Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Jan 5;30(1):106-115.
doi: 10.1158/1078-0432.CCR-23-1180.

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

Ankush Bhatia #  1   2 , Raquel Moreno #  3 , Anne S Reiner  4 , Subhiksha Nandakumar  4 , Henry S Walch  4 , Teena M Thomas  3 , Philip J Nicklin  3 , Ye Choi  3 , Anna Skakodub  1 , Rachna Malani  1 , Vivek Prabhakaran  5 , Pallavi Tiwari  5 , Maria Diaz  1 , Katherine S Panageas  4 , Ingo K Mellinghoff  1 , Tejus A Bale #  6 , Robert J Young #  3
Affiliations

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

Ankush Bhatia et al. Clin Cancer Res. .

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.

PubMed Disclaimer

Conflict of interest statement

Conflict of interest disclosure statement:

Ankush Bhatia, Raquel Moreno, Anne S Reiner, Subhiksha Nandakumar, Henry S Walch, Teena M Thomas, Philip J Nicklin, Ye Choi, Anna Skakodua, Rachna Malani, Maria Diaz, Vivek Prabhakaran, Pallavi Tiwari, and Tejus Bale have no COI to disclose. Robert J Young has consulted for ICON plc, NordicNeuroLab, Olea Sphere, and owns stock in Agios. Katherine S. Panageas receives funding from AACR Project GENIE. Ingo K Mellinghoff reports serving as a consultant for 501c3 Global Coalition for Adaptive Research; reports honoraria from the Doris Duke Charitable Foundation; reports serving on advisory board for Black Diamond Therapeutics, Roche Therapeutics, Prelude Therapeutics Incorporated, Voyager Therapeutics; reports research support from Erasca Therapeutics, Servier Pharmaceuticals LLC, Kazia Therapeutics, Vigeo Therapeutics, and Samus Therapeutics, Inc

Figures

Figure 1.
Figure 1.. CONSORT diagram and schematic overview for this study.
Clinical data, neuroimaging, and genomic data were acquired using MSKCC’s Institutional Database leading to an integrated molecular diagnosis. IDH-mt gliomas were subsequently analyzed in a multi-dimensional approach involving neuroimaging, volumetrics, and growth curve modeling.
Figure 2.
Figure 2.. Tumor Volume Growth Rates and Molecular Grading.
A) Individual patient growth trajectories in the entire cohort for IDH-mutant low-grade gliomas with representative linear (red) and exponential (blue) growth models. B) The distribution of tumor volume growth rates per 6 months in the IDH-mutant glioma cohort. C) Low, intermediate, and high molecular grade IDH-mt gliomas are plotted with associated exponential model-based trajectories. D) Representative neuroimaging of an individual patient with low, intermediate, and high molecular grade growth.
See this image and copyright information in PMC

Comment in

References

    1. van den Bent MJ, Smits M, Kros JM, Chang SM. Diffuse Infiltrating Oligodendroglioma and Astrocytoma. J Clin Oncol 2017;35(21):2394–401 doi 10.1200/JCO.2017.72.6737. - DOI - PubMed
    1. Schiff D, Van den Bent M, Vogelbaum MA, Wick W, Miller CR, Taphoorn M, et al. Recent developments and future directions in adult lower-grade gliomas: Society for Neuro-Oncology (SNO) and European Association of Neuro-Oncology (EANO) consensus. Neuro Oncol 2019;21(7):837–53 doi 10.1093/neuonc/noz033. - DOI - PMC - PubMed
    1. Yan H, Parsons DW, Jin GL, McLendon R, Rasheed BA, Yuan WS, et al. IDH1 and IDH2 Mutations in Gliomas. New Engl J Med 2009;360(8):765–73 doi DOI 10.1056/NEJMoa0808710. - DOI - PMC - PubMed
    1. Pala A, Coburger J, Scherer M, Ahmeti H, Roder C, Gessler F, et al. To treat or not to treat? A retrospective multicenter assessment of survival in patients with IDH-mutant low-grade glioma based on adjuvant treatment. J Neurosurg 2019:1–8 doi 10.3171/2019.4.JNS183395. - DOI - PubMed
    1. Miller JJ, Gonzalez Castro LN, McBrayer S, Weller M, Cloughesy T, Portnow J, et al. Isocitrate dehydrogenase (IDH) mutant gliomas: A Society for Neuro-Oncology (SNO) consensus review on diagnosis, management, and future directions. Neuro Oncol 2023;25(1):4–25 doi 10.1093/neuonc/noac207. - DOI - PMC - PubMed

Publication types

Substances