Mynarek, Martin and von Hoff, Katja and Pietsch, Torsten and Ottensmeier, Holger and Warmuth-Metz, Monika and Bison, Brigitte and Pfister, Stefan and Korshunov, Andrey and Sharma, Tanvi and Jaeger, Natalie and Ryzhova, Marina and Zheludkova, Olga and Golanov, Andrey and Rushing, Elisabeth Jane and Hasselblatt, Martin and Koch, Arend and Schueller, Ulrich and von Deimling, Andreas and Sahm, Felix and Sill, Martin and Riemenschneider, Markus J. and Dohmen, Hildegard and Monoranu, Camelia Maria and Sommer, Clemens and Staszewski, Ori and Mawrin, Christian and Schittenhelm, Jens and Brueck, Wolfgang and Filipski, Katharina and Hartmann, Christian and Meinhardt, Matthias and Pietschmann, Klaus and Haberler, Christine and Slavc, Irene and Gerber, Nicolas U. and Grotzer, Michael and Benesch, Martin and Schlegel, Paul Gerhardt and Deinlein, Frank and von Bueren, Andre O. and Friedrich, Carsten and Juhnke, Bjoern-Ole and Obrecht, Denise and Fleischhack, Gudrun and Kwiecien, Robert and Faldum, Andreas and Kortmann, Rolf Dieter and Kool, Marcel and Rutkowski, Stefan (2020) Nonmetastatic Medulloblastoma of Early Childhood: Results From the Prospective Clinical Trial HIT-2000 and An Extended Validation Cohort. JOURNAL OF CLINICAL ONCOLOGY, 38 (18). 2028-+. ISSN 0732-183X, 1527-7755
Full text not available from this repository. (Request a copy)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; 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). 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | THAN 3 YEARS; YOUNG-CHILDREN; INTENSIVE CHEMOTHERAPY; MOLECULAR SUBGROUPS; THERAPY; CLASSIFICATION; SURVIVAL; TUMORS; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Abteilung für Neuropathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 22 Mar 2021 06:58 |
| Last Modified: | 22 Mar 2021 06:58 |
| URI: | https://pred.uni-regensburg.de/id/eprint/44370 |
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