Final Analysis of a Phase 2 Trial of Once Weekly Hypofractionated Whole Breast Irradiation for Early-Stage Breast Cancer

Abstract

Purpose: We hypothesize that 5-fraction once weekly hypofractionated (WH) whole breast irradiation (WBI) would be safe and effective after breast-conserving surgery for medically underserved patients with breast cancer. We report the protocol-specified primary endpoint of in-breast tumor recurrence (IBTR) at 5 years.

Methods and materials: After provided informed consent, patients were treated with WH-WBI after breast-conserving surgery were followed prospectively on an institutional review board-approved protocol. Women included in this study had stage 0-II breast cancer treated with negative surgical margins and met prespecified criteria for being underserved. WH-WBI was 28.5 or 30 Gy delivered to the whole breast with no elective coverage of lymph nodes. The primary endpoint was IBTR at 5 years. Secondary endpoints were distant disease-free survival, recurrence-free survival, overall survival, adverse events, and cosmesis.

Results: One hundred fifty-eight patients received WH-WBI on protocol from 2010 to 2015. Median follow-up was 5.5 years (range, 0.2-10.0 years). Stage distribution was 22% ductal carcinoma in situ, 68% invasive pN0, and 10% invasive pN1. Twenty-eight percent of patients had grade 3 tumors, 10% were estrogen receptor negative, and 24% required adjuvant chemotherapy. There were 6 IBTR events. The 5-, 7-, and 10-year risks of IBTR for all patients were 2.7% (95% confidence interval [CI], 0.89-6.34), 4.7% (95% CI, 1.4-11.0) and 7.2% (95% CI, 2.4-15.8), respectively. The 5-, 7-, and 10-year rates of distant disease-free survival were 96.4%, 96.4%, and 86.4%; the recurrence-free survival rates were 95.8%, 93.6%, and 80.7%; and the overall survival rates were 96.7%, 88.6%, and 76.7%, respectively. Improvement in IBTR-free time was seen in ductal carcinoma in situ, lobular histology, low-grade tumors, T1 stage, Her2-negative tumors, and receipt of a radiation boost to the lumpectomy bed.

Conclusions: Postoperative WH-WBI has favorable disease-specific outcomes that are comparable to those seen with conventional and moderately hypofractionated radiation techniques. WH-WBI could improve access to care for underserved patients with stage 0-II breast cancer.

Keywords: breast cancer, radiation therapy, hypofractionated radiotherapy, ultra-hypofractionated radiotherapy, whole breast radiation therapy.