Current Treatment Options in Oncology

, Volume 1, Issue 5, pp 459–468 | Cite as

Malignant gliomas

  • Eric C. Burton
  • Michael D. Prados
Article

Opinion statement

Gliomas are a heterogeneous group of neoplasms that comprise the majority of tumors originating in the central nervous system (CNS). In adults, the most frequently encountered of these are high-grade or malignant neoplasms of astrocytic and oligodendrocytic lineage, ie, anaplastic astrocytoma (AA), glioblastoma multiforme (GBM), and anaplastic oligodendroglioma (AO), respectively. Tumors of mixed lineage are also seen, the most common of which is designated anaplastic oligoastrocytoma (AOA). Standard treatment for these tumors is typically surgery, followed by radiation then chemotherapy. Surgery is required for a definitive histopathologic diagnosis, which in turn will dictate subsequent therapy options. Moreover, aggressive tumor resection improves survival outcomes, and in many cases, the patient's neurologic function. We generally advocate the safest, maximal resection attainable for patients with these tumors as a way to improve prognosis. In almost all cases, surgery is followed by radiation therapy.

Postsurgical irradiation is the most effective treatment currently available for improving survival. There is also mounting evidence to suggest that additional radiation, given in the form of brachytherapy or radiosurgery, at initial diagnosis as a “boost” to standard radiation or at tumor recurrence, may provide added improvement in survival outcome. Radiosurgery and brachytherapy are therapies often used to treat eligible patients at this institution. Adjuvant chemotherapy, conventionally given after radiation, may offer a modest survival benefit in some patients with GBM. Bischloroethylnitrosourea (BCNU) is the typical first-line agent used, but chemotherapy seems to be most beneficial in young patients, with little if any impact on survival for patients over 60 years old. At this institution, we often defer treatment with adjuvant chemotherapy for elderly patients with GBM due to lack of efficacy and the attendant risk with chemotherapy. For anaplastic astrocytomas, oligodendrogliomas, and oligoastrocytomas, a commonly accepted standard is adjuvant chemotherapy following irradiation with the three-drug regimen—procarbazine, CCNU, and vincristine (PCV). This is due to an earlier clinical trial that showed a survival advantage in patients treated with adjuvant PCV compared with patients that received BCNU. However, recent data suggest that treatment with either PCV or BCNU may be appropriate. Both regimens now appear to have equal efficacy for anaplastic gliomas in light of a more recent analysis done with larger numbers of patients. AOs are a unique case with respect to tumor chemosensitivity and patient survival. Molecular studies have identified a subpopulation of patients with AO whose tumors have lost chromosomes 1p and 19q. Patients with this molecular pattern have an exceptional responsiveness to PCV chemotherapy and have prolonged survival. Currently, trials are being conducted to confirm this finding and to determine the best treatment regimen for these patients, with particular regard to the timing of radiation and chemotherapy.

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References and Recommended Reading

  1. 1.
    Kleihues P, Burger PC, Scheithauer BW: The new WHO classification of brain tumours. Brain Pathol 1993, 3:255–268.PubMedGoogle Scholar
  2. 2.
    Curran WJ Jr, Scott CB, Horton J, et al.: Recursive partitioning analysis of prognostic factors in three Radiation Therapy Oncology Group malignant glioma trials [see comments]. J Natl Cancer Inst 1993, 85:704–710.PubMedCrossRefGoogle Scholar
  3. 3.
    Devaux BC, O'Fallon JR, Kelly PJ: Resection, biopsy, and survival in malignant glial neoplasms. A retrospective study of clinical parameters, therapy, and outcome. J Neurosurg 1993, 78:767–775.PubMedCrossRefGoogle Scholar
  4. 4.
    Kowalczuk A, Macdonald RL, Amidei C, et al.: Quantitative imaging study of extent of surgical resection and prognosis of malignant astrocytomas [see comments]. Neurosurgery 1997, 41:1028–1036.PubMedCrossRefGoogle Scholar
  5. 5.
    Barnett GH: The role of image-guided technology in the surgical planning and resection of gliomas. J Neurooncol 1999, 42:247–258.PubMedCrossRefGoogle Scholar
  6. 6.
    Matz PG, Cobbs C, Berger MS: Intraoperative cortical mapping as a guide to the surgical resection of gliomas. J Neurooncol 1999, 42:233–245.PubMedCrossRefGoogle Scholar
  7. 7.
    Martin A, Hall W, Liu H, et al.: Brain tumor resection: intraoperative monitoring with high-field-strength MR imaging—initial results. Radiology 2000, 215:221–228.PubMedGoogle Scholar
  8. 8.
    Wirtz C, Knauth M, Staubert A, et al.: Clinical evaluation and follow-up results for intraoperative magnetic resonance imaging in neurosurgery. Neurosurgery 2000, 46:1112–1119. This study demonstrates the potential benefit of intraoperative imaging by showing that the extent of glioma resection can be maximized using this technique in some patients.PubMedCrossRefGoogle Scholar
  9. 9.
    Knauth M, Wirtz CR, Tronnier VM, et al.: Intraoperative MR imaging increases the extent of tumor resection in patients with high-grade gliomas [see comments]. AJNR Am J Neuroradiol 1999, 20:1642–1646.PubMedGoogle Scholar
  10. 10.
    Barker FG, 2nd, Chang SM, Gutin PH, et al.: Survival and functional status after resection of recurrent glioblastoma multiforme. Neurosurgery 1998, 42:709–720.PubMedCrossRefGoogle Scholar
  11. 11.
    Diaz AZ, Coderre JA, Chanana AD, Ma R : Boron neutron capture therapy for malignant gliomas. Anm Med, 32:81–85.Google Scholar
  12. 12.
    Loeffler JS, Alexander ED, Wen PY, et al.: Results of stereotactic brachytherapy used in the initial management of patients with glioblastoma. J Natl Cancer Inst 1990, 82:1918–1921.PubMedCrossRefGoogle Scholar
  13. 13.
    Patel S, Breneman J, Warnick R, et al.: Permanent iodine -125 interstitial implants for the treatment of recurrent glioblastoma multiforme. Neurosurgery 2000, 46:1123–1130. This study demonstrates a survival benefit, using permanent 125 I implants for patients with recurrent glioblastoma, similar to previously published reports, but with less morbidity.PubMedCrossRefGoogle Scholar
  14. 14.
    Videtic GM, Gaspar LE, Zamorano L, et al.: Use of the RTOG recursive partitioning analysis to validate the benefit of iodine-125 implants in the primary treatment of malignant gliomas. Int J Radiat Oncol Biol Phys 1999, 45:687–692.PubMedCrossRefGoogle Scholar
  15. 15.
    Laperriere NJ, Leung PM, McKenzie S, et al.: Randomized study of brachytherapy in the initial management of patients with malignant astrocytoma. Int J Radiat Oncol Biol Phys 1998, 41:1005–1011.PubMedCrossRefGoogle Scholar
  16. 16.
    Loeffler JS, Alexander Ed, Shea WM, et al.: Radiosurgery as part of the initial management of patients with malignant gliomas [see comments]. J Clin Oncol 1992, 10:1379–1385.PubMedGoogle Scholar
  17. 17.
    Shrieve DC, Alexander E 3rd, Black PM, et al.: Treatment of patients with primary glioblastoma multiforme with standard postoperative radiotherapy and radiosurgical boost: prognostic factors and long-term outcome. J Neurosurg 1999, 90:72–77.PubMedGoogle Scholar
  18. 18.
    Shrieve DC, Alexander E, 3rd, Wen PY, et al.: Comparison of stereotactic radiosurgery and brachytherapy in the treatment of recurrent glioblastoma multiforme. Neurosurgery 1995, 36:275–282.PubMedCrossRefGoogle Scholar
  19. 19.
    Fine HA, Dear KB, Loeffler JS, et al.: Meta-analysis of radiation therapy with and without adjuvant chemotherapy for malignant gliomas in adults [see comments]. Cancer 1993, 71:2585–2597.PubMedCrossRefGoogle Scholar
  20. 20.
    Levin VA, Silver P, Hannigan J, et al.: Superiority of post-radiotherapy adjuvant chemotherapy with CCNU, procarbazine, and vincristine (PCV) over BCNU for anaplastic gliomas: NCOG 6G61 final report. Int J Radiat Oncol Biol Phys 1990, 18:321–324.PubMedGoogle Scholar
  21. 21.
    Prados MD, Scott C, Curran WJ Jr, et al.: Procarbazine, lomustine, and vincristine (PCV) chemotherapy for anaplastic astrocytoma: a retrospective review of radiation therapy oncology group protocols comparing survival with carmustine or PCV adjuvant chemotherapy. J Clin Oncol 1999, 17:3389–3395.PubMedGoogle Scholar
  22. 22.
    Yung WK, Prados MD, Yaya-Tur R, et al.: Multicenter phase II trial of temozolomide in patients with anaplastic astrocytoma or anaplastic oligoastrocytoma at first relapse. Temodal Brain Tumor Group. J Clin Oncol 1999, 17:2762–2771.PubMedGoogle Scholar
  23. 23.
    Yung A, Levin V, Albright R: Randomized trial of Temodal versus procarbazine in glioblastoma multiforme at first relapse. Proc ASCO 1999, 18:139a.Google Scholar
  24. 24.
    Osoba D, Brada M, Yung WK, Prados M: Health-related quality of life in patients treated with temozolomide versus procarbazine for recurrent glioblastoma multiforme. J Clin Oncol, 18:1481–1491.Google Scholar
  25. 25.
    Brem H, Ewend MG, Piantadosi S, et al.: The safety of interstitial chemotherapy with BCNU-loaded polymer followed by radiation therapy in the treatment of newly diagnosed malignant gliomas: phase I trial. J Neurooncol 1995, 26:111–123.PubMedCrossRefGoogle Scholar
  26. 26.
    Subach BR, Witham TF, Kondziolka D, et al.: Morbidity and survival after 1,3-bis(2-chloroethyl)-1- nitrosourea wafer implantation for recurrent glioblastoma: a retrospective case-matched cohort series. Neurosurgery 1999, 45:17–22.PubMedCrossRefGoogle Scholar
  27. 27.
    Cairncross JG, Ueki K, Zlatescu MC, et al.: Specific genetic predictors of chemotherapeutic response and survival in patients with anaplastic oligodendrogliomas. J Natl Cancer Inst 1998, 90:1473–1479. This study supports the principle that molecular characteristics of a tumor can predict patient outcomes and response to therapy.PubMedCrossRefGoogle Scholar
  28. 28.
    Fine H, Figg W, Jaekle K, et al.: Phase II trial of the antiangiogenc agent thalidomide in patients with recurrent high-grade gliomas. J Clin Oncol 2000, 18:708–715.PubMedGoogle Scholar
  29. 29.
    Preul MC, Caramanos Z, Collins DL, et al.: Accurate, noninvasive diagnosis of human brain tumors by using proton magnetic resonance spectroscopy. Nat Med 1996, 2:323–325.PubMedCrossRefGoogle Scholar
  30. 30.
    Graves EE, Nelson SJ, Vigneron DB, et al.: A preliminary study of the prognostic value of proton magnetic resonance spectroscopic imaging in gamma knife radiosurgery of recurrent malignant gliomas. Neurosurgery 2000, 46:319–326. MRS may improve the selection and treatment planning of patients with malignant glioma.PubMedCrossRefGoogle Scholar
  31. 31.
    Preul MC, Caramanos Z, Villemure JG, et al.: Using proton magnetic resonance spectroscopic imaging to predict in vivo the response of recurrent malignant gliomas to tamoxifen chemotherapy. Neurosurgery 2000, 46:306–318. MRS may be used as a method to predict response to chemotherapy for patients with recurrent malignant glioma.PubMedCrossRefGoogle Scholar

Copyright information

© Current Science Inc 2000

Authors and Affiliations

  • Eric C. Burton
    • 1
  • Michael D. Prados
    • 1
  1. 1.Department of Neurological SurgeryUniversity of California, San FranciscoSan FranciscoUSA

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