Markov decision analysis of neoadjuvant treatment pathway versus surgery first pathway for resectable pancreatic cancer

Background: Surgery first (SF) versus neoadjuvant approach (NAT) to management of potentially resectable pancreatic ductal adenocarcinoma (PDAC) is controversial. This study is unique in utilizing institutional data to offer Markov decision-analysis of overall treatment pathways for resectable PDAC. Methods: An advanced Markov decision analysis model was constructed and populated with data from a retrospective institutional database. Patients presenting with resectable PDAC from 2008-2012 were included in the SF arm. Those presenting with resectable PDAC from 2012-2016 and treated within NAT pathway populated the NAT arm. Model uncertainties were tested with one and two-way deterministic sensitivity analysis and probabilistic Monte Carlo sensitivity analysis set to 1000 cycles with variables altered between highest and lowest observed values. Results: NAT pathway gave an additional 0.58 QALMs (22.43 vs. 21.85 QALMs). Monte Carlo analysis reported indifference between treatment strategies. One-way deterministic sensitivity analysis showed that probability of resection in the SF pathway must be greater than 0.82, or below 0.72 in NAT pathway, and probability of receiving adjuvant therapy above 0.6 to alter pathway superiority. Two-way deterministic sensitivity analysis demonstrated treatment superiority depended on resection rate in each pathway and receiving adjuvant therapy in SF pathway. Markov cohort analysis demonstrated superiority of neoadjuvant pathway (Table). Conclusions: Optimal treatment pathway remains debatable on an intention-to-treat Markov decision analysis. Markov cohort analysis of treatment received demonstrated benefit with NAT pathway

The role of induction chemotherapy + chemoradiotherapy in localised pancreatic cancer: initial experience in Scotland

Background: Despite being relatively rare pancreatic cancer is one of the highest causes of death. Even within the potentially resectable group outcomes are poor. We present our initial experiences utilising a neoadjuvant approach to localised pancreatic cancer, evaluating survival, response rates and tolerability. Methods: This was a retrospective analysis of a prospectively maintained database. Patients from 2012 to 2015 referred to a busy regional Hepato-Pancreatic Biliary (HPB) MDT were included. Patients were classified according to respectability criteria (utilising NCCN guidelines) and a treatment plan agreed. Systemic therapy with either FOLFIRINOX or Gem/Cap was delivered followed by chemoradiotherapy if disease remained localised. Toxicity, response, pathological outcomes and survival were all recorded. Results: A total of 85 patients were included in the study: 45 had initially resectable disease; 19 required a response for resection and 21 had locally advanced inoperable disease; 34 patients underwent resection. The median survival for the potentially resectable group was 22.2 months while for those undergoing resection it was 37 months. Conclusions: We have demonstrated that a neoadjuvant approach is deliverable and tolerable. In addition we have demonstrated impressive survival results in patients undergoing resection with no detriment in outcome for those not proceeding to surgery

The role of induction chemotherapy + chemoradiotherapy in localised pancreatic cancer: initial experience in Scotland

Background: Despite being relatively rare pancreatic cancer is one of the highest causes of death. Even within the potentially resectable group outcomes are poor. We present our initial experiences utilising a neoadjuvant approach to localised pancreatic cancer, evaluating survival, response rates and tolerability. Methods: This was a retrospective analysis of a prospectively maintained database. Patients from 2012 to 2015 referred to a busy regional Hepato-Pancreatic Biliary (HPB) MDT were included. Patients were classified according to respectability criteria (utilising NCCN guidelines) and a treatment plan agreed. Systemic therapy with either FOLFIRINOX or Gem/Cap was delivered followed by chemoradiotherapy if disease remained localised. Toxicity, response, pathological outcomes and survival were all recorded. Results: A total of 85 patients were included in the study: 45 had initially resectable disease; 19 required a response for resection and 21 had locally advanced inoperable disease; 34 patients underwent resection. The median survival for the potentially resectable group was 22.2 months while for those undergoing resection it was 37 months. Conclusions: We have demonstrated that a neoadjuvant approach is deliverable and tolerable. In addition we have demonstrated impressive survival results in patients undergoing resection with no detriment in outcome for those not proceeding to surgery

Feasibility and clinical utility of endoscopic ultrasound guided biopsy of pancreatic cancer for next-generation molecular profiling.

Next-generation sequencing is enabling molecularly guided therapy for many cancer types, yet failure rates remain relatively high in pancreatic cancer (PC). The aim of this study is to investigate the feasibility of genomic profiling using endoscopic ultrasound (EUS) biopsy samples to facilitate personalised therapy for PC. Ninty-five patients underwent additional research biopsies at the time of diagnostic EUS. Diagnostic formalin-fixed (FFPE) and fresh frozen EUS samples underwent DNA extraction, quantification and targeted gene sequencing. Whole genome (WGS) and RNA sequencing was performed as proof of concept. Only 2 patients (2%) with a diagnosis of PC had insufficient material for targeted sequencing in both FFPE and frozen specimens. Targeted panel sequencing (n=54) revealed mutations in PC genes (KRAS, GNAS, TP53, CDKN2A, SMAD4) in patients with histological evidence of PC, including potentially actionable mutations (BRCA1, BRCA2, ATM, BRAF). WGS (n=5) of EUS samples revealed mutational signatures that are potential biomarkers of therapeutic responsiveness. RNA sequencing (n=35) segregated patients into clinically relevant molecular subtypes based on transcriptome. Integrated multi-omic analysis of PC using standard EUS guided biopsies offers clinical utility to guide personalized therapy and study the molecular pathology in all patients with PC

'Step-port' laparoscopic cystgastrostomy for the management of organized solid predominant post-acute fluid collections after severe acute pancreatitis

Background: Post-acute pancreatic collections (PAPCs) may require intervention when persistent, large or symptomatic. An open cystgastrostomy is an effective treatment option particularly for larger, solid predominant collections. A laparoscopic cystgastrostomy (LCG) as initially described, could be technically challenging. This report describes the evolution of the operative technique and the results from LCG in a tertiary referral centre.<p></p> Methods: Retrospective analysis of the unit's prospectively populated database was conducted. All patients who underwent a surgical cystgastrostomy (SCG) were identified. Patient demographics, outcome and complications were collected and analysed.<p></p> Results: Forty-four patients underwent SCG: 8 open and 36 laparoscopic. Of the 36 LCG, 6 required open conversion, although with evolution of the technique all of the last 17 cases were completed laparoscopically. The median interquartile range (IQR) length of stay in patients completed laparoscopically was 6 (2–10) compared with 15.5 days (8–19) in those patients who were converted (P = 0.0351). The only peri-operative complication after a LCG was a self-limiting upper gastrointestinal bleed. With a median (IQR) follow-up of 891 days (527–1495) one patient required re-intervention for a residual collection with no recurrent collections identified.<p></p> Conclusion: LCG is a safe and effective procedure in patients with large, solid predominant PAPCs. With increased experience and technical expertise conversion rates can be lowered and outcome optimized