von Martin Benedikt ; Eckard Böde ; Andreas Bossert ; Jens Braband ; Tino Brade ; Niklas Braun ; Tobias Braun ; Simon Burton ; Thomas Dallmann ; Werner Damm ; Tobias Düser ; Lukas Elster ; Tim Fingscheidt ; Marco Fistler ; Marzena Franek ; Martin Fränzle ; Jonas Freyer ; Roland Galbas ; Roman Gansch ; Dirk Geyer ; Lukas Haas ; Arsalan Haider ; Peter Heidl ; Matthias Hein ; Andreas Heyl ; Johannes Hiller ; Hardi Hungar ; Dieter Hutter ; Rolf Jung ; Cornel Klein ; Jörg Krüger ; Thomas Kuhn ; Jacob Langner ; Markus Maurer ; Kerstin Mayr ; André Meyer-Vitali ; Eike Möhlmann ; Adam Molin ; Björn Möller ; Jürgen Niehaus ; Bastian Nolte ; Marcus Nolte ; Stefan Otten ; Jan Peleska ; Steven Peters ; Tim Poguntke ; Florian Poprawa ; Jan Reich ; Philipp Rosenberger ; Nayel Fabian Salem ; Bernhard Schick ; Daniel Schneider ; Stefan-Alexander Schneider ; Christian Schyr ; Carsten Thomas ; Mario Trapp ; Florence Wagner ; Nicolas Wagener ; Timo Woopen ; Thomas Zeh
von Dorothee Hodapp ; Christian Buschbaum ; Jörg Dutz ; Michael Kleyer ; Helmut Hillebrand ; Thorsten Brinkhoff ; Bert Engelen ; Martin Könneke ; Ingrid Kröncke ; Rolf Niedringhaus
von Anne Gläser ; Franziska Hammerl ; Markus Gräler ; Sina Coldewey ; Christin Völkner ; Moritz Johannes Frech ; Fan Yang ; Jiankai Luo ; Eric Tönnies ; Oliver von Bohlen und Halbach ; Nicola Brandt ; Diana Heimes ; Anna-Maria Neßlauer ; Christoph Korenke ; Marta Owczarek-Lipska ; John Neidhardt ; Arndt Rolfs ; Andreas Wree ; Martin Witt ; Anja U. Bräuer
von Martin Mynarek ; Katja von Hoff ; Torsten Pietsch ; Holger Ottensmeier ; Monika Warmuth-Metz ; Brigitte Bison ; Stefan Pfister ; Andrey Korshunov ; Tanvi Sharma ; Natalie Jäger ; Marina Ryzhova ; Olga Zheludkova ; Andrey Golanov ; Elisabeth Jane Rushing ; Martin Hasselblatt ; Arend Wolfgang Koch ; Ulrich Schüller ; Andreas von Deimling ; Felix Sahm ; Martin Sill ; Markus Johannes Riemenschneider ; Hildegard Dohmen ; Camelia Maria Monoranu ; Clemens Sommer ; Ori Staszewski ; Christian Mawrin ; Jens Florian Schittenhelm ; Wolfgang Brück ; Katharina Johanna Filipski ; Christian Hartmann ; Matthias Meinhardt ; Klaus Pietschmann ; Christine Haberler ; Irene Slavc ; Nicolas U. Gerber ; Michael Grotzer ; Martin Benesch ; Paul-Gerhardt Schlegel ; Frank Deinlein ; André von Bueren ; Carsten Friedrich ; Björn-Ole Juhnke ; Denise Obrecht ; Gudrun Fleischhack ; Robert Kwiecien ; Andreas Faldum ; Rolf-Dieter Kortmann ; Marcel Kool ; Stefan Rutkowski
PURPOSEThe HIT-2000-BIS4 trial aimed to avoid highly detrimental craniospinal irradiation (CSI) in children < 4 years of age with nonmetastatic medulloblastoma by systemic chemotherapy, intraventricular methotrexate, and risk-adapted local radiotherapy.PATIENTS AND METHODSFrom 2001-2011, 87 patients received systemic chemotherapy and intraventricular methotrexate. Until 2006, CSI was reserved for nonresponse or progression. After 2006, local radiotherapy was introduced for nonresponders or patients with classic medulloblastoma (CMB) or large-cell/anaplastic medulloblastoma (LCA). DNA methylation profiles of infantile sonic hedgehog-activated medulloblastoma (SHH-INF) were subdivided into iSHH-I and iSHH-II subtypes in the HIT-2000-BIS4 cohort and a validation cohort (n = 71) from the HIT group and Russia.RESULTSFive years after diagnosis, patients with desmoplastic medulloblastoma (DMB) or medulloblastoma with extensive nodularity (MBEN; n = 42) had 93% progression-free survival (5y-PFS), 100% overall survival (5y-OS), and 93% CSI-free (5y-CSI-free) survival. Patients with CMB/LCA (n = 45) had 37% 5y-PFS, 62% 5y-OS, and 39% 5y-CSI-free survival. Local radiotherapy did not improve survival in patients with CMB/LCA. All DMB/MBEN assessed by DNA methylation profiling belonged to the SHH-INF subgroup. Group 3 patients (5y-PFS, 36%; n = 14) relapsed more frequently than the SHH-INF group (5y-PFS, 93%; n = 28) or group 4 patients (5y-PFS, 83%; n = 6; P < .001). SHH-INF split into iSHH-I and iSHH-II subtypes in HIT-2000-BIS4 and the validation cohort, without prognostic impact (5y-PFS: iSHH-I, 73%, v iSHH-II, 83%; P = .25; n = 99). Intelligence quotient (IQ) was significantly lower in patients after CSI (mean IQ, 90 [no radiotherapy], v 74 [CSI]; P = .012).CONCLUSIONSystemic chemotherapy and intraventricular methotrexate led to favorable survival in both iSHH subtypes of SHH-activated DMB/MBEN with acceptable neurotoxicity. Survival in patients with non-wingless (WNT)/non-SHH disease with CMB/LCA was not improved by local radiotherapy. Patients with group 4 disease had more favorable survival rates than those with group 3 medulloblastoma.
Journal of clinical oncology Alexandria, Va. : American Society of Clinical Oncology, 1983 38(2020), 18, Seite 2028-2040 Online-Ressource
