Related Experiment Video
Updated: Jun 17, 2026
Primary Orthotopic Glioma Xenografts Recapitulate Infiltrative Growth and Isocitrate Dehydrogenase I Mutation
Published on: January 14, 2014
Tumor Volume Growth Rates and Doubling Times during Active Surveillance of IDH-mutant Low-Grade Glioma
Ankush Bhatia1,2, Raquel Moreno3, Anne S Reiner4
1Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York.
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.
Insights
Tumor volume growth rate (TVGR) on MRI can predict clinical benefit in isocitrate dehydrogenase-mutant (IDH-mt) gliomas. Faster growth correlates with higher grade and increased mortality risk, suggesting TVGR
Area of Science:
- Neuro-oncology
- Medical imaging
- Molecular genetics
Background:
- Isocitrate dehydrogenase-mutant (IDH-mt) gliomas are primary brain tumors with a slow initial growth phase followed by rapid malignant progression.
- Current surveillance methods may not capture early signs of clinical benefit or disease acceleration.
Purpose of the Study:
- To evaluate if tumor volume growth rate (TVGR) on MRI can serve as an early indicator of clinical benefit in IDH-mt gliomas during active surveillance.
- To understand the relationship between tumor growth kinetics, molecular genetics, and overall survival in IDH-mt gliomas.
Main Methods:
- Retrospective analysis of 128 IDH-mt glioma patients post-surgical resection.
- Integration of 3D volumetric MRI measurements with clinical, radiologic, and molecular data.
- Application of log-linear mixed modeling and joint modeling to analyze TVGR and survival data.
Main Results:
- The overall cohort exhibited a continuous %TVGR of 10.46% per 6 months, with a doubling time of 3.5 years.
- High molecular grade IDH-mt gliomas (with CDKN2A/B homozygous deletion) showed significantly faster growth (%TVGR of 19.17% per 6 months) compared to low molecular grade gliomas (%TVGR of 9.54% per 6 months).
- Each unit increase in log tumor volume was associated with a 3.83-fold increased risk of death, indicating a strong correlation between TVGR and survival.
Conclusions:
- TVGR on MRI is a potential early measure of clinical benefit in IDH-mt gliomas.
- TVGR correlates with the WHO 2021 molecular classification and overall survival.
- Incorporating TVGR as a surrogate endpoint in future trials could accelerate drug development for IDH-mt gliomas.
