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.
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  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.
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  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.
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