lung cancer

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Malignant tumour of the lung. Four major types (squamous-cell carcinoma, adenocarcinoma, large-cell carcinoma, and small-cell carcinoma) have roughly equal prevalence. Most cases are due to long-term cigarette smoking. Heavy smoking and starting smoking earlier in life increase the risk. Passive inhalation ("secondhand smoke") is linked to lung cancer in nonsmokers. Other risk factors include exposure to radon or asbestos. Symptoms, including coughing (sometimes with blood), chest pain, and shortness of breath, seldom appear until lung cancer is advanced, when treatment with surgery, chemotherapy, and radiation or some combination of the three is less effective. Most patients die within a year of diagnosis.

For more information on lung cancer, visit Britannica.com.

Definition

Lung cancer is a disease in which the cells of the lung tissues grow uncontrollably and form tumors. It is the leading cause of death from cancer among both men and women in the United States. The American Cancer Society (ACS) estimated that in 1998, at least 172,000 new cases of lung cancer were diagnosed, and that lung cancer accounted for 28% of all cancer deaths, or approximately 160,000 people. In 2002, the ACS reported that more than 150,000 Americans die from the disease every year. Only 15 percent of people with lung cancer will live five years.

Description

Types of Lung Cancer

There are two kinds of lung cancers, primary and secondary. Primary lung cancer (also called adenocarcinoma) starts in the lung itself. Primary lung cancer is divided into small cell lung cancer and non-small cell lung cancer, depending on how the cells look under the microscope. Secondary lung cancer is cancer that starts somewhere else in the body (for example, the breast or colon) and spreads to the lungs.

Small cell cancer was formerly called oat cell cancer, because the cells resemble oats in their shape. About one-fourth of all lung cancers are small cell cancers. This type is a very aggressive cancer and spreads to other organs within a short time. It generally is found in people who are heavy smokers. Non-small cell cancers account for the remaining 75% of lung cancers. They can be further subdivided into three categories.

Incidence of Lung Cancer

Lung cancer is rare among young adults. It usually is found in people who are 50 years of age or older, with an average age at diagnosis of 60. While the incidence of the disease is decreasing among Caucasian men, it is steadily rising among African-American men, and among both Caucasian and African-American women. This change probably is due to the increase in the number of smokers in these groups. In 1987, lung cancer replaced breast cancer as the number one cancer killer among women.

Causes & Symptoms

Causes

SMOKING. Tobacco smoking is the leading cause of lung cancer. Ninety percent of lung cancers can be prevented by completely giving up tobacco. Smoking marijuana cigarettes is considered yet another risk factor for cancer of the lung. These cigarettes have a higher tar content than tobacco cigarettes. In addition, they are inhaled very deeply; as a result, the smoke is held in the lungs for a longer period of time.

EXPOSURE TO ASBESTOS AND TOXIC CHEMICALS. Repeated exposure to asbestos fibers, either at home or in the workplace, also is considered a risk factor for lung cancer. Studies show that compared to the general population, asbestos workers are seven times more likely to die from lung cancer. Asbestos workers who smoke increase their risk of developing lung cancer by 50-100 times. Besides asbestos, mining industry workers who are exposed to coal products or radioactive substances, such as uranium, and workers exposed to chemicals, such as arsenic, vinyl chloride, mustard gas, and other carcinogens, also have a higher than average risk of contracting lung cancer.

ENVIRONMENTAL CONTAMINATION. High levels of a radioactive gas (radon) that cannot be seen or smelled pose a risk for lung cancer. This gas is produced by the breakdown of uranium, and does not present any problem outdoors. In the basements of some houses that are built over soil containing natural uranium deposits, however, radon may accumulate and reach dangerous levels. Having one's house inspected for the presence of radon gas when buying or renting is a good idea. Other forms of environmental pollution (e.g., auto exhaust fumes) also may slightly increase the risk of lung cancer.

In 2002, a study in the Journal of the American Medical Association (JAMA) linked for the first time long-term exposure to fine-particle air pollution to lung cancer deaths. The risk of death from lung cancer increased substantially for people living in the most heavily polluted metropolitan areas. Tiny particles from the air pollution emitted from coal-fired power plants, factories and diesel vehicles are to blame.

CHRONIC LUNG INFLAMMATION AND SCARRING. Inflammation and scar tissue sometimes are produced in the lung by diseases, such as silicosis and berylliosis, which are caused by inhalation of certain minerals, tuberculosis, and certain types of pneumonia. This scarring may increase the risk of developing lung cancer.

FAMILY HISTORY. Although the exact cause of lung cancer is not known, people with a family history of lung cancer appear to have a slightly higher risk of contracting the disease. In 2003, researchers were continuing work aimed at learning why some smokers were more susceptible to lung cancer than others. They discovered a type of DNA repair characteristic apparent in smokers who were less likely to get lung cancer. Continued work along these lines could lead to possible screening for DNA that makes some people at higher risk for lung cancer.

Symptoms

Lung cancers tend to spread very early, and only 15% are detected in their early stages. The chances of early detection, however, can be improved by seeking medical care at once if any of the following symptoms appear:

• a cough that does not go away
• chest pain
• shortness of breath
• persistent hoarseness
• swelling of the neck and face
• significant weight loss that is not due to dieting or vigorous exercise
• fatigue and loss of appetite
• bloody or brown-colored spit or phlegm (sputum)
• unexplained fever
• recurrent lung infections, such as bronchitis or pneumonia

However, these symptoms may be caused by diseases other than lung cancer. It is vital, however, to consult a doctor to rule out the possibility that they are the first symptoms of lung cancer.

If the lung cancer has spread to other organs, the patient may have other symptoms, such as headaches, bone fractures, pain, bleeding, or blood clots. Early detection and treatment can increase the chances of a cure for some patients. For others, it can at least prolong life.

Diagnosis

Physical Examination and Initial Tests

If the patient's doctor suspects lung cancer, he or she will take a detailed medical history to check all the symptoms and assess the risk factors. The assessment of the patient's medical history will be followed by a complete physical examination. The doctor will examine the patient's throat to rule out other possible causes of hoarseness or coughing, and listen to the patient's breathing and the sounds made when the patient's chest and upper back are tapped (percussed). The physical examination, however, is not conclusive.

If the doctor has reason to suspect lung cancer—particularly if the patient has a history of heavy smoking or occupational exposure to substances that are known to irritate the lungs—he or she may order a chest x ray to see if there are any masses in the lungs. Special imaging techniques, such as CT scans or MRIs, may provide more precise information about the possibility, size, shape, and location of any tumors.

A technology called spiral CT, which rotates allowing for images of the chest from all angles, can detect lung cancer when tumors are smaller than a dime. A report in 2002 said spiral CT technology could help doctors screen the population for lung cancer, but the idea of screening remains controversial. Until clinicians and insurers receive more proof the scans produce fewer false positive (a seemingly positive result or nodule that turns out not to be a cancerous mass), widespread screening won't occur. And in 2002, the cost of a spiral CT chest study to screen for lung cancer averaged about $400. However, researchers were recommending further trials to determine the effectiveness of the screening tool for future use.

In 2003, a new radiology technique emerged for staging lung cancer. By combining positron emission tomography (PET) with CT, or PET-CT, physicians could more accurately see the details of the tumorís progression (or regression after treatment) and to diagnose a lung tumor better.

Sputum Analysis

Sputum analysis involves microscopic examination of the cells that are either coughed up from the lungs, or are collected through a special instrument called a bronchoscope. Sputum analyses can diagnose at least 30% of lung cancers, some of which do not show up even on chest x rays. In addition, the test can help detect cancer in its very early stages, before it spreads to other regions. The sputum test does not, however, provide any information about the location of the tumor and must be followed by other tests, such as bronchoscopy, where machines can detect cancerous cells without the need to open the chest.

Lung Biopsy

Lung biopsy is the most definitive diagnostic tool for cancer. It can be performed in several different ways. The doctor can perform a bronchoscopy, which involves the insertion of a slender, lighted tube, called a bronchoscope, down the patient's throat and into the lungs. In addition to viewing the passageways of the lungs, the doctor can use the bronchoscope to obtain samples of the lung tissue. In another procedure known as a needle biopsy, the location of the tumor first is identified using a CT scan or MRI. The doctor then inserts a needle through the chest wall and collects a sample of tissue from the tumor. In the third procedure, known as surgical biopsy, the chest wall is opened up and a part of the tumor, or all of it, is removed. A doctor who specializes in the study of diseased tissue (a pathologist) examines the tumor samples to identify the cancer's type and stage.

Treatment

Alternative therapies should complement conventional treatment, not replace it. Before participating in any alternative treatment programs, patients should consult their doctors concerning the appropriateness and the role of such programs in overall cancer treatment plans. Appropriate alternative treatments can help prolong a patient's life or at least improve quality of life, prevent recurrence of tumors, or prolong the remission period and reduce adverse reactions to chemotherapy and radiation.

The use of beta-carotene and vitamin A supplements in lung cancer patients is controversial. Vitamin A and beta-carotene were advocated as antioxidants with lung-protective effects that may decrease the risk of lung cancer. However, recent studies suggest that betacarotene supplements may have no demonstrated effect in smokers and no effects on nonsmokers. Therefore, use of beta-carotene supplement in lung cancer patients or as preventive measure in smokers is not recommended at the present time. However, researchers believe that patients benefit from nature's source of beta-carotene and vitamin A. Beta-carotene in food carries all the benefits, yet does not have the harmful effects controversial high-dose supplements may carry.

The effectiveness of many of the anticancer drugs used to treat lung cancer can be reduced when patients take megadoses of antioxidants. These antioxidants in patients not undergoing chemotherapy can be helpful in protecting the body against cancer. However, taken during chemotherapy, these antioxidants protect the cancer cells from being killed by chemotherapy drugs. Because high-dose supplementation of antioxidants can interfere with conventional chemotherapy treatment, patients should check with their physicians concerning dosage and recommended daily allowance (RDA) during chemotherapy or radiation therapy.

Dietary Guidelines

The following dietary changes may help improve a patient's quality of life, as well as boost the immune function to better fight the disease. They also may help prevent lung cancer.

• Avoiding fatty and spicy foods. A high-fat diet may be associated with increased risk of lung cancer. Also, lung cancer patients may have a hard time digesting heavy foods.
• Eating new and exciting foods. Tasty foods stimulate appetite so that patients can eat more and have the energy to fight cancer.
• Increasing consumption of fresh fruits and vegetables. They are nature's best sources of antioxidants, as well as vitamins and minerals. Especially helpful are the yellow and orange fruits (orange, cantaloupes) and dark green vegetables. They contain high amounts of vitamin A and carotene.
• Eating more broccoli sprouts. These young sprouts are a good source of sulforaphane, a lung cancer fighting substance.
• Eating multiple (5-6) meals per day. Small meals are easier to digest.
• Establishing a regular eating time and not eating around bedtime.
• Avoiding foods containing preservatives or artificial coloring.
• Monitoring weight and intake of adequate calories and protein.

In 2002, a report in Family Practice News said that daily consumption of a soup used in Traditional Chinese Medicine helped slow the progression of non-small cell lung cancer for patients with advanced stages of the disease. The soup consisted of herbs and vegetables containing natural ingredients that boost immunity and help fight tumors. Patients should check with their doctors and with a licensed Traditional Chine Medicine specialist for more information. The soup does not prevent or reverse the disease, but helped prolong survival for a percentage of patients in a clinical study.

Nutritional Supplements

A naturopath may recommend some of the following nutritional supplements to boost the patient's immune function and help fight tumor progression:

• Vitamins and minerals. Vitamins that are considered particularly beneficial to cancer patients include B-complex vitamins, especially vitamins B₆, C, D, E, and K. Most important minerals are calcium, chromium, copper, iodine, molybdenum, germanium, selenium, tellurium, and zinc. Many of these vitamins and minerals are strong antioxidants or cofactors for antioxidant enzymes. However, patients should not take mega doses of these supplements without first consulting their doctors. Significant adverse or toxic effects may occur at high dosages, which is especially true for the minerals.
• Other nutritional supplements may help fight cancer and support the body. They include essential fatty acids (fish or flaxseed oil), flavonoids, pancreatic enzymes (to help digest foods), hormones such as DHEA, melatonin, or phytoestrogens.

Traditional Chinese Medicine

Conventional treatment for leukemia is associated with significant side effects. These adverse effects (such as nausea, vomiting, and fatigue) can be reduced with Chinese herbal preparations. Patients should consult an experienced herbalist who will prescribe remedies to treat specific symptoms that are caused by conventional cancer treatments.

Juice Therapy

Juice therapy may be helpful for patients with cancer. Patients should mix one part of pure juice with one part of water before drinking.

Homeopathy

There is conflicting evidence regarding the effectiveness of homeopathy in cancer treatment. Because cancer chemotherapy may suppress the body's response to homeopathic treatment, homeopathy may not be effective during chemotherapy. Therefore, patients should wait until after chemotherapy to try this relatively safe alternative treatment.

Acupuncture

Acupunture is the use of needles on the body to stimulate or direct the meridians (channels) of energy flow in the body. Acupuncture has not been shown to have any anticancer effects. However, it is an effective treatment for nausea, and other common side effects of chemotherapy and radiation.

Other Treatments

Other alternative treatments include stress reduction, meditation, yoga, t'ai chi, and the use of guided imagery A new report in 2003 showed early results for bee venomís possible antitumor effects on lung cancer. However, further, research was needed.

Allopathic Treatment

Treatment for lung cancer depends on the type of cancer, its location, and its stage. Treating the cancer early is key. In 2002, researchers announced the discovery of a chromosomal region that shows the earliest genetic change in the development of lung cancer. Eventually, this discovery could lead to earlier detection, diagnosis, prevention, and treatment of lung cancer. The most commonly used modes of treatment are surgery, radiation therapy, and chemotherapy.

Surgery

Surgery is not usually an option for small cell lung cancers, because they have likely spread beyond the lung by the time they are diagnosed. Because non-small cell lung cancers are less aggressive, however, surgery can be used to treat them. The surgeon will decide on the type of surgery, depending on how much of the lung is affected. Surgery may be the primary method of treatment, or radiation therapy and/or chemotherapy may be used to shrink the tumor before surgery is attempted.

There are three different types of surgical operations:

• Wedge resection. This procedure involves removing a small part of the lung.
• Lobectomy. A lobectomy is the removal of one lobe of the lung. If the cancer is limited to one part of the lung, the surgeon will perform a lobectomy.
• Pneumonectomy. A pneumonectomy is the removal of an entire lung. If the surgeon feels that removal of the entire lung is the best option for curing the cancer, a pneumonectomy will be performed.

The pain that follows surgery can be relieved by medications. A more serious side effect of surgery is the patient's increased vulnerability to bacterial and viral infections. Antibiotics, antiviral medications, and vaccines are often needed.

Radiation Therapy

Radiation therapy involves the use of high-energy rays to kill cancer cells. It is used either by itself or in combination with surgery or chemotherapy. There are two types of radiation therapy treatments: external beam radiation therapy and internal (or interstitial) radiotherapy. In external radiation therapy, the radiation is delivered from a machine positioned outside the body. Internal radiation therapy uses a small pellet of radioactive materials placed inside the body in the area of the cancer.

Radiation therapy may produce such side effects as tiredness, skin rashes, upset stomach, and diarrhea. Dry or sore throats, difficulty in swallowing, and loss of hair in the treated area are all minor side effects of radiation. These may disappear either during the course of the treatment or after the treatment is over. The side effects should be discussed with the doctor.

Chemotherapy

Chemotherapy uses anticancer medications that are either given intravenously or taken by mouth (orally). These drugs enter the bloodstream and travel to all parts of the body, killing cancer cells that have spread to different organs. Chemotherapy is used as the primary treatment for cancers that have spread beyond the lung and cannot be removed by surgery. It also can be used in addition to surgery or radiation therapy.

Chemotherapy is tailored to each patient's needs. Most patients are given a combination of several different drugs. Besides killing the cancer cells, these drugs also harm normal cells. Hence, the dose has to be carefully adjusted to minimize damage to normal cells. Chemotherapy often has severe side effects, including nausea, vomiting, hair loss, anemia, weakening of the immune system, and sometimes infertility. Most of these side effects end when the treatment is over. Other medications can be given to lessen the unpleasant side effects of chemotherapy.

Expected Results

If the lung cancer is detected before it has had a chance to spread to other organs, and if it is treated appropriately, at least 49% of patients can survive five years or longer after the initial diagnosis. Only 15% of lung cancers, however, are found at this early stage.

Due to improvements in surgical technique and the development of new approaches to treatment, the one-year survival rate for lung cancer has improved considerably. As of 1998, approximately 40% of patients survive for at least a year after diagnosis, as opposed to 30% that survived 20 years ago. In 2003, 14% of people diagnosed with lung cancer were reported to be long-term survivors.

Prevention

The best way to prevent lung cancer is to not smoke or to quit smoking if one has already started. Secondhand smoke from other people's tobacco also should be avoided when possible. In 2002, a report on the impact of cigarette smoking said that in California, decreases in smoking among residents had resulted in reduced lung cancer death rates.

Appropriate precautions should be taken when working with cancer-causing substances (carcinogens). Monitoring the diet and eating well-balanced meals that consist of whole foods, vegetables, and fruits; eliminating toxins, exercising routinely, and weight reduction; testing houses for the presence of radon gas, and removing asbestos from buildings also are useful preventive strategies.

Resources

Books

Dollinger, Malin, Ernest H. Rosenbaum, and Greg Cable. Everyone's Guide to Cancer Therapy. Kansas City, MO: Somerville House Books Limited, 1994.

Labriola, Dan. Complementary Cancer Therapies: Combining Traditional and Alternative Approaches for the Best Possible Outcome. Roseville, CA: Prima Health, 2000.

"Lung Cancer." In Reader's Digest Guide to Medical Cures and Treatments. Canada: The Reader's Digest Association, Inc., 1996.

Morra, Marion E., and Eve Potts. Choices. New York: Avon Books, 1994.

"Pulmonary Disorders: Tumors of the Lung." In The Merck Manual of Diagnosis and Therapy, edited by Robert Berkow, et al. Rahway, NJ: Merck Research Laboratories, 1992.

Periodicals

"Annual Smoking-Attributable Mortality, Years of Potential Life Lost, and Economic Cost - United States, 1995-1999. (From the Centers for Disease Control and Prevention)." JAMA, Journal of the American Medical Association (May 8, 2002):2355-2362.

"Bee Venom Inhibits COX and PGE-2, Inducing Apoptosis of Lung Cancer Cells." Immunotherapy Weekly (July 23, 2003):11.

"It Is Important to Attend to Physical, Emotional Needs of Lung Cancer Survivors." Mental Health Weekly Digest (August 11, 2003):15.

"New Technology Can Find Tumors Earlier." Cancer Weekly (June 25, 2002):15.

"Researchers Identify Tumor Suppressor Genes." Cancer Weekly (May 28, 2002):6.

"Risk from Particulates." Environment (May 2002):5.

Ryanna, K. "Integrated PET-CT Improves Accuracy in Staging NSCLC Compared with PET and CT Alone." Thorax (September 2003):789.

Seppa N. "Enzyme May Reveal Cancer Susceptibility." Science News (September 13, 2003):164.

Walsh, Nancy. "A Bowl of Chinese Vegetables a Day May Keep Tumors Away (Lung Cancer Pilot Study)." Family Practice News (May 1, 2002):21.

Organizations

American Cancer Society. 1599 Clifton Road, N.E., Atlanta, GA 30329. (800)227-2345.

American Lung Association. 1740 Broadway, New York, NY 10019-4374. (800) 586-4872.

Cancer Research Institute. 681 Fifth Avenue, New York, NY 10022. (800) 992-2623.

National Cancer Institute (National Institutes of Health). 9000 Rockville Pike, Bethesda, MD 20892. (800) 422-6237.

Other

"Beta Carotene and Vitamin A Halted in Lung Cancer Prevention Trial." Medical Sciences Bulletin.http://pharminfo.com.

Rosenberg, Z'ev. "Treating the Undesirable Effect of Radiation and Chemotherapy with Chinese Medicine." Oriental Chinese Journal.http://www.healthypeople.com.

[Article by: Mai Tran; Teresa G. Odle]

Lung cancer is a malignant disease in which lung cells become abnormal, characterized by uncontrollable, unlimited growth. These cells can then invade nearby normal tissue and destroy organ structure, a process called "invasion." Lung cancer cells can also break down lung tissue structure and enter the bloodstream or lymphatic system and thus spreads to distant organs in other parts of the body, a process called metastasis. Clinically, lung cancer can be classified into two groups according to its cell types under microscopy: non-small cell lung cancer and small cell lung cancer. Non-small cell lung cancer includes cancers of three cell types: squamous cell carcinoma, adenocarcinoma, and large cell carcinoma. Small cell lung cancer, also called oat cell cancer, is a less common cancer that grows faster, and is more likely to spread to other parts of the body than non-small cell lung cancer.

Lung cancer is a highly lethal disease in the United States and worldwide. According to Parkin et al. (1999), lung cancer was the most frequent cancer in 1990, worldwide, with 1.04 million new cases (771,800 in men and 265,100 in women). It is the most common cancer in men and the fifth most frequent cancer in women. Lung cancer is the leading cause of cancer deaths worldwide, with a total of 921,000 deaths per year (692,600 in men and 228,400 in women) in 1990. In the United States, it was estimated that 169,500 new lung cancer patients (90,700 men and 78,800 women) would be diagnosed and 157,400 (90,100 men and 67,300 women) would die of lung cancer in 2001. The five-year survival rate of lung cancer is 13.7 percent in the United States, 7.8 percent in developing countries, 7 percent in Eastern Europe, 7.9 percent in China, and 6.7 percent in India.

The changes (increase or decrease) of lung cancer incidence corresponds to the alterations of prevalence of smoking in the population twenty to thirty years earlier, representing a latent period between tobacco exposure and the occurrence of lung cancer. A significant decrease in the incidence of lung and bronchus cancer in males in North America started in the late 1980s. Between 1990 and 1996 there was a 2.6 percent decline in incidence per year. Incidence rates of lung and bronchus cancer in females are stabilizing in the United States. Although the death rate from lung cancer in males is decreasing, it is increasing among females, and it has now exceeded the breast cancer death rate among females.

Tobacco smoking is a major cause of lung cancer. Over 4,000 chemical compounds have been identified in the tobacco leaf. Carcinogens in tobacco smoke can damage the cells in the lungs, which may lead to the development of lung cancer. More than fifty chemical compounds in tobacco smoke have been recognized as known or probable human carcinogens, some of which may be formed during combustion (or smoking) and some which may exist naturally in tobacco. Several groups of carcinogens in tobacco smoke are related to lung cancer, including polycyclic aromatic hydrocarbons (PAHs), aromatic amines, benzene, hydrazine, and vinyl chloride. Smoking results in damage to the bronchial and lung epithelium, which leads to lung cell proliferation and finally to lung cancer. Animal studies confirm the carcinogenic potential of tobacco smoke in tissues having smoke contact: in these studies smoke exposure leads to laryngeal tumors and pulmonary adenomas. In humans, cigarette smokers have increased levels of tobacco carcinogen DNA adducts in the lung and bronchus when compared with nonsmokers.

A very strong association between cigarette smoking and lung cancer has been consistently observed in studies done since the early 1950s. These studies have shown that cigarette smoking precedes lung cancer occurrence. It has been estimated that cigarette smokers have a ten-fold higher risk of lung cancer, in comparison with nonsmokers. With the increased number of cigarettes smoked per day, the risk is increased—heavy smokers are at greater risk of lung cancer than moderate smokers; and moderate smokers are at higher risk than light smokers and nonsmokers. The risk for individuals who smoke two or more packs per day is about twenty times that of nonsmokers, and longer smoking duration has a stronger effect on the risk of lung cancer. Beginning to smoke at an early age is also related to an increased risk, and the lung cancer risk declines with an increased duration of cessation. The percentage of reduction in risk after quitting smoking depends on the duration of exposure to smoking. The observed relationship between cigarette smoking and the risk of lung cancer is consistent with different study designs and in studies of different populations all over the world. Over eighty-five percent of deaths from lung cancer can be attributed to cigarette smoking. It is estimated that tobacco smoking accounts for over ninety percent of male lung cancer deaths and seventy-nine percent of female lung cancer deaths in the United States.

Smoking of other tobacco products, such as cigar and pipe smoking, is also associated with an increased risk of lung cancer. Like cigarette smoking, the risk of lung cancer is increased with the frequency and years of cigar and pipe smoking. Environmental tobacco smoke (ETS), also known as secondhand smoke, increases the risk of lung cancer among nonsmokers. It is estimated that ETS may lead to 3,000 new cases of lung cancer per year in nonsmokers in the United States. Other risk factors for lung cancer include race, occupational exposures (e.g., arsenic, asbestos, chromium, mustard gas, PAHs), residential radon exposure, radiation, air pollution, and nutritional factors. The host susceptibility factors for lung cancer include inheritance of different polymorphic genotypes that may interact with tobacco smoke in determining the risk of lung cancer.

Smoking cessation or lifelong abstinence from smoking offer the best opportunities to reduce lung cancer incidence and death rates. Reducing the prevalence of smoking will lead to a dramatic decrease in the incidence of lung cancer in the general population. According to the Centers for Disease Control and Prevention (CDC), cigarette smoking is the single most preventable cause of premature death in the United States. More than 400,000 people die from causes attributable to cigarette smoking each year, including 276,000 men and 142,000 women. The promotion of smoking cessation is the most cost-effective tool against lung and other smoking-related cancers and diseases.

Control of other risk factors, such as workplace exposures associated with the increased risk of lung cancer, environmental tobacco smoke, and radon exposure in residences, may also lead to a reduced risk of lung cancer. Sputum cytology and chest radiographs are not recommended for lung cancer screening because no favorable impact of the screening on lung cancer mortality has been demonstrated. Recent developments have pointed out that the molecular genetic alterations associated with progression toward lung cancer, such as p53 mutations in sputum samples, may help to identify high-risk individuals for early detection and chemoprevention.

(SEE ALSO: Cancer; Causes of Death; Chronic Illness; Environmental Tobacco Smoke; Noncommunicable Disease Control; Smoking Behavior; Smoking Cessation; Women's Health)

Bibliography

Baron, J. A., and Rohan, T. (1997). "Tobacco." In Cancer Epidemiology and Prevention, ed. D. Schottenfeld. New York: Oxford University Press.

Centers for Disease Control and Prevention (1993). "Smoking-Attributable Mortality and Years of Potential Life Lost—United States, 1990." Morbidity and Mortality Weekly Report 42(33):645–648.

Greenlee, R. T.; Hill-Harmon, M. B.; Murray, T.; and Thun, M. (2001). "Cancer Statistics, 2001." CA: A Cancer Journal for Clinicians 51:15–36.

International Agency for Research on Cancer (1986). Evaluation of the Carcinogenic Risk of Chemicals to Humans: Tobacco Smoking. IARC Monographs, Volume 38. Lyon, France: World Health Organization.

National Cancer Institute (1999). Health Effects of Exposure to Environmental Tobacco Smoking. The Reportof the California Environmental Protection Agency. Smoking and Tobacco Control Monograph No. 10. Bethesda, MD: National Cancer Institute.

Parkin, D. M.; Pisani, P.; and Ferlay, J. (1999). "Estimates of the Worldwide Incidence of 25 Major Cancers in 1990." International Journal of Cancer 80: 827–841.

Pisani, P.; Parkin, D. M.; Bray F.; and Ferlay, J. (1999). "Estimates of the Worldwide Mortality from 25 Cancers in 1990." International Journal of Cancer 83:18–29.

Samet, J. M. (1995). "Lung Cancer." In Cancer Prevention and Control, eds. P. Greenwald, B. S. Kramer, and D. L. Weed. New York: Marcel Dekker.

— ZUO-FENG ZHANG

Lung cancer
Classification and external resources
Cross section of a human lung. The white area in the upper lobe is cancer; the black areas are discoloration due to smoking.
ICD-10	C33.-C34.
ICD-9	162
DiseasesDB	7616
MedlinePlus	007194
eMedicine	med/1333 med/1336 emerg/335 radio/807 radio/405 radio/406
MeSH	D002283

Lung cancer is a disease of uncontrolled cell growth in tissues of the lung. This growth may lead to metastasis, which is the invasion of adjacent tissue and infiltration beyond the lungs. The vast majority of primary lung cancers are carcinomas of the lung, derived from epithelial cells. Lung cancer, the most common cause of cancer-related death in men and also the most common in women, is responsible for 1.3 million deaths worldwide annually.^[1] The most common symptoms are shortness of breath, coughing (including coughing up blood), and weight loss.^[2]

The main types of lung cancer are small cell lung carcinoma and non-small cell lung carcinoma. This distinction is important, because the treatment varies; non-small cell lung carcinoma (NSCLC) is sometimes treated with surgery, while small cell lung carcinoma (SCLC) usually responds better to chemotherapy and radiation.^[3] The most common cause of lung cancer is long-term exposure to tobacco smoke.^[4] The occurrence of lung cancer in nonsmokers, who account for as many as 15% of cases ^[5], is often attributed to a combination of genetic factors,^[6][7] radon gas,^[8] asbestos,^[9] and air pollution,^[10][11][12] including secondhand smoke.^[13][14]

Lung cancer may be seen on chest radiograph and computed tomography (CT scan). The diagnosis is confirmed with a biopsy. This is usually performed via bronchoscopy or CT-guided biopsy. Treatment and prognosis depend upon the histological type of cancer, the stage (degree of spread), and the patient's performance status. Possible treatments include surgery, chemotherapy, and radiotherapy. With treatment, the five-year survival rate is 14%.^[2]

Contents 1 Classification 1.1 Non-small cell lung carcinoma (NSCLC) 1.2 Small cell lung carcinoma (SCLC) 1.3 Others 1.4 Secondary cancers 1.5 Staging 2 Signs and symptoms 3 Causes 3.1 Smoking 3.2 Radon gas 3.3 Asbestos 3.4 Viruses 4 Pathogenesis 5 Diagnosis 6 Prevention 7 Screening 8 Treatment 8.1 Surgery 8.2 Chemotherapy 8.2.1 Adjuvant chemotherapy for NSCLC 8.3 Radiotherapy 8.4 Interventional radiology 8.5 Targeted therapy 9 Prognosis 10 Epidemiology 11 History 12 Gallery 13 See also 14 References 15 External links

Classification

The vast majority of lung cancers are carcinomas—malignancies that arise from epithelial cells. There are two main types of lung carcinoma, categorized by the size and appearance of the malignant cells seen by a histopathologist under a microscope: non-small cell (80.4%) and small-cell (16.8%) lung carcinoma.^[15] This classification, based on histological criteria, has important implications for clinical management and prognosis of the disease.

Frequency of histological types of lung cancer^[15]

Histological type	Frequency (%)
Non-small cell lung carcinoma	80.4
Small cell lung carcinoma	16.8
Carcinoid[16]	0.8
Sarcoma[17]	0.1
Unspecified lung cancer	1.9

Non-small cell lung carcinoma (NSCLC)

The non-small cell lung carcinomas are grouped together because their prognosis and management are similar. There are three main sub-types: squamous cell lung carcinoma, adenocarcinoma, and large cell lung carcinoma.

Sub-types of non-small cell lung cancer in
smokers and never-smokers^[18]

Histological sub-type		Frequency of non-small cell lung cancers (%)
		Smokers	Never-smokers
Squamous cell lung carcinoma		42	33
Adenocarcinoma	Adenocarcinoma (not otherwise specified)	39	35
	Bronchioloalveolar carcinoma	4	10
Carcinoid		7	16
Other		8	6

Accounting for 25% of lung cancers,^[19] squamous cell lung carcinoma usually starts near a central bronchus. A hollow cavity and associated necrosis are commonly found at the center of the tumor. Well-differentiated squamous cell lung cancers often grow more slowly than other cancer types.^[3]

Adenocarcinoma accounts for 40% of lung cancers.^[19] It usually originates in peripheral lung tissue. Most cases of adenocarcinoma are associated with smoking; however, among people who have never smoked ("never-smokers"), adenocarcinoma is the most common form of lung cancer.^[20] A subtype of adenocarcinoma, the bronchioloalveolar carcinoma, is more common in female never-smokers, and may have different responses to treatment.^[21]

Small cell lung carcinoma (SCLC)

Small cell lung carcinoma (microscopic view of a core needle biopsy).

Small cell lung carcinoma (SCLC, also called "oat cell carcinoma") is less common. It tends to arise in the larger airways (primary and secondary bronchi) and grows rapidly, becoming quite large.^[22] The "oat" cell contains dense neurosecretory granules (vesicles containing neuroendocrine hormones), which give this an endocrine/paraneoplastic syndrome association.^[23] While initially more sensitive to chemotherapy, it ultimately carries a worse prognosis and is often metastatic at presentation. Small cell lung cancers are divided into limited stage and extensive stage disease. This type of lung cancer is strongly associated with smoking.^[24]

Others

In infants and children, the most common primary lung cancers are pleuropulmonary blastoma and carcinoid tumor.^[25]

Secondary cancers

The lung is a common place for metastasis from tumors in other parts of the body. These secondary cancers are identified by the site of origin; thus, a breast cancer metastasis to the lung is still known as breast cancer. They often have a characteristic round appearance on chest radiograph.^[26] In children, the majority of lung cancers are secondary.^[25]

Primary lung cancers themselves most commonly metastasize to the adrenal glands, liver, brain, and bone.^[3]

Staging

See also: Lung cancer staging

Lung cancer staging is an assessment of the degree of spread of the cancer from its original source. It is an important factor affecting the prognosis and potential treatment of lung cancer. Non-small cell lung carcinoma is staged from IA ("one A"; best prognosis) to IV ("four"; worst prognosis).^[27] Small cell lung carcinoma is classified as limited stage if it is confined to one half of the chest and within the scope of a single radiotherapy field; otherwise, it is extensive stage.^[22]

Signs and symptoms

Symptoms that suggest lung cancer include:^[28]

• dyspnea (shortness of breath)
• hemoptysis (coughing up blood)
• chronic coughing or change in regular coughing pattern
• wheezing
• chest pain or pain in the abdomen
• cachexia (weight loss), fatigue, and loss of appetite
• dysphonia (hoarse voice)
• clubbing of the fingernails (uncommon)
• dysphagia (difficulty swallowing).

If the cancer grows in the airway, it may obstruct airflow, causing breathing difficulties. This can lead to accumulation of secretions behind the blockage, predisposing the patient to pneumonia. Many lung cancers have a rich blood supply. The surface of the cancer may be fragile, leading to bleeding from the cancer into the airway. This blood may subsequently be coughed up.

Depending on the type of tumor, so-called paraneoplastic phenomena may initially attract attention to the disease.^[29] In lung cancer, these phenomena may include Lambert-Eaton myasthenic syndrome (muscle weakness due to auto-antibodies), hypercalcemia, or syndrome of inappropriate antidiuretic hormone (SIADH). Tumors in the top (apex) of the lung, known as Pancoast tumors,^[30] may invade the local part of the sympathetic nervous system, leading to changed sweating patterns and eye muscle problems (a combination known as Horner's syndrome) as well as muscle weakness in the hands due to invasion of the brachial plexus.

Many of the symptoms of lung cancer (bone pain, fever, and weight loss) are nonspecific; in the elderly, these may be attributed to comorbid illness.^[3] In many patients, the cancer has already spread beyond the original site by the time they have symptoms and seek medical attention. Common sites of metastasis include the brain, bone, adrenal glands, contralateral (opposite) lung, liver, pericardium, and kidneys.^[31] About 10% of people with lung cancer do not have symptoms at diagnosis; these cancers are incidentally found on routine chest radiograph.^[2]

Causes

The main causes of lung cancer (and cancer in general) include carcinogens (such as those in tobacco smoke), ionizing radiation, and viral infection. This exposure causes cumulative changes to the DNA in the tissue lining the bronchi of the lungs (the bronchial epithelium). As more tissue becomes damaged, eventually a cancer develops.^[3]

Smoking

Following an increase in smoking in the population, the rate of lung cancer death increases. Source: NIH.

Smoking, particularly of cigarettes, is by far the main contributor to lung cancer.^[32] Across the developed world, almost 90% of lung cancer deaths are caused by smoking.^[33] In the United States, smoking is estimated to account for 87% of lung cancer cases (90% in men and 85% in women).^[34] Among male smokers, the lifetime risk of developing lung cancer is 17.2%; among female smokers, the risk is 11.6%. This risk is significantly lower in nonsmokers: 1.3% in men and 1.4% in women.^[35] Cigarette smoke contains over 60 known carcinogens,^[36] including radioisotopes from the radon decay sequence, nitrosamine, and benzopyrene. Additionally, nicotine appears to depress the immune response to malignant growths in exposed tissue.^[37]

The length of time a person smokes (as well as rate of smoking) increases the person's chance of developing lung cancer. If a person stops smoking, this chance steadily decreases as damage to the lungs is repaired and contaminant particles are gradually removed.^[38] In addition, there is evidence that lung cancer in never-smokers has a better prognosis than in smokers,^[39] and that patients who smoke at the time of diagnosis have shorter survival times than those who have quit.^[40]

Passive smoking—the inhalation of smoke from another's smoking—is a cause of lung cancer in nonsmokers. A passive smoker can be classified as someone living or working with a smoker as well. Studies from the U.S.,^[41] Europe,^[42] the UK,^[43] and Australia^[44] have consistently shown a significant increase in relative risk among those exposed to passive smoke. Recent investigation of sidestream smoke suggests that it is more dangerous than direct smoke inhalation.^[45]

Roughly ten-fifteen percent of lung cancer patients have never smoked.^[46] That means between 20,000 to 30,000 never-smokers are diagnosed with lung cancer in the United States each year. Because of the five-year survival rate, each year in the U.S. more never-smokers die of lung cancer than do patients of leukemia, ovarian cancer, or AIDS.^[47]

Radon gas

Radon is a colorless and odorless gas generated by the breakdown of radioactive radium, which in turn is the decay product of uranium, found in the Earth's crust. The radiation decay products ionize genetic material, causing mutations that sometimes turn cancerous. Radon exposure is the second major cause of lung cancer, after smoking.^[8] Radon gas levels vary by locality and the composition of the underlying soil and rocks. For example, in areas such as Cornwall in the UK (which has granite as substrata), radon gas is a major problem, and buildings have to be force-ventilated with fans to lower radon gas concentrations. The United States Environmental Protection Agency (EPA) estimates that one in 15 homes in the U.S. has radon levels above the recommended guideline of 4 picocuries per liter (pCi/L) (148 Bq/m³).^[48] Iowa has the highest average radon concentration in the United States; studies performed there have demonstrated a 50% increased lung cancer risk, with prolonged radon exposure above the EPA's action level of 4 pCi/L.^[49][50]

Asbestos

Asbestos can cause a variety of lung diseases, including lung cancer. There is a synergistic effect between tobacco smoking and asbestos in the formation of lung cancer.^[9] In the UK, asbestos accounts for 2–3% of male lung cancer deaths.^[51] Asbestos can also cause cancer of the pleura, called mesothelioma (which is different from lung cancer).

Viruses

Viruses are known to cause lung cancer in animals,^[52][53] and recent evidence suggests similar potential in humans. Implicated viruses include human papillomavirus,^[54] JC virus,^[55] simian virus 40 (SV40), BK virus, and cytomegalovirus.^[56] These viruses may affect the cell cycle and inhibit apoptosis, allowing uncontrolled cell division.

Pathogenesis

Main article: Carcinogenesis

Similar to many other cancers, lung cancer is initiated by activation of oncogenes or inactivation of tumor suppressor genes.^[57] Oncogenes are genes that are believed to make people more susceptible to cancer. Proto-oncogenes are believed to turn into oncogenes when exposed to particular carcinogens.^[58] Mutations in the K-ras proto-oncogene are responsible for 10–30% of lung adenocarcinomas.^[59][60] The epidermal growth factor receptor (EGFR) regulates cell proliferation, apoptosis, angiogenesis, and tumor invasion.^[59] Mutations and amplification of EGFR are common in non-small cell lung cancer and provide the basis for treatment with EGFR-inhibitors. Her2/neu is affected less frequently.^[59] Chromosomal damage can lead to loss of heterozygosity. This can cause inactivation of tumor suppressor genes. Damage to chromosomes 3p, 5q, 13q, and 17p are particularly common in small cell lung carcinoma. The p53 tumor suppressor gene, located on chromosome 17p, is affected in 60-75% of cases.^[61] Other genes that are often mutated or amplified are c-MET, NKX2-1, LKB1, PIK3CA, and BRAF.^[59]

Several genetic polymorphisms are associated with lung cancer. These include polymorphisms in genes coding for interleukin-1,^[62] cytochrome P450,^[63] apoptosis promoters such as caspase-8,^[64] and DNA repair molecules such as XRCC1.^[65] People with these polymorphisms are more likely to develop lung cancer after exposure to carcinogens.

A recent study suggested that the MDM2 309G allele is a low-penetrant risk factor for developing lung cancer in Asians.^[66]

Diagnosis

Chest radiograph showing a cancerous tumor in the left lung.

Performing a chest radiograph is the first step if a patient reports symptoms that may be suggestive of lung cancer. This may reveal an obvious mass, widening of the mediastinum (suggestive of spread to lymph nodes there), atelectasis (collapse), consolidation (pneumonia), or pleural effusion. If there are no radiographic findings but the suspicion is high (such as a heavy smoker with blood-stained sputum), bronchoscopy and/or a CT scan may provide the necessary information. Bronchoscopy or CT-guided biopsy is often used to identify the tumor type.^[2]

Abnormal findings in cells ("atypia") in sputum are associated with an increased risk of lung cancer. Sputum cytologic examination combined with other screening examinations may have a role in the early detection of lung cancer.^[67]

CT scan showing a cancerous tumor in the left lung.

The differential diagnosis for patients who present with abnormalities on chest radiograph includes lung cancer as well as nonmalignant diseases. These include infectious causes such as tuberculosis or pneumonia, or inflammatory conditions such as sarcoidosis. These diseases can result in mediastinal lymphadenopathy or lung nodules, and sometimes mimic lung cancers.^[3] Lung cancer can also be an incidental finding: a solitary pulmonary nodule (also called a coin lesion) on a chest radiograph or CT scan taken for an unrelated reason.

Prevention

See also: Smoking ban and List of smoking bans

Prevention is the most cost-effective means of fighting lung cancer. While in most countries industrial and domestic carcinogens have been identified and banned, tobacco smoking is still widespread. Eliminating tobacco smoking is a primary goal in the prevention of lung cancer, and smoking cessation is an important preventative tool in this process.^[68] Most importantly, are prevention programs that target the young. In 1998 the Master Settlement Agreement entitled 46 states in the USA to an annual payout from the tobacco companies.^[69] Between the settlement money and tobacco taxes, each state's public health department funds their prevention programs, although none of the states are living up to the Center for Disease Control's recommended amount by spending 15 percent of tobacco taxes and settlement revenues on these prevention efforts.^[69]

Policy interventions to decrease passive smoking in public areas such as restaurants and workplaces have become more common in many Western countries, with California taking a lead in banning smoking in public establishments in 1998. Ireland played a similar role in Europe in 2004, followed by Italy and Norway in 2005, Scotland as well as several others in 2006, England in 2007, France in 2008 and Turkey in 2009. New Zealand has banned smoking in public places as of 2004. The state of Bhutan has had a complete smoking ban since 2005.^[70] In many countries, pressure groups are campaigning for similar bans. In 2007, Chandigarh became the first city in India to become smoke-free. India introduced a total ban on smoking at public places on Oct 2 2008.

Arguments cited against such bans are criminalisation of smoking, increased risk of smuggling, and the risk that such a ban cannot be enforced.^[71]

The long-term use of supplemental multivitamins—such as vitamin C, vitamin E, and folate—does not reduce the risk of lung cancer. Indeed long-term intake of high doses of vitamin E supplements may even increase the risk of lung cancer.^[72]

The World Health Organization has called for governments to institute a total ban on tobacco advertising in order to prevent young people from taking up smoking. They assess that such bans have reduced tobacco consumption by 16% where already instituted.^[73]

Screening

Main article: Lung cancer screening

Screening refers to the use of medical tests to detect disease in asymptomatic people. Possible screening tests for lung cancer include chest radiograph or computed tomography (CT) of the chest. So far, screening programs for lung cancer have not demonstrated any clear benefit. Randomized controlled trials are underway in this area to see if decreased long-term mortality can be directly observed from CT screening.^[74]

Treatment

Treatment for lung cancer depends on the cancer's specific cell type, how far it has spread, and the patient's performance status. Common treatments include surgery, chemotherapy, and radiation therapy.^[2][75]

Surgery

Main article: Lung cancer surgery

Gross appearance of the cut surface of a pneumonectomy specimen containing a lung cancer, here a squamous cell carcinoma (the whitish tumor near the bronchi).

If investigations confirm lung cancer, CT scan and often positron emission tomography (PET) are used to determine whether the disease is localized and amenable to surgery or whether it has spread to the point where it cannot be cured surgically.

Blood tests and spirometry (lung function testing) are also necessary to assess whether the patient is well enough to be operated on. If spirometry reveals poor respiratory reserve (often due to chronic obstructive pulmonary disease), surgery may be contraindicated.

Surgery itself has an operative death rate of about 4.4%, depending on the patient's lung function and other risk factors.^[76] Surgery is usually only an option in non-small cell lung carcinoma limited to one lung, up to stage IIIA. This is assessed with medical imaging (computed tomography, positron emission tomography). A sufficient preoperative respiratory reserve must be present to allow adequate lung function after the tissue is removed.

Procedures include wedge resection (removal of part of a lobe), segmentectomy (removal of an anatomic division of a particular lobe of the lung), lobectomy (one lobe), bilobectomy (two lobes), or pneumonectomy (whole lung). In patients with adequate respiratory reserve, lobectomy is the preferred option, as this minimizes the chance of local recurrence. If the patient does not have enough functional lung for this, wedge resection may be performed.^[77] Radioactive iodine brachytherapy at the margins of wedge excision may reduce recurrence to that of lobectomy.^[78]

Video-assisted thoracoscopic surgery and VATS lobectomy have allowed for minimally invasive approaches to lung cancer surgery that may have the advantages of quicker recovery, shorter hospital stay and diminished hospital costs.^[79]

Chemotherapy

Small cell lung carcinoma is treated primarily with chemotherapy and radiation, as surgery has no demonstrable influence on survival. Primary chemotherapy is also given in metastatic non-small cell lung carcinoma.

The combination regimen depends on the tumor type. Non-small cell lung carcinoma is often treated with cisplatin or carboplatin, in combination with gemcitabine, paclitaxel, docetaxel, etoposide, or vinorelbine.^[80] In small cell lung carcinoma, cisplatin and etoposide are most commonly used.^[81] Combinations with carboplatin, gemcitabine, paclitaxel, vinorelbine, topotecan, and irinotecan are also used.^[82][83] in extensive-stage small-cell lung cancer celecoxib may safely be combined with etoposide, this combination showed improve outcomes.^[84]

Adjuvant chemotherapy for NSCLC

Adjuvant chemotherapy refers to the use of chemotherapy after surgery to improve the outcome. During surgery, samples are taken from the lymph nodes. If these samples contain cancer, the patient has stage II or III disease. In this situation, adjuvant chemotherapy may improve survival by up to 15%.^[85][86] Standard practice is to offer platinum-based chemotherapy (including either cisplatin or carboplatin).^[87]

Adjuvant chemotherapy for patients with stage IB cancer is controversial, as clinical trials have not clearly demonstrated a survival benefit.^[88][89] Trials of preoperative chemotherapy (neoadjuvant chemotherapy) in resectable non-small cell lung carcinoma have been inconclusive.^[90]

Radiotherapy

Radiotherapy is often given together with chemotherapy, and may be used with curative intent in patients with non-small cell lung carcinoma who are not eligible for surgery. This form of high intensity radiotherapy is called radical radiotherapy.^[91] A refinement of this technique is continuous hyperfractionated accelerated radiotherapy (CHART), in which a high dose of radiotherapy is given in a short time period.^[92] For small cell lung carcinoma cases that are potentially curable, chest radiation is often recommended in addition to chemotherapy.^[93] The use of adjuvant thoracic radiotherapy following curative intent surgery for non-small cell lung carcinoma is not well established and is controversial. Benefits, if any, may only be limited to those in whom the tumor has spread to the mediastinal lymph nodes.^[94][95]

For both non-small cell lung carcinoma and small cell lung carcinoma patients, smaller doses of radiation to the chest may be used for symptom control (palliative radiotherapy). Unlike other treatments, it is possible to deliver palliative radiotherapy without confirming the histological diagnosis of lung cancer.

Brachytherapy (localized radiotherapy) may be given directly inside the airway when cancer affects a short section of bronchus.^[96] It is used when inoperable lung cancer causes blockage of a large airway.^[97]

Patients with limited stage small cell lung carcinoma are usually given prophylactic cranial irradiation (PCI). This is a type of radiotherapy to the brain, used to reduce the risk of metastasis.^[98] More recently, PCI has also been shown to be beneficial in those with extensive small cell lung cancer. In patients whose cancer has improved following a course of chemotherapy, PCI has been shown to reduce the cumulative risk of brain metastases within one year from 40.4% to 14.6%.^[99]

Recent improvements in targeting and imaging have led to the development of extracranial stereotactic radiation in the treatment of early-stage lung cancer. In this form of radiation therapy, very high doses are delivered in a small number of sessions using stereotactic targeting techniques. Its use is primarily in patients who are not surgical candidates due to medical comorbidities.^[100]

Interventional radiology

Radiofrequency ablation should currently be considered an investigational technique in the treatment of bronchogenic carcinoma. It is done by inserting a small heat probe into the tumor to kill the tumor cells.^[101]

Targeted therapy

In recent years, various molecular targeted therapies have been developed for the treatment of advanced lung cancer. Gefitinib (Iressa) is one such drug, which targets the tyrosine kinase domain of the epidermal growth factor receptor (EGFR), expressed in many cases of non-small cell lung carcinoma. It was not shown to increase survival, although females, Asians, nonsmokers, and those with bronchioloalveolar carcinoma appear to derive the most benefit from gefitinib.^[21][102]

Erlotinib (Tarceva), another tyrosine kinase inhibitor, has been shown to increase survival in lung cancer patients^[103] and has recently been approved by the FDA for second-line treatment of advanced non-small cell lung carcinoma. Similar to gefitinib, it also appeared to work best in females, Asians, nonsmokers, and those with bronchioloalveolar carcinoma.^[102]

The angiogenesis inhibitor bevacizumab, (in combination with paclitaxel and carboplatin), improves the survival of patients with advanced non-small cell lung carcinoma.^[104] However, this increases the risk of lung bleeding, particularly in patients with squamous cell carcinoma.

Advances in cytotoxic drugs,^[105] pharmacogenetics^[106] and targeted drug design^[107] show promise. A number of targeted agents are at the early stages of clinical research, such as cyclo-oxygenase-2 inhibitors,^[108] the apoptosis promoter exisulind,^[109] proteasome inhibitors,^[110] bexarotene,^[111] the epidermal growth factor receptor inhibitor cetuximab,^[112] and vaccines.^[113] Future areas of research include ras proto-oncogene inhibition, phosphoinositide 3-kinase inhibition, histone deacetylase inhibition, and tumor suppressor gene replacement.^[114]

Prognosis

Main articles: Non-small cell lung carcinoma staging and Manchester score

Prognostic factors in non-small cell lung cancer include presence or absence of pulmonary symptoms, tumor size, cell type (histology), degree of spread (stage) and metastases to multiple lymph nodes, and vascular invasion. For patients with inoperable disease, prognosis is adversely affected by poor performance status and weight loss of more than 10%.^[115] Prognostic factors in small-cell lung cancer include performance status, gender, stage of disease, and involvement of the central nervous system or liver at the time of diagnosis.^[116]

For non-small cell lung carcinoma, prognosis is generally poor. Following complete surgical resection of stage IA disease, five-year survival is 67%. With stage IB disease, five-year survival is 57%.^[117] The five-year survival rate of patients with stage IV NSCLC is about 1%.^[4]

For small cell lung carcinoma, prognosis is also generally poor. The overall five-year survival for patients with SCLC is about 5%.^[2] Patients with extensive-stage SCLC have an average five-year survival rate of less than 1%. The median survival time for limited-stage disease is 20 months, with a five-year survival rate of 20%.^[4]

According to data provided by the National Cancer Institute, the median age of incidence of lung cancer is 70 years, and the median age of death by lung cancer is 71 years.^[118]

Epidemiology

Age-standardized death from tracheal, bronchial, and lung cancers per 100,000 inhabitants in 2004.^[119]

     no data      ≤ 5      5-10      10-15      15-20      20-25      25-30      30-35      35-40      40-45      45-50      50-55      ≥ 55

Lung cancer distribution in the United States

Worldwide, lung cancer is the most common cancer in terms of both incidence and mortality (1.35 million new cases per year and 1.18 million deaths), with the highest rates in Europe and North America.^[120] The population segment most likely to develop lung cancer is over-fifties who have a history of smoking. Lung cancer is the second most commonly occurring form of cancer in most Western countries, and it is the leading cancer-related cause of death. In contrast to the mortality rate in men, which began declining more than 20 years ago, women's lung cancer mortality rates have been rising for over the last decades, and are just recently beginning to stabilize.^[121] The evolution of "Big Tobacco" plays a significant role in the smoking culture.^[122] Tobacco companies have focused their efforts since the 1970s at marketing their product toward women and girls, especially with "light" and "low-tar" cigarettes [1]. Among lifetime nonsmokers, men have higher age-standardized lung cancer death rates than women.

Not all cases of lung cancer are due to smoking, but the role of passive smoking is increasingly being recognized as a risk factor for lung cancer—leading to policy interventions to decrease undesired exposure of nonsmokers to others' tobacco smoke. Emissions from automobiles, factories, and power plants also pose potential risks.^{[10][12][123]}

Eastern Europe has the highest lung cancer mortality among men, while northern Europe and the U.S. have the highest mortality among women. Lung cancer incidence is currently less common in developing countries.^[124] With increased smoking in developing countries, the incidence is expected to increase in the next few years, notably in China^[125] and India.^[126]

Lung cancer incidence (by country) has an inverse correlation with sunlight and UVB exposure. One possible explanation is a preventative effect of vitamin D (which is produced in the skin on exposure to sunlight).^[127]

From the 1950s, the incidence of lung adenocarcinoma started to rise relative to other types of lung cancer.^[128] This is partly due to the introduction of filter cigarettes. The use of filters removes larger particles from tobacco smoke, thus reducing deposition in larger airways. However the smoker has to inhale more deeply to receive the same amount of nicotine, increasing particle deposition in small airways where adenocarcinoma tends to arise.^[129] The incidence of lung adenocarcinoma in the U.S. has fallen since 1999. This may be due to reduction in environmental air pollution.^[128]

History

Lung cancer was uncommon before the advent of cigarette smoking; it was not even recognized as a distinct disease until 1761.^[130] Different aspects of lung cancer were described further in 1810.^[131] Malignant lung tumors made up only 1% of all cancers seen at autopsy in 1878, but had risen to 10–15% by the early 1900s.^[132] Case reports in the medical literature numbered only 374 worldwide in 1912,^[133] but a review of autopsies showed that the incidence of lung cancer had increased from 0.3% in 1852 to 5.66% in 1952.^[134] In Germany in 1929, physician Fritz Lickint recognized the link between smoking and lung cancer,^[132] which led to an aggressive antismoking campaign.^[135] The British Doctors Study, published in the 1950s, was the first solid epidemiological evidence of the link between lung cancer and smoking.^[136] As a result, in 1964 the Surgeon General of the United States recommended that smokers should stop smoking.^[137]

The connection with radon gas was first recognized among miners in the Ore Mountains near Schneeberg, Saxony. Silver has been mined there since 1470, and these mines are rich in uranium, with its accompanying radium and radon gas. Miners developed a disproportionate amount of lung disease, eventually recognized as lung cancer in the 1870s. An estimated 75% of former miners died from lung cancer.^[138] Despite this discovery, mining continued into the 1950s, due to the USSR's demand for uranium.^[139]

The first successful pneumonectomy for lung cancer was performed in 1933.^[140] Palliative radiotherapy has been used since the 1940s.^[141] Radical radiotherapy, initially used in the 1950s, was an attempt to use larger radiation doses in patients with relatively early stage lung cancer but who were otherwise unfit for surgery.^[142] In 1997, continuous hyperfractionated accelerated radiotherapy (CHART) was seen as an improvement over conventional radical radiotherapy.^[92]

With small cell lung carcinoma, initial attempts in the 1960s at surgical resection^[143] and radical radiotherapy^[144] were unsuccessful. In the 1970s, successful chemotherapy regimens were developed.^[145]

Gallery

Chest radiograph showing lung cancer.

See also

• Bronchioloalveolar carcinoma
• Pulmonary sulcus tumor

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External links

Wikimedia Commons has media related to: Lung cancers

• Detailed guide: Lung cancer - small cell American Cancer Society
• Detailed guide: Lung cancer - non-small cell American Cancer Society
• Lung cancer tutorial ChestRadiology.net
• Lung cancer at the Open Directory Project
• LungCancer.org — free resources and support services
• Lung cancer National Cancer Institute
• Tobacco smoke and involuntary smoking, summary of data reported and evaluation (2004) IARC
• Lung Cancer Articles & Information Stop smoking articles & information at National Institutes of Health
• Chouaid, C.; Atsou, K.; Hejblum, G.; Vergnenegre, A. (2009). "Economics of treatments for non-small cell lung cancer". PharmacoEconomics 27 (2): 113–125. doi:10.2165/00019053-200927020-00003. PMID 19254045.  edit
• Medical Encyclopedia WebMD: Lung Cancer Health Center
• Medical Encyclopedia MayoClinic: Lung cancer

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