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INTRODUCTION

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  • Lung cancer is a solid tumor originating from the bronchial epithelial cells. This chapter distinguishes between non–small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC) because they have different natural histories and responses to therapy.

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PATHOPHYSIOLOGY

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  • Lung carcinomas arise from normal bronchial epithelial cells that have acquired multiple genetic lesions and are capable of expressing a variety of phenotypes.

  • Activation of proto-oncogenes, inhibition or mutation of tumor suppressor genes, and production of autocrine growth factors contribute to cellular proliferation and malignant transformation. Molecular changes, such as overexpression of c-KIT in SCLC and epidermal growth factor receptor (EGFR) in NSCLC, also affect disease prognosis and response to therapy.

  • Cigarette smoking is responsible for approximately 80% of lung cancer cases. Other risk factors are exposure to environmental respiratory carcinogens (eg, asbestos, benzene, and arsenic), genetic risk factors, and history of other lung diseases (eg, chronic obstructive pulmonary disease [COPD] and asthma).

  • The major cell types are SCLC (~15% of all lung cancers), adenocarcinoma (~50%), squamous cell carcinoma (<30%), and large cell carcinoma. The last three types are grouped together and referred to as NSCLC.

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CLINICAL PRESENTATION

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  • The most common initial signs and symptoms are cough, dyspnea, chest pain, or discomfort, with or without hemoptysis. Many patients also exhibit systemic symptoms such as anorexia, weight loss, and fatigue.

  • Disseminated disease can cause neurologic deficits from CNS metastases, bone pain, or pathologic fractures secondary to bone metastases, or liver dysfunction from hepatic involvement.

  • Paraneoplastic syndromes may be the first sign of an underlying malignancy; examples include hypercalcemia, syndrome of inappropriate antidiuretic hormone secretion, and hypercoagulable state.

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DIAGNOSIS

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  • Chest radiographs, endobronchial ultrasound, computed tomography (CT) scan, and positron emission tomography (PET) scan are the most valuable diagnostic tests. Integrated CT–PET technology appears to improve diagnostic accuracy in staging NSCLC over CT or PET alone.

  • Pathologic confirmation is established by examination of sputum cytology and/or tumor biopsy by bronchoscopy, mediastinoscopy, percutaneous needle biopsy, or open-lung biopsy.

  • All patients must have a thorough history and physical examination to detect signs and symptoms of the primary tumor, regional spread of the tumor, distant metastases, paraneoplastic syndromes, and ability to withstand aggressive surgery or chemotherapy.

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STAGING

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  • The World Health Organization has established a TNM staging classification for NSCLC based on primary tumor size and extent (T), regional lymph node involvement (N), and presence or absence of distant metastases (M).

  • A simpler system is commonly used to compare treatments. Stage I includes tumors confined to the lung without lymphatic spread, Stage II includes large tumors with ipsilateral peribronchial or hilar lymph node involvement, Stage III includes other lymph node and regional involvement, and Stage IV includes any tumor with distant metastases.

  • A two-stage classification is widely used for SCLC. Limited disease is confined to one hemithorax and can be encompassed by a single radiation port. All other disease is classified as extensive.

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TREATMENT

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