Infants and very young children with brain tumors have a worse prognosis than older children. They are also at higher risk for neurotoxicity including mental retardation, growth failure, and leukoencephalopathy. Due to these factors there is reluctance to treat infants and young children with radiation therapy. Recent studies have been designed to use chemotherapy and to either withhold radiation therapy or postpone its use to a time when the patient is older. Postoperative chemotherapy with cyclophosphamide, vincristine, cisplatin, and etoposide in children under 36 months of age at diagnosis (Table 17-4) is utilized followed by delayed radiation. Chemotherapy is administered for 48-96 weeks, depending on age at diagnosis, to delay radiation until as close to age 3 as possible or beyond. Ongoing studies are evaluating adding high-dose methotrexate to higher-risk cases. Newer approaches using high-dose chemotherapy with autologous stem cell rescue (Table 17-8) to intensify the chemotherapeutic regimen have been employed in an attempt to avoid radiation altogether.
Average-risk medulloblastoma and other PNETs have a 5-year PFS of about 40% in those who received chemotherapy and delayed reduced craniospinal irradiation. This increases to 60% for patients with a gross total resection. Gliomas may not do as well with this therapy. The 5-year PFS is between 0 and 43% in completely resected disease. The 5-year PFS of ependymoma is 66%, decreasing to 25% for those with subtotal resection.
Trials of intensive chemotherapy followed by stem cell rescue have also been attempted in young children with malignant brain tumors with promising results with the avoidance of radiation therapy. The current COG study uses three tandem autolo-gous stem cell rescues after three cycles of chemotherapy. These approaches require further research. Additionally, with 3-D conformal radiation and IMRT, the timing and use of radiation therapy in subsets of disease that do worse with poor prognoses (i.e., subtotal resections) should be studied. The use of second-look surgery is also being evaluated in current trials.
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