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High-Dose Chemo Before RT Results in High Survival in Pediatric Brain Tumors

High-Dose Chemo Before RT Results in High Survival in Pediatric Brain Tumors

High-dose chemotherapy plus conventional radiotherapy resulted in a high 3-year overall survival in children and adolescents with newly diagnosed medulloblastoma and supratentorial primitive neuroectodermal tumor (sPNET).

Christelle Dufour, MD, of Gustave Roussy, France, presented the results of the phase II study (abstract 10007) at the 2014 American Society of Clinical Oncology (ASCO) Annual Meeting.

“The strategy based on intensified chemotherapy before craniospinal radiation provides high survival rates in children and adolescents with newly diagnosed high-risk cerebral PNET,” Dufour said during her presentation. “Analyses of neurocognitive and endocrinologic outcomes of these patients are ongoing.”

Medulloblastoma is the most common brain tumor in children. Patients with high-risk disease are those with residual postoperative disease or metastatic disease. More recently, patients with large-cell, anaplastic, or myc amplified medulloblastoma are also considered high risk. Standard treatment of this disease is craniospinal radiation with a boost on the primitive tumor bed, which results in a 5-year progression-free survival of about 50% to 60%.

In contrast, sPNET are rare tumors with a very poor prognosis of only 20% to 50% progression-free survival at 5 years. Despite differences in outcomes, patients with sPNET are treated according to the high-risk medulloblastoma protocols.

In this study, Dufour and colleagues wanted to improve 3-year progression-free survival in children with high-risk medulloblastoma or sPNET with treatment based on intensified chemotherapy before standard craniospinal radiotherapy and maintenance treatment with temozolomide. All patients in the study were aged 5 to 20 years and received no prior therapy.

After biopsy or initial surgery patients received postoperative induction chemotherapy two cycles of etoposide/carboplatin, followed by two courses of thiotepa (600mg/m2 per course) with autologous stem cell rescue. Risk-adapted conventional radiotherapy was delivered around day 45 after second transplantation. Maintenance treatment with six cycles of temozolomide was planned to start between 1 and 3 months after the end of radiotherapy. The median age of patients with medulloblastoma was 8; the median age of patients with sPNET was 13 years.

The median follow-up was 32 months. The 3-year progression-free survival rate was 79% for patients with medulloblastoma and 85% for patients with sPNET. The 3-year overall survival was 84% for patients with high-risk medulloblastoma and 92% for sPNET.

According to Dufour, patients experienced no major unexpected adverse events and no treatment-related deaths were reported.

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