Reirradiation With Proton Therapy for Recurrent Malignancies of the Esophagus and Gastroesophageal Junction: Results of the Proton Collaborative Group Multi-Institutional Prospective Registry Trial

Abstract

Background and purposeTreatment options for recurrent esophageal cancer (EC) previously treated with radiation therapy are limited. Reirradiation (reRT) with proton beam therapy (PBT) can offer lower toxicities by limiting doses to surrounding tissues. In this study, we present the first multi-institutional series reporting on toxicities and outcomes after reRT for locoregionally recurrent EC with PBT. Materials and methodsAnalysis of the prospective, multicenter, Proton Collaborative Group registry of patients with recurrent EC who had previously received photon-based RT and underwent PBT reRT was performed. Patient/tumor characteristics, treatment details, outcomes, and toxicities were collected. Local control (LC), distant-metastasis free survival (DMFS), and overall survival (OS) were estimated using the Kaplan-Meier method. Event time was determined from reRT start. ResultsBetween 2012 and 2020, 31 patients received reRT via uniform scanning/passive scattering (61.3%) or pencil beam scanning (38.7%) PBT at seven institutions. Median prior RT, PBT reRT, and cumulative doses were 50.4 Gy (range, 37.5 – 110.4), 48.6 Gy (RBE) (25.2-72.1), and 99.9 Gy (79.1-182.5), respectively. 12.9% of patients had two prior RT courses, and 67.7% received PBT with concurrent chemotherapy. Median follow-up was 7.2 months (0.9-64.7). Post PBT, there were 16.7% locoregional only, 11.1% distant only, and 16.7% locoregional and distant recurrences. Six-month LC, DMFS, and OS were 80.5%, 83.4%, and 69.1%, respectively. One-year LC, DMFS, and OS were 67.1%, 83.4%, and 27%, respectively. Acute grade ≥3 toxicities occurred in 23% of patients, with one acute grade 5 toxicity secondary to esophageal hemorrhage, unclear if related to reRT or disease progression. No grade ≥3 late toxicities were reported. ConclusionIn the largest report to date of PBT for reRT in patients with recurrent EC, we observed acceptable acute toxicities and encouraging rates of disease control. However, these findings are limited by the poor prognoses of these patients, who are at high risk of mortality. Further research is needed to better assess the long-term benefits and toxicities of PBT in this specific patient population.