Concurrent Chemo-Proton Therapy For Esophageal Cancer

Although concurrent use of chemotherapy in radiation therapy (RT) has improved treatment outcomes of esophageal cancer patients, but cardio-pulmonary dysfunction as late adverse effects of RT is still an issue of concern. Protons are known to have physical advantages in RT because they exhibit a spread-out Bragg peak and allow a desirable dose distribution for the target volume using limited numbers of portals. Protons are also suitable particles, unlike the carbon-ions, in concurrent chemo-radiation therapy (CCRT), because their relative biological effectiveness is similar to that of photon. The aim of the present study is to evaluate single institutional experience of concurrent chemo-proton therapy (CCPT) for esophageal cancer. Between November 2008 and May 2014, CCPT (cisplatin, 70mg/m2 day 1, and 5-fluorouracil (5-FU), 700 mg/m2on days 1-4, every 28 days, 2-4 cycles) had been performed for 67 esophageal cancer patients (57 men and 10 women). Their median age was 70 years, ranging from 36 to 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, they were stratified into stage I in 27, II in 16, III in 23, and IV in 1, respectively. A total dose of 60 gray equivalent (GyE) with a conventional fractional dose of 2 GyE was delivered, and an additional boost of 2 to 10 GyE was given when residual tumors were suspected by the endoscopy at 50 GyE. The median follow-up time of the present study was 32 months (range, 4-84 months). Based on diagnostic evaluation by endoscopy and chest CT at 1-2 month after CCPT, tumors regressed completely (n = 50) and partially (n = 15). Recurrences were observed at esophagus alone in 13, at mediastinal lymph node alone in 6, at both of the esophagus and mediastinal lymph node in 1, and at the distant organs in 6 patients. The three-year loco-regional control rate was 73%. Curative salvage treatments including surgery or endoscopic submucosal dissection were performed for 10 of 20 non-distant recurrences, and all but one developed no further recurrence. The 3-year overall survival rates of stage I, II, and III were 96%, 93%, and 38%, respectively (P<0.01). Esophageal stricture and ulcer developed in 1 and 4 patients, respectively, but an additional boost was not related with adverse effects at the esophagus. None of grade 3 late cardio-pulmonary toxicity was observed except in one patient (1.5%). CCPT for esophageal cancer would be a promising CCRT method to reduce the incidence of cardio-pulmonary toxicity and to give higher irradiation doses to the target safely.