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First published on June 24, 2008
This version was published on August 1, 2008
Neuro Oncol 2008 10(4):599-607; DOI:10.1215/15228517-2008-029
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Duke University Press

Clinical Investigations

Preradiation chemotherapy may improve survival in pediatric diffuse intrinsic brainstem gliomas: Final results of BSG 98 prospective trial

Didier Frappaz, Matthias Schell, Philippe Thiesse, Perrine Marec-Bérard, Carmine Mottolese, David Perol, Christophe Bergeron, Thierry Philip, Anne Claire Ricci, Sophie Galand-Desme, Alexandru Szathmari and Christian Carrie

Pediatric Department, Radiotherapy Department, and Biostatistical Unit, Centre Léon Bérard, Lyon, France (D.F., M.S., P.T., P.M.-B., D.P., C.B., T.P., S.G.-D., C.C.); Pediatric Neurosurgical Unit, Hôpital Pierre Wertheimer, Lyon, France (C.M., A.C.R., A.S.)

Address correspondence to Didier Frappaz, Pediatric Department, Centre Léon Bérard, 28 Rue Laënnec, 69373 Lyon Cedex 08, France (frappaz{at}lyon.fnclcc.fr).

Radiation therapy remains the only treatment that provides clinical benefit to children with diffuse brainstem tumors. Their median survival, however, rarely exceeds 9 months. The authors report a prospective trial of frontline chemotherapy aimed at delaying radiation until time of clinical progression. The aim was to investigate the possibility that radiotherapy would maintain its activity in children whose disease progressed after chemotherapy. Twenty-three patients took part in this protocol, the BSG 98 protocol, which consisted of frontline chemotherapy alternating hematotoxic and nonhematotoxic schedules. Each cycle included three courses delivered monthly; the first course was 1,3-bis(2-chloroethyl)-1-nitrosoureacisplatin, and the second and third were high-dose methotrexate. Three patients underwent one cycle; 5 patients each, two and three cycles; and 10 patients, four cycles. Twenty of the 23 patients eventually received local radiation therapy. A historical cohort of 14 patients who received at least local radiation therapy served as controls. Four patients experienced severe iatrogenic infections, and 11 patients required platelet transfusions. Median survival increased significantly in patients participating in the protocol compared to that in the historical controls (17 months, 95% confidence interval [CI], 10-23 months, vs. 9 months, 95% CI, 8-10 months; p = 0.022), though hospitalization was prolonged (57 vs. 25 days, p = 0.001). Although frontline chemotherapy alternating hematotoxic and nonhematotoxic schedules significantly increases overall median survival, its cost from infection and hospitalization deserves honest discussion with the children and their parents.

Key Words: brainstem • chemotherapy • glioma • radiotherapy







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Copyright 2008 by Society for Neuro-Oncology