Response assessment during chemoradiation using a hypercellular/hyperperfused imaging phenotype predicts survival in patients with newly diagnosed glioblastoma. Issue 9 (18th February 2021)

• Record Type: Journal Article
• Authors: Kim, Michelle M; Aryal, Madhava P; Sun, Yilun; Parmar, Hemant A; Li, Pin; Schipper, Matthew; Wahl, Daniel R; Lawrence, Theodore S; Cao, Yue
• Is Part Of: Neuro-oncology. Volume 23:Issue 9(2021)
• Page Start: 1537
• Page End: 1546
• Publication Date: 2021-02-18
• Subjects: glioblastoma -- multiparametric MRI -- overall survival -- radiation therapy -- response assessment; Brain Neoplasms -- Periodicals; Brain -- Tumors -- Periodicals; Brain -- Cancer -- Periodicals; Nervous system -- Cancer -- Periodicals; 616.99481
• DOI: 10.1093/neuonc/noab038
• Languages: English
• ISSNs: 1522-8517

Abstract

Abstract: Background: Adversely prognostic hypercellular and hyperperfused regions of glioblastoma (GBM) predict progression-free survival, and are a novel target for dose-intensified chemoradiation (chemoRT) recently implemented in a phase II clinical trial. As a secondary aim, we hypothesized that dose-intensified chemoRT would induce greater mid-treatment response of hypercellular/hyperperfused tumor regions vs standard chemoradiation, and that early response would improve overall survival (OS). Methods: Forty-nine patients with newly diagnosed GBM underwent prospective, multiparametric high b value diffusion-weighted MRI (DW-MRI) and perfusion dynamic contrast-enhanced MRI (DCE-MRI) pre-RT and 3-4 weeks into RT. The hypercellular tumor volume (TVHCV, mean contralateral normal brain + 2SD) and hyperperfused tumor volume (TVCBV, contralateral normal frontal gray matter + 1SD) were generated using automated thresholding. Twenty-six patients were enrolled on a dose-escalation trial targeting TVHCV /TVCBV with 75 Gy in 30 fractions, and 23 non-trial patients comprised the control group. OS was estimated using the Kaplan-Meier method and compared using the log-rank test. The effect of TVHCV /TVCBV and Gd-enhanced tumor volume on OS was assessed using multivariable Cox proportional-hazard regression. Results: Most patients had gross total (47%) or subtotal resection (37%), 25% were MGMT-methylated. Patients treated on the dose-escalation trial had significantly greater reduction in TVHCV /TVCBV (41% reduction, IQR 17%-75%) vs non-trial patients (6% reduction, IQR 6%-22%, P = .002). An increase in TVHCV /TVCBV during chemoRT was associated with worse OS (adjusted hazard ratio [aHR] 1.2, 95%CI 1.0-1.4, P = .02), while pre-treatment tumor volumes ( P > .5) and changes in Gd-enhanced volume ( P = .9) were not. Conclusions: Multiparametric MRI permits identification of therapeutic resistance during chemoRT and supports adaptive strategies in future trials.