Lung cancer
Classification and external resources
Three-dimensional volume rendering of a thorax CT showing a tumor in the lung (marked by arrow)
ICD-10 | C 33-C 34
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 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 and, eventually, into 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 cause of lung cancer is long-term exposure to tobacco smoke,[1] which causes 80?90% of lung cancers.[2] Nonsmokers account for 10?15% of lung cancer cases,[3] and these cases are often attributed to a combination of genetic factors,[4] radon gas,[4] asbestos,[5] and air pollution[4] including secondhand smoke.[6][7]

The most common symptoms are coughing (including coughing up blood), weight loss and shortness of breath.[2] Lung cancer may be seen on chest radiograph and computed tomography (CT scan). The diagnosis is confirmed with a biopsy.[8] This is usually performed by bronchoscopy or CT-guided biopsy. Treatment and prognosis depend on the histological type of cancer, the stage (degree of spread), and the patient's general well-being, measured by performance status. Common treatments include surgery, chemotherapy, and radiotherapy. NSCLC is sometimes treated with surgery, whereas SCLC usually responds better to chemotherapy and radiotherapy.[9]

Survival depends on stage, overall health, and other factors. Overall, 15% of people in the United States diagnosed with lung cancer survive five years after the diagnosis.[10] 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.[11]

## Classification[edit]

Age-adjusted incidence of lung cancer by histological type[4]
Histological type | Incidence (per 100,000 per year)
--- | ---
All types | 66.9
Adenocarcinoma | 22.1
Squamous-cell carcinoma | 14.4
Small-cell carcinoma | 9.8

Lung cancers are classified according to histological type.[8] This classification has important implications for clinical management and prognosis 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.[12]

### Non-small-cell lung carcinoma[edit]

Micrograph of squamous carcinoma, a type of non-small-cell carcinoma, FNA specimen, Pap stain

The three main subtypes of NSCLC are adenocarcinoma, squamous-cell lung carcinoma, and large-cell lung carcinoma.[2]

Nearly 40% of lung cancers are adenocarcinoma, which usually originates in peripheral lung tissue.[8] Most cases of adenocarcinoma are associated with smoking; however, among people who have smoked fewer than 100 cigarettes in their lifetimes ("never-smokers"),[2] adenocarcinoma is the most common form of lung cancer.[13] A subtype of adenocarcinoma, the bronchioloalveolar carcinoma, is more common in female never-smokers, and may have different responses to treatment.[14]

Squamous-cell carcinoma accounts for about 30% of lung cancers. They typically occur close to large airways. A hollow cavity and associated necrosis are commonly found at the center of the tumor.[8]

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.[8]

### Small-cell lung carcinoma[edit]

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 neuroendocrine hormones), which give this tumor an endocrine/paraneoplastic syndrome association.[15] Most cases arise in the larger airways (primary and secondary bronchi).[10] 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.[2]

### Others[edit]

Four main histological subtypes are recognized, although some cancers may contain a combination of different subtypes.[12] Rare subtypes include glandular tumors, carcinoid tumors, and undifferentiated carcinomas.[2]

### Metastasis[edit]

The lung is a common place for metastasis 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.[16]

Typical immunostaining in lung cancer[2]
Histological type | Immunostain
--- | ---
Squamous-cell carcinoma | CK5/6 positive CK7 negative
Adenocarcinoma | CK7 positive TTF-1 positive
Large-cell carcinoma | TTF-1 negative
Small-cell carcinoma | TTF-1 positive CD56 positive Chromogranin positive Synaptophysin positive

Primary lung cancers themselves most commonly metastasize to the brain, bones, liver, and adrenal glands.[8] Immunostaining of a biopsy is often helpful to determine the original source.[17]

## Signs and symptoms[edit]

See also: List of cutaneous conditions associated with internal malignancy

Symptoms and signs that may suggest lung cancer include:[2]

- coughing
- weight loss
- dyspnea (shortness of breath)
- chest pain
- hemoptysis (coughing up blood)
- bone pain
- clubbing of the fingernails
- fever
- fatigue
- superior vena cava obstruction
- dysphagia (difficulty swallowing)
- wheezing

If the cancer grows in the airway, it may obstruct airflow, causing breathing difficulties. The obstruction can lead to accumulation of secretions behind the blockage, and predispose to pneumonia.[2]

Depending on the type of tumor, so-called paraneoplastic phenomena may initially attract attention to the disease.[18] In lung cancer, these phenomena may include Lambert?Eaton myasthenic syndrome (muscle weakness due to autoantibodies), hypercalcemia, or syndrome of inappropriate antidiuretic hormone (SIADH). Tumors in the top (apex) of the lung, known as Pancoast tumors, may invade the local part of the sympathetic nervous system, leading to Horner's syndrome, as well as damage to the brachial plexus.[2]

Many of the symptoms of lung cancer (poor appetite, weight loss, fever, fatigue) are not specific.[8] 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.[19] About 10% of people with lung cancer do not have symptoms at diagnosis; these cancers are incidentally found on routine chest radiograph.[10]

## Causes[edit]

Cancer develops following genetic damage to DNA. This genetic damage affects 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.[20]

### Smoking[edit]

NIH 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 incidence 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.

Smoking, particularly of cigarettes, is by far the main contributor to lung cancer.[21] Cigarette smoke contains over 60 known carcinogens,[22] including radioisotopes from the radon decay sequence, nitrosamine, and benzopyrene. Additionally, nicotine appears to depress the immune response to malignant growths in exposed tissue.[23] Across the developed world, 90% of lung cancer deaths in men during the year 2000 were attributed to smoking (70% for women).[24] Smoking accounts for 80?90% of lung cancer cases.[2]

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,[25][26] Europe,[27] the UK,[28] and Australia[29] have consistently shown a significantly increased risk among those exposed to passive smoke.[30] 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.[31] Investigations of sidestream smoke suggest it is more dangerous than direct smoke.[32] Passive smoking causes about 3,400 deaths from lung cancer each year in the USA.[26]

### Radon gas[edit]

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.[26] The risk increases 8?16% for every 100 Bq/m? increase in the radon concentration.[33] 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/m?).[34]

### Asbestos[edit]

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.[5] Asbestos can also cause cancer of the pleura, called mesothelioma (which is different from lung cancer).[35]

### Air pollution[edit]

Outdoor air pollution has a small effect on increasing the risk of lung cancer.[4] Fine particulates (PM2.5) and sulfate aerosols, which may be released in traffic exhaust fumes, are associated with slightly increased risk.[4][36] For nitrogen dioxide, an incremental increase of 10 parts per billion increases the risk of lung cancer by 14%.[37] Outdoor air pollution is estimated to account for 1?2% of lung cancers.[4]

### Genetics[edit]

Some people have a genetic predisposition to lung cancer. In relatives of people with lung cancer, the risk is increased 2.4 times. This may be due to genetic polymorphisms.[38]

### Other causes[edit]

Numerous other substances, occupations, and environmental exposures have been linked to the genesis of cancer in lung tissue of humans. In its List of Classifications by Cancer Sites,[39]the International Agency for Research on Lung Cancer (IARC) states there is "sufficient evidence" to show the following are carcinogenic in lung:

- Aluminum production
- Arsenic and inorganic arsenic compounds
- Beryllium and beryllium compounds
- Bis-(chloromethyl) ether
- Methyl ether (technical grade)
- Cadmium and cadmium compounds
- Chromium(VI) compounds
- Coal (indoor emissions from household coal burning)
- Combustion (incomplete)
- Coal gasification
- Coal-tar pitch
- Coke production
- Diesel engine exhaust
- Gamma radiation
- Hematite mining (underground)
- Iron and steel founding
- MOPP (vincristine-prednisone-nitrogen mustard-procarbazine mixture)
- Nickel compounds
- Painting
- Plutonium
- Radon-222 and its decay products
- Rubber production industry
- Silica dust (crystalline)
- Soot
- Sulfur mustard
- X-radiation

## Pathogenesis[edit]

Main article: Carcinogenesis

Similar to many other cancers, lung cancer is initiated by activation of oncogenes or inactivation of tumor suppressor genes.[40] Oncogenes are believed to make people more susceptible to cancer. Proto-oncogenes are believed to turn into oncogenes when exposed to particular carcinogens.[41] Mutations in the K-ras proto-oncogene are responsible for 10?30% of lung adenocarcinomas.[42][43] The epidermal growth factor receptor (EGFR) regulates cell proliferation, apoptosis, angiogenesis, and tumor invasion.[42] 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.[42] 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.[44] Other genes that are often mutated or amplified are c-MET, NKX2-1, LKB1, PIK3CA, and BRAF.[42]

## Diagnosis[edit]

Chest radiograph showing a cancerous tumor in the left lung

Performing a chest radiograph is one of the first investigative steps if a patient reports symptoms that may suggest 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.[1] CT imaging is typically used to provide more information about the type and extent of disease. Bronchoscopy or CT-guided biopsy is often used to sample the tumor for histopathology.[10]

CT scan showing a cancerous tumor in the left lung

Lung cancer often appears as a solitary pulmonary nodule on a chest radiograph. However, the differential diagnosis is wide. Many other diseases can also give this appearance, including tuberculosis, fungal infections, metastatic cancer, or organizing pneumonia. Less common causes of a solitary pulmonary nodule include hamartomas, bronchogenic cysts, adenomas, arteriovenous malformation, pulmonary sequestration, rheumatoid nodules, Wegener's granulomatosis, or lymphoma.[45] Lung cancer can also be an incidental finding, as a solitary pulmonary nodule on a chest radiograph or CT scan taken for an unrelated reason.[46] The definitive diagnosis of lung cancer is based on histological examination of the suspicious tissue in the context of the clinical and radiological features.[2]

### Staging[edit]

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 one of the factors affecting the prognosis and potential treatment of lung cancer.[2]

The initial evaluation of non-small-cell lung cancer (NSCLC) staging uses the TNM classification. This 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 estimate of prognosis.[47] 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).[2] However, the TNM classification and grouping are useful in estimating prognosis.[47]

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 intra- or postoperatively, and is based on the combined results of surgical and clinical findings, including surgical sampling of thoracic lymph nodes.[8]

## Prevention[edit]

See also: Smoking ban

Prevention is the most cost-effective means of mitigating 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.[48]

Policy interventions to decrease passive smoking in public areas such as restaurants and workplaces have become more common in many Western countries.[49] Bhutan has had a complete smoking ban since 2005.[50] India introduced a ban on smoking in public in October 2008.[51]

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.[52]

The long-term use of supplemental vitamin A,[53][54] vitamin C,[53] vitamin D[55] or vitamin E[53] does not reduce the risk of lung cancer. Some studies suggest people who eat diets with a higher proportion of vegetables and fruit tend have a lower risk,[26][56] but this is likely due to confounding. More rigorous studies have not demonstrated a clear association.[56]

### Screening[edit]

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 sputum cytology, chest radiograph (CXR), and computed tomography (CT). Screening programs using CXR or cytology have not demonstrated any benefit.[57] 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%).[58][59] The potential risks of screening however are not well known.[60]

## Treatment[edit]

Main article: Treatment of lung cancer

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 palliative care,[61] surgery, chemotherapy, and radiation therapy.[2]

### Surgery[edit]

Main article: Lung cancer surgery
Pneumonectomy specimen containing a squamous-cell carcinoma, seen as a white area near the bronchi

If investigations confirm NSCLC, the stage must be reassessed 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. CT scan and positron emission tomography (PET) are used.[2] If mediastinal lymph node involvement is suspected, mediastinoscopy may be used to sample the nodes and assist staging.[62]

Blood tests and pulmonary function testing are also necessary to assess whether the patient is well enough for surgery.[10] If pulmonary function tests reveal poor respiratory reserve, surgery may be contraindicated.[2]

In most cases of early-stage NSCLC, removal of a lobe of lung (lobectomy) is the surgical treatment of choice. In patients who are unfit for a full lobectomy, a smaller sublobar excision (wedge resection) may be performed. However, wedge resection has a higher risk of recurrent disease than lobectomy.[63] Radioactive iodine brachytherapy at the margins of wedge excision may reduce the risk of recurrence.[64] Rarely, removal of a whole lung (pneumonectomy) is performed.[63]

Video-assisted thoracoscopic surgery and VATS lobectomy use a minimally invasive approach to lung cancer surgery.[65] VATS lobectomy is equally effective compared to conventional open lobectomy, and with less postoperative illness.[66]

In SCLC, chemotherapy and/or radiotherapy is typically used.[67] However the role of surgery in SCLC is being reconsidered. Surgery might improve outcomes when added to chemotherapy and radiation in early stage SCLC.[68]

### Radiotherapy[edit]

Radiotherapy is often given together with chemotherapy, and may be used with curative intent in patients with NSCLC who are not eligible for surgery. This form of high-intensity radiotherapy is called radical radiotherapy.[69] 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.[70] Postoperative thoracic radiotherapy generally should not be used after curative intent surgery for NSCLC.[71] Some patients with mediastinal N2 lymph node involvement might benefit from post-operative radiotherapy.[72]

For potentially curable SCLC cases, chest radiotherapy is often recommended in addition to chemotherapy.[8]

If cancer growth blocks a short section of bronchus, brachytherapy (localized radiotherapy) may be given directly inside the airway to open the passage.[73] Compared to external beam radiotherapy, brachytherapy allows a reduction in treatment time and reduced radiation exposure to healthcare staff.[74]

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%.[75]

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.[76]

For both NSCLC and SCLC patients, smaller doses of radiation to the chest may be used for symptom control (palliative radiotherapy).[77]

### Chemotherapy[edit]

The chemotherapy regimen depends on the tumor type.[8]

#### Small-cell lung carcinoma[edit]

Even if relatively early stage, SCLC is treated primarily with chemotherapy and radiation.[78] In SCLC, cisplatin and etoposide are most commonly used.[79] Combinations with carboplatin, gemcitabine, paclitaxel, vinorelbine, topotecan, and irinotecan are also used.[80][81]

#### Non-small cell lung carcinoma[edit]

In advanced NSCLC, chemotherapy improves survival and is used as first-line treatment, provided the patient is well enough for the treatment.[82] Typically, two drugs are used, of which one is often platinum-based (either cisplatin or carboplatin). Other commonly used drugs are gemcitabine, paclitaxel and docetaxel.[83]

Advanced NSCLC is often treated with cisplatin or carboplatin, in combination with gemcitabine, paclitaxel, docetaxel, etoposide, or vinorelbine.[84] Recently, pemetrexed has become available.[85]

#### Adjuvant chemotherapy[edit]

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.[86][87] The combination of vinorelbine and cisplatin is more effective than older regimens.[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 NSCLC have been inconclusive.[90]

### Palliative care[edit]

In patients with terminal disease, palliative care or hospice management may be appropriate.[10] These approaches allow additional discussion of treatment options and provide opportunities to arrive at well-considered decisions[91][92] and may avoid unhelpful but expensive care at the end of life.[92]

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.[93] 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.[94][95] The NSCLC Meta-Analyses Collaborative Group recommends if the recipient wants and can tolerate treatment, then chemotherapy should be considered in advanced NSCLC.[82][96]

## Prognosis[edit]

Main articles: Lung cancer staging and Manchester score

Prognosis in lung cancer according to clinical stage[47]
Clinical stage | Five-year survival (%)
--- | ---
Non-small cell lung carcinoma | Small cell lung carcinoma
IA | 50 | 38
IB | 47 | 21
IIA | 36 | 38
IIB | 26 | 18
IIIA | 19 | 13
IIIB | 7 | 9
IV | 2 | 1

Prognostic factors in NSCLC 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%.[97] 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.[98]

Prognosis is generally poor. Of all patients with lung cancer, 15% survive for five years after diagnosis.[1] 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.[8]

For NSCLC, the best prognosis is achieved with complete surgical resection of stage IA disease, with up to 70% five-year survival.[99] For SCLC, the overall five-year survival for patients 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%.[1]

According to data provided by the National Cancer Institute, the median age at diagnosis of lung cancer in the United States is 70 years,[100] and the median age at death is 72 years.[101] In the US, people with medical insurance are more likely to have a better outcome.[102]

## Epidemiology[edit]

Age-standardized death from tracheal, bronchial, and lung cancers per 100,000?inhabitants in 2004[103]

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. 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.[11] The population segment most likely to develop lung cancer is people 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.[104] In the USA, the lifetime risk of developing lung cancer is 8% in men and 6% in women.[2]

For every 3?4 million cigarettes smoked, one lung cancer death occurs.[2][105] The influence of "Big Tobacco" plays a significant role in the smoking culture.[106] Young nonsmokers who see tobacco advertisements are more likely to take up smoking.[107]

The role of passive smoking is increasingly being recognized as a risk factor for lung cancer,[30] leading to policy interventions to decrease undesired exposure of nonsmokers to others' tobacco smoke.[108] Emissions from automobiles, factories, and power plants also pose potential risks.[4]

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.[109] Lung cancer incidence is currently less common in developing countries.[110] With increased smoking in developing countries, the incidence is expected to increase in the next few years, notably in China[111] and India.[112]

From the 1960s, the incidence 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.[113] The incidence of lung adenocarcinoma continues to rise.[114]

## History[edit]

Lung cancer was uncommon before the advent of cigarette smoking; it was not even recognized as a distinct disease until 1761.[115] Different aspects of lung cancer were described further in 1810.[116] 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.[117] Case reports in the medical literature numbered only 374 worldwide in 1912,[118] but a review of autopsies showed the incidence of lung cancer had increased from 0.3% in 1852 to 5.66% in 1952.[119] In Germany in 1929, physician Fritz Lickint recognized the link between smoking and lung cancer,[117] which led to an aggressive antismoking campaign.[120] The British Doctors Study, published in the 1950s, was the first solid epidemiological evidence of the link between lung cancer and smoking.[121] As a result, in 1964 the Surgeon General of the United States recommended smokers should stop smoking.[122]

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.[123] Miners developed a disproportionate amount of lung disease, eventually recognized as lung cancer in the 1870s.[124] Despite this discovery, mining continued into the 1950s, due to the USSR's demand for uranium.[123] Radon was confirmed as a cause of lung cancer in the 1960s.[125]

The first successful pneumonectomy for lung cancer was performed in 1933.[126] Palliative radiotherapy has been used since the 1940s.[127] 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.[128] In 1997, continuous hyperfractionated accelerated radiotherapy was seen as an improvement over conventional radical radiotherapy.[129]

With small-cell lung carcinoma, initial attempts in the 1960s at surgical resection[130] and radical radiotherapy[131] were unsuccessful. In the 1970s, successful chemotherapy regimens were developed.[132]

## References[edit]

1. ^ a b c d "Lung Carcinoma: Tumors of the Lungs". Merck Manual Professional Edition, Online edition. Retrieved 2007-08-15.
2. ^ a b c d e f g h i j k l m n o p q r s t Horn, L; Pao W, Johnson DH (2012). "89". Harrison's Principles of Internal Medicine (18th ed.). McGraw-Hill. ISBN 0-07-174889-X.
3. ^ Thun, MJ; Hannan LM, Adams-Campbell LL et al. (September 2008). "Lung Cancer Occurrence in Never-Smokers: An Analysis of 13 Cohorts and 22 Cancer Registry Studies". PLoS Medicine 5 (9): e185. doi:10.1371/journal.pmed.0050185. PMC 2531137. PMID 18788891.
4. ^ a b c d e f g h Alberg AJ, Samet JM (2010). "46". Murray Nadel's Textbook of Respiratory Medicine (5th ed.). Saunders Elsevier. ISBN 978-1-4160-4710-0.
5. ^ a b O'Reilly, KM; Mclaughlin AM, Beckett WS, Sime PJ (March 2007). "Asbestos-related lung disease". American Family Physician 75 (5): 683?688. PMID 17375514.
6. ^ Carmona, RH (2006-06-27). "The Health Consequences of Involuntary Exposure to Tobacco Smoke: A Report of the Surgeon General". U.S. Department of Health and Human Services. "Secondhand smoke exposure causes disease and premature death in children and adults who do not smoke."
7. ^ "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)."
8. ^ a b c d e f g h i j k Lu, C; Onn A, Vaporciyan AA et al. (2010). "78: Cancer of the Lung". Holland-Frei Cancer Medicine (8th ed.). People's Medical Publishing House. ISBN 9781607950141.
9. ^ Chapman, S; Robinson G, Sradling J, West S (2009). "31". Oxford Handbook of Respiratory Medicine (2nd ed.). Oxford University Press. ISBN 9-780199-545162.
10. ^ a b c d e f Collins, LG; Haines C, Perkel R, Enck RE (January 2007). "Lung cancer: diagnosis and management". American Family Physician (American Academy of Family Physicians) 75 (1): 56?63. PMID 17225705.
11. ^ a b Ferlay, J; Shin HR, Bray F et al. (December 2010). "Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008". International Journal of Cancer 127 (12): 2893?2917. doi:10.1002/ijc.25516. PMID 21351269.
12. ^ a b Maitra, A; Kumar V (2007). Robbins Basic Pathology (8th ed.). Saunders Elsevier. pp. 528?529. ISBN 978-1-4160-2973-1.
13. ^ 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. PMID 17290066.
14. ^ Raz, DJ; He B, Rosell R, Jablons DM (March 2006). "Bronchioloalveolar carcinoma: a review". Clinical Lung Cancer 7 (5): 313?322. doi:10.3816/CLC.2006.n.012. PMID 16640802.
15. ^ Rosti, G; Bevilacqua G, Bidoli P et al. (March 2006). "Small cell lung cancer". Annals of Oncology 17 (Suppl. 2): 5?10. doi:10.1093/annonc/mdj910. PMID 16608983.
16. ^ Seo, JB; Im JG, Goo JM et al. (1 March 2001). "Atypical pulmonary metastases: spectrum of radiologic findings". Radiographics 21 (2): 403?417. PMID 11259704.
17. ^ Tan D, Zander DS (2008). "Immunohistochemistry for Assessment of Pulmonary and Pleural Neoplasms: A Review and Update". Int J Clin Exp Pathol 1 (1): 19?31. PMC 2480532. PMID 18784820.
18. ^ Honnorat, J; Antoine JC (May 2007). "Paraneoplastic neurological syndromes". Orphanet Journal of Rare Diseases (BioMed Central) 2 (1): 22. doi:10.1186/1750-1172-2-22. PMC 1868710. PMID 17480225.
19. ^ Greene, Frederick L. (2002). AJCC cancer staging manual. Berlin: Springer-Verlag. ISBN 0-387-95271-3.
20. ^ Brown, KM; Keats JJ, Sekulic A et al. (2010). "8". Holland-Frei Cancer Medicine (8th ed.). People's Medical Publishing House USA. ISBN 978-1607950141.
21. ^ 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. PMID 9594919.
22. ^ Hecht, S (October 2003). "Tobacco carcinogens, their biomarkers and tobacco-induced cancer". Nature Reviews. Cancer (Nature Publishing Group) 3 (10): 733?744. doi:10.1038/nrc1190. PMID 14570033.
23. ^ Sopori, M (May 2002). "Effects of cigarette smoke on the immune system". Nature Reviews. Immunology 2 (5): 372?7. doi:10.1038/nri803. PMID 12033743.
24. ^ Peto, R; Lopez AD, Boreham J et al. (2006). Mortality from smoking in developed countries 1950?2000: Indirect estimates from National Vital Statistics. Oxford University Press. ISBN 0-19-262535-7.
25. ^ California Environmental Protection Agency (1997). "Health effects of exposure to environmental tobacco smoke. California Environmental Protection Agency". Tobacco Control 6 (4): 346?353. doi:10.1136/tc.6.4.346. PMC 1759599. PMID 9583639.
    * CDC (December 2001). "State-specific prevalence of current cigarette smoking among adults, and policies and attitudes about secondhand smoke?United States, 2000". Morbidity and Mortality Weekly Report (Atlanta, Georgia: CDC) 50 (49): 1101?1106. PMID 11794619. More than one of `|author1=` and `|last=` specified (help)
26. ^ a b c d Alberg, AJ; Samet JM (September 2007). "Epidemiology of lung cancer". Chest (American College of Chest Physicians) 132 (S3): 29S?55S. doi:10.1378/chest.07-1347. PMID 17873159.
27. ^ Jaakkola, MS; Jaakkola JJ (August 2006). "Impact of smoke-free workplace legislation on exposures and health: possibilities for prevention". European Respiratory Journal 28 (2): 397?408. doi:10.1183/09031936.06.00001306. PMID 16880370.
28. ^ Parkin, DM (December 2011). "Tobacco?attributable cancer burden in the UK in 2010". British Journal of Cancer 105 (Suppl. 2): S6?S13. doi:10.1038/bjc.2011.475. PMC 3252064. PMID 22158323.
29. ^ National Health and Medical Research Council (April 1994). The health effects and regulation of passive smoking. Australian Government Publishing Service. Archived from the original on September 29, 2007. Retrieved 2007-08-10.
30. ^ a b Taylor, R; Najafi F, Dobson A (October 2007). "Meta-analysis of studies of passive smoking and lung cancer: effects of study type and continent". International Journal of Epidemiology 36 (5): 1048?1059. doi:10.1093/ije/dym158. PMID 17690135.
31. ^ "Frequently asked questions about second hand smoke". World Health Organization. Retrieved 25 July 2012.
32. ^ Schick, S; Glantz S (December 2005). "Philip Morris toxicological experiments with fresh sidestream smoke: more toxic than mainstream smoke". Tobacco Control 14 (6): 396?404. doi:10.1136/tc.2005.011288. PMC 1748121. PMID 16319363.
33. ^ Schmid K, Kuwert T, Drexler H (March 2010). "Radon in Indoor Spaces: An Underestimated Risk Factor for Lung Cancer in Environmental Medicine". Dtsch Arztebl Int 107 (11): 181?6. doi:10.3238/arztebl.2010.0181. PMC 2853156. PMID 20386676.
34. ^ EPA (October 2006). "Radiation information: radon". EPA. Retrieved 2007-08-11.
35. ^ Davies, RJO; Lee YCG (2010). "18.19.3". Oxford Textbook Medicine (5th ed.). OUP Oxford. ISBN 978-0199204854.
36. ^ 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 Health 23 (4): 243?297. PMID 19235364.
37. ^ Clapp, RW; Jacobs MM, Loechler EL (Jan-Mar 2008). "Environmental and Occupational Causes of Cancer New Evidence, 2005?2007". Reviews on Environmental Health 23 (1): 1?37. PMC 2791455. PMID 18557596.
38. ^ Kern JA, McLennan G (2008). Fishman's Pulmonary Diseases and Disorders (4th ed.). McGraw-Hill. p. 1802. ISBN 0-07-145739-9.
39. ^ http://monographs.iarc.fr/ENG/Classification/Table4.pdf
40. ^ Fong, KM; Sekido Y, Gazdar AF, Minna JD (October 2003). "Lung cancer ? 9: Molecular biology of lung cancer: clinical implications". Thorax (BMJ Publishing Group Ltd.) 58 (10): 892?900. doi:10.1136/thorax.58.10.892. PMC 1746489. PMID 14514947.
41. ^ Salgia, R; Skarin AT (March 1998). "Molecular abnormalities in lung cancer". Journal of Clinical Oncology 16 (3): 1207?1217. PMID 9508209.
42. ^ a b c d Herbst, RS; Heymach JV, Lippman SM (September 2008). "Lung cancer". New England Journal of Medicine 359 (13): 1367?1380. doi:10.1056/NEJMra0802714. PMID 18815398.
43. ^ 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. PMID 16870043.
44. ^ 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. PMID 8598134.
45. ^ Miller, WT (2008). Fishman's Pulmonary Diseases and Disorders (4th ed.). McGraw-Hill. p. 486. ISBN 0-07-145739-9.
46. ^ Kaiser, LR (2008). Fishman's Pulmonary Diseases and Disorders (4th ed.). McGraw-Hill. pp. 1815?1816. ISBN 0-07-145739-9.
47. ^ a b c Rami-Porta, R; Crowley JJ, Goldstraw P (February 2009). "The revised TNM staging system for lung cancer". Annals of Thoracic and Cardiovascular Surgery 15 (1): 4?9. PMID 19262443.
48. ^ Goodman, GE (November 2002). "Lung cancer. 1: prevention of lung cancer". Thorax 57 (11): 994?999. PMC 1746232. PMID 12403886.
49. ^ McNabola, A; Gill LW (February 2009). "The control of environmental tobacco smoke: a policy review". International Journal of Environmental Research and Public Health 6 (2): 741?758. doi:10.3390/ijerph6020741. PMC 2672352. PMID 19440413.
50. ^ Pandey, G (February 2005). "Bhutan's smokers face public ban". BBC. Retrieved 2007-09-07.
51. ^ Pandey, G (2 October 2008). "Indian ban on smoking in public". BBC. Retrieved 2012-04-25.
52. ^ "UN health agency calls for total ban on tobacco advertising to protect young" (Press release). United Nations News service. 30 May 2008.
53. ^ a b c Fabricius, P; Lange P (July?September 2003). "Diet and lung cancer". Monaldi Archives for Chest Disease 59 (3): 207?211. PMID 15065316.
54. ^ Fritz, H; Kennedy D, Fergusson D et al. (2011). "Vitamin A and Retinoid Derivatives for Lung Cancer: A Systematic Review and Meta Analysis". PLoS ONE 6 (6): e21107 Extra `|pages=` or `|at=` (help). doi:10.1371/journal.pone.0021107. PMC 3124481. PMID 21738614.
55. ^ Herr, C; Greulich T, Koczulla RA et al. (March 2011). "The role of vitamin D in pulmonary disease: COPD, asthma, infection, and cancer". Respiratory Research 12 (1): 31. doi:10.1186/1465-9921-12-31. PMC 3071319. PMID 21418564.
56. ^ a b Key, TJ (January 2011). "Fruit and vegetables and cancer risk". British Journal of Cancer 104 (1): 6?11. doi:10.1038/sj.bjc.6606032. PMC 3039795. PMID 21119663.
57. ^ Manser, RL; Irving LB, Stone C et al. (2004). "Screening for lung cancer". Cochrane Database of Systematic Reviews (1): CD001991. doi:10.1002/14651858.CD001991.pub2. PMID 14973979.
58. ^ 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 Surgery 144 (1): 33?38. doi:10.1016/j.jtcvs.2012.05.060. PMID 22710039.
59. ^ 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 Association 307 (22): 2418?2429. doi:10.1001/jama.2012.5521. PMID 22610500.
60. ^ Bach PB, Mirkin JN, Oliver TK, et al. (June 2012). "Benefits and harms of CT screening for lung cancer: a systematic review". JAMA 307 (22): 2418?29. doi:10.1001/jama.2012.5521. PMID 22610500.
61. ^ Ferrell, B; Koczywas M, Grannis F, Harrington A (April 2011). "Palliative care in lung cancer". Surgical Clinics of North America 91 (2): 403?417. doi:10.1016/j.suc.2010.12.003. PMID 21419260.
62. ^ Kaiser LR (2008). Fishman's Pulmonary Diseases and Disorders (4th ed.). McGraw-Hill. pp. 1853?1854. ISBN 0-07-145739-9.
63. ^ a b Kaiser LR (2008). Fishman's Pulmonary Diseases and Disorders (4th ed.). McGraw-Hill. pp. 1855?1856. ISBN 0-07-145739-9.
64. ^ 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 Surgery 22 (1): 32?37. doi:10.1053/j.semtcvs.2010.04.003. PMID 20813314.
65. ^ Alam, N; Flores RM (July?September 2007). "Video-assisted thoracic surgery (VATS) lobectomy: the evidence base". Journal of the Society of Laparoendoscopic Surgeons 11 (3): 368?374. PMC 3015831. PMID 17931521.
66. ^ Rueth, NM; Andrade RS (June 2010). "Is VATS lobectomy better: perioperatively, biologically and oncologically?". Annals of Thoracic Surgery 89 (6): S2107?S2111. doi:10.1016/j.athoracsur.2010.03.020. PMID 20493991.
67. ^ Simon GR, Turrisi A (September 2007). "Management of small cell lung cancer: ACCP evidence-based clinical practice guidelines (2nd edition)". Chest 132 (3 Suppl): 324S?339S. doi:10.1378/chest.07-1385. PMID 17873178.
68. ^ Goldstein, SD; Yang SC (October 2011). "Role of surgery in small cell lung cancer". Surgical Oncology Clinics of North America 20 (4): 769?777. doi:10.1016/j.soc.2011.08.001. PMID 21986271.
69. ^ Arriagada, R; Goldstraw P, Le Chevalier T (2002). Oxford Textbook of Oncology (2nd ed.). Oxford University Press. p. 2094. ISBN 0-19-262926-3.
70. ^ 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. PMID 20399629.
71. ^ 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. PMID 15846628.
72. ^ Le P?choux, C (2011). "Role of postoperative radiotherapy in resected non-small cell lung cancer: a reassessment based on new data". Oncologist 16 (5): 672?681. doi:10.1634/theoncologist.2010-0150. PMC 3228187. PMID 21378080.
73. ^ Cardona, AF; Reveiz L, Ospina EG et al. (April 2008). "Palliative endobronchial brachytherapy for non-small cell lung cancer". Cochrane Database of Systematic Reviews (2): CD004284. doi:10.1002/14651858.CD004284.pub2. PMID 18425900.
74. ^ Ikushima, H (February 2010). "Radiation therapy: state of the art and the future". Journal of Medical Investigation 57 (1?2): 1?11. PMID 20299738.
75. ^ Paumier, A; Cuenca X, Le P?choux C (June 2011). "Prophylactic cranial irradiation in lung cancer". Cancer Treatment Reviews 37 (4): 261?265. doi:10.1016/j.ctrv.2010.08.009. PMID 20934256.
76. ^ Girard, N; Mornex F (October 2011). "Stereotactic radiotherapy for non-small cell lung cancer: From concept to clinical reality. 2011 update". Cancer Radioth?rapie 15 (6?7): 522?526. doi:10.1016/j.canrad.2011.07.241. PMID 21889901.
77. ^ Fairchild, A; Harris K, Barnes E et al. (August 2008). "Palliative thoracic radiotherapy for lung cancer: a systematic review". Journal of Clinical Oncology 26 (24): 4001?4011. doi:10.1200/JCO.2007.15.3312. PMID 18711191.
78. ^ Hann CL, Rudin CM (2008-11-30). "Management of small-cell lung cancer: incremental changes but hope for the future". Oncology (Williston Park) 22 (13): 1486?92. PMID 19133604.
79. ^ Murray, N; Turrisi AT (March 2006). "A review of first-line treatment for small-cell lung cancer". Journal of Thoracic Oncology 1 (3): 270?278. PMID 17409868.
80. ^ Azim, HA; Ganti AK (March 2007). "Treatment options for relapsed small-cell lung cancer". Anticancer drugs 18 (3): 255?261. doi:10.1097/CAD.0b013e328011a547. PMID 17264756.
81. ^ MacCallum, C; Gillenwater HH (July 2006). "Second-line treatment of small-cell lung cancer". Current Oncology Reports 8 (4): 258?264. doi:10.1007/s11912-006-0030-8. PMID 17254525.
82. ^ a b NSCLC Meta-Analyses Collaborative Group (October 2008). "Chemotherapy in Addition to Supportive Care Improves Survival in Advanced Non?Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis of Individual Patient Data From 16 Randomized Controlled Trials". J. Clin. Oncol. 26 (28): 4617?25. doi:10.1200/JCO.2008.17.7162. PMC 2653127. PMID 18678835.
83. ^ Mehra R, Treat J (2008). Fishman's Pulmonary Diseases and Disorders (4th ed.). McGraw-Hill. p. 1876. ISBN 0-07-145739-9.
84. ^ Clegg, A; Scott DA, Hewitson P et al. (January 2002). "Clinical and cost effectiveness of paclitaxel, docetaxel, gemcitabine, and vinorelbine in non-small cell lung cancer: a systematic review". Thorax (BMJ Publishing Group) 57 (1): 20?28. doi:10.1136/thorax.57.1.20. PMC 1746188. PMID 11809985.
85. ^ Fuld AD, Dragnev KH, Rigas JR (June 2010). "Pemetrexed in advanced non-small-cell lung cancer". Expert Opin Pharmacother 11 (8): 1387?402. doi:10.1517/14656566.2010.482560. PMID 20446853.
86. ^ Carbone, DP; Felip E (September 2011). "Adjuvant therapy in non-small cell lung cancer: future treatment prospects and paradigms". Clinical Lung Cancer 12 (5): 261?271. doi:10.1016/j.cllc.2011.06.002. PMID 21831720.
87. ^ a b Le Chevalier, T (October 2010). "Adjuvant chemotherapy for resectable non-small-cell lung cancer: where is it going?". Annals of Oncology 21 (Suppl. 7): vii196?198. doi:10.1093/annonc/mdq376. PMID 20943614.
88. ^ 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 Oncology 2 (5): 377?383. doi:10.1097/01.JTO.0000268669.64625.bb. PMID 17473651.
89. ^ 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. PMID 16870041.
90. ^ 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. ISBN 1-905545-00-2. ISSN 1475-9225.
91. ^ Kelley AS, Meier DE (August 2010). "Palliative care--a shifting paradigm". N. Engl. J. Med. 363 (8): 781?2. doi:10.1056/NEJMe1004139. PMID 20818881.
92. ^ a b Prince-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. PMID 19856592.
93. ^ 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. PMID 7551923.
94. ^ S?renson S, Glimelius B, Nygren P (2001). "A systematic overview of chemotherapy effects in non-small cell lung cancer". Acta Oncol 40 (2?3): 327?39. PMID 11441939.
95. ^ 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 Assess 5 (32): 1?195. PMID 12065068.
96. ^ Non-Small Cell Lung Cancer Collaborative Group (2010). "Chemotherapy and supportive care versus supportive care alone for advanced non-small cell lung cancer". In Burdett, Sarah. Cochrane Database of Systematic Reviews (5): CD007309. doi:10.1002/14651858.CD007309.pub2. PMID 20464750. Unknown parameter `|group=` ignored (help); Unknown parameter `|review=` ignored (help)
97. ^ "Non-Small Cell Lung Cancer Treatment". PDQ for Health Professionals. National Cancer Institute. Retrieved 2008-11-22.
98. ^ "Small Cell Lung Cancer Treatment". PDQ for Health Professionals. National Cancer Institute. 2012. Retrieved 2012-05-16.
99. ^ Spiro, SG (2010). "18.19.1". Oxford Textbook Medicine (5th ed.). OUP Oxford. ISBN 978-0199204854.
100. ^ SEER data (SEER.cancer.gov) Median Age of Cancer Patients at Diagnosis 2002-2003
101. ^ SEER data (SEER.cancer.gov) Median Age of Cancer Patients at Death 2002-2006
102. ^ Slatore, CG; Au DH, Gould MK (November 2010). "An official American Thoracic Society systematic review: insurance status and disparities in lung cancer practices and outcomes". American Journal of Respiratory and Critical Care Medicine 182 (9): 1195?1205. doi:10.1164/rccm.2009-038ST. PMID 21041563.
103. ^ "WHO Disease and injury country estimates". World Health Organization. 2009. Retrieved November 11, 2009.
104. ^ Jemal A, Tiwari RC, Murray T, et al. (2004). "Cancer statistics, 2004". CA Cancer J Clin 54 (1): 8?29. doi:10.3322/canjclin.54.1.8. PMID 14974761.
105. ^ Proctor, RN (March 2012). "The history of the discovery of the cigarette-lung cancer link: evidentiary traditions, corporate denial, global toll". Tobacco Control 21 (2): 87?91. doi:10.1136/tobaccocontrol-2011-050338. PMID 22345227.
106. ^ Lum, KL; Polansky JR, Jackler RK, Glantz SA (October 2008). "Signed, sealed and delivered: "big tobacco" in Hollywood, 1927?1951". Tobacco Control 17 (5): 313?323. doi:10.1136/tc.2008.025445. PMC 2602591. PMID 18818225.
107. ^ Lovato, C; Watts A, Stead LF (October 2011). "Impact of tobacco advertising and promotion on increasing adolescent smoking behaviours". Cochrane Database of Systematic Reviews (10): CD003439. doi:10.1002/14651858.CD003439.pub2. PMID 21975739.
108. ^ Kemp, FB (Jul?Sep 2009). "Smoke free policies in Europe. An overview". Pneumologia 58 (3): 155?158. PMID 19817310.
109. ^ National Cancer Institute; SEER stat fact sheets: Lung and Bronchus. Surveillance Epidemiology and End Results. 2010 [1]
110. ^ "Gender in lung cancer and smoking research" (PDF). World Health Organization. 2004. Retrieved 2007-05-26.
111. ^ Zhang, J; Ou JX, Bai CX (November 2011). "Tobacco smoking in China: prevalence, disease burden, challenges and future strategies". Respirology 16 (8): 1165?1172. doi:10.1111/j.1440-1843.2011.02062.x. PMID 21910781.
112. ^ Behera, D; Balamugesh T (2004). "Lung cancer in India" (PDF). Indian Journal of Chest Diseases and Allied Sciences 46 (4): 269?281. PMID 15515828.
113. ^ Charloux, A; Quoix E, Wolkove N et al. (February 1997). "The increasing incidence of lung adenocarcinoma: reality or artefact? A review of the epidemiology of lung adenocarcinoma". International Journal of Epidemiology 26 (1): 14?23. doi:10.1093/ije/26.1.14. PMID 9126499.
114. ^ Kadara, H; Kabbout M, Wistuba II (January 2012). "Pulmonary adenocarcinoma: a renewed entity in 2011". Respirology 17 (1): 50?65. doi:10.1111/j.1440-1843.2011.02095.x. PMID 22040022.
115. ^ Morgagni, Giovanni Battista (1761). De sedibus et causis morborum per anatomen indagatis. OL 24830495M.
116. ^ Bayle, Gaspard-Laurent (1810). Recherches sur la phthisie pulmonaire (in French). Paris. OL 15355651W.
117. ^ a b Witschi, H (November 2001). "A short history of lung cancer". Toxicological Sciences 64 (1): 4?6. doi:10.1093/toxsci/64.1.4. PMID 11606795.
118. ^ Adler, I (1912). Primary Malignant Growths of the Lungs and Bronchi. New York: Longmans, Green, and Company. OCLC 14783544. OL 24396062M. , cited in Spiro SG, Silvestri GA (2005). "One hundred years of lung cancer". American Journal of Respiratory and Critical Care Medicine 172 (5): 523?529. doi:10.1164/rccm.200504-531OE. PMID 15961694.
119. ^ Grannis, FW. "History of cigarette smoking and lung cancer". smokinglungs.com. Archived from the original on July 18, 2007. Retrieved 2007-08-06.
120. ^ Proctor, R (2000). The Nazi War on Cancer. Princeton University Press. pp. 173?246. ISBN 0-691-00196-0.
121. ^ Doll, R; Hill AB (November 1956). "Lung Cancer and Other Causes of Death in Relation to Smoking". British Medical Journal 2 (5001): 1071?1081. doi:10.1136/bmj.2.5001.1071. PMC 2035864. PMID 13364389.
122. ^ US Department of Health Education and Welfare (1964). "Smoking and health: report of the advisory committee to the Surgeon General of the Public Health Service" (PDF). Washington, DC: US Government Printing Office.
123. ^ a b Greaves, M (2000). Cancer: the Evolutionary Legacy. Oxford University Press. pp. 196?197. ISBN 0-19-262835-6.
124. ^ 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 Hygiene 37 (1): 5?14. PMID 8460878.
125. ^ Samet, JM (April 2011). "Radiation and cancer risk: a continuing challenge for epidemiologists". Environmental Health 10 (Suppl. 1): S4. doi:10.1186/1476-069X-10-S1-S4. PMC 3073196. PMID 21489214.
126. ^ Horn, L; Johnson DH (July 2008). "Evarts A. Graham and the first pneumonectomy for lung cancer". Journal of Clinical Oncology 26 (19): 3268?3275. doi:10.1200/JCO.2008.16.8260. PMID 18591561.
127. ^ Edwards, AT (1946). "Carcinoma of the Bronchus". Thorax 1 (1): 1?25. doi:10.1136/thx.1.1.1. PMC 1018207. PMID 20986395.
128. ^ Kabela, M (1956). "Erfahrungen mit der radikalen R?ntgenbestrahlung des Bronchienkrebses" [Experience with radical irradiation of bronchial cancer]. Ceskoslovensk? Onkol?gia (in German) 3 (2): 109?115. PMID 13383622.
129. ^ 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. PMID 9250182.
130. ^ 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. PMID 4176258.
131. ^ 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. PMID 4184834.
132. ^ Cohen, M; Creaven PJ, Fossieck BE Jr et al. (1977). "Intensive chemotherapy of small cell bronchogenic carcinoma". Cancer Treatment Reports 61 (3): 349?354. PMID 194691.

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Tumors: Mediastinal tumors/Thoracic neoplasm/respiratory neoplasia (C30–C34/D14, 160–163/212.0–212.4)
Upper RT | Nasal cavity Esthesioneuroblastoma Nasopharynx Nasopharyngeal carcinoma Nasopharyngeal angiofibroma Larynx Laryngeal cancer Laryngeal papillomatosis
Lower RT |
Trachea | Tracheal tumor
Lung |
Non-small-cell lung carcinoma | Squamous cell carcinoma Adenocarcinoma of the lung (Mucinous cystadenocarcinoma) Large-cell lung carcinoma Rhabdoid carcinoma Sarcomatoid carcinoma Carcinoid Salivary gland-like carcinoma of the lung Adenosquamous carcinoma Papillary adenocarcinoma Giant cell carcinoma
Small-cell carcinoma | Combined small-cell carcinoma
Non-carcinoma | Sarcoma Lymphoma Immature teratoma Melanoma
By location | Pancoast tumor Solitary pulmonary nodule Central lung Peripheral lung
Pleura | Mesothelioma Malignant solitary fibrous tumor
M: RES | anat (n, x, l, c)/phys/devp | noco (c, p)/cong/tumr, sysi/epon, injr | proc, drug (R1/2/3/5/6/7)