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000154606 0247_ $$2doi$$a10.1200/JCO.19.03057
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000154606 1001_ $$aMynarek, Martin$$b0
000154606 245__ $$aNonmetastatic Medulloblastoma of Early Childhood: Results From the Prospective Clinical Trial HIT-2000 and An Extended Validation Cohort.
000154606 260__ $$aAlexandria, Va.$$bAmerican Society of Clinical Oncology$$c2020
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000154606 500__ $$a2020 Jun 20;38(18):2028-2040
000154606 520__ $$aThe 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.From 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.Five 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).Systemic 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.
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000154606 7001_ $$avon Hoff, Katja$$b1
000154606 7001_ $$aPietsch, Torsten$$b2
000154606 7001_ $$aOttensmeier, Holger$$b3
000154606 7001_ $$aWarmuth-Metz, Monika$$b4
000154606 7001_ $$aBison, Brigitte$$b5
000154606 7001_ $$0P:(DE-He78)f746aa965c4e1af518b016de3aaff5d9$$aPfister, Stefan$$b6$$udkfz
000154606 7001_ $$0P:(DE-He78)8d9c904a6cea14d4c99c78ba46e41f93$$aKorshunov, Andrey$$b7$$udkfz
000154606 7001_ $$0P:(DE-He78)36e1ec4777d5b7887344177dca41eae9$$aSharma, Tanvi$$b8$$udkfz
000154606 7001_ $$aJaeger, Natalie$$b9
000154606 7001_ $$aRyzhova, Marina$$b10
000154606 7001_ $$aZheludkova, Olga$$b11
000154606 7001_ $$aGolanov, Andrey$$b12
000154606 7001_ $$aRushing, Elisabeth Jane$$b13
000154606 7001_ $$aHasselblatt, Martin$$b14
000154606 7001_ $$aKoch, Arend$$b15
000154606 7001_ $$aSchüller, Ulrich$$b16
000154606 7001_ $$0P:(DE-He78)a8a10626a848d31e70cfd96a133cc144$$avon Deimling, Andreas$$b17$$udkfz
000154606 7001_ $$0P:(DE-He78)a1f4b408b9155beb2a8f7cba4d04fe88$$aSahm, Felix$$b18$$udkfz
000154606 7001_ $$0P:(DE-He78)45440b44791309bd4b7dbb4f73333f9b$$aSill, Martin$$b19$$udkfz
000154606 7001_ $$aRiemenschneider, Markus J$$b20
000154606 7001_ $$aDohmen, Hildegard$$b21
000154606 7001_ $$aMonoranu, Camelia Maria$$b22
000154606 7001_ $$aSommer, Clemens$$b23
000154606 7001_ $$aStaszewski, Ori$$b24
000154606 7001_ $$aMawrin, Christian$$b25
000154606 7001_ $$aSchittenhelm, Jens$$b26
000154606 7001_ $$aBrück, Wolfgang$$b27
000154606 7001_ $$0P:(DE-He78)832f5277c0186f22e7704f1930239636$$aFilipski, Katharina$$b28$$udkfz
000154606 7001_ $$aHartmann, Christian$$b29
000154606 7001_ $$aMeinhardt, Matthias$$b30
000154606 7001_ $$aPietschmann, Klaus$$b31
000154606 7001_ $$aHaberler, Christine$$b32
000154606 7001_ $$aSlavc, Irene$$b33
000154606 7001_ $$aGerber, Nicolas U$$b34
000154606 7001_ $$aGrotzer, Michael$$b35
000154606 7001_ $$aBenesch, Martin$$b36
000154606 7001_ $$aSchlegel, Paul Gerhardt$$b37
000154606 7001_ $$aDeinlein, Frank$$b38
000154606 7001_ $$avon Bueren, André O$$b39
000154606 7001_ $$aFriedrich, Carsten$$b40
000154606 7001_ $$aJuhnke, Björn-Ole$$b41
000154606 7001_ $$aObrecht, Denise$$b42
000154606 7001_ $$aFleischhack, Gudrun$$b43
000154606 7001_ $$aKwiecien, Robert$$b44
000154606 7001_ $$aFaldum, Andreas$$b45
000154606 7001_ $$aKortmann, Rolf Dieter$$b46
000154606 7001_ $$0P:(DE-He78)4c28e2aade5f44d8eca9dd8e97638ec8$$aKool, Marcel$$b47$$udkfz
000154606 7001_ $$aRutkowski, Stefan$$b48
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