Impact of radiotherapy parameters on outcome in the International Society of Paediatric Oncology/United Kingdom Children's Cancer Study Group PNET-3 study of preradiotherapy chemotherapy for M0-M1 medulloblastoma

Abstract Purpose To analyze the impact of radiotherapy (RT) parameters on outcome in a randomized study of pre-RT chemotherapy for M0-M1 medulloblastoma. Methods and materials Patients were randomized to RT alone or RT preceded by chemotherapy with vincristine, etoposide, carboplatin, and cyclophosphamide. RT consisted of craniospinal RT, 35 Gy in 21 fractions, followed by a posterior fossa (PF) boost of 20 Gy in 12 fractions. The accuracy of cribriform fossa, skull base, and PF field placement was assessed. Results Between 1992 and 2000, 217 patients were randomized, of whom 179 were eligible for analysis. At a median follow-up of 5.4 years, the 3- and 5-year overall survival rate was 79.5% and 70.7%, respectively. The 3- and 5-year event-free survival (EFS) rate was 71.6% and 67.0%, respectively. EFS was significantly better for the chemotherapy plus RT group (3-year EFS rate 78.5% vs. 64.8%, p = 0.0366). Overall survival and EFS were significantly better for patients completing RT within 50 days compared with those taking >50 days to complete RT (3-year overall survival rate 84.1% vs. 70.9%, p = 0.0356, 3-year EFS rate 78.5% vs. 53.7%, p = 0.0092). Multivariate analysis identified the use of chemotherapy ( p = 0.0248) and RT duration ( p = 0.0100) as predictive of better EFS. Planning films were reviewed for 131 (74.4%) of 176 patients. Sixty-five (49.6%) had no targeting deviations and 58 (44.3%) had one or more deviations. PF recurrence occurred in 11 (34.4%) of 32 with a PF targeting deviation compared with 13 (16.3%) of 80 without ( p = 0.043). No statistically significant impact of other targeting deviations on recurrence risk or EFS were found. Conclusion The results of this study have confirmed the importance of the duration of RT for medulloblastoma. Also, attention to detail when planning RT is important, as illustrated in the case of PF field placement.