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Survival after chemotherapy and stem cell transplant followed by delayed craniospinal irradiation is comparable to upfront craniospinal irradiation in pediatric embryonal brain tumor patients

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Abstract

Pediatric embryonal brain tumor patients treated with craniospinal irradiation (CSI) are at risk for adverse effects, with greater severity in younger patients. Here we compare outcomes of CSI vs. high-dose chemotherapy (HD), stem cell transplant (SCT) and delayed CSI in newly diagnosed patients. Two hundred one consecutive patients treated for medulloblastoma (72 %), supratentorial primitive neuroectodermal tumor (sPNET; 18 %) or pineoblastoma (10 %) at two institutions between 1988 and 2014 were retrospectively identified. Progression free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method and compared by log-rank tests. Adjuvant CSI regimens were used for 56 % of patients (upfront-CSI), and HD/SCT regimens were used in 32 % of patients. HD/SCT patients were significantly younger than those receiving upfront-CSI (2.9 vs. 7.8 years; P < 0.0001). There were no differences in metastases, extent of resection, or CSI dose between upfront-CSI and HD/SCT patients, but median follow-up was shorter in the HD/SCT group (6.2 vs. 3.9 years; P = 0.007). There were no significant outcome differences between upfront-CSI and HD/SCT patients who received CSI as a prophylaxis or following relapse (OS 66 % vs. 61 %, P = 0.13; PFS 67 % vs. 62 %, P = 0.12). Outcomes were equivalent when restricting analyses to HD/SCT patients who received prophylactic CSI prior to relapse (OS 66 % vs. 65 %, P = 0.5; PFS 67 % vs. 74 %, P = 0.8). At last follow-up, 48 % of HD/SCT patients had received neither definitive nor salvage radiotherapy. In this retrospective cohort, outcomes with adjuvant HD/SCT followed by delayed CSI are comparable to upfront-CSI for carefully surveyed pediatric embryonal brain tumor patients. Future prospective studies are required to validate this finding, and also to assess the impact of delayed CSI on neurocognitive outcomes.

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Abbreviations

CI:

Confidence interval

CSI:

Craniospinal irradiation

GTR:

Gross total resection

HD:

High dose chemotherapy

HR:

Hazard ratio

MRI:

Magnetic resonance imaging

OS:

Overall survival

PFS:

Progression free survival

RT:

Radiotherapy

SCT:

Stem cell transplant

sPNET:

Supratentorial primitive neuroectodermal tumor

STR:

Subtotal resection

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Authors and Affiliations

  1. Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA

    David R. Raleigh & Steve E. Braunstein

  2. Department of Economics, California State University Chanel Islands, Camarillo, CA, USA

    Bryan Tomlin

  3. Department of Pediatrics, University of California San Francisco, San Francisco, CA, USA

    Benedict Del Buono, Erika Roddy, Katherine Sear, Lennox Byer, Erin Felton, Anu Banerjee, Biljana Horn & Sabine Mueller

  4. Pediatric Hematology-Oncology, UCSF Benioff Children’s Hospital Oakland, Oakland, CA, USA

    Joseph Torkildson

  5. Pediatric Hematology-Oncology, Valley Children’s Healthcare, Madera, CA, USA

    David Samuel

  6. Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA, USA

    Daphne A. Haas-Kogan

  7. Department of Neurology, Neurosurgery and Pediatrics, University of California San Francisco, 550 Sandler Neuroscience, 625 Nelson Rising Lane, 402B, Box 0434, San Francisco, CA, 94143, USA

    Sabine Mueller

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  1. David R. Raleigh
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  2. Bryan Tomlin
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Correspondence to Sabine Mueller.

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Electronic supplementary material

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11060_2016_2307_MOESM1_ESM.pdf

Supplemental Figure 1. Medulloblastoma outcomes in patients younger than 3 years of age at diagnosis according to adjuvant treatment regimen. (A) OS and (B) PFS in patients with medulloblastoma who were younger than 3 years of age at diagnosis, analyzed according to adjuvant regimen. (PDF 329 KB)

Supplementary material 2 (DOCX 71 KB)

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Raleigh, D.R., Tomlin, B., Buono, B.D. et al. Survival after chemotherapy and stem cell transplant followed by delayed craniospinal irradiation is comparable to upfront craniospinal irradiation in pediatric embryonal brain tumor patients. J Neurooncol 131, 359–368 (2017). https://doi.org/10.1007/s11060-016-2307-6

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  • DOI: https://doi.org/10.1007/s11060-016-2307-6

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