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000153356 0247_ $$2doi$$a10.1200/JCO.19.03057
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000153356 037__ $$aDZNE-2020-01353
000153356 041__ $$aEnglish
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000153356 1001_ $$aMynarek, Martin$$b0
000153356 245__ $$aNonmetastatic Medulloblastoma of Early Childhood: Results From the Prospective Clinical Trial HIT-2000 and An Extended Validation Cohort
000153356 260__ $$aAlexandria, Va.$$bAmerican Society of Clinical Oncology$$c2020
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000153356 520__ $$aPURPOSEThe 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.
000153356 536__ $$0G:(DE-HGF)POF3-344$$a344 - Clinical and Health Care Research (POF3-344)$$cPOF3-344$$fPOF III$$x0
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000153356 650_2 $$2MeSH$$aCerebellar Neoplasms: drug therapy
000153356 650_2 $$2MeSH$$aCerebellar Neoplasms: mortality
000153356 650_2 $$2MeSH$$aCerebellar Neoplasms: radiotherapy
000153356 650_2 $$2MeSH$$aChild, Preschool
000153356 650_2 $$2MeSH$$aCranial Irradiation: adverse effects
000153356 650_2 $$2MeSH$$aDNA Methylation
000153356 650_2 $$2MeSH$$aFemale
000153356 650_2 $$2MeSH$$aHumans
000153356 650_2 $$2MeSH$$aInfant
000153356 650_2 $$2MeSH$$aMale
000153356 650_2 $$2MeSH$$aMedulloblastoma: drug therapy
000153356 650_2 $$2MeSH$$aMedulloblastoma: mortality
000153356 650_2 $$2MeSH$$aMedulloblastoma: radiotherapy
000153356 650_2 $$2MeSH$$aMethotrexate: administration & dosage
000153356 650_2 $$2MeSH$$aNeuropsychological Tests
000153356 650_2 $$2MeSH$$aProspective Studies
000153356 7001_ $$avon Hoff, Katja$$b1
000153356 7001_ $$0P:(DE-2719)2812617$$aPietsch, Torsten$$b2$$udzne
000153356 7001_ $$aOttensmeier, Holger$$b3
000153356 7001_ $$aWarmuth-Metz, Monika$$b4
000153356 7001_ $$aBison, Brigitte$$b5
000153356 7001_ $$aPfister, Stefan$$b6
000153356 7001_ $$aKorshunov, Andrey$$b7
000153356 7001_ $$aSharma, Tanvi$$b8
000153356 7001_ $$aJaeger, Natalie$$b9
000153356 7001_ $$aRyzhova, Marina$$b10
000153356 7001_ $$aZheludkova, Olga$$b11
000153356 7001_ $$aGolanov, Andrey$$b12
000153356 7001_ $$aRushing, Elisabeth Jane$$b13
000153356 7001_ $$aHasselblatt, Martin$$b14
000153356 7001_ $$aKoch, Arend$$b15
000153356 7001_ $$0P:(DE-HGF)0$$aSchüller, Ulrich$$b16
000153356 7001_ $$avon Deimling, Andreas$$b17
000153356 7001_ $$aSahm, Felix$$b18
000153356 7001_ $$aSill, Martin$$b19
000153356 7001_ $$aRiemenschneider, Markus J.$$b20
000153356 7001_ $$aDohmen, Hildegard$$b21
000153356 7001_ $$aMonoranu, Camelia Maria$$b22
000153356 7001_ $$aSommer, Clemens$$b23
000153356 7001_ $$aStaszewski, Ori$$b24
000153356 7001_ $$aMawrin, Christian$$b25
000153356 7001_ $$aSchittenhelm, Jens$$b26
000153356 7001_ $$aBrück, Wolfgang$$b27
000153356 7001_ $$aFilipski, Katharina$$b28
000153356 7001_ $$0P:(DE-HGF)0$$aHartmann, Christian$$b29
000153356 7001_ $$aMeinhardt, Matthias$$b30
000153356 7001_ $$aPietschmann, Klaus$$b31
000153356 7001_ $$aHaberler, Christine$$b32
000153356 7001_ $$aSlavc, Irene$$b33
000153356 7001_ $$aGerber, Nicolas U.$$b34
000153356 7001_ $$aGrotzer, Michael$$b35
000153356 7001_ $$aBenesch, Martin$$b36
000153356 7001_ $$aSchlegel, Paul Gerhardt$$b37
000153356 7001_ $$aDeinlein, Frank$$b38
000153356 7001_ $$avon Bueren, André O.$$b39
000153356 7001_ $$aFriedrich, Carsten$$b40
000153356 7001_ $$aJuhnke, Björn-Ole$$b41
000153356 7001_ $$aObrecht, Denise$$b42
000153356 7001_ $$aFleischhack, Gudrun$$b43
000153356 7001_ $$aKwiecien, Robert$$b44
000153356 7001_ $$aFaldum, Andreas$$b45
000153356 7001_ $$aKortmann, Rolf Dieter$$b46
000153356 7001_ $$aKool, Marcel$$b47
000153356 7001_ $$0P:(DE-HGF)0$$aRutkowski, Stefan$$b48$$eCorresponding author
000153356 773__ $$0PERI:(DE-600)2005181-5$$a10.1200/JCO.19.03057$$gVol. 38, no. 18, p. 2028 - 2040$$n18$$p2028 - 2040$$tJournal of clinical oncology$$v38$$x1527-7755$$y2020
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