THE TREATMENT OF INFANTS AND VERY YOUNG CHILDREN WITH BRAIN TUMORS: THE U.S. COOPERATIVE GROUP EXPERIENCE: 1986–2006

Survivals of young children with malignant brain tumors are worse than any other age group and they also suffer the brunt of radiation-induced neurotoxicity. As such, the Pediatric Oncology Group (POG) in 1986 mounted a group-wide study in which children <3 years of age with malignant brain tumors were treated with prolonged postoperative chemotherapy (vincristine, cyclophosphamide, cisplatinum and VP16) in an effort to delay radiation for two years in children <2 years of age at diagnosis and for one year in children 2–3 years. “Baby POG” became the basis of all U.S. cooperative group infant brain tumor studies over the following 20 years. By 2006, over 1000 infants had been treated. Prognostic factors identified by Baby POG 1 were: 1) supratentorial PNETs had the worst prognosis, 2) age did not significantly impact survival, 3) delay in radiation from 1 to 2 years only affected survival in ependymomas, 4) groß total resection (GTR) significantly improved survival, 5) metastases did not significantly worsen outcome, 6) those with GTR and no metastases had the best outcome.

The second generation of baby studies were Baby POG 2 and CCG 9921. Dose intensification was given in both in an effort to reduce early failures. In addition, radiation was eliminated if there was no evidence of disease following chemotherapy. In both studies (1992–1998), significantly more children had a GTR and response rates were higher than on Baby POG 1. Despite these successes, five-year survivals were no better than on Baby POG 1. Baby POG 3 (Mo medulloblastoma) built on the previous studies while including 3-D conformal radiation to the tumor bed. Whether distant failures will be a consequence is not known.

Although a great deal about infant brain tumors has been learned, survivals for many children remain sub-optimal. High-dose chemotherapy with bone marrow transplantation/stem cell support, intrathecal chemotherapy, and risk stratification are currently being studied.