Outcome for metastatic (M+) medulloblastoma (MB) treated with carboplatin during craniospinal radiotherapy (CSRT) followed by cyclophosphamide (CPM) and vincristine (VCR): Preliminary results of COG 99701

Abstract

2017 Background: The outcome for patients with metastatic medulloblastoma has historically been poor. Carboplatin is both a potent radiosensitizer and has activity against medulloblastoma. In this study, we evaluated the feasibility of administering carboplatin during CSRT and the impact of anaplasia as an independent predictor of outcome. Methods: All patients underwent surgical debulking followed by 36 Gy CSRT with boosts to the posterior fossa and sites of bulk disease. During CSRT, patients received weekly VCR as well as carboplatin doses ranging from 30 mg/m2/dose x 15 to 45 mg/m2/dose x 30 given 1–4 hours prior to each RT fraction, using a Phase I design. G-CSF was given for neutropenia during CSRT. Six weeks after completing chemoradiotherapy, patients received six courses of monthly CPM (2 gm/m2) and VCR. Central pathology review was performed to confirm the diagnosis and assess for anaplasia. Results: 57 patients (median age 7.3 yrs, range 3.1–18.1 years, M/F ratio of 2.6:1) with centrally reviewed M+ MB were enrolled. Thrombocytopenia was dose limiting and 35 mg/m2/dose x 30 was selected as the maximum tolerated carboplatin dose. 20 patients (35%) had severe anaplasia. There was no difference in age, M/F ratio or distribution of M-stage between those with or without anaplasia. Median follow-up for surviving patients is 4.5 yrs. Four-year overall survival (OS) and event-free survival (EFS) for the entire group is 81 ± 5% and 66 ± 6%. Four-year OS is 89 ± 5% for patients without anaplasia vs. 65 ± 11% for those with anaplasia (log-rank p=0.002). Four-year EFS is 76 ± 7% for patients without anaplasia vs. 48 ± 12% for those with anaplasia (log-rank p=0.02). There was no difference in survival based on M-stage. Conclusions: The use of daily carboplatin as a radiosensitizer appears to be a promising strategy for patients with metastatic MB. The presence of anaplasia is a significant negative predictor of outcome. No significant financial relationships to disclose.