A Feasibility Study of Mass-Based Response Drug Screening to Guide Personalized Hyperthermic Intraperitoneal Chemotherapy for Appendiceal and Colorectal Adenocarcinoma with Peritoneal Metastasis.

BACKGROUND

Current treatment of metastatic peritoneal surface malignancies (PSM) arising from colorectal cancer (CRC) and appendiceal cancer involves cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) [Elias (J Clin Oncol 28:63-68, 2010), McMullen (Oncotarget 8: 43481-43490, 2017), Lemoine (Int J Hyperthermia 33:582-592, 2017)]. There have been several intraperitoneal (IP) trials of appendix and colon cancer with conflicting results and insufficient evidence regarding both HIPEC efficacy and optimal HIPEC regimens [Quenet (Lancet Oncology 22:256-266, 2021), Arjona-Sánchez (JAMA Surgery 158:683, 2023), Verwaal (Ann Surg Oncol 12:65-71, 2004), Benzaquen (Can J Surg 64: E111-E118, 2021), Turaga (Ann Surg Oncol 21: 1501-1505, 2014), Nash (J Clin Oncol 41: 160, 2023)]. Given the heterogeneity of prior data and the variability in patient responses to different HIPEC regimens, further research is needed to optimize and personalize treatment.

METHODS

This is a single-center, phase II, open-label clinical trial evaluating the feasibility of performing mass-based response testing to identify and deliver personalized intraperitoneal chemotherapy regimens to patients with unresectable high-grade appendiceal or colorectal peritoneal metastases undergoing HIPEC. Per SOC, there are currently multiple chemotherapy combinations used for HIPEC [Lemoine (Int J Hyperthermia 33:582-592, 2017), Dubé (Curr Oncol 22:100-112, 2015), Valle (Indian J Surg Oncol 7:152-159, 2016)]. MRT analysis will identify which SOC regimen to use for HIPEC based on the patient's tumor susceptibility.

DISCUSSION

Mass-based response testing (MRT) is a novel screening tool that enables rapid and reliable assessment of tumor susceptibility to various HIPEC drugs. MRT generates a report of patient-specific intraperitoneal chemotherapy sensitivities by analyzing a portion of biopsy tissue collected from the patient's standard of care (SOC) diagnostic laparoscopy [Kimmerling (J Clin Oncol 41: 3132, 2024)]. With multiple HIPEC regimens currently used as the SOC for PSM from appendiceal and colorectal cancer, MRT facilitates the selection of personalized SOC regimens tailored to each patient.Results of this study will inform future clinical trials evaluating the efficacy of MRT-selected HIPEC regimens for patients with PM from appendiceal cancer and CRC.