Faculty Bibliography

BACKGROUND: To determine the impact of diagnostic serum and/or cerebrospinal fluid (CSF) alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin (b-HCG) elevations on survival in newly diagnosed patients with central nervous system germ cell tumors (CNS GCT) treated with chemotherapy with the intent to avoid irradiation. PROCEDURE: Seventy-five patients with newly diagnosed CNS GCT enrolled in two sequential internationally conducted clinical trials with serum and CSF AFP and b-HCG levels available from initial diagnosis were retrospectively analyzed. Subjects received platinum based chemotherapy and were followed with serial imaging and tumor marker evaluations. RESULTS: The 5-year overall survival (OS) and event free survival (EFS) for patients with normal tumor markers compared with those with elevated markers at diagnosis was 78% (95% CI 51-91%) versus 60% (95% CI 46-72%) (P = 0.08) and 22% (95% CI 7-43%) versus 28% (95% CI 16-40%) (P = 0.68). The hazard ratio of death for patients with elevated markers was 1.9 times as high as that for those with normal markers (95% CI 0.58-6.5) after adjusting for other baseline characteristics. There was no observed difference in survival among patients with histologically confirmed germinomas, irrespective of level of b-HCG. CONCLUSIONS: Patients with elevated tumor markers appear to have poorer OS independent of tumor histology, although these differences do not reach statistical significance (P < or = 0.05). No differences were observed in EFS between groups likely due to the poor response of chemotherapy only approach to patients with normal markers. b-HCG elevations in biopsy proven germinomas do not seem to alter a patient's prognosis

PURPOSE: Children and adolescents with malignant astrocytomas recurring after initial treatment have a dismal prognosis, with only rare patients surviving 1-year beyond recurrence. The purpose of this study was to attempt to improve their survival. METHODS: Twenty-seven children and adolescents with malignant astrocytomas [17 glioblastoma multiforme and 10 anaplastic astrocytoma (AA)] following initial tumor progression, received myeloablative chemotherapy followed by autologous marrow rescue with one of three thiotepa and etoposide-based chemotherapy regimens, administered alone (n = 11) or combined with carmustine (n = 5) or carboplatin (n = 11). Time to progression and death following myeloablative chemotherapy for these patients was compared non-randomly with outcome of a contemporaneously treated cohort of similar patients who received only conventional chemotherapy following initial tumor progression. The two cohorts were compared for age, histology, prior therapies, extent of surgical resection at progression, and time from initial diagnosis to progression. RESULTS: Five of 27 children (two with glioblastoma multiforme and three with AA) survive event-free from 8.3 to 13.3 years (median of 11.1 years) following myeloablative chemotherapy. Of 56 children with recurrent malignant astrocytoma who received conventional chemotherapy following initial progression, no patient survives. Differences in distributions of survival were not significant when stratified by surgical debulking (P = 0.39). However, for patients who were surgically debulked, the survival distributions are significantly different (P = 0.017). CONCLUSIONS: Myeloablative chemotherapy with autologous marrow rescue can produce durable remissions in children and young adults with recurrent malignant gliomas, in the setting of minimal residual tumor burden achieved surgically

BACKGROUND: Central nervous system (CNS) atypical teratoid rhabdoid tumors (AT/RT) are rare tumors of childhood with a dismal prognosis. Historically, surgery and standard dose chemotherapy have resulted in a median survival of 8.5 months from diagnosis. METHODS: Thirteen children newly diagnosed with CNS AT/RT were treated with either the 'Head Start I' (HS I) or 'Head Start II' (HS II) regimens. Therapy included resection followed by five cycles of cisplatin, vincristine, cyclophosphamide, and etoposide. High dose methotrexate was added to each of the five induction courses in HS II. Consolidation for both regimens included carboplatin, thiotepa, and etoposide with autologous hematopoietic progenitor cell rescue (AHPCR). RESULTS: Six children, median age of 36 months, were treated on HS I between 1992 and 1997. Seven children, median age of 28 months, were treated on HS II between 1997 and 2002. One patient received craniospinal irradiation following AHPCR but prior to recurrence. There are presently three event-free survivors 42+, 54+, and 67+ months following diagnosis; none received RT. All three survivors were enrolled on HS II. Eight patients died of disease (six on HS I); one patient died from infection; one patient died from secondary malignancy following treatment for recurrent AT/RT. CONCLUSION: Three of seven children with CNS AT/RT treated on HS II have experienced long term remissions. Long term survival can be achieved in a subset of young children with CNS AT/RT following resection with the use of multi-drug chemotherapy including high dose methotrexate and myeloablative chemotherapy without radiation therapy (RT)