MODL-20. PRECLINICAL MODELING OF LASER INTERSTITIAL THERMAL THERAPY IN MURINE BRAIN TUMORS FOR TRANSLATIONAL IMMUNO-ONCOLOGY

Abstract

Abstract INTRODUCTION Cytoreductive surgery is a cornerstone of management for intracranial tumors. However, resection may remove an important source of neoantigen. In the case of laser interstitial thermal therapy (LITT), ablated tumor remans in situ, allowing for an anti-tumor immune response. To characterize these phenomena, we developed a murine model of LITT for use with syngeneic brain tumor cell lines. RESULTS & METHODS To establish anatomical boundaries for our ablation, we characterized our CT-2A glioma model on T2 MRI, selecting 10 days post-implantation for LITT based on lesion size. We simultaneously implanted a 400 μm laser fiber and thermocouple probe into the center and edge of the target volume, respectively, for simultaneous ablation and temperature monitoring. Using a clinical 1064 nm Nd:YAG laser, we first performed a dose titration of laser power/time in normal mouse brains, finding that doses above 1.5 W for 60s produced cavitary lesions with charring that resulted in death at 24h post-LITT. We therefore selected 1 W for 60s as a safe laser power dose in our tumor model. Ablations at this setting rapidly heated the lesion edge to a peak temperature of mean 43.79 ± 2.993 °C, sparing the surrounding brain. MRI imaging at 1, 3, and 7 days post-LITT revealed expansile T2 hyperintense lesions that resolved over time, with hemorrhage and necrosis on H&E. LITT increased survival to 28 from 25.5 days (vs sham, P = 0.0172). CONCLUSIONS Our model successfully recapitulates the essential clinical features of LITT: a cytoreductive survival benefit; lesion expansion on MRI; and focal necrosis with hemorrhagic vasculature on H&E. This model is well suited for study of LITT-adjunctive interventions and characterization of the immunobiology of hyperthermia.