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| Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2020 Apr 24. doi: 10.1200/JCO.19.03057 |
| Nonmetastatic Medulloblastoma of Early Childhood: Results From the Prospective Clinical Trial HIT-2000 and An Extended Validation Cohort. |
| Mynarek M1, von Hoff K2, Pietsch T3, Ottensmeier H4, Warmuth-Metz M5, Bison B6, Pfister S7, Korshunov A8, Sharma T9, Jaeger N10, Ryzhova M11, Zheludkova O12, Golanov A13, Rushing EJ14, Hasselblatt M15, Koch A16, Schüller U17, von Deimling A18, Sahm F19, Sill M20, Riemenschneider MJ21, Dohmen H22, Monoranu CM23, Sommer C24, Staszewski O25, Mawrin C26, Schittenhelm J27, Brück W28, Filipski K29, Hartmann C30, Meinhardt M31, Pietschmann K32, Haberler C33, Slavc I34, Gerber NU35, Grotzer M36, Benesch M37, Schlegel PG38, Deinlein F39, von Bueren AO40, Friedrich C41, Juhnke BO42, Obrecht D43, Fleischhack G44, Kwiecien R45, Faldum A46, Kortmann RD47, Kool M48, Rutkowski S49 |
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Abstract PURPOSE: The 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 METHODS: 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. RESULTS: 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; < .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%, iSHH-II, 83%; = .25; n = 99). Intelligence quotient (IQ) was significantly lower in patients after CSI (mean IQ, 90 [no radiotherapy], 74 [CSI]; = .012). CONCLUSION: 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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Publikations ID: 32330099 Quelle: öffnen |
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