A Phase II Study of Dose-Intensified Chemoradiation Using Biologically-Based Target Volume Definition in Patients with Newly Diagnosed Glioblastoma
Mené sur 26 patients adultes atteints d'un glioblastome récemment diagnostiqué, cet essai de phase II évalue l'efficacité, du point de vue de l'amélioration de la survie globale à 12 mois, de l'intensification de la dose de chiomioradiothérapie dans les zones tumorales hypercellulaires
Purpose/Objectives: We hypothesized that dose-intensified chemoradiation (chemoRT) targeting adversely prognostic hypercellular (TV HCV) and hyperperfused (TV CBV) tumor volumes would improve outcomes in patients with glioblastoma (GBM). Materials/Methods: This single-arm phase II trial enrolled adult patients with newly diagnosed GBM. Patients with >1cc TV HCV/TV CBV identified using high b-value diffusion-weighted MRI and dynamic contrast-enhanced perfusion MRI were treated over 30 fractions to 75 Gy to the TV HCV/TV CBV with temozolomide. The primary objective was to estimate improvement in 12-month overall survival (OS) versus historical control. Secondary objectives included evaluating the effect of 3-month TV HCV/TV CBV reduction on OS using Cox proportional-hazard regression, and characterizing coverage (95%IDL) of metabolic tumor volumes (MTV) identified using correlative 11C-Methionine PET. Clinically meaningful change was assessed for quality of life (QOL) by EORTC-QLQ-C30, symptom burden by MDASI-BT, and neurocognitive function (NCF) by COWA, Trail Making Test A/B, and HVLT-R. Results: Between 2016-2018, 26 patients were enrolled. Initial patients were boosted to TV HCV alone, and 13 patients to both TV HCV/TV CBV. Gross or subtotal resection was performed in 87% of patients, 22% were MGMT methylated. With 26-month follow-up (95%CI 19-NR), among patients boosted to the combined TV HCV/TV CBV 12-month OS was 92% (95%CI 78-100%, p=0.03) and median OS was 20 months (95%CI 18-NR), and OS 20 months (95%CI 14-29) for the whole study cohort. Patients whose 3-month TV HCV/TV CBV decreased to <median (3 cc) had superior OS (29 vs 12 months, p=0.02). Only 5 patients had central or in-field failures, and 93% (IQR 59-100) of the 11C-Methionine MTV received high-dose coverage. Late grade 3 neurologic toxicity occurred in 2 patients. Among non-progressing patients, 1 and 7-month deterioration in QOL, symptoms and NCF were similar in incidence to standard therapy. Conclusions: Dose-intensification against hypercellular/hyperperfused tumor regions in GBM yields promising OS, particularly among patients with greater tumor reduction 3-months post-RT, with favorable NCF, symptom burden and QOL.
International Journal of Radiation Oncology, Biology, Physics 2021