Diffusion MRI phenotypes predict overall survival benefit from anti-VEGF monotherapy in recurrent glioblastoma : Converging evidence from phase II trials
A partir de données portant sur 258 patients atteints d'un glioblastome récidivant et inclus dans 5 essais de phase II évaluant un traitement anti-VEGF, cette étude met en évidence l'intérêt de réaliser une IRM de diffusion avant le traitement pour prédire l'effet de ce dernier sur la survie globale des patients
Purpose : Anti-VEGF therapies remain controversial in the treatment of recurrent glioblastoma (GBM). In the current study we demonstrate that recurrent GBM patients with a specific diffusion MR imaging signature have an overall survival (OS) advantage when treated with cediranib, bevacizumab, cabozantinib, or aflibercept monotherapy at first or second recurrence. These findings were validated using a separate trial comparing bevacizumab with lomustine.
Experimental Design : Patients with recurrent GBM and diffusion MRI from the monotherapy arms of 5 separate Phase II clinical trials were included : 1) cediranib (NCT00035656); 2) bevacizumab (BRAIN Trial, AVF3708g; NCT00345163); 3) cabozantinib (XL184-201; NCT00704288); 4) aflibercept (VEGF Trap; NCT00369590); and 5) bevacizumab or lomustine (BELOB; NTR1929). Apparent diffusion coefficient (ADC) histogram analysis was performed prior to therapy to estimate "ADCL", the mean of the lower ADC distribution. Pre-treatment ADCL, enhancing volume, and clinical variables were tested as independent prognostic factors for OS.
Results : The coefficient of variance (COV) in double baseline ADCL measurements was 2.5% and did not significantly differ (P=0.4537). An ADCL threshold of 1.24 um2/ms produced the largest OS differences between patients (HR~0.5) and patients with an ADCL>1.24 um2/ms had close to double the OS in all anti-VEGF therapeutic scenarios tested. Training and validation data confirmed baseline ADCL was an independent predictive biomarker for OS in anti-VEGF therapies, but not lomustine, after accounting for age and baseline enhancing tumor volume.
Conclusions : Pre-treatment diffusion MRI is a predictive imaging biomarker for OS in patients with recurrent GBM treated with anti-VEGF monotherapy at first or second relapse.
Clinical Cancer Research , résumé, 2016