IMG-89. Volumetric (3D) compared with traditional bidirectional (2D) assessment in patients with Grade 2, isocitrate dehydrogenase 1/2 mutant (mIDH1/2) glioma receiving vorasidenib or placebo in the Phase 3 INDIGO trial

Abstract While Response Assessment in Neuro-oncology (RANO) criteria remain the standard for brain tumor evaluation, 3D volumetric measurements may provide more accurate tumor assessments. We compared 2D RANO per blinded independent review committee (BIRC) with 3D volumetric RANO to evaluate correlation, progression detection and clinical outcomes in patients with mIDH1/2 diffuse glioma from INDIGO (NCT04164901). Data comparing vorasidenib (n=168) with placebo (n=163) were analyzed. Per RANO criteria for low-grade gliomas, analyses of 2D versus 3D volumetric progression-free survival (PFS) by BIRC, correlation between measurements, time to next intervention (TTNI), and response concordance were performed. Mixed models evaluated longitudinal correlation; weighted kappa statistics assessed agreement in response categorization. Strong positive correlation was observed between 2D and 3D measurements (Pearson, r=0.858; mixed model, r=0.861). 3D volumetric assessment demonstrated a stronger treatment effect (HR 0.24; 95% CI 0.15, 0.37) than 2D assessment (HR 0.35; 95% CI 0.25, 0.49). 3D volumetric assessment detected fewer progression events (vorasidenib, 16.1%; placebo, 44.2%) than 2D assessment (vorasidenib, 32.1%; placebo, 63.8%). Importantly, 3D volumetric PFS visually matched TTNI with similar treatment effect sizes. Weighted kappa analysis showed fair agreement between methods for best overall response (0.382) and all timepoint assessments (0.325). However, across all timepoint responses, 2D assessments identified more minor response (MR) and progressive disease (PD) classifications (MR: 2D, n=80; 3D n=54; PD: 2D, n=389; 3D, n=266) while 3D volumetric assessments identified more stable disease classifications (2D, n=1410; 3D, n=1552). 3D volumetric assessments demonstrated stronger treatment effects than 2D assessments, with similar treatment effect sizes for 3D PFS and TTNI. 3D volumetric assessments yielded fewer PD but more SD classifications versus 2D, suggesting a more conservative progression threshold or stable tumor burden measurement over time. Volumetric assessment may provide a more clinically meaningful determination of progression in Grade 2 glioma trials, potentially impacting future trial design and endpoint selection.

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Journal
Neuro-Oncology
Published
2025-11-01
DOI
https://doi.org/10.1093/neuonc/noaf201.1168
Primary Topic
Glioma Diagnosis and Treatment
Type
article
Field-Weighted Citation Impact
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article

IMG-89. Volumetric (3D) compared with traditional bidirectional (2D) assessment in patients with Grade 2, isocitrate dehydrogenase 1/2 mutant (mIDH1/2) glioma receiving vorasidenib or placebo in the Phase 3 INDIGO trial

Andreas Felix Hottinger, Shlomit Yust‐Katz, Warren Mason, Lori Steelman et al.
Neuro-Oncology
Glioma Diagnosis and Treatment
article

IMG-89. Volumetric (3D) compared with traditional bidirectional (2D) assessment in patients with Grade 2, isocitrate dehydrogenase 1/2 mutant (mIDH1/2) glioma receiving vorasidenib or placebo in the Phase 3 INDIGO trial

Andreas Felix Hottinger, Shlomit Yust‐Katz, Warren Mason, Lori Steelman, Martin J. van den Bent, Islam Hassan, Joe Sammy Mendez, Pierre Giglio, Ingo K. Mellinghoff, Patrick Yung Wen, Benjamin M. Ellingson, Deborah T. Blumenthal, Yoshie Umemura, Macarena I. de la Fuente, Liam Welsh, Jennifer Clarke, François Ducray, Yoshiki Arakawa, Elizabeth A. Maher, Timothy F. Cloughesy, Mehdi Touat, Katherine B. Peters, Burt Nabors, Juan Manuel Sepúlveda-Sánchez, Wolfgang Wick, Matthias Holdhoff, Riccardo Soffietti, Dan Zhao, James Perry, Shuchi S. Pandya
article en

Abstract

Abstract While Response Assessment in Neuro-oncology (RANO) criteria remain the standard for brain tumor evaluation, 3D volumetric measurements may provide more accurate tumor assessments. We compared 2D RANO per blinded independent review committee (BIRC) with 3D volumetric RANO to evaluate correlation, progression detection and clinical outcomes in patients with mIDH1/2 diffuse glioma from INDIGO (NCT04164901). Data comparing vorasidenib (n=168) with placebo (n=163) were analyzed. Per RANO criteria for low-grade gliomas, analyses of 2D versus 3D volumetric progression-free survival (PFS) by BIRC, correlation between measurements, time to next intervention (TTNI), and response concordance were performed. Mixed models evaluated longitudinal correlation; weighted kappa statistics assessed agreement in response categorization. Strong positive correlation was observed between 2D and 3D measurements (Pearson, r=0.858; mixed model, r=0.861). 3D volumetric assessment demonstrated a stronger treatment effect (HR 0.24; 95% CI 0.15, 0.37) than 2D assessment (HR 0.35; 95% CI 0.25, 0.49). 3D volumetric assessment detected fewer progression events (vorasidenib, 16.1%; placebo, 44.2%) than 2D assessment (vorasidenib, 32.1%; placebo, 63.8%). Importantly, 3D volumetric PFS visually matched TTNI with similar treatment effect sizes. Weighted kappa analysis showed fair agreement between methods for best overall response (0.382) and all timepoint assessments (0.325). However, across all timepoint responses, 2D assessments identified more minor response (MR) and progressive disease (PD) classifications (MR: 2D, n=80; 3D n=54; PD: 2D, n=389; 3D, n=266) while 3D volumetric assessments identified more stable disease classifications (2D, n=1410; 3D, n=1552). 3D volumetric assessments demonstrated stronger treatment effects than 2D assessments, with similar treatment effect sizes for 3D PFS and TTNI. 3D volumetric assessments yielded fewer PD but more SD classifications versus 2D, suggesting a more conservative progression threshold or stable tumor burden measurement over time. Volumetric assessment may provide a more clinically meaningful determination of progression in Grade 2 glioma trials, potentially impacting future trial design and endpoint selection.

Neuro-OncologyVol. 27(Supplement_5)
Sunnybrook Health Science Centre (CA), Barrow Neurological Institute (US), Memorial Sloan Kettering Cancer Center (US), University of Miami (US), University of California, Los Angeles (US), Tel Aviv University (IL), German Cancer Research Center (DE), University of California, San Francisco (US), University of Toronto (CA), Kyoto University (JP), University of Utah (US), Heidelberg University (DE), Rabin Medical Center (IL), Huntsman Cancer Institute (US), Toronto General Hospital (CA), Erasmus MC (NL), University Hospital Heidelberg (DE), Centre Hospitalier Universitaire Vaudois (CH), Health Sciences Centre (CA), The Ohio State University Wexner Medical Center (US), University of Alabama at Birmingham (US), Sorbonne Université (FR), Assistance Publique – Hôpitaux de Paris (FR), Hospices Civils de Lyon (FR), Hospital Universitario 12 De Octubre (ES), Hôpital Pierre Wertheimer (FR), Michigan Medicine (US), Dana-Farber Cancer Institute (US), Michigan Center for Translational Pathology (US), Royal Marsden Hospital (GB), Pitié-Salpêtrière Hospital (FR), Centre de Recherche en Cancérologie de Lyon (FR), Duke Medical Center (US), Sidney Kimmel Comprehensive Cancer Center (US), University of Turin (IT), University of San Francisco (US), The University of Texas Southwestern Medical Center (US)
Openalex Percentile: Top 52%
Glioma Diagnosis and Treatment
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