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Key Clinical Updates in Bronchogenic Carcinoma

ROS1-rearranged lung cancers respond to crizotinib (ALK, cMET, and ROS1 tyrosine kinase inhibitor) and entrectinib (multikinase inhibitor, including ROS-1) with response rates over 70%.

For patients whose NSCLC reveals NTRK 1/2/3 gene fusion, treatment with larotrectinib (TRKA/B/C inhibitor) or entrectinib (multikinase inhibitor, including TRKA/B/C) is recommended.

Selpercatinib and pralsetinib (RET inhibitors) are recommended first-line treatments for RET fusion-positive NSCLC.

ESSENTIALS OF DIAGNOSIS

  • New cough or change in chronic cough.

  • Dyspnea, hemoptysis, anorexia, weight loss.

  • Enlarging lung nodule or mass; persistent opacity, atelectasis, or pleural effusion on chest radiograph or CT scan.

  • Cytologic or histologic findings of lung cancer in sputum, pleural fluid, or biopsy specimen.

GENERAL CONSIDERATIONS

Lung cancer is the leading cause of cancer deaths in both men and women. The American Cancer Society estimates 228,820 new diagnoses and 135,720 deaths from lung cancer in the United States in 2020, accounting for approximately 13% of new cancer diagnoses and 22% of all cancer deaths. More Americans die of lung cancer than of colorectal, breast, and prostate cancers combined. In 2012 worldwide, an estimated 1.8 million cases of lung cancer and 1.5 million deaths due to lung cancer were reported.

Cigarette smoking causes 85–90% of cases of lung cancer. The causal connection between cigarettes and lung cancer is established not only epidemiologically but also through identification of carcinogens in tobacco smoke and analysis of the effect of these carcinogens on specific oncogenes expressed in lung cancer.

Starting in the early 1990s, mortality from lung cancer fell among US men, reflecting changing patterns of tobacco use over the past 30 years (see Chapter 1). Among US women, mortality rates have started to fall since the early 2000s. Other environmental risk factors for the development of lung cancer include exposure to environmental tobacco smoke, radon, asbestos (60- to 100-fold increased risk in smokers with asbestos exposure), diesel exhaust, ionizing radiation, metals (arsenic, chromium, nickel, iron oxide), and industrial carcinogens (bis-chloromethyl ether). A familial predisposition to lung cancer is recognized. Certain diseases are associated with an increased risk of lung cancer, including pulmonary fibrosis, chronic obstructive pulmonary disease, and sarcoidosis. Second primary lung cancers are more frequent in patients who survive their initial lung cancer.

The median age at diagnosis of lung cancer in the United States is 70; it is unusual under the age of 40. The combined relative 5-year survival rate for all stages of lung cancer is currently 21%.

There are five main histologic categories of bronchogenic carcinoma. Squamous cell carcinomas (23% of cases, based on US SEER data 2013–2017) arise from the bronchial epithelium and often present as intraluminal masses. They are usually centrally located and can present with hemoptysis. Squamous cell carcinomas stain for P63 and P40 on immunohistochemistry. Adenocarcinomas (50% of cases) arise from mucous glands or from any epithelial cell ...

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