Improved outcome of central nervous system germ cell tumors: implications for the role of risk-adapted intensive chemotherapy

Abstract

To determine the impact of treatment protocols on the outcome of central nervous system germ cell tumors (CNS-GCTs), we reviewed the medical records of 53 patients who received front-line chemotherapy from September 1997 to September 2006. Pure germinoma, normal alpha-fetoprotein level and beta-human chorionic gonadotropin level <50 mIU/mL were regarded as low-risk features and the others as high-risk. Patients from different time periods were divided into 3 groups according to the chemotherapy protocols. Group 1 (n=19) received 4 cycles of chemotherapy comprising cisplatin, etoposide and bleomycin. Group 2 (n=16) and group 3 (n=18) received 4 cycles of chemotherapy with cisplatin, etoposide, cyclophosphamide and vincristine in the former and with carboplatin, etoposide, cyclophosphamide and bleomycin in the latter. In group 2 and group 3, high-risk patients received double doses of cisplatin, carboplatin and cyclophosphamide. Radiotherapy was given after chemotherapy according to the clinical requirements. The event-free survivals of groups 1, 2, and 3 were 67.0%, 93.8%, and 100%, respectively (group 1 vs. 2, P=0.06; group 2 vs. 3, P=0.29; group 1 vs. 3, P=0.02). Our data suggest that risk-adapted intensive chemotherapy may improve the outcome of patients with malignant CNS-GCTs.

Keywords: Central Nervous System; Drug Therapy; Neoplasms, Germ Cell and Embryonal; Survival.

Fig. 1

Risk-adapted chemotherapy. CECO regimen is for group 2 and CECB regimen for group 3. In each regimen, course [a] and course [b] were administered alternatively as '[a]-[b]-[a]-[b]' every 3 week intervals and were completed after 4 cycles in total. ^*For high-risk patients. CDDP, cisplatin; VP-16, etoposide; VCR, vincristine; CPM, cyclophosphamide; CBDCA, carboplatin; Bleo, bleomycin.

Fig. 2

The Kaplan-Meier estimate of survival. The 5-yr overall survival (OS) and event-free survival (EFS) of 53 patients were 90.6% and 85.5%, respectively (A). Low-risk patients show better EFS than high-risk patients (92.6% vs. 79.3%, P=0.24) without a statistical significance (B).

Fig. 3

The Kaplan-Meier estimate of event-free survival (EFS). In group 1, the high-risk patients show inferior EFS compared to the low-risk patients without a statistical significance (A). In group 2 (B) and group 3 (C), even the high-risk patients show excellent EFS. The EFS of group 3 is superior to that of group 1 (P=0.02), while the difference between group 1 and group 2 (P=0.06) as well as group 2 and group 3 (P=0.29) do not show a statistical significance (D).