Long-Term Follow-Up Results Of Concurrent Chemo-Proton Therapy For Esophageal Cancer

Protons are known to have physical advantages in radiation therapy (RT) for deep-seated tumors because of spread-out Bragg peak making a desirable dose distribution for the target volume. Although treatment outcomes of RT for esophageal cancer had been improved using concurrent chemotherapy and 3-dimensional conformal RT technique, cardio-pulmonary dysfunction as late adverse effects of RT worsen the patients’ quality of life. The purpose of the present study is to retrospectively evaluate update results of concurrent chemo-proton therapy (CCPT) for esophageal cancer. Sixty-seven esophageal cancer patients (men: 57, women: 10) had received proton therapy concurrently combined with chemotherapy (cisplatin, 70mg/m2 day 1, and 5-fluorouracil (5-FU), 700 mg/m2 on days 1-4, every 28 days, 2-4 cycles) between November 2008 and June 2014. Their median age was 70 years (range, 36-83 years), and the tumors were located at cervical, the upper thoracic, middle thoracic, lower thoracic, and abdominal esophagus in 2, 17, 30, 14, and 4 patients, respectively. According to the UICC TNM classification (7th edition), their clinical stage were classified into stage I in 27, II in 16, III in 23, and IV in 1, respectively. Forty-five (67%) patients denied receiving surgery but 22 (33%) patients were inoperable mainly due to their co-existing diseases. A total dose of 60 gray equivalent (GyE) in 30 fractions with a conventional fractionation was delivered, and an additional boost of 2 to 10 GyE was given when residual tumors were suspected by examination under endoscopy at 50 GyE. The median follow-up time of the study was 49 months (range, 6-105 months). For evaluation of initial treatment responses based on endoscopy and chest CT at 1-2 month after CCPT, tumors regressed completely (n=50) and partially (n=15) but 2 tumors were judged as progressive diseases. Recurrences were observed at esophagus alone in 14, including 3 recurrences outside RT field, at mediastinal lymph node alone in 6, at both of the esophagus and mediastinal lymph node in 1, and at the distant organs in 7 patients. The three-year loco-regional control rate was 73%. Salvage treatments including surgery or endoscopic submucosal dissection were curatively performed for 12 of 21 patients with non-distant recurrences, and 9 patients developed no further recurrence. The 4-year overall survival rates of stage I, II, and III were 96%, 73%, and 40%, respectively (p<0.01). Esophageal stricture and ulcer developed in 1 and 4 patients, respectively, but an additional boost was unrelated with adverse effects at the esophagus. None of grade 3 late cardiopulmonary toxicity was observed except in one patient who had dialysis because of renal dysfunction observed before CCPT. Proton therapy would be a promising RT modality to reduce the incidence of cardio-pulmonary toxicity after CCRT for esophageal cancer.