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Review
. 2024 Oct 3;26(10):1805-1822.
doi: 10.1093/neuonc/noae107.

The biological significance of tumor grade, age, enhancement, and extent of resection in IDH-mutant gliomas: How should they inform treatment decisions in the era of IDH inhibitors?

Martin J van den Bent  1 , Pim J French  1 , Daniel Brat  2 , Joerg C Tonn  3   4 , Mehdi Touat  5   6 , Benjamin M Ellingson  7 , Robert J Young  8 , Johan Pallud  9   10 , Andreas von Deimling  11 , Felix Sahm  11 , Dominique Figarella Branger  12 , Raymond Y Huang  13 , Michael Weller  14 , Ingo K Mellinghoff  15 , Tim F Cloughsey  16 , Jason T Huse  17 , Kenneth Aldape  18 , Guido Reifenberger  19 , Gilbert Youssef  20 , Philipp Karschnia  4   3 , Houtan Noushmehr  21 , Katherine B Peters  22 , Francois Ducray  23   24 , Matthias Preusser  25 , Patrick Y Wen  20
Affiliations
Review

The biological significance of tumor grade, age, enhancement, and extent of resection in IDH-mutant gliomas: How should they inform treatment decisions in the era of IDH inhibitors?

Martin J van den Bent et al. Neuro Oncol. .

Erratum in

Abstract

The 2016 and 2021 World Health Organization 2021 Classification of central nervous system tumors have resulted in a major improvement in the classification of isocitrate dehydrogenase (IDH)-mutant gliomas. With more effective treatments many patients experience prolonged survival. However, treatment guidelines are often still based on information from historical series comprising both patients with IDH wild-type and IDH-mutant tumors. They provide recommendations for radiotherapy and chemotherapy for so-called high-risk patients, usually based on residual tumor after surgery and age over 40. More up-to-date studies give a better insight into clinical, radiological, and molecular factors associated with the outcome of patients with IDH-mutant glioma. These insights should be used today for risk stratification and for treatment decisions. In many patients with IDH-mutant grades 2 and 3 glioma, if carefully monitored postponing radiotherapy and chemotherapy is safe, and will not jeopardize the overall outcome of patients. With the INDIGO trial showing patient benefit from the IDH inhibitor vorasidenib, there is a sizable population in which it seems reasonable to try this class of agents before recommending radio-chemotherapy with its delayed adverse event profile affecting quality of survival. Ongoing trials should help to further identify the patients that are benefiting from this treatment.

Keywords: WHO brain tumor classification; astrocytoma IDH-mutant; oligodendroglioma IDH-mutant and 1p/19q codeleted; prognosis; vorasidenib.

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Conflict of interest statement

MvdB has received honoraria for consultancy from Anheart Therapeutics, Boehringer Ingelheim, Fore Biotherapeutics, Genenta, Incyte, Mundipharm, Chimerix, Roche, and Servier and support for travel to meetings by Servier. PJF is providing consultancy to Servier. JCT has received honoraria for consultancy, lecture or research grants from the following for-profit companies: Novocure, Novartis, Munich Surgical imaging, Seagen. DB has nothing to declare. MT received honoraria for lectures, consultation or advisory board participation from Medscape, Novocure, Ono, Servier. BME is a Paid Consultant and Advisor Alpheus Medical, Chimerix, Erasca, Global Coalition for Adaptive Research, Imaging Endpoints, Medicenna, Voiant, Monteris, Neosoma, Orbus Therapeutics, Sagimet Biosciences, Sapience Therapeutics, Servier Pharmaceuticals, SonALAsense, and Sumitomo Dianippon Pharma Oncology. BME also has a research grant from Siemens and is a paid member of the data monitoring board for Carthera. RJY: Is a consultant for NordicNeuroImaging, Turing Medical, Olea Medical, ICON plc, RadMD. JP has nothing to declare. AvD: Shareholder and cofounder of Heidelberg Epignostix GmbH, honoraria from Illumina. FS is shareholder and cofounder of Heidelberg Epignostix GmbH, honoraria from Illumina.

DFB has nothing to declare. RYH has consulting/advisory board activities for Vysioneer and Nuvation Bio. MW has received research grants from Novartis, Quercis and Versameb, and honoraria for lectures or advisory board participation or consulting from Anheart Therapeutics, Bayer, Curevac, Medac, Neurosense, Novartis, Novocure, Orbus, Pfizer, Philogen, Roche and Servier. IKM has received research funding from General Electric, Agios, and Lilly and honoraria from Roche for a presentation. IKM has served in advisory roles for Agios, Amgen, Debiopharm, Novartis, Puma Biotechnology, and Voyager Therapeutics. TFC is cofounder, major stock holder, consultant and board member of Katmai. Pharmaceuticals, holds stock for Erasca, member of the board and paid consultant for the 501c3 Global Coalition for Adaptive Research, holds stock in Chimerix and receives milestone payments and possible future royalties, member of the scientific advisory board for Break Through Cancer, member of the scientific advisory board for Cure Brain Cancer Foundation, has provided paid consulting services to Symbio, Mundipharma, Tango BlueRock, Vida Ventures, Lista Therapeutics, Stemline, Novartis, Roche, Sonalasense, Sagimet, Clinical Care Options, Ideology Health, Servier, Jubilant, Immvira, Gan & Lee, BrainStorm, Katmai, Sapience, Inovio, Vigeo Therapeutics, DNATrix, Tyme, SDP, Kintara, Bayer, Merck, Boehinger Ingelheim, VBL, Amgen, Kiyatec, Bayer, Abbvie, VBI, Deciphera, VBL, Agios, Novocure, Medscape and has contracts with UCLA for the Brain Tumor Program with Roche, VBI, Merck, Novartis, BMS. The Regents of the University of California (T.F.C. employer) has licensed intellectual property co-invented by TFC to Katmai Pharmaceuticals. JTH has nothing to disclose. KMA has nothing to disclose. GR has nothing to disclose. GY has nothing to disclose. PK has nothing to disclose. HN has nothing to disclose. KBP has received research support: Biomimetix, LLC, Servier, Ono Pharmaceutical. Advisory Board/Consultant: Anheart, Rigel, Sapience, Servier, Telix, Varian. PYW has received research Support from Astra Zeneca, Black Diamond, Bristol Meyers Squibb, Chimerix, Eli Lily, Erasca, Global Coalition For Adaptive Research, Kazia, MediciNova, Merck, Novartis, Quadriga, Servier, VBI Vaccines. Advisory Board/Consultant: Anheart, Astra Zeneca, Black Diamond, Celularity, Chimerix, Day One Bio, Genenta, Glaxo Smith Kline, Kintara, Merck, Mundipharma, Novartis, Novocure, Prelude Therapeutics, Sagimet, Sapience, Servier, Symbio, Tango, Telix, VBI Vaccines. FD has received honoraria for consultancy and lectures from Servier and Novocure. MP has received honoraria for lectures, consultation or advisory board participation from the following for-profit companies: Bayer, Bristol-Myers Squibb, Novartis, Gerson Lehrman Group (GLG), CMC Contrast, GlaxoSmithKline, Mundipharma, Roche, BMJ Journals, MedMedia, Astra Zeneca, AbbVie, Lilly, Medahead, Daiichi Sankyo, Sanofi, Merck Sharp & Dome, Tocagen, Adastra, Gan & Lee Pharmaceuticals, Janssen, Servier, Miltenyi, Böhringer-Ingelheim, Telix, Medscape.

Figures

Figure 1.
Figure 1.
Schematic representation of the retinoblastoma (Rb) and receptor tyrosine kinase (RTK) pathway.
See this image and copyright information in PMC

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