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      Resistance, rebound, and recurrence regrowth patterns in pediatric low-grade glioma treated by MAPK inhibition: A modified Delphi approach to build international consensus-based definitions—International Pediatric Low-Grade Glioma Coalition

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          Abstract

          Pediatric low-grade glioma (pLGG) is the most common childhood brain tumor group. The natural history, when curative resection is not possible, is one of a chronic disease with periods of tumor stability and episodes of tumor progression. While there is a high overall survival rate, many patients experience significant and potentially lifelong morbidities. The majority of pLGGs have an underlying activation of the RAS/MAPK pathway due to mutational events, leading to the use of molecularly targeted therapies in clinical trials, with recent regulatory approval for the combination of BRAF and MEK inhibition for BRAFV600E mutated pLGG. Despite encouraging activity, tumor regrowth can occur during therapy due to drug resistance, off treatment as tumor recurrence, or as reported in some patients as a rapid rebound growth within 3 months of discontinuing targeted therapy. Definitions of these patterns of regrowth have not been well described in pLGG. For this reason, the International Pediatric Low-Grade Glioma Coalition, a global group of physicians and scientists, formed the Resistance, Rebound, and Recurrence (R3) working group to study resistance, rebound, and recurrence. A modified Delphi approach was undertaken to produce consensus-based definitions and recommendations for regrowth patterns in pLGG with specific reference to targeted therapies.

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          Most cited references48

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          iRECIST: guidelines for response criteria for use in trials testing immunotherapeutics

          Tumours respond differently to immunotherapies compared with chemotherapeutic drugs, raising questions about the assessment of changes in tumour burden—a mainstay of evaluation of cancer therapeutics that provides key information about objective response and disease progression. A consensus guideline—iRECIST—was developed by the RECIST working group for the use of modified Response Evaluation Criteria in Solid Tumours (RECIST version 1.1) in cancer immunotherapy trials, to ensure consistent design and data collection, facilitate the ongoing collection of trial data, and ultimate validation of the guideline. This guideline describes a standard approach to solid tumour measurements and definitions for objective change in tumour size for use in trials in which an immunotherapy is used. Additionally, it defines the minimum datapoints required from future trials and those currently in development to facilitate the compilation of a data warehouse to use to later validate iRECIST. An unprecedented number of trials have been done, initiated, or are planned to test new immune modulators for cancer therapy using a variety of modified response criteria. This guideline will allow consistent conduct, interpretation, and analysis of trials of immunotherapies.
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            Research guidelines for the Delphi survey technique.

            Consensus methods such as the Delphi survey technique are being employed to help enhance effective decision-making in health and social care. The Delphi survey is a group facilitation technique, which is an iterative multistage process, designed to transform opinion into group consensus. It is a flexible approach, that is used commonly within the health and social sciences, yet little guidance exists to help researchers undertake this method of data collection. This paper aims to provide an understanding of the preparation, action steps and difficulties that are inherent within the Delphi. Used systematically and rigorously, the Delphi can contribute significantly to broadening knowledge within the nursing profession. However, careful thought must be given before using the method; there are key issues surrounding problem identification, researcher skills and data presentation that must be addressed. The paper does not claim to be definitive; it purports to act as a guide for those researchers who wish to exploit the Delphi methodology.
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              An Experimental Application of the DELPHI Method to the Use of Experts

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                Author and article information

                Contributors
                Journal
                Neuro Oncol
                Neuro Oncol
                neuonc
                Neuro-Oncology
                Oxford University Press (US )
                1522-8517
                1523-5866
                August 2024
                14 May 2024
                14 May 2024
                : 26
                : 8
                : 1357-1366
                Affiliations
                Department of Paediatric Oncology, Royal Belfast Hospital for Sick Children , Northern Ireland, UK
                Dana-Farber/Boston Children’s Cancer and Blood Disorders Center , Boston, Massachusetts, USA
                Department of Pediatrics, Harvard Medical School, Broad Institute , Cambridge, Massachusetts, USA
                Day One Biopharmaceuticals , Boston, Massachusetts, USA
                Dana-Farber/Boston Children’s Cancer and Blood Disorders Center , Boston, Massachusetts, USA
                Department of Pediatrics, Harvard Medical School, Broad Institute , Cambridge, Massachusetts, USA
                University of Cincinnati College of Medicine and Cincinnati Children’s Hospital Medical Center , Cincinnati, Ohio, USA
                Department of Neurology, Washington University School of Medicine , St. Louis, Missouri, USA
                Day One Biopharmaceuticals , Boston, Massachusetts, USA
                Clinical Pediatric Oncology, Hopp Children’s Cancer Center (KiTZ) , Heidelberg, Germany
                Heidelberg University Hospital, Heidelberg , Germany
                German Cancer Research Center, National Center for Tumor Diseases (NCT) , Heidelberg, Germany
                Aflac Cancer and Blood Disorders Center, Children’s Healthcare of Atlanta and Emory University School of Medicine , Atlanta, Georgia, USA
                Division of Oncology, The Children’s Hospital of Philadelphia , Philadelphia, Pennsylvania, USA
                Department of Radiology, Alder Hey Children’s NHS Foundation Trust , Liverpool, UK
                Brain Tumor Institute, Center for Neuroscience and Behavioral Medicine, Children’s National Hospital , Washington, District of Columbia, USA
                Department of Hematology/Oncology, Saitama Children’s Medical Center , Saitama, Japan
                Department of Radiology, Great Ormond Street Hospital for Children NHS Foundation Trust, Department of Radiology , London, UK
                Department of Neurology, Neurosurgery and Pediatrics, University of California, San Francisco , San Francisco, California, USA
                Department of Pediatrics, Northwestern University Feinberg School of Medicine , Chicago, Illinois, USA
                Paediatric Haematology, Oncology and Stem Cell Transplant Division, Padua University Hospital , Padua, Italy
                The Hospital for Sick Children and Department of Paediatrics, University of Toronto , Toronto, Ontario, Canada
                Division of Pediatric Oncology, Department of Oncology, Johns Hopkins University School of Medicine , Baltimore, Maryland, USA
                Department of Pathology, Johns Hopkins University School of Medicine , Baltimore, Maryland, USA
                Pediatric Onco-Hematology Department, University Hospital of Strasbourg. UMR CNRS 7021, University of Strasbourg , Strasbourg, France
                Department of Pediatrics and Adolescent Medicine and Comprehensive Centre of Pediatrics, Medical University of Vienna , Vienna, Austria
                Division of Hematology & Oncology, Children’s Hospital Los Angeles, University of Southern California Keck School of Medicine , Los Angeles, California, USA
                Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, German HIT-LOGGIC-Registry for LGG in children and adolescents, Department of Pediatric Oncology/Hematology , Berlin, Germany
                Novartis Pharmaceuticals Corporation, East Hanover , New Jersey, USA
                Princess Maxima Center for Pediatric Oncology , Utrecht, Netherlands
                Clinical Pediatric Oncology, Hopp Children’s Cancer Center (KiTZ) , Heidelberg, Germany
                Heidelberg University Hospital, Heidelberg , Germany
                German Cancer Research Center, National Center for Tumor Diseases (NCT) , Heidelberg, Germany
                Department of Paediatrics and Adolescent Medicine, The University Hospital Rigshospitalet , Copenhagen, Denmark
                Department of Pediatric and Adolescent Oncology , Villejuif, France
                Dana-Farber/Boston Children’s Cancer and Blood Disorders Center , Boston, Massachusetts, USA
                Department of Pediatrics, Harvard Medical School, Broad Institute , Cambridge, Massachusetts, USA
                The Centre for Paediatric, Teenage and Young Adult Cancer, Institute of Cancer Sciences, University of Manchester, and Royal Manchester Children’s Hospital , Manchester, UK
                Clinical Pediatric Oncology, Hopp Children’s Cancer Center (KiTZ) , Heidelberg, Germany
                Heidelberg University Hospital, Heidelberg , Germany
                German Cancer Research Center, National Center for Tumor Diseases (NCT) , Heidelberg, Germany
                Department of Neurosurgery, The Preston Robert Tisch Brain Tumor Center. Pediatric Neuro-Oncology, Preuss Laboratory for Brain Tumor Research, Durham , North Carolina, USA
                Department of Diagnostic Imaging, The Hospital for Sick Children , Toronto, Ontario, Canada
                The Hospital for Sick Children and Department of Paediatrics, University of Toronto , Toronto, Ontario, Canada
                UCL Great Ormond Street Institute of Child Health, Great Ormond Street Hospital for Children , London, UK
                Author notes
                Corresponding Author: Darren Hargrave, MB.ChB (Hons), MRCP, FRCPCH, MD, UCL Great Ormond Street Institute of Child Health, Great Ormond Street Hospital for Children, Great Ormond Street, LONDON, WC1N 3JH, UK ( d.hargrave@ 123456ucl.ac.uk ).

                Uri Tabori and Darren R. Hargrave Authors contributed equally.

                Author information
                https://orcid.org/0000-0003-2568-0877
                https://orcid.org/0000-0002-6832-6539
                https://orcid.org/0000-0003-4773-3001
                https://orcid.org/0000-0002-0539-215X
                https://orcid.org/0000-0002-5019-2683
                https://orcid.org/0000-0001-8219-9807
                Article
                noae074
                10.1093/neuonc/noae074
                11300023
                38743009
                7beb3cf6-6bd5-4912-8da6-4654f6ae3807
                © The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Page count
                Pages: 10
                Funding
                Funded by: National Institute for Health Research/Biomedical Research Center at Great Ormond Street Hospital for Children;
                Funded by: NHS Foundation Trust;
                Funded by: University College London, DOI 10.13039/501100000765;
                Categories
                Consensus Reviews
                AcademicSubjects/MED00300
                AcademicSubjects/MED00310
                Editor's Choice

                Oncology & Radiotherapy
                child,low-grade glioma,mapk,pediatric brain tumor,rebound,resistance,recurrence
                Oncology & Radiotherapy
                child, low-grade glioma, mapk, pediatric brain tumor, rebound, resistance, recurrence

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