Liquid biopsy in gliomas: A RANO review and proposals for clinical applications


Riccardo Soffietti, Division of Neuro-Oncology, Department of Neuroscience, University and City of Health and Science Hospital, Turin, Italy.
Chetan Bettegowda, Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Ingo K. Mellinghoff, Department of Neurology, Memorial Sloan Kettering Cancer Center New York, USA.
Katherine E. Warren, Department of Pediatric Oncology, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Manmeet S. Ahluwalia, Brain Tumor and Neuro-Oncology Center, Cleveland Clinic, Cleveland, Ohio, USA.
John F. De Groot, Department of Neuro-Oncology, University of Texas, MD Anderson Cancer Center Houston, Houston, Texas, USA.
Evanthia Galanis, Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota, USA.
Mark R. Gilbert, Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Kurt A. Jaeckle, Department of Neurology, Mayo Clinic Florida, Jacksonville, Florida, USA.
Emilie Le Rhun, Departments of Neurology & Neurosurgery, Clinical Neuroscience Center, University Hospital and University of Zurich, Zurich, Switzerland.
Roberta Rudà, Department of Neurology, Castelfranco Veneto/Treviso Hospital and Division of Neuro-Oncology, Department of Neuroscience, University of Turin, Turin, Italy.
Joan Seoane, Vall d'Hebron Institute of Oncology (VHIO) University Hospital, Universitat Autònoma de Barcelona, ICREA,CIBERONC, Barcelona, Spain.
Niklas Thon, Division of Neuro-Oncology, Department of Neurosurgery, Ludwig Maximilians University School of Medicine, Munich, Germany.
Yoshie Umemura, Division of Neuro-Oncology, Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA.
Michael Weller, Department of Neurology, Clinical Neuroscience Center, University Hospital and University of Zurich, Zurich, Switzerland.
Martin J. van den Bent, Department of Neurology, Brain Tumor Center at Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Michael A. Vogelbaum, Department of Neurosurgery, Cleveland Clinic, Cleveland, Ohio, USA.
Susan M. Chang, Division of Neuro-Oncology, University of California San Francisco, San Francisco, California, USA.
Patrick Y. Wen, Center for Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School, Boston, Massachusetts, USA.

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BACKGROUND: There is an extensive literature highlighting the utility of blood-based liquid biopsies in several extracranial tumors for diagnosis and monitoring. METHODS: The RANO (Response Assessment in Neuro-Oncology) group developed a multidisciplinary international Task Force to review the English literature on liquid biopsy in gliomas focusing on the most frequently used techniques, that is circulating tumor DNA, circulating tumor cells, and extracellular vesicles in blood and CSF. RESULTS: ctDNA has a higher sensitivity and capacity to represent the spatial and temporal heterogeneity in comparison to circulating tumor cells. Exosomes have the advantages to cross an intact blood-brain barrier and carry also RNA, miRNA, and proteins. Several clinical applications of liquid biopsies are suggested: to establish a diagnosis when tissue is not available, monitor the residual disease after surgery, distinguish progression from pseudoprogression, and predict the outcome. CONCLUSIONS: There is a need for standardization of biofluid collection, choice of an analyte, and detection strategies along with rigorous testing in future clinical trials to validate findings and enable entry into clinical practice.

Medical Subject Headings

Biomarkers, Tumor; Circulating Tumor DNA (genetics); DNA, Neoplasm; Glioma (diagnosis); Humans; Liquid Biopsy (methods); Neoplastic Cells, Circulating (metabolism)

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