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Purpose: Regional nodal irradiation (RNI) for breast cancer yields improvements in disease outcomes, yet comprehensive target coverage often increases cardiac radiation therapy (RT) dose. Volumetric modulated arc therapy (VMAT) may mitigate high-dose cardiac exposure, although it often increases the volume of low-dose exposure. The cardiac implications of this dosimetric configuration (in contrast to historic 3D conformal techniques) remain uncertain. Methods and Materials: Eligible patients receiving adjuvant RNI using VMAT for locoregional breast cancer were prospectively enrolled in an IRB-approved study. Echocardiograms were performed prior to RT, at the conclusion of RT, and 6 months following RT. Echocardiographic parameters were measured by a single reader and measures were compared pre- and post-RT via the signed-rank test. Changes in echocardiographic parameters over time were compared to mean and max heart doses via the Spearman correlation test. Results: Among 19 evaluable patients (median age 38 years), 89% (n = 17) received doxorubicin and 37% (n = 7) received trastuzumab/pertuzumab combination therapy. All patients received VMAT-based whole-breast/chest wall and RNI. The average mean heart dose was 456 cGy (range, 187-697 cGy) and the average max heart dose was 3001 cGy (1560-4793 cGy). Among salient echocardiographic parameters, no significant decrement in cardiac function was observed when comparing pre-RT to 6 months post-RT: mean left ventricular ejection fraction (LVEF) was 61.8% (SD 4.4%) pre-RT and 62.7% (SD 3.8%) 6 months post-RT (P = .493); mean global longitudinal strain (GLS) was –19.3% (SD 2.2%) pre-RT and –19.6% (SD 1.8%) 6 months post-RT (P = .627). No individual patient exhibited reduced LVEF or sustained decrement in GLS. No correlations were observed for changes in LVEF or GLS when compared to mean or maximum heart doses (P > .1 for all). Conclusions: VMAT for left-sided RNI yielded no significant early decrement in echocardiographic parameters of cardiac function, including LVEF and GLS, within this limited cohort. No patient exhibited significant LVEF changes, and none exhibited sustained decrements in GLS. VMAT may be a reasonable approach to cardiac avoidance in patients requiring RNI, including those receiving anthracyclines and HER2-directed therapy. Larger cohorts with longer follow-ups will be needed to validate these findings.

Purpose: Radiation therapy (RT) after breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS) reduces invasive and in situ recurrences. Whereas landmark studies suggest that a tumor bed boost improves local control for invasive breast cancer, the benefit in DCIS remains less certain. We evaluated outcomes of patients with DCIS treated with or without a boost. Methods and Materials: The study cohort comprised patients with DCIS who underwent BCS at our institution from 2004 to 2018. Clinicopathologic features, treatment parameters, and outcomes were ascertained from medical records. Patient and tumor characteristics were evaluated relative to outcomes using univariable and multivariable Cox models. Recurrence-free survival (RFS) estimates were generated using the Kaplan-Meier method. Results: We identified 1675 patients who underwent BCS for DCIS (median age, 56 years; interquartile range, 49-64 years). Boost RT was used in 1146 cases (68%) and hormone therapy in 536 (32%). At a median follow-up of 4.2 years (interquartile range, 1.4-7.0 years), we observed 61 locoregional recurrence events (56 local, 5 regional) and 21 deaths. Univariable logistic regression demonstrated that boost RT was more common among younger patients (P < .001) with positive or close margins (P < .001) and with larger tumors (P < .001) of higher grade (P = .025). The 10-year RFS rate was 88.8% among those receiving a boost and 84.3% among those without a boost (P = .3), and neither univariable nor multivariable analyses revealed an association between boost RT and locoregional recurrence. Conclusions: Among patients with DCIS who underwent BCS, use of a tumor bed boost was not associated with locoregional recurrence or RFS. Despite a preponderance of adverse features among the boost cohort, outcomes were similar to those of patients not receiving a boost, suggesting that a boost may mitigate risk of recurrence among patients with high-risk features. Ongoing studies will elucidate the extent to which a tumor bed boost influences disease control rates.

Purpose: Proton therapy (PT) for partial breast irradiation (PBI) in early-stage breast cancer can decrease morbidity versus photon PBI with superior organs-at-risk sparing. We report 3-year outcomes of the first prospective, multicenter, phase II trial of proton PBI. Methods and Materials: This Proton Collaborative Group phase II trial (PCG BRE007-12) recruited women ≥ 50 years with node-negative, estrogen receptor (ER)-positive, ≤3cm, invasive ductal carcinoma (IDC) or ductal carcinoma in situ undergoing breast conserving surgery followed by proton PBI (40 Gy(RBE), 10 daily fractions). Primary endpoint was freedom from ipsilateral breast cancer recurrence. Adverse events were prospectively graded using CTCAEv4.0. Breast Cancer Treatment Outcome Scale (BCTOS) assessed patient-reported quality of life (PRQOL). Results: Thirty-eight evaluable patients enrolled between 2/2013–11/2016. Median age was 67 years (range 50–79); 55 % had left-sided disease, and median tumor size was 0.9 cm. Treatment was delivered in ≥ 2 fields predominantly with uniform scanning PT (n = 37). At 35-month median follow-up (12–62), all patients were alive, and none had local, regional or distant disease progression. One patient developed an ER-negative contralateral IDC. Seven grade 2 adverse events occurred; no radiotherapy-related grade ≥ 3 toxicities occurred. Changes in BCTOS subdomain mean scores were maximum 0.36, indicating no meaningful change in PRQOL. Median heart volume receiving 5 Gy (V5Gy), lung V20Gy, and lung V10Gy were 0 %, 0 % and 0.19 %, respectively. Conclusion: At 3 years, proton PBI provided 100 % cancer control for early-stage, ER-positive breast cancer. Toxicities are minimal, and PRQOL remains acceptable with continued follow-up. These findings support PT as a safe and effective PBI delivery option.

Purpose: : Guidelines for early-stage breast cancer allow for radiation therapy (RT) omission after breast conserving surgery among older women, though high utilization of RT persists. This study explored surgeon referral and the effect of a productivity-based bonus metric for radiation oncologists in an academic institution with centralized quality assurance review. Methods and materials: : We evaluated patients ≥70 years of age treated with breast conserving surgery for estrogen receptor (ER)+ pT1N0 breast cancer at a single tertiary cancer network between 2015 and 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 = .57). RT receipt was associated with younger patient age (70-74 years; odds ratio [OR], 2.66; 95% confidence interval [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 (Karnofsky performance status ≥90; OR, 5.34; 95% CI, 2.63-10.83). Conclusions: : Nonreferral to radiation oncology accounted for half of RT omission but was based on age and Karnofsky performance status, in accordance with guidelines. Lack of radiation oncologist practice change in response to misaligned financial incentives is reassuring, potentially reflecting incentive design and/or centralized quality assurance review. Multi-institutional studies are needed to confirm these findings.

Purpose: A radiation anatomist was trained and integrated into clinical practice at a multi-site academic center. The primary objective of this quality improvement study was to determine whether a radiation anatomist improves the quality of organ-at-risk (OAR) contours, and secondarily to determine the impact on efficiency in the treatment planning process. Methods and Materials: From March to August 2020, all patients undergoing computed tomography–based radiation planning at 2 clinics at Memorial Sloan Kettering Cancer Center were assigned using an “every other” process to either (1) OAR contouring by a radiation anatomist (intervention) or (2) contouring by the treating physician (standard of care). Blinded dosimetrists reported OAR contour quality using a 3-point scoring system based on a common clinical trial protocol deviation scale (1, acceptable; 2, minor deviation; and 3, major deviation). Physicians reported time spent contouring for all cases. Analyses included the Fisher exact test and multivariable ordinal logistic regression. Results: There were 249 cases with data available for the primary endpoint (66% response rate). The mean OAR quality rating was 1.1 ± 0.4 for the intervention group and 1.4 ± 0.7 for the standard of care group (P < .001), with subset analysis showing a significant difference for gastrointestinal cases (n = 49; P

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.

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: 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: 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