The Role of Hyperthermia in the Treatment of Peritoneal Surface Malignancies

Guerra-Londono, Carlos E.; Tarazona, Carlos G.; Sánchez-Monroy, J. A.; Heppell, Olivia; Guerra-Londono, Juan Jose; Shah, Rupen

doi:10.1007/s11912-022-01275-3

Cited by 6 publications

(1 citation statement)

References 87 publications

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“…In line with data from the literature, where there is a clear global consensus on the adoption of hyperthermia during intraperitoneal chemotherapy [ 32 , 33 ], we have shown this treatment is most effective when performed under hyperthermic conditions (intra-abdominal operative temperature of 42.5 °C). Chemotherapy combined with hyperthermia has been proposed to eliminate microscopic disease, thus improving the outcome of CRCPM patients [ 34 ], with the added benefit of a direct cytotoxic effect on tumor cells [ 35 ].…”

Section: Discussionsupporting

confidence: 87%

Colorectal carcinoma peritoneal metastases-derived organoids: results and perspective of a model for tailoring hyperthermic intraperitoneal chemotherapy from bench-to-bedside

Varinelli,

Battistessa,

Guaglio

et al. 2024

J Exp Clin Cancer Res

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Background Peritoneal metastases from colorectal cancer (CRCPM) are related to poor prognosis. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been reported to improve survival, but peritoneal recurrence rates are still high and there is no consensus on the drug of choice for HIPEC. The aim of this study was to use patient derived organoids (PDO) to build a relevant CRCPM model to improve HIPEC efficacy in a comprehensive bench-to-bedside strategy. Methods Oxaliplatin (L-OHP), cisplatin (CDDP), mitomycin-c (MMC) and doxorubicin (DOX) were used to mimic HIPEC on twelve PDO lines derived from twelve CRCPM patients, using clinically relevant concentrations. After chemotherapeutic interventions, cell viability was assessed with a luminescent assay, and the obtained dose–response curves were used to determine the half-maximal inhibitory concentrations. Also, induction of apoptosis by different HIPEC interventions on PDOs was studied by evaluating CASPASE3 cleavage. Results Response to drug treatments varied considerably among PDOs. The two schemes with better response at clinically relevant concentrations included MMC alone or combined with CDDP. L-OHP showed relative efficacy only when administered at low concentrations over a long perfusion period. PDOs showed that the short course/high dose L-OHP scheme did not appear to be an effective choice for HIPEC in CRCPM. HIPEC administered under hyperthermia conditions enhanced the effect of chemotherapy drugs against cancer cells, affecting PDO viability and apoptosis. Finally, PDO co-cultured with cancer-associated fibroblast impacted HIPEC treatments by increasing PDO viability and reducing CASPASES activity. Conclusions Our study suggests that PDOs could be a reliable in vitro model to evaluate HIPEC schemes at individual-patient level and to develop more effective treatment strategies for CRCPM.

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