Clinical Outcomes in Patients Receiving Pencil Beam Proton Re-Irradiation for New or Locoregionally Recurrent Breast Cancer

Abstract

<h3>Purpose/Objective(s)</h3> Local-regional recurrence of breast cancer (BC) after prior radiation (RT) presents clinical and dosimetric challenges. Proton beam therapy (PBT), and in particular pencil beam scanning (PBS), offers a unique dosimetric advantage due to its lack of exit dose and high conformality, which may allow safer delivery of a second RT course. Recently, there has been a retrospective report of 46 patients (pts) treated with uniform or PBS PBT. Here, we present the largest series to date using PBS PBT. We analyzed treatment patterns, toxicities, and clinical outcomes of BC pts receiving PBS-proton reradiating (reRT). Our hypothesis was that PBS PBT reRT to breast/chest wall (CW) provides reasonable local control (LC) and toxicities. <h3>Materials/Methods</h3> A single-institution retrospective IRB-approved analysis was conducted of all pts who underwent reRT for recurrent or new BC, between 4/2017 and 11/2021. Descriptive statistics were used to describe pt, tumor and treatment characteristics. Local failure-free survival (LFFS), distant metastasis-free survival (DMFS), and overall survival (OS) were measured from reRT start to the first event, by Kaplan-Meier method. Pts who remained alive were censored at last follow-up. Toxicities were scored according to CTCAE v4.0. Comparisons of pts, tumor, and treatment characteristics between those with any grade ≥ 3 acute toxicity (AT) or any late toxicity (LT) vs. none were performed using two-sample t-tests and chi-square tests. Multivariable analysis for LFFS and OS was conducted using cox-proportional hazards models. Statistical software used for analysis. <h3>Results</h3> A total of 68 pts with breast/CW reRT with PBS PBT were identified. Only pts who completed treatment were included in analyses (3 pts were excluded; final N=65). Median follow-up was 26.6 months. The median age was 61 yrs (range 30-89). 60% of pts were white, 32% black and 8% from other races. 65% of treated BCs were hormone positive, 1% HER2/neu enriched and 34% triple negative. Median time between initial and reRT was 52 months (range 6-328). Median cumulative previous RT dose (EQD2) was 48.4 Gy (range 43.2-66.0). Median cumulative PBS PBT dose (EQD2) was 57.0 Gy (range 30.2-76.9). 8 pts (12%) underwent BID treatment, 22 pts (34%) received concurrent hyperthermia and 13 pts (20%) underwent concurrent chemotherapy. 14 pts (22%) experienced grade 3 AT, including 13 dermatitis (20%) and 1 fatigue and pain (1.5%). No grade 4/5 toxicities were observed. 6 pts were lost in follow-up. 33 pts (56%) experienced any grade LT (skin changes [N=21; 36%], soft tissue fibrosis [N=7; 12%], CW discomfort [N=10; 17%], arm discomfort [N=6; 10%], lymphedema [N=11; 19%] and rib fracture [N=3; 5%]). At 2 yrs, LFFS=93% and DMFS=88%. OS was 89%. No explanatory variables were associated with toxicity or survival outcomes <h3>Conclusion</h3> Our analysis indicates that PBS PBT reRT for BC is well tolerated and offers meaningful rates of LC, toxicities and survival.