Open Access

Peter Hau, Didier Frappaz, Elizabeth Hovey, Martin G. McCabe, Kristian Wilfried Pajtler, Benedikt Wiestler, Clemens Seidel, Stephanie Combs, Linda Dirven, Martin Klein, Antoinette Anazodo, Elke Hattingen, Silvia Hofer, Stefan Pfister, Claus Zimmer, Rolf-Dieter Kortmann, Marie-Pierre Sunyach, Ronan Tanguy, Rachel Effeney, Andreas von Deimling, Felix Sahm, Stefan Rutkowski, Anna 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

• 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.