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.

Figures

Fig. 1

Schedule of the BSG 98 prospective protocol. Abbreviations: Tamox, tamoxifen; HD-MTX, high-dose methotrexate; SD, stable disease; PD, progressive disease; RT, radiotherapy. Modified Grossmann refers to treatment of continuous infusion of BCNU and cisplatin based on Grossman et al., as modified here (see “Materials and Methods”). *Tamoxifen was omitted in latest patients.

Fig. 2

Overall survival of patients in the current protocol versus historical controls (p = 0.022, log-rank test). CI, confidence interval.

Fig. 3

Overall survival of patients in the current protocol versus historical controls with time from radiation therapy as the starting point (p = not significant [NS], log-rank test). CI, confidence interval.

Fig. 4

Triangular test of Bellissant et al. for patients in the current protocol versus historical controls. Abbreviations: RT, radiotherapy; PCB, procarbazine; Carbo, carboplatin.