Germinoma medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Simrat Sarai, M.D. [2]

Overview

The predominant therapy for CNS germ cell tumors is radiation therapy. Adjunctive chemotherapy and surgery may be required.[1][2][3][4]

Medical Therapy

Radiotherapy

  • Germinomas are highly responsive to radiation therapy; however NGGCTs are less radiosensitive than pure germinomas.
  • Since studies comparing full-dose craniospinal irradiation CSI with reduced-volume radiation, whether whole-ventricular or whole-brain have shown no significant difference in the pattern of relapse in germinomas, therefore, CSI is no longer used for localized germinomas.
  • Trials to determine the best regimen for radiation therapy are still ongoing.
  • Since patients who received radiation therapy to the localized tumor alone had a higher rate of recurrence, radiation therapy to include the whole ventricles is recommended.
  • The majority of clinicians advocate a boost to the primary tumor bed in order to prevent local recurrence.
  • Studies to prove the efficacy of radiation therapy alone versus neoadjuvant chemotherapy followed by response-based radiotherapy are currently under way. The use of intensive chemotherapy alone without radiation therapy has proven less effective compared with chemotherapeutic regimens and radiation therapy together.
  • In patients with pure CNS germinomas, no deterioration in neurocognitive function and no compromise in outcome was found when chemotherapy was administered followed by reduced dose radiation therapy.[5][6][7][8][9][10][11][12][13][14][15][16][17][18][1][2][3][4]

Chemotherapy

Treatment of patients with germinomas

  • In patients with germinomas, neoadjuvant therapy prior to lower-dose and lower-volume radiation therapy is recommended. Germinomas are chemosensitive, specifically to platinum based agents. To permit the use of a lower radiation dose in patients with germinomas, chemotherapy has been recently added to the treatment regimen. This neoadjuvant therapy reduces the long-term morbidity associated with radiation therapy while maintaining the excellent survival rates.

Treatment of patients with nongerminomatous germ cell tumors

  • Combined therapy with adjuvant and neoadjuvant chemotherapy with radiation therapy is intended to improve outcome in patients with NGGCTs. When compared with patients with germinomas, patients with NGGCTs have an inferior outcome. The role of full-dose craniospinal irradiation CSI is controversial in patients with localized NGGCTs.
  • The agents that have shown the best activity against CNS GCTs are cisplatin, etoposide, vinblastine, bleomycin, and carboplatin. Ifosfamide and cyclophosphamide are also used. Therapy may be based on classification of CNS GCTs into good prognosis, intermediate prognosis, and poor prognosis. Patients with progressive or relapsed disease, especially those with NGGCTs, have a poor prognosis. In this group of patients high-dose chemotherapy followed by autologous stem cell transplant may be effective.[19][20][6][7][21][9][22][23][24][25][26][27]

Treatment options in CNS germ cell tumors is shown below in a tabular form:

Stage or Tumor Type Treatment Options
Newly diagnosed childhood germinomas
  • Radiation therapy
  • Neoadjuvant chemotherapy followed by response-based radiation therapy
Newly diagnosed childhood teratomas
Newly diagnosed childhood nongerminomatous GCTs
  • Chemotherapy followed by radiation therapy
  • Surgery
Recurrent childhood CNS GCTs
  • Chemotherapy followed by radiation therapy
  • High-dose chemotherapy with stem cell rescue

Chemotherapeutic agents, which are used to treat germinomas and desmopressin acetate, which is used for the treatment of diabetes insipidus are shown below in a tabular form:

Drug name Mechanism of action
Cisplatin
  • Cisplatin inhibits DNA synthesis and, thus, cell proliferation by causing DNA cross-links and denaturation of double helix
Bleomycin
  • Bleomycin is a glycopeptide antibiotic that inhibits DNA synthesis. For palliation in management of several neoplasms.
Etoposide, VP-16
  • Inhibits topoisomerase II and causes DNA strand breakage, causing cell proliferation to arrest in late S or early G2 phase of cell cycle.
Cyclophosphamide
  • It is chemically related to nitrogen mustards. As alkylating agent, mechanism of action of active metabolites may involve cross-linking of DNA, which may interfere with growth of normal and neoplastic cells
Desmopressin acetate
  • Increases cellular permeability of collecting ducts, resulting in reabsorption of water by kidneys.

References

  1. ↑ 1.0 1.1 Kellie SJ, Boyce H, Dunkel IJ, Diez B, Rosenblum M, Brualdi L; et al. (2004). "Primary chemotherapy for intracranial nongerminomatous germ cell tumors: results of the second international CNS germ cell study group protocol". J Clin Oncol. 22 (5): 846–53. doi:10.1200/JCO.2004.07.006. PMID 14990640.
  2. ↑ 2.0 2.1 Ogawa K, Toita T, Nakamura K, Uno T, Onishi H, Itami J; et al. (2003). "Treatment and prognosis of patients with intracranial nongerminomatous malignant germ cell tumors: a multiinstitutional retrospective analysis of 41 patients". Cancer. 98 (2): 369–76. doi:10.1002/cncr.11495. PMID 12872359.
  3. ↑ 3.0 3.1 Balmaceda C, Finlay J (2004). "Current advances in the diagnosis and management of intracranial germ cell tumors". Curr Neurol Neurosci Rep. 4 (3): 253–62. PMID 15102352.
  4. ↑ 4.0 4.1 Modak S, Gardner S, Dunkel IJ, Balmaceda C, Rosenblum MK, Miller DC; et al. (2004). "Thiotepa-based high-dose chemotherapy with autologous stem-cell rescue in patients with recurrent or progressive CNS germ cell tumors". J Clin Oncol. 22 (10): 1934–43. doi:10.1200/JCO.2004.11.053. PMID 15143087.
  5. ↑ Jennings MT, Gelman R, Hochberg F (1985). "Intracranial germ-cell tumors: natural history and pathogenesis". J Neurosurg. 63 (2): 155–67. doi:10.3171/jns.1985.63.2.0155. PMID 2991485.
  6. ↑ 6.0 6.1 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): 285–91. doi:10.1002/pbc.20815. PMC 4086720. PMID 16598761.
  7. ↑ 7.0 7.1 Finlay J, da Silva NS, Lavey R, Bouffet E, Kellie SJ, Shaw E; et al. (2008). "The management of patients with primary central nervous system (CNS) germinoma: current controversies requiring resolution". Pediatr Blood Cancer. 51 (2): 313–6. doi:10.1002/pbc.21555. PMID 18421722.
  8. ↑ Kaur H, Singh D, Peereboom DM (2003). "Primary central nervous system germ cell tumors". Curr Treat Options Oncol. 4 (6): 491–8. PMID 14585229.
  9. ↑ 9.0 9.1 Blakeley JO, Grossman SA (2006). "Management of pineal region tumors". Curr Treat Options Oncol. 7 (6): 505–16. PMID 17032562.
  10. ↑ Haas-Kogan DA, Missett BT, Wara WM, Donaldson SS, Lamborn KR, Prados MD; et al. (2003). "Radiation therapy for intracranial germ cell tumors". Int J Radiat Oncol Biol Phys. 56 (2): 511–8. PMID 12738328.
  11. ↑ Kellie SJ, Boyce H, Dunkel IJ, Diez B, Rosenblum M, Brualdi L; et al. (2004). "Intensive cisplatin and cyclophosphamide-based chemotherapy without radiotherapy for intracranial germinomas: failure of a primary chemotherapy approach". Pediatr Blood Cancer. 43 (2): 126–33. doi:10.1002/pbc.20026. PMID 15236278.
  12. ↑ Matsutani, Masao (2004). "Clinical management of primary central nervous system germ cell tumors". Seminars in Oncology. 31 (5): 676–683. doi:10.1053/j.seminoncol.2004.07.010. ISSN 0093-7754.
  13. ↑ Shim KW, Kim TG, Suh CO, Cho JH, Yoo CJ, Choi JU; et al. (2007). "Treatment failure in intracranial primary germinomas". Childs Nerv Syst. 23 (10): 1155–61. doi:10.1007/s00381-007-0394-6. PMID 17610071.
  14. ↑ Yasuda K, Taguchi H, Sawamura Y, Ikeda J, Aoyama H, Fujieda K; et al. (2008). "Low-dose craniospinal irradiation and ifosfamide, cisplatin and etoposide for non-metastatic embryonal tumors in the central nervous system". Jpn J Clin Oncol. 38 (7): 486–92. doi:10.1093/jjco/hyn049. PMID 18573848.
  15. ↑ Schoenfeld GO, Amdur RJ, Schmalfuss IM, Morris CG, Keole SR, Mendenhall WM; et al. (2006). "Low-dose prophylactic craniospinal radiotherapy for intracranial germinoma". Int J Radiat Oncol Biol Phys. 65 (2): 481–5. doi:10.1016/j.ijrobp.2005.12.012. PMID 16530341.
  16. ↑ Khatua S, Dhall G, O'Neil S, Jubran R, Villablanca JG, Marachelian A; et al. (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): 42–6. doi:10.1002/pbc.22468. PMID 20222020.
  17. ↑ da Silva NS, Cappellano AM, Diez B, Cavalheiro S, Gardner S, Wisoff J; et al. (2010). "Primary chemotherapy for intracranial germ cell tumors: results of the third international CNS germ cell tumor study". Pediatr Blood Cancer. 54 (3): 377–83. doi:10.1002/pbc.22381. PMID 20063410.
  18. ↑ 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): 36–9. PMID 16394891.
  19. ↑ Saran, Frank; Peoples, Sharon (2008). "Pineal Tumors: Germinomas and Non-Germinomatous Germ Cell Tumors": 310–317. doi:10.1002/9781444300222.ch41.
  20. ↑ Matsutani M, Japanese Pediatric Brain Tumor Study Group (2001). "Combined chemotherapy and radiation therapy for CNS germ cell tumors--the Japanese experience". J Neurooncol. 54 (3): 311–6. PMID 11767296.
  21. ↑ Echevarría ME, Fangusaro J, Goldman S (2008). "Pediatric central nervous system germ cell tumors: a review". Oncologist. 13 (6): 690–9. doi:10.1634/theoncologist.2008-0037. PMID 18586924.
  22. ↑ Cho J, Choi JU, Kim DS, Suh CO (2009). "Low-dose craniospinal irradiation as a definitive treatment for intracranial germinoma". Radiother Oncol. 91 (1): 75–9. doi:10.1016/j.radonc.2008.10.012. PMID 19019472.
  23. ↑ Matsutani M, Sano K, Takakura K, Fujimaki T, Nakamura O (1998). "Combined treatment with chemotherapy and radiation therapy for intracranial germ cell tumors". Childs Nerv Syst. 14 (1–2): 59–62. PMID 9548343.
  24. ↑ Shikama N, Ogawa K, Tanaka S, Toita T, Nakamura K, Uno T; et al. (2005). "Lack of benefit of spinal irradiation in the primary treatment of intracranial germinoma: a multiinstitutional, retrospective review of 180 patients". Cancer. 104 (1): 126–34. doi:10.1002/cncr.21169. PMID 15895370.
  25. ↑ Aoyama H (2009). "Radiation therapy for intracranial germ cell tumors". Prog Neurol Surg. 23: 96–105. doi:10.1159/000210056. PMID 19329864.
  26. ↑ Bamberg M, Kortmann RD, Calaminus G, Becker G, Meisner C, Harms D; et al. (1999). "Radiation therapy for intracranial germinoma: results of the German cooperative prospective trials MAKEI 83/86/89". J Clin Oncol. 17 (8): 2585–92. PMID 10561326.
  27. ↑ Sawamura Y (2009). "Strategy of combined treatment of germ cell tumors". Prog Neurol Surg. 23: 86–95. doi:10.1159/000210055. PMID 19329863.


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