RANO 2.0: Proposal for an update to the Response Assessment in Neuro-Oncology (RANO) Criteria for high- and low-grade gliomas in adults.

person Patrick Y. Wen Dana-Farber Cancer Institute, Boston, MA info_outline Patrick Y. Wen, Martin J. Van Den Bent, Gilbert Youssef, Timothy Francis Cloughesy, Benjamin M. Ellingson, Michael Weller, Evanthia Galanis, Daniel Barboriak, John Frederick de Groot, Mark R. Gilbert, Raymond Yi-kun Huang, Andrew B. Lassman, Minesh P. Mehta, Annette Molinaro, Matthias Preusser, Lalitha Krishna Shankar, Wolfgang Wick, David A. Reardon, Michael A. Vogelbaum, Susan Marina Chang

Authors person Patrick Y. Wen Dana-Farber Cancer Institute, Boston, MA info_outline Patrick Y. Wen, Martin J. Van Den Bent, Gilbert Youssef, Timothy Francis Cloughesy, Benjamin M. Ellingson, Michael Weller, Evanthia Galanis, Daniel Barboriak, John Frederick de Groot, Mark R. Gilbert, Raymond Yi-kun Huang, Andrew B. Lassman, Minesh P. Mehta, Annette Molinaro, Matthias Preusser, Lalitha Krishna Shankar, Wolfgang Wick, David A. Reardon, Michael A. Vogelbaum, Susan Marina Chang Organizations Dana-Farber Cancer Institute, Boston, MA, Erasmus MC Cancer Institute, Rotterdam, Netherlands, Ronald Reagan UCLA Medical Center, Los Angeles, CA, Department of Radiology, Radiology, Brain Research Institute, University of California, Los Angeles, Los Angeles, CA, Department of Neurology, University Hospital and University of Zurich, Zürich, Switzerland, Mayo Clinic, Rochester, MN, Duke University, Durham, NC, University of California, San Francisco, San Francisco, CA, National Cancer Institute/National Institutes of Health, Bethesda, MD, Brigham and Women's Hospital, Boston, MA, Neuro-Oncology, Columbia University, New York, NY, Miami Cancer Institute, Baptist Health South Florida, Miami, FL, University of California San Francisco, San Francisco, CA, Division of Oncology, Department of Medicine I, Medical University of Vienna, Vienna, Vienna, Austria, National Cancer Institute, Bethesda, MD, University of Heidelberg, Heidelberg, Germany, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, Department of Neurosurgery & Division of Neuro-Oncology, University of San Francisco, San Francisco, CA Abstract Disclosures Research Funding No funding received None. Background: Response Assessment in Neuro-Oncology (RANO) criteria for high-grade and low-grade glioma (HGG and LGG) were developed to improve reliability of response assessment in glioma trials. Several limitations of the original RANO criteria have been reported. Methods: To address limitations of the original RANO criteria, a large cohort of patients with newly diagnosed and recurrent glioblastoma were evaluated comparing RANO-HGG with modified RANO (mRANO) and immunotherapy RANO (iRANO) criteria to inform the following proposed updates (RANO 2.0). Results: Based on the 2021 WHO classification of glioma, we recommend a single common set of criteria for all gliomas regardless of WHO grade and IDH mutational status. These criteria will be used for all trials regardless of the treatment modalities being evaluated. In newly diagnosed glioblastoma, the post-radiotherapy MRI, usually obtained approximately 4 weeks after completion of radiotherapy, rather than the post-surgical MRI as proposed in original RANO criteria, will be used as the baseline for comparison of subsequent scans. Since the incidence of pseudoprogression is high in the first 3 months following radiotherapy, confirmation of progression during this period with a repeat MRI (in 4-8 weeks) will be required for determining radiographic progression of disease (PD) if the patient is clinically stable. However, confirmation scans are not mandatory after this period nor for recurrent tumors since these scans do not appear to improve reliability in determining progression. For agents with a high likelihood of producing pseudoprogression such as viral therapies and some other immunotherapies, mandatory confirmation of progression with a repeat MRI is an option. The primary measurement will remain the 2-dimensional maximum cross-sectional area of tumor as the simplest method, but where resources are available, volumetric measurements are an option. For IDH wild-type tumors with contrast enhancement, non-enhancing tumor will no longer be evaluated with the possible exception of patients receiving antiangiogenic therapies. However, in tumors with a significant non-enhancing component, both the contrast enhancing and non-enhancing components will be evaluated as target lesions. Conclusions: We hope that these and other proposed changes by the RANO working group will improve response assessment in glioma clinical trials and help the development of more effective therapy for patients.