2ND MALIGNANCIES IN YOUNG-CHILDREN WITH PRIMARY BRAIN-TUMORS FOLLOWING TREATMENT WITH PROLONGED POSTOPERATIVE CHEMOTHERAPY AND DELAYED IRRADIATION - A PEDIATRIC-ONCOLOGY-GROUP STUDY

Between 1986 and 1990, the Pediatric Oncology Group conducted a study in which 198 children younger than 3 years of age with malignant brain tumors were treated with prolonged postoperative chemotherapy in an e ffort to delay irradiation and reduce long-term neurotoxicity. Childre n younger than 2 years of age received 24 months of chemotherapy follo wed by irradiation, and those between 2 and 3 years of age received 12 months of chemotherapy plus irradiation. Chemotherapy was given in 28 -day cycles (AAB, AAB), with cycle A = vincristine (0.065 mg/kg) intra venously on days 1 and 8 and cyclophosphamide (65 mg/kg) intravenously on day 1, and cycle B = cisplatinum (4 mg/kg) intravenously on day 1 and etoposide (6.5 mg/kg) intravenously on days 3 and 4. Five of the 1 98 children developed second malignancies, with a cumulative risk at 8 years of 11.3% (95% confidence interval [CI], 0-39%). Four of the fiv e second malignancies occurred in children younger than 2 years of age at diagnosis, with a cumulative risk at 8 years of 18.9% (CI, 0-70%). Initial diagnoses were choroid plexus carcinoma (2 children), ependym oma (1 child), desmoplastic infantile ganglioglioma (2 children), and medulloblastoma (1 child). Duration from diagnosis of initial tumor to second malignancy was 33, 35, 57, 66, and 92 months. Three children y ounger than 2 years of age developed lymphoproliferative disease, that is, myelodysplastic syndrome (2 children), both with monosomy 7 delet ions, and acute myelogenous leukemia (1 child), after 24 to 26 cycles of chemotherapy, including 8 cycles of etoposide. Two of 3 received cr aniospinal irradiation (2,560/3,840 cGy) and (3,520/5,320 cGy). Time t o second malignancy was 7 years 8 months, 4 years 9 months, and 2 year s 9 months. Two children developed solid tumors, at 5 years 6 months a nd 2 years 11 months, respectively, after initiation of treatment. A s arcoma developed after 26 cycles of chemotherapy and no irradiation, a nd a meningioma developed after 12 cycles of chemotherapy and local cr aniospinal irradiation. Potential causative factors for this high rate of secondary malignancies include prolonged use of alkylating agents and etoposide with or without irradiation.