The Response Assessment in Neuro-Oncology (RANO) criteria for high-grade gliomas (RANO-HGG) and low-grade gliomas (RANO-LGG) were developed to improve reliability of response assessment in glioma trials. Over time, some limitations of these criteria were identified, and challenges emerged regarding integrating features of the modified RANO (mRANO) or the immunotherapy RANO (iRANO) criteria.

Informed by data from studies evaluating the different criteria, updates to the RANO criteria are proposed (RANO 2.0).

We recommend a standard set of criteria for both high- and low-grade gliomas, to be used for all trials regardless of the treatment modalities being evaluated. In the newly diagnosed setting, the postradiotherapy magnetic resonance imaging (MRI), rather than the postsurgical MRI, will be used as the baseline for comparison with subsequent scans. Since the incidence of pseudoprogression is high in the 12 weeks after radiotherapy, continuation of treatment and confirmation of progression during this period with a repeat MRI, or histopathologic evidence of unequivocal recurrent tumor, are required to define tumor progression. However, confirmation scans are not mandatory after this period nor for the evaluation of treatment for recurrent tumors. For treatments with a high likelihood of pseudoprogression, mandatory confirmation of progression with a repeat MRI is highly recommended. The primary measurement remains the maximum cross-sectional area of tumor (two-dimensional) but volumetric measurements are an option. For IDH wild-type glioblastoma, the nonenhancing disease will no longer be evaluated except when assessing response to antiangiogenic agents. In IDH-mutated tumors with a significant nonenhancing component, clinical trials may require evaluating both the enhancing and nonenhancing tumor components for response assessment.

The revised RANO 2.0 criteria refine response assessment in gliomas.

© 2023 by American Society of Clinical Oncology
CONTEXT

  • Key Objective

  • Response Assessment in Neuro-Oncology (RANO) 2.0 is an update of the response criteria for gliomas in adults on the basis of data from evaluation of the original RANO criteria and variations such as the modified RANO criteria (mRANO) and the immunotherapy RANO criteria (iRANO).

  • Knowledge Generated

  • RANO 2.0 recommends a standard set of criteria for both high- and low-grade gliomas, to be used for all trials regardless of the treatment modalities being evaluated. Response criteria for contrast-enhancing tumors, non–contrast-enhancing tumors, and tumors with both enhancing and nonenhancing components are proposed, in addition to other guidance to improve the assessment of response and progression in glial tumors.

  • Relevance (J.P.S. Knisely)

  • RANO 2.0 provides unified, standardized guidelines for glioma response assessments that are applicable for all low- and high-grade tumors. Subclassifications for enhancing or nonenhancing tumors or for the type of antitumor therapy employed are no longer needed.*

    *Relevance section written by JCO Associate Editor Jonathan P.S. Knisely, MD.

Conception and design: Patrick Y. Wen, Martin van den Bent, Gilbert Youssef, Timothy F. Cloughesy, Benjamin M. Ellingson, Michael Weller, Mark R. Gilbert, Raymond Huang, Andrew B. Lassman, Minesh Mehta, Lalitha K. Shankar, Javier E. Villanueva-Meyer, David R. Macdonald, David A. Reardon, Michael A. Vogelbaum, Susan M. Chang

Administrative support: Patrick Y. Wen

Collection and assembly of data: Patrick Y. Wen, Martin van den Bent, Gilbert Youssef, Timothy F. Cloughesy, Benjamin M. Ellingson, Evanthia Galanis, Raymond Huang, Minesh Mehta, Javier E. Villanueva-Meyer, David A. Reardon, Susan M. Chang

Data analysis and interpretation: Patrick Y. Wen, Martin van den Bent, Gilbert Youssef, Timothy F. Cloughesy, Benjamin M. Ellingson, Michael Weller, Daniel P. Barboriak, John de Groot, Mark R. Gilbert, Raymond Huang, Minesh Mehta, Annette M. Molinaro, Matthias Preusser, Rifaquat Rahman, Lalitha K. Shankar, Roger Stupp, Javier E. Villanueva-Meyer, David A. Reardon, Michael A. Vogelbaum, Susan M. Chang

Manuscript writing: All authors

Final approval of manuscript: All authors

Accountable for all aspects of the work: All authors

RANO 2.0: Update to the Response Assessment in Neuro-Oncology Criteria for High- and Low-Grade Gliomas in Adults

The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/authors/author-center.

Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).

Patrick Y. Wen

Consulting or Advisory Role: AstraZeneca, Vascular Biogenics, VBI Vaccines, Bayer, Karyopharm Therapeutics, ElevateBio, Integral Health, Prelude Therapeutics, Novocure, Mundipharma, Black Diamond Therapeutics, Day One Biopharmaceuticals, Sapience Therapeutics, Nuvation Bio, Celularity, Novartis, Merck, Boston Pharmaceuticals, Chimerix, Servier, Insightec, Novocure, Sagimet Biosciences, Boehringer Ingelheim, Servier, Genenta Science, Prelude Therapeutics, GlaxoSmithKline

Research Funding: AstraZeneca (Inst), Merck (Inst), Novartis (Inst), Oncoceutics (Inst), Lilly (Inst), Beigene (Inst), Kazia Therapeutics (Inst), MediciNova (Inst), Vascular Biogenics (Inst), VBI Vaccines (Inst), Puma Biotechnology (Inst), Celgene (Inst), Bayer (Inst), Nuvation Bio (Inst), Chimerix (Inst), Karyopharm Therapeutics (Inst), Servier (Inst)

Martin van den Bent

Employment: AstraZeneca

Consulting or Advisory Role: Boehringer Ingelheim, carthera, Genenta Science, Nerviano Medical Sciences, Chimerix, AstraZeneca, Servier, Roche, Incyte, Fore Biotherapeutics

Research Funding: AbbVie (Inst)

Timothy F. Cloughesy

Leadership: Katmai Pharmaceuticals

Stock and Other Ownership Interests: Katmai Pharmaceuticals, Chimerix, Erasca, Inc

Consulting or Advisory Role: Roche/Genentech, Tocagen, VBL Therapeutics, Novartis, Merck, Boehringer Ingelheim, KIYATEC, Bayer, DelMar Pharmaceuticals, QED Therapeutics, Amgen, Katmai Pharmaceuticals, Global Coalition for Adaptive Research, Inovio Pharmaceuticals, Sapience Therapeutics, SonaCare Medical, SERVIER, Lista, Chimerix

Patents, Royalties, Other Intellectual Property: US Provisional Application No.: 62/819,322 Title: Compositions and Methods for Treating Cancer Filing Date: March 15, 2019 Inventor(s): David A. Nathanson et al. FH Reference No.: UCH-17760 (32246-17760) Your Reference No.: (UCLA 2019-630-1) US

Other Relationship: Global Coalition for Adaptive Research, Break Through Cancer

Benjamin M. Ellingson

Consulting or Advisory Role: Siemens, Medicenna, MedQIA, Imaging Endpoints, Neosoma, Kazia Therapeutics, VBL Therapeutics, Global Coalition for Adaptive Research, Servier, Janssen, Chimerix, Sumitomo Dainippon Pharma Oncology, ImmunoGenesis, Ellipses Pharma, Monteris Medical, Alpheus Medical

Research Funding: Siemens, Janssen

Travel, Accommodations, Expenses: Siemens

Michael Weller

Honoraria: Novocure, Bayer, Pierre Fabre

Consulting or Advisory Role: Curevac, Medac, Novartis, Orbus Therapeutics, Philogen, Roche, Sandoz, Janssen, Seagen, LEO Pharma, Bayer

Research Funding: Quercegen Pharmaceuticals (Inst), Versameb (Inst)

Evanthia Galanis

Consulting or Advisory Role: KIYATEC, Karyopharm Therapeutics (Inst), Boston Scientific (Inst), Servier (Inst)

Research Funding: MedImmune (Inst), Servier (Inst), Celgene (Inst), Denovo Biopharma (Inst), Denovo Biopharma (Inst)

Daniel P. Barboriak

Uncompensated Relationships: Blue Earth Diagnosticds

John de Groot

Employment: Alaunos Therapeutics, Brii Biosciences

Stock and Other Ownership Interests: WuXi Biologics, Alaunos Therapeutics, Brii Biosciences

Consulting or Advisory Role: Merck, Mundipharma Research, Bioasis Technologies, InSightec, Samus Therapeutics, Karyopharm Therapeutics, Cure Brain Cancer Foundation, Sapience Therapeutics, Monteris Medical, Kintara Therapeutics, Kazia Therapeutics, CarThera, Sumitomo Dainippon Pharma Oncology, VBI Vaccines, Chimerix, Aucentra Therapeutics, Midatech Pharma, Servier, Telix Pharmaceuticals, Alpha Pharmaceutical

Research Funding: CarThera (Inst), Haihe Pharmaceutical (Inst), Taiho Pharmaceutical (Inst)

Other Relationship: VBI Vaccines, Chimerix

Raymond Huang

Consulting or Advisory Role: Agios, Nuvation Bio, Nuvation Bio, Vysioneer

Research Funding: Agios, Bristol Myers Squibb

Andrew B. Lassman

Honoraria: Clinical Education Alliance

Consulting or Advisory Role: Sapience Therapeutics, Orbus Therapeutics, Novocure, Vivacitas Oncology, Chimerix, Affinia Therapeutics, Neuron-D, Leal Therapeutics, AlphaDetail, AlphaSights, Bluestar Bioadvisors, Clarion Healthcare, ExpertConnect, Gerson Lehrman Group, Guidepoint Global, IP2IPO, KJT, Tavistock Life Sciences, techspert.io, BioClinica, RadMD, Global Coalition for Adaptive Research

Research Funding: AbbVie, Genentech/Roche, Aeterna Zentaris, VBI Vaccines, Pfizer, Karyopharm Therapeutics, Bayer, QED Therapeutics, Orbus Therapeutics, BMS, Chimerix, NextSource, DelMar, Polaris (Inst), Kintara (Inst) Pharmaceuticals, Corden, Kazia Therapeutics, Servier, Biohaven Pharmaceuticals, Vigeo Therapeutics, Incyte, Abbott Laboratories

Travel, Accommodations, Expenses: AbbVie, Chimerix, Karyopharm Therapeutics, Pfizer, Bridgebio, VBI Vaccines, Helsinn Healthcare, Foundation Medicine, Servier, Anheart Therapeutics

Minesh Mehta

Stock and Other Ownership Interests: Chimerix

Consulting or Advisory Role: Mevion Medical Systems, ZappRx, Xoft, Kazia Therapeutics, Novocure

Patents, Royalties, Other Intellectual Property: WARF patent 14/934,27, Topical Vasoconstritor Preparations and Methods for Protecting Cells During Cancer Chemotherapy and Radiotherapy

Uncompensated Relationships: Xcision Medical Systems

Matthias Preusser

Honoraria: Roche, GlaxoSmithKline, Bayer, Bristol Myers Squibb, Novartis, Gerson Lehrman Group, CMC Contrast, Mundipharma, BMJ Journals, MedMedia, AstraZeneca, AbbVie, Lilly, Medahead, Daiichi Sankyo, Sanofi, Merck Sharp & Dome, Tocagen, Adastra Pharmaceuticals, Gan & Lee, Servier

Consulting or Advisory Role: Roche, Bristol Myers Squibb, Novartis, Gerson Lehrman Group, CMC Contrast, GlaxoSmithKline, Mundipharma, AbbVie, Bayer, AstraZeneca, Lilly, Daiichi Sankyo/Astra Zeneca, Sanofi, Merck Sharp & Dome, Tocagen, Adastra Pharmaceuticals, Gan & Lee, Servier

Research Funding: Roche (Inst), GlaxoSmithKline (Inst), Boehringer Ingelheim (Inst), Merck Sharp & Dohme, Bristol Myers Squibb (Inst), Daiichi Sankyo (Inst), AbbVie (Inst)

Travel, Accommodations, Expenses: Roche, GlaxoSmithKline, Bristol Myers Squibb, MSD, Mundipharma, Servier

Rifaquat Rahman

Consulting or Advisory Role: Beijing Saint Lucia Consulting

Research Funding: Bristol Myers Squibb (Inst), Puma Biotechnology (Inst), Lilly (Inst)

Roger Stupp

Stock and Other Ownership Interests: Alpheus Medical, CarThera

Consulting or Advisory Role: Celgene, Northwest Biotherapeutics, Zai Lab, InSightec, Celularity, CranioVation, Triact Therapeutics, Hemispherian, GT Medical Technologies, Novocure, AstraZeneca, Boston Scientific, Carthera, The Lockwood Group, Boston Biomedical, Novartis, AimedBio

Research Funding: CarThera, Bristol Myers Squibb/Celgene (Inst)

Patents, Royalties, Other Intellectual Property: Methods of Determining Responsiveness to Chemotherapeutic Compounds for Cancer Therapy Type: Provisional Serial No. 63/202,761 Filed: June 23, 2021 (Inst)

Javier E. Villanueva-Meyer

Consulting or Advisory Role: GE Healthcare, MedQIA, Alpheus Medical

Research Funding: GE Healthcare

Wolfgang Wick

Consulting or Advisory Role: MSD Oncology (Inst), Roche/Genentech (Inst), SERVIER, GlaxoSmithKline

Research Funding: Roche (Inst), Apogenix (Inst), Pfizer (Inst)

David R. Macdonald

Research Funding: Celgene (Inst), Servier (Inst)

David A. Reardon

Honoraria: Merck, Novocure, Regeneron, Bristol Myers Squibb, Oncorus, Agenus, EMD Serono, Merck KGaA, Taiho Pharmaceutical, Advantagene, Bayer, DelMar Pharmaceuticals, Imvax, Medicenna, Sumitono Dainippon Pharma, Vivacitas Oncology, Anheart Therapeutics, Deciphera, Ellipses Pharma, Genenta Science, Inovio Pharmaceuticals, Kintara Therapeutics, Kintara Therapeutics, KIYATEC, NEUVOGEN, Taiho Pharmaceutical, Y-mAbs Therapeutics

Consulting or Advisory Role: Merck, Novocure, Regeneron, Bristol Myers Squibb, Oncorus, Agenus, EMD Serono, Merck KGaA, Taiho Pharmaceutical, Delmar Pharmaceuticals, Advantagene, Bayer, Imvax, Medicenna, Vivacitas Oncology, Anheart Therapeutics, Ellipses Pharma, Genenta Science, Kintara Therapeutics, Kiyatec, Agios

Research Funding: Celldex (Inst), Incyte (Inst), Agenus (Inst), EMD Serono (Inst), Acerta Pharma (Inst), Omniox, Enterome (Inst)

Michael A. Vogelbaum

Stock and Other Ownership Interests: Infusion Therapeutics

Honoraria: Plus Therapeutics, Chimerix

Consulting or Advisory Role: Olympus, Midatech Pharma

Research Funding: Infusion Therapeutics (Inst), Celgene (Inst), Oncosynergy (Inst), Denovo Biopharma (Inst)

Patents, Royalties, Other Intellectual Property: Patents for drug delivery devices for the brain

Susan M. Chang

Consulting or Advisory Role: AstraZeneca

No other potential conflicts of interest were reported.

COMPANION ARTICLES

No companion articles

ARTICLE CITATION

DOI: 10.1200/JCO.23.01059 Journal of Clinical Oncology 41, no. 33 (November 20, 2023) 5187-5199.

Published online September 29, 2023.

PMID: 37774317

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