Harnessing the Hippocratic Fire: The Role and Comprehensive Consolidation of HITHOC in Pleural Malignancy Management

Abstract

Hyperthermic intrathoracic chemotherapy (HITHOC) has emerged as a significant multimodal therapeutic adjunct for the management of aggressive pleural malignancies, primarily malignant pleural mesothelioma and stage IVA thymoma. By combining surgical cytoreduction with the local administration of heated chemotherapeutic agents, HITHOC aims to eliminate microscopic residual disease while minimizing systemic toxicity. A comprehensive Boolean search was conducted using PubMed/Medline, Google Scholar, Embase and Scopus to identify relevant studies on the use of HITHOC for pleural malignancies. Findings were summarised regarding HITHOC’s biological rationale, applications, integration with surgery and methodological challenges. While large retrospective analyses suggest meaningful improvements in overall survival and locoregional control, the technique is currently characterized by a high degree of protocol heterogeneity across global centers. This review synthesizes current evidence on the biological rationale, clinical outcomes across various histologies, safety profiles, and the methodological barriers that must be addressed for the formal consolidation of HITHOC into international treatment guidelines.