The use of minor response, volumetric assessment, and growth rate kinetics as endpoints in grade 1-3 glioma clinical trials: a RANO perspective.

Van Den Bent MJ, Cloughesy TF, Ellingson BM, Allen JE, Blackman SC, Kieran MW, Tonn JC, Karschnia P, Wijnenga M, Pallud J, Young RJ, Huang RY, Mellinghoff IK, De Groot J, Van Der Hoorn A, Youssef G, Hervey-Jumper SL, Vogelbaum MA, Chang SM, Wen PY (2025)

Publication Type: Journal article, Review article

Publication year: 2025

Journal

Neuro-Oncology Oxford University Press

Book Volume: 27

Pages Range: 2514-2523

Journal Issue: 10

DOI: 10.1093/neuonc/noaf173

Abstract

The Response Assessment in NeuroOncology (RANO) criteria for response to treatment in glioma make a distinction between enhancing and unenhancing tumors, which reflects assessment of a different biological process underlying the magnetic resonance imaging findings in enhancing and nonenhancing tumors. The recent regulatory approval of tovorafenib has also considered the patients with minor responses (25%-50% decrease) based on the 2D measurement on T2/FLAIR MR imaging while incorporating other measures of patient benefit. The INDIGO placebo controlled trial led to the regulatory approval of vorasidenib based on the increase in PFS in the active treatment arm, as measured by blinded independent radiology review using the 2D RANO criteria. With that, more insight in the regulatory requirements for approval in low-grade tumors has been obtained, but other issues in assessing outcome in studies on low-grade enhancing tumors remain. These include the added value of volumetric assessment instead of 2D assessments, and assessment of tumor growth rate as an early marker of outcome. This manuscript gives an overview of the current perspective on and challenges of assessing outcome in trials on unenhancing glioma, with both regulatory and clinical perspectives.

Authors with CRIS profile

Philipp Karschnia Department of Neurosurgery

Involved external institutions

University of California Los Angeles (UCLA) US United States (USA) (US) University of California San Francisco (UCSF) US United States (USA) (US) Erasmus University Medical Center (MC) NL Netherlands (NL) Chimerix US United States (USA) (US) Harvard University US United States (USA) (US) H. Lee Moffitt Cancer Center & Research Institute US United States (USA) (US) Google Ireland Limited IE Ireland (IE) Day One Biopharmaceuticals US United States (USA) (US) Deutsches Krebsforschungszentrum (DKFZ) DE Germany (DE) Université Paris Cité FR France (FR) Memorial Sloan Kettering Cancer Center US United States (USA) (US) University Medical Center Groningen (UMCG) / Universitair Medisch Centrum Groningen NL Netherlands (NL)

How to cite

APA:

Van Den Bent, M.J., Cloughesy, T.F., Ellingson, B.M., Allen, J.E., Blackman, S.C., Kieran, M.W.,... Wen, P.Y. (2025). The use of minor response, volumetric assessment, and growth rate kinetics as endpoints in grade 1-3 glioma clinical trials: a RANO perspective. Neuro-Oncology, 27(10), 2514-2523. https://doi.org/10.1093/neuonc/noaf173

MLA:

Van Den Bent, Martin J., et al. "The use of minor response, volumetric assessment, and growth rate kinetics as endpoints in grade 1-3 glioma clinical trials: a RANO perspective." Neuro-Oncology 27.10 (2025): 2514-2523.

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