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Lung cancer is the leading cause of cancer-related deaths in the United States and worldwide (1,2). The high rate of mortality results from both the high incidence and the late stage of disease at diagnosis. It is estimated that in the year 2009, approximately 219,440 new cases will be diagnosed and 159,390 deaths due to lung cancer will occur in the United States. These numbers represent approximately 15% of all new cancer cases and 28% of cancer deaths in this population (1).

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These statistics emphasize that lung cancer is a lethal disease, with poor overall survival. Only 15% of patients diagnosed with lung cancer are alive 5 years later (1,2). More than 70% of patients will be diagnosed with advanced disease that is not amenable to curative therapy (3). Even those who present with early-stage disease have a high rate of recurrence.

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Lung cancer is broadly divided into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). Approximately 85% of lung cancer is NSCLC. This chapter briefly describes the epidemiology, etiology, histology, prevention, and molecular biology of NSCLC. The major focus of this chapter is to describe and discuss the clinical presentation, diagnosis, staging, and treatment of NSCLC based on current clinical knowledge, with an emphasis on our approach to the management of NSCLC at the University of Texas MD Anderson Cancer Center (MDACC).

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Lung cancer is rarely diagnosed in people less than 35 years old. Incidence and death rates rise exponentially among patients older than 35, then approximately plateau among patients greater than 75 years old (4). NSCLC accounts for the greatest number of deaths from cancer in both men and women over age 60 (1).

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Analysis of the incidences of smoking and lung cancer in the United States over the past century demonstrates parallel courses, with a latency period of about 20 years between the former and latter events. The current epidemic of lung cancer began with a sharp increase in incidence among men in the 1930s, following the availability of manufactured cigarettes in the 1910s. The increase in lung cancer incidence among women did not start until the 1960s, again following an increase in exposure to tobacco (this time due to changes in smoking practices after World War II), and by 1987 lung cancer surpassed breast cancer as the leading cause of cancer-related death in women (5). In the 1990s, the incidence of lung cancer in the United States decreased among men. In women, the rates of lung cancer stabilized from 2003 to 2005. In the year 2009, the estimated ratio of male-to-female deaths due to lung cancer in the United States was 1.3:1 (1). There is some evidence that women are at a greater risk for lung cancer; however, other studies have not confirmed this finding.

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