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Evaluation of Prognostic Factors and Role of Participation in a Randomized Trial or a Prospective Registry in Pediatric and Adolescent Nonmetastatic Medulloblastoma – A Report From the HIT 2000 Trial

Lookup NU author(s): Professor Steven CliffordORCiD



This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).


© 2020 The AuthorsPurpose: We aimed to compare treatment results in and outside of a randomized trial and to confirm factors influencing outcome in a large retrospective cohort of nonmetastatic medulloblastoma treated in Austria, Switzerland and Germany. Methods and Materials: Patients with nonmetastatic medulloblastoma (n = 382) aged 4 to 21 years and primary neurosurgical resection between 2001 and 2011 were assessed. Between 2001 and 2006, 176 of these patients (46.1%) were included in the randomized HIT SIOP PNET 4 trial. From 2001 to 2011 an additional 206 patients were registered to the HIT 2000 study center and underwent the identical central review program. Three different radiation therapy protocols were applied. Genetically defined tumor entity (former molecular subgroup) was available for 157 patients. Results: Median follow-up time was 7.3 (range, 0.09-13.86) years. There was no difference between HIT SIOP PNET 4 trial patients and observational patients outside the randomized trial, with 7 years progression-free survival rates (PFS) of 79.5% ± 3.1% versus 78.7% ± 3.1% (P =.62). On univariate analysis, the time interval between surgery and irradiation (≤ 48 days vs ≥ 49 days) showed a strong trend to affect PFS (80.4% ± 2.2% vs 64.6% ± 9.1%; P =.052). Furthermore, histologically and genetically defined tumor entities and the extent of postoperative residual tumor influenced PFS. On multivariate analyses, a genetically defined tumor entity wingless-related integration site-activated vs non-wingless-related integration site/non-SHH, group 3 hazard ratio, 5.49; P =.014) and time interval between surgery and irradiation (hazard ratio, 2.2; P =.018) were confirmed as independent risk factors. Conclusions: Using a centralized review program and risk-stratified therapy for all patients registered to the study center, outcome was identical for patients with nonmetastatic medulloblastoma treated on and off the randomized HIT SIOP PNET 4 trial. The prognostic values of prolonged time to RT and genetically defined tumor entity were confirmed.

Publication metadata

Author(s): Dietzsch S, Placzek F, Pietschmann K, von Bueren AO, Matuschek C, Gluck A, Guckenberger M, Budach V, Welzel J, Pottgen C, Schmidberger H, Heinzelmann F, Paulsen F, Escudero MP, Schwarz R, Hornung D, Martini C, Grosu AL, Stueben G, Jablonska K, Dunst J, Stranzl-Lawatsch H, Dieckmann K, Timmermann B, Pietsch T, Warmuth-Metz M, Bison B, Kwiecien R, Benesch M, Gerber NU, Grotzer MA, Pfister SM, Clifford SC, von Hoff K, Klagges S, Rutkowski S, Kortmann R-D, Mynarek M

Publication type: Article

Publication status: Published

Journal: Advances in Radiation Oncology

Year: 2020

Volume: 5

Issue: 3

Pages: 1158-1169

Print publication date: 01/11/2020

Online publication date: 06/10/2020

Acceptance date: 17/09/2020

Date deposited: 12/03/2021

ISSN (electronic): 2452-1094

Publisher: Elsevier Inc.


DOI: 10.1016/j.adro.2020.09.018


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