Elsevier

Seminars in Oncology

Volume 31, Issue 5, October 2004, Pages 676-683
Seminars in Oncology

Clinical management of primary central nervous system germ cell tumors

https://doi.org/10.1053/j.seminoncol.2004.07.010Get rights and content

Despite excellent long-term results for patients with germinoma treated with radiation therapy, the potential for late effects makes the treatment controversial. On the other hand, most patients with non-germinomatous tumors treated by conventional treatment with surgery and radiation therapy fail to survive longer than 3 years. After combination chemotherapy with cisplatin was confirmed to be effective in gonadal germ cell tumors, germ cell tumors of the brain became candidates for chemotherapy. The author reviews several prospective phase II studies that are being investigated to assess the effect of combination chemotherapy and radiation therapy for germ cell tumors. The aim of these studies is to reduce the volume and dose of radiation therapy for germinoma and prolong the survival of patients of non-germinomatous tumors. For germinoma, a trial with chemotherapy alone failed, with a high rate of recurrence, but Japanese and European trials with reduced-dose chemotherapy and a smaller volume of radiation therapy have resulted in high event-free survival (EFS) rates. Ongoing phase II studies with combined chemotherapy and radiation therapy for non-germinomatous tumors will result in a 5-year survival rate of greater than 50%, which is better than that achieved by radiation therapy alone.

Section snippets

Histological classification

According to the World Health Organization (WHO)3 classification of tumors of the nervous system, germ cell tumors are categorized into five basic types (germinomas, teratomas, choriocarcinomas, yolk sac or endodermal sinus tumors, and embryonal carcinomas) and their mixture (mixed germ cell tumor).

Germinomas are composed of large polygonal cells with a pale eosinophilic or clear cytoplasms, and small lymphocytes. Their cytoplasm stains positive for placental alkaline phosphatase (PLAP), and

Germinoma

As germinoma may disseminate throughout the CSF pathways, this tumor has traditionally been treated with surgical biopsy followed by prophylactic craniospinal irradiation with a boost to local disease, resulting in excellent 10-year survival rates (>80%). However, with modern imaging procedures, the proportion of patients presenting with metastatic disease at the time of diagnosis is low, and the risk of secondary seeding outside the irradiated volume does not exceed 12% in histologically

Ongoing phase II or phase III studies for intracranial germ cell tumors

Despite excellent long-term results for patients with germinoma treated with radiation therapy, the potential for late effects makes the treatment controversial. On the other hand, most patients with non-germinomatous tumors treated by conventional treatment with surgery and radiation therapy failed to survive longer than 3 years. Today several prospective phase II or phase III studies are being investigated to assess the effect of combination chemotherapy and radiation therapy for germ cell

Summary of treatment results and future prospects

Based on our analysis of treatment outcomes obtained in the Tokyo University series,4, 27 we divided patients with intracranial germ cell tumors into three therapeutic groups with a good, intermediate, and poor prognosis (Table 4). The first step should be histological verification of surgical specimens and, where possible, extensive reduction of tumor mass. In Japan, due to advances in microsurgical techniques and radioimaging techniques, surgery for pineal tumors is now much safer, and the

References (35)

  • M.T. Jennings et al.

    Intracranial germ-cell tumorsNatural history and pathogenesis

    J Neurosurg

    (1985)
  • D.M. Ho et al.

    Primary intracranial germ cell tumor. Pathologic study of 51 patients

    Cancer

    (1992)
  • H.J. Hoffman et al.

    Intracranial germ cell tumors in children

    J Neurosurg

    (1991)
  • Y. Itoyama et al.

    Clinical study of intracranial nongerminomatous germ cell tumors producing α-fetoprotein

    Neurosurgery

    (1990)
  • J. Bjornsson et al.

    Intracranial germ cell tumorsPathological and immunohistochemical aspects of 70 cases

    J Neuropathol Exp Neurol

    (1985)
  • T. Fujimaki et al.

    CT and MRI features of intracranial germ cell tumors

    J Neurooncol

    (1994)
  • M. Matsutani et al.

    Long-term follow-up of patients with primary intracranial germinomas

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