Tumor Volume Growth Rates and Doubling Times during Active Surveillance of IDH-mutant Low-Grade Glioma.

Overview

abstract

PURPOSE: Isocitrate-dehydrogenase-mutant (IDH-mt) gliomas are incurable primary brain tumors characterized by a slow-growing phase over several years followed by a rapid-growing malignant phase. We hypothesized that tumor volume growth rate (TVGR) on magnetic resonance imaging may act as an earlier measure of clinical benefit during the active surveillance period. EXPERIMENTAL DESIGN: We integrated 3-dimensional volumetric measurements with clinical, radiological, and molecular data in a retrospective cohort of IDH-mt gliomas that were observed after surgical resection in order to understand tumor growth kinetics and the impact of molecular genetics. RESULTS: Using log-linear mixed modeling, the entire cohort (n=128) had a continuous %TVGR per 6 months of 10.46% (95% CI: [9.11%, 11.83%]) and a doubling time of 3.5 years (95% CI: [3.10-3.98]). High molecular grade IDH-mt gliomas, defined by the presence of homozygous deletion of CDKN2A/B, had %TVGR per 6 months of 19.17% (95% CI: [15.57%, 22.89%]) which was significantly different from low molecular grade IDH-mt gliomas with a growth rate per 6 months of 9.54% (95% CI: [7.32%, 11.80%]) (P < 0.0001). Using joint modeling to co-model the longitudinal course of TVGR and overall survival, we found each one natural logarithm tumor volume increase resulted in more than a 3-fold increase in risk of death (HR=3.83, 95% CI: [2.32-6.30], P < 0.0001). CONCLUSIONS: TVGR may be used as an earlier measure of clinical benefit and correlates well with the WHO 2021 molecular classification of gliomas and survival. Incorporation of TVGR as a surrogate endpoint into future prospective studies of IDH-mt gliomas may accelerate drug development.