Article Text
Abstract
Background Peritoneal metastasis from pancreatic cancer (PM-PC) may be treated with repeated pressurised intraperitoneal aerosol chemotherapy (PIPAC). Utility of next-generation sequencing (NGS) to detect cancer-related mutations in peritoneal quadrant biopsies (QBs) and peritoneal fluid (PF) after systemic and PIPAC treatment has not been evaluated. Around 90% of pancreatic cancers (PCs) harbour a KRAS mutation, making PC ideal for the evaluation of this aspect.
Aims Evaluation of PM-PC in terms of (1) histological response to PIPAC using Peritoneal Regression Grading Score (PRGS), (2) clinical characteristics and (3) frequency of mutations in QBs and PF before and after PIPAC.
Methods Peritoneal QBs and PF were obtained prior to each PIPAC. NGS for 22 cancer-related genes was performed on primary tumours, QBs and PFs. Response was assessed by the four-tiered PRGS.
Results Sixteen patients treated with a median of three PIPAC procedures were included. The mean PRGS was reduced from 1.91 to 1.58 (p=0.02). Fifty-seven specimens (13 primary tumours, 2 metastatic lymph nodes, 16 PFs and 26 QB sets) were analysed with NGS. KRAS mutation was found in 14/16 patients (87.50%) and in QBs, primary tumours and PF in 8/12 (66.67%), 8/13 (61.53%) and 6/9 (66.67%). The median overall survival was 9.9 months (SE 1.5, 95% CI 4.9 to 13.9).
Conclusion PIPAC induces histological response in the majority of patients with PM-PC. KRAS mutation can be found in PM-PC after PIPAC at a frequency similar to the primaries. NGS may be used to detect predictive mutations in PM-PC of various origins, also when only post-PIPAC QBs or PFs are available.
- pancreatic neoplasms
- pancreas
- peritoneum
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Footnotes
Handling editor Runjan Chetty.
Contributors The study was designed by SDE and MBM. All authors contributed to the data collection and data analysis, discussed the results, and commented on and approved the final manuscript. MN and SD prepared the manuscript draft. SD was the main supervisor.
Funding This study was supported by funding from Odense Pancreas Center.
Competing interests None declared.
Patient consent for publication Not required.
Ethics approval The study was conducted according to the Helsinki Declaration and approved by The Regional Committees on Health Research Ethics for Southern Denmark (project-ID S-20180185) and the Danish Data Protection Agency (project-ID 19/10354).
Provenance and peer review Not commissioned; internally peer reviewed.
Data availability statement Data are available upon reasonable request. Participant data will be retained at the study facility for five years after completion of the trial according to Danish law. After this time period, it will be de-identified and made available for other researchers upon reasonable request to the corresponding author.