Histopathological response to preoperative chemoradiation for resectable pancreatic adenocarcinoma: The French Phase II FFCD 9704-SFRO trial

Purpose: This study suggests that pancreatic adenocarcinoma is a chemoradiosensitive tumor and that preoperative chemoradiation provides antitumoral effect associated with major histopathological response in 50% of patients and a high R0 resection rate. Evaluation of histopathological response to neoadjuvant therapy may serve as a surrogate marker for treatment efficacy and remains an active area of investigation. Objectives: The chemoradiosensitivity of pancreatic adenocarcinoma has not yet fully been assessed. The purpose of this study is to determine the efficacy of preoperative chemoradiation, measured by the impact on the R0 resection rate and the histopathological response rate in patients presenting with resectable pancreatic adenocarcinoma. Methods: Patients with localized, potentially resectable pancreatic adenocarcinoma were treated with 50 Gy irradiation combined with 5-fluorouracil by continuous infusion (300 mg·m ^-2·d^-1; day 1-5; week 1-5) and cisplatin (20 mg·m^-2·d^-1; day 1-5 and day 29-33). Patients presenting with resectable disease at restaging, without metastatic dissemination, underwent surgical resection. Results: Forty-one patients were enrolled. Twenty-seven patients (67.5%) completed chemoradiation receiving at least 75% prescribed chemotherapy dose without grade 4 nonhematological toxicity. Twenty-six patients (63%) underwent surgical resection with curative intent and 21 (80.7%) had R0 resection. Thirteen of 26 specimens (50%) presented a major pathologic response with more than 80% of severely degenerative cancer cells. Complete pathologic response was observed in one specimen. Median survival time and 2-year survival rate were 9.4 months and 20% for the entire cohort. The local recurrence and 2-year survival rates were 4% and 32%, respectively, for the 26 operated patients. Conclusions: This study suggests that some pancreatic adenocarcinomas are chemoradiosensitive and that preoperative chemoradiation provides antitumoral effect associated with major histopathological response in 50% of patients and a high R0 resection rate. Further research is needed to determine the biologic difference between responders and nonresponders, to evaluate the predictive value of treatment response parameters, and to optimize the chemoradiation regimen.