Proton Reirradiation for Recurrent or New Primary Breast Cancer in the Setting of Prior Breast Irradiation

Abstract

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.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.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.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.