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Treatment and survival of primary intracranial germ cell tumors: a population-based study using SEER database

  • Steven Denyer
  • Abhiraj D. Bhimani
  • Shashank N. Patil
  • Andrew Mudreac
  • Mandana Behbahani
  • Ankit I. MehtaEmail author
Original Article – Clinical Oncology
  • 53 Downloads

Abstract

Introduction

Primary intracranial germ cell tumors are rare neoplasms derived from gonadal cells. They are categorized as germinoma, non-germinomatous germ cell tumor (NGCCT), or teratoma, with the latter two sparking controversy regarding the role of different treatment strategies. We provide the largest multicenter analysis of treatment outcomes for iGCTs to date.

Methods

The Surveillance, Epidemiology, and End Result (SEER) database were used to record patient demographics, tumor, and treatment characteristics. Cox proportional hazards model and multiple comparisons for the Logrank test with Sidak correction was applied to compare the different treatment regimens and survival.

Results

1043 iGCT cases were divided into three cohorts of Germinoma, Malignant Teratoma (MT), and NGGCT. The mean age was 17.7 years for germinoma, 9.5 years for MT, and 14.4 years for NGGCT groups. Males comprised 77% of overall patient population. For Germinomas, both biopsy (hazard ratio [HR] = 4.6) and resection (HR = 14.1) had significantly worse survival outcomes compared to solo radiation therapy, with no difference between radiation and chemotherapy. For MT, no treatment combination had significantly different survival outcomes compared to resection alone. For NGGCTs, resection + chemotherapy + radiotherapy (HR = 0.012) and resection + chemotherapy (HR = 0.0049) had significantly better survival compared to resection alone.

Conclusion

In germinomas, radiotherapy alone had superior survival outcomes compared to biopsy and resection, but no change in survival when compared to chemotherapy alone. Addition of radiotherapy or chemotherapy did not improve survival in MTs when compared to resection alone. Adding chemotherapy in NGGCT patients undergoing resection improved survival compared to resection alone.

Keywords

CNS Germ cell tumors Gernomina Malignant teratoma Treatment 

Notes

Acknowledgements

None.

Author contribution

Conception and design: SD, ADB, AIM; collection and assembly of data: SD, SNP, AM; data analysis and interpretation: SD, ADB, MB; manuscript writing: SD, ADB, SNP, AM; critical review of the manuscript: MB, AIM; final approval of manuscript: All authors.

Funding

The authors have not received any funding for this work.

Compliance with ethical standards

Conflict of interest

The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

Supplementary material

432_2019_3088_MOESM1_ESM.docx (28 kb)
Supplementary material 1 (DOCX 27 kb)

References

  1. Allen JC, Kim JH, Packer RJ (1987) Neoadjuvant chemotherapy for newly diagnosed germ-cell tumors of the central nervous system. J Neurosurg 67(1):65–70.  https://doi.org/10.3171/jns.1987.67.1.0065 CrossRefPubMedGoogle Scholar
  2. Allen JC, DaRosso RC, Donahue B, Nirenberg A (1994) A phase II trial of preirradiation carboplatin in newly diagnosed germinoma of the central nervous system. Cancer 74(3):940–944CrossRefGoogle Scholar
  3. Balmaceda C, Heller G, Rosenblum M, Diez B, Villablanca JG, Kellie S, Maher P, Vlamis V, Walker RW, Leibel S, Finlay JL (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.  https://doi.org/10.1200/jco.1996.14.11.2908 CrossRefPubMedGoogle Scholar
  4. Bamberg M, Kortmann RD, Calaminus G, Becker G, Meisner C, Harms D, Göbel U (1999) Radiation therapy for intracranial germinoma: results of the German cooperative prospective trials MAKEI 83/86/89. J Clin Oncol 17(8):2585–2592.  https://doi.org/10.1200/JCO.1999.17.8.2585 CrossRefPubMedGoogle Scholar
  5. Bowzyk Al-Naeeb A, Murray M, Horan G, Harris F, Kortmann RD, Nicholson J, Ajithkumar T (2018) Current management of intracranial germ cell tumours. Clin Oncol 30(4):204–214.  https://doi.org/10.1016/j.clon.2018.01.009 CrossRefGoogle Scholar
  6. Bromberg JE, Baumert BG, de Vos F, Gijtenbeek JM, Kurt E, Westermann AM, Wesseling P (2013) Primary intracranial germ-cell tumors in adults: a practical review. J Neurooncol 113(2):175–183.  https://doi.org/10.1007/s11060-013-1114-6 CrossRefPubMedGoogle Scholar
  7. Buckner JC, Peethambaram PP, Smithson WA, Groover RV, Schomberg PJ, Kimmel DW, Raffel C, O’Fallon JR, Neglia J, Shaw EG (1999) Phase II trial of primary chemotherapy followed by reduced-dose radiation for CNS germ cell tumors. J Clin Oncol 17(3):933–940.  https://doi.org/10.1200/JCO.1999.17.3.933 CrossRefPubMedGoogle Scholar
  8. Calaminus G, Kortmann R, Worch J, Nicholson JC, Alapetite C, Garrè ML, Patte C, Ricardi U, Saran F, Frappaz D (2013) SIOP CNS GCT 96: final report of outcome of a prospective, multinational nonrandomized trial for children and adults with intracranial germinoma, comparing craniospinal irradiation alone with chemotherapy followed by focal primary site irradiation for patients with localized disease. Neuro Oncol 15(6):788–796.  https://doi.org/10.1093/neuonc/not019 CrossRefPubMedPubMedCentralGoogle Scholar
  9. Cheng S, Kilday JP, Laperriere N, Janzen L, Drake J, Bouffet E, Bartels U (2016) Outcomes of children with central nervous system germinoma treated with multi-agent chemotherapy followed by reduced radiation. J Neurooncol 127(1):173–180.  https://doi.org/10.1007/s11060-015-2029-1 CrossRefPubMedGoogle Scholar
  10. Crawford JR, Santi MR, Vezina G, Myseros JS, Keating RF, LaFond DA, Rood BR, MacDonald TJ, Packer RJ (2007) CNS germ cell tumor (CNSGCT) of childhood: presentation and delayed diagnosis. Neurology 68(20):1668–1673.  https://doi.org/10.1212/01.wnl.0000261908.36803.ac CrossRefPubMedGoogle Scholar
  11. da Silva NS, Cappellano AM, Diez B, Cavalheiro S, Gardner S, Wisoff J, Kellie S, Parker R, Garvin J, Finlay J (2010) Primary chemotherapy for intracranial germ cell tumors: results of the third international CNS germ cell tumor study. Pediatr Blood Cancer 54(3):377–383.  https://doi.org/10.1002/pbc.22381 CrossRefPubMedGoogle Scholar
  12. Douglas JG, Rockhill JK, Olson JM, Ellenbogen RG, Geyer JR (2006) Cisplatin-based chemotherapy followed by focal, reduced-dose irradiation for pediatric primary central nervous system germinomas. J Pediatr Hematol Oncol 28(1):36–39PubMedGoogle Scholar
  13. Duggan MA, Anderson WF, Altekruse S, Penberthy L, Sherman ME (2016) The surveillance, epidemiology, and end results (SEER) program and pathology: toward strengthening the critical relationship. Am J Surg Pathol 40(12):e94–e102.  https://doi.org/10.1097/PAS.0000000000000749 CrossRefPubMedPubMedCentralGoogle Scholar
  14. Echevarría ME, Fangusaro J, Goldman S (2008) Pediatric central nervous system germ cell tumors: a review. Oncologist 13(6):690–699.  https://doi.org/10.1634/theoncologist.2008-0037 CrossRefPubMedGoogle Scholar
  15. Fouladi M, Grant R, Baruchel S, Chan H, Malkin D, Weitzman S, Greenberg ML (1998) Comparison of survival outcomes in patients with intracranial germinomas treated with radiation alone versus reduced-dose radiation and chemotherapy. Childs Nerv Syst 14(10):596–601.  https://doi.org/10.1007/s003810050279 CrossRefPubMedGoogle Scholar
  16. Hoffman HJ, Otsubo H, Hendrick EB, Humphreys RP, Drake JM, Becker LE, Greenberg M, Jenkin D (1991) Intracranial germ-cell tumors in children. J Neurosurg 74(4):545–551.  https://doi.org/10.3171/jns.1991.74.4.0545 CrossRefPubMedGoogle Scholar
  17. Huang X, Zhang R, Zhou LF (2009) Diagnosis and treatment of intracranial immature teratoma. Pediatr Neurosurg 45(5):354–360.  https://doi.org/10.1159/000257524 CrossRefPubMedGoogle Scholar
  18. Huang X, Zhang R, Mao Y, Zhou LF, Zhang C (2016) Recent advances in molecular biology and treatment strategies for intracranial germ cell tumors. World J Pediatr WJP 12(3):275–282.  https://doi.org/10.1007/s12519-016-0021-2 CrossRefPubMedGoogle Scholar
  19. Jennings MT, Gelman R, Hochberg F (1985) Intracranial germ-cell tumors: natural history and pathogenesis. J Neurosurg 63(2):155–167.  https://doi.org/10.3171/jns.1985.63.2.0155 CrossRefPubMedGoogle Scholar
  20. Joo JH, Park JH, Ra YS, Im HJ, Koh KN, Khang SK, Do Ahn S (2014) Treatment outcome of radiation therapy for intracranial germinoma: adaptive radiation field in relation to response to chemotherapy. Anticancer Res 34(10):5715–5721PubMedGoogle Scholar
  21. Kanamori M, Kumabe T, Saito R, Yamashita Y, Sonoda Y, Ariga H, Takai Y, Tominaga T (2009) Optimal treatment strategy for intracranial germ cell tumors: a single institution analysis. J Neurosurg Pediatr 4(6):506–514.  https://doi.org/10.3171/2009.7.PEDS08288 CrossRefPubMedGoogle Scholar
  22. Kellie SJ, Boyce H, Dunkel IJ, Diez B, Rosenblum M, Brualdi L, Finlay JL (2004a) Intensive cisplatin and cyclophosphamide-based chemotherapy without radiotherapy for intracranial germinomas: failure of a primary chemotherapy approach. Pediatr Blood Cancer 43(2):126–133.  https://doi.org/10.1002/pbc.20026 CrossRefPubMedGoogle Scholar
  23. Kellie SJ, Boyce H, Dunkel IJ, Diez B, Rosenblum M, Brualdi L, Finlay JL (2004b) Primary chemotherapy for intracranial nongerminomatous germ cell tumors: results of the second international CNS germ cell study group protocol. J Clin Oncol 22(5):846–853.  https://doi.org/10.1200/JCO.2004.07.006 CrossRefPubMedGoogle Scholar
  24. Khatua S, Dhall G, O’Neil S, Jubran R, Villablanca JG, Marachelian A, Nastia A, Lavey R, Olch AJ, Gonzalez I, Gilles F, Nelson M, Panigrahy A, McComb G, Krieger M, Fan J, Sposto R, Finlay JL (2010) Treatment of primary CNS germinomatous germ cell tumors with chemotherapy prior to reduced dose whole ventricular and local boost irradiation. Pediatr Blood Cancer 55(1):42–46.  https://doi.org/10.1002/pbc.22468 CrossRefPubMedGoogle Scholar
  25. Kirkpatrick P (2000) Neurosurgical management of aneurysmal subarachnoid haemorrhage. J Neurol Neurosurg Psychiatry 68(4):538eCrossRefGoogle Scholar
  26. Kretschmar C, Kleinberg L, Greenberg M, Burger P, Holmes E, Wharam M (2007) Pre-radiation chemotherapy with response-based radiation therapy in children with central nervous system germ cell tumors: a report from the Children’s Oncology Group. Pediatr Blood Cancer 48(3):285–291.  https://doi.org/10.1002/pbc.20815 CrossRefPubMedPubMedCentralGoogle Scholar
  27. Lee YH, Park EK, Park YS, Shim KW, Choi JU, Kim DS (2009) Treatment and outcomes of primary intracranial teratoma. Childs Nerv Syst 25(12):1581–1587.  https://doi.org/10.1007/s00381-009-0974-8 CrossRefPubMedGoogle Scholar
  28. Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, Scheithauer BW, Kleihues P (2007) The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 114(2):97–109.  https://doi.org/10.1007/s00401-007-0243-4 CrossRefPubMedPubMedCentralGoogle Scholar
  29. Matsutani M, Sano K, Takakura K, Fujimaki T, Nakamura O, Funata N, Seto T (1997) Primary intracranial germ cell tumors: a clinical analysis of 153 histologically verified cases. J Neurosurg 86(3):446–455.  https://doi.org/10.3171/jns.1997.86.3.0446 CrossRefPubMedGoogle Scholar
  30. McCarthy BJ, Shibui S, Kayama T, Miyaoka E, Narita Y, Murakami M, Matsuda A, Matsuda T, Sobue T, Palis BE, Dolecek TA, Kruchko C, Engelhard HH, Villano JL (2012) Primary CNS germ cell tumors in Japan and the United States: an analysis of 4 tumor registries. Neuro Oncol 14(9):1194–1200.  https://doi.org/10.1093/neuonc/nos155 CrossRefPubMedPubMedCentralGoogle Scholar
  31. Murray MJ, Bartels U, Nishikawa R, Fangusaro J, Matsutani M, Nicholson JC (2015) Consensus on the management of intracranial germ-cell tumours. Lancet Oncol 16(9):e470–e477.  https://doi.org/10.1016/s1470-2045(15)00244-2 CrossRefPubMedGoogle Scholar
  32. Murray MJ, Bailey S, Heinemann K, Mann J, Gobel UK, Saran F, Hale JP, Calaminus G, Nicholson JC (2017) Treatment and outcomes of UK and German patients with relapsed intracranial germ cell tumors following uniform first-line therapy. Int J Cancer 141(3):621–635.  https://doi.org/10.1002/ijc.30755 CrossRefPubMedGoogle Scholar
  33. Ogawa K, Toita T, Nakamura K, Uno T, Onishi H, Itami J, Shikama N, Saeki N, Yoshii Y, Murayama S (2003) Treatment and prognosis of patients with intracranial nongerminomatous malignant germ cell tumors: a multiinstitutional retrospective analysis of 41 patients. Cancer 98(2):369–376.  https://doi.org/10.1002/cncr.11495 CrossRefPubMedGoogle Scholar
  34. Poynter JN, Fonstad R, Tolar J, Spector LG, Ross JA (2014) Incidence of intracranial germ cell tumors by race in the United States, 1992–2010. J Neurooncol 120(2):381–388.  https://doi.org/10.1007/s11060-014-1562-7 CrossRefPubMedPubMedCentralGoogle Scholar
  35. Robertson PL, DaRosso RC, Allen JC (1997) Improved prognosis of intracranial non-germinoma germ cell tumors with multimodality therapy. J Neurooncol 32(1):71–80CrossRefGoogle Scholar
  36. Sano K (1999) Pathogenesis of intracranial germ cell tumors reconsidered. J Neurosurg 90(2):258–264.  https://doi.org/10.3171/jns.1999.90.2.0258 CrossRefPubMedGoogle Scholar
  37. Sano K, Matsutani M, Seto T (1989) So-called intracranial germ cell tumours: personal experiences and a theory of their pathogenesis. Neurol Res 11(2):118–126CrossRefGoogle Scholar
  38. Scott RA, Schwartz JR, Cramer SP (1985) Effect of cyanide binding on the copper sites of cytochrome c oxidase: an X-ray absorption spectroscopic study. J Inorg Biochem 23(3–4):199–205CrossRefGoogle Scholar
  39. Villano JL, Propp JM, Porter KR, Stewart AK, Valyi-Nagy T, Li X, Engelhard HH, McCarthy BJ (2008) Malignant pineal germ-cell tumors: an analysis of cases from three tumor registries. Neuro Oncol 10(2):121–130.  https://doi.org/10.1215/15228517-2007-054 CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of NeurosurgeryUniversity of Illinois at Chicago College of MedicineChicagoUSA
  2. 2.Department of NeurosurgeryIcahn School of Medicine at Mount SinaiNew YorkUSA

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