Excellent outcome of young children with nodular desmoplastic medulloblastoma treated on "head Start" III: A multi-institutional, prospective clinical trial

Girish Dhall*, Sharon H. O'Neil, Lingyun Ji, Kelley Haley, Ashley M. Whitaker, Marvin D. Nelson, Floyd Gilles, Sharon L. Gardner, Jeffrey C. Allen, Albert S. Cornelius, Kamnesh Pradhan, James H. Garvin, Randal S. Olshefski, Juliette Hukin, Melanie Comito, Stewart Goldman, Mark P. Atlas, Andrew W. Walter, Stephen Sands, Richard SpostoJonathan L. Finlay

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Background: "Head Start"III, was a prospective clinical trial using intensive induction followed by myeloablative chemotherapy and autologous hematopoietic cell rescue (AuHCR) to either avoid or reduce the dose/volume of irradiation in young children with medulloblastoma. Methods: Following surgery, patients received 5 cycles of induction followed by myeloablative chemotherapy using carboplatin, thiotepa, and etoposide with AuHCR. Irradiation was reserved for children >6 years old at diagnosis or with residual tumor post-induction. Results: Between 2003 and 2009, 92 children <10 years old with medulloblastoma were enrolled. Five-year event-free survival (EFS) and overall survival (OS) rates (±SE) were 46 ± 5% and 62 ± 5% for all patients, 61 ± 8% and 77 ± 7% for localized medulloblastoma, and 35 ± 7% and 52 ± 7% for disseminated patients. Nodular/desmoplastic (ND) medulloblastoma patients had 5-year EFS and OS (±SE) rates of 89 ± 6% and 89 ± 6% compared with 26 ± 6% and 53 ± 7% for classic and 38 ± 13% and 46 ± 14% for large-cell/anaplastic (LCA) medulloblastoma, respectively. In multivariate Cox regression analysis, histology was the only significant independent predictor of EFS after adjusting for stage, extent of resection, regimen, age, and sex (P <0.0001). Five-year irradiation-free EFS was 78 ± 8% for ND and 21 ± 5% for classic/LCA medulloblastoma patients. Myelosuppression was the most common toxicity, with 2 toxic deaths. Twenty-four survivors completed neurocognitive evaluation at a mean of 4.9 years post-diagnosis. IQ and memory scores were within average range overall, whereas processing speed and adaptive functioning were low-average. Conclusion: We report excellent survival and preservation of mean IQ and memory for young children with ND medulloblastoma using high-dose chemotherapy, with most patients surviving without irradiation.

Original languageEnglish (US)
Pages (from-to)1862-1872
Number of pages11
JournalNeuro-oncology
Volume22
Issue number12
DOIs
StatePublished - Dec 1 2020

Keywords

  • desmoplastic
  • infants
  • medulloblastoma
  • myeloablative chemotherapy

ASJC Scopus subject areas

  • Oncology
  • Clinical Neurology
  • Cancer Research

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