Journal of Neuro-Oncology

, Volume 137, Issue 1, pp 103–110 | Cite as

Survival outcomes in pediatric recurrent high-grade glioma: results of a 20-year systematic review and meta-analysis

  • Cassie Kline
  • Erin Felton
  • I. Elaine Allen
  • Peggy Tahir
  • Sabine Mueller
Clinical Study


Recurrent pediatric high-grade glioma is a leading cause of cancer-related death in children. We report results of a systematic review and meta-analysis investigating survival outcome in pediatric patients with recurrent high-grade glioma over the last 20 years. MEDLINE/PubMed, EMBASE, Web of Science and Cochrane Review databases were searched for relevant studies reporting on survival outcomes for pediatric patients with recurrent high-grade glioma treated between 1996 and 2016. Progression-free survival (PFS) and overall survival (OS) were calculated cumulatively over all studies, by therapy subgroup, and by decade of treatment. Random effects models were used to control for heterogeneity as measured by the I2 statistic. A total of 17 studies across 4 treatment strategies were included. Eleven investigated traditional chemotherapy, 1 investigated targeted therapy, 3 investigated immunotherapy, and 2 investigated radiotherapy. A total of 129 patients were included with a median age of 10.0 years. Cumulative PFS was 3.5 months (95% CI 2.1–5.0). Cumulative OS was 5.6 months (95% CI 3.9–7.3). OS was 4.0 months (95% CI 1.9–6.1) using traditional chemotherapy, 9.3 months using targeted therapies (95% CI 5.4–13), 6.9 months using immunotherapy (95% CI 2.1–12), and 14 months using reirradiation (95% CI 2.8–25). OS between 1996 and 2006 was 4.2 months (95% CI 2.1–6.2) compared to 8.5 months (95% CI 5.6–11) after 2006. Pediatric patients with recurrent high-grade glioma suffer from poor PFS and OS, regardless of therapy. There may be a trend towards improved OS in the last decade.


Pediatric high-grade glioma Recurrence Survival Outcomes 



C.N.K. is supported by the National Institutes of Health T32 Grant (T32CA128583-07), UCSF Clinical and Translational Science Institute Strategic Opportunities Support Program (UL1 TR001872), Alex’s Lemonade Stand Foundation (A120729), and Frank A. Campini Foundation. S.M. is supported by the National Institutes of Health National Center for Advancing Translational Sciences through UCSF-CTSI (KL2TR000143). This work was presented as a podium presentation at the 4th Pediatric Neuro-Oncology Basic and Translational Research Conference in New York, NY on June 16, 2017 and as an eTalk at the Society of Neuro-Oncology Annual Meeting on November 17, 2017.


No external funding was used to directly support this study.

Compliance with ethical standards

Conflict of interest

No contributing authors have any conflict of interest to declare.

Supplementary material

11060_2017_2701_MOESM1_ESM.docx (106 kb)
Table of all studies included in final statistical analyses. Thio = thiotepa; BCNU = carmustine; O6-BG = O6-benzylguanine; TMZ = temozolomide; Chemo = varied chemotherapy; Topo = topotecan; Carbo = carboplatin; HD = high-dose; ASCR = autologous stem cell rescue; Etopo = etoposide; DC = dendritic cell. (DOCX 105 KB)
11060_2017_2701_MOESM2_ESM.tiff (1.5 mb)
Forest plot representing PFS by therapy (TIFF 1522 KB)
11060_2017_2701_MOESM3_ESM.tiff (1.5 mb)
Forest plot representing PFS by decade (TIFF 1522 KB)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2017

Authors and Affiliations

  1. 1.Division of Hematology/Oncology, Department of PediatricsUniversity of California, San FranciscoSan FranciscoUSA
  2. 2.Department of NeurologyUniversity of California, San FranciscoSan FranciscoUSA
  3. 3.Department of Epidemiology & BiostatisticsUniversity of California, San FranciscoSan FranciscoUSA
  4. 4.UCSF LibraryUniversity of California, San FranciscoSan FranciscoUSA
  5. 5.Department of Neurological SurgeryUniversity of California, San FranciscoSan FranciscoUSA

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