TY - JOUR
T1 - Development of randomized trials in adults with medulloblastoma—the example of eortc 1634-btg/noa-23
AU - Hau, Peter
AU - Frappaz, Didier
AU - Hovey, Elizabeth
AU - McCabe, Martin G.
AU - Pajtler, Kristian W.
AU - Wiestler, Benedikt
AU - Seidel, Clemens
AU - Combs, Stephanie E.
AU - Dirven, Linda
AU - Klein, Martin
AU - Anazodo, Antoinette
AU - Hattingen, Elke
AU - Hofer, Silvia
AU - Pfister, Stefan M.
AU - Zimmer, Claus
AU - Kortmann, Rolf Dieter
AU - Sunyach, Marie Pierre
AU - Tanguy, Ronan
AU - Effeney, Rachel
AU - von Deimling, Andreas
AU - Sahm, Felix
AU - Rutkowski, Stefan
AU - Berghoff, Anna S.
AU - Franceschi, Enrico
AU - Pineda, Estela
AU - Beier, Dagmar
AU - Peeters, Ellen
AU - Gorlia, Thierry
AU - Vanlancker, Maureen
AU - Bromberg, Jacoline E.C.
AU - Gautier, Julien
AU - Ziegler, David S.
AU - Preusser, Matthias
AU - Wick, Wolfgang
AU - Weller, Michael
N1 - Funding: This research is funded by Deutsche Krebshilfe, grant number 70113453; by Canteen Australia; by Cancer Australia, grant number 1165910; by the Dutch Cancer Society, grant number 2021-1/13555; by the French Ministry of Health, grant number PHRC-K20-179; by the Swiss Brain Tumor Foundation; by an internal grant of the EORTC Brain Tumor Group, and by an educational grant of Sun Pharmaceuticals Industries Ltd.
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/7/9
Y1 - 2021/7/9
N2 - Medulloblastoma is a rare brain malignancy. Patients after puberty are rare and bear an intermediate prognosis. Standard treatment consists of maximal resection plus radio-chemother-apy. 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 (Odomzo™, 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 trans-lated into treatment changes in post-pubertal patients with medulloblastoma and will help to design future clinical trials.
AB - Medulloblastoma is a rare brain malignancy. Patients after puberty are rare and bear an intermediate prognosis. Standard treatment consists of maximal resection plus radio-chemother-apy. 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 (Odomzo™, 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 trans-lated into treatment changes in post-pubertal patients with medulloblastoma and will help to design future clinical trials.
UR - http://www.scopus.com/inward/record.url?scp=85109260286&partnerID=8YFLogxK
U2 - 10.3390/cancers13143451
DO - 10.3390/cancers13143451
M3 - Article
C2 - 34298664
AN - SCOPUS:85109260286
SN - 2072-6694
VL - 13
JO - Cancers
JF - Cancers
IS - 14
M1 - 3451
ER -
