Radioimmunotherapy for peritoneal carcinomatosis: Preclinical proof of concept to clinical translation.

Abstract

Peritoneal carcinomatosis (PC), characterized by the dissemination of metastatic tumor cells throughout the peritoneal cavity from several gastrointestinal and gynecological malignancies, has significantly compromised patient survival. The standard of care is cytoreductive surgery with or without intraperitoneal chemotherapy. However, surgical resection often leaves behind microscopic or clinically occult disease due to the complex anatomy of the peritoneum, where intraperitoneal chemotherapy and systemic chemotherapy have shown limited success. To improve the therapeutic outcome, targeted therapy using radionuclides such as alpha, beta, and Auger emitters delivered by antibodies is actively being investigated. While preclinical murine models of PC have shown the potential of radioimmunotherapy (RIT) using various radioisotopes across a wide spectrum of antigen targets and tumor diagnoses with acceptable toxicities, successful clinical trials are lacking. Here, we retrospectively summarize preclinical and clinical PC studies, consider their translational potential, and examine paths to development that maximize the clinical benefit of RIT in this context.