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Background: Breast conserving surgery (BCS) is typically followed by adjuvant radiotherapy (RT) based on several landmark trials demonstrating improvements in disease control and survival. Since completion of these historical trials, the advent of molecular subtyping has revealed that breast cancer is not a single disease entity, but rather a class of cancers with differential risk profiles. We evaluated whether RT could be safely omitted following BCS for patients with the most favorable subtype as defined by the Prosigna PAM50 assay. Methods: We conducted a multicenter prospective single-arm cohort study with IRB approval and an FDA investigational device exemption (IDE). Eligible patients were women 50 to 75 years of age (inclusive) who had undergone BCS revealing tumors ≤2cm in size, that were estrogen or progesterone receptor positive (HR+), HER2 negative, grade 1-2, node negative (N0), with negative excision margins (no ink on tumor). Intent to take endocrine therapy was required. Upon registration, tumors were submitted for central Prosigna testing and those with Risk of Recurrence (ROR) score ≤40 were deemed eligible for the investigational omission of RT. The primary endpoint was the 5-year locoregional recurrence rate (LRR). Anticipating a total of 345 RT-omitting patients to enroll over 3.5 years, the study was designed with 90% power to exclude a 5-year LRR of 5% using a one-sample exponential test with one-sided type I error of 0.025. Results: From 2016 to 2020, 671 patients were registered from 13 centers, inclusive of affiliated regional network sites. Of these, 382 patients had a ROR Score ≤40 and opted to forego RT, comprising the main intention-to-treat (ITT) study population. Median age was 65 years (range 50 to 75), and median tumor size was 0.9 cm (range 0.1 to 2.0 cm). At a median follow-up of 26.9 months, 12 events were observed: 4 patients had ipsilateral in-breast recurrences, 7 had contralateral breast cancers, and 1 developed an unrelated melanoma. There were no regional-nodal or distant recurrences. The 2-year cumulative rate of LRR was 0.3% (95% CI: 0 – 1.0%). Of the 4 ipsilateral breast recurrences, 2 were in the same quadrant as the original primary tumor. Conclusion: In this preliminary report of the PRECISION trial, patients 50-75 years of age undergoing BCS and endocrine therapy for pT1N0 HR+ HER2-negative breast cancer with ROR score ≤40 had exceedingly low rates of LRR in the absence of adjuvant RT at a median follow-up of 26.9 months. Additional follow-up is required to determine whether these favorable results are durable. Citation Format: Lior Z. Braunstein, Julia Wong, Deborah A. Dillon, Yu-Hui Chen, Paul Catalano, Oren Cahlon, Mahmoud B. El-Tamer, Rachel Jimenez, Atif Khan, Carmen Perez, Rinaa Punglia, Ron Shiloh, Laura Warren, David Wazer, Jean Wright, Elizabeth Buckley, Tari King, Simon Powell, Eric Winer, Jennifer Bellon. Preliminary report of the PRECISION Trial (Profiling Early Breast Cancer for Radiotherapy Omission): A Phase II Study of Breast-Conserving Surgery Without Adjuvant Radiotherapy for Favorable-Risk Breast Cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT1-12-02.

Although mentorship has been associated with promotion, job satisfaction, and retention, data are limited on the mentorship experience of clinical- versus research-track physicians as well as feasibility and relative priority of formal program components.Within a single-institution, multi-site, academic network, we implemented a Radiation Oncology AcaDemic Mentorship Program (ROADMAP) for junior faculty. Validated surveys assessing mentee satisfaction were distributed at baseline and 1 year. The statistical analysis included Wilcoxon rank sum and signed tests. Mentees assessed the likelihood to recommend each program component (10-point Likert-type scale), and means with standard error (SE) are reported.Among 42 eligible junior faculty, 36 (86%) opted into the program. The median time since residency was 2.5 years (interquartile range, 1.75-5.25) on the clinical track (n = 12) and 3 years (interquartile range, 2.75-5.00) on the research track (n = 24). At baseline, research-track physicians reported higher satisfaction with mentoring than physicians on the clinical track (2.92 vs 2.16; P = .02). Among 32 physicians completing 1 year, overall satisfaction with mentoring increased compared with baseline (2.72 vs 3.87; P.001), which persisted on subset analysis for both clinical- (2.16 vs 4.03; P.001) and research-track physicians (2.99 vs 3.77; P = .005). At 1 year, 28 mentees (88%) opted to continue the program. Program components were rated 8.25 (SE, 0.37) for mentor-mentee pairings, 7.22 (SE, 0.39) for goal setting, 6.84 (SE, 0.47) for administrative support, 6.69 (SE, 0.44) for peer mentoring, and 6.53 (SE, 0.45) for steering committee oversight. Ratings of peer mentoring were not associated with track (P = .59) or years in practice (P = .29).Clinical-track physicians may be less satisfied with mentorship than research-track faculty. However, all junior faculty, regardless of track, appeared to benefit from formalizing dyadic mentor-mentee relationships, goal setting, and peer mentoring. Further work is needed to determine the role of mentorship in addressing physician burnout.

PURPOSE/OBJECTIVES: Dosimetric and technical challenges often limit radiotherapy (RT) target coverage for breast cancer patients who require bilateral breast/chest wall and regional nodal irradiation (RNI). We evaluated the feasibility of using volumetric modulated arc therapy (VMAT) to administer bilateral comprehensive RNI including the internal mammary nodes. MATERIALS/METHODS: We analyzed all patients treated at our institution with bilateral RNI using VMAT from 2017–2020. Medical records were reviewed to ascertain clinicopathologic features, radiotherapeutic parameters and treatment-related adverse events. RESULTS: The cohort comprised 12 patients who underwent VMAT for bilateral RNI, with a median follow-up of 14.5 months. Median V5Gy for bilateral lungs was 96.1% (range: 84.5%−99.8%). Median V20Gy for each lung was 27.5% (range: 14.9–38.1%). Cardiac mean dose was a median of 699 cGy (range: 527–1117 cGy). Five patients (41%) developed grade 1 cough/dyspnea, with one patient developing grade 3 dyspnea. Of note, three of these (60%) were current or former smokers. No patient received glucocorticoid therapy or required respiratory intervention and none developed longer term pulmonary complaints. Decline in ejection fraction occurred in one patient with a pre-existing cardiac condition who also received anthracycline-based chemotherapy and trastuzumab. Only one patient experienced locoregional recurrence with synchronous distant progression and subsequently succumbed to her disease. No secondary cancers have been noted to date. CONCLUSION: VMAT appears to be a feasible and tolerable RT modality for breast cancer patients who require bilateral comprehensive adjuvant RT with RNI obtaining excellent target coverage. No patients required medical intervention for pulmonary complaints despite a median bilateral V5 approaching 100%, providing further evidence that V5 is not predictive for complications.

OBJECTIVE: Patient experience scores are increasingly important in measuring quality of care and determining reimbursement from payers, including the Hospital Value Based Purchasing Program and the Radiation Oncology Model. However, the role of bias in patient experience scores in oncology is unknown, raising the possibility that such payment structures may inadvertently perpetuate bias in reimbursement. Therefore, we characterized patient-, physician-, and practice-level predictors of patient experience scores in patients undergoing radiation therapy. METHODS: We retrospectively reviewed patient experience surveys for radiation oncology patients treated at two large multi-site academic cancer centers. The outcome was responses on four survey questions. Co-variates included self-reported patient demographics, physician characteristics, practice setting characteristics, and wait time rating linked to each survey. We fitted multivariable ordinal regression models to identify predictors of receiving a higher score on each of the survey questions. RESULTS: 2,868 patients completed surveys and were included in the analysis. Patient experience scores were generally high, with >90% of respondents answering 5/5 on the 4 survey items. Physician gender was not associated with any measured patient experience outcomes (all p-values>0.4). Independent predictors of higher score included a wait-time experience classified as “good” as compared to “not good” (all q-values

Purpose/Objective(s) Local breast cancer recurrences and new primary breast cancers are an increasingly common clinical challenge without clear treatment guidelines. To date, photon reirradiation (reRT) has not been widely adopted due to concerns for toxicities. Proton beam therapy (PBT) can optimize normal tissue sparing and may allow for safer delivery of a second definitive radiotherapy (RT) course. We hypothesize salvage PBT reRT can be safely delivered, and we present clinical outcomes and toxicities of patients with recurrent or new primary non-metastatic breast cancer who received prior RT and PBT reRT. Materials/Methods In an IRB-approved retrospective study, all consecutive patients with recurrent or new primary non-metastatic breast cancer treated with breast or chest wall (CW) RT and PBT reRT from a single institution were identified. Patient and tumor characteristics, treatment parameters, clinical outcomes and toxicities were collected. Distant metastasis-free survival (DMFS) and overall survival (OS) were defined from PBT reRT start to date of distant recurrence, death or last follow-up and estimated using Kaplan-Meier methodology. Results Forty-six consecutive patients were assessed. Eight patients (17.4%) were reirradiated to an intact breast, 13 (28.3%) to CW without reconstruction, 20 (43.5%) to CW with reconstruction, and 5 (10.9%) to regional lymph nodes (LN) alone. PBT reRT was delivered with uniform (70%) or pencil beam (30%) scanning PBT. Median first course dose was 60Gy (45-66Gy); median PBT reRT dose was 50.4Gy (RBE) (40-66.6Gy); median cumulative dose was 108.9Gy2, a/b = 3(RBE) (95.0-168.8 Gy2, a/b = 3 (RBE)). When regional LN were retreated, median first course dose was 50.4 Gy (48.6-66.6Gy) and median PBT reRT dose was 50 Gy2, a/b = 3 (46.7-66.0Gy2, a/b = 3). Four patients had significant brachial plexus overlap with cumulative doses up to 99.0 Gy. At a median follow-up of 21 months, there were no local or regional recurrences; 8 patients (17%) developed distant recurrence, of whom three died. Estimated 3-year DMFS and OS were 60% and 88%, respectively. Grade 3 acute toxicities were limited exclusively to RT dermatitis (30.4%). Grade 3 late toxicities occurred in 4 patients (8.7%) (3 capsular contracture requiring surgical intervention, 1 breast pain requiring mastectomy). Two patients developed rib fracture. No cases of neuropathies, skin ulceration or other acute or late grade ≥3 toxicities occurred. Conclusion In the largest series to date of PBT reRT for breast cancer recurrence or new primary after prior definitive breast or CW RT, PBT reRT provided excellent locoregional control with a low rate of high-grade toxicities limited to target tissue not amenable to sparing from full reRT dose. These data are encouraging and suggest PBT reRT may provide patients with a relatively safe and highly effective salvage option. Longer follow-up and additional patients are needed to correlate composite normal tissue doses with toxicities and assess long-term outcomes.

We aimed to develop and study the implementation of a remote system for toxicity assessment and management of acute side effects of breast radiation using electronic patient-reported outcomes (ePROs).A response-adapted Patient-Reported Outcomes Common Terminology Criteria for Adverse Events-based assessment for breast radiation toxicity was administered weekly during and for 8 weeks after radiation from June 2019 to July 2020. The care team received alerts when "severe" symptoms were reported by patients, who were then contacted. Treatment, clinic, and sociodemographic characteristics were abstracted from patient records. A subsample of patients and care team members was qualitatively interviewed at follow-up.Overall, 5787 assessments were sent to 678 patients, of whom 489 (72%) completed 2607 assessments (45%). Moderate or greater toxicity was reported by 419 responders (86%; 95% CI, 82%-89%). Clinician alerts for severe toxicity were generated for 264 assessments among 139 unique patients, of which 83% occurred posttreatment. The proportion of surveys that prompted an alert was significantly higher after treatment (219 [13%]) than during treatment (45 [5%]) (P.001). Survey completion rates in the posttreatment period were higher among patients undergoing partial breast irradiation than postmastectomy radiation (incidence rate ratio, 0.70; 95% CI, 0.60-0.81) (P.001) despite these patients experiencing less severe toxicity. Interviews (15) found that patients had a positive experience with ePROs, although many thought the primary purpose was for research rather than symptom management.With the majority of toxicity occurring after breast radiation has ended, remote symptom monitoring with ePROs appears to fill a gap in clinical practice, particularly for patients undergoing shorter courses of radiation. It is important to properly onboard patients and explain that the purpose of ePROs is to aid clinical care. Further research is needed to determine whether the costs associated with ePROs can be offset by reducing routine clinic visits and whether this approach is acceptable and appropriate.

PURPOSE ATM, a gene that controls repair of DNA double-strand breaks, confers an excess lifetime risk of breast cancer among carriers of germline pathogenic variants (PV). ATM PV homozygotes are particularly sensitive to DNA damage caused by ionizing radiation. Consequently, there is concern that adjuvant radiotherapy (RT) may cause excess morbidity among heterozygous carriers of ATM PV. We evaluated the tolerability of breast RT among carriers of ATM germline variants. METHODS Of 167 patients with ATM germline variants presenting to our institution with breast cancer, 91 received RT. Treatment-related toxicity was ascertained from medical records and graded across organ systems. Toxicities grade > 2 were recorded from the end of treatment to last evaluable follow-up and were analyzed according to ATM variant pathogenicity. RESULTS Of 91 evaluable carriers of ATM variants, with a median follow-up of 32 months following RT, 25% (n = 23) harbored a PV, whereas 75% (n = 68) harbored a variant of uncertain significance (VUS). Prevalence of grade ≥ 2 toxicity unrelated to post-mastectomy reconstruction among patients with ATM PV was: 32% at the end of treatment ( v 34% for VUS carriers), 11% at 1 year of follow-up ( v 4% for VUS carriers), and 8% at the last follow-up ( v 13% for VUS carriers), consistent with previous studies of RT among unselected populations. No grade 4 or 5 toxicities were observed. ATM variant pathogenicity was not associated with local toxicity, contralateral breast cancer, or secondary malignancy in this limited cohort of patients who received breast RT. CONCLUSION We found no evidence of excess RT-associated toxicity among carriers of pathogenic ATM germline variants. Breast-conserving therapy and adjuvant RT may be safely considered among appropriately selected carriers of ATM germline variants.

Background:The COVID-19 pandemic has transformed cancer care with the rapid expansion of telemedicine, but given the limited use of telemedicine in oncology, concerns have been raised about the quality of care being delivered. We assessed the patient experience with telemedicine in routine radiation oncology practice to determine satisfaction, quality of care, and opportunities for optimization.Patients and Methods:Patients seen within a multistate comprehensive cancer center for prepandemic office visits and intrapandemic telemedicine visits in December 2019 through June 2020 who completed patient experience questionnaires were evaluated. Patient satisfaction between office and telemedicine consultations were compared, patient visit-type preferences were assessed, and factors associated with an office visit preference were determined.Results:In total, 1,077 patients were assessed (office visit, n=726; telemedicine, n=351). The telemedicine-consult survey response rate was 40%. No significant differences were seen in satisfaction scores between office and telemedicine consultations, including the appointment experience versus expectation, quality of physician’s explanation, and level of physician concern and friendliness. Among telemedicine survey respondents, 45% and 34% preferred telemedicine and office visits, respectively, and 21% had no preference for their visit type. Most respondents found their confidence in their physician (90%), understanding of the treatment plan (88%), and confidence in their treatment (87%) to be better or no different than with an office visit. Patients with better performance status and who were married/partnered were more likely to prefer in-person office visit consultations (odds ratio [OR], 1.04 [95% CI, 1.00–1.08];P=.047, and 2.41 [95% CI, 1.14–5.47];P=.009, respectively). Patients with telephone-only encounters were more likely to report better treatment plan understanding with an office visit (OR, 2.25; 95% CI, 1.00–4.77;P=.04).Conclusions:This study is the first to assess telemedicine in routine radiation oncology practice, and found high patient satisfaction and confidence in their care. Optimization of telemedicine in oncology should be a priority, specifically access to audiovisual capabilities that can improve patient–oncologist communication.

Radiation therapy plays an important role in the multidisciplinary management of breast cancer. Recent years have seen improvements in breast cancer survival and a greater appreciation of potential long-term morbidity associated with the dose and volume of irradiated organs. Proton therapy reduces the dose to nontarget structures while optimizing target coverage. However, there remain additional financial costs associated with proton therapy, despite reductions over time, and studies have yet to demonstrate that protons improve upon the treatment outcomes achieved with photon radiation therapy. There remains considerable heterogeneity in proton patient selection and techniques, and the rapid technological advances in the field have the potential to affect evidence evaluation, given the long latency period for breast cancer radiation therapy recurrence and late effects. In this consensus statement, we assess the data available to the radiation oncology community of proton therapy for breast cancer, provide expert consensus recommendations on indications and technique, and highlight ongoing trials' cost-effectiveness analyses and key areas for future research. (c) 2021 Elsevier Inc. All rights reserved.

PURPOSE: Community-academic partnerships have the potential to improve access to clinical trials for under-represented minority patients who more often receive cancer treatment in community settings. In 2017, the Memorial Sloan Kettering (MSK) Cancer Center began opening investigator-initiated clinical trials in radiation oncology in targeted community-based partner sites with a high potential to improve diverse population accrual. This study evaluates the effectiveness of a set of implementation strategies for increasing overall community-based enrollment and the resulting proportional enrollment of Hispanic patients on trials on the basis of availability in community-based partner sites. METHODS: An interrupted time series analysis evaluating implementation strategies was conducted from April 2018 to September 2021. Descriptive analysis ofHispanic enrollment on investigator-initiated randomized therapeutic radiation trials open at community-based sites was compared with those open only at themain academic center. RESULTS: Overall, 84 patients were enrolled in clinical trials in the MSK Alliance, of which 48 (56%) identified as Hispanic. The quarterly patient enrollment pre- vs postimplementation increased from 1.39 (95% CI, –3.67 to 6.46) to 9.42 (95% CI, 2.05 to 16.78; P5 .017). In the investigator-initiated randomized therapeutic radiation trials open in the MSK Alliance, Hispanic representation was 11.5% and 35.9% in twometastatic trials and 14.2% in a proton versus photon trial. Inmatched trials open only at the main academic center, Hispanic representation was 5.6%, 6.0%, and 4.0%, respectively. CONCLUSION: A combination of practice-level and physician-level strategies implemented at community-based partner sites was associated with increased clinical trial enrollment, which translated to improved Hispanic representation. This supports the role Q:2 of strategic community-academic partnerships in addressing disparities in clinical trial enrollment.

BACKGROUND For patients with breast cancer undergoing breast-conserving surgery (BCS), adjuvant radiation (RT) and hormonal therapy (HT) reduce the risk of locoregional recurrence (LRR). Although several studies have evaluated adjuvant HT ± RT, the outcomes of HT versus RT monotherapy remain less clear. In this study, the risk of LRR is characterized among older patients with early-stage breast cancer following adjuvant RT alone, HT alone, neither, or both. METHODS This study included female patients from the Memorial Sloan Kettering Cancer Center (New York, New York) who were aged ≥65 years with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) T1N0 breast cancer treated with BCS. The primary endpoint was time to LRR evaluated by Cox regression analysis. RESULTS There were 888 women evaluated with a median age of 71 years (range, 65-100 years) and median follow-up of 4.9 years (range, 0.0-9.5 years). There were 27 LRR events (3.0%). Five-year LRR was 11% for those receiving no adjuvant treatment, 3% for HT alone, 4% for RT alone, and 1% for HT and RT. LRR rates were significantly different between the groups (P < .001). Compared with neither HT nor RT, HT or RT monotherapy each yielded similar LRR reductions: HT alone (HR, 0.27; 95% CI, 0.10-0.68; P = .006) and RT alone (HR, 0.32; 95% CI, 0.11-0.92; P = .034). Distant recurrence and breast cancer-specific survival rates did not significantly differ between groups. CONCLUSIONS LRR risk following BCS is low among women aged ≥65 years with T1N0, ER+/HER2- breast cancer. Adjuvant RT and HT monotherapy each similarly reduce this risk; the combination yields a marginal improvement. Further study is needed to elucidate whether appropriate patients may feasibly receive adjuvant RT monotherapy versus the current standards of HT monotherapy or combined RT/HT.

Highlights • Contemporary trends in radiation technique and fractionation for bone metastases at a large academic center with a specialized metastatic program. • Stereotactic body radiation therapy (SBRT) is replacing long-course conventional RT for bone metastases. • Complexity of RT is increasing, particularly in the community-based regional clinic setting. • Single-fraction conventional RT is preferentially employed at the end of life, but prognostic algorithms are needed to further optimize use., Background Bone metastases cause significant morbidity in patients with cancer, and radiation therapy (RT) is an effective treatment approach. Indications for more complex ablative techniques are emerging. We sought to evaluate RT trends at a large multi-site tertiary cancer center. Methods Patients who received RT for bone metastases at a single institution (including regional outpatient clinics) from 2016 to 2018 were identified. Patients were grouped by RT regimen: single-fraction conventional RT (8 Gy × 1), 30 Gy in 10 fractions, SBRT, and “other”. Multinomial logistic regression was performed to assess trends in regimens over time. Binary logistic regression was performed to evaluate factors associated with receipt of SBRT. Results Between 2016 and 2018, 5,952 RT episodes were received by 2,969 patients with bone metastases. Overall, 76% of episodes were ≤ 5 fractions. The median number of fractions planned for SBRT and non-SBRT episodes was 3 (IQR 3–3) and 5 (IQR 5–10), respectively. Use of SBRT increased from 2016 to 2018 (39% to 53%, p

Purpose Telemedicine was rapidly implemented for initial consultations and radiation treatment planning in the wake of the coronavirus disease 2019 (COVID-19) pandemic. In this study, we explore utilization of and physician perspectives on this approach in an attempt to identify patient populations that may benefit most from virtual care. Methods and Materials This is a mixed-methods study with a convergent design. Approximately 6 to 8 weeks after implementation of telemedicine, all radiation oncologists in a single academic radiation oncology department were invited to participate in either semistructured interviews with embedded survey questions or a concurrently administered survey only. Rapid qualitative analysis was used to identify common themes, and quantitative data was assessed using descriptive statistics and univariable analyses. Results At the apex of the pandemic, 92% of radiation oncology visits were conducted via telemedicine. In total, 51 of 61 radiation oncologists participated in the study (response rate 84%). Most (71%) reported no difference in ability to treat cancer appropriately via telemedicine, which was more common among specialized physicians (P = .01) but not those with higher visit volume or years of experience. Over half (55%) perceived no difference or even improvement in overall visit quality with telemedicine. Virtual visits were deemed acceptable for a median of 70% to 96% of patients, which varied by disease site. Need for physical examination, and availability of an acceptable proxy, factored into telemedicine acceptability. Most (88%) found telemedicine better than expected, but opinions were split on how telemedicine would affect physician burnout. Almost all (96%) foresaw a role for telemedicine beyond the pandemic and would opt for a median of 50% (interquartile range 20%-66%) of visits conducted via telemedicine. Conclusions Among radiation oncologists in an academic setting, telemedicine was perceived to be highly appropriate and acceptable for most patients. Future studies should focus on identifying the 5% to 30% of patients whose care may be optimized with in-person visits, and if there is alignment with patient preferences.

PURPOSE: To evaluate physician-reported assessments of an established faculty orientation program for new radiation oncology physicians at a large academic center and to prospectively analyze the effects of an onboarding improvement program based on those assessments. MATERIALS AND METHODS: An anonymous survey was designed and distributed to physicians new to the department who received onboarding orientation between 2013 and 2017. Survey questions addressed the comprehensiveness, effectiveness, and utility of various orientation activities. On the basis of the survey results, an improved onboarding program was designed and implemented for nine new faculty members between May 2018 and November 2018. A post-intervention survey querying topics similar to those in the pre-intervention survey was distributed to the new faculty members. Descriptive statistics were generated to compare the pre-intervention and post-intervention groups. RESULTS: The overall rate of survey completion was 85% (17 of 20). The intervention program markedly improved physician assessment of comprehensiveness and effectiveness of the onboarding process. Physicians strongly and consistently identified mentor shadowing, on-the-job training, and other faculty mentorship activities as the most important components of an effective onboarding experience. CONCLUSION: An enhanced, tailored, person-oriented, formal onboarding improvement program significantly increased physician assessment scores of comprehensiveness and effectiveness of the faculty onboarding process. This model can serve as a framework for increasing physician preparedness, encouraging early physician mentorship, and ensuring a universal standard of quality across large practices.

Background: With advances in neoadjuvant chemotherapy (NAC), an increasing number of breast cancer patients achieve a pathologic complete response (pCR). Efforts are underway to non-invasively identify pCR in the breast, such that characterization of the concomitant nodal response will be invaluable for locoregional treatment planning. Here, we sought to evaluate the correlation between in-breast response and residual nodal disease among early stage breast cancer patients. Materials/Methods: We identified 728 patients who received NAC at our institution from 2006 to 2016. Breast and nodal response rates were evaluated and further stratified by clinicopathologic features, and biologic subtype approximation (hormone receptor positive [HR+], HER2 negative [HER2-] and low or intermediate grade = luminal A; HR+/HER2- and high grade = luminal B; HER2/neu-amplified = HER2+; ER-/HER2- = triple negative). Descriptive statistics and univariate analyses were employed to evaluate the correlation between breast and nodal response. Results: Of 728 patients, 269 (37%) were clinically node negative (cN0) and 459 (63%) were clinically node positive (cN+). Median age was 51 and median tumor size was 4.0cm (IQR 2.7 - 5.5cm). The cohort comprised 13% luminal A patients, 20% luminal B, 38% HER2, and 29% triple negative. Following NAC, the overall pCR rate (breast and nodes) was 29.8%. Among all cN0 patients who had a breast pCR (ypT0; n = 96), none exhibited residual nodal disease (100% ypN0). Among cN+ patients who had a breast pCR (n = 128), only 5.4% (n = 7) had residual nodal disease (ypN+). Rates of residual nodal disease among cN+ patients who achieved breast pCR varied by biologic subtype: luminal A patients with pCR in the breast had a 50.0% probability of residual nodal disease (n = 1/2 were ypT0N+), luminal B 6.7% (1/15), HER2+ 2.5% (2/80) and triple-negative 9.6% (3/31) (p=0.03). Conversely, among cN+ patients who exhibited nodal pCR following NAC, the rate of residual in-breast disease varied by receptor subtype: 80.0% of clinically node-positive luminal A patients who became ypN0 had residual in-breast disease (ypT+N0; n = 4/5), 60.0% of luminal B (21/35), 38.1% HER2+ (48/126), and 50.9% triple negative (29/57) (p=0.03). Conclusions: Among early stage breast cancer patients receiving NAC, in-breast pCR is predictive of nodal pCR. Among 96 cN0 patients who had in-breast pCR, we found none with residual nodal disease, representing a population that may be suitable for further limiting nodal therapy. The ability to pre-operatively identify in-breast pCR in this population would be particularly valuable if nodal pCR can consequently be inferred, potentially paving the way for studies of therapeutic de-escalation. Citation Format: Achraf Shamseddine, Jessica Flynn, Zhigang Zhang, Monica Morrow, Boris Mueller, Erin Gillespie, Atif Khan, Beryl McCormick, Oren Cahlon, Simon Powell, Andrea Barrio, Lior Z Braunstein. In-breast pathologic complete response (pCR) following neoadjuvant chemotherapy predicts nodal pCR in early stage breast cancer [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 P2-16-06.

Purpose The 2016 American Society for Radiation Oncology consensus guidelines for the use of accelerated partial-breast irradiation (APBI) define “suitable,” “cautionary,” and “unsuitable” populations for this adjuvant breast radiation therapy technique. We sought to determine whether patients in the cautionary group exhibited adverse outcomes after APBI compared with their suitable counterparts. Methods and Materials We identified 252 consecutively treated patients from a single institution with in situ or early-stage invasive breast cancer who underwent APBI between 2008 and 2017. Treatment technique was uniform throughout the population, consisting of 3-dimensional conformal radiation therapy to 40 Gy administered in 10 daily fractions. Results One hundred seventy-eight patients (70%) were classified as suitable, 69 (27%) as cautionary, and 5 (2.0%) as unsuitable. Because unsuitable patients were few and had no recurrences, they were excluded from analysis. At a median follow-up time of 3.9 years, 97.2% of patients were free of recurrence. Four patients (1.5% overall; 3 suitable and 1 cautionary) experienced ipsilateral in-breast recurrences, and 1 cautionary patient developed an ipsilateral regional recurrence in an axillary lymph node. There was no significant difference in the rate of ipsilateral breast recurrence (2.4% vs 1.0%) between cautionary and suitable groups. Conclusions Local recurrences are rare among guideline-defined cautionary patients with in situ or invasive breast cancer treated with APBI delivered via daily 3-dimensional conformal radiation therapy to 40 Gy. At a median follow-up of 3.9 years, no significant differences in local control were noted between cautionary and suitable patient groups. Further study is needed to characterize long-term disease outcomes among various risk groups.

Purpose: Guidelines for early-stage breast cancer allow for radiotherapy (RT) omission following breast conserving surgery (BCS) among older women, though high utilization of RT persists. This study explores surgeon referral and the effect of a productivity-based bonus metric for radiation oncologists in an academic institution with centralized quality assurance (QA) review.Methods: We evaluated patients >70 years of age treated with BCS for ER+ pT1N0 breast cancer at a single tertiary cancer network between 2015-2018. The primary outcomes were radiation oncology referral and RT receipt. Covariables included patient and physician characteristics, and treatment decisions before versus after productivity metric implementation. Univariable generalized linear effects models explored associations between these outcomes and covariables. Results: Of 703 patients included, 483 (69%) were referred to radiation oncology and 273 (39%) received RT (among those referred, 57% received RT). No difference in RT receipt pre- versus post- productivity metric implementation was observed (p=0.57). RT receipt was associated with younger patient age (70-74 years, OR 2.66, 95% CI 1.54-4.57) and higher grade (grade 3, OR 7.75, 95% CI 3.33-18.07). Initial referral was associated with younger age (70-74, OR 5.64, 95% CI 3.37-0.45) and higher performance status (KPS ³90, OR 5.34, 95% CI 2.63-10.83). Conclusion: Non-referral to radiation oncology accounted for half of RT omission, but was based on age and KPS, in accordance with guidelines. Lack of radiation oncologist practice change in response to misaligned financial incentives is reassuring, potentially reflecting centralized QA review. Multi-institutional studies are needed to confirm these findings.

Highlights • Atlas-based method for contouring heart substructures on breast radiotherapy CT. • Excellent agreement between automatic and manual contours for most patients. • Dice similarity coefficient for LAD was low (0.06) because a narrow, long structure. • Doses derived from automatic and manual contours agree within observer variability. • For left breast treatment, right ventricle and LAD dose most senstive to contour shift., Background and purpose Quantifying radiation dose to cardiac substructures is important for research on the etiology and prevention of complications following radiotherapy; however, segmentation of substructures is challenging. In this study we demonstrate the application of our atlas-based automatic segmentation method to breast cancer radiotherapy plans for generating radiation doses in support of late effects research. Material and methods We applied our segmentation method to contour heart substructures on the computed tomography (CT) images of 70 breast cancer patients who received external photon radiotherapy. Two cardiologists provided manual segmentation of the whole heart (WH), left/right atria, left/right ventricles, and left anterior descending artery (LAD). The automatically contours were compared with manual delineations to evaluate similarity in terms of geometry and dose. Results The mean Dice similarity coefficient between manual and automatic segmentations was 0.96 for the WH, 0.65 to 0.82 for the atria and ventricles, and 0.06 for the LAD. The mean average surface distance was 1.2 mm for the WH, 3.4 to 4.1 mm for the atria and ventricles, and 6.4 mm for the LAD. We found the dose to the cardiac substructures based on our automatic segmentation agrees with manual segmentation within expected observer variability. For left breast patients, the mean absolute difference in mean dose was 0.1 Gy for the WH, 0.2 to 0.7 Gy for the atria and ventricles, and 1.8 Gy for the LAD. For right breast patients, these values were 0.0 Gy, 0.1 to 0.4 Gy, and 0.4 Gy, respectively. Conclusion Our automatic segmentation method will facilitate the development of radiotherapy prescriptive criteria for mitigating cardiovascular complications.

Radiation-associated cardiac disease, a heterogeneous and complex disease, manifests years or even decades following radiation exposure to the chest. It is associated with a significantly higher morbidity and mortality. Often, the presentation is vague and overlaps with many diseases, presenting unique diagnostic and management issues. As a result, a high index of suspicion followed by multimodality imaging is crucial, along with comprehensive screening to enable early detection. Timing of intervention should be carefully considered in these patients, because surgery is often complex with an emerging role of percutaneous interventions. (C) 2019 by the American College of Cardiology Foundation.

Purpose: Internal mammary node recurrence after definitive breast cancer treatment is poorly characterized, with limited data to guide clinical management. The aim of this study was to analyze the outcomes of patients with recurrent breast cancer involving internal mammary nodes to understand their natural history and determine prognostic factors associated with improved overall survival. Methods and Materials: We performed a retrospective analysis of 553 patients with recurrent breast cancer and identified 161 patients with radiographic evidence of locoregional recurrence as a first event. A total of 67 patients (42%) were identified with internal mammary involvement. Median follow-up times were 76 months from date of initial diagnosis and 30 months from date of recurrence. Results: Of the 67 patients identified with internal mammary node failures, 10 (15%) presented with isolated recurrence, 14 (21%) presented with other sites of locoregional disease, and 43 (64%) presented with concomitant distant metastases. Median overall survival was 2.5 years and significantly associated with extent of disease (P

Purpose The primary goal was to map the anatomic pattern of isolated nodal recurrences (NR) in the supraclavicular (SCV), axillary, and internal mammary nodes (IMNs) in patients with breast cancer treated with curative-intent surgery with or without radiation therapy (RT). Secondary objectives were to assess clinical and pathologic factors associated with patterns of NR and survival rates. Methods and Materials Patients with NR after treatment at a single cancer center during 1998 to 2013 were identified. Patients with prior distant metastases or NR without correlative imaging were excluded. All NRs were overlaid onto representative axial computed tomographic images. Multivariable analysis was performed to identify clinical and pathologic characteristics associated with NR. Kaplan-Meier curves were generated to assess the rate of relapse by nodal region according to pathologic feature or radiation treatment status. Results The locations of 243 NRs among 153 eligible patients were mapped. The majority of NR occurred in the axilla (42%; 102/243), followed by the IMN (32.5%; 79/243) and the SCV (25.5%; 62/243). Radiation Therapy Oncology Group (RTOG) or European Society for Radiation therapy and Oncology (ESTRO) clinical target volume encompassed 82% (198/243) of NRs. The majority of out-of-field NRs were located in the lateral and posterior SCV region for both RTOG (67%; 30/45) and ESTRO (89%; 49/55) guidelines. The high-risk patients who received regional RT to the SCV relapsed at a similar rate in the medial, but a higher rate in lateral SCV (P = .009), compared with low-risk patients who received no nodal RT. Lymphovascular invasion most strongly associated with IMN NR (P = .001); grade 3 disease highly associated with both IMN (P = .001) and SCV NR (P = .02). The presence of an IMN NR portended for significantly inferior overall survival (OS), compared with an axillary NR, with a 5-year OS of 59% versus 72%, respectively (P = .03). Conclusions In this 3-dimensional image-based analysis of NR patterns in breast cancer patients treated with contemporary therapies, the lateral and posterior SCV represented a distinct site of NR that is not routinely included within current breast cancer contouring atlases. Grade 3 breast cancer and LVI were most commonly associated with the development of NR in the SCV. Modifying the CTV to encompass the lateral and posterior SCV in patients with breast cancer with these features might be justified.

Purpose/Objective(s) Accelerated partial breast irradiation (APBI) following breast conserving surgery offers a convenient and well-tolerated adjuvant radiotherapy option in comparison to whole breast irradiation. While several APBI regimens exhibit excellent disease control among appropriately selected patients, patient-reported outcomes and toxicity assessments may vary. We sought to describe patient-reported acute toxicity as a function of salient dosimetric parameters, during and after an APBI regimen of 40 Gy in 10 once-daily fractions. Materials/Methods From June 2019 to July 2020 patients undergoing APBI were assigned a weekly, response adapted, PRO-CTCAE-based acute toxicity assessment. Symptoms assessed included pain, fatigue, breast enlargement, skin toxicity, and psychosocial concerns. Patients reported acute toxicity during treatment, and for up to 8-weeks following treatment. Socio-demographic characteristics and dosimetric treatment parameters were collected. Descriptive statistics were used to summarize patient-reported outcomes and corresponding dosimetric measures. Results Overall, 55 patients who received APBI (40 Gy in 10 fractions administered once-daily) completed more than one assessment during or after treatment. A total of 351 assessments were included in this analysis. Median patient age was 59 (range 37-78), and median planning target volume (PTV) was 210cc (range 64-580cc). Median PTV:ipsilateral breast volume ratio was 0.17 (range 0.05-0.44) and median maximum hotspot dose was 112% (range 108-115%). Breast V20 Gy ranged from 16% to 65% with a median of 45%. When queried weekly, 22% of patients reported moderate breast enlargement at least once, occurring at a median of 3 weeks after the initiation of treatment. More commonly, 71% reported maximum skin toxicity of moderate to very severe (42% moderate, 22% severe, 5% very severe) arising at a median of 3 weeks after the initiation of treatment. Furthermore, 70% of patients reported maximum fatigue as moderate to severe (42% moderate, 15% severe), and 44% patients reported maximum pain in the radiated area as moderate to very severe. Median time to first report of any moderate to very severe symptom was 10 days (IQR 6-27 days). By 8 weeks following APBI, 9 patients (16%) reported residual moderate symptoms and none endorsed severe or very severe symptoms. Conclusion Weekly assessments during and after APBI revealed that several patients experienced severe or very severe toxicities by their estimation, but that these universally resolved by 8 weeks following treatment at which point a minority endorsed moderate symptoms. Depending on toxicity type, peak effect could be noted as early as 1 week from the initiation of treatment for fatigue, or as late as 4 weeks for skin toxicity. More comprehensive evaluations among larger cohorts will help to define the precise dosimetric parameters that correspond to each outcome of interest.

Purpose/objective(s) Although clinical trial enrollment is critical to development of new cancer therapies, Materials/methods All patients enrolled on radiation oncology therapeutic clinical trials at community-based partner sites from Q2 2018 - Q1 2021 were included in this analysis. Guided by Expert Recommendation for Implementing Change (ERIC), strategies to increase trial enrollment were implemented prior to Q2 2020, and included: 1) altered incentive structure (per-patient cost paid to partner site, leaderboards), 2) building a coalition of physicians in metastatic disease, and 3) practice facilitation. An interrupted time series analysis included a two-tailed student's t-test to compare mean trial enrollments per quarter pre- and post-implementation. Protocol deviations were assessed in quality assurance (QA) review. Results Among 52 total patients enrolled in community-based, partner sites, 28 (54%) identify as Black or Hispanic. The number of clinical trials open to enrollment pre- and post-implementation was 5 vs. 8, respectively, while the number of patients enrolled was 6 vs. 46, respectively, representing an overall increase in mean number of quarterly patient enrollments from 1 to 11 (P Conclusion These implementation strategies were associated with increased therapeutic trial enrollment in community-based partner sites. With high variation in enrollment between physicians and prior research suggesting limited impact of site-level financial incentives, qualitative research will further investigate non-financial incentives and other facilitators to clinical trial enrollment within community-academic partnerships. Over-representation of minority patients further supports the benefit of enrolling patients on clinical trials in the community-based setting.

1044 Background: HER2-Low (or HER2-equivocal, FISH negative) breast cancer has historically been treated as HER2-negative; however, recent evidence suggests that there may be prognostic and/or predictive differences between the two. We explore demographic characteristics and clinical outcomes of HER2-negative and HER2-low metastatic breast cancer (MBC) patients using real world data. Methods: We queried the National Cancer Database to identify MBC patients that were HER2 0, HER2 1+, or HER2 2+ per immunohistochemical staining, with the latter two defined as HER2-low and the former HER2-negative. A multivariable binomial regression analysis identified demographic and clinical correlates of each subtype. A Cox multivariable regression analysis (MVA), propensity matched to HER2 status, was performed to identify correlates of survival. Results: After excluding missing data, 24,636 MBC patients diagnosed between 2008-2015 were identified, 6,865 (27.9%) of whom were HER2-negative and 17,771(72.1%) of whom were HER2-low. There were no differences between the two groups with respect to age, race, year treated, location, income, insurance status, Charles Deyo comorbidity score, laterality, T stage, N stage, or use of systemic therapy. HER2-low tumors were half as likely to have concomitant hormone receptor-negative status (OR = 0.49, 95% CI 0.46-0.53). The 3-year survival rate among hormone receptor-negative patients was 33.8% for HER2-low and 32.2% for HER2-negative, and 60.9% and 55.6% in HER2-low and HER2-negative cases among hormone receptor-positive patients, respectively. HER2-low cases were associated with better survival on MVA (HR = 0.91, 95% CI 0.87-0.95), and remained superior with propensity-matching (HR = 0.92, 95% CI 0.89-0.96). In a subset analysis isolated to hormone receptor-positive cases, HER2-low remained correlated with improved survival (HR = 0.93, 95% CI 0.89-0.98) with propensity-matched MVA. Correlates of worse survival include older age as a continuous variable (HR = 1.02), Black race (HR = 1.13), uninsured (HR = 1.18), comorbidity score > 0 (HR = 1.28), higher T stage (HR = 1.17 to 2.34), node positivity (HR = 1.17) and, as the most influential, hormone receptor-negative status (HR = 1.94) [all P < 0.01]. Conclusions: Consistent with recent data in non-MBC, our study demonstrates a small but statistically significant association with improved survival for HER2-low tumors compared to HER2-negative tumors in MBC. Randomized data are necessary to further validate this discrepancy and determine if different management is warranted for each subtype.

Guidelines on proton craniospinal irradiation (p-CSI) target volume selection in children are lacking. We examined the impact of target volume selection on growth of children receiving p-CSI at a institution. Records of 58 patients who received p-CSI were reviewed. Median age at treatment initiation was 8 years (range, 2 to 18 y). Spinal target volumes included whole vertebral body (WVB) in 67% and partial vertebral body (PVB) in 33%. Height z-scores before and after p-CSI were assessed using Centers for Disease Control and Prevention stature-for-age charts. Maximal Cobb angle and height z-score change were compared for WVB versus PVB p-CSI using a t test. Among 93% of patients with detailed data, median follow-up was 19 months (range, 2 to 58 mo) after radiation therapy initiation. Quantitative growth evaluations were available for 64% of patients. Median change in height z-score was -0.5 (range, -2.1 to +0.7) after treatment, representing a decrease (P0.001) in age-adjusted height. WVB patients had significantly greater reduction in height z-score versus PVB patients (P=0.004) but no difference in Cobb angle change (P0.05). Despite reluctance surrounding its use in younger patients, PVB p-CSI was associated with similar spinal curvature and less growth suppression as compared with WVB p-CSI; a trial comparing WVB versus PVB in children may be warranted.

Palliative care and radiation therapy have played an expanding role in the management of patients with advanced cancers. Recent advances in our understanding of oligometastatic disease have led to increasing demand for familiarity with ablative techniques. Recognizing the demands of hospitalized patients for rapid access to care, we created an inpatient radiation oncology consult service (IROC) with consolidated expertise in palliative radiation and ablative techniques. In this quality improvement cohort study, we analyzed inpatient radiation oncology consults placed before and after IROC implementation and found that IROC led to increased delivery of specialty care and decreased hospital length of stay (median 8 days v 7 days, P = .005). This difference was most pronounced for patients for whom radiation therapy was indicated (14.5 v 11 days, P = .007). Our institutional experience demonstrates the value of recognizing metastatic disease as a distinct discipline and providing rapid access to palliative treatments for patients with advanced malignancies.

Mastectomy has long been the preferred approach for local salvage of recurrent breast cancer following breast-conservation therapy (BCT). Growing interest in avoiding mastectomy prompted RTOG 1014, a landmark phase two study demonstrating the feasibility of repeat BCT using a novel radiotherapy (RT) regimen (i.e., 45 Gy administered in 30 fractions of 1.5 Gy twice-daily to the partial breast, “rePBI”). We adopted this regimen as our institutional standard and report our observations regarding the safety and efficacy of rePBI as salvage therapy. All patients at our institution who underwent repeat BCT and subsequently received rePBI from 2011 to 2019 were identified. Clinicopathologic features and treatment characteristics for both primary breast cancers and recurrences were collected, as were rates of subsequent recurrence and treatment-associated toxicities. The cohort included 34 patients with a median age of 65.8 (46.2–78.2) at the time of rePBI. At a median follow-up of 23.5 months, there were two subsequent locoregional recurrences (2-year local control rate 97%). There was no grade ≥ 3 toxicity. The most common acute toxicity ( 3 months) included fibrosis in 14 (41%), breast asymmetry in 12 (35%), and chest wall pain in 11 (32%). Repeat breast conservation using the hyperfractionated partial breast RT regimen defined by RTOG 1014 (45 Gy administered in 30 1.5 Gy twice-daily fractions) appears effective and well tolerated. No grade 3 or higher toxicities were observed and local control was excellent. Longer term follow-up among larger cohorts will define whether salvage mastectomy should remain the preferred standard.

Purpose Guidelines for early-stage breast cancer allow for radiotherapy (RT) omission following breast conserving surgery (BCS) among older women, though high utilization of RT persists. This study explores surgeon referral and the effect of a productivity-based bonus metric for radiation oncologists in an academic institution with centralized quality assurance (QA) review. Methods We evaluated patients ≥ 70 years of age treated with BCS for ER + pT1N0 breast cancer at a single institution between 2015–2018. The primary outcomes were radiation oncology referral and RT receipt. Covariables included patient and physician characteristics, and treatment decisions before versus after productivity metric implementation. Univariable generalized linear effects models explored associations between these outcomes and covariables. Results Of 703 patients included, 483 (69%) were referred to radiation oncology and 273 (39%) received RT (among those referred, 57% received RT). No difference in RT receipt pre- versus post- productivity metric implementation was observed (p = 0.57). RT receipt was associated with younger patient age (70–74 years, OR 2.66, 95% CI 1.54–4.57) and higher grade (grade 3, OR 7.75, 95% CI 3.33–18.07). Initial referral was associated with younger age (70–74, OR 5.64, 95% CI 3.37–0.45) and higher performance status (KPS ≥90, OR 5.34, 95% CI 2.63–10.83). Conclusion Non-referral to radiation oncology accounted for half of RT omission, but was based on age and KPS, in accordance with guidelines. Lack of radiation oncologist practice change in response to misaligned financial incentives is reassuring, potentially reflecting centralized QA review. Multi-institutional studies are needed to confirm these findings.

Mastectomy has long been the preferred approach for local salvage of recurrent breast cancer following breast-conservation therapy (BCT). Growing interest in avoiding mastectomy prompted RTOG 1014, a landmark phase two study demonstrating the feasibility of repeat BCT using a novel radiotherapy (RT) regimen (i.e., 45 Gy administered in 30 fractions of 1.5 Gy twice-daily to the partial breast, "rePBI"). We adopted this regimen as our institutional standard and report our observations regarding the safety and efficacy of rePBI as salvage therapy.All patients at our institution who underwent repeat BCT and subsequently received rePBI from 2011 to 2019 were identified. Clinicopathologic features and treatment characteristics for both primary breast cancers and recurrences were collected, as were rates of subsequent recurrence and treatment-associated toxicities.The cohort included 34 patients with a median age of 65.8 (46.2-78.2) at the time of rePBI. At a median follow-up of 23.5 months, there were two subsequent locoregional recurrences (2-year local control rate 97%). There was no grade ≥ 3 toxicity. The most common acute toxicity ( 3 months) was radiation dermatitis (100%), and common grade 1-2 late toxicities ( 3 months) included fibrosis in 14 (41%), breast asymmetry in 12 (35%), and chest wall pain in 11 (32%).Repeat breast conservation using the hyperfractionated partial breast RT regimen defined by RTOG 1014 (45 Gy administered in 30 1.5 Gy twice-daily fractions) appears effective and well tolerated. No grade 3 or higher toxicities were observed and local control was excellent. Longer term follow-up among larger cohorts will define whether salvage mastectomy should remain the preferred standard.

Radiotherapy has long been used in the management of malignant and benign conditions alike, but only in recent decades have the long term implications of cardiac exposure been comprehensively delineated. In this chapter, we present the evolution of radiotherapy technologies, image guided targeting approaches, and patient positioning maneuvers, that have significantly reduced treatment-related morbidity, particularly as related to long term cardiac outcomes.

Key Points Question Following resection of a localized breast cancer, why does adjuvant regional nodal irradiation (RNI) reduce distant recurrences to a greater extent than regional recurrences, despite only targeting the regional lymph nodes? Findings In this cohort study of 597 patients with de novo metastatic breast cancer, 85.8% harbored regional disease at the time of metastatic presentation. The consistent detection of concurrent regional and metastatic disease, along with the reduction in distant recurrences observed following RNI, is consistent with the hypothesis that regional nodal disease may precede metastatic dissemination. Meaning These findings suggest that RNI may reduce distant recurrences by sterilizing occult regional nodal disease prior to systemic seeding., This cohort study examines whether and why regional node irradiation in patients with de novo metastatic breast cancer has different levels of effectiveness for preventing recurrences of cancer in regional nodes and distant mestastases., Importance Regional nodal irradiation (RNI) for node-positive breast cancer reduces distant metastases and improves survival, albeit with limited reduction in regional nodal recurrences. The mechanism by which RNI robustly reduces distant metastases while modestly influencing nodal recurrences (ie, the presumed target of RNI) remains unclear. Objective To determine whether some distant metastases putatively arise from occult regional nodal disease and whether regional recurrences otherwise remain largely undetected until an advanced cancer presentation. Design, Setting, and Participants This cohort study examined patients presenting with de novo stage IV breast cancer to the Memorial Sloan Kettering Cancer Center in New York, New York, from 2006 to 2018. Medical records were reviewed to ascertain clinicopathological parameters, including estrogen receptor status and survival. Pretreatment positron emission tomography–computed tomography (PET-CT) imaging was reviewed to ascertain the extent of regional nodal involvement at metastatic diagnosis using standard nodal assessment criteria. A subset underwent regional lymph node biopsy for diagnostic confirmation and served to validate the radiographic nodal assessment. Data analysis was performed from October 2019 to February 2020. Exposures Untreated metastatic breast cancer. Main Outcome and Measures The primary outcome was the likelihood of regional nodal involvement at the time of metastatic breast cancer presentation and was determined by reviewing pretreatment PET-CT imaging and lymph node biopsy findings. Results Among 597 women (median [interquartile range] age, 53 [44–65] years) with untreated metastatic breast cancer, 512 (85.8%) exhibited regional lymph node involvement by PET-CT or nodal biopsy, 509 (85%) had involvement of axillary level I, 328 (55%) had involvement in axillary level II, 136 (23%) had involvement in axillary level III, 101 (17%) had involvement in the supraclavicular fossa, and 96 (16%) had involvement in the internal mammary chain. Lymph node involvement was more prevalent among estrogen receptor–negative tumors (92.4%) than estrogen receptor–positive tumors (83.6%). Nodal involvement at the time of metastatic diagnosis was not associated with overall survival. Conclusions and Relevance These findings suggest that a majority of patients with de novo metastatic breast cancer harbor regional lymph node disease at presentation, consistent with the hypothesis that regional involvement may precede metastatic dissemination. This is in alignment with the findings of landmark trials suggesting that RNI reduces distant recurrences. It is possible that this distant effect of RNI may act via eradication of occult regional disease prior to systemic seeding. The challenges inherent in detecting isolated nodal disease (which is typically asymptomatic) may account for the more modest observed benefit of RNI on regional recurrences. Alternative explanations of nodal involvement that arises concurrently or after metastatic dissemination remain possible, but do not otherwise explain the association of RNI with distant recurrence.

Breast cancer diagnosis at a very young age has been independently correlated with worse outcomes. Appropriately intensifying treatment in these patients is warranted, even as we acknowledge the risks of potentially mutagenic adjuvant therapies. We examined local control, distant control, overall survival, and secondary malignancy rates by age cohort and by initial surgical strategy.Female patients less than or equal to 35 years of age diagnosed with invasive breast cancer from January 1, 1990, to December 31, 2010, were identified. Control groups of those aged 36 to 50 years (n = 6246) and 51 to 70 years (n = 7294) were delineated from an institutional registry. Clinicopathologic and follow-up information was collected. Chi-squared test was used to compare frequencies of categorical variables. Survival endpoints were evaluated using Kaplan-Meier methodology.A total of 529 patients ≤35 years of age met criteria for analysis. The median age of diagnosis was 32 years (range 20-35). Median follow-up was 10.3 years. On multivariable analysis, factors associated with overall survival (OS) were tumor size (hazard ratio [HR] 1.14, P = .02), presence of lymphovascular invasion (HR 2.2, P.001), estrogen receptor positivity (HR 0.64, P = .015), receipt of adjuvant chemotherapy (HR 0.52, P = .035), and black race (HR 2.87, P.001). The ultra-young were more likely to experience local failure compared with the aged 36 to 50 group (HR 2.2, 95% CI 1.8-2.6, P.001) and aged 51 to 70 group (HR 3.1, 95% CI 2.45 - 3.9, P.001). The cumulative incidence of secondary malignancies at 5 and 10 years was 2.2% and 4.4%, respectively. Receipt of radiation was not significantly associated with secondary malignancies or contralateral breast cancer.Survival and recurrence outcomes in breast cancer patients ≤35 years are worse compared with those aged 36 to 50 or 51 to 70 years. Based on our data, breast conservation therapy is appropriate for these patients, and the concern for second malignancies should not impinge on the known indications for postoperative radiation therapy.

BackgroundIn an attempt to reduce interruptions in radiation treatment, our department implemented universal SARS-CoV-2 PCR testing during the peak of the New York City COVID-19 epidemic.MethodsStarting 4/18/20, outpatients coming into the Department of Radiation Oncology for either simulation or brachytherapy were required to undergo PCR testing for SARS-CoV-2. Starting on 5/6/20, patients were offered simultaneous SARS CoV-2 IgG antibody testing.ResultsBetween 4/18/20-6/25/20, 1360 patients underwent 1,401 outpatient screening visits (Table 1). Of the patients screened, 411 were screened between 4/18/20 and 5/6/20 (Phase 1) with PCR testing: 13 (3.1%) patients were PCR positive. From 5/7/20 to 6/25/20, 990 patients were scheduled for both PCR and antibody testing (Phase 2), including 41 previously screened in Phase 1. Of those with known antibody status (n=952), 5.5% were seropositive. After 5/21/20, no screened patient (n=605) tested PCR positive. In the month prior to screening (3/17/20-4/19/20), 24 of 625 patients initiating external radiation had treatment interrupted due to COVID-19 infection (3.8%) vs 7 of 600 patients (1.1%) in the month post screening (4/20/20-5/24/20) (p=0.002).ConclusionsState-wide mitigation efforts, coupled with intensive departmental screening, helped prevent interruptions in radiation during the COVID-19 epidemic that could have compromised treatment efficacy.