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

Clin Cancer Res. 2024 Jan 5;30(1):106-115. doi: 10.1158/1078-0432.CCR-23-1180.

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 MRI may act as an earlier measure of clinical benefit during the active surveillance period.

Experimental design: We integrated three-dimensional volumetric measurements with clinical, radiologic, 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% confidence interval (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 comodel 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain Neoplasms* / diagnostic imaging
  • Brain Neoplasms* / genetics
  • Brain Neoplasms* / pathology
  • Glioma* / diagnostic imaging
  • Glioma* / genetics
  • Glioma* / metabolism
  • Homozygote
  • Humans
  • Isocitrate Dehydrogenase / genetics
  • Mutation
  • Prospective Studies
  • Retrospective Studies
  • Sequence Deletion
  • Tumor Burden
  • Watchful Waiting

Substances

  • Isocitrate Dehydrogenase