Outcomes of intracranial non-germinomatous germ cell tumors: a retrospective Asian multinational study on treatment strategies and prognostic factors

J Neurooncol. 2022 Oct;160(1):41-53. doi: 10.1007/s11060-022-04100-w. Epub 2022 Aug 31.


Purpose: Non-germinomatous germ cell tumors (NGGCTs) are rare pediatric conditions. This multicenter study using Asian multinational patient data investigated treatment outcomes and prognostic factors for NGGCTs.

Methods: Medical records of 251 patients with NGGCTs treated from 1995 to 2015 were retrospectively analyzed from participating centers in Asian countries (Korea, Taiwan, Singapore, and Japan).

Results: The median follow up was 8.5 years (95% CI 7.8-9.9). In the total cohort, 5-year event-free survival (EFS) and overall survival (OS) rates were 78.2% and 85.4%, respectively. In 17.9% of the patients, diagnosis was determined by tumor markers alone (alpha-fetoprotein ≥ 10 ng/mL (Korea) or > 25 ng/mL (Taiwan and Singapore), and/or β-human chorionic gonadotropin (β-hCG) ≥ 50 mIU/mL). Patients with immature teratomas and mature teratomas comprised 12.0% and 8.4%, respectively. The 5-year EFS rate was higher in patients with histologically confirmed germinoma with elevated β-hCG (n = 28) than those in patients with malignant NGGCTs (n = 127). Among malignant NGGCTs, patients with choriocarcinoma showed the highest 5-year OS of 87.6%, while yolk sac tumors showed the lowest OS (68.8%). For malignant NGGCT subgroups, an increase in serum β-hCG levels by 100 mIU/mL was identified as a significant prognostic factor associated with the EFS and OS.

Conclusion: Our result shows excellent survival outcomes of overall CNS NGGCT. However, treatment outcome varied widely across the histopathologic subgroup of NGGCT. Hence, this study suggests the necessity for accurate diagnosis by surgical biopsy and further optimization of diagnosis and treatment according to the histopathology of NGGCTs. Future clinical trials should be designed for individualized treatments for different NGGCTs subsets.

Keywords: Central nervous system; Event-free survival; Non-germinomatous germ cell tumor; Overall survival; Prognostic factor.

Publication types

  • Multicenter Study

MeSH terms

  • Brain Neoplasms* / drug therapy
  • Brain Neoplasms* / therapy
  • Child
  • Chorionic Gonadotropin, beta Subunit, Human
  • Germinoma* / pathology
  • Humans
  • Male
  • Neoplasms, Germ Cell and Embryonal* / diagnosis
  • Neoplasms, Germ Cell and Embryonal* / therapy
  • Prognosis
  • Retrospective Studies


  • Chorionic Gonadotropin, beta Subunit, Human

Supplementary concepts

  • Nonseminomatous germ cell tumor