Abstract
Simple SummaryEfficacy of cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) depends on patient selection, tumor type, delivery technique, and treatment parameters such as temperature, carrier solution, type of drug, dosage, volume, and treatment duration. Preclinical research offers a powerful tool to investigate the impact of these parameters and to assists in designing potentially more effective treatment protocols and clinical trials. This study aims to review the objectives, methods, and clinical relevance of in vivo preclinical HIPEC studies found in the literature. In total, 60 articles were included in this study. The selected articles were screened on the HIPEC parameters. Recommendations are provided and possible pitfalls are discussed on the choice of type of animal and tumor model per stratified parameters and study goal. The guidelines presented in this paper can improve the clinical relevance and impact of future in vivo HIPEC experiments.Hyperthermic intraperitoneal chemotherapy (HIPEC) is a treatment modality for patients with peritoneal metastasis (PM) of various origins which aims for cure in combination with cytoreductive surgery (CRS). Efficacy of CRS-HIPEC depends on patient selection, tumor type, delivery technique, and treatment parameters such as temperature, carrier solution, type of drug, dosage, volume, and treatment duration. Preclinical research offers a powerful tool to investigate the impact of these parameters and to assist in designing potentially more effective treatment protocols and clinical trials. The different methodologies for peritoneal disease and HIPEC are variable. This study aims to review the objectives, methods, and clinical relevance of in vivo preclinical HIPEC studies found in the literature. In this review, recommendations are provided and possible pitfalls are discussed on the choice of type of animal and tumor model per stratified parameters and study goal. The guidelines presented in this paper can improve the clinical relevance and impact of future in vivo HIPEC experiments.
Highlights
Metastatic lesions in the peritoneum are commonly originating from primary malignancies such as ovarian, colorectal, appendiceal, and gastric cancer [1]
Others argued that the treatment parameters used during the PRODIGE-7 trial were not adequately chosen and that the results cannot be regarded as representative of hyperthermic intraperitoneal chemotherapy (HIPEC) in general [8,9,10]
This review provides an overview of in vivo HIPEC methods in animal models and their clinical relevance
Summary
Metastatic lesions in the peritoneum are commonly originating from primary malignancies such as ovarian, colorectal, appendiceal, and gastric cancer [1]. The recently randomized trial performed by van Driel et al showed a median overall survival of 45.7 months for ovarian cancer patients with peritoneal metastasis (PM) treated with CRS and cisplatin-based HIPEC, which was significantly higher than the median 33.9 months for CRS alone [5]. The trial showed no survival benefit and increased morbidity in the CRS plus HIPEC arm, compared to CRS alone This opened up the debate on the benefit of HIPEC, for patients with PM from colorectal origin. In a recent review by Auer et al, evidence-based indications were investigated for the application of HIPEC and CRS for patients diagnosed with mesothelioma, appendiceal, colorectal, gastric ovarian, and primary peritoneal carcinoma. This clinical evidence is vital for successful application of HIPEC and these study protocols should be designed to be able to provide solid recommendations on optimal treatment
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