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Passive exposures of children to volatile trihalomethanes during domestic cleaning activities of their parents

Domestic cleaning has been proposed as a determinant of trihalomethanes (THMs) exposure in adult females. We hypothesized that parental housekeeping activities could influence children's passive exposures to THMs from their mere physical presence during domestic cleaning. In a recent cross-sectional study (n=382) in Cyprus [41 children (<18y) and 341 adults (≥18y)], we identified 29 children who met the study's inclusion criteria. Linear regression models were applied to understand the association between children sociodemographic variables, their individual practices influencing ingestion and noningestion exposures to ΣTHMs, and their urinary THMs levels. Among the children-specific variables, age alone showed a statistically significant inverse association with their creatinine-adjusted urinary ΣTHMs (r{sub S}=−0.59, p<0.001). A positive correlation was observed between urinary ΣTHMs (ng g{sup −1}) of children and matched-mothers (r{sub S}=0.52, p=0.014), but this was not the case for their matched-fathers (r{sub S}=0.39, p=0.112). Time spent daily by the matched-mothers for domestic mopping, toilet and other cleaning activities using chlorine-based cleaning products was associated with their children's urinary THMs levels (r{sub S}=0.56, p=0.007). This trend was not observed between children and their matched-fathers urinary ΣTHMs levels, because of minimum amount of time spent by the latter in performing domestic cleaning. The proportion of variance of creatinine-unadjusted and adjusted urinary ΣTHMs levels in children that was explained by the matched-mothers covariates was 76% and 74% (p<0.001), respectively. A physiologically-based pharmacokinetic model adequately predicted urinary chloroform excretion estimates, being consistent with the corresponding measured levels. Our findings highlighted the influence of mothers' domestic cleaning activities towards enhancing passive THMs exposures of their children. The duration of such activities could be further tested as a valid indicator of children's THMs body burden. - Highlights: • First report on THMs exposure assessment in matched parents and children. • Duration of domestic cleaning by mothers influenced passive exposure to THMs in children. • Matched-fathers did little cleaning and thereby no contribution to passive exposure to THMs in children. • Reverse dosimetry showed a good agreement between predicted and observed urinary chloroform. • Passive exposures to THMs require new attention in survey questionnaires and epidemiology.

54 ENVIRONMENTAL SCIENCES↗

Lung cancer risk of airborne particles for Italian population

Airborne particles, including both ultrafine and supermicrometric particles, contain various carcinogens. Exposure and risk-assessment studies regularly use particle mass concentration as dosimetry parameter, therefore neglecting the potential impact of ultrafine particles due to their negligible mass compared to supermicrometric particles. The main purpose of this study was the characterization of lung cancer risk due to exposure to polycyclic aromatic hydrocarbons and some heavy metals associated with particle inhalation by Italian non-smoking people. A risk-assessment scheme, modified from an existing risk model, was applied to estimate the cancer risk contribution from both ultrafine and supermicrometric particles. Exposure assessment was carried out on the basis of particle number distributions measured in 25 smoke-free microenvironments in Italy. The predicted lung cancer risk was then compared to the cancer incidence rate in Italy to assess the number of lung cancer cases attributed to airborne particle inhalation, which represents one of the main causes of lung cancer, apart from smoking. Ultrafine particles are associated with a much higher risk than supermicrometric particles, and the modified risk-assessment scheme provided a more accurate estimate than the conventional scheme. Great attention has to be paid to indoor microenvironments and, in particular, to cooking and eating times, which represent the major contributors to lung cancer incidence in the Italian population. The modified risk assessment scheme can serve as a tool for assessing environmental quality, as well as setting up exposure standards for particulate matter. - Highlights: • Lung cancer risk for non-smoking Italian population due to particle inhalation. • The average lung cancer risk for Italian population is equal to 1.90×10{sup −2}. • Ultrafine particle is the aerosol metric mostly contributing to lung cancer risk. • B(a)P is the main (particle-bounded) compound contributing to lung cancer risk. • Cooking activities represent the principal contributor to the lung cancer risk.

54 ENVIRONMENTAL SCIENCES↗

Comparing dietary and non-dietary source contribution of BPA and DEHP to prenatal exposure: A Catalonia (Spain) case study

Highlights: • Comparing dietary and non-dietary prenatal exposure to BPA and DEHP. • PBPK model predict the fetus’ toxicokinetic profile based on mother exposure. • Non-diet sources exposure contribution is smaller than diet sources. • First-pass metabolism is lacking in dermal and inhalation exposure. • More unconjugated BPA is expected due to a lack of the first-pass metabolism. Bisphenol A (BPA) and Di-(2-ethylhexyl) phthalate (DEHP) are two wide spread chemicals classified as endocrine disruptors (ED). The present study aims to estimate the non-dietary (dermal, non-dietary ingestion and inhalation) exposure to BPA and DEHP for a pregnant women cohort. In addition, to assess the prenatal exposure for the fetus, a physiologically based pharmacokinetic (PBPK) model was used. It was adapted for pregnancy in order to assess the internal dosimetry levels of EDs (BPA and DEHP) in the fetus. Estimates of exposure to BPA and DEHP from all pathways along with their relative importance were provided in order to establish which proportion of the total exposure came from diet and which came from non-dietary exposures. In this study, the different oral dosing scenarios (dietary and non-dietary) were considered keeping inhalation as a continuous exposure case. Total non-dietary mean values were 0.002 µg/kg{sub bw}/day (0.000; 0.004 µg/kg{sub bw}/day for 5th and 95th percentile, respectively) for BPA and 0.597 µg/kg{sub bw}/day (0.116 µg/kg{sub bw}/day and 1.506 µg/kg{sub bw}/day for 5th and 95th percentile, respectively) for DEHP. Indoor environments and especially dust ingestion were the main non-dietary contributors to the total exposure of BPA and DEHP with 60% and 81%. However, as expected, diet showed the higher contribution to total exposure with > 99.9% for BPA and 63% for DEHP. Although diet was considered the primary source of exposure to BPA and phthalates, it must be taken into account that with non-dietary sources the first-pass metabolism is lacking, so these may be of equal or even higher toxicological relevance than dietary sources. The present study is in the framework of “Health and environmental-wide associations based on large population surveys” (HEALS) project (FP7–603946).

54 ENVIRONMENTAL SCIENCES↗

Risk of Radiation Retinopathy in Patients With Orbital and Ocular Lymphoma

Purpose: Radiation retinopathy is a potential long-term complication of radiation therapy to the orbit. The risk of developing this adverse effect is dose dependent; however, the threshold is unclear. The aim of this study was to identify the risk of developing radiation retinopathy at increasing radiation doses. Methods and Materials: A 40-year retrospective review was performed of patients who received external beam radiation therapy for ocular/orbital non-Hodgkin lymphoma (NHL). Results: Sixty-seven patients who had at least one ophthalmic follow-up examination were included in this study. Most patients (52%) were diagnosed with NHL involving the orbit. Patients received external beam radiation therapy at doses between 1886 and 5400 cGy (mean, 3033 {+-} 782 cGy). Radiation retinopathy developed in 12% of patients, and the median time to diagnosis was 27 months (range, 15-241months). The mean prescribed radiation dose in patients with retinopathy was 3309 {+-} 585 cGy, and the estimated retinal dose (derived by reviewing the dosimetry) was 3087 {+-} 1030 cGy. The incidence of retinopathy increased with dose. The average prescribed daily fractionated dose was higher in patients who developed retinopathy than in patients who did not (mean, 202 cGy vs 180 cGy, respectively; P = .04). More patients with radiation retinopathy had comorbid diabetes mellitus type 2 than patients without retinopathy (P = .015). In our study, the mean visual acuity of the eyes that received radiation was worse than that of the eyes that did not (P = .027). Other postradiotherapy ocular findings included keratitis (6%), dry eyes (39%), and cataract (33%). Conclusions: Radiation retinopathy, a known complication of radiotherapy for orbital tumors, relates to vascular comorbidities and dose. Higher total doses and larger daily fractions (>180 cGy) appear to be related to higher rates of retinopathy. Future larger studies are required to identify a statistically significant threshold for the development of retinopathy.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Quality Assurance Peer Review Chart Rounds in 2011: A Survey of Academic Institutions in the United States

Purpose: In light of concerns regarding the quality of radiation treatment delivery, we surveyed the practice of quality assurance peer review chart rounds at American academic institutions. Methods and Materials: An anonymous web-based survey was sent to the chief resident of each institution across the United States. Results: The response rate was 80% (57/71). The median amount of time spent per patient was 2.7 minutes (range, 0.6-14.4). The mean attendance by senior physicians and residents was 73% and 93%, respectively. A physicist was consistently present at peer review rounds in 66% of departments. There was a close association between attendance by senior physicians and departmental organization: in departments with protected time policies, good attendance was 81% vs. 31% without protected time (p = 0.001), and in departments that documented attendance, attending presence was 69% vs. 29% in departments without documentation (p < 0.05). More than 80% of institutions peer review all external beam therapy courses; however, rates were much lower for other modalities (radiosurgery 58%, brachytherapy 40%-47%). Patient history, chart documentation, and dose prescription were always peer reviewed in >75% of institutions, whereas dosimetric details (beams, wedges), isodose coverage, intensity-modulated radiation therapy constraints, and dose-volume histograms were always peer reviewed in 63%, 59%, 42%, and 50% of cases, respectively. Chart rounds led to both minor (defined as a small multileaf collimator change/repeated port film) and major (change to dose prescription or replan with dosimetry) treatment changes. Whereas at the majority of institutions changes were rare (<10% of cases), 39% and 11% of institutions reported that minor and major changes, respectively, were made to more than 10% of cases. Conclusion: The implementation of peer review chart rounds seems inconsistent across American academic institutions. Brachytherapy and radiosurgical procedures are rarely reviewed. Attendance by senior physicians is variable, but it improves when scheduling clashes are avoided. The potential effect of a more thorough quality assurance peer review on patient outcomes is not known.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Dosimetric Benefit of a New Ophthalmic Radiation Plaque

Purpose: To determine whether the computed dosimetry of a new ophthalmic plaque, EP917, when compared with the standard Collaborative Ocular Melanoma Study (COMS) plaques, could reduce radiation exposure to vision critical structures of the eye. Methods and Materials: One hundred consecutive patients with uveal melanoma treated with COMS radiation plaques between 2007 and 2010 were included in this study. These treatment plans were generated with the use of Bebig Plaque Simulator treatment-planning software, both for COMS plaques and for EP917 plaques using I-125. Dose distributions were calculated for a prescription of 85 Gy to the tumor apex. Doses to the optic disc, opposite retina, lens, and macula were obtained, and differences between the 2 groups were analyzed by standard parametric methods. Results: When compared with the COMS plaques, the EP917 plaques used fewer radiation seeds by an average difference of 1.94 (P<.001; 95% confidence interval [CI], -2.8 to -1.06) and required less total strength of radiation sources by an average of 17.74 U (air kerma units) (P<.001; 95% CI, -20.16 to -15.32). The total radiation doses delivered to the optic disc, opposite retina, and macula were significantly less by 4.57 Gy, 0.50 Gy, and 11.18 Gy, respectively, with the EP917 plaques vs the COMS plaques. Conclusion: EP917 plaques deliver less overall radiation exposure to critical vision structures than COMS treatment plaques while still delivering the same total therapeutic dose to the tumor.

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Adaptive/Nonadaptive Proton Radiation Planning and Outcomes in a Phase II Trial for Locally Advanced Non-small Cell Lung Cancer

Purpose: To analyze dosimetric variables and outcomes after adaptive replanning of radiation therapy during concurrent high-dose protons and chemotherapy for locally advanced non-small cell lung cancer (NSCLC). Methods and Materials: Nine of 44 patients with stage III NSCLC in a prospective phase II trial of concurrent paclitaxel/carboplatin with proton radiation [74 Gy(RBE) in 37 fractions] had modifications to their original treatment plans after re-evaluation revealed changes that would compromise coverage of the target volume or violate dose constraints; plans for the other 35 patients were not changed. We compared patients with adaptive plans with those with nonadaptive plans in terms of dosimetry and outcomes. Results: At a median follow-up of 21.2 months (median overall survival, 29.6 months), no differences were found in local, regional, or distant failure or overall survival between groups. Adaptive planning was used more often for large tumors that shrank to a greater extent (median, 107.1 cm{sup 3} adaptive and 86.4 cm{sup 3} nonadaptive; median changes in volume, 25.3% adaptive and 1.2% nonadaptive; P<.01). The median number of fractions delivered using adaptive planning was 13 (range, 4-22). Adaptive planning generally improved sparing of the esophagus (median absolute decrease in V{sub 70}, 1.8%; range, 0%-22.9%) and spinal cord (median absolute change in maximum dose, 3.7 Gy; range, 0-13.8 Gy). Without adaptive replanning, target coverage would have been compromised in 2 cases (57% and 82% coverage without adaptation vs 100% for both with adaptation); neither patient experienced local failure. Radiation-related grade 3 toxicity rates were similar between groups. Conclusions: Adaptive planning can reduce normal tissue doses and prevent target misses, particularly for patients with large tumors that shrink substantially during therapy. Adaptive plans seem to have acceptable toxicity and achieve similar local, regional, and distant control and overall survival, even in patients with larger tumors, vs nonadaptive plans.

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Hypopharyngeal Dose Is Associated With Severe Late Toxicity in Locally Advanced Head-and-Neck Cancer: An RTOG Analysis

Purpose: Concurrent chemoradiation therapy (CCRT) for squamous cell carcinoma of the head and neck (SCCHN) increases local tumor control but at the expense of increased toxicity. We recently showed that several clinical/pretreatment factors were associated with the occurrence of severe late toxicity. This study evaluated the potential relationship between radiation dose delivered to the pharyngeal wall and toxicity. Methods and Materials: This was an analysis of long-term survivors from 3 previously reported Radiation Therapy Oncology Group (RTOG) trials of CCRT for locally advanced SCCHN (RTOG trials 91-11, 97-03, and 99-14). Severe late toxicity was defined in this secondary analysis as chronic grade 3-4 pharyngeal/laryngeal toxicity and/or requirement for a feeding tube {>=}2 years after registration and/or potential treatment-related death (eg, pneumonia) within 3 years. Radiation dosimetry (2-dimensional) analysis was performed centrally at RTOG headquarters to estimate doses to 4 regions of interest along the pharyngeal wall (superior oropharynx, inferior oropharynx, superior hypopharynx, and inferior hypopharynx). Case-control analysis was performed with a multivariate logistic regression model that included pretreatment and treatment potential factors. Results: A total of 154 patients were evaluable for this analysis, 71 cases (patients with severe late toxicities) and 83 controls; thus, 46% of evaluable patients had a severe late toxicity. On multivariate analysis, significant variables correlated with the development of severe late toxicity, including older age (odds ratio, 1.062 per year; P=.0021) and radiation dose received by the inferior hypopharynx (odds ratio, 1.023 per Gy; P=.016). The subgroup of patients receiving {<=}60 Gy to the inferior hypopharynx had a 40% rate of severe late toxicity compared with 56% for patients receiving >60 Gy. Oropharyngeal dose was not associated with this outcome. Conclusions: Severe late toxicity following CCRT is common in long-term survivors. Age is the most significant factor, but hypopharyngeal dose also was associated.

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Quality Control Quantification (QCQ): A Tool to Measure the Value of Quality Control Checks in Radiation Oncology

Purpose: To quantify the error-detection effectiveness of commonly used quality control (QC) measures. Methods: We analyzed incidents from 2007-2010 logged into a voluntary in-house, electronic incident learning systems at 2 academic radiation oncology clinics. None of the incidents resulted in patient harm. Each incident was graded for potential severity using the French Nuclear Safety Authority scoring scale; high potential severity incidents (score >3) were considered, along with a subset of 30 randomly chosen low severity incidents. Each report was evaluated to identify which of 15 common QC checks could have detected it. The effectiveness was calculated, defined as the percentage of incidents that each QC measure could detect, both for individual QC checks and for combinations of checks. Results: In total, 4407 incidents were reported, 292 of which had high-potential severity. High- and low-severity incidents were detectable by 4.0 {+-} 2.3 (mean {+-} SD) and 2.6 {+-} 1.4 QC checks, respectively (P<.001). All individual checks were less than 50% sensitive with the exception of pretreatment plan review by a physicist (63%). An effectiveness of 97% was achieved with 7 checks used in combination and was not further improved with more checks. The combination of checks with the highest effectiveness includes physics plan review, physician plan review, Electronic Portal Imaging Device-based in vivo portal dosimetry, radiation therapist timeout, weekly physics chart check, the use of checklists, port films, and source-to-skin distance checks. Some commonly used QC checks such as pretreatment intensity modulated radiation therapy QA do not substantially add to the ability to detect errors in these data. Conclusions: The effectiveness of QC measures in radiation oncology depends sensitively on which checks are used and in which combinations. A small percentage of errors cannot be detected by any of the standard formal QC checks currently in broad use, suggesting that further improvements are needed. These data require confirmation with a broader incident-reporting database.

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Gamma Knife Radiosurgery for the Treatment of Cystic Cerebral Metastases

Purpose: To assess the role of Gamma Knife radiosurgery (GKRS) in the treatment of nonsurgical cystic brain metastasis, and to determine predictors of response to GKRS. Methods: We reviewed a prospectively maintained database of brain metastases patients treated at our institution between 2006 and 2010. All lesions with a cystic component were identified, and volumetric analysis was done to measure percentage of cystic volume on day of treatment and consecutive follow-up MRI scans. Clinical, radiologic, and dosimetry parameters were reviewed to establish the overall response of cystic metastases to GKRS as well as identify potential predictive factors of response. Results: A total of 111 lesions in 73 patients were analyzed; 57% of lesions received prior whole-brain radiation therapy (WBRT). Lung carcinoma was the primary cancer in 51% of patients, 10% breast, 10% colorectal, 4% melanoma, and 26% other. Fifty-seven percent of the patients were recursive partitioning analysis class 1, the remainder class 2. Mean target volume was 3.3 mL (range, 0.1-23 mL). Median prescription dose was 21 Gy (range, 15-24 Gy). Local control rates were 91%, 63%, and 37% at 6, 12, and 18 months, respectively. Local control was improved in lung primary and worse in patients with prior WBRT (univariate). Only lung primary predicted local control in multivariate analysis, whereas age and tumor volume did not. Lesions with a large cystic component did not show a poorer response compared with those with a small cystic component. Conclusions: This study supports the use of GKRS in the management of nonsurgical cystic metastases, despite a traditionally perceived poorer response. Our local control rates are comparable to a matched cohort of noncystic brain metastases, and therefore the presence of a large cystic component should not deter the use of GKRS. Predictors of response included tumor subtype. Prior WBRT decreased effectiveness of SRS for local control rates.

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A Paired, Double-Blind, Randomized Comparison of a Moisturizing Durable Barrier Cream to 10% Glycerine Cream in the Prophylactic Management of Postmastectomy Irradiation Skin Care: Trans Tasman Radiation Oncology Group (TROG) 04.01

Purpose: A previous, unblinded study demonstrated that an alcohol-free barrier film containing an acrylate terpolymer (ATP) was effective in reducing skin reactions compared with a 10% glycerine cream (sorbolene). The different appearances of these products precluded a blinded comparison. To test the acrylate terpolymer principle in a double-blinded manner required the use of an alternative cream formulation, a moisturizing durable barrier cream (MDBC); the study was conducted by the Trans Tasman Radiation Oncology Group (TROG) as protocol 04.01. Methods and Materials: A total of 333 patients were randomized; 1 patient was ineligible and 14 patients withdrew or had less than 7 weeks' observations, leaving 318 for analysis. The chest wall was divided into medial and lateral compartments, and patients were randomized to have MDBC applied daily to the medial or lateral compartment and sorbolene to the other compartment. Weekly observations, photographs, and symptom scores (pain and pruritus) were collected to week 12 or resolution of skin reactions if earlier. Skin dose was confirmed by centrally calibrated thermoluminescent dosimeters. Results: Rates of medial and lateral compartment Common Toxicity Criteria (CTC), version 3, greater than or equal to grade 3 skin reactions were 23% and 41%, but rates by skin care product were identical at 32%. There was no significant difference between MDBC and sorbolene in the primary endpoint of peak skin reactions or secondary endpoints of area-under-the-curve skin reaction scores. Conclusions: The MDBC did not reduce the peak skin reaction compared to sorbolene. It is possible that this is related to the difference in the formulation of the cream compared with the film formulation. Skin dosimetry verification and double blinding are essential for radiation skin care comparative studies.

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{sup 32}P Brachytherapy Conformal Source Model RIC-100 for High-Dose-Rate Treatment of Superficial Disease: Monte Carlo Calculations, Diode Measurements, and Clinical Implementation

Purpose: A novel {sup 32}P brachytherapy source has been in use at our institution intraoperatively for temporary radiation therapy of the spinal dura and other localized tumors. We describe the dosimetry and clinical implementation of the source. Methods and Materials: Dosimetric evaluation for the source was done with a complete set of MCNP5 Monte Carlo calculations preceding clinical implementation. In addition, the depth dose curve and dose rate were measured by use of an electron field diode to verify the Monte Carlo calculations. Calibration procedures using the diode in a custom-designed phantom to provide an absolute dose calibration and to check dose uniformity across the source area for each source before treatment were established. Results: Good agreement was established between the Monte Carlo calculations and diode measurements. Quality assurance measurements results are provided for about 100 sources used to date. Clinical source calibrations were usually within 10% of manufacturer specifications. Procedures for safe handling of the source are described. Discussion: Clinical considerations for using the source are discussed.

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Stereotactic Ablative Radiation Therapy for Subcentimeter Lung Tumors: Clinical, Dosimetric, and Image Guidance Considerations

Purpose: Use of stereotactic ablative radiation therapy (SABR) for subcentimeter lung tumors is controversial. We report our outcomes for tumors with diameter ≤1 cm and their visibility on cone beam computed tomography (CBCT) scans and retrospectively evaluate the planned dose using a deterministic dose calculation algorithm (Acuros XB [AXB]). Methods and Materials: We identified subcentimeter tumors from our institutional SABR database. Tumor size was remeasured on an artifact-free phase of the planning 4-dimensional (4D)-CT. Clinical plan doses were generated using either a pencil beam convolution or an anisotropic analytic algorithm (AAA). All AAA plans were recalculated using AXB, and differences among D95 and mean dose for internal target volume (ITV) and planning target volume (PTV) on the average intensity CT dataset, as well as for gross tumor volume (GTV) on the end respiratory phases were reported. For all AAA patients, CBCT scans acquired during each treatment fraction were evaluated for target visibility. Progression-free and overall survival rates were calculated using the Kaplan-Meier method. Results: Thirty-five patients with 37 subcentimeter tumors were eligible for analysis. For the 22 AAA plans recalculated using AXB, Mean D95 ± SD values were 2.2 ± 4.4% (ITV) and 2.5 ± 4.8% (PTV) lower using AXB; whereas mean doses were 2.9 ± 4.9% (ITV) and 3.7 ± 5.1% (PTV) lower. Calculated AXB doses were significantly lower in one patient (difference in mean ITV and PTV doses, as well as in mean ITV and PTV D95 ranged from 22%-24%). However, the end respiratory phase GTV received at least 95% of the prescription dose. Review of 92 CBCT scans from all AAA patients revealed that the tumor was visualized in 82 images, and its position could be inferred in other images. The 2-year local progression-free survival was 100%. Conclusions: Patients with subcentimeter lung tumors are good candidates for SABR, given the dosimetry, ability to localize tumors with image guidance, and excellent local control.

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A Dose–Response Analysis of Biochemical Control Outcomes After {sup 125}I Monotherapy for Patients With Favorable-Risk Prostate Cancer

Purpose: To define the optimal dose for {sup 125}I prostate implants by correlating postimplantation dosimetry findings with biochemical failure and toxicity. Methods and Materials: Between 2003 and 2009, 683 patients with prostate cancer were treated with {sup 125}I prostate brachytherapy without supplemental external beam radiation therapy and were followed up for a median time of 80 months. Implant dose was defined as the D90 (the minimal dose received by 90% of the prostate) on postoperative day 1 and 1 month after implantation. Therefore, 2 dosimetric variables (day 1 D90 and day 30 D90) were analyzed for each patient. We investigated the dose effects on biochemical control and toxicity. Results: The 7-year biochemical failure-free survival (BFFS) rate for the group overall was 96.4% according to the Phoenix definition. A multivariate analysis found day 1 D90 and day 30 D90 to be the most significant factors affecting BFFS. The cutoff points for day 1 D90 and day 30 D90, calculated from ROC curves, were 163 Gy and 175 Gy, respectively. By use of univariate analysis, various dosimetric cutoff points for day 30 D90 were tested. We found that day 30 D90 cutoff points from 130 to 180 Gy appeared to be good for the entire cohort. Greater D90s were associated with an increase in late genitourinary or gastrointestinal toxicity ≥ grade 2, but the increase was not statistically significant. Conclusions: Improvements in BFFS rates were seen with increasing D90 levels. Day 30 D90 doses of 130 to 180 Gy were found to serve as cutoff levels. For low-risk and low-tier intermediate-risk prostate cancer patients, high prostate D90s, even with doses exceeding 180 Gy, achieve better treatment results and are feasible.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Adaptive Replanning to Account for Lumpectomy Cavity Change in Sequential Boost After Whole-Breast Irradiation

Purpose: To evaluate the efficiency of standard image-guided radiation therapy (IGRT) to account for lumpectomy cavity (LC) variation during whole-breast irradiation (WBI) and propose an adaptive strategy to improve dosimetry if IGRT fails to address the interfraction LC variations. Methods and Materials: Daily diagnostic-quality CT data acquired during IGRT in the boost stage using an in-room CT for 19 breast cancer patients treated with sequential boost after WBI in the prone position were retrospectively analyzed. Contours of the LC, treated breast, ipsilateral lung, and heart were generated by populating contours from planning CTs to boost fraction CTs using an auto-segmentation tool with manual editing. Three plans were generated on each fraction CT: (1) a repositioning plan by applying the original boost plan with the shift determined by IGRT; (2) an adaptive plan by modifying the original plan according to a fraction CT; and (3) a reoptimization plan by a full-scale optimization. Results: Significant variations were observed in LC. The change in LC volume at the first boost fraction ranged from a 70% decrease to a 50% increase of that on the planning CT. The adaptive and reoptimization plans were comparable. Compared with the repositioning plans, the adaptive plans led to an improvement in target coverage for an increased LC case (1 of 19, 7.5% increase in planning target volume evaluation volume V{sub 95%}), and breast tissue sparing for an LC decrease larger than 35% (3 of 19, 7.5% decrease in breast evaluation volume V{sub 50%}; P=.008). Conclusion: Significant changes in LC shape and volume at the time of boost that deviate from the original plan for WBI with sequential boost can be addressed by adaptive replanning at the first boost fraction.

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Detection and Automated Scoring of Dicentric Chromosomes in Nonstimulated Lymphocyte Prematurely Condensed Chromosomes After Telomere and Centromere Staining

Purpose: To combine telomere and centromere (TC) staining of premature chromosome condensation (PCC) fusions to identify dicentrics, centric rings, and acentric chromosomes, making possible the realization of a dose–response curve and automation of the process. Methods and Materials: Blood samples from healthy donors were exposed to {sup 60}Co irradiation at varying doses up to 8 Gy, followed by a repair period of 8 hours. Premature chromosome condensation fusions were carried out, and TC staining using peptide nucleic acid probes was performed. Chromosomal aberration (CA) scoring was carried out manually and automatically using PCC-TCScore software, developed in our laboratory. Results: We successfully optimized the hybridization conditions and image capture parameters, to increase the sensitivity and effectiveness of CA scoring. Dicentrics, centric rings, and acentric chromosomes were rapidly and accurately detected, leading to a linear-quadratic dose–response curve by manual scoring at up to 8 Gy. Using PCC-TCScore software for automatic scoring, we were able to detect 95% of dicentrics and centric rings. Conclusion: The introduction of TC staining to the PCC fusion technique has made possible the rapid scoring of unstable CAs, including dicentrics, with a level of accuracy and ease not previously possible. This new approach can be used for biological dosimetry in radiation emergency medicine, where the rapid and accurate detection of dicentrics is a high priority using automated scoring. Because there is no culture time, this new approach can also be used for the follow-up of patients treated by genotoxic therapy, creating the possibility to perform the estimation of induced chromosomal aberrations immediately after the blood draw.

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Radiotherapy Quality Assurance Report From Children's Oncology Group AHOD0031

Purpose: A phase 3 trial assessing response-based therapy in intermediate-risk Hodgkin lymphoma mandated real-time central review of involved field radiation therapy (IFRT) and imaging records by a centralized review center to maximize protocol compliance. We report the impact of centralized radiation therapy review on protocol compliance. Methods and Materials: Review of simulation films, port films, and dosimetry records was required before and after treatment. Records were reviewed by study-affiliated or review center–affiliated radiation oncologists. A deviation of 6% to 10% from protocol-specified dose was scored as “minor”; a deviation of >10% was “major.” A volume deviation was scored as “minor” if margins were less than specified or “major” if fields transected disease-bearing areas. Interventional review and final compliance review scores were assigned to each radiation therapy case and compared. Results: Of 1712 patients enrolled, 1173 underwent IFRT at 256 institutions in 7 countries. An interventional review was performed in 88% of patients and a final review in 98%. Overall, minor and major deviations were found in 12% and 6% of patients, respectively. Among the cases for which ≥1 pre-IFRT modification was requested by the Quality Assurance Review Center and subsequently made by the treating institution, 100% were made compliant on final review. By contrast, among the cases for which ≥1 modification was requested but not made by the treating institution, 10% were deemed compliant on final review. Conclusions: In a large trial with complex treatment pathways and heterogeneous radiation therapy fields, central review was performed in a large percentage of cases before IFRT and identified frequent potential deviations in a timely manner. When suggested modifications were performed by the institutions, deviations were almost eliminated.

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The American Society for Radiation Oncology's 2015 Core Physics Curriculum for Radiation Oncology Residents

Purpose: The American Society for Radiation Oncology (ASTRO) Physics Core Curriculum Subcommittee (PCCSC) has updated the recommended physics curriculum for radiation oncology resident education to improve consistency in teaching, intensity, and subject matter. Methods and Materials: The ASTRO PCCSC is composed of physicists and physicians involved in radiation oncology residency education. The PCCSC updated existing sections within the curriculum, created new sections, and attempted to provide additional clinical context to the curricular material through creation of practical clinical experiences. Finally, we reviewed the American Board of Radiology (ABR) blueprint of examination topics for correlation with this curriculum. Results: The new curriculum represents 56 hours of resident physics didactic education, including a 4-hour initial orientation. The committee recommends completion of this curriculum at least twice to assure both timely presentation of material and re-emphasis after clinical experience. In addition, practical clinical physics and treatment planning modules were created as a supplement to the didactic training. Major changes to the curriculum include addition of Fundamental Physics, Stereotactic Radiosurgery/Stereotactic Body Radiation Therapy, and Safety and Incidents sections, and elimination of the Radiopharmaceutical Physics and Dosimetry and Hyperthermia sections. Simulation and Treatment Verification and optional Research and Development in Radiation Oncology sections were also added. A feedback loop was established with the ABR to help assure that the physics component of the ABR radiation oncology initial certification examination remains consistent with this curriculum. Conclusions: The ASTRO physics core curriculum for radiation oncology residents has been updated in an effort to identify the most important physics topics for preparing residents for careers in radiation oncology, to reflect changes in technology and practice since the publication of previous recommended curricula, and to provide practical training modules in clinical radiation oncology physics and treatment planning. The PCCSC is committed to keeping the curriculum current and consistent with the ABR examination blueprint.

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