Synapse - Tumor volume growth rates and doubling times during active surveillance of IDH-mutant low-grade glioma

Tumor volume growth rates and doubling times during active surveillance of IDH-mutant low-grade glioma Journal Article

Authors:	Bhatia, A.; Moreno, R.; Reiner, A. S.; Nandakumar, S.; Walch, H. S.; Thomas, T. M.; Nicklin, P. J.; Choi, Y.; Skakodub, A.; Malani, R.; Prabhakaran, V.; Tiwari, P.; Diaz, M.; Panageas, K. S.; Mellinghoff, I. K.; Bale, T. A.; Young, R. J.
Article Title:	Tumor volume growth rates and doubling times during active surveillance of IDH-mutant low-grade glioma
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 1⁄4 128) 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 1⁄4 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. ©2023 American Association for Cancer Research.
Keywords:	retrospective studies; gene deletion; genetics; mutation; sequence deletion; brain tumor; glioma; brain neoplasms; prospective study; prospective studies; metabolism; pathology; diagnostic imaging; retrospective study; tumor burden; watchful waiting; homozygote; isocitrate dehydrogenase; humans; human
Journal Title:	Clinical Cancer Research
Volume:	30
Issue:	1
ISSN:	1078-0432
Publisher:	American Association for Cancer Research
Date Published:	2024-01-01
Start Page:	106
End Page:	115
Language:	English
DOI:	10.1158/1078-0432.Ccr-23-1180
PUBMED:	37910594
PROVIDER:	scopus
PMCID:	PMC10841595
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85181760924&doi=10.1158%2f1078-0432.CCR-23-1180&partnerID=40&md5=d680e2a6e31b382576025d315e707a35
Notes:	The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF -- Source: Scopus