No Difference in Event-free Survival with Chemotherapy before vs after Radiation Therapy in Children with High-risk Medulloblastoma
A number of different strategies for combining chemotherapy and radiation therapy have been evaluated in the effort to improve survival in patients with high-risk medulloblastoma. In a trial (POG 9031) reported in Journal of Clinical Oncology, Nancy J. Tarbell, MD, of Massachusetts General Hospital and colleagues in the Pediatric Oncology Group assessed the effects of chemotherapy before vs after radiation therapy following surgery in children with high-risk medulloblastoma. They found no difference in 5-year event-free survival with the two strategies.
Study Details
In the trial, 224 patients aged 3 to 21 years with high-risk medulloblastoma were randomly assigned after surgery to chemotherapy with three cycles of cisplatin at 90 mg/m2 and etoposide at 150 mg/m2 over 7 weeks followed by radiation (n = 112) or radiation therapy followed by the same chemotherapy (n = 112). Patients were considered high risk if they had M1-4 disease by modified Chang staging classification, exhibited T3b/T4 disease at time of surgery, or had greater than 1.5 cm3 of residual tumor after surgery.
Radiation therapy consisted of craniospinal irradiation of 35.2 to 44.0 Gy and posterior fossa boost of 53.2 to 54.4 Gy. All patients received consolidation chemotherapy consisting of vincristine and cyclophosphamide for 28 weeks. The median age was 7.8 years (range 3.0-21.4 years). The chemotherapy-first and radiation therapy–first groups were balanced for sex (55% and 62% male), race (79% and 74% white), M stage (52% M0 in both groups), and T stage (3b or 4 in 73% and 70%); 40 patients in the chemotherapy-first group and 32 in the radiation therapy–first group were T3b/T4 M0 with no residual disease.
Event-free Survival Outcomes
Median follow-up was 6.4 years. Five-year event-free survival was 66.0% in the chemotherapy-first group and 70.0% in the radiation therapy–first group (P = .54), and 5-year overall survival in the two groups was 73.1% and 76.1% (P = .47). There was no evidence of a difference in event-free survival between treatments after stratifying for stage.
In patients with M0 and residual disease after surgery, 5-year event-free survival was 59.6% in the chemotherapy-first group and 65.1% in the radiation therapy–first group (P = .40). In patients with M+ and residual disease, 5-year event-free survival was 51.2% and 64.0% (P = .20). Objective response rates in evaluable patients were 66% in the chemotherapy-first group and 86% in the radiation therapy–first group (P = .01). There was no significant difference in 5-year event-free survival between patients in the chemotherapy-first group who achieved response and those who did not (73% vs 56%, P =.1).
With regard to acute toxicity, there were more episodes of thrombocytopenia in the radiation therapy–first group, but toxicity was otherwise similar in the two groups. Treatment-induced disease included myelodysplastic syndrome in two patients and ossifying fibroma in one patient.
The investigators concluded, “The event-free survival and overall survival reported in this study compare favorably with other trials examining high-risk medulloblastoma. Preirradiation chemotherapy fails to confer a survival advantage over radiation before chemotherapy.”
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