Thilo Hackert

This statement was developed to promote international consensus on the definition of borderline resectable pancreatic ductal adenocarcinoma (BR-PDAC) which was adopted by the National Comprehensive Cancer Network (NCCN) in 2006, but which has changed yearly and become more complicated. Based on a symposium held during the 20th meeting of the International Association of Pancreatology (IAP) in Sendai, Japan, in 2016, the presenters sought consensus on issues related to BR-PDAC. We defined patients with BR-PDAC according to the three distinct dimensions: anatomical (A), biological (B), and conditional (C). Anatomic factors include tumor contact with the superior mesenteric artery and/or celiac artery of less than 180° without showing stenosis or deformity, tumor contact with the common hepatic artery without showing tumor contact with the proper hepatic artery and/or celiac artery, and tumor contact with the superior mesenteric vein and/or portal vein including bilateral narrowing or occlusion without extending beyond the inferior border of the duodenum. Biological factors include potentially resectable disease based on anatomic criteria but with clinical findings suspicious for (but unproven) distant metastases or regional lymph nodes metastases diagnosed by biopsy or positron emission tomography-computed tomography. This also includes a serum carbohydrate antigen (CA) 19-9 level more than 500 units/ml. Conditional factors include the patients with potentially resectable disease based on anatomic and biologic criteria and with Eastern Cooperative Oncology Group (ECOG) performance status of 2 or more. The definition of BR-PDAC requires one or more positive dimensions (e.g. A, B, C, AB, AC, BC or ABC). The present definition acknowledges that resectability is not just about the anatomic relationship between the tumor and vessels, but that biological and conditional dimensions are also important. The aim in presenting this consensus definition is also to highlight issues which remain controversial and require further research.

OBJECTIVE: For patients with locally advanced and unresectable pancreatic cancer (PDAC), neodadjuvant treatment and consecutive surgical exploration have been studied during the last decade with various neoadjuvant therapies including chemotherapy and combinations with radiation. Aim of the study was the evaluation of neoadjuvant therapy with a focus on Folfirinox. METHODS: All consecutive patients undergoing surgery for PDAC after neoadjuvant treatment were analyzed (clinico-pathological characteristics, secondary resection rates, outcome). Patients receiving Folfirinox were compared with other treatment regimens. RESULTS: Between December 2001 and June 2015, 575 patients received neoadjuvant treatment and were scheduled for resection after re-staging. A successful resection was achieved in 292 patients (50.8%). Resection rates following Folfirinox were 61% (76/125 patients) compared with 46% (150/322 patients) after gemcitabine and radiation, and 52% (66/128 patients) after other treatments (P = 0.026). Median overall survival was 15.3 months after resection vs 8.5 months after exploration alone (P < 0.0001). Subgroup median survival was 16.0 months (Folfirinox) vs 16.5 months (gemcitabine) and 14.5 months (others) with 3-year survival of 28.1%, 23.2%, and 19.7%, respectively (P = 0.8582). By multivariable analysis, Folfirinox was confirmed to be independently associated with a favorable prognosis. CONCLUSIONS: Folfirinox is a valuable treatment option in the neoadjuvant therapy of PDAC. From the present data, which represent the largest available study population to date, Folfirinox seems to be the most effective protocol resulting in a significantly better secondary resection rate and overall survival than other treatments. It should be considered in all patients fit for this regimen and consecutive surgical exploration.