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

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 eventfree 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.