Outcome of patients with intracranial non-germinomatous germ cell tumors-lessons from the SIOP-CNS-GCT-96 trial

Abstract

Background: Following promising results to increase survival and reduce treatment burden in intracranial non-germinomatous germ cell tumors (NGGCTs), we conducted a European study using dose-intense chemotherapy followed by risk-adapted radiotherapy.

Methods: All patients received 4 courses of cisplatin/etoposide/ifosfamide. Non-metastatic patients then received focal radiotherapy only (54 Gy); metastatic patients received 30 Gy craniospinal radiotherapy with 24 Gy boost to primary tumor and macroscopic metastatic sites.

Results: Patients with localized malignant NGGCT (n = 116) demonstrated 5-year progression-free survival (PFS) and overall survival (OS) of 0.72 ± 0.04 and 0.82 ± 0.04, respectively. Primary tumor sites were: 67 pineal, 35 suprasellar, 5 bifocal, 9 others. One patient died postsurgery in clinical remission; 3 patients progressed during treatment and 27 (23%) relapsed afterward. Fourteen were local, 6 combined, and 7 distant relapses (outside radiation field). Seventeen of the 27 relapsed patients died of disease. Patients with metastatic disease (n = 33) demonstrated 5-year PFS and OS of 0.68 ± 0.09 and 0.75 ± 0.08, respectively; 1 patient died following progression on treatment and 9 (27%) relapsed afterward (5 local, 1 combined, 3 distant). Only one metastatic patient with recurrence was salvaged. Multivariate analysis identified diagnostic alpha-fetoprotein level (serum and/or cerebrospinal fluid level >1000 ng/mL, 19/149 patients, of whom 11 relapsed; P < 0.0003) and residual disease following treatment, including after second-look surgery (n = 52/145 evaluable patients, 26 relapsed; P = 0.0002) as significant prognostic indicators in this cohort.

Conclusion: In localized malignant NGGCT, craniospinal radiotherapy could be avoided without increased relapses outside the radiotherapy field. Chemotherapy and craniospinal radiotherapy remain the gold standard for metastatic disease.

Keywords: chemotherapy; intracranial non-germinoma; radiotherapy; relapse; toxicity.

Fig. 1

CONSORT diagram of the 219 patients enrolled on the SIOP-CNS-GCT-96 trial; 149 patients were eligible.

Fig. 2

Overview of the treatment regimen for the treatment of patients with intracranial malignant NGGCTs on the SIOP-CNS-GCT-96 trial protocol.

Fig. 3

PFS for the 149 eligible patients on the SIOP-CNS-GCT-96 protocol (116 localized vs 33 metastatic patients).

Fig. 4

OS for the 149 eligible patients on the SIOP-CNS-GCT-96 protocol (116 localized vs 33 metastatic patients).

Fig. 5

PFS for the 149 eligible patients on the SIOP-CNS-GCT-96 protocol by diagnostic AFP level (130 patients with AFP ≤1000 ng/mL vs 19 patients with AFP >1000 ng/mL).

Fig. 6

PFS for the 145 evaluable patients on the SIOP-CNS-GCT-96 protocol by end-of-treatment status (93 patients without residual tumor vs 52 with residual).