Neoadjuvant therapy and major arterial resection for potentially reconstructable arterial involvement by stage 3 adenocarcinoma of the pancreas.

BACKGROUND: Stage 3 pancreatic ductal adenocarcinoma (PDAC) is defined by arterial involvement. This study objective was to evaluate outcomes for patients with stage 3 PDAC with potentially reconstructable arterial involvement, considered for neoadjuvant therapy (NAT) and pancreatic resection, and to compare outcomes following arterial (AR) and non-arterial resection (NAR). METHODS: This study included patients from 2009 to 2016 with biopsy-proven stage 3 PDAC who were offered NAT before surgical exploration. AR was performed if required to achieve R0 resection. Time to event outcomes were analysed from diagnosis date. RESULTS: 87/89 patients (97.8%) received NAT (chemotherapy 41.6%, chemotherapy/radiotherapy 56.2%). 46/89 (51.7%) underwent exploration; 31 underwent resection (AR n = 20, NAR n = 11). AR patients had longer operative time (681 vs. 563 min, p = 0.006) and more blood loss (1600 vs. 575 mL, p = 0.0004), with no difference for blood transfusion, pancreatic fistula, length of stay, reoperation, or mortality. R0 rate was 30/31. Post-resection 90-day mortality was 3.2%. Median overall survival was statistically comparable between the AR and NAR groups (19.7 vs. 28.4 months, p = 0.41). CONCLUSIONS: AR had comparable clinical and oncologic outcomes to NAR. Following careful selection and non-progression after NAT, major AR may cautiously be considered if required to obtain a negative resection margin.

Genomics-Driven Precision Medicine for Advanced Pancreatic Cancer: Early Results from the COMPASS Trial.

Purpose: To perform real-time whole genome sequencing (WGS) and RNA sequencing (RNASeq) of advanced pancreatic ductal adenocarcinoma (PDAC) to identify predictive mutational and transcriptional features for better treatment selection.Experimental Design: Patients with advanced PDAC were prospectively recruited prior to first-line combination chemotherapy. Fresh tumor tissue was acquired by image-guided percutaneous core biopsy for WGS and RNASeq. Laser capture microdissection was performed for all cases. Primary endpoint was feasibility to report WGS results prior to first disease assessment CT scan at 8 weeks. The main secondary endpoint was discovery of patient subsets with predictive mutational and transcriptional signatures.Results: Sixty-three patients underwent a tumor biopsy between December 2015 and June 2017. WGS and RNASeq were successful in 62 (98%) and 60 (95%), respectively. Genomic results were reported at a median of 35 days (range, 19-52 days) from biopsy, meeting the primary feasibility endpoint. Objective responses to first-line chemotherapy were significantly better in patients with the classical PDAC RNA subtype compared with those with the basal-like subtype (P = 0.004). The best progression-free survival was observed in those with classical subtype treated with m-FOLFIRINOX. GATA6 expression in tumor measured by RNA in situ hybridization was found to be a robust surrogate biomarker for differentiating classical and basal-like PDAC subtypes. Potentially actionable genetic alterations were found in 30% of patients.Conclusions: Prospective genomic profiling of advanced PDAC is feasible, and our early data indicate that chemotherapy response differs among patients with different genomic/transcriptomic subtypes. Clin Cancer Res; 24(6); 1344-54. ©2017 AACR.