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costs associated with premature deaths, and direct costs of medical care. In 2005 in the CASE STUDY A 65-year-old man had a dry cough for several months. He had smoked one pack of cigarettes a day for 35 years and quit five years earlier. He had a history of chronic obstructive pulmonary disease (COPD). A chest radiograph showed a mass in the left lower lobe with lymph node enlargement. A chest computed tomography (CT) scan confirmed these findings. A positron emission tomography (PET) scan showed abnormalities in the mass and lymph nodes, but no other areas. Magnetic resonance imaging (MRI) of the brain was normal. A bronchoscopy with endobronchial ultrasound confirmed lung cancer, with adenocarcinoma histology. The cancer was staged by its size and spread as T2aN2M0, clinical stage IIIA. (T is for tumor size and location; N is for lymph node spread; and M is for distant metastasis.) Comment Lung cancer symptoms typically include persistent cough, difficulty breathing, coughing up blood, and chest discomfort, though many patients are asymptomatic. Patients with advanced disease often have weight loss, fatigue, or pain outside the chest. This patient’s evaluation included diagnostic studies generally performed in a lung cancer evaluation, the purpose of which is to determine the cancer stage. Staging predicts prognosis and influences treatment. Whitebook_breathing_Ch11.indd 111 6/25/10 12:51:18 PM Lung Cancer Chapter 11 112 United States, lung cancer caused 2.4 million person-years-of-life-lost (personyears-of-life-lost is the difference between the actual age at death due to disease and the expected age of death). For this statistic, lung cancer far exceeds any other type of cancer (3). The economic costs associated with those lost years of life are substantial. One study estimated that those costs in 2000 in the United States were $289.4 billion (4). Direct medical costs related to treatment for lung cancer are also staggering. In 2004, the National Cancer Institute estimated lung cancer treatment expenditures at $9.6 billion (3). Unfortunately, because of the lack of effective screening technology, only about a third of patients are identified at an early stage. Most patients do not seek medical attention until the disease is advanced, and at that point, treatment is of limited success. Overall survival is poor. What we are learning about the disease Epidemiology, prevalence, economic burden, vulnerable populations The pathophysiology of lung cancer is best described as a “multi-hit” event. Carcinogens, most commonly those in cigarette smoke but also including many different environmental exposures, can result in DNA damage or mutation. The cumulative effect of several “hits” may result in irreversible effects on the biologic mechanisms that control growth, proliferation, vascular supply, and death of normal cells. Collective dysregulation of these mechanisms is felt to lead to lung cancer. Many factors affect lung cancer risk, but cigarette smoking has been the largest single factor contributing to the dramatic rise in lung cancer rates in the United States. Since the 1964 Surgeon General’s report on the health consequences of smoking, the yearly per capita consumption of cigarettes in the United States has declined. Nonetheless, almost one quarter of Americans continue to smoke, which makes it likely that lung cancer will remain the most important cancer in this country for years to come. Cigar and pipe smoking also increase risk, but less so than cigarettes. While it is certainly one of the greatest risk factors for lung cancer, tobacco smoking is not the only risk factor. An estimated 15 percent of lung cancers in women in the United States and a much larger percentage of lung cancers in women in Asia occur in non-smokers. Epidemiologic studies show that in the Whitebook_breathing_Ch11.indd 112 6/25/10 12:51:18 PM Chapter 11 Lung Cancer 113 United States, smoking is responsible for 90 percent of lung cancer cases, occupational exposures to carcinogens cause 9 to 15 percent of cases, and radon accounts for 10 percent of cases (5). (The sum of these risk estimates exceeds 100 percent because many individuals have multiple risk factors, and these factors are synergistic.) A number of occupational