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.

Pediatric Brain Tumors: Current Treatment Strategies and Future Therapeutic Approaches

“…The results were compared with a historical cohort and demonstrated a median survival of 17 months in the treatment group compared with 9 months in the control group, but therapy was associated with significant toxicity and prolonged hospitalizations. 139 TMZ in combination with cis-retinoic acid and radiation therapy has been tested in a small number of patients with brain stem glioma with limited success and a reported median survival of 13.5 months (Ϯ 3.6 months). 140 One difficulty in assessing the benefit of different chemotherapy regimens is the inconsistency between trials regarding eligibility criteria, assessment of tumor progression, and different endpoints.…”

Pre-radiation chemotherapy improves survival in pediatric diffuse intrinsic pontine gliomas

“…It is generally assumed that both adjuvant chemotherapy (CT) before RT and radiosensitizers have no effect on prognosis [1][2][3][4][5][6][7][8][9]. However, one trial conducted by our team showed an improvement in median overall survival (OS) compared to standard RT protocol [10]. In this study, we used our pre-radiation chemotherapy protocol named BSG 98 protocol with BCNU, cisplatin, and high-dose methotrexate in patient with newly diagnosed DIPG.…”

“…At the end of chemotherapy, or before the end in patients with disease progression, RT was given to patients. Biopsy was not required for patient inclusion [10].…”

Oncologic Treatment of Pediatric Brainstem Tumors

“…There were only three long-term survivors of more than 2 years [ 30 ]. Despite these discouraging results, Frappaz et al decided to test the feasibility of preradiation chemotherapy in 23 pediatric patients with diffuse intrinsic brainstem glioma [ 31 ]. The chemotherapy protocol consisted of alternating hematotoxic and nonhematotoxic schedules.…”