Development of Randomized Trials in Adults with Medulloblastoma—The Example of EORTC 1634-BTG/NOA-23
Creators: name: Hau, Peter
name: Frappaz, Didier
name: Hovey, Elizabeth
name: McCabe, Martin G.
name: Pajtler, Kristian W.
name: Wiestler, Benedikt
name: Seidel, Clemens
name: Combs, Stephanie E.
name: Dirven, Linda
name: Klein, Martin
name: Anazodo, Antoinette
name: Hattingen, Elke
name: Hofer, Silvia
name: Pfister, Stefan M.
name: Zimmer, Claus
name: Kortmann, Rolf-Dieter
name: Sunyach, Marie-Pierre
name: Tanguy, Ronan
name: Effeney, Rachel
name: von Deimling, Andreas
name: Sahm, Felix
name: Rutkowski, Stefan
name: Berghoff, Anna S.
name: Franceschi, Enrico
name: Pineda, Estela
name: Beier, Dagmar
name: Peeters, Ellen
name: Gorlia, Thierry
name: Vanlancker, Maureen
name: Bromberg, Jacoline E. C.
name: Gautier, Julien
name: Ziegler, David S.
name: Preusser, Matthias
name: Wick, Wolfgang
name: Weller, Michael
Publisher: name: Universität Regensburg
Year: 2021
Subjects: subject: medulloblastoma; adult; clinical trial; randomized; subgrouping; cerebrospinal fluid; magnetic resonance imaging; radiotherapy; chemotherapy; targeted therapy
subject: 610 Medizin

description: Simple Summary Medulloblastoma is rare after puberty. Among several molecular subgroups that have been described, the sonic hedgehog (SHH) subgroup is highly overrepresented in the post-pubertal population and can be targeted with smoothened (SMO) inhibitors. However, no practice-changing prospective clinical trials have been published in adults to date. Tumors often recur, and treatment toxicity is relevant. Thus, the EORTC 1634-BTG/NOA-23 trial for post-pubertal patients with standard risk medulloblastoma will aim to increase treatment efficacy and to decrease treatment toxicity. Patients will be randomized between standard-dose vs. reduced-dosed radiotherapy, and SHH-subgroup patients will also be randomized between the SMO inhibitor sonidegib (OdomzoTM,, Sun Pharmaceuticals Industries, Inc., New York, USA) in addition to standard radio-chemotherapy vs. standard radio-chemotherapy alone. In ancillary studies, we will investigate tumor tissue, blood and cerebrospinal fluid samples, magnetic resonance images, and radiotherapy plans to gain information that may improve future treatment. Patients will also be monitored long-term for late side effects of therapy, health-related quality of life, cognitive function, social and professional live outcomes, and reproduction and fertility. In summary, EORTC 1634-BTG/NOA-23 is a unique multi-national effort that will help to council patients and clinical scientists for the appropriate design of treatments and future clinical trials for post-pubertal patients with medulloblastoma. 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.