AR1 - Expanded Mutation Profiling in Appendix Peritoneal Metastasis Has Prognostic and Therapeutic Utility When Managed with Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy

INTRODUCTION Identification of biological pathways and mutations is integral to improving outcomes in appendix peritoneal metastases (APM) Interrogation with NGS mutation panels has become more widely utilized identifying prognostic and actionable mutations. This is a dedicated analysis of the value of expanded mutation analysis in APM. METHODS IRB approved study, 50 APM patients where data was retrospectively collected from a prospective registry. Standard 50-gene NGS analysis was performed in CLIA approved lab. All underwent CRS/HIPEC with mitomycin C delivered for 90 minutes at 41-42 C. PCI, CC-score, length of stay (LOS), PFS, OS was collected along with the rates and types of mutation in APM. OS and PFS analysis was performed on all, high grade (HG), and low grade (LG) APM, evaluating the impact of smad4 and p53 mutations on survival. RESULTS Eighty-two percent of APM had a mutation identified, 52% had ≥2 mutations. Kras was most frequent, 75% (90% LG 40% HG) and GNAS identified in 90% of LG APM. Smad4 or p53 mutation occurred in 21% of APM and a significant reduction in OS in all APM (55 vs 88 months p=0.045) and HG APM (20 vs 50 months p=0.049) was observed. Smad4 mutation was associated with reduced PFS (3.5 vs 11 months p=0.017). CONCLUSIONS Smad4 and p53 mutation were associated with more aggressive APM and maybe useful in patient selection and outcome. Extended mutation profiles is valuable in APM and further investigation is warranted. Kras, p53 and smad4 pathways research and drug development will benefit APM.