Skip to main content

Advertisement

Log in

High-dose radiation therapy is needed for intracranial control and long-term survival in patients with non-seminomatous germ cell tumor brain metastases

  • Clinical Study
  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

Purpose

The presence of brain metastases (BM) in patients with non-seminomatous germ cell tumor (NSGCT) is associated with poor prognosis. While radiation therapy (RT) is an important treatment for patients with NSGCT BM, there is a paucity of data on the optimal regimen. We sought to investigate the impact of RT on clinical outcomes in patients with NSGCT BM.

Methods

Patients with NSGCT BM who received RT at our institution from 2002 to 2017 were included. Sixty-three consecutive patients were identified. Clinical factors associated with intracranial control (ICC) and overall survival (OS) were evaluated using cox regression analysis and Kaplan Meier method.

Results

Median age was 31 years and number of BM was three. Fifteen patients presented with BM at diagnosis, while 48 developed BM at a median time of 8.4 months from diagnosis. At a median follow-up of 3.6 years, ICC and OS were 39.7% and 30.1%. On multivariate analysis, ICC (hazard ratio [HR] = 0.93, p = 0.03) and OS (HR = 0.93, p = 0.005) were both significantly associated with biologically effective dose (BED) of RT. The 4-year OS of patients who received BED < 39Gy, 39 Gy, 40–50 Gy, and ≥ 50 Gy were 0%, 14.7%, 34.1%, and 70.0%, respectively. Patients who achieved ICC after RT were able to achieve long-term survival (4-year OS 68.1% vs. 0%, p < 0.0001).

Conclusions

Our data supports that a higher BED is required for durable ICC, and that ICC is needed for patients with NSGCT to achieve long-term survival. Prospective studies evaluating radiation dose-escalation for the treatment of NSGCT BM should be considered.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Feldman DR, Lorch A, Kramar A, Albany C, Einhorn LH, Giannatempo P, Necchi A, Flechon A, Boyle H, Chung P et al (2016) Brain metastases in patients with germ cell tumors: prognostic factors and treatment options—an analysis from the global germ cell cancer group. J Clin Oncol 34(4):345–351

    Article  PubMed  Google Scholar 

  2. Wilkinson PM, Read G (1997) International germ cell consensus classification : a prognostic factor-based staging system for metastatic germ cell cancers. International Germ Cell Cancer Collaborative Group. J Clin Oncol 15(2):594–603

    Article  Google Scholar 

  3. Raina V, Singh SP, Kamble N, Tanwar R, Rao K, Dawar R, Rath GK (1993) Brain metastasis as the site of relapse in germ cell tumor of testis. Cancer 72(7):2182–2185

    Article  CAS  PubMed  Google Scholar 

  4. Fossa SD, Bokemeyer C, Gerl A, Culine S, Jones WG, Mead GM, Germa-Luch JR, Pont J, Schmoll HJ, Tjulandin S (1999) Treatment outcome of patients with brain metastases from malignant germ cell tumors. Cancer 85(4):988–997

    Article  CAS  PubMed  Google Scholar 

  5. Boyle HJ, Jouanneau E, Droz JP, Flechon A (2013) Management of brain metastases from germ cell tumors: a single center experience. Oncology 85(1):21–26

    Article  CAS  PubMed  Google Scholar 

  6. Balmaceda C, Heller G, Rosenblum M, Diez B, Villablanca JG, Kellie S, Maher P, Vlamis V, Walker RW, Leibel S et al (1996) Chemotherapy without irradiation—a novel approach for newly diagnosed CNS germ cell tumors: results of an international cooperative trial. The first international central nervous system germ cell tumor study. J Clin Oncol 14(11):2908–2915

    Article  CAS  PubMed  Google Scholar 

  7. Hardt A, Krell J, Wilson PD, Harding V, Chowdhury S, Mazhar D, Berney D, Stebbing J, Shamash J (2014) Brain metastases associated with germ cell tumors may be treated with chemotherapy alone. Cancer 120(11):1639–1646

    Article  CAS  PubMed  Google Scholar 

  8. Spears WT, Morphis JG II, Lester SG, Williams SD, Einhorn LH (1992) Brain metastases and testicular tumors: long-term survival. Int J Radiat Oncol Biol Phys 22(1):17–22

    Article  CAS  PubMed  Google Scholar 

  9. Girones R, Aparicio J, Roure P, Germa-Lluch JR, Garcia Del Muro X, Vazquez-Estevez S, Saenz A, Sastre J, Arranz Arija J, Gallardo E et al (2014) Synchronous versus metachronous brain metastasis from testicular germ cell tumors (TGCT): an analysis from the Spanish germ cell cancer group data base. Clin Transl Oncol 16(11):959–965

    Article  CAS  PubMed  Google Scholar 

  10. Mahalati K, Bilen CY, Ozen H, Aki FT, Kendi S (1999) The management of brain metastasis in nonseminomatous germ cell tumours. BJU Int 83(4):457–461

    Article  CAS  PubMed  Google Scholar 

  11. Nonomura N, Nagahara A, Oka D, Mukai M, Nakai Y, Nakayama M, Nishimura K, Kakimoto K, Nakamura T, Usami M et al (2009) Brain metastases from testicular germ cell tumors: a retrospective analysis. Int J Urol 16(11):887–893

    Article  PubMed  Google Scholar 

  12. Kollmannsberger C, Nichols C, Bamberg M, Hartmann JT, Schleucher N, Beyer J, Schofski P, Derigs G, Ruther U, Bohlke I et al (2000) First-line high-dose chemotherapy +/− radiation therapy in patients with metastatic germ-cell cancer and brain metastases. Ann Oncol 11(5):553–559

    Article  CAS  PubMed  Google Scholar 

  13. Doyle DM, Einhorn LH (2008) Delayed effects of whole brain radiotherapy in germ cell tumor patients with central nervous system metastases. Int J Radiat Oncol Biol Phys 70(5):1361–1364

    Article  PubMed  Google Scholar 

  14. Gondi V, Pugh SL, Tome WA, Caine C, Corn B, Kanner A, Rowley H, Kundapur V, DeNittis A, Greenspoon JN et al (2014) Preservation of memory with conformal avoidance of the hippocampal neural stem-cell compartment during whole-brain radiotherapy for brain metastases (RTOG 0933): a phase II multi-institutional trial. J Clin Oncol 32(34):3810–3816

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Funding

NIH Grant P30 CA 008748.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to T. Jonathan Yang.

Ethics declarations

Conflict of interest

No relevant conflicts of interest. K.B. reports serving as a shareholder of MMT, outside of the submitted work.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Casey, D.L., Pitter, K.L., Imber, B.S. et al. High-dose radiation therapy is needed for intracranial control and long-term survival in patients with non-seminomatous germ cell tumor brain metastases. J Neurooncol 142, 523–528 (2019). https://doi.org/10.1007/s11060-019-03123-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11060-019-03123-0

Keywords

Navigation