Malignant germ cell tumors in childhood: results of the first Italian Cooperative Study TCG 91

Background and Aims. About 20% of patients with germ cell tumor (GCT) are still resistant to therapy. To investigate which features are present in resistant patients, a multicenter study on GCT in children was undertaken to correlate clinical and laboratory parameters with the outcome. Methods. Patients aged less than 16 years, with histologically proven extracranial GCT were included. Results. Ninety-five patients (median age 33 months, 45 males) were eligible. The site of the primary tumor was gonadal in 59, extragonadal in 36. The stage was I in 39; II in 5; IIIa (microscopic residue) in 7; IIIb (macroscopic residue) in 16; IIIc (unresectable) in 13; IV in 15. The treatment was surgery alone in 31; surgery plus radiotherapy in 1; chemotherapy surgery in 63. Post-chemotherapy resection in 19 (10 complete, 9 partial). The chemotherapy regimen was carboplatin 400 mg/m(2)/day on days 1, 2; etoposide 150 mg/m(2)/day on days 1, 2; ifosfamide 1,500 mg/m(2)/day on days 21, 22; dactinomycin 1.5 mg/m(2)/day on day 21; vincristine 1.5 mg/m(2)/day on day 21. Three patients died because of toxicity and two non-responders (to primary chemotherapy), died of progression; among the remaining 90 patients 20 relapsed, 9 are in second remission, 2 are alive with disease, and 9 died of disease progression (one from progression and intracranial hemorrhage). Overall survival was 82.7% and event-free survival: 71.5%. Survival according to: (a) site: testis: 100%; ovary: 88%; sacrococcyx: 69.6%; other sites: 33.3% (P< 0.001); (b) stage: I and II: 100%; IIIa: 83.3%; IIIb: 84.6%; IIIc: 60.6%; IV: 53.2% (P< 0.001); (c) AFP levels: normal: 85.5%; 429,470 ng/ml: 84.6%; greater than or equal to10,000 ng/ml: 58.7% (P=0.02). All the pts who had complete resection of the primary tumor at diagnosis or at delayed surgery, remained in remission. Conclusions. Multivariate analysis showed that the primary site of tumor was the only independent prognostic factor for survival and EFS. (C) 2003 Wiley-Liss, Inc.