Feasibility and outcome of patients with medulloblastoma treated with pre-irradiation chemotherapy and reduced dose craniospinal radiotherapy (csrh) using mycc as a molecular marker for prognosis

Abstract

10040 Background: Children with medulloblastoma are more susceptible to the deleterious effects of craniospinal irradiation (CSRT) and have a higher relapse rate when treated with low-dose CSRT alone. Cytogenetic abnormalities that have been described in childhood medulloblastoma include loss of 17p, amplification of MYCC, amplification of MYCN and isochromosome 17q. This study was undertaken to determine the feasibility and efficacy of treating children with medulloblastoma with pre-irradiation chemotherapy and reduced-dose craniospinal radiotherapy and investigated the frequency and prognostic significance of MYCC amplification. Methods: 65 patients received 3 cycles of alternating chemotherapy (vincristine, etoposide and carboplatin and vincristine, etoposide and cyclophosphamide). All patients received radiotherapy to the craniospinal axis (25 Gy followed by a boost to posterior fossa with 30 Gy). After completion of CSRT, the patients received additional 3 cycles of alternating chemotherapy. Fluorescence in situ hybridization (FISH) was used to detect amplification of the MYCC oncogene. Results: Among the 65 patients, the median survival time was 21.0 months (3–52.0 months) from the date of diagnosis. The overall response rate was 89%. The estimated four-year progression-free survival was 78 percent and the four-year overall survival was 84 percent. The most predominant toxicity with post-irradiation chemotherapy was myelosuppression. Grade III neutropenia occurred in ≥60% of patients in each cycle. MYCC amplification was founded in 4 positive cases (6%). Estimate of the survival distributions for patients with and without MYCC amplification, reveals sufficient evidence to conclude that survival among MYCC-amplified patients is poorer than among non-amplified patients (P < .0001). Conclusions: This study has demonstrated the feasibility and benefits of administering pre-irradiation chemotherapy with reduced dose craniospinal irradiation in patients with medulloblastoma and confirmed the frequency of MYCC amplification in a large cohort of patients and further suggest that MYCC amplification may be a marker of poor prognosis. No significant financial relationships to disclose.