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

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Abstract

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.

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Data availability

The datasets generated and analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This study was supported by National Cancer Center, Korea (Grant No. 2110352).

Author information

Author notes

  1. Kyung Taek Hong and Jung Woo Han have contributed equally to this manuscript.

  2. Enrica Ee Kar Tan, Tai-Tong Wong and Joo-Young Kim are corresponding authors equally contributed to the manuscript.

Authors and Affiliations

  1. Department of Pediatrics, Seoul National University Children’s Hospital, Seoul National University College of Medicine, Seoul, Korea

    Kyung Taek Hong, Jung Yoon Choi & Hyoung Jin Kang

  2. Division of Pediatric Hematology and Oncology, Department of Pediatrics, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea

    Jung Woo Han & Chuhl Joo Lyu

  3. Department of Radiation Oncology, Research Institute and Hospital, National Cancer Center, Goyang, Korea

    Yang-Gun Suh & Joo-Young Kim

  4. Department of Radiation Oncology, National Center for Child Health and Development, Tokyo, Japan

    Hiroshi Fuji

  5. Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea

    Hwa Kyung Byun & Hong In Yoon

  6. Division of Pediatric Hematology/Oncology, Department of Pediatrics, Asan Medical Center Children’s Hospital, University of Ulsan College of Medicine, Seoul, Korea

    Kyung-Nam Koh & Ho Joon Im

  7. Department of Radiation Oncology, National Cancer Centre, Singapore, Singapore

    Ru Xin Wong & Wen Shen Looi

  8. Division of Radiation Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan

    Yi-Wei Chen

  9. Department of Radiation Oncology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea

    Joo Ho Lee

  10. Division of Pediatric Neurosurgery, Seoul National University Children’s Hospital, Seoul National University College of Medicine, Seoul, Korea

    Ji Hoon Phi & Seung-Ki Kim

  11. Department of Neurosurgery, Yonsei University College of Medicine, Seoul, Korea

    Dong-Seok Kim

  12. Division of Pediatric Neurosurgery, Department of Neurosurgery, Asan Medical Center Children’s Hospital, University of Ulsan College of Medicine, Seoul, Korea

    Young-Shin Ra

  13. Division of Pediatric Neurosurgery, Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan

    Yi-Yen Lee

  14. Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

    Seung Do Ahn

  15. National Neuroscience Institute, Singapore, Singapore

    Sharon Yin Yee Low

  16. Center for Pediatric Oncology, National Cancer Center, Goyang, Korea

    Hyeon Jin Park

  17. Department of Radiation Oncology, CHA Bundang Medical Center, CHA University, Seongnam, South Korea

    Chang-Ok Suh

  18. Neuro-Oncology Clinic, National Cancer Center, Goyang, Korea

    Kyu-Chang Wang

  19. Department of Pediatric Subspecialties, Pediatric Hematology/Oncology Service, KK Women’s and Children’s Hospital, Singapore, Singapore

    Enrica Ee Kar Tan

  20. Pediatric Brain Tumor Program, Taipei Cancer Center, and Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan

    Tai-Tong Wong

  21. Department of Radiation Oncology, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan

    Hsin-Lun Lee

Authors
  1. Kyung Taek Hong
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  2. Jung Woo Han
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  3. Hiroshi Fuji
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  5. Kyung-Nam Koh
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Contributions

Conceptualization and design: JYK, EEKT and TTW. Acquisition of data: KTH, JWH, HF, HKB, KNK, WRX, HLL, HIY, JHL, JHP, SKK, DSK, CJL, JYC, HJK, YWC, YYL, HJI, YSR, SDA, SYYL, WSL, HJP, YGS, COS, KCW, EEKT, TTW, and JYK. Analysis of data: KTH, JWH, and JYK. Manuscript writing: KTH, JWH, EEKT, TTW, and JYK. Final editing and approval of the manuscript: KTH, JWH, HF, HKB, KNK, WRX, HLL, HIY, JHL, JHP, SKK, DSK, CJL, JYC, HJK, YWC, YYL, HJI, YSR, SDA, SYYL, WSL, HJP, YGS, COS, KCW, EEKT, TTW, and JYK. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Enrica Ee Kar Tan, Tai-Tong Wong or Joo-Young Kim.

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Conflict of interest

There is no conflict of interest for all authors.

Ethical approval

The Institutional Review Board at each institute approved the procedure of reviewing medical records.

Informed consent

Informed consent was waived because all data analyzed in this paper are anonymous.

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Supplementary Information

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11060_2022_4100_MOESM1_ESM.pptx

Supplementary file1 (PPTX 2600 kb)—Figure S1 Distribution of tumor markers according to pathology. Shown is the distribution of serum β-hCG (A, B) and AFP (C, D) markers according to the pathological diagnosis of tumor by various x-axis scales. Secreting germinoma is mainly associated with elevated β-hCG, and elevation of tumor markers was observed even when the final diagnosis was mature teratoma and immature teratoma. Figure S2 Treatment patterns according to pathology. Shown are the surgical details (A), the timing of chemotherapy (B), and the volume of radiotherapy (C) according to the pathological findings of the tumor. Figure S3 Kaplan–Meier curves according to radiotherapy. Shown are the overall survival (A), and the event-free survival (B) of malignant germ cell tumors according to the radiotherapy field. The overall survival (C), and the event-free survival (D) of immature teratoma (IMT) and mature teratoma (MT) according to the radiotherapy field are followed. In (C) and (D), events of relapse and death for IMT and MT are indicated as blue arrows and pink arrows, respectively. Figure S4 Comparison of treatment outcomes of the Unknown pathology group according to tumor marker levels. Overall survival (A) and event-free survival (B).

Supplementary file2 (DOCX 52 kb)

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Hong, K.T., Han, J.W., Fuji, H. et al. Outcomes of intracranial non-germinomatous germ cell tumors: a retrospective Asian multinational study on treatment strategies and prognostic factors. J Neurooncol 160, 41–53 (2022). https://doi.org/10.1007/s11060-022-04100-w

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