Overview of Lung Cancer

Cancer Connect - Overview of Lung Cancer

Overview of Lung Cancer

Medically reviewed by C.H. Weaver M.D. Medical editor 8/2018

Lung cancer is the most common cancer in the world and is the leading cause of cancer death, with 160,000 deaths in the U.S. annually. While there are more than a dozen different kinds of lung cancer there are two main types; non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), which together account for over 90% of all lung cancers. Malignant mesothelioma is a rare cancer that develops in the tissues that comprise the lining of the lung. Non-small cell lung cancer accounts for approximately 75% of these cancers and consists of squamous cell, adenocarcinoma and large cell types. Small cell lung cancer represents 20-25% of all lung cancers and is also referred to as “oat cell cancer”

The following is an overview of the signs and symptoms of lung cancer, how its diagnosed, who's at risk and how it can be prevented. For treatment information readers can go directly

Lung cancer is characterized by the uncontrolled growth of abnormal cells in one or both of the lungs. The majority of lung cancers begin in the bronchial tubes that conduct air in and out of the lungs. Cancers of the lung are classified by how they appear under a microscope.

Precision cancer treatments have emerged and are improving the treatment of lung cancer. Precision cancer medicine utilizes molecular diagnostic and genomic testing, including DNA sequencing, to identify cancer-driving abnormalities in a cancer’s genome. Once a genetic abnormality is identified, a specific targeted therapy can be designed to attack a specific mutation or other cancer-related change in the DNA programming of the cancer cells. Precision cancer medicine uses targeted drugs and immunotherapies engineered to directly attack the cancer cells with specific abnormalities, leaving normal cells largely unharmed. As a result, patients with lung cancer now typically receive molecular testing that guides their physicians in determining which therapies are more likely to boost the chances of survival while limiting the potential for adverse effects.

Signs and Symptoms of Lung Cancer

The most common symptoms of lung cancer are a persistent cough, shortness of breath and blood in the sputum.

  • Persistent cough
  • Shortness of breath
  • Chest discomfort or pain
  • Trouble breathing
  • Wheezing
  • Blood in sputum (mucus coughed up from the lungs)
  • Hoarseness
  • Loss of appetite
  • Fatigue
  • Difficulty swallowing
  • Weigh loss
  • Loss of appetite

Risk factors for Lung Cancer

Anything that increases your chance of getting a disease is called a risk factor. Having a risk factor does not mean that you will get lung cancer and not having risk factors doesn’t mean that you will not get cancer, it simply means that you are at greater risk than normal to develop the cancer.

Smoking is the major risk factor for lung cancer

Smoking of cigarettes, cigars, or pipes, now or in the past is the most important risk factor for lung cancer. The earlier in life a person starts smoking, the more often a person smokes, and the more years a person smokes, the greater the risk of developing lung cancer.

Other Risk factors for lung cancer include the following:

  • Exposure to “secondhand” smoke (other individuals cigarette smoke)
  • Being exposed to radiation from
    • Previous radiation therapy to the breast or chest
    • Diagnostic imaging tests like CT scans
    • Atomic bomb radiation
  • Radon exposure in the home or workplace.
  • Exposure to asbestos, arsenic, soot or tar in the workplace

Older age is also a risk factor for most cancers. The chance of getting cancer increases as you get older.

Diagnosis & Tests for Lung Cancer

When lung cancer is diagnosed, the doctor must determine the type (small cell or non small cell), the presence of biomarkers, and the extent of spread or stage of the cancer in order to determine the best treatment. Lung cancer may grow locally in the lungs or spread (metastasize) to other more distant sites in the body, including the lymph nodes, bones, and the brain. Determining the presence of a lung cancer and the type of lung cancer requires a biopsy to examine tissues from the lung. A biopsy is the removal of a small piece of tissue for examination under a microscope and is obtained using one or more of the following procedures.

  • Bronchoscopy: During a bronchoscopy, a surgeon inserts a bronchoscope (thin, lighted tube) through the nose or mouth into the trachea (windpipe) and bronchi (air passages that lead to the lung). Through this tube, the surgeon can examine the inside of the trachea, bronchi and lung and collect cells or small tissue samples.
  • Fine Needle Aspiration: During this procedure, a surgeon inserts a needle through the chest into the cancer to remove a tissue sample for examination under the microscope.
  • Thoracentesis: During a thoracentesis, a surgeon uses a needle to remove a sample of the fluid that surrounds the lungs in order to check for the presence of cancer cells.
  • Thoracotomy: A thoracotomy is a major operation, which involves opening the chest in order to diagnose lung cancer.
  • Sputum Cytology: Sputum cytology is a procedure used to examine mucus that is coughed up from the lungs or breathing tubes. The mucus is examined under a microscope in order to detect cancer cells.

Staging of Lung Cancer

In addition to diagnosing the type of lung cancer doctors also need to determine the stage or the extent of the spread of the cancer. A cancer’s stage is a key factor in determining the best treatment. This requires a number of additional tests.

  • Computed Tomography (CT) Scan: A CT scan is a technique for imaging body tissues and organs, during which X-ray transmissions are converted to detailed images, using a computer to synthesize X-ray data. A CT scan is conducted with a large machine positioned outside the body that can rotate to capture detailed images of the organs and tissues inside the body. This method is more sensitive and precise than an X-ray.
  • Magnetic Resonance Imaging (MRI): MRI uses a magnetic field rather than X-rays, and can often distinguish more accurately between healthy and diseased tissue. MRI gives better pictures of tumors located near bone than CT, does not use radiation as CT does, and provides pictures from various angles that enable doctors to construct a three-dimensional image of the tumor.
  • Mediastinoscopy A mediastinoscopy is a procedure that can indicate whether the cancer has spread to the lymph nodes in the chest. During a mediastinoscopy, a surgeon inserts a mediastinoscope (lighted tube) through a small incision in the neck while a patient is under general anesthesia. This mediastinoscope allows the surgeon to examine the center of the chest (mediastinum) and nearby lymph nodes, as well as remove a tissue sample.
  • Positron emission tomography (PET): Positron emission tomography (PET) scanning has been used to improve the detection of cancer in lymph nodes. One characteristic of living tissue is the metabolism of sugar. Prior to a PET scan, a substance containing a type of sugar attached to a radioactive isotope (a molecule that spontaneously emits radiation) is injected into the patient’s vein. The cancer cells “take up” the sugar and attached isotope, which emits positively charged, low energy radiation (positrons). The positrons react with electrons in the cancer cells, which creates the production of gamma rays. The gamma rays are then detected by the PET machine, which transforms the information into a picture. If no gamma rays are detected in the scanned area, it is unlikely that the mass in question contains living cancer cells.
  • Bone Scan: A bone scan is used to determine whether cancer has spread to the bones. Prior to a bone scan, a surgeon injects a small amount of radioactive substance into a vein. This substance travels through the bloodstream and collects in areas of abnormal bone growth. An instrument called a scanner measures the radioactivity levels in these areas and records them on x-ray film.

Genomic or Biomarker Testing-Precision Cancer Medicine

The purpose of precision cancer medicine is to define the genomic alterations in a lung cancers DNA that are driving that specific cancer. Cancer used to be diagnosed solely by a visual microscopic examination of tumor tissue and all patients received the same chemotherapy. Precision cancer medicine utilizes molecular diagnostic & genomic testing, including DNA sequencing, to identify cancer-driving abnormalities in a cancer’s genome. Once a genetic abnormality is identified, a specific targeted therapy can be designed to attack a specific mutation or other cancer-related change in the DNA programming of the cancer cells. Precision cancer medicine uses targeted drugs and immunotherapies engineered to directly attack the cancer cells with specific abnormalities, leaving normal cells largely unharmed.

By testing an individual’s lung cancer for specific unique biomarkers doctors can offer the most personalized treatment approach utilizing precision medicines.

Lung Cancer Biomarkers

PD-1: PD-1 is a protein that inhibits certain types of immune responses, allowing cancer cells to evade an attack by certain immune cells. Drugs that block the PD-1 pathway enhance the ability of the immune system to fight cancer and are referred to as checkpoint inhibitors for their ability to help the immune system recognize and attack cancer. Overall two thirds of lung cancer patients have some expression of PD-1, and one third are “high expressers” meaning over 50% of the tested tumor expresses PD-1.(2,3)

Epidermal growth factor receptor (EGFR): The EGFR pathway is a normal biologic pathway found in healthy cells. It is involved in regular cellular division and growth. However, certain mutations within the EGFR gene can lead to an overactive EGFR pathway, leading to the development and/or spread of cancer. These cancers are referred to as EGFR-positive, and there are several FDA-approved medications to block the activity of EGFR and slow cancer growth for EGFR-positive cancers. EGFR mutations are most common in individuals who never smoked, woman, people of Asian ethnicity, and those with a type of lung cancer known as adenocarcinoma.(4,5)

ALK+ Lung Cancer: Approximately 5% of all NSCLC have an identified mutation referred to as the anaplastic lymphoma kinase (ALK) mutation. The ALK mutation is responsible for initiating and promoting cancer growth. Individuals with ALK+ lung cancer tend to be non-smokers or former light smokers; younger, and are a type of NSCLC referred to as adenocarcinoma (based upon the cells affected); and respond worse to standard chemotherapy regimens than patients who do not have the ALK mutation.(6)

ROS-1+ Lung Cancer: The ROS-1 mutation is an uncommon mutation found in only 1% of individuals with NSCLC. Research has indicated that the ROS-1 mutation plays a role in the development and progression of some lung cancers, and patient characteristics are similar to those who have ALK+ NSCLC.(7)

Screening & Prevention of Lung Cancer

Information about the prevention of cancer and the science of screening appropriate individuals at high-risk of developing cancer is gaining interest. Physicians and individuals alike recognize that the best “treatment” of cancer is preventing its occurrence in the first place or detecting it early when it may be most treatable.

The chance of an individual developing cancer depends on both genetic and non-genetic factors. A genetic factor is an inherited, unchangeable trait, while a non-genetic factor is a variable in a person’s environment, which can often be changed. Non-genetic factors may include smoking, diet, exercise, or exposure to other substances present in our surroundings. These non-genetic factors are often referred to as environmental factors. Some non-genetic factors play a role in facilitating the process of healthy cells turning cancerous (i.e. the correlation between smoking and lung cancer) while other cancers have no known environmental correlation but are known to have a genetic predisposition. A genetic predisposition means that a person may be at higher risk for a certain cancer if a family member has that type of cancer.

Heredity or Genetic Factors

While lung cancer has mainly been associated with environmental factors, there is emerging evidence that indicates that some individuals have a genetic predisposition for the disease. For example, individuals with chronic obstructive pulmonary disease appear to have an increased risk of developing lung cancer regardless of whether or not they smoke. Research is ongoing to further define the genetic factors associated with lung cancer.

Environmental or Non-Genetic Factors

Lung cancer is primarily associated with environmental factors, especially smoking. Several environmental agents have been associated with the development of lung cancer. Some are more easily avoidable than others.1

Cigarettes: There is a large body of research that indicates that individuals who smoke are at a significantly increased risk of developing lung cancer. Approximately 85% of the lung cancer cases diagnosed each year can be associated with smoking. Over time, carcinogens in cigarettes damage the cells in the lungs and eventually, these damaged cells may become cancerous. Several factors contribute to a smoker’s risk of developing lung cancer, such as the age at initiation of smoking, the number of years smoked, the depth of inhalation, and the number of cigarettes smoked daily.

Cigars and Pipes: Individuals who smoke cigars or pipes appear to be at an increased risk of developing lung cancer, although this risk appears lower than that of cigarette smokers. Again, the number of years smoked, the amount smoked and the depth of inhalation all play a role in whether or not lung cancer will develop. Researchers have speculated that the reason for the decreased risk among cigar and pipe smokers when compared with cigarette smokers may be that cigar and pipe smokers do not inhale as deeply as cigarette smokers because cigar smoke tends to be more irritating. Cigar smokers also tend to smoke less each day, as it takes about 1-2 hours to completely smoke a cigar, whereas it takes less than 10 minutes to smoke a cigarette.

Environmental Tobacco Smoke (ETS): Exposure to environmental tobacco smoke (also called secondhand smoke) is often referred to as involuntary or passive smoking. Prolonged exposure to ETS has been associated with an increased risk for developing lung cancer. Like smokers, nonsmokers who are exposed to ETS absorb nicotine and other carcinogens, however these carcinogens are less concentrated than if they were directly inhaled. Still, the carcinogens from ETS pose health risks for nonsmokers. Researchers have estimated that ETS is responsible for approximately 3,000 lung cancer deaths per year among nonsmokers in the U.S. In addition, children of smokers appear to have reduced lung function and more respiratory tract infections than children of nonsmokers.

Lung Diseases: Some lung diseases, including tuberculosis (TB), have been associated with an increased risk of developing lung cancer. Lung diseases leave scarred tissue on the lungs that appear to increase susceptibility to lung cancer.

Air Pollution: Although the relationship between lung cancer and air pollution has not been clearly defined, some research indicates that exposure to certain air pollutants may be associated with lung cancer. These air pollutants include by-products of fossil fuel combustion, exhaust from motor vehicles and diesel engines, and emissions from power plants and industrial centers.

Asbestos: Asbestos is the general name applied to a group of naturally occurring minerals that form fibers. These asbestos fibers have been used in a variety of applications such as textiles, cement, paper, wicks, ropes, floor and roofing tiles, water pipes, wallboard, fireproof clothing, gaskets and brake linings.

Asbestos fibers easily break into particles. When inhaled, these dust particles can lodge in the lungs and cause damage that leads to an increased risk of lung cancer. It is estimated that since the beginning of World War II, approximately 8 million people have been exposed to asbestos in the workplace. Approximately 5% of the lung cancer cases diagnosed each year are caused by asbestos.

Clinical studies have demonstrated that individuals who are exposed to large amounts of asbestos have a 5 times greater risk of developing lung cancer than individuals who have not been exposed. In addition, individuals who smoke and are exposed to asbestos have an even greater risk. Studies show that smokers who are exposed to asbestos are 90 times more likely to develop lung cancer than individuals who do not smoke and have not been exposed to asbestos.

Asbestos also increases the risk of developing mesothelioma, a rare type of lung cancer that develops in the lining of the lung. Mesothelioma can result from neighborhood or environmental exposure to asbestos, occupational exposure, and household contact with asbestos dust. The rates of mesothelioma peaked for individuals born around 1910 and have steadily declined over time. Currently, there are about 2,000 cases of mesothelioma each year. This is primarily an asbestos-related cancer; only a fraction of mesothelioma cases are unrelated to asbestos exposure. Individuals involved in shipbuilding during World War II have an increased risk of mesothelioma. In fact, several shipbuilding areas such as Virginia, England, Wales and Japan, have higher rates of mesothelioma. In addition, workers who are heavily exposed to asbestos bring the dust into their homes on their clothing, hair and skin, thus exposing their family members and placing them at a higher risk of developing mesothelioma. Smoking does not appear to increase the risk of developing mesothelioma.

Radon: Radon is a carcinogen that can cause damage to the lungs that may eventually lead to lung cancer. It is estimated that radon is responsible for about 10% of the lung cancer cases diagnosed each year. Individuals who smoke and are exposed to radon are at an even higher increased risk of developing lung cancer. Most of the cancer deaths associated with radon occur among smokers.

Radon is a naturally occurring, invisible radioactive gas. It is present in soil and rocks and can seep into homes and other buildings. In situations where ventilation is restricted, radon can accumulate in the atmosphere and lead to higher levels of exposure. Individuals who work in mines are often exposed to higher concentrations of radon than the general population. However, radon can also be present in many homes. Some geographic areas have higher concentrations of radon, but radon can also seep into homes in geographic areas that are not considered high risk. When ventilation is restricted in basements in order to conserve energy, radon can seep from the soil into the basement and accumulate in the poorly ventilated area.

Prevention of Lung Cancer

Cancer is largely a preventable illness. Two-thirds of cancer deaths in the U.S. can be linked to tobacco use, poor diet, obesity, and lack of exercise. All of these factors can be modified. Nevertheless, an awareness of the opportunity to prevent cancer through changes in lifestyle is still under-appreciated.

Research is ongoing to determine the causes of lung cancer and find ways to prevent it. Avoiding the environmental risk factors may help to prevent lung cancer. In particular, refraining from smoking is an important factor in the prevention of lung cancer.(8)

Radon: The only way to determine if a home has elevated radon levels is to perform a test. Homeowners can purchase kits designed to test the radon levels in their homes. Geographic location is not a good indicator of radon levels. Homes that are located in the same area often have different indoor radon levels. Several factors contribute to increased radon levels including soil composition under and around the house and ventilation conditions. In addition, barometric pressure and precipitation can cause radon levels to vary over time.

Because of the variances in radon levels, homeowners can utilize both short and long term tests to measure the radon levels in their homes. The tests are simple and inexpensive. Usually, a local or state radon official can assist homeowners in choosing the appropriate test.

If elevated radon levels are detected in a home, the homeowner will need to take steps to reduce the radon levels. Once a radon problem is addressed and corrected, the risk is permanently eliminated.

Asbestos: Nearly everyone has been exposed to asbestos at some point. Asbestos is widely used and small amounts may be found in a variety of products. In addition, the breakdown of asbestos products as well as natural deposits of the fiber can cause the release of asbestos particles into the environment.

Three agencies are responsible for regulating the use of asbestos products and the exposure caused to the general public. The Environmental Protection Agency (EPA) regulates asbestos in buildings, drinking water and the environment. The Consumer Product Safety Commission (CPSC) regulates asbestos in consumer products. The Food and Drug Administration (FDA) monitors asbestos contamination in food, drugs and cosmetics.

Still, individuals may be exposed to asbestos at work or in other environments. The Occupational Safety and Health Administration (OSHA) has issued regulations for employers regarding the treatment of asbestos exposure in the workplace. In addition, the Mine Safety and Health Administration (MSHA) regulates mine safety. Often, workers are provided with protective equipment and instructions regarding work practices and safety procedures. Individuals concerned about asbestos exposure at work may wish to discuss safety precautions with their employers or request information from OSHA. Individuals who are or have been exposed to asbestos should refrain from smoking.

Diet: Diet is a fertile area for immediate individual and societal intervention to decrease the risk of developing certain cancers. Numerous studies have provided a wealth of often-contradictory information about the detrimental and protective factors of different foods.

There is convincing evidence that excess body fat substantially increases the risk for many types of cancer. While much of the cancer-related nutrition information cautions against a high-fat diet, the real culprit may be an excess of calories. Studies indicate that there is little, if any, relationship between body fat and fat composition of the diet. These studies show that excessive caloric intake from both fats and carbohydrates lead to the same result of excess body fat. The ideal way to avoid excess body fat is to limit caloric intake and/or balance caloric intake with ample exercise.

It is still important, however, to limit fat intake, as evidence still supports a relationship between cancer and polyunsaturated, saturated and animal fats. Specifically, studies show that high consumption of red meat and dairy products can increase the risk of certain cancers. One strategy for positive dietary change is to replace red meat with chicken, fish, nuts and legumes.

High fruit and vegetable consumption has been associated with a reduced risk for developing at least 10 different cancers. This may be a result of potentially protective factors such as carotenoids, folic acid, vitamin C, flavonoids, phytoestrogens and isothiocyanates. These are often referred to as antioxidants.
There is strong evidence that moderate to high alcohol consumption also increases the risk of certain cancers. One reason for this relationship may be that alcohol interferes with the availability of folic acid. Alcohol in combination with tobacco creates an even greater risk of certain types of cancer.

Exercise: Higher levels of physical activity may reduce the incidence of some cancers. According to researchers at Harvard, if the entire population increased their level of physical activity by 30 minutes of brisk walking per day (or the equivalent energy expenditure in other activities), we would observe a 15% reduction in the incidence of colon cancer.

Screening and Early Detection of Lung Cancer

For many types of cancer, progress in the areas of cancer screening and treatment has offered promise for earlier detection and higher cure rates. The term screening refers to the regular use of certain examinations or tests in persons who do not have any symptoms of a cancer but are at high risk for that cancer.
Several key organizations now recommend screening for lung cancer with helical low-dose computed tomography (LDCT) for selected patients at high risk of developing the cancer.

These recommendations were largely based on results from The National Lung Screening Trial (NLST). The NLST enrolled current and former heavy smokers and screened them annually with either chest x-rays or low-dose spiral CT. People in the CT group were 20% less likely to die of lung cancer.

Low-dose CT scans are a special type of imaging scan that can identify smaller nodules than chest x-rays, making them a strong candidate for lung cancer screening. Although low-dose CT scans can detect lung cancer early, they also can have false-positive results, which means they may not be appropriate for standard use because false-positive results can lead to unnecessary invasive procedures that can have deadly complications. However, in high-risk populations—such as older individuals who are current or former smokers—the benefits of screening with low-dose CT scans appears to outweigh the harms.

The guidelines recommend that smokers and former smokers ages 55 to 74 who have smoked for 30 pack years or more and either continue to smoke or have quit within the past 15 years should undergo annual screening with low-dose CT scan.(9,10)

References

[1] American Cancer Society. Cancer Facts & Figures 2017.

[2] cancer.gov/types/lung/patient/non-small-cell-lung-treatment-pdq

[3] KEYTRUDA (pembrolizumab) demonstrates superior progression-free and overall survival compared to chemotherapy as first line treatment in patients with advanced non-small cell lung cancer. [Press release.] http://www.mercknewsroom.com/news-release/oncology-newsroom/mercks-keytruda%C2%A0pembrolizumab-demonstrates-superior-progression-free- Accessed June 21, 2016.

[4] Borghaei H, Paz-Ares L, Horn L, et al. Nivolumab versus Docetaxel in Advanced Nonsquamous Non–Small-Cell Lung Cancer. New England Journal of Medicine. 2015; 373:1627-1639.

[5] OSI Pharmaceuticals. FDA Approves Tarceva as a Maintenance Therapy for Advanced Non-small Cell Lung Cancer. Available at: http://investor.osip.com/releasedetail.cfm?ReleaseID=460783. Accessed April 19, 2010.

[6] Zhou C, Wu Y-L, Chen G et al. Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): A multicentre, open-label, randomized, phase 3 study. Lancet Oncology. Early online publication July 22, 2011.8. Shaw AT, Kim DW, Mehra R, et al: Ceritinib in ALK-rearranged non–small-cell lung cancer. New England Journal of Medicine. 2014; 370: 1189-1197.

[7] United States Food and Drug Administration (FDA). FDA expands use of Xalkori to treat rare form of advanced non-small cell lung cancer. Available at: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm490329.htm. Accessed March 11, 2016.

[8] cancer.gov/types/lung/patient/lung-prevention-pdq#section/_12

[9] The National Lung Screening Trial Research Team. Reduced lung-cancer mortality with low-dose computed tomographic screening. New England Journal of Medicine. 2011;365:395-409.

[10] NCCN press release. NCCN announces new addition to library of guidelines: NCCN guidelines for lung cancer screening. November 9, 2011.

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