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Simple intensity modulation of radiation therapy reduces acute toxicity compared with 2-dimensional techniques in adjuvant breast cancer treatment, but it remains unknown whether more complex or inverse-planned intensity modulated radiation therapy (IMRT) offers an advantage over forward-planned, 3-dimensional conformal radiation therapy (3DCRT).Using prospective data regarding patients receiving adjuvant whole breast radiation therapy without nodal irradiation at 23 institutions from 2011 to 2018, we compared the incidence of acute toxicity (moderate-severe pain or moist desquamation) in patients receiving 3DCRT versus IMRT (either inverse planned or, if forward-planned, using ≥5 segments per gantry angle). We evaluated associations between technique and toxicity using multivariable models with inverse-probability-of-treatment weighting, adjusting for treatment facility as a random effect.Of 1185 patients treated with 3DCRT and conventional fractionation, 650 (54.9%) experienced acute toxicity; of 774 treated with highly segmented forward-planned IMRT, 458 (59.2%) did; and of 580 treated with inverse-planned IMRT, 245 (42.2%) did. Of 1296 patients treated with hypofractionation and 3DCRT, 432 (33.3%) experienced acute toxicity; of 709 treated with highly segmented forward-planned IMRT, 227 (32.0%) did; and of 623 treated with inverse-planned IMRT, 164 (26.3%) did. On multivariable analysis with inverse-probability-of-treatment weighting, the odds ratio for acute toxicity after inverse-planned IMRT versus 3DCRT was 0.64 (95% confidence interval, 0.45-0.91) with conventional fractionation and 0.41 (95% confidence interval, 0.26-0.65) with hypofractionation.This large, prospective, multicenter comparative effectiveness study found a significant benefit from inverse-planned IMRT compared with 3DCRT in reducing acute toxicity of breast radiation therapy. Future research should identify the dosimetric differences that mediate this association and evaluate cost-effectiveness.

Purpose Questions remain about whether moderately hypofractionated whole-breast irradiation is appropriate for patients with triple-negative breast cancer. Methods and Materials Using the prospective database of a multicenter, collaborative quality improvement consortium, we identified patients with node-negative, triple-negative breast cancer who received whole-breast irradiation with either moderate hypofractionation or conventional fractionation. Using inverse probability of treatment weighting (IPTW), we compared outcomes using the Kaplan-Meier product-limit estimation method with Cox regression models estimating the hazard ratio for time-to-event endpoints between groups. Results The sample included 538 patients treated at 18 centers in 1 state in the United States, of whom 307 received conventionally fractionated whole-breast irradiation and 231 received moderately hypofractionated whole-breast irradiation. The median follow-up time was 5.0 years (95% confidence interval [CI], 4.77-5.15 years). The 5-year IPTW estimates for freedom from local recurrence were 93.6% (95% CI, 87.8%-96.7%) in the moderate hypofractionation group and 94.4% (95% CI, 90.3%-96.8%) in the conventional fractionation group. The hazard ratio was 1.05 (95% CI, 0.51-2.17; P = .89). The 5-year IPTW estimates for recurrence-free survival were 87.8% (95% CI, 81.0%-92.4%) in the moderate hypofractionation group and 88.4% (95% CI 83.2%-92.1%) in the conventional fractionation group. The hazard ratio was 1.02 (95% CI, 0.62-1.67; P = .95). The 5-year IPTW estimates for overall survival were 96.6% (95% CI, 92.0%-98.5%) in the moderate hypofractionation group and 93.4% (95% CI, 88.7%-96.1%) in the conventional fractionation group. The hazard ratio was 0.65 (95% CI, 0.30-1.42; P = .28). Conclusions Analysis of outcomes in this large observational cohort of patients with triple-negative, node-negative breast cancer treated with whole-breast irradiation revealed no differences by dose fractionation. This adds evidence to support the use of moderate hypofractionation in patients with triple-negative disease.

Purpose Brachytherapy is an essential technique to deliver radiation therapy and is involved in the treatment of multiple disease sites as monotherapy or as an adjunct to external beam radiation therapy. With a growing focus on the cost and value of cancer treatments as well new payment models, it is essential that standardized quality measures and metrics exist to allow for straightforward assessment of brachytherapy quality and for the development of clinically significant and relevant clinical data elements. We present the American Brachytherapy Society consensus statement on quality measures and metrics for brachytherapy as well as suggested clinical data elements. Methods and Materials Members of the American Brachytherapy Society with expertise in disease site specific brachytherapy created a consensus statement based on a literature review and clinical experience. Results Key quality measures (ex. workup, clinical indications), dosimetric metrics, and clinical data elements for brachytherapy were evaluated for each modality including breast cancer, cervical cancer, endometrial cancer, prostate cancer, keratinocyte carcinoma, soft tissue sarcoma, and uveal melanoma. Conclusions This consensus statement provides standardized quality measures and dosimetric quality metrics as well as clinical data elements for each disease site to allow for standardized assessments of brachytherapy quality. Moving forward, a similar paradigm can be considered for external beam radiation therapy as well, providing comprehensive radiation therapy quality measures, metrics, and clinical data elements that can be incorporated into new payment models.

Radiation therapy (RT) is an essential component in the management of breast cancer. Following breast-conserving surgery (BCS), adjuvant RT is the standard of care for most patients. Traditionally, RT was delivered with standard whole breast irradiation (WBI) over 5-7 weeks following BCS. However, WBI regimens have evolved; hypofractionated WBI now represents the standard approach, reducing the duration of treatment to 3-4 weeks. Over the past year, five-fraction WBI regimens have also emerged as standard of care for some patients based on data from the FAST and FAST-Forward trials. An alternative to WBI that is also available for patients with early-stage breast cancer following BCS is partial breast irradiation, which can reduce the duration of treatment and the volume of breast tissue irradiated. Outcomes from multiple randomized trials with over a 10-year follow-up have demonstrated the safety and efficacy of partial breast irradiation approaches. Single-fraction intraoperative RT has also been evaluated in two prospective trials although the outcomes available, as well as current guidelines, do not support its utilization outside of prospective studies. For patients requiring RT to the regional lymph nodes, data have demonstrated the safety of hypofractionated approaches for those undergoing BCS or mastectomy without reconstruction. Future directions for early-stage breast cancer radiotherapy include the study of even shorter regimens and studies evaluating the omission of RT versus omission of endocrine therapy for favorable-risk patients. Furthermore, studies are also underway evaluating shorter courses of radiation in patients undergoing breast reconstruction and the use of tumor genomics to identify appropriate patients for omission of radiation with limited nodal involvement.

PURPOSE: Adjuvant therapy in patients with ductal carcinoma in situ who undergo partial mastectomy remains controversial, particularly for low-risk patients (60 years or older, estrogen-positive, tumor extent < 2.5 cm, grade 1 or 2, and margins ≥ 3 mm). We performed a cost-effectiveness analysis comparing three strategies: no adjuvant treatment after surgery, a five-fraction course of accelerated partial breast irradiation using intensity-modulated radiation therapy (accelerated partial breast irradiation [APBI]–alone), or APBI plus an aromatase inhibitor for 5 years. MATERIALS AND METHODS: Outcomes including local recurrence, distant metastases, and survival as well as toxicity data were modeled by a patient-level Markov microsimulation model, which were validated against trial data. Costs of treatment and possible adverse events were included from the societal perspective over a lifetime horizon, adjusted to 2019 US dollars and extracted from Medicare reimbursement data. Quality-adjusted life-years (QALYs) were calculated based on utilities extracted from the literature. RESULTS: No adjuvant therapy was the least costly approach ($5,744), followed by APBI-alone ($11,070); combined therapy was costliest ($16,052). Adjuvant therapy resulted in slightly higher QALYs (no adjuvant, 11.320; APBI-alone, 11.343; and combination, 11.381). In the base case, no treatment was the cost-effective strategy, with an incremental cost-effectiveness ratio of $239,109/QALY for APBI-alone and $171,718/QALY for combined therapy. The incremental cost-effectiveness ratio for combined therapy compared with APBI-alone was $131,949. Probabilistic sensitivity analyses found that no therapy was cost effective (defined as $100,000/QALY of lower) in 63% of trials, APBI-alone in 19%, and the combination in 18%. CONCLUSION: No adjuvant therapy represents the most cost-effective approach for postmenopausal women 60 years or older who receive partial mastectomy for low-risk ductal carcinoma in situ.

Background The role of radiation therapy (RT) following breast-conserving surgery (BCS) in ductal carcinoma in situ (DCIS) remains controversial. Trials have not identified a low-risk cohort, based on clinicopathologic features, who do not benefit from RT. A biosignature (DCISionRT®) that evaluates recurrence risk has been developed and validated. We evaluated the impact of DCISionRT on clinicians’ recommendations for adjuvant RT. Methods The PREDICT study is a prospective, multi-institutional, observational registry in which patients underwent DCISionRT testing. The primary endpoint was to identify the percentage of patients where testing led to a change in RT recommendations. Results Overall, 539 women were included in this study. Pre DCISionRT testing, RT was recommended to 69% of patients; however, post-testing, a change in the RT recommendation was made for 42% of patients compared with the pre-testing recommendation; the percentage of women who were recommended RT decreased by 20%. For women initially recommended not to receive an RT pre-test, 35% had their recommendation changed to add RT following testing, while post-test, 46% of patients had their recommendation changed to omit RT after an initial recommendation for RT. When considered in conjunction with other clinicopathologic factors, the elevated DCISionRT score risk group (DS > 3) had the strongest association with an RT recommendation (odds ratio 43.4) compared with age, grade, size, margin status, and other factors. Conclusions DCISionRT provided information that significantly changed the recommendations to add or omit RT. Compared with traditional clinicopathologic features used to determine recommendations for or against RT, the factor most strongly associated with RT recommendations was the DCISionRT result, with other factors of importance being patient preference, tumor size, and grade.

BACKGROUND: Current national guidelines encourage consideration for treating the at-risk regional nodes (axillary, supraclavicular, and/or internal mammary) with directed regional nodal irradiation (RNI) during post-lumpectomy radiotherapy for high risk N0 (node negative) and N1 (1-3 nodes positive) breast cancer patients. This recommendation is based on the results of several randomized trials published over the last decade. Evidence regarding translation of these trials into clinical practice in the United States has been limited to date. In this study, we sought to characterize the temporal changes in and clinical factors associated with the utilization of RNI during post-lumpectomy radiotherapy for N0-N1 breast cancer across a contemporary, statewide consortium of radiation oncology practices. METHODS: Within a statewide radiation oncology quality consortium, 12,170 breast cancer patients were consecutively enrolled between 1/1/2013 and 10/31/2019 in both academic (teaching) and community (non-teaching) facilities. Data on receptor status, adjuvant systemic therapy, age, TNM stage, extent of axillary surgery, race, body mass index (BMI), type of treating facility, and year completing radiotherapy (RT) were collected. Eligibility for the present analysis was limited to patients with N0 and N1 disease not receiving neoadjuvant systemic therapy and receiving adjuvant radiotherapy after lumpectomy for non-metastatic breast cancer. Multiple variable logistic regression models were separately fit to explain the use of directed RNI (to the axilla, supraclavicular region, and/or internal mammary region) for the N0 and N1 populations separately and described using odds ratios (OR), with significant ORs (p RESULTS: A total of 8,468 patients from 29 treating facilities met the inclusion criteria: 6,929 (81.8%) with N0 and 1,539 (18.2%) N1 disease. RNI was performed in addition to whole breast radiation in 95 (1.4%) and 908 (59%) patients in the N0 and N1 cohorts respectively. For the N0 cohort, significant correlates of RNI on multivariable analysis (MVA) were receipt of adjuvant chemotherapy (OR 2.7), higher T-stage (OR 1.9 for T2 vs T1 and 27.3 for T3/T4 vs T1), axillary surgery [compared to sentinel node biopsy (SLN) alone : no axillary surgery (OR 14.5), axillary lymph node dissection (ALND) with 10+ nodes removed (OR 15.1) ALND after SLN (OR 2.7)], and underweight BMI (OR 4.9 compared to overweight, which was the reference as the largest BMI category). For the N1 cohort, MVA suggested adjuvant chemotherapy (OR 1.8) and larger tumors (OR 1.6 [T2 vs T1]) were significantly associated with use of RNI. The year completing RT was also significantly associated with RNI use, with 22% and 15% increases per year from 2013 to 2019 in the N0 and N1 cohorts, respectively. Lastly, receiving treatment in an academic facility compared to a community facility was significantly associated with receipt of RNI in both the N0 (OR 1.8) and N1 (OR 2.2) cohorts. CONCLUSION: In this large cohort, selective use of RNI added to post-lumpectomy whole breast radiotherapy is estimated to have increased over time, suggesting growing implementation of recent trial data and current clinical practice guidelines. Patient, treatment, and tumor characteristics appear to factor into the decision to treat with RNI, but differences in use between academic and community practices suggest opportunities for improving the consistency of care across care delivery settings. Ongoing trials seeking to identify subgroups of N1 patients in whom RNI can safely be omitted may be especially important to inform decisions, given the almost even split (59% receiving, 41% not) in practice observed in this large American cohort. Citation Format: Derek Bergsma, Kent Griffith, Reshma Jagsi, Michael Dominello, Thomas Boike, Joshua Dilworth, Amit Bhatt, Frank Vicini, Maggie Grubb, Jean Moran, James Hayman, Lori Pierce, on behalf of MROQC, the Michigan Radiation Oncology Quality Consortium. Contemporary practice patterns for the use of regional nodal irradiation during post-lumpectomy radiotherapy for patients with N0/N1 breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD4-07.

BACKGROUND: Evaluating whether physicians (MDs) accurately detect symptoms in patients (pts) is important because recognition of symptoms facilitates supportive care and because clinical trials often rely on MD assessments using the Common Toxicity Criteria for Adverse Events (CTCAE). METHODS: Breast cancer pts who received radiotherapy (RT) after lumpectomy at 29 practices were enrolled in a quality initiative, MROQC. Of 13,725 pts who completed RT between 1/1/2012 and 3/31/2020, 9,941 completed at least one pt-reported outcomes (PRO) questionnaire during RT. Where MD CTCAE assessments were available within 3 days of PRO evaluation, pt and MD ratings of 4 symptoms were compared. Pts reported breast pain via an approved modification of the Brief Pain Inventory, asking for ratings in the last 24 hours of pain at its worst, least, average, and “right now.” MDs were deemed to under-recognize pain when pts reported moderate pain (score 4-6) but MDs graded pain as 0 (absent) on the CTCAE, or when pts reported severe pain (score 7-10) but MDs’ CTCAE grade was ≤1. Bother from pruritis and edema were measured by modified scaled measures adapted from the Skindex. MDs were deemed to under-recognize pruritus and edema if they graded these as absent (grade 0) when pts reported bother often or all of the time from itching or swelling, respectively. MDs were deemed to under-recognize fatigue if they graded fatigue as absent (grade 0) when pts reported having significant fatigue most of the time or always.We describe the proportion of pts for whom under-recognition of at least 1 of these 4 symptoms occurred at least once during the treatment course and use multivariable logistic regression to evaluate predictors of this under-recognition, hypothesizing that it would be more common in racial minorities. RESULTS: 3,434/9,940 pts (34.5%) reported substantial breast pain, 3,039/9,923 (30.6%) frequent bother from pruritus, 2,363/9,906 (23.9%) frequent bother from edema, and 2,209/8,860 (24.9%) severe fatigue. We could evaluate under-recognition in 9,868 pts, with 37,593 independent paired observations of pt and MD reports (35,797 on the same date and 1,796 within 3 days). Under-recognition existed in 2,094/6,781 (30.9%) observations of pt-reported moderate/severe pain, 748/2,039 (36.7%) of pt-reported frequent pruritis, 2,309/4,492 (51.4%) of pt-reported frequent edema, and 390/2,079 (18.8%) of pt-reported severe fatigue. Under-recognition of at least 1 of these 4 symptoms occurred at least once during the pt’s treatment course for 2,933/5,510 (53.2%) of the pts who reported at least 1 substantial symptom during RT.Factors independently associated with under-recognition were (Table): younger age (OR=1.4 and 1.2 for CONCLUSIONS: PRO collection appears essential for trials because relying on the CTCAE to detect adverse events may miss important symptoms. Moreover, since MDs systematically miss substantial symptoms in certain patients, including pts who are younger or of black or other race, improving symptom detection may be a targetable mechanism to reduce disparities in RT experiences and outcomes. Multivariable model of symptom under-recognitionOR95% CIpAge--0.001 Citation Format: Reshma Jagsi, Kent A. Griffith, Frank Vicini, Thomas Boike, Michael Dominello, Gregory Gustafson, James A. Hayman, Jean M. Moran, Jeffrey Radawski, Eleanor Walker, Lori J. Pierce, on behalf of MROQC, the Michigan Radiation Oncology Quality Consortium. Identifying patients whose symptoms are under-recognized during breast radiotherapy: Comparison of patient and physician reports of toxicity in a multicenter cohort [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr GS3-07.

BACKGROUND: When considering health-related, quality-of-life and monetary costs associated with post-surgical treatments for women diagnosed with Ductal Carcinoma In Situ (DCIS), there remains a need for prognostic and predictive tools to help design individual treatment planning. DCISionRT (PreludeDx, Laguna Hills, CA) is a validated biologic signature to assess the 10-year event risk for DCIS patients managed with breast conserving surgery (BCS). The 10-year risks are provided separately for patients treated with and without adjuvant radiation therapy (RT) after BCS. The study was designed to measure the change in adjuvant RT recommendation. This is a planned interim analysis of the study, which will eventually comprise up to 2,500 patients and 100 sites. METHODS: The registry includes females over the age of 25 who are candidates for breast conserving surgery and eligible for RT. Survey forms are completed pre- and post-DCISionRT test to capture treatment recommendations and patient preferences. This interim analysis was performed to assess changes in RT recommendation for patients treated with BCS in different clinicopathologic subgroups. Specifically, ‘good risk’ profiles were based on the RTOG 9804 and ECOG 5194 study designs. RTOG 9804 like criteria was screening detected tumors with nuclear grade of 1 or 2, size of ≤ 2.5 cm, and clear (≥ 2 mm) surgical margins. ECOG 5194 like criteria was tumors with nuclear grade of 1 or 2, size of ≤ 2.5 cm, and clear surgical margins, or nuclear grade of 3, size of ≤ 1 cm, and clear surgical margins. Statistics were provided as percentages and counts, and McNemar’s test was used to assess change in RT with a p-value of RESULTS: There were 513 patients from 32 sites with testing completed after treatment with BCS. Of these patients, 16% were ≤ 50 years of age, 60% were ≥ 60 years of age, and 26% were ≥ 70 years of age. The DCIS tumor nuclear grade was high in 32% of patients, and the size of the tumor was ≤ 1 cm for 68% of patients. There were 49% of patients who met RTOG 9804 like criteria, 51% who met the ECOG 5194 (grade 1 or 2) criteria, and 45% of patients who met the ECOG 5194 (grade 3) criteria. RT was recommended to 52% and 53% patients for RTOG 9804/ECOG 5194 (grade 1 or 2) criteria pre-testing, and 42% post-testing. For ECOG 5194 (grade 3) like criteria, 64% of patients were recommended RT pre-test, and 40% were recommended RT post-test. In all criteria groups, for patients whom were initially recommended RT pre-test, 51% to 54% were not recommended RT post-test, while patients initially not recommended RT pre-test, 25% to 37% were recommended RT post-test. Overall, the post-test RT recommendation was significantly changed from between 42% and 46% for patients with ‘good-risk’ clinicopathologic criteria. CONCLUSIONS: The PREDICT study interim analysis demonstrates a significant absolute overall change post DCISionRT testing for RT recommendation in patients with ‘good-risk’ clinicopathology. RT recommendations were changed post-test for 42% to 46% of patients meeting RTOG 9804/ECOG 5194 like criteria. Integration of DCISionRT testing had a significant impact on the RT recommendations aimed at reducing overtreatment and minimizing undertreatment. Table 1. Pre-Post DCISionRT Impact by ‘good-risk’ criteria.n% RTPre-testYes% RTPost-test Yes% RTPre-Yes, Post-No% RTPre-No, Post-Yes% Total Decision Change95% CIp-valueRTOG 9804 criteriaGrade 1 or 2, Size ≤ 2.5 cm, screen detected, wide margins2525242543746%40 - 52%1.2E-02ECOG E5194 criteriaGrade 1 and 2, Size ≤ 2.5 cm, wide margins2625342533645%39 - 51%0.010Grade 3, Size ≤ 1 cm, wide margins2316440512542%36 - 48%2.4E-08 Citation Format: Chirag Shah, Frank Vicini, Steven C Shivers, Pat W Whitworth, Rakesh Patel, Charles E Cox, Troy Bremer. Clinical utility of a biologic signature to assess DCIS recurrence risk in patients meeting ‘good-risk’ criteria (RTOG 9804, ECOG 5194): Interim analysis of the DCISionRT PREDICT study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS6-17.

Adjuvant radiation therapy (RT) following breast-conserving surgery (BCS) represents a standard approach for most patients treated with breast-conserving therapy (BCT) for early-stage breast cancer. The first-generation of adjuvant RT schedules delivered daily treatment to the whole breast over 5–7 weeks. Although efficacious, this presented patients with a protracted course of treatment, reducing compliance and quality of life. While hypofractionated whole-breast irradiation (WBI) has become the standard, and part of the second-generation of RT regimens, it still requires 3–4 weeks. Concurrently, partial-breast irradiation (PBI) has also been explored as a technique to complete RT in a much shorter time period (1–3 weeks). There are now seven trials confirming the efficacy of this shorter treatment approach compared with standard WBI. In an effort to further reduce treatment duration, ultra-short WBI and PBI regimens have recently emerged as the third-generation of breast radiation schedules, allowing for the completion of treatment in 5 days or less. With respect to WBI, recent data from the FAST-Forward trial (which evaluated five fractions of WBI delivered in 1 week) demonstrated no difference in clinical outcomes at 5 years, with limited difference in toxicity, compared with hypofractionated 3-week WBI. Regarding PBI, published data on five-fraction regimens delivered in 2 weeks have also demonstrated comparable outcomes at 10 years, with reduced toxicities with long-term follow-up. This report will review additional ongoing studies evaluating even shorter courses of adjuvant RT treatment (one to five fractions), including single-fraction PBI or WBI.

Several randomized trials have been performed comparing partial breast irradiation (PBI) and whole breast irradiation (WBI) though controversy remains, including regarding differences by PBI technique. We performed a meta-analysis to compare results between WBI versus PBI and between PBI techniques. A systematic review was performed to identify modern randomized studies listed in MEDLINE from 2005 to 2020. PBI trials were divided into external beam radiation and brachytherapy techniques, with intraoperative radiation excluded. A Bayesian logistic regression model evaluated the risk of ipsilateral breast tumor recurrence (IBTR) and acute and chronic toxicities. The primary outcome was IBTR at 5 years with WBI compared with PBI. A total of 9758 patients from 7 studies were included (4840-WBI, 4918-PBI). At 5 years, no statistically significant difference in the rate of IBTR was noted between PBI (1.8%, 95% HPD 0.68–3.2%) and WBI (1.7%, 95% HPD 0.92–2.4%). By PBI technique, the 5-year rate of IBTR rate for external beam was 1.7% and 2.2% for brachytherapy. Rates of grade 2 + acute toxicity were 7.1% with PBI versus 47.5% with WBI. For late toxicities, grade 2/3 rates were 0%/0% with PBI compared with 1.0%/0% with WBI. IBTR rates were similar between PBI and WBI with no significant differences noted by PBI technique; PBI had reduced acute toxicities compared to WBI. Because studies did not provide toxicity data in a consistent fashion, definitive conclusions cannot be made with additional data from randomized trials needed to compare toxicity profiles between PBI techniques.

We sought to evaluate time trends and correlates of the use of a radiation tumor bed boost (TBB) after breast-conserving surgery and either conventional or hypofractionated whole-breast irradiation (CWBI or HWBI) for patients with early stage breast cancer.The National Cancer Database was queried for patients diagnosed between 2012 and 2016. We evaluated the utilization of TBB before and after publication of the Society of Surgical Oncology-American Society for Radiation Oncology margin guidelines in relation to sociodemographic variables, treatment facility, tumor characteristics, and whole-breast fractionation.The population included 380,387 patients, of whom 76.7% received a TBB. Utilization of TBB decreased over time (2012-2013: 79.2%; 2014: 76.6%; 2015-2016: 74.7%; P.001); this was seen for most subgroups evaluated. Rates of TBB differed by facility type and region. There was a decrease in TBB use in patients treated with CWBI over time (2012-2013: 84.9%; 2014: 83.5%; 2015-2016: 82.3%; P.001) but an increase among patients treated with HWBI (2012-2013: 55.5%; 2014: 60.7%; 2015-2016: 65.1%; P.001); this was also seen for low-risk patients (age70 years, negative margins). Among patients undergoing HWBI, TBB was more frequently used when 15 fractions were used compared with 16 fractions (76.8% vs 59.1%; P.001).The use of TBB decreased over time, coinciding with the publication of new margin guidelines, for patients receiving CWBI and those with negative margins, but TBB use increased for patients treated with HWBI. Hence, fractionation regimen is a critical variable in analyzing changes over time in the practice patterns of TBB.

Purpose Breast cancer-related lymphedema (BCRL) represents a significant concern for patients following breast cancer treatment, and assessment for BCRL represents a key component of survivorship efforts. Growing data has demonstrated the benefits of early detection and treatment of BCRL. Traditional diagnostic modalities are less able to detect reversible subclinical BCRL while newer techniques such as bioimpedance spectroscopy (BIS) have shown the ability to detect subclinical BCRL, allowing for early intervention and low rates of chronic BCRL with level I evidence. We present updated clinical practice guidelines for BIS utilization to assess for BCRL. Methods and Results Review of the literature identified a randomized controlled trial and other published data which form the basis for the recommendations made. The final results of the PREVENT trial, with 3-year follow-up, demonstrated an absolute reduction of 11.3% and relative reduction of 59% in chronic BCRL (through utilization of compression garment therapy) with BIS as compared to tape measurement. This is in keeping with real-world data demonstrating the effectiveness of BIS in a prospective surveillance model. For optimal outcomes patients should receive an initial pre-treatment measurement and subsequently be followed at a minimum quarterly for first 3 years then biannually for years 4–5, then annually as appropriate, consistent with previous guidelines; the target for intervention has been changed from a change in L-Dex of 10 to 6.5. The lack of pre-operative measure does not preclude inclusion in the prospective surveillance model of care. Conclusion The updated clinical practice guidelines present a standardized approach for a prospective model of care using BIS for BCRL assessment and supported by evidence from a randomized controlled trial as well as real-world data.

PURPOSE Understanding acute toxicities after whole-breast radiotherapy is important to inform patients, guide treatment decisions, and target supportive care. We evaluated patient-reported outcomes prospectively collected from a cohort of patients with breast cancer. METHODS We describe the maximal toxicity reported by 8,711 patients treated between 2012 and 2019 at 27 practices. Multivariable models identified characteristics associated with (1) breast pain, (2) bother from itching, stinging/burning, swelling, or hurting of the treated breast, and (3) fatigue within 7 days of completing whole-breast radiotherapy. RESULTS Moderate or severe breast pain was reported by 3,233 (37.1%): 1,282 (28.9%) of those receiving hypofractionation and 1,951 (45.7%) of those receiving conventional fractionation. Frequent bother from at least one breast symptom was reported by 4,424 (50.8%): 1,833 (41.3%) after hypofractionation and 2,591 (60.7%) after conventional fractionation. Severe fatigue was reported by 2,008 (23.1%): 843 (19.0%) after hypofractionation and 1,165 (27.3%) after conventional fractionation. Among patients receiving hypofractionated radiotherapy, younger age ( P < .001), higher body mass index (BMI; P < .001), Black ( P < .001) or other race ( P = .002), smoking status ( P < .001), larger breast volume ( P = .002), lack of chemotherapy receipt ( P = .004), receipt of boost treatment ( P < .001), and treatment at a nonteaching center predicted breast pain. Among patients receiving conventionally fractionated radiotherapy, younger age ( P < .001), higher BMI ( P = .003), Black ( P < .001) or other race ( P = .002), diabetes ( P = .001), smoking status ( P < .001), and larger breast volume ( P < .001) predicted breast pain. CONCLUSION In this large observational data set, substantial differences existed according to radiotherapy dose fractionation. Race-related differences in pain existed despite controlling for multiple other factors; additional research is needed to understand what drives these differences to target potentially modifiable factors. Intensifying supportive care may be appropriate for subgroups identified as being vulnerable to greater toxicity.

The American Brachytherapy Society brachytherapy schools have been pivotal in teaching and evolving the art of brachytherapy over the past decades. Founded in 1995, the schools have consistently provided content for the major disease sites including gynecologic, prostate, and breast with ocular, vascular, head and neck, pediatric, intraluminal, systemic, and intraoperative approaches more selectively addressed. In addition, Physics schools, either coupled with clinical schools or as stand-alone venues, have provided an essential educational component for practicing physicists, a pivotal part of the brachytherapy team. Celebrating 25 years in existence, this historical overview of the American Brachytherapy Society brachytherapy schools is a tribute to the many teachers who have shared their expertise, to the many students who have been enthusiastic and interactive participants, and the staff who have made it all possible, with the reward of perpetuating the important and timely art of brachytherapy.

The role of radiation therapy in the management of breast cancer continues to evolve. For patients with early stage breast cancer, hypofractionated whole breast irradiation following breast conserving surgery now represents the standard of care based on randomized data with long-term efficacy and toxicity outcomes. Partial breast irradiation has been found, in several randomized trials, to be effective and appropriate in selected patients with the potential to reduce toxicities as compared to whole breast irradiation. The study of tumor biology and genetics and its role in radiation therapy decision making continues to grow and the advances may help identify patients where radiation therapy can be safely omitted, with future studies looking at de-intensification approaches. Recent randomized data has demonstrated a growing role for regional nodal irradiation in patients with more advanced disease, with future studies looking to identify whether nodal radiation is indicated following neoadjuvant chemotherapy or with certain favorable tumor biologies. While postmastectomy radiation therapy represents a standard approach for patients with locally advanced breast cancer, new data supports the role of hypofractionated regimens as well as its use in patients previously considered lower risk with unfavorable tumor biology. Oligometastatic disease represents a new area of study in breast cancer with prospective trials underway and current data supporting consideration of techniques such as stereotactic body radiation therapy in appropriately selected patients.

The optimal tumor-free margin definition and width following breast-conserving therapy (BCT) for early-stage invasive cancers has been evaluated in previous meta-analyses and guidelines. We performed an updated meta-analysis to assess how improvements in treatment over time have affected the impact of margins on local recurrence (LR) rates over time. A systematic literature review identified 38 eligible studies comprising 54,502 patients treated between 1968 and 2010. Inclusion criteria included patients treated with BCT and minimum follow-up of 50 months, pathologic definitions of margin status explicitly stated, and LR data in relation to margin status. Data were pooled using a Bayesian logistic regression model to evaluate the risk of LR in relation to both margin status and study enrollment periods. Median follow-up was 7.25 years. Absolute LR rates decreased over time for each margin width cohort, with maximum differences between negative margin groups of less than 1% for the most recent enrollment period. However, relative rates of LR between different margin groups remained stable over time. With an additional 22,000 patients compared with the previous meta-analysis, this updated meta-analysis supports the consensus guideline of “no tumor on ink” for the majority of patients. Additionally, while concerns exist regarding a benefit with wider margins from previous studies, the analysis demonstrates the impact of margin width on LR rates has declined substantially over time, with very small differences between the narrowest and widest margin groups in the most recent cohort. Hence, older studies appear to have limited value to inform current management guidelines.

Purpose: An interim analysis of 508 patients who completed 12 months of prospective surveillance in the lymphedema PREVENT study found a significant difference in the time to preventive intervention trigger between those measured with Bioelectrical Impedance Spectroscopy (BIS) (9.5 months) vs. Tape Measure (TM) (2.8 months). However, questions emerged as to the reason for the difference and associated factors. Therefore, a study was performed to determine the factors that influenced the time to intervention trigger in patients randomized to either BIS or TM during the first 2 years post-operatively. Methods: Post-randomization to BIS or TM groups patients were assessed with the assigned measurement method at intervals of at least 3, 6, 12, 18, and 24 months post-operatively. A lymphedema prevention intervention consisting of wearing a compression sleeve and a gauntlet for 12 hours a day for 28 days was triggered when subclinical lymphedema was indicated. A change from baseline measures in the BIS group ≥ 6.5 L-DEX units and in TM ≥ 5% but Citation Format: Sheila Hedden Ridner, Mary S Dietrich, Chirag Shah, Frank Vicini. Factors associated with triggering events on the PREVENT trial at 2 years post-operatively [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-13-15.

There is an unmet need to identify women diagnosed with ductal carcinoma in situ (DCIS) with a low risk of in-breast recurrence (IBR) after breast conserving surgery (BCS), which could omit radiation therapy (RT), and also to identify those with elevated IBR risk remaining after BCS plus RT. We evaluated a novel biosignature for a residual risk subtype (RRt) to help identify patients with elevated IBR risk after BCS plus RT.Women with DCIS treated with BCS with or without RT at centers in the US, Australia, and Sweden (n = 926) were evaluated. Patients were classified into 3 biosignature risk groups using the decision score (DS) and the RRt category: (1) Low Risk (DS ≤2.8 without RRt), (2) Elevated Risk (DS2.8 without RRt), and (3) Residual Risk (DS2.8 with RRt). Total and invasive IBR rates were assessed by risk group and treatment.In patients at low risk, there was no significant difference in IBR rates with or without RT (total, P = .8; invasive IBR, P = .7), and there were low overall 10-year rates (total, 5.1%; invasive, 2.7%). In patients with elevated risk, IBR rates were decreased with RT (total: hazard ratio [HR], 0.25; P.001; invasive: HR, 0.28; P = .005); 10-year rates were 20.6% versus 4.9% (total) and 10.9% versus 3.1% (invasive). In patients with residual risk, although IBR rates decreased with RT after BCS (total: HR, 0.21; P.001; invasive: HR, 0.29; P = .028), IBR rates remained significantly higher after RT compared with patients with elevated risk (HR, 2.5; 95% CI, 1.2-5.4; P = .018), with 10-year rates of 42.1% versus 14.7% (total) and 18.3% versus 6.5% (invasive).The novel biosignature identified patients with 3 distinct risk profiles: Low Risk patients with a low recurrence risk with or without adjuvant RT, Elevated Risk patients with excellent outcomes after BCS plus RT, and Residual Risk patients with an elevated recurrence risk remaining after BCS plus RT, warranting potential intensified or alternative treatment approaches.

We investigated whether the use of chemotherapy before whole breast irradiation (WBI) using either conventional fractionation (CWBI) or hypofractionation (HWBI) is associated with increased toxic effects or worse cosmetic outcome compared with WBI alone.We identified 6754 patients who received WBI alone (without a third field covering the superior axillary and supraclavicular nodal regions) with data prospectively collected in a statewide consortium. We reported rates of 4 toxic effects: physician-reported acute moist desquamation, patient-reported acute moderate/severe breast pain, a composite acute toxic effect measure (including moist desquamation and either patient- or physician-reported moderate/significant breast pain), and physician-reported impaired cosmetic outcome at 1 year after WBI. Successive multivariable models were constructed to estimate the effect of chemotherapy on these outcomes.Rates of moist desquamation, patient-reported pain, composite acute toxic effects, and impaired cosmetic outcome were 23%, 34%, 42%, and 10% for 2859 patients receiving CWBI and 13%, 28%, 31%, and 11% for 3895 patients receiving HWBI. Receipt of chemotherapy before CWBI was not associated with higher rates of patient-reported pain, composite acute toxic effects, or impaired cosmetic outcome compared with CWBI without chemotherapy but was associated with more moist desquamation (odds ratio, 1.32 [1.07-1.63]; P = .01). Receipt of chemotherapy before HWBI was not associated with higher rates of any of the 4 toxic effects compared with HWBI alone.In this cohort, use of chemotherapy before WBI was generally well tolerated. CWBI with chemotherapy but not HWBI with chemotherapy was associated with higher rates of moist desquamation. Rates of acute breast pain and impaired cosmetic outcome at 1 year were comparable in patients receiving chemotherapy before either CWBI or HWBI. These data support the use of HWBI after chemotherapy.

Background: NCCN treatment guidelines support de-escalation of radiotherapy (RT) for “low risk” patients with ductal carcinoma in situ (DCIS) treated with breast conserving surgery (BCS) for which improved specificity in identifying patients with low in-breast recurrence (IBR) rates who are unlikely to benefit from RT is needed. “low risk” has been defined as the absence of “high risk” clinicopathological (CP) factors, which include younger age (2.8 without RRt) and Residual Risk groups (DS>2.8 with RRt), where 10-yr total IBR rates were evaluated using Cox Proportional Hazards and Kaplan Meier analysis by treatment, biosignature Risk group, and CP criteria. Results: The biosignature classified 37% of women treated with BCS as Low Risk (n=338) and 63% (n=588) were classified into the combined Elevated/Residual Risk group. Among patients who did not receive RT, those in the Elevated/Residual Risk group had higher IBR rates (p Citation Format: Rachel Rabinovitch, Frank A. Vicini, Chirag Shah, Julie Margenthaler, Brian Czerniecki, Pat Whitworth, Sheila Weinmann, Michael C. Leo, Fredrik Wärnberg, G. Bruce Mann, Steven C. Shivers, David Dabbs, Karuna Mittal, Troy Bremer. Guiding de-escalation of treatment for patients with DCIS using a predictive 7-gene biosignature: Identification of a clinically low-risk patient group [abstract]. In: Proceedings of the AACR Special Conference on Rethinking DCIS: An Opportunity for Prevention?; 2022 Sep 8-11; Philadelphia, PA. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_1): Abstract nr B016.

Following partial mastectomy, whole-breast irradiation (WBI), delivered over 3 to 6 weeks, has been the standard adjuvant radiation approach for early-stage breast cancer. A growing body of literature over the past decade has suggested that irradiation of the partial breast, including the tumor bed plus a margin, may be a suitable alternative for appropriately selected patients. The use of partial breast irradiation (PBI) has been studied in multiple prospective randomized trials, now with up to 10 years of follow-up, establishing similar safety and efficacy compared with WBI. Advantages of PBI include (1) reduced treatment duration, (2) potential reductions in treatment-related toxicity, (3) improved cosmetic outcomes, and (4) reduced costs. The purpose of this article is to review appropriate patient selection criteria, clinical and toxicity outcomes data, clinical consensus practice guidelines, and the various PBI techniques. The National Surgical Adjuvant Breast and Bowel Project (NSABP) B39/Radiation Therapy Oncology Group (RTOG) 0413 study (NRG Oncology) is the most recently published (abstract form only) prospective randomized trial comparing PBI using 3D conformal external beam radiation therapy (3D-CRT, 38.5 Gy/10 fractions, twice daily) or brachytherapy (interstitial catheters or applicator based, 34 Gy/10 fractions, twice daily), vs. WBI (50 Gy ± tumor a bed boost). With a median follow-up of 10.2 years, the 10-year ipsilateral breast tumor recurrence-free interval was 95.2% vs. 95.9% for PBI and WBI, although it did not meet the statistical significance for equivalence. Similarly, the randomized trial of accelerated partial breast irradiation using 3-dimensional conformal radiotherapy (RAPID) trial is a prospective randomized trial comparing primarily 3D-CRT (38.5 Gy/10 fractions, twice daily) with WBI, (42.5 Gy/16 daily fractions or 50 Gy/25 daily fractions ± tumor bed boost). Rates of ipsilateral breast tumor recurrence (IBTR) at 8 years were not statistically significantly different (PBI vs WBI, 3% vs. 2.8%; HR = 1.27; 90% VI, 0.84–1.91). There is a growing body of literature supporting the use of PBI in appropriately selected patients and its use should continue to increase.

Purpose Although radiation therapy has traditionally been delivered with external beam or brachytherapy, intraoperative radiation therapy (IORT) represents an alternative that may shorten the course of therapy, reduce toxicities, and improve patient satisfaction while potentially lowering the cost of care. At this time, there are limited evidence-based guidelines to assist clinicians with patient selection for IORT. As such, the American Brachytherapy Society presents a consensus statement on the use of IORT. Methods Physicians and physicists with expertise in intraoperative radiation created a site-directed guideline for appropriate patient selection and utilization of IORT. Results Several IORT techniques exist including radionuclide-based high-dose-rate, low-dose-rate, electron, and low-energy electronic. In breast cancer, IORT as monotherapy should only be used on prospective studies. IORT can be considered in the treatment of sarcomas with close/positive margins or recurrent sarcomas. IORT can be considered in conjunction with external beam radiotherapy for retroperitoneal sarcomas. IORT can be considered for colorectal malignancies with concern for positive margins and in the setting of recurrent gynecologic cancers. For thoracic, head and neck, and central nervous system malignancies, utilization of IORT should be evaluated on a case-by-case basis. Conclusions The present guidelines provide clinicians with a summary of current data regarding IORT by treatment site and guidelines for the appropriate patient selection and safe utilization of the technique. High-dose-rate, low-dose-rate brachytherapy methods are appropriate when IORT is to be delivered as are electron and low-energy based on the clinical scenario.

Following breast conserving surgery, the standard of care has been to deliver adjuvant radiation therapy directed to the whole breast (WBI) over a period of 3-7 weeks. Over the past decade, increasing data have supported the concept that treatment to the whole breast may not be required in selected patients, allowing for the emergence of partial breast irradiation (PBI). Multiple randomized trials with 5-10 years of follow-up have been published documenting the safety and efficacy associated with PBI using multiple techniques. Questions that remain to be answered include (a) what is the optimal PBI technique for each clinical scenario, (b) are there additional patients that can be effectively managed with PBI approaches, and (c) are there different techniques/dose schedules that allow for further reduction in treatment duration and/or toxicities? Partial breast irradiation represents a standard approach for appropriately selected patients. PBI provides comparable clinical outcomes to WBI while allowing for a reduction in the duration treatment and the potential for reduced toxicities. Future studies may also help to better define which patients require no radiation, PBI, hypofractionated WBI or conventional WBI, based upon patient, clinical, pathologic features as well as potentially using tumor genetics.

Objective: Elderly patients with low-risk hormone-positive breast cancer are at risk of over treatment. Avoidance of radiation therapy (RT) in favor of endocrine therapy alone was first heralded as the optimal conservative strategy due to logistical simplicity, low acute sequelae and a reduction of contralateral cancers not seen with RT. However, long-term use of aromatase inhibitors (AI) is not without costs and morbidity, often leading to low compliance and notable late effects. We therefore performed a cost-effectiveness analysis to compare the outcomes and costs between AI for five years without RT versus hypofractionated RT alone without endocrine therapy. Materials and Methods: Using data from available phase III trials and meta-analyses, we constructed a patient-level microsimulation Markov decision model to replicate the comparative outcomes between the strategies above from the societal perspective among 200,000 simulated patients. Five years of anastrozole was compared to a 15-fraction hypofractionated whole breast RT course without boost in a cohort of patients with low-risk disease as defined by CALGB 9343 entry criteria. Noncompliance with AI was modeled from recent population-based data. Relative effectiveness on ipsilateral breast tumor recurrence and contralateral breast cancers were based off the NSABP B-21 trial, adjusted to match the modern outcomes demonstrated in CALGB 9343 and PRIME II with further adjustment for AI over tamoxifen (ATAC, EBCTCG meta-analysis). Indirect costs of travel were accounted for, as were the costs of common and serious side-effects from RT (dermatitis, fibrosis, second malignancy, heart disease) and AI (arthralgia, hot flashes, osteopenia, fracture, thrombosis). A 1-year cycle time and lifetime horizon were used, with all costs adjusted to 2018 US dollars and extracted primarily from Medicare reimbursement data. The primary measure of efficacy was the quality-adjusted life-year (QALY) with age-adjusted utilities extracted from the literature. Half-cycle correction and a 3% discount rate were applied. Probabilistic sensitivity analysis was used to vary all parameters simultaneously. Results: On average, RT was approximately $3,981 more expensive than endocrine therapy over the lifetime horizon. Under a number of assumptions, RT appeared similar in long-term effectiveness to AI therapy, with a difference of less than 0.03 quality-adjusted life years. Given the low value of the denominator in the incremental cost-effectiveness ratio (ICER), RT did not meet the formally defined $100,000/QALY threshold. On one-way sensitivity analysis, the ICER was particularly sensitive to the incidence and impact of salvage strategies for recurrence, treatment of contralateral breast cancers, cardiac events and fracture rates. Conclusions: Modeling with the available evidence suggests it is likely that quality-of-life after RT-alone is nearly identical to an AI-alone strategy but associated with a small increase in cost. These results suggest select patients at risk of noncompliance can safely be treated with RT-alone rather than AI alone. Given the relative pros and cons of each strategy, RT-alone should be considered for select elderly low-risk breast patients. Citation Format: Ward MC, Vicini F, Chadha M, Pierce L, Recht A, Hayman J, Thaker N, Khan A, Keisch M, Shah C. Evaluating the cost of endocrine therapy vs. radiation therapy alone for low risk hormone positive early stage breast cancer in elderly patients [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-15-02.

Purpose/Objective(s) There is an unmet need to identify women diagnosed with DCIS who have a low recurrence risk and could omit radiotherapy (RT) after breast conserving surgery (BCS), or an elevated recurrence risk after treatment with BCS plus RT. Materials/Methods Pathology, clinical data, and FFPE tissue samples were evaluable for 485 women treated for DCIS with BCS with negative margins, with or without whole breast RT, at centers in Sweden, US and Australia. A subset with large tumor size (> 2.5 cm) &/or nuclear grade III DCIS was assessed (n = 250). A validated biosignature (Prelude, Laguna Hills CA) and a novel response subtype biosignature to RT after BCS were determined using protein biomarkers (p16/INK4A, Ki-67, COX-2, PgR, HER2, FOXA1, SIAH2) assayed on FFPE tissue. The two biosignatures classified women into three risk groups: Low risk, Elevated risk with a good response subtype (Rst) and Elevated risk with a poor Rst to RT after BCS. Ipsilateral breast tumor recurrence (IBTR) included DCIS or Invasive Breast Cancer (IBC) that was local, regional, or metastatic. Hazard ratios and 10-year risks were calculated using Cox proportional hazards and Kaplan-Meier analyses. Results Of 250 women with nuclear grade III DCIS and/or size > 2.5 cm, biosignatures classified 72% (n = 179) of patients into an Elevated risk group consisting of those with a good (n = 122) or a poor (n = 57) response subtype (Rst) to RT after BCS. The remaining 28% of women were classified into a low-risk group (n = 71). In the low-risk group (n = 71), women treated without RT had good 10-year outcomes with no (0%) 10-year IBC events, and derived no significant RT benefit (1%) in 10-year IBTR rates (IBTR P = 0.81). Of all women treated without RT (n = 102), those in the elevated risk group (good and poor Rst combined, n = 61) had significantly worse 10-year IBTR/IBC rates (31%/17%) than those in the low-risk group, (IBTR HR = 12, P = 0.01). Women treated with RT in the elevated risk group with a good Rst (n = 77) had significantly reduced 10-year IBTR/IBC rates of 5%/3%. However, no significant benefit to RT was noted for women within the elevated risk group with a poor Rst (n = 41) who had 10-year IBTR/IBC rates of 25%/20%. Of all women treated with RT in the elevated risk group (n = 118), those with a poor Rst had significantly worse outcomes than those with a good Rst (IBTR HR = 4.1, P = 0.035, IBC HR = 8, P = 0.053). Conclusion In women with nuclear grade III DCIS &/or size > 2.5 cm, DCISionRT combined with a novel response subtype biosignature (Rst) identified an elevated risk group with two distinct subtypes of women: (1) a poor Rst that had high IBTR/IBC rates with or without RT and (2) a good Rst deriving significant benefit from adjuvant RT. Women in the corresponding low risk group had low 10-year IBTR/IBC rates and derived no significant benefit from adjuvant RT.

502 Background: Breast conserving surgery (BCS) followed by radiotherapy (RT) has been the mainstay for DCIS treatment. Adjuvant endocrine therapy (ET) has often been recommended based on multiple randomized clinical trials (RCT). However, these studies have failed to identify subsets of patients who did or did not benefit from adjuvant RT/ET therapy after BCS. We evaluated the association of a 7-gene predictive DCIS biosignature (PreludeDx, Laguna Hills, CA) to assess the impact of ET on 10-yr ipsilateral breast recurrence (IBR) risk after BCS alone or with RT. Methods: DCISionRT with integrated Residual Risk subtype (RRt) reported a decision score (DS) and three risk groups, a) Low Risk (DS≤2.8), b) Elevated Risk (DS > 2.8 without RRt) and c) Residual Risk (DS > 2.8 with RRt). DCISionRT/RRt was evaluated in 926 patients from 4 cohorts who were treated with BCS alone or with RT/ET. The three risk groups were assessed for 10-yr total (invasive and in situ) IBR risk by Kaplan Meier and Cox proportional hazards survival analysis. Results: DCISionRT/RRt classified 338 (37%) women as Low Risk, 399 (43%) as Elevated Risk, and 189 (20%) as Residual Risk. Overall, patients treated with ET had a significantly lower 10-yr IBR risk in multivariable analysis independent of RT (HR = 0.55, p = 0.033). In the Low Risk group treated with BCS without RT, the average 10-yr IBR risk was 5.6% (95% CI 2.5-12.1%, n = 124) and was not significantly different with vs without ET (p = 0.33). The 10-yr IBR risk after BCS alone was 22.6% in the Elevated Risk group and 50.3% in the Residual Risk group. Compared to BCS alone, the 10-year IBR risk tended to be lower in patients prescribed ET without RT in the Elevated (11.6%, 95% CI 3.9-32%) and Residual (15.4%, 95% CI 4.1-49%) Risk groups. 10-yr IBR risk was not significantly reduced by RT within the Low Risk group (p = 0.7) but was significantly reduced to 6.3% (95% CI 3.4-12%) by RT within the Elevated Risk (HR = 0.2, p < 0.001) and to 12.5% (95% CI 6.4-23%) within the Residual Risk (HR = 0.2, p < 0.001) groups. 10-yr IBR risk was significantly higher after RT in the Residual (HR = 2.5, p = 0.013) vs. Elevated Risk groups. After BCS and RT, there was no significant reduction in 10-yr IBR risk for those treated with vs without ET in the Elevated (p = 0.22) and Residual (p = 0.87) risk groups. Conclusions: The DCISionRT/RRt biosignature demonstrated prognostic and predictive RT response in Elevated and Residual Risk patients. Consistent with prior RCT data, ET was associated with lower 10-yr IBR risk overall, and within the DCISionRT Elevated and Residual Risk groups without RT. However, neither ET nor RT were asssociated with significant risk reduction in the Low Risk group. There was no added benefit of ET in the Elevated and Residual Risk groups after BCS+RT; the Residual Risk group patients still had a high IBR risk after RT.

Several randomized trials have been performed comparing partial breast irradiation (PBI) and whole breast irradiation (WBI) though controversy remains, including regarding differences by PBI technique. We performed a meta-analysis to compare results between WBI versus PBI and between PBI techniques.A systematic review was performed to identify modern randomized studies listed in MEDLINE from 2005 to 2020. PBI trials were divided into external beam radiation and brachytherapy techniques, with intraoperative radiation excluded. A Bayesian logistic regression model evaluated the risk of ipsilateral breast tumor recurrence (IBTR) and acute and chronic toxicities. The primary outcome was IBTR at 5 years with WBI compared with PBI.A total of 9758 patients from 7 studies were included (4840-WBI, 4918-PBI). At 5 years, no statistically significant difference in the rate of IBTR was noted between PBI (1.8%, 95% HPD 0.68-3.2%) and WBI (1.7%, 95% HPD 0.92-2.4%). By PBI technique, the 5-year rate of IBTR rate for external beam was 1.7% and 2.2% for brachytherapy. Rates of grade 2 + acute toxicity were 7.1% with PBI versus 47.5% with WBI. For late toxicities, grade 2/3 rates were 0%/0% with PBI compared with 1.0%/0% with WBI.IBTR rates were similar between PBI and WBI with no significant differences noted by PBI technique; PBI had reduced acute toxicities compared to WBI. Because studies did not provide toxicity data in a consistent fashion, definitive conclusions cannot be made with additional data from randomized trials needed to compare toxicity profiles between PBI techniques.

To compare the risk of subclinical breast cancer-related lymphedema (sBCRL) using bioimpedance spectroscopy (BIS) or tape measure (TM) by the extent of axillary surgery and regional nodal irradiation (RNI).Patients were randomized to surveillance with TM or BIS. A BIS ≥6.5 L-Dex units or TM volume change ≥5 and10% above presurgical baselines "triggered" sBCRL. The incidence of sBCRL by sentinel node biopsy or axillary lymph node dissection (ALND) with or without RNI was examined for 484 patients. Radiation was categorized as "limited RNI" (axilla level I/II only) or "extensive RNI" (axilla level III or supraclavicular fossa with or without level I/II).At a median follow-up of 20.5 months, 109 of 498 patients (21.9%) triggered sBCRL (BIS 13.5% vs TM 25.6%; P.001). In patients not receiving RNI, BIS triggered 12.9% of patients undergoing SNB and 25.0% undergoing ALND (P = .18). Extensive RNI significantly increased triggering with BIS versus no RNI after sentinel node biopsy (SNB; 33.3% vs 12.9%; P = .03) but not ALND (30.8% vs 25.0%; P = .69). Triggering by TM was greater than 25% for most subgroups and was inferior to BIS in discriminating the risk of sBCRL by utilization of RNI or axillary surgery.The lower triggering rates with BIS and its better discrimination of the risk of sBCRL by receipt and type of RNI compared with TM support its use for posttreatment surveillance to detect sBCRL and to initiate early intervention. The risk of sBCRL increased with more extensive axillary treatment. Patients having ALND or extensive RNI require close surveillance for BCRL. Longer follow-up is required to determine rates of progression to clinical lymphedema.

We performed a cost-effectiveness analysis of three strategies for the adjuvant treatment of early breast cancer in women age 70 years or older: an aromatase inhibitor (AI-alone) for 5 years, a 5-fraction course of accelerated partial-breast irradiation using intensity-modulated radiation therapy (APBI-alone), or their combination. We constructed a patient-level Markov microsimulation from the societal perspective. Effectiveness data (local recurrence, distant metastases, survival), and toxicity data were obtained from randomized trials when possible. Costs of side effects were included. Costs were adjusted to 2019 US dollars and extracted from Medicare reimbursement data. Quality-adjusted life-years (QALY) were calculated using utilities extracted from the literature. The strategy of AI-alone ($12,637) was cheaper than both APBI-alone ($13,799) and combination therapy ($18,012) in the base case. All approaches resulted in similar QALY outcomes (AI-alone 7.775; APBI-alone 7.768; combination 7.807). In the base case, AI-alone was the cost-effective strategy and dominated APBI-alone, while combined therapy was not cost-effective when compared to AI-alone ($171,451/QALY) or APBI-alone ($107,932/QALY). In probabilistic sensitivity analyses, AI-alone was cost-effective at $100,000/QALY in 50% of trials, APBI-alone in 28% and the combination in 22%. Scenario analysis demonstrated that APBI-alone was more effective than AI-alone when AI compliance was lower than 26% at 5 years. Based on a Markov microsimulation analysis, both AI-alone and APBI-alone are appropriate options for patients 70 years or older with early breast cancer with small cost differences noted. A prospective trial comparing the approaches is warranted.

Hypofractionated radiation therapy is a less burdensome and less costly approach that is efficacious for most patients with early-stage breast cancer. Concerns about racial disparities in adoption of medical advances motivate investigation of the use of hypofractionated radiation in diverse populations. The goal of our study was to determine whether hypofractionated whole breast radiation therapy after breast-conserving surgery was being similarly used across racial groups in the state of Michigan.A prospectively collected statewide quality consortium database from 25 institutions was queried for patients with breast cancer who completed hypofractionated (HF) or conventionally fractionated whole breast radiation therapy from January 2012 to December 2018. We used patient-level multivariable modeling to evaluate associations between HF use and race, controlling for patient and facility factors, and multilevel modeling to account for patient clustering within facilities.Of 9634 patients analyzed, 81% self-reported race as white, 17% as black, and 2% as Asian, similar to statewide and national distributions. In addition, 31.7% of whites were treated at teaching centers compared with 66.7% of blacks and 64.8% of Asians. In 2018, HF was used in 72.7% of whites versus 56.7% of blacks and 67.6% of Asians (P = .0411). On patient-level multivariable analysis, black and Asian races were significantly associated with a lower likelihood of HF receipt (P.001), despite accounting for treatment year, age, laterality, body mass index, breast volume, comorbidities, stage, triple-negative status, intensity modulated radiation therapy use, teaching center treatment, and 2011 American Society for Radiation Oncology Hypofractionation Guideline eligibility. On multilevel analysis, race was no longer significantly associated with HF receipt.We observed that black and Asian patients receive hypofractionated whole breast radiation therapy less often than whites, despite more frequent treatment at teaching centers. Multilevel modeling eliminated this disparity, suggesting that differences in facility-specific HF use appear to have contributed. Further inquiry is needed to determine whether reduction of facility-level variation may reduce disparities in accessing HF treatment.

Background: We report outcomes using prospective BIS surveillance in a high-risk cohort of patients who all underwent axillary lymph node dissection (ALND). Methods: From 8/2010 through 12/2016, 206 consecutive patients were evaluated with BIS as part of a prospective surveillance program. 30 underwent ALND and constitute the study population. The program included pre-operative BIS measurement as well as post-operative assessments at regular intervals. Patients with L-Dex readings increasing by more than 10 from baseline were considered to have subclinical BCRL and treated with an over-the-counter (OTC) compression sleeve for 4 weeks. For the purpose of this analysis, additional high-risk features were defined as receipt of axillary radiation, a high body mass index (BMI) or the use of taxane based chemotherapy. Chronic BCRL was defined as the need for complex decongestive physiotherapy (CDP). Results: Median follow-up was 36 months (range: 4.8-122.1 months). The median number of nodes removed was 18 (range: 5-32) and the median number of positive nodes was two. The median age for the cohort was 57.5 years old with 70% of patients undergoing mastectomy and the remainder breast conserving therapy. With respect to additional high-risk features, 77% also received taxane-based chemotherapy, 62% axillary irradiation, and 48% had an elevated BMI. Overall, 86% of patients had at least one additional high-risk feature, 70% at least two, and 23% had all three additional high-risk features. Seven patients (23%) had an elevated L-Dex score at some point during follow-up and underwent intervention with an OTC sleeve for 4 weeks. To date, no patients have required CDP at any time. Conclusions: Prospective surveillance with BIS in a high-risk cohort of patients all undergoing ALND (plus additional high-risk features) led to no patients requiring CDP. These excellent findings are consistent with growing data supporting the use of BIS in prospective BCRL surveillance programs. Citation Format: Kaufman D, Shah C, Vicini F. Low rates of chronic breast cancer related lymphedema (BCRL) in a cohort of high-Risk patients undergoing prospective surveillance with bioimpedance spectroscopy (BIS) [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-14-09.

Background: Electron intraoperative radiotherapy (IORT) can be used during breast conservation surgery to treat early-stage invasive breast cancer. While IORT may be an attractive alternative to traditional post-operative radiotherapy for many patients, its effectiveness in preventing local recurrence is still being evaluated. Using data from current clinical and observational studies, we aimed to assess the impact of single-fraction electron IORT on local recurrence rates. Methods: Studies on single-fraction electron IORT during breast conservation surgery were identified through a search of PubMed and Google Scholar, as well as secondary referencing. Local recurrence rate was the main outcome of interest. Protocols from each publication were assessed for potential sources of heterogeneity. A meta-analysis of proportions, using binomial distribution to model the within-study variability and a random effects model, was conducted to estimate a pooled local recurrence rate. In order to estimate a 5-year recurrence rate, we applied a single-sample Poisson-normal model to model the probability of events occurring during a fixed period of time (60 months). Results: A total of 13 independent publications were identified for abstraction. The analysis demonstrated a pooled monthly local recurrence rate of 0.02% per person-month (95% CI: 0.00 – 0.06%) for the studies with < 5 years of follow-up, 0.03% per person-month (0.02 – 0.06%) for studies with ≥ 5 years of follow-up, and 0.02% per person-month (0.01 – 0.04%) overall. Based on this model, the predicted 5-year recurrence rate is 2.7%, with a 95% confidence interval of 1.9% - 3.7%. Conclusions: According to the published literature, the rate of breast cancer local recurrence after electron IORT was 0.02% per person-month; with an adjusted 5-year recurrence rate of 2.7%. These findings support the recent guidelines from the American Society for Radiation Oncology (ASTRO) supporting the use of electron IORT in low-risk patients. Citation Format: Harness J, Shah C, Brooks E, Via C, Vicini F. Meta-analysis of local recurrence of invasive breast cancer after electron intraoperative radiotherapy [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-11-13.

Background: We evaluated the impact of structured surveillance using bioimpedance spectroscopy (BIS) to prevent clinical BCRL in a group of high-risk (axillary lymph node dissection) patients. Methods: From April 2010 through November 2016, 93 patients who were treated with axillary lymph node dissection (ALND) were prospectively monitored with BIS using L-Dex (Impedimed). Patients received a pre-operative baseline L-Dex measurement followed by post-operative assessments at regular intervals. An elevated L-Dex score was defined as an increase of ≥10 points above baseline (considered subclinical BCRL). Intervention consisted of applying an over the counter (OTC) sleeve for 4 weeks followed by re-evaluation. The need for complete decongestive physiotherapy (CDP) represented a surrogate for the development of clinically significant, chronic BCRL. Results: Median follow-up was 24 months (range: 0.3-206.4 months). The median number of nodes removed was 19 (range: 5-41) and the median number of positive nodes was 3. Median age was 53 years old. Eighty five percent of patients underwent mastectomy and the remainder breast conserving therapy. 55% of patients received taxane based chemotherapy, 24% received some form of axillary RT (15% high tangents and 9% comprehensive regional nodal RT) and 74% had an elevated body mass index (BMI, > 25). Overall, 75% of these patients had at least one additional high-risk feature, 48% had at least two, and 6% had 3 (either taxane chemotherapy, axillary RT or elevated BMI). Thirty-three patients (35.4%) developed an elevated L-Dex score at some point during follow up. Overall, 10 patients (11%) required CDP at any point after treatment. Conclusions: The results of this analysis support previously published data on the efficacy of prospective BCRL surveillance and early intervention using BIS. Of the 93 high-risk patients prospectively followed and managed in this structured BCRL protocol, 11% required CDP. These results compare favorably to all contemporary studies reporting BCRL rates in high-risk patients. Citation Format: Whitworth P, Cooper A, Shah C, Vicini F. The impact of a structured surveillance protocol using bioimpedance spectroscopy (BIS) on preventing breast cancer related lymphedema (BCRL) in high-Risk patients [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-14-08.

Background: With improved breast cancer outcomes, an increasing focus on sequelae of treatment as part of survivorship has emerged. Breast cancer related lymphedema (BCRL) represents one such sequelae. Increasing data and recent NCCN guidelines support the use of prospective BCRL surveillance to allow for early detection and intervention as a method to reduce chronic, irreversible BCRL. Therefore, this study was performed to evaluate the impact early detection and treatment of BCRL in breast cancer patients undergoing prospective surveillance with bioimpedance spectroscopy (BIS). Methods: From 8/2010 through 12/2016, 206 patients were evaluated with BIS as part of a prospective surveillance program.The protocol included pre-operative assessment with BIS as well as post-operative assessments with BIS at regular intervals. Patients with L-Dex readings increasing by more than 10 from baseline were considered to have subclinical BCRL and treated with a compression sleeve for 4 weeks. For the purpose of this analysis, high-risk was defined as receipt of ALND, regional nodal irradiation, or taxane chemotherapy. Chronic BCRL was defined as the need for complex decongestive physiotherapy. Results: A total of 206 patients were analyzed, with a mean age of 61 years old and a median follow up of 25.9 months. Overall, 17% of patients had least one high-risk feature, 8% had two factors, and 7% had all three factors. A total of 21 patients (9.8%) were diagnosed with subclinical BCRL. Increased rates of subclinical BCRL were seen in patients undergoing ALND (23% vs. 7%, p=0.01) with ALND and receipt of RNI associated with development of subclinical BCRL. At last follow-up, no patients had persistent, chronic BCRL following early, conservative intervention measures. Conclusions: The results of this study support prospective surveillance and early treatment utilizing BIS. Intervention triggered by subclinical BCRL detection with an elevated L-Dex score was associated with a very low rate of chronic BCRL. Citation Format: Kaufman D, Shah C, Vicini F. Utilization of bioimpedance spectroscopy in the prevention of chronic breast cancer related lymphedema [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-12-03.

PURPOSE: To develop clinical guidelines for the quality practice of accelerated partial breast irradiation (APBI) as part of breast-conserving therapy for women with early-stage breast cancer. METHODS AND MATERIALS: Members of the American Brachytherapy Society with expertise in breast cancer and breast brachytherapy in particular devised updated guidelines for appropriate patient evaluation and selection based on an extensive literature search and clinical experience. RESULTS: Increasing numbers of randomized and single and multi-institution series have been published documenting the efficacy of various APBI modalities. With more than 10-year followup, multiple series have documented excellent clinical outcomes with interstitial APBI. Patient selec- tion for APBI should be based on a review of clinical and pathologic factors by the clinician with particular attention paid to age ($50 years old), tumor size (#3 cm), histology (all invasive subtypes and ductal carcinoma in situ), surgical margins (negative), lymphovascular space invasion (not present), and nodal status (negative). Consistent dosimetric guidelines should be used to improve target coverage and limit potential for toxicity following treatment. CONCLUSIONS: These guidelines have been created to provide clinicians with appropriate patient selection criteria to allow clinicians to use APBI in a manner that will optimize clinical outcomes and patient satisfaction. These guidelines will continue to be evaluated and revised as future publications further stratify optimal patient selection. 2013 Published by Elsevier Inc. on behalf of American Brachytherapy Society.

This phase III post-NC trial evaluates if CWRNRT post-Mx or whole breast irradiation (WBI) with RNRT after BCS significantly reduces the IBCR-FI rate in pts with PPAx nodes that are pathologically negative after NC. Secondary aims are OS, LRR-FI, DR-FI, DFS-DCIS, second primary cancer, and comparison of RT effect on cosmesis in reconstructed Mx pts. Correlative science examines RT effect by tumor subtype, molecular outcome predictors for residual disease, and predictors for the degree of reduction in loco-regional recurrence. Methods: Clinical T1-3, N1 IBC PPAx nodes (FNA or core needle biopsy) pts complete ≥8 weeks of NC (anthracycline and/or taxane). HER2+ pts receive anti-HER2 therapy. Following NC, BCS or Mx, sentinel node biopsy (≥2 nodes) and/or Ax dissection with histologically negative nodes is performed. ER/PR and HER-2neu status before NC is required. Pts may receive appropriate adjuvant systemic therapy. Radiation credentialing with a facility questionnaire/case benchmark is required. Random assignment for Mx pts is to no CWRNRT or CWRNRT and for BCS pts to WBI or WBI+RNRT. Statistics: 1,636 pts are to be enrolled over 5 yrs (definitive analysis at 7.5 yrs). Study is powered at 80% to test that RT reduces the annual hazard rate of events for IBCR-FI by 35% for an absolute risk reduction of 4.6% (5-yr cumulative rate). Intent-to-treat analysis with 3 interim analyses (43, 86, and 129 events) and a 4th/final analysis at 172 events. Pt-reported outcomes focusing on RT effect will be provided by 736 pts before random assignment and at 3, 6, 12, and 24 mos. Accrual as of 6-21-18 is 967 (59.11%). Contacts: Protocol: CTSU member website https://www.ctsu.org. Questions: NRG Oncology Pgh Clin Coord Dpt: 1-800-477-7227 or ccd@nsabp.org. Pt entry: OPEN at https://open.ctsu.org or the OPEN tab on CTSU member website. NCT01872975 Support: U10 CA-2166; -180868, -180822; 189867; Elekta Citation Format: Mamounas EP, Bandos H, White JR, Julian TB, Khan AJ, Shaitelman SF, Torres MA, Vicini FA, Ganz PA, McCloskey SA, Paik S, Gupta N, Li XA, DiCostanzo DJ, Curran WJ, Wolmark N. Phase III trial to determine if chest wall and regional nodal radiotherapy (CWRNRT) post mastectomy (Mx) or the addition of RNRT to whole breast RT post breast-conserving surgery (BCS) reduces invasive breast cancer recurrence-free interval (IBCR-FI) in patients (pts) with pathologically positive axillary (PPAx) nodes who are ypN0 after neoadjuvant chemotherapy (NC): NRG Oncology/NSABP B-51/RTOG 1304 [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr OT2-04-01.

Purpose/Objective(s) Shorter courses of breast radiotherapy are offered as an alternative to 4-6 weeks of whole breast irradiation after lumpectomy, including brachytherapy. A prospective phase II multi-institution clinical trial to study 3-fraction accelerated partial breast irradiation (APBI) delivered by brachytherapy was conducted. Materials/Methods The trial treated selected breast cancers after breast-conserving surgery with brachytherapy applicators that delivered 22.5 Gy in 3 fractions of 7.5 Gy. The planning treatment volume was 1 to 2 cm beyond the surgical cavity. Eligible women were age ≥ 45 years with unicentric invasive or in situ tumors ≤ 3 cm excised with negative margins and with positive estrogen or progesterone receptors and no metastases to axillary nodes. Strict dosimetric parameters were required to be met and follow up information was collected from the participating sites. Results A total of 175 patients who were enrolled were followed for a median of 3.63 years. Three-fraction brachytherapy was associated with low chronic toxicity. There was excellent or good cosmesis in 95% of patients. There were no grade 4 toxicities. Grade 3 fibrosis at the treatment site was present in 1.7% and 32% percent had grades 1 or 2 fibrosis at the treatment site. There was 1 rib fracture. Other late toxicities included 7.4% grade 1 hyperpigmentation, 2% grade 1 telangiectasias, 1.7% symptomatic seromas, 1.7% abscessed cavities, and 1.1% symptomatic fat necrosis. There were 2 (1.1%) ipsilateral local recurrences, 2 (1.1%) nodal recurrences and no distant recurrences. Other incidents included one contralateral breast cancer and 2 second malignancies (lung). Conclusion Ultra-short breast brachytherapy is feasible and with acceptable late toxicity and could be an alternative to standard 5-day, 10 fraction APBI in eligible patients. Patients from this prospective trial will continue to be followed to evaluate long term outcomes.

PURPOSE/OBJECTIVE(S) Regional collaborative quality initiatives that incent participation through direct payment and streamlined reimbursement for high-performing sites have been shown to drive improvements in surgical outcomes. Numerous quality measures have been proposed in radiation oncology, and research has identified readily measurable indicators like dose to critical structures that predict for subsequent toxicity in patients. A decade ago, we initiated a voluntary statewide collaboration for quality improvement in radiation oncology and now describe its impact on care delivery. MATERIALS/METHODS Following SQUIRE guidelines, we describe the approach and measures that the program has implemented. To evaluate impact, we describe compliance at baseline and now with active measures among participating practices. RESULTS Since beginning data collection in 2012, radiation oncologists, physicists, data abstractors, and practice administrators from sites in one state (currently numbering 27) have convened thrice yearly. At these meetings, experts have spoken regarding trends within the field and inspired discussions regarding potential targets for quality improvement within the consortium. Blinded data on practices at various sites have also been regularly presented, and the group has iteratively developed new initiatives and consensus-based benchmarks to improve radiation oncology care delivery, patient experiences, and outcomes. An observational dataset with detailed information from over 20,000 patients has been assembled to evaluate quality. Compliance with select measures is described in the table, including use of guideline-concordant hypofractionated radiotherapy, motion management, doses to targets/normal tissues, and consistency in delineating and naming contoured structures (a precondition for quality evaluation). CONCLUSION Although observational analysis cannot fully exclude secular trends, contextual data revealing slow uptake of best practices elsewhere in the US suggests that this initiative has improved the consistency, efficiency, and quality of radiation oncology care in its member practices and may be a model for other regions.

In the original publication of the article, under the heading, Study limitations in the Discussion section, the second paragraph, fifth sentence was published incorrectly as “Patients with an L-Dex increase of ≥ 5.5 undergo…sleeve for 4 weeks”.

Breast brachytherapy represents a radiation technique that can be utilized as both monotherapy and as a tumor bed boost following breast conserving surgery. As monotherapy, the rationale for brachytherapy is that the majority of residual disease and therefore recurrences occur in close proximity to the lumpectomy cavity; for boost treatment, brachytherapy represents a technique that provided a more conformal approach prior to 3D treatment planning, and more recently can be used in conjunction with oncoplastic surgery. Multiple guidelines are available to assist clinicians with patient selection for accelerated partial breast irradiation (APBI), and recent guidelines support brachytherapy as an appropriate technique to deliver APBI. Modern breast brachytherapy can be performed with interstitial or applicator-based brachytherapy with multilumen and strut devices offering the ability to provide greater skin, chest wall, and normal breast sparing than previous devices. Novel strategies are being evaluated, including high dose rate perioperative/intraoperative radiotherapy, permanent breast seed implants, and noninvasive breast brachytherapy. Additionally, studies are evaluating shorter courses of brachytherapy. Multiple Level I studies are now available supporting interstitial brachytherapy to deliver APBI while prospective data and the National Surgical Adjuvant Breast and Bowel Project B-39/Radiation Therapy Oncology Group 0413 trial are available with applicator brachytherapy and provide standardized prescriptions, target volume definitions, and dosimetric goals.

Summary Background Whole-breast irradiation after breast-conserving surgery for patients with early-stage breast cancer decreases ipsilateral breast-tumour recurrence (IBTR), yielding comparable results to mastectomy. It is unknown whether accelerated partial breast irradiation (APBI) to only the tumour-bearing quadrant, which shortens treatment duration, is equally effective. In our trial, we investigated whether APBI provides equivalent local tumour control after lumpectomy compared with whole-breast irradiation. Methods We did this randomised, phase 3, equivalence trial (NSABP B-39/RTOG 0413) in 154 clinical centres in the USA, Canada, Ireland, and Israel. Adult women (>18 years) with early-stage (0, I, or II; no evidence of distant metastases, but up to three axillary nodes could be positive) breast cancer (tumour size ≤3 cm; including all histologies and multifocal breast cancers), who had had lumpectomy with negative (ie, no detectable cancer cells) surgical margins, were randomly assigned (1:1) using a biased-coin-based minimisation algorithm to receive either whole-breast irradiation (whole-breast irradiation group) or APBI (APBI group). Whole-breast irradiation was delivered in 25 daily fractions of 50 Gy over 5 weeks, with or without a supplemental boost to the tumour bed, and APBI was delivered as 34 Gy of brachytherapy or 38·5 Gy of external bream radiation therapy in 10 fractions, over 5 treatment days within an 8-day period. Randomisation was stratified by disease stage, menopausal status, hormone-receptor status, and intention to receive chemotherapy. Patients, investigators, and statisticians could not be masked to treatment allocation. The primary outcome of invasive and non-invasive IBTR as a first recurrence was analysed in the intention-to-treat population, excluding those patients who were lost to follow-up, with an equivalency test on the basis of a 50% margin increase in the hazard ratio (90% CI for the observed HR between 0·667 and 1·5 for equivalence) and a Cox proportional hazard model. Survival was assessed by intention to treat, and sensitivity analyses were done in the per-protocol population. This trial is registered with ClinicalTrials.gov , NCT00103181 . Findings Between March 21, 2005, and April 16, 2013, 4216 women were enrolled. 2109 were assigned to the whole-breast irradiation group and 2107 were assigned to the APBI group. 70 patients from the whole-breast irradiation group and 14 from the APBI group withdrew consent or were lost to follow-up at this stage, so 2039 and 2093 patients respectively were available for survival analysis. Further, three and four patients respectively were lost to clinical follow-up (ie, survival status was assessed by phone but no physical examination was done), leaving 2036 patients in the whole-breast irradiation group and 2089 in the APBI group evaluable for the primary outcome. At a median follow-up of 10·2 years (IQR 7·5–11·5), 90 (4%) of 2089 women eligible for the primary outcome in the APBI group and 71 (3%) of 2036 women in the whole-breast irradiation group had an IBTR (HR 1·22, 90% CI 0·94–1·58). The 10-year cumulative incidence of IBTR was 4·6% (95% CI 3·7–5·7) in the APBI group versus 3·9% (3·1–5·0) in the whole-breast irradiation group. 44 (2%) of 2039 patients in the whole-breast irradiation group and 49 (2%) of 2093 patients in the APBI group died from recurring breast cancer. There were no treatment-related deaths. Second cancers and treatment-related toxicities were similar between the two groups. 2020 patients in the whole-breast irradiation group and 2089 in APBI group had available data on adverse events. The highest toxicity grade reported was: grade 1 in 845 (40%), grade 2 in 921 (44%), and grade 3 in 201 (10%) patients in the APBI group, compared with grade 1 in 626 (31%), grade 2 in 1193 (59%), and grade 3 in 143 (7%) in the whole-breast irradiation group. Interpretation APBI did not meet the criteria for equivalence to whole-breast irradiation in controlling IBTR for breast-conserving therapy. Our trial had broad eligibility criteria, leading to a large, heterogeneous pool of patients and sufficient power to detect treatment equivalence, but was not designed to test equivalence in patient subgroups or outcomes from different APBI techniques. For patients with early-stage breast cancer, our findings support whole-breast irradiation following lumpectomy; however, with an absolute difference of less than 1% in the 10-year cumulative incidence of IBTR, APBI might be an acceptable alternative for some women. Funding National Cancer Institute, US Department of Health and Human Services.