Abstract
PurposeMedulloblastoma is one of the most common malignant brain tumors in children. To date, the treatment of average-risk (non-metastatic, completely resected) medulloblastoma includes craniospinal radiation therapy and adjuvant chemotherapy. Modern treatment modalities and now risk stratification of subgroups have extended the survival of these patients, exposing the long-term morbidities associated with radiation therapy. Prior to advances in molecular subgrouping, we sought to reduce the late effects of radiation in patients with average-risk medulloblastoma.MethodsWe performed a single-arm, multi-institution study, reducing the dose of craniospinal irradiation by 25% to 18 Gray (Gy) with the goal of maintaining the therapeutic efficacy as described in CCG 9892 with maintenance chemotherapy.ResultsTwenty-eight (28) patients aged 3-30 years were enrolled across three institutions between April 2001 and December 2010. Median age at enrollment was 9 years with a median follow-up time of 11.7 years. The 3-year relapse-free (RFS) and overall survival (OS) were 79% (95% confidence interval [CI] 58% to 90%) and 93% (95% CI 74% to 98%), respectively. The 5-year RFS and OS were 71% (95% CI 50% to 85%) and 86% (95% CI 66% to 94%), respectively. Toxicities were similar to those seen in other studies; there were no grade 5 toxicities.ConclusionsGiven the known neurocognitive adverse effects associated with cranial radiation therapy, studies to evaluate the feasibility of dose reduction are needed. In this study, we demonstrate that select patients with average-risk medulloblastoma may benefit from a reduced craniospinal radiation dose of 18 Gy without impacting relapse-free or overall survival.Clinical Trial RegistrationClinicalTrials.gov identifier: NCT00031590
Highlights
Medulloblastoma is the most common malignant brain tumor in children, with an annual incidence of 0.4 per 100,000 population aged 0-19 years [1]
The 3-year relapse-free (RFS) and overall survival (OS) were 79% (95% confidence interval [CI] 58% to 90%) and 93%, respectively
Given the known neurocognitive adverse effects associated with cranial radiation therapy, studies to evaluate the feasibility of dose reduction are needed
Summary
Medulloblastoma is the most common malignant brain tumor in children, with an annual incidence of 0.4 per 100,000 population aged 0-19 years [1]. In a clinical trial from the Children’s Cancer Group (CCG) and Pediatric Oncology Group (POG) for low-stage (gross totally resected tumor with no metastasis and no brainstem invasion) medulloblastoma that randomized patients to 23.4 Gy or 36 Gy CSI without adjuvant chemotherapy, early relapses and increased exoprimary failure rate were seen in the lower radiation dose arm [2]. Studies that incorporated adjuvant chemotherapy in average-risk medulloblastoma demonstrated 5-year event free survival (EFS) over 80% in the late 1990s [3, 4]. In the Children’s Oncology Group trial ACNS0331 children ages 3 to 7 years diagnosed with medulloblastoma were randomized to 18 Gray (Gy) or 23.4 Gy CSI with variable posterior fossa radiation boosts, followed by nine cycles of alkylator-based chemotherapy [11]
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