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All sourcesNASA NTRSDOE OSTI
DOE OSTI2022

Comparison of All Solid Cancer Mortality and Incidence Dose-Response in the Life Span Study of Atomic Bomb Survivors, 1958–2009

Recent analysis of all solid cancer incidence (1958–2009) in the Life Span Study (LSS) revealed evidence of upward curvature in the radiation dose response among males but not females. Upward curvature in sex-averaged excess relative risk (ERR) for all solid cancer mortality (1950–2003) was also observed in the 0–2 Gy dose range. As reasons for non-linearity in the LSS are not completely understood, we conducted dose response analyses for all solid cancer mortality and incidence applying similar methods (1958–2009 follow-up, DS02R1 doses, including subjects notin-city (NIC) at the time of the bombing) and statistical models. Incident cancers were ascertained from Hiroshima and Nagasaki cancer registries, while cause of death was ascertained from death certificates over entire Japan. The study included 105,444 LSS subjects who were alive and not known to have cancer before Jan 1, 1958 (80,205 with dose estimates and 25,239 NIC subjects). Between 1958 and 2009, there were 3.1 million person-years (PY) and 22,538 solid cancers for incidence analysis and 3.8 million PY and 15,419 solid cancer deaths for mortality analysis. We fitted sex-specific ERR models adjusted for smoking to both types of data. Over the entire range of doses, solid cancer mortality dose response exhibited a borderline significant upward curvature among males (P=0.062) and significant upward curvature among females (P=0.010); for solid cancer incidence, as before, we found a significant upward curvature among males (P=0.001) but not among females (P=0.624). The sex difference in magnitude of dose response curvature was statistically significant for cancer incidence (P=0.017) but not for cancer mortality (P=0.781). The results of analyses in the 0–2 Gy range and restricted lower dose ranges generally supported inferences made about the sex-specific dose response shape over the entire range of doses for each outcome. Patterns of sex-specific curvature by calendar period (1958–1987 vs 1988–2009) and age at exposure (0–19 vs 20–83) varied between mortality and incidence data, particularly among females, although for each outcome there was an indication of curvature among 0–19 year old male survivors in both calendar periods and among 0–19 year old female survivors in the recent period. Collectively, our findings indicate that the upward curvature in all solid cancer dose response in the LSS is neither specific to males nor to incidence data; it appears to depend on composition of case series and age at exposure or time. Further follow-up and site-specific analyses of cancer mortality and incidence will be important to confirm the emerging trend in dose response curvature among young survivors and unveil the contributing factors and sites.

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTAN↗
DOE OSTI2021

Dose-Rate Effects of Protons and Light Ions for DNA Damage Induction, Survival and Transformation in Apparently Normal Primary Human Fibroblasts

In this work, we report on effects of low-dose exposures of accelerated protons delivered at high-dose rate (HDR) or a simulated solar-particle event (SPE) like low-dose rate (LDR) on immediate DNA damage induction and processing, survival and in vitro transformation of low passage NFF28 apparently normal primary human fibroblasts. Cultures were exposed to 50, 100 and 1,000 MeV monoenergetic protons in the Bragg entrance/plateau region and cesium-137 γ rays at 20 Gy/h (HDR) or 1 Gy/h (LDR). DNA double-strand breaks (DSB) and clustered DNA damages (containing oxypurines and abasic sites) were measured using transverse alternating gel electrophoresis (TAFE) and immunocytochemical detection/scoring of colocalized γ-H2AX pS139/53BP1 foci, with their induction being linear energy transfer (LET) dependent and dose-rate sparing observed for the different damage classes. Relative biological effectiveness (RBE) values for cell survival after proton irradiation at both dose-rates ranged from 0.61–0.73. Transformation RBE values were dose-rate dependent, ranging from ~1.8–3.1 and ~0.6–1.0 at low doses (≤30 cGy) for HDR and LDR irradiations, respectively. However peak transformation frequencies were significantly higher (1.3–7.3-fold) for higher doses of 0.5–1 Gy delivered at SPE-like LDR. Cell survival and transformation frequencies measured after low-dose 500 MeV/n He-4, 290 MeV/n C-12 and 600 MeV/n Si-28 ion irradiations also showed an inverse dose-rate effect for transformation at SPE-like LDR. This work demonstrates the existence of inverse dose-rate effects for proton and light-ion-induced postirradiation cell survival and in vitro transformation for space mission-relevant doses and dose rates.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS2010

Non-Targeted Effects and the Dose Response for Heavy Ion Tumorigenesis

BACKGROUND: There is no human epidemiology data available to estimate the heavy ion cancer risks experienced by astronauts in space. Studies of tumor induction in mice are a necessary step to estimate risks to astronauts. Previous experimental data can be better utilized to model dose response for heavy ion tumorigenesis and plan future low dose studies. DOSE RESPONSE MODELS: The Harderian Gland data of Alpen et al.[1-3] was re-analyzed [4] using non-linear least square regression. The data set measured the induction of Harderian gland tumors in mice by high-energy protons, helium, neon, iron, niobium and lanthanum with LET s ranging from 0.4 to 950 keV/micron. We were able to strengthen the individual ion models by combining data for all ions into a model that relates both radiation dose and LET for the ion to tumor prevalence. We compared models based on Targeted Effects (TE) to one motivated by Non-targeted Effects (NTE) that included a bystander term that increased tumor induction at low doses non-linearly. When comparing fitted models to the experimental data, we considered the adjusted R2, the Akaike Information Criteria (AIC), and the Bayesian Information Criteria (BIC) to test for Goodness of fit.In the adjusted R2test, the model with the highest R2values provides a better fit to the available data. In the AIC and BIC tests, the model with the smaller values of the summary value provides the better fit. The non-linear NTE models fit the combined data better than the TE models that are linear at low doses. We evaluated the differences in the relative biological effectiveness (RBE) and found the NTE model provides a higher RBE at low dose compared to the TE model. POWER ANALYSIS: The final NTE model estimates were used to simulate example data to consider the design of new experiments to detect NTE at low dose for validation. Power and sample sizes were calculated for a variety of radiation qualities including some not considered in the Harderian Gland data set and with different background tumor incidences. We considered different experimental designs with varying number of doses and varying low doses dependant on the LET of the radiation. The optimal design to detect a NTE for an individual ion had 4 doses equally spaced below a maximal dose where bending due to cell sterilization was < 2%. For example at 100 keV/micron we would irradiate at 0.03 Gy, 0.065 Gy, 0.13 Gy, and 0.26 Gy and require 850 mice including a control dose for a sensitivity to detect NTE with 80% power. Sample sizes could be improved by combining ions similar to the methods used with the Harderian Gland data.

Chappelli, Lori J.↗
DOE OSTI2015

Efficacy of a Radiation Absorbing Shield in Reducing Dose to the Interventionalist During Peripheral Endovascular Procedures: A Single Centre Pilot Study

PurposeThis prospective pilot study was undertaken to evaluate the feasibility and effectiveness of using a radiation absorbing shield to reduce operator dose from scatter during lower limb endovascular procedures.Materials and MethodsA commercially available bismuth shield system (RADPAD) was used. Sixty consecutive patients undergoing lower limb angioplasty were included. Thirty procedures were performed without the RADPAD (control group) and thirty with the RADPAD (study group). Two separate methods were used to measure dose to a single operator. Thermoluminescent dosimeter (TLD) badges were used to measure hand, eye, and unshielded body dose. A direct dosimeter with digital readout was also used to measure eye and unshielded body dose. To allow for variation between control and study groups, dose per unit time was calculated.ResultsTLD results demonstrated a significant reduction in median body dose per unit time for the study group compared with controls (p = 0.001), corresponding to a mean dose reduction rate of 65 %. Median eye and hand dose per unit time were also reduced in the study group compared with control group, however, this was not statistically significant (p = 0.081 for eye, p = 0.628 for hand). Direct dosimeter readings also showed statistically significant reduction in median unshielded body dose rate for the study group compared with controls (p = 0.037). Eye dose rate was reduced for the study group but this was not statistically significant (p = 0.142).ConclusionInitial results are encouraging. Use of the shield resulted in a statistically significant reduction in unshielded dose to the operator’s body. Measured dose to the eye and hand of operator were also reduced but did not reach statistical significance in this pilot study.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2015

A Measurement and Analysis of Buildup Region Dose for Open Field Photon Beams (Cobalt-60 through 24 MV)

The central axis depth dose in the build-up region (surface to d{sub max}) of single open field photon beams (cobalt-60 through 24 MV) has been measured utilizing parallel plate and extrapolation chamber methodology. These data were used to derive, for a prescription dose of 100 cGy, values of surface dose, the maximum value of dose along the central axis (D{sub max}) and the depth (nearest the surface) at which 90% of the prescription dose occurs (d{sub 90}). For both single and parallel opposed pair (POP) open field configurations, data are presented at field sizes of 5 × 5, 15 × 15 and 25 × 25 cm{sup 2} for prescription depths of 10, 15 and 20 cm (midplane for POP). For the treatment machines, field sizes, and prescription depths studied, it is possible to conclude that: for single open field irradiation, surface dose values (as a percentage of the prescription dose) can be either low (<10%) or comparable to the prescription dose itself; for POP open fields, surface dose values are relatively independent of photon energy and midplane depth, and range between 30% and 70% of prescription dose, being principally dependent on field size; the depth of the initial 90 cGy point for a prescription dose of 100 cGy, d{sub 90}, was larger for POP fields. For either single or POP open field treatments, d{sub 90} was always less than 22 mm, while for 6 MV or less, values of d{sub 90} were less than 4 mm; D{sub max} values can be very large (e.g., above 300 cGy) for certain treatment situations and are reduced significantly for POP treatments; for open field POP treatments, the percent reduction in D{sub max} with each increment in beam energy above 10 MV is reduced over that seen at 10 MV or less and, possibly, this further reduction may be clinically insignificant; for open field POP treatments, changes in surface dose, d{sub 90} and D{sub max} with beam energy above 10 MV do not suggest, with regard to these specific build-up curve parameters, any obvious advantage for treatment with beam energies greater than 10 MV for the specific machines and situations studied.

61 RADIATION PROTECTION AND DOSIMETRY↗
DOE OSTI2013

Dose to the Developing Dentition During Therapeutic Irradiation: Organ at Risk Determination and Clinical Implications

Purpose: Irradiation of pediatric facial structures can cause severe impairment of permanent teeth later in life. We therefore focused on primary and permanent teeth as organs at risk, investigating the ability to identify individual teeth in children and infants and to correlate dose distributions with subsequent dental toxicity. Methods and Materials: We retrospectively reviewed 14 pediatric patients who received a maximum dose >20 Gy(relative biological effectiveness, RBE) to 1 or more primary or permanent teeth between 2003 and 2009. The patients (aged 1-16 years) received spot-scanning proton therapy with 46 to 66 Gy(RBE) in 23 to 33 daily fractions for a variety of tumors, including rhabdomyosarcoma (n=10), sarcoma (n=2), teratoma (n=1), and carcinoma (n=1). Individual teeth were contoured on axial slices from planning computed tomography (CT) scans. Dose-volume histogram data were retrospectively obtained from total calculated delivered treatments. Dental follow-up information was obtained from external care providers. Results: All primary teeth and permanent incisors, canines, premolars, and first and second molars were identifiable on CT scans in all patients as early as 1 year of age. Dose-volume histogram analysis showed wide dose variability, with a median 37 Gy(RBE) per tooth dose range across all individuals, and a median 50 Gy(RBE) intraindividual dose range across all teeth. Dental follow-up revealed absence of significant toxicity in 7 of 10 patients but severe localized toxicity in teeth receiving >20 Gy(RBE) among 3 patients who were all treated at <4 years of age. Conclusions: CT-based assessment of dose distribution to individual teeth is feasible, although delayed calcification may complicate tooth identification in the youngest patients. Patterns of dental dose exposure vary markedly within and among patients, corresponding to rapid dose falloff with protons. Severe localized dental toxicity was observed in a few patients receiving the largest doses of radiation at the youngest ages; however, multiple factors including concurrent chemotherapy confounded the dose-effect relationship. Further studies with larger cohorts and appropriate controls will be required.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2014

Dependence of Coronary 3-Dimensional Dose Maps on Coronary Topologies and Beam Set in Breast Radiation Therapy: A Study Based on CT Angiographies

Purpose: In left-side breast radiation therapy (RT), doses to the left main (LM) and left anterior descending (LAD) coronary arteries are usually assessed after delineation by prior anatomic knowledge on the treatment planning computed tomography (CT) scan. In this study, dose sensitivity due to interindividual coronary topology variation was assessed, and hot spots were located. Methods and Materials: Twenty-two detailed heart models, created from heart computed tomography angiographies, were fitted into a single representative female thorax. Two breast RT protocols were then simulated into a treatment planning system: the first protocol comprised tangential and tumoral bed beams (TGs{sub T}B) at 50 + 16 Gy, the second protocol added internal mammary chain beams at 50 Gy to TGs{sub T}B (TGs{sub T}B{sub I}MC). For the heart, the LAD, and the LM, several dose indicators were calculated: dose-volume histograms, mean dose (D{sub mean}), minimal dose received by the most irradiated 2% of the volume (D{sub 2%}), and 3-dimensional (3D) dose maps. Variations of these indicators with anatomies were studied. Results: For the LM, the intermodel dispersion of D{sub mean} and D{sub 2%} was 10% and 11%, respectively, with TGs{sub T}B and 40% and 80%, respectively, with TGs{sub T}B{sub I}MC. For the LAD, these dispersions were 19% (D{sub mean}) and 49% (D{sub 2%}) with TGs{sub T}B and 35% (D{sub mean}) and 76% (D{sub 2%}) with TGs{sub T}B{sub I}MC. The 3D dose maps revealed that the internal mammary chain beams induced hot spots between 20 and 30 Gy on the LM and the proximal LAD for some coronary topologies. Without IMC beams, hot spots between 5 and 26 Gy are located on the middle and distal LAD. Conclusions: Coronary dose distributions with hot spot location and dose level can change significantly depending on coronary topology, as highlighted by 3D coronary dose maps. In clinical practice, coronary imaging may be required for a relevant coronary dose assessment, especially in cases of internal mammary chain irradiation.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2015

Dose Response for Radiation Cataractogenesis: A Meta-Regression of Hematopoietic Stem Cell Transplantation Regimens

Purpose/Objective(s): To perform a meta-regression on published data and to model the 5-year probability of cataract development after hematopoietic stem cell transplantation (HSCT) with and without total body irradiation (TBI). Methods and Materials: Eligible studies reporting cataract incidence after HSCT with TBI were identified by a PubMed search. Seventeen publications provided complete information on radiation dose schedule, fractionation, dose rate, and actuarial cataract incidence. Chemotherapy-only regimens were included as zero radiation dose regimens. Multivariate meta-regression with a weighted generalized linear model was used to model the 5-year cataract incidence and contributory factors. Results: Data from 1386 patients in 21 series were included for analysis. TBI was administered to a total dose of 0 to 15.75 Gy with single or fractionated schedules with a dose rate of 0.04 to 0.16 Gy/min. Factors significantly associated with 5-year cataract incidence were dose, dose times dose per fraction (D•dpf), pediatric versus adult status, and the absence of an ophthalmologist as an author. Dose rate, graft versus host disease, steroid use, hyperfractionation, and number of fractions were not significant. Five-fold internal cross-validation showed a model validity of 83% ± 8%. Regression diagnostics showed no evidence of lack-of-fit and no patterns in the studentized residuals. The α/β ratio from the linear quadratic model, estimated as the ratio of the coefficients for dose and D•dpf, was 0.76 Gy (95% confidence interval [CI], 0.05-1.55). The odds ratio for pediatric patients was 2.8 (95% CI, 1.7-4.6) relative to adults. Conclusions: Dose, D•dpf, pediatric status, and regimented follow-up care by an ophthalmologist were predictive of 5-year cataract incidence after HSCT. The low α/β ratio indicates the importance of fractionation in reducing cataracts. Dose rate effects have been observed in single institution studies but not in the combined data analyzed here. Although data were limited to articles with 5-year actuarial estimates, the development of radiation-induced cataracts extends beyond this time.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2015

Impact of Fractionation and Dose in a Multivariate Model for Radiation-Induced Chest Wall Pain

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.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

Dose and Fractionation in Radiation Therapy of Curative Intent for Non-Small Cell Lung Cancer: Meta-Analysis of Randomized Trials

Purpose: The optimum dose and fractionation in radiation therapy of curative intent for non-small cell lung cancer remains uncertain. We undertook a published data meta-analysis of randomized trials to examine whether radiation therapy regimens with higher time-corrected biologically equivalent doses resulted in longer survival, either when given alone or when given with chemotherapy. Methods and Materials: Eligible studies were randomized comparisons of 2 or more radiation therapy regimens, with other treatments identical. Median survival ratios were calculated for each comparison and pooled. Results: 3795 patients in 25 randomized comparisons of radiation therapy dose were studied. The median survival ratio, higher versus lower corrected dose, was 1.13 (95% confidence interval [CI] 1.04-1.22) when radiation therapy was given alone and 0.83 (95% CI 0.71-0.97) when it was given with concurrent chemotherapy (P for difference=.001). In comparisons of radiation therapy given alone, the survival benefit increased with increasing dose difference between randomized treatment arms (P for trend=.004). The benefit increased with increasing dose in the lower-dose arm (P for trend=.01) without reaching a level beyond which no further survival benefit was achieved. The survival benefit did not differ significantly between randomized comparisons where the higher-dose arm was hyperfractionated and those where it was not. There was heterogeneity in the median survival ratio by geographic region (P<.001), average age at randomization (P<.001), and year trial started (P for trend=.004), but not for proportion of patients with squamous cell carcinoma (P=.2). Conclusions: In trials with concurrent chemotherapy, higher radiation therapy doses resulted in poorer survival, possibly caused, at least in part, by high levels of toxicity. Where radiation therapy was given without chemotherapy, progressively higher radiation therapy doses resulted in progressively longer survival, and no upper dose level was found above which there was no further benefit. These findings support the consideration of further radiation therapy dose escalation trials, making use of modern treatment methods to reduce toxicity.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2024

Fundamentals of wildlife dosimetry and lessons learned from a decade of measuring external dose rates in the field

Methods for determining the radiation dose received by exposed biota require major improvements to reduce uncertainties and increase precision. We share our experiences in attempting to quantify external dose rates to free-ranging wildlife using GPS-coupled dosimetry methods. The manuscript is a primer on fundamental concepts in wildlife dosimetry in which the complexities of quantifying dose rates are highlighted, and lessons learned are presented based on research with wild boar and snakes at Fukushima, wolves at Chornobyl, and reindeer in Norway. GPS-coupled dosimeters produced empirical data to which numerical simulations of external dose using computer software were compared. Our data did not support a standing paradigm in risk analyses: Using averaged soil contaminant levels to model external dose rates conservatively overestimate the dose to individuals within a population. Following this paradigm will likely lead to misguided recommendations for risk management. The GPS-dosimetry data also demonstrated the critical importance of how modeled external dose rates are impacted by the scale at which contaminants are mapped. When contaminant mapping scales are coarse even detailed knowledge about each animal’s home range was inadequate to accurately predict external dose rates. Importantly, modeled external dose rates based on a single measurement at a trap site did not correlate to actual dose rates measured on free ranging animals. These findings provide empirical data to support published concerns about inadequate dosimetry in much of the published Chernobyl and Fukushima dose-effects research. Furthermore, our data indicate that a huge portion of that literature should be challenged, and that improper dosimetry remains a significant source of controversy in radiation dose-effect research.

61 RADIATION PROTECTION AND DOSIMETRY↗
DOE OSTI2017

Influence of computed tomography contrast agent on radiotherapy dose calculation for pancreatic carcinoma: A dosimetric study based on tomotherapy and volumetric-modulated arc therapy techniques

The main purpose of our investigation was to quantify the dosimetric influence of intravenous contrast agent for pancreatic cancer radiotherapy treatment. This study focused on complex modulated irradiation techniques of tomotherapy (TOMO) and volumetric-modulated arc therapy (VMAT) to investigate if novel conformal treatment methods could reduce the influence of contrast agent. In our study, patients with pancreatic cancer were enrolled to have 2 computed tomography (CT) scans in the same position without and with intravenous contrast agent for treatment planning. Then tumors and organ at risks were countered on contrast-enhanced CT (CECT) images. Each patient's CECT was assigned a TOMO plan and a VMAT plan. Then these plans were copied onto the non-CECT image and dose distribution was calculated with the same algorithm and structure sets. Finally, the dose distribution and the dose difference were analyzed for the target volume and organs at risk between the 2 sets of images. The statistic dosimetric result showed that for both TOMO and VMAT, no significant dose difference between CECT and non-CECT-based plan was observed. Dose difference was clinically negligible because the average relative percentage dose difference was 1% ± 1% for target volume, except a blurring effect at the higher dose region of the target volume. It implied that intravenous contrast agent will not affect dose calculation for pancreatic cancer radiotherapy significantly. Also the dose deviation based on TOMO showed no statistical difference compared with that on VMAT. For both superposition/conversation algorithm used by TOMO and Monte Carlo algorithm used by VMAT, the dosimetric difference was nonsignificant. A full analysis demonstrated a negligible dose difference of less than 1% between CECT-based plan and non-CECT-based plan. Therefore, contrast-enhanced CT image can be used directly for dose calculation of TOMO and VMAT plans for pancreatic cancer. It is unnecessary to scan twice then make a fusion of CECT and non-CECT, which would result to additional unnecessary radiation dose to patient and decrease work efficiency.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2013

Dosimetric evaluation of photon dose calculation under jaw and MLC shielding

Purpose: The accuracy of photon dose calculation algorithms in out-of-field regions is often neglected, despite its importance for organs at risk and peripheral dose evaluation. The present work has assessed this for the anisotropic analytical algorithm (AAA) and the Acuros-XB algorithms implemented in the Eclipse treatment planning system. Specifically, the regions shielded by the jaw, or the MLC, or both MLC and jaw for flattened and unflattened beams have been studied.Methods: The accuracy in out-of-field dose under different conditions was studied for two different algorithms. Measured depth doses out of the field, for different field sizes and various distances from the beam edge were compared with the corresponding AAA and Acuros-XB calculations in water. Four volumetric modulated arc therapy plans (in the RapidArc form) were optimized in a water equivalent phantom, PTW Octavius, to obtain a region always shielded by the MLC (or MLC and jaw) during the delivery. Doses to different points located in the shielded region and in a target-like structure were measured with an ion chamber, and results were compared with the AAA and Acuros-XB calculations. Photon beams of 6 and 10 MV, flattened and unflattened were used for the tests.Results: Good agreement between calculated and measured depth doses was found using both algorithms for all points measured at depth greater than 3 cm. The mean dose differences (±1SD) were −8%± 16%, −3%± 15%, −16%± 18%, and −9%± 16% for measurements vs AAA calculations and −10%± 14%, −5%± 12%, −19%± 17%, and −13%± 14% for Acuros-XB, for 6X, 6 flattening-filter free (FFF), 10X, and 10FFF beams, respectively. The same figures for dose differences relative to the open beam central axis dose were: −0.1%± 0.3%, 0.0%± 0.4%, −0.3%± 0.3%, and −0.1%± 0.3% for AAA and −0.2%± 0.4%, −0.1%± 0.4%, −0.5%± 0.5%, and −0.3%± 0.4% for Acuros-XB. Buildup dose was overestimated with AAA, while Acuros-XB gave results more consistent with measurements. From RapidArc plan analysis the average difference between calculation and measurement in the shielded region was −0.3%± 0.4% and −2.5%± 1.2% for AAA and Acuros-XB, respectively, relative to the mean target dose value (1.6%± 2.3%, −12.7%± 4.0% if relative to each local value). These values were compared with the corresponding differences in the target structure: −0.7%± 2.3% for AAA, and −0.5%± 2.3% for Acuros-XB.Conclusions: The two algorithms analyzed showed encouraging results in predicting out-of-field region dose for clinical use.

61 RADIATION PROTECTION AND DOSIMETRY↗
DOE OSTI2013

Patient dose simulations for scanning-beam digital x-ray tomosynthesis of the lungs

Purpose: An improved method of image guidance for lung tumor biopsies could help reduce the high rate of false negatives. The aim of this work is to optimize the geometry of the scanning-beam digital tomography system (SBDX) for providing real-time 3D tomographic reconstructions for target verification. The unique geometry of the system requires trade-offs between patient dose, imaging field of view (FOV), and tomographic angle.Methods: Tomosynthetic angle as a function of tumor-to-detector distance was calculated. Monte Carlo Software (PCXMC) was used to calculate organ doses and effective dose for source-to-detector distances (SDDs) from 90 to 150 cm, patient locations with the tumor at 20 cm from the source to 20 cm from the detector, and FOVs centered on left lung and right lung as well as medial and distal peripheries of the lungs. These calculations were done for two systems, a SBDX system and a GE OEC-9800 C-arm fluoroscopic unit. To evaluate the dose effect of the system geometry, results from PCXMC were calculated using a scan of 300 mAs for both SBDX and fluoroscopy. The Rose Criterion was used to find the fluence required for a tumor SNR of 5, factoring in scatter, air-gap, system geometry, and patient position for all models generated with PCXMC. Using the calculated fluence for constant tumor SNR, the results from PCXMC were used to compare the patient dose for a given SNR between SBDX and fluoroscopy.Results: Tomographic angle changes with SDD only in the region near the detector. Due to their geometry, the source array and detector have a peak tomographic angle for any given SDD at a source to tumor distance that is 69.7% of the SDD assuming constant source and detector size. Changing the patient location in order to increase tomographic angle has a significant effect on organ dose distribution due to geometrical considerations. With SBDX and fluoroscopy geometries, the dose to organs typically changes in an opposing manner with changing patient location. When tumor SNR is held constant (i.e., x-ray fluence is scaled appropriately), SBDX gives 2–10 times less dose than fluoroscopy for the same conditions within the typical range of patient locations. The relative position of the patient (as a percent of SDD) has a much more significant impact on dose than either SDD or patient position. The patient position providing the minimum dose for a given tumor SNR and SDD is approximately the same as the position of maximum tomographic angle.Conclusions: SBDX offers a significant dose advantage over currently used C-arm fluoroscopy. The patient location with lowest dose coincides with the location of maximum tomographic angle. In order to provide adequate space for the patient and for the pulmonologists’ equipment, a SDD of 100 cm is recommended.

61 RADIATION PROTECTION AND DOSIMETRY↗
DOE OSTI2014

SU-E-T-29: A Web Application for GPU-Based Monte Carlo IMRT/VMAT QA with Delivered Dose Verification

Purpose: To enable an existing web application for GPU-based Monte Carlo (MC) 3D dosimetry quality assurance (QA) to compute “delivered dose” from linac logfile data. Methods: We added significant features to an IMRT/VMAT QA web application which is based on existing technologies (HTML5, Python, and Django). This tool interfaces with python, c-code libraries, and command line-based GPU applications to perform a MC-based IMRT/VMAT QA. The web app automates many complicated aspects of interfacing clinical DICOM and logfile data with cutting-edge GPU software to run a MC dose calculation. The resultant web app is powerful, easy to use, and is able to re-compute both plan dose (from DICOM data) and delivered dose (from logfile data). Both dynalog and trajectorylog file formats are supported. Users upload zipped DICOM RP, CT, and RD data and set the expected statistic uncertainty for the MC dose calculation. A 3D gamma index map, 3D dose distribution, gamma histogram, dosimetric statistics, and DVH curves are displayed to the user. Additional the user may upload the delivery logfile data from the linac to compute a 'delivered dose' calculation and corresponding gamma tests. A comprehensive PDF QA report summarizing the results can also be downloaded. Results: We successfully improved a web app for a GPU-based QA tool that consists of logfile parcing, fluence map generation, CT image processing, GPU based MC dose calculation, gamma index calculation, and DVH calculation. The result is an IMRT and VMAT QA tool that conducts an independent dose calculation for a given treatment plan and delivery log file. The system takes both DICOM data and logfile data to compute plan dose and delivered dose respectively. Conclusion: We sucessfully improved a GPU-based MC QA tool to allow for logfile dose calculation. The high efficiency and accessibility will greatly facilitate IMRT and VMAT QA.

07 ISOTOPE AND RADIATION SOURCES↗
DOE OSTI2014

SU-E-T-356: Accuracy of Eclipse Electron Macro Monte Carlo Dose Algorithm for Use in Bolus Electron Conformal Therapy

Purpose: To evaluate the accuracy of electron dose distribution calculated by the Varian Eclipse electron Monte Carlo (eMC) algorithm for use with recent commercially available bolus electron conformal therapy (ECT). Methods: eMC-calculated electron dose distributions for bolus ECT have been compared to those previously measured for cylindrical phantoms (retromolar trigone and nose), whose axial cross sections were based on the mid-PTV CT anatomy for each site. The phantoms consisted of SR4 muscle substitute, SR4 bone substitute, and air. The bolus ECT treatment plans were imported into the Eclipse treatment planning system and calculated using the maximum allowable histories (2×10{sup 9}), resulting in a statistical error of <0.2%. Smoothing was not used for these calculations. Differences between eMC-calculated and measured dose distributions were evaluated in terms of absolute dose difference as well as distance to agreement (DTA). Results: Results from the eMC for the retromolar trigone phantom showed 89% (41/46) of dose points within 3% dose difference or 3 mm DTA. There was an average dose difference of −0.12% with a standard deviation of 2.56%. Results for the nose phantom showed 95% (54/57) of dose points within 3% dose difference or 3 mm DTA. There was an average dose difference of 1.12% with a standard deviation of 3.03%. Dose calculation times for the retromolar trigone and nose treatment plans were 15 min and 22 min, respectively, using 16 processors (Intel Xeon E5-2690, 2.9 GHz) on a Varian Eclipse framework agent server (FAS). Results of this study were consistent with those previously reported for accuracy of the eMC electron dose algorithm and for the .decimal, Inc. pencil beam redefinition algorithm used to plan the bolus. Conclusion: These results show that the accuracy of the Eclipse eMC algorithm is suitable for clinical implementation of bolus ECT.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

WE-D-BRE-06: Quantification of Dose-Response for High Grade Esophagtis Patients Using a Novel Voxel-To-Voxel Method

Purpose: Radiation induces an inflammatory response in the esophagus, discernible on CT studies. This work objectively quantifies the voxel esophageal radiation-response for patients with acute esophagitis. This knowledge is an important first-step towards predicting the effect of complex dose distributions on patient esophagitis symptoms. Methods: A previously validated voxel-based methodology of quantifying radiation esophagitis severity was used to identify the voxel dose-response for 18 NSCLC patients with severe esophagitis (CTCAE grading criteria, grade2 or higher). The response is quantified as percent voxel volume change for a given dose. During treatment (6–8 weeks), patients had weekly 4DCT studies and esophagitis scoring. Planning CT esophageal contours were deformed to each weekly CT using a demons DIR algorithm. An algorithm using the Jacobian Map from the DIR of the planning CT to all weekly CTs was used to quantify voxel-volume change, along with corresponding delivered voxel dose, to the planning voxel. Dose for each voxel for each time-point was calculated on each previous weekly CT image, and accumulated using DIR. Thus, for each voxel, the volume-change and delivered dose was calculated for each time-point. The data was binned according to when the volume-change first increased by a threshold volume (10%–100%, in 10% increments), and the average delivered dose calculated for each bin. Results: The average dose resulting in a voxel volume increase of 10–100% was 21.6 to 45.9Gy, respectively. The mean population dose to give a 50% volume increase was 36.3±4.4Gy, (range:29.8 to 43.5Gy). The average week of 50% response was 4.1 (range:4.9 to 2.8 weeks). All 18 patients showed similar dose to first response curves, showing a common trend in the initial inflammatoryresponse. Conclusion: We extracted the dose-response curve of the esophagus on a voxel-to-voxel level. This may be useful for estimating the esophagus response (and patient symptoms) to complicated dose distributions.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

WE-E-BRE-04: Dual Focal Spot Dose Painting for Precision Preclinical Radiobiological Investigations

Purpose: Recent progress in small animal radiotherapy systems has provided the foundation for delivering the heterogeneous, millimeter scale dose distributions demanded by preclinical radiobiology investigations. Despite advances in preclinical dose planning, delivery of highly heterogeneous dose distributions is constrained by the fixed collimation systems and large x-ray focal spot common in small animal radiotherapy systems. This work proposes a dual focal spot dose optimization and delivery method with a large x-ray focal spot used to deliver homogeneous dose regions and a small focal spot to paint spatially heterogeneous dose regions. Methods: Two-dimensional dose kernels were measured for a 1 mm circular collimator with radiochromic film at 10 mm depth in a solid water phantom for the small and large x-ray focal spots on a recently developed small animal microirradiator. These kernels were used in an optimization framework which segmented a desired dose distribution into low- and high-spatial frequency regions for delivery by the large and small focal spot, respectively. For each region, the method determined an optimal set of stage positions and beam-on times. The method was demonstrated by optimizing a bullseye pattern consisting of 0.75 mm radius circular target and 0.5 and 1.0 mm wide rings alternating between 0 and 2 Gy. Results: Compared to a large focal spot technique, the dual focal spot technique improved the optimized dose distribution: 69.2% of the optimized dose was within 0.5 Gy of the intended dose for the large focal spot, compared to 80.6% for the dual focal spot method. The dual focal spot design required 14.0 minutes of optimization, and will require 178.3 minutes for automated delivery. Conclusion: The dual focal spot optimization and delivery framework is a novel option for delivering conformal and heterogeneous dose distributions at the preclinical level and provides a new experimental option for unique radiobiological investigations. Funding Support: this work is supported by funding the National Sciences and Engineering Research Council of Canada, and a Mitacs-accelerate fellowship. Conflict of Interest: Dr. Lindsay and Dr. Jaffray are listed as inventors of the small animal microirradiator described herein. This system has been licensed for commercial development.

60 APPLIED LIFE SCIENCES↗