Establishment of a new valid animal model for the evaluation of hyperthermic intraperitoneal chemotherapy (HIPEC) in pediatric rhabdomyosarcoma

Background Cytoreductive surgery in combination with hyperthermic intraperitoneal chemotherapy has been established as a novel treatment approach for peritoneal sarcomatosis. Despite promising clinical reports, there is still a lack of knowledge regarding optimal drug usage and local effects. Therefore, we intended to establish a murine animal model for further evaluation. Procedure Alveolar rhabdomyosarcoma cells were xenotransplanted into NOD/LtSz-scid IL2R gamma nullmice (n = 100). The mice received a continuous intraperitoneal lavage with isotonic saline solution as control or with cisplatin (30 or 60 mg/m(2)) as treatment group for 60 minutes at 37 degrees C or 42 degrees C (6 subgroups, each n = 16). Tumor spread was documented by an adapted peritoneal cancer index and MRI (n = 4). Tumor and tissue samples, harvested at the end of the perfusion, were evaluated regarding morphology, proliferation, and apoptosis (H&E-, Ki-67-, cleaved caspase 3-staining, TUNEL assay). Results Extensive peritoneal sarcomatosis in over 91% of the cases was observed. HIPEC was feasible without acute side effects. Ki-67 staining revealed concentration- or temperature-dependent effects of cisplatin-based HIPEC on the tumors. Although cleaved caspase-3 showed only sporadic apoptotic effects. TUNEL assay detected concentration- or temperature-dependent apoptotic effects at the outer tumor surface. MRI scans confirmed the observed tumor dissemination. Conclusion This is the first animal model for evaluation of HIPEC in pediatric RMS in mice. Cisplatin-based HIPEC had early effects on the proliferation whereas circumscribed apoptotic effects could be detected at the tumor surface. This model allows further insights on the possible efficiency of HIPEC in RMS. Further studies using other drug combinations and treatment will follow.

Automated summary

The established mouse model for evaluation of HIPEC in pediatric RMS showed early effects on tumor proliferation and circumstantial apoptosis effects at the tumor surface with cisplatin-based HIPEC. MRI scans confirmed tumor dissemination.