Investigating the utility of extended mutation analysis in gastrointestinal peritoneal metastasis

Jason M. Foster, Asish Patel, Chunmeng Zhang, Valerie Shostrom, Krista Brown, Allison Cushman-Volkoun

Research output: Contribution to journalArticle

Abstract

Background and Objectives: Outcomes for gastrointestinal peritoneal metastases (GI-PM) are worse compared to systemic metastases, with a paucity of data exploring extended mutation profiling. An exploratory mutation analysis in GI-PMs was performed as a “proof of concept” of potential predictive values of profiling in GI-PM and rates of actionable mutations. Methods: The study included 40 GI-PM patients: 14 low-grade mucinous carcinoma peritonei and 26 HG-PM (12 colons, 10 appendix, 4 small bowels). Demographics, histologies, peritoneal cancer indexes, cytoreduction scores, and survival data were collected. NGS 50-gene mutation profiling was performed on 38 specimens. The association of mutations with survival was evaluated in high-grade PM. Results: KRAS, TP53, and SMAD4 mutations were observed in 61%, 29%, and 8% of cases across all tumor histologies. In 66% cases >1 mutations occurred, associated with decreased survival in HG-PM: 32 vs 73 months, P =.03. TP53 or SMAD4 mutations were associated with decreased survival in HG-PM: 22 vs 48 months, P =.02. Actionable mutations were detected in 70%. Conclusion: Actionable mutations were detected at high rates. GI-PMs have similar mutational profiles and TP53, SMAD4, and/or >1 mutation were associate with decreased survival in HG-PM. This data supports the concept of the extended mutation profiling utility in GI-PM warranting further investigation.

Original languageEnglish (US)
JournalJournal of Surgical Oncology
DOIs
StateAccepted/In press - 2020

Keywords

  • HIPEC
  • carcinomatosis
  • mutations
  • peritoneal metastasis
  • survival

ASJC Scopus subject areas

  • Surgery
  • Oncology

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