Outcome of children less than three years old at diagnosis with non-metastatic medulloblastoma treated with chemotherapy on the “Head Start” I and II protocols: Final report

Abstract

9507 Background: The use of dose-intensive chemotherapy with autologous hematopoietic cell rescue (AuHCR) is a potentially curative approach to the management of infants and young children with non-metastatic (M-0) medulloblastoma, with the additional benefit of avoiding the late effects of irradiation. We report the results of the “Head Start” I (1991 to 1997) and “Head Start” II (1997 to 2002) clinical trials, using this approach, to treat children with M-0 medulloblastoma, who were less than three years of age at diagnosis. Methods: Twenty one children were enrolled on these two serial studies. After surgery, patients received a uniform induction chemotherapy regimen consisting of five cycles of vincristine, cisplatin, cyclophosphamide and etoposide. Following completion of induction, all patients underwent myeloablative consolidation chemotherapy using carboplatin, thiotepa and etoposide followed by AuHCR, and did not receive irradiation. Irradiation was used only at relapse. Quality of life (QoL) and social and emotional behavior were evaluated on “Head Start” I, and cognitive functioning was evaluated on “Head Start” II survivors. Results: The five-year event-free (EFS) and overall survival (OS) rates (±SE) for all patients, patients with gross total resection, and patients with residual tumor were 52 ± 11% and 70 ± 10%, 64 ± 13% and 79 ± 17%, and 29 ± 17% and 57 ± 19%, respectively. The five-year EFS and OS (±SE) for patients with desmoplastic and classical medulloblastoma were 67 ± 16% and 78 ± 14%, and 42 ± 14 and 67 ± 14%, respectively. Young age (<2 years versus 2 to 3 years) at diagnosis did not appear to impact adversely upon outcome. There were four treatment related deaths. A majority of survivors (71%) avoided irradiation altogether. Neuropsychological functioning in children surviving without irradiation was well within the normal range for most patients. Conclusions: The strategy of brief intensive chemotherapy without irradiation for young children with M-0 medulloblastoma has eliminated the need for craniospinal irradiation in over half (52%) of the patients, with preservation of QoL and cognitive functioning in the majority. No significant financial relationships to disclose.