NEIM-08 A PHASE II STUDY OF MULTIPARAMETRIC MR-GUIDED HIGH DOSE ADAPTIVE RADIOTHERAPY WITH CONCURRENT TEMOZOLOMIDE IN PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA

BACKGROUND: Biologically-informed radiotherapy (RT) targeting an adversely prognostic hypercellular/hyperperfused imaging phenotype in patients with newly diagnosed glioblastoma (GBM) may improve outcomes by identifying emerging regions of treatment resistance associated with survival (OS), and is under investigation as a target for individualized, adaptive RT in an ongoing Phase II trial (NCT04574856). METHODS: In this single-arm study, patients with newly diagnosed GBM following resection undergo dose-intensified chemoRT targeting the residual hypercellular (TV(HCV), mean contralateral normal brain+2SD) and hyperperfused tumor volume (TV(CBV), contralateral normal frontal grey matter+1SD) identified using high b-value diffusion-weighted and dynamic contrast-enhanced perfusion MRI. TV(HCV)/TV(CBV) is treated to 50 Gy in 20 fractions (2.5 Gy/fraction), and following mid-RT reassessment, the persistent and developing TV(HCV)/TV(CBV) is treated to 30 Gy in 10 fractions (3 Gy/fraction). The primary endpoint is improvement in OS, with planned interim safety analysis. RESULTS: Since October 2020, 16 of 30 patients have been enrolled. Median age was 58 years (range, 29-75) and 69% were male. No patient underwent biopsy, and 50% had gross total resection; 23% had MGMT methylated tumors, and all except 2 were IDHwt. Median TV(HCV)/TV(CBV )was 6.9 cc (range, 1.9-42.8) pre-RT and 30% (range, 1-72%) was nonenhancing. By mid-RT, TV(HCV)/TV(CBV) was reduced to 4.2 cc (range, 0.8-34.3) and 47% (range, 3-74%) was nonenhancing. The TV(HCV)/TV(CBV) persisting from pre- to mid-RT was 2.3 cc (range, 0-24.2), with an additional 1.8 cc (range, 0.3-20.6) newly developing outside of the initial region. All patients underwent adaptive replanning for boost without interruption. Planned interim analysis determined an acceptable rate of neurologic toxicity and safety to continue enrollment. CONCLUSION: Individualized, adaptive radiotherapy using an advanced imaging biomarker to assess emerging and especially non-enhancing regions of treatment resistance in patients with GBM is feasible, with short term safety in an early cohort and longer-term efficacy outcomes anticipated with ongoing accrual.