesions were treated, with the majority (97%) treated with ≥700 cGy; mean follow-up was 41.3 months (range, 3-180 months). Response rate by lesion was assessed, with a complete response (CR) in 255 (94.4%) lesions, a partial response in 10 (3.7%) lesions, a partial response converted to a CR after a second treatment in 4 (1.5%) lesions, and no response in 1 (0.4%) lesion. The CR in lower extremity lesions was lower than in other sites (P=.0016). Lesions treated with photons had lower CR than those treated with electrons (P=.017). Patients with lesions exhibiting large cell transformation and tumor morphology had lower CR (P=.04 and P=.035, respectively). Immunophenotype did not impact response rate (P=.23). Overall survival was significantly lower for patients with Sézary syndrome (P=.0003) and erythroderma (P<.0001). The cost of multifractionated radiation was >200% higher than that for single-fraction radiation. Conclusions: A single fraction of 700 cGy-800 cGy provides excellent palliation for CTCL lesions and is cost effective and convenient for the patient.
Matsuyama, Tomohiko; Kogo, Kasei; Oya, Natsuo
2013-03-15
Purpose: To evaluate the efficacy and toxicity of fractionated stereotactic radiation therapy (FSRT) based on biological effective dose (BED), a novel approach to deliver a fixed BED irrespective of dose fractionation, for brain metastases from non-small cell lung cancer (NSCLC). Methods and Materials: Between March 2005 and March 2009 we treated 299 patients with 1 to 5 lesions from NSCLC (573 total brain metastases) with FSRT using Novalis. The dose fractionation schedules were individually determined to deliver a peripheral BED10 (α/β ratio = 10) of approximately 80 Gy{sub 10}. The median number of fractions was 3 (range, 2-10), the median peripheral BED10 was 83.2 Gy (range, 19.1-89.6 Gy). Patients were followed up with magnetic resonance imaging (MRI) studies performed at 1- to 2-month intervals. The local tumor control rate and overall local progression-free and intracranial relapse-free survival were calculated by the Kaplan-Meier method. Results: Local control rates for all 573 lesions at 6 and 12 months were 96.3% and 94.5%, respectively. By multivariate analysis the tumor diameter was the only factor predictive of the local control rate (P=.001). The median overall survival, local progression-free survival, and intracranial relapse-free survival were 17.1, 14.9, and 4.4 months, respectively. The overall survival, local progression-free survival, and intracranial relapse-free survival rates at 6 and 12 months were 78.5% and 63.3%, 74.3% and 57.8%, and 41.0% and 21.8%, respectively. Six patients (2%) manifested progressive radiation injury to the brain even during therapy with corticosteroids; they underwent hyperbaric oxygen therapy, and follow-up MRI showed improvement. Conclusions: This study showed that BED-based FSRT for brain metastases from NSCLC is a promising strategy that may yield excellent outcomes with acceptable toxicity. Criteria must be established to determine the optimal dose fractionation for individual patients.
Bangotra, Pargin; Mehra, Rohit; Kaur, Kirandeep; Kanse, Sandeep; Mishra, Rosaline; Sahoo, B K
2015-10-01
High concentration of radon ((222)Rn), thoron ((220)Rn) and their decay products in environment may increase the risk of radiological exposure to the mankind. The (222)Rn, (220)Rn concentration and their separate attached and unattached progeny concentration in units of EEC have been measured in the dwellings of Muktsar and Mansa districts of Punjab (India), using Pin-hole cup dosimeters and deposition based progeny sensors (DTPS/DRPS). The indoor (222)Rn and (220)Rn concentration was found to vary from 21 Bqm(-3) to 94 Bqm(-3) and 17 Bqm(-3) to 125 Bqm(-3). The average EEC (attached + unattached) of (222)Rn and (220)Rn was 25 Bqm(-3) and 1.8 Bqm(-3). The equilibrium factor for (222)Rn and (220)Rn in studied area was 0.47 ± 0.13 and 0.05 ± 0.03. The equilibrium factor and unattached fraction of (222)Rn and (220)Rn has been calculated separately. Dose conversion factors (DCFs) of different models have been calculated from unattached fraction for the estimation of annual effective dose in the studied area. From the experimental data a correlation relationship has been observed between unattached fraction (f(p)(Rn)) and equilibrium factor (F(Rn)). The present work also aims to evaluate an accurate expression among available expression in literature for the estimation of f(p)(Rn). PMID:26117280
Shimura, T; Kobayashi, J; Komatsu, K; Kunugita, N
2014-01-01
Cyclin D1 expression is precisely controlled during cell-cycle progression. However, repeated exposure to low-dose fractionated radiation (FR) abrogates cell cycle-dependent cyclin D1 degradation by constitutive activation of AKT survival signaling in normal human fibroblasts. The resulting abnormal nuclear cyclin D1 accumulation induces defects in DNA replication and resulting DNA double-strand breaks, and is associated with induction of genomic instability in low-dose irradiated cells. Here, we investigated the role of DNA damage signaling against such perturbed cell-cycle control of cyclin D1 expression. Nuclear cyclin D1 accumulation was induced within 7 days after low-dose FR (0.01 Gy or 0.05 Gy per fraction) in ATM-deficient cells (AT5BIVA), but appeared later in AT5BIVA cells harboring human ATM cDNA. Thus, ATM prevents abnormal nuclear cyclin D1 accumulation at early time points after low-dose FR. We further demonstrated that ATM-mediated downregulation of protein phosphatase 2A activity caused activation of the AKT/cyclin D1 pathway after long-term FR. Perturbation of cyclin D1 expression induced Rad51 foci that indicate homologous recombination repair (HRR) in control cells, while ATM- and NBS1-deficient cells (GM7166) failed to induce Rad51 foci after long-term low-dose FR. After 21 days of FR, NBS1- and ATM-deficient cells showed a decrease in nuclear cyclin D1-positive cells, and an increase in apoptotic cells. Similarly, inhibition of ATM with KU55933 abrogated nuclear cyclin D1 accumulation by induction of apoptosis in ATM-complemented cells exposed to low-dose FR. In conclusion, we here demonstrate that ATM is involved in controlling cyclin D1 levels after low-dose FR. DNA damage signaling mitigates the harmful effects of low-dose long-term FR by suppression of cell death induced by perturbation of cyclin D1 expression. PMID:25486524
Lanini, Juliana; Galduróz, José Carlos Fernandes; Pompéia, Sabine
2016-01-01
Caffeine is widely used, often consumed with food, and improves simple and complex/executive attention under fasting conditions. We investigated whether these cognitive effects are observed when personalized habitual doses of caffeine are ingested by caffeine consumers, whether they are influenced by nutriments and if various executive domains are susceptible to improvement. This was a double-blind, placebo-controlled study including 60 young, healthy, rested males randomly assigned to one of four treatments: placebo fasting, caffeine fasting, placebo meal and caffeine meal. Caffeine doses were individualized for each participant based on their self-reported caffeine consumption at the time of testing (morning). The test battery included measures of simple and sustained attention, executive domains (inhibiting, updating, shifting, dual tasking, planning and accessing long-term memory), control measures of subjective alterations, glucose and insulin levels, skin conductance, heart rate and pupil dilation. Regardless of meal intake, acute habitual doses of caffeine decreased fatigue, and improved simple and sustained attention and executive updating. This executive effect was not secondary to the habitual weekly dose consumed, changes in simple and sustained attention, mood, meal ingestion and increases in cognitive effort. We conclude that the morning caffeine "fix" has positive attentional effects and selectively improved executive updating whether or not caffeine is consumed with food. PMID:26621326
Liu, Junyang; Kaidu, Motoki; Sasamoto, Ryuta; Ayukawa, Fumio; Yamana, Nobuko; Sato, Hiraku; Tanaka, Kensuke; Kawaguchi, Gen; Ohta, Atsushi; Maruyama, Katsuya; Abe, Eisuke; Kasahara, Takashi; Nishiyama, Tsutomu; Tomita, Yoshihiko; Aoyama, Hidefumi
2016-01-01
We investigated the outcomes of treatment for patients with localized prostate cancer (PCa) treated with 3D conformal radiation therapy (3D-CRT) followed by two-fraction high-dose-rate brachytherapy within a single day (2-fr.-HDR-BT/day) at a single institution. A total of 156 consecutive Asian males (median age, 67 years) were enrolled. To compare our findings with those of other studies, we analyzed our results using the D'Amico classification, assigning the patients to low- (n =5; 3.2%), intermediate- (n =36; 23.1%) and high-risk (n =115; 73.7%) groups (Stage T3 PCa patients were classified as high-risk). One patient in the D'Amico low-risk group (20%), 13 intermediate-risk patients (36.1%) and 99 high-risk patients (86.1%) underwent androgen deprivation therapy. We administered a prescription dose of 39 Gy in 13 fractions of 3D-CRT combined with 18 Gy of HDR-BT in two 9-Gy fractions delivered within a single day. We did not distinguish between risk groups in determining the prescription dose. The median follow-up period was 38 months. Of the 156 patients, one died from primary disease and five died from other diseases. The 3-year overall survival (OS) rates were 100%, 100% and 93.7%, and the 3-year ‘biochemical no evidence of disease (bNED)’ rates were 100%, 100% and 96.9% for the D'Amico low-, intermediate- and high-risk groups, respectively. No patient developed ≥ Grade 3 early toxicity. The Grade 3 late genitourinary toxicity rate was 2.6%, and no ≥ Grade 3 late gastrointestinal toxicity occurred. The efficacy and safety of this study were satisfactory, and longer-term follow-up is necessary. PMID:26983988
Pilorge, Sylvain; Rigaudeau, Sophie; Rabian, Florence; Sarkozy, Clémentine; Taksin, Anne L; Farhat, Hassan; Merabet, Fathia; Ghez, Stéphanie; Raggueneau, Victoria; Terré, Christine; Garcia, Isabelle; Renneville, Aline; Preudhomme, Claude; Castaigne, Sylvie; Rousselot, Philippe
2014-04-01
Gemtuzumab ozogamicin (fGO), a humanized anti-CD33 monoclonal antibody linked to calicheamicin in combination with intensive chemotherapy gives high response rates in adult acute myeloid leukemia (AML) patients in relapse. However, reduced intensity chemotherapy in combination with fractionated GO has not been tested in aged relapsing patients. Patients from our institution with CD33+ AML aged 55 years or more in first late relapse (≥ 6 months) were proposed participation in a GO compassionate use program. Induction therapy consisted in fractionated GO (fGO; 3 mg/m², days 1, 4, 7) with standard-dose cytarabine (200 mg/m² /day, 7 days). Patients were consolidated with two courses of GO and intermediate dose cytarabine. Twenty-four patients (median age 68 years) received fGO with cytarabine. Median follow-up was 42 months. The response rate was 75%, including complete remission (CR) in 16 patients and CR with incomplete platelet recovery (CRp) in two patients. Two-year overall survival (OS) was 51% (95% CI: 28-69) and 2 years relapse-free survival (RFS) was 51% (95%CI: 25-72). Duration of second CR (CR2) was longer than first CR (CR1) in 9 out of 18 patients. Minimal residual disease (MRD) was negative in evaluable patients in CR2, particularly in NPM1 mutated cases. Toxicity was in line with that of the same fractionated single agent GO schedule. Fractionated GO with low intensity chemotherapy produced high response rates and prolonged CR2 in aged AML patients in first late relapse. PMID:24375467
Desai, Sejal; Kumar, Amit; Laskar, S; Pandey, B N
2013-01-01
Cytokines are known to play pivotal roles in cancer initiation, progression and pathogenesis. Accumulating evidences suggest differences in basal and stress-induced cytokine profiles of cancers with diverse origin. However, a comprehensive investigation characterising the cytokine profile of various tumor types after acute and fractionated doses of gamma-irradiation, and its effect on survival of bystander cells is not well known in literature. In the present study, we have evaluated the cytokine secretion profile of human tumor cell lines (HT1080, U373MG, HT29, A549 and MCF-7) either before (basal) or after acute (2, 6 Gy) and fractionated doses (3×2 Gy) of gamma-irradiation in culture medium obtained from these cells by multiplex bead array/ELISA. Moreover, clonogenic assays were performed to evaluate the effect of conditioned medium (CM) on the survival and growth of respective cells. Based on the screening of 28 analytes, our results showed that the basal profiles of these cell lines varied considerably in terms of the number and magnitude of secreted factors, which was minimum in MCF-7. Interestingly, TNF-α, IL-1β, PDGF-AA, TGF-β1, fractalkine, IL-8, VEGF and GCSF were found in CM of all the cell lines. However, secretion of certain cytokines was cell line-specific. Moreover, CM caused increase in clonogenic survival of respective tumor cells (in the order HT1080>U373MG>HT29>A549>MCF-7), which was correlated with the levels of IL-1β, IL-6, IL-8, GMCSF and VEGF in their CM. After irradiation, the levels of most of the cytokines increased markedly in a dose dependent manner. The fold change in cytokine levels was lower in irradiated conditioned medium (ICM) of tumor cells collected after fractionated than respective acute dose, except in MCF-7. Interestingly, amongst these cell lines, the radiation-induced fold increase in cytokine levels was maximum in ICM of A549 cells. Moreover, bystander A549 cells treated with respective ICM showed dose dependent
Arruda Viani, Gustavo; Stefano, Eduardo Jose; Vendito Soares, Francisco; Afonso, Sergio Luis
2011-07-15
Purpose: To evaluate whether the risk of local recurrence depends on the biologic effective dose (BED) or fractionation dose in patients with resectable rectal cancer undergoing preoperative radiotherapy (RT) compared with surgery alone. Methods and Materials: A meta-analysis of randomized controlled trials (RCTs) was performed. The MEDLINE, Embase, CancerLit, and Cochrane Library databases were systematically searched for evidence. To evaluate the dose-response relationship, we conducted a meta-regression analysis. Four subgroups were created: Group 1, RCTs with a BED >30 Gy{sub 10} and a short RT schedule; Group 2, RCTs with BED >30 Gy{sub 10} and a long RT schedule; Group 3, RCTs with BED {<=}30 Gy{sub 10} and a short RT schedule; and Group 4, RCTs with BED {<=}30 Gy{sub 10} and a long RT schedule. Results: Our review identified 21 RCTs, yielding 9,097 patients. The pooled results from these 21 randomized trials of preoperative RT showed a significant reduction in mortality for groups 1 (p = .004) and 2 (p = .03). For local recurrence, the results were also significant in groups 1 (p = .00001) and 2 (p = .00001).The only subgroup that showed a greater sphincter preservation (SP) rate than surgery was group 2 (p = .03). The dose-response curve was linear (p = .006), and RT decreased the risk of local recurrence by about 1.7% for each Gy{sub 10} of BED. Conclusion: Our data have shown that RT with a BED of >30 Gy{sub 10} is more efficient in reducing local recurrence and mortality rates than a BED of {<=}30 Gy{sub 10}, independent of the schedule of fractionation used. A long RT schedule with a BED of >30 Gy{sub 10} should be recommended for sphincter preservation.
Morton, Gerard C.; Loblaw, D. Andrew; Chung, Hans; Tsang, Gail; Sankreacha, Raxa; Deabreu, Andrea; Zhang Liying; Mamedov, Alexandre; Cheung, Patrick; Batchelar, Deidre; Danjoux, Cyril; Szumacher, Ewa
2011-08-01
Purpose: To investigate the change in health-related quality of life for men after high-dose-rate brachytherapy and external beam radiotherapy for prostate cancer and the factors associated with this change. Methods and Materials: Eligible patients had clinically localized intermediate-risk prostate cancer. The patients received high-dose-rate brachytherapy as a single 15-Gy implant, followed by external beam radiotherapy to 37.5 Gy in 15 fractions. The patients were monitored prospectively for toxicity (Common Terminology Criteria for Adverse Events, version 3.0) and health-related quality of life (Expanded Prostate Cancer Index Composite [EPIC]). The proportion of patients developing a clinically significant difference in the EPIC domain score (minimally important difference of >0.5 standard deviation) was determined and correlated with the baseline clinical and dosimetric factors. The study accrued 125 patients, with a median follow-up of 24 months. Results: By 24 months, 23% had Grade 2 urinary toxicity and only 5% had Grade 2 bowel toxicity, with no Grade 3 toxicity. The proportion of patients reporting a significant decrease in EPIC urinary, bowel, sexual, and hormonal domain scores was 53%, 51%, 45%, and 40% at 12 months and 57%, 65%, 51%, and 30% at 24 months, respectively. The proportion with a >1 standard deviation decrease in the EPIC urinary, bowel, sexual, and hormonal domain scores was 38%, 36%, 24%, and 20% at 12 months and 46%, 48%, 19%, and 8% at 24 months, respectively. On multivariate analysis, the dose to 10% of the urethra was associated with a decreasing EPIC urinary domain score (p = .0089) and, less strongly (p = .0312) with a decreasing hormonal domain score. No association was found between the prostate volume, bladder dose, or high-dose volume and urinary health-related quality of life. A high baseline International Index of Erectile Function score was associated (p = .0019) with a decreasing sexual domain score. The optimal maximal dose
Rovirosa, Angeles; Ascaso, Carlos; Sanchez-Reyes, Alberto; Herreros, Antonio; Abellana, Rosa; Pahisa, Jaume; Lejarcegui, Jose Antonio; Biete, Albert
2011-10-01
Purpose: To evaluate the results of high-dose-rate brachytherapy (HDRBT) using a schedule of three or four fractions per week, when possible, in 89 patients on local control and toxicity in postoperative treatment of endometrial carcinoma. The effect of the overall HDRBT treatment time (OTT) on toxicity was also evaluated. Patients and Methods: Federation Internationale de Gynecologie Obstetrique Stage: 24 IB, 45 IC, 4 IIA, 6 IIB, 4 IIIA, 2 IIIB, and 4 IIIC. Radiotherapy: Group 1-67 of 89 patients received external beam irradiation (EBI; 44-50 Gy) plus HDRBT (3 fractions of 4-6 Gy); Group 2-22 of 89 patients received HDRBT alone (6 fractions of 4-5 Gy). OTT: Group 1-HDRBT was completed in a median of 5 days in 32 patients and in >5 days in 35; Group 2-HDRBT was completed in <15 days in 11 patients and in {>=}16 days in 11. Toxicity was evaluated using Radiation Therapy Oncology Group scores and the bioequivalent dose (BED) study was performed in vaginal mucosa surface. Statistics included Student's t test, chi-square test, and receiving operator curves. Results: With a mean follow-up of 31 months (range, 6-70), 1 of 89 patients had vaginal relapse. Early toxicity appeared in 8 of 89 (9%) patients and was resolved. Late toxicity appeared in 13/89 (14%): vaginal nine Grade 1, three Grade 2, one Grade 4; bladder two Grade 2; rectal three Grade 1, one Grade 2. No differences were found in relation to OTT in Groups 1 and 2. Mean BED was 88.48 Gy in Group 1 and 165.28 Gy in Group 2. Cases with Grade 2 late vaginal toxicity received >75 Gy after EBI and >165 Gy in Group 2. Conclusions: Three fractions of 4-5 Gy in 3-5 days after EBI or 6 fractions in <15 days in patients receiving HDRBT alone was a safe treatment in relation to toxicity and local control. Vaginal surface BED less than 75 Gy after EBI and less than 160 Gy in HDRBT alone may be safe to avoid G2 toxicity.
Regan, Jessica A.; Mauro, Adolfo Gabriele; Carbone, Salvatore; Marchetti, Carlo; Gill, Rabia; Mezzaroma, Eleonora; Valle Raleigh, Juan; Salloum, Fadi N.; Van Tassell, Benjamin W.; Abbate, Antonio
2015-01-01
Heart failure (HF) with preserved ejection fraction (HFpEF) is a clinical syndrome of HF symptoms associated with impaired diastolic function. Although it represents ∼50% of patients with HF, the mechanisms of disease are poorly understood, and therapies are generally ineffective in reducing HF progression. Animal models of HFpEF not due to pressure or volume overload are lacking, therefore limiting in-depth understanding of the pathophysiological mechanisms and the development of novel therapies. We hypothesize that a continuous infusion of low-dose angiotensin II (ATII) is sufficient to induce left ventricular (LV) diastolic dysfunction and HFpEF, without increasing blood pressure or inducing LV hypertrophy or dilatation. Osmotic pumps were implanted subcutaneously in 8-wk-old male mice assigned to the ATII (0.2 mg·kg−1·day−1) or volume-matched vehicle (N = 8/group) for 4 wk. We measured systolic and diastolic arterial blood pressures through a tail-cuff transducer, LV dimensions and ejection fraction through echocardiography, and LV relaxation through pulsed-wave Doppler and LV catheterization. Myocardial fibrosis and cardiomyocyte cross-sectional area were measured. ATII infusion had no effects on systemic arterial blood pressure. ATII induced significant impairment in LV diastolic function, as measured by an increase (worsening) in LV isovolumetric relaxation time, myocardial performance index, isovolumetric relaxation time constant, and LV end-diastolic pressure without altering LV dimensions, mass, or ejection fraction. Chronic infusion of low-dose ATII recapitulates the HFpEF phenotype in the mouse, without increasing systemic arterial blood pressure. This mouse model may provide insight into the mechanisms of HFpEF. PMID:26188021
Regan, Jessica A; Mauro, Adolfo Gabriele; Carbone, Salvatore; Marchetti, Carlo; Gill, Rabia; Mezzaroma, Eleonora; Valle Raleigh, Juan; Salloum, Fadi N; Van Tassell, Benjamin W; Abbate, Antonio; Toldo, Stefano
2015-09-01
Heart failure (HF) with preserved ejection fraction (HFpEF) is a clinical syndrome of HF symptoms associated with impaired diastolic function. Although it represents ∼50% of patients with HF, the mechanisms of disease are poorly understood, and therapies are generally ineffective in reducing HF progression. Animal models of HFpEF not due to pressure or volume overload are lacking, therefore limiting in-depth understanding of the pathophysiological mechanisms and the development of novel therapies. We hypothesize that a continuous infusion of low-dose angiotensin II (ATII) is sufficient to induce left ventricular (LV) diastolic dysfunction and HFpEF, without increasing blood pressure or inducing LV hypertrophy or dilatation. Osmotic pumps were implanted subcutaneously in 8-wk-old male mice assigned to the ATII (0.2 mg·kg(-1)·day(-1)) or volume-matched vehicle (N = 8/group) for 4 wk. We measured systolic and diastolic arterial blood pressures through a tail-cuff transducer, LV dimensions and ejection fraction through echocardiography, and LV relaxation through pulsed-wave Doppler and LV catheterization. Myocardial fibrosis and cardiomyocyte cross-sectional area were measured. ATII infusion had no effects on systemic arterial blood pressure. ATII induced significant impairment in LV diastolic function, as measured by an increase (worsening) in LV isovolumetric relaxation time, myocardial performance index, isovolumetric relaxation time constant, and LV end-diastolic pressure without altering LV dimensions, mass, or ejection fraction. Chronic infusion of low-dose ATII recapitulates the HFpEF phenotype in the mouse, without increasing systemic arterial blood pressure. This mouse model may provide insight into the mechanisms of HFpEF. PMID:26188021
Gupta, Seema; Koru-Sengul, Tulay; Arnold, Susanne M; Devi, Gayathri R; Mohiuddin, Mohammed; Ahmed, Mansoor M
2011-02-01
In this study, the role of hyper-radiation sensitivity (HRS) in potentiating the effects of cisplatin by low-dose fractionated radiation (LDFRT) was evaluated in four human non-small cell lung cancer cell lines. Presence of HRS and cisplatin enhancement ratio (CER) by LDFRT/2 Gy was assessed using colony-forming and apoptotic assays. Cell-cycle disturbances were studied by flow cytometry. Expression of genes involved in apoptosis was assessed using real-time reverse transcriptase PCR arrays. H-157 cells showed a distinct HRS region, followed by UKY-29 and A549 cells, whereas it was absent in H460 cells, which when lack HRS showed maximum CER with LDFRT (4 × 0.5 Gy) both by clonogenic inhibition and by apoptosis compared with single fraction of 2 Gy whereas the most radioresistant A549 cells had the least CER, with no significant differences between LDFRT or 2 Gy. Interestingly, in H-157 cells, a more pronounced CER was observed with LDFRT when assessed by apoptosis but clonogenic inhibition-CER was higher with 2 Gy than with LDFRT. Excluding H-157 cells, the CER by LDFRT was inversely proportional to radioresistance [(determined by D(0), the dose to reduce survival by 67% from any point on the linear portion of the survival curve or surviving fraction (SF) at 2 Gy (SF(2))] of the cells. LDFRT alone or in combination with cisplatin induced larger number of proapoptotic genes than 2 Gy or cisplatin + 2 Gy in cells showing HRS when compared to H460 cells that lack HRS. These findings indicate that chemopotentiation by LDFRT is correlated more with the intrinsic radiation sensitivity of the non-small lung cancer cells than the HRS phenomenon whereas the mode of cell killing is both through apoptosis and clonogenic inhibition. PMID:21216938
Abouaf, Lucie; Girard, Nicolas; Lefort, Thibaud; D'hombres, Anne; Tilikete, Caroline; Vighetto, Alain; Mornex, Francoise
2012-03-01
Purpose: Radiotherapy has shown its efficacy in controlling optic nerve sheath meningiomas (ONSM) tumor growth while allowing visual acuity to improve or stabilize. However, radiation-induced toxicity may ultimately jeopardize the functional benefit. The purpose of this study was to identify predictive factors of poor visual outcome in patients receiving radiotherapy for ONSM. Methods and Materials: We conducted an extensive analysis of 10 patients with ONSM with regard to clinical, radiologic, and dosimetric aspects. All patients were treated with conformal radiotherapy and subsequently underwent biannual neuroophthalmologic and imaging assessments. Pretreatment and posttreatment values of visual acuity and visual field were compared with Wilcoxon's signed rank test. Results: Visual acuity values significantly improved after radiotherapy. After a median follow-up time of 51 months, 6 patients had improved visual acuity, 4 patients had improved visual field, 1 patient was in stable condition, and 1 patient had deteriorated visual acuity and visual field. Tumor control rate was 100% at magnetic resonance imaging assessment. Visual acuity deterioration after radiotherapy was related to radiation-induced retinopathy in 2 patients and radiation-induced mature cataract in 1 patient. Study of radiotherapy parameters showed that the mean eye dose was significantly higher in those 3 patients who had deteriorated vision. Conclusions: Our study confirms that radiotherapy is efficient in treating ONSM. Long-term visual outcome may be compromised by radiation-induced side effects. Mean eye dose has to be considered as a limiting constraint in treatment planning.
Horton, Janet K.; Blitzblau, Rachel C.; Yoo, Sua; Geradts, Joseph; Chang, Zheng; Baker, Jay A.; Georgiade, Gregory S.; Chen, Wei; Siamakpour-Reihani, Sharareh; Wang, Chunhao; Broadwater, Gloria; Groth, Jeff; Palta, Manisha; Dewhirst, Mark; Barry, William T.; Duffy, Eileen A.; and others
2015-07-15
Purpose: Women with biologically favorable early-stage breast cancer are increasingly treated with accelerated partial breast radiation (PBI). However, treatment-related morbidities have been linked to the large postoperative treatment volumes required for external beam PBI. Relative to external beam delivery, alternative PBI techniques require equipment that is not universally available. To address these issues, we designed a phase 1 trial utilizing widely available technology to 1) evaluate the safety of a single radiation treatment delivered preoperatively to the small-volume, intact breast tumor and 2) identify imaging and genomic markers of radiation response. Methods and Materials: Women aged ≥55 years with clinically node-negative, estrogen receptor–positive, and/or progesterone receptor–positive HER2−, T1 invasive carcinomas, or low- to intermediate-grade in situ disease ≤2 cm were enrolled (n=32). Intensity modulated radiation therapy was used to deliver 15 Gy (n=8), 18 Gy (n=8), or 21 Gy (n=16) to the tumor with a 1.5-cm margin. Lumpectomy was performed within 10 days. Paired pre- and postradiation magnetic resonance images and patient tumor samples were analyzed. Results: No dose-limiting toxicity was observed. At a median follow-up of 23 months, there have been no recurrences. Physician-rated cosmetic outcomes were good/excellent, and chronic toxicities were grade 1 to 2 (fibrosis, hyperpigmentation) in patients receiving preoperative radiation only. Evidence of dose-dependent changes in vascular permeability, cell density, and expression of genes regulating immunity and cell death were seen in response to radiation. Conclusions: Preoperative single-dose radiation therapy to intact breast tumors is well tolerated. Radiation response is marked by early indicators of cell death in this biologically favorable patient cohort. This study represents a first step toward a novel partial breast radiation approach. Preoperative radiation should
Ghilezan, Michel; Martinez, Alvaro; Gustason, Gary; Krauss, Daniel; Antonucci, J. Vito; Chen, Peter; Fontanesi, James; Wallace, Michelle; Ye Hong; Casey, Alyse; Sebastian, Evelyn; Kim, Leonard; Limbacher, Amy
2012-07-01
Purpose: To report the toxicity profile of high-dose-rate (HDR)-brachytherapy (BT) as monotherapy in a Human Investigation Committee-approved study consisting of a single implant and two fractions (12 Gy Multiplication-Sign 2) for a total dose of 24 Gy, delivered within 1 day. The dose was subsequently increased to 27 Gy (13.5 Gy Multiplication-Sign 2) delivered in 1 day. We report the acute and early chronic genitourinary and gastrointestinal toxicity. Methods and Materials: A total of 173 patients were treated between December 2005 and July 2010. However, only the first 100 were part of the IRB-approved study and out of these, only 94 had a minimal follow-up of 6 months, representing the study population for this preliminary report. All patients had clinical Stage T2b or less (American Joint Committee on Cancer, 5th edition), Gleason score 6-7 (3+4), and prostate-specific antigen level of {<=}12 ng/mL. Ultrasound-guided HDR-BT with real-time dosimetry was used. The prescription dose was 24 Gy for the first 50 patients and 27 Gy thereafter. The dosimetric goals and constraints were the same for the two dose groups. Toxicity was scored using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3. The highest toxicity scores encountered at any point during follow-up are reported. Results: The median follow-up was 17 months (range, 6-40.5). Most patients had Grade 0-1 acute toxicity. The Grade 2 acute genitourinary toxicity was mainly frequency/urgency (13%), dysuria (5%), hematuria, and dribbling/hesitancy (2%). None of the patients required a Foley catheter at any time; however, 8% of the patients experienced transient Grade 1 diarrhea. No other acute gastrointestinal toxicities were found. The most common chronic toxicity was Grade 2 urinary frequency/urgency in 16% of patients followed by dysuria in 4% of patients; 2 patients had Grade 2 rectal bleeding and 1 had Grade 4, requiring laser treatment. Conclusions: Favorable
van de Glind, Gerline; Rebel, Heggert; van Kempen, Marika; Tensen, Kees; de Gruijl, Frank
2016-01-01
Sunburns and especially sub-sunburn chronic UV exposure are associated with increased risk of squamous cell carcinomas (SCCs). Here we focus on a possible difference in tumor initiation from a single severe-sunburn dose (on day 1, 21 hairless mice) and from an equal dose fractionated into very low sub-sunburn doses not causing any (growth-promoting) epidermal hyperplasia (40 days daily exposure, n=20). From day 47 all mice received 12-O-Tetradecanoylphorbol-13-acetate (TPA) applications (2x/wk) for 20 weeks to promote tumor development within the lifetime of the animals. After the sub-sunburn regimen sparse DNA damage-retaining basal cells (quiescent stem cells, QSCs) remained in the non-hyperplastic epidermis. These cells were forced to divide by TPA. After discontinuation of TPA tumors regressed and disappeared in the ‘sunburn group’ but persisted and grew in the ‘sub-sunburn group’ (0.06 vs 2.50 SCCs and precursors ≥4mm/mouse after 280 days, p=0.03). As the tumors carried no mutations in p53, H/K/N-Ras and Notch1/2, these ‘usual suspects' were not involved in the UV-driven tumor initiation. Although we could not selectively eliminate QSCs (unknown phenotype) to establish causality, our data suggest that forcing specifically DNA damage-retaining QSCs to divide – with high mutagenic risk - gives rise to persisting (mainly ‘in situ’) skin carcinomas. PMID:26797757
van de Glind, Gerline; Rebel, Heggert; van Kempen, Marika; Tensen, Kees; de Gruijl, Frank
2016-02-16
Sunburns and especially sub-sunburn chronic UV exposure are associated with increased risk of squamous cell carcinomas (SCCs). Here we focus on a possible difference in tumor initiation from a single severe-sunburn dose (on day 1, 21 hairless mice) and from an equal dose fractionated into very low sub-sunburn doses not causing any (growth-promoting) epidermal hyperplasia (40 days daily exposure, n=20). From day 47 all mice received 12-O-Tetradecanoylphorbol-13-acetate (TPA) applications (2x/wk) for 20 weeks to promote tumor development within the lifetime of the animals. After the sub-sunburn regimen sparse DNA damage-retaining basal cells (quiescent stem cells, QSCs) remained in the non-hyperplastic epidermis. These cells were forced to divide by TPA. After discontinuation of TPA tumors regressed and disappeared in the 'sunburn group' but persisted and grew in the 'sub-sunburn group' (0.06 vs 2.50 SCCs and precursors ≥4 mm/mouse after 280 days, p=0.03). As the tumors carried no mutations in p53, H/K/N-Ras and Notch1/2, these 'usual suspects' were not involved in the UV-driven tumor initiation. Although we could not selectively eliminate QSCs (unknown phenotype) to establish causality, our data suggest that forcing specifically DNA damage-retaining QSCs to divide--with high mutagenic risk--gives rise to persisting (mainly 'in situ') skin carcinomas. PMID:26797757
Kirchheiner, Kathrin; Czajka-Pepl, Agnieszka; Scharbert, Gisela; Wetzel, Léonore; Sturdza, Alina; Dörr, Wolfgang; Pötter, Richard
2014-06-01
Purpose: To investigate the psychological consequences of high-dose-rate brachytherapy with 2 fractions in 1 application under spinal/epidural anesthesia in the treatment of locally advanced cervical cancer. Methods and Materials: In 50 patients with locally advanced cervical cancer, validated questionnaires were used for prospective assessment of acute and posttraumatic stress disorder (ASD/PTSD) (Impact of Event Scale–Revision), anxiety/depression (Hospital Anxiety and Depression Scale), quality of life (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30/Cervical Cancer 24), physical functioning (World Health Organization performance status), and pain (visual analogue scale), before and during treatment and 1 week and 3 months after treatment. Qualitative interviews were recorded in open format for content analysis. Results: Symptoms of ASD occurred in 30% of patients 1 week after treatment; and of PTSD in 41% 3 months after treatment in association with this specific brachytherapy procedure. Pretreatment predictive variables explain 82% of the variance of PTSD symptoms. Helpful experiences were the support of the treatment team, psychological support, and a positive attitude. Stressful factors were pain, organizational problems during treatment, and immobility between brachytherapy fractions. Conclusions: The specific brachytherapy procedure, as performed in the investigated mono-institutional setting with 2 fractions in 1 application under spinal/epidural anesthesia, bears a considerable risk of traumatization. The source of stress seems to be not the brachytherapy application itself but the maintenance of the applicator under epidural anesthesia in the time between fractions. Patients at risk may be identified before treatment, to offer targeted psycho-social support. The patients' open reports regarding helpful experiences are an encouraging feedback for the treatment team; the reported stressful factors
Videtic, Gregory M.M. Stephans, Kevin L.; Woody, Neil M.; Reddy, Chandana A.; Zhuang, Tingliang; Magnelli, Anthony; Djemil, Toufik
2014-09-01
Purpose: To review outcomes of 2 single-fraction lung stereotactic body radiation therapy (SBRT) schedules used for medically inoperable early stage lung cancer. Methods and Materials: Patients in our institution have been treated on and off protocols using single-fraction SBRT (30 Gy and 34 Gy, respectively). All patients had node-negative lung cancer measuring ≤5 cm and lying ≥2 cm beyond the trachea-bronchial tree and were treated on a Novalis/BrainLAB system with the ExactTrac positioning system for daily image guidance. Results: For the interval from 2009 to 2012, 80 patients with 82 lesions were treated with single-fraction lung SBRT. Fifty-five patients (69%) and 25 patients (31%) received 30 Gy and 34 Gy, respectively. In a comparison of 30 Gy and 34 Gy cohorts, patient and tumor characteristics were balanced and median follow-up in months was 18.7 and 17.8, respectively. The average heterogeneity-corrected mean doses to the target were 33.75 Gy and 37.94 Gy for the 30-Gy and 34-Gy prescriptions, respectively. Comparing 30-Gy and 34-Gy cohorts, 92.7% and 84.0% of patients, respectively, experienced no toxicity (P was not significant), and had neither grade 3 nor higher toxicities. For the 30-Gy and 34-Gy patients, rates of 1-year local failure, overall survival, and lung cancer-specific mortality were 2.0% versus 13.8%, 75.0% versus 64.0%, and 2. 1% versus 16.0%, respectively (P values for differences were not significant). Conclusions: This is the largest single-fraction lung SBRT series yet reported. and it confirms the safety, efficacy, and minimal toxicity of this schedule for inoperable early stage lung cancer.
Nacif, Marcelo Souto; Liu, Yixun; Yao, Jianhua; Liu, Songtao; Sibley, Christopher T.; Summers, Ronald M.; Bluemke, David A.
2014-01-01
Background Myocardial fibrosis leads to impaired cardiac function and events. Extracellular volume fraction (ECV) assessed with an iodinated contrast agent and measured by cardiac CT may be a useful noninvasive marker of fibrosis. Objective The purpose of this study was to develop and evaluate a 3-dimensional (3D) ECV calculation toolkit (ECVTK) for ECV determination by cardiac CT. Methods Twenty-four subjects (10 systolic heart failure, age, 60 ± 17 years; 5 diastolic failure, age 56 ± 20 years; 9 matched healthy subjects, age 59 ± 7 years) were evaluated. Cardiac CT examinations were done on a 320-multidetector CT scanner before and after 130 mL of iopamidol (Isovue-370; Bracco Diagnostics, Plainsboro, NJ, USA) was administered. A calcium score type sequence was performed before and 7 minutes after contrast with single gantry rotation during 1 breath hold and single cardiac phase acquisition. ECV was calculated as (ΔHUmyocardium/ΔHUblood) × (1 − Hct) where Hct is the hematocrit, and ΔHU is the change in Hounsfield unit attenuation = HUafter iodine − HUbefore iodine. Cardiac magnetic resonance imaging was performed to assess myocardial structure and function. Results Mean 3D ECV values were significantly higher in the subjects with systolic heart failure than in healthy subjects and subjects with diastolic heart failure (mean, 41% ± 6%, 33% ± 2%, and 35% ± 5%, respectively; P = 0.02). Interobserver and intraobserver agreements were excellent for myocardial, blood pool, and ECV (intraclass correlation coefficient, >0.90 for all). Higher 3D ECV by cardiac CT was associated with reduced systolic circumferential strain, greater end-diastolic and -systolic volumes, and lower ejection fraction (r = 0.70, r = 0.60, r = 0.73, and r = −0.68, respectively; all P < 0.001). Conclusion 3D ECV by cardiac CT can be performed with ECVTK. We demonstrated increased ECV in subjects with systolic heart failure compared with healthy subjects. Cardiac CT results also
NASA Astrophysics Data System (ADS)
Burigo, Lucas; Pshenichnov, Igor; Mishustin, Igor; Bleicher, Marcus
2015-04-01
Depth and radial dose profiles for therapeutic 1H, 4He, 12C and 16O beams are calculated using the Geant4-based Monte Carlo model for Heavy-Ion Therapy (MCHIT). 4He and 16O ions are presented as alternative options to 1H and 12C broadly used for ion-beam cancer therapy. Biological dose profiles and survival fractions of cells are estimated using the modified Microdosimetric Kinetic model. Depth distributions of cell survival of healthy tissues, assuming 10% and 50% survival of tumor cells, are calculated for 6 cm SOBPs at two tumor depths and for different tissues radiosensitivities. It is found that the optimal ion choice depends on (i) depth of the tumor, (ii) dose levels and (iii) the contrast of radiosensitivities of tumor and surrounding healthy tissues. Our results indicate that 12C and 16O ions are more appropriate to spare healthy tissues in the case of a more radioresistant tumor at moderate depths. On the other hand, a sensitive tumor surrounded by more resistant tissues can be better treated with 1H and 4He ions. In general, 4He beam is found to be a good candidate for therapy. It better spares healthy tissues in all considered cases compared to 1H. Besides, the dose conformation is improved for deep-seated tumors compared to 1H, and the damage to surrounding healthy tissues is reduced compared to heavier ions due to the lower impact of nuclear fragmentation. No definite advantages of 16O with respect to 12C ions are found in this study.
James, S.J.; Enger, S.M.; Peterson, W.J.; Makinodan, T. )
1990-06-01
Very low doses of ionizing radiation can enhance immune responsiveness and extend life span in normal mice. Total lymphoid irradiation at relatively high doses of radiation can retard autoimmune disease in genetically susceptible mice, but may impair immune function. In order to determine whether fractionated low dose exposure would enhance immune response and retard lymphadenopathy in autoimmune-prone mice, groups of C57B1/6 lpr/lpr mice were sham irradiated, exposed 5 days/week for 4 weeks to 0.04 Gy/day, or to 0.1 Gy/day. After the radiation protocol, the mice were evaluated for splenic T cell proliferative capacity, T cell subset distribution, and total spleen cell numbers. The independent and additive effect of caloric restriction was additionally assessed since this intervention has been shown to increase immune responsiveness and retard disease progression in autoimmune-prone mice. The congenic C57B1/6 +/+ immunologically normal strain was evaluated in parallel as congenic control. The results indicated that mitogen-stimulated proliferation was up-regulated in both strains of mice after exposure to 0.04 Gy/day. The proliferative capacity was additively enhanced when radiation at this dose level was combined with caloric restriction. Exposure to 0.1 Gy/day resulted in further augmentation of proliferative response in the lpr/lpr mice, but was depressive in the +/+ mice. Although the proportions of the various T cell subpopulations were altered in both strains after exposure to LDR, the specific subset alterations were different within each strain. Additional experiments were subsequently performed to assess whether the thymus is required for LDR-induced immune potentiation. Thymectomy completely abrogated the LDR effect in the +/+ mice, suggesting that thymic processing and/or trafficking is adaptively altered with LDR in this strain.
Burigo, Lucas; Pshenichnov, Igor; Mishustin, Igor; Bleicher, Marcus
2015-04-21
Depth and radial dose profiles for therapeutic (1)H, (4)He, (12)C and (16)O beams are calculated using the Geant4-based Monte Carlo model for Heavy-Ion Therapy (MCHIT). (4)He and (16)O ions are presented as alternative options to (1)H and (12)C broadly used for ion-beam cancer therapy. Biological dose profiles and survival fractions of cells are estimated using the modified Microdosimetric Kinetic model. Depth distributions of cell survival of healthy tissues, assuming 10% and 50% survival of tumor cells, are calculated for 6 cm SOBPs at two tumor depths and for different tissues radiosensitivities. It is found that the optimal ion choice depends on (i) depth of the tumor, (ii) dose levels and (iii) the contrast of radiosensitivities of tumor and surrounding healthy tissues. Our results indicate that (12)C and (16)O ions are more appropriate to spare healthy tissues in the case of a more radioresistant tumor at moderate depths. On the other hand, a sensitive tumor surrounded by more resistant tissues can be better treated with (1)H and (4)He ions. In general, (4)He beam is found to be a good candidate for therapy. It better spares healthy tissues in all considered cases compared to (1)H. Besides, the dose conformation is improved for deep-seated tumors compared to (1)H, and the damage to surrounding healthy tissues is reduced compared to heavier ions due to the lower impact of nuclear fragmentation. No definite advantages of (16)O with respect to (12)C ions are found in this study. PMID:25825827
Huang, Eng-Yen; Sun, Li-Min; Lin, Hao; Lan, Jen-Hong; Chanchien, Chan-Chao; Huang, Yu-Jie; Wang, Chang-Yu; Wang, Chong-Jong
2013-01-01
Purpose: To compare the treatment results of 2 fractionation schedules for high-dose-rate intracavitary brachytherapy (HDR-ICBT) in patients with cervical cancer. Methods and Materials: From June 2001 through January 2008, 267 patients with stage IB-IVA cervical cancer were enrolled in the study. All patients underwent 4-field pelvic irradiation and HDR-ICBT. The median central and parametrial doses were 39.6 Gy and 45 Gy, respectively. Patient underwent either 6 Gy Multiplication-Sign 4 (HDR-4) (n=144) or 4.5 Gy Multiplication-Sign 6 (HDR-6) (n=123) to point A of ICBT using {sup 192}Ir isotope twice weekly. The rates of overall survival, locoregional failure, distant metastasis, proctitis, cystitis, and enterocolitis were compared between HDR-4 and HDR-6. Results: There were no significant differences in the demographic data between HDR-4 and HDR-6 except for total treatment time. The 5-year proctitis rates were 23.0% and 21.5% in HDR-4 and HDR-6 (P=.399), respectively. The corresponding rates of grade 2-4 proctitis were 18.7% and 9.6% (P=.060). The corresponding rates of grades 3-4 proctitis were 5.2% and 1.3% (P=.231). Subgroup analysis revealed that HDR-4 significantly increased grade 2-4 proctitis in patients aged {>=}62 years old (P=.012) but not in patients aged <62 years (P=.976). The rates of overall survival, locoregional failure, distant metastasis, cystitis, and enterocolitis were not significantly different between HDR-4 and HDR-6 schedules. Conclusion: The small fraction size of HDR-ICBT is associated with grade 2 proctitis without compromise of prognosis in elderly patients. This schedule is suggested for patients who tolerate an additional 2 applications of HDR-ICBT.
Sakaguchi, N.; Sakaguchi, S. Scripps Research Institute, La Jolla, CA PRESTO, JRDC, Institute of Phical and Chemical Research, Tsukuba, Ibaraki ); Miyai, K. )
1992-11-01
Ionizing radiation can functionally alter the immune system and break self-tolerance. High dose (42.5 Gy), fractionated (2.5 Gy 17 times) total lymphoid irradiation (TLI) on mice caused various organ-specific autoimmune diseases, such as gastritis, thyroiditis, and orchitis, depending on the radiation dosages, the extent of lymphoid irradiation, and the genetic background of the mouse strains. Radiation-induced tissue damage is not the primary cause of the autoimmune disease because irradiation of the target organs alone failed to elicit the autoimmunity and shielding of the organs from irradiation was unable to prevent it. In contrast, irradiation of both the thymus and the peripheral lymphoid organs/tissues was required for efficient induction of autoimmune disease by TLI. TLI eliminated the majority of mature thymocytes and the peripheral T cells for 1 mo, and inoculation of spleen cell, thymocyte, or bone marrow cell suspensions (prepared from syngeneic nonirradiated mice) within 2 wk after TLI effectively prevented the autoimmune development. Depletion of T cells from the inocula abrogated the preventive activity. CD4[sup +] T cells mediated the autoimmune prevention but CD8[sup +] T cells did not. CD4[sup +] T cells also appeared to mediate the TLI-induced autoimmune disease because CD4[sup +] T cells from disease-bearing TLI mice adoptively transferred the autoimmune disease to syngeneic naive mice. Taken together, these results indicate that high dose, fractionated ionizing radiation on the lymphoid organs/tissues can cause autoimmune disease by affecting the T cell immune system, rather than the target self-Ags, presumably by altering T cell-dependent control of self-reactive T cells. 62 refs., 9 figs., 2 tabs.
Cury, Fabio L.; Duclos, Marie; Aprikian, Armen; Patrocinio, Horacio; Kassouf, Wassim; Shenouda, George; Faria, Sergio; David, Marc; Souhami, Luis
2012-03-15
Purpose: We present the long-term results of a cohort of patients with intermediate-risk prostate cancer (PC) treated with single-fraction high-dose-rate brachytherapy (HDRB) combined with hypofractionated external beam radiation therapy (HypoRT). Methods and Materials: Patients were treated exclusively with HDRB and HypoRT. HDRB delivered a dose of 10 Gy to the prostate surface and HypoRT consisted of 50 Gy delivered in 20 daily fractions. The first 121 consecutive patients with a minimum of 2 years posttreatment follow-up were assessed for toxicity and disease control. Results: The median follow-up was 65.2 months. No acute Grade III or higher toxicity was seen. Late Grade II gastrointestinal toxicity was seen in 9 patients (7.4%) and Grade III in 2 (1.6%). Late Grade III genitourinary toxicity was seen in 2 patients (1.6%). After a 24-month follow-up, a rebiopsy was offered to the first 58 consecutively treated patients, and 44 patients agreed with the procedure. Negative biopsies were found in 40 patients (91%). The 5-year biochemical relapse-free survival rate was 90.7% (95% CI, 84.5-96.9%), with 13 patients presenting biochemical failure. Among them, 9 were diagnosed with distant metastasis. Prostate cancer-specific and overall survival rates at 5 years were 100% and 98.8% (95% CI, 96.4-100%), respectively. Conclusion: The combination of HDRB and HypoRT is well tolerated, with acceptable toxicity rates. Furthermore, results from rebiopsies revealed an encouraging rate of local control. These results confirm that the use of conformal RT techniques, adapted to specific biological tumor characteristics, have the potential to improve the therapeutic ratio in intermediate-risk PC patients.
Bretschneider, Tina; Mohnike, Konrad; Hass, Peter; Seidensticker, Ricarda; Göppner, Daniela; Dudeck, Oliver; Streitparth, Florian
2015-01-01
Purpose Computed tomography (CT) or magnetic resonance imaging (MRI) guided brachytherapy provides high tumor control rates in hepatocellular carcinoma (HCC) and colorectal liver metastases. In contrast to thermal ablation methods such as radiofrequency ablation (RFA), much less restrictions apply with respect to tumor location or size. In this study, we determined the efficacy and safety of CT- or MRI-guided brachytherapy in metastatic melanoma. Material and methods Fifty-two metastases of malignant melanoma in 14 patients were included in this retrospective study. Local tumor control and safety were evaluated as primary and secondary endpoints. Furthermore, we evaluated overall survival and progression free survival. Tumor locations were liver (n = 31), lung (n = 15), adrenal (n = 3), lymph nodes (n = 2), and kidney (n = 1). Treatment planning was performed using three-dimensional CT or MRI data acquired after percutaneous applicator positioning under CT or open MRI guidance. Subsequently, single fraction high-dose-rate (HDR) brachytherapy was applied using a 192Iridium source. Clinical and cross-sectional follow-up were performed every 3 months post intervention. Results The median diameter of treated lesions was 1.5 cm (range: 0.7-10 cm). Doses between 15 and 20 Gy were applied (median dose: 19.9 Gy). The mean irradiation time ranged between 7-45 minutes. After treatment, there was one patient with a cholangitis. After a median follow up of five months, the median local tumor control was 90%. The median overall survival of the patients was 8 months. The median progression free survival of the patients was 6 months. Conclusions Image-guided HDR brachytherapy is a safe and effective treatment procedure in metastatic malignant melanoma. PMID:26034497
McCarthy, Ian D; Nicholls, Ruth; Malham, Shelagh K; Whiteley, Nia M
2016-01-01
For the first time, use of the flooding dose technique using (3)H-Phenylalanine is validated for measuring whole-animal and tissue-specific rates of protein synthesis in the blue mussel Mytilus edulis (61mm shell length; 4.0g fresh body mass). Following injection, the phenylalanine-specific radioactivities in the gill, mantle and whole-animal free pools were elevated within one hour and remained elevated and stable for up to 6h following injection of (3)H-phenylalanine into the posterior adductor muscle. Incorporation of (3)H-phenylalanine into body protein was linear over time following injection and the non-significant intercepts for the regressions suggested incorporation into body protein occurred rapidly after injection. These results validate the technique for measuring rates of protein synthesis in mussels. There were no differences in the calculated rates following 1-6h incubation in gill, mantle or whole-animal and fractional rates of protein synthesis from the combined time course data were 9.5±0.8%d(-1) for the gill, 2.5±0.3%d(-1) for the mantle and 2.6±0.3%d(-1) for the whole-animal, respectively (mean values±SEM). The whole-animal absolute rate of protein synthesis was calculated as 18.9±0.6mg protein day(-1). The use of this technique in measuring one of the major components of maintenance metabolism and growth will provide a valuable and convenient tool in furthering our understanding of the protein metabolism and energetics of this keystone marine invertebrate and its ability to adjust and respond to fluctuations, such as that expected as a result of climate change. PMID:26497279
Perez, C.A.; Stanley, K.; Rubin, P.; Kramer, S.; Brady, L.; Perez-Tamayo, R.; Brown, G.S.; Concannon, J.; Rotman, M.; Seydel, H.G.
1980-06-01
Analysis is presented of a prospective randomized study involving 365 patients with histologically proven unresectable non-oat-cell carcinoma of the lung treated with deffinitive radiotherapy. The patients were radomized to one of four treatment regimens: 4000 rad split course, or 4000, 5000, or 6000-rad continuous courses in five fractions per week. Ninety to 100 patients were accessioned to each group. The one-year survival rate is 50% and the two-year survival rate, 25%. The patients treated with the split course have the lowest survival rate in comparison with the other groups. The complete and partial local regression of tumor was 49% in patients treated with 4000 rad and 55% in the groups treated with 5000 and 6000 rad. For patients who achieved complete regression of the tumor following irradiation, the two-year survival rate is 40%, in contrast to 20% for those with partial regression, and no survivors among the patients with stable or progressive disease. The incidence of intrathoracic recurrence was 33% for patients treated with 6000 rad, 39% for those receiving 5000 rad, and 44 to 49% for those treated with a 4000-rad split or continuous course. At present, the data stongly suggest that patients treated with 5000 or 6000 rad have a better response, tumor control, and survival rate than those receiving lower doses. Patients with high performance status or with tumors in earlier stages have a two-year survival rate of approx. 40%, in comparison with 20% for other patients. The various irradiation regimens have been well tolerated, with complications being slightly higher in the 4000-rad split course group and in the 6000-rad continuous course group. The most frequent complications have been pneumonitis, pulmonary fibrosis, and dyspagia due to transient esophagitis. Further investigation will be necessary before the optimal management of patients with bronchogenic carcinoma by irradiation is established.
Howe, G.R.
1995-06-01
Current lung cancer risk estimates after exposure to low-linear energy transfer radiation such as X rays are based on studies of people exposed to such radiation at high dose rates, for example the atomic bomb survivors. Radiobiology and animal experiments suggest that risks from exposure at low to moderate dose rates, for example medical diagnostic procedures, may be overestimated by such risk models, but data for humans to examine this issue are limited. In this paper we report on lung cancer mortality between 1950 and 1987 in a cohort of 64,172 Canadian tuberculosis patients, of whom 39% were exposed to highly fractionated multiple chest fluoroscopies leading to a mean lung radiation dose of 1.02 Sv received at moderate dose rates. These data have been used to estimate the excess relative risk per sievert of lung cancer mortality, and this is compared directly to estimates derived from 75,991 atomic bomb survivors. Based on 1,178 lung cancer deaths in the fluoroscopy study, there was no evidence of any positive association between risk and dose, with the relative risk at 1 Sv being 1.00 (95% confidence interval 0.94, 1.07), which contrasts with that based on the atomic bomb survivors, 1.60 (1.27, 1.99). The difference in effect between the two studies almost certainly did not arise by chance (P = 0.0001). This study provides strong support from data for humans for a substantial fractionation/dose-rate effect for low-linear energy transfer radiation and lung cancer risk. This implies that lung cancer risk from exposures to such radiation at present-day dose rates is likely to be lower than would be predicted by current radiation risk models based on studies of high-dose-rate exposures. 25 refs., 8 tabs.
2014-01-01
; Aspartate aminotransferase, ↓2.2×] origin. Surprisingly, the immunoblot analysis of the same PM resolved by 2D-ELFO indicated that the “active”, morphine-induced pool of Gβ subunits represented just a minor fraction of the total signal of Gβ which was decreased 1.2x only. The dominant signal of Gβ was unchanged. Conclusion Brain cortex of rats exposed to increasing doses of morphine is far from being adapted. Significant up-regulation of proteins functionally related to oxidative stress and apoptosis suggests a major change of energy metabolism resulting in the state of severe brain cell “discomfort” or even death. PMID:24528483
Lauche, Olivier; Delouya, Guila; Taussky, Daniel; Menard, Cynthia; Béliveau-Nadeau, Dominic; Hervieux, Yannick; Larouche, Renée
2016-01-01
Purpose To validate the feasibility of a single-fraction high-dose-rate brachytherapy (HDRBT) boost for prostate cancer using real-time transrectal ultrasound (TRUS) based planning. Material and methods From August 2012 to September 2015, 126 patients underwent a single-fraction HDRBT boost of 15 Gy using real-time TRUS based planning. External beam radiation therapy (EBRT) (37.5 Gy/15 fractions, 44 Gy/22 fractions, or 45 Gy/25 fractions) was performed before (31%) or after (69%) HDRBT boost. Genito-urinary (GU) and gastro-intestinal (GI) toxicity were assessed 4 and 12 months after the end of combined treatment using the international prostate symptom score scale (IPSS) and the common terminology criteria for adverse events (CTCAE) v3.0. Results All dose-planning objectives were achieved in 90% of patients. Prostate D90 ≥ 105% and ≤ 115% was achieved in 99% of patients, prostate V150 ≤ 40% in 99%, prostate V200 < 11% in 96%, urethra D10 < 120% for 99%, urethra V125 = 0% in 100%, and rectal V75 < 1 cc in 93% of patients. Median IPSS score was 4 at baseline and did not change at 4 and 12 months after combined treatment. No patients developed ≥ grade 2 GI toxicity. With a median follow-up of 10 months, only two patients experienced biochemical failure. Among patients who didn't receive ADT, cumulative percentage of patients with PSA ≤ 1 ng/ml at 4 and 18 months was respectively 23% and 66%. Conclusions Single-fraction HDRBT boost of 15 Gy using real-time TRUS based planning achieves consistently high dosimetry quality. In combination with EBRT, toxicity outcomes appear promising. A longer follow-up is needed to assess long-term outcome and toxicities.
Blaickner, Matthias; Kindl, Peter
2008-12-01
Current dose assessment in nuclear medicine patient studies relies on published S-values, which are, in turn, based on calculated specific absorbed fractions (SAFs) available for a limited number of anthro-pomorphic computational phantoms. In order to take the individual physiognomy of patients more into account, this study aimed to broaden the supply of phantoms and their respective SAFs. An ensemble of 21 mathematical phantoms was submitted to the Monte Carlo Code MCNP4c2 for the purpose of calculation of SAFs for annihilation radiation. These values were incorporated into an internal dose assessment following the Medical Internal Radiation Dose (MIRD) schema and relying on published biokinetic data for intravenous administration of (18)F-FDG. The results were compared with data from the ICRP, MIRD reports and concurrent calculations with OLINDA/EXM. A very good agreement with sources relying on the SAFs of Cristy and Eckerman (i.e., the ICRP and OLINDA/EXM) was observed, with the absorbed dose in lung being the only exception. In the case of dose to red marrow, the King Spiers factors were omitted in the three-factor approximation, which led to a precise accordance with the Cristy/Eckerman values. Summarizing, one can say that the coincidence with published data justifies the method chosen and demonstrates successfully the expansion of available reference phantoms for dose assessment in nuclear medicine. PMID:19111050
NASA Astrophysics Data System (ADS)
Manabe, Kentaro; Sato, Kaoru; Endo, Akira
2014-03-01
In order to study the effects of body sizes and masses of organs and tissues on internal dose assessment, the values corresponding to effective dose coefficients for intakes of radionuclides were calculated using the specific absorbed fractions (SAFs) of two phantoms: the average adult Japanese male phantom (JM-103) and the reference computational phantom-adult male (RCP-AM) of the International Commission on Radiological Protection. SAFs were evaluated using the phantoms and Monte Carlo radiation transport code MCNPX or were taken from published data. As a result of a comparison for 2894 cases of 923 radionuclides, the maximum discrepancy in the effective dose coefficients between the JM-103 and RCP-AM was about 40%. However, the discrepancies were smaller than 10% in 97% of all cases.
2012-01-01
Background The OneDosePlusTM system, based on MOSFET solid-state radiation detectors and a handheld dosimetry reader, has been used to evaluate intra-fraction movements of patients with breast and prostate cancer. Methods An Action Threshold (AT), defined as the maximum acceptable discrepancy between measured dose and dose calculated with the Treatment Planning System (TPS) (for each field) has been determined from phantom data. To investigate the sensitivity of the system to direction of the patient movements, fixed displacements have been simulated in phantom. The AT has been used as an indicator to establish if patients move during a treatment session, after having verified the set-up with 2D and/or 3D images. Phantom tests have been performed matching different linear accelerators and two TPSs (TPS1 and TPS2). Results The ATs have been found to be very similar (5.0% for TPS1 and 4.5% for TPS2). From statistical data analysis, the system has been found not sensitive enough to reveal displacements smaller than 1 cm (within two standard deviations). The ATs applied to in vivo treatments showed that among the twenty five patients treated for breast cancer, only four of them moved during each measurement session. Splitting data into medial and lateral field, two patients have been found to move during all these sessions; the others, instead, moved only in the second part of the treatment. Patients with prostate cancer have behaved better than patients with breast cancer. Only two out of twenty five moved in each measurement session. Conclusions The method described in the paper, easily implemented in the clinical practice, combines all the advantages of in vivo procedures using the OneDosePlusTM system with the possibility of detecting intra-fraction patient movements. PMID:22716260
Multiple daily fractionation schedules
Peschel, R.E.; Fischer, J.J.
1982-10-01
Although conventional fractionation schedules have been satisfactory for the treatment of some tumors, there is reason to believe that the results of radiation therapy could be improved in some cases by appropriate alterations in treatment schedules. The pharmacological characteristics of some of the electron affinic radiation sensitizers have provided added incentive to investigate newer fractionation schemes, particularly ones which deliver the majority of the radiation dose in short periods of time. This editorial discusses three papers describing preliminary clinical studies using multi-daily fractionated (MDF) radiation therapy. Two of these studies also make use of the radiation sensitizer misonidazole. (KRM)
Steffen, Ingo G.; Wust, Peter; Ruehl, Ricarda
2010-07-15
Purpose: To determine the additional value of fluorodeoxyglucose-positron emission tomography (PET) for clinical target volume definition in the planning of computed tomography (CT)-guided interstitial brachytherapy for liver metastases. Patients and Methods: A total of 19 patients with liver metastases from colorectal cancer treated in 25 sessions were included in the present study. All patients had undergone fluorodeoxyglucose-PET for patient evaluation before interstitial CT-guided brachytherapy. A contrast-enhanced CT scan of the upper abdomen was obtained for radiation planning. The clinical target volume (CTV) was defined by a radiation oncologist and radiologist. After registration of the CT scan with the PET data set, the target volume was defined again using the fusion images. Results: PET revealed one additional liver lesion that was not visible on CT. The median CT-CTV (defined using CT and magnetic resonance imaging) was 68 cm{sup 3} (range 4-260). The PET/CT-CTV (median, 78 cm{sup 3}; range, 4-273) was significantly larger, with a median gain of 24.5% (interquartile range, 2.1-71.5%; p = .022). An increased CTV was observed in 15 cases and a decrease in 6; in 4 cases, the CT-CTV and PET/CT-CTV were equal. Incomplete dose coverage of PET/CT-CTVs was indicative of early local progression (p = .004); however, CT-based radiation plans did not show significant differences in the local control rates when stratified by dose coverage. Conclusion: Retrospective implementation of fluorodeoxyglucose-PET for CTV specification for CT-guided brachytherapy for colorectal liver metastases revealed a significant change in the CTVs. Additional PET-positive tumor regions with incomplete dose coverage could explain unexpected early local progression.
Cho, Jaeho; Kodym, Reinhard; Seliounine, Serguei
2010-07-01
Purpose: To investigate the underlying biology associated with stereotactic body radiotherapy (SBRT), both in vivo models and image-guided, highly focal irradiation systems are necessary. Here, we describe such an irradiation system and use it to examine normal tissue toxicity in a small-animal model at lung volumes similar to those associated with human therapy. Methods and Materials: High-dose radiation was delivered to a small volume of the left lung of C3H/HeJCr mice using a small-animal stereotactic irradiator. The irradiator has a collimation mechanism to produce focal radiation beams, an imaging subsystem consisting of a fluorescent screen coupled to a charge-coupled device camera, and a manual positioning stage. Histopathologic examination and micro-CT were used to evaluate the radiation response. Results: Focal obliteration of the alveoli by fibrous connective tissue, hyperplasia of the bronchiolar epithelium, and presence of a small number of inflammatory cells are the main reactions to low-volume/high-dose irradiation of the mouse lung. The tissue response suggested a radiation dose threshold for early phase fibrosis lying between 40 and 100 Gy. The irradiation system satisfied our requirements of high-dose-rate, small beam diameter, and precise localization and verification. Conclusions: We have established an experimental model and image-guided animal irradiation system for the study of high dose per fraction irradiations such as those used with SBRT at volumes analogous to those used in human beings. It will also allow the targeting of specific anatomical structures of the thorax or ultimately, orthotopic tumors of the lung.
Pacilio, Massimiliano; Ventroni, Guido; Cassano, Bartolomeo; Ialongo, Pasquale; Lorenzon, Leda; Di Castro, Elisabetta; Recine, Federica; Sternberg, Cora N; Mango, Lucio
2016-02-01
A 70-year-old man affected by bone metastases from castration resistant prostate cancer underwent Alpharadin ((223)Ra-dichloride) therapy (6 administrations of 50 kBq per kg i.v., once every 4 weeks). The inter-fraction variability of the absorbed dose to lesions was evaluated for four injections. Dosimetric assessments were performed following the MIRD approach and a recently published methodology. The mean absorbed dose and standard deviation for 4 lesions [mean (σ %)] were: 434 mGy (15%) and 516 mGy (21%) for the right and left humeral head, 1205 mGy (14%) and 781 mGy (8%) for the right and left glenoid. The estimated total absorbed dose after the whole treatment, considering also the relative-biological effectiveness of alpha particles (RBE = 5), yielded a D RBE range of 13-36 Gy. A good correlation between (99m)Tc and (223)Ra uptake was obtained (R (2) = 0.7613). The tumour-non-tumour (TNT) ratio of 8 lesions (those above, plus 4 additional), monitored by six (99m)Tc-MDP bone scans over a period of about 10 months, evidenced a TNT reduction in two lesions (-42 and -48 %), but in most lesions the TNT remained fairly constant, evidencing that (223)Ra-dichloride therapy tends to prevent further progression of osseous disease, leading to chronicity of the metastatic status. PMID:26613714
ASHIDA, SHINGO; YAMASAKI, ICHIRO; TAMURA, KENJI; SHIMAMOTO, TSUTOMU; INOUE, KEIJI; KARIYA, SHINJI; KOBAYASHI, KANA; YAMAGAMI, TAKUJI; SHUIN, TARO
2016-01-01
The aim of the present study was to evaluate the feasibility and preliminary outcomes of high-dose-rate (HDR)-brachytherapy as a monotherapy in two fractions within 1 day for localized prostate cancer, including high-/very high-risk cases. Among the 68 patients treated with HDR monotherapy between July 2011 and December 2014, 65 had a minimal follow-up of 12 months without adjuvant androgen deprivation therapy and were enrolled in the present study [42/65 (64.6%) exhibited high-/very high-risk diseases]. HDR monotherapy was performed in two fractions with a minimal interval of 6 h and the prescribed dose was 13.5 Gy (×2). Adverse events (AEs) were assessed using Common Terminology Criteria for Adverse Events (version 4; http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm#ctc_40), and biochemical failure was assessed by the Phoenix definition. The median follow-up time was 30.1 months. The majority of patients had Grade 0–1 acute AEs. Four patients (6.2%) exhibited urinary retention, requiring a Foley catheter. Grade 3 acute AEs occurred at a frequency of 3.1% and hematuria at 1.5%. The majority of patients also exhibited Grade 0–1 chronic AEs. Grade 3 chronic AEs occurred at a frequency of 1.5% and urethral stricture at 1.5%, for which endoscopic treatment was indicated. Acute and chronic gastrointestinal AEs were uncommon, and no Grade 3 or above AEs developed. Biochemical failure occurred in 4 patients who all exhibited high-/very high-risk diseases. Kaplan-Meier estimated that 3 year biochemical failure-free survival was 91.6% overall and 88.0% in high-/very high-risk cases. The present two-fraction 1 day HDR monotherapy is feasible with minimal AEs and achieved acceptable biochemical control of localized prostate cancer, including high-/very high-risk cases, although long-term follow-up is required. PMID:27123280
Morton, Gerard C.; Loblaw, D. Andrew; Sankreacha, Raxa
2010-07-01
Purpose: To determine the short- and medium-term effects of a single high-dose-rate brachytherapy fraction of 15Gy and hypofractionated external beam radiation therapy for prostate cancer. Methods and Materials: Eligible patients had localized prostate cancer with a Gleason score of 7 and a prostate-specific antigen (PSA) concentration of <20 ng/ml or a Gleason score of 6 with a PSA concentration of 10 to 20 ng/ml. Patients received high-dose-rate brachytherapy as a single 15-Gy dose, followed by external beam radiation therapy at 37.5Gy in 15 fractions, and were followed prospectively for toxicity (using Common Terminology Criteria for Adverse Events version 3.0), urinary symptoms (using the International Prostate Symptom Score [IPSS]), erectile function (with the International Index of Erectile Function [IIEF]), and health-related quality of life (with the Expanded Prostate Cancer Index Composite [EPIC]). Clinical examinations and PSA measurements were performed at every visit, and prostate biopsies were repeated at 2 years. The trial accrued 125 patients, with a median follow-up of 1.14 years. Results: Acute grade 2 and 3 genitourinary toxicity occurred in 62% and 1.6% of patients, respectively, and acute grade 2 gastrointestinal toxicity occurred in 6.5% of patients. No grade 3 late toxicity has occurred: 47% of patients had grade 2 genitourinary and 10% of patients had grade 2 gastrointestinal toxicity. Median IPSSs rose from 5 at baseline to 12 at 1 month and returned to 7 at 3 months. Of the total number of patients who were initially potent (IIEF, >21), 8% of patients developed mild to moderate dysfunction, and 27% of patients developed severe erectile dysfunction. Baseline EPIC bowel, urinary, and sexual bother scores decreased by 9, 7, and 19 points, respectively, at 1 year. No patient has experienced biochemical failure, and 16 of the first 17 biopsy results showed no malignancy. Conclusions: Treatment is well tolerated in the short and medium term, with
Stanislavsky, A A
2004-11-01
We consider a fractional oscillator which is a generalization of the conventional linear oscillator in the framework of fractional calculus. It is interpreted as an ensemble average of ordinary harmonic oscillators governed by a stochastic time arrow. The intrinsic absorption of the fractional oscillator results from the full contribution of the harmonic oscillator ensemble: these oscillators differ a little from each other in frequency so that each response is compensated by an antiphase response of another harmonic oscillator. This allows one to draw a parallel in the dispersion analysis for media described by a fractional oscillator and an ensemble of ordinary harmonic oscillators with damping. The features of this analysis are discussed. PMID:15600586
Takeda, Atsuya; Sanuki, Naoko; Kunieda, Etsuo Ohashi, Toshio; Oku, Yohei; Takeda, Toshiaki; Shigematsu, Naoyuki; Kubo, Atsushi
2009-02-01
Purpose: To retrospectively analyze the clinical outcomes of stereotactic body radiotherapy (SBRT) for patients with Stages 1A and 1B non-small-cell lung cancer. Methods and Materials: We reviewed the records of patients with non-small-cell lung cancer treated with curative intent between Dec 2001 and May 2007. All patients had histopathologically or cytologically confirmed disease, increased levels of tumor markers, and/or positive findings on fluorodeoxyglucose positron emission tomography. Staging studies identified their disease as Stage 1A or 1B. Performance status was 2 or less according to World Health Organization guidelines in all cases. The prescribed dose of 50 Gy total in five fractions, calculated by using a superposition algorithm, was defined for the periphery of the planning target volume. Results: One hundred twenty-one patients underwent SBRT during the study period, and 63 were eligible for this analysis. Thirty-eight patients had Stage 1A (T1N0M0) and 25 had Stage 1B (T2N0M0). Forty-nine patients were not appropriate candidates for surgery because of chronic pulmonary disease. Median follow-up of these 49 patients was 31 months (range, 10-72 months). The 3-year local control, disease-free, and overall survival rates in patients with Stages 1A and 1B were 93% and 96% (p = 0.86), 76% and 77% (p = 0.83), and 90% and 63% (p = 0.09), respectively. No acute toxicity was observed. Grade 2 or higher radiation pneumonitis was experienced by 3 patients, and 1 of them had fatal bacterial pneumonia. Conclusions: The SBRT at 50 Gy total in five fractions to the periphery of the planning target volume calculated by using a superposition algorithm is feasible. High local control rates were achieved for both T2 and T1 tumors.
Warner, Andrew; Pickles, Tom; Crook, Juanita; Martin, Andre-Guy; Souhami, Luis; Catton, Charles; Lukka, Himu
2015-01-01
Purpose: Although several clinical nomograms predictive of biochemical failure-free survival (BFFS) for localized prostate cancer exist in the medical literature, making valid comparisons can be challenging due to variable definitions of biochemical failure, the disparate distribution of prognostic factors, and received treatments in patient populations. The aim of this investigation was to develop and validate clinically-based nomograms for 5-year BFFS using the ASTRO II “Phoenix” definition for two patient cohorts receiving low-dose rate (LDR) brachytherapy or conventionally fractionated external beam radiation therapy (EBRT) from a large Canadian multi-institutional database. Methods and Materials: Patients were selected from the GUROC (Genitourinary Radiation Oncologists of Canada) Prostate Cancer Risk Stratification (ProCaRS) database if they received (1) LDR brachytherapy ≥ 144 Gy (n=4208) or (2) EBRT ≥ 70 Gy (n=822). Multivariable Cox regression analysis for BFFS was performed separately for each cohort and used to generate clinical nomograms predictive of 5-year BFFS. Nomograms were validated using calibration plots of nomogram predicted probability versus observed probability via Kaplan-Meier estimates. Results: Patients receiving LDR brachytherapy had a mean age of 64 ± 7 years, a mean baseline PSA of 6.3 ± 3.0 ng/mL, 75% had a Gleason 6, and 15% had a Gleason 7, whereas patients receiving EBRT had a mean age of 70 ± 6 years, a mean baseline PSA of 11.6 ± 10.7 ng/mL, 30% had a Gleason 6, 55% had a Gleason 7, and 14% had a Gleason 8-10. Nomograms for 5-year BFFS included age, use and duration of androgen deprivation therapy (ADT), baseline PSA, T stage, and Gleason score for LDR brachytherapy and an ADT (months), baseline PSA, Gleason score, and biological effective dose (Gy) for EBRT. Conclusions: Clinical nomograms examining 5-year BFFS were developed for patients receiving either LDR brachytherapy or conventionally fractionated EBRT and
Fraction Reduction through Continued Fractions
ERIC Educational Resources Information Center
Carley, Holly
2011-01-01
This article presents a method of reducing fractions without factoring. The ideas presented may be useful as a project for motivated students in an undergraduate number theory course. The discussion is related to the Euclidean Algorithm and its variations may lead to projects or early examples involving efficiency of an algorithm.
COMMERCIAL SNF ACCIDENT RELEASE FRACTIONS
S.O. Bader
1999-10-18
The purpose of this design analysis is to specify and document the total and respirable fractions for radioactive materials that are released from an accident event at the Monitored Geologic Repository (MGR) involving commercial spent nuclear fuel (CSNF) in a dry environment. The total and respirable release fractions will be used to support the preclosure licensing basis for the MGR. The total release fraction is defined as the fraction of total CSNF assembly inventory, typically expressed as an activity inventory (e.g., curies), of a given radionuclide that is released to the environment from a waste form. The radionuclides are released from the inside of breached fuel rods (or pins) and from the detachment of radioactive material (crud) from the outside surfaces of fuel rods and other components of fuel assemblies. The total release fraction accounts for several mechanisms that tend to retain, retard, or diminish the amount of radionuclides that are available for transport to dose receptors or otherwise can be shown to reduce exposure of receptors to radiological releases. The total release fraction includes a fraction of airborne material that is respirable and could result in inhalation doses. This subset of the total release fraction is referred to as the respirable release fraction. Potential accidents may involve waste forms that are characterized as either bare (unconfined) fuel assemblies or confined fuel assemblies. The confined CSNF assemblies at the MGR are contained in shipping casks, canisters, or disposal containers (waste packages). In contrast to the bare fuel assemblies, the container that confines the fuel assemblies has the potential of providing an additional barrier for diminishing the total release fraction should the fuel rod cladding breach during an accident. However, this analysis will not take credit for this additional bamer and will establish only the total release fractions for bare unconfined CSNF assemblies, which may however be
Maximizing Tumor Immunity With Fractionated Radiation
Schaue, Doerthe; Ratikan, Josephine A.; Iwamoto, Keisuke S.; McBride, William H.
2012-07-15
Purpose: Technologic advances have led to increased clinical use of higher-sized fractions of radiation dose and higher total doses. How these modify the pathways involved in tumor cell death, normal tissue response, and signaling to the immune system has been inadequately explored. Here we ask how radiation dose and fraction size affect antitumor immunity, the suppression thereof, and how this might relate to tumor control. Methods and Materials: Mice bearing B16-OVA murine melanoma were treated with up to 15 Gy radiation given in various-size fractions, and tumor growth followed. The tumor-specific immune response in the spleen was assessed by interferon-{gamma} enzyme-linked immunospot (ELISPOT) assay with ovalbumin (OVA) as the surrogate tumor antigen and the contribution of regulatory T cells (Tregs) determined by the proportion of CD4{sup +}CD25{sup hi}Foxp3{sup +} T cells. Results: After single doses, tumor control increased with the size of radiation dose, as did the number of tumor-reactive T cells. This was offset at the highest dose by an increase in Treg representation. Fractionated treatment with medium-size radiation doses of 7.5 Gy/fraction gave the best tumor control and tumor immunity while maintaining low Treg numbers. Conclusions: Radiation can be an immune adjuvant, but the response varies with the size of dose per fraction. The ultimate challenge is to optimally integrate cancer immunotherapy into radiation therapy.
van den Bogaert, W.; van der Schueren, E.; Horiot, J.C.; Chaplain, G.; Arcangeli, G.; Gonzalez, D.; Svoboda, V.
1982-10-01
From 1978 to the end of 1980, 179 patients with advanced head and neck tumors were accrued in a multicenter pilot study of the EORTC Radiotherapy Group, investigating the feasibility of high dose multiple daily fractionation (MDF) and its combination with misonidazole. The irradiation scheme consisted of three daily fractions of 1.6 Gy (four hour intervals) to a total dose of 48 Gy in two weeks, followed 3 to 4 weeks later by a boost to a total of about 70 Gy in 6 to 7 weeks. Misonidazole was given in daily doses of 1 g/m/sup 2/ (total 13 or 14 g/m/sup 2/) to 53 patients, thus sensitizing every radiation session. All patients had large head and neck tumors, with a poor prognosis. Acute reactions were well tolerated. Skin reactions were very moderate: mucosal reaction started at day 10 to 12. Tumor regression was very impressive, so that palliation was obtained quickly. Nine patients died from treatment related causes. It is difficult to assess local control at this time, but at the time of analysis (August 1981), the actuarial control rate was 48% at 20 months, with misonidazole 57%. This difference, however, is not statistically significant. Survival of the total group is 31% at 20 months. In these patients with a heavy tumor burden the early results were considered a success by all participants. For patients with sufficient follow-up, late reactions can be evaluated. Some edema and fibrosis is seen, but did not exceed a degree which could be expected with single daily fractionation to the same dose. This study demonstrates the possibility of giving highly concentrated treatments to total doses equal to those used in conventional fractionation.
Commercial SNF Accident Release Fractions
J. Schulz
2004-11-05
The purpose of this analysis is to specify and document the total and respirable fractions for radioactive materials that could be potentially released from an accident at the repository involving commercial spent nuclear fuel (SNF) in a dry environment. The total and respirable release fractions are used to support the preclosure licensing basis for the repository. The total release fraction is defined as the fraction of total commercial SNF assembly inventory, typically expressed as an activity inventory (e.g., curies), of a given radionuclide that is released to the environment from a waste form. Radionuclides are released from the inside of breached fuel rods (or pins) and from the detachment of radioactive material (crud) from the outside surfaces of fuel rods and other components of fuel assemblies. The total release fraction accounts for several mechanisms that tend to retain, retard, or diminish the amount of radionuclides that are available for transport to dose receptors or otherwise can be shown to reduce exposure of receptors to radiological releases. The total release fraction includes a fraction of airborne material that is respirable and could result in inhalation doses; this subset of the total release fraction is referred to as the respirable release fraction. Accidents may involve waste forms characterized as: (1) bare unconfined intact fuel assemblies, (2) confined intact fuel assemblies, or (3) canistered failed commercial SNF. Confined intact commercial SNF assemblies at the repository are contained in shipping casks, canisters, or waste packages. Four categories of failed commercial SNF are identified: (1) mechanically and cladding-penetration damaged commercial SNF, (2) consolidated/reconstituted assemblies, (3) fuel rods, pieces, and debris, and (4) nonfuel components. It is assumed that failed commercial SNF is placed into waste packages with a mesh screen at each end (CRWMS M&O 1999). In contrast to bare unconfined fuel assemblies, the
Fractional vector calculus and fractional Maxwell's equations
Tarasov, Vasily E.
2008-11-15
The theory of derivatives and integrals of non-integer order goes back to Leibniz, Liouville, Grunwald, Letnikov and Riemann. The history of fractional vector calculus (FVC) has only 10 years. The main approaches to formulate a FVC, which are used in the physics during the past few years, will be briefly described in this paper. We solve some problems of consistent formulations of FVC by using a fractional generalization of the Fundamental Theorem of Calculus. We define the differential and integral vector operations. The fractional Green's, Stokes' and Gauss's theorems are formulated. The proofs of these theorems are realized for simplest regions. A fractional generalization of exterior differential calculus of differential forms is discussed. Fractional nonlocal Maxwell's equations and the corresponding fractional wave equations are considered.
Initialized Fractional Calculus
NASA Technical Reports Server (NTRS)
Lorenzo, Carl F.; Hartley, Tom T.
2000-01-01
This paper demonstrates the need for a nonconstant initialization for the fractional calculus and establishes a basic definition set for the initialized fractional differintegral. This definition set allows the formalization of an initialized fractional calculus. Two basis calculi are considered; the Riemann-Liouville and the Grunwald fractional calculi. Two forms of initialization, terminal and side are developed.
NASA Astrophysics Data System (ADS)
Sabzikar, Farzad; Meerschaert, Mark M.; Chen, Jinghua
2015-07-01
Fractional derivatives and integrals are convolutions with a power law. Multiplying by an exponential factor leads to tempered fractional derivatives and integrals. Tempered fractional diffusion equations, where the usual second derivative in space is replaced by a tempered fractional derivative, govern the limits of random walk models with an exponentially tempered power law jump distribution. The limiting tempered stable probability densities exhibit semi-heavy tails, which are commonly observed in finance. Tempered power law waiting times lead to tempered fractional time derivatives, which have proven useful in geophysics. The tempered fractional derivative or integral of a Brownian motion, called a tempered fractional Brownian motion, can exhibit semi-long range dependence. The increments of this process, called tempered fractional Gaussian noise, provide a useful new stochastic model for wind speed data. A tempered fractional difference forms the basis for numerical methods to solve tempered fractional diffusion equations, and it also provides a useful new correlation model in time series.
Sabzikar, Farzad; Meerschaert, Mark M.; Chen, Jinghua
2015-07-15
Fractional derivatives and integrals are convolutions with a power law. Multiplying by an exponential factor leads to tempered fractional derivatives and integrals. Tempered fractional diffusion equations, where the usual second derivative in space is replaced by a tempered fractional derivative, govern the limits of random walk models with an exponentially tempered power law jump distribution. The limiting tempered stable probability densities exhibit semi-heavy tails, which are commonly observed in finance. Tempered power law waiting times lead to tempered fractional time derivatives, which have proven useful in geophysics. The tempered fractional derivative or integral of a Brownian motion, called a tempered fractional Brownian motion, can exhibit semi-long range dependence. The increments of this process, called tempered fractional Gaussian noise, provide a useful new stochastic model for wind speed data. A tempered fractional difference forms the basis for numerical methods to solve tempered fractional diffusion equations, and it also provides a useful new correlation model in time series.
MEERSCHAERT, MARK M.; SABZIKAR, FARZAD; CHEN, JINGHUA
2014-01-01
Fractional derivatives and integrals are convolutions with a power law. Multiplying by an exponential factor leads to tempered fractional derivatives and integrals. Tempered fractional diffusion equations, where the usual second derivative in space is replaced by a tempered fractional derivative, govern the limits of random walk models with an exponentially tempered power law jump distribution. The limiting tempered stable probability densities exhibit semi-heavy tails, which are commonly observed in finance. Tempered power law waiting times lead to tempered fractional time derivatives, which have proven useful in geophysics. The tempered fractional derivative or integral of a Brownian motion, called a tempered fractional Brownian motion, can exhibit semi-long range dependence. The increments of this process, called tempered fractional Gaussian noise, provide a useful new stochastic model for wind speed data. A tempered difference forms the basis for numerical methods to solve tempered fractional diffusion equations, and it also provides a useful new correlation model in time series. PMID:26085690
FRACTIONAL INTEGRATION TOOLBOX
Marinov, Toma M.; Ramirez, Nelson; Santamaria, Fidel
2014-01-01
The problems formulated in the fractional calculus framework often require numerical fractional integration/differentiation of large data sets. Several existing fractional control toolboxes are capable of performing fractional calculus operations, however, none of them can efficiently perform numerical integration on multiple large data sequences. We developed a Fractional Integration Toolbox (FIT), which efficiently performs fractional numerical integration/differentiation of the Riemann-Liouville type on large data sequences. The toolbox allows parallelization and is designed to be deployed on both CPU and GPU platforms. PMID:24812536
ERIC Educational Resources Information Center
Graham, Alan; Graham, Louise
2003-01-01
Describes a very successful attempt to teach fractions to year 5 pupils based on pupils making their own fraction pack. Children decided for themselves how to make the fractional slices used in the activity using colored cardboard sheets and templates of a paper circle consisting of 24 equal slices. (Author/NB)
Gupta, Pramod Kumar; Lal, Punita; Bajpai, Ranjeet; Goel, Anshu; Yadav, Rajan; Verma, Mranalini; Kumar, Shaleen
2016-01-01
Aim and Objective: Weekly administration of cisplatin (cis-diamminedichloroplatinum [CDDP]) appears more feasible and substantially more popular than the 3 weekly schedules due to better compliance. Different concurrent cisplatin schedules have been attempted including a daily schedule. We did a comparison of two consecutive single arm studies, i.e., use of weekly cisplatin versus daily cisplatin when used with concurrently with a moderately accelerated radiotherapy (RT) schedule. Patients and Methods: Two prospective feasibility, safety and efficacy studies were carried out consecutively within the department. The weekly CDDP study was done from August 2003 to August 2005 and daily CDDP study was conducted from November 2005 to June 2007. Both studies included locally advanced stage III and IV squamous cell carcinoma of the head and neck region with RT dose of 70 Gy. Concurrent single-agent cisplatin was administered weekly (35 mg/m2) in the first and daily (6 mg/m2) in the second study. Results: Weekly cisplatin study had 68 and daily CDDP study had 52 patients. The median follow-up in the two studies was 93 and 63 months, respectively. Compliance in the two studies was comparable. Acute Grade III/IV mucositis and dysphagia were significantly higher in weekly cisplatin study. Late Grade II/III toxicities such as xerostomia, dysphagia, ototoxicity and nephrotoxicity were similar. The 5 years locoregional control was 18% and 25% and 5 years overall survival rate was 32% and 31% in weekly and daily cisplatin studies, respectively. Conclusions: Modest acceleration along with either weekly or daily cisplatin, whichever is possible in one's setup, is do-able, provided due attention is paid to patient selection and supportive care. PMID:27275456
Multiple anatomy optimization of accumulated dose
Watkins, W. Tyler Siebers, Jeffrey V.; Moore, Joseph A.; Gordon, James; Hugo, Geoffrey D.
2014-11-01
Purpose: To investigate the potential advantages of multiple anatomy optimization (MAO) for lung cancer radiation therapy compared to the internal target volume (ITV) approach. Methods: MAO aims to optimize a single fluence to be delivered under free-breathing conditions such that the accumulated dose meets the plan objectives, where accumulated dose is defined as the sum of deformably mapped doses computed on each phase of a single four dimensional computed tomography (4DCT) dataset. Phantom and patient simulation studies were carried out to investigate potential advantages of MAO compared to ITV planning. Through simulated delivery of the ITV- and MAO-plans, target dose variations were also investigated. Results: By optimizing the accumulated dose, MAO shows the potential to ensure dose to the moving target meets plan objectives while simultaneously reducing dose to organs at risk (OARs) compared with ITV planning. While consistently superior to the ITV approach, MAO resulted in equivalent OAR dosimetry at planning objective dose levels to within 2% volume in 14/30 plans and to within 3% volume in 19/30 plans for each lung V20, esophagus V25, and heart V30. Despite large variations in per-fraction respiratory phase weights in simulated deliveries at high dose rates (e.g., treating 4/10 phases during single fraction beams) the cumulative clinical target volume (CTV) dose after 30 fractions and per-fraction dose were constant independent of planning technique. In one case considered, however, per-phase CTV dose varied from 74% to 117% of prescription implying the level of ITV-dose heterogeneity may not be appropriate with conventional, free-breathing delivery. Conclusions: MAO incorporates 4DCT information in an optimized dose distribution and can achieve a superior plan in terms of accumulated dose to the moving target and OAR sparing compared to ITV-plans. An appropriate level of dose heterogeneity in MAO plans must be further investigated.
Multiple anatomy optimization of accumulated dose
Watkins, W. Tyler; Moore, Joseph A.; Gordon, James; Hugo, Geoffrey D.; Siebers, Jeffrey V.
2014-01-01
Purpose: To investigate the potential advantages of multiple anatomy optimization (MAO) for lung cancer radiation therapy compared to the internal target volume (ITV) approach. Methods: MAO aims to optimize a single fluence to be delivered under free-breathing conditions such that the accumulated dose meets the plan objectives, where accumulated dose is defined as the sum of deformably mapped doses computed on each phase of a single four dimensional computed tomography (4DCT) dataset. Phantom and patient simulation studies were carried out to investigate potential advantages of MAO compared to ITV planning. Through simulated delivery of the ITV- and MAO-plans, target dose variations were also investigated. Results: By optimizing the accumulated dose, MAO shows the potential to ensure dose to the moving target meets plan objectives while simultaneously reducing dose to organs at risk (OARs) compared with ITV planning. While consistently superior to the ITV approach, MAO resulted in equivalent OAR dosimetry at planning objective dose levels to within 2% volume in 14/30 plans and to within 3% volume in 19/30 plans for each lung V20, esophagus V25, and heart V30. Despite large variations in per-fraction respiratory phase weights in simulated deliveries at high dose rates (e.g., treating 4/10 phases during single fraction beams) the cumulative clinical target volume (CTV) dose after 30 fractions and per-fraction dose were constant independent of planning technique. In one case considered, however, per-phase CTV dose varied from 74% to 117% of prescription implying the level of ITV-dose heterogeneity may not be appropriate with conventional, free-breathing delivery. Conclusions: MAO incorporates 4DCT information in an optimized dose distribution and can achieve a superior plan in terms of accumulated dose to the moving target and OAR sparing compared to ITV-plans. An appropriate level of dose heterogeneity in MAO plans must be further investigated. PMID:25370619
Dividing Fractions: A Pedagogical Technique
ERIC Educational Resources Information Center
Lewis, Robert
2016-01-01
When dividing one fraction by a second fraction, invert, that is, flip the second fraction, then multiply it by the first fraction. To multiply fractions, simply multiply across the denominators, and multiply across the numerators to get the resultant fraction. So by inverting the division of fractions it is turned into an easy multiplication of…
Leonenko, Nikolai N.; Meerschaert, Mark M.
2013-01-01
Pearson diffusions are governed by diffusion equations with polynomial coefficients. Fractional Pearson diffusions are governed by the corresponding time-fractional diffusion equation. They are useful for modeling sub-diffusive phenomena, caused by particle sticking and trapping. This paper provides explicit strong solutions for fractional Pearson diffusions, using spectral methods. It also presents stochastic solutions, using a non-Markovian inverse stable time change. PMID:23626377
Temporal Optimization of Radiotherapy Treatment Fractions
Stewart, Robert D. ); Traub, Richard J. )
2001-01-01
Absorbed dose calculations for 1 MeV, monodirectional photon beams targeted at an idealized neck cancer have been performed using the MCNP computer code. The dose-depth profiles for the individual beams were then used to calculate the cell-killing effects of representative treatment designs using the lethal and potentially lethal (LPL) radiobiological model. Our calculations, which are based on LPL parameter values for colon adenocarcinoma cells, suggest that increasing the time required to deliver each dose fraction from less than a minute up to 1 or 2 hours can decrease the overall cell-killing effects of some treatments by factors as high as 2 to 20. Moreover, dose protraction effects alter the iso-effect treatment dose by factors on the order of 5 to 10%. That is, a 75 Gy treatment produces about the same tumor control probability (TCP) as a 70 Gy treatment if the dose fractions are delivered in 1 to 2 hours instead of a few minutes. American Nuclear Society (ANS) Topical Meeting on Radiation Protection for our National Priorities, Medicine, the Environment, and the Legacy (RPS 2000), Spokane, WA, September 17-21, 2000.
ERIC Educational Resources Information Center
Wilkerson, Trena L.; Bryan, Tommy; Curry, Jane
2012-01-01
This article describes how using candy bars as models gives sixth-grade students a taste for learning to represent fractions whose denominators are factors of twelve. Using paper models of the candy bars, students explored and compared fractions. They noticed fewer different representations for one-third than for one-half. The authors conclude…
Can Kindergartners Do Fractions?
ERIC Educational Resources Information Center
Cwikla, Julie
2014-01-01
Mathematics professor Julie Cwikla decided that she needed to investigate young children's understandings and see what precurricular partitioning notions young minds bring to the fraction table. Cwikla realized that only a handful of studies have examined how preschool-age and early elementary school-age students solve fraction problems…
ERIC Educational Resources Information Center
Usiskin, Zalman P.
2007-01-01
In the 1970s, the movement to the metric system (which has still not completely occurred in the United States) and the advent of hand-held calculators led some to speculate that decimal representation of numbers would render fractions obsolete. This provocative proposition stimulated Zalman Usiskin to write "The Future of Fractions" in 1979. He…
(Carbon isotope fractionation inplants)
O'Leary, M.H.
1990-01-01
The objectives of this research are: To develop a theoretical and experimental framework for understanding isotope fractionations in plants; and to develop methods for using this isotope fractionation for understanding the dynamics of CO{sub 2} fixation in plants. Progress is described.
Radiation dose estimates for radiopharmaceuticals
Stabin, M.G.; Stubbs, J.B.; Toohey, R.E.
1996-04-01
Tables of radiation dose estimates based on the Cristy-Eckerman adult male phantom are provided for a number of radiopharmaceuticals commonly used in nuclear medicine. Radiation dose estimates are listed for all major source organs, and several other organs of interest. The dose estimates were calculated using the MIRD Technique as implemented in the MIRDOSE3 computer code, developed by the Oak Ridge Institute for Science and Education, Radiation Internal Dose Information Center. In this code, residence times for source organs are used with decay data from the MIRD Radionuclide Data and Decay Schemes to produce estimates of radiation dose to organs of standardized phantoms representing individuals of different ages. The adult male phantom of the Cristy-Eckerman phantom series is different from the MIRD 5, or Reference Man phantom in several aspects, the most important of which is the difference in the masses and absorbed fractions for the active (red) marrow. The absorbed fractions for flow energy photons striking the marrow are also different. Other minor differences exist, but are not likely to significantly affect dose estimates calculated with the two phantoms. Assumptions which support each of the dose estimates appears at the bottom of the table of estimates for a given radiopharmaceutical. In most cases, the model kinetics or organ residence times are explicitly given. The results presented here can easily be extended to include other radiopharmaceuticals or phantoms.
Cheng, Jonathan C.; Schultheiss, Timothy E. Wong, Jeffrey Y.C.
2008-08-01
Purpose: To demonstrate a radiation dose response and to determine the dosimetric and chemotherapeutic factors that influence the incidence of late renal toxicity following total body irradiation (TBI). Methods and Materials: A comprehensive retrospective review was performed of articles reporting late renal toxicity, along with renal dose, fractionation, dose rate, chemotherapy regimens, and potential nephrotoxic agents. In the final analysis, 12 articles (n = 1,108 patients), consisting of 24 distinct TBI/chemotherapy conditioning regimens were included. Regimens were divided into three subgroups: adults (age {>=}18 years), children (age <18 years), and mixed population (both adults and children). Multivariate logistic regression was performed to identify dosimetric and chemotherapeutic factors significantly associated with late renal complications. Results: Individual analysis was performed on each population subgroup. For the purely adult population, the only significant variable was total dose. For the mixed population, the significant variables included total dose, dose rate, and the use of fludarabine. For the pediatric population, only the use of cyclosporin or teniposide was significant; no dose response was noted. A logistic model was generated with the exclusion of the pediatric population because of its lack of dose response. This model yielded the following significant variables: total dose, dose rate, and number of fractions. Conclusion: A dose response for renal damage after TBI was identified. Fractionation and low dose rates are factors to consider when delivering TBI to patients undergoing bone marrow transplantation. Drug therapy also has a major impact on kidney function and can modify the dose-response function.
Zhang Hualin Wang, Jian Z.; Mayr, Nina; Kong Xiang; Yuan Jiankui; Gupta, Nilendu; Lo, Simon; Grecula, John; Montebello, Joseph; Martin, Douglas; Yuh, William
2008-01-01
Purpose: To evaluate the conventionally fractionated and hypofractionated grid therapy in debulking cervical cancers using the linear quadratic (LQ) model. Methods and Materials: A Monte Carlo technique was used to calculate the dose distribution of a commercially available grid in a 6-MV photon beam. The LQ model was used to evaluate the therapeutic outcome of both the conventionally fractionated (2 Gy/fraction) and hypofractionated (15 Gy/fraction) grid therapy regimens to debulk cervical cancers with different LQ parameters. The equivalent open-field dose (EOD) to the cancer cells and therapeutic ratio (TR) were defined by comparing grid therapy with the open debulking field. The clinical outcomes from 114 patients were used to verify our theoretical model. Results: The cervical cancer and normal tissue cell survival statistics for grid therapy in two regimens were calculated. The EODs and TRs were derived. The EOD was only a fraction of the prescribed dose. The TR was dependent on the prescribed dose and the LQ parameters of both the tumor and normal tissue cells. The grid therapy favors the acutely responding tumors inside radiosensitive normal tissues. Theoretical model predictions were consistent with the clinical outcomes. Conclusions: Grid therapy provided a pronounced therapeutic advantage in both the hypofractionated and conventionally fractionated regimens compared with that seen with single fraction, open debulking field regimens, but the true therapeutic advantage exists only in the hypofractionated grid therapy. The clinical outcomes and our study indicated that a course of open-field radiotherapy is necessary to control tumor growth fully after a grid therapy.
Minimizing metastatic risk in radiotherapy fractionation schedules
NASA Astrophysics Data System (ADS)
Badri, Hamidreza; Ramakrishnan, Jagdish; Leder, Kevin
2015-11-01
Metastasis is the process by which cells from a primary tumor disperse and form new tumors at distant anatomical locations. The treatment and prevention of metastatic cancer remains an extremely challenging problem. This work introduces a novel biologically motivated objective function to the radiation optimization community that takes into account metastatic risk instead of the status of the primary tumor. In this work, we consider the problem of developing fractionated irradiation schedules that minimize production of metastatic cancer cells while keeping normal tissue damage below an acceptable level. A dynamic programming framework is utilized to determine the optimal fractionation scheme. We evaluated our approach on a breast cancer case using the heart and the lung as organs-at-risk (OAR). For small tumor α /β values, hypo-fractionated schedules were optimal, which is consistent with standard models. However, for relatively larger α /β values, we found the type of schedule depended on various parameters such as the time when metastatic risk was evaluated, the α /β values of the OARs, and the normal tissue sparing factors. Interestingly, in contrast to standard models, hypo-fractionated and semi-hypo-fractionated schedules (large initial doses with doses tapering off with time) were suggested even with large tumor α/β values. Numerical results indicate the potential for significant reduction in metastatic risk.
Fractional calculus in bioengineering.
Magin, Richard L
2004-01-01
Fractional calculus (integral and differential operations of noninteger order) is not often used to model biological systems. Although the basic mathematical ideas were developed long ago by the mathematicians Leibniz (1695), Liouville (1834), Riemann (1892), and others and brought to the attention of the engineering world by Oliver Heaviside in the 1890s, it was not until 1974 that the first book on the topic was published by Oldham and Spanier. Recent monographs and symposia proceedings have highlighted the application of fractional calculus in physics, continuum mechanics, signal processing, and electromagnetics, but with few examples of applications in bioengineering. This is surprising because the methods of fractional calculus, when defined as a Laplace or Fourier convolution product, are suitable for solving many problems in biomedical research. For example, early studies by Cole (1933) and Hodgkin (1946) of the electrical properties of nerve cell membranes and the propagation of electrical signals are well characterized by differential equations of fractional order. The solution involves a generalization of the exponential function to the Mittag-Leffler function, which provides a better fit to the observed cell membrane data. A parallel application of fractional derivatives to viscoelastic materials establishes, in a natural way, hereditary integrals and the power law (Nutting/Scott Blair) stress-strain relationship for modeling biomaterials. In this review, I will introduce the idea of fractional operations by following the original approach of Heaviside, demonstrate the basic operations of fractional calculus on well-behaved functions (step, ramp, pulse, sinusoid) of engineering interest, and give specific examples from electrochemistry, physics, bioengineering, and biophysics. The fractional derivative accurately describes natural phenomena that occur in such common engineering problems as heat transfer, electrode/electrolyte behavior, and sub
Golden, S.W.; Martin, G.R.; Sloley, A.W. )
1993-03-01
Structured packing use in fluid catalytic cracker (FCC) main fractionators significantly impacts unit pressure profile. Unit pressure balance links the FCC main fractionator, reactor, regenerator, air compressor and wet gas compressor. Unit pressure balance should be viewed as a design variable when evaluating FCC unit revamps. Depending upon limitations of the particular FCC unit, capacity increases of 12.5% to 22.5% have been achieved without modifications to major rotating equipment, by revamping FCC main fractionators with structured packing. An examination of three FCC main fractionator revamps show improvements to pressure profiles and unit capacity. The three revamps described included a wet gas compressor volume limit; an air blower limitation; and a wet gas compressor motor limitation.
Intracellular Cadmium Isotope Fractionation
NASA Astrophysics Data System (ADS)
Horner, T. J.; Lee, R. B.; Henderson, G. M.; Rickaby, R. E.
2011-12-01
Recent stable isotope studies into the biological utilization of transition metals (e.g. Cu, Fe, Zn, Cd) suggest several stepwise cellular processes can fractionate isotopes in both culture and nature. However, the determination of fractionation factors is often unsatisfactory, as significant variability can exist - even between different organisms with the same cellular functions. Thus, it has not been possible to adequately understand the source and mechanisms of metal isotopic fractionation. In order to address this problem, we investigated the biological fractionation of Cd isotopes within genetically-modified bacteria (E. coli). There is currently only one known biological use or requirement of Cd, a Cd/Zn carbonic anhydrase (CdCA, from the marine diatom T. weissfloggii), which we introduce into the E. coli genome. We have also developed a cleaning procedure that allows for the treating of bacteria so as to study the isotopic composition of different cellular components. We find that whole cells always exhibit a preference for uptake of the lighter isotopes of Cd. Notably, whole cells appear to have a similar Cd isotopic composition regardless of the expression of CdCA within the E. coli. However, isotopic fractionation can occur within the genetically modified E. coli during Cd use, such that Cd bound in CdCA can display a distinct isotopic composition compared to the cell as a whole. Thus, the externally observed fractionation is independent of the internal uses of Cd, with the largest Cd isotope fractionation occurring during cross-membrane transport. A general implication of these experiments is that trace metal isotopic fractionation most likely reflects metal transport into biological cells (either actively or passively), rather than relating to expression of specific physiological function and genetic expression of different metalloenzymes.
Panprasitwech, Oranit; Laohakosol, Vichian; Chaichana, Tuangrat
2010-11-11
Explicit formulae for continued fractions with symmetric patterns in their partial quotients are constructed in the field of formal power series. Similar to the work of Cohn in 1996, which generalized the so-called folding lemma to {kappa}-fold symmetry, the notion of {kappa}-duplicating symmetric continued fractions is investigated using a modification of the 1995 technique due to Clemens, Merrill and Roeder.
Dose Rate Effects in Linear Bipolar Transistors
NASA Technical Reports Server (NTRS)
Johnston, Allan; Swimm, Randall; Harris, R. D.; Thorbourn, Dennis
2011-01-01
Dose rate effects are examined in linear bipolar transistors at high and low dose rates. At high dose rates, approximately 50% of the damage anneals at room temperature, even though these devices exhibit enhanced damage at low dose rate. The unexpected recovery of a significant fraction of the damage after tests at high dose rate requires changes in existing test standards. Tests at low temperature with a one-second radiation pulse width show that damage continues to increase for more than 3000 seconds afterward, consistent with predictions of the CTRW model for oxides with a thickness of 700 nm.
soil organic matter fractionation
NASA Astrophysics Data System (ADS)
Osat, Maryam; Heidari, Ahmad
2010-05-01
Carbon is essential for plant growth, due to its effects on other soil properties like aggregation. Knowledge of dynamics of organic matter in different locations in the soil matrix can provide valuable information which affects carbon sequestration and soil the other soil properties. Extraction of soil organic matter (SOM) fractions has been a long standing approach to elucidating the roles of soil organic matter in soil processes. Several kind fractionation methods are used and all provide information on soil organic matter function. Physical fractionation capture the effects on SOM dynamics of the spatial arrangement of primary and secondary organomineral particles in soil while chemical fractionation can not consider the spatial arrangement but their organic fractions are suitable for advanced chemical characterization. Three method of physical separation of soil have been used, sieving, sedimentation and densitometry. The distribution of organic matter within physical fractions of the soil can be assessed by sieving. Sieving separates soil particles based strictly on size. The study area is located on north central Iran, between 35° 41'- 36° 01' N and 50° 42'- 51° 14' E. Mean annual precipitation about 243.8 mm and mean annual air temperature is about 14.95 °C. The soil moisture and temperature regime vary between aridic-thermic in lower altitudes to xeric-mesic in upper altitudes. More than 36 surface soil samples (0-20 cm) were collected according to land-use map units. After preliminary analyzing of samples 10 samples were selected for further analyses in five size fractions and three different time intervals in September, January and April 2008. Fractionation carried out by dry sieving in five classes, 1-2 mm, 0.5-1 mm, 270 μm-0.5mm, 53-270 μm and <53 μm. Organic matter and C/N ratio were determined for all fractions at different time intervals. Chemical fractionation of organic matter also carried out according to Tan (2003), also Mineralogical
Burnouf, Thierry
2007-04-01
Protein products fractionated from human plasma are an essential class of therapeutics used, often as the only available option, in the prevention, management, and treatment of life-threatening conditions resulting from trauma, congenital deficiencies, immunologic disorders, or infections. Modern plasma product production technology remains largely based on the ethanol fractionation process, but much has evolved in the last few years to improve product purity, to enhance the recovery of immunoglobulin G, and to isolate new plasma proteins, such as alpha1-protease inhibitor, von Willebrand factor, and protein C. Because of the human origin of the starting material and the pooling of 10,000 to 50,000 donations required for industrial processing, the major risk associated to plasma products is the transmission of blood-borne infectious agents. A complete set of measures--and, most particularly, the use of dedicated viral inactivation and removal treatments--has been implemented throughout the production chain of fractionated plasma products over the last 20 years to ensure optimal safety, in particular, and not exclusively, against HIV, hepatitis B virus, and hepatitis C virus. In this review, we summarize the practices of the modern plasma fractionation industry from the collection of the raw plasma material to the industrial manufacture of fractionated products. We describe the quality requirements of plasma for fractionation and the various treatments applied for the inactivation and removal of blood-borne infectious agents and provide examples of methods used for the purification of the various classes of plasma protein therapies. We also highlight aspects of the good manufacturing practices and the regulatory environment that govern the whole chain of production. In a regulated and professional environment, fractionated plasma products manufactured by modern processes are certainly among the lowest-risk therapeutic biological products in use today. PMID:17397761
Robison, W.L.; Conrado, C.L.; Bogen, K.T
1999-10-06
radionuclides. However, we continually see {sup 137}Cs in the groundwater at all contaminated atolls; the turnover time of the groundwater is about 5 y. The {sup 137}Cs can only get to the groundwater by leaching through the soil column when a portion of the soluble fraction of {sup 137}Cs inventory in the soil is transported to the groundwater when rainfall is heavy enough to cause recharge of the aquifer. This process is causing a loss of {sup 137}Cs out of the root zone of the plants that provides an environmental loss constant ({lambda}{sub env}) in addition to radiological decay {lambda}{sub rad}. Consequently, there is an effective rate of loss, {lambda}{sub eff} = {lambda}{sub rad} + {lambda}{sub env} that is the sum of the radiological and environmental-loss decay constants. We have had, and continue to have, a vigorous program to determine the rate of the environmental loss process. What we do know at this time is that the loss of {sup 137}Cs over time is greater than the estimate based on radiological decay only, and that the actual dose received by the Utirik people over 30-, 50-, or 70-y will be less than those presented in this report.
A discrete fractional random transform
NASA Astrophysics Data System (ADS)
Liu, Zhengjun; Zhao, Haifa; Liu, Shutian
2005-11-01
We propose a discrete fractional random transform based on a generalization of the discrete fractional Fourier transform with an intrinsic randomness. Such discrete fractional random transform inheres excellent mathematical properties of the fractional Fourier transform along with some fantastic features of its own. As a primary application, the discrete fractional random transform has been used for image encryption and decryption.
FRACTIONAL CRYSTALLIZATION FEED ENVELOPE
HERTING DL
2008-03-19
Laboratory work was completed on a set of evaporation tests designed to establish a feed envelope for the fractional crystallization process. The feed envelope defines chemical concentration limits within which the process can be operated successfully. All 38 runs in the half-factorial design matrix were completed successfully, based on the qualitative definition of success. There is no feed composition likely to be derived from saltcake dissolution that would cause the fractional crystallization process to not meet acceptable performance requirements. However, some compositions clearly would provide more successful operation than other compositions.
Multipartite Fully Entangled Fraction
NASA Astrophysics Data System (ADS)
Xu, Jianwei
2016-06-01
Fully entangled fraction is a definition for bipartite states, which is tightly related to bipartite maximally entangled states, and has clear experimental and theoretical significance. In this work, we generalize it to multipartite case, we call the generalized version multipartite fully entangled fraction (MFEF). MFEF measures the closeness of a state to GHZ states. The analytical expressions of MFEF are very difficult to obtain except for very special states, however, we show that, the MFEF of any state is determined by a system of finite-order polynomial equations. Therefore, the MFEF can be efficiently numerically computed.
Bamberger, Judith A.; Glissmeyer, John A.
2004-01-01
This document presents results of experiments conducted to measure release fractions during certain tank retrieval processes. The tests were performed in a 1/4 scale model of a waste storage tank. The retrieval processes simulated were: (1) Discharging liquid or slurry from the mouth of a vertically oriented two-in. Schedule 40 pipe. The discharging material was in free-fall from the mouth of the pipe near the top of the tank into a liquid or slurry pool at the bottom of the tank. (2) The jet from a 9/16-in.-diameter nozzle transferring liquid or slurry waste from one side of the tank to the other. The discharging liquid was aimed at the opposite side of the tank from the nozzle and either impacted the tank wall or fell into a liquid or slurry pool in the bottom of the tank. (3) A high pressure fan jet of liquid striking a steel plate or simulated waste from a stand-off distance of a few inches. For each process, a water-soluble fluorescent dye was added to the liquid fraction as a tracer. Kaolin clay was used to represent the solids. The tank was covered and there was no forced ventilation in the tank during the tests. Six air samples were collected during each test. The air samples were collected at fixed positions in the tank. The air sample filters were dried and weighed to determine the solids collection. The fluorescent dye was then leached from each filter and quantified with a fluorometer to determine the collection of liquid. Samples of the slurry and liquid simulants were also collected to determine the quantities of simulant used in each test. To calculate the release fraction, the quantity collected on each air sample was adjusted for the fraction of the tank volume sampled and divided by the quantity of material exposed in the simulation. The method was not as sensitive for the solids content as it was for the liquid content, but in those instances where a solids release fraction was determined, it was in relatively good agreement with that of the
Assessing dose rate distributions in VMAT plans
NASA Astrophysics Data System (ADS)
Mackeprang, P.-H.; Volken, W.; Terribilini, D.; Frauchiger, D.; Zaugg, K.; Aebersold, D. M.; Fix, M. K.; Manser, P.
2016-04-01
Dose rate is an essential factor in radiobiology. As modern radiotherapy delivery techniques such as volumetric modulated arc therapy (VMAT) introduce dynamic modulation of the dose rate, it is important to assess the changes in dose rate. Both the rate of monitor units per minute (MU rate) and collimation are varied over the course of a fraction, leading to different dose rates in every voxel of the calculation volume at any point in time during dose delivery. Given the radiotherapy plan and machine specific limitations, a VMAT treatment plan can be split into arc sectors between Digital Imaging and Communications in Medicine control points (CPs) of constant and known MU rate. By calculating dose distributions in each of these arc sectors independently and multiplying them with the MU rate, the dose rate in every single voxel at every time point during the fraction can be calculated. Independently calculated and then summed dose distributions per arc sector were compared to the whole arc dose calculation for validation. Dose measurements and video analysis were performed to validate the calculated datasets. A clinical head and neck, cranial and liver case were analyzed using the tool developed. Measurement validation of synthetic test cases showed linac agreement to precalculated arc sector times within ±0.4 s and doses ±0.1 MU (one standard deviation). Two methods for the visualization of dose rate datasets were developed: the first method plots a two-dimensional (2D) histogram of the number of voxels receiving a given dose rate over the course of the arc treatment delivery. In similarity to treatment planning system display of dose, the second method displays the dose rate as color wash on top of the corresponding computed tomography image, allowing the user to scroll through the variation over time. Examining clinical cases showed dose rates spread over a continuous spectrum, with mean dose rates hardly exceeding 100 cGy min-1 for conventional
The effect of small radiation doses on the rat spinal cord: the concept of partial tolerance
Ang, K.K.; Van Der Kogel, A.J.; Van Der Schueren, E.
1983-10-01
To evaluate the tolerance of the rat spinal cord to small radiation doses per fraction, an increasing number of fractions is required for induction of paralysis. The assessment of doses of 1-2 Gy, as used in the clinic, would require that over 100 fractions be given. The validity of replacing part of a fractionated irradiation of the spinal cord by a single large dose has been tested. Fractionated irradiation doses with 18 MeV X rays were followed by a ''top-up'' dose of 15 Gy as a single treatment. This is the fraction size of a treatment with two irradiation doses leading to paralysis in 50% of the animals (ED 50). Fractionated treatments were carried out with 2, 5, 10 and 20 fractions followed by the top-up dose of 15 Gy. the isoeffect curve, as a function of the number of fractions, has the same slope as experiments performed without top-up dose. The results show that the quality and quantity of cellular repair is not modified when part of a multifractionated exposure is replaced by a larger top-dose. An important consequence of this finding is, that in treatments with unequal fraction sizes, the partial tolerances can simply be added. Since a top-up dose can replace a sizable number of irradiation treatments, its application will allow investigations of the extent of sublethal damage repair for fraction sizes as low as 1 Gy.
Antimicrobial activity of the solvent fractions from Bulbine natalensis Tuber.
Yakubu, M T; Mostafa, M; Ashafa, A O T; Afolayan, A J
2012-01-01
Bulbine natalensis Baker has been acclaimed to be used as an antimicrobial agent in the folklore medicine of South Africa without scientific evidence to substantiate or refute this claim. In view of this, the in vitro antimicrobial activity of solvent fractions (ethanol, ethyl acetate, n-butanol and water) from Bulbine natalensis Tuber against 4 Gram positive and 12 Gram negative bacteria as well as 3 fungal species were investigated using agar dilution. The ethanolic extract, n-butanol and ethyl acetate fractions inhibited 75, 87.5 and 100% respectively of the bacterial species in this study. The ethanolic, n-butanol and ethyl acetate fractions produced growth inhibition at MIC range of 1-10, 3-10 as well as 1 and 5 mg/ml respectively whereas the water fraction did not inhibit the growth of any of the bacterial species. Again, it was only the ethyl acetate fraction that inhibited the growth of Shigelli flexneri, Staphyloccus aureus and Escherichia coli. The ethanolic, ethyl acetate and n-butanolic fractions dose dependently inhibited the growth of Aspergillus niger and A. flavus whereas the water fraction produced 100% growth inhibition of the Aspergillus species at all the doses investigated. In contrast, no growth inhibition was produced on Candida albicans. The growth inhibition produced by the solvent fractions of B. natalensis Tuber in this study thus justifies the acclaimed use of the plant as an antimicrobial agent. The ethyl acetate fraction was the most potent. PMID:23983381
ERIC Educational Resources Information Center
Vinogradova, Natalya; Blaine, Larry
2013-01-01
Almost everyone loves chocolate. However, the same cannot be said about fractions, which are loved by markedly fewer. Middle school students tend to view them with wary respect, but little affection. The authors attempt to sweeten the subject by describing a type of game involving division of chocolate bars. The activity they describe provides a…
Momentum fractionation on superstrata
NASA Astrophysics Data System (ADS)
Bena, Iosif; Martinec, Emil; Turton, David; Warner, Nicholas P.
2016-05-01
Superstrata are bound states in string theory that carry D1, D5, and momentum charges, and whose supergravity descriptions are parameterized by arbitrary functions of (at least) two variables. In the D1-D5 CFT, typical three-charge states reside in high-degree twisted sectors, and their momentum charge is carried by modes that individually have fractional momentum. Understanding this momentum fractionation holographically is crucial for understanding typical black-hole microstates in this system. We use solution-generating techniques to add momentum to a multi-wound supertube and thereby construct the first examples of asymptotically-flat superstrata. The resulting supergravity solutions are horizonless and smooth up to well-understood orbifold singularities. Upon taking the AdS3 decoupling limit, our solutions are dual to CFT states with momentum fractionation. We give a precise proposal for these dual CFT states. Our construction establishes the very nontrivial fact that large classes of CFT states with momentum fractionation can be realized in the bulk as smooth horizonless supergravity solutions.
Fraction collector for electrophoresis
NASA Technical Reports Server (NTRS)
Bier, M.
1977-01-01
Rotating-tube electrophoresis apparatus employs rotating jet of eluting buffer to reduce effects of convection during separation. Designed for separation of microorganisms and biological species, system combines gravity/gradient compensating of lumen with buffer flush at fraction outlet to increase separation efficiency.
Fractionation of Soil Phosphorus
Technology Transfer Automated Retrieval System (TEKTRAN)
An understanding of the qualitative and quantitative information provided by soil phosphorus (P) fractionation methods is important for addressing agronomic and water quality problems, as well as evaluating P biogeochemistry in extreme environments. This chapter provides a schematic overview of and ...
ERIC Educational Resources Information Center
Caldwell, Karin D.
1988-01-01
Describes a technique for separating samples that range over 15 orders of magnitude in molecular weight. Discusses theory, apparatus, and sample preparation techniques. Lists several types of field-flow fractionation (FFF) and their uses: sedimentation FFF, thermal FFF, flow FFF, electrical FFF, and steric FFF. (ML)
Fractional statistics and confinement
NASA Astrophysics Data System (ADS)
Gaete, P.; Wotzasek, C.
2005-02-01
It is shown that a pointlike composite having charge and magnetic moment displays a confining potential for the static interaction while simultaneously obeying fractional statistics in a pure gauge theory in three dimensions, without a Chern-Simons term. This result is distinct from the Maxwell-Chern-Simons theory that shows a screening nature for the potential.
In vitro studies on the adjuvanticity of Brucella fractions.
Serre, A; Vendrell, J P; Huguet, M F; Cannat, A
1982-01-01
Two Brucella fractions, the murein-linked fraction PI and the murein-free fraction SF, behave as in vitro adjuvants for primary anti-sheep erythrocyte responses: added to Mishell and Dutton-type cultures of spleen cells from B6/DB F1 mice they significantly enhance the number of direct anti-sheep erythrocyte PFC observed on day 5. They exert both nonspecific, polyclonal activating effects and antigen-dependent specific adjuvanticity. These two functions, however, differ in their dose responses and in their cellular requirements and can therefore be dissociated. Thus, polyclonal activation requires high doses of the "adjuvant fraction," is enhanced by adherent-cell depletion, and is not impaired by T-cell depletion. Specific adjuvanticity, on the other hand, requires lower doses of the adjuvant fractions (very high doses are in fact suppressive) and is T-cell and adherent-cell dependent. Moreover, adjuvanticity can be transferred to unstimulated spleen cells (or restored in adherent-cell-depleted populations) by PI- or SF-stimulated adherent cells or by the filtered supernatants of such cultures; adjuvant-soluble factors are therefore involved in the phenomena of adherent, T- and B-cell cooperation required for the adjuvanticity of Brucella fractions. PMID:6982864
Helical tomotherapy superficial dose measurements
Ramsey, Chester R.; Seibert, Rebecca M.; Robison, Benjamin; Mitchell, Martha
2007-08-15
Helical tomotherapy is a treatment technique that is delivered from a 6 MV fan beam that traces a helical path while the couch moves linearly into the bore. In order to increase the treatment delivery dose rate, helical tomotherapy systems do not have a flattening filter. As such, the dose distributions near the surface of the patient may be considerably different from other forms of intensity-modulated delivery. The purpose of this study was to measure the dose distributions near the surface for helical tomotherapy plans with a varying separation between the target volume and the surface of an anthropomorphic phantom. A hypothetical planning target volume (PTV) was defined on an anthropomorphic head phantom to simulate a 2.0 Gy per fraction IMRT parotid-sparing head and neck treatment of the upper neck nodes. A total of six target volumes were created with 0, 1, 2, 3, 4, and 5 mm of separation between the surface of the phantom and the outer edge of the PTV. Superficial doses were measured for each of the treatment deliveries using film placed in the head phantom and thermoluminescent dosimeters (TLDs) placed on the phantom's surface underneath an immobilization mask. In the 0 mm test case where the PTV extends to the phantom surface, the mean TLD dose was 1.73{+-}0.10 Gy (or 86.6{+-}5.1% of the prescribed dose). The measured superficial dose decreases to 1.23{+-}0.10 Gy (61.5{+-}5.1% of the prescribed dose) for a PTV-surface separation of 5 mm. The doses measured by the TLDs indicated that the tomotherapy treatment planning system overestimates superficial doses by 8.9{+-}3.2%. The radiographic film dose for the 0 mm test case was 1.73{+-}0.07 Gy, as compared to the calculated dose of 1.78{+-}0.05 Gy. Given the results of the TLD and film measurements, the superficial calculated doses are overestimated between 3% and 13%. Without the use of bolus, tumor volumes that extend to the surface may be underdosed. As such, it is recommended that bolus be added for these
21 years of Biologically Effective Dose
Fowler, J F
2010-01-01
In 1989 the British Journal of Radiology published a review proposing the term biologically effective dose (BED), based on linear quadratic cell survival in radiobiology. It aimed to indicate quantitatively the biological effect of any radiotherapy treatment, taking account of changes in dose-per-fraction or dose rate, total dose and (the new factor) overall time. How has it done so far? Acceptable clinical results have been generally reported using BED, and it is in increasing use, although sometimes mistaken for “biologically equivalent dose”, from which it differs by large factors, as explained here. The continuously bending nature of the linear quadratic curve has been questioned but BED has worked well for comparing treatments in many modalities, including some with large fractions. Two important improvements occurred in the BED formula. First, in 1999, high linear energy transfer (LET) radiation was included; second, in 2003, when time parameters for acute mucosal tolerance were proposed, optimum overall times could then be “triangulated” to optimise tumour BED and cell kill. This occurs only when both early and late BEDs meet their full constraints simultaneously. New methods of dose delivery (intensity modulated radiation therapy, stereotactic body radiation therapy, protons, tomotherapy, rapid arc and cyberknife) use a few large fractions and obviously oppose well-known fractionation schedules. Careful biological modelling is required to balance the differing trends of fraction size and local dose gradient, as explained in the discussion “How Fractionation Really Works”. BED is now used for dose escalation studies, radiochemotherapy, brachytherapy, high-LET particle beams, radionuclide-targeted therapy, and for quantifying any treatments using ionising radiation. PMID:20603408
Dose rate mapping of VMAT treatments.
Podesta, Mark; Popescu, I Antoniu; Verhaegen, Frank
2016-06-01
Human tissues exhibit a varying response to radiation dose depending on the dose rate and fractionation scheme used. Dose rate effects have been reported for different radiations, and tissue types. The literature indicates that there is not a significant difference in response for low-LET radiation when using dose rates between 1 Gy min(-1) and 12 Gy min(-1) but lower dose rates have an observable sparing effect on tissues and a differential effect between tissues. In intensity-modulated radiotherapy such as volumetric modulated arc therapy (VMAT) the dose can be delivered with a wide range of dose rates. In this work we developed a method based on time-resolved Monte Carlo simulations to quantify the dose rate frequency distribution for clinical VMAT treatments for three cancer sites, head and neck, lung, and pelvis within both planning target volumes (PTV) and normal tissues. The results show a wide range of dose rates are used to deliver dose in VMAT and up to 75% of the PTV can have its dose delivered with dose rates <1 Gy min(-1). Pelvic plans on average have a lower mean dose rate within the PTV than lung or head and neck plans but a comparable mean dose rate within the organs at risk. Two VMAT plans that fulfil the same dose objectives and constraints may be delivered with different dose rate distributions, particularly when comparing single arcs to multiple arc plans. It is concluded that for dynamic plans, the dose rate range used varies to a larger degree than previously assumed. The effect of the dose rate range in VMAT on clinical outcome is unknown. PMID:27164221
Dose rate mapping of VMAT treatments
NASA Astrophysics Data System (ADS)
Podesta, Mark; Antoniu Popescu, I.; Verhaegen, Frank
2016-06-01
Human tissues exhibit a varying response to radiation dose depending on the dose rate and fractionation scheme used. Dose rate effects have been reported for different radiations, and tissue types. The literature indicates that there is not a significant difference in response for low-LET radiation when using dose rates between 1 Gy min‑1 and 12 Gy min‑1 but lower dose rates have an observable sparing effect on tissues and a differential effect between tissues. In intensity-modulated radiotherapy such as volumetric modulated arc therapy (VMAT) the dose can be delivered with a wide range of dose rates. In this work we developed a method based on time-resolved Monte Carlo simulations to quantify the dose rate frequency distribution for clinical VMAT treatments for three cancer sites, head and neck, lung, and pelvis within both planning target volumes (PTV) and normal tissues. The results show a wide range of dose rates are used to deliver dose in VMAT and up to 75% of the PTV can have its dose delivered with dose rates <1 Gy min‑1. Pelvic plans on average have a lower mean dose rate within the PTV than lung or head and neck plans but a comparable mean dose rate within the organs at risk. Two VMAT plans that fulfil the same dose objectives and constraints may be delivered with different dose rate distributions, particularly when comparing single arcs to multiple arc plans. It is concluded that for dynamic plans, the dose rate range used varies to a larger degree than previously assumed. The effect of the dose rate range in VMAT on clinical outcome is unknown.
An Introduction to Continued Fractions.
ERIC Educational Resources Information Center
Moore, Charles G.
Provided is an introduction to the properties of continued fractions for the intellectually curious high school student. Among the topics included are (1) Expansion of Rational Numbers into Simple Continued Fractions, (2) Convergents, (3) Continued Fractions and Linear Diophantine Equations of the Type am + bn = c, (4) Continued Fractions and…
Goal Sketches in Fraction Learning
ERIC Educational Resources Information Center
Sophian, Catherine; Madrid, Samara
2003-01-01
To examine how conceptual knowledge about fraction magnitudes changes as students' learning progresses, 5th and 7th-grade students were asked to solve fraction magnitude problems that entailed finding a fraction between two given fractions and then to evaluate solutions for similar problems that were modeled for them. When the given fractions…
Optimal fractionation in radiotherapy with multiple normal tissues.
Saberian, Fatemeh; Ghate, Archis; Kim, Minsun
2016-06-01
The goal in radiotherapy is to maximize the biological effect (BE) of radiation on the tumour while limiting its toxic effects on healthy anatomies. Treatment is administered over several sessions to give the normal tissue time to recover as it has better damage-repair capabilities than tumour cells. This is termed fractionation. A key problem in radiotherapy involves finding an optimal number of treatment sessions (fractions) and the corresponding dosing schedule. A major limitation of existing mathematically rigorous work on this problem is that it includes only a single normal tissue. Since essentially no anatomical region of interest includes only one normal tissue, these models may incorrectly identify the optimal number of fractions and the corresponding dosing schedule. We present a formulation of the optimal fractionation problem that includes multiple normal tissues. Our model can tackle any combination of maximum dose, mean dose and dose-volume type constraints for serial and parallel normal tissues as this is characteristic of most treatment protocols. We also allow for a spatially heterogeneous dose distribution within each normal tissue. Furthermore, we do not a priori assume that the doses are invariant across fractions. Finally, our model uses a spatially optimized treatment plan as input and hence can be seamlessly combined with any treatment planning system. Our formulation is a mixed-integer, non-convex, quadratically constrained quadratic programming problem. In order to simplify this computationally challenging problem without loss of optimality, we establish sufficient conditions under which equal-dosage or single-dosage fractionation is optimal. Based on the prevalent estimates of tumour and normal tissue model parameters, these conditions are expected to hold in many types of commonly studied tumours, such as those similar to head-and-neck and prostate cancers. This motivates a simple reformulation of our problem that leads to a closed
Testing fractional action cosmology
NASA Astrophysics Data System (ADS)
Shchigolev, V. K.
2016-08-01
The present work deals with a combined test of the so-called Fractional Action Cosmology (FAC) on the example of a specific model obtained by the author earlier. In this model, the effective cosmological term is proportional to the Hubble parameter squared through the so-called kinematic induction. The reason of studying this cosmological model could be explained by its ability to describe two periods of accelerated expansion, that is in agreement with the recent observations and the cosmological inflation paradigm. First of all, we put our model through the theoretical tests, which gives a general conception of the influence of the model parameters on its behavior. Then, we obtain some restrictions on the principal parameters of the model, including the fractional index, by means of the observational data. Finally, the cosmography parameters and the observational data compared to the theoretical predictions are presented both analytically and graphically.
NASA Technical Reports Server (NTRS)
McKay, David S.; Cooper, Bonnie L.
2010-01-01
This slide presentation describes new fractionation methods that are used to create dust that is respirable for testing the effects of inhalation of lunar dust in preparation for future manned lunar exploration. Because lunar dust is a very limited commodity, a method that does not result in loss of the material had to be developed. The dust separation system that is described incorporates some traditional methods, while preventing the dust from being contaminated or changed in reactivity properties while also limiting losses.
Fractional Galilean symmetries
NASA Astrophysics Data System (ADS)
Hosseiny, Ali; Rouhani, Shahin
2016-09-01
We generalize the differential representation of the operators of the Galilean algebras to include fractional derivatives. As a result a whole new class of scale invariant Galilean algebras are obtained. The first member of this class has dynamical index z = 2 similar to the Schrödinger algebra. The second member of the class has dynamical index z = 3 / 2, which happens to be the dynamical index Kardar-Parisi-Zhang equation.
Model Fractional Chern Insulators.
Behrmann, Jörg; Liu, Zhao; Bergholtz, Emil J
2016-05-27
We devise local lattice models whose ground states are model fractional Chern insulators-Abelian and non-Abelian topologically ordered states characterized by exact ground state degeneracies at any finite size and infinite entanglement gaps. Most saliently, we construct exact parent Hamiltonians for two distinct families of bosonic lattice generalizations of the Z_{k} parafermion quantum Hall states: (i) color-entangled fractional Chern insulators at band filling fractions ν=k/(C+1) and (ii) nematic states at ν=k/2, where C is the Chern number of the lowest band. In spite of a fluctuating Berry curvature, our construction is partially frustration free: the ground states reside entirely within the lowest band and exactly minimize a local (k+1) body repulsion term by term. In addition to providing the first known models hosting intriguing states such as higher Chern number generalizations of the Fibonacci anyon quantum Hall states, the remarkable stability and finite-size properties make our models particularly well suited for the study of novel phenomena involving, e.g., twist defects and proximity induced superconductivity, as well as being a guide for designing experiments. PMID:27284668
Model Fractional Chern Insulators
NASA Astrophysics Data System (ADS)
Behrmann, Jörg; Liu, Zhao; Bergholtz, Emil J.
2016-05-01
We devise local lattice models whose ground states are model fractional Chern insulators—Abelian and non-Abelian topologically ordered states characterized by exact ground state degeneracies at any finite size and infinite entanglement gaps. Most saliently, we construct exact parent Hamiltonians for two distinct families of bosonic lattice generalizations of the Zk parafermion quantum Hall states: (i) color-entangled fractional Chern insulators at band filling fractions ν =k /(C +1 ) and (ii) nematic states at ν =k /2 , where C is the Chern number of the lowest band. In spite of a fluctuating Berry curvature, our construction is partially frustration free: the ground states reside entirely within the lowest band and exactly minimize a local (k +1 ) body repulsion term by term. In addition to providing the first known models hosting intriguing states such as higher Chern number generalizations of the Fibonacci anyon quantum Hall states, the remarkable stability and finite-size properties make our models particularly well suited for the study of novel phenomena involving, e.g., twist defects and proximity induced superconductivity, as well as being a guide for designing experiments.
Dose audit failures and dose augmentation
NASA Astrophysics Data System (ADS)
Herring, C.
1999-01-01
Standards EN 552 and ISO 11137, covering radiation sterilization, are technically equivalent in their requirements for the selection of the sterilization dose. Dose Setting Methods 1 and 2 described in Annex B of ISO 11137 can be used to meet these requirements for the selection of the sterilization dose. Both dose setting methods require a dose audit every 3 months to determine the continued validity of the sterilization dose. This paper addresses the subject of dose audit failures and investigations into their cause. It also presents a method to augment the sterilization dose when the number of audit positives exceeds the limits imposed by ISO 11137.
Radiation Dose-Volume Effects in the Spinal Cord
Kirkpatrick, John P.; Kogel, Albert J. van der; Schultheiss, Timothy E.
2010-03-01
Dose-volume data for myelopathy in humans treated with radiotherapy (RT) to the spine is reviewed, along with pertinent preclinical data. Using conventional fractionation of 1.8-2 Gy/fraction to the full-thickness cord, the estimated risk of myelopathy is <1% and <10% at 54 Gy and 61 Gy, respectively, with a calculated strong dependence on dose/fraction (alpha/beta = 0.87 Gy.) Reirradiation data in animals and humans suggest partial repair of RT-induced subclinical damage becoming evident about 6 months post-RT and increasing over the next 2 years. Reports of myelopathy from stereotactic radiosurgery to spinal lesions appear rare (<1%) when the maximum spinal cord dose is limited to the equivalent of 13 Gy in a single fraction or 20 Gy in three fractions. However, long-term data are insufficient to calculate a dose-volume relationship for myelopathy when the partial cord is treated with a hypofractionated regimen.
The emergence of nonuniform spatiotemporal fractionation schemes within the standard BED model
Unkelbach, Jan Papp, Dávid
2015-05-15
Purpose: Nonuniform spatiotemporal radiotherapy fractionation schemes, i.e., delivering distinct dose distributions in different fractions can potentially improve the therapeutic ratio. This is possible if the dose distributions are designed such that similar doses are delivered to normal tissues (exploit the fractionation effect) while hypofractionating subregions of the tumor. In this paper, the authors develop methodology for treatment planning with nonuniform fractions and demonstrate this concept in the context of intensity-modulated proton therapy (IMPT). Methods: Treatment planning is performed by simultaneously optimizing (possibly distinct) IMPT dose distributions for multiple fractions. This is achieved using objective and constraint functions evaluated for the cumulative biologically equivalent dose (BED) delivered at the end of treatment. BED based treatment planning formulations lead to nonconvex optimization problems, such that local gradient based algorithms require adequate starting positions to find good local optima. To that end, the authors develop a combinatorial algorithm to initialize the pencil beam intensities. Results: The concept of nonuniform spatiotemporal fractionation schemes is demonstrated for a spinal metastasis patient treated in two fractions using stereotactic body radiation therapy. The patient is treated with posterior oblique beams with the kidneys being located in the entrance region of the beam. It is shown that a nonuniform fractionation scheme that hypofractionates the central part of the tumor allows for a skin and kidney BED reduction of approximately 10%–20%. Conclusions: Nonuniform spatiotemporal fractionation schemes represent a novel approach to exploit fractionation effects that deserves further exploration for selected disease sites.
Single fraction radiotherapy for bone metastases: are all questions answered?
Chander, S S; Sarin, R
1999-08-01
All randomized trials show comparable pain relief rates with single or fractionated radiotherapy (RT) in selected patients. Further studies are required to determine the optimal single dose (our analysis suggests 6-8 Gy), its efficacy in preventing fractures/cord compression and defining criteria for recommending fractionated RT for a select few. Besides this, a 'lingua franca' for pain assessment tools is urgently required. PMID:10577706
Statistical iterative reconstruction using adaptive fractional order regularization
Zhang, Yi; Wang, Yan; Zhang, Weihua; Lin, Feng; Pu, Yifei; Zhou, Jiliu
2016-01-01
In order to reduce the radiation dose of the X-ray computed tomography (CT), low-dose CT has drawn much attention in both clinical and industrial fields. A fractional order model based on statistical iterative reconstruction framework was proposed in this study. To further enhance the performance of the proposed model, an adaptive order selection strategy, determining the fractional order pixel-by-pixel, was given. Experiments, including numerical and clinical cases, illustrated better results than several existing methods, especially, in structure and texture preservation. PMID:27231604
Solvent Fractionation of Lignin
Chatterjee, Sabornie; Saito, Tomonori
2014-01-01
Lignin is a highly abundant source of renewable carbon that can be considered as a valuable sustainable source of biobased materials. The major issues for the commercial production of value added high performance lignin products are lignin s physical and chemical heterogenities. To overcome these problems, a variety of procedures have been developed to produce pure lignin suitable for high performace applications such as lignin-derived carbon materials. However, most of the isolation procedures affect lignin s properties and structure. In this chapter, a short review of the effect of solvent fractionation on lignin s properties and structure is presented.
Fractional channel multichannel analyzer
Brackenbush, L.W.; Anderson, G.A.
1994-08-23
A multichannel analyzer incorporating the features of the present invention obtains the effect of fractional channels thus greatly reducing the number of actual channels necessary to record complex line spectra. This is accomplished by using an analog-to-digital converter in the asynchronous mode, i.e., the gate pulse from the pulse height-to-pulse width converter is not synchronized with the signal from a clock oscillator. This saves power and reduces the number of components required on the board to achieve the effect of radically expanding the number of channels without changing the circuit board. 9 figs.
Fractional channel multichannel analyzer
Brackenbush, Larry W.; Anderson, Gordon A.
1994-01-01
A multichannel analyzer incorporating the features of the present invention obtains the effect of fractional channels thus greatly reducing the number of actual channels necessary to record complex line spectra. This is accomplished by using an analog-to-digital converter in the asynscronous mode, i.e., the gate pulse from the pulse height-to-pulse width converter is not synchronized with the signal from a clock oscillator. This saves power and reduces the number of components required on the board to achieve the effect of radically expanding the number of channels without changing the circuit board.
Fractionated total body irradiation for metastatic neuroblastoma
Kun, L.E.; Casper, J.T.; Kline, R.W.; Piaskowski, V.D.
1981-11-01
Twelve patients over one year old with neuroblastoma (NBL) metastatic to bone and bone marrow entered a study of adjuvant low-dose, fractionated total body irradiation (TBI). Six children who achieved a ''complete clinical response'' following chemotherapy (cyclophosphamide and adriamycin) and surgical resection of the abdominal primary received TBI (10 rad/fraction to totals of 100-120 rad/10-12 fx/12-25 days). Two children received concurrent local irradiation for residual abdominal tumor. The intervals from cessation of chemotherapy to documented progression ranged from 2-16 months, not substatially different from patients receiving similar chemotherapy and surgery without TBI. Three additional children with progressive NBL received similar TBI (80-120 rad/8-12 fx) without objective response.
Clean fractionation of biomass
1995-09-01
The US DOE Alternative Feedstocks (AF) program is forging new links between the agricultural community and the chemicals industry through support of research and development (R&D) that uses green feedstocks to produce chemicals. The program promotes cost-effective industrial use of renewable biomass as feedstocks to manufacture high-volume chemical building blocks. Industrial commercialization of such processes would stimulate the agricultural sector by increasing the demand of agricultural and forestry commodities. A consortium of five DOE national laboratories has been formed with the objectives of providing industry with a broad range of expertise and helping to lower the risk of new process development through federal cost sharing. The AF program is conducting ongoing research on a clean fractionation process, designed to convert biomass into materials that can be used for chemical processes and products. The focus of the clean fractionation research is to demonstrate to industry that one technology can successfully separate all types of feedstocks into predictable types of chemical intermediates.
Stewart, F.A.; Oussoren, Y.; Luts, A.; Begg, A.C.; Dewit, L.; Lebesque, J.; Bartelink, H.
1987-05-01
Functional kidney damage in mice was measured after a series of fractionated X-irradiations. Doses per fraction of 0.75-12.5 Gy were given as 2, 5, 10, 30, 40, 60, or 80 equal doses in a total treatment time of 4 weeks. Renal function (measured by clearance of /sup 51/CrEDTA or hematocrit levels) deteriorated progressively, in a dose related manner, from 20 to 46 weeks after the start of treatment. The changes in renal function versus time were fitted by a polynomial regression through all data and interpolated values for /sup 51/CrEDTA clearance were then calculated at 30 and 40 weeks after treatment. Steep dose response curves were obtained and these were used to calculate isoeffective doses for the different fractionation schedules. There was a marked increase in total isoeffective doses from 2-30 fractions and these data were well described by a linear quadratic (L.Q.) expression for damage with an alpha/beta ratio of 2.3 +/- 0.2 Gy. There was only a slight increase in the total isoeffect dose as the size of the dose per fraction was decreased below 2 Gy and the measured isoeffect doses after 40 to 80 fractions were lower than predicted on the basis of an L.Q. model assuming complete repair between successive irradiations. The flexure dose for mouse kidneys irradiated 3 times per day was, effectively, 1 to 2 Gy and hyperfractionation using lower doses per fraction did not lead to significant, additional repair.
Four-Dimensional Patient Dose Reconstruction for Scanned Ion Beam Therapy of Moving Liver Tumors
Richter, Daniel; Saito, Nami; Chaudhri, Naved; Härtig, Martin; Ellerbrock, Malte; Jäkel, Oliver; Combs, Stephanie E.; Habermehl, Daniel; Herfarth, Klaus; Durante, Marco; Bert, Christoph
2014-05-01
Purpose: Estimation of the actual delivered 4-dimensional (4D) dose in treatments of patients with mobile hepatocellular cancer with scanned carbon ion beam therapy. Methods and Materials: Six patients were treated with 4 fractions to a total relative biological effectiveness (RBE)–weighted dose of 40 Gy (RBE) using a single field. Respiratory motion was addressed by dedicated margins and abdominal compression (5 patients) or gating (1 patient). 4D treatment dose reconstructions based on the treatment records and the measured motion monitoring data were performed for the single-fraction dose and a total of 17 fractions. To assess the impact of uncertainties in the temporal correlation between motion trajectory and beam delivery sequence, 3 dose distributions for varying temporal correlation were calculated per fraction. For 3 patients, the total treatment dose was formed from the fractional distributions using all possible combinations. Clinical target volume (CTV) coverage was analyzed using the volumes receiving at least 95% (V{sub 95}) and 107% (V{sub 107}) of the planned doses. Results: 4D dose reconstruction based on daily measured data is possible in a clinical setting. V{sub 95} and V{sub 107} values for the single fractions ranged between 72% and 100%, and 0% and 32%, respectively. The estimated total treatment dose to the CTV exhibited improved and more robust dose coverage (mean V{sub 95} > 87%, SD < 3%) and overdose (mean V{sub 107} < 4%, SD < 3%) with respect to the single-fraction dose for all analyzed patients. Conclusions: A considerable impact of interplay effects on the single-fraction CTV dose was found for most of the analyzed patients. However, due to the fractionated treatment, dose heterogeneities were substantially reduced for the total treatment dose. 4D treatment dose reconstruction for scanned ion beam therapy is technically feasible and may evolve into a valuable tool for dose assessment.
What is a fractional derivative?
NASA Astrophysics Data System (ADS)
Ortigueira, Manuel D.; Tenreiro Machado, J. A.
2015-07-01
This paper discusses the concepts underlying the formulation of operators capable of being interpreted as fractional derivatives or fractional integrals. Two criteria for required by a fractional operator are formulated. The Grünwald-Letnikov, Riemann-Liouville and Caputo fractional derivatives and the Riesz potential are accessed in the light of the proposed criteria. A Leibniz rule is also obtained for the Riesz potential.
Fractional diffusion on bounded domains
Defterli, Ozlem; D'Elia, Marta; Du, Qiang; Gunzburger, Max Donald; Lehoucq, Richard B.; Meerschaert, Mark M.
2015-03-13
We found that the mathematically correct specification of a fractional differential equation on a bounded domain requires specification of appropriate boundary conditions, or their fractional analogue. In this paper we discuss the application of nonlocal diffusion theory to specify well-posed fractional diffusion equations on bounded domains.
Using Steffe's Advanced Fraction Schemes
ERIC Educational Resources Information Center
McCloskey, Andrea V.; Norton, Anderson H.
2009-01-01
Recognizing schemes, which are different from strategies, can help teachers understand their students' thinking about fractions. Using Steffe's advanced fraction schemes, the authors describe a progression of development that upper elementary and middle school students might follow in understanding fractions. Each scheme can be viewed as a…
How Weird Are Weird Fractions?
ERIC Educational Resources Information Center
Stuffelbeam, Ryan
2013-01-01
A positive rational is a weird fraction if its value is unchanged by an illegitimate, digit-based reduction. In this article, we prove that each weird fraction is uniquely weird and initiate a discussion of the prevalence of weird fractions.
Fractions--Concepts before Symbols.
ERIC Educational Resources Information Center
Bennett, Albert B., Jr.
The learning difficulties that students experience with fractions begin immediately when they are shown fraction symbols with one numeral written above the other and told that the "top number" is called the numerator and the "bottom number" is called the denominator. This introduction to fractions will usually include a few visual diagrams to help…
NASA Astrophysics Data System (ADS)
Aharony, Ofer; Bergman, Oren; Jafferis, Daniel Louis
2008-11-01
We consider two generalizations of the Script N = 6 superconformal Chern-Simons-matter theories with gauge group U(N) × U(N). The first generalization is to Script N = 6 superconformal U(M) × U(N) theories, and the second to Script N = 5 superconformal O(2M) × USp(2N) and O(2M+1) × USp(2N) theories. These theories are conjectured to describe M2-branes probing C4/Zk in the unitary case, and C4/{\\widehat{D}}k in the orthogonal/symplectic case, together with a discrete flux, which can be interpreted as |M-N| fractional M2-branes localized at the orbifold singularity. The classical theories with these gauge groups have been constructed before; in this paper we focus on some quantum aspects of these theories, and on a detailed description of their M theory and type IIA string theory duals.
Fractionation of Subcellular Organelles.
Graham, John M
2015-01-01
This unit provides both a theoretical and a practical background to all the techniques associated with the application of differential and density gradient centrifugation for the analysis of subcellular membranes. The density gradient information focuses on the use of the modern gradient solute iodixanol, chosen for its ease of use, versatility, and compatibility with biological particles. Its use in both pre-formed discontinuous and continuous gradients and in self-generated gradients is discussed. Considerable emphasis is given to selection of the appropriate centrifuge rotors and tubes and their influence on the methods used for creation, fractionation, and analysis of density gradients. Without proper consideration of these critical ancillary procedures, the resolving power of the gradient can be easily compromised. PMID:26621372
NASA Technical Reports Server (NTRS)
Greenberg, Paul S.; Ku, Jerry C.
1994-01-01
A new technique is described for the full-field determination of soot volume fractions via laser extinction measurements. This technique differs from previously reported point-wise methods in that a two-dimensional array (i.e., image) of data is acquired simultaneously. In this fashion, the net data rate is increased, allowing the study of time-dependent phenomena and the investigation of spatial and temporal correlations. A telecentric imaging configuration is employed to provide depth-invariant magnification and to permit the specification of the collection angle for scattered light. To improve the threshold measurement sensitivity, a method is employed to suppress undesirable coherent imaging effects. A discussion of the tomographic inversion process is provided, including the results obtained from numerical simulation. Results obtained with this method from an ethylene diffusion flame are shown to be in close agreement with those previously obtained by sequential point-wise interrogation.
Delivery verification and dose reconstruction in tomotherapy
NASA Astrophysics Data System (ADS)
Kapatoes, Jeffrey Michael
2000-11-01
It has long been a desire in photon-beam radiation therapy to make use of the significant fraction of the beam exiting the patient to infer how much of the beam energy was actually deposited in the patient. With a linear accelerator and corresponding exit detector mounted on the same ring gantry, tomotherapy provides a unique opportunity to accomplish this. Dose reconstruction describes the process in which the full three-dimensional dose actually deposited in a patient is computed. Dose reconstruction requires two inputs: an image of the patient at the time of treatment and the actual energy fluence delivered. Dose is reconstructed by computing the dose in the CT with the verified energy fluence using any model-based algorithm such as convolution/superposition or Monte Carlo. In tomotherapy, the CT at the time of treatment is obtained by megavoltage CT, the merits of which have been studied and proven. The actual energy fluence delivered to the patient is computed in a process called delivery verification. Methods for delivery verification and dose reconstruction in tomotherapy were investigated in this work. It is shown that delivery verification can be realized by a linear model of the tornotherapy system. However, due to the measurements required with this initial approach, clinical implementation would be difficult. Therefore, a clinically viable method for delivery verification was established, the details of which are discussed. With the verified energy fluence from delivery verification, an assessment of the accuracy and usefulness of dose reconstruction is performed. The latter two topics are presented in the context of a generalized dose comparison tool developed for intensity modulated radiation therapy. Finally, the importance of having a CT from the time of treatment for reconstructing the dose is shown. This is currently a point of contention in modern clinical radiotherapy and it is proven that using the incorrect CT for dose reconstruction can lead
Fraction reduction in membrane systems.
Guo, Ping; Zhang, Hong; Chen, Haizhu; Liu, Ran
2014-01-01
Fraction reduction is a basic computation for rational numbers. P system is a new computing model, while the current methods for fraction reductions are not available in these systems. In this paper, we propose a method of fraction reduction and discuss how to carry it out in cell-like P systems with the membrane structure and the rules with priority designed. During the application of fraction reduction rules, synchronization is guaranteed by arranging some special objects in these rules. Our work contributes to performing the rational computation in P systems since the rational operands can be given in the form of fraction. PMID:24772037
Toward lattice fractional vector calculus
NASA Astrophysics Data System (ADS)
Tarasov, Vasily E.
2014-09-01
An analog of fractional vector calculus for physical lattice models is suggested. We use an approach based on the models of three-dimensional lattices with long-range inter-particle interactions. The lattice analogs of fractional partial derivatives are represented by kernels of lattice long-range interactions, where the Fourier series transformations of these kernels have a power-law form with respect to wave vector components. In the continuum limit, these lattice partial derivatives give derivatives of non-integer order with respect to coordinates. In the three-dimensional description of the non-local continuum, the fractional differential operators have the form of fractional partial derivatives of the Riesz type. As examples of the applications of the suggested lattice fractional vector calculus, we give lattice models with long-range interactions for the fractional Maxwell equations of non-local continuous media and for the fractional generalization of the Mindlin and Aifantis continuum models of gradient elasticity.
Fractionally charged skyrmions in fractional quantum Hall effect.
Balram, Ajit C; Wurstbauer, U; Wójs, A; Pinczuk, A; Jain, J K
2015-01-01
The fractional quantum Hall effect has inspired searches for exotic emergent topological particles, such as fractionally charged excitations, composite fermions, abelian and nonabelian anyons and Majorana fermions. Fractionally charged skyrmions, which support both topological charge and topological vortex-like spin structure, have also been predicted to occur in the vicinity of 1/3 filling of the lowest Landau level. The fractional skyrmions, however, are anticipated to be exceedingly fragile, suppressed by very small Zeeman energies. Here we show that, slightly away from 1/3 filling, the smallest manifestations of the fractional skyrmion exist in the excitation spectrum for a broad range of Zeeman energies, and appear in resonant inelastic light scattering experiments as well-defined resonances slightly below the long wavelength spin wave mode. The spectroscopy of these exotic bound states serves as a sensitive tool for investigating the residual interaction between composite fermions, responsible for delicate new fractional quantum Hall states in this filling factor region. PMID:26608906
Fractionally charged skyrmions in fractional quantum Hall effect
Balram, Ajit C.; Wurstbauer, U.; Wójs, A.; Pinczuk, A.; Jain, J. K.
2015-11-26
The fractional quantum Hall effect has inspired searches for exotic emergent topological particles, such as fractionally charged excitations, composite fermions, abelian and nonabelian anyons and Majorana fermions. Fractionally charged skyrmions, which support both topological charge and topological vortex-like spin structure, have also been predicted to occur in the vicinity of 1/3 filling of the lowest Landau level. The fractional skyrmions, however, are anticipated to be exceedingly fragile, suppressed by very small Zeeman energies. Here we show that, slightly away from 1/3 filling, the smallest manifestations of the fractional skyrmion exist in the excitation spectrum for a broad range of Zeeman energies, and appear in resonant inelastic light scattering experiments as well-defined resonances slightly below the long wavelength spin wave mode. The spectroscopy of these exotic bound states serves as a sensitive tool for investigating the residual interaction between composite fermions, responsible for delicate new fractional quantum Hall states in this filling factor region.
Fractionally charged skyrmions in fractional quantum Hall effect
Balram, Ajit C.; Wurstbauer, U.; Wójs, A.; Pinczuk, A.; Jain, J. K.
2015-01-01
The fractional quantum Hall effect has inspired searches for exotic emergent topological particles, such as fractionally charged excitations, composite fermions, abelian and nonabelian anyons and Majorana fermions. Fractionally charged skyrmions, which support both topological charge and topological vortex-like spin structure, have also been predicted to occur in the vicinity of 1/3 filling of the lowest Landau level. The fractional skyrmions, however, are anticipated to be exceedingly fragile, suppressed by very small Zeeman energies. Here we show that, slightly away from 1/3 filling, the smallest manifestations of the fractional skyrmion exist in the excitation spectrum for a broad range of Zeeman energies, and appear in resonant inelastic light scattering experiments as well-defined resonances slightly below the long wavelength spin wave mode. The spectroscopy of these exotic bound states serves as a sensitive tool for investigating the residual interaction between composite fermions, responsible for delicate new fractional quantum Hall states in this filling factor region. PMID:26608906
Fractionally charged skyrmions in fractional quantum Hall effect
NASA Astrophysics Data System (ADS)
Balram, Ajit C.; Wurstbauer, U.; Wójs, A.; Pinczuk, A.; Jain, J. K.
2015-11-01
The fractional quantum Hall effect has inspired searches for exotic emergent topological particles, such as fractionally charged excitations, composite fermions, abelian and nonabelian anyons and Majorana fermions. Fractionally charged skyrmions, which support both topological charge and topological vortex-like spin structure, have also been predicted to occur in the vicinity of 1/3 filling of the lowest Landau level. The fractional skyrmions, however, are anticipated to be exceedingly fragile, suppressed by very small Zeeman energies. Here we show that, slightly away from 1/3 filling, the smallest manifestations of the fractional skyrmion exist in the excitation spectrum for a broad range of Zeeman energies, and appear in resonant inelastic light scattering experiments as well-defined resonances slightly below the long wavelength spin wave mode. The spectroscopy of these exotic bound states serves as a sensitive tool for investigating the residual interaction between composite fermions, responsible for delicate new fractional quantum Hall states in this filling factor region.
Functional fractionation-ratchets
NASA Astrophysics Data System (ADS)
Griess, G. A.; Serwer, P.
2002-08-01
Electrophoretic ratchets have been developed for both analytical and preparative electrophoresis. These ratchets use a new type of pulsed field. The quality of the fractionations meets the usual standards for biochemistry-based electrophoresis. The supporting medium is either an agarose gel or a capillary-contained polymer solution. The electrophoretic ratchets are effective with a particle that has an electrophoretic mobility (μ=velocity/electrical field) that varies as the electrical field varies. A ratchet developed for DNA molecules is effective because μ increases in magnitude as the electrical field increases in magnitude. Ratchets developed for both DNA-protein complexes and spheres are effective because of the opposite dependence of μ on the electrical field. Ratchet-based gel electrophoresis can be performed in a continuous, preparative mode. Ratchet-based capillary electrophoresis provides a necessary component for cyclic capillary electrophoresis. Cyclic capillary electrophoresis of DNA is a procedure for analyzing a DNA profile in several segments. These segments are separated by electrophoretic enhancements of the DNA profile. Cyclic capillary electrophoresis is being developed for increasing both the length and the accuracy of the analysis of a DNA-sequencing ladder.
Dynamical fractional chaotic inflation
NASA Astrophysics Data System (ADS)
Harigaya, Keisuke; Ibe, Masahiro; Schmitz, Kai; Yanagida, Tsutomu T.
2014-12-01
Chaotic inflation based on a simple monomial scalar potential, V (ϕ )∝ϕp, is an attractive large-field model of inflation capable of generating a sizable tensor-to-scalar ratio r . Therefore, assuming that future cosmic microwave background observations will confirm the large r value reported by BICEP2, it is important to determine what kind of dynamical mechanism could possibly endow the inflaton field with such a simple effective potential. In this paper, we answer this question in the context of field theory, i.e. in the framework of dynamical chaotic inflation, where strongly interacting supersymmetric gauge dynamics around the scale of grand unification dynamically generate a fractional power-law potential via the quantum effect of dimensional transmutation. In constructing explicit models, we significantly extend our previous work, as we now consider a large variety of possible underlying gauge dynamics and relax our conditions on the field content of the model. This allows us to realize almost arbitrary rational values for the power p in the inflaton potential. The present paper may hence be regarded as a first step toward a more complete theory of dynamical chaotic inflation.
Fractional telegrapher's equation from fractional persistent random walks
NASA Astrophysics Data System (ADS)
Masoliver, Jaume
2016-05-01
We generalize the telegrapher's equation to allow for anomalous transport. We derive the space-time fractional telegrapher's equation using the formalism of the persistent random walk in continuous time. We also obtain the characteristic function of the space-time fractional process and study some particular cases and asymptotic approximations. Similarly to the ordinary telegrapher's equation, the time-fractional equation also presents distinct behaviors for different time scales. Specifically, transitions between different subdiffusive regimes or from superdiffusion to subdiffusion are shown by the fractional equation as time progresses.
Fractional telegrapher's equation from fractional persistent random walks.
Masoliver, Jaume
2016-05-01
We generalize the telegrapher's equation to allow for anomalous transport. We derive the space-time fractional telegrapher's equation using the formalism of the persistent random walk in continuous time. We also obtain the characteristic function of the space-time fractional process and study some particular cases and asymptotic approximations. Similarly to the ordinary telegrapher's equation, the time-fractional equation also presents distinct behaviors for different time scales. Specifically, transitions between different subdiffusive regimes or from superdiffusion to subdiffusion are shown by the fractional equation as time progresses. PMID:27300830
Dose to lung from inhaled tritiated particles.
Richardson, R B; Hong, A
2001-09-01
Tritiated particulate materials are of potential hazard in fission, fusion, and other tritium handling facilities. The absorbed fractions (fraction of energy emitted that is absorbed by the target region) are calculated for tritiated particles deposited in the alveolar-interstitial (AI) region of the respiratory tract. The energy absorbed by radiologically sensitive tissue irradiated by tritiated particles, in regions of the lung other than in the AI region, is negligible. The ICRP Publication 71 assumes the absorbed fraction is unity for tritium deposited in the AI region. We employed Monte Carlo methods in a model to evaluate the energy deposition in the wall of the alveolar sac from particles of tritiated beryllium, tritiated graphite, titanium tritide, tritiated iron hydroxide and zirconium tritide. For the five materials examined, the absorbed fraction in alveolar tissue ranged from 0.31 to 0.61 for particles of 1 microm physical diameter and 0.07 to 0.21 for 5 microm diameter particles. The dose to alveolar tissue, for an acute inhalation of tritiated particles by an adult male worker, was calculated based on the ICRP 66 lung model and the particle dissolution model of Mercer (1967). For particles of 5 microm activity median aerodynamic diameter (AMAD), the committed equivalent dose to alveolar tissue, calculated for the five materials, ranged from 32-42%, respectively, of the committed equivalent dose derived assuming the absorbed fractions were unity. PMID:11513464
MOSFET sensitivity dependence on integrated dose from high-energy photon beams.
Tanyi, James A; Krafft, Shane P; Hagio, Tomoe; Fuss, Martin; Salter, Bill J
2008-01-01
The ability of a commercially available dual bias, dual MOSFET dosimetry system to measure therapeutic doses reproducibly throughout its vendor-defined dose-based lifetime has been evaluated by characterizing its sensitivity variation to integrated/cumulative doses from,high-energy (6 and 15 MV) photon radiotherapy beams. The variation of sensitivity as a function of total integrated dose was studied for three different dose-per-fraction levels; namely, 50, 200, and 1200 cGy/fraction. In standard sensitivity mode (i.e., measurements involving dose-per-fraction levels > or =100 cGy), the response of the MOSFET system to identical irradiations increased with integrated dose for both energies investigated. Dose measurement reproducibility for the low (i.e., 50 cGy) dose fractions was within 2.1% (if the system was calibrated before each in-phantom measurement) and 3.1% [if the system was calibrated prior to first use, with no intermediate calibration(s)]. Similarly, dose measurement reproducibility was between 2.2% and 6.6% for the conventional (i.e., 200 cGy) dose fractions and between 1.8% and 7.9% for escalated (i.e., 1200 cGy) dose fractions. The results of this study suggest that, due to the progressively increasing sensitivity resulting from the dual-MOSFET design, frequent calibrations are required to achieve measurement accuracy of < or =3% (within one standard deviation). PMID:18293559
NASA Astrophysics Data System (ADS)
Hanin, Leonid; Zaider, Marco
2014-08-01
We revisit a long-standing problem of optimization of fractionated radiotherapy and solve it in considerable generality under the following three assumptions only: (1) repopulation of clonogenic cancer cells between radiation exposures follows linear birth-and-death Markov process; (2) clonogenic cancer cells do not interact with each other; and (3) the dose response function s(D) is decreasing and logarithmically concave. Optimal schedules of fractionated radiation identified in this work can be described by the following ‘greedy’ principle: give the maximum possible dose as soon as possible. This means that upper bounds on the total dose and the dose per fraction reflecting limitations on the damage to normal tissue, along with a lower bound on the time between successive fractions of radiation, determine the optimal radiation schedules completely. Results of this work lead to a new paradigm of dose delivery which we term optimal biologically-based adaptive boosting (OBBAB). It amounts to (a) subdividing the target into regions that are homogeneous with respect to the maximum total dose and maximum dose per fraction allowed by the anatomy and biological properties of the normal tissue within (or adjacent to) the region in question and (b) treating each region with an individual optimal schedule determined by these constraints. The fact that different regions may be treated to different total dose and dose per fraction mean that the number of fractions may also vary between regions. Numerical evidence suggests that OBBAB produces significantly larger tumor control probability than the corresponding conventional treatments.
Fractionation, rearrangement and subgenome dominance
Sankoff, David; Zheng, Chunfang
2012-01-01
Motivation: Fractionation is arguably the greatest cause of gene order disruption following whole genome duplication, causing severe biases in chromosome rearrangement-based estimates of evolutionary divergence. Results: We show how to correct for this bias almost entirely by means of a ‘consolidation’ algorithm for detecting and suitably transforming identifiable regions of fractionation. We characterize the process of fractionation and the performance of the algorithm through realistic simulations. We apply our method to a number of core eudicot genomes, we and by studying the fractionation regions detected, are able to address topical issues in polyploid evolution. Availability and implementation: Code for the consolidation algorithm, and sample data, is available at: http://137.122.149.195/Software/Fractionation/fractionation.html Contact: sankoff@uottawa.ca PMID:22962459
Method development for VOST Fractionator
St. Germain Wickham, M.E.; Cummins, S.B.; Radolovich, G. )
1994-01-01
A VOST Fractionator was designed and tested to fractionate an original VOST sample into two samples: one large and one small sample. The device allows for quantitation of high levels of compounds in the small fraction and trace levels in the large fraction. Several preliminary validation samples were prepared, split, and analyzed to test the feasibility of the VOST Fractionator. These validation samples contained 40,000 ng of three terpene compounds and 100 ng of 42 other volatile target analytes. Analyte recoveries ranged from 70 to 130 percent, except for five water-soluble compounds. Recovery for the terpene compounds was 110 to 118 percent. Precision for triplicate spiked samples was less than 30 percent relative standard deviation (%RSD) for most compounds. Results indicate that the VOST Fractionator accurately splits the sample and allows quantitation of extremely high levels of compounds without sacrificing sensitivity for trace compounds. 3 refs., 1 fig., 3 tabs.
Nonbiological fractionation of iron isotopes
NASA Technical Reports Server (NTRS)
Anbar, A. D.; Roe, J. E.; Barling, J.; Nealson, K. H.
2000-01-01
Laboratory experiments demonstrate that iron isotopes can be chemically fractionated in the absence of biology. Isotopic variations comparable to those seen during microbially mediated reduction of ferrihydrite are observed. Fractionation may occur in aqueous solution during equilibration between inorganic iron complexes. These findings provide insight into the mechanisms of iron isotope fractionation and suggest that nonbiological processes may contribute to iron isotope variations observed in sediments.
Fractional (Chern and topological) insulators
NASA Astrophysics Data System (ADS)
Neupert, Titus; Chamon, Claudio; Iadecola, Thomas; Santos, Luiz H.; Mudry, Christopher
2015-12-01
We review various features of interacting Abelian topological phases of matter in two spatial dimensions, placing particular emphasis on fractional Chern insulators (FCIs) and fractional topological insulators (FTIs). We highlight aspects of these systems that challenge the intuition developed from quantum Hall physics—for instance, FCIs are stable in the limit where the interaction energy scale is much larger than the band gap, and FTIs can possess fractionalized excitations in the bulk despite the absence of gapless edge modes.
Accessible solitons of fractional dimension
NASA Astrophysics Data System (ADS)
Zhong, Wei-Ping; Belić, Milivoj; Zhang, Yiqi
2016-05-01
We demonstrate that accessible solitons described by an extended Schrödinger equation with the Laplacian of fractional dimension can exist in strongly nonlocal nonlinear media. The soliton solutions of the model are constructed by two special functions, the associated Legendre polynomials and the Laguerre polynomials in the fraction-dimensional space. Our results show that these fractional accessible solitons form a soliton family which includes crescent solitons, and asymmetric single-layer and multi-layer necklace solitons.
Yang, Haihua; Tu, Yu; Wang, Wei; Hu, Wei; Ding, Weijun; Yu, Changhui; Zhou, Chao
2013-01-01
The purpose of this study was to compare anatomical and dosimetric variations in first 15 fractions, and between fractions 16 and 25, during intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC). Twenty-three NPC patients who received IMRT in 33 fractions were enrolled. Each patient had two repeat computed tomography (CT) scans before the 16th and 25th fraction. Hybrid IMRT plans were generated to evaluate the dosimetric changes. There was a significant decrease of the transverse diameter of nasopharyngeal and neck as well as gross tumor volume (GTV) in the primary nasopharyngeal carcinoma (GTVnx) and involved lymph nodes (GTVnd) during the first 15 fractions, and between fraction 16 and 25 (p < 0.05). Consequently, there was a significant reduction of the percentage of the volume receiving the prescribed dose (V100) of CTV1 and GTVnd, which was more prominent after the first 15 fractions treatment compared to that between fraction 16 and 25 (p < 0.05). Additionally, there was a significant increase in the mean dose (Dmean) and percentage of volume receiving ≥ 30 Gy (V30) to the bilateral parotid in the first 15 fractions (p < 0.05), but not between fraction 16 and 25. While the maximum dose to the spinal cord was significantly increased both in the first 15 fractions, and between fraction 16 and 25 (p < 0.05), the increase of the percent of spinal cord volume receiving ≥ 40 Gy (V40) was significantly higher in the first 15 fractions compared to that between fraction 16 and 25 (p < 0.05). Based on the dose constraint criterion in the RTOG0225 protocol, a total 39.1% (9/23) of phantom plan 1 (generated by applying the beam configurations of the original IMRT treatment plan to the anatomy of the second CT scan) and 17.4% (4/23) of phantom 2 (generated by applying the beam configurations of the replan 1 to the anatomy of the third CT scan) were out of limit for the dose to the normal critical structures. In conclusion, our data indicated that
Trigonometric Integrals via Partial Fractions
ERIC Educational Resources Information Center
Chen, H.; Fulford, M.
2005-01-01
Parametric differentiation is used to derive the partial fractions decompositions of certain rational functions. Those decompositions enable us to integrate some new combinations of trigonometric functions.
Dose sculpting with generalized equivalent uniform dose
Wu Qiuwen; Djajaputra, David; Liu, Helen H.; Dong Lei; Mohan, Radhe; Wu, Yan
2005-05-01
With intensity-modulated radiotherapy (IMRT), a variety of user-defined dose distribution can be produced using inverse planning. The generalized equivalent uniform dose (gEUD) has been used in IMRT optimization as an alternative objective function to the conventional dose-volume-based criteria. The purpose of this study was to investigate the effectiveness of gEUD optimization to fine tune the dose distributions of IMRT plans. We analyzed the effect of gEUD-based optimization parameters on plan quality. The objective was to determine whether dose distribution to selected structures could be improved using gEUD optimization without adversely altering the doses delivered to other structures, as in sculpting. We hypothesized that by carefully defining gEUD parameters (EUD{sub 0} and n) based on the current dose distributions, the optimization system could be instructed to search for alternative solutions in the neighborhood, and we could maintain the dose distributions for structures already satisfactory and improve dose for structures that need enhancement. We started with an already acceptable IMRT plan optimized with any objective function. The dose distribution was analyzed first. For structures that dose should not be changed, a higher value of n was used and EUD{sub 0} was set slightly higher/lower than the EUD value at the current dose distribution for critical structures/targets. For structures that needed improvement in dose, a higher to medium value of n was used, and EUD{sub 0} was set to the EUD value or slightly lower/higher for the critical structure/target at the current dose distribution. We evaluated this method in one clinical case each of head and neck, lung and prostate cancer. Dose volume histograms, isodose distributions, and relevant tolerance doses for critical structures were used for the assessment. We found that by adjusting gEUD optimization parameters, the dose distribution could be improved with only a few iterations. A larger value of n
Absorbed Dose and Dose Equivalent Calculations for Modeling Effective Dose
NASA Technical Reports Server (NTRS)
Welton, Andrew; Lee, Kerry
2010-01-01
While in orbit, Astronauts are exposed to a much higher dose of ionizing radiation than when on the ground. It is important to model how shielding designs on spacecraft reduce radiation effective dose pre-flight, and determine whether or not a danger to humans is presented. However, in order to calculate effective dose, dose equivalent calculations are needed. Dose equivalent takes into account an absorbed dose of radiation and the biological effectiveness of ionizing radiation. This is important in preventing long-term, stochastic radiation effects in humans spending time in space. Monte carlo simulations run with the particle transport code FLUKA, give absorbed and equivalent dose data for relevant shielding. The shielding geometry used in the dose calculations is a layered slab design, consisting of aluminum, polyethylene, and water. Water is used to simulate the soft tissues that compose the human body. The results obtained will provide information on how the shielding performs with many thicknesses of each material in the slab. This allows them to be directly applicable to modern spacecraft shielding geometries.
Rational Exponentials and Continued Fractions
ERIC Educational Resources Information Center
Denny, J. K.
2012-01-01
Using continued fraction expansions, we can approximate constants, such as pi and e, using an appropriate integer n raised to the power x[superscript 1/x], x a suitable rational. We review continued fractions and give an algorithm for producing these approximations.
Searches for Fractionally Charged Particles
Perl, Martin L.; Lee, Eric R.; Loomba, Dinesh; /New Mexico U.
2012-04-12
Since the initial measurements of the electron charge were made a century ago, experimenters have faced the persistent question of the existence of elementary particles with charges that are fractional multiples of the electron charge. In this review, we discuss the results of recent searches for these fractionally charged particles.
Fractionation process for petroleum wax
Jones, R.L.; Mitchael, M.R.; Krenowicz, R.A.; Southard, W.M.
1991-07-16
This patent describes a process which comprises separating a petroleum wax into a lower boiling wax fraction of a narrow melting range and a higher boiling wax fraction of wider melting range by subjecting the petroleum wax to distillation in a wiped film evaporator.
Understanding Magnitudes to Understand Fractions
ERIC Educational Resources Information Center
Gabriel, Florence
2016-01-01
Fractions are known to be difficult to learn and difficult to teach, yet they are vital for students to have access to further mathematical concepts. This article uses evidence to support teachers employing teaching methods that focus on the conceptual understanding of the magnitude of fractions.
Dividing Fractions and Problem Solving
ERIC Educational Resources Information Center
Cramer, Kathleen; Monson, Debra; Whitney, Stephanie; Leavitt, Seth; Wyberg, Terry
2010-01-01
Fraction division is generally introduced in sixth or seventh grade with this rule: "Invert and multiply." The authors examined current commercial curricula and found that few textbooks use context as a way to build meaning for the division of fractions. When context is used, the connection between the invert-and-multiply rule and the context is…
Unwrapping Students' Ideas about Fractions
ERIC Educational Resources Information Center
Lewis, Rebecca M.; Gibbons, Lynsey K.; Kazemi, Elham; Lind, Teresa
2015-01-01
Supporting students to develop an understanding of the meaning of fractions is an important goal of elementary school mathematics. This involves developing partitioning strategies, creating representations, naming fractional quantities, and using symbolic notation. This article describes how teachers can use a formative assessment problem to…
Radiating subdispersive fractional optical solitons.
Fujioka, J; Espinosa, A; Rodríguez, R F; Malomed, B A
2014-09-01
It was recently found [Fujioka et al., Phys. Lett. A 374, 1126 (2010)] that the propagation of solitary waves can be described by a fractional extension of the nonlinear Schrödinger (NLS) equation which involves a temporal fractional derivative (TFD) of order α > 2. In the present paper, we show that there is also another fractional extension of the NLS equation which contains a TFD with α < 2, and in this case, the new equation describes the propagation of radiating solitons. We show that the emission of the radiation (when α < 2) is explained by resonances at various frequencies between the pulses and the linear modes of the system. It is found that the new fractional NLS equation can be derived from a suitable Lagrangian density, and a fractional Noether's theorem can be applied to it, thus predicting the conservation of the Hamiltonian, momentum and energy. PMID:25273201
Radiating subdispersive fractional optical solitons
NASA Astrophysics Data System (ADS)
Fujioka, J.; Espinosa, A.; Rodríguez, R. F.; Malomed, B. A.
2014-09-01
It was recently found [Fujioka et al., Phys. Lett. A 374, 1126 (2010)] that the propagation of solitary waves can be described by a fractional extension of the nonlinear Schrödinger (NLS) equation which involves a temporal fractional derivative (TFD) of order α > 2. In the present paper, we show that there is also another fractional extension of the NLS equation which contains a TFD with α < 2, and in this case, the new equation describes the propagation of radiating solitons. We show that the emission of the radiation (when α < 2) is explained by resonances at various frequencies between the pulses and the linear modes of the system. It is found that the new fractional NLS equation can be derived from a suitable Lagrangian density, and a fractional Noether's theorem can be applied to it, thus predicting the conservation of the Hamiltonian, momentum and energy.
Radiating subdispersive fractional optical solitons
Fujioka, J. Espinosa, A.; Rodríguez, R. F.; Malomed, B. A.
2014-09-01
It was recently found [Fujioka et al., Phys. Lett. A 374, 1126 (2010)] that the propagation of solitary waves can be described by a fractional extension of the nonlinear Schrödinger (NLS) equation which involves a temporal fractional derivative (TFD) of order α > 2. In the present paper, we show that there is also another fractional extension of the NLS equation which contains a TFD with α < 2, and in this case, the new equation describes the propagation of radiating solitons. We show that the emission of the radiation (when α < 2) is explained by resonances at various frequencies between the pulses and the linear modes of the system. It is found that the new fractional NLS equation can be derived from a suitable Lagrangian density, and a fractional Noether's theorem can be applied to it, thus predicting the conservation of the Hamiltonian, momentum and energy.
Fractional active disturbance rejection control.
Li, Dazi; Ding, Pan; Gao, Zhiqiang
2016-05-01
A fractional active disturbance rejection control (FADRC) scheme is proposed to improve the performance of commensurate linear fractional order systems (FOS) and the robust analysis shows that the controller is also applicable to incommensurate linear FOS control. In FADRC, the traditional extended states observer (ESO) is generalized to a fractional order extended states observer (FESO) by using the fractional calculus, and the tracking differentiator plus nonlinear state error feedback are replaced by a fractional proportional-derivative controller. To simplify controller tuning, the linear bandwidth-parameterization method has been adopted. The impacts of the observer bandwidth ωo and controller bandwidth ωc on system performance are then analyzed. Finally, the FADRC stability and frequency-domain characteristics for linear single-input single-output FOS are analyzed. Simulation results by FADRC and ADRC on typical FOS are compared to demonstrate the superiority and effectiveness of the proposed scheme. PMID:26928516
Ojima, Mitsuaki; Ito, Maki; Suzuki, Keiji; Kai, Michiaki
2015-01-01
We determined the frequencies of dicentric chromosomes per cell in non-dividing confluent normal human fibroblasts (MRC-5) irradiated with a single 1 Gy dose or a fractionated 1 Gy dose (10X0.1 Gy, 5X0.2 Gy, and 2X0.5 Gy). The interval between fractions was between 1 min to 1440 min. After the completion of X-irradiation, the cells were incubated for 24 hours before re-plating at a low density. Then, demecolcine was administrated at 6 hours, and the first mitotic cells were collected for 42 hours. Our study demonstrated that frequencies of dicentric chromosomes in cells irradiated with a 1 Gy dose at different fractions were significantly reduced if the fraction interval was increased from 1 min to 5 min (p<0.05, χ2-test). Further increasing the fraction interval from 5 up to 1440 min did not significantly affect the frequency of dicentric chromosomes. Since misrejoining of two independent chromosome breaks introduced in close proximity gives rise to dicentric chromosome, our results indicated that such circumstances might be quite infrequent in cells exposed to fractionated X-irradiation with prolonged fraction intervals. Our findings should contribute to improve current estimation of cancer risk from chronic low-dose-rate exposure, or intermittent exposure of low-dose radiation by medical exposure. PMID:25723489
Finite doses are employed in experimental toxicology studies. Under the traditional methodology, the point of departure (POD) value for low dose extrapolation is identified as one of these doses. Dose spacing necessarily precludes a more accurate description of the POD value. ...
Low dose neutron late effects: Cataractogenesis
Worgul, B.V.
1991-12-01
The work is formulated to resolve the uncertainty regarding the relative biological effectiveness (RBE) of low dose neutron radiation. The study exploits the fact that cataractogenesis is sensitive to the inverse dose-rate effect as has been observed with heavy ions and was an endpoint considered in the follow-up of the A-bomb survivors. The neutron radiations were initiated at the Radiological Research Accelerator facility (RARAF) of the Nevis Laboratory of Columbia University. Four week old ({plus minus} 1 day) rats were divided into eight dose groups each receiving single or fractionated total doses of 0.2, 1.0, 5.0 and 25.0 cGy of monoenergetic 435 KeV neutrons. Special restraining jigs insured that the eye, at the midpoint of the lens, received the appropriate energy and dose with a relative error of {plus minus}5%. The fractionation regimen consisted of four exposures, each administered at three hour ({plus minus}) intervals. The neutron irradiated groups are being compared to rats irradiated with 250kVp X-rays in doses ranging from 0.5 to 7 Gy. The animals are being examined on a biweekly basis utilizing conventional slit-lamp biomicroscopy and the Scheimpflug Slit Lamp Imaging System (Zeiss). The follows-ups, entering their second year, will continue throughout the life-span of the animals. This is essential inasmuch as given the extremely low doses which are being utilized clinically detectable opacities were not anticipated until a significant fraction of the life span has lapsed. Current data support this contention. At this juncture cataracts in the irradiated groups are beginning to exceed control levels.
Peripheral doses from pediatric IMRT
Klein, Eric E.; Maserang, Beth; Wood, Roy; Mansur, David
2006-07-15
from 0.47-0.94) doses {approx}[0.4-1.8 cGy]/[0.9-2.9 cGy]/fraction, respectively. Prior phantom reports are for fields 10 cm or greater, while pediatric central nervous system fields range from 4 to 7 cm, and effectively much smaller for IMRT (2-6 cm). Peripheral dose in close proximity (<10 cm from the field edge) is dominated by internal scatter; therefore, field-size differences overwhelm phantom size affects and increased MU. Distant peripheral dose, dominated by head leakage, was higher than predicted, even when accounting for MUs ({approx}factor of 3) likely due to the pediatric phantom size. The ratio of the testes dose ranged from 3.3-5.3 for IMRT/conventional. PD to OAR for pediatric IMRT cannot be predicted from large-field full phantom studies. For regional OAR, doses are likely lower than predicted by existing ''large field'' data, while the distant PD is higher.
Variability of Marker-Based Rectal Dose Evaluation in HDR Cervical Brachytherapy
Wang Zhou; Jaggernauth, Wainwright; Malhotra, Harish K.; Podgorsak, Matthew B.
2010-01-01
In film-based intracavitary brachytherapy for cervical cancer, position of the rectal markers may not accurately represent the anterior rectal wall. This study was aimed at analyzing the variability of rectal dose estimation as a result of interfractional variation of marker placement. A cohort of five patients treated with multiple-fraction tandem and ovoid high-dose-rate (HDR) brachytherapy was studied. The cervical os point and the orientation of the applicators were matched among all fractional plans for each patient. Rectal points obtained from all fractions were then input into each clinical treated plan. New fractional rectal doses were obtained and a new cumulative rectal dose for each patient was calculated. The maximum interfractional variation of distances between rectal dose points and the closest source positions was 1.1 cm. The corresponding maximum variability of fractional rectal dose was 65.5%. The percentage difference in cumulative rectal dose estimation for each patient was 5.4%, 19.6%, 34.6%, 23.4%, and 13.9%, respectively. In conclusion, care should be taken when using rectal markers as reference points for estimating rectal dose in HDR cervical brachytherapy. The best estimate of true rectal dose for each fraction should be determined by the most anterior point among all fractions.
Photo-induced isotopic fractionation
NASA Astrophysics Data System (ADS)
Miller, Charles E.; Yung, Yuk L.
2000-12-01
This paper presents a systematic method for the analysis of photo-induced isotopic fractionation. The physical basis for this fractionation mechanism centers on the fact that isotopic substitution alters the energy levels, molecular symmetries, spin statistical weights and other fundamental molecular properties, producing spectroscopic signatures distinguishable from that of the parent isotopomer. These mass-dependent physical properties are identical to those invoked by Urey to explain stable isotope fractionation in chemical systems subject to thermodynamic equilibrium. Photo-induced isotopic fractionation is a completely general phenomenon and should be observable in virtually all gas phase photochemical systems. Water photo-induced isotopic fractionation has been examined in detail using experimental and theoretical data. These results illustrate the salient features of this fractionation mechanism for molecules possessing continuous UV absorption spectra and unit photodissociation quantum yields. Using the photo-induced isotopic fractionation methodology in conjunction with standard photochemical models, we predict substantial deuterium enrichment of water vapor in the planetary atmospheres of Earth and Mars.
An Introduction to Fractional Diffusion
NASA Astrophysics Data System (ADS)
Henry, B. I.; Langlands, T. A. M.; Straka, P.
The mathematical description of diffusion has a long history with many different formulations including phenomenological models based on conservation of mass and constitutive laws; probabilistic models based on random walks and central limit theorems; microscopic stochastic models based on Brownian motion and Langevin equations; and mesoscopic stochastic models based on master equations and Fokker-Planck equations. A fundamental result common to the different approaches is that the mean square displacement of a diffusing particle scales linearly with time. However there have been numerous experimental measurements in which the mean square displacement of diffusing particles scales as a fractional order power law in time. In recent years a great deal of progress has been made in extending the different models for diffusion to incorporate this fractional diffusion. The tools of fractional calculus have proven very useful in these developments, linking together fractional constitutive laws, continuous time random walks, fractional Langevin equations and fractional Brownian motions. These notes provide a tutorial style overview of standard and fractional diffusion processes.
Sudahar, H.; Kurup, P.G.G.; Murali, V.; Mahadev, P.; Velmurugan, J.
2013-01-01
The present study is to analyze the CyberKnife hypofractionated dose distribution of localized prostate cancer in terms of high–dose rate (HDR) brachytherapy equivalent doses to assess the degree of HDR brachytherapy resemblance of CyberKnife dose distribution. Thirteen randomly selected localized prostate cancer cases treated using CyberKnife with a dose regimen of 36.25 Gy in 5 fractions were considered. HDR equivalent doses were calculated for 30 Gy in 3 fractions of HDR brachytherapy regimen. The D{sub 5%} of the target in the CyberKnife hypofractionation was 41.57 ± 2.41 Gy. The corresponding HDR fractionation (3 fractions) equivalent dose was 32.81 ± 1.86 Gy. The mean HDR fractionation equivalent dose, D{sub 98%}, was 27.93 ± 0.84 Gy. The V{sub 100%} of the prostate target was 95.57% ± 3.47%. The V{sub 100%} of the bladder and the rectum were 717.16 and 79.6 mm{sup 3}, respectively. Analysis of the HDR equivalent dose of CyberKnife dose distribution indicates a comparable resemblance to HDR dose distribution in the peripheral target doses (D{sub 98%} to D{sub 80%}) reported in the literature. However, there is a substantial difference observed in the core high-dose regions especially in D{sub 10%} and D{sub 5%}. The dose fall-off within the OAR is also superior in reported HDR dose distribution than the HDR equivalent doses of CyberKnife.
Strenge, D.L.; Peloquin, R.A.
1981-04-01
The computer code HADOC (Hanford Acute Dose Calculations) is described and instructions for its use are presented. The code calculates external dose from air submersion and inhalation doses following acute radionuclide releases. Atmospheric dispersion is calculated using the Hanford model with options to determine maximum conditions. Building wake effects and terrain variation may also be considered. Doses are calculated using dose conversion factor supplied in a data library. Doses are reported for one and fifty year dose commitment periods for the maximum individual and the regional population (within 50 miles). The fractional contribution to dose by radionuclide and exposure mode are also printed if requested.
Fractionally charged skyrmions in fractional quantum Hall effect
Balram, Ajit C.; Wurstbauer, U.; Wójs, A.; Pinczuk, A.; Jain, J. K.
2015-11-26
The fractional quantum Hall effect has inspired searches for exotic emergent topological particles, such as fractionally charged excitations, composite fermions, abelian and nonabelian anyons and Majorana fermions. Fractionally charged skyrmions, which support both topological charge and topological vortex-like spin structure, have also been predicted to occur in the vicinity of 1/3 filling of the lowest Landau level. The fractional skyrmions, however, are anticipated to be exceedingly fragile, suppressed by very small Zeeman energies. Here we show that, slightly away from 1/3 filling, the smallest manifestations of the fractional skyrmion exist in the excitation spectrum for a broad range of Zeemanmore » energies, and appear in resonant inelastic light scattering experiments as well-defined resonances slightly below the long wavelength spin wave mode. The spectroscopy of these exotic bound states serves as a sensitive tool for investigating the residual interaction between composite fermions, responsible for delicate new fractional quantum Hall states in this filling factor region.« less
Relationship between fractional calculus and fractional Fourier transform
NASA Astrophysics Data System (ADS)
Zhang, Yanshan; Zhang, Feng; Lu, Mingfeng
2015-09-01
The fractional calculus (FC) deals with integrals and derivatives of arbitrary (i.e., non-integer) order, and shares its origins with classical integral and differential calculus. The fractional Fourier transform (FRFT), which has been found having many applications in optics and other areas, is a generalization of the usual Fourier transform. The FC and the FRFT are two of the most interesting and useful fractional areas. In recent years, it appears many papers on the FC and FRFT, however, few of them discuss the connection of the two fractional areas. We study their relationship. The relational expression between them is deduced. The expectation of interdisciplinary cross fertilization is our motivation. For example, we can use the properties of the FC (non-locality, etc.) to solve the problem which is difficult to be solved by the FRFT in optical engineering; we can also through the physical meaning of the FRFT optical implementation to explain the physical meaning of the FC. The FC and FRFT approaches can be transposed each other in the two fractional areas. It makes that the success of the fractional methodology is unquestionable with a lot of applications, namely in nonlinear and complex system dynamics and image processing.
Packing fraction of continuous distributions
NASA Astrophysics Data System (ADS)
Brouwers, Jos
2014-03-01
This study addresses the packing and void fraction of polydisperse particles with geometric and lognormal size distribution. It is demonstrated that a bimodal discrete particle distribution can be transformed into said continuous particle-size distributions. Furthermore, original and exact expressions are presented that predict the packing fraction of these particle assemblies. For a number of particle shapes and their packing modes (close, loose) the applicable parameters are given. The closed-form analytical expression governing the packing fractions are thoroughly compared with empirical and computational data reported in the literature, and good agreement is found.
Fractional trajectories: Decorrelation versus friction
NASA Astrophysics Data System (ADS)
Svenkeson, A.; Beig, M. T.; Turalska, M.; West, B. J.; Grigolini, P.
2013-11-01
The fundamental connection between fractional calculus and subordination processes is explored and affords a physical interpretation of a fractional trajectory, that being an average over an ensemble of stochastic trajectories. Heretofore what has been interpreted as intrinsic friction, a form of non-Markovian dissipation that automatically arises from adopting the fractional calculus, is shown to be a manifestation of decorrelations between trajectories. We apply the general theory developed herein to the Lotka-Volterra ecological model, providing new insight into the final equilibrium state. The relaxation time to achieve this state is also considered.
Toxic Membrane Fractions from Mycoplasma fermentans1
Gabridge, Michael G.; Murphy, William H.
1971-01-01
A recent isolate of Mycoplasma fermentans (strain K10, from human leukemic bone marrow) induced a lethal toxicity syndrome in mice. High doses of both viable and inactivated cells were toxic when injected intraperitoneally. Whole lysates and membranes from osmotically shocked cells killed mice, but cytoplasm did not. When membranes were dissolved in detergents and reaggregated by dialysis in the presence of Mg2+, the lipid-protein complex thus formed was toxic. Lipids extracted from membranes with chloroform-methanol did not kill mice. Protein-rich fractions (obtained by reaggregation plus acetone washes or ammonium sulfate precipitation of dissolved membranes) were also not toxic. No qualitative differences in proteins from three toxic isolates and three nontoxic laboratory strains of M. fermentans were detectable by polyacrylamide gel electrophoresis. The toxic factor contained in reaggregated membranes was heat-stable but sensitive to Pronase, trypsin, and lipase. Images PMID:5154902
Fractional Carbon Dioxide Laser Resurfacing
Ramsdell, William M.
2012-01-01
Currently available ablative fractional CO2 lasers provide excellent results and diminish down time with fewer complications than previous generation CO2 lasers. Mechanisms of action, treatment parameters, as well as pre- and postoperative care will be discussed. PMID:23904820
Ejection Fraction Heart Failure Measurement
... 70. You can have a normal ejection fraction reading and still have heart failure (called HFpEF or ... to be made. Here we delve into the importance of shared decision making. HF Resources For Life ...
The Future of Fractional Lasers.
Paasch, Uwe
2016-06-01
Recent insights to the potential of fractional skin treatments have established standard laser procedures to treat aged, sun-damaged skin and scars. On top of this, the concept has been extended to fibrosing conditions, to remove foreign bodies and to treat inflammatory skin diseases. The biggest potential, however, is foreseen with the option of a contact-free temporary opening of the epidermal barrier (TOR, German: gate) to promote new and intensified treatment regimen. To date these concepts are predominantly experimental, although first clinical studies already show a better response rate if actinic keratoses are treated by fractional laser-intensified photodynamic therapy (PDT) in comparison to the conventional PDT. Possible risks may arise due to the fact that fractional laser home devices are at hand. Used in conjunction with topicals of all origins, toxic and allergic reactions may occur. Principles of current fractional laser interventions are presented as facts while visions are given as future indications. PMID:27248023
Australia's Next Top Fraction Model
ERIC Educational Resources Information Center
Gould, Peter
2013-01-01
Peter Gould suggests Australia's next top fraction model should be a linear model rather than an area model. He provides a convincing argument and gives examples of ways to introduce a linear model in primary classrooms.
Mah, K; Van Dyk, J; Keane, T; Poon, P Y
1987-02-01
Acute radiation-induced pulmonary damage can be a significant cause of morbidity in radiation therapy of the thorax. A prospective, clinical study was conducted to obtain dose-response data on acute pulmonary damage caused by fractionated radiation therapy. The endpoint was a visible increase in lung density within the irradiated volume on a computed tomographic (CT) examination as observed independently by three diagnostic radiologists. Fifty-four patients with various malignancies of the thorax completed the study. CT chest scans were taken before and at preselected times following radiotherapy. To represent different fractionation schedules of equivalent biological effect, the estimated single dose (ED) model, ED = D X N-0.377 X T-0.058 was used in which D was the average lung dose within the high dose region in cGy, N was the number of fractions, and T was the overall treatment time in days. Patients were grouped according to ED and the percent incidence of pulmonary damage for each group was determined. Total average lung doses ranged from 29.8 Gy to 53.6 Gy given in 10 to 30 fractions over a range of 12 to 60 days. Five patient groups with incidence ranging from 30% (ED of 930) to 90% (ED of 1150) were obtained. The resulting dose-response curve predicted a 50% incidence level at an ED value (ED50) of 1000 +/- 40 ED units. This value represents fractionation schedules equivalent to a total average lung dose of 32.9 Gy given in 15 fractions over 19 days. Over the linear portion of the dose-response curve, a 5% increase in ED (or total dose if N and T remain constant), predicts a 12% increase in the incidence of acute radiation-induced pulmonary damage. PMID:3818385
Tolerance doses for treatment planning
Lyman, J.T.
1985-10-01
Data for the tolerance of normal tissues or organs to (low-LET) radiation has been compiled from a number of sources which are referenced at the end of this document. This tolerance dose data are ostensibly for uniform irradiation of all or part of an organ, and are for either 5% (TD/sub 5/) or 50% (TD/sub 50/) complication probability. The ''size'' of the irradiated organ is variously stated in terms of the absolute volume or the fraction of the organ volume irradiated, or the area or the length of the treatment field. The accuracy of these data is questionable. Much of the data represents doses that one or several experienced therapists have estimated could be safely given rather than quantitative analyses of clinical observations. Because these data have been obtained from multiple sources with possible different criteria for the definition of a complication, there are sometimes different values for what is apparently the same endpoint. The data from some sources shows a tendancy to be quantized in 5 Gy increments. This reflects the size of possible round off errors. It is believed that all these data have been accumulated without the benefit of 3-D dose distributions and therefore the estimates of the size of the volume and/or the uniformity of the irradiation may be less accurate than is now possible. 19 refs., 4 figs.
Chavan, Machindra J; Wakte, Pravin S; Shinde, Devanand B
2012-01-01
The sesquiterpene fraction of Annona reticulata bark was studied by GC/MS. Three major components were identified: copaene (35.40%), patchoulane (13.49%) and 1H-cycloprop(e)azulene (22.77%). The fraction was also screened for its analgesic and anti-inflammatory activities. The sesquiterpene fraction at doses 12.5 and 25 mg kg⁻¹ and the unsaponified petroleum ether extract at a dose of 50 mg kg⁻¹ exhibited significant central as well as peripheral analgesic and anti-inflammatory activities. These activities were comparable with the standard drugs used in the respective experiments. PMID:22007723
Alternatives to dose, quality factor and dose equivalent for low level irradiation
Sondhaus, C.A.; Bond, V.P.; Feinendegen, L.E.
1988-01-01
Randomly occurring energy deposition events produced by low levels of ionizing radiation interacting with tissue deliver variable amounts of energy to the sensitive target volumes within a small fraction of the cell population. A model is described in which an experimentally derived function relating event size to cell response probability operates mathematically on the microdosimetric event size distribution characterizing a given irradiation and thus determines the total fractional number of responding cells; this fraction measures the effectiveness of the given radiation. Normalizing to equal numbers of events produced by different radiations and applying this cell response or hit size effectiveness function (HSEF) should define radiation quality, or relative effectiveness, on a more nearly absolute basis than do the absorbed dose and dose evaluation, which are confounded when applied to low level irradiations. Examples using both calculation and experimental data are presented. 15 refs., 18 figs.
Fractionated Stereotactic Radiotherapy for Facial Nerve Schwannomas.
Shi, Wenyin; Jain, Varsha; Kim, Hyun; Champ, Colin; Jain, Gaurav; Farrell, Christopher; Andrews, David W; Judy, Kevin; Liu, Haisong; Artz, Gregory; Werner-Wasik, Maria; Evans, James J
2016-02-01
Purpose Data on the clinical course of irradiated facial nerve schwannomas (FNS) are lacking. We evaluated fractionated stereotactic radiotherapy (FSRT) for FNS. Methods Eight consecutive patients with FNS treated at our institution between 1998 and 2011 were included. Patients were treated with FSRT to a median dose of 50.4 Gy (range: 46.8-54 Gy) in 1.8 or 2.0 Gy fractions. We report the radiographic response, symptom control, and toxicity associated with FSRT for FNS. Results The median follow-up time was 43 months (range: 10-75 months). All patients presented with symptoms including pain, tinnitus, facial asymmetry, diplopia, and hearing loss. The median tumor volume was 1.57 cc. On the most recent follow-up imaging, five patients were noted to have stable tumor size; three patients had a net reduction in tumor volume. Additionally, six patients had improvement in clinical symptoms, one patient had stable clinical findings, and one patient had worsened House-Brackmann grade due to cystic degeneration. Conclusion FSRT treatment of FNS results in excellent control of growth and symptoms with a small rate of radiation toxicity. Given the importance of maintaining facial nerve function, FSRT could be considered as a primary management modality for enlarging or symptomatic FNS. PMID:26949592
Low dose neutron late effects: Cataractogenesis
Worgul, B.V.
1991-04-01
The work is formulated to resolve the uncertainty regarding the relative biological effectiveness. The endpoint which is being utilized is cataractogenesis. The advantages conferred by this system stems primarily from the non-invasive longitudinal analysis which it allows. It also exploits a well defined system and one which has demonstrated sensitivity to the inverse dose rate effect observed with heavy ions. Four week old rats were divided into 8 dose groups which received single or fractionated total doses of .2, 1.0, 5.0 and 25 cGy of monoenergetic 435 keV neutrons. Special restraining jigs were devised to insure that the eye at the midpoint of the lens received the appropriate energy and dose with a relative error of {plus minus} 5%. The fractionated regimen consisted of four exposures, each administered at 3 hour intervals. The reference radiations, 250 kVp X-rays, were administered in the same fashion but in doses ranging from .5 to 6.0 Gy. The animals are examined on a bi-weekly basis utilizing conventional slit-lamp biomicroscopy and the Scheimpflug Slit-lamp Imaging System. The follow-ups will continue throughout the lifespan of the animals. When opacification begins full documentation will involve the Zeiss imaging system and Oxford retroillumination photography. The processing routinely employs the Merriam/Focht scoring system for cross-referencing with previous cataract studies and establish cataractogenecity using a proven scoring method.
Fractional characteristic times and dissipated energy in fractional linear viscoelasticity
NASA Astrophysics Data System (ADS)
Colinas-Armijo, Natalia; Di Paola, Mario; Pinnola, Francesco P.
2016-08-01
In fractional viscoelasticity the stress-strain relation is a differential equation with non-integer operators (derivative or integral). Such constitutive law is able to describe the mechanical behavior of several materials, but when fractional operators appear, the elastic and the viscous contribution are inseparable and the characteristic times (relaxation and retardation time) cannot be defined. This paper aims to provide an approach to separate the elastic and the viscous phase in the fractional stress-strain relation with the aid of an equivalent classical model (Kelvin-Voigt or Maxwell). For such equivalent model the parameters are selected by an optimization procedure. Once the parameters of the equivalent model are defined, characteristic times of fractional viscoelasticity are readily defined as ratio between viscosity and stiffness. In the numerical applications, three kinds of different excitations are considered, that is, harmonic, periodic, and pseudo-stochastic. It is shown that, for any periodic excitation, the equivalent models have some important features: (i) the dissipated energy per cycle at steady-state coincides with the Staverman-Schwarzl formulation of the fractional model, (ii) the elastic and the viscous coefficients of the equivalent model are strictly related to the storage and the loss modulus, respectively.
Hoffmann, Aswin L.; Troost, Esther G.C.; Huizenga, Henk; Kaanders, Johannes H.A.M.; Bussink, Johan
2012-08-01
Purpose: Local tumor control and outcome remain poor in patients with advanced non-small-cell lung cancer (NSCLC) treated by external beam radiotherapy. We investigated the therapeutic gain of individualized dose prescription with dose escalation based on normal tissue dose constraints for various hypofractionation schemes delivered with intensity-modulated radiation therapy. Methods and Materials: For 38 Stage III NSCLC patients, the dose level of an existing curative treatment plan with standard fractionation (66 Gy) was rescaled based on dose constraints for the lung, spinal cord, esophagus, brachial plexus, and heart. The effect on tumor total dose (TTD) and biologic tumor effective dose in 2-Gy fractions (TED) corrected for overall treatment time (OTT) was compared for isotoxic and maximally tolerable schemes given in 15, 20, and 33 fractions. Rescaling was accomplished by altering the dose per fraction and/or the number of fractions while keeping the relative dose distribution of the original treatment plan. Results: For 30 of the 38 patients, dose escalation by individualized hypofractionation yielded therapeutic gain. For the maximally tolerable dose scheme in 33 fractions (MTD{sub 33}), individualized dose escalation resulted in a 2.5-21% gain in TTD. In the isotoxic schemes, the number of fractions could be reduced with a marginal increase in TED. For the maximally tolerable dose schemes, the TED could be escalated up to 36.6%, and for all patients beyond the level of the isotoxic and the MTD{sub 33} schemes (range, 3.3-36.6%). Reduction of the OTT contributed to the therapeutic gain of the shortened schemes. For the maximally tolerable schemes, the maximum esophageal dose was the dominant dose-limiting constraint in most patients. Conclusions: This modeling study showed that individualized dose prescription for hypofractionation in NSCLC radiotherapy, based on scaling of existing treatment plans up to normal tissue dose constraints, enables dose
Fractionation of radioactivity in the milk of goats administered UC-aflatoxin B1
Goto, T.; Hsieh, D.P.
1985-05-01
A detailed fractionation of radioactivity in the milk of goats administered UC-aflatoxin B1 at low doses was performed. The milk collected in the first 24 h following dosing contained radioactivity equivalent to 0.45-1.1% of the dose given. The radioactivity in each sample was partitioned into 4 fractions: ether, protein, dichloromethane, and water-alcohol. Over 80% of the radioactivity was detected in the dichloromethane fraction, of which over 95% was attributable to aflatoxin M1. No aflatoxin B1 or other known aflatoxin metabolites were detected in any fraction. The results indicate that the major metabolite of aflatoxin B1 in goat milk is aflatoxin M1 and that other metabolites, including conjugates, are of minor significance.
Jia, J; Tian, Z; Gu, X; Yan, H; Jia, X; Jiang, S
2014-06-15
Purpose: We studied dosimetric effects of inter-fraction deformation in lung stereotactic body radiotherapy (SBRT), in order to investigate the necessity of adaptive re-planning for lung SBRT treatments. Methods: Six lung cancer patients with different treatment fractions were retrospectively investigated. All the patients were immobilized and localized with a stereotactic body frame and were treated under cone-beam CT (CBCT) image guidance at each fraction. We calculated the actual delivered dose of the treatment plan using the up-to-date patient geometry of each fraction, and compared the dose with the intended plan dose to investigate the dosimetric effects of the inter-fraction deformation. Deformable registration was carried out between the treatment planning CT and the CBCT of each fraction to obtain deformed planning CT for more accurate dose calculations of the delivered dose. The extent of the inter-fraction deformation was also evaluated by calculating the dice similarity coefficient between the delineated structures on the planning CT and those on the deformed planning CT. Results: The average dice coefficients for PTV, spinal cord, esophagus were 0.87, 0.83 and 0.69, respectively. The volume of PTV covered by prescription dose was decreased by 23.78% on average for all fractions and all patients. For spinal cord and esophagus, the volumes covered by the constraint dose were increased by 4.57% and 3.83%. The maximum dose was also increased by 4.11% for spinal cord and 4.29% for esophagus. Conclusion: Due to inter-fraction deformation, large deterioration was found in both PTV coverage and OAR sparing, which demonstrated the needs for adaptive re-planning of lung SBRT cases to improve target coverage while reducing radiation dose to nearby normal tissues.
Black raspberry extract and fractions contain angiogenesis inhibitors.
Liu, Zhijun; Schwimer, Joshua; Liu, Dong; Greenway, Frank L; Anthony, Catherine T; Woltering, Eugene A
2005-05-18
Targeted therapies, such as agents that inhibit angiogenesis, offer hope as complementary agents in cancer therapy. Angiogenesis-inhibiting agents have the potential for inhibiting tumor growth and limiting the dissemination of metastasis, thus keeping cancers in a static growth state for prolonged periods. Black raspberry (Rubus occidentalis) extract was discovered to be antiangiogenic (0.1% w/v) in a novel human tissue-based in vitro fibrin clot angiogenesis assay. Assay-guided fractionation of a crude black raspberry extract resulted in a highly potent antiangiogenic fraction that accounted for only 1% of the fresh weight of whole black raspberries. At 0.075% (w/v), the active fraction completely inhibited angiogenic initiation and angiogenic vessel growth. Further subfractionation of this active fraction revealed the coexistence of multiple antiangiogenic compounds, one of which has been identified as gallic acid. However, the individual subfractions did not outperform the active whole fraction. These findings suggest that an active black raspberry fraction may be a promising complementary cancer therapy. It is natural and potent enough for manageable dosing regimens. These extracts contain multiple active ingredients that may be additive or synergistic in their antiangiogenic effects. These observations warrant further investigations in animals and human trials. PMID:15884816
Papp, D; Unkelbach, J
2014-06-01
Purpose: Non-uniform fractionation, i.e. delivering distinct dose distributions in two subsequent fractions, can potentially improve outcomes by increasing biological dose to the target without increasing dose to healthy tissues. This is possible if both fractions deliver a similar dose to normal tissues (exploit the fractionation effect) but high single fraction doses to subvolumes of the target (hypofractionation). Optimization of such treatment plans can be formulated using biological equivalent dose (BED), but leads to intractable nonconvex optimization problems. We introduce a novel optimization approach to address this challenge. Methods: We first optimize a reference IMPT plan using standard techniques that delivers a homogeneous target dose in both fractions. The method then divides the pencil beams into two sets, which are assigned to either fraction one or fraction two. The total intensity of each pencil beam, and therefore the physical dose, remains unchanged compared to the reference plan. The objectives are to maximize the mean BED in the target and to minimize the mean BED in normal tissues, which is a quadratic function of the pencil beam weights. The optimal reassignment of pencil beams to one of the two fractions is formulated as a binary quadratic optimization problem. A near-optimal solution to this problem can be obtained by convex relaxation and randomized rounding. Results: The method is demonstrated for a large arteriovenous malformation (AVM) case treated in two fractions. The algorithm yields a treatment plan, which delivers a high dose to parts of the AVM in one of the fractions, but similar doses in both fractions to the normal brain tissue adjacent to the AVM. Using the approach, the mean BED in the target was increased by approximately 10% compared to what would have been possible with a uniform reference plan for the same normal tissue mean BED.
The Dose Response Relationship for Radiation Carcinogenesis
NASA Astrophysics Data System (ADS)
Hall, Eric
2008-03-01
Recent surveys show that the collective population radiation dose from medical procedures in the U.S. has increased by 750% in the past two decades. It would be impossible to imagine the practice of medicine today without diagnostic and therapeutic radiology, but nevertheless the widespread and rapidly increasing use of a modality which is a known human carcinogen is a cause for concern. To assess the magnitude of the problem it is necessary to establish the shape of the dose response relationship for radiation carcinogenesis. Information on radiation carcinogenesis comes from the A-bomb survivors, from occupationally exposed individuals and from radiotherapy patients. The A-bomb survivor data indicates a linear relationship between dose and the risk of solid cancers up to a dose of about 2.5 Sv. The lowest dose at which there is a significant excess cancer risk is debatable, but it would appear to be between 40 and 100 mSv. Data from the occupation exposure of nuclear workers shows an excess cancer risk at an average dose of 19.4 mSv. At the other end of the dose scale, data on second cancers in radiotherapy patients indicates that cancer risk does not continue to rise as a linear function of dose, but tends towards a plateau of 40 to 60 Gy, delivered in a fractionated regime. These data can be used to estimate the impact of diagnostic radiology at the low dose end of the dose response relationship, and the impact of new radiotherapy modalities at the high end of the dose response relationship. In the case of diagnostic radiology about 90% of the collective population dose comes from procedures (principally CT scans) which involve doses at which there is credible evidence of an excess cancer incidence. While the risk to the individual is small and justified in a symptomatic patient, the same is not true of some screening procedures is asymptomatic individuals, and in any case the huge number of procedures must add up to a potential public health problem. In the
Harrison, J D; Balonov, M; Martin, C J; Ortiz Lopez, P; Menzel, H-G; Simmonds, J R; Smith-Bindman, R; Wakeford, R
2016-06-01
International Commission on Radiological Protection (ICRP) Publication 103 provided a detailed explanation of the purpose and use of effective dose and equivalent dose to individual organs and tissues. Effective dose has proven to be a valuable and robust quantity for use in the implementation of protection principles. However, questions have arisen regarding practical applications, and a Task Group has been set up to consider issues of concern. This paper focusses on two key proposals developed by the Task Group that are under consideration by ICRP: (1) confusion will be avoided if equivalent dose is no longer used as a protection quantity, but regarded as an intermediate step in the calculation of effective dose. It would be more appropriate for limits for the avoidance of deterministic effects to the hands and feet, lens of the eye, and skin, to be set in terms of the quantity, absorbed dose (Gy) rather than equivalent dose (Sv). (2) Effective dose is in widespread use in medical practice as a measure of risk, thereby going beyond its intended purpose. While doses incurred at low levels of exposure may be measured or assessed with reasonable reliability, health effects have not been demonstrated reliably at such levels but are inferred. However, bearing in mind the uncertainties associated with risk projection to low doses or low dose rates, it may be considered reasonable to use effective dose as a rough indicator of possible risk, with the additional consideration of variation in risk with age, sex and population group. PMID:26980800
Radiation dose to the lens and cataract formation
Henk, J.M.; Whitelocke, R.A.F.; Warrington, A.P.; Bessell, E.M. )
1993-04-02
The purpose of this work was to determine the radiation tolerance of the lens of the eye and the incidence of radiation-induced lens changes in patients treated by fractionated supervoltage radiation therapy for orbital tumors. Forty patients treated for orbital lymphoma and pseudotumor with tumor doses of 20--40 Gy were studied. The lens was partly shielded using lead cylinders in most cases. The dose to the germinative zone of the lens was estimated by measurements in a tissue equivalent phantom using both film densitometry and thermoluminescent dosimetry. Opthalmological examination was performed at 6 monthly intervals after treatment. The lead shield was found to reduce the dose to the germinative zone of the lens to between 36--50% of the tumor dose for Cobalt beam therapy, and to between 11--18% for 5 MeV x-rays. Consequently, the lens doses were in the range 4.5--30 Gy in 10--20 fractions. Lens opacities first appeared from between 3 and 9 years after irradiation. Impairment of visual acuity ensued in 74% of the patients who developed lens opacities. The incidence of lens changes was strongly dose-related. None was seen after doses of 5 Gy or lower, whereas doses of 16.5 Gy or higher were all followed by lens opacities which impaired visual acuity. The largest number of patients received a maximum lens dose of 15 Gy; in this group the actuarial incidence of lens opacities at 8 years was 57% with visual impairment in 38%. The adult lens can tolerate a total dose of 5 Gy during a fractionated course of supervoltage radiation therapy without showing any changes. Doses of 16.5 Gy or higher will almost invariably lead to visual impairment. The dose which causes a 50% probability of visual impairment is approximately 15 Gy. 10 refs., 4 figs., 1 tab.
Delayed coker fractionator advanced control
Jaisinghani, R.; Minter, B. ); Tica, A.; Puglesi, A.; Ojeda, R. )
1993-08-01
In a delayed coking process, as coke drum switches are made, rapid changes occur in both the fractionator feed rate and composition. With conventional control, it is not unusual to see long transient behavior of large swings in both quality and flowrates of coker gas oils. This can extract a heavy economic toll, not only in coker operation, but in the operation of downstream units as the upset is propagated. An advanced process control application (APC) was recently implemented on the coker fractionator at the Yacimentos Petroliferos Fiscales (YPF), Lujan de Cuyo Refinery, in Mendoza, Argentina. This coker fractionator control design was unique as it handled two different operating objectives: control of product qualities via tower temperature profile during normal operation and control of gas oil product flow ratio during drum switch. This combination of control objectives in one multivariable predictive control program was achieved by including special logic to decouple the individual tuning requirements. Also, additional logic was included to unambiguously detect and identify drum switch and drum steam out as discrete events within 30 seconds of their actual occurrence. These discrete events were then used as disturbance variables to minimize fractionator transient behavior. As a performance measure, the overhead temperature was controlled within 2 C to 2.5 C of its target, gas oil flows were stabilized during drum switches and steam generation via pump around was maximized. Overall, implementing advanced control for the delayed coker fractionator resulted in substantial benefits from product quality control, product flow control and minimized energy consumption.
Radiotherapy of advanced laryngeal cancer using three small fractions daily
Bradley, P.J.; Morgan, D.A. )
1991-06-01
Since 1983, the authors have treated advanced (UICC stages 3 and 4) squamous carcinomas of the larynx by primary radiotherapy, using three small fractions a day, 3-4 h interfraction interval, 5 days per week. The early patients received doses per fraction of 1.5 Gy, and a total dose of approximately 70 Gy, given as a split-course over 6 to 7 weeks. While overall tumor control and laryngeal preservation was good, a number of severe late radiation reactions were seen. The schedule was then modified, with a reduction in the fraction size to 1.1 Gy, the total dose to 60 Gy, and the overall time to 4 weeks, with omission of the mid-treatment split. Since 1986, we have treated 26 patients in this way. Acute reactions are brisk, but rapidly healing. Loco-regional control was achieved in 22 patients, only one of whom has relapsed to date, in a solitary node, salvaged by radical neck dissection. Four have died of uncontrolled loco-regional malignancy, and three of intercurrent disease while in clinical remission. No serious late morbidity has been observed in surviving patients, and vocal quality is good in the majority. These results suggest that this hyperfractionated and accelerated radiotherapy schedule may offer an acceptable nonsurgical, voice-preserving treatment for advanced laryngeal carcinoma; it can be used in a normally working radiotherapy department.
DMLC tracking and gating can improve dose coverage for prostate VMAT
Colvill, E.; Poulsen, P. R.; Booth, J. T.; O’Brien, R. T.; Keall, P. J.; Ng, J. A.
2014-09-15
Purpose: To assess and compare the dosimetric impact of dynamic multileaf collimator (DMLC) tracking and gating as motion correction strategies to account for intrafraction motion during conventionally fractionated prostate radiotherapy. Methods: A dose reconstruction method was used to retrospectively assess the dose distributions delivered without motion correction during volumetric modulated arc therapy fractions for 20 fractions of five prostate cancer patients who received conventionally fractionated radiotherapy. These delivered dose distributions were compared with the dose distributions which would have been delivered had DMLC tracking or gating motion correction strategies been implemented. The delivered dose distributions were constructed by incorporating the observed prostate motion with the patient's original treatment plan to simulate the treatment delivery. The DMLC tracking dose distributions were constructed using the same dose reconstruction method with the addition of MLC positions from Linac log files obtained during DMLC tracking simulations with the observed prostate motions input to the DMLC tracking software. The gating dose distributions were constructed by altering the prostate motion to simulate the application of a gating threshold of 3 mm for 5 s. Results: The delivered dose distributions showed that dosimetric effects of intrafraction prostate motion could be substantial for some fractions, with an estimated dose decrease of more than 19% and 34% from the planned CTVD{sub 99%} and PTV D{sub 95%} values, respectively, for one fraction. Evaluation of dose distributions for DMLC tracking and gating deliveries showed that both interventions were effective in improving the CTV D{sub 99%} for all of the selected fractions to within 4% of planned value for all fractions. For the delivered dose distributions the difference in rectum V{sub 65%} for the individual fractions from planned ranged from −44% to 101% and for the bladder V{sub 65
Fractionated Stereotactic Radiotherapy of Vestibular Schwannomas Accelerates Hearing Loss
Rasmussen, Rune; Claesson, Magnus; Stangerup, Sven-Eric; Roed, Henrik; Christensen, Ib Jarle; Caye-Thomasen, Per; Juhler, Marianne
2012-08-01
Objective: To evaluate long-term tumor control and hearing preservation rates in patients with vestibular schwannoma treated with fractionated stereotactic radiotherapy (FSRT), comparing hearing preservation rates to an untreated control group. The relationship between radiation dose to the cochlea and hearing preservation was also investigated. Methods and Materials: Forty-two patients receiving FSRT between 1997 and 2008 with a minimum follow-up of 2 years were included. All patients received 54 Gy in 27-30 fractions during 5.5-6.0 weeks. Clinical and audiometry data were collected prospectively. From a 'wait-and-scan' group, 409 patients were selected as control subjects, matched by initial audiometric parameters. Radiation dose to the cochlea was measured using the original treatment plan and then related to changes in acoustic parameters. Results: Actuarial 2-, 4-, and 10-year tumor control rates were 100%, 91.5%, and 85.0%, respectively. Twenty-one patients had serviceable hearing before FSRT, 8 of whom (38%) retained serviceable hearing at 2 years after FSRT. No patients retained serviceable hearing after 10 years. At 2 years, hearing preservation rates in the control group were 1.8 times higher compared with the group receiving FSRT (P=.007). Radiation dose to the cochlea was significantly correlated to deterioration of the speech reception threshold (P=.03) but not to discrimination loss. Conclusion: FSRT accelerates the naturally occurring hearing loss in patients with vestibular schwannoma. Our findings, using fractionation of radiotherapy, parallel results using single-dose radiation. The radiation dose to the cochlea is correlated to hearing loss measured as the speech reception threshold.
NASA Astrophysics Data System (ADS)
F Petit, Steven; Dekker, André L. A. J.; Seigneuric, Renaud; Murrer, Lars; van Riel, Natal A. W.; Nordsmark, Marianne; Overgaard, Jens; Lambin, Philippe; Wouters, Bradly G.
2009-04-01
The purpose of this study was to increase the potential of dose redistribution by incorporating estimates of oxygen heterogeneity within imaging voxels for optimal dose determination. Cellular oxygen tension (pO2) distributions were estimated for imaging-size-based voxels by solving oxygen diffusion-consumption equations around capillaries placed at random locations. The linear-quadratic model was used to determine cell survival in the voxels as a function of pO2 and dose. The dose distribution across the tumour was optimized to yield minimal survival after 30 × 2 Gy fractions by redistributing the dose based on differences in oxygen levels. Eppendorf data of a series of 69 tumours were used as a surrogate of what might be expected from oxygen imaging datasets. Dose optimizations were performed both taking into account cellular heterogeneity in oxygenation within voxels and assuming a homogeneous cellular distribution of oxygen. Our simulations show that dose redistribution based on derived cellular oxygen distributions within voxels result in dose distributions that require less total dose to obtain the same degree of cell kill as dose distributions that were optimized with a model that considered voxels as homogeneous with respect to oxygen. Moderately hypoxic tumours are expected to gain most from dose redistribution. Incorporating cellular-based distributions of radiosensitivity into dose-planning algorithms theoretically improves the potential gains from dose redistribution algorithms.
Lee, Larissa J.; Sadow, Cheryl A.; Russell, Anthony; Viswanathan, Akila N.
2009-11-01
Purpose: To compare high dose rate (HDR) point B to pelvic lymph node dose using three-dimensional-planned brachytherapy for cervical cancer. Methods and Materials: Patients with FIGO Stage IB-IIIB cervical cancer received 70 tandem HDR applications using CT-based treatment planning. The obturator, external, and internal iliac lymph nodes (LN) were contoured. Per fraction (PF) and combined fraction (CF) right (R), left (L), and bilateral (Bil) nodal doses were analyzed. Point B dose was compared with LN dose-volume histogram (DVH) parameters by paired t test and Pearson correlation coefficients. Results: Mean PF and CF doses to point B were R 1.40 Gy +- 0.14 (CF: 7 Gy), L 1.43 +- 0.15 (CF: 7.15 Gy), and Bil 1.41 +- 0.15 (CF: 7.05 Gy). The correlation coefficients between point B and the D100, D90, D50, D2cc, D1cc, and D0.1cc LN were all less than 0.7. Only the D2cc to the obturator and the D0.1cc to the external iliac nodes were not significantly different from the point B dose. Significant differences between R and L nodal DVHs were seen, likely related to tandem deviation from irregular tumor anatomy. Conclusions: With HDR brachytherapy for cervical cancer, per fraction nodal dose approximates a dose equivalent to teletherapy. Point B is a poor surrogate for dose to specific nodal groups. Three-dimensional defined nodal contours during brachytherapy provide a more accurate reflection of delivered dose and should be part of comprehensive planning of the total dose to the pelvic nodes, particularly when there is evidence of pathologic involvement.
Fractionalized gapless quantum vortex liquids
NASA Astrophysics Data System (ADS)
Wang, Chong; Senthil, T.
2015-05-01
The standard theoretical approach to gapless spin liquid phases of two-dimensional frustrated quantum antiferromagnets invokes the concept of fermionic slave particles into which the spin fractionalizes. As an alternate we explore different kinds of gapless spin liquid phases in frustrated quantum magnets with X Y anisotropy where the vortex of the spin fractionalizes into gapless itinerant fermions. The resulting gapless fractionalized vortex liquid phases are studied within a slave particle framework that is dual to the usual one. We demonstrate the stability of some such phases and describe their properties. We give an explicit construction in an X Y -spin-1 system on triangular lattice, and interpret it as a critical phase in the vicinity of spin-nematic states.
Search for fractionally charged particles
Lackner, K.S.; Zweig, G.
1982-01-01
Quarks, the constituents of hadrons and fermion fields of quantum chromodynamics, have fractional charges -1/3e and 2/3e. All charges are integral multiples of 1/3e and not e, as was previously believed. Therefore it is natural to ask if isolated particles of fractional charge exist, either as an intrinsic part of matter, or as particles that can be produced at high energy accelerators. This question can only be answered by experiment, and remains interesting even if quantum chromodynamics turns out to be an absolutely confining theory of quarks. For example, small deviations from the standard version of quantum chromodynamics, or the incorporation of quantum chromodynamics into a more comprehensive theory, could require the existence of free fractionally charged particles.
REFractions: The Representing Equivalent Fractions Game
ERIC Educational Resources Information Center
Tucker, Stephen I.
2014-01-01
Stephen Tucker presents a fractions game that addresses a range of fraction concepts including equivalence and computation. The REFractions game also improves students' fluency with representing, comparing and adding fractions.
Anisotropic fractional diffusion tensor imaging
Meerschaert, Mark M; Magin, Richard L; Ye, Allen Q
2015-01-01
Traditional diffusion tensor imaging (DTI) maps brain structure by fitting a diffusion model to the magnitude of the electrical signal acquired in magnetic resonance imaging (MRI). Fractional DTI employs anomalous diffusion models to obtain a better fit to real MRI data, which can exhibit anomalous diffusion in both time and space. In this paper, we describe the challenge of developing and employing anisotropic fractional diffusion models for DTI. Since anisotropy is clearly present in the three-dimensional MRI signal response, such models hold great promise for improving brain imaging. We then propose some candidate models, based on stochastic theory.
On Fractional Model Reference Adaptive Control
Shi, Bao; Dong, Chao
2014-01-01
This paper extends the conventional Model Reference Adaptive Control systems to fractional ones based on the theory of fractional calculus. A control law and an incommensurate fractional adaptation law are designed for the fractional plant and the fractional reference model. The stability and tracking convergence are analyzed using the frequency distributed fractional integrator model and Lyapunov theory. Moreover, numerical simulations of both linear and nonlinear systems are performed to exhibit the viability and effectiveness of the proposed methodology. PMID:24574897
On fractional Model Reference Adaptive Control.
Shi, Bao; Yuan, Jian; Dong, Chao
2014-01-01
This paper extends the conventional Model Reference Adaptive Control systems to fractional ones based on the theory of fractional calculus. A control law and an incommensurate fractional adaptation law are designed for the fractional plant and the fractional reference model. The stability and tracking convergence are analyzed using the frequency distributed fractional integrator model and Lyapunov theory. Moreover, numerical simulations of both linear and nonlinear systems are performed to exhibit the viability and effectiveness of the proposed methodology. PMID:24574897
Soleymanifard, Shokouhozaman; Bahreyni Toossi, Mohammad Taghi; Kamran Samani, Roghayeh; Mohebbi, Shokoufeh
2016-01-01
Objective Radiation effects induced in non-irradiated cells are termed radiation-induced bystander effects (RIBE). The present study intends to examine the RIBE response of QU-DB bystander cells to first, second and third radiation fractions and compare their cumulative outcome with an equal, single acute dose. Materials and Methods This experimental study irradiated three groups of target cells for one, two and three times with60Co gamma rays. One hour after irradiation, we transferred their culture media to non-irradiated (bystander) cells. We used the cytokinesis block micronucleus assay to evaluate RIBE response in the bystander cells. The numbers of micronuclei generated in bystander cells were determined. Results RIBE response to single acute doses increased up to 4 Gy, then decreased, and finally at the 8 Gy dose disappeared. The second and third fractions induced RIBE in bystander cells, except when RIBE reached to the maximum level at the first fraction. We split the 4 Gy acute dose into two fractions, which decreased the RIBE response. However, fractionation of 6 Gy (into two fractions of 3 Gy or three fractions of 2 Gy) had no effect on RIBE response. When we split the 8 Gy acute dose into two fractions we observed RIBE, which had disappeared following the single 8 Gy dose. Conclusion The impact of dose fractionation on RIBE induced in QU-DB cells de- pended on the RIBE dose-response relationship. Where RIBE increased proportion- ally with the dose, fractionation reduced the RIBE response. In contrast, at high dos- es where RIBE decreased proportionally with the dose, fractionation either did not change RIBE (at 6 Gy) or increased it (at 8 Gy). PMID:27602316
Brush border intestinal enzymes after multiple daily fractionation
Becciolini, A.; Giache, V.; Balzi, M.; Morrone, A.
1987-03-01
The modifications in brush border enzyme activity of the epithelial cell of the small intestine were studied after multiple daily fractionation (MDF) of 3 Gy X and 3 Gy X 2 X 2 (12 h split). Disaccharase and dipeptidase activities changed in the same way after irradiation. The results show that both total doses caused the three known phases of increase, decrease, and a return to normal. With MDF, activity at the end of irradiation was similar to or greater than that of controls and remained higher longer than a single dose of 8 Gy. However, the return to normal occurred sooner than after a single dose of 8 Gy. After 11 days, circadian oscillations of brush border enzyme activity appeared similar to those of controls in many segments of the intestine, reaching the highest activity during the night and the lowest in the afternoon.
Geneser, S; Cunha, J; Pouliot, J; Hsu, I
2014-06-15
Purpose: HDR brachytherapy consensus dose tolerance recommendations for organs at risk (OARs) remain widely debated. Prospective trials reporting metrics must be sufficiently data-dense to assess adverse affects and identify optimally predictive tolerances. We explore the tradeoffs between reporting dose-metrics versus volume-metrics and the potential impact on trial outcome analysis and tolerance recommendations. Methods: We analyzed 26 prostate patients receiving 15 Gy HDR single-fraction brachytherapy boost to 45 Gy external beam radiation therapy and 28 cervical patients receiving 28 Gy HDR brachytherapy monotherapy in 4 fractions using 2 implants. For each OAR structure, a robust linear regression fit was performed for the dose-metrics as a function of the volume-metrics. The plan quality information provided by recommended dose-metric and volume-metric values were compared. Results: For prostate rectal dose, D2cc and V75 lie close to the regression line, indicating they are similarly informative. Two outliers for prostate urethral dose are substantially different from the remaining cohort in terms of D0.1cc and V75, but not D1cc, suggesting the choice of reporting dose metric is essential. For prostate bladder and cervical bladder, rectum, and bowel, dose outliers are more apparent via V75 than recommended dose-metrics. This suggests that for prostate bladder dose and all cervical OAR doses, the recommended volume-metrics may be better predictors of clinical outcome than dose-metrics. Conclusion: For plan acceptance criteria, dose and volume-metrics are reciprocally equivalent. However, reporting dosemetrics or volume-metrics alone provides substantially different information. Our results suggest that volume-metrics may be more sensitive to differences in planned dose, and if one metric must be chosen, volumemetrics are preferable. However, reporting discrete DVH points severely limits the ability to identify planning tolerances most predictive of adverse
Comparison of fractionation schedules in the large heterogeneity limit
Guerrero, M.
2009-04-15
The author develops an analytical formula that relates total doses in different fractionation schemes using the linear-quadratic (LQ) model in the limit when the interpatient variation in radiosensitivity is large. We use published formulas for tumor control probability and parameter dependence developed for the large heterogeneity limit. We consider the isoeffect equation and uses simple algebraic manipulation to obtain the new fractionation formula valid for the large heterogeneity limit. We study the case of going from a dose per fraction of 1.8 Gy to a dose per fraction of 3 Gy, which is relevant for current hypofractionation schemes for prostate and breast cancer. We find that the total dose for the new fractionation depends not only on the {alpha}/{beta} ratio r but also on the ratio of the corresponding standard deviations {sigma}{sub {alpha}}/{sigma}{sub {beta}} and on the ratio between the original dose D{sub 1} and D{sub 50}. In some special cases, notably when D{sub 1}=D{sub 50(1)}, the standard LQ model is recovered. In general, when the relative widths of the distributions for {alpha} and {beta} are equal or similar, the deviation from the standard LQ model is small, mostly within 5% for D{sub 1}/D{sub 50(1)} from 0.4 up to 1.6. When the width of the distribution for {alpha} is much larger than the one for {beta}, larger deviations from the standard LQ model are found for small values of r but they fall within 10% for r larger than 4 Gy and within 5% for r larger than 10 Gy. The most unforgiving case is when the width of the distribution for {alpha} is much smaller than the one for {beta}, where the largest differences with the standard LQ model are found. While, in general, the formula can give a significantly different result than the standard LQ model equation, we find a range of parameters for which the difference is surprisingly small.
Antihepatoma activity of Artocarpus communis is higher in fractions with high artocarpin content.
Tzeng, Cheng-Wei; Yen, Feng-Lin; Lin, Liang-Tzung; Lee, Chiang-Wen; Yen, Ming-Hong; Tzeng, Wen-Sheng; Lin, Chun-Ching
2014-01-01
Extracts from natural plants have been used in traditional medicine for many centuries worldwide. Artocarpus communis is one such plant that has been used to treat liver cirrhosis, hypertension, and diabetes. To our knowledge, this study is the first to investigate the antihepatoma activity of A. communis toward HepG2 and PLC/PRF/5 cells and the first to explore the relationship between antihepatoma activity and the active compound artocarpin content in different fractions of A. communis. A. communis methanol extract and fractions induced dose-dependent reduction of tumor cell viability. DNA laddering analysis revealed that A. communis extract and fractions did not induce apoptosis in HepG2 and PLC/PRF/5 cells. Instead, acridine orange staining revealed that A. communis triggered autophagic cell death in a dose-dependent manner. The antihepatoma activity of A. communis is attributable to artocarpin. The fractions with the highest artocarpin content were also the fractions with the highest antihepatoma activity in the following order: dichloromethane fraction > methanol extract > ethyl acetate fraction > n-butanol fraction > n-hexane fraction. Taken together, A. communis showed antihepatoma activity through autophagic cell death. The effect was related to artocarpin content. Artocarpin could be considered an indicator of the anticancer potential of A. communis extract. PMID:25133268
Isotopic Fractionation in Interstellar Chemistry
NASA Technical Reports Server (NTRS)
Charnley, Steven
2009-01-01
Isotopically fractionated material is found in many solar system objects, including meteorites and comets. It is thought, in some cases, to trace interstellar material that was incorporated into the solar sys tem without undergoing significant processing. In this poster, we sho w the results of several models of the nitrogen, oxygen, and carbon f ractionation in proto-stellar cores.
Staircase and Fractional Part Functions
ERIC Educational Resources Information Center
Amram, Meirav; Dagan, Miriam; Ioshpe, Michael; Satianov, Pavel
2016-01-01
The staircase and fractional part functions are basic examples of real functions. They can be applied in several parts of mathematics, such as analysis, number theory, formulas for primes, and so on; in computer programming, the floor and ceiling functions are provided by a significant number of programming languages--they have some basic uses in…
Activities: Understanding Division of Fractions.
ERIC Educational Resources Information Center
Bezuk, Nadine S.; Armstrong, Barbara E.
1993-01-01
Presents a series of five activities that introduce division of fractions through real-world situations. Discusses problems related to resurfacing a highway, painting dividing stripes on a highway, covering one area A with another area B, looking for patterns, and maximizing the result of a division problem. Includes reproducible worksheets. (MDH)
Pythagorean Approximations and Continued Fractions
ERIC Educational Resources Information Center
Peralta, Javier
2008-01-01
In this article, we will show that the Pythagorean approximations of [the square root of] 2 coincide with those achieved in the 16th century by means of continued fractions. Assuming this fact and the known relation that connects the Fibonacci sequence with the golden section, we shall establish a procedure to obtain sequences of rational numbers…
Fractional quantum Hall effect revisited
NASA Astrophysics Data System (ADS)
Jacak, J.; Łydżba, P.; Jacak, L.
2015-10-01
The topology-based explanation of the fractional quantum Hall effect (FQHE) is summarized. The cyclotron braid subgroups crucial for this approach are introduced in order to identify the origin of the Laughlin correlations in 2D (two-dimensional) Hall systems. Flux-tubes and vortices for composite fermions in their standard constructions are explained in terms of cyclotron braids. The derivation of the hierarchy of the FQHE is proposed by mapping onto the integer effect within the topology-based approach. The experimental observations of the FQHE supporting the cyclotron braid picture are reviewed with a special attention paid to recent experiments with a suspended graphene. The triggering role of a carrier mobility for organization of the fractional state in Hall configuration is emphasized. The prerequisites for the FQHE are indicated including topological conditions substantially increasing the previously accepted set of physical necessities. The explanation of numerical studies by exact diagonalizations of the fractional Chern insulator states is formulated in terms of the topology condition applied to the Berry field flux quantization. Some new ideas withz regard to the synthetic fractional states in the optical lattices are also formulated.
ERIC Educational Resources Information Center
Mokashi, Neelima A.
2009-01-01
This article depicts the rewarding experience of creating mathematical environments for kindergarten and elementary students by focusing on one of the most important and often difficult-to-grasp concepts (fractions) through play methods incorporated into a math fair. The basic concept of a math fair is threefold: (1) to create preplanned,…
The Bootstrap Fraction in TFTR
Hoang, G. T.
1997-04-15
The TRANSP plasma analysis code is used to calculate the bootstrap current generated during neutral-beam injection and ion cyclotron resonance frequency heating for a wide variety of TFTR discharges. An empirical scaling relation is given for the bootstrap current fraction using the ratio of the peakedness of the thermal pressure and the total current density.
Fractions, trees and unfinished business
NASA Astrophysics Data System (ADS)
Shraiman, Boris
In this talk, mourning the loss of a teacher and a dear friend, I would like to share some unfinished thoughts loosely connecting - via Farey fraction trees - Kadanoff's study of universality of quasi-periodic route to chaos with the effort to understand universal features of genealogical trees.
Optimization in fractional aircraft ownership
NASA Astrophysics Data System (ADS)
Septiani, R. D.; Pasaribu, H. M.; Soewono, E.; Fayalita, R. A.
2012-05-01
Fractional Aircraft Ownership is a new concept in flight ownership management system where each individual or corporation may own a fraction of an aircraft. In this system, the owners have privilege to schedule their flight according to their needs. Fractional management companies (FMC) manages all aspects of aircraft operations, including utilization of FMC's aircraft in combination of outsourced aircrafts. This gives the owners the right to enjoy the benefits of private aviations. However, FMC may have complicated business requirements that neither commercial airlines nor charter airlines faces. Here, optimization models are constructed to minimize the number of aircrafts in order to maximize the profit and to minimize the daily operating cost. In this paper, three kinds of demand scenarios are made to represent different flight operations from different types of fractional owners. The problems are formulated as an optimization of profit and a daily operational cost to find the optimum flight assignments satisfying the weekly and daily demand respectively from the owners. Numerical results are obtained by Genetic Algorithm method.
Benefits of online in vivo dosimetry for single-fraction total body irradiation
Eaton, David J.; Warry, Alison J.; Trimble, Rachel E.; Vilarino-Varela, Maria J.; Collis, Christopher H.
2014-01-01
Use of a patient test dose before single-fraction total body irradiation (TBI) allows review of in vivo dosimetry and modification of the main treatment setup. However, use of computed tomography (CT) planning and online in vivo dosimetry may reduce the need for this additional step. Patients were treated using a supine CT-planned extended source-to-surface distance (SSD) technique with lead compensators and bolus. In vivo dosimetry was performed using thermoluminescent dosimeters (TLDs) and diodes at 10 representative anatomical locations, for both a 0.1-Gy test dose and the treatment dose. In total, 28 patients were treated between April 2007 and July 2013, with changes made in 10 cases (36%) following test dose results. Overall, 98.1% of measured in vivo treatment doses were within 10% of the prescribed dose, compared with 97.0% of test dose readings. Changes made following the test dose could have been applied during the single-fraction treatment itself, assuming that the dose was delivered in subportions and online in vivo dosimetry was available for all clinically important anatomical sites. This alleviates the need for a test dose, saving considerable time and resources.
Benefits of online in vivo dosimetry for single-fraction total body irradiation.
Eaton, David J; Warry, Alison J; Trimble, Rachel E; Vilarino-Varela, Maria J; Collis, Christopher H
2014-01-01
Use of a patient test dose before single-fraction total body irradiation (TBI) allows review of in vivo dosimetry and modification of the main treatment setup. However, use of computed tomography (CT) planning and online in vivo dosimetry may reduce the need for this additional step. Patients were treated using a supine CT-planned extended source-to-surface distance (SSD) technique with lead compensators and bolus. In vivo dosimetry was performed using thermoluminescent dosimeters (TLDs) and diodes at 10 representative anatomical locations, for both a 0.1-Gy test dose and the treatment dose. In total, 28 patients were treated between April 2007 and July 2013, with changes made in 10 cases (36%) following test dose results. Overall, 98.1% of measured in vivo treatment doses were within 10% of the prescribed dose, compared with 97.0% of test dose readings. Changes made following the test dose could have been applied during the single-fraction treatment itself, assuming that the dose was delivered in subportions and online in vivo dosimetry was available for all clinically important anatomical sites. This alleviates the need for a test dose, saving considerable time and resources. PMID:25151596
Repair in mouse lung between multiple small doses of X rays
Travis, E.L.; Parkins, C.S.; Down, J.D.; Fowler, J.F.; Thames, H.D.
1983-05-01
Multiple fraction experiments have been carried out to determine the response of mouse lung to repeated small doses of 240 kV X rays down to 150 rad/fraction using breathing rate and lethality to assess damage. Two experimental approaches were used to measure the effect of small doses in vivo: (1) multiple equal doses and (2) multiple priming doses followed by a large test dose. Analysis was performed using the multitarget two-component model and the linear test dose. The amount of repair was calculated as a function of either dose per fraction (F/sub R/) or total dose (F/sub rec/). Both F/sub R/ and F/sub rec/ increased with decreasing dose per fraction but the change in F/sub R/ was small. The advantage of F/sub rec/ was that it varied more rapidly with dose per fraction than F/sub R/, so that possible differences between tissue repair capabilities are more visible on plots of repair as a function of dose per fraction. F/sub R/ and F/sub rec/ both decreased with the level of single-dose isoeffect injury; thus neither parameter is acceptable for comparing repair capability of different normal tissues with widely differing single-dose end point levels. Beta/alpha values were calculated and found to be a more acceptable index of repair capability than either F/sub R/ or F/sub rec/ because unlike those two parameters, ..beta../..cap alpha.. varied little with level of damage. Beta/alpha values of 1.7 to 4.2 krad/sup -1/ were obtained for both lung death and increased breathing rate and are clearly intermediate between the lower ..beta../..cap alpha.. ratios for acute reactions, i.e., skin and intestine, and the higher values for late reactions in kidney and spinal cord.
Olsher, Richard H.; Hsu, Hsiao-Hua; Casson, William H.; Vasilik, Dennis G.; Kleck, Jeffrey H.; Beverding, Anthony
1996-01-01
A neutron dose equivalent detector for measuring neutron dose capable of accurately responding to neutron energies according to published fluence to dose curves. The neutron dose equivalent meter has an inner sphere of polyethylene, with a middle shell overlying the inner sphere, the middle shell comprising RTV.RTM. silicone (organosiloxane) loaded with boron. An outer shell overlies the middle shell and comprises polyethylene loaded with tungsten. The neutron dose equivalent meter defines a channel through the outer shell, the middle shell, and the inner sphere for accepting a neutron counter tube. The outer shell is loaded with tungsten to provide neutron generation, increasing the neutron dose equivalent meter's response sensitivity above 8 MeV.
Zeng Chuan; Giantsoudi, Drosoula; Grassberger, Clemens; Goldberg, Saveli; Niemierko, Andrzej; Paganetti, Harald; Efstathiou, Jason A.; Trofimov, Alexei
2013-05-15
Purpose: Biological effect of radiation can be enhanced with hypofractionation, localized dose escalation, and, in particle therapy, with optimized distribution of linear energy transfer (LET). The authors describe a method to construct inhomogeneous fractional dose (IFD) distributions, and evaluate the potential gain in the therapeutic effect from their delivery in proton therapy delivered by pencil beam scanning. Methods: For 13 cases of prostate cancer, the authors considered hypofractionated courses of 60 Gy delivered in 20 fractions. (All doses denoted in Gy include the proton's mean relative biological effectiveness (RBE) of 1.1.) Two types of plans were optimized using two opposed lateral beams to deliver a uniform dose of 3 Gy per fraction to the target by scanning: (1) in conventional full-target plans (FTP), each beam irradiated the entire gland, (2) in split-target plans (STP), beams irradiated only the respective proximal hemispheres (prostate split sagittally). Inverse planning yielded intensity maps, in which discrete position control points of the scanned beam (spots) were assigned optimized intensity values. FTP plans preferentially required a higher intensity of spots in the distal part of the target, while STP, by design, employed proximal spots. To evaluate the utility of IFD delivery, IFD plans were generated by rearranging the spot intensities from FTP or STP intensity maps, separately as well as combined using a variety of mixing weights. IFD courses were designed so that, in alternating fractions, one of the hemispheres of the prostate would receive a dose boost and the other receive a lower dose, while the total physical dose from the IFD course was roughly uniform across the prostate. IFD plans were normalized so that the equivalent uniform dose (EUD) of rectum and bladder did not increase, compared to the baseline FTP plan, which irradiated the prostate uniformly in every fraction. An EUD-based model was then applied to estimate tumor
Tomiyama, Yuuki; Araki, Fujio; Oono, Takeshi; Hioki, Kazunari
2014-07-01
Our purpose in this study was to implement three-dimensional (3D) gamma analysis for structures of interest such as the planning target volume (PTV) or clinical target volume (CTV), and organs at risk (OARs) for intensity-modulated radiation therapy (IMRT) dose verification. IMRT dose distributions for prostate and head and neck (HN) cancer patients were calculated with an analytical anisotropic algorithm in an Eclipse (Varian Medical Systems) treatment planning system (TPS) and by Monte Carlo (MC) simulation. The MC dose distributions were calculated with EGSnrc/BEAMnrc and DOSXYZnrc user codes under conditions identical to those for the TPS. The prescribed doses were 76 Gy/38 fractions with five-field IMRT for the prostate and 33 Gy/17 fractions with seven-field IMRT for the HN. TPS dose distributions were verified by the gamma passing rates for the whole calculated volume, PTV or CTV, and OARs by use of 3D gamma analysis with reference to MC dose distributions. The acceptance criteria for the 3D gamma analysis were 3/3 and 2 %/2 mm for a dose difference and a distance to agreement. The gamma passing rates in PTV and OARs for the prostate IMRT plan were close to 100 %. For the HN IMRT plan, the passing rates of 2 %/2 mm in CTV and OARs were substantially lower because inhomogeneous tissues such as bone and air in the HN are included in the calculation area. 3D gamma analysis for individual structures is useful for IMRT dose verification. PMID:24796955
Role of Rad52 in fractionated irradiation induced signaling in A549 lung adenocarcinoma cells.
Ghosh, Somnath; Krishna, Malini
2012-01-01
The effect of fractionated doses of γ-irradiation (2Gy per fraction over 5 days), as delivered in cancer radiotherapy, was compared with acute doses of 10 and 2Gy, in A549 cells. A549 cells were found to be relatively more radioresistant if the 10Gy dose was delivered as a fractionated regimen. Microarray analysis showed upregulation of DNA repair and cell cycle arrest genes in the cells exposed to fractionated irradiation. There was intense activation of DNA repair pathway-associated genes (DNA-PK, ATM, Rad52, MLH1 and BRCA1), efficient DNA repair and phospho-p53 was found to be translocated to the nucleus of A549 cells exposed to fractionated irradiation. MCF-7 cells responded differently in fractionated regimen. Silencing of the Rad52 gene in fractionated group of A549 cells made the cells radiosensitive. The above result indicated increased radioresistance in A549 cells due to the activation of Rad52 gene. PMID:22001234
Pimenta, Lúcia Pinheiro Santos; Garcia, Giani Martins; Gonçalves, Samuel Geraldo do Vale; Dionísio, Bárbara Lana; Braga, Erika Martins; Mosqueira, Vanessa Carla Furtado
2014-01-01
Annona crassiflora and Annonaceae plants are known to be used to treat malaria by traditional healers. In this work, the antimalarial efficacy of different fractions of A. crassiflora, particularly acetogenin, alkaloids and flavonoid-rich fractions, was determined in vivo using Plasmodium berghei-infected mice model and toxicity was accessed by brine shrimp assay. The A. crassiflora fractions were administered at doses of 12.5 mg/kg/day in a 4-day test protocol. The results showed that some fractions from woods were rich in acetogenins, alkaloids and terpenes, and other fractions from leaves were rich in alkaloids and flavonoids. The parasitaemia was significantly (p < 0.05, p < 0.001) reduced (57-75%) with flavonoid and alkaloid-rich leaf fractions, which also increased mean survival time of mice after treatment. Our results confirm the usage of this plant in folk medicine as an antimalarial remedy. PMID:24678811
Evaluating fractionated space systems - Status
NASA Astrophysics Data System (ADS)
Cornford, S.; Jenkins, S.; Wall, S.; Cole, B.; Bairstow, B.; Rouquette, N.; Dubos, G.; Ryan, T.; Zarifian, P.; Boutwell, J.
DARPA has funded a number of teams to further refine its Fractionated Spacecraft vision. Several teams, including this team led by JPL, have been tasked to develop a tool for the evaluation of the Business case for a fractionated system architecture. This evaluation is to understand under what conditions and constraints the fractionated architecture make more sense (in a cost/benefit sense) than the traditional monolithic paradigm. Our approach to this evaluation is to generate and evaluate a variety of trade space options. These options include various sets of stimuli, various degrees of fractionation and various subsystem element properties. The stimuli include many not normally modeled such as technology obsolescence, funding profile changes and changes in mission objectives during the mission itself. The degrees of fractionation enable various traditional subsystem elements to be distributed across different free flyers which then act in concert as needed. This will enable key technologies to be updated as need dictates and availability allows. We have described our approach in a previous IEEE Aerospace conference paper but will briefly summarize here. Our approach to generate the Business Case evaluation is to explicitly model both the implementation and operation phases for the life cycle of a fractionated constellation. A variety of models are integrated into the Phoenix ModelCenter framework and are used to generate various intermediate data which is aggregated into the Present Strategic Value (PSV). The PSV is essentially the value (including the value of the embedded real options) minus the cost. These PSVs are calculated for a variety of configurations and scenarios including variations of various stimuli or uncertainties (e.g. supply chain delays, launch vehicle failures and orbital debris events). There are various decision options (e.g. delay, accelerate, cancel) which can now be exercised for each stimulus. We can compute the PSV for the various comb
Radiation Dose-Volume Effects in the Brain
Lawrence, Yaacov Richard; Li, X. Allen; El Naqa, Issam; Hahn, Carol A.; Marks, Lawrence B.; Merchant, Thomas E.; Dicker, Adam P.
2010-03-01
We have reviewed the published data regarding radiotherapy (RT)-induced brain injury. Radiation necrosis appears a median of 1-2 years after RT; however, cognitive decline develops over many years. The incidence and severity is dose and volume dependent and can also be increased by chemotherapy, age, diabetes, and spatial factors. For fractionated RT with a fraction size of <2.5 Gy, an incidence of radiation necrosis of 5% and 10% is predicted to occur at a biologically effective dose of 120 Gy (range, 100-140) and 150 Gy (range, 140-170), respectively. For twice-daily fractionation, a steep increase in toxicity appears to occur when the biologically effective dose is >80 Gy. For large fraction sizes (>=2.5 Gy), the incidence and severity of toxicity is unpredictable. For single fraction radiosurgery, a clear correlation has been demonstrated between the target size and the risk of adverse events. Substantial variation among different centers' reported outcomes have prevented us from making toxicity-risk predictions. Cognitive dysfunction in children is largely seen for whole brain doses of >=18 Gy. No substantial evidence has shown that RT induces irreversible cognitive decline in adults within 4 years of RT.
Using Number Sense to Compare Fractions
ERIC Educational Resources Information Center
Bray, Wendy S.; Abreu-Sanchez, Laura
2010-01-01
One mathematical focus for third graders is to develop deep understanding of fractions and fraction equivalence, including comparing fractions through use of models and reasoning strategies. Before reading further, consider how you might solve the following problem: Which fraction is greater, 14/24 or 17/36? The initial impulse of many adults is…
STOCHASTIC INTEGRATION FOR TEMPERED FRACTIONAL BROWNIAN MOTION
MEERSCHAERT, MARK M.; SABZIKAR, FARZAD
2014-01-01
Tempered fractional Brownian motion is obtained when the power law kernel in the moving average representation of a fractional Brownian motion is multiplied by an exponential tempering factor. This paper develops the theory of stochastic integrals for tempered fractional Brownian motion. Along the way, we develop some basic results on tempered fractional calculus. PMID:24872598
12 CFR 5.67 - Fractional shares.
Code of Federal Regulations, 2011 CFR
2011-01-01
... fair price upon the fraction not being issued through its sale, or the purchase of the additional fraction required for a full share, if there is an established and active market in the national bank's stock; (c) Remit the cash equivalent of the fraction not being issued to those to whom fractional...
Astrophysical Applications of Fractional Calculus
NASA Astrophysics Data System (ADS)
Stanislavsky, Aleksander A.
The paradigm of fractional calculus occupies an important place for the macroscopic description of subdiffusion. Its advance in theoretical astrophysics is expected to be very attractive too. In this report we discuss a recent development of the idea to some astrophysical problems. One of them is connected with a random migration of bright points associated with magnetic fields at the solar photosphere. The transport of the bright points has subdiffusive features that require the fractional generalization of the Leighton's model. Another problem is related to the angular distribution of radio beams, being propagated through a medium with random inhomogeneities. The peculiarity of this medium is that radio beams are trapped because of random wave localization. This idea can be useful for the diagnostics of interplanetary and interstellar turbulent media.
Symmetry fractionalization and twist defects
NASA Astrophysics Data System (ADS)
Tarantino, Nicolas; Lindner, Netanel H.; Fidkowski, Lukasz
2016-03-01
Topological order in two-dimensions can be described in terms of deconfined quasiparticle excitations—anyons—and their braiding statistics. However, it has recently been realized that this data does not completely describe the situation in the presence of an unbroken global symmetry. In this case, there can be multiple distinct quantum phases with the same anyons and statistics, but with different patterns of symmetry fractionalization—termed symmetry enriched topological order. When the global symmetry group G, which we take to be discrete, does not change topological superselection sectors—i.e. does not change one type of anyon into a different type of anyon—one can imagine a local version of the action of G around each anyon. This leads to projective representations and a group cohomology description of symmetry fractionalization, with the second cohomology group {H}2(G,{{ A }}{{abelian}}) being the relevant group. In this paper, we treat the general case of a symmetry group G possibly permuting anyon types. We show that despite the lack of a local action of G, one can still make sense of a so-called twisted group cohomology description of symmetry fractionalization, and show how this data is encoded in the associativity of fusion rules of the extrinsic ‘twist’ defects of the symmetry. Furthermore, building on work of Hermele (2014 Phys. Rev. B 90 184418), we construct a wide class of exactly-solvable models which exhibit this twisted symmetry fractionalization, and connect them to our formal framework.
Electrochemically controlled iron isotope fractionation
NASA Astrophysics Data System (ADS)
Black, Jay R.; Young, Edward D.; Kavner, Abby
2010-02-01
Variations in the stable isotope abundances of transition metals have been observed in the geologic record and trying to understand and reconstruct the physical/environmental conditions that produced these signatures is an area of active research. It is clear that changes in oxidation state lead to large fractionations of the stable isotopes of many transition metals such as iron, suggesting that transition metal stable isotope signatures could be used as a paleo-redox proxy. However, the factors contributing to these observed stable isotope variations are poorly understood. Here we investigate how the kinetics of iron redox electrochemistry generates isotope fractionation. Through a combination of electrodeposition experiments and modeling of electrochemical processes including mass-transport, we show that electron transfer reactions are the cause of a large isotope separation, while mass transport-limited supply of reactant to the electrode attenuates the observed isotopic fractionation. Furthermore, the stable isotope composition of electroplated transition metals can be tuned in the laboratory by controlling parameters such as solution chemistry, reaction overpotential, and solution convection. These methods are potentially useful for generating isotopically-marked metal surfaces for tracking and forensic purposes. In addition, our studies will help interpret stable isotope data in terms of identifying underlying electron transfer processes in laboratory and natural samples.
Haney, J
2015-02-01
The mouse dose at the lowest water concentration used in the National Toxicology Program hexavalent chromium (CrVI) drinking water study (NTP, 2008) is about 74,500 times higher than the approximate human dose corresponding to the 35-city geometric mean reported in EWG (2010) and over 1000 times higher than that based on the highest reported tap water concentration. With experimental and environmental doses differing greatly, it is a regulatory challenge to extrapolate high-dose results to environmental doses orders of magnitude lower in a meaningful and toxicologically predictive manner. This seems particularly true for the low-dose extrapolation of results for oral CrVI-induced carcinogenesis since dose-dependent differences in the dose fraction absorbed by mouse target tissues are apparent (Kirman et al., 2012). These data can be used for a straightforward adjustment of the USEPA (2010) draft oral slope factor (SFo) to be more predictive of risk at environmentally-relevant doses. More specifically, the evaluation of observed and modeled differences in the fraction of dose absorbed by target tissues at the point-of-departure for the draft SFo calculation versus lower doses suggests that the draft SFo be divided by a dose-specific adjustment factor of at least an order of magnitude to be less over-predictive of risk at more environmentally-relevant doses. PMID:25445295
Dose tracking and dose auditing in a comprehensive computed tomography dose-reduction program.
Duong, Phuong-Anh; Little, Brent P
2014-08-01
Implementation of a comprehensive computed tomography (CT) radiation dose-reduction program is a complex undertaking, requiring an assessment of baseline doses, an understanding of dose-saving techniques, and an ongoing appraisal of results. We describe the role of dose tracking in planning and executing a dose-reduction program and discuss the use of the American College of Radiology CT Dose Index Registry at our institution. We review the basics of dose-related CT scan parameters, the components of the dose report, and the dose-reduction techniques, showing how an understanding of each technique is important in effective auditing of "outlier" doses identified by dose tracking. PMID:25129210
Ir-192 HDR transit dose and radial dose function determination using alanine/EPR dosimetry.
Calcina, Carmen S Guzmán; de Almeida, Adelaide; Rocha, José R Oliveira; Abrego, Felipe Chen; Baffa, Oswaldo
2005-03-21
Source positioning close to the tumour in high dose rate (HDR) brachytherapy is not instantaneous. An increment of dose will be delivered during the movement of the source in the trajectory to its static position. This increment is the transit dose, often not taken into account in brachytherapeutic treatment planning. The transit dose depends on the prescribed dose, number of treatment fractions, velocity and activity of the source. Combining all these factors, the transit dose can be 5% higher than the prescribed absorbed dose value (Sang-Hyun and Muller-Runkel, 1994 Phys. Med. Biol. 39 1181-8, Nath et al 1995 Med. Phys. 22 209-34). However, it cannot exceed this percentage (Nath et al 1995). In this work, we use the alanine-EPR (electron paramagnetic resonance) dosimetric system using analysis of the first derivative of the signal. The transit dose was evaluated for an HDR system and is consistent with that already presented for TLD dosimeters (Bastin et al 1993 Int. J. Radiat. Oncol. Biol. Phys. 26 695-702). Also using the same dosimetric system, the radial dose function, used to evaluate the geometric dose degradation around the source, was determined and its behaviour agrees better with those obtained by Monte Carlo simulations (Nath et al 1995, Williamson and Nath 1991 Med. Phys. 18 434-48, Ballester et al 1997 Med. Phys. 24 1221-8, Ballester et al 2001 Phys. Med. Biol. 46 N79-90) than with TLD measurements (Nath et al 1990 Med. Phys. 17 1032-40). PMID:15798311
Ameer, O Z; Salman, I M; Siddiqui, M J A; Yam, M F; Sriramaneni, R N; Sadikun, A; Ismail, Z; Shah, A M; Asmawi, M Z
2010-02-01
We investigated the vascular responses and the blood pressure reducing effects of different fractions obtained from the methanol extract of Loranthus ferrugineus Roxb. (F. Loranthaceae). By means of solvent-solvent extraction, L. ferrugineus methanol extract (LFME) was successively fractionated with chloroform, ethyl acetate and n-butanol. The ability of these LFME fractions to relax vascular smooth muscle against phenylephrine (PE)- and KCl-induced contractions in isolated rat aortic rings was determined. In another set of experiments, LFME fractions were tested for blood pressure lowering activity in anesthetized adult male Sprague-Dawley rats (250-300 g, 14-18 weeks). The n-butanol fraction of LFME (NBF-LFME) produced a significant concentration-dependent inhibition of PE- and KCl-induced aortic ring contractions compared to other fractions. Moreover, NBF-LFME had a significantly higher relaxant effect against PE- than against high K+-induced contractions. In anesthetized Sprague-Dawley rats, NBF-LFME significantly lowered blood pressure in a dose-dependent manner and with a relatively longer duration of action compared to the other fractions. HPLC, UV and IR spectra suggested the presence of terpenoid constituents in both LFME and NBF-LFME. Accordingly, we conclude that NBF-LFME is the most potent fraction producing a concentration-dependent relaxation in vascular smooth muscle in vitro and a dose-dependent blood pressure lowering activity in vivo. The cardiovascular effects of NBF-LFME are most likely attributable to its terpenoid content. PMID:20084331
Fire effects on silica fractionation
NASA Astrophysics Data System (ADS)
Unzué-Belmonte, Dácil; Schaller, Jörg; Vandevenne, Floor; Barao, Lúcia; Struyf, Eric; Meire, Patrick
2015-04-01
Fire events are expected to increase due to climate change, both in number and intensity Effects range from changes in soil biogeochemistry up to the whole ecosystem functioning and morphology. While N, P and C cycling have received quite some attention, little attention was paid to fire effects on the biogeochemical Si cycle and the consequences after a fire event. The Si cycle is a globally important biogeochemical cycle, with strong connections to other biogeochemical cycles, including C. Dissolved silica is taken up by plants to form protective structures called phytoliths, which become a part of the soil and contribute strongly to soil Si cycling upon litter burial. Different silica fractions are found in soils, with phytoliths among the most easily soluble, especially compared to silicate minerals. A whole set of secondary non-biogenic fractions exist, that also have a high reactivity (adsorbed Si, reactive secondary minerals…). Biogenic and other pedogenic secondary Si stocks form an important filter between weathering of mineral silicates and eventual transport of dissolved Si to rivers and the coastal zone. We used a new method to analyze the different reactive fractions of silica in the litter layer of 3 ecosystems after different fire treatments. Using a continuous extraction of Si and Al in 0.5M NaOH at 85°C, biogenic and non-biogenic alkaline reactive Si fractions can be separated based on their Si/Al ratios and their reactivity. We analyzed the silica fractionation after two burning treatments (no heating, 350°C and 550°C) from three types of litter (spruce forest, beech forest and Sphagnum peat). Reactive Si from litter of spruce and beech forest was purely biogenic, based on the observed Si/Al ratio. Beech litter (~2.2 % BSi) had two different biogenic silica pools, one reactive and one more refractory. Spruce litter (~1.5% BSi) showed only one fraction of biogenic Si. There was negligible biogenic Si present in the peat samples (<0.1%). While
Rathi, Anshu; Srivastava, Arvind Kumar; Shirwaikar, Annie; Singh Rawat, Ajay Kumar; Mehrotra, Shanta
2008-06-01
The present investigation demonstrates the hepatoprotective potential of 50% ethanolic water extract of whole plant of Fumaria indica and its three fractions viz., hexane, chloroform and butanol against d-galactosamine induced hepatotoxicity in rats. The hepatoprotection was assessed in terms reduction in histological damage, changes in serum enzymes (SGOT, SGPT, ALP) and metabolites bilirubin, reduced glutathione (GSH) and lipid peroxidation (MDA content). Among fractions more than 90% protection was found with butanol fraction in which alkaloid protopine was quantified as highest i.e. about 0.2mg/g by HPTLC. The isolated protopine in doses of 10-20mg p.o. also proved equally effective hepatoprotectants as standard drug silymarine (single dose 25mg p.o.). In general all treatments excluding hexane fraction proved hepatoprotective at par with silymarine (p
Receptor occupancy and brain free fraction.
Watson, Jeanette; Wright, Sara; Lucas, Adam; Clarke, Kirsten L; Viggers, Jean; Cheetham, Sharon; Jeffrey, Phil; Porter, Rod; Read, Kevin D
2009-04-01
This study was designed to investigate whether brain unbound concentration (C(u,brain)) is a better predictor of dopamine D(2) receptor occupancy than total brain concentration, cerebrospinal fluid concentration (C(CSF)), or blood unbound concentration (C(u,blood)). The ex vivo D(2) receptor occupancy and concentration-time profiles in cerebrospinal fluid, blood, and brain of six marketed antipsychotic drugs were determined after oral administration in rats at a range of dose levels. The C(u,brain) was estimated from the product of total brain concentration and unbound fraction, which was determined using a brain homogenate method. In conclusion, the C(u,brain) of selected antipsychotic agents is a good predictor of D(2) receptor occupancy in rats. Furthermore, C(u,brain) seems to provide a better prediction of D(2) receptor occupancy than C(CSF) or C(u,blood) for those compounds whose mechanism of entry into brain tissue is influenced by factors other than simple passive diffusion. PMID:19158315
Verification of Gamma Knife extend system based fractionated treatment planning using EBT2 film
Natanasabapathi, Gopishankar; Bisht, Raj Kishor
2013-12-15
Purpose: This paper presents EBT2 film verification of fractionated treatment planning with the Gamma Knife (GK) extend system, a relocatable frame system for multiple-fraction or serial multiple-session radiosurgery.Methods: A human head shaped phantom simulated the verification process for fractionated Gamma Knife treatment. Phantom preparation for Extend Frame based treatment planning involved creating a dental impression, fitting the phantom to the frame system, and acquiring a stereotactic computed tomography (CT) scan. A CT scan (Siemens, Emotion 6) of the phantom was obtained with following parameters: Tube voltage—110 kV, tube current—280 mA, pixel size—0.5 × 0.5 and 1 mm slice thickness. A treatment plan with two 8 mm collimator shots and three sectors blocking in each shot was made. Dose prescription of 4 Gy at 100% was delivered for the first fraction out of the two fractions planned. Gafchromic EBT2 film (ISP Wayne, NJ) was used as 2D verification dosimeter in this process. Films were cut and placed inside the film insert of the phantom for treatment dose delivery. Meanwhile a set of films from the same batch were exposed from 0 to 12 Gy doses for calibration purposes. An EPSON (Expression 10000 XL) scanner was used for scanning the exposed films in transparency mode. Scanned films were analyzed with inhouse written MATLAB codes.Results: Gamma index analysis of film measurement in comparison with TPS calculated dose resulted in high pass rates >90% for tolerance criteria of 1%/1 mm. The isodose overlay and linear dose profiles of film measured and computed dose distribution on sagittal and coronal plane were in close agreement.Conclusions: Through this study, the authors propose treatment verification QA method for Extend frame based fractionated Gamma Knife radiosurgery using EBT2 film.
Identification and characterization of specific hydatid antigen fraction(s).
Maher, K M; Kaddah, M A; Hassanein, H I; Shaker, Z A; Khalafallah, A M
1992-08-01
A specific hydatid antigen was prepared in this study from Echinococcus granulosus cyst in livers and lungs of camels. Elimination of host "camel" protein from crude hydatid fluid was achieved by two methods: Salting out using ammonium sulfate precipitation method and immunoaffinity purification using coupled anticamel antibody to cyanogenbromide activated sepharose 4B gel. Testing the prepared hydatid antigen against anticamel serum, using immunodiffusion method, indicated that the affinity purified hydatid antigen was almost completely purified from camel protein. Characterization of the affinity purified hydatid antigen, using immunoelectrophoresis, showed positive arc 5 precipitation when tested against known positive antihydatid sera. Further characterization with gradient gel electrophoresis, showed with silver stain that the dominant and most consistently demonstrable proteins occurred as a complex in the 52/62 KDa region. Strong reaction with the 52/62 KDa complex was consistently observed when the affinity purified hydatid antigen was probed with known positive reference antihydatid sera. The identified hydatid antigen fraction(s) with 52/62 KDa complex can provide promising non-invasive parameter for diagnosis of Hydatidosis. PMID:1500792
Theory of fractional-ordered thermoelastic diffusion
NASA Astrophysics Data System (ADS)
Shaw, Soumen; Mukhopadhyay, Basudeb
2016-06-01
In this note, the traditional theory of thermoelastic diffusion is replaced by fractional ordered thermoelasticity based on fractional conservation of mass, fractional Taylor series and fractional divergence theorem. We replace the integer-order Taylor series approximation for flux with the fractional-order Taylor series approximation which can remove the restriction that the flux has to be linear, or piece-wise linear and the restriction that the control volume must be infinitesimal. There are two important distinctions between the traditional thermoelastic diffusion, and its fractional equivalent. The first is that the divergence term in the heat conduction and mass diffusion equations are the fractional divergence, and the second is the appearance of strain tensor term in the fractional equation is in the form of "incomplete fractional-strain measures".
Adaptive Dose Painting by Numbers for Head-and-Neck Cancer
Duprez, Frederic; De Neve, Wilfried; De Gersem, Werner; Coghe, Marc; Madani, Indira
2011-07-15
Purpose: To investigate the feasibility of adaptive intensity-modulated radiation therapy (IMRT) using dose painting by numbers (DPBN) for head-and-neck cancer. Methods and Materials: Each patient's treatment used three separate treatment plans: fractions 1-10 used a DPBN ([{sup 18}-F]fluoro-2-deoxy-D-glucose positron emission tomography [{sup 18}F-FDG-PET]) voxel intensity-based IMRT plan based on a pretreatment {sup 18}F-FDG-PET/computed tomography (CT) scan; fractions 11-20 used a DPBN plan based on a {sup 18}F-FDG-PET/CT scan acquired after the eighth fraction; and fractions 21-32 used a conventional (uniform dose) IMRT plan. In a Phase I trial, two dose prescription levels were tested: a median dose of 80.9 Gy to the high-dose clinical target volume (CTV{sub highdose}) (dose level I) and a median dose of 85.9 Gy to the gross tumor volume (GTV) (dose level II). Between February 2007 and August 2009, 7 patients at dose level I and 14 patients at dose level II were enrolled. Results: All patients finished treatment without a break, and no Grade 4 acute toxicity was observed. Treatment adaptation (i.e., plans based on the second {sup 18}F-FDG-PET/CT scan) reduced the volumes for the GTV (41%, p = 0.01), CTV{sub highdose} (18%, p = 0.01), high-dose planning target volume (14%, p = 0.02), and parotids (9-12%, p < 0.05). Because the GTV was much smaller than the CTV{sub highdose} and target adaptation, further dose escalation at dose level II resulted in less severe toxicity than that observed at dose level I. Conclusion: To our knowledge, this represents the first clinical study that combines adaptive treatments with dose painting by numbers. Treatment as described above is feasible.
SU-E-J-105: Stromal-Epithelial Responses to Fractionated Radiotherapy
Qayyum, M
2014-06-01
Purpose: The stromal-epithelial-cell interactions that are responsible for directing normal breast-tissue development and maintenance play a central role in the progression of breast cancer. In the present study, we developed three-dimensional (3-D) cell co-cultures used to study cancerous mammary cell responses to fractionated radiotherapy. In particular, we focused on the role of the reactive stroma in determining the therapeutic ratio for postsurgical treatment. Methods: Cancerous human mammary epithelial cells were cultured in a 3-D collagen matrix with human fibroblasts stimulated by various concentrations of transforming growth factor beta 1 (TGF-β1). These culture samples were designed to model the post-lumpectomy mammary stroma in the presence of residual cancer cells. We tracked over time the changes in medium stiffness, fibroblast-cell activation (conversion to cancer activated fibroblasts (CAF)), and proliferation of both cell types under a variety of fractionated radiotherapy protocols. Samples were exposed to 6 MV X-rays from a linear accelerator in daily fraction sizes of 90, 180 and 360 cGy over five days in a manner consistent with irradiation exposure during radiotherapy. Results: We found in fractionation studies with fibroblasts and CAF that higher doses per fraction may be more effective early on in deactivating cancer-harboring cellular environments. Higher-dose fraction schemes inhibit contractility in CAF and prevent differentiation of fibroblasts, thereby metabolically uncoupling tumor cells from their surrounding stroma. Yet, over a longer time period, the higher dose fractions may slow wound healing and increase ECM stiffening that could stimulate proliferation of surviving cancer cells. Conclusion: The findings suggest that dose escalation to the region with residual disease can deactivate the reactive stroma, thus minimizing the cancer promoting features of the cellular environment. Large-fraction irradiation may be used to sterilize
Long-Term Results and Prognostic Factors of Fractionated Strontium-90 Eye Applicator for Pterygium
Arruda Viani, Gustavo Stefano, Eduardo Jose; Fendi, Ligia Issa de; Carrara Fonseca, Ellen
2008-11-15
Purpose: To evaluate the long-term safety, effectiveness, and prognostic factors of fractionated postoperative {beta}-irradiation. Methods and Materials: Between 1993 and 2005, 623 patients with 737 pterygium lesions were treated with a strontium-90 eye applicator after surgical excision. The median follow-up period was 60 months (range, 6.7-139.5). Of the 737 lesions, 644 were primary and 93 were recurrences after surgical removal alone. Fractionated radiotherapy (RT) to a total dose of 35 Gy in five to seven fractions was used. Results: A total of 73 local pterygium recurrences (9.9%) were noted. Of the recurrent cases, 80% were noted within 3 years after treatment. The 5- and 10-year probability of local control was 90% and 88%, respectively. The multivariate analysis for all cases demonstrated that gender, age, total radiation dose, recurrent pterygia, and interval between surgery and RT affected the overall local control rate. Late toxicities that might have been associated with strontium-90 RT included scleromalacia (scleral thinning) in nine eyes, adhesion of the eyelids in eight, cataracts in six, and scleral ulcer in five eyes. Conclusion: Fractionated strontium-90 RT to a total dose of approximately 35 Gy in five to seven fractions results in a similar local control rate as higher doses in other series, with an acceptable complication rate.
Intensity Modulated Radiation Therapy With Dose Painting to Treat Rhabdomyosarcoma
Yang, Joanna C.; Dharmarajan, Kavita V.; Wexler, Leonard H.; La Quaglia, Michael P.; Happersett, Laura; Wolden, Suzanne L.
2012-11-01
Purpose: To examine local control and patterns of failure in rhabdomyosarcoma patients treated with intensity modulated radiation therapy (RT) with dose painting (DP-IMRT). Patients and Methods: A total of 41 patients underwent DP-IMRT with chemotherapy for definitive treatment. Nineteen also underwent surgery with or without intraoperative RT. Fifty-six percent had alveolar histologic features. The median interval from beginning chemotherapy to RT was 17 weeks (range, 4-25). Very young children who underwent second-look procedures with or without intraoperative RT received reduced doses of 24-36 Gy in 1.4-1.8-Gy fractions. Young adults received 50.4 Gy to the primary tumor and lower doses of 36 Gy in 1.8-Gy fractions to at-risk lymph node chains. Results: With 22 months of median follow-up, the actuarial local control rate was 90%. Patients aged {<=}7 years who received reduced overall and fractional doses had 100% local control, and young adults had 79% (P=.07) local control. Three local failures were identified in young adults whose primary target volumes had received 50.4 Gy in 1.8-Gy fractions. Conclusions: DP-IMRT with lower fractional and cumulative doses is feasible for very young children after second-look procedures with or without intraoperative RT. DP-IMRT is also feasible in adolescents and young adults with aggressive disease who would benefit from prophylactic RT to high-risk lymph node chains, although dose escalation might be warranted for improved local control. With limited follow-up, it appears that DP-IMRT produces local control rates comparable to those of sequential IMRT in patients with rhabdomyosarcoma.
Radiotherapy with thrice-a-day fractionation in a short overall time: clinical experiences
Peracchia, G.; Salti, C.
1981-01-01
Forty-seven patients with head and neck cancer were treated with thrice-a-day fractionation (200 rad Co/sup 60/ three times per day, 5 days per week) to a total tumor dose of 4800 to 5400 rad over 9 to 11 days. Of this group, 22 advanced oral and pharyngo-laryngeal cancer patients had a 24-month follow-up. While early tolerance and skin reaction were quite acceptable, the rate of serious mucosal radionecrosis was high (55%) and 2-year survival was poor (14%). Less advantage was found over conventional fractionation; the probable causes, i.e., single dose size and irradiation volume dimension, are discussed.
Paithankar, Karthik S.; Garman, Elspeth F.
2010-01-01
The program RADDOSE is widely used to compute the dose absorbed by a macromolecular crystal during an X-ray diffraction experiment. A number of factors affect the absorbed dose, including the incident X-ray flux density, the photon energy and the composition of the macromolecule and of the buffer in the crystal. An experimental dose limit for macromolecular crystallography (MX) of 30 MGy at 100 K has been reported, beyond which the biological information obtained may be compromised. Thus, for the planning of an optimized diffraction experiment the estimation of dose has become an additional tool. A number of approximations were made in the original version of RADDOSE. Recently, the code has been modified in order to take into account fluorescent X-ray escape from the crystal (version 2) and the inclusion of incoherent (Compton) scattering into the dose calculation is now reported (version 3). The Compton cross-section, although negligible at the energies currently commonly used in MX, should be considered in dose calculations for incident energies above 20 keV. Calculations using version 3 of RADDOSE reinforce previous studies that predict a reduction in the absorbed dose when data are collected at higher energies compared with data collected at 12.4 keV. Hence, a longer irradiation lifetime for the sample can be achieved at these higher energies but this is at the cost of lower diffraction intensities. The parameter ‘diffraction-dose efficiency’, which is the diffracted intensity per absorbed dose, is revisited in an attempt to investigate the benefits and pitfalls of data collection using higher and lower energy radiation, particularly for thin crystals. PMID:20382991
Stromal-epithelial dynamics in response to fractionated radiotherapy
NASA Astrophysics Data System (ADS)
Qayyum, Muqeem Abdul
Radiotherapy is central to the management of a number of human cancers, either as an adjuvant or primary treatment modality. The principal objective in irradiating tumors is to permanently inhibit their proliferative ability. More than half of all malignancies are primarily treated with radiation, but the heterotypic nature of tumor cells greatly complicates their response to radiotherapy. The need for reliable parameters to predict tumor and normal tissue response to radiation is therefore a prime concern of clinical oncology. Post-operative radiotherapy has commonly been used for early stage breast cancer to treat residual disease. There is continued debate as to what might be the proper dose per fraction as well as the total dose of radiation that needs to be prescribed to prevent disease recurrence. Countries outside the US have adopted increased dose fractionation (i.e., hypofractionation) schemes for early stage breast cancer as a standard of practice; however there is a lack of confidence in these approaches in the United States. The tumor microenvironment plays a significant role in regulating the progression of carcinomas, although the mechanisms are not entirely clear. The primary objective of this work was to characterize, through mechanobiological and radiobiological modeling, a test bed for radiotherapy fractionation techniques assessment. Our goal is to understand how the tumor microenvironment responds to dose fractionation schemes for Breast Conserving Therapy (BCT). Although carcinomas are the major concern for oncology, in this project, the goal is to understand how the stromal microenvironment influences behavior of the cancer cell populations. By classifying 3-D cellular co-cultures as having a reactive or quiescent stroma using the mechanobiology profile (culture stiffness,cellular activation, differentiation, and proliferation) we aim to differentiate the effectiveness of various fractionation schemes. The benefits of understanding heterotypic
An experimental investigation on intra-fractional organ motion effects in lung IMRT treatments
NASA Astrophysics Data System (ADS)
Jiang, Steve B.; Pope, Cynthia; Jarrah, Khaled M. Al; Kung, Jong H.; Bortfeld, Thomas; Chen, George T. Y.
2003-06-01
Respiration-induced tumour motion can potentially compromise the use of intensity-modulated radiotherapy (IMRT) as a dose escalation tool for lung tumour treatment. We have experimentally investigated the intra-fractional organ motion effects in lung IMRT treatments delivered by multi-leaf collimator (MLC). An in-house made motor-driven platform, which moves sinusoidally with an amplitude of 1 cm and a period of 4 s, was used to mimic tumour motion. Tumour motion was simulated along cranial-caudal direction while MLC leaves moved across the patient from left to right, as in most clinical cases. The dose to a point near the centre of the tumour mass was measured according to geometric and dosimetric parameters from two five-field lung IMRT plans. For each field, measurement was done for two dose rates (300 and 500 MU min-1), three MLC delivery modes (sliding window, step-and-shoot with 10 and 20 intensity levels) and eight equally spaced starting phases of tumour motion. The dose to the measurement point delivered from all five fields was derived for both a single fraction and 30 fractions by randomly sampling from measured dose values of each field at different initial phases. It was found that the mean dose to a moving tumour differs slightly (<2-3%) from that to a static tumour. The variation in breathing phase at the start of dose delivery results in a maximum variation around the mean dose of greater than 30% for one field. The full width at half maximum for the probability distribution of the point dose is up to 8% for all five fields in a single fraction, but less than 1-2% after 30 fractions. In general, lower dose rate can reduce the motion-caused dose variation and therefore might be preferable for lung IMRT when no motion mitigation techniques are used. From the two IMRT cases we studied where tumour motion is perpendicular to MLC leaf motion, the dose variation was found to be insensitive to the MLC delivery mode.
An experimental investigation on intra-fractional organ motion effects in lung IMRT treatments.
Jiang, Steve B; Pope, Cynthia; Al Jarrah, Khaled M; Kung, Jong H; Bortfeld, Thomas; Chen, George T Y
2003-06-21
Respiration-induced tumour motion can potentially compromise the use of intensity-modulated radiotherapy (IMRT) as a dose escalation tool for lung tumour treatment. We have experimentally investigated the intra-fractional organ motion effects in lung IMRT treatments delivered by multi-leaf collimator (MLC). An in-house made motor-driven platform, which moves sinusoidally with an amplitude of 1 cm and a period of 4 s, was used to mimic tumour motion. Tumour motion was simulated along cranial-caudal direction while MLC leaves moved across the patient from left to right, as in most clinical cases. The dose to a point near the centre of the tumour mass was measured according to geometric and dosimetric parameters from two five-field lung IMRT plans. For each field, measurement was done for two dose rates (300 and 500 MU min(-1)), three MLC delivery modes (sliding window, step-and-shoot with 10 and 20 intensity levels) and eight equally spaced starting phases of tumour motion. The dose to the measurement point delivered from all five fields was derived for both a single fraction and 30 fractions by randomly sampling from measured dose values of each field at different initial phases. It was found that the mean dose to a moving tumour differs slightly (<2-3%) from that to a static tumour. The variation in breathing phase at the start of dose delivery results in a maximum variation around the mean dose of greater than 30% for one field. The full width at half maximum for the probability distribution of the point dose is up to 8% for all five fields in a single fraction, but less than 1-2% after 30 fractions. In general, lower dose rate can reduce the motion-caused dose variation and therefore might be preferable for lung IMRT when no motion mitigation techniques are used. From the two IMRT cases we studied where tumour motion is perpendicular to MLC leaf motion, the dose variation was found to be insensitive to the MLC delivery mode. PMID:12870582
Modeling equilibrium Fe isotope fractionation
NASA Astrophysics Data System (ADS)
Anbar, A.; Jarzecki, A.; Spiro, T.
2003-04-01
Research into the stable isotope biogeochemistry of Fe and other transition metals has been driven primarily by analytical innovations which have revealed significant isotope effects in nature and the laboratory. Further development of these new isotope systems requires complementary theoretical research to guide analytical efforts. The results of the first such studies show some discrepancies with experiments. For example, Johnson et al. (2002) report an experimentally-determined 56Fe/54Fe equilibrium fractionation factor between Fe(II) and Fe(III) aquo complexes of ˜1.0025. This effect is ˜50% smaller than predicted theoretically by Schauble et al. (2001). It is important to resolve such discrepancies. Equilibrium isotope fractionation factors can be predicted from vibrational spectroscopic data of isotopically-substituted complexes, or from theoretical predictions of some or all of these frequencies obtained using force field models. The pioneering work of Schauble et al. (2001) utilized a modified Urey-Bradley force field (MUBFF) model. This approach is limiting in at least three ways: First, it is not ab initio, requiring as input some measured vibrational frequencies. Such data are not always available, or may have significant uncertainties. Second, the MUBFF does not include potentially important effects of solvent interaction. Third, because it makes certain assumptions about molecular symmetry, the MUBFF-based approach is not able to model the spectra of mixed-ligand complexes. To address these limitations, we are evaluating the use of density functional theory (DFT) as an ab initio method to predict vibrational frequencies of isotopically-substituted complexes and, hence, equilibrium fractionation factors. In a preliminary examination of the frequency shift upon isotope substitution of the bending and asymmetric stretching modes of the tetrahedral FeCl_42- complex, we find substantial differences between MUBFF and DFT predictions. Results for other Fe
FRACTIONATING COLUMN PRODUCT COLLECTOR CONTROL
Paxson, G.D. Jr.
1964-03-10
Means for detecting minute fluid products from a chemical separation column and for advancing a collector tube rack in order to automatically separate and collect successive fractionated products are described. A charge is imposed on the forming drops at the column orifice to create an electric field as the drop falls in the vicinity of a sensing plate. The field is detected by an electrometer tube coupled to the plate causing an output signal to actuate rotation of a collector turntable rack, thereby positioning new collectors under the orifice. The invention provides reliable automatic collection independent of drop size, rate of fall, or chemical composition. (AEC)
Conformable Fractional Nikiforov—Uvarov Method
NASA Astrophysics Data System (ADS)
Karayer, H.; Demirhan, D.; Büyükkılıç, F.
2016-07-01
We introduce conformable fractional Nikiforov—Uvarov (NU) method by means of conformable fractional derivative which is the most natural definition in non-integer calculus. Since, NU method gives exact eigenstate solutions of Schrödinger equation (SE) for certain potentials in quantum mechanics, this method is carried into the domain of fractional calculus to obtain the solutions of fractional SE. In order to demonstrate the applicability of the conformable fractional NU method, we solve fractional SE for harmonic oscillator potential, Woods—Saxon potential, and Hulthen potential.
Contralateral breast dose from partial breast brachytherapy.
Robinson, R Cole; Nelson, Christopher L; Bloom, Elizabeth S; Kisling, Kelly D; Mason, Bryan E; Fisher, Gary D; Kirsner, Steven M
2015-01-01
The purpose of this study was to determine the dose to the contralateral breast during accelerated partial breast irradiation (APBI) and to compare it to external beam-published values. Thermoluminescent dosimeter (TLD) packets were used to measure the dose to the most medial aspect of the contralateral breast during APBI simulation, daily quality assurance (QA), and treatment. All patients in this study were treated with a single-entry, multicatheter device for 10 fractions to a total dose of 34 Gy. A mark was placed on the patient's skin on the medial aspect of the opposite breast. Three TLD packets were taped to this mark during the pretreatment simulation. Simulations consisted of an AP and Lateral scout and a limited axial scan encompassing the lumpectomy cavity (miniscan), if rotation was a concern. After the simulation the TLD packets were removed and the patients were moved to the high-dose-rate (HDR) vault where three new TLD packets were taped onto the patients at the skin mark. Treatment was administered with a Nucletron HDR afterloader using Iridium-192 as the treatment source. Post-treatment, TLDs were read (along with the simulation and QA TLD and a set of standards exposed to a known dose of 6 MV photons). Measurements indicate an average total dose to the contralateral breast of 70 cGy for outer quadrant implants and 181 cGy for inner quadrant implants. Compared to external beam breast tangents, these results point to less dose being delivered to the contralateral breast when using APBI. PMID:26699549
ICRP dose coefficients: computational development and current status.
Bolch, W E; Petoussi-Henss, N; Paquet, F; Harrison, J
2016-06-01
Major current efforts within Committee 2 of the International Commission on Radiological Protection (ICRP) involve the development of dose coefficients for inhalation and ingestion of radionuclides, and those for exposure to environmental radiation fields. These efforts build upon changes in radiation and tissue weighting factors (Publication 103), radionuclide decay schemes (Publication 107), computational phantoms of the adult reference male and female (Publication 110), external dose coefficients for adult reference workers for idealised radiation fields (Publication 116), models of radionuclide intake (Publications 66, 100 and 130), and models of radionuclide systemic biokinetics (Publication 130). This paper will review the overall computational framework for both internal and external dose coefficients. For internal exposures, the work entails assessment of organ self-dose and cross-dose from monoenergetic particle emissions (specific absorbed fraction), absorbed dose per nuclear transformation (S value), time-integrated activity of the radionuclide in source tissues (inhalation, ingestion, and systemic biokinetic models), and their numerical combination to yield the organ equivalent dose or effective dose per activity inhaled or ingested. Various challenges are reviewed that were not included in the development of Publication 30 dose coefficients, which were based upon much more simplified biokinetic models and computational phantoms. For external exposures, the computations entail the characterisation of environmental radionuclide distributions, the transport of radiation particles through that environment, and the tracking of energy deposition to the organs of the exposed individual. Progress towards the development of dose coefficients to members of the general public (adolescents, children, infants and fetuses) are also reviewed. PMID:27048756
Clinically Relevant Doses of Enalapril Mitigate Multiple Organ Radiation Injury.
Cohen, Eric P; Fish, Brian L; Moulder, John E
2016-03-01
Angiotensin-converting enzyme inhibitors (ACEi) are effective mitigators of radiation nephropathy. To date, their experimental use has been in fixed-dose regimens. In clinical use, doses of ACEi and other medication may be escalated to achieve greater benefit. We therefore used a rodent model to test the ACEi enalapril as a mitigator of radiation injury in an escalating-dose regimen. Single-fraction partial-body irradiation (PBI) with one hind limb out of the radiation field was used to model accidental or belligerent radiation exposures. PBI doses of 12.5, 12.75 and 13 Gy were used to establish multi-organ injury. One third of the rats underwent PBI alone, and two thirds of the rats had enalapril started five days after PBI at a dose of 30 mg/l in the drinking water. When there was established azotemic renal injury enalapril was escalated to a 60 mg/l dose in half of the animals and then later to a 120 mg/l dose. Irradiated rats on enalapril had significant mitigation of combined pulmonary and renal morbidity and had significantly less azotemia. Dose escalation of enalapril did not significantly improve outcomes compared to fixed-dose enalapril. The current data support use of the ACEi enalapril at a fixed and clinically usable dose to mitigate radiation injury after partial-body radiation exposure. PMID:26934483
Comparison of measured and computed portal dose for IMRT treatment.
Cilla, Savino; Viola, Pietro; Azario, Luigi; Grimaldi, Luca; Craus, Maurizio; D'Onofrio, Guido; Fidanzio, Andrea; Morganti, Alessio Giuseppe; Piermattei, Angelo
2006-01-01
A new 2D array Seven 29T model (PTW, Freiburg), equipped with 729 vented plane-parallel ion chambers, projected for pretreatment verification of radiotherapy plans, was used as a detector for the transmitted or portal dose measurements below a Rando phantom. The dosimetric qualities of the 2D array make it attractive for measuring transmitted dose maps from step-and-shoot intensity-modulated radiotherapy (IMRT). It is well known that for step-and-shoot IMRT beams that use a small number of monitor units (MUs) per sequence, the early and recent electronic portal imaging devices (EPIDs) present a different response at X-ray start-up that affects the accuracy of the measured transmitted dose. The comparison of portal doses measured to those calculated by a commercial treatment-planning system (TPS) can verify correct dose delivery during treatment. This direct validation was tested by irradiating a simulated head tumor in a Rando anthropomorphic phantom by step-and-shoot IMRT beams. The absolute transmitted doses on a plane orthogonal to the beam central axis below the phantom were measured by the 2D array calibrated in terms of dose to water and compared with the computed portal dose extracted by custom software. In a previous paper, the comparison between the IMRT portal doses, computed by a commercial TPS and measured by a linear array that supplied a 1 mm spatial dose resolution, was carried out. The gamma-index analysis supplied an agreement of more than 95% of the dose point with acceptance criteria, in terms of dose difference, DeltaDmax, and distance agreement, deltadmax, equal to 4% and 4 mm, respectively. In this paper, we verify the possible use of the PTW 2D array for measurements of the transmitted doses during several fractions of head and neck tumor radiotherapy. There are two advantages in the use of this 2D array as a portal dose device for the IMRT quality assurance program: first is the ability to perform absolute dose comparisons for hundreds of
Palorini, F; Botti, A; Carillo, V; Gianolini, S; Improta, I; Iotti, C; Rancati, T; Cozzarini, C; Fiorino, C
2016-03-01
The purpose of this study was to quantify the impact of inter-fraction modifications of bladder during RT of prostate cancer on bladder dose surface maps (DSM). Eighteen patients treated with daily image-guided Tomotherapy and moderate hypofractionation (70-72.8Gy at 2.5-2.6Gy/fr in 28 fractions and full bladder) were considered. Bladder contours were delineated on co-registered daily Megavoltage CT (MVCT) by a single observer and copied on the planning CT to generate dose-volume/surface histograms (DVH/DSH) and bladder DSMs. Discrepancies between planned and daily absorbed doses were analyzed through the average of individual systematic errors, the population systematic errors and the population random errors for the DVH/DSHs and DSMs. In total, 477 DVH/DSH and 472 DSM were available. DSH and DVH showed small population systematic errors of absolute surfaces (<3.4cm(2)) and volumes (<8.4cm(3)) at the highest doses. The dose to the posterior bladder base assessed on DSMs showed a mean systematic error below 1Gy, with population systematic and random errors within 4 and 3Gy, respectively. The region surrounding this area shows higher mean systematic errors (1-3Gy), population systematic (8-11Gy) and random (5-7Gy) errors. In conclusion, DVH/DSH and DSMs are quite stable with respect to inter-fraction variations in the high-dose region, within about 2cm from bladder base. Larger systematic variations occur in the anterior portion and cranially 2.5-3.5cm from the base. Results suggest that dose predictors related to the high dose area (including the trigone dose) are likely to be sufficiently reliable with respect to the expected variations due to variable bladder filling. PMID:27053449
Acetaminophen dosing for children
Taking acetaminophen (Tylenol) can help children with colds and fever feel better. As with all drugs, it is important to give children the correct dose. Acetaminophen is safe when taken as directed. But taking ...
2016-09-01
Numeracy and calculation are key skills for nurses. As nurses are directly accountable for ensuring medicines are prescribed, dispensed and administered safely, they must be able to understand and calculate drug doses. PMID:27615351
Dean flow fractionation of chromosomes
NASA Astrophysics Data System (ADS)
Hockin, Matt; Sant, Himanshu J.; Capecchi, Mario; Gale, Bruce K.
2016-03-01
Efforts to transfer intact mammalian chromosomes between cells have been attempted for more than 50 years with the consistent result being transfer of sub unit length pieces regardless of method. Inertial microfluidics is a new field that has shown much promise in addressing the fractionation of particles in the 2-20 μm size range (with unknown limits) and separations are based upon particles being carried by curving confined flows (within a spiral shaped, often rectangular flow chamber) and migrating to stable "equilibrium" positions of varying distance from a chamber wall depending on the balance of dean and lift forces. We fabricated spiral channels for inertial microfluidic separations using a standard soft lithography process. The concentration of chromosomes, small contaminant DNA and large cell debris in each outlets were evaluated using microscope (60X) and a flow cytometer. Using Dean Flow Fractionation, we were able to focus 4.5 times more chromosomes in outlet 2 compared to outlet 4 where most of the large debris is found. We recover 16% of the chromosomes in outlet #1- 50% in 2, 23% in 3 and 11% in 4. It should be noted that these estimates of recovery do not capture one piece of information- it actually may be that the chromosomes at each outlet are physically different and work needs to be done to verify this potential.
NASA Astrophysics Data System (ADS)
Blockhuys, S; Vanhoecke, B; Paelinck, L; Bracke, M; DeWagter, C
2009-03-01
We present different in vitro experimental models which allow us to evaluate the effect of spatially fractionated dose distributions on metabolic activity. We irradiated a monolayer of MCF-7/6 human breast cancer cells with a steep and a smooth 6 MV x-ray dose gradient. In the steep gradient model, we irradiated the cells with three separate small fields. We also developed two smooth gradient models. In the first model, the cells are cultured in a T25 flask and irradiated with a smooth dose gradient over the length of the flask, while in the second one, the cells are cultured in a 96-well plate and also irradiated over the length of the plate. In an attempt to correlate the spatially fractionated dose distributions with metabolic activity, the effect of irradiation was evaluated by means of the MTT assay. This assay is used to determine the metabolic activity by measuring the amount of formazan formed after the conversion of MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) by cellular dehydrogenases. The results obtained with our different models suggest a dose-specific effect on metabolic activity, characterized by an increased formazan optical density occurring in the dose range 1.0-4.0 Gy in the steep dose gradient model and in the dose ranges 4.2-6.5 Gy and 2.3-5.1 Gy in the two smooth dose gradient models. The corresponding times for maximal formazan accumulation were 5-7 days in the steep dose gradient model and day 9-13 and day 9-11 in the smooth dose gradient models. Altogether, our results suggest that the MTT assay may be used as a biological dose-response meter to monitor the radiotherapeutic effectiveness.
[FRACTIONATED STEREOTACTIC RADIOSURGERY: A GAME CHANGER FOR NEUROSURGERY].
Nissim, Ouzi; Spiegelmann, Roberto
2016-05-01
The article by Dr. Cohen-Inbar published in this issue of Harefuah is a timely review that brings to the general medical community the recent important developments in the field of radiosurgery--the evolution of multi-session radiosurgery [or "FSR", standing for Fractionated Stereotactic Radiation]. Radiosurgery and FSR continue to have a tremendous impact on modern neurosurgery. Sharing sub-millimetric accuracy in radiation delivery made possible by real-time-imaging positioning, frameless single and multisession radiosurgery have become two faces of a therapeutic technique with wide application in the field of intracranial pathology. Blending dose fractionation with delivery precision, FSR is a hybrid tool that can be implemented safely and effectively for practically any intra-cranial pathology without restrictions of volume or location. Dr. Cohen Inbar reviews the available data regarding doses, fractionation schemes, and results for the different pathologies in which FSR is being increasingly applied. FSR, as single-dose radiosurgery since the late 1980s, has changed the practice of neurosurgery. Radical microsorgical tumor removal at any cost in demanding intracranial locations has been replaced by upfront conservative volume-reduction surgery, leaving the more complicated part of those tumors to safer elimination by precise irradiation in single or multiple sessions. In Israel, further to the first unit operative since 1993 at the Sheba Medical Center, 3 new active LINAC based treatment sites have been added in recent years, with facilities either planned or under construction in the remaining major medical centers with neurosurgical and radiotherapy resources. They are evidence of the central role this modality has captured in the management of intracranial pathology. PMID:27526561
Guerrero, Mariana; Carlone, Marco
2010-08-15
Purpose: In recent years, several models were proposed that modify the standard linear-quadratic (LQ) model to make the predicted survival curve linear at high doses. Most of these models are purely phenomenological and can only be applied in the particular case of acute doses per fraction. The authors consider a mechanistic formulation of a linear-quadratic-linear (LQL) model in the case of split-dose experiments and exponentially decaying sources. This model provides a comprehensive description of radiation response for arbitrary dose rate and fractionation with only one additional parameter. Methods: The authors use a compartmental formulation of the LQL model from the literature. They analytically solve the model's differential equations for the case of a split-dose experiment and for an exponentially decaying source. They compare the solutions of the survival fraction with the standard LQ equations and with the lethal-potentially lethal (LPL) model. Results: In the case of the split-dose experiment, the LQL model predicts a recovery ratio as a function of dose per fraction that deviates from the square law of the standard LQ. The survival fraction as a function of time between fractions follows a similar exponential law as the LQ but adds a multiplicative factor to the LQ parameter {beta}. The LQL solution for the split-dose experiment is very close to the LPL prediction. For the decaying source, the differences between the LQL and the LQ solutions are negligible when the half-life of the source is much larger than the characteristic repair time, which is the clinically relevant case. Conclusions: The compartmental formulation of the LQL model can be used for arbitrary dose rates and provides a comprehensive description of dose response. When the survival fraction for acute doses is linear for high dose, a deviation of the square law formula of the recovery ratio for split doses is also predicted.
NASA Technical Reports Server (NTRS)
Brenner, D. J.; Hall, E. J.
1992-01-01
There is now a substantial body of evidence for end points such as oncogenic transformation in vitro, and carcinogenesis and life shortening in vivo, suggesting that dose protraction leads to an increase in effectiveness relative to a single, acute exposure--at least for radiations of medium linear energy transfer (LET) such as neutrons. Table I contains a summary of the pertinent data from studies in which the effect is seen. [table: see text] This phenomenon has come to be known as the "inverse dose rate effect," because it is in marked contrast to the situation at low LET, where protraction in delivery of a dose of radiation, either by fractionation or low dose rate, results in a decreased biological effect; additionally, at medium and high LET, for radiobiological end points such as clonogenic survival, the biological effectiveness is independent of protraction. The quantity and quality of the published reports on the "inverse dose rate effect" leaves little doubt that the effect is real, but the available evidence indicates that the magnitude of the effect is due to a complex interplay between dose, dose rate, and radiation quality. Here, we first summarize the available data on the inverse dose rate effect and suggest that it follows a consistent pattern in regard to dose, dose rate, and radiation quality; second, we describe a model that predicts these features; and, finally, we describe the significance of the effect for radiation protection.
Fractionated Stereotactic Gamma Knife Radiosurgery for Medial Temporal Lobe Epilepsy: A Case Report.
Park, Hye Ran; Chung, Hyun-Tai; Lee, Sang Kun; Kim, Dong Gyu; Paek, Sun Ha
2016-04-01
An 18-year-old left-handed male harbored intractable medial temporal lobe epilepsy (MTLE) underwent fractionated gamma knife surgery (GKS) instead of open surgery, considering the mental retardation and diffuse cerebral dysfunction. GKS treatment parameters were: target volume, 8.8 cm(3); total marginal dose, 24 Gy in 3 fractionations at the 50% isodose line. The patient has been free from seizures since 9 months after GKS, with notable improvement in cognitive outcome. Fractionated GKS could be considered as a safe tool for seizure control and neuropsychological improvement in patients with MTLE. PMID:27122996
Fractionated Stereotactic Gamma Knife Radiosurgery for Medial Temporal Lobe Epilepsy: A Case Report
Park, Hye Ran; Chung, Hyun-Tai; Lee, Sang Kun; Kim, Dong Gyu
2016-01-01
An 18-year-old left-handed male harbored intractable medial temporal lobe epilepsy (MTLE) underwent fractionated gamma knife surgery (GKS) instead of open surgery, considering the mental retardation and diffuse cerebral dysfunction. GKS treatment parameters were: target volume, 8.8 cm3; total marginal dose, 24 Gy in 3 fractionations at the 50% isodose line. The patient has been free from seizures since 9 months after GKS, with notable improvement in cognitive outcome. Fractionated GKS could be considered as a safe tool for seizure control and neuropsychological improvement in patients with MTLE. PMID:27122996
Fractional diffusions with time-varying coefficients
NASA Astrophysics Data System (ADS)
Garra, Roberto; Orsingher, Enzo; Polito, Federico
2015-09-01
This paper is concerned with the fractionalized diffusion equations governing the law of the fractional Brownian motion BH(t). We obtain solutions of these equations which are probability laws extending that of BH(t). Our analysis is based on McBride fractional operators generalizing the hyper-Bessel operators L and converting their fractional power Lα into Erdélyi-Kober fractional integrals. We study also probabilistic properties of the random variables whose distributions satisfy space-time fractional equations involving Caputo and Riesz fractional derivatives. Some results emerging from the analysis of fractional equations with time-varying coefficients have the form of distributions of time-changed random variables.
Fractional Topological Insulators in Three Dimensions
Maciejko, Joseph; Zhang Shoucheng; Qi Xiaoliang; Karch, Andreas
2010-12-10
Topological insulators can be generally defined by a topological field theory with an axion angle {theta} of 0 or {pi}. In this work, we introduce the concept of fractional topological insulator defined by a fractional axion angle and show that it can be consistent with time reversal T invariance if ground state degeneracies are present. The fractional axion angle can be measured experimentally by the quantized fractional bulk magnetoelectric polarization P{sub 3}, and a 'halved' fractional quantum Hall effect on the surface with Hall conductance of the form {sigma}{sub H}=(p/q)(e{sup 2}/2h) with p, q odd. In the simplest of these states the electron behaves as a bound state of three fractionally charged 'quarks' coupled to a deconfined non-Abelian SU(3) 'color' gauge field, where the fractional charge of the quarks changes the quantization condition of P{sub 3} and allows fractional values consistent with T invariance.
Cassatt, David R.; McCarthy, Michael P. . E-mail: mccarthym@medimmune.com
2005-03-01
Purpose: The cytoprotective drug amifostine (Ethyol) protects rats from oral mucositis resulting from a single dose of {gamma}-irradiation. We expanded earlier studies to determine whether multiple doses of amifostine protect against fractionated or hyperfractionated radiation and whether the active metabolite of amifostine (WR-1065) accumulates in tissues upon repeated administration. Methods and materials: Rats received amifostine daily for 5 days in conjunction with a 1-week fractionated radiation schedule and were evaluated for oral mucositis. Rats also received amifostine before the am or pm exposure or b.i.d. in conjunction with hyperfractionated radiation. To determine the pharmacokinetics of WR-1065 after repeated dosing, amifostine was given 5 days a week for 1 or 3 weeks, and rat tissue and plasma were collected at intervals during and after treatment and analyzed for WR-1065. Results: Amifostine protected rats from mucositis resulting from fractionated or hyperfractionated radiation. When the number of days of amifostine administration was reduced, protection was diminished. A dose of 100 mg/kg given in the morning or 2 doses at 50 mg/kg provided the best protection against hyperfractionated radiation. WR-1065 did not accumulate in tissues or tumor upon repeated administration. Conclusions: Amifostine prevented radiation-induced mucositis in a rat model; protection was dose and schedule dependent.
Serum calcium fractions in sheep treated with Solanum malacoxylon.
Bingley, J B; Ruksan, B E; Carrillo, B J
1976-07-01
Sheep treated with a single dose of an extract of the dried leaves of Solanum malacoxylon (SM) at the rate of 0-2 g of leaves per kg liveweight produced a pronounced hypercalcaemia (49 per cent, P less than 0-005) after 24 h, which persisted for at least six days. The ultra-filtrable fraction of the serum calcium rose to approximately the same extent as the protein-bound calcium. This finding is consistent with osteosclerosis and parathyroid atrophy found to occur in cases of experimental SM intoxication. At the dose level given serum inorganic phosphorus was not significantly increased and packed cell volume, serum proteins and ceruloplasmin concentrations remained constant. PMID:951523
Howell, Roger W; Neti, Prasad V S V
2005-02-01
Radiopharmaceuticals are distributed nonuniformly in tissue. While distributions of radioactivity often appear uniform at the organ level, in fact, microscopic examination reveals that only a fraction of the cells in tissue are labeled. Labeled cells and unlabeled cells often receive different absorbed doses depending on the extent of the nonuniformity and the characteristics of the emitted radiations. The labeled cells receive an absorbed dose from radioactivity within the cell (self-dose) as well as an absorbed dose from radioactivity in surrounding labeled cells (cross-dose). Unlabeled cells receive only a cross-dose. In recent communications, a multicellular cluster model was used to investigate the lethality of microscopic nonuniform distributions of 131I iododeoxyuridine (131IdU). For a given mean absorbed dose to the tissue, the dose response depended on the percentage of cells that were labeled. Specifically, when 1, 10 and 100% of the cells were labeled, a D37 of 6.4, 5.7 and 4.5 Gy, respectively, was observed. The reason for these differences was recently traced to differences in the cellular response to the self- and cross-doses delivered by 131IdU. Systematic isolation of the effects of self-dose resulted in a D37 of 1.2 +/- 0.3 Gy. The cross-dose component yielded a D37 of 6.4 +/- 0.5 Gy. In the present work, the overall survival of multicellular clusters containing 1, 10 and 100% labeled cells is modeled using a semi-empirical approach that uses the mean lethal self- and cross-doses and the fraction of cells labeled. There is excellent agreement between the theoretical model and the experimental data when the surviving fraction is greater than 1%. Therefore, when the distribution of 131I in tissue is nonuniform at the microscopic level, and the cellular response to self- and cross-doses differs, multicellular dosimetry can be used successfully to predict biological response, whereas the mean absorbed dose fails in this regard. PMID:15658898
Two Realistic Beagle Models for Dose Assessment.
Stabin, Michael G; Kost, Susan D; Segars, William P; Guilmette, Raymond A
2015-09-01
Previously, the authors developed a series of eight realistic digital mouse and rat whole body phantoms based on NURBS technology to facilitate internal and external dose calculations in various species of rodents. In this paper, two body phantoms of adult beagles are described based on voxel images converted to NURBS models. Specific absorbed fractions for activity in 24 organs are presented in these models. CT images were acquired of an adult male and female beagle. The images were segmented, and the organs and structures were modeled using NURBS surfaces and polygon meshes. Each model was voxelized at a resolution of 0.75 × 0.75 × 2 mm. The voxel versions were implemented in GEANT4 radiation transport codes to calculate specific absorbed fractions (SAFs) using internal photon and electron sources. Photon and electron SAFs were then calculated for relevant organs in both models. The SAFs for photons and electrons were compatible with results observed by others. Absorbed fractions for electrons for organ self-irradiation were significantly less than 1.0 at energies above 0.5 MeV, as expected for many of these small-sized organs, and measurable cross irradiation was observed for many organ pairs for high-energy electrons (as would be emitted by nuclides like 32P, 90Y, or 188Re). The SAFs were used with standardized decay data to develop dose factors (DFs) for radiation dose calculations using the RADAR Method. These two new realistic models of male and female beagle dogs will be useful in radiation dosimetry calculations for external or internal simulated sources. PMID:26222214
Fractional Levy motion through path integrals
Calvo, Ivan; Sanchez, Raul; Carreras, Benjamin A
2009-01-01
Fractional Levy motion (fLm) is the natural generalization of fractional Brownian motion in the context of self-similar stochastic processes and stable probability distributions. In this paper we give an explicit derivation of the propagator of fLm by using path integral methods. The propagators of Brownian motion and fractional Brownian motion are recovered as particular cases. The fractional diffusion equation corresponding to fLm is also obtained.
Qader, Suhailah Wasman; Abdulla, Mahmood Ameen; Chua, Lee Suan; Sirat, Hasnah Mohd; Hamdan, Salehhuddin
2012-01-01
The leaves of Polygonum minus were fractionated using an eluting solvent to evaluate the pharmacological mechanisms underlying the anti-ulcerogenic activity of P. minus. Different P. minus fractions were obtained and evaluated for their ulcer preventing capabilities using the ethanol induction method. In this study, Sprague Dawley rats weighing 150–200 g were used. Different parameters were estimated to identify the active fraction underlying the mechanism of the gastroprotective action of P. minus: the gastric mucus barrier, as well as superoxide dismutase, total hexosamine, and prostaglandin synthesis. Amongst the five fractions from the ethanolic extract of P. minus, the ethyl acetate:methanol 1:1 v/v fraction (F2) significantly (p < 0.005) exhibited better inhibition of ulcer lesions in a dose-dependent manner. In addition, rats pre-treated with F2 showed a significant elevation in superoxide dismutase (SOD), hexosamine and PGE2 levels in the stomach wall mucosa in a dose-dependent matter. Based on these results, the ethyl acetate:methanol 1:1 v/v fraction was considered to be the best fraction for mucous protection in the ethanol induction model. The mechanisms underlying this protection were attributed to the synthesis of antioxidants and PGE2. PMID:22408403
Qader, Suhailah Wasman; Abdulla, Mahmood Ameen; Chua, Lee Suan; Sirat, Hasnah Mohd; Hamdan, Salehhuddin
2012-01-01
The leaves of Polygonum minus were fractionated using an eluting solvent to evaluate the pharmacological mechanisms underlying the anti-ulcerogenic activity of P. minus. Different P. minus fractions were obtained and evaluated for their ulcer preventing capabilities using the ethanol induction method. In this study, Sprague Dawley rats weighing 150-200 g were used. Different parameters were estimated to identify the active fraction underlying the mechanism of the gastroprotective action of P. minus: the gastric mucus barrier, as well as superoxide dismutase, total hexosamine, and prostaglandin synthesis. Amongst the five fractions from the ethanolic extract of P. minus, the ethyl acetate:methanol 1:1 v/v fraction (F2) significantly (p < 0.005) exhibited better inhibition of ulcer lesions in a dose-dependent manner. In addition, rats pre-treated with F2 showed a significant elevation in superoxide dismutase (SOD), hexosamine and PGE2 levels in the stomach wall mucosa in a dose-dependent matter. Based on these results, the ethyl acetate:methanol 1:1 v/v fraction was considered to be the best fraction for mucous protection in the ethanol induction model. The mechanisms underlying this protection were attributed to the synthesis of antioxidants and PGE2. PMID:22408403
Early Predictors of Middle School Fraction Knowledge
ERIC Educational Resources Information Center
Bailey, Drew H.; Siegler, Robert S.; Geary, David C.
2014-01-01
Recent findings that earlier fraction knowledge predicts later mathematics achievement raise the question of what predicts later fraction knowledge. Analyses of longitudinal data indicated that whole number magnitude knowledge in first grade predicted knowledge of fraction magnitudes in middle school, controlling for whole number arithmetic…
12 CFR 5.67 - Fractional shares.
Code of Federal Regulations, 2010 CFR
2010-01-01
... 12 Banks and Banking 1 2010-01-01 2010-01-01 false Fractional shares. 5.67 Section 5.67 Banks and... CORPORATE ACTIVITIES Payment of Dividends § 5.67 Fractional shares. To avoid complicated recordkeeping in connection with fractional shares, a national bank issuing additional stock by stock dividend,...
Identifying Fractions on a Number Line
ERIC Educational Resources Information Center
Wong, Monica
2013-01-01
Fractions are generally introduced to students using the part--whole model. Yet the number line is another important representation which can be used to build fraction concepts (Australian Curriculum Assessment and Reporting Authority [ACARA], 2012). Number lines are recognised as key in students' number development not only of fractions, but…
Stretching Student Teachers' Understanding of Fractions
ERIC Educational Resources Information Center
Harvey, Roger
2012-01-01
The teaching of fractions in elementary school is known to be challenging. Literature indicates that teachers' and prospective teachers' lack of depth of fraction content knowledge and associated pedagogical knowledge is of concern. This study investigated the fraction content knowledge of prospective teachers and their ability to use that…
Mode analysis in optics through fractional transforms.
Alieva, T; Bastiaans, M J
1999-09-01
The relationship between the mode content and the fractional Fourier and fractional Hankel transforms of a function is established. It is shown that the Laguerre-Gauss spectrum of a rotationally symmetric wave front can be determined from the wave front's fractional Hankel transforms taken at the optical axis. PMID:18073985
Code of Federal Regulations, 2011 CFR
2011-01-01
... 16 Commercial Practices 1 2011-01-01 2011-01-01 false Fractions. 500.17 Section 500.17 Commercial... LABELING ACT § 500.17 Fractions. (a) SI metric declarations of net quantity of contents of any consumer commodity may contain only decimal fractions. Other declarations of net quantity of contents may...
Teaching Fractions. Educational Practices Series-22
ERIC Educational Resources Information Center
Fazio, Lisa; Siegler, Robert
2011-01-01
Students around the world have difficulties in learning about fractions. In many countries, the average student never gains a conceptual knowledge of fractions. This research guide provides suggestions for teachers and administrators looking to improve fraction instruction in their classrooms or schools. The recommendations are based on a…
Code of Federal Regulations, 2010 CFR
2010-01-01
... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Fractions. 500.17 Section 500.17 Commercial... LABELING ACT § 500.17 Fractions. (a) SI metric declarations of net quantity of contents of any consumer commodity may contain only decimal fractions. Other declarations of net quantity of contents may...
An Alternative Starting Point for Fraction Instruction
ERIC Educational Resources Information Center
Cortina, José Luis; Višnovská, Jana; Zúñiga, Claudia
2015-01-01
We analyze the results of a study conducted for the purpose of assessing the viability of an alternative starting point for teaching fractions. The alternative is based on Freudenthal's insights about fraction as comparison. It involves portraying the entities that unit fractions quantify as always being apart from the reference unit, instead of…
Locating Fractions on a Number Line
ERIC Educational Resources Information Center
Wong, Monica
2013-01-01
Understanding fractions remains problematic for many students. The use of the number line aids in this understanding, but requires students to recognise that a fraction represents the distance from zero to a dot or arrow marked on a number line which is a linear scale. This article continues the discussion from "Identifying Fractions on a…
Building Understanding of Multiplication of Fractions.
ERIC Educational Resources Information Center
Burns, Marilyn
It is not complex to teach the algorithm for multiplying fractions so that children can multiply numerators and denominators to arrive at correct answers. However, it is a challenge to teach so that students build understanding of multiplication of fractions, extending what they have already learned about fractions and about multiplication of…
Isosorbide Mononitrate in Heart Failure with Preserved Ejection Fraction
Redfield, Margaret M.; Anstrom, Kevin J.; Levine, James A.; Koepp, Gabe A.; Borlaug, Barry A.; Chen, Horng H.; LeWinter, Martin M.; Joseph, Susan M.; Shah, Sanjiv J.; Semigran, Marc J.; Felker, G. Michael; Cole, Robert T.; Reeves, Gordon R.; Tedford, Ryan J.; Tang, W.H. Wilson; McNulty, Steven E.; Velazquez, Eric J.; Shah, Monica R.; Braunwald, Eugene
2015-01-01
BACKGROUND Nitrates are commonly prescribed to enhance activity tolerance in patients with heart failure and a preserved ejection fraction. We compared the effect of isosorbide mononitrate or placebo on daily activity in such patients. METHODS In this multicenter, double-blind, crossover study, 110 patients with heart failure and a preserved ejection fraction were randomly assigned to a 6-week dose-escalation regimen of isosorbide mononitrate (from 30 mg to 60 mg to 120 mg once daily) or placebo, with subsequent crossover to the other group for 6 weeks. The primary end point was the daily activity level, quantified as the average daily accelerometer units during the 120-mg phase, as assessed by patient-worn accelerometers. Secondary end points included hours of activity per day during the 120-mg phase, daily accelerometer units during all three dose regimens, quality-of-life scores, 6-minute walk distance, and levels of N-terminal pro–brain natriuretic peptide (NT-proBNP). RESULTS In the group receiving the 120-mg dose of isosorbide mononitrate, as compared with the placebo group, there was a nonsignificant trend toward lower daily activity (−381 accelerometer units; 95% confidence interval [CI], −780 to 17; P = 0.06) and a significant decrease in hours of activity per day (−0.30 hours; 95% CI, −0.55 to −0.05; P = 0.02). During all dose regimens, activity in the isosorbide mononitrate group was lower than that in the placebo group (−439 accelerometer units; 95% CI, −792 to −86; P = 0.02). Activity levels decreased progressively and significantly with increased doses of isosorbide mononitrate (but not placebo). There were no significant between-group differences in the 6-minute walk distance, quality-of-life scores, or NT-proBNP levels. CONCLUSIONS Patients with heart failure and a preserved ejection fraction who received isosorbide mononitrate were less active and did not have better quality of life or submaximal exercise capacity than did
Inhibitory activity of the ethyl acetate fraction from Viscum coloratum on bone resorption.
Yin, Jun; Han, Na; Xu, Xinyang; Liu, Zhihui; Zhang, Baoyan; Kadota, Shigetoshi
2008-02-01
The effects of four fractions, a hexane fraction, an ethyl acetate fraction, an N-butanol fraction and a water fraction, from a water extract of Herba Visci were investigated to find the fraction, in IN VITRO experiments, with the greatest ability to inhibit the formation of osteoclast-like multinucleated cells from mouse bone marrow cells and also to inhibit (45)Ca release from a mouse parietal bone organ culture system. The ethyl acetate fraction was able to inhibit the formation of osteoclast-like cells in a dose-dependent manner and was also able to potently inhibit the release of (45)Ca even at a low concentration. Therefore, a further IN VIVO experiment was performed to determine if the ethyl acetate fraction had antiosteoporotic activity. It was found to inhibit the decreases in total and cancellous bone mineral density, in cancellous and cortical bone mineral content as well as in cortical bone thickness and in the X-axis strength index of tibiae of ovariectomized rats. The principle constituents of the ethyl acetate fraction were determined to be (+)-syringaresinol O- beta-glucopyranoside, 2-homoeriodictyol 7- O-glucoside and viscumneoside I by HPLC analysis. PMID:18247260
Tomotherapy – a different way of dose delivery in radiotherapy
Skórska, Małgorzata; Jodda, Agata; Ryczkowski, Adam; Kaźmierska, Joanna; Adamska, Krystyna; Karczewska-Dzionk, Aldona; Żmijewska-Tomczak, Małgorzata; Włodarczyk, Hanna
2012-01-01
Aim of the study Helical tomotherapy is one of the methods of radiotherapy. This method enables treatment implementation for a wide spectrum of clinical cases. The vast array of therapeutic uses of helical tomotherapy results directly from the method of dose delivery, which is significantly different from the classic method developed for conventional linear accelerators. The paper discusses the method of dose delivery by a tomotherapy machine. Moreover, an analysis and presentation of treatment plans was performed in order to show the therapeutic possibilities of the applied technology. Dose distributions were obtained for anaplastic medulloblastoma, multifocal metastases to brain, vulva cancer, tongue cancer, metastases to bones, and advanced skin cancer. Tomotherapy treatment plans were compared with conventional linear accelerator plans. Results Following the comparative analysis of tomotherapy and conventional linear accelerator plans, in each case we obtained the increase in dose distribution conformity manifested in greater homogeneity of doses in the radiation target area for anaplastic medulloblastoma, multifocal metastases to brain, vulva cancer, metastases to bones, and advanced skin cancer, and the reduction of doses in organs at risk (OAR) for anaplastic medulloblastoma, vulva cancer, tongue cancer, and advanced skin cancer. The time of treatment delivery in the case of a tomotherapy machine is comparable to the implementation of the plan prepared in intensity-modulated radiotherapy (IMRT) technique for a conventional linear accelerator. In the case of tomotherapy the application of a fractional dose was carried out in each case during one working period of the machine. For a conventional linear accelerator the total value of the fractional dose in the case of anaplastic medulloblastoma and metastases to bones was delivered using several treatment plans, for which a change of set-up was necessary during a fraction. Conclusion The obtained results
The Radiation Dose-Response of the Human Spinal Cord
Schultheiss, Timothy E.
2008-08-01
Purpose: To characterize the radiation dose-response of the human spinal cord. Methods and Materials: Because no single institution has sufficient data to establish a dose-response function for the human spinal cord, published reports were combined. Requisite data were dose and fractionation, number of patients at risk, number of myelopathy cases, and survival experience of the population. Eight data points for cervical myelopathy were obtained from five reports. Using maximum likelihood estimation correcting for the survival experience of the population, estimates were obtained for the median tolerance dose, slope parameter, and {alpha}/{beta} ratio in a logistic dose-response function. An adequate fit to thoracic data was not possible. Hyperbaric oxygen treatments involving the cervical cord were also analyzed. Results: The estimate of the median tolerance dose (cervical cord) was 69.4 Gy (95% confidence interval, 66.4-72.6). The {alpha}/{beta} = 0.87 Gy. At 45 Gy, the (extrapolated) probability of myelopathy is 0.03%; and at 50 Gy, 0.2%. The dose for a 5% myelopathy rate is 59.3 Gy. Graphical analysis indicates that the sensitivity of the thoracic cord is less than that of the cervical cord. There appears to be a sensitizing effect from hyperbaric oxygen treatment. Conclusions: The estimate of {alpha}/{beta} is smaller than usually quoted, but values this small were found in some studies. Using {alpha}/{beta} = 0.87 Gy, one would expect a considerable advantage by decreasing the dose/fraction to less than 2 Gy. These results were obtained from only single fractions/day and should not be applied uncritically to hyperfractionation.
Helices of fractionalized Maxwell fluid
NASA Astrophysics Data System (ADS)
Jamil, Muhammad; Abro, Kashif Ali; Khan, Najeeb Alam
2015-12-01
In this paper the helical flows of fractionalized Maxwell fluid model, through a circular cylinder, is studied. The motion is produced by the cylinder that at the initial moment begins to rotate around its axis with an angular velocity Omegatp, and to slide along the same axis with linear velocity Utp. The solutions that have been obtained using Laplace and finite Hankel transforms and presented in series form in terms of the newly defined special function M(z), satisfy all imposed initial and boundary conditions. Moreover, the corresponding solutions for ordinary Maxwell and Newtonian fluid obtained as special cases of the present general solution. Finally, the influence of various pertinent parameters on fluid motion as well as the comparison among different fluids models is analyzed by graphical illustrations.
Copolyamino acid fractionation and protobiochemistry
NASA Technical Reports Server (NTRS)
Fox, S. W.
1981-01-01
Investigation of the origins of living things by the uniquely appropriate method of successive approximation in attempted retracement of steps in molecular evolution has yielded: a comprehensive theoretical flowsheet from archaic inanimate matter to an infrastructured, microscopic, protoreproductive, protometabolic protocell; a laboratory model of the same; and an explanatory assessment of the natural variation component of Darwinian evolution. For each of these, the significance is dependent upon awareness of the intrinsic tendency of amino acids, in mixed sets, to order themselves. Without such awareness, it is believed these vistas would have been delayed for decades. Selfordering would have in turn been difficult to recognize and support were it not for the chromatographic developments in fractionation of copolyamino acids.
Fractional-calculus diffusion equation
2010-01-01
Background Sequel to the work on the quantization of nonconservative systems using fractional calculus and quantization of a system with Brownian motion, which aims to consider the dissipation effects in quantum-mechanical description of microscale systems. Results The canonical quantization of a system represented classically by one-dimensional Fick's law, and the diffusion equation is carried out according to the Dirac method. A suitable Lagrangian, and Hamiltonian, describing the diffusive system, are constructed and the Hamiltonian is transformed to Schrodinger's equation which is solved. An application regarding implementation of the developed mathematical method to the analysis of diffusion, osmosis, which is a biological application of the diffusion process, is carried out. Schrödinger's equation is solved. Conclusions The plot of the probability function represents clearly the dissipative and drift forces and hence the osmosis, which agrees totally with the macro-scale view, or the classical-version osmosis. PMID:20492677
Calculates External and Inhalation Doses from Acute Radionuclide Releases on the Hanford Site.
Energy Science and Technology Software Center (ESTSC)
1984-03-02
HADOC (Hanford Acute Dose Calculations) calculates external and inhalation doses resulting from postulated accidental radionuclide releases on the Hanford site. It generates doses to an individual at a specified location and to the population in the region near the Hanford site for specified organs. Doses reported include the maximally exposed individual's dose (by organ and exposure mode) and the total population dose (by organ and exposure mode) in the sector having the highest population exposuremore » factor. The first year and fifty-year dose commitments are reported. Optional reports giving the fractional contribution to total dose by radionuclide for each organ and dose commitment period for a maximally exposed individual and the population may be printed.« less
NASA Technical Reports Server (NTRS)
Sparrow, A. H.; Underbrink, A. G.; Rossi, H. H.
1972-01-01
Dose-response curves for pink somatic mutations in Tradescantia stamen hairs were analyzed after neutron and X-ray irradiation with doses ranging from a fraction of a rad to the region of saturation. The dose-effect relation for neutrons indicates a linear dependence from 0.01 to 8 rads; between 0.25 and 5 rads, a linear dependence is indicated for X-rays also. As a consequence the relative biological effectiveness reaches a constant value (about 50) at low doses. The observations are in good agreement with the predictions of the theory of dual radiation action and support its interpretation of the effects of radiation on higher organisms. The doubling dose of X-rays was found to be nearly 1 rad.
Holloway, Lois Charlotte; Miller, Julie-Anne; Kumar, Shivani; Whelan, Brendan M.; Vinod, Shalini K.
2012-10-01
Treatment planning studies often require the calculation of a large number of dose and radiobiological metrics. To streamline these calculations, a computer program called Comp Plan was developed using MATLAB. Comp Plan calculates common metrics, including equivalent uniform dose, tumor control probability, and normal tissue complication probability from dose-volume histogram data. The dose and radiobiological metrics can be calculated for the original data or for an adjusted fraction size using the linear quadratic model. A homogeneous boost dose can be added to a given structure if desired. The final output is written to an Excel file in a format convenient for further statistical analysis. Comp Plan was verified by independent calculations. A lung treatment planning study comparing 45 plans for 7 structures using up to 6 metrics for each structure was successfully analyzed within approximately 5 minutes with Comp Plan. The code is freely available from the authors on request.
Equation of motion using fractional calculus
Kihong, Kwon.
1991-01-01
One-dimensional motion of a particle was studied using fractional calculus, which is the differentiation and the integration of arbitrary order. By fractional differentiation, equation of motion could be written in compact form. Fractional parameters were numerically calculated by using the known solutions of general relativistic free fall motion. Also, from the approximate forms for fractional parameters, the physical meanings were found. The fractional parameters depended on the proper time, the mass of gravitating body, and the initial radial coordinate of the particle.
Bachhav, R. S.; Sambathkumar, R.
2016-01-01
Trichopus zeylanicus Gaertn, (Trichopodaceae) is also known as “Arogyappacha” meaning the greener of health by tribal inhabitants (Kani tribes). This plant used as health tonic and rejuvenator. The whole plant material of Trichopus zeylanicus is defatted and successively extracted with methanol. The alkaloid fraction of Trichopus zeylanicus was obtained from methanol extract. Up to the dose of 2000 mg/kg b.w. per orally alkaloid fraction of Trichopus zeylanicus did not show any mortality or toxicity. Immunomodulatory activity of alkaloid fraction of Trichopus zeylanicus Gaertn was evaluated using various in vivo models including neutrophil adhesion test, delayed type hypersensitivity reaction, and effect on hematological parameter like, total white blood cell's, red blood cell's and hemoglobin and cyclophosphamide induce immunosupression. Sheep red blood cells were used to immunized the animals. The percentage of neutrophils adhesion to the nylon fiber was dose dependently increased in alkaloid fraction of Trichopus zeylanicus75, 150 and 300 mg/kg, p.o treated groups (50.57, 52.99 and 54.21%), respectively compared to control group. A dose dependent potentiating of delayed type hypersensitivity reaction induced by sheep red blood cells was also observed from the alkaloid fraction of Trichopus zeylanicus. On chronic administration of alkaloid fraction of Trichopus zeylanicus (75, 150 and 300 mg/kg. p.o.) caused significant (P<0.001) increased in hematological parameter like, total white blood cell's, red blood cell's and hemoglobin. Alkaloid fraction of Trichopus zeylanicus also prevented the myelosupression in mice treated cyclophosphamide (30 mg/kg, p.o.). The result of present investigation suggested that alkaloid fraction of Trichopus zeylanicus stimulate defense system by modulating several immunological parameters. PMID:27168696
Bachhav, R S; Sambathkumar, R
2016-01-01
Trichopus zeylanicus Gaertn, (Trichopodaceae) is also known as "Arogyappacha" meaning the greener of health by tribal inhabitants (Kani tribes). This plant used as health tonic and rejuvenator. The whole plant material of Trichopus zeylanicus is defatted and successively extracted with methanol. The alkaloid fraction of Trichopus zeylanicus was obtained from methanol extract. Up to the dose of 2000 mg/kg b.w. per orally alkaloid fraction of Trichopus zeylanicus did not show any mortality or toxicity. Immunomodulatory activity of alkaloid fraction of Trichopus zeylanicus Gaertn was evaluated using various in vivo models including neutrophil adhesion test, delayed type hypersensitivity reaction, and effect on hematological parameter like, total white blood cell's, red blood cell's and hemoglobin and cyclophosphamide induce immunosupression. Sheep red blood cells were used to immunized the animals. The percentage of neutrophils adhesion to the nylon fiber was dose dependently increased in alkaloid fraction of Trichopus zeylanicus75, 150 and 300 mg/kg, p.o treated groups (50.57, 52.99 and 54.21%), respectively compared to control group. A dose dependent potentiating of delayed type hypersensitivity reaction induced by sheep red blood cells was also observed from the alkaloid fraction of Trichopus zeylanicus. On chronic administration of alkaloid fraction of Trichopus zeylanicus (75, 150 and 300 mg/kg. p.o.) caused significant (P<0.001) increased in hematological parameter like, total white blood cell's, red blood cell's and hemoglobin. Alkaloid fraction of Trichopus zeylanicus also prevented the myelosupression in mice treated cyclophosphamide (30 mg/kg, p.o.). The result of present investigation suggested that alkaloid fraction of Trichopus zeylanicus stimulate defense system by modulating several immunological parameters. PMID:27168696
De Ruysscher, D.; Waer, M.; Vandeputte, M.; van der Schueren, E. )
1989-12-01
The immunologic effects of fractionated irradiation to both hind limbs and the tail of adult mice were investigated. A dose of 34 Gy given in 17 fractions of 2 Gy, 1 fraction per day, 5 days per week, was delivered with a 60Co source. A significant decrease of the total splenocyte count and of the PHA(phytohemagglutinin)-induced proliferation of T cells was found immediately after irradiation. Both parameters normalized within 30 days after irradiation. Immediately after irradiation, the MLC (mixed lymphocyte culture) was supranormal, dropped to 45% 1 week later, and normalized within 1 month after radiotherapy. The NK (natural killer) activity was significantly decreased only the first week after loco-regional irradiation, while the LAK (lymphokine activated killer) activity was not altered at all. The percentage of goat-anti-mouse+ cells (mainly B lymphocytes) was not changed immediately after loco-regional irradiation, but rose to supranormal values (175% of control level) 3 months after irradiation. A persistent decrease of the percentage and the absolute numbers of the Lyt2+ cells (= CD8+ cells, suppressor/cytotoxic phenotype) was observed up to 3 months after irradiation, while the percentage of L3T4+ cells (= CD4+ cells, helper phenotype) remained normal for the total follow-up. No differences in allogeneic skin graft survival could be demonstrated between irradiated and control animals. The observed immunological effects could not be explained by the scatter irradiation to the whole body as total body irradiation (TBI) administered in a dose and dose rate similar to the scatter dose did not result in persistent immunologic changes. No dose-rate effect could be demonstrated in a low dose fractionated total body irradiation schedule. A total body irradiation similar to the scatter dose in humans did not result in significant immunologic changes.
Shibamoto, Yuta; Miyakawa, Akifumi; Otsuka, Shinya; Iwata, Hiromitsu
2016-01-01
In hypofractionated stereotactic radiotherapy (SRT), high doses per fraction are usually used and the dose delivery pattern is different from that of conventional radiation. The daily dose is usually given intermittently over a longer time compared with conventional radiotherapy. During prolonged radiation delivery, sublethal damage repair takes place, leading to the decreased effect of radiation. In in vivo tumors, however, this decrease in effect may be counterbalanced by rapid reoxygenation. Another issue related to hypofractionated SRT is the mathematical model for dose evaluation and conversion. The linear–quadratic (LQ) model and biologically effective dose (BED) have been suggested to be incorrect when used for hypofractionation. The LQ model overestimates the effect of high fractional doses of radiation. BED is particularly incorrect when used for tumor responses in vivo, since it does not take reoxygenation into account. Correction of the errors, estimated at 5–20%, associated with the use of BED is necessary when it is used for SRT. High fractional doses have been reported to exhibit effects against tumor vasculature and enhance host immunity, leading to increased antitumor effects. This may be an interesting topic that should be further investigated. Radioresistance of hypoxic tumor cells is more problematic in hypofractionated SRT, so trials of hypoxia-targeted agents are encouraged in the future. In this review, the radiobiological characteristics of hypofractionated SRT are summarized, and based on the considerations, we would like to recommend 60 Gy in eight fractions delivered three times a week for lung tumors larger than 2 cm in diameter. PMID:27006380
Hydrologic transport and partitioning of phosphorus fractions
NASA Astrophysics Data System (ADS)
Berretta, C.; Sansalone, J.
2011-06-01
SummaryPhosphorus (P) in rainfall-runoff partitions between dissolved and particulate matter (PM) bound phases. This study investigates the transport and partitioning of P to PM fractions in runoff from a landscaped and biogenically-loaded carpark in Gainesville, FL (GNV). Additionally, partitioning and concentration results are compared to a similarly-sized concrete-paved source area of a similar rainfall depth frequency distribution in Baton Rouge, LA (BTR), where in contrast vehicular traffic represents the main source of pollutants. Results illustrate that concentrations of P fractions (dissolved, suspended, settleable and sediment) for GNV are one to two orders of magnitude higher than BTR. Despite these differences the dissolved fraction ( f d) and partitioning coefficient ( K d) distributions are similar, illustrating that P is predominantly bound to PM fractions. Examining PM size fractions, specific capacity for P (PSC) indicates that the P concentration order is suspended > settleable > sediment for GNV, similarly to BTR. For GNV the dominant PM mass fraction is sediment (>75 μm), while the mass of P is distributed predominantly between sediment and suspended (<25 μm) fractions since these PM mass fractions dominated the settleable one. With respect to transport of PM and P fractions the predominance of events for both areas is mass-limited first-flush, although each fraction illustrated unique washoff parameters. However, while transport is predominantly mass-limited, the transport of each PM and P fraction is influenced by separate hydrologic parameters.
Antitumor activity of fermented noni exudates and its fractions.
Li, Jinhua; Chang, Leng-Chee; Wall, Marisa; Wong, D K W; Yu, Xianzhong; Wei, Yanzhang
2013-01-01
Noni has been extensively used in folk medicine by Polynesians for over 2000 year. Recent studies have shown that noni has a wide spectrum of therapeutic activities including inhibition of angiogenesis, anti-inflammatory effects and anti-cancer activities. Intraperitoneal (i.p.) injection of fermented noni exudates (fNE) were previously found to induce significant tumor rejection in a S180 mouse sarcoma tumor model, while natural killer (NK) cells were demonstrated to be markedly involved in fNE-induced antitumor activity. In this study, fNE was partitioned into three fractions and their antitumor effects were examined using i.p. injection or as water supplement. The in vivo animal study results showed that when delivered by i.p. injection, n-butanol fraction of fNE (BuOH) effectively rejected (100%) tumor challenge and eradicated existing tumors (75%). When delivered as a water supplement, 62.5% of the mice receiving the n-butanol or ethyl acetate fractions resisted tumor cells. The tumor-resistant mice effectively rejected more and higher doses of tumor challenge, indicating that the immune system was activated. The findings confirm those of an earlier study showing fNE to have anti-tumor activity and demonstrating that the n-butanol fraction of fNE contains active antitumor components, to be further identified. More importantly, the antitumor effect of fNE and its fractions as water supplements renders a significant potential for identifying novel and powerful new dietary products for cancer prevention. PMID:24649140
Swyngedauw, J
1975-05-01
In the radiotherapy of cancer, two conditions are necessary:-- 1 degree sterilisation of the tumor; 2 degrees safeguard of surrounding tissues. In discontinuous irradiation, sterilisation depends on the administration of a certain tumour-dose within a suitable period or number of sessions. At the rate of 5 sessions weekly, the following dose-number law may be formulated (ELLIS): DT = 2,500.N0,22. Perfect tolerance of the connective tissue is in fact obtained if the total dose is equal or less than: N.S.D..N0,24.T0,11. The nominal standard dose of ELLIS, is a limiting dose of about 1,800 rads. ORTON and ELLIS have published tables which permit one to obtain, without an index of saturation of the supporting tissue by means of a series of double entry tables corresponding each to a frequency of 1, 2, 3, 4, 5 sessions per week. Each table provides the T.D.F. factor in relation to the number of sessions and the elementary dose. The T.D.F. factor is about 100 whatever the periodicity, and whatever the subdivisions of the dose when ELLIS' equation is satisfied, i.e. when one is at the limit of tolerance. Furthermore, the T.D.F. factor of two parts, of treatment under various regimens may be added together. It is sufficient for the sum to be equal to 100 to ensure full tolerance, which eliminates all difficulty of manipulation of a fractionated formula. The conditions of obtention of continuous irradiation do not permit one to separate the doses of sterilisation and tolerance, as was the case with discontinuous irradiation but, generally speaking, both in continuous and discontinuous administration the shorter the period of treatment the more the sterilising dose exceeds the tolerance dose, whereas with very small tumours, one may obtain tumour sterilisation within the limits of tolerance of the supporting tissues. For very large or radio-resistant tumours, one may have to, in order to obtain sterilisation, exceed more or less the perfect tolerance defined by T.D.F. 100 or
Yang, Ruijie; Zhao, Nan; Liao, Anyan; Wang, Hao; Qu, Ang
2016-01-01
To investigate the dosimetric and radiobiological differences among volumetric modulated arc therapy (VMAT), high-dose rate (HDR) brachytherapy, and low-dose rate (LDR) permanent seeds implant for localized prostate cancer. A total of 10 patients with localized prostate cancer were selected for this study. VMAT, HDR brachytherapy, and LDR permanent seeds implant plans were created for each patient. For VMAT, planning target volume (PTV) was defined as the clinical target volume plus a margin of 5mm. Rectum, bladder, urethra, and femoral heads were considered as organs at risk. A 78Gy in 39 fractions were prescribed for PTV. For HDR and LDR plans, the dose prescription was D90 of 34Gy in 8.5Gy per fraction, and 145Gy to clinical target volume, respectively. The dose and dose volume parameters were evaluated for target, organs at risk, and normal tissue. Physical dose was converted to dose based on 2-Gy fractions (equivalent dose in 2Gy per fraction, EQD2) for comparison of 3 techniques. HDR and LDR significantly reduced the dose to rectum and bladder compared with VMAT. The Dmean (EQD2) of rectum decreased 22.36Gy in HDR and 17.01Gy in LDR from 30.24Gy in VMAT, respectively. The Dmean (EQD2) of bladder decreased 6.91Gy in HDR and 2.53Gy in LDR from 13.46Gy in VMAT. For the femoral heads and normal tissue, the mean doses were also significantly reduced in both HDR and LDR compared with VMAT. For the urethra, the mean dose (EQD2) was 80.26, 70.23, and 104.91Gy in VMAT, HDR, and LDR brachytherapy, respectively. For localized prostate cancer, both HDR and LDR brachytherapy were clearly superior in the sparing of rectum, bladder, femoral heads, and normal tissue compared with VMAT. HDR provided the advantage in sparing of urethra compared with VMAT and LDR. PMID:27400663
A real time dose monitoring and dose reconstruction tool for patient specific VMAT QA and delivery
Tyagi, Neelam; Yang Kai; Gersten, David; Yan Di
2012-12-15
Purpose: To develop a real time dose monitoring and dose reconstruction tool to identify and quantify sources of errors during patient specific volumetric modulated arc therapy (VMAT) delivery and quality assurance. Methods: The authors develop a VMAT delivery monitor tool called linac data monitor that connects to the linac in clinical mode and records, displays, and compares real time machine parameters with the planned parameters. A new measure, called integral error, keeps a running total of leaf overshoot and undershoot errors in each leaf pair, multiplied by leaf width, and the amount of time during which the error exists in monitor unit delivery. Another tool reconstructs Pinnacle{sup 3} Trade-Mark-Sign format delivered plan based on the saved machine logfile and recalculates actual delivered dose in patient anatomy. Delivery characteristics of various standard fractionation and stereotactic body radiation therapy (SBRT) VMAT plans delivered on Elekta Axesse and Synergy linacs were quantified. Results: The MLC and gantry errors for all the treatment sites were 0.00 {+-} 0.59 mm and 0.05 {+-} 0.31 Degree-Sign , indicating a good MLC gain calibration. Standard fractionation plans had a larger gantry error than SBRT plans due to frequent dose rate changes. On average, the MLC errors were negligible but larger errors of up to 6 mm and 2.5 Degree-Sign were seen when dose rate varied frequently. Large gantry errors occurred during the acceleration and deceleration process, and correlated well with MLC errors (r= 0.858, p= 0.0004). PTV mean, minimum, and maximum dose discrepancies were 0.87 {+-} 0.21%, 0.99 {+-} 0.59%, and 1.18 {+-} 0.52%, respectively. The organs at risk (OAR) doses were within 2.5%, except some OARs that showed up to 5.6% discrepancy in maximum dose. Real time displayed normalized total positive integral error (normalized to the total monitor units) correlated linearly with MLC (r= 0.9279, p < 0.001) and gantry errors (r= 0.742, p= 0.005). There
Absorbed dose measurements and predictions on LDEF
NASA Technical Reports Server (NTRS)
Frank, A. L.; Benton, E. V.; Armstrong, T. W.; Colborn, B. L.
1993-01-01
The overall radiation environment of the Long Duration Exposure Facility (LDEF) was determined in part through the use of thermoluminescent detectors (TLD's) which were included in several experiments. The results given are from four experiments (A0015 Biostack, M0004 Fiber Optics Data Link, P0004 Seeds in Space, and P0006 Linear Energy Transfer Spectrum Measurement) and represent a large fraction of existing absorbed dose data. The TLD's were located on the leading and the trailing edges and the Earth end of the spacecraft under various shielding depths (0.48 to 15.4 g/sq cm). The measured absorbed doses were found to reflect both directional dependence of incident trapped protons and shielding. At the leading edge, doses ranged from 2.10 to 2.58 Gy under shielding of 2.90 to 1.37 g/sq cm Al equivalent (M0004). At the trailing edge, doses varied from 3.04 to 4.49 Gy under shielding of 11.7 to 3.85 g/sq cm (A0015), doses varied from 2.91 to 6.64 Gy under shielding of 11.1 to 0.48 g/sq cm (P0004), and a dose range of 2.66 to 6.48 Gy was measured under shielding of 15.4 to 0.48 g/sq cm (P0006). At the Earth end of the spacecraft, doses from 2.41 to 3.93 Gy were found under shielding of 10.0 to 1.66 g/sq cm (A0015). The effect of the trapped proton anisotropy was such that the western side of LDEF received more than 2 times the dose of the eastern side at shielding depths of approximately 1 g/sq cm. Calculations utilizing a directional model of trapped proton spectra predict smaller doses than those measured, being about 50 percent of measured values at the trailing edge and Earth end, and about 80 percent near the leading edge.
Mammography-oncogenecity at low doses.
Heyes, G J; Mill, A J; Charles, M W
2009-06-01
dose exposure, it is not a low dose rate examination, and protraction of dose should not be confused with fractionation. Although there is potential for a suppressive effect at low doses, recent epidemiological data, and several international radiation risk assessments, continue to promote the linear no-threshold (LNT) model. Finally, recent studies have shown that magnetic resonance imaging (MRI) is more sensitive than mammography in detecting invasive breast cancer in women with a genetic sensitivity. Since an increase in the risk associated with mammographic screening would blur the justification of exposure for this high risk subgroup, the use of other (non-ionising) screening modalities is preferable. PMID:19454801
Goldsmith, Christy; Price, Patricia; Cross, Timothy; Loughlin, Sheila; Cowley, Ian; Plowman, Nicholas
2016-04-01
Pancreatic carcinoma is an aggressive disease and radiotherapy treatment delivery to the primary tumor is constrained by the anatomical close location of the duodenum, stomach, and small bowel. Duodenal dose tolerance for radiosurgery in 2-5 fractions has been largely unknown. The literature was surveyed for quantitative models of risk in 1-5 fractions and we analyzed our own patient population of 44 patients with unresectable pancreatic tumors who received 3 or 5 fractions of stereotactic body radiotherapy (SBRT) between March 2009 and March 2013. A logistic model was constructed in the dose-volume histogram (DVH) Evaluator software for the duodenal D50%, D30cc, D5cc, D1cc, and maximum point dose D0.035cc. Dose tolerance limits from the literature were overlaid onto the clinical duodenal data in the form of a DVH Risk Map, with risk levels of the published limits estimated from the model of clinical data. In 3 fractions, Kopek 2010 found a statistically significant difference in D1cc of patients with no common terminology criteria for adverse events (CTCAE) v3 grade 2 or higher duodenal complications (mean D1cc = 25.3Gy) as compared with patients with grade 2 or higher toxicity (mean D1cc = 37.4Gy). From the logistic model of our duodenal data in 3 fractions, D1cc = 25.3Gy had 4.7% risk of grade 3-4 hemorrhage or stricture and D1cc = 37.4Gy had 20% risk. The 10% risk level was D1cc = 31.4Gy and we were able to keep duodenum dose for all our patients later this level. PMID:27000512
Rades, Dirk; Huttenlocher, Stefan; Šegedin, Barbara; Perpar, Ana; Conde, Antonio J.; Garcia, Raquel; Veninga, Theo; Stalpers, Lukas J.A.; Cacicedo, Jon; Rudat, Volker; Schild, Steven E.
2015-10-01
Purpose: This study compared single-fraction to multi-fraction short-course radiation therapy (RT) for symptomatic metastatic epidural spinal cord compression (MESCC) in patients with limited survival prognosis. Methods and Materials: A total of 121 patients who received 8 Gy × 1 fraction were matched (1:1) to 121 patients treated with 4 Gy × 5 fractions for 10 factors including age, sex, performance status, primary tumor type, number of involved vertebrae, other bone metastases, visceral metastases, interval between tumor diagnosis and MESCC, pre-RT ambulatory status, and time developing motor deficits prior to RT. Endpoints included in-field repeated RT (reRT) for MESCC, overall survival (OS), and impact of RT on motor function. Univariate analyses were performed with the Kaplan-Meier method and log-rank test for in-field reRT for MESCC and OS and with the ordered-logit model for effect of RT on motor function. Results: Doses of 8 Gy × 1 fraction and 4 Gy × 5 fractions were not significantly different with respect to the need for in-field reRT for MESCC (P=.11) at 6 months (18% vs 9%, respectively) and 12 months (30% vs 22%, respectively). The RT regimen also had no significant impact on OS (P=.65) and post-RT motor function (P=.21). OS rates at 6 and 12 months were 24% and 9%, respectively, after 8 Gy × 1 fraction versus 25% and 13%, respectively, after 4 Gy × 5 fractions. Improvement of motor function was observed in 17% of patients after 8 Gy × 1 fraction and 23% after 4 Gy × 5 fractions, respectively. Conclusions: There were no significant differences with respect to need for in-field reRT for MESCC, OS, and motor function by dose fractionation regimen. Thus, 8 Gy × 1 fraction may be a reasonable option for patients with survival prognosis of a few months.
WAGGONER, L.O.
2000-05-16
As radiation safety specialists, one of the things we are required to do is evaluate tools, equipment, materials and work practices and decide whether the use of these products or work practices will reduce radiation dose or risk to the environment. There is a tendency for many workers that work with radioactive material to accomplish radiological work the same way they have always done it rather than look for new technology or change their work practices. New technology is being developed all the time that can make radiological work easier and result in less radiation dose to the worker or reduce the possibility that contamination will be spread to the environment. As we discuss the various tools and techniques that reduce radiation dose, keep in mind that the radiological controls should be reasonable. We can not always get the dose to zero, so we must try to accomplish the work efficiently and cost-effectively. There are times we may have to accept there is only so much you can do. The goal is to do the smart things that protect the worker but do not hinder him while the task is being accomplished. In addition, we should not demand that large amounts of money be spent for equipment that has marginal value in order to save a few millirem. We have broken the handout into sections that should simplify the presentation. Time, distance, shielding, and source reduction are methods used to reduce dose and are covered in Part I on work execution. We then look at operational considerations, radiological design parameters, and discuss the characteristics of personnel who deal with ALARA. This handout should give you an overview of what it takes to have an effective dose reduction program.
Magnetite fractionation of "chalcophile" elements
NASA Astrophysics Data System (ADS)
Mavrogenes, J. A.; Jenner, F. E.; Arculus, R. J.
2008-12-01
Submarine-quenched glasses provide the clearest record of magmatic evolution available, especially with respect to potentially volatile elements and compounds. A comprehensive suite of arc- and backarc glasses recovered during several research voyages in the SW Pacific are being analysed by a number of research teams in an effort to document genesis and fractionation processes involved in the evolution of subduction- related magma systems. As part of these studies, a suite of basalt to dacite composition glasses recovered from the arc-like Pacmanus Site in the Manus Backarc Basin have been examined in detail. Sun et al. (2004) found trends of increasing enrichments of Re, Cu, and Au with SiO2 in the range from 50 to 60 wt% SiO2. From this stage of magmatic evolution, marked depletions in all these elements are observed in glasses of higher SiO2 contents. The reasons for this trend have been unclear, although a mechanism involving the cessation of olivine and initiation of magnetite saturation was proposed by Sun et al. Our analysis of a larger suite of glasses from the Manus Basin has now confirmed these trends, and found the same behaviour for Zn and Mn. Similarly, analysis of a suite of basalt to dacite glasses recovered from the arc-like Valu Fa Ridge in the Lau Backarc Basin has produced trends for these elements very similar to those of the Pacmanus location. LA-ICP-MS analysis of microphenocrysts in these glasses has shown that magnetite is highly enriched in Re relative to the coexisting melt (Kd up to 7.8 for Re). Magnetite/melt partition coefficients for Re, Mn and Yb can be used to precisely model the liquid line of descent during magnetite (plus clinopyroxene and plagioclase) fractionation using Re vs. Mn/Yb. The variation of Pt abundances with SiO2 for both these suites contrasts with other nominally chalcophile trace elements in showing rapid early depletion from the most Mg-rich basalt through to more SiO2-rich compositions, with no maximum at 60 wt
Energy Science and Technology Software Center (ESTSC)
1997-06-10
VENTSAR XL is an EXCEL Spreadsheet that can be used to calculate downwind doses as a result of a hypothetical atmospheric release. Both building effects and plume rise may be considered. VENTSAR XL will run using any version of Microsoft EXCEL version 4.0 or later. Macros (the programming language of EXCEL) was used to automate the calculations. The user enters a minimal amount of input and the code calculates the resulting concentrations and doses atmore » various downwind distances as specified by the user.« less
Schneider, Uwe
2009-04-15
A simple mechanistic model for predicting cancer induction after fractionated radiotherapy is developed. The model is based upon the linear-quadratic model. The inductions of carcinomas and sarcomas are modeled separately. The linear-quadratic model of cell kill is applied to normal tissues which are unintentionally irradiated during a cancer treatment with radiotherapy. Tumor induction is modeled such that each transformation process results in a tumor cell. The microscopic transformation parameter was chosen such that in the limit of low dose and acute exposure, the parameters of the linear-no-threshold model for tumor induction were approached. The differential equations describing carcinoma and sarcoma inductions can be solved analytically. Cancer induction in this model is a function of treatment dose, the cell kill parameters ({alpha},{beta}), the tumor induction variable ({mu}), and the repopulation parameter ({xi}). Carcinoma induction shows a bell shaped behavior as long as cell repopulation is small. Assuming large cell repopulation rates, a plateaulike function is approached. In contrast, sarcoma induction is negligible for low doses and increases with increasing dose up to a constant value. The proposed model describes carcinoma and sarcoma inductions after fractionated radiotherapy as an analytical function of four parameters. In the limit of low dose and for an instant irradiation it reproduces the results of the linear-no-threshold model. The obtained dose-response curves for cancer induction can be implemented with other models such as the organ-equivalent dose model to predict second cancers after radiotherapy.
[The effectiveness of fractionated exposure of sarcoma M-1 to gamma-radiation and fast neutrons].
Iuzhakov, V V; Sevan'kaeva, L E; Ul'ianenko, S E; Iakovleva, N D; Kuznetsova, M N; Tsyganova, M G; Fomina, N K; Ingel', I E; Lychagin, A A
2013-01-01
The effectiveness of fractionated exposure to gamma- and neutron radiation in their separate and combined use on the growth and functional morphology of mutant p53 sarcoma M-1 in rats was studied. Investigation techniques included immunostaining of PCNA and mutant p53 expressing cells, determination of mitotic activity and apoptotic death of tumor cells, as well as computer analysis of microscopic images. The antitumor efficacy of different types of radiation is shown to be determined by different levels of apoptosis induction, reduced proliferation and cellularity. Neutron radiation of the impulse generator has a marked damaging effect on the vasculature and the development of tumor necrosis. Fractionated irradiation at equal daily doses led to the decrease in the relative effectiveness of radio-inactivation of tumor cells. After 9 fractions of irradiation, the calculated value of the RBE of fast neutrons normalized to the input dose of 1 Gy by the coefficient of tumor growth inhibition, a reduced proliferative activity of PCNA and induced apoptosis of tumor cells was 3.4, 3.7 and 3.1, respectively. In the mode of daily superfractionation with splitting the dose in two fractions, the effectiveness of the combined exposure corresponded to the additive effect of gamma- and neutron radiation with a tendency toward synergism. There are reasons to believe that high resistance of sarcoma M-1 to the ionizing radiation impact is due not only to a fraction of hypoxic cells, but also the mutant status of p53 gene. PMID:24450208
Agwaramgbo, Amanze; Ilodigwe, Emmanuel Emeka; Ajaghaku, Daniel Lotanna; Onuorah, Maureen Ugochukwu; Mbagwu, Sonne Ikechukwu
2014-01-01
Gongronema latifolium fruit has wide application in ethnomedicine, especially in maintaining healthy living and general body healing. We therefore investigated the antioxidant, immunomodulatory activities, and safety of its ethanol extract and fractions. The in vitro antioxidant activities of the extract and fractions were determined using 2,2-diphenyl-1-picrylhydrazyl (DPPH) test while in vivo activities were determined using carbon tetrachloride (CCL4) induced oxidative stress. Cell and humoral mediated immune responses were also evaluated together with toxicity studies. The extract, ethyl acetate, and methanol fractions showed inhibition of DPPH radical with IC50s 120, 90, and 60 μg/mL, respectively. Methanol fraction at 200 mg/kg produced significant (P < 0.05) inhibition of lipid peroxidation (MDA conc. 1.2 μmol/L) compared to control (2.8 μmol/L). Both ethyl acetate and methanol fractions at 200 mg/kg produced significant (P < 0.05) phagocytic index of 0.021 and 0.025, respectively, compared with control (0.01). Significant (P < 0.05) elevations of white blood cells, aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase were noticed on the 91st day at higher doses. Generally, this study justified the traditional use of G. latifolium fruit for general body healing and maintenance of healthy living. Long term administration is safe on the haematological and biochemical systems especially at lower doses and its toxicity at higher doses is reversible. PMID:27433504
Agwaramgbo, Amanze; Ilodigwe, Emmanuel Emeka; Ajaghaku, Daniel Lotanna; Onuorah, Maureen Ugochukwu; Mbagwu, Sonne Ikechukwu
2014-01-01
Gongronema latifolium fruit has wide application in ethnomedicine, especially in maintaining healthy living and general body healing. We therefore investigated the antioxidant, immunomodulatory activities, and safety of its ethanol extract and fractions. The in vitro antioxidant activities of the extract and fractions were determined using 2,2-diphenyl-1-picrylhydrazyl (DPPH) test while in vivo activities were determined using carbon tetrachloride (CCL4) induced oxidative stress. Cell and humoral mediated immune responses were also evaluated together with toxicity studies. The extract, ethyl acetate, and methanol fractions showed inhibition of DPPH radical with IC50s 120, 90, and 60 μg/mL, respectively. Methanol fraction at 200 mg/kg produced significant (P < 0.05) inhibition of lipid peroxidation (MDA conc. 1.2 μmol/L) compared to control (2.8 μmol/L). Both ethyl acetate and methanol fractions at 200 mg/kg produced significant (P < 0.05) phagocytic index of 0.021 and 0.025, respectively, compared with control (0.01). Significant (P < 0.05) elevations of white blood cells, aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase were noticed on the 91st day at higher doses. Generally, this study justified the traditional use of G. latifolium fruit for general body healing and maintenance of healthy living. Long term administration is safe on the haematological and biochemical systems especially at lower doses and its toxicity at higher doses is reversible. PMID:27433504
Effect of frequency of dosing of plant sterols on plasma cholesterol levels and synthesis rate
Technology Transfer Automated Retrieval System (TEKTRAN)
The objective was to compare the effects of plant sterols (PS) consumed as a single dose (single) at breakfast or as three doses consumed with breakfast, lunch and dinner (divided) on plasma lipoprotien levels and cholesterol endogenous fractional synthesis rate (FSR). A randomized, placebo-controll...
Koukourakis, Michael I.; Abatzoglou, Ioannis; Touloupidis, Stavros; Manavis, Ioannis
2007-01-15
Radiobiological data suggest that prostate cancer has a low {alpha}/{beta} ratio. Large radiotherapy fractions may, therefore, prove more efficacious than standard radiotherapy, while radiotherapy acceleration should further improve control rates. This study describes the radiobiology of a conformal hypofractionated accelerated radiotherapy scheme for the treatment of high risk prostate cancer. Anteroposterior fields to the pelvis deliver a daily dose of 2.7 Gy, while lateral fields confined to the prostate and seminal vesicles deliver an additional daily dose of 0.7 Gy. Radiotherapy is accomplished within 19 days (15 fractions). Dose volume histograms, calculated for tissue specific {alpha}/{beta} ratios and time factors, predict a high biological dose to the prostate and seminal vesicles (77-93 Gy). The biological dose to normal pelvic tissues is maintained at standard levels. Radiobiological dosimetry suggests that, using hypofractionated and accelerated radiotherapy, high biological radiation dose can be given to the prostate without overdosing normal tissues.
Woody, Neil M.; Videtic, Gregory M.M.; Stephans, Kevin L.; Djemil, Toufik; Kim, Yongbok; Xia Ping
2012-05-01
Purpose: Recent studies with two fractionation schemes predicted that the volume of chest wall receiving >30 Gy (V30) correlated with chest wall pain after stereotactic body radiation therapy (SBRT) to the lung. This study developed a predictive model of chest wall pain incorporating radiobiologic effects, using clinical data from four distinct SBRT fractionation schemes. Methods and Materials: 102 SBRT patients were treated with four different fractionations: 60 Gy in three fractions, 50 Gy in five fractions, 48 Gy in four fractions, and 50 Gy in 10 fractions. To account for radiobiologic effects, a modified equivalent uniform dose (mEUD) model calculated the dose to the chest wall with volume weighting. For comparison, V30 and maximum point dose were also reported. Using univariable logistic regression, the association of radiation dose and clinical variables with chest wall pain was assessed by uncertainty coefficient (U) and C statistic (C) of receiver operator curve. The significant associations from the univariable model were verified with a multivariable model. Results: 106 lesions in 102 patients with a mean age of 72 were included, with a mean of 25.5 (range, 12-55) months of follow-up. Twenty patients reported chest wall pain at a mean time of 8.1 (95% confidence interval, 6.3-9.8) months after treatment. The mEUD models, V30, and maximum point dose were significant predictors of chest wall pain (p < 0.0005). mEUD improved prediction of chest wall pain compared with V30 (C = 0.79 vs. 0.77 and U = 0.16 vs. 0.11). The mEUD with moderate weighting (a = 5) better predicted chest wall pain than did mEUD without weighting (a = 1) (C = 0.79 vs. 0.77 and U = 0.16 vs. 0.14). Body mass index (BMI) was significantly associated with chest wall pain (p = 0.008). On multivariable analysis, mEUD and BMI remained significant predictors of chest wall pain (p = 0.0003 and 0.03, respectively). Conclusion: mEUD with moderate weighting better predicted chest wall pain than
Cyclical magnetic field flow fractionation
NASA Astrophysics Data System (ADS)
Tasci, T. O.; Johnson, W. P.; Gale, B. K.
2012-04-01
In this study, a new magnetic field flow fractionation (FFF) system was designed and modeled by using finite element simulations. Other than current magnetic FFF systems, which use static magnetic fields, our system uses cyclical magnetic fields. Results of the simulations show that our cyclical magnetic FFF system can be used effectively for the separation of magnetic nanoparticles. Cyclical magnetic FFF system is composed of a microfluidic channel (length = 5 cm, height = 30 μm) and 2 coils. Square wave currents of 1 Hz (with 90 deg of phase difference) were applied to the coils. By using Comsol Multiphysics 3.5a, magnetic field profile and corresponding magnetic force exerted on the magnetite nanoparticles were calculated. The magnetic force data were exported from Comsol to Matlab. In Matlab, a parabolic flow profile with maximum flow speed of 0.4 mL/h was defined. Particle trajectories were obtained by the calculation of the particle speeds resulted from both magnetic and hydrodynamic forces. Particle trajectories of the particles with sizes ranging from 10 to 50 nm were simulated and elution times of the particles were calculated. Results show that there is a significant difference between the elution times of the particles so that baseline separation of the particles can be obtained. In this work, it is shown that by the application of cyclical magnetic fields, the separation of magnetic nanoparticles can be done efficiently.
WATER FRACTIONS IN EXTRASOLAR PLANETESIMALS
Jura, M.; Xu, S. E-mail: sxu@astro.ucla.edu
2012-01-15
With the goal of using externally polluted white dwarfs to investigate the water fractions of extrasolar planetesimals, we assemble from the literature a sample that we estimate to be more than 60% complete of DB white dwarfs warmer than 13,000 K, more luminous than 3 Multiplication-Sign 10{sup -3} L{sub Sun }, and within 80 pc of the Sun. When considering all the stars together, we find that the summed mass accretion rate of heavy atoms exceeds that of hydrogen by over a factor of 1000. If so, this sub-population of extrasolar asteroids treated as an ensemble has little water and is at least a factor of 20 drier than CI chondrites, the most primitive meteorites. Furthermore, while an apparent 'excess' of oxygen in a single DB can be interpreted as evidence that the accreted material originated in a water-rich parent body, we show that at least in some cases, there can be sufficient uncertainties in the time history of the accretion rate that such an argument may be ambiguous. Regardless of the difficulty associated with interpreting the results from an individual object, our analysis of the population of polluted DBs provides indirect observational support for the theoretical view that a snow line is important in disks where rocky planetesimals form.
Variation of the unattached fraction of radon progeny and its contribution to radon exposure.
Guo, Lu; Zhang, Lei; Guo, Qiuju
2016-06-01
The unattached fraction of radon progeny is one of the most important factors for radon exposure evaluation through the dosimetric approach. To better understand its level and variation in the real environment, a series of field measurements were carried out indoors and outdoors, and radon equilibrium equivalent concentration was also measured. The dose contribution of unattached radon progeny was evaluated in addition. The results show that no clear variation trend of the unattached fraction of radon progeny is observed in an indoor or outdoor environment. The average unattached fraction of radon progeny for the indoors and outdoors are (8.7 ± 1.6)% and (9.7 ± 2.1)%, respectively. The dose contribution of unattached radon progeny to total radon exposure is some 38.8% in an indoor environment, suggesting the importance of the evaluation on unattached radon progeny. PMID:27171653
Low-Dose Carcinogenicity Studies
One of the major deficiencies of cancer risk assessments is the lack of low-dose carcinogenicity data. Most assessments require extrapolation from high to low doses, which is subject to various uncertainties. Only 4 low-dose carcinogenicity studies and 5 low-dose biomarker/pre-n...
Multiple-dose acetaminophen pharmacokinetics.
Sahajwalla, C G; Ayres, J W
1991-09-01
Four different treatments of acetaminophen (Tylenol) were administered in multiple doses to eight healthy volunteers. Each treatment (325, 650, 825, and 1000 mg) was administered five times at 6-h intervals. Saliva acetaminophen concentration versus time profiles were determined. Noncompartmental pharmacokinetic parameters were calculated and compared to determine whether acetaminophen exhibited linear or dose-dependent pharmacokinetics. For doses less than or equal to 18 mg/kg, area under the curve (AUC), half-life (t1/2), mean residence time (MRT), and ratio of AUC to dose for the first dose were compared with the last dose. No statistically significant differences were observed in dose-corrected AUC for the first or last dose among subjects or treatments. Half-lives and MRT were not significantly different among treatments for the first or the last dose. Statistically significant differences in t1/2 and MRT were noted (p less than 0.05) among subjects for the last dose. A plot of AUC versus dose for the first and the last doses exhibited a linear relationship. Dose-corrected saliva concentration versus time curves for the treatments were superimposable. Thus, acetaminophen exhibits linear pharmacokinetics for doses of 18 mg/kg or less. Plots of AUC versus dose for one subject who received doses higher than 18 mg/kg were curved, suggesting nonlinear behavior of acetaminophen in this subject. PMID:1800709
LADTAPXL Aqueous Dose Spreadsheet
Energy Science and Technology Software Center (ESTSC)
1999-08-10
LADTAPXL is an EXCEL spreadsheet model of the NRC computer code LADTAP. LADTAPXL calculates maximally exposed individual and population doses from chronic liquid releases. Environmental pathways include external exposure resulting from recreational activities on the Savannah River and ingestion of water, fish, and invertebrates of Savannah River origin.
Pineda, Leslie C.; Watt, Kevin M.
2015-01-01
Infection is common in premature infants and can cause significant morbidity and mortality. To prevent these devastating consequences, most infants admitted to the neonatal intensive care unit (NICU) are exposed to antibiotics. However, dosing regimens are often extrapolated from data in adults and older children, increasing the risk for drug toxicity and lack of clinical efficacy because they fail to account for developmental changes in infant physiology. Despite legislation promoting and, in some cases, requiring pediatric drug studies, infants remain therapeutic orphans who often receive drugs "off-label" without data from clinical trials. Pharmacokinetic (PK) studies in premature infants have been scarce due to low study consent rates; limited blood volume available to conduct PK studies; difficulty in obtaining blood from infants; limited use of sensitive, low-volume drug concentration assays; and a lack of expertise in pediatric modeling and simulation. However, newer technologies are emerging with minimal-risk study designs, including ultra-low-volume assays, PK modeling and simulation, and opportunistic drug protocols. With minimal-risk study designs, PK data and dosing regimens for infants are now available for antibiotics commonly used in the NICU, including ampicillin, clindamycin, meropenem, metronidazole, and piperacillin/tazobactam. The discrepancy between previous dosing recommendations extrapolated from adult data and newer dosing regimens based on infant PK studies highlights the need to conduct PK studies in premature infants. PMID:25678003
Small Bowel Dose Tolerance for Stereotactic Body Radiation Therapy.
LaCouture, Tamara A; Xue, Jinyu; Subedi, Gopal; Xu, Qianyi; Lee, Justin T; Kubicek, Gregory; Asbell, Sucha O
2016-04-01
Inconsistencies permeate the literature regarding small bowel dose tolerance limits for stereotactic body radiation therapy (SBRT) treatments. In this review, we organized these diverse published limits with MD Anderson at Cooper data into a unified framework, constructing the dose-volume histogram (DVH) Risk Map, demonstrating low-risk and high-risk SBRT dose tolerance limits for small bowel. Statistical models of clinical data from 2 institutions were used to assess the safety spectrum of doses used in the exposure of the gastrointestinal tract in SBRT; 30% of the analyzed cases had vascular endothelial growth factor inhibitors (VEGFI) or other biological agents within 2 years before or after SBRT. For every dose tolerance limit in the DVH Risk Map, the probit dose-response model was used to estimate the risk level from our clinical data. Using the current literature, 21Gy to 5cc of small bowel in 3 fractions has low toxicity and is reasonably safe, with 6.5% estimated risk of grade 3 or higher complications, per Common Terminology Criteria for Adverse Events version 4.0. In the same fractionation for the same volume, if lower risk is required, 16.2Gy has an estimated risk of only 2.5%. Other volumes and fractionations are also reviewed; for all analyzed high-risk small bowel limits, the risk is 8.2% or less, and the low-risk limits have 4% or lower estimated risk. The results support current clinical practice, with some possibility for dose escalation. PMID:27000513
Dose specification for radiation therapy: dose to water or dose to medium?
Ma, C-M; Li, Jinsheng
2011-05-21
The Monte Carlo method enables accurate dose calculation for radiation therapy treatment planning and has been implemented in some commercial treatment planning systems. Unlike conventional dose calculation algorithms that provide patient dose information in terms of dose to water with variable electron density, the Monte Carlo method calculates the energy deposition in different media and expresses dose to a medium. This paper discusses the differences in dose calculated using water with different electron densities and that calculated for different biological media and the clinical issues on dose specification including dose prescription and plan evaluation using dose to water and dose to medium. We will demonstrate that conventional photon dose calculation algorithms compute doses similar to those simulated by Monte Carlo using water with different electron densities, which are close (<4% differences) to doses to media but significantly different (up to 11%) from doses to water converted from doses to media following American Association of Physicists in Medicine (AAPM) Task Group 105 recommendations. Our results suggest that for consistency with previous radiation therapy experience Monte Carlo photon algorithms report dose to medium for radiotherapy dose prescription, treatment plan evaluation and treatment outcome analysis. PMID:21508447
Duodenal Toxicity After Fractionated Chemoradiation for Unresectable Pancreatic Cancer
Kelly, Patrick; Das, Prajnan; Pinnix, Chelsea C.; Beddar, Sam; Briere, Tina; Pham, Mary; Krishnan, Sunil; Delclos, Marc E.; Crane, Christopher H.
2013-03-01
Purpose: Improving local control is critical to improving survival and quality of life for patients with locally advanced unresectable pancreatic cancer (LAPC). However, previous attempts at radiation dose escalation have been limited by duodenal toxicity. In order to guide future studies, we analyzed the clinical and dosimetric factors associated with duodenal toxicity in patients undergoing fractionated chemoradiation for LAPC. Methods and Materials: Medical records and treatment plans of 106 patients with LAPC who were treated with chemoradiation between July 2005 and June 2010 at our institution were reviewed. All patients received neoadjuvant and concurrent chemotherapy. Seventy-eight patients were treated with conventional radiation to 50.4 Gy in 28 fractions; 28 patients received dose-escalated radiation therapy (range, 57.5-75.4 Gy in 28-39 fractions). Treatment-related toxicity was graded according to Common Terminology Criteria for Adverse Events, version 4.0. Univariate and multivariate analyses were performed to assess prognostic influence of clinical, pathologic, and treatment-related factors by using Kaplan-Meier and Cox regression methods. Results: Twenty patients had treatment-related duodenal toxicity events, such as duodenal inflammation, ulceration, and bleeding. Four patients had grade 1 events, 8 had grade 2, 6 had grade 3, 1 had grade 4, and 1 had grade 5. On univariate analysis, a toxicity grade ≥2 was associated with tumor location, low platelet count, an absolute volume (cm{sup 3}) receiving a dose of at least 55 Gy (V{sub 55} {sub Gy} > 1 cm{sup 3}), and a maximum point dose >60 Gy. Of these factors, only V{sub 55} {sub Gy} ≥1 cm{sup 3} was associated with duodenal toxicity on multivariate analysis (hazard ratio, 6.7; range, 2.0-18.8; P=.002). Conclusions: This study demonstrates that a duodenal V{sub 55} {sub Gy} >1 cm{sup 3} is an important dosimetric predictor of grade 2 or greater duodenal toxicity and establishes it as a
Reporting small bowel dose in cervix cancer high-dose-rate brachytherapy.
Liao, Yixiang; Dandekar, Virag; Chu, James C H; Turian, Julius; Bernard, Damian; Kiel, Krystyna
2016-01-01
Small bowel (SB) is an organ at risk (OAR) that may potentially develop toxicity after radiotherapy for cervix cancer. However, its dose from brachytherapy (BT) is not systematically reported as in other OARs, even with image-guided brachytherapy (IGBT). This study aims to introduce consideration of quantified objectives for SB in BT plan optimization and to evaluate the feasibility of sparing SB while maintaining adequate target coverage. In all, 13 patients were included in this retrospective study. All patients were treated with external beam radiotherapy (EBRT) 45Gy in 25 fractions followed by high dose rate (HDR)-BT boost of 28Gy in 4 fractions using tandem/ring applicator. Magnetic resonance imaging (MRI) and computed tomographic (CT) images were obtained to define the gross tumor volume (GTV), high-risk clinical target volume (HR-CTV) and OARs (rectum, bladder, sigmoid colon, and SB). Treatment plans were generated for each patient using GEC-ESTRO recommendations based on the first CT/MRI. Treatment plans were revised to reduce SB dose when the [Formula: see text] dose to SB was > 5Gy, while maintaining other OAR constraints. For the 7 patients with 2 sets of CT and MRI studies, the interfraction variation of the most exposed SB was analyzed. Plan revisions were done in 6 of 13 cases owing to high [Formula: see text] of SB. An average reduction of 19% in [Formula: see text] was achieved. Meeting SB and other OAR constraints resulted in less than optimal target coverage in 2 patients (D90 of HR-CTV < 77Gyαβ10). The highest interfraction variation was observed for SB at 16 ± 59%, as opposed to 28 ± 27% for rectum and 21 ± 16% for bladder. Prospective reporting of SB dose could provide data required to establish a potential correlation with radiation-induced late complication for SB. PMID:26235549
Bond, V.P.
1991-01-01
Although an enormous amount of progress has been made in the fields of radiation protection and risk assessment, a number of significant problems remain. The one problem which transcends all the rest, and which has been subject to considerable misunderstanding, involves what has come to be known as the 'linear non-threshold hypothesis', or 'linear hypothesis'. Particularly troublesome has been the interpretation that any amount of radiation can cause an increase in the excess incidence of cancer. The linear hypothesis has dominated radiation protection philosophy for more than three decades, with enormous financial, societal and political impacts and has engendered an almost morbid fear of low-level exposure to ionizing radiation in large segments of the population. This document presents a different interpretation of the linear hypothesis. The basis for this view lies in the evolution of dose-response functions, particularly with respect to their use initially in the context of early acute effects, and then for the late effects, carcinogenesis and mutagenesis. 11 refs., 4 figs. (MHB)
Stambaugh, Cassandra; Nelms, Benjamin E.; Dilling, Thomas; Stevens, Craig; Latifi, Kujtim; Zhang, Geoffrey; Moros, Eduardo; Feygelman, Vladimir
2013-09-15
Purpose: The effects of respiratory motion on the tumor dose can be divided into the gradient and interplay effects. While the interplay effect is likely to average out over a large number of fractions, it may play a role in hypofractionated [stereotactic body radiation therapy (SBRT)] treatments. This subject has been extensively studied for intensity modulated radiation therapy but less so for volumetric modulated arc therapy (VMAT), particularly in application to hypofractionated regimens. Also, no experimental study has provided full four-dimensional (4D) dose reconstruction in this scenario. The authors demonstrate how a recently described motion perturbation method, with full 4D dose reconstruction, is applied to describe the gradient and interplay effects during VMAT lung SBRT treatments.Methods: VMAT dose delivered to a moving target in a patient can be reconstructed by applying perturbations to the treatment planning system-calculated static 3D dose. Ten SBRT patients treated with 6 MV VMAT beams in five fractions were selected. The target motion (motion kernel) was approximated by 3D rigid body translation, with the tumor centroids defined on the ten phases of the 4DCT. The motion was assumed to be periodic, with the period T being an average from the empirical 4DCT respiratory trace. The real observed tumor motion (total displacement ≤8 mm) was evaluated first. Then, the motion range was artificially increased to 2 or 3 cm. Finally, T was increased to 60 s. While not realistic, making T comparable to the delivery time elucidates if the interplay effect can be observed. For a single fraction, the authors quantified the interplay effect as the maximum difference in the target dosimetric indices, most importantly the near-minimum dose (D{sub 99%}), between all possible starting phases. For the three- and five-fractions, statistical simulations were performed when substantial interplay was found.Results: For the motion amplitudes and periods obtained from
Voxel-Based Dose Reconstruction for Total Body Irradiation With Helical TomoTherapy
Chao Ming; Penagaricano, Jose; Yan Yulong; Moros, Eduardo G.; Corry, Peter; Ratanatharathorn, Vaneerat
2012-04-01
Purpose: We have developed a megavoltage CT (MVCT)-based dose reconstruction strategy for total body irradiation (TBI) with helical TomoTherapy (HT) using a deformable registration model to account for the patient's interfraction changes. The proposed technique serves as an efficient tool for delivered dose verification and, potentially, plan adaptation. Methods and Materials: Four patients with acute myelogenous leukemia treated with TBI using HT were selected for this study. The prescription was 12 Gy, 2 Gy/fraction, twice per day, given at least 6 h apart. The original plan achieved coverage of 80% of the clinical target volume (CTV) by the 12 Gy isodose surface. MVCTs were acquired prior to each treatment. Regions of interest were contoured on each MVCT. The dose for each fraction was calculated based on the MVCT using the HT planned adaptive station. B-spline deformable registration was conducted to establish voxel-to-voxel correspondence between the MVCT and the planning CT. The resultant deformation vector was employed to map the reconstructed dose from each fraction to the same point as the plan dose, and a voxel-to-voxel summed dose from all six fractions was obtained. The reconstructed dose distribution and its dosimetric parameters were compared with those of the original treatment plan. Results: While changes in CTV contours occurred in all patients, the reconstructed dose distribution showed that the dose-volume histogram for CTV coverage was close (<1.5%) to that of the original plan. For sensitive structures, the differences between the reconstructed and the planned doses were less than 3.0%. Conclusion: Voxel-based dose reconstruction strategy that takes into account interfraction anatomical changes using MVCTs is a powerful tool for treatment verification of the delivered doses. This proposed technique can also be applied to adaptive TBI therapy using HT.
Stereotactic fractionated radiotherapy for the treatment of benign meningiomas
Candish, Charles; McKenzie, Michael . E-mail: mmckenzi@bccancer.bc.edu; Clark, Brenda G.; Ma, Roy; Lee, Richard; Vollans, Emily; Robar, James; Gete, Ermias; Martin, Monty
2006-11-15
Purpose: To assess the use of stereotactic fractionated radiotherapy (SRT) for the treatment of meningiomas. Methods and Materials: Between April 1999 and October 2004, 38 patients underwent SRT. Of 34 patients (36 tumors) assessed, the median age was 53 years. The indication was primary treatment in 26 cases (no histology) and postoperative in 10 cases. The most common sites were cavernous sinus (17), optic nerve (6), and cerebellopontine angle (5). The median gross target volume and planning target volume were 8.9 cm{sup 3} and 18.9 cm{sup 3}, respectively. Stereotactic treatment was delivered with 6-MV photons with static conformal fields (custom-made blocks, 9 patients, and micromultileaf collimator, 25 patients). Median number of fields was six. The median dose prescribed was 50 Gy (range, 45-50.4 Gy) in 28 fractions. The median homogeneity and conformality indices were 1.1 and 1.79, respectively. Results: Treatment was well tolerated. Median follow-up was 26 months with 100% progression-free survival. One patient developed an area of possible radionecrosis related to previous radiotherapy, and 2 men developed mild hypogonadism necessitating testosterone replacement. The vision of 5 of 6 patients with optic pathway meningiomas improved or remained static. Conclusions: Stereotactic fractionated radiotherapy for the treatment of meningiomas is practical, and with early follow-up, seems to be effective.
Fractionated Proton Radiotherapy for Benign Cavernous Sinus Meningiomas
Slater, Jerry D.; Loredo, Lilia N.; Chung, Arthur; Bush, David A.; Patyal, Baldev; Johnson, Walter D.; Hsu, Frank P.K.; Slater, James M.
2012-08-01
Purpose: To evaluate the efficacy of fractionated proton radiotherapy for a population of patients with benign cavernous sinus meningiomas. Methods and Materials: Between 1991 and 2002, 72 patients were treated at Loma Linda University Medical Center with proton therapy for cavernous sinus meningiomas. Fifty-one patients had biopsy or subtotal resection; 47 had World Health Organization grade 1 pathology. Twenty-one patients had no histologic verification. Twenty-two patients received primary proton therapy; 30 had 1 previous surgery; 20 had more than 1 surgery. The mean gross tumor volume was 27.6 cm{sup 3}; mean clinical target volume was 52.9 cm{sup 3}. Median total doses for patients with and without histologic verification were 59 and 57 Gy, respectively. Mean and median follow-up periods were 74 months. Results: The overall 5-year actuarial control rate was 96%; the control rate was 99% in patients with grade 1 or absent histologic findings and 50% for those with atypical histology. All 21 patients who did not have histologic verification and 46 of 47 patients with histologic confirmation of grade 1 tumor demonstrated disease control at 5 years. Control rates for patients without previous surgery, 1 surgery, and 2 or more surgeries were 95%, 96%, and 95%, respectively. Conclusions: Fractionated proton radiotherapy for grade 1 cavernous sinus meningiomas achieves excellent control rates with minimal toxicities, regardless of surgical intervention or use of histologic diagnosis. Disease control for large lesions can be achieved by primary fractionated proton therapy.
2011-01-01
Background An advantage of the Intensity Modulated Radiotherapy (IMRT) technique is the feasibility to deliver different therapeutic dose levels to PTVs in a single treatment session using the Simultaneous Integrated Boost (SIB) technique. The paper aims to describe an automated tool to calculate the dose to be delivered with the SIB-IMRT technique in different anatomical regions that have the same Biological Equivalent Dose (BED), i.e. IsoBED, compared to the standard fractionation. Methods Based on the Linear Quadratic Model (LQM), we developed software that allows treatment schedules, biologically equivalent to standard fractionations, to be calculated. The main radiobiological parameters from literature are included in a database inside the software, which can be updated according to the clinical experience of each Institute. In particular, the BED to each target volume will be computed based on the alpha/beta ratio, total dose and the dose per fraction (generally 2 Gy for a standard fractionation). Then, after selecting the reference target, i.e. the PTV that controls the fractionation, a new total dose and dose per fraction providing the same isoBED will be calculated for each target volume. Results The IsoBED Software developed allows: 1) the calculation of new IsoBED treatment schedules derived from standard prescriptions and based on LQM, 2) the conversion of the dose-volume histograms (DVHs) for each Target and OAR to a nominal standard dose at 2Gy per fraction in order to be shown together with the DV-constraints from literature, based on the LQM and radiobiological parameters, and 3) the calculation of Tumor Control Probability (TCP) and Normal Tissue Complication Probability (NTCP) curve versus the prescribed dose to the reference target. PMID:21554675
Generalized hydrodynamic correlations and fractional memory functions
NASA Astrophysics Data System (ADS)
Rodríguez, Rosalio F.; Fujioka, Jorge
2015-12-01
A fractional generalized hydrodynamic (GH) model of the longitudinal velocity fluctuations correlation, and its associated memory function, for a complex fluid is analyzed. The adiabatic elimination of fast variables introduces memory effects in the transport equations, and the dynamic of the fluctuations is described by a generalized Langevin equation with long-range noise correlations. These features motivate the introduction of Caputo time fractional derivatives and allows us to calculate analytic expressions for the fractional longitudinal velocity correlation function and its associated memory function. Our analysis eliminates a spurious constant term in the non-fractional memory function found in the non-fractional description. It also produces a significantly slower power-law decay of the memory function in the GH regime that reduces to the well-known exponential decay in the non-fractional Navier-Stokes limit.
Possible isotopic fractionation effects in sputtered minerals
NASA Technical Reports Server (NTRS)
Haff, P. K.; Watson, C. C.; Tombrello, T. A.
1980-01-01
A model which makes definite predictions for the fractionation of isotopes in sputtered material is discussed. The fractionation patterns are nonlinear, and the pattern for a particular set of isotopes depends on the chemical matrix within which those isotopes are contained. Calculations are presented for all nonmonoisotopic elements contained in the minerals perovskite, anorthite, ackermanite, enstatite, and troilite. All isotopes are fractionated at the level of approximately 4-6 deg/o per atomic mass unit. Oxygen is always positively fractionated (heavier isotopes sputtered preferentially), and heavier elements are generally negatively fractioned (light isotopes sputtered preferentially). The value of Delta (O-18:O-16) is always less by about 1.8 deg/o than a linear extrapolation based upon the calculated delta (O-17:O-16) value would suggest. The phenomenon of both negative and positive fractionation patterns from a single target mineral are used to make an experimental test of the proposed model.
Alexander, Catherine P; Kirubakaran, C John Wesly; Michael, R Dinakaran
2010-11-01
The present paper describes the effect of water-soluble fraction of the leaves of the Indian medicinal plant, Tinospora cordifolia (Miers) on the non-specific immunity and disease resistance in Oreochromis mossambicus (Peters). Fish were intraperitoneally injected with 0, 6, 60 or 600 mg kg(-1) body weight, of the water soluble fraction. The non-specific humoral (lysozyme, antiprotease and complement) and cellular (production of reactive oxygen and nitrogen species and myeloperoxidase) responses and disease resistance against Aeromonas hydrophila were tested. All the doses of water-soluble fraction tested, significantly enhanced the serum lysozyme, antiprotease and natural haemolytic complement activities on most of the days tested. Similarly, all the doses of water-soluble fraction used, enhanced the cellular myeloperoxidase activity on all the days tested. The enhancement in the ROS and RNI production by peripheral blood leucocytes was observed on almost all the days tested, in most of the treated groups. All the doses of water-soluble fraction when administered as a single or double dose gave protection in terms of reduced percent mortality which is reflected in the increased Relative Percent Survival (RPS) values. The results clearly indicate the immunostimulatory and disease resistance properties of T. cordifolia leaf fraction and so its potential to be used as an immunoprophylactic in finfish aquaculture. PMID:20624469
Fractionated exposure of high energy iron ions has a sparing effect in vivo
NASA Astrophysics Data System (ADS)
Chang, P. Y.; Bakke, J.; Puey, A.
The radiation environment in deep space is complex and includes a broad spectrum of charged and highly energetic particle radiations. Exposure to these types of radiations may pose potential health risks in manned space missions. The detection of particle radiation-induced genomic alterations in vivo, particularly in slow or non-dividing tissues, is therefore important to provide relevant information in estimating risks. We are using a plasmid-based lacZ transgenic mouse model system to rapidly measure, in a statistically reliable way, the mutagenic potential of charged particle radiations relevant in the space environment. The lacZ transgenic mouse has been constructed so that every cell of the animal contains multiple copies of an integrated target reporter gene, allowing us to measure tissue-specific radiation-induced changes as a function of dosing regime. The nature of these mutations can also be characterized by restriction fragment length polymorphisms (RFLP). To examine the impact of dose protraction, animals were exposed to a single dose or daily fractions of 1 GeV/n iron ions. Cytotoxicity in the peripheral blood was measured by enumerating the frequency of circulating micronucleated reticulocytes (fMN-RET) in a time course from 24 h up to 1 week after completion of the radiation protocol. Brain and spleen tissues were harvested at 8 weeks after exposure and mutant frequencies (MF) in the transgene in these tissues were measured. Results from the fractionated protocol were compared to the responses obtained after the animals were exposed to the single dose treatment. We noted significantly lower levels of micronucleated reticulocytes in peripheral blood at 48 h after fractionated doses of iron ions when compared to the same total dose delivered in a single exposure demonstrating that protracted exposures of particle radiation resulted in an overall sparing effect in cytogenetic toxicity in the hematopoietic system in animals. Transgene mutation analysis
Single oral dose proportionality pharmacokinetics of almitrine bismesylate in humans.
Stavchansky, S; Doluisio, J T; Macleod, C M; Szalkowski, M B; Bachand, R T; Heilman, R; Sebree, T B; Geary, R S
1989-01-01
A single-blind study was conducted in 10 healthy male subjects. Each subject was tested with four single oral doses of capsules containing 25, 50, 100, 200mg almitrine bismesylate and one dose of placebo. Blood samples were drawn as a function of time and the concentration of almitrine in plasma was determined by gas chromatography utilizing nitrogen-phosphorus detection. Linear regression analysis of the data suggested that a deviation from linearity existed between the area under the plasma concentration time curves and the dose (R = 0.96). Linear analysis of the individual data indicates that a slight negative deviation from linearity is apparent for the 200 mg dose. The same trend was observed for the mean maximum almitrine plasma concentration, Cmax, which ranged from 38.9 +/- 11.8 to 286.2 +/- 99.1 ng ml-1 for the 25 and 200 mg dose, respectively. The time to peak was relatively constant regardless of the administered dose and ranged from 2.4 +/- 0.5 h to 2.8 +/- 0.8 h. Good agreement was obtained between the observed bioavailability parameters and those predicted from the nonlinear fit of the data. Further kinetic analysis of the data revealed mean total body clearance over fraction of dose absorbed ranging from 268.2 +/- 132.8 to 436.4 +/- 191.4 ml min-1 for doses 50 and 200mg, respectively. PMID:2566337
Unpacking the Division Interpretation of a Fraction
ERIC Educational Resources Information Center
Poon, Rebecca C.; Lewis, Priscilla Eide
2015-01-01
One of the challenges in learning fractions is understanding how and why a fraction can have multiple interpretations. As presented in one textbook, a fraction is "a symbol, such as 2/3, 5/1, or 8/5, used to name a part of a whole, a part of a set, a location on a number line, or a division of whole numbers" (Charles et al. 2012, p.…
Space–time fractional Zener wave equation
Atanackovic, T.M.; Janev, M.; Oparnica, Lj.; Pilipovic, S.; Zorica, D.
2015-01-01
The space–time fractional Zener wave equation, describing viscoelastic materials obeying the time-fractional Zener model and the space-fractional strain measure, is derived and analysed. This model includes waves with finite speed, as well as non-propagating disturbances. The existence and the uniqueness of the solution to the generalized Cauchy problem are proved. Special cases are investigated and numerical examples are presented. PMID:25663807
Complex order fractional derivatives in viscoelasticity
NASA Astrophysics Data System (ADS)
Atanacković, Teodor M.; Konjik, Sanja; Pilipović, Stevan; Zorica, Dušan
2016-06-01
We introduce complex order fractional derivatives in models that describe viscoelastic materials. This cannot be carried out unrestrictedly, and therefore we derive, for the first time, real valued compatibility constraints, as well as physical constraints that lead to acceptable models. As a result, we introduce a new form of complex order fractional derivative. Also, we consider a fractional differential equation with complex derivatives, and study its solvability. Results obtained for stress relaxation and creep are illustrated by several numerical examples.
Low-Dose Palliative Radiotherapy for Cutaneous B- and T-Cell Lymphomas
Neelis, Karen J. Schimmel, Erik C.; Vermeer, Maarten H.; Senff, Nancy J.; Willemze, Rein; Noordijk, Evert M.
2009-05-01
Purpose: To determine the efficacy of low-dose palliative radiotherapy for both low-grade malignant cutaneous B-cell lymphomas (CBCLs) and cutaneous T-cell lymphomas (mycosis fungoides). Methods and Materials: A total of 18 patients with low-grade CBCL (10 primary cutaneous marginal zone B-cell and 8 primary cutaneous follicle center lymphomas) with 44 symptomatic plaques and tumors underwent low-dose (4 Gy in two fractions) local radiotherapy. A total of 31 patients with mycosis fungoides were treated at 82 symptomatic sites, initially with 4 Gy and later with 8 Gy in two fractions. Results: The complete response rate for CBCL lesions was 72%. Of the 44 B-cell lymphoma lesions, 13 were re-treated to the same site after a median of 6.3 months because of persistent (n = 8) or recurrent (n = 5) symptomatic disease. Of the mycosis fungoides patients treated with 4 Gy in two fractions (17 lesions), 70% failed to respond. Increasing the dose to 8 Gy in two fractions yielded a complete response rate of 92% (60 of 65 lesions). The patients in whom low-dose radiotherapy failed were retreated with 20 Gy in eight fractions. Conclusion: Our results have demonstrated that low-dose involved-field radiotherapy induces a high response rate in both CBCL and cutaneous T-cell lymphoma lesions without any toxicity. Therefore, this treatment is now our standard palliative treatment. At progression, it is safe and feasible to apply greater radiation doses.
Delivery of formoterol from a novel multi-dose inhaler Airmax.
Zeng, X M; Jones, S; O'Leary, D; Phelan, M; Colledge, J
2002-06-01
Using a proprietary technology known as the X-ACT system--Active-metering, Cyclone-separator Technology, a novel multi-dose inhaler (Airmax) was developed to provide accurate and consistent dosing and a high-fine particle fraction ofthe drug. Formoterol, present as a blend with lactose monohydrate was delivered from Airmax to obtain a nominal formoterol dose of 6 or 12 microg. The devices were tested using a five-stage liquid impinger and a unit dose sampling apparatus, operated under conditions specified in European Pharmacopoeia (2000). Fine-particle dose (FPD) was defined as the dose of the aerosolized drug particles with an aerodynamic diameter < 5 microm and fine particle fraction (FPF) was the ratio of FPD to the total recovered dose. Dose per actuation was found to be 97.0+/-11.5% label claim (LC) or 5.8+/-0.7 microg (n = 140), and 100+/-9.4% LC or 12+/-1.1 microg (n=440), for the 6 and 12 microg strengths, respectively. The mass median aerodynamic diameter was 2.4+/-0.1 microm (n = 14), the geometric standard deviation 2.1+/-0.1 (n = 14), and FPF 44.4+/-24% (n= 14) for both strengths. Thus, the combination of active metering and cyclone separator produces highly consistent doses of formoterol that have a large respirable fraction. PMID:12117038
Soares, Raquel; Meireles, Manuela; Rocha, Ana; Pirraco, Ana; Obiol, Diego; Alonso, Eliana; Joos, Gisela; Balogh, Gabriela
2011-06-01
For many years mushrooms have been used empirically in traditional medicine to treat several diseases. Study of the maitake mushroom, with its immunomodulatory and antitumoral properties, has led to the isolation of several bioactive compounds. One of these, D fraction, is known to reduce tumor cell viability. This study examined the effect of isolated D fraction on viability and apoptosis of human breast cancer cells (MCF7). These cells were treated with maitake (D fraction) extract at 18 μg/mL, 36 μg/mL, 91 μg/mL, 183 μg/mL, or 367 μg/mL or were left untreated (control) for 24 hours. MCF7 incubation with the maitake extract resulted in decreased cell viability [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay] in a dose-dependent manner. Apoptosis was statistically significantly increased in a dose-dependent manner at every concentration tested (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling assay). Upon incubation with D fraction, a microarray assay revealed upregulation of BAK-1 and cytochrome c transcripts, 2 proteins directly involved in the apoptotic pathway. Reverse transcriptase polymerase chain reaction studies confirmed these findings; BAK-1 was one of most overexpressed gene, as observed by microarray assay. These findings confirm the apoptotic effect of maitake D fraction in breast cancer cells and further highlight the involvement of cytochrome c release to the cytoplasm. Cytoplasmic release of cytochrome c, another player in the apoptotic pathway, was also increased after incubation with D fraction in a dose-dependent manner. This finding indicates that the effect of this compound involves mitochondrial dysfunction. The identification of the molecular mechanisms by which D fraction exerts its effects is crucial for the development of preventive and therapeutic strategies for cancer. PMID:21480800
Response of human tumor cell lines in vitro to fractionated irradiation.
Matthews, J H; Meeker, B E; Chapman, J D
1989-01-01
The surviving fraction of human tumor cell lines after 2 Gy (SF2) varies between 0.1 and 0.8. It has been postulated that differences in inherent radiosensitivity of tumor cells are a major determinant of radiation response in vivo. Assays of inherent radiosensitivity based on acute survival are being developed as predictors of tumor response which often assume that the same inherent radiosensitivity persists throughout a fractionated treatment. We have investigated the response of 2 human tumor cell lines (A549 and MCF7) with different inherent radiosensitivities to in vitro fractionated irradiation. A549 cells had an SF2 of 0.62 and a mean inactivation dose (D) of 3.07 Gy whereas MCF7 cells had an SF2 of 0.30 and a D of 1.52 Gy. Split dose repair capacity (at equal survival levels) was less for A549 than for MCF7 cells and recovery kinetics for both cell lines were substantially longer than those of rodent cell lines. Survival after 5 fractions of 2 Gy given 12 hr apart at 37 degrees C was near to that predicted from the acute survival curve, assuming complete repair and no proliferation. Acute survival of A549 cells which survived 5 fractions of 2 Gy given 12 hr apart was similar to the acute survival of unirradiated cells. When A549 cells were incubated at 22 degrees C between 5 fractions of 2 Gy given 12 hr apart, proliferation and split dose repair were substantially inhibited. These studies support the proposals to use in vitro inherent radiosensitivity assays for the prediction of in vivo response of tumors to fractionated treatment. PMID:2912934
THEORETICAL AND EXPERIMENTAL ASPECTS OF ISOTOPIC FRACTIONATION.
O'Neil, James R.
1986-01-01
Essential to the interpretation of natural variations of light stable isotope ratios is knowledge of the magnitude and temperature dependence of isotopic fractionation factors between the common minerals and fluids. These fractionation factors are obtained in three ways: (1) Semi-empirical calculations using spectroscopic data and the methods of statistical mechanics. (2) Laboratory calibration studies. (3) Measurements of natural samples whose formation conditions are well-known or highly constrained. In this chapter methods (1) and (2) are evaluated and a review is given of the present state of knowledge of the theory of isotopic fractionation and the fraction that influence the isotopic properties of minerals.
The derivative of a continued fraction
Bowman, Kimiko o
2009-01-01
The paper considers second order continued fractions associated with (I) the Psi function {psi}(z), (II) the continued fraction component in ln {Gamma}(z) due to Stieltjes. The second order sequences k*{sub s}/k{sub s} provide approximants, some of which are remarkably close. In addition a series form for the convergent {chi}{sub s}={omega}{sub s} associated with a continued fraction provides an expression for the derivatives of a continued fraction. The implementation uses a Maple code for derivatives.
Fractionalized topological defects in optical lattices
NASA Astrophysics Data System (ADS)
Zhang, Xing-Hai; Fan, Wen-Jun; Shi, Jin-Wei; Kou, Su-Peng
2015-10-01
Topological objects are interesting topics in various fields of physics ranging from condensed matter physics to the grand unified and superstring theories. Among those, ultracold atoms provide a playground to study the complex topological objects. In this paper we present a proposal to realize an optical lattice with stable fractionalized topological objects. In particular, we generate the fractionalized topological fluxes and fractionalized skyrmions on two-dimensional optical lattices and fractionalized monopoles on three-dimensional optical lattices. These results offer a new approach to study the quantum many-body systems on optical lattices of ultracold quantum gases with controllable topological defects, including dislocations, topological fluxes and monopoles.
Control of Initialized Fractional-Order Systems
NASA Technical Reports Server (NTRS)
Hartly, Tom T.; Lorenzo, Carl F.
2002-01-01
Due to the importance of historical effects in fractional-order systems, this paper presents a general fractional-order control theory that includes the time-varying initialization response. Previous studies have not properly accounted for these historical effects. The initialization response, along with the forced response, for fractional-order systems is determined. Stability properties of fractional-order systems are presented in the complex Airplane, which is a transformation of the s-plane. Time responses are discussed with respect to pole positions in the complex Airplane and frequency response behavior is included. A fractional-order vector space representation, which is a generalization of the state space concept, is presented including the initialization response. Control methods for vector representations of initialized fractional-order systems are shown. Nyquist, root-locus, and other input-output control methods are adapted to the control of fractional-order systems. Finally, the fractional-order differintegral is generalized to continuous order-distributions that have the possibility of including a continuum of fractional orders in a system element.
On the entangled fractional squeezing transformation
NASA Astrophysics Data System (ADS)
Fan, Hong-Yi; Chen, Jun-Hua; Zhang, Peng-Fei
2015-04-01
We propose an entangled fractional squeezing transformation (EFrST) generated by using two mutually conjugate entangled state representations with the following operator: ; this transformation sharply contrasts the complex fractional Fourier transformation produced by using (see Front. Phys. DOI: 10.1007/s11467-014-0445-x). The EFrST is obtained by converting the triangular functions in the integration kernel of the usual fractional Fourier transformation into hyperbolic functions, i.e., tan α → tanh α and sin α → sinh α. The fractional property of the EFrST can be well described by virtue of the properties of the entangled state representations.
Oxygen isotope fractionation in double carbonates.
Zheng, Yong-Fei; Böttcher, Michael E
2016-01-01
Oxygen isotope fractionations in double carbonates of different crystal structures were calculated by the increment method. Synthesis experiments were performed at 60 °C and 100 °C to determine oxygen and carbon isotope fractionations involving PbMg[CO3]2. The calculations suggest that the double carbonates of calcite structure are systematically enriched in (18)O relative to those of aragonite and mixture structures. Internally consistent oxygen isotope fractionation factors are obtained for these minerals with respect to quartz, calcite and water at a temperature range of 0-1200 °C. The calculated fractionation factors for double carbonate-water systems are generally consistent with the data available from laboratory experiments. The experimentally determined fractionation factors for PbMg[CO3]2, BaMg[CO3]2 and CaMg[CO3]2 against H2O not only fall between fractionation factors involving pure carbonate end-members but are also close to the calculated fractionation factors. In contrast, experimentally determined carbon isotope fractionation factors between PbMg[CO3]2 and CO2 are much closer to theoretical predictions for the cerussite-CO2 system than for the magnesite-CO2 system, similar to the fractionation behavior for BaMg[CO3]2. Therefore, the combined theoretical and experimental results provide insights into the effects of crystal structure and exchange kinetics on oxygen isotope partitioning in double carbonates. PMID:25393769
Iwai, Hiroyuki; Matsuno, Etsuko ); Sasai, Keisuke; Abe, Mitsuyuki; Shibamoto, Yuta )
1994-06-15
In a clinical trial in which a 2-nitroimidazole radiosensitizer was administered repeatedly, the dose-limiting toxicity was found to be peripheral neuropathy. In the present study, the in vivo radiosensitizing activity of KU-2285 in combination with radiation dose fractionation, and the pharmacokinetics of cumulative dosing of KU-2285 in the peripheral nerves were examined. The ability of three nitroimidazoles, misonidazole (MISO), etanidazole (SR-2508) and KU-2285, to sensitize SCCVII tumors to radiation treatment has been compared for drug doses in the range 0-200 mg/kg. Single radiation doses or two different fractionation schedules (6 Gy/fractions [times] three fractions/48 h or 5 Gy/fractions [times] five fractions/48 h) were used; the tumor cell survival was determined using an in vivo/in vitro colony assay. The pharmacokinetics in the sciatic nerves were undertaken, when KU-2285 or etanidazole were injected at a dose of 200 mg/kg intravenously one, two, three, or four times at 2-h intervals. At less than 100 mg/kg, KU-2285 sensitized SCCVII tumors more than MISO and SR-2508 by fractionated irradiation. Evaluation of pharmacokinetics in the peripheral nerves showed that the apparent biological half-life of SR-2508 increased with the increases in the number of administrations, whereas that of KU-2285 became shorter. Since most clinical radiotherapy is given in small multiple fractions, KU-2285 appears to be a hypoxic cell radiosensitizer that could be useful in such regimens, and that poses no risk of chronic peripheral neurotoxicity. 12 refs., 5 figs., 1 tab.
NASA Astrophysics Data System (ADS)
Ng, J. A.; Booth, J.; Poulsen, P.; Kuncic, Z.; Keall, P. J.
2013-09-01
Kilovoltage intratreatment monitoring (KIM) is a novel real-time localization modality where the tumor position is continuously measured during intensity modulated radiation therapy (IMRT) or intensity modulated arc therapy (IMAT) by a kilovoltage (kV) x-ray imager. Adding kV imaging during therapy adds radiation dose. The additional effective dose is quantified for prostate radiotherapy and compared to dose from other localization modalities. The software PCXMC 2.0 was used to calculate the effective dose delivered to a phantom as a function of imager angle and field size for a Varian On-Board Imager. The average angular effective dose was calculated for a field size of 6 cm × 6 cm. The average angular effective dose was used in calculations for different treatment scenarios. Treatment scenarios considered were treatment type and fractionation. For all treatment scenarios, (i.e. conventionally fractionated and stereotactic body radiotherapy (SBRT), IMRT and IMAT), the total KIM dose at 1 Hz ranged from 2-10 mSv. This imaging dose is less than the Navotek radioactive implant dose (64 mSv) and a standard SBRT cone beam computed tomography pretreatment scan dose (22 mSv) over an entire treatment regime. KIM delivers an acceptably low effective dose for daily use as a real-time image-guidance method for prostate radiotherapy.
Low-dose radiation: a cause of breast cancer
Land, C.E.
1980-08-15
It is likely that the breast is the organ most sensitive to radiation carcinogenesis in postpubertal women. Studies of different exposed populations have yielded remarkably consistent results, in spite of wide differences in underlying breast cancer rates and conditions of exposure. Excess risk is approximately proportional to dose, and is relatively independent of ionization density and fractionization of dose. This implies that the risk associated with low-dose exposures to ionizing radiation can be estimated with some confidence from higher-dose data. Excess risk is heavily dependent on age at exposure but relatively independent of population differences in normal risk. The temporal patterns after exposure of both radiation-induced and naturally occurring breast cancer are similar, suggesting a strong influence of factors other than radiation on radiation-induced breast cancer. Uncertainties remain about risks from exposures before puberty and after menopause.
Kronenberg, S.; Siebentritt, C.R.
1981-07-28
A combined dose rate meter and charger unit therefor which does not require the use of batteries but on the other hand produces a charging potential by means of a piezoelectric cylinder which is struck by a manually triggered hammer mechanism. A tubular type electrometer is mounted in a portable housing which additionally includes a geiger-muller (Gm) counter tube and electronic circuitry coupled to the electrometer for providing multi-mode operation. In one mode of operation, an rc circuit of predetermined time constant is connected to a storage capacitor which serves as a timed power source for the gm tube, providing a measurement in terms of dose rate which is indicated by the electrometer. In another mode, the electrometer indicates individual counts.
A Fractional Variational Approach to the Fractional Basset-Type Equation
NASA Astrophysics Data System (ADS)
Baleanu, Dumitru; Garra, Roberto; Petras, Ivo
2013-08-01
In this paper we discuss an application of fractional variational calculus to the Basset-type fractional equations. It is well known that the unsteady motion of a sphere immersed in a Stokes fluid is described by an integro-differential equation involving derivative of real order. Here we study the inverse problem, i.e. we consider the problem from a Lagrangian point of view in the framework of fractional variational calculus. In this way we find an application of fractional variational methods to a classical physical model, finding a Basset-type fractional equation starting from a Lagrangian depending on derivatives of fractional order.
Estimation of the Dose and Dose Rate Effectiveness Factor
NASA Technical Reports Server (NTRS)
Chappell, L.; Cucinotta, F. A.
2013-01-01
Current models to estimate radiation risk use the Life Span Study (LSS) cohort that received high doses and high dose rates of radiation. Transferring risks from these high dose rates to the low doses and dose rates received by astronauts in space is a source of uncertainty in our risk calculations. The solid cancer models recommended by BEIR VII [1], UNSCEAR [2], and Preston et al [3] is fitted adequately by a linear dose response model, which implies that low doses and dose rates would be estimated the same as high doses and dose rates. However animal and cell experiments imply there should be curvature in the dose response curve for tumor induction. Furthermore animal experiments that directly compare acute to chronic exposures show lower increases in tumor induction than acute exposures. A dose and dose rate effectiveness factor (DDREF) has been estimated and applied to transfer risks from the high doses and dose rates of the LSS cohort to low doses and dose rates such as from missions in space. The BEIR VII committee [1] combined DDREF estimates using the LSS cohort and animal experiments using Bayesian methods for their recommendation for a DDREF value of 1.5 with uncertainty. We reexamined the animal data considered by BEIR VII and included more animal data and human chromosome aberration data to improve the estimate for DDREF. Several experiments chosen by BEIR VII were deemed inappropriate for application to human risk models of solid cancer risk. Animal tumor experiments performed by Ullrich et al [4], Alpen et al [5], and Grahn et al [6] were analyzed to estimate the DDREF. Human chromosome aberration experiments performed on a sample of astronauts within NASA were also available to estimate the DDREF. The LSS cohort results reported by BEIR VII were combined with the new radiobiology results using Bayesian methods.
Optimization of temporal dose modulation: Comparison of theory and experiment