title: Preradiation chemotherapy may improve survival in pediatric diffuse intrinsic brainstem gliomas: final results of BSG 98 prospective trial.
abstract: 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.
authors.affiliation: Pediatric Department, Centre Léon Bérard, Lyon, France. frappaz@lyon.fnclcc.fr
authors.forename: Didier
authors.initials: D
authors.lastname: Frappaz
authors.forename: Matthias
authors.initials: M
authors.lastname: Schell
authors.forename: Philippe
authors.initials: P
authors.lastname: Thiesse
authors.forename: Perrine
authors.initials: P
authors.lastname: Marec-Bérard
authors.forename: Carmine
authors.initials: C
authors.lastname: Mottolese
authors.forename: David
authors.initials: D
authors.lastname: Perol
authors.forename: Christophe
authors.initials: C
authors.lastname: Bergeron
authors.forename: Thierry
authors.initials: T
authors.lastname: Philip
authors.forename: Anne Claire
authors.initials: AC
authors.lastname: Ricci
authors.forename: Sophie
authors.initials: S
authors.lastname: Galand-Desme
authors.forename: Alexandru
authors.initials: A
authors.lastname: Szathmari
authors.forename: Christian
authors.initials: C
authors.lastname: Carrie
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D020295:Brain Stem Neoplasms / Q000401:mortality* / Q000473:pathology / Q000628:therapy*; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D005260:Female; D005910:Glioma / Q000401:mortality* / Q000473:pathology / Q000628:therapy*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D020360:Neoadjuvant Therapy; D011788:Quality of Life; D011878:Radiotherapy