A Phase II Trial of Escalated Dose Proton Radiotherapy With Elective Nodal Irradiation and Concomitant Chemotherapy for Patients with Unresectable, Borderline Resectable or Medically Inoperable Pancreatic Adenocarcinoma

Abstract

To report outcomes of a phase II single-institution trial of escalated dose proton therapy with elective nodal irradiation and concomitant chemotherapy for patients with unresectable, borderline resectable, or medically inoperable pancreatic adenocarcinoma.Patients were treated to 40.5 GyE in 18 fractions to gross disease and elective nodal volumes with a 22.5 GyE in a 10-fraction boost to gross disease, for a total of 63 GyE. Oral capecitabine (1000mg orally twice a day) was given on radiation treatment days. The primary objective of this study was to achieve a 1-year overall survival rate of 75%. Secondary objectives included assessing gastrointestinal toxicity and patient quality of life during treatment, as well as evaluating the safety of subsequent surgical resection. The single-institution study was closed to accrual once opened as the multicenter PAN009-18 trial by the Proton Collaborative Group.At enrollment, 10 (67%) of patients were unresectable, 3 (20%) were borderline, and 2 (13%) refused surgery. Thirteen patients (87%) had previously received chemotherapy. All 15 patients successfully completed radiation therapy as prescribed. With regard to toxicity, a single patient experienced grade 3 nausea requiring cessation of capecitabine, which ultimately resolved at treatment completion. All other patients received concurrent capecitabine for the duration of their radiotherapy treatment. Radiation did not result in any other significant gastrointestinal toxicity during or after treatment. Median percentage weight loss during treatment was -3.0% (-9.6% - +12.0%). Two (13%) initially borderline patients ultimately underwent resection. Their total operating room times were 267 and 410 minutes; blood loss was 700mL and 400mL. Neither patient experienced intraoperative or postoperative complications. Both patients were discharged on postoperative day six. Median follow-up was 0.93 years (0.21-2.14). The 1-year overall survival rate was 47%. Three enrolled patients are currently alive: 2 with no evidence of disease and 1 with stable disease. One patient died of intercurrent disease. Of the remaining 11 patients who died following tumor recurrence, only 3 failed locally, with the remaining 8 failing distantly.Protocol therapy was well-tolerated. Patients undergoing surgery did not experience operative or perioperative complications - suggesting that patients with borderline resectable or even resectable disease may benefit from this regimen as neoadjuvant therapy. The Proton Collaborative Group will test this premise as patients accrue to the multicenter PAN009-18 trial.