OS02.4 Long-term Outcome of Infants and Young Children with Newly Diagnosed Nodular Desmoplastic Medulloblastoma Treated on “Head Start” III Protocol

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). Nodular desmoplastic medulloblastoma (NDMB) patients have been shown to have a favorable outcome in most contemporary infant clinical trials. We report the outcome of young children with NDMB treated on “Head Start” 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, of whom 27 patients had NDMB. 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: The 2-year event-free (EFS) and overall survival (OS) rates (+/- SE) for patients with ND medulloblastoma enrolled on HS III (primary objective of the study) were 89 ± 6% and 93 ± 5%, respectively. The 5-year EFS and OS rates were 89 ± 6% and 89 ± 6%, respectively. For 15 patients with localized NDMB (M0), the 5-year EFS and OS rates were 93 ± 6% and 93 ± 6%, respectively. Only one patient died, from CNS hemorrhage related to an accidental fall while undergoing induction. The remaining 14 patients are surviving without having received any irradiation. For 11 patients with disseminated NDMB (M+), the 5-year EFS and OS rates were 82 ± 12% and 81 ± 12%, respectively. One patient died from progressive disease post-transplant and one patient died of toxicity (6 months of age at diagnosis) from veno-occlussive disease and multi-organ failure post-transplant. Only 3 of remaining 9 surviving patients with M+ disease received CSI (2340cGy, 2160cGy, and 2700cGy, respectively, along with posterior fossa boost to a total dose of 5400cGy) according to protocol guidelines. One patient did not have staging work-up performed. Multi-variate Cox regression analyses of the entire cohort revealed ND medulloblastoma histology to be the only significant independent predictor of EFS after adjusting for metastatic status, initial extent of resection of the primary tumor, regimen, age and sex (p<0.001). The 5-year irradiation-free EFS rate for Desmoplastic patients was 88+/-6%. Conclusion: These are among the best survival data published so far on young children with ND medulloblastoma, while avoiding CSI in most patients, including 6 of 9 patients with disseminated disease.