Cancers (Jul 2021)
Development of Randomized Trials in Adults with Medulloblastoma—The Example of EORTC 1634-BTG/NOA-23
- Peter Hau,
- Didier Frappaz,
- Elizabeth Hovey,
- Martin G. McCabe,
- Kristian W. Pajtler,
- Benedikt Wiestler,
- Clemens Seidel,
- Stephanie E. Combs,
- Linda Dirven,
- Martin Klein,
- Antoinette Anazodo,
- Elke Hattingen,
- Silvia Hofer,
- Stefan M. Pfister,
- Claus Zimmer,
- Rolf-Dieter Kortmann,
- Marie-Pierre Sunyach,
- Ronan Tanguy,
- Rachel Effeney,
- Andreas von Deimling,
- Felix Sahm,
- Stefan Rutkowski,
- Anna S. Berghoff,
- Enrico Franceschi,
- Estela Pineda,
- Dagmar Beier,
- Ellen Peeters,
- Thierry Gorlia,
- Maureen Vanlancker,
- Jacoline E. C. Bromberg,
- Julien Gautier,
- David S. Ziegler,
- Matthias Preusser,
- Wolfgang Wick,
- Michael Weller
Affiliations
- Peter Hau
- Wilhelm Sander-NeuroOncology Unit, Regensburg University Hospital, 93053 Regensburg, Germany
- Didier Frappaz
- Neuro-Oncology Unit, Centre Léon Bérard, 69008 Lyon, France
- Elizabeth Hovey
- Department of Medical Oncology, Sydney 2052, Australia
- Martin G. McCabe
- Faculty of Medicine, Biology and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester M20 4GJ, UK
- Kristian W. Pajtler
- Hopp-Children’s Cancer Center Heidelberg (KiTZ), Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
- Benedikt Wiestler
- Department of Diagnostic and Interventional Neuroradiology, Klinikum Rechts der Isar der Technischen Universität München, TUM School of Medicine, 81675 Munich, Germany
- Clemens Seidel
- Department of Radiation-Oncology, University Hospital Leipzig, 04103 Leipzig, Germany
- Stephanie E. Combs
- Department of Radiation Oncology, Klinikum Rechts der Isar der Technischen Universität München, TUM School of Medicine, 81675 Munich, Germany
- Linda Dirven
- Department of Neurology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands
- Martin Klein
- Department of Medical Psychology, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands
- Antoinette Anazodo
- Nelune Comprehensive Cancer Centre, Prince of Wales Cancer Centre, Sydney 2031, Australia
- Elke Hattingen
- Department of Neuroradiology, University Hospital Frankfurt, Goethe University, 60528 Frankfurt, Germany
- Silvia Hofer
- Department of Neurology, University Hospital Zurich, 8091 Zurich, Switzerland
- Stefan M. Pfister
- Hopp-Children’s Cancer Center Heidelberg (KiTZ), Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
- Claus Zimmer
- Department of Diagnostic and Interventional Neuroradiology, Klinikum Rechts der Isar der Technischen Universität München, TUM School of Medicine, 81675 Munich, Germany
- Rolf-Dieter Kortmann
- Department of Radiation-Oncology, University Hospital Leipzig, 04103 Leipzig, Germany
- Marie-Pierre Sunyach
- Department of Radiation Oncology, Centre Leon Berard, 69008 Lyon, France
- Ronan Tanguy
- Department of Radiation Oncology, Centre Leon Berard, 69008 Lyon, France
- Rachel Effeney
- Department of Radiation Oncology, Royal Brisbane and Women’s Hospital, Brisbane 4029, Australia
- Andreas von Deimling
- Department of Neuropathology, University Hospital Heidelberg, 69120 Heidelberg, Germany
- Felix Sahm
- Department of Neuropathology, University Hospital Heidelberg, 69120 Heidelberg, Germany
- Stefan Rutkowski
- Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
- Anna S. Berghoff
- Division of Oncology, Department of Medicine I, Medical University of Vienna, 1090 Vienna, Austria
- Enrico Franceschi
- Medical Oncology Department, Azienda USL/IRCCS Institute of Neurological Sciences, 40139 Bologna, Italy
- Estela Pineda
- Barcelona Translational Genomics and Targeted Therapeutics in Solid Tumors Group, Department of Medical Oncology, Hospital Clinic Barcelona, 08036 Barcelona, Spain
- Dagmar Beier
- Department of Neurology, Odense University Hospital, DK-5000 Odense, Denmark
- Ellen Peeters
- EORTC Headquarters, 1200 Brussels, Belgium
- Thierry Gorlia
- EORTC Headquarters, 1200 Brussels, Belgium
- Maureen Vanlancker
- EORTC Headquarters, 1200 Brussels, Belgium
- Jacoline E. C. Bromberg
- Erasmus Medical Center Cancer Institute, Department of Neuro-Oncology, 3015 GD Rotterdam, The Netherlands
- Julien Gautier
- Clinical Research Department, Centre Léon Bérard, 69008 Lyon, France
- David S. Ziegler
- Kids Cancer Centre, Sydney Children’s Hospital, Sydney 2031, Australia
- Matthias Preusser
- Division of Oncology, Department of Medicine I, Medical University of Vienna, 1090 Vienna, Austria
- Wolfgang Wick
- Department of Neurology, University Hospital Heidelberg, 69120 Heidelberg, Germany
- Michael Weller
- Department of Neurology, University Hospital Zurich, 8091 Zurich, Switzerland
- DOI
- https://doi.org/10.3390/cancers13143451
- Journal volume & issue
-
Vol. 13,
no. 14
p. 3451
Abstract
Medulloblastoma is a rare brain malignancy. Patients after puberty are rare and bear an intermediate prognosis. Standard treatment consists of maximal resection plus radio-chemotherapy. Treatment toxicity is high and produces disabling long-term side effects. The sonic hedgehog (SHH) subgroup is highly overrepresented in the post-pubertal and adult population and can be targeted by smoothened (SMO) inhibitors. No practice-changing prospective randomized data have been generated in adults. The EORTC 1634-BTG/NOA-23 trial will randomize patients between standard-dose vs. reduced-dosed craniospinal radiotherapy and SHH-subgroup patients between the SMO inhibitor sonidegib (OdomzoTM, Sun Pharmaceuticals Industries, Inc., New York, USA) in addition to standard radio-chemotherapy vs. standard radio-chemotherapy alone to improve outcomes in view of decreased radiotherapy-related toxicity and increased efficacy. We will further investigate tumor tissue, blood, and cerebrospinal fluid as well as magnetic resonance imaging and radiotherapy plans to generate information that helps to further improve treatment outcomes. Given that treatment side effects typically occur late, long-term follow-up will monitor classic side effects of therapy, but also health-related quality of life, cognition, social and professional outcome, and reproduction and fertility. In summary, we will generate unprecedented data that will be translated into treatment changes in post-pubertal patients with medulloblastoma and will help to design future clinical trials.
Keywords