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

<h3>Purpose/Objective(s)</h3> Salvage treatment options for locoregional recurrences of esophageal/gastroesophageal junction (GEJ) cancers previously treated with radiation therapy are limited. Photon reirradiation, which has historically been employed as one such modality in these cases, is associated with high toxicity rates. Proton therapy provides superior normal tissue sparing and may permit safer dose escalation during reirradiation. However, there are limited current data on proton reirradiation. Thus, we sought to evaluate patient outcomes and toxicities after proton reirradiation for recurrent esophageal/GEJ cancers. <h3>Materials/Methods</h3> The Proton Collaborative Group prospective, multi-institutional registry was queried for patients with recurrent esophageal/GEJ cancers retreated with proton therapy. All patients included in this analysis received prior photon radiotherapy, either in the definitive or adjuvant setting. Baseline demographics, treatment details, outcomes, and acute toxicities (CTCAEv4.0) were evaluated. Local control (LC) and overall survival (OS) were estimated using the Kaplan-Meier method, with the time to event determined from the start of reirradiation for LC and the time from first recurrence for OS. <h3>Results</h3> Thirty-one patients retreated between May 2012 and October 2020 were analyzed. The median age was 68 years (range 40-87 years), and most were male (74%) and non-Hispanic Caucasian (81%) with adenocarcinoma (55%). The initial stages of their cancers were as follows: T1 6%, T2 10%, T3 77%, unknown 6%; N0 29%, N+ 67%, unknown 3%; stage I 0%, IIA 3%, IIB 23%, IIIA 29%, IV 10%, unknown 35%. During their first course of radiation therapy, they received a median of 49.5 Gy (10.8-66.0 Gy) in 6-33 fractions. Additionally, 71% received concurrent chemotherapy and 35% underwent resection. The median time to recurrence was 22.1 months (3.7–134.1 months). Proton reirradiation was primarily delivered using uniform scanning/passive scattering (n=18) or pencil beam scanning (n=12) to a median dose of 46.17 Gy relative biological effectiveness (RBE) (25.2 – 72.1 Gy(RBE)) in 12- fractions, given daily or twice daily, and 71% (n=22) received concurrent chemotherapy. Median follow-up from reirradiation completion was 9.2 months (0-63.3). OS at 6 and 12 months were 93.5% and 60.1%, respectively, and LC at 6 and 12 months were 80.5% and 69.0%, respectively. Grade 3 acute toxicities occurred in 13% (anorexia=1; dyspnea=1; dysphagia=1; cough=1; esophagitis=2) and grade 2 in 45% (most commonly, fatigue=7). No grade 4 or 5 acute events occurred. Additionally, zero patients developed an esophageal fistula or stricture, or experienced esophageal necrosis. <h3>Conclusion</h3> In this multi-institutional cohort, proton reirradiation for locoregionally recurrent esophageal/GEJ cancers resulted in high rates of early local control with acceptable acute toxicities. Longer follow-up to assess for late adverse events and additional prospective investigations are warranted.