A Pilot Study of Hypofractionated Simultaneous Integrated Boost Radiotherapy in Stage 0-IIIB Breast Cancer Patients

Abstract

In the UK START and Canadian hypofractionated whole breast radiotherapy (RT) trials, few patients were Black, received prior chemotherapy, or had large breast size, all factors associated with RT-induced breast toxicity. The purpose of this prospective trial was to assess the safety and efficacy of delivering 15 fractions of hypofractionated simultaneous integrated boost (SIB) RT to patients under-represented on trials of hypofractionated breast RT and who have characteristics which increase their risk for local recurrence and cutaneous toxicity from breast RT.We conducted a prospective, single-arm pilot study to evaluate a once daily 15 fraction SIB RT regimen of 39.9 Gy in 2.66 Gy fractions to the breast/chest wall with or without regional nodal irradiation (RNI) and SIB of 8.1 Gy in 0.54 Gy fractions. Women with Stage 0-IIIB breast cancer who had one or more of the following characteristics were approached for enrollment: 1) prior chemotherapy for breast cancer; 2) > 25 cm breast/chest wall separation; 3) non-White race; 4) ≤ 50 years old; or 5) requiring RNI. Primary endpoint was Grade 3 cutaneous toxicity rate by CTCAE v.5. Among patients who received RNI (n = 30), rates of Grade 3 brachial plexopathy by RTOG criteria and 20% or greater increase in arm lymphedema, were additional primary endpoints. Patients were assessed prior to RT, last day of RT, and 3 weeks, 9 weeks and 1 year post RT. Local regional recurrence free survival (LRFS) was a secondary endpoint.Among 74 participants, 57% received prior chemotherapy, 19% had breast/chest wall separation > 25cm, 39% were Black, 36% were ≤ 50 years old, and 41% were prescribed RNI. Median body mass index was 30.0 (range 17.3 - 54.9). Ten patients received post mastectomy RT. One patient developed Grade 3 radiation dermatitis 3 weeks post RT. No other Grade 3 or higher cutaneous toxicities were observed up to 1 year post RT. One patient developed a grade 3 axillary infection 3 weeks post RT, which resolved after intravenous antibiotics. No patients who received RNI developed grade 3 brachial plexopathy or a 20% increase in the ipsilateral arm volume during the study period. With a median follow up of 60 months (range 12-113 months), one in-breast recurrence with simultaneous distant metastases occurred. Two additional patients developed distant metastases alone. The 5-year LRFS and overall survival rates were 98.6% and 98.5%, respectively.Our results indicate that SIB radiation therapy is well-tolerated with acceptable cutaneous toxicity rates up to 1 year post RT even among patients who are at high risk for RT-induced breast side effects. The high rates of local control and overall survival following SIB treatment are promising and support condensed courses of RT in patients who would typically receive a sequential boost due to higher risk for local recurrence.