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
von David Capper ; David T. W. Jones ; Daniel Schrimpf ; Dominik Sturm ; Christian Kölsche ; Felix Sahm ; David Reuss ; Annekathrin Kratz ; Annika K. Wefers ; Kristin Huang ; Kristian Wilfried Pajtler ; Leonille Schweizer ; Damian Stichel ; Florian Selt ; Hendrik Witt ; Till Milde ; Olaf Witt ; Wolfram Scheurlen ; Christoph Geisenberger ; Stefanie Brehmer ; Marcel Seiz-Rosenhagen ; Daniel Hänggi ; Andreas Kulozik ; Axel Benner ; Martin Bendszus ; Jürgen Debus ; Michael Platten ; Andreas Unterberg ; Wolfgang Wick ; Marcel Kool ; Christel Herold-Mende ; Andreas von Deimling ; Stefan Pfister ; Hermann L. Müller
Accurate pathological diagnosis is crucial for optimal management of patients with cancer. For the approximately 100 known tumour types of the central nervous system, standardization of the diagnostic process has been shown to be particularly challenging—with substantial inter-observer variability in the histopathological diagnosis of many tumour types. Here we present a comprehensive approach for the DNA methylation-based classification of central nervous system tumours across all entities and age groups, and demonstrate its application in a routine diagnostic setting. We show that the availability of this method may have a substantial impact on diagnostic precision compared to standard methods, resulting in a change of diagnosis in up to 12% of prospective cases. For broader accessibility, we have designed a free online classifier tool, the use of which does not require any additional onsite data processing. Our results provide a blueprint for the generation of machine-learning-based tumour classifiers across other cancer entities, with the potential to fundamentally transform tumour pathology.
Nature London [u.a.] : Nature Publ. Group, 1869 555(2018), 7697, Seite 469-474 Online-Ressource
Deutsche Stiftung für Recht und Informatik (18. : 2017 : Heidelberg) Recht 4.0 - Innovationen aus den rechtswissenschaftlichen Laboren Edewecht : OlWIR, Oldenburger Verlag für Wirtschaft, Informatik und Recht, 2017 (2017), Seite 389-407 XVII, 940 Seiten
