Abstract PD3-04: Locoregional Stereotactic Body Radiotherapy in Breast Cancer Patients Unsuitable for Surgical Resection

Abstract Purpose: Breast cancer (BC) patients (pts) who are not surgical candidates or decline surgical resection are usually managed with palliative systemic therapy alone or palliative radiotherapy if clinically appropriate. Stereotactic body radiotherapy (SBRT) has shown excellent results for different primary malignancies, and we hypothesized it could improve outcomes in this context with acceptable toxicity. This study aims to assess the local control (LC) and toxicity rates of breast SBRT in pts unsuitable for surgical resection. Methods and Materials: We performed a retrospective analysis using an institutional registry of all BC pts unsuitable for resection who underwent breast and/or regional lymph node (LN) SBRT to a dose of 35-40 Gy in 5 fractions from 2014 to 2021. Patients were deemed unsuitable for resection if they were medically inoperable, declined surgery, had unresectable tumors, or where surgery was not appropriate, such as due to metastatic disease. The primary endpoint was LC (defined as no evidence of progression of the treated lesion as per RECIST 1.1 criteria) and toxicity grade ≥ 3 (as per CTCAE v5.0). Secondary endpoints included radiological response (RR) of the target tumor at the last follow-up, progression-free survival (PFS), and overall survival (OS). All endpoints were assessed per course of treatment, with death as a competing factor for LC. Results: This study included 61 treatment courses in 57 pts. The median age was 81 years (range 38-99), 74% being older than 70 years of age. Eighteen percent had stage I-II, 44% stage III, and 38% stage IV disease. Unresectable tumor (10%), patient refusal (18%), medically inoperability (34%), and metastatic disease (38%) were the main causes of not having surgery. The molecular subtypes were HER-2 in 3%, basal-like 23%, and luminal disease 74%. Previous systemic treatment consisted of endocrine therapy (ET) alone (49%), chemotherapy (CT) or target therapy (TT) alone (11%), both ET and CT/TT (18%), or none (21%). Seventy-two percent of tumors were progressing on ET (44%) or CT/TT (28%) at the time of SBRT. The median interval from cancer diagnosis to SBRT was 14.6 (range 0.5-180) months (mos). Fifty-four percent had breast SBRT, 15% LN SBRT, and 31% both. For LN treatment, axillary, internal mammary, and supraclavicular nodes were the target in 43%, 3%, and 2% of treatments, respectively. The median clinical and radiological follow-up was 16.8 (range 0.2-87) and 13.4 mos (range 1-81), respectively. The worst acute and late grade ≥ 3 toxicity was 16% and 4%, respectively, and all cases consisted of radiation dermatitis. No patient was unable to complete treatment due to acute toxicity. There was one case of grade 4 skin necrosis 6.3 mos after 35 Gy in 5 fractions to an axillary LN. The LC rate at 1 year was 100% and 2 years 88.6% (95% CI = 79-99%). The median time to local progression among those who progressed was 18.2 mos (95% CI = 12-not reached). At last FU, the RR of treated tumors was: complete response = 8%, partial response = 46%, stable disease = 38%, and progressive disease = 8%. The PFS and OS rates at 1 year was 69.8 % (95% CI = 58-82) and 74.6% (95% IC = 63-86), 2 years 39.1% (95% CI = 26—52) and 50.6% (95% IC = 36-65), 3 years 26.7 % (95% CI =14-39) and 38.7% (95% IC = 24-54), and 4 years 18.5 % (95% CI = 8-29) and 29.2% (95% CI = 14-44), respectively. The median PFS was 21.7 mos (95% CI = 17-28) and OS 31.1 mos (95% CI = 21- 38). Ongoing analysis intends to identify clinical and pathological predictors of LC, PFS, and OS. Conclusion: Our initial data suggest that breast SBRT safely provides excellent LC rates in non-operable BC pts. This approach may be a treatment option in pts who are not good surgical candidates, particularly in elderly pts with multiple comorbidities, which comprised 74% of our cohort. A clinical trial is underway to determine the optimal dose and side effect profile for primary breast SBRT with curative intent in pts not undergoing definitive surgery. Citation Format: Daniel Palhares, Hanbo Chen, Benazir Khan, Claire McCann, Sandi Bosnic, Ezra Hahn, Hany Soliman, Eileen Rakovitch, Justin Lee, Danny Vesprini. Locoregional Stereotactic Body Radiotherapy in Breast Cancer Patients Unsuitable for Surgical Resection [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 PD3-04.