Lung cancer overview

# Overview
Prior to the introduction of cigarette smoking and industrial carcinogens, lung cancer was thought to be a rare disease. Of all the tumors detected on autopsy, lung cancer accounted for only 1% of cancers in the 1800s. The majority of cases of lung cancer were associated with occupational hazards due to radon exposure. The association between lung cancer and smoking was not defined until the mid-20th century. Primary lung cancers may be classified into small cell lung cancer (~15%) and non small cell lung cancer (~85%).  Non small cell lung cancer are a heterogeneous group of lung cancers that are often grouped together because they share similar clinical features (e.g. prognosis and management). The 2015 WHO histological classification of tumors of the lung categorized lung tumors into malignant epithelial tumors, benign epithelial tumors, lymphoproliferative tumors, miscellaneous tumors, and metastatic tumors. The pathophysiology of lung cancer includes both genetic and environmental factors. Causality of the majority of lung cancer is linked to tobacco usage. Carcinogenic effects of tobacco smoking may result in DNA mis-replication and mutation. Smoking starts a cascade of events that leads to cancer development, even decades after smoking cessation. Besides smokers, patients with the history of prior respiratory tract or gastrointestinal tract cancer comprise a high-risk population. Other environmental factors include radon, asbestos, viral infections, and states of chronic lung inflammation, all of which may predispose to cellular damage and DNA mutations that predispose to the development of lung cancers. The direct cause of lung cancer is DNA mutations that often result in either activation of proto-oncogenes (e.g. K-RAS) or the inactivation of tumors suppressor genes (e.g. TP53) or both. The risk of these genetic mutations may be increased following exposure to environmental insults. Lung cancer must be differentiated from other conditions that cause hemoptysis, cough, dyspnea, wheezing, chest pain, dysphonia, dysphagia, unexplained weight loss, unexplained loss of appetite, and fatigue. These conditions include pneumonia, bronchitis, metastatic cancer from a non-thoracic primary site, infectious granuloma, pulmonary tuberculosis, tracheal tumors, and a thyroid mass. Lung cancer is the most common cause of cancer-associated mortality and the second most common type of cancer among both genders. Individuals > 50 years of age who have a history of smoking are at increased risk. Historically, the incidence of lung cancer is significantly higher among males compared to females. This increased ratio is thought to be attributed to the increased rates of smoking among men. However, more women are being diagnosed with lung cancer due to the increased rate of smoking among women. In 2014, the incidence of lung cancer in the United States was approximately 70 cases per 100,000. The most potent risk factor in the development of lung cancer is tobacco smoking. Other risk factors include second hand smoke, air pollution, family history of lung cancer, radiation therapy to the chest, and exposure to radon, asbestos and other chemical carcinogens. Lung cancer screening is a strategy used to identify early lung cancer in people, before they develop symptoms. Screening refers to the use of medical tests to detect disease in asymptomatic people. Screening studies for lung cancer have only been done in high risk populations, such as smokers and workers with occupational exposure to certain substances. This is because radiation exposure from screening could actually induce carcinogenesis in a small percentage of screened subjects, so this risk should be mitigated by a (relatively) high prevalence of lung cancer in the population being screened. A pulmonary nodule larger than 5 - 6 mm is considered a positive result for screening with x-ray or computed tomography. The majority of lung cancers present with advanced disease because the symptoms tend to occur later in the course of the disease. Patients experience non-specific symptoms such as cough, hemoptysis, dyspnea, chest pain, difficulty speaking, difficulty swallowing, lack of appetite, weight loss, and fatigue from 3 weeks to 3 months before seeking medical attention. There are a variety of complications associated with lung cancer, such as pleural effusion, leg weakness, paresthesias, bladder dysfunction, seizures, hemiplegia, cranial nerve palsies, confusion, personality changes, skeletal pain, pleuritic pain, atelectasis, and bronchopleural fistula. The prognosis of lung cancer is poor if diagnosed at the advanced stages. Chest CT scan is the modality of choice in the diagnosis of lung cancer. Findings on CT scan suggestive of lung cancer include a solitary pulmonary nodule, centrally located masses, mediastinal invasion CT scans help stage the lung cancer. A CT scan of the abdomen and brain can help visualize the common sights of metastases such as adrenal glands, liver, and brain. CT scans diagnose lung cancer by providing anatomical detail to locate the tumor, demonstrating proximity to the nearby structures, and deciphering whether lymph nodes are enlarged in the mediastinum. Common symptoms of lung cancer include difficulty breathing, hemoptysis, chronic coughing, chest pain, weakness and wasting, difficulty speaking, and symptoms related to paraneoplastic syndromes. Common physical examination findings of lung cancer include decreased/absent breath sounds, pallor, low-grade fever, and tachypnea. The laboratory findings associated with lung cancer are the following neutropenia, hyponatremia, hypokalemia, hypercalcemia, respiratory acidosis, hypercarbia, hypoxia, and tumor cells in sputum and pleural effusion cytology. Performing a chest x-ray is the first step if a patient reports symptoms that may be suggestive of lung cancer. Lung cancers are usually detected on a routine chest x-ray in a person experiencing no symptoms. There are no echocardiography/ultrasound findings associated with lung cancer. Chest CT scan is the modality of choice in the diagnosis of lung cancer. Findings on CT scan suggestive of lung cancer include a solitary pulmonary nodule, centrally located masses, mediastinal invasion CT scans help stage the lung cancer. A CT scan of the abdomen and brain can help visualize the common sights of metastases such as adrenal glands, liver, and brain. CT scans diagnose lung cancer by providing anatomical detail to locate the tumor, demonstrating proximity to the nearby structures, and deciphering whether lymph nodes are enlarged in the mediastinum. The indication of MRI in lung cancer is when there is a suspicion of spinal cord canal invasion and/or in the presence of pancoast tumor (superior sulcus tumor) and brachial plexus tumors. There are no other imaging findings associated with lung cancer. Other diagnostic studies include bone scintigraphy, PET scan, and molecular tests. Medical therapy for lung cancer consists of radiation therapy, chemotherapy, and targeted therapy. Lung cancer surgery involves the surgical excision of the cancerous tissue. It is used mainly in non-small cell lung cancer with the intention of curing the patient. Effective measures for the primary prevention of lung cancer include smoking cessation and avoidance of second hand smoking. Lifestyle changes, such as healthy diet rich with fruits and vegetables and regular exercise, might decrease the risk of developing cancer in general. Secondary prevention of lung cancer consists of smoking cessation and screening. Secondary chemoprevention focuses on blocking the development of lung cancer in individuals in whom a precancerous lesion has been detected.

# Historical Perspective
Prior to the introduction of cigarette smoking and industrial carcinogens, lung cancer was thought to be a rare disease. Of all the tumors detected on autopsy, lung cancer accounted for only 1% of cancers in the 1800s. The majority of cases of lung cancer were associated with occupational hazards due to radon exposure. The association between lung cancer and smoking was not defined until the mid-20th century.

# Classification
Primary lung cancers may be classified into small cell lung cancer (~15%) and non small cell lung cancer (~85%).  Non small cell lung cancer are a heterogeneous group of lung cancers that are often grouped together because they share similar clinical features (e.g. prognosis and management). The 2015 WHO histological classification of tumors of the lung categorized lung tumors into malignant epithelial tumors, benign epithelial tumors, lymphoproliferative tumors, miscellaneous tumors, and metastatic tumors.

# Pathophysiology
The pathophysiology of lung cancer includes both genetic and environmental factors. Causality of the majority of lung cancer is linked to tobacco usage. Carcinogenic effects of tobacco smoking may result in DNA mis-replication and mutation. Smoking starts a cascade of events that leads to cancer development, even decades after smoking cessation. Besides smokers, patients with the history of prior respiratory tract or gastrointestinal tract cancer comprise a high-risk population. Other environmental factors include radon, asbestos, viral infections, and states of chronic lung inflammation, all of which may predispose to cellular damage and DNA mutations that predispose to the development of lung cancers.

# Causes
The direct cause of lung cancer is DNA mutations that often result in either activation of proto-oncogenes (e.g. K-RAS) or the inactivation of tumors suppressor genes (e.g. TP53) or both. The risk of these genetic mutations may be increased following exposure to environmental insults.

# Differential Diagnosis
Lung cancer must be differentiated from other conditions that cause hemoptysis, cough, dyspnea, wheezing, chest pain, dysphonia, dysphagia, unexplained weight loss, unexplained loss of appetite, and fatigue. These conditions include pneumonia, bronchitis, metastatic cancer from a non-thoracic primary site, infectious granuloma, pulmonary tuberculosis, tracheal tumors, and a thyroid mass.

# Epidemiology and Demographics
Lung cancer is the most common cause of cancer-associated mortality and the second most common type of cancer among both genders. Individuals > 50 years of age who have a history of smoking are at increased risk. Historically, the incidence of lung cancer is significantly higher among males compared to females. This increased ratio is thought to be attributed to the increased rates of smoking among men. However, more women are being diagnosed with lung cancer due to the increased rate of smoking among women. In 2014, the incidence of lung cancer in the United States was approximately 70 cases per 100,000.

# Risk Factors
The most potent risk factor in the development of lung cancer is tobacco smoking. Other risk factors include second hand smoke, air pollution, family history of lung cancer, radiation therapy to the chest, and exposure to radon, asbestos and other chemical carcinogens.

# Screening
Lung cancer screening is a strategy used to identify early lung cancer in people, before they develop symptoms. Screening refers to the use of medical tests to detect disease in asymptomatic people. Screening studies for lung cancer have only been done in high risk populations, such as smokers and workers with occupational exposure to certain substances. This is because radiation exposure from screening could actually induce carcinogenesis in a small percentage of screened subjects, so this risk should be mitigated by a (relatively) high prevalence of lung cancer in the population being screened. A pulmonary nodule larger than 5 - 6 mm is considered a positive result for screening with x-ray or computed tomography.

# Natural History, Complications, and Prognosis
The majority of lung cancers present with advanced disease because the symptoms tend to occur later in the course of the disease. Patients experience non-specific symptoms such as cough, hemoptysis, dyspnea, chest pain, difficulty speaking, difficulty swallowing, lack of appetite, weight loss, and fatigue from 3 weeks to 3 months before seeking medical attention. There are a variety of complications associated with lung cancer, such as pleural effusion, leg weakness, paresthesias, bladder dysfunction, seizures, hemiplegia, cranial nerve palsies, confusion, personality changes, skeletal pain, pleuritic pain, atelectasis, and bronchopleural fistula. The prognosis of lung cancer is poor if diagnosed at the advanced stages.

# Diagnosis

## Diagnostic Study of Choice
Chest CT scan is the modality of choice in the diagnosis of lung cancer. Findings on CT scan suggestive of lung cancer include a solitary pulmonary nodule, centrally located masses, mediastinal invasion CT scans help stage the lung cancer. A CT scan of the abdomen and brain can help visualize the common sights of metastases such as adrenal glands, liver, and brain. CT scans diagnose lung cancer by providing anatomical detail to locate the tumor, demonstrating proximity to the nearby structures, and deciphering whether lymph nodes are enlarged in the mediastinum.

## History and Symptoms
Common symptoms of lung cancer include difficulty breathing, hemoptysis, chronic coughing, chest pain, weakness and wasting, difficulty speaking, and symptoms related to paraneoplastic syndromes.

## Physical Examination
Common physical examination findings of lung cancer include decreased/absent breath sounds, pallor, low-grade fever, and tachypnea.

# Diagnostic Studies

## Diagnostic study of choice
Chest CT scan is the modality of choice in the diagnosis of lung cancer. Findings on CT scan suggestive of lung cancer include, a solitary pulmonary nodule, centrally located masses, mediastinal invasion. A CT scan of the abdomen and brain can help visualize the common sites of metastases: adrenal glands, liver, and brain. CT scans diagnose lung cancer by providing anatomical detail to locate the tumor, demonstrating proximity to nearby structures, and deciphering whether lymph nodes are enlarged in the mediastinum.

## Laboratory Findings
The laboratory findings associated with lung cancer are the following neutropenia, hyponatremia, hypokalemia, hypercalcemia, respiratory acidosis, hypercarbia, hypoxia, and tumor cells in sputum and pleural effusion cytology.

## Electrocardiograpgy
ECG is a simple method for finding evidence of pulmonary artery stenosis in metastatic lung cancer and should be routinely performed in such patients. Findings on ECG associated mediastinal metastatic of lung cancer led to pulmonary artery stenosis and right ventricular strain include right axis deviation, deepened S wave in lead 1, sustantial R wave in lead avR, inverted/flattened T waves in limb and precordial leads.

## X-ray
Performing a chest x-ray is the first step if a patient reports symptoms that may be suggestive of lung cancer. Lung cancers are usually detected on a routine chest x-ray in a person experiencing no symptoms.

## Echocardiography and Ultrasound
There are no echocardiography/ultrasound findings associated with lung cancer.

## CT scan
Chest CT scan is the modality of choice in the diagnosis of lung cancer. Findings on CT scan suggestive of lung cancer include a solitary pulmonary nodule, centrally located masses, mediastinal invasion CT scans help stage the lung cancer. A CT scan of the abdomen and brain can help visualize the common sights of metastases such as adrenal glands, liver, and brain. CT scans diagnose lung cancer by providing anatomical detail to locate the tumor, demonstrating proximity to the nearby structures, and deciphering whether lymph nodes are enlarged in the mediastinum.

## MRI
The indication of MRI in lung cancer is when there is a suspicion of spinal cord canal invasion and/or in the presence of pancoast tumor (superior sulcus tumor) and brachial plexus tumors.

## Other Imaging Findings
There are no other imaging findings associated with lung cancer.

## Other Diagnostic Studies
Other diagnostic studies include bone scintigraphy, PET scan, and molecular tests.

# Treatment

## Medical Therapy
Medical therapy for lung cancer consists of radiation therapy, chemotherapy, and targeted therapy.

## Surgery
Lung cancer surgery involves the surgical excision of the cancerous tissue. It is used mainly in non-small cell lung cancer with the intention of curing the patient.

## Primary Prevention
Effective measures for the primary prevention of lung cancer include smoking cessation and avoidance of second hand smoking. Lifestyle changes, such as healthy diet rich with fruits and vegetables and regular exercise, might decrease the risk of developing cancer in general.

## Secondary Prevention
Secondary prevention of lung cancer consists of smoking cessation and screening. Secondary chemoprevention focuses on blocking the development of lung cancer in individuals in whom a precancerous lesion has been detected.