© Copyright 2008 by the Society for Neuro-Oncology
Received May 8, 2008
Accepted August 14, 2008
Treatment of Early Childhood Medulloblastoma by Postoperative Chemotherapy and Deferred Radiotherapy
Stefan Rutkowski 1*,
Nicolas Ulrich Gerber 2,
Katja von Hoff 2,
Astrid Gnekow 3,
Udo Bode 4,
Norbert Graf 5,
Frank Berthold 6,
Günter Henze 7,
Johannes E.A. Wolff 8,
Monika Warmuth-Metz 9,
Niels Soerensen 10,
Angela Emser 11,
Holger Ottensmeier 2,
Frank Deinlein 3,
Paul-Gerhardt Schlegel 2,
Rolf-Dieter Kortmann 12,
Torsten Pietsch 13,
Joachim Kuehl† for the German Pediatric Brain Tumor Study Group 2
1 Children's University Hospital, University of Wuerzburg, Josef-Schneider-Str. 2, D-97080 Wuerzburg, Germany
2 Children's Hospital, University of Wuerzburg, Wuerzburg, Germany
3 Pediatric Oncology, Klinikum Augsburg, Augsburg, Germany
4 Pediatric Oncology, University of Bonn, Bonn, Germany
5 Pediatric Oncology, University of Homburg/Saar, Homburg, Germany
6 Pediatric Oncology, University of Cologne, Cologne, Germany
7 Pediatric Oncology, Charité-Virchow-Klinikum, University of Berlin, Berlin, Germany
8 Pediatric Oncology, Texas Children's Cancer Center, Houston, Texas, USA
9 Department of Neuroradiology, University of Wuerzburg, Wuerzburg, Germany
10 Department of Pediatric Neurosurgery, University of Wuerzburg, Wuerzburg, Germany
11 Institute for Medical Biostatistics, Epidemiology, and Informatics, University of Mainz, Mainz, Germany
12 Department of Radiation Oncology, University of Leipzig, Leipzig, Germany
13 Department of Neuropathology, University of Bonn, Bonn, Germany
* To whom correspondence should be addressed. E-mail: rutkowski{at}mail.uni-wuerzburg.de.
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Abstract |
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Purpose. To investigate the utility of postoperative chemotherapy to delay radiotherapy and to identify prognostic factors in early childhood medulloblastoma.
Patients. From 1987–1993, children below three years of age registered to the HIT-SKK87 trial received systemic interval chemotherapy until craniospinal radiotherapy was applied at three years of age or at relapse. Children with postoperative residual tumor or metastatic disease received systemic induction chemotherapy prior to interval chemotherapy.
Results. 29 children were eligible for analyses (median age, 1.7 years; median follow-up, 12.6 years). In children without macroscopic metastases, rates for 10-year progression-free and overall survival were 52.9±12.1% and 58.8±11.9% (complete resection), and 55.6±16.6% and 66.7±15.7% (incomplete resection), compared to 0% and 0% in children with macroscopic metastases. Survival was superior in 9 children with desmoplastic or extensive nodular histology compared to 20 children with classic medulloblastoma (10-year PFS 88.9±10.5% and 30.0±10.3%; P=.003; OS 88.9±10.5 and 40.0±11.0%; P=.006). Eleven out of twelve children with tumor progression during chemotherapy had classic medulloblastoma. After treatment, IQ-scores were inferior compared to non-irradiated children from the subsequent study HIT-SKK92. Classic histology, metastatic disease, and male gender, were independent adverse risk factors for PFS and OS in 72 children from this study and from HIT-SKK92.
Conclusions. In terms of survival, craniospinal radiotherapy was successfully delayed especially in young children with medulloblastoma of desmoplastic/extensive nodular histology, which was a strong independent favourable prognostic factor. In consequence to the neurocognitive deficits of survivors, the emerging concepts to avoid craniospinal radiotherapy should rely on the histologic medulloblastoma subtype.
Key Words:
Medulloblastoma, Histology, Prognosis, Radiotherapy, Chemotherapy
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