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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 at 200,000 new cases per year in the United States, based on a 10% to 15% incidence (1). In comparison, the incidence of primary brain and spinal cord tumors for 2014 was estimated at 23,380 new cases (American Cancer Society 2014 Facts and Figures [ (or,]).

Because of the heterogeneous histology and often-refractory nature of primary brain tumors, their management is complex, ideally requiring a multidisciplinary team and individualized treatment. The diagnosis is made on the basis of histology, so an accurate characterization of the lesion pathology is crucial, often necessitating confirmation at a specialized cancer center. Optimal outcomes involve the coordination of neurosurgery, radiation oncology, and neuro-oncology specialists. Despite advances in neurosurgical techniques, radiation therapy, and chemotherapy, the prognosis for patients with high-grade gliomas such as glioblastoma (GBM), the most common form of glioma, remains dismal. Recent large clinical trials have reported a median survival of only 14 to 16 months with a 26% to 33% 2-year survival rate (2,3). A review of eight consecutive phase II chemotherapy trials for recurrent GBM 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 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 because new therapies target patients from initial diagnosis, with presurgical protocols, to salvage therapy at relapse. This chapter provides basic principles that can be used for diagnosing and treating patients with brain tumors along with an introduction to the molecular mechanisms underlying gliomagenesis.


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

Primary brain tumors are classified by the World Health Organization (WHO) grading system (Table 40-1), which is based on the histologic pattern of cell differentiation in the tumor, in addition to histologic features associated with biological aggressiveness (ie, mitotic figures, necrosis, vascular proliferation). Tumor grade is inversely correlated with prognosis. The most common primary brain tumors are gliomas (all glial tumors), followed by meningiomas, nerve ...

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