Survival benefit for patients with diffuse intrinsic pontine glioma (DIPG) undergoing re-irradiation at first progression: A matched-cohort analysis on behalf of the SIOP-E-HGG/DIPG working group |
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| Affiliation: | 1. Department of Radiation Oncology, University Medical Center Utrecht and Princess Maxima Center for Pediatric Oncology, Utrecht, The Netherlands;2. Pediatric Radiotherapy Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy;3. Department of Radiotherapy, Gustave Roussy Cancer Campus, Villejuif Cedex, France;4. Department of Clinical Oncology, The Royal Marsden NHS Foundation Trust, Sutton, UK;5. Department of Radiation Oncology, Hospital Vall d''Hebron, Barcelona, Spain;6. Department of Radiation Oncology, Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium;7. Department of Clinical Oncology, University Hospital Birmingham, Birmingham, UK;8. Department of Radiation Oncology, Radboud University Medical Centre, Nijmegen, The Netherlands;9. Department of Pediatric Hematology and Oncology, Hospital Sant Joan de Deu, Barcelona, Spain;10. Department of Radiation Therapy, University Hospital Leipzig, Leipzig, Germany;11. Pediatric Oncology Unit, Great Ormond Street Hospital, London, UK;12. Pediatrics Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy;13. Department of Hematology & Oncology, University of Geneva, Geneva, Switzerland;14. Department of Pediatric Hematology & Oncology, University Hospital Goettingen, Goettingen, Germany;15. Department of Pediatric Oncology & Hematology, VU University Medical Center, Amsterdam, The Netherlands;p. Division of Pediatric Neuro-oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany;1. Department of Radiation Oncology, St Jude Children''s Research Hospital, Memphis, Tennessee;3. Department of Diagnostic Imaging, St Jude Children''s Research Hospital, Memphis, Tennessee;4. Department of Biostatistics, St Jude Children''s Research Hospital, Memphis, Tennessee;6. Department of Pathology, St Jude Children''s Research Hospital, Memphis, Tennessee;5. Department of Oncology, St Jude Children''s Research Hospital, Memphis, Tennessee;2. College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee;1. Institute for Biomedical Sciences, George Washington University School of Medicine, Washington, DC, USA;2. Research Center for Genetic Medicine, Children''s National Health System, Washington, DC, USA;3. Department of Neurosurgery, Georgetown University School of Medicine, Washington, DC, USA;4. Division of Oncology, Center for Cancer and Immunology Research, Children''s National Health System, Washington, DC, USA;5. Brain Tumor Institute, Center for Neuroscience and Behavioral Medicine, Children''s National Health System, Washington, DC, USA;6. Department of Integrative Systems Biology, George Washington University School of Medicine and Health Sciences, Washington, DC, USA;1. University of Tennessee West Cancer Center, Department of Radiation Oncology, Germantown, USA;2. St. Jude Children’s Research Hospital, Department of Radiation Oncology, Memphis, USA;3. Emory University Winship Cancer Institute, Department of Radiation Oncology, Atlanta, USA;4. University of Tennessee, College of Medicine, Memphis, USA;5. St. Jude Children’s Research Hospital, Department of Pediatric Oncology, Memphis, USA;6. St. Jude Children’s Research Hospital, Department of Surgery, Memphis, USA;1. Department of Radiation Oncology, Radboud University Medical Center, Nijmegen, Netherlands;2. Department of Radiation Oncology, Centre Léon Bérard, Lyon, France;3. Department of Particle Therapy, University Hospital Essen, West German Proton Therapy Centre Essen, West German Cancer Center, German Cancer Consortium, Essen, Germany;4. Department of Radiotherapy, Royal Marsden Hospital, Sutton, UK;5. Pediatric Radiotherapy Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy;6. Department of Radiation Oncology, Universität Klinik für Strahlentherapie und Strahlenbiologie, Vienna, Austria;7. Hospital Universitari de la Vall d''Hebron, Barcelona, Spain;8. Department of Oncology, Oslo University Hospital (Norwegian Radium Hospital), Oslo, Norway;9. Danish Centre for Particle Therapy, Aarhus University Hospital, Aarhus, Denmark;10. Proton Therapy Center Czech, Prague, Czech Republic;11. Department of Oncology, Cambridge University Hospitals, Cambridge, UK;12. Department of Radiation Oncology, Institut Curie, Paris and Orsay, France;13. Department of Radiation Oncology, Academic Medical Center, Amsterdam, Netherlands;14. Department of Radiation Oncology, Gustave Roussy, Villejuif, France;15. Bristol Haematology and Oncology Centre, University Hospitals Bristol NHS Foundation Trust, Bristol, UK;p. Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, Netherlands;q. Princess Maxima Center for Pediatric Oncology, Utrecht, Netherlands;r. Department of Radiation Oncology, University of Leipzig, Leipzig, Germany;s. Department of Radiation Oncology, Centre François Baclesse, Caen, France;t. Department of Radiation Oncology, Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse-Oncopole, Toulouse, France;u. Toulouse NeuroImaging Center, ToNIC, INSERM Université Toulouse III Paul Sabatier, Toulouse, France;v. Department of Radiation Oncology, Saarland University Hospital, Homburg, Germany;w. Department of Radiation Oncology, Assistance Publique Hôpitaux de Marseille, Marseille, France;x. Proton Therapy Center, Santa Chiara Hospital, Trento, Italy;y. Radiotherapy Department, Istituto Oncologico Veneto IRCCS, Padua, Italy;z. Department of Radiation Oncology, Medical Center Hamburg-Eppendorf, Hamburg, Germany;11. Department of Oncology, Clatterbridge Cancer Centre, Liverpool, UK;12. Manchester Academic Health Science Centre, University of Manchester, The Christie NHS Foundation Trust, Manchester, UK;13. The Children''s Brain Tumour Research Network, University of Manchester, Royal Manchester Children''s Hospital, Manchester, UK;14. Department of Radiation Oncology, Ghent University Hospital, Ghent, Belgium;1. Department of Radiation and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center Johns Hopkins School of Medicine, Baltimore, Maryland;2. Department of Radiation Oncology, Centro Infantil Boldrini, São Paulo, Brazil;3. Department of Radiation Oncology, Federal Research and Clinical Centre of Pediatric Hematology, Oncology and Immunology, Moscow, Russia;4. Department of Radiation Oncology, Uppsala University Hospital, Uppsala, Sweden;6. Department of Radiation Oncology, Universitätklinik Für Strahlentherapie und Strahlenbiologie, Wien, Germany;5. Department of Radiation Oncology, University of Washington, Seattle, Washington;7. Department of Radiation Oncology, Grupo de Apoio ao Adolescente e à Criança com Câncer, São Paulo, Brazil |
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| Abstract: | BackgroundOverall survival (OS) of patients with diffuse intrinsic pontine glioma (DIPG) is poor. The purpose of this study is to analyse benefit and toxicity of re-irradiation at first progression.MethodsAt first progression, 31 children with DIPG, aged 2–16 years, underwent re-irradiation (dose 19.8–30.0 Gy) alone (n = 16) or combined with systemic therapy (n = 15). At initial presentation, all patients had typical symptoms and characteristic MRI features of DIPG, or biopsy-proven high-grade glioma. An interval of ≥3 months after upfront radiotherapy was required before re-irradiation. Thirty-nine patients fulfilling the same criteria receiving radiotherapy at diagnosis, followed by best supportive care (n = 20) or systemic therapy (n = 19) at progression but no re-irradiation, were eligible for a matched-cohort analysis.ResultsMedian OS for patients undergoing re-irradiation was 13.7 months. For a similar median progression-free survival after upfront radiotherapy (8.2 versus 7.7 months; P = .58), a significant benefit in median OS (13.7 versus 10.3 months; P = .04) was observed in favour of patients undergoing re-irradiation. Survival benefit of re-irradiation increased with a longer interval between end-of-radiotherapy and first progression (3–6 months: 4.0 versus 2.7; P < .01; 6–12 months: 6.4 versus 3.3; P = .04). Clinical improvement with re-irradiation was observed in 24/31 (77%) patients. No grade 4–5 toxicity was recorded. On multivariable analysis, interval to progression (corrected hazard ratio = .27–.54; P < .01) and re-irradiation (corrected hazard ratio = .18–.22; P < .01) remained prognostic for survival. A risk score (RS), comprising 5 categories, was developed to predict survival from first progression (ROC: .79). Median survival ranges from 1.0 month (RS-1) to 6.7 months (RS-5).ConclusionsThe majority of patients with DIPG, responding to upfront radiotherapy, do benefit of re-irradiation with acceptable tolerability. |
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| Keywords: | Diffuse intrinsic pontine glioma (DIPG) Radiotherapy Re-irradiation Matched-cohort analysis Survival prediction model |
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