Exploring the prognostic and therapeutic utility of expanded mutation profiling in appendix peritoneal metastasis managed with CRS/HIPEC

Chunmeng Zhang, Benjamin D. Plambeck, Margaret E. Craig, Alexander Tu, Ryan J. Mikus, Valerie Shostrom, Sean P. McDermott, Ikponmwosa Igbinigie, Krista Brown, Allison Cushman-Vokoun, Jason M. Foster

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction: Interrogation of cancers with next-generation sequencing (NGS) mutation panels has become widely utilized, identifying prognostic and actionable mutations. This study explored the value of expanded mutation analysis in appendix peritoneal metastases (APM). Methods: Forty-eight APM patients treated 2013–2018 were retrospectively collected from a registry. Fifty-gene NGS analysis was performed in CLIA approved lab to obtain mutation profiles. All patients underwent cytoreductive surgery (CRS)/hyperthermic intraperitoneal chemotherapy (HIPEC) with mitomycin C. Peritoneal cancer index (PCI), optimal CRS, survival (overall survival [OS] and progression-free survival [PFS]) data were collected. Survival analyses were performed on all APM, high-grade (HG), and low grade (LG) subsets, evaluating the impact of specific mutations on the outcome. Results: Eighty-three percent of APM had a mutation identified. KRAS was most frequent, 65% (88% LG 42% HG) with GNAS identified in 92% of LG-APM. SMAD4 and/or TP53 mutations occurred in 25% of APM with observed decreased OS (46 vs. 81 months p =.0029); worse in HG-APM (26 vs. 49 months p =.0451). SMAD4 was associated with the most significant reduction in PFS in APM (p =.0085). Actionable mutations were identified in 73% of APM patients. Conclusions: Most frequent mutations were KRAS, TP53, and SMAD4, and actionable mutation detection was common. SMAD4 and TP53 were associated with decreased OS. NGS mutation profiling has potential utility in APM.

Original languageEnglish (US)
Pages (from-to)1599-1609
Number of pages11
JournalJournal of Surgical Oncology
Volume123
Issue number7
DOIs
StatePublished - Jun 2021

Keywords

  • HIPEC
  • appendix
  • carcinomatosis
  • mutations
  • peritoneal metastasis
  • survival

ASJC Scopus subject areas

  • Surgery
  • Oncology

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