Pre-irradiation intensive induction and marrow-ablative consolidation chemotherapy in young children with newly diagnosed high-grade brainstem gliomas: report of the “head-start” I and II clinical trials

Diana S. Osorio, Neha Patel, Lingyun Ji, Richard Sposto, Joseph Stanek, Sharon L. Gardner, Jeffrey C. Allen, Albert Cornelius, Geoffrey B. McCowage, Amanda Termuhlen, Ira J. Dunkel, Melanie Comito, James Garvin, Jonathan L. Finlay

Research output: Contribution to journalArticle

Abstract

Background: The dismal outcome in children with high-grade brainstem gliomas (BSG) accentuates the need for effective therapeutic strategies. We investigated the role of intensive, including marrow-ablative, chemotherapy regimens in the treatment of young children with newly-diagnosed high-grade BSG. Methods: Between 1991-and-2002, 15 eligible children less than 10 years of age with a diagnosis of high-grade BSG were treated on “Head-Start” I and II protocols (HSI and HSII). Treatment included Induction with 4–5 cycles of one of three intensive chemotherapy regimens followed by Consolidation with one cycle of marrow-ablative chemotherapy (thiotepa, carboplatin and etoposide) with autologous hematopoietic cell rescue (AHCR). Irradiation was required for children over 6 years of age or for those with residual tumor at the end of Consolidation. Results: We had two long-term survivors who were found retrospectively to harbor low-grade glial tumors and thus were not included in the survival analysis. Of the remaining 13 patients, the 1-year event-free (EFS) and overall (OS) survival for these children were 31% (95% CI 9–55%) and 38% (95% CI 14–63%), respectively. Median EFS and OS were 6.6 (95% CI 2.7, 12.7) and 8.7 months (95% CI 6.9, 20.9), respectively. Eight patients developed progressive disease during study treatment (seven during Induction and one at the end of Consolidation). Ten children received focal irradiation, five for residual tumor (three following Induction and two following Consolidation) and five due to disease progression. Conclusions: Children with high-grade BSG did not benefit from this intensive chemotherapy strategy administered prior to irradiation.

Original languageEnglish (US)
Pages (from-to)717-725
Number of pages9
JournalJournal of neuro-oncology
Volume140
Issue number3
DOIs
StatePublished - Dec 15 2018
Externally publishedYes

Keywords

  • Brainstem
  • Brainstem glioma
  • DIPG
  • Diffuse intrinsic pontine glioma
  • High-dose chemotherapy
  • High-grade glioma
  • Marrow-ablative therapy

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    Osorio, D. S., Patel, N., Ji, L., Sposto, R., Stanek, J., Gardner, S. L., Allen, J. C., Cornelius, A., McCowage, G. B., Termuhlen, A., Dunkel, I. J., Comito, M., Garvin, J., & Finlay, J. L. (2018). Pre-irradiation intensive induction and marrow-ablative consolidation chemotherapy in young children with newly diagnosed high-grade brainstem gliomas: report of the “head-start” I and II clinical trials. Journal of neuro-oncology, 140(3), 717-725. https://doi.org/10.1007/s11060-018-03003-z