title: Immunotherapy response assessment in neuro-oncology: a report of the RANO working group.
abstract: Immunotherapy is a promising area of therapy in patients with neuro-oncological malignancies. However, early-phase studies show unique challenges associated with the assessment of radiological changes in response to immunotherapy reflecting delayed responses or therapy-induced inflammation. Clinical benefit, including long-term survival and tumour regression, can still occur after initial disease progression or after the appearance of new lesions. Refinement of the response assessment criteria for patients with neuro-oncological malignancies undergoing immunotherapy is therefore warranted. Herein, a multinational and multidisciplinary panel of neuro-oncology immunotherapy experts describe immunotherapy Response Assessment for Neuro-Oncology (iRANO) criteria based on guidance for the determination of tumour progression outlined by the immune-related response criteria and the RANO working group. Among patients who demonstrate imaging findings meeting RANO criteria for progressive disease within 6 months of initiating immunotherapy, including the development of new lesions, confirmation of radiographic progression on follow-up imaging is recommended provided that the patient is not significantly worse clinically. The proposed criteria also include guidelines for the use of corticosteroids. We review the role of advanced imaging techniques and the role of measurement of clinical benefit endpoints including neurological and immunological functions. The iRANO guidelines put forth in this Review will evolve successively to improve their usefulness as further experience from immunotherapy trials in neuro-oncology accumulate.
authors.affiliation: Department of Neurological Surgery, University of California, San Francisco, CA, USA. Electronic address: hideho.okada@ucsf.edu.
authors.forename: Hideho
authors.initials: H
authors.lastname: Okada
authors.affiliation: Department of Neurology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Weller
authors.affiliation: Department of Radiology, Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: Raymond
authors.initials: R
authors.lastname: Huang
authors.affiliation: Department of Neuro-Oncology, Istituto Neurologico Besta, Milan, Italy.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Finocchiaro
authors.affiliation: Neuro-Oncology Branch, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Gilbert
authors.affiliation: Department of Neurooncology, Heidelberg University Hospital, Heidelberg, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wick
authors.affiliation: Departments of Radiological Sciences, Bioengineering, Biomedical Physics, and Psychiatry, David Geffen School of Medicine University of California, Los Angeles, CA, USA.
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Ellingson
authors.affiliation: Department of Neurosurgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Hashimoto
authors.affiliation: Department of Neurological Surgery, University of Pittsburgh School of Medicine, Children's Hospital of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Ian F
authors.initials: IF
authors.lastname: Pollack
authors.affiliation: Department of Medical Oncology, Azienda USL-IRCCS Institute of Neurological Science, Bologna, Italy.
authors.forename: Alba A
authors.initials: AA
authors.lastname: Brandes
authors.affiliation: Department of Medical Oncology, Azienda USL-IRCCS Institute of Neurological Science, Bologna, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Franceschi
authors.affiliation: Department of Neurosurgery, Division of Experimental Neurosurgery, Heidelberg University Hospital, Heidelberg, Germany.
authors.forename: Christel
authors.initials: C
authors.lastname: Herold-Mende
authors.affiliation: Center for Neuro Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Nayak
authors.affiliation: Department of Radiology, University of Pittsburgh School of Medicine, Children's Hospital of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Ashok
authors.initials: A
authors.lastname: Panigrahy
authors.affiliation: Department of Radiology, David Geffen School of Medicine University of California, Los Angeles, CA, USA.
authors.forename: Whitney B
authors.initials: WB
authors.lastname: Pope
authors.affiliation: Department of Neurosurgery, David Geffen School of Medicine University of California, Los Angeles, CA, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Prins
authors.affiliation: Department of Neurosurgery, Duke University School of Medicine, Durham, NC, USA.
authors.forename: John H
authors.initials: JH
authors.lastname: Sampson
authors.affiliation: Center for Neuro Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
authors.forename: Patrick Y
authors.initials: PY
authors.lastname: Wen
authors.affiliation: Center for Neuro Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Reardon
mesh_terms: D000465:Algorithms; D018450:Disease Progression; D006801:Humans; D007167:Immunotherapy; D009423:Nervous System Neoplasms / Q000175:diagnosis / Q000628:therapy*; D017410:Practice Guidelines as Topic