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 five 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. 5-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 to 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). 5-year irradiation-free EFS was 78+/-8% for ND and 21+/-5% for classic/LCA medulloblastoma patients. Myelosuppression was the most common toxicity with two 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.