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Brain tumors are a heterogeneous group of lesions that range from benign, slow-growing tumors found only incidentally on autopsy to malignant, rapidly growing tumors that cause death within months. The most common intracranial tumors are brain metastases from systemic cancer, estimated to be up to 200,000 per year in the United States, based on a 10 to 15% incidence (1,2), whereas the expected number of all new cancer diagnoses in 2009 was 1.48 million (3). In comparison, the incidence of primary brain tumors in 2009 was an estimated 22,070 new cases (3). Because of the heterogeneous histology and often refractory nature of these tumors, their management is complex, ideally requiring a multidisciplinary team and individualized treatment. Diagnosis is made on the basis of histology, so an accurate characterization of the lesion's pathology is crucial, often necessitating confirmation at a specialized cancer center. Optimal outcomes involve the coordination of neurosurgery, radiation oncology, and neuro-oncology, although low-grade tumors may not require initial therapy other than observation following optimal surgical resection. Despite advances in neurosurgical techniques, radiation therapy, and chemotherapy, the prognosis for patients with high-grade gliomas such as glioblastoma (GB), the most common form of glioma, remains dismal. For patients with GB, median survival is approximately 1 year. A review of eight consecutive phase II chemotherapy trials for recurrent GB demonstrated only a 6% response rate (complete response [CR] and partial response [PR]), with a 6-month progression-free survival (PFS) of 15% and a 1-year overall survival of 21% (4). It is, therefore, important to consider patients with high-grade gliomas for entry into clinical trials at all stages of disease, since new therapies target patients from initial diagnosis with presurgical protocols to salvage therapy at relapse. This chapter aims to provide basic principles that can be used for diagnosing and treating patients with brain tumors. Areas that present special challenges for the treating physician are highlighted, along with an introduction to the underlying molecular mechanisms of gliomagenesis.

Brain tumors are either primary tumors that arise de novo or secondary brain metastases, the latter being far more common. The most common brain metastases result from lung cancer, followed by breast, melanoma, renal, and colorectal cancers (5). Most patients with brain metastases die from progression of their systemic cancer, although, because of improvements in systemic therapy, brain metastases are seen more frequently and have produced escalating morbidity and mortality (1). On a more hopeful note, advances in treating brain metastasis with surgery and radiotherapy have improved overall survival when the patient's systemic disease is controlled.

Primary brain tumors are classified by the World Health Organization (WHO) grading system (Table 37-1), which is based on the histologic pattern of cell differentiation in the tumor. Tumor grade is inversely correlated with prognosis. The most common primary brain tumors are gliomas (all glial tumors), followed by meningiomas, nerve sheath tumors, and pituitary tumors (6...

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