466 Evaluating Intratumoral Carboplatin Concentrations Following LITT in Glioblastoma and the Impact of Combined Therapy on Murine Overall Survival

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INTRODUCTION: Tight regulation of the blood-brain barrier (BBB) presents significant challenges in the delivery of chemotherapeutics in glioblastoma (GBM). Laser interstitial thermal therapy (LITT) induces coagulative necrosis of neoplastic tissue while directly opening the BBB potentially allowing for the passage of BBB-impermeable systemic chemotherapeutics. METHODS: C57BL6 wild-type mice underwent intracranial KR158-luciferase tumor injection followed by LITT on day 14. Treatment groups to evaluate intratumoral carboplatin concentrations included untreated, carboplatin only, LITT only, LITT + carboplatin at 30 minutes and 1 hour (all n = 3). 0.14 mg/ml Carboplatin was injected immediately after LITT. Mouse brains and plasma were harvested for inductively coupled plasma mass spectrometry (ICP-MS) to detect carboplatin at the specified time point. One-way ANOVA was used to compare carboplatin concentrations. To evaluate OS, intraperitoneal injections of carboplatin were performed once every 7 days for 5 weeks. Treatment groups included untreated, carboplatin only, LITT only, adjuvant LITT + carboplatin, and neoadjuvant carboplatin + LITT (all n = 8). Kaplan-Meier survival curves were used to compare OS among groups. RESULTS: Mice treated with LITT + carboplatin at 30 minutes (p = 0.0001) and 1 hour (p = 0.0054) demonstrated significantly increased intratumoral carboplatin concentrations as compared with carboplatin only. Plasma concentrations of carboplatin were significantly increased in mice treated with LITT + carboplatin at 30 minutes compared with carboplatin only (p = 0.0009). Mice treated with neoadjuvant carboplatin + LITT were found to have significantly increased OS as compared adjuvant LITT + Carboplatin (p = 0.0218) and LITT only (p = 0.0098). CONCLUSIONS: LITT facilitates the delivery of carboplatin across the BBB and has significant impacts on murine OS.

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