Lung cancer is a disease characterized by uncontrolled cell growth in tissues of the lung. If left untreated, this growth can spread beyond the lung in a process called metastasis into nearby tissue or other parts of the body. Most cancers that start in lung, known as primary lung cancers, are carcinomas that derive from epithelial cells. The main types of lung cancer are small-cell lung carcinoma (SCLC), also called oat cell cancer, and non-small-cell lung carcinoma (NSCLC). The most common symptoms are coughing (including coughing up blood), weight loss, shortness of breath, and chest pains.
Common treatments include surgery, chemotherapy, and radiotherapy. NSCLC is sometimes treated with surgery, whereas SCLC usually responds better to chemotherapy and radiotherapy. Overall, 15% of people in the United States diagnosed with lung cancer survive five years after the diagnosis. Outcomes are worse in the developing world. Worldwide, lung cancer is the most common cause of cancer-related death in men and women, and is responsible for 1.38 million deaths annually, as of 2008.
Many of the symptoms of lung cancer (poor appetite, weight loss, fever, fatigue) are not specific. In many people, the cancer has already spread beyond the original site by the time they have symptoms and seek medical attention. Common sites of spread include the brain, bone, adrenal glands, opposite lung, liver, pericardium, and kidneys. About 10% of people with lung cancer do not have symptoms at diagnosis; these cancers are incidentally found on routine chest radiography.
Cancer develops following genetic damage to DNA and epigenetic changes. These changes affect the normal functions of the cell, including cell proliferation, programmed cell death (apoptosis) and DNA repair. As more damage accumulates, the risk of cancer increases.
Graph showing how a general increase in sales of tobacco products in the USA in the first four decades of the 20th century (cigarettes per person per year) led to a corresponding rapid increase in the rate of lung cancer during the 1930s, '40s and '50s (lung cancer deaths per 100,000 male population per year)
Cross section of a human lung: The white area in the upper lobe is cancer; the black areas are discoloration due to smoking.
Lung cancer, incidence, mortality and survival, England 1971–2011
Smoking, particularly of cigarettes, is by far the main contributor to lung cancer. Cigarette smoke contains over 60 known carcinogens, including radioisotopes from the radon decay sequence, nitrosamine, and benzopyrene. Additionally, nicotine appears to depress the immune response to cancerous growths in exposed tissue. Across the developed world, 90% of lung cancer deaths in men during the year 2000 were attributed to smoking (70% for women). Smoking accounts for 80–90% of lung cancer cases.
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. Studies from the US, Europe, the UK, and Australia have consistently shown a significantly increased risk among those exposed to passive smoke. Those who live with someone who smokes have a 20–30% increase in risk while those who work in an environment with second hand smoke have a 16–19% increase in risk. Investigations of sidestream smoke suggest it is more dangerous than direct smoke. Passive smoking causes about 3,400 deaths from lung cancer each year in the USA.
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 is the second-most common cause of lung cancer in the USA, after smoking. The risk increases 8–16% for every 100 Bq/m³ increase in the radon concentration. 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 one in 15 homes in the US has radon levels above the recommended guideline of 4 picocuries per liter (pCi/l) (148 Bq/m³).
Asbestos can cause a variety of lung diseases, including lung cancer. Tobacco smoking and asbestos have a synergistic effect on the formation of lung cancer. Asbestos can also cause cancer of the pleura, called mesothelioma (which is different from lung cancer).
Outdoor air pollution has a small effect on increasing the risk of lung cancer. Fine particulates (PM2.5) and sulfate aerosols, which may be released in traffic exhaust fumes, are associated with slightly increased risk. For nitrogen dioxide, an incremental increase of 10 parts per billion increases the risk of lung cancer by 14%. Outdoor air pollution is estimated to account for 1–2% of lung cancers.
Tentative evidence supports an increased risk of lung cancer from indoor air pollution related to the burning of wood, charcoal, dung or crop residue for cooking and heating. Women who are exposed to indoor coal smoke have about twice the risk and a number of the by-products of burning biomass are known or suspected carcinogens. This risk affects about 2.4 billion people globally, and is believed to account for 1.5% of lung cancer deaths.
It is estimated that 8 to 14% of lung cancer is due to inherited factors. In relatives of people with lung cancer, the risk is increased 2.4 times. This is likely due to a combination of genes.
Numerous other substances, occupations, and environmental exposures have been linked to lung cancer. The International Agency for Research on Cancer (IARC) states there is "sufficient evidence" to show the following are carcinogenic in lung:
Some metals (aluminum production, cadmium and cadmium compounds, chromium(VI) compounds, beryllium and beryllium compounds, iron and steel founding, nickel compounds, arsenic and inorganic arsenic compounds, underground hematite mining)
Some products of combustion (incomplete combustion, coal (indoor emissions from household coal burning), coal gasification, coal-tar pitch, coke production, soot, diesel engine exhaust)
Similar to many other cancers, lung cancer is initiated by activation of oncogenes or inactivation of tumor suppressor genes. Oncogenes are believed to make people more susceptible to cancer. Proto-oncogenes are believed to turn into oncogenes when exposed to particular carcinogens.Mutations in the K-ras proto-oncogene are responsible for 10–30% of lung adenocarcinomas. The epidermal growth factor receptor (EGFR) regulates cell proliferation, apoptosis, angiogenesis, and tumor invasion. 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.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. Other genes that are often mutated or amplified are c-MET, NKX2-1, LKB1, PIK3CA, and BRAF.
CT scan showing a cancerous tumor in the left lung
Age-adjusted incidence of lung cancer by histological type
Incidence per 100,000 per year
Lung cancers are classified according to histological type. This classification is important for determining management and predicting outcomes of the disease. The vast majority of lung cancers are carcinomas—malignancies that arise from epithelial cells. Lung carcinomas are categorized by the size and appearance of the malignant cells seen by a histopathologist under a microscope. The two broad classes are non-small-cell and small-cell lung carcinoma.
Nearly 40% of lung cancers are adenocarcinoma, which usually originates in peripheral lung tissue. Most cases of adenocarcinoma are associated with smoking; however, among people who have smoked fewer than 100 cigarettes in their lifetimes ("never-smokers"), adenocarcinoma is the most common form of lung cancer. A subtype of adenocarcinoma, the bronchioloalveolar carcinoma, is more common in female never-smokers, and may have a better long term survival.
Squamous-cell carcinoma accounts for about 30% of lung cancers. They typically occur close to large airways. A hollow cavity and associated cell death are commonly found at the center of the tumor. About 9% of lung cancers are large-cell carcinoma. These are so named because the cancer cells are large, with excess cytoplasm, large nuclei and conspicuous nucleoli.
Small-cell lung carcinoma
Small-cell lung carcinoma (microscopic view of a core needle biopsy)
In small-cell lung carcinoma (SCLC), the cells contain dense neurosecretory granules (vesicles containing neuroendocrinehormones), which give this tumor an endocrine/paraneoplastic syndrome association. Most cases arise in the larger airways (primary and secondary bronchi). These cancers grow quickly and spread early in the course of the disease. Sixty to seventy percent have metastatic disease at presentation. This type of lung cancer is strongly associated with smoking.
Four main histological subtypes are recognized, although some cancers may contain a combination of different subtypes. Rare subtypes include glandular tumors, carcinoid tumors, and undifferentiated carcinomas.
The lung is a common place for the spread of tumors from other parts of the body. Secondary cancers are classified by the site of origin; e.g., breast cancer that has spread to the lung is called metastatic breast cancer. Metastases often have a characteristic round appearance on chest radiograph.
Primary lung cancers themselves most commonly metastasize to the brain, bones, liver, and adrenal glands.Immunostaining of a biopsy is often helpful to determine the original source.
Lung cancer staging is an assessment of the degree of spread of the cancer from its original source. It is one of the factors affecting the prognosis and potential treatment of lung cancer.
The initial evaluation of non-small-cell lung cancer (NSCLC) staging uses the TNM classification. This is based on the size of the primary tumor, lymph node involvement, and distant metastasis. After this, using the TNM descriptors, a group is assigned, ranging from occult cancer, through stages 0, IA (one-A), IB, IIA, IIB, IIIA, IIIB and IV (four). This stage group assists with the choice of treatment and estimation of prognosis. Small-cell lung carcinoma (SCLC) has traditionally been classified as 'limited stage' (confined to one half of the chest and within the scope of a single tolerable radiotherapy field) or 'extensive stage' (more widespread disease). However, the TNM classification and grouping are useful in estimating prognosis.
For both NSCLC and SCLC, the two general types of staging evaluations are clinical staging and surgical staging. Clinical staging is performed prior to definitive surgery. It is based on the results of imaging studies (such as CT scans and PET scans) and biopsy results. Surgical staging is evaluated either during or after the operation, and is based on the combined results of surgical and clinical findings, including surgical sampling of thoracic lymph nodes.
Prevention is the most cost-effective means of decreasing lung cancer development. 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 preventive tool in this process.
Policy interventions to decrease passive smoking in public areas such as restaurants and workplaces have become more common in many Western countries.Bhutan has had a complete smoking ban since 2005 while India introduced a ban on smoking in public in October 2008. The World Health Organization has called for governments to institute a total ban on tobacco advertising to prevent young people from taking up smoking. They assess that such bans have reduced tobacco consumption by 16% where instituted.
The long-term use of supplemental vitamin A, vitamin C, vitamin D or vitamin E does not reduce the risk of lung cancer. Some studies suggest people who eat diets with a higher proportion of vegetables and fruit tend to have a lower risk, but this is likely due to confounding. More rigorous studies have not demonstrated a clear association.
Screening refers to the use of medical tests to detect disease in asymptomatic people. Possible screening tests for lung cancer include sputumcytology, chest radiograph (CXR), and computed tomography (CT). Screening programs using CXR or cytology have not demonstrated benefit. Screening those at high risk (i.e. age 55 to 79 who have smoked more than 30 pack years or those who have had previous lung cancer) annually with low-dose CT scans may reduce the chance of death from lung cancer by an absolute amount of 0.3% (relative amount of 20%). There is, however, a high rate of falsely positive scans which may result in unneeded invasive procedures as well as substantial financial cost. For each true positive scan there are more than 19 false positives. Radiation exposure is another potential harm from screening.
If investigations confirm NSCLC, the stage is assessed to determine whether the disease is localized and amenable to surgery or if it has spread to the point where it cannot be cured surgically. CT scan and positron emission tomography are used for this determination. If mediastinal lymph node involvement is suspected, mediastinoscopy may be used to sample the nodes and assist staging.Blood tests and pulmonary function testing are used to assess whether a person is well enough for surgery. If pulmonary function tests reveal poor respiratory reserve, surgery may not be a possibility.
In most cases of early-stage NSCLC, removal of a lobe of lung (lobectomy) is the surgical treatment of choice. In people who are unfit for a full lobectomy, a smaller sublobar excision (wedge resection) may be performed. However, wedge resection has a higher risk of recurrence than lobectomy. Radioactive iodinebrachytherapy at the margins of wedge excision may reduce the risk of recurrence. Rarely, removal of a whole lung (pneumonectomy) is performed.Video-assisted thoracoscopic surgery and VATS lobectomy use a minimally invasive approach to lung cancer surgery. VATS lobectomy is equally effective compared to conventional open lobectomy, with less postoperative illness.
In SCLC, chemotherapy and/or radiotherapy is typically used. However the role of surgery in SCLC is being reconsidered. Surgery might improve outcomes when added to chemotherapy and radiation in early stage SCLC.
Radiotherapy is often given together with chemotherapy, and may be used with curative intent in people with NSCLC who are not eligible for surgery. This form of high-intensity radiotherapy is called radical radiotherapy. 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. Postoperative thoracic radiotherapy generally should not be used after curative intent surgery for NSCLC. Some people with mediastinal N2 lymph node involvement might benefit from post-operative radiotherapy.
For potentially curable SCLC cases, chest radiotherapy is often recommended in addition to chemotherapy.
If cancer growth blocks a short section of bronchus, brachytherapy (localized radiotherapy) may be given directly inside the airway to open the passage. Compared to external beam radiotherapy, brachytherapy allows a reduction in treatment time and reduced radiation exposure to healthcare staff.
Prophylactic cranial irradiation (PCI) is a type of radiotherapy to the brain, used to reduce the risk of metastasis. PCI is most useful in SCLC. In limited-stage disease, PCI increases three-year survival from 15% to 20%; in extensive disease, one-year survival increases from 13% to 27%.
Recent improvements in targeting and imaging have led to the development of stereotactic radiation in the treatment of early-stage lung cancer. In this form of radiotherapy, 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.
For both NSCLC and SCLC patients, smaller doses of radiation to the chest may be used for symptom control (palliative radiotherapy).
Adjuvant chemotherapy refers to the use of chemotherapy after apparently curative surgery to improve the outcome. In NSCLC, samples are taken of nearby lymph nodes during surgery to assist staging. If stage II or III disease is confirmed, adjuvant chemotherapy improves survival by 5% at five years. The combination of vinorelbine and cisplatin is more effective than older regimens. Adjuvant chemotherapy for people with stage IB cancer is controversial, as clinical trials have not clearly demonstrated a survival benefit. Trials of preoperative chemotherapy (neoadjuvant chemotherapy) in resectable NSCLC have been inconclusive.
In people with terminal disease, palliative care or hospice management may be appropriate. These approaches allow additional discussion of treatment options and provide opportunities to arrive at well-considered decisions and may avoid unhelpful but expensive care at the end of life.
Chemotherapy may be combined with palliative care in the treatment of the NSCLC. In advanced cases, appropriate chemotherapy improves average survival over supportive care alone, as well as improving quality of life. With adequate physical fitness, maintaining chemotherapy during lung cancer palliation offers 1.5 to 3 months of prolongation of survival, symptomatic relief, and an improvement in quality of life, with better results seen with modern agents. The NSCLC Meta-Analyses Collaborative Group recommends if the recipient wants and can tolerate treatment, then chemotherapy should be considered in advanced NSCLC.
Outcomes in lung cancer according to clinical stage
Five-year survival (%)
Non-small cell lung carcinoma
Small cell lung carcinoma
Prognosis is generally poor. Of all people with lung cancer, about 15% survive for five years after diagnosis in the United States. Outcomes are generally worse in the developing world. Stage is often advanced at the time of diagnosis. At presentation, 30–40% of cases of NSCLC are stage IV, and 60% of SCLC are stage IV.
For NSCLC, the best prognosis is achieved with complete surgical resection of stage IA disease, with up to 70% five-year survival. For SCLC, the overall five-year survival is about 5%. People with extensive-stage SCLC have an average five-year survival rate of less than 1%. The average survival time for limited-stage disease is 20 months, with a five-year survival rate of 20%.
According to data provided by the National Cancer Institute, the median age at diagnosis of lung cancer in the United States is 70 years, and the median age at death is 72 years. In the US, people with medical insurance are more likely to have a better outcome.
Worldwide, lung cancer is the most common cancer in terms of both incidence and mortality. In 2008, there were 1.61 million new cases, and 1.38 million deaths due to lung cancer. The highest rates are in Europe and North America. The population segment most likely to develop lung cancer is people aged over 50 who have a history of smoking. 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 over the last decades, and are just recently beginning to stabilize. In the USA, the lifetime risk of developing lung cancer is 8% in men and 6% in women.
For every 3–4 million cigarettes smoked, one lung cancer death occurs. The influence of "Big Tobacco" plays a significant role in the smoking culture. Young nonsmokers who see tobacco advertisements are more likely to take up smoking. 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.
Eastern Europe has the highest lung cancer mortality among men, while northern Europe and the US have the highest mortality among women. In the United States, black men and women have a higher incidence. Lung cancer rates are currently lower in developing countries. With increased smoking in developing countries, the rates are expected to increase in the next few years, notably in China and India.
From the 1960s, the rates of lung adenocarcinoma started to rise relative to other types of lung cancer. 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. The incidence of lung adenocarcinoma continues to rise.
Lung cancer was uncommon before the advent of cigarette smoking; it was not even recognized as a distinct disease until 1761. Different aspects of lung cancer were described further in 1810. 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. Case reports in the medical literature numbered only 374 worldwide in 1912, but a review of autopsies showed the incidence of lung cancer had increased from 0.3% in 1852 to 5.66% in 1952. In Germany in 1929, physician Fritz Lickint recognized the link between smoking and lung cancer, which led to an aggressive antismoking campaign. The British Doctors Study, published in the 1950s, was the first solid epidemiological evidence of the link between lung cancer and smoking. As a result, in 1964 the Surgeon General of the United States recommended smokers should stop smoking.
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. Despite this discovery, mining continued into the 1950s, due to the USSR's demand for uranium. Radon was confirmed as a cause of lung cancer in the 1960s.
The first successful pneumonectomy for lung cancer was performed in 1933. Palliative radiotherapy has been used since the 1940s. 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. In 1997, continuous hyperfractionated accelerated radiotherapy was seen as an improvement over conventional radical radiotherapy. With small-cell lung carcinoma, initial attempts in the 1960s at surgical resection and radical radiotherapy were unsuccessful. In the 1970s, successful chemotherapy regimens were developed.
^ abcdefghijklmnopqrstHorn, L; Pao W, Johnson DH (2012). "Chapter 89". In Longo, DL; Kasper, DL; Jameson, JL; Fauci, AS; Hauser, SL; Loscalzo, J. Harrison's Principles of Internal Medicine (18th ed.). McGraw-Hill. ISBN0-07-174889-X.Cite uses deprecated parameters (help)
^"Tobacco Smoke and Involuntary Smoking" (PDF). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans (WHO International Agency for Research on Cancer) 83. 2002. "There is sufficient evidence that involuntary smoking (exposure to secondhand or 'environmental' tobacco smoke) causes lung cancer in humans. ... Involuntary smoking (exposure to secondhand or 'environmental' tobacco smoke) is carcinogenic to humans (Group 1)."
^ abcdefghijkLu, C; Onn A, Vaporciyan AA et al. (2010). "78: Cancer of the Lung". Holland-Frei Cancer Medicine (8th ed.). People's Medical Publishing House. ISBN978-1-60795-014-1.Cite uses deprecated parameters (help)
^Chapman, S; Robinson G, Stradling J, West S (2009). "Chapter 31". Oxford Handbook of Respiratory Medicine (2nd ed.). Oxford University Press. ISBN978-0-19-954516-2.Cite uses deprecated parameters (help)
^ abFerlay, J; Shin HR, Bray F et al. (December 2010). "Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008". International Journal of Cancer127 (12): 2893–2917. doi:10.1002/ijc.25516. PMID21351269.Cite uses deprecated parameters (help)
^Greene, Frederick L. (2002). AJCC cancer staging manual. Berlin: Springer-Verlag. ISBN0-387-95271-3.
^Brown, KM; Keats JJ, Sekulic A et al. (2010). "8". Holland-Frei Cancer Medicine (8th ed.). People's Medical Publishing House USA. ISBN978-1-60795-014-1.Cite uses deprecated parameters (help)
^Biesalski, HK; Bueno de Mesquita B, Chesson A et al. (1998). "European Consensus Statement on Lung Cancer: risk factors and prevention. Lung Cancer Panel". CA Cancer J Clin (Smoking is the major risk factor, accounting for about 90% of lung cancer incidence.) 48 (3): 167–176; discussion 164–166. doi:10.3322/canjclin.48.3.167. PMID9594919.Cite uses deprecated parameters (help)
^Davies, RJO; Lee YCG (2010). "18.19.3". Oxford Textbook Medicine (5th ed.). OUP Oxford. ISBN978-0-19-920485-4.Cite uses deprecated parameters (help)
^Chen, H; Goldberg MS, Villeneuve PJ (Oct-Dec 2008). "A systematic review of the relation between long-term exposure to ambient air pollution and chronic diseases". Reviews on Environmental Health23 (4): 243–297. PMID19235364.Cite uses deprecated parameters (help)
^Aviel-Ronen, S; Blackhall FH, Shepherd FA, Tsao MS (July 2006). "K-ras mutations in non-small-cell lung carcinoma: a review". Clinical Lung Cancer (Cancer Information Group) 8 (1): 30–38. doi:10.3816/CLC.2006.n.030. PMID16870043.Cite uses deprecated parameters (help)
^Devereux, TR; Taylor JA, Barrett JC (March 1996). "Molecular mechanisms of lung cancer. Interaction of environmental and genetic factors". Chest (American College of Chest Physicians) 109 (Suppl 3): 14S–19S. doi:10.1378/chest.109.3_Supplement.14S. PMID8598134.Cite uses deprecated parameters (help)
^Miller, WT (2008). Fishman's Pulmonary Diseases and Disorders (4th ed.). McGraw-Hill. p. 486. ISBN0-07-145739-9.
^Kaiser, LR (2008). Fishman's Pulmonary Diseases and Disorders (4th ed.). McGraw-Hill. pp. 1815–1816. ISBN0-07-145739-9.
^ abMaitra, A; Kumar V (2007). Robbins Basic Pathology (8th ed.). Saunders Elsevier. pp. 528–529. ISBN978-1-4160-2973-1.Cite uses deprecated parameters (help)
^Subramanian, J; Govindan R (February 2007). "Lung cancer in never smokers: a review". Journal of Clinical Oncology (American Society of Clinical Oncology) 25 (5): 561–570. doi:10.1200/JCO.2006.06.8015. PMID17290066.Cite uses deprecated parameters (help)
^Jaklitsch, MT; Jacobson FL, Austin JH et al. (July 2012). "The American Association for Thoracic Surgery guidelines for lung cancer screening using low-dose computed tomography scans for lung cancer survivors and other high-risk groups". Journal of Thoracic and Cardiovascular Surgery144 (1): 33–38. doi:10.1016/j.jtcvs.2012.05.060. PMID22710039.Cite uses deprecated parameters (help)
^Bach, PB; Mirkin JN, Oliver TK et al. (June 2012). "Benefits and harms of CT screening for lung cancer: a systematic review". JAMA: the Journal of the American Medical Association307 (22): 2418–2429. doi:10.1001/jama.2012.5521. PMID22610500.Cite uses deprecated parameters (help)
^Bach PB, Mirkin JN, Oliver TK, et al. (June 2012). "Benefits and harms of CT screening for lung cancer: a systematic review". JAMA307 (22): 2418–29. doi:10.1001/jama.2012.5521. PMID22610500.Cite uses deprecated parameters (help)
^Aberle, DR; Abtin, F; Brown, K (Mar 10, 2013). "Computed tomography screening for lung cancer: has it finally arrived? Implications of the national lung screening trial.". Journal of clinical oncology : official journal of the American Society of Clinical Oncology31 (8): 1002–8. doi:10.1200/JCO.2012.43.3110. PMID23401434.Cite uses deprecated parameters (help)
^Ferrell, B; Koczywas M, Grannis F, Harrington A (April 2011). "Palliative care in lung cancer". Surgical Clinics of North America91 (2): 403–417. doi:10.1016/j.suc.2010.12.003. PMID21419260.Cite uses deprecated parameters (help)
^Kaiser LR (2008). Fishman's Pulmonary Diseases and Disorders (4th ed.). McGraw-Hill. pp. 1853–1854. ISBN0-07-145739-9.
^ abKaiser LR (2008). Fishman's Pulmonary Diseases and Disorders (4th ed.). McGraw-Hill. pp. 1855–1856. ISBN0-07-145739-9.
^Odell, DD; Kent MS, Fernando HC (Spring 2010). "Sublobar resection with brachytherapy mesh for stage I non-small cell lung cancer". Seminars in Thoracic and Cardiovascular Surgery22 (1): 32–37. doi:10.1053/j.semtcvs.2010.04.003. PMID20813314.Cite uses deprecated parameters (help)
^Goldstein, SD; Yang SC (October 2011). "Role of surgery in small cell lung cancer". Surgical Oncology Clinics of North America20 (4): 769–777. doi:10.1016/j.soc.2011.08.001. PMID21986271.Cite uses deprecated parameters (help)
^Arriagada, R; Goldstraw P, Le Chevalier T (2002). Oxford Textbook of Oncology (2nd ed.). Oxford University Press. p. 2094. ISBN0-19-262926-3.Cite uses deprecated parameters (help)
^Hatton, MQ; Martin JE (June 2010). "Continuous hyperfractionated accelerated radiotherapy (CHART) and non-conventionally fractionated radiotherapy in the treatment of non-small cell lung cancer: a review and consideration of future directions". Clinical Oncology (Royal College of Radiologists)22 (5): 356–364. doi:10.1016/j.clon.2010.03.010. PMID20399629.Cite uses deprecated parameters (help)
^PORT Meta-analysis Trialists Group (2005). "Postoperative radiotherapy for non-small cell lung cancer". In Rydzewska, Larysa. Cochrane Database of Systematic Reviews (2): CD002142. doi:10.1002/14651858.CD002142.pub2. PMID15846628.
^Horn, L; Sandler AB, Putnam JB Jr, Johnson DH (May 2007). "The rationale for adjuvant chemotherapy in stage I non-small cell lung cancer". Journal of Thoracic Oncology2 (5): 377–383. doi:10.1097/01.JTO.0000268669.64625.bb. PMID17473651.Cite uses deprecated parameters (help)
^Wakelee, HA; Schiller JH, Gandara DR (July 2006). "Current status of adjuvant chemotherapy for stage IB non-small-cell lung cancer: implications for the New Intergroup Trial". Clinical Lung Cancer (Cancer Information Group) 8 (1): 18–21. doi:10.3816/CLC.2006.n.028. PMID16870041.Cite uses deprecated parameters (help)
^BMJ (December 2005). Clinical evidence concise : the international resource of the best available evidence for effective health care. (14). London: BMJ Publishing Group. pp. 486–488. ISBN1-905545-00-2. ISSN1475-9225.Cite uses deprecated parameters (help)
^ abPrince-Paul M (April 2009). "When hospice is the best option: an opportunity to redefine goals". Oncology (Williston Park, N.Y.)23 (4 Suppl Nurse Ed): 13–7. PMID19856592.Cite uses deprecated parameters (help)
^Souquet PJ, Chauvin F, Boissel JP, Bernard JP (April 1995). "Meta-analysis of randomised trials of systemic chemotherapy versus supportive treatment in non-resectable non-small cell lung cancer". Lung Cancer. 12 Suppl 1: S147–54. doi:10.1016/0169-5002(95)00430-9. PMID7551923.Cite uses deprecated parameters (help)
^Sörenson S, Glimelius B, Nygren P (2001). "A systematic overview of chemotherapy effects in non-small cell lung cancer". Acta Oncol40 (2–3): 327–39. PMID11441939.
^Clegg A, Scott DA, Sidhu M, Hewitson P, Waugh N (2001). "A rapid and systematic review of the clinical effectiveness and cost-effectiveness of paclitaxel, docetaxel, gemcitabine and vinorelbine in non-small-cell lung cancer". Health Technol Assess5 (32): 1–195. PMID12065068.
^Adler, I (1912). Primary Malignant Growths of the Lungs and Bronchi. New York: Longmans, Green, and Company. OCLC14783544. OL24396062M., cited in Spiro SG, Silvestri GA (2005). "One hundred years of lung cancer". American Journal of Respiratory and Critical Care Medicine172 (5): 523–529. doi:10.1164/rccm.200504-531OE. PMID15961694.
^ abGreaves, M (2000). Cancer: the Evolutionary Legacy. Oxford University Press. pp. 196–197. ISBN0-19-262835-6.
^Greenberg, M; Selikoff IJ (February 1993). "Lung cancer in the Schneeberg mines: a reappraisal of the data reported by Harting and Hesse in 1879". Annals of Occupational Hygiene37 (1): 5–14. PMID8460878.Cite uses deprecated parameters (help)
^Kabela, M (1956). "Erfahrungen mit der radikalen Röntgenbestrahlung des Bronchienkrebses" [Experience with radical irradiation of bronchial cancer]. Ceskoslovenská Onkológia (in German) 3 (2): 109–115. PMID13383622.
^Saunders, M; Dische S, Barrett A et al. (July 1997). "Continuous hyperfractionated accelerated radiotherapy (CHART) versus conventional radiotherapy in non-small-cell lung cancer: a randomised multicentre trial". Lancet (Elsevier) 350 (9072): 161–165. doi:10.1016/S0140-6736(97)06305-8. PMID9250182.Cite uses deprecated parameters (help)
^Lennox, SC; Flavell G, Pollock DJ et al. (November 1968). "Results of resection for oat-cell carcinoma of the lung". Lancet (Elsevier) 2 (7575): 925–927. doi:10.1016/S0140-6736(68)91163-X. PMID4176258.Cite uses deprecated parameters (help)
^Miller, AB; Fox W, Tall R (September 1969). "Five-year follow-up of the Medical Research Council comparative trial of surgery and radiotherapy for the primary treatment of small-celled or oat-celled carcinoma of the bronchus". Lancet (Elsevier) 2 (7619): 501–505. doi:10.1016/S0140-6736(69)90212-8. PMID4184834.Cite uses deprecated parameters (help)
^Cohen, M; Creaven PJ, Fossieck BE Jr et al. (1977). "Intensive chemotherapy of small cell bronchogenic carcinoma". Cancer Treatment Reports61 (3): 349–354. PMID194691.Cite uses deprecated parameters (help)