Skip to main content
Top
Published in: Journal of Neuro-Oncology 3/2019

01-05-2019 | Metastasis | Clinical Study

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

Authors: Dana L. Casey, Kenneth L. Pitter, Brandon S. Imber, Andrew Lin, Timothy A. Chan, Kathryn Beal, Yoshiya Yamada, Darren R. Feldman, T. Jonathan Yang

Published in: Journal of Neuro-Oncology | Issue 3/2019

Login to get access

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.
Literature
1.
go back to reference 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):345–351CrossRefPubMed 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):345–351CrossRefPubMed
2.
go back to reference 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):594–603CrossRef 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):594–603CrossRef
3.
go back to reference 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):2182–2185CrossRefPubMed 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):2182–2185CrossRefPubMed
4.
go back to reference 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):988–997CrossRefPubMed 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):988–997CrossRefPubMed
5.
go back to reference Boyle HJ, Jouanneau E, Droz JP, Flechon A (2013) Management of brain metastases from germ cell tumors: a single center experience. Oncology 85(1):21–26CrossRefPubMed Boyle HJ, Jouanneau E, Droz JP, Flechon A (2013) Management of brain metastases from germ cell tumors: a single center experience. Oncology 85(1):21–26CrossRefPubMed
6.
go back to reference 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):2908–2915CrossRefPubMed 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):2908–2915CrossRefPubMed
7.
go back to reference 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):1639–1646CrossRefPubMed 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):1639–1646CrossRefPubMed
8.
go back to reference 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):17–22CrossRefPubMed 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):17–22CrossRefPubMed
9.
go back to reference 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):959–965CrossRefPubMed 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):959–965CrossRefPubMed
10.
go back to reference 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):457–461CrossRefPubMed 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):457–461CrossRefPubMed
11.
go back to reference 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):887–893CrossRefPubMed 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):887–893CrossRefPubMed
12.
go back to reference 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):553–559CrossRefPubMed 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):553–559CrossRefPubMed
13.
go back to reference 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):1361–1364CrossRefPubMed 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):1361–1364CrossRefPubMed
14.
go back to reference 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):3810–3816CrossRefPubMedPubMedCentral 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):3810–3816CrossRefPubMedPubMedCentral
Metadata
Title
High-dose radiation therapy is needed for intracranial control and long-term survival in patients with non-seminomatous germ cell tumor brain metastases
Authors
Dana L. Casey
Kenneth L. Pitter
Brandon S. Imber
Andrew Lin
Timothy A. Chan
Kathryn Beal
Yoshiya Yamada
Darren R. Feldman
T. Jonathan Yang
Publication date
01-05-2019
Publisher
Springer US
Keyword
Metastasis
Published in
Journal of Neuro-Oncology / Issue 3/2019
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI
https://doi.org/10.1007/s11060-019-03123-0

Other articles of this Issue 3/2019

Journal of Neuro-Oncology 3/2019 Go to the issue