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Clinical Investigations |
Children's Hospital, University of Wuerzburg, Wuerzburg, Germany (S.R., N.U.G., K.H., H.O., F.D., P.-G.S., J.K.); Pediatric Oncology, Klinikum Augsburg, Augsburg, Germany (A.G.); Pediatric Oncology, University of Bonn, Bonn, Germany (U.B.); Pediatric Oncology, University of Homburg/Saar, Homburg, Germany (N.G.); Pediatric Oncology, University of Cologne, Cologne, Germany (F.B.); Pediatric Oncology, Charité-Virchow-Klinikum, University of Berlin, Berlin, Germany (G.H.); Pediatric Oncology, Texas Children's Cancer Center, Houston, Texas, USA (J.E.A.W.); Department of Neuroradiology (M.W.-M.) and Department of Pediatric Neurosurgery (N.S.), University of Wuerzburg, Wuerzburg, Germany; Institute for Medical Biostatistics, Epidemiology, and Informatics, University of Mainz, Mainz, Germany (A.E.); Department of Radiation Oncology, University of Leipzig, Leipzig, Germany (R.-D.K.); Department of Neuropathology, University of Bonn, Bonn, Germany (T.P.)
Address correspondence to Stefan Rutkowski, Children's University Hospital, University of Wuerzburg, Josef-Schneider-Str. 2, D-97080 Wuerzburg, Germany (rutkowski{at}mail.uni-wuerzburg.de).
To investigate the utility of postoperative chemotherapy in delaying radiotherapy and to identify prognostic factors in early childhood medulloblastoma, we studied children younger than 3 years of age registered to the HIT-SKK'87 (Therapieprotokoll für Säuglinge und Kleinkinder mit Hirntumoren [Brain Tumor Radiotherapy for Infants and Toddlers with Medulloblastoma] 1987) trial who received systemic interval chemotherapy until craniospinal radiotherapy was applied at 3 years of age or at relapse, from 1987 to 1993. Children with postoperative residual tumor or metastatic disease received systemic induction chemotherapy prior to interval chemotherapy. Twenty-nine children were eligible for analyses (median age, 1.7 years; median follow-up, 12.6 years). In children without macroscopic metastases, rates (±SEM) for 10-year progression-free survival (PFS) and overall survival (OS) 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 with 0% and 0% in children with macroscopic metastases. Survival was superior in nine children with desmoplastic or extensive nodular histology compared with 20 children with classic medulloblastoma (10-year PFS, 88.9% ± 10.5% and 30.0% ± 10.3%, p = 0.003; OS, 88.9% ± 10.5% and 40.0% ± 11.0%, p = 0.006). Eleven of 12 children with tumor progression during chemotherapy had classic medulloblastoma. After treatment, IQ scores were inferior compared with nonirradiated children from the subsequent study, HIT-SKK'92. Classic histology, metastatic disease, and male gender were independent adverse risk factors for PFS and OS in 72 children from HIT-SKK'87 and HIT-SKK'92 combined. 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 favorable prognostic factor. Because of the neurocognitive deficits of survivors, the emerging concepts to avoid craniospinal radiotherapy should rely on the histological medulloblastoma subtype.
Key Words: chemotherapy • histology • medulloblastoma • prognosis • radiotherapy
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