Primary Central Nervous System Germ Cell Tumors: A Review and Update
Main Article Content
Abstract
Primary central nervous system (CNS) germ cell tumors (GCT) are a heterogeneous group of tumors that are still poorly understood. In North America, GCTs comprise approximately 1% of primary brain tumors in pediatric and young adult patients. GCTs can occur as pure or mixed subtypes; they are divided into germinomas, which are the most common subtype, and non-germinomatous germ cell tumors (NGGCTs), which consist of approximately one-third of GCTs and include teratomas, embryonal carcinomas, choriocarcinomas, and yolk sac tumors. While the etiology of primary CNS GCT is not entirely clear, the various subtypes are lineage-related and may involve progenitor germ cells that fail to migrate and become trapped in midline locations. Primary CNS GCT most commonly arises in the pineal region but also occur in other areas. Presenting symptoms can include headache, Parinaud syndrome, diabetes insipidus, precosious puberty, ataxia, or hemiparesis. Treatment plans differ depending on the subtype of GCT and may vary among physicians and institutions. Germinomas have a favorable prognosis with a greater than 90% overall survival, while NGGCTs only have survival rates ranging from 40-70%. Primary CNS GCTs are rare tumors and can be hard to diagnose. Germinomas are most effectively treated with chemotherapy and radiation, while NGGCT usually require surgical resection, chemotherapy, and radiation with the exception of mature teratomas frequently curable with surgery alone.
Keywords:
CNS germ cell tumor, intracranial germ cell tumor, germinomas, nongerminomas
Article Details
How to Cite
DEY, Mahua; FETCKO, Kaleigh.
Primary Central Nervous System Germ Cell Tumors: A Review and Update.
Medical Research Archives, [S.l.], v. 6, n. 3, mar. 2018.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/1719>. Date accessed: 25 apr. 2024.
doi: https://doi.org/10.18103/mra.v6i3.1719.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
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2. Goodwin TL, Sainani K, Fisher PG. Incidence patterns of central nervous system germ cell tumors: a SEER Study. Journal of pediatric hematology/oncology. 2009;31(8):541-544.
3. Murray MJ, Bartels U, Nishikawa R, Fangusaro J, Matsutani M, Nicholson JC. Consensus on the management of intracranial germ-cell tumours. The Lancet. Oncology. 2015;16(9):e470-e477.
4. Al-Hussaini M, Sultan I, Abuirmileh N, Jaradat I, Qaddoumi I. Pineal gland tumors: experience from the SEER database. Journal of neuro-oncology. 2009;94(3):351-358.
5. Bohrnsen F, Enders C, Ludwig HC, Bruck W, Fuzesi L, Gutenberg A. Common molecularcytogenetic alterations in tumors originating from the pineal region. Oncology letters. 2015;10(3):1853-1857.
6. Dufour C, Guerrini-Rousseau L, Grill J. Central nervous system germ cell tumors: an update. Current opinion in oncology. 2014;26(6):622-626.
7. Georgiu C, Opincariu I, Cebotaru CL, et al. Intracranial immature teratoma with a primitive neuroectodermal malignant transformation - case report and review of the literature. Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie. 2016;57(4):1389-1395.
8. Matsutani M. Combined chemotherapy and radiation therapy for CNS germ cell tumors--the Japanese experience. Journal of neuro-oncology. 2001;54(3):311-316.
9. Huang X, Zhang R, Mao Y, Zhou LF, Zhang C. Recent advances in molecular biology and treatment strategies for intracranial germ cell tumors. World journal of pediatrics : WJP. 2016;12(3):275-282.
10. Matsutani M, Sano K, Takakura K, et al. Primary intracranial germ cell tumors: a clinical analysis of 153 histologically verified cases. Journal of neurosurgery. 1997;86(3):446-455.
11. Jorsal T, Rorth M. Intracranial germ cell tumours. A review with special reference to endocrine manifestations. Acta oncologica (Stockholm, Sweden). 2012;51(1):3-9.
12. Sethi RV, Marino R, Niemierko A, Tarbell NJ, Yock TI, MacDonald SM. Delayed diagnosis in children with intracranial germ cell tumors. The Journal of pediatrics. 2013;163(5):1448-1453.
13. Phi JH, Kim SK, Lee YA, et al. Latency of intracranial germ cell tumors and diagnosis delay. Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery. 2013;29(10):1871-1881.
14. Villano JL, Propp JM, Porter KR, et al. Malignant pineal germ-cell tumors: an analysis of cases from three tumor registries. Neuro-oncology. 2008;10(2):121-130.
15. Bartkova J, Hoei-Hansen CE, Krizova K, et al. Patterns of DNA damage response in intracranial germ cell tumors versus glioblastomas reflect cell of origin rather than brain environment: implications for the anti-tumor barrier concept and treatment. Molecular oncology. 2014;8(8):1667-1678.
16. Lee SH, Appleby V, Jeyapalan JN, et al. Variable methylation of the imprinted gene, SNRPN, supports a relationship between intracranial germ cell tumours and neural stem cells. Journal of neuro-oncology. 2011;101(3):419-428.
17. Tan C, Scotting PJ. Stem cell research points the way to the cell of origin for intracranial germ cell tumours. The Journal of pathology. 2013;229(1):4-11.
18. Kakkar A, Biswas A, Kalyani N, et al. Intracranial germ cell tumors: a multi-institutional experience from three tertiary care centers in India. Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery. 2016.
19. Herrada-Pineda T, Revilla-Pacheco F, Manrique-Guzman S. Endoscopic approach for the treatment of pineal region tumors. Journal of neurological surgery. Part A, Central European neurosurgery. 2015;76(1):8-12.
20. Cardellicchio S, Farina S, Buccoliero AM, et al. Successful treatment of metastatic betaHCG-secreting germ cell tumor occurring 3 years after total resection of a pineal mature teratoma. Eur J Pediatr. 2014;173(8):1011-1015.
21. Raiyawa T, Khorprasert C, Lertbutsayanukul C, et al. Management of intracranial germ cell tumors at the King Chulalongkorn Memorial Hospital. Journal of the Medical Association of Thailand = Chotmaihet thangphaet. 2012;95(10):1327-1334.
22. Huang X, Zhang R, Zhou LF. Diagnosis and treatment of intracranial immature teratoma. Pediatric neurosurgery. 2009;45(5):354-360.
23. Calaminus G, Bamberg M, Harms D, et al. AFP/beta-HCG secreting CNS germ cell tumors: long-term outcome with respect to initial symptoms and primary tumor resection. Results of the cooperative trial MAKEI 89. Neuropediatrics. 2005;36(2):71-77.
24. Gao Y, Jiang J, Liu Q. Clinicopathological and immunohistochemical features of primary central nervous system germ cell tumors: a 24-years experience. International journal of clinical and experimental pathology. 2014;7(10):6965-6972.
25. Cheng S, Kilday JP, Laperriere N, et al. Outcomes of children with central nervous system germinoma treated with multi-agent chemotherapy followed by reduced radiation. Journal of neuro-oncology. 2016;127(1):173-180.
26. Jeong YB, Wang KC, Phi JH, et al. A Case of Nongerminomatous Germ Cell Tumor with Fulminant Course Concomitant Leptomeningeal Metastasis. Brain tumor research and treatment. 2016;4(1):21-25.
27. Frappaz D, Conter CF, Szathmari A, Valsijevic A, Mottolese C. The management of pineal tumors as a model for a multidisciplinary approach in neuro-oncology. Neuro-Chirurgie. 2015;61(2-3):208-211.
28. Aizer AA, Sethi RV, Hedley-Whyte ET, et al. Bifocal intracranial tumors of nongerminomatous germ cell etiology: diagnostic and therapeutic implications. Neuro-oncology. 2013;15(7):955-960.
29. Robertson PL, Jakacki R, Hukin J, Siffert J, Allen JC. Multimodality therapy for CNS mixed malignant germ cell tumors (MMGCT): results of a phase II multi-institutional study. Journal of neuro-oncology. 2014;118(1):93-100.
30. Sun XF, Zhang F, Zhen ZJ, et al. The clinical characteristics and treatment outcome of 57 children and adolescents with primary central nervous system germ cell tumors. Chinese journal of cancer. 2014;33(8):395-401.
31. Afzal S, Wherrett D, Bartels U, et al. Challenges in management of patients with intracranial germ cell tumor and diabetes insipidus treated with cisplatin and/or ifosfamide based chemotherapy. Journal of neuro-oncology. 2010;97(3):393-399.
32. Wong K, Opimo AB, Olch AJ, et al. Re-irradiation of Recurrent Pineal Germ Cell Tumors with Radiosurgery: Report of Two Cases and Review of Literature. Cureus. 2016;8(4):e585.
33. Claude L, Faure-Conter C, Frappaz D, Mottolese C, Carrie C. Radiation therapy in pediatric pineal tumors. Neuro-Chirurgie. 2015;61(2-3):212-215.
34. Bouffet E, Baranzelli MC, Patte C, et al. Combined treatment modality for intracranial germinomas: results of a multicentre SFOP experience. Societe Francaise d'Oncologie Pediatrique. British journal of cancer. 1999;79(7-8):1199-1204.
35. Malogolowkin MH, Krailo M, Marina N, Olson T, Frazier AL. Pilot study of cisplatin, etoposide, bleomycin, and escalating dose cyclophosphamide therapy for children with high risk germ cell tumors: a report of the children's oncology group (COG). Pediatric blood & cancer. 2013;60(10):1602-1605.
36. Foo AS, Lim C, Chong DQ, Tan DY, Tham CK. Primary intracranial germ cell tumours: experience of a single South-East Asian institution. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia. 2014;21(10):1761-1766.
37. Fukuoka K, Yanagisawa T, Suzuki T, et al. Malignant transformation of germinoma 14 years after onset: Favorable efficacy of oral etoposide. Pediatrics international : official journal of the Japan Pediatric Society. 2015;57(3):483-486.
38. Jinguji S, Yoshimura J, Nishiyama K, et al. Long-term outcomes in patients with pineal nongerminomatous malignant germ cell tumors treated by radical resection during initial treatment combined with adjuvant therapy. Acta neurochirurgica. 2015;157(12):2175-2183.
39. Kellie SJ, Boyce H, Dunkel IJ, et al. Primary chemotherapy for intracranial nongerminomatous germ cell tumors: results of the second international CNS germ cell study group protocol. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2004;22(5):846-853.
40. Calaminus G, Frappaz D, Kortmann RD, et al. Outcome of patients with intracranial non-germinomatous germ cell tumors-lessons from the SIOP-CNS-GCT-96 trial. Neuro-oncology. 2017;19(12):1661-1672.
41. Kim JW, Kim WC, Cho JH, et al. A multimodal approach including craniospinal irradiation improves the treatment outcome of high-risk intracranial nongerminomatous germ cell tumors. International journal of radiation oncology, biology, physics. 2012;84(3):625-631.
42. Khafaga Y, El Weshi A, Nazmy M, et al. Intracranial germ cell tumors: a single-institution experience. Annals of Saudi medicine. 2012;32(4):359-365.
43. Kochi M, Itoyama Y, Shiraishi S, Kitamura I, Marubayashi T, Ushio Y. Successful treatment of intracranial nongerminomatous malignant germ cell tumors by administering neoadjuvant chemotherapy and radiotherapy before excision of residual tumors. Journal of neurosurgery. 2003;99(1):106-114.
44. Li W, Zhang B, Kang W, et al. Gamma knife radiosurgery (GKRS) for pineal region tumors: a study of 147 cases. World journal of surgical oncology. 2015;13:304.
45. Gardner SL. Application of stem cell transplant for brain tumors. Pediatric transplantation. 2004;8 Suppl 5:28-32.
46. Tada T, Takizawa T, Nakazato F, et al. Treatment of intracranial nongerminomatous germ-cell tumor by high-dose chemotherapy and autologous stem-cell rescue. Journal of neuro-oncology. 1999;44(1):71-76.
47. Osada T, Fujimaki T, Takamizawa M, Tsuno NH, Kirino T, Shibata Y. Dendritic cells activate antitumor immunity for malignant intracranial germ cell tumor: a case report. Japanese journal of clinical oncology. 2001;31(8):403-406.
48. Schneider DT, Zahn S, Sievers S, et al. Molecular genetic analysis of central nervous system germ cell tumors with comparative genomic hybridization. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc. 2006;19(6):864-873.
49. Terashima K, Yu A, Chow WY, et al. Genome-wide analysis of DNA copy number alterations and loss of heterozygosity in intracranial germ cell tumors. Pediatric blood & cancer. 2014;61(4):593-600.
50. Taylor MD, Mainprize TG, Squire JA, Rutka JT. Molecular genetics of pineal region neoplasms. Journal of neuro-oncology. 2001;54(3):219-238.
51. Schulte SL, Waha A, Steiger B, et al. CNS germinomas are characterized by global demethylation, chromosomal instability and mutational activation of the Kit-, Ras/Raf/Erk- and Akt-pathways. Oncotarget. 2016;7(34):55026-55042.
52. Wang L, Yamaguchi S, Burstein MD, et al. Novel somatic and germline mutations in intracranial germ cell tumours. Nature. 2014;511(7508):241-245.
53. Osorio DS, Finlay JL, Dhall G, Goldman S, Eisenstat D, Brown RJ. Feasibility of dasatinib in children and adolescents with new or recurrent central nervous system germinoma. Pediatric blood & cancer. 2013;60(9):E100-102.
54. Nakamura H, Makino K, Kochi M, Ushio Y, Kuratsu J. Evaluation of neoadjuvant therapy in patients with nongerminomatous malignant germ cell tumors. Journal of neurosurgery. Pediatrics. 2011;7(4):431-438.
55. Acharya S, DeWees T, Shinohara ET, Perkins SM. Long-term outcomes and late effects for childhood and young adulthood intracranial germinomas. Neuro-oncology. 2015;17(5):741-746.
56. Goldman S, Bouffet E, Fisher PG, et al. Phase II Trial Assessing the Ability of Neoadjuvant Chemotherapy With or Without Second-Look Surgery to Eliminate Measurable Disease for Nongerminomatous Germ Cell Tumors: A Children's Oncology Group Study. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2015;33(22):2464-2471.
57. Chen YW, Huang PI, Ho DM, et al. Change in treatment strategy for intracranial germinoma: long-term follow-up experience at a single institute. Cancer. 2012;118(10):2752-2762.
58. Alapetite C, Brisse H, Patte C, et al. Pattern of relapse and outcome of non-metastatic germinoma patients treated with chemotherapy and limited field radiation: the SFOP experience. Neuro-oncology. 2010;12(12):1318-1325.
59. Calaminus G, Kortmann R, Worch J, et al. 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-oncology. 2013;15(6):788-796.
60. Smith AA, Weng E, Handler M, Foreman NK. Intracranial germ cell tumors: a single institution experience and review of the literature. Journal of neuro-oncology. 2004;68(2):153-159.
2. Goodwin TL, Sainani K, Fisher PG. Incidence patterns of central nervous system germ cell tumors: a SEER Study. Journal of pediatric hematology/oncology. 2009;31(8):541-544.
3. Murray MJ, Bartels U, Nishikawa R, Fangusaro J, Matsutani M, Nicholson JC. Consensus on the management of intracranial germ-cell tumours. The Lancet. Oncology. 2015;16(9):e470-e477.
4. Al-Hussaini M, Sultan I, Abuirmileh N, Jaradat I, Qaddoumi I. Pineal gland tumors: experience from the SEER database. Journal of neuro-oncology. 2009;94(3):351-358.
5. Bohrnsen F, Enders C, Ludwig HC, Bruck W, Fuzesi L, Gutenberg A. Common molecularcytogenetic alterations in tumors originating from the pineal region. Oncology letters. 2015;10(3):1853-1857.
6. Dufour C, Guerrini-Rousseau L, Grill J. Central nervous system germ cell tumors: an update. Current opinion in oncology. 2014;26(6):622-626.
7. Georgiu C, Opincariu I, Cebotaru CL, et al. Intracranial immature teratoma with a primitive neuroectodermal malignant transformation - case report and review of the literature. Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie. 2016;57(4):1389-1395.
8. Matsutani M. Combined chemotherapy and radiation therapy for CNS germ cell tumors--the Japanese experience. Journal of neuro-oncology. 2001;54(3):311-316.
9. Huang X, Zhang R, Mao Y, Zhou LF, Zhang C. Recent advances in molecular biology and treatment strategies for intracranial germ cell tumors. World journal of pediatrics : WJP. 2016;12(3):275-282.
10. Matsutani M, Sano K, Takakura K, et al. Primary intracranial germ cell tumors: a clinical analysis of 153 histologically verified cases. Journal of neurosurgery. 1997;86(3):446-455.
11. Jorsal T, Rorth M. Intracranial germ cell tumours. A review with special reference to endocrine manifestations. Acta oncologica (Stockholm, Sweden). 2012;51(1):3-9.
12. Sethi RV, Marino R, Niemierko A, Tarbell NJ, Yock TI, MacDonald SM. Delayed diagnosis in children with intracranial germ cell tumors. The Journal of pediatrics. 2013;163(5):1448-1453.
13. Phi JH, Kim SK, Lee YA, et al. Latency of intracranial germ cell tumors and diagnosis delay. Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery. 2013;29(10):1871-1881.
14. Villano JL, Propp JM, Porter KR, et al. Malignant pineal germ-cell tumors: an analysis of cases from three tumor registries. Neuro-oncology. 2008;10(2):121-130.
15. Bartkova J, Hoei-Hansen CE, Krizova K, et al. Patterns of DNA damage response in intracranial germ cell tumors versus glioblastomas reflect cell of origin rather than brain environment: implications for the anti-tumor barrier concept and treatment. Molecular oncology. 2014;8(8):1667-1678.
16. Lee SH, Appleby V, Jeyapalan JN, et al. Variable methylation of the imprinted gene, SNRPN, supports a relationship between intracranial germ cell tumours and neural stem cells. Journal of neuro-oncology. 2011;101(3):419-428.
17. Tan C, Scotting PJ. Stem cell research points the way to the cell of origin for intracranial germ cell tumours. The Journal of pathology. 2013;229(1):4-11.
18. Kakkar A, Biswas A, Kalyani N, et al. Intracranial germ cell tumors: a multi-institutional experience from three tertiary care centers in India. Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery. 2016.
19. Herrada-Pineda T, Revilla-Pacheco F, Manrique-Guzman S. Endoscopic approach for the treatment of pineal region tumors. Journal of neurological surgery. Part A, Central European neurosurgery. 2015;76(1):8-12.
20. Cardellicchio S, Farina S, Buccoliero AM, et al. Successful treatment of metastatic betaHCG-secreting germ cell tumor occurring 3 years after total resection of a pineal mature teratoma. Eur J Pediatr. 2014;173(8):1011-1015.
21. Raiyawa T, Khorprasert C, Lertbutsayanukul C, et al. Management of intracranial germ cell tumors at the King Chulalongkorn Memorial Hospital. Journal of the Medical Association of Thailand = Chotmaihet thangphaet. 2012;95(10):1327-1334.
22. Huang X, Zhang R, Zhou LF. Diagnosis and treatment of intracranial immature teratoma. Pediatric neurosurgery. 2009;45(5):354-360.
23. Calaminus G, Bamberg M, Harms D, et al. AFP/beta-HCG secreting CNS germ cell tumors: long-term outcome with respect to initial symptoms and primary tumor resection. Results of the cooperative trial MAKEI 89. Neuropediatrics. 2005;36(2):71-77.
24. Gao Y, Jiang J, Liu Q. Clinicopathological and immunohistochemical features of primary central nervous system germ cell tumors: a 24-years experience. International journal of clinical and experimental pathology. 2014;7(10):6965-6972.
25. Cheng S, Kilday JP, Laperriere N, et al. Outcomes of children with central nervous system germinoma treated with multi-agent chemotherapy followed by reduced radiation. Journal of neuro-oncology. 2016;127(1):173-180.
26. Jeong YB, Wang KC, Phi JH, et al. A Case of Nongerminomatous Germ Cell Tumor with Fulminant Course Concomitant Leptomeningeal Metastasis. Brain tumor research and treatment. 2016;4(1):21-25.
27. Frappaz D, Conter CF, Szathmari A, Valsijevic A, Mottolese C. The management of pineal tumors as a model for a multidisciplinary approach in neuro-oncology. Neuro-Chirurgie. 2015;61(2-3):208-211.
28. Aizer AA, Sethi RV, Hedley-Whyte ET, et al. Bifocal intracranial tumors of nongerminomatous germ cell etiology: diagnostic and therapeutic implications. Neuro-oncology. 2013;15(7):955-960.
29. Robertson PL, Jakacki R, Hukin J, Siffert J, Allen JC. Multimodality therapy for CNS mixed malignant germ cell tumors (MMGCT): results of a phase II multi-institutional study. Journal of neuro-oncology. 2014;118(1):93-100.
30. Sun XF, Zhang F, Zhen ZJ, et al. The clinical characteristics and treatment outcome of 57 children and adolescents with primary central nervous system germ cell tumors. Chinese journal of cancer. 2014;33(8):395-401.
31. Afzal S, Wherrett D, Bartels U, et al. Challenges in management of patients with intracranial germ cell tumor and diabetes insipidus treated with cisplatin and/or ifosfamide based chemotherapy. Journal of neuro-oncology. 2010;97(3):393-399.
32. Wong K, Opimo AB, Olch AJ, et al. Re-irradiation of Recurrent Pineal Germ Cell Tumors with Radiosurgery: Report of Two Cases and Review of Literature. Cureus. 2016;8(4):e585.
33. Claude L, Faure-Conter C, Frappaz D, Mottolese C, Carrie C. Radiation therapy in pediatric pineal tumors. Neuro-Chirurgie. 2015;61(2-3):212-215.
34. Bouffet E, Baranzelli MC, Patte C, et al. Combined treatment modality for intracranial germinomas: results of a multicentre SFOP experience. Societe Francaise d'Oncologie Pediatrique. British journal of cancer. 1999;79(7-8):1199-1204.
35. Malogolowkin MH, Krailo M, Marina N, Olson T, Frazier AL. Pilot study of cisplatin, etoposide, bleomycin, and escalating dose cyclophosphamide therapy for children with high risk germ cell tumors: a report of the children's oncology group (COG). Pediatric blood & cancer. 2013;60(10):1602-1605.
36. Foo AS, Lim C, Chong DQ, Tan DY, Tham CK. Primary intracranial germ cell tumours: experience of a single South-East Asian institution. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia. 2014;21(10):1761-1766.
37. Fukuoka K, Yanagisawa T, Suzuki T, et al. Malignant transformation of germinoma 14 years after onset: Favorable efficacy of oral etoposide. Pediatrics international : official journal of the Japan Pediatric Society. 2015;57(3):483-486.
38. Jinguji S, Yoshimura J, Nishiyama K, et al. Long-term outcomes in patients with pineal nongerminomatous malignant germ cell tumors treated by radical resection during initial treatment combined with adjuvant therapy. Acta neurochirurgica. 2015;157(12):2175-2183.
39. Kellie SJ, Boyce H, Dunkel IJ, et al. Primary chemotherapy for intracranial nongerminomatous germ cell tumors: results of the second international CNS germ cell study group protocol. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2004;22(5):846-853.
40. Calaminus G, Frappaz D, Kortmann RD, et al. Outcome of patients with intracranial non-germinomatous germ cell tumors-lessons from the SIOP-CNS-GCT-96 trial. Neuro-oncology. 2017;19(12):1661-1672.
41. Kim JW, Kim WC, Cho JH, et al. A multimodal approach including craniospinal irradiation improves the treatment outcome of high-risk intracranial nongerminomatous germ cell tumors. International journal of radiation oncology, biology, physics. 2012;84(3):625-631.
42. Khafaga Y, El Weshi A, Nazmy M, et al. Intracranial germ cell tumors: a single-institution experience. Annals of Saudi medicine. 2012;32(4):359-365.
43. Kochi M, Itoyama Y, Shiraishi S, Kitamura I, Marubayashi T, Ushio Y. Successful treatment of intracranial nongerminomatous malignant germ cell tumors by administering neoadjuvant chemotherapy and radiotherapy before excision of residual tumors. Journal of neurosurgery. 2003;99(1):106-114.
44. Li W, Zhang B, Kang W, et al. Gamma knife radiosurgery (GKRS) for pineal region tumors: a study of 147 cases. World journal of surgical oncology. 2015;13:304.
45. Gardner SL. Application of stem cell transplant for brain tumors. Pediatric transplantation. 2004;8 Suppl 5:28-32.
46. Tada T, Takizawa T, Nakazato F, et al. Treatment of intracranial nongerminomatous germ-cell tumor by high-dose chemotherapy and autologous stem-cell rescue. Journal of neuro-oncology. 1999;44(1):71-76.
47. Osada T, Fujimaki T, Takamizawa M, Tsuno NH, Kirino T, Shibata Y. Dendritic cells activate antitumor immunity for malignant intracranial germ cell tumor: a case report. Japanese journal of clinical oncology. 2001;31(8):403-406.
48. Schneider DT, Zahn S, Sievers S, et al. Molecular genetic analysis of central nervous system germ cell tumors with comparative genomic hybridization. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc. 2006;19(6):864-873.
49. Terashima K, Yu A, Chow WY, et al. Genome-wide analysis of DNA copy number alterations and loss of heterozygosity in intracranial germ cell tumors. Pediatric blood & cancer. 2014;61(4):593-600.
50. Taylor MD, Mainprize TG, Squire JA, Rutka JT. Molecular genetics of pineal region neoplasms. Journal of neuro-oncology. 2001;54(3):219-238.
51. Schulte SL, Waha A, Steiger B, et al. CNS germinomas are characterized by global demethylation, chromosomal instability and mutational activation of the Kit-, Ras/Raf/Erk- and Akt-pathways. Oncotarget. 2016;7(34):55026-55042.
52. Wang L, Yamaguchi S, Burstein MD, et al. Novel somatic and germline mutations in intracranial germ cell tumours. Nature. 2014;511(7508):241-245.
53. Osorio DS, Finlay JL, Dhall G, Goldman S, Eisenstat D, Brown RJ. Feasibility of dasatinib in children and adolescents with new or recurrent central nervous system germinoma. Pediatric blood & cancer. 2013;60(9):E100-102.
54. Nakamura H, Makino K, Kochi M, Ushio Y, Kuratsu J. Evaluation of neoadjuvant therapy in patients with nongerminomatous malignant germ cell tumors. Journal of neurosurgery. Pediatrics. 2011;7(4):431-438.
55. Acharya S, DeWees T, Shinohara ET, Perkins SM. Long-term outcomes and late effects for childhood and young adulthood intracranial germinomas. Neuro-oncology. 2015;17(5):741-746.
56. Goldman S, Bouffet E, Fisher PG, et al. Phase II Trial Assessing the Ability of Neoadjuvant Chemotherapy With or Without Second-Look Surgery to Eliminate Measurable Disease for Nongerminomatous Germ Cell Tumors: A Children's Oncology Group Study. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2015;33(22):2464-2471.
57. Chen YW, Huang PI, Ho DM, et al. Change in treatment strategy for intracranial germinoma: long-term follow-up experience at a single institute. Cancer. 2012;118(10):2752-2762.
58. Alapetite C, Brisse H, Patte C, et al. Pattern of relapse and outcome of non-metastatic germinoma patients treated with chemotherapy and limited field radiation: the SFOP experience. Neuro-oncology. 2010;12(12):1318-1325.
59. Calaminus G, Kortmann R, Worch J, et al. 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-oncology. 2013;15(6):788-796.
60. Smith AA, Weng E, Handler M, Foreman NK. Intracranial germ cell tumors: a single institution experience and review of the literature. Journal of neuro-oncology. 2004;68(2):153-159.