POSTOPERATIVE CHEMOTHERAPY AND DELAYED RADIATION IN CHILDREN LESS-THAN 3 YEARS OF AGE WITH MALIGNANT BRAIN-TUMORS

Background. Among patients with malignant brain tumors, infants and ve ry young children have the worst prognosis and the most severe treatme nt-related neurotoxic effects. Therefore, in 1986, the Pediatric Oncol ogy Group began a study in which postoperative chemotherapy was given in order to permit a delay in the delivery of radiation to the develop ing brain. Methods. Children under 36 months of age with biopsy-proved malignant brain tumors were treated postoperatively with two 28-day c ycles of cyclophosphamide plus vincristine, followed by one 28-day cyc le of cisplatin plus etoposide. This sequence was repeated until the d isease progressed or for two years in 132 children under 24 months of age at diagnosis and for one year in 66 children 24 to 36 months of ag e at diagnosis. After this, the patients received radiation therapy. T he response to the first two cycles of chemotherapy was measured in 10 2 patients with residual postoperative disease. Results. The first two cycles of cyclophosphamide and vincristine produced complete or parti al responses in 39 percent of the 102 patients who could be evaluated. The response rates were highest among patients with medulloblastomas, malignant gliomas, or ependymomas. Patients with brain-stem gliomas o r embryonal tumors (primitive neuroectodermal tumors) had little or no response. The progression-free survival rate was 41 percent at one ye ar for children who were 24 to 36 months old at diagnosis and 39 perce nt at two years for those under 24 months of age at diagnosis. Multiva riate analysis identified embryonal tumors as a significant adverse pr ognostic feature (relative risk, 2.2; 95 percent confidence interval, 1.4 to 3.4) and complete resection as a favorable feature (relative ri sk, 0.33; 95 percent confidence interval, 0.20 to 0.54). Complete resp onses to chemotherapy were associated with a progression-free survival rate approaching that achieved with gross total resection. A comparis on of cognitive evaluations obtained at base line and after one year o f chemotherapy revealed no evidence of deterioration in cognitive func tion. Conclusions. Chemotherapy appears to be an effective primary pos toperative treatment for many malignant brain tumors in young children . Disease control for one or two years in a large minority of patients permitted a delay in the delivery of radiation and, on the basis of p reliminary results, a reduction in neurotoxicity. For patients who had undergone total surgical resection or who had a complete response to chemotherapy, the results are sufficiently encouraging to suggest that radiation therapy may not be needed in this subgroup of children afte r at least one year of chemotherapy.