Mutational signatures in appendiceal adenocarcinomas: potential for future personalization in hyperthermic intraperitoneal chemotherapy?

Abstract

Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) has become increasingly utilized in the treatment of appendiceal adenocarcinoma (AA) with peritoneal metastases. There are multiple intraperitoneal chemotherapeutic agents and protocols used at different centers, however there is little data available to guide clinicians on the optimal treatment strategy for individual patients. While it is often treated with paradigms extrapolated from colorectal cancer, AA has been shown to have a distinct mutational profile. Commonly mutated genes in AA such as KRAS and GNAS have been targeted by recently described systemic therapies for various tumors with positive results, suggesting that there may be a role for a patient-centered approach to HIPEC as well. Data specific to AA remains limited, however ongoing research into novel strategies such as next-generation sequencing of tumor samples and in vitro testing of patient-derived organoids for a variety of gastrointestinal cancers with peritoneal metastases has shown promise in personalizingHIPEC regimens.