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Introduction

Small cell lung cancer (SCLC) is, in many ways, a unique tumor. Untreated, it is a highly virulent malignancy, with a life expectancy best measured in weeks. Conversely, it displays exquisite chemosensitivity, resulting in partial or complete responses in the majority of cases. Unfortunately, these responses are typically short-lived, and as a result, more than 95% of SCLC patients die from their disease. Over the past 25 years, little progress has been made in prolonging the survival of patients with SCLC, despite numerous attempts to refine and improve the present therapy. This chapter reviews the biology, epidemiology, diagnosis, clinical presentation, staging, and current management of this difficult disease.

Epidemiology

Lung cancer remains the leading cause of cancer death in men and women in the United States. In 2012, estimates called for 226,160 cases of newly diagnosed lung cancer (116,470 men and 109,690 women) and 160,340 deaths (87,750 in men and 72,590 in women) from this disease.1 A review of data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Cancer Incidence Public Use database found that the proportion of lung cancer cases ascribed to SCLC has declined from a peak of 17.62% in 1986 to 12.95% in 2002.2 A similar review of the National Cancer Database (NCDB) identified that SCLC constituted 19.5% of all new lung cancer diagnoses in 1992 and that this had decreased to 15.7% by 2007.3 Of note, women now make up approximately 50% of SCLC cases, which is up from 28% in 1973.

The primary etiologic agent responsible for SCLC is tobacco smoke. A recent meta-analysis of nine case-control studies that included 11 European countries and Canada reported that the odds ratios in current smokers for the development of SCLC are 45.7 and 21.7 in men and women, respectively.4 In the analysis, the risk increased markedly with both the intensity and duration of smoking, with males currently smoking >30 cigarettes daily having an odds ratio of 111.3 of developing SCLC. While >95% of cases of SCLC occur in current or former smokers, other etiologic agents including bischloromethyl esters, nickel, vinyl chloride, asbestos, cadmium, radon, arsenic, and radiation have been implicated as possible contributors to the development of this disease.5 However, the true impact of exposure to each of these agents is not well quantified in the literature.

Pathology

Barnard6 published the first report of SCLC in 1926, in which he described mediastinal tumors of epithelial origin that he called “Oat Cell Sarcoma” due to the histologic resemblance of the cells to oat grains. Since that description, the pathologic classification of SCLC has undergone frequent and extensive revision. Specifically, over the past five decades, the World Health Organization (WHO) proposed several different classification schemas that divided SCLC into a variety of subtypes that were, in retrospect, of limited utility in defining ...

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