Abstract
PURPOSE: To evaluate the safety and efficacy of pencil beam scanning (PBS) proton radiation therapy (RT) in trimodality therapy for esophageal cancer. METHODS AND MATERIALS: This prospective pilot study was planned to accrue 30 patients with locally advanced esophageal or gastroesophageal junction carcinoma medically suitable for chemoradiation therapy (CRT) followed by esophagectomy. PBS proton RT consisted of 25 fractions, 50 Gy to tumor + 1 cm and 45 Gy to a 3.5 cm mucosal expansion and regional lymph nodes. Chemotherapy included weekly carboplatin (area under the curve, 2 mg/mL/min) and paclitaxel (50 mg/m(2)). At 4 to 8 weeks after CRT, patients underwent restaging and potential esophagectomy. The primary endpoint was acute grade 3+ adverse events (AEs) attributed to CRT. Overall survival and progression-free survival were assessed using the Kaplan-Meier methodology; local-regional recurrence and distant metastases rates were assessed using the cumulative incidence methodology. The Functional Assessment of Cancer Therapy-Esophagus assessed quality of life. RESULTS: Thirty eligible patients were enrolled from June 2015 to April 2017. Median age was 68 years. Histology was adenocarcinoma in 87%, and location was distal esophagus/gastroesophageal junction in 90%. Stage was T3 to T4 in 87% and N1 to N3 in 80%. All patients completed the planned RT dose. Acute grade 3+ AEs occurred in 30%, most commonly leukopenia and neutropenia. Acute grade 3+ nonhematologic AEs occurred in 3%. Esophagectomy was performed in 90% of patients (R0 in 93%). Pathologic complete response rate was 40%. Major postoperative complications (Clavien-Dindo score, ≥3) occurred in 34%. Postoperative mortality at 30 days was 3.7%. Median follow-up was 5.2 years. Five-year outcome estimates were overall survival at 46%, progression-free survival at 39%, local-regional recurrence at 17%, and distant metastases at 40%. Functional Assessment of Cancer Therapy-Esophagus scores (medians) at baseline, at the end of CRT, before esophagectomy, at 12 months, and at 24 months were 145, 136 (p = .0002 vs baseline), 144, 146 and 157, respectively. CONCLUSIONS: PBS proton RT is feasible and safe as a component of trimodality therapy for esophageal cancer.