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Relapse patterns and outcome after relapse in standard risk medulloblastoma: a report from the HIT-SIOP-PNET4 study

Journal article
Authors Magnus Sabel
G. Fleischhack
S. Tippelt
G. Gustafsson
F. Doz
R. Kortmann
M. Massimino
A. Navajas
K. von Hoff
S. Rutkowski
M. Warmuth-Metz
S.C. Clifford
T. Pietsch
B. Pizer
Birgitta Lannering
Published in Journal of Neuro-Oncology
Volume 129
Issue 3
Pages 515–524
ISSN 0167-594X
Publication year 2016
Published at Institute of Clinical Sciences, Department of Pediatrics
Pages 515–524
Language en
Keywords Chemotherapy , Clinical trial , Medulloblastoma , Paediatric , Radiotherapy , Relapse , Secondary tumours , Survival , Treatment
Subject categories Cancer and Oncology, Pediatrics


© 2016 The Author(s)The HIT-SIOP-PNET4 randomised trial for standard risk medulloblastoma (MB) (2001–2006) included 338 patients and compared hyperfractionated and conventional radiotherapy. We here report the long-term outcome after a median follow up of 7.8 years, including detailed information on relapse and the treatment of relapse. Data were extracted from the HIT Group Relapsed MB database and by way of a specific case report form. The event-free and overall (OS) survival at 10 years were 76 ± 2 % and 78 ± 2 % respectively with no significant difference between the treatment arms. Seventy-two relapses and three second malignant neoplasms were reported. Thirteen relapses (18 %) were isolated local relapses in the posterior fossa (PF) and 59 (82 %) were craniospinal, metastatic relapses (isolated or multiple) with or without concurrent PF disease. Isolated PF relapse vs all other relapses occurred at mean/median of 38/35 and 28/26 months respectively (p = 0.24). Late relapse, i.e. >5 years from diagnosis, occurred in six patients (8 %). Relapse treatment consisted of combinations of surgery (25 %), focal radiotherapy (RT 22 %), high dose chemotherapy with stem cell rescue (HDSCR 21 %) and conventional chemotherapy (90 %). OS at 5 years after relapse was 6.0 ± 4 %. In multivariate analysis; isolated relapse in PF, and surgery were significantly associated with prolonged survival whereas RT and HDSCR were not. Survival after relapse was not related to biological factors and was very poor despite several patients receiving intensive treatments. Exploration of new drugs is warranted, preferably based on tumour biology from biopsy of the relapsed tumour.

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