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

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.