Concurrent Chemoradiation Therapy Using Proton Beams for Esophageal Cancer

Abstract

Concurrent chemoradiation therapy (CCRT) has yielded significantly better outcomes of patients with esophageal cancer than radiation therapy (RT) alone, but high occurrence rates of cardio-pulmonary dysfunction after CCRT for esophageal cancer mainly due to the large irradiated volumes of the lung and heart. Proton beam therapy (PBT) is thought to be a promising RT method because it can decrease the irradiated volumes of those organs. The aim of the present study is to evaluate outcomes of PBT combined with concurrent chemotherapy for patients with esophageal cancer. Between November 2008 and November 2013, 56 esophageal cancer patients were treated with definitive PBT concurrently combined with chemotherapy (cisplatin, 70mg/m2 day 1, and 5-fluorouracil (5-FU), 700 mg/m2/24 h on days 1-4, every 28 days, 2-4 cycles) The subjects in the present study consisted of 49 men and 7 women and their median age was 70 years, ranging from 36 to 83 years. The tumors were located at cervical, the upper thoracic, middle thoracic, lower thoracic, and abdominal esophagus in 2, 16, 26, 10, and 2 subjects, respectively and were stratified into stage I in 21, II in 13, III in 21, and IVA in 4, respectively. A total dose of 60 gray equivalent (GyE) with a conventional fractionation was delivered with conformal PBT, but an additional boost of 2 to 10 GyE was given for 33 patients because residual tumors were suspected based on the endoscopic examination at 50 GyE. The median follow-up time for the subjects was 21 months (range, 4-72 months). PBT was successfully completed for all subjects. Based on diagnostic evaluation by endoscopy and chest CT at 1-2 month after completion of PBT, all tumors except two showed definite reduction in the overall sizes and 40 (71%) tumors regressed completely. Recurrences were observed in 22 (39%) subjects; 11 at the esophagus alone, 5 at mediastinal lymph node alone, 1 at both of the esophagus and mediastinal lymph node, and 5 at the distant organs, and the 2-year local control rate was 75%. Salvage treatments including surgery or endoscopic submucosal dissection were successfully performed for 8 subjects as a curative intent and all but one had no further recurrence. The 2-year overall survival rate was 79%; 100% for stage I-II and 50% for stage III-IVA. Esophageal ulcer developed in 2 patients. No grade 3 late cardio-pulmonary toxicity in this study was observed at the current, but a small amount of pericardial effusion without any symptoms (grade 2) was observed in 6 (11%) patients. Irrespective of the small number of the subjects and short follow-up time in the present study, PBT with concurrent chemotherapy for esophageal cancer seems to be a promising CCRT method with special regard to the late cardio-pulmonary toxicity. Effectiveness of dose escalation and prophylactic nodal irradiation using PBT needs to be further investigated.