P11.02 Long-term Outcome of Infants and Young Children with Newly Diagnosed Non-Nodular/Desmoplastic Medulloblastoma Treated on “Head Start” III Protocol

Abstract

Abstract Background: High-dose chemotherapy with autologous hematopoietic cell rescue (AuHCR) is a potentially curative approach used in the management young children with medulloblastoma), with the additional benefit of avoiding the late effects of craniospinal irradiation (CSI). We report the outcome of infants and young children with classic and large cell/anaplastic (LCA) medulloblastoma treated on “Head Start (HS)” III, a prospective, multi-national clinical trial. Methods: Between April 2003 and December 2009, 92 children with newly-diagnosed medulloblastoma were enrolled amongst 29 participating institutions. All children were to receive 5 induction cycles (vincristine, cisplatin, cyclophosphamide, etoposide, high dose methotrexate - cycles 1, 3, 5), and vincristine, cyclophosphamide, oral VP-16 and temozolomide (cycles 2, 4), followed by 1 consolidation cycle of myeloablative chemotherapy (thiotepa, carboplatin, etoposide) and AuHCR. Only children between 6-10 years old or with residual tumor pre-consolidation, were to receive irradiation after consolidation. Results: Of 92 children with medulloblastoma enrolled on HSIII, 52 patients had classic and 13 had LCA medulloblastoma. Eighteen patients with classic and 6 with LCA medulloblastoma had localized disease (M0) whereas 33 patients with classic and 7 patients with LCA medulloblastoma had evidence of dissemination (M+). The 2-year event-free (EFS) and overall survival (OS) rates (+/- SE) for patients with classic medulloblastoma (primary objective of the study) were 37 ± 7% and 62 ± 7%, and for patients with LCA medulloblastoma were 54 ± 14% and 62 ± 13%, respectively. The 5-year EFS and OS rates were 26 ± 6% and 53 ± 7% for classic medulloblastoma and 38 ± 13% and 46 ± 14% for LCA medulloblastoma patients, respectively. For patients with M0 medulloblastoma, the 5-year EFS and OS rates were 38 ± 12% and 66 ± 11% for patients with classic histology and 50 ± 20% and 67 ± 19% for patients with LCA histology. Similarly, for patients with M+ medulloblastoma, the 5-year EFS and OS rates were 21 ± 7% and 48 ± 9% for patients with classic histology and 29 ± 17% and 29 ± 17% for patients with LCA histology. In multivariate Cox regression analyses, no significant difference in EFS was found between classic and LCA tumors. 5-year irradiation free-EFS for non-nodular/desmoplastic patients was 29 +/- 6%. Conclusion: Encouraging survival figures are reported for patients with classic medulloblastoma, similar to other contemporary infant protocols, whereas patients with LCA medulloblastoma had equivalent survival when compared to patients with classic medulloblastoma when treated with high-dose chemotherapy with AuHCR. These are among the best survival data published so far on infants and young children with LCA medulloblastoma. Approximately third of the survivors were able to avoid irradiation.