Search

PURPOSE It remains unknown whether or not short-term androgen deprivation (STAD) improves survival among men with intermediate-risk prostate cancer (IRPC) treated with dose-escalated radiotherapy (RT). METHODS The NRG Oncology/Radiation Therapy Oncology Group 0815 study randomly assigned 1,492 patients with stage T2b-T2c, Gleason score 7, or prostate-specific antigen (PSA) value >10 and ≤20 ng/mL to dose-escalated RT alone (arm 1) or with STAD (arm 2). STAD was 6 months of luteinizing hormone–releasing hormone agonist/antagonist therapy plus antiandrogen. RT modalities were external-beam RT alone to 79.2 Gy or external beam (45 Gy) with brachytherapy boost. The primary end point was overall survival (OS). Secondary end points included prostate cancer–specific mortality (PCSM), non-PCSM, distant metastases (DMs), PSA failure, and rates of salvage therapy. RESULTS Median follow-up was 6.3 years. Two hundred nineteen deaths occurred, 119 in arm 1 and 100 in arm 2. Five-year OS estimates were 90% versus 91%, respectively (hazard ratio [HR], 0.85; 95% CI, 0.65 to 1.11]; P = .22). STAD resulted in reduced PSA failure (HR, 0.52; P CONCLUSION STAD did not improve OS rates for men with IRPC treated with dose-escalated RT. Improvements in metastases rates, prostate cancer deaths, and PSA failures should be weighed against the risk of adverse events and the impact of STAD on quality of life.

Purpose/Objectives: Local immune activity as measured by tumor infiltrating lymphocytes (TILs) has been correlated with improved outcomes in triple negative breast cancer (TNBC) and HER2+ disease. Furthermore, increased TILs after pre-operative systemic therapy for TNBC are also correlated with improved outcomes. However, the role of TILs in predicting outcomes in ER/PR+ breast cancer is less well-established. Radiation therapy (RT) can enhance immune cell infiltration in various tumors. However, breast cancer RT is typically given post-operatively, limiting the ability to determine whether RT enhances the %TILs in breast tumors. Here we report %TILs and tumor responses after pre-operative accelerated partial breast irradiation (APBI) as part of a clinical trial to determine whether RT enhances %TILs and whether this correlates with RT response. Materials/Methods: A breast pathologist assessed blindly the % stromal TILs and % tumor cellularity in biopsy and post-RT surgical specimens for patients treated on an in-house pre-operative APBI trial in patients with ER/PR+ breast cancer (NCT02728076). Patients received APBI to 30 Gy in 5 fractions on non-consecutive days, followed by surgery after no less than 5 weeks. Correlation between %TILs and pathologic response was assessed. Results: Thirty-five patients were enrolled and completed treatment. Median age was 65 (50-80). All patients were clinically node-negative and ER/PR+; one was HER2+. Median MRI tumor size was 0.9 cm (0.4-2.1 cm); 54% were grade 2 and 46% grade 1. 23/35 patients had 21- or 70-gene recurrence scores (RS), with 1 high RS; 2 patients received adjuvant chemotherapy and 33/35 received endocrine therapy after surgery. Most patients demonstrated robust tumor responses to RT, with 16/35 (46%) having &lt5% cellularity after RT. With a median cellularity at diagnosis of 40%, 27/35 (77%) had a >20% decrease in cellularity, with only 3 patients having no decrease (range 0-59%). All tumors had low levels of TILs (median 5%, range 1-20%). There was minimal change in %TILs from biopsy to surgery, with 10/35 (28%) patients having increase of TILs &gt4%, 2/35 with an increase of 10%, 2/35 having a decrease of 10% and the remainder with no %TIL increase. There were no correlations between %TILs (at diagnosis or post-RT) and tumor response to RT or RS. Conclusions: Pre-operative APBI in ER/PR+ breast cancers did not significantly increase the %TILs after 5 weeks, despite leading to significant tumor responses as measured by % cellularity. Low %TILs were seen, with no more than a 10% TIL increase after RT. These findings suggest this RT dose and fractionation schedule causes only mild immune changes, as measured by TILs, in this mostly favorable cohort of ER/PR+ cancers. Alternatively, the timing of surgery may have missed maximum TIL levels. Further characterization of TILs along with further studies in similar cohorts and in other breast cancer subtypes are warranted and will be performed to examine the role of pre-operative RT on breast cancer immune responses. Citation Format: Adam Currey, Julie M Jorns, Nina Desai, Tracy R Kelly, Joseph Bovi, Amanda L Kong, Anubha Wadhwa, Eric Paulson, Carmen Bergom. Minimal increases in tumor infiltrating lymphocytes despite excellent tumor responses after pre-operative accelerated partial breast irradiation in early stage ER+ breast cancer patients [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-19-04.

Purpose There remains limited data as to the feasibility, safety, and efficacy of higher doses of elective radiation therapy to the pelvic lymph nodes in men with high-risk prostate cancer. We conducted a phase II study to evaluate moderate dose escalation to the pelvic lymph nodes using a simultaneous integrated boost to the prostate. Methods and Materials Patients were eligible with biopsy-proven adenocarcinoma of the prostate, a calculated lymph node risk of at least 25%, Karnofsky performance scale ≥70, and no evidence of M1 disease. Acute and late toxicity were prospectively collected at each follow-up using Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0). The pelvic lymph nodes were treated to a dose of 56 Gy over 28 fractions with a simultaneous integrated boost to the prostate to a total dose of 70 Gy over 28 fractions using intensity-modulated radiation therapy. Results Thirty patients were prospectively enrolled from October 2010 to August 2014. Median patient age was 70 years (57-83), pretreatment prostate-specific antigen was 11.5 ng/mL (3.23-111.5), T stage was T2c (T1c-T3b), and Gleason score was 9 (6-9). CTCAE v4.0 rate of any grade 1 or 2 genitourinary and gastrointestinal toxicity were 55% and 44%, respectively, and there was 1 reported acute grade 3 genitourinary and gastrointestinal toxicity, both unrelated to protocol therapy. With a median follow-up of 6.4 years, the biochemical failure free survival rate was 80.2%, and mean biochemical progression free survival was 8.3 years (95% confidence interval [CI], 7.2-9.4). The prostate cancer specific survival was 95.2%, and mean prostate cancer specific survival was 8.7 years (95% CI, 8.0-9.4). Five-year distant metastases free survival was 96%. Medians were not reached. Conclusions In this single arm, small, prospective feasibility study, nodal radiation therapy dose escalation was safe, feasible, and seemingly well tolerated. Rates of progression free survival are highly encouraging in this population of predominately National Comprehensive Cancer Network very high-risk patients.

Management of axillary lymph nodes in breast cancer has undergone significant change over the past decade through landmark clinical trials. This study aimed to assess national practice patterns in axillary management in patients undergoing upfront mastectomy and examines what guides provider recommendations. A national case-based survey study was performed of surgeons and radiation oncologists from July to August 2020. Surgeons were identified through the American Society of Breast Surgeons (ASBrS) after review and approval by the ASBrS Research Committee, and radiation oncologists were identified through an institutional database. Both descriptive and comparative statistical analyses were performed. Overall, 994 providers responded—680 surgeons and 314 radiation oncologists. Surgeons were older and in practice longer (p 30% of surgeons recommended ALND, while radiation oncologists recommend axillary radiotherapy over axillary clearance (p

BACKGROUND Clinical trials have demonstrated methods to minimize the risk of breast cancer-related lymphedema while preserving regional control. We sought to determine the percent lifetime-risk of breast cancer-related lymphedema that surgeons and radiation oncologists discuss with patients before axillary interventions. METHODS A nationwide survey of surgeons and radiation oncologists was performed from July to August 2020. Participants were asked to identify what number they discuss with patients when estimating the percent lifetime-risk of breast cancer-related lymphedema after different axillary interventions. RESULTS Six hundred and eighty surgeons and 324 radiation oncologists responded (14% response rate). While the estimated rate after sentinel lymph node biopsy was clinically similar between surgeons and radiation oncologists, statistically surgeons quoted a higher percent lifetime-risk (5.7% vs 5.0%, P = .03). Surgeons estimated significantly higher rates of breast cancer-related lymphedema compared with radiation oncologists (P < .001) for axillary lymph node dissection (21.8% vs 17.5%), sentinel lymph node biopsy with regional nodal irradiation (14.1% vs 11.2%), and axillary lymph node dissection with regional nodal irradiation (34.8% vs 26.2%). CONCLUSION There is variability in the estimated rates of breast cancer-related lymphedema providers discuss with patients. These findings highlight the need for physician education on the current evidence of percent lifetime-risk of breast cancer-related lymphedema to provide patients with accurate estimates before axillary interventions.

Purpose: Radiation dose to the heart correlates with cardiac-related deaths and may partially diminish the benefit of radiation for breast cancer. This study assessed the current nationwide trends in heart-sparing techniques for breast cancer radiation. Methods and Materials: In November 2017, an institutional review board–approved survey was sent to radiation oncologists in the United States. Questions assessed demographics and the type and frequency of heart-sparing techniques. Data were analyzed using descriptive statistics and χ2 tests. Results: In total, 530 responses (13%) were obtained. Most physicians had practiced >15 years (46%), with most in a private setting (59%). Eighty-three percent of physicians offered prone positioning and/or deep inspiration breath hold (DIBH). This was more common in academic practice (P 20% of practitioners, with lung and heart sparing cited as reasons for use. More data are needed to determine if and when this technique should be used in right-sided cases.

Management of axillary lymph nodes in breast cancer has undergone significant change over the past decade through landmark clinical trials. This study aimed to assess national practice patterns in axillary management in patients undergoing upfront mastectomy and examines what guides provider recommendations.A national case-based survey study was performed of surgeons and radiation oncologists from July to August 2020. Surgeons were identified through the American Society of Breast Surgeons (ASBrS) after review and approval by the ASBrS Research Committee, and radiation oncologists were identified through an institutional database. Both descriptive and comparative statistical analyses were performed.Overall, 994 providers responded-680 surgeons and 314 radiation oncologists. Surgeons were older and in practice longer (p 0.05) and treated a higher percentage of breast patients (81% vs. 40%, p 0.001). Most surgeons were hospital-employed (43%), whereas most radiation oncologists were in private practice (40%; p 0.001). Fifty-two percent of surgeons routinely send sentinel lymph nodes (SLNs) for frozen section (52%) during mastectomy, of which 78% proceed directly to axillary lymph node dissection (ALND) if positive. There was significant variability in treatment recommendations between the two groups among the hypothetical cases (p 0.001). In the setting of low disease burden in the SLNs, 30% of surgeons recommended ALND, while radiation oncologists recommend axillary radiotherapy over axillary clearance (p 0.001).There is significant heterogeneity in the management of the axilla in mastectomy patients with pathologically positive SLNs, both between and among surgeons and radiation oncologists. Efforts should be made to assist both groups in identifying de-escalation opportunities to ensure that mastectomy patients with positive SLNs are treated appropriately.

Purpose The Expanded Prostate Cancer Index Composite (EPIC) is the most commonly used patient reported outcome (PRO) tool in prostate cancer (PC) clinical trials, but health utilities associated with the different health states assessed with this tool are unknown, limiting our ability to perform cost-utility analyses. This study aimed to map EPIC tool to EuroQoL-5D-3L (EQ5D) to generate EQ5D health utilities. Methods and materials This is a secondary analysis of a prospective, randomized non-inferiority clinical trial, conducted between 04/2006 and 12/2009 at cancer centers across the United States, Canada, and Switzerland. Eligible patients included men >18 years with a known diagnosis of low-risk PC. Patient HRQoL data were collected using EPIC and health utilities were obtained using EQ5D. Data were divided into an estimation sample (n = 765, 70%) and a validation sample (n = 327, 30%). The mapping algorithms that capture the relationship between the instruments were estimated using ordinary least squares (OLS), Tobit, and two-part models. Five-fold cross-validation (in-sample) was used to compare the predictive performance of the estimated models. Final models were selected based on root mean square error (RMSE). Results A total of 565 patients in the estimation sample had complete information on both EPIC and EQ5D questionnaires at baseline. Mean observed EQ5D utility was 0.90±0.13 (range: 0.28–1) with 55% of patients in full health. OLS models outperformed their counterpart Tobit and two-part models for all pre-determined model specifications. The best model fit was: “EQ5D utility = 0.248541 + 0.000748*(Urinary Function) + 0.001134*(Urinary Bother) + 0.000968*(Hormonal Function) + 0.004404*(Hormonal Bother)– 0.376487*(Zubrod) + 0.003562*(Urinary Function*Zubrod)”; RMSE was 0.10462. Conclusions This is the first study to identify a comprehensive set of mapping algorithms to generate EQ5D utilities from EPIC domain/ sub-domain scores. The study results will help estimate quality-adjusted life-years in PC economic evaluations.

Purpose/objective(s) Telehealth, until recently, has been underutilized. With the pandemic, telehealth has quickly taken on new prominence that will likely sustain in the post-pandemic setting. Mobile health applications (apps) can be used as part of the oncologic telehealth encounter to monitor patient-reported outcomes (PROs), recorded sensor data and facilitate rapid communication. The goal of this study was to describe the characteristics of patient-centered oncology apps and associated functionalities that can improve outcomes and enhance patient-physician relationships. Materials/methods A review of apps with symptom tracking capabilities available on the iOS-based App Store and Android-based Play Store was completed in late 2020. The search terms used included: cancer, oncology, symptom tracker, radiation oncology, radiotherapy and radiation therapy. Apps were initially included if they had symptom tracking capabilities, and were further evaluated to assess patient journaling, wearable device syncing, bi-directional communication, and specificity for radiation oncology. Functionalities were tallied and compared using Microsoft Excel to examine totals and percentage distributions. Results The primary search in the app stores populated 1240 unique applications in English with 91 included in the secondary selection process after title and descriptive screening. After downloading free apps to confirm capabilities, 33 apps were eligible for the study. Of the 33 included apps, 21 (63.60%) were general symptom trackers, and 12 (36.40%) were oncology specific. None of the oncology-specific symptom tracking apps were specific for radiation oncology, but 6 (50%) of the oncology-specific apps allowed for the addition of custom symptoms. Of the 12 oncology-specific apps, 7 (58.3%) allowed for patient journaling, 3 (25%) could sync data from wearable devices, and 2 (16.7%) allowed for bi-directional communication between the patient and medical team. Of the 2 apps that included bi-directional communication, 1 (50%) app provided a chat function, and 1 (50%) app provided a video function. Comparisons of the prevalence of important functionalities between general symptom and oncology symptom trackers is shown in Table 1. Conclusion We present a comprehensive characterization of oncology-specific apps currently available. Apps focused on oncology are limited and largely unexplored. Future app development to optimize PRO collection, mobile sensor data assessment, and integration with telehealth encounters in needed. Such data can increase symptom recognition, provide timely feedback and improve quality of data collection for oncologists.

Purpose/Objective(s) Pre-procedural medical checklists have been robustly shown in the surgical literature to be associated with numerous clinical improvements, including reductions in postoperative complications and death. The use of pre-procedure checklists within radiation oncology is poorly understood. We sought to assess the use of checklists by radiation oncologists in the U.S. and identify factors associated with their use. Materials/Methods A survey consisting of seven questions was created using Qualtrics (an online survey platform). Each question followed a multiple-choice format, with some questions allowing multiple responses. These questions aimed to examine radiation oncologists’ perceptions regarding the value of checklists in medical practice. This survey was distributed to radiation oncology residents and attending physicians. Responses to each question along with demographic data from each respondent were collected and examined. Where applicable, univariate analysis via Fisher's exact test was performed. Incomplete surveys were excluded from data analysis. The survey and methods of collection were approved by institutional review board. Results A total of 349 respondents completed the survey. The majority of respondents were physicians who have been in practice for “greater than ten years” (78.5%). The majority of respondents work in private practice (47.6%), followed by academic institutions (42.7%). Of these, 296 respondents indicated that they used checklists (84.8%). Of those individuals, 207 reported routine use (69.9%). Neither amount of time in practice nor type of practice were found to be significantly associated with use of checklists (P-values 0.344 and 0.715, respectively). Most respondents felt that checklists played an important role in ensuring patient safety, accountability, and procedure efficiency (92.8%, 88.8%, 88.2%), but significantly fewer respondents felt that checklists played a role in decreasing mortality (75.6%). The majority of respondents believed that the usefulness of checklists is supported by retrospective quality assurance studies (64.1%). Significantly fewer respondents believed that randomized clinical trials supported their usefulness (35.3%) and some believed that checklists have not been formally evaluated (13.4%). Conclusion We present data characterizing radiation oncologists’ perceptions of medical checklist use, demonstrating significant interest and frequent use across the community. Given widespread interest in checklists, initiatives within radiation oncology professional societies may facilitate advancement of medical checklists while increasing awareness of the data supporting their use. Additional studies exploring automated methods of checklist creation and outcomes following implementation within radiation oncology are warranted. IRB approval: PRO00036824

Preoperative or neo-adjuvant chemotherapy in the management of breast cancer is a treatment approach that has gained in popularity in recent years. However, it is unclear if the treatment paradigms often employed for patients treated with surgery first hold true for those treated with preoperative chemotherapy. The role of sentinel node biopsy and the data supporting its use is different for those with clinically negative and clinically positive nodes prior to chemotherapy. For clinically node-negative patients, sentinel node biopsy after neo-adjuvant chemotherapy may be appropriate. For those node-positive patients whose axillary disease resolves clinically, the false-negative rate of the sentinel node biopsy is high. However, there are measures that can reduce that rate. After surgery, the radiation oncologist is often faced with complicated decisions surrounding the optimal radiotherapy in this setting. Tailoring radiation plans based on chemotherapy response holds promise and is the subject of ongoing clinical trials. In the accompanying article, we review the current literature on both surgery and radiation in axillary management and describe the interplay between these two treatment modalities. This highlights the need for multidisciplinary management in making treatment decisions for patients treated in this manner.

PURPOSE/OBJECTIVE(S) Some perceptions exist regarding potential decline in the utilization of radiation therapy (RT) with expanding systemic therapy options. We sought to understand the recommended utilization of RT across a broad range of solid tumors by examining National Comprehensive Cancer Network (NCCN) Guidelines. We conducted a comprehensive review and categorization of RT recommendations, with their subsequent supporting evidence categories, in NCCN Guidelines from 2000 through 2019. MATERIALS/METHODS The 2000, 2009, and 2019 versions of NCCN Guidelines were individually examined for RT-specific recommendations among the 10 most common solid tumors. The presence of RT as a recommended modality was recorded for each tumor type, along with the branch of management. Recommendation categories including Category 1, 2A, 2B and 3 were tallied and compared descriptively to examine totals and percentage distributions. RESULTS 3858 recommendations were individually reviewed. The presence of a recommendation inclusive of RT increased by 129% from 2000 to 2009 and by 111% from 2009 to 2019. From 2000 to 2019, RT recommendations overall increased by 206%. In 2019 NCCN Guidelines, the most Category 1 RT recommendations were found within small cell lung (13%), non-small cell lung (5%), breast (5%), bladder (2%), rectal (2%) and non-Hodgkin lymphoma (1%). Pancreatic, uterine, prostate, melanoma, kidney, and colon cancer guidelines had no Category 1 RT recommendations. Of note, rectal cancer had 31 (27%) preferred recommendations. The majority (89%) of 2019 RT recommendations were for initial therapy, while 9% were specific to salvage therapy. Tumor sites with the highest proportion of RT Category 1 evidence were small cell lung (29%), non-small cell lung (24%), and breast cancer (24%). CONCLUSION The frequency of RT recommendations in NCCN Guidelines has increased over the past 20 years among the 10 most common solid tumors. A majority of recommendations remain Category 2A, and this proportional percentage of 2A recommendations is increasing. Consideration of evidence categories by solid tumor type is highly relevant to identify areas in need of expanded prospective, randomized, evidence regarding the use of RT.

Purpose/Objective(s) Androgen suppression can improve outcomes when added to radiotherapy (RT) for intermediate risk prostate cancer, but no study to date has reported its utility in the context of contemporary, dose-escalated RT. Herein, the clinical outcomes of a phase III prospective trial evaluating the utility of total androgen suppression (TAS) combined with dose-escalated RT for patients with intermediate risk prostate cancer are reported. Materials/Methods Eligible patients had intermediate risk prostate cancer defined as harboring ≥ 1 of the following risk factors: clinical stage T2b-T2c, Gleason score 7, or PSA value > 10 and ≤ 20 ng/mL. Patients with all three risk factors and ≥ 50% of biopsy cores positive were ineligible. After stratification by number of intermediate risk factors (single vs. multiple), RT boost modality, and baseline comorbidity (ACE-27 comorbidity index ≥ vs. Results The study completed its accrual objective. Between 2009 and 2016, 1538 patients were randomized. There were 750 eligible patients on Arm 1 and 742 on Arm 2 comprising the modified intent-to-treat population. 67% had a single intermediate risk factor. 88% were treated with EBRT with the remainder receiving EBRT plus brachytherapy boost. 33% had an ACE-27 score ≥ grade 2. With a median follow up of 6.2 years, 219 deaths occurred, 119 in Arm 1 and 100 in Arm 2, yielding 5-year overall survival estimates of 90% vs. 91%, respectively [HR 0.85 (95% CI 0.65-1.11); P = 0.22]. 193 patients experienced PSA failure, 125 in Arm 1 and 68 in Arm 2 [HR 0.52 (0.39-0.70); P Conclusion While the addition of TAS to dose-escalated RT did not improve overall survival for men with intermediate risk prostate cancer, significant improvements in rates of metastases, deaths due to prostate cancer, and PSA failures support the continued use of combination dose-escalated RT and TAS. Benefits will need to be weighed against the increased risk of adverse events and the patient reported outcomes analysis.

Purpose To determine the associated toxicity, tolerance, and safety of partial-breast reirradiation. Methods and Materials Eligibility criteria included in-breast recurrence occurring >1 year after whole-breast irradiation, Results Between 2010 and 2013, 65 patients were accrued, and the first 55 eligible and with 1 year follow-up were analyzed. Median age was 68 years. Twenty-two patients had ductal carcinoma in situ, and 33 had invasive disease: 19 ≤1 cm, 13 >1 to ≤2 cm, and 1 >2 cm. All patients were clinically node negative. Systemic therapy was delivered in 51%. All treatment plans underwent quality review for contouring accuracy and dosimetric compliance. All treatment plans scored acceptable for tumor volume contouring and tumor volume dose-volume analysis. Only 4 (7%) scored unacceptable for organs at risk contouring and organs at risk dose-volume analysis. Treatment-related skin, fibrosis, and/or breast pain AEs were recorded as grade 1 in 64% and grade 2 in 7%, with only 1 ( Conclusion Partial-breast reirradiation with 3-dimensional conformal radiation therapy after second lumpectomy for patients experiencing in-breast failures after whole-breast irradiation is safe and feasible, with acceptable treatment quality achieved. Skin, fibrosis, and breast pain toxicity was acceptable, and grade 3 toxicity was rare.

Inflammatory breast cancer (IBC) is a rare yet aggressive form of breast cancer. We examined differences in patient demographics and outcomes in IBC compared to locally advanced breast cancer (LABC) and all other breast cancer patients from the Breast and Prostate Cancer Data Quality and Patterns of Care Study (POC-BP), containing information from cancer registries in seven states. Out of 7,624 cases of invasive carcinoma, IBC and LABC accounted for 2.2% (N=170) and 4.9% (N=375), respectively. IBC patients were more likely to have a higher number (P=0.03) and severity (P=0.01) of comorbidities than other breast cancer patients. Among IBC patients, a higher percentage of patients with metastatic disease versus nonmetastatic disease were black, on Medicaid, and from areas of higher poverty and more urban areas. Black and Hispanic IBC patients had worse overall and breast cancer-specific survival than white patients; moreover, IBC patients with Medicaid, patients from urban areas, and patients from areas of higher poverty and lower education had worse outcomes. These data highlight the effects of disparities in race and socioeconomic status on the incidence of IBC as well as IBC outcomes. Further work is needed to reveal the causes behind these disparities and methods to improve IBC outcomes.

Purpose To investigate patterns of failure in institutional credentialing submissions to NRG/RTOG 1005 with the aim of improving the quality and consistency for future breast cancer protocols. Methods and Materials NRG/RTOG 1005 allowed the submission of 3-dimensional conformal radiation therapy (3DCRT), intensity-modulated radiation therapy (IMRT), and simultaneous integrated boost (SIB) breast plans. Credentialing required institutions to pass a 2-step quality assurance (QA) process: (1) benchmark, requiring institutions to create a plan with no unacceptable deviations and ≤1 acceptable variation among the dose volume (DV) criteria, and (2) rapid review, requiring each institution's first protocol submission to have no unacceptable deviations among the DV criteria or contours. Overall rates, number of resubmissions, and reasons for resubmission were analyzed for each QA step. Results In total, 352 institutions participated in benchmark QA and 280 patients enrolled had rapid review QA. Benchmark initial failure rates were similar for 3DCRT (18%), IMRT (17%), and SIB (18%) plans. For 3DCRT and IMRT benchmark plans, ipsilateral lung most frequently failed the DV criteria, and SIB DV failures were seen most frequently for the heart. Rapid review contour initial failures (35%) were due to target rather than organs at risk. For 29% of the rapid review initial failures, the planning target volume boost eval volume was deemed an unacceptable deviation. Conclusions The review of the benchmark and rapid review QA submissions indicates that acceptable variations or unacceptable deviations for the ipsilateral lung and heart dose constraints were the most commonly observed cause of benchmark QA failure, and unacceptable deviations in target contouring, rather than normal structure contouring, were the most common cause of rapid review QA failure. These findings suggest that a rigorous QA process is necessary for high quality and homogeneity in radiation therapy in multi-institutional trials of breast cancer to ensure that the benefits of radiation therapy far outweigh the risks.

Purpose Our purpose was to present and evaluate expert consensus on contouring primary breast tumors on magnetic resonance imaging (MRI) in the setting of neoadjuvant partial breast irradiation in trials. Methods and Materials Expert consensus on contouring guidelines for target definition of primary breast tumors on contrast-enhanced MRI in trials was developed by an international team of experienced breast radiation oncologists and a dedicated breast radiologist during 3 meetings. At the first meeting, draft guidelines were developed through discussing and contouring 2 cases. At the second meeting 6 breast radiation oncologists delineated gross tumor volume (GTV) in 10 patients with early-stage breast cancer (cT1N0) according to draft guidelines. GTV was expanded isotropically (20 mm) to generate clinical target volume (CTV), excluding skin and chest wall. Delineations were reviewed for disagreement and guidelines were clarified accordingly. At the third meeting 5 radiation oncologists redelineated 6 cases using consensus-based guidelines. Interobserver variation of GTV and CTV was assessed using generalized conformity index (CI). CI was calculated as the sum of volumes each pair of observers agreed upon, divided by the sum of encompassing volumes for each pair of observers. Results For the 2 delineation sessions combined, mean GTV ranged between 0.19 and 2.44 cm3, CI for GTV ranged between 0.28 and 0.77, and CI for CTV between 0.77 and 0.94. The largest interobserver variation in GTV delineations was observed in cases with extended tumor spiculae, blood vessels near or markers within the tumor, or with increased enhancement of glandular breast tissue. Consensus-based guidelines stated to delineate all visible tumors on contrast enhanced–MRI scan 1 to 2 minutes after contrast injection and if a marker was inserted in the tumor to include this. Conclusions Expert-based consensus on contouring primary breast tumors on MRI in trials has been reached. This resulted in low interobserver variation for CTV in the context of a uniform 20 mm GTV to CTV expansion margin.

Background In prostate cancer, end points that reliably portend prognosis and treatment benefit (surrogate end points) can accelerate therapy development. Although surrogate end point candidates have been evaluated in the context of radiotherapy and short-term androgen deprivation (AD), potential surrogates under long-term (24 month) AD, a proven therapy in high-risk localized disease, have not been investigated. Materials and Methods In the NRG/RTOG 9202 randomized trial (N = 1,520) of short-term AD (4 months) versus long-term AD (LTAD; 28 months), the time interval free of biochemical failure (IBF) was evaluated in relation to clinical end points of prostate cancer–specific survival (PCSS) and overall survival (OS). Survival modeling and landmark analysis methods were applied to evaluate LTAD benefit on IBF and clinical end points, association between IBF and clinical end points, and the mediating effect of IBF on LTAD clinical end point benefits. Results LTAD was superior to short-term AD for both biochemical failure (BF) and the clinical end points. Men remaining free of BF for 3 years had relative risk reductions of 39% for OS and 73% for PCSS. Accounting for 3-year IBF status reduced the LTAD OS benefit from 12% (hazard ratio [HR], 0.88; 95% CI, 0.79 to 0.98) to 6% (HR, 0.94; 95% CI, 0.83 to 1.07). For PCSS, the LTAD benefit was reduced from 30% (HR, 0.70; 95% CI, 0.52 to 0.82) to 6% (HR, 0.94; 95% CI, 0.72 to 1.22). Among men with BF, by 3 years, 50% of subsequent deaths were attributed to prostate cancer, compared with 19% among men free of BF through 3 years. Conclusion The IBF satisfied surrogacy criteria and identified the benefit of LTAD on disease-specific survival and OS. The IBF may serve as a valid end point in clinical trials and may also aid in risk monitoring after initial treatment.

60 Background: Mapping algorithms informing economic evaluations are often derived using baseline data from clinical trials. It is unclear if these algorithms can predict health utilities accurately in post-intervention data. Thus, this study examines the longitudinal predictive ability of mapping algorithms derived from baseline trial data and explores the factors associated with prediction errors. Methods: This methodological study utilized data from an international, multicenter, randomized controlled trial of patients with low-risk prostate cancer (PC), conducted by NRG Oncology (NCT00331773). In addition to patient demographic and clinical data, this study utilized PRO data collected at baseline and 6, 12 and 24 months post-intervention. The Expanded Prostate Cancer Index Composite (EPIC) questionnaire measures health-related quality-of-life (HRQoL) and has four domains (urinary, sexual, hormonal, and bowel) and two subdomains per domain (function and bother); EuroQOL-5D-3L (EQ5D) captures health utilities. Ordinary Least Squares (OLS) regression models were used to map EPIC scores to EQ5D utilities in the baseline data through 5-fold cross-validation. Predictive performance was tested in the post-intervention data; predicted and reported utilities were compared using t-tests, and the absolute prediction error was modeled using fixed effects, as a function of baseline demographic and clinical covariates, as well as observed and predicted EQ5D utilities. Results: A total of 267 (199) patients had complete EQ5D and EPIC domain (or subdomain) data at baseline and all subsequent assessments. In the EPIC domain sample, mean ± standard deviation observed EQ5D utility was 0.90±0.13 at baseline, 0.92±0.11 at 6 months, 0.90±0.13 at 12 months and 0.89±0.14 at 24 months. Mean absolute differences (MDs) between reported and predicted were lower for models using EPIC subdomain data compared to EPIC domain data, and generally decreased as the time of assessment increased. The mapping functions over-predicted utilities for patients in perfect health while the prediction errors were increasingly negative for lower reported EQ5D scores. According to the fixed effects model for EPIC domain data, lower observed and predicted baseline EQ5D scores, and time of assessment were significant predictors of the absolute prediction error; for EPIC subdomain data, lower observed and predicted baseline EQ5D scores, hormonal bother and function, and bowel function significantly predicted the absolute prediction error. Conclusions: This study is the first to demonstrate the longitudinal validity of EPIC questionnaire, and builds upon existing research on longitudinal validity of mapping functions. The low MDs in prediction errors in post-intervention data indicate that the mapping functions are sensitive to treatment effect, thereby increasing confidence in their use in economic evaluations in PC.

Background: Breast cancer is the most common solid tumor to cause cutaneous metastases. These are incurable and the treatment goal is geared toward local control with surgical excision, radiation, and chemotherapy. However, treatment can be challenging in subjects with end-stage liver disease and a multidisciplinary approach is warranted. Case Report: In this case report, we present a 61-year-old female with primary biliary cirrhosis and human epidermal growth factor-2 (HER-2)-positive breast cancer, who subsequently developed cutaneous metastases. We briefly describe the treatment challenges due to underlying end-stage liver disease, and an exceptional response to trastuzumab and nab-paclitaxel. Conclusion: A multidisciplinary approach to local control and attenuated doses of nab-paclitaxel and trastuzumab suggest a durable response to HER-2-positive breast cancer with cutaneous metastasis. Subjects with end-stage liver disease pose unique challenges and toxicities, warranting additional research and drug development for less hepatotoxic antineoplastic agents.

Purpose Obesity, as measured by the body mass index (BMI), is a risk factor for distant recurrence and decreased survival in breast cancer. We sought to determine whether the BMI correlated with local recurrence and reduced survival in a cohort of predominantly obese women treated with breast conservation therapy. Methods and Materials From 1998 to 2010, 154 women with early-stage invasive breast cancer and 39 patients with ductal carcinoma in situ underwent prone whole breast irradiation. Cox proportional hazards regression, Kaplan-Meier methods with the log-rank test, and multivariate analysis were used to explore the association of the outcomes with the BMI. Results The median patient age was 60 years, and the median follow-up duration was 73 months. The median BMI was 33.2 kg/m 2 ; 91% of the patients were overweight (BMI ≥25 kg/m 2 ) and 69% of the patients were clinically obese (BMI ≥30 kg/m 2 ). The BMI was significantly associated with the locoregional recurrence-free interval for patients with invasive cancer and ductal carcinoma in situ (hazard ratio [HR], 1.09; P =.047). Also, a trend was seen for increased locoregional recurrence with a higher BMI ( P =.09) for patients with invasive disease, which was significant when examining the outcomes with a BMI stratified by the median value of 33.2 kg/m 2 ( P =.008). A greater BMI was also significantly associated with decreased distant recurrence-free interval (HR, 1.09; P =.011) and overall survival (HR, 1.09; P =.004); this association remained on multivariate analysis (distant recurrence-free interval, P =.034; overall survival, P =.0007). Conclusions These data suggest that the BMI might affect the rate of locoregional recurrence in breast cancer patients. A higher BMI predicted a worse distant recurrence-free interval and overall survival. The present investigation adds to the increasing evidence that BMI is an important prognostic factor in early-stage breast cancer treated with breast conservation therapy.

Purpose To compare lumpectomy cavity (LC) and planning target volume (PTV) delineated with the use of magnetic resonance imaging (MRI) and computed tomography (CT) and to examine the possibility of replacing CT with MRI for radiation therapy (RT) planning for breast cancer. Methods and Materials MRI and CT data were acquired for 15 patients with early-stage breast cancer undergoing lumpectomy during RT simulation in prone positions, the same as their RT treatment positions. The LCs were delineated manually on both CT (LC-CT) and MRI acquired with 4 sequences: T1, T2, STIR, and DCE. Various PTVs were created by expanding a 15-mm margin from the corresponding LCs and from the union of the LCs for the 4 MRI sequences (PTV-MRI). Differences were measured in terms of cavity visualization score (CVS) and dice coefficient (DC). Results The mean CVSs for T1, T2, STIR, DCE, and CT defined LCs were 3.47, 3.47, 3.87, 3.50. and 2.60, respectively, implying that the LC is mostly visible with a STIR sequence. The mean reductions of LCs from those for CT were 22%, 43%, 36%, and 17% for T1, T2, STIR, and DCE, respectively. In 14 of 15 cases, MRI (union of T1, T2, STIR, and DCE) defined LC included extra regions that would not be visible from CT. The DCs between CT and MRI (union of T1, T2, STIR, and DCE) defined volumes were 0.65 ± 0.20 for LCs and 0.85 ± 0.06 for PTVs. There was no obvious difference between the volumes of PTV-MRI and PTV-CT, and the average PTV-STIR/PTV-CT volume ratio was 0.83 ± 0.23. Conclusions The use of MRI improves the visibility of LC in comparison with CT. The volumes of LC and PTV generated based on a MRI sequence are substantially smaller than those based on CT, and the PTV-MRI volumes, defined by the union of T1, T2, STIR, and DCE, were comparable with those of PTV-CT for most of the cases studied.

Purpose Radiation oncology curriculum development is challenging because of limited numbers of trainees at any single institution. The goal of this project is to implement and evaluate a standardized medical student clerkship curriculum following the multi-institutional cooperative group research model. Methods During the 2013 academic year, a standardized curriculum was implemented at 11 academic medical centers consisting of three 1-hour lectures and a hands-on radiation treatment planning workshop. After the curriculum, students completed anonymous evaluations using Likert-type scales (1 = "not at all" to 5 = "extremely") and free responses. Evaluations asked students to rate their comfort, before and after the curriculum, with radiation oncology as a specialty, knowledge of radiotherapy planning methods, and ability to function as a radiation oncology resident. Nonparametric statistical tests were used in the analysis. Results Eighty-eight students at 11 academic medical centers completed the curriculum de novo, with a 72.7% (64 of 88) survey response rate. Fifty-seven students (89.1%) reported intent to pursue radiation oncology as their specialty. Median (interquartile range) student ratings of the importance of curricular content were as follows: overview, 4 (4-5); radiation biology/physics, 5 (4-5); practical aspects/emergencies, 5 (4-5); and planning workshop, 4 (4-5). Students reported that the curriculum helped them better understand radiation oncology as a specialty (5 [4-5]), increased specialty decision comfort (4 [3-5]), and would help the transition to radiation oncology residency (4 [4-5]). Students rated their specialty decision comfort significantly higher after completing the curriculum (4 [4-5] versus 5 [5-5]; P Conclusions A national standardized curriculum was successfully implemented at 11 academic medical centers, providing proof of principle that curriculum development can follow the multi-institutional cooperative group research model.

55 Background: To compare the predictive ability of health utility mapping algorithms derived using cross-sectional and longitudinal data specific to the Expanded Prostate Cancer Index Composite (EPIC). Methods: This mapping study utilized data from an international, multicenter, randomized controlled trial of patients with low-risk prostate cancer conducted by NRG Oncology (NCT00331773). Health-related quality-of-life (HRQoL) data were collected using EPIC, and health utilities were obtained using EuroQOL-5D (EQ5D) at baseline and 6, 12 and 24 months post-intervention. Data were split into an estimation sample (70%) and a validation sample (30%). Ordinary Least Squares (OLS) regression models were estimated using baseline cross-sectional data as well as pooled data from all assessment periods. Random effects (RE) specifications that explicitly model the longitudinal nature of the data were also estimated. Candidate models were selected based on root mean square error (RMSE). Results: A total of 196 (147) patients in the estimation sample had complete EQ5D and EPIC domain (subdomain) data at all time points. OLS models using combined data outperformed the counter-part RE models as well as OLS models using baseline data in the five-fold cross-validation. Addition of covariates to the models resulted in improved predictive ability. In the external validation, when only EPIC domain/ subdomain data are available, the OLS model using combined data predicted EQ5D utilities better than the counterpart RE model and OLS model using baseline data (RMSE=0.121108 & 0.111345). OLS model using baseline data outperformed other model types for algorithms with EPIC domains and demographics (RMSE=0.121757), while RE models outperformed the other two model types for algorithms with EPIC subdomains and demographic data, (0.112782) and for algorithms with EPIC domains/ subdomains, demographics, and clinical covariates (RMSE=0.123589 & 0.163093). Conclusions: While algorithms using pooled data outperformed other model types in internal validation, RE models showed better predictive ability in external validation for algorithms with covariates. Clinical trial information: NCT00331773.

Importance Mastectomy is standard for recurrence of breast cancer after breast conservation therapy with whole breast irradiation. The emergence of partial breast irradiation led to consideration of its application for reirradiation after a second lumpectomy for treatment of recurrence of breast cancer in the ipsilateral breast. Objectives To assess the effectiveness and adverse effects of partial breast reirradiation after a second lumpectomy and whether the treatment is an acceptable alternative to mastectomy. Design, Setting, and Participants The NRG Oncology/Radiation Therapy Oncology Group 1014 trial is a phase 2, single-arm, prospective clinical trial of 3-dimensional, conformal, external beam partial breast reirradiation after a second lumpectomy for recurrence of breast cancer in the ipsilateral breast after previous whole breast irradiation. The study opened on June 4, 2010, and closed June 18, 2013. Median follow-up was 5.5 years. This analysis used all data received at NRG Oncology through November 18, 2018. Eligible patients experienced a recurrence of breast tumor that was less than 3 cm and unifocal in the ipsilateral breast more than 1 year after breast-conserving therapy with whole breast irradiation and who had undergone excision with negative margins. Interventions Adjuvant partial breast reirradiation, 1.5 Gy twice daily for 30 treatments during 15 days (45 Gy), using a 3-dimensional conformal technique. Main Outcomes and Measures The main outcomes of the present study were the predefined secondary study objectives of recurrence of breast cancer in the ipsilateral breast, late adverse events (>1 year after treatment), mastectomy incidence, distant metastasis–free survival, overall survival, and circulating tumor cell incidence. Results A total of 65 women were enrolled, with 58 evaluable for analysis (mean [SD] age, 65.12 [9.95] years; 48 [83%] white). Of the recurrences of breast cancer in the ipsilateral breast, 23 (40%) were noninvasive and 35 (60%) were invasive. In all 58 patients, 53 (91%) had tumors 2 cm or smaller. All tumors were clinically node negative. A total of 44 patients (76%) tested positive for estrogen receptor, 33 (57%) for progesterone receptor, and 10 (17%) forERBB2(formerlyHER2orHER2/neu) overexpression. Four patients had breast cancer recurrence, with a 5-year cumulative incidence of 5% (95% CI, 1%-13%). Seven patients underwent ipsilateral mastectomies for a 5-year cumulative incidence of 10% (95% CI, 4%-20%). Both distant metastasis–free survival and overall survival rates were 95% (95% CI, 85%-98%). Four patients (7%) had grade 3 and none had grade 4 or higher late treatment adverse events. Conclusions and Relevance For patients experiencing recurrence of breast cancer in the ipsilateral breast after lumpectomy and whole breast irradiation, a second breast conservation was achievable in 90%, with a low risk of re-recurrence of cancer in the ipsilateral breast using adjuvant partial breast reirradiation. This finding suggests that this treatment approach is an effective alternative to mastectomy.

Radiation therapy is an important modality in the treatment of patients with breast cancer. While its efficacy in the treatment of breast cancer was known shortly after the discovery of x-rays, significant advances in radiation delivery over the past 20 years have resulted in improved patient outcomes. With the development of improved systemic therapy, optimizing local control has become increasingly important and has been shown to improve survival. Better understanding of the magnitude of treatment benefit, as well as patient and biological factors that confer an increased recurrence risk, have allowed radiation oncologists to better tailor treatment decisions to individual patients. Furthermore, significant technological advances have occurred that have reduced the acute and long-term toxicity of radiation treatment. These advances continue to reduce the human burden of breast cancer. It is important for radiation oncologists and nonradiation oncologists to understand these advances, so that patients are appropriately educated about the risks and benefits of this important treatment modality.

Objective/Purpose External beam accelerated partial breast irradiation (EB-aPBI) can have potential challenges in daily reproducibility, although it has broader potential use than aPBI using brachytherapy. Image-guide radiotherapy (IGRT) can improve daily reproducibility and allow smaller treatment margins. Our institution utilized IG-IMRT to administer EB-aPBI in the prone position in a Phase I/II study to increase dose homogeneity, conformality, normal tissue avoidance, and reliable targeting. Our preliminary results and toxicity were promising. Here we report final physician- and patient-reported cosmetic outcomes from this prospective trial. Materials and Methods Women with node-negative invasive breast cancer or DCIS, tumors less than 3.0 cm, a negative sentinel lymph node biopsy, and surgical clips demarcating the lumpectomy cavity underwent prone EB-aPBI using IG-IMRT on an IRB-approved phase I/II study. The lumpectomy PTV represented a 2.0 cm lumpectomy cavity expansion. 38.5 Gy was delivered in 10 fractions over 5 days, such that 95% of the prescribed dose covered greater than 99% of the PTV. Dose constraints for the whole breast, lungs and heart were met. Results Twenty patients were enrolled, with a median patient age of 61.5 and a mean tumor size of 1.0 cm. 35% of patients had DCIS. At a median follow-up of 18.9 months, 40% and 10% of patients had G1 and G2 fibrosis, respectively, and 95% of patients had good to excellent physician-assessed cosmesis. At a median follow-up of 60.0 months (range 54-79 months), physician-assessed cosmetic outcome was good to excellent in 80%, with 30% and 20% of patients experiencing G1 and G2 fibrosis. Patient-reported outcomes at one year yielded 90% of patients with good to excellent cosmetic outcomes. At 3 years, 75% of patients reported good to excellent cosmesis. Eighty-eight percent of patients were completely satisfied with the treatment and results, and 94% of patients would choose aPBI again. With one local recurrence, the actuarial five year rate of local control was 95%. Conclusions These data demonstrate that EB-aPBI in the prone position using IG-IMRT continues to yield acceptable cosmetic outcomes at longer term follow-up, and a very high percentage of patients would choose this treatment again. (Supported by Komen Grant: BCTR0504070). Citation Format: Carmen Bergom, Phillip Prior, Kristofer Kainz, Natalya V Morrow, Ergun E Ahunbay, Alonzo Walker, X Allen Li, Tracy Kelly, Adam D Currey, Julia White. Sustained acceptable cosmetic outcomes and local control following accelerated partial breast irradiation using CT-guided IMRT in the prone position: Results from a phase I/II feasibility study [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-15-17.

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 95% ), and breast tissue sparing for an LC decrease larger than 35% (3 of 19, 7.5% decrease in breast evaluation volume V 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.

Patient comorbidities may affect the applicability of performance measures that are inherent in multidisciplinary cancer treatment guidelines. This article describes the distribution of common comorbid conditions by disease site and by patient and facility characteristics in patients who received radiation therapy as part of treatment for cancer of the breast, cervix, lung, prostate, and stomach, and investigates the association of comorbidities with treatment decisions.Stratified two-stage cluster sampling provided a random sample of radiation oncology facilities. Eligible patients were randomly sampled from each participating facility for each disease site, and data were abstracted from medical records. The Adult Comorbidity Evaluation Index (ACE-27) was used to measure comorbid conditions and their severity. National estimates were calculated using SUDAAN statistical software.Multivariable logistic regression models predicted the dependent variable "treatment changed or contraindicated due to comorbidities." The final model showed that ACE-27 was highly associated with change in treatment for patients with severe or moderate index values compared to those with none or mild (P.001). Two other covariates, age and medical coverage, had no (age) or little (medical coverage) significant contribution to predicting treatment change in the multivariable model. Disease site was associated with treatment change after adjusting for other covariates in the model.ACE-27 is highly predictive of treatment modifications for patients treated for these cancers who receive radiation as part of their care. A standardized tool identifying patients who should be excluded from clinical performance measures allows more accurate use of these measures.

Background: The purpose of this study is to quantitatively characterize interfraction variations of lumpectomy cavity (LC) in accelerated partial breast irradiation (APBI) and their dosimetric impacts, and to explore the use of an online adaptive replanning scheme to address these variations. Methods: A total of about 100 diagnostic-quality CT sets acquired using an in-room CT at each fraction during image-guided radiation therapy (IGRT) for ten randomly-selected patients treated with APBI in the supine position were analyzed. The LC, treated breast, lung and heart were delineated on each fraction CT. Organ volume change and deformation were quantified. For each fraction CT, three types of plans were created: adaptive, repositioning, and fully re-optimized plans. The plan qualities were compared. Results: Significant changes in LC shape and volume were observed during APBI. On average, the LC volume decreases by 23% from the planning CT. The average change in LC shape, as measured by the Dice’s coefficient, is 80%. For all patients, the adaptive plans were comparable to the re-optimization plans. For small and moderate LC changes (70%), the three types of plans were comparable, indicating that the current IGRT with the standard margins was sufficient to account for the interfraction variations. For cases with extreme LC change (30%), the adaptive plans offered improved target coverage and/or normal tissue sparing as compared with the repositioning plans. Conclusions: Significant variations in the LC between planning and treatment were found for APBI. The current practice of IGRT with standard planning target volume margins can account for these variations for most cases. Online adaptive replanning was needed for cases with extremely large changes in LC.

PurposeInflammatory breast cancer (IBC) is an aggressive subtype of breast cancer for which treatments vary, so we sought to identify factors that affect the receipt of guideline-concordant care.MethodsPatients diagnosed with IBC in 2004 were identified from the Breast and Prostate Cancer Data Quality and Patterns of Care Study, containing information from cancer registries in seven states. Variation in guideline-concordant care for IBC, based on National Comprehensive Cancer Network (NCCN) guidelines, was assessed according to patient, physician, and hospital characteristics.ResultsOf the 107 IBC patients in the study without distant metastasis at the time of diagnosis, only 25.8% received treatment concordant with guidelines. Predictors of non-concordance included patient age (≥70 years), non-white race, normal body mass index (BMI 18.5-25 kg/m(2)), patients with physicians graduating from medical school >15 years prior, and smaller hospital size (

Radiotherapy is a valuable adjuvant treatment in breast cancer that improves loco-regional control and overall survival. However, the breast cancer-specific survival advantage for patients receiving radiation therapy may be partially negated by higher non-breast cancer mortality, which may be due to cardiac mortality. Older data shows patients with left-sided breast cancer receiving radiation had increased cardiac mortality, and the rates of major coronary events and cardiac deaths increased with extrapolated mean heart radiation dose. Breast cancer radiation treatments in more modern eras have lower excess cardiac mortality. Advances in radiotherapy such as three-dimensional conformal radiation therapy, prone breast radiation and proton therapy have been demonstrated to decrease cardiac radiation doses in some patients. Deep inspiration breath hold (DIBH) is another tool radiation oncologists use to reduce dose to the heart. This technique exploits the increase in the separation of the heart and the chest wall when the lung expands with inspiration in order to decrease the radiation doses received by the heart. DIBH unambiguously reduces cardiac dose in dosimetric analyses, and early clinical data suggest that this reduction in cardiac dose translates into avoidance of the expected changes in cardiac perfusion. Although additional clinical data are required, DIBH offers the tantalizing potential of maintaining the benefits of radiotherapy while minimizing cardiac risks. Further research aimed to refine techniques and to optimize patient selection is ongoing. This chapter reviews DIBH techniques, DIBH dosimetric advantages, and practical considerations of DIBH.