Surgical removal is recommended for most types of brain tumors in most locations, and their removal should be as complete as possible within the constraints of preservation of neurologic function.[1] An exception to this role for surgery is deep-seated tumors such as pontine gliomas, which are diagnosed on clinical evidence and treated without initial surgery approximately 50% of the time. In most cases, however, diagnosis by biopsy is preferred. Stereotaxic biopsy can be used for lesions that are difficult to reach and resect.

Radiation therapy has a major role in the treatment of patients, as evidenced in the EORTC-22845 and MRC-BR04 trials, for example, with most tumor types and can increase the cure rate or prolong disease-free survival.[2] Radiation therapy may also be useful in the treatment of recurrences in patients initially treated with surgery alone.

Chemotherapy may prolong survival in patients with some tumor types and has been reported to lengthen disease-free survival in patients with gliomas, medulloblastoma, and some germ cell tumors.[3] Local chemotherapy with a nitrosourea applied to a polymer placed directly in the brain during surgery has been shown to be a safe modality and is under clinical evaluation.[1,4]

Surgery and radiation therapy are the primary modalities used to treat tumors of the spinal axis; therapeutic options vary according to the histology of the tumor.[5] The experience with chemotherapy for primary spinal cord tumors is rare; no reports of controlled clinical trials are available for these types of tumors.[5,6] Chemotherapy is indicated for most patients with leptomeningeal involvement (from a primary or metastatic tumor) and a positive cerebrospinal fluid cytology.[5] Most patients require treatment with corticosteroids, particularly if they are receiving radiation therapy.

For patients with brain tumors, two primary goals of surgery include: (1) establishing a histologic diagnosis and (2) reducing intracranial pressure by removing as much tumor as is safely possible to preserve neurological function.[5] Total elimination of primary intraparenchymal tumors by surgery alone is extremely rare. Radiation therapy and chemotherapy options vary according to histology and anatomic site of the brain tumor. Therapy involving surgically implanted carmustine-impregnated polymer combined with postoperative external-beam radiation therapy (EBRT) has a role in the treatment of high-grade gliomas.[7] Dexamethasone, mannitol, and furosemide are used to treat the peritumoral edema associated with brain tumors. Use of anticonvulsants is mandatory for patients with seizures.[5]

Novel biologic therapies under clinical evaluation for patients with brain tumors include dendritic cell vaccination,[8] tyrosine kinase receptor inhibitors,[9] farnesyl transferase inhibitors, viral-based gene therapy,[10,11] oncolytic viruses, epidermal growth factor receptor inhibitors and vascular endothelial growth factor inhibitors,[12] and other antiangiogenesis agents.

Patients who have brain tumors that are either infrequently curable or unresectable should be considered candidates for clinical trials that evaluate radiosensitizers, hyperthermia, or interstitial brachytherapy used in conjunction with EBRT to improve local control of the tumor or for studies that evaluate new drugs and biological response modifiers.[12]

Information about ongoing clinical trials is available from the NCI Web site.

Metastatic Brain Tumors

The optimal therapy for patients with brain metastases continues to evolve.[13-15] Corticosteroids, anticonvulsants, radiation therapy, surgery, and radiosurgery have an established place in management. Because most cases of brain metastases involve multiple metastases, the current practice is to treat the lesions with whole-brain radiation therapy (WBRT). Adjuvant WBRT with surgery or radiosurgery may be useful. Surgical therapy is useful for resection of a single brain metastasis and large, symptomatic, or life-threatening lesions. The role of radiosurgery continues to be defined; it may be useful as a substitute for surgical treatment in patients with lesions smaller than 3 cm in diameter. Chemotherapy is usually not the primary therapy for most patients; however, it may have a role in the treatment of patients with brain metastases from chemosensitive tumors.[13,16]

References

1. Brem H, Piantadosi S, Burger PC, et al.: Placebo-controlled trial of safety and efficacy of intraoperative controlled delivery by biodegradable polymers of chemotherapy for recurrent gliomas. The Polymer-brain Tumor Treatment Group. Lancet 345 (8956): 1008-12, 1995.  [PUBMED Abstract]
   
   
2. Karim AB, Afra D, Cornu P, et al.: Randomized trial on the efficacy of radiotherapy for cerebral low-grade glioma in the adult: European Organization for Research and Treatment of Cancer Study 22845 with the Medical Research Council study BRO4: an interim analysis. Int J Radiat Oncol Biol Phys 52 (2): 316-24, 2002.  [PUBMED Abstract]
   
   
3. Cokgor I, Friedman HS, Friedman AH: Chemotherapy for adults with malignant glioma. Cancer Invest 17 (4): 264-72, 1999.  [PUBMED Abstract]
   
   
4. 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 26 (2): 111-23, 1995.  [PUBMED Abstract]
   
   
5. Cloughesy T, Selch MT, Liau L: Brain. In: Haskell CM: Cancer Treatment. 5th ed. Philadelphia, Pa: WB Saunders Co, 2001, pp 1106-42. 
   
   
6. Levin VA, Leibel SA, Gutin PH: Neoplasms of the central nervous system. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds.: Cancer: Principles and Practice of Oncology. 6th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2001, pp 2100-60. 
   
   
7. Lallana EC, Abrey LE: Update on the therapeutic approaches to brain tumors. Expert Rev Anticancer Ther 3 (5): 655-70, 2003.  [PUBMED Abstract]
   
   
8. Fecci PE, Mitchell DA, Archer GE, et al.: The history, evolution, and clinical use of dendritic cell-based immunization strategies in the therapy of brain tumors. J Neurooncol 64 (1-2): 161-76, 2003 Aug-Sep.  [PUBMED Abstract]
   
   
9. Newton HB: Molecular neuro-oncology and development of targeted therapeutic strategies for brain tumors. Part 1: Growth factor and Ras signaling pathways. Expert Rev Anticancer Ther 3 (5): 595-614, 2003.  [PUBMED Abstract]
   
   
10. Kew Y, Levin VA: Advances in gene therapy and immunotherapy for brain tumors. Curr Opin Neurol 16 (6): 665-70, 2003.  [PUBMED Abstract]
    
    
11. Chiocca EA, Aghi M, Fulci G: Viral therapy for glioblastoma. Cancer J 9 (3): 167-79, 2003 May-Jun.  [PUBMED Abstract]
    
    
12. Fine HA: Promising new therapies for malignant gliomas. Cancer J 13 (6): 349-54, 2007 Nov-Dec.  [PUBMED Abstract]
    
    
13. Patchell RA: The management of brain metastases. Cancer Treat Rev 29 (6): 533-40, 2003.  [PUBMED Abstract]
    
    
14. Wen PY, Black PM, Loeffler JS: Treatment of metastatic cancer. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds.: Cancer: Principles and Practice of Oncology. 6th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2001, pp 2655-70. 
    
    
15. Soffietti R, Cornu P, Delattre JY, et al.: EFNS Guidelines on diagnosis and treatment of brain metastases: report of an EFNS Task Force. Eur J Neurol 13 (7): 674-81, 2006.  [PUBMED Abstract]
    
    
16. Ogawa K, Yoshii Y, Nishimaki T, et al.: Treatment and prognosis of brain metastases from breast cancer. J Neurooncol 86 (2): 231-8, 2008.  [PUBMED Abstract]
    
    

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