Wednesday, 15 April 2009

Lung cancer

Lung cancer is a disease of uncontrolled cell growth in tissues of the lung. This growth may lead to metastasis, which is the invasion of adjacent tissue and infiltration beyond the lungs. The vast majority of primary lung cancers are carcinomas of the lung, derived from epithelial cells. Lung cancer, the most common cause of cancer-related death in men and the second most common in women (after breast cancer),[1] is responsible for 1.3 million deaths worldwide annually.[2] The most common symptoms are shortness of breath, coughing (including coughing up blood), and weight loss.[3]

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

Lung cancer may be seen on chest radiograph and computed tomography (CT scan). The diagnosis is confirmed with a biopsy. This is usually performed via bronchoscopy or CT-guided biopsy. Treatment and prognosis depend upon the histological type of cancer, the stage (degree of spread), and the patient's performance status. Possible treatments include surgery, chemotherapy, and radiotherapy. With treatment, the five-year survival rate is 14%.[3]


Classification

The vast majority of lung cancers are carcinomas—malignancies that arise from epithelial cells. There are two main types of lung carcinoma, categorized by the size and appearance of the malignant cells seen by a histopathologist under a microscope: non-small cell (80.4%) and small-cell (16.8%) lung carcinoma.[16] This classification, based on histological criteria, has important implications for clinical management and prognosis of the disease.

Frequency of histological types of lung cancer[16]
Histological type Frequency (%)
Non-small cell lung carcinoma 80.4
Small cell lung carcinoma 16.8
Carcinoid[17] 0.8
Sarcoma[18] 0.1
Unspecified lung cancer 1.9

Non-small cell lung carcinoma (NSCLC)

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

Sub-types of non-small cell lung cancer in
smokers and never-smokers[19]
Histological sub-type Frequency of non-small cell lung cancers (%)
Smokers Never-smokers
Squamous cell lung carcinoma 42 33
Adenocarcinoma Adenocarcinoma (not otherwise specified) 39 35
Bronchioloalveolar carcinoma 4 10
Carcinoid 7 16
Other 8 6

Accounting for 31.2% of lung cancers,[16] squamous cell lung carcinoma usually starts near a central bronchus. Cavitation and necrosis within the center of the cancer is a common finding. Well-differentiated squamous cell lung cancers often grow more slowly than other cancer types.[4]

Adenocarcinoma accounts for 29.4% of lung cancers.[16] It usually originates in peripheral lung tissue. Most cases of adenocarcinoma are associated with smoking; however, among people who have never smoked ("never-smokers"), adenocarcinoma is the most common form of lung cancer.[20] A subtype of adenocarcinoma, the bronchioloalveolar carcinoma, is more common in female never-smokers, and may have different responses to treatment.[21]

Small cell lung carcinoma (SCLC)

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

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

Others

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

Secondary cancers

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

Primary lung cancers themselves most commonly metastasize to the adrenal glands, liver, brain, and bone.[4]

Staging

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

Signs and symptoms

Symptoms that suggest lung cancer include:[28]

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

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

Many of the symptoms of lung cancer (bone pain, fever, and weight loss) are nonspecific; in the elderly, these may be attributed to comorbid illness.[4] In many patients, the cancer has already spread beyond the original site by the time they have symptoms and seek medical attention. Common sites of metastasis include the brain, bone, adrenal glands, contralateral (opposite) lung, liver, pericardium, and kidneys.[31] About 10% of people with lung cancer do not have symptoms at diagnosis; these cancers are incidentally found on routine chest radiograph.[3]

Causes

The main causes of lung cancer (and cancer in general) include carcinogens (such as those in tobacco smoke), ionizing radiation, and viral infection. This exposure causes cumulative changes to the DNA in the tissue lining the bronchi of the lungs (the bronchial epithelium). As more tissue becomes damaged, eventually a cancer develops.[4]

Smoking

The incidence of lung cancer is highly correlated with smoking. Source: NIH.

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

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

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

Radon gas

Radon is a colorless and odorless gas generated by the breakdown of radioactive radium, which in turn is the decay product of uranium, found in the Earth's crust. The radiation decay products ionize genetic material, causing mutations that sometimes turn cancerous. Radon exposure is the second major cause of lung cancer, after smoking.[9] Radon gas levels vary by locality and the composition of the underlying soil and rocks. For example, in areas such as Cornwall in the UK (which has granite as substrata), radon gas is a major problem, and buildings have to be force-ventilated with fans to lower radon gas concentrations. The United States Environmental Protection Agency (EPA) estimates that one in 15 homes in the U.S. has radon levels above the recommended guideline of 4 picocuries per liter (pCi/L) (148 Bq/m³).[46] Iowa has the highest average radon concentration in the United States; studies performed there have demonstrated a 50% increased lung cancer risk, with prolonged radon exposure above the EPA's action level of 4 pCi/L.[47][48]

Asbestos

Asbestos can cause a variety of lung diseases, including lung cancer. There is a synergistic effect between tobacco smoking and asbestos in the formation of lung cancer.[10] In the UK, asbestos accounts for 2–3% of male lung cancer deaths.[49] Asbestos can also cause cancer of the pleura, called mesothelioma (which is different from lung cancer).

Viruses

Viruses are known to cause lung cancer in animals,[50][51] and recent evidence suggests similar potential in humans. Implicated viruses include human papillomavirus,[52] JC virus,[53] simian virus 40 (SV40), BK virus, and cytomegalovirus.[54] These viruses may affect the cell cycle and inhibit apoptosis, allowing uncontrolled cell division.

Genetics

Similar to many other cancers, lung cancer is initiated by activation of oncogenes or inactivation of tumor suppressor genes.[55] Oncogenes are genes that are believed to make people more susceptible to cancer. Proto-oncogenes are believed to turn into oncogenes when exposed to particular carcinogens.[56] Mutations in the K-ras proto-oncogene are responsible for 10–30% of lung adenocarcinomas.[57][58] The epidermal growth factor receptor (EGFR) regulates cell proliferation, apoptosis, angiogenesis, and tumor invasion.[57] 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.[57] 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.[59] Other genes that are often mutated or amplified are c-MET, NKX2-1, LKB1, PIK3CA, and BRAF.[57]

Several genetic polymorphisms are associated with lung cancer. These include polymorphisms in genes coding for interleukin-1,[60] cytochrome P450,[61] apoptosis promoters such as caspase-8,[62] and DNA repair molecules such as XRCC1.[63] People with these polymorphisms are more likely to develop lung cancer after exposure to carcinogens.

A recent study suggested that the MDM2 309G allele is a low-penetrant risk factor for developing lung cancer in Asians.[64]

Diagnosis

Chest radiograph showing a cancerous tumor in the left lung.

Performing a chest radiograph is the first step if a patient reports symptoms that may be suggestive of lung cancer. This may reveal an obvious mass, widening of the mediastinum (suggestive of spread to lymph nodes there), atelectasis (collapse), consolidation (pneumonia), or pleural effusion. If there are no radiographic findings but the suspicion is high (such as a heavy smoker with blood-stained sputum), bronchoscopy and/or a CT scan may provide the necessary information. Bronchoscopy or CT-guided biopsy is often used to identify the tumor type.[3]

Sputum atypia is associated with an increased risk of lung cancer. Sputum cytologic examination combined with other screening examinations may play an important role in the early detection of lung cancer.[65]

CT scan showing a cancerous tumor in the left lung.

The differential diagnosis for patients who present with abnormalities on chest radiograph includes lung cancer as well as nonmalignant diseases. These include infectious causes such as tuberculosis or pneumonia, or inflammatory conditions such as sarcoidosis. These diseases can result in mediastinal lymphadenopathy or lung nodules, and sometimes mimic lung cancers.[4] Lung cancer can also be an incidental finding: a solitary pulmonary nodule (also called a coin lesion) on a chest radiograph or CT scan taken for an unrelated reason.

Prevention

Prevention is the most cost-effective means of fighting lung cancer. While in most countries industrial and domestic carcinogens have been identified and banned, tobacco smoking is still widespread. Eliminating tobacco smoking is a primary goal in the prevention of lung cancer, and smoking cessation is an important preventative tool in this process.[66] Most importantly, are prevention programs that target the youth. In 1998 the Master Settlement Agreement entitled 46 states in the USA to an annual payout from the tobacco companies.[67] Between the settlement money and tobacco taxes, each state's public health department funds their prevention programs, although none of the states are living up to the Center for Disease Control's recommended amount by spending 15 percent of tobacco taxes and settlement revenues on these prevention efforts.[67]

Policy interventions to decrease passive smoking in public areas such as restaurants and workplaces have become more common in many Western countries, with California taking a lead in banning smoking in public establishments in 1998. Ireland played a similar role in Europe in 2004, followed by Italy and Norway in 2005, Scotland as well as several others in 2006, England in 2007, and France in 2008. New Zealand has banned smoking in public places as of 2004. The state of Bhutan has had a complete smoking ban since 2005.[68] In many countries, pressure groups are campaigning for similar bans. In 2007, Chandigarh became the first city in India to become smoke-free. India introduced a total ban on smoking at public places on Oct 2 2008.

Arguments cited against such bans are criminalisation of smoking, increased risk of smuggling, and the risk that such a ban cannot be enforced.[69]

A 2008 study performed in over 75,000 middle-aged and elderly people demonstrated that the long-term use of supplemental multivitamins—such as vitamin C, vitamin E, and folate—did not reduce the risk of lung cancer. To the contrary, the study indicates that the long-term intake of high doses of vitamin E supplements may even increase the risk of lung cancer.[70]

The World Health Organization has called for governments to institute a total ban on tobacco advertising in order to prevent young people from taking up smoking. They assess that such bans have reduced tobacco consumption by 16% where already instituted.[71]

Screening

Screening refers to the use of medical tests to detect disease in asymptomatic people. Possible screening tests for lung cancer include chest radiograph or computed tomography (CT) of the chest. So far, screening programs for lung cancer have not demonstrated any clear benefit. Randomized controlled trials are underway in this area to see if decreased long-term mortality can be directly observed from CT screening.[72]

Treatment

Treatment for lung cancer depends on the cancer's specific cell type, how far it has spread, and the patient's performance status. Common treatments include surgery, chemotherapy, and radiation therapy.[3][73]

Surgery

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

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

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

Surgery itself has an operative death rate of about 4.4%, depending on the patient's lung function and other risk factors.[74] Surgery is usually only an option in non-small cell lung carcinoma limited to one lung, up to stage IIIA. This is assessed with medical imaging (computed tomography, positron emission tomography). A sufficient preoperative respiratory reserve must be present to allow adequate lung function after the tissue is removed.

Procedures include wedge resection (removal of part of a lobe), segmentectomy (removal of an anatomic division of a particular lobe of the lung), lobectomy (one lobe), bilobectomy (two lobes), or pneumonectomy (whole lung). In patients with adequate respiratory reserve, lobectomy is the preferred option, as this minimizes the chance of local recurrence. If the patient does not have enough functional lung for this, wedge resection may be performed.[75] Radioactive iodine brachytherapy at the margins of wedge excision may reduce recurrence to that of lobectomy.[76]

Chemotherapy

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

The combination regimen depends on the tumor type. Non-small cell lung carcinoma is often treated with cisplatin or carboplatin, in combination with gemcitabine, paclitaxel, docetaxel, etoposide, or vinorelbine.[77] In small cell lung carcinoma, cisplatin and etoposide are most commonly used.[78] Combinations with carboplatin, gemcitabine, paclitaxel, vinorelbine, topotecan, and irinotecan are also used.[79][80] in extensive-stage small-cell lung cancer celecoxib may safely be combined with etoposide, this combination showed improve outcomes.[81]

Adjuvant chemotherapy for NSCLC

Adjuvant chemotherapy refers to the use of chemotherapy after surgery to improve the outcome. During surgery, samples are taken from the lymph nodes. If these samples contain cancer, the patient has stage II or III disease. In this situation, adjuvant chemotherapy may improve survival by up to 15%.[82][83] Standard practice is to offer platinum-based chemotherapy (including either cisplatin or carboplatin).[84]

Adjuvant chemotherapy for patients with stage IB cancer is controversial, as clinical trials have not clearly demonstrated a survival benefit.[85][86] Trials of preoperative chemotherapy (neoadjuvant chemotherapy) in resectable non-small cell lung carcinoma have been inconclusive.[87]

Radiotherapy

Radiotherapy is often given together with chemotherapy, and may be used with curative intent in patients with non-small cell lung carcinoma who are not eligible for surgery. This form of high intensity radiotherapy is called radical radiotherapy.[88] 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.[89] For small cell lung carcinoma cases that are potentially curable, chest radiation is often recommended in addition to chemotherapy.[90] The use of adjuvant thoracic radiotherapy following curative intent surgery for non-small cell lung carcinoma is not well established and is controversial. Benefits, if any, may only be limited to those in whom the tumor has spread to the mediastinal lymph nodes.[91][92]

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

Brachytherapy (localized radiotherapy) may be given directly inside the airway when cancer affects a short section of bronchus.[93] It is used when inoperable lung cancer causes blockage of a large airway.[94]

Patients with limited stage small cell lung carcinoma are usually given prophylactic cranial irradiation (PCI). This is a type of radiotherapy to the brain, used to reduce the risk of metastasis.[95] More recently, PCI has also been shown to be beneficial in those with extensive small cell lung cancer. In patients whose cancer has improved following a course of chemotherapy, PCI has been shown to reduce the cumulative risk of brain metastases within one year from 40.4% to 14.6%.[96]

Recent improvements in targeting and imaging have led to the development of extracranial stereotactic radiation in the treatment of early-stage lung cancer. In this form of radiation therapy, very high doses are delivered in a small number of sessions using stereotactic targeting techniques. Its use is primarily in patients who are not surgical candidates due to medical comorbidities.[97]

Interventional radiology

Radiofrequency ablation should currently be considered an investigational technique in the treatment of bronchogenic carcinoma. It is done by inserting a small heat probe into the tumor to kill the tumor cells.[98]

Targeted therapy

In recent years, various molecular targeted therapies have been developed for the treatment of advanced lung cancer. Gefitinib (Iressa) is one such drug, which targets the tyrosine kinase domain of the epidermal growth factor receptor (EGF-R), expressed in many cases of non-small cell lung carcinoma. It was not shown to increase survival, although females, Asians, nonsmokers, and those with bronchioloalveolar carcinoma appear to derive the most benefit from gefitinib.[21][99]

Erlotinib (Tarceva), another tyrosine kinase inhibitor, has been shown to increase survival in lung cancer patients[100] and has recently been approved by the FDA for second-line treatment of advanced non-small cell lung carcinoma. Similar to gefitinib, it also appeared to work best in females, Asians, nonsmokers, and those with bronchioloalveolar carcinoma.[99]

The angiogenesis inhibitor bevacizumab, (in combination with paclitaxel and carboplatin), improves the survival of patients with advanced non-small cell lung carcinoma.[101] However, this increases the risk of lung bleeding, particularly in patients with squamous cell carcinoma.

Advances in cytotoxic drugs,[102] pharmacogenetics[103] and targeted drug design[104] show promise. A number of targeted agents are at the early stages of clinical research, such as cyclo-oxygenase-2 inhibitors,[105] the apoptosis promoter exisulind,[106] proteasome inhibitors,[107] bexarotene,[108] and vaccines.[109] Future areas of research include ras proto-oncogene inhibition, phosphoinositide 3-kinase inhibition, histone deacetylase inhibition, and tumor suppressor gene replacement.[110]

Prognosis

Prognostic factors in non-small cell lung cancer include presence or absence of pulmonary symptoms, tumor size, cell type (histology), degree of spread (stage) and metastases to multiple lymph nodes, and vascular invasion. For patients with inoperable disease, prognosis is adversely affected by poor performance status and weight loss of more than 10%.[111] 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.[112]

For non-small cell lung carcinoma, prognosis is generally poor. Following complete surgical resection of stage IA disease, five-year survival is 67%. With stage IB disease, five-year survival is 57%.[113] The five-year survival rate of patients with stage IV NSCLC is about 1%.[5]

For small cell lung carcinoma, prognosis is also generally poor. The overall five-year survival for patients with SCLC is about 5%.[3] 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%.[5]

According to data provided by the National Cancer Institute, the median age of incidence of lung cancer is 70 years, and the median age of death by lung cancer is 71 years.[114]

Epidemiology

Lung cancer distribution in the United States

Worldwide, lung cancer is the most common cancer in terms of both incidence and mortality (1.35 million new cases per year and 1.18 million deaths), with the highest rates in Europe and North America.[115] The population segment most likely to develop lung cancer is over-fifties who have a history of smoking. Lung cancer is the second most commonly occurring form of cancer in most Western countries, and it is the leading cancer-related cause of death. Although the rate of men dying from lung cancer is declining in Western countries, it is increasing for women, due to the increased takeup of smoking by this group. The evolution of "Big Tobacco" plays a significant role in the smoking culture.[116] Tobacco companies have focused their efforts since the 1970s at marketing their product toward women and girls, especially with "light" and "low-tar" cigarettes [1]. Among lifetime nonsmokers, men have higher age-standardized lung cancer death rates than women.

Not all cases of lung cancer are due to smoking, but the role of passive smoking is increasingly being recognized as a risk factor for lung cancer—leading to policy interventions to decrease undesired exposure of nonsmokers to others' tobacco smoke. Emissions from automobiles, factories, and power plants also pose potential risks.[11][13][117]

Eastern Europe has the highest lung cancer mortality among men, while northern Europe and the U.S. have the highest mortality among women. Lung cancer incidence is currently less common in developing countries.[118] With increased smoking in developing countries, the incidence is expected to increase in the next few years, notably in China[119] and India.[120]

Lung cancer incidence (by country) has an inverse correlation with sunlight and UVB exposure. One possible explanation is a preventative effect of vitamin D (which is produced in the skin on exposure to sunlight).[121]

From the 1950s, the incidence of lung adenocarcinoma started to rise relative to other types of lung cancer.[122] 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.[123] The incidence of lung adenocarcinoma in the U.S. has fallen since 1999. This may be due to reduction in environmental air pollution.[122]

History

Lung cancer was uncommon before the advent of cigarette smoking; it was not even recognized as a distinct disease until 1761.[124] Different aspects of lung cancer were described further in 1810.[125] 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.[126] Case reports in the medical literature numbered only 374 worldwide in 1912,[127] but a review of autopsies showed that the incidence of lung cancer had increased from 0.3% in 1852 to 5.66% in 1952.[128] In Germany in 1929, physician Fritz Lickint recognized the link between smoking and lung cancer,[126] which led to an aggressive antismoking campaign.[129] The British Doctors Study, published in the 1950s, was the first solid epidemiological evidence of the link between lung cancer and smoking.[130] As a result, in 1964 the Surgeon General of the United States recommended that smokers should stop smoking.[131]

The connection with radon gas was first recognized among miners in the Ore Mountains near Schneeberg, Saxony. Silver has been mined there since 1470, and these mines are rich in uranium, with its accompanying radium and radon gas. Miners developed a disproportionate amount of lung disease, eventually recognized as lung cancer in the 1870s. An estimated 75% of former miners died from lung cancer.[132] Despite this discovery, mining continued into the 1950s, due to the USSR's demand for uranium.[133]

The first successful pneumonectomy for lung cancer was performed in 1933.[134] Palliative radiotherapy has been used since the 1940s.[135] 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.[136] In 1997, continuous hyperfractionated accelerated radiotherapy (CHART) was seen as an improvement over conventional radical radiotherapy.[89]

With small cell lung carcinoma, initial attempts in the 1960s at surgical resection[137] and radical radiotherapy[138] were unsuccessful. In the 1970s, successful chemotherapy regimens were developed.[139]

References

  1. ^ WHO (2004). "Deaths by cause, sex and mortality stratum" (PDF). World Health Organization. http://www.who.int/whr/2004/annex/topic/en/annex_2_en.pdf. Retrieved on 2008-12-25.
  2. ^ WHO (February 2006). "Cancer". World Health Organization. http://www.who.int/mediacentre/factsheets/fs297/en/. Retrieved on 2007-06-25.
  3. ^ a b c d e f Minna, JD; Schiller JH (2008). Harrison's Principles of Internal Medicine (17th ed.). McGraw-Hill. pp. 551–562. ISBN 0-07-146633-9.
  4. ^ a b c d e f Vaporciyan, AA; Nesbitt JC, Lee JS et al. (2000). Cancer Medicine. B C Decker. pp. 1227–1292. ISBN 1-55009-113-1.
  5. ^ a b c "Lung Carcinoma: Tumors of the Lungs". Merck Manual Professional Edition, Online edition. http://www.merck.com/mmpe/sec05/ch062/ch062b.html#sec05-ch062-ch062b-1405. Retrieved on 2007-08-15.
  6. ^ Thun, MJ; Hannan LM, Adams-Campbell LL et al. (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.005018510.1002/ijc.22615.
  7. ^ Gorlova, OY; Weng SF, Zhang Y et al. (July 2007). "Aggregation of cancer among relatives of never-smoking lung cancer patients". International Journal of Cancer 121 (1): 111–118. doi:10.1002/ijc.22615. PMID 17304511.
  8. ^ Hackshaw, AK; Law MR, Wald NJ (1997-10-18). "The accumulated evidence on lung cancer and environmental tobacco smoke". British Medical Journal 315 (7114): 980–988. PMID 9365295. http://www.bmj.com/cgi/content/full/315/7114/980.
  9. ^ a b Catelinois O, Rogel A, Laurier D, et al (September 2006). "Lung cancer attributable to indoor radon exposure in france: impact of the risk models and uncertainty analysis". Environ. Health Perspect. 114 (9): 1361–6. doi:0.1289/ehp.9070. PMID 16966089. PMC: 1570096. http://www.ehponline.org/members/2006/9070/9070.html.
  10. ^ 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. http://www.aafp.org/afp/20070301/683.html.
  11. ^ a b Kabir, Z; Bennett K, Clancy L (February 2007). "Lung cancer and urban air-pollution in dublin: a temporal association?". Irish Medical Journal 100 (2): 367–369. PMID 17432813.
  12. ^ Coyle, YM; Minahjuddin AT, Hynan LS, Minna JD (September 2006). "An ecological study of the association of metal air pollutants with lung cancer incidence in Texas.". Journal of Thoracic Oncology 1 (7): 654–661. PMID 17409932.
  13. ^ a b Chiu, HF; Cheng MH, Tsai SS et al. (December 2006). "Outdoor air pollution and female lung cancer in Taiwan.". Inhalation Toxicology 18 (13): 1025–1031. doi:10.1080/08958370600904561. PMID 16966302.
  14. ^ 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. http://www.surgeongeneral.gov/library/secondhandsmoke. "Secondhand smoke exposure causes disease and premature death in children and adults who do not smoke."
  15. ^ "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. http://monographs.iarc.fr/ENG/Monographs/vol83/volume83.pdf. "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).".
  16. ^ a b c d Travis, WD; Travis LB, Devesa SS (January 1995). "Lung cancer". Cancer 75 (Suppl. 1): 191–202. doi:10.1002/1097-0142(19950101)75:1 <191::aid-cncr2820751307>3.0.CO;2-Y. PMID 8000996.
  17. ^ Morandi, U; Casali C, Rossi G (2006). "Bronchial typical carcinoid tumors". Seminars in Thoracic and Cardiovascular Surgery 18 (3): 191–198. doi:10.1053/j.semtcvs.2006.08.005. PMID 17185178.
  18. ^ Etienne-Mastroianni, B; Falchero L, Chalabreysse L et al. (December 2002). "Primary sarcomas of the lung: a clinicopathologic study of 12 cases". Lung Cancer 38 (3): 283–289. doi:10.1016/S0169-5002(02)00303-3. PMID 12445750.
  19. ^ Bryant, A; Cerfolio RJ (July 2007). "Differences in epidemiology, histology, and survival between cigarette smokers and never-smokers who develop non-small cell lung cancer". Chest 132 (1): 198–192. doi:10.1378/chest.07-0442. PMID 17573517. http://www.chestjournal.org/cgi/content/full/132/1/185.
  20. ^ 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.
  21. ^ a b Raz, DJ; He B, Rosell R, Jablons DM (March 2006). "Bronchioloalveolar carcinoma: a review". Clinical Lung Cancer (Cancer Information Group) 7 (5): 313–322. doi:10.3816/CLC.2006.n.012. PMID 16640802.
  22. ^ a b 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. http://www.aafp.org/afp/20070101/56.html.
  23. ^ 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. http://annonc.oxfordjournals.org/cgi/reprint/17/suppl_2/ii5.
  24. ^ Barbone, F; Bovenzi M, Cavallieri F, Stanta G (December 1997). "Cigarette smoking and histologic type of lung cancer in men" (PDF). Chest (American College of Chest Physicians) 112 (6): 1474–1479. doi:10.1378/chest.112.6.1474. PMID 9404741. http://www.chestjournal.org/cgi/reprint/112/6/1474.
  25. ^ a b Dishop MK, Kuruvilla S (July 2008). "Primary and metastatic lung tumors in the pediatric population: a review and 25-year experience at a large children's hospital". Arch. Pathol. Lab. Med. 132 (7): 1079–103. PMID 18605764. http://journals.allenpress.com/jrnlserv/?request=get-abstract&issn=0003-9985&volume=132&page=1079.
  26. ^ Seo, JB; Im JG, Goo JM et al. (03/01/2001). "Atypical pulmonary metastases: spectrum of radiologic findings". Radiographics 21 (2): 403–417. PMID 11259704. http://radiographics.rsnajnls.org/cgi/content/full/21/2/403.
  27. ^ Mountain, CF; Libshitz HI, Hermes KE (2003). A Handbook for Staging, Imaging, and Lymph Node Classification. Charles P Young. http://www.ctsnet.org/book/mountain/index.html. Retrieved on 2007-09-01.
  28. ^ Hamilton, W; Peters TJ, Round A, Sharp D (December 2005). "What are the clinical features of lung cancer before the diagnosis is made? A population based case-control study". Thorax (BMJ Publishing Group) 60 (12): 1059–1065. doi:10.1136/thx.2005.045880. PMID 16227326.
  29. ^ Honnorat, J; Antoine JC (May 2007). "Paraneoplastic neurological syndromes". Orphanet Journal of Rare Diseases (BioMed Central) 2: 22. doi:10.1186/1750-1172-2-22. PMID 17480225. http://www.ojrd.com/content/2/1/22.
  30. ^ Jones, DR; Detterbeck FC (July 1998). "Pancoast tumors of the lung". Current Opinion in Pulmonary Medicine 4 (4): 191–197. doi:10.1097/00063198-199807000-00001. PMID 10813231.
  31. ^ Greene, Frederick L. (2002). AJCC cancer staging manual. Berlin: Springer-Verlag. ISBN 0-387-95271-3.
  32. ^ 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 48 (3): 167–176; discussion 164–166. doi:10.3322/canjclin.48.3.167. PMID 9594919. http://caonline.amcancersoc.org/cgi/pmidlookup?view=long&pmid=9594919.
  33. ^ 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. http://www.ctsu.ox.ac.uk/~tobacco/.
  34. ^ Samet, JM; Wiggins CL, Humble CG, Pathak DR (May 1988). "Cigarette smoking and lung cancer in New Mexico". American Review of Respiratory Disease 137 (5): 1110–1113. PMID 3264122.
  35. ^ Villeneuve, PJ; Mao Y (November 1994). "Lifetime probability of developing lung cancer, by smoking status, Canada". Canadian Journal of Public Health 85 (6): 385–388. PMID 7895211.
  36. ^ 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. http://www.nature.com/nrc/journal/v3/n10/abs/nrc1190_fs.html;jsessionid=A78B217DFCAD36DD965F2DBA685CF121.
  37. ^ 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.
  38. ^ US Department of Health and Human Services (1990-09-30) (PDF), The Health Benefits of Smoking Cessation: a Report of the Surgeon General, Centers for Disease Control (CDC), Office on Smoking and Health., pp. vi, 130, 148, 152, 155, 164, 166, http://profiles.nlm.nih.gov/NN/B/B/C/T/_/nnbbct.pdf, retrieved on 2007-11-18
  39. ^ Nordquist, LT; Simon GR, Cantor A et al. (August 2004). "Improved survival in never-smokers vs current smokers with primary adenocarcinoma of the lung". Chest (American College of Chest Physicians) 126 (2): 347–351. doi:10.1378/chest.126.2.347. PMID 15302716. http://www.chestjournal.org/cgi/content/full/126/2/347.
  40. ^ Tammemagi, CM; Neslund-Dudas C, Simoff M, Kvale P (January 2004). "Smoking and lung cancer survival: the role of comorbidity and treatment". Chest (American College of Chest Physicians) 125 (1): 27–37. doi:10.1378/chest.125.1.27. PMID 14718417. http://www.chestjournal.org/cgi/content/full/125/1/27.
  41. ^ CDC (December 1986). "1986 Surgeon General's report: the health consequences of involuntary smoking". CDC. http://www.cdc.gov/mmwr/preview/mmwrhtml/00000837.htm. Retrieved on 2007-08-10.
    * National Research Council (1986). Environmental tobacco smoke: measuring exposures and assessing health effects. National Academy Press. ISBN 0-309-07456-8. http://www.nap.edu/catalog.php?record_id=943#toc.
    * EPA (1992). Respiratory health effects of passive smoking: lung cancer and other disorders. EPA. http://cfpub2.epa.gov/ncea/cfm/recordisplay.cfm?deid=2835. Retrieved on 2007-08-10.
    * California Environmental Protection Agency (1997). "Health effects of exposure to environmental tobacco smoke". Tobacco Control 6 (4): 346–353. PMID 9583639. http://www.druglibrary.org/schaffer/tobacco/caets/ets-main.htm.
    * 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. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5049a1.htm.
    * Alberg, AJ; Samet JM (January 2003). "Epidemiology of lung cancer". Chest (American College of Chest Physicians) 123 (S1): 21S–49S. doi:10.1378/chest.123.1_suppl.21S. PMID 12527563. http://www.chestjournal.org/cgi/content/full/123/1_suppl/21S.
  42. ^ Boffetta, P; Agudo A, Ahrens W et al. (October 1998). "Multicenter case-control study of exposure to environmental tobacco smoke and lung cancer in Europe". Journal of the National Cancer Institute (Oxford University Press) 90 (19): 1440–1450. doi:10.1093/jnci/90.19.1440. PMID 9776409. http://jnci.oxfordjournals.org/cgi/reprint/90/19/1440.
  43. ^ "Report of the Scientific Committee on Tobacco and Health". Department of Health. March 1998. http://www.archive.official-documents.co.uk/document/doh/tobacco/contents.htm. Retrieved on 2007-07-09.
    * Hackshaw, AK (June 1998). "Lung cancer and passive smoking". Statistical Methods in Medical Research 7 (2): 119–136. doi:10.1191/096228098675091404. PMID 9654638.
  44. ^ National Health and Medical Research Council (April 1994). The health effects and regulation of passive smoking. Australian Government Publishing Service. http://www.obpr.gov.au/publications/submission/healthef/index.html. Retrieved on 2007-08-10.
  45. ^ 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. PMID 16319363.
  46. ^ EPA (October 2006). "Radiation information: radon". EPA. http://www.epa.gov/rpdweb00/radionuclides/radon.html. Retrieved on 2007-08-11.
  47. ^ Field, RW; Steck DJ, Smith BJ et al. (06/01/2000). "Residential radon gas exposure and lung cancer: the Iowa Radon Lung Cancer Study". American Journal of Epidemiology (Oxford Journals) 151 (11): 1091–1102. PMID 10873134. http://aje.oxfordjournals.org/cgi/reprint/151/11/1091.
  48. ^ EPA (June 2000). "Iowa Radon Lung Cancer Study". EPA. http://www.epa.gov/radon/iowastudy.html. Retrieved on 2007-08-11.
  49. ^ Darnton, AJ; McElvenny DM, Hodgson JT (January 2006). "Estimating the number of asbestos-related lung cancer deaths in Great Britain from 1980 to 2000". Annals of Occupational Hygiene 50 (1): 29–38. doi:10.1093/annhyg/mei038. PMID 16126764. http://annhyg.oxfordjournals.org/cgi/content/full/50/1/29.
  50. ^ Leroux, C; Girard N, Cottin V et al. (March-April 2007). "Jaagsiekte Sheep Retrovirus (JSRV): from virus to lung cancer in sheep". Veterinary Research 38 (2): 211–228. doi:10.1051/vetres:2006060. PMID 17257570.
  51. ^ Palmarini, M; Fan H (November 2001). "Retrovirus-induced ovine pulmonary adenocarcinoma, an animal model for lung cancer". Journal of the National Cancer Institute (Oxford University Press) 93 (21): 1603–1614. doi:10.1093/jnci/93.21.1603. PMID 11698564. http://jnci.oxfordjournals.org/cgi/content/full/93/21/1603.
  52. ^ Cheng, YW; Chiou HL, Sheu GT et al. (04/01/2001). "The association of human papillomavirus 16/18 infection with lung cancer among nonsmoking Taiwanese women". Cancer Research (American Association for Cancer Research) 61 (7): 2799–2803. PMID 11306446. http://cancerres.aacrjournals.org/cgi/content/full/61/7/2799.
  53. ^ Zheng, H; Aziz HA, Nakanishi Y et al. (May 2007). "Oncogenic role of JC virus in lung cancer". Journal of Pathology 212 (3): 306–315. doi:10.1002/path.2188. PMID 17534844.
  54. ^ Giuliani, L; Jaxmar T, Casadio C et al. (September 2007). "Detection of oncogenic viruses (SV40, BKV, JCV, HCMV, HPV) and p53 codon 72 polymorphism in lung carcinoma". Lung Cancer 57 (3): 273–281. doi:10.1016/j.lungcan.2007.02.019. PMID 17400331.
  55. ^ 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. PMID 14514947.
  56. ^ Salgia, R; Skarin AT (March 1998). "Molecular abnormalities in lung cancer". Journal of Clinical Oncology 16 (3): 1207–1217. PMID 9508209.
  57. ^ a b c d Herbst, RS; Heymach JV, Lippman SM (September 2008). "Molecular origins of cancer: lung cancer". N Engl J Med 359 (13): 1367–1380. doi:10.1056/NEJMra0802714. PMID 18815398. http://content.nejm.org/cgi/content/full/359/13/1367.
  58. ^ 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.
  59. ^ 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. http://www.chestjournal.org/cgi/reprint/109/3/14S.
  60. ^ Engels, EA; Wu X, Gu J et al. (July 2007). "Systematic evaluation of genetic variants in the inflammation pathway and risk of lung cancer". Cancer Research (American Association for Cancer Research) 67 (13): 6520–6527. doi:10.1158/0008-5472.CAN-07-0370. PMID 17596594.
  61. ^ Wenzlaff, AS; Cote ML, Bock CH et al. (December 2005). "CYP1A1 and CYP1B1 polymorphisms and risk of lung cancer among never smokers: a population-based study". Carcinogenesis (Oxford University Press) 26 (12): 2207–2212. doi:10.1093/carcin/bgi191. PMID 16051642.
  62. ^ Son, JW; Kang HK, Chae MH et al. (September 2006). "Polymorphisms in the caspase-8 gene and the risk of lung cancer". Cancer Genetics and Cytogenetics 169 (2): 121–127. doi:10.1016/j.cancergencyto.2006.04.001. PMID 16938569.
  63. ^ Yin, J; Vogel U, Ma Y et al. (May 2007). "The DNA repair gene XRCC1 and genetic susceptibility of lung cancer in a northeastern Chinese population". Lung Cancer 56 (2): 153–160. doi:10.1016/j.lungcan.2006.12.012. PMID 17316890.
  64. ^ Tomoda K, Ohkoshi T, Hirota K, et al (February 2009). "Preparation and properties of inhalable nanocomposite particles for treatment of lung cancer". Colloids Surf B Biointerfaces. doi:10.1016/j.colsurfb.2009.02.001. PMID 19264458. http://linkinghub.elsevier.com/retrieve/pii/S0927-7765(09)00055-1.
  65. ^ Fan YG, Hu P, Jiang Y, et al (March 2009). "Association between sputum atypia and lung cancer risk in an occupational cohort in yunnan, china". Chest 135 (3): 778–85. doi:10.1378/chest.08-1469. PMID 19265088.
  66. ^ Vineis, P; Hoek G, Krzyzanowski M et al. (February 2007). "Lung cancers attributable to environmental tobacco smoke and air pollution in non-smokers in different European countries: a prospective study". Environmental Health (BioMed Central) 6: 7. doi:10.1186/1476-069X-6-7. PMID 17302981.
  67. ^ a b "A Decade of Broken Promises: The 1998 State Tobacco Settlement Ten Years Later". Campaign for Tobacco-Free Kids. http://www.tobaccofreekids.org/reports/settlements/2009/fullreport.pdf. Retrieved on 2008-12-03.
  68. ^ Pandey, G (February 2005). "Bhutan's smokers face public ban". BBC. http://news.bbc.co.uk/2/hi/south_asia/4305715.stm. Retrieved on 2007-09-07.
  69. ^ Gray, N (February 2003). "A global approach to tobacco policy". Lung Cancer (BioMed Central) 39 (2): 113–117. doi:10.1016/S0169-5002(02)00456-7. PMID 12581561.
  70. ^ Slatore CG, Littman AJ, Au DH, Satia JA, White E (2008). "Long-term use of supplemental multivitamins, vitamin C, vitamin E, and folate does not reduce the risk of lung cancer". American Journal of Respiratory and Critical Care Medicine 177 (5): 524–30. doi:10.1164/rccm.200709-1398OC. PMID 17989343.
  71. ^ United Nations News service (30 May 2008). UN health agency calls for total ban on tobacco advertising to protect young. Press release. http://www.un.org/apps/news/story.asp?NewsID=26857.
  72. ^ Gohagan, JK; Marcus PM, Fagerstrom RM et al. (January 2005). "Final results of the Lung Screening Study, a randomized feasibility study of spiral CT versus chest X-ray screening for lung cancer". Lung Cancer 47 (1): 9–15. doi:10.1016/j.lungcan.2004.06.007. PMID 15603850.
  73. ^ Schiller JH, Vidaver RM, Novello S, Brahmer J, Monroe L (2007). "Living with a Diagnosis of Lung Cancer". [National Lung Cancer Partnership]. http://www.nationallungcancerpartnership.org/index.cfm?page=treatment. Retrieved on 2008-12-01.
  74. ^ Strand, TE; Rostad H, Damhuis RA, Norstein J (June 2007). "Risk factors for 30-day mortality after resection of lung cancer and prediction of their magnitude". Thorax (BMJ Publishing Group) 62: 991. doi:10.1136/thx.2007.079145. PMID 17573442.
  75. ^ El-Sherif, A; Gooding WE, Santos R et al. (August 2006). "Outcomes of sublobar resection versus lobectomy for stage I non-small cell lung cancer: a 13-year analysis". Annals of Thoracic Surgery 82 (2): 408–415. doi:10.1016/j.athoracsur.2006.02.029. PMID 16863738.
  76. ^ Fernando, HC; Santos RS, Benfield JR et al. (February 2005). "Lobar and sublobar resection with and without brachytherapy for small stage IA non-small cell lung cancer". Journal of Thoracic and Cardiovascular Surgery 129 (2): 261–267. doi:10.1016/j.jtcvs.2004.09.025. PMID 15678034.
  77. ^ 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. PMID 11809985.
  78. ^ 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.
  79. ^ 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.
  80. ^ 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.
  81. ^ Araujo AM, Mendez JC, Coelho AL, et al (March 2009). "Phase II Study of Celecoxib with Cisplatin Plus Etoposide in Extensive-Stage Small Cell Lung Cancer". Cancer Invest.: 1. doi:10.1080/07357900802232756. PMID 19266367. http://www.informaworld.com/openurl?genre=article&doi=10.1080/07357900802232756&magic=pubmed||1B69BA326FFE69C3F0A8F227DF8201D0.
  82. ^ Winton, T; Livingston R, Johnson D, et al. (June 2005). "Vinorelbine plus cisplatin vs. observation in resected non-small-cell lung cancer". New England Journal of Medicine (Massachusetts Medical Society) 352 (25): 2589–2597. doi:10.1056/NEJMoa043623. PMID 15972865. "Adjuvant vinorelbine plus cisplatin has an acceptable level of toxicity and prolongs disease-free and overall survival among patients with completely resected early-stage non-small-cell lung cancer.".
  83. ^ Douillard, JY; Rosell R, De Lena M et al. (September 2006). "Adjuvant vinorelbine plus cisplatin versus observation in patients with completely resected stage IB-IIIA non-small-cell lung cancer (Adjuvant Navelbine International Trialist Association [ANITA]): a randomised controlled trial". Lancet Oncology (Elsevier) 7 (9): 719–727. doi:10.1016/S1470-2045(06)70804-X. PMID 16945766.
  84. ^ Tsuboi, M; Ohira T, Saji H et al. (April 2007). "The present status of postoperative adjuvant chemotherapy for completely resected non-small cell lung cancer" (PDF). Annals of Thoracic and Cardiovascular Surgery 13 (2): 73–77. PMID 17505412. http://www.atcs.jp/pdf/2007_13_2/73.pdf.
  85. ^ 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.
  86. ^ 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.
  87. ^ BMJ (December 2005). Clinical evidence concise : the international resource of the best available evidence for effective health care.. London: BMJ Publishing Group. pp. 486–488. ISBN 1-905545-00-2.
  88. ^ Arriagada, R; Goldstraw P, Le Chevalier T (2002). Oxford Textbook of Oncology (2nd ed.). Oxford University Press. p. 2094. ISBN 0-19-262926-3.
  89. ^ a b 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.
  90. ^ Wagner, H (January 1998). "Radiation therapy in the management of limited small cell lung cancer: when, where, and how much?". Chest (American College of Chest Physicians) 113 (Suppl. 1): 92S–100S. doi:10.1378/chest.113.1_Supplement.92S. PMID 9438697. http://www.chestjournal.org/cgi/reprint/113/1/92S.
  91. ^ "Postoperative radiotherapy for non-small cell lung cancer". Cochrane database of systematic reviews (Online) (2): CD002142. 2005. doi:10.1002/14651858.CD002142.pub2. PMID 15846628. http://mrw.interscience.wiley.com/cochrane/clsysrev/articles/CD002142/frame.html.
  92. ^ Lally, BE; Zelterman D, Colasanto JM et al. (July 2006). "Postoperative Radiotherapy for Stage II or III Non–Small-Cell Lung Cancer Using the Surveillance, Epidemiology, and End Results Database". Journal of Clinical Oncology (John Wiley & Sons) 24 (19): 2998–3006. doi:10.1200/JCO.2005.04.6110. PMID 16769986. http://jco.ascopubs.org/cgi/content/full/24/19/2998.
  93. ^ Raben, A; Mychalczak B (October 1997). "Brachytherapy for non-small cell lung cancer and selected neoplasms of the chest". Chest (American College of Chest Physicians) 112 (Suppl. 4): 276S–286S. doi:10.1378/chest.112.4_Supplement.276S. PMID 9337304. http://www.chestjournal.org/cgi/reprint/112/4_Supplement/276S.
  94. ^ Celebioglu, B; Gurkan OU, Erdogan S et al. (November 2002). "High dose rate endobronchial brachytherapy effectively palliates symptoms due to inoperable lung cancer". Japanese Journal of Clinical Oncology (Oxford University Press) 32 (11): 443–448. doi:10.1093/jjco/hyf102. PMID 12499415. http://jjco.oxfordjournals.org/cgi/content/full/32/11/443.
  95. ^ Ng, M; Chong J, Milner A et al. (June 2007). "Tolerability of accelerated chest irradiation and impact on survival of prophylactic cranial irradiation in patients with limited-stage small cell lung cancer: review of a single institution's experience". Journal of Thoracic Oncology (International Association for the Study of Lung Cancer) 2 (6): 506–513. doi:10.1097/JTO.0b013e318060095b. PMID 17545845.
  96. ^ Slotman, B; Faivre-Finn C, Kramer G et al. (August 2007). "Prophylactic cranial irradiation in extensive small-cell lung cancer". New England Journal of Medicine 357 (7): 664–672. doi:10.1056/NEJMoa071780. PMID 17699816. http://content.nejm.org/cgi/content/full/357/7/664.
  97. ^ Hof, H; Muenter M, Oetzel D et al. (July 2007). "Stereotactic single-dose radiotherapy (radiosurgery) of early stage nonsmall-cell lung cancer (NSCLC)". Cancer (Wiley InterScience) 110 (1): 148–155. doi:10.1002/cncr.22763. PMID 17516437. http://www3.interscience.wiley.com/cgi-bin/fulltext/114265991/PDFSTART.
  98. ^ Simon, CJ; Dupuy DE, DiPetrillo TA et al. (April 2007). "Pulmonary radiofrequency ablation: long-term safety and efficacy in 153 patients". Radiology 243 (1): 268–275. doi:10.1148/radiol.2431060088. PMID 17392258.
  99. ^ a b Bencardino, K; Manzoni M, Delfanti S et al. (March 2007). "Epidermal growth factor receptor tyrosine kinase inhibitors for the treatment of non-small-cell lung cancer: results and open issues". Internal and Emergency Medicine 2 (1): 3–12. doi:10.1007/s11739-007-0002-5. PMID 17551677.
  100. ^ Feld, R; Sridhar SS, Shepherd FA et al. (May 2006). "Use of the epidermal growth factor receptor inhibitors gefitinib and erlotinib in the treatment of non-small cell lung cancer: a systematic review". Journal of Thoracic Oncology (International Association for the Study of Lung Cancer) 1 (4): 367–376. doi:10.1097/01243894-200605000-00018. PMID 17409886.
  101. ^ Sandler, A; Gray R, Perry M et al. (December 2006). "Paclitaxel–carboplatin alone or with bevacizumab for non–small cell lung cancer". New England Journal of Medicine (Massachusetts Medical Society) 355 (24): 2542–2550. doi:10.1056/NEJMoa061884. PMID 17167137.
  102. ^ Edelman, MJ (September 2006). "Novel cytotoxic agents for non-small cell lung cancer". Journal of Thoracic Oncology 1 (7): 752–755. PMID 17409954.
  103. ^ Danesi, R; Pasqualetti G, Giovannetti E, Del Tacca M (May 2007). "The role of pharmacogenetics in adjuvant treatment of non-small cell lung cancer". Journal of Thoracic Oncology 2 (5 Suppl.): S27–S30. doi:10.1097/01.JTO.0000268638.10332.07. PMID 17457227.
  104. ^ Blackhall, FH; Shepherd FA (March 2007). "Small cell lung cancer and targeted therapies". Current Opinion in Oncology 19 (2): 103–108. doi:10.1097/CCO.0b013e328011bec3. PMID 17272981.
  105. ^ Lee, JM; Mao JT, Krysan K, Dubinett SM (April 2007). "Significance of cyclooxygenase-2 in prognosis, targeted therapy and chemoprevention of NSCLC". Future Oncology 2 (2): 149–153. doi:10.2217/14796694.3.2.149. PMID 17381414.
  106. ^ Whitehead, CM; Earle KA, Fetter J et al. (05/01/2003). "Exisulind-induced Apoptosis in a Non-Small Cell Lung Cancer Orthotopic Lung Tumor Model Augments Docetaxel Treatment and Contributes to Increased Survival". Molecular Cancer Therapeutics (American Association for Cancer Research) 2 (5): 479–488. PMID 12748310. http://mct.aacrjournals.org/cgi/content/full/2/5/479.
  107. ^ Scagliotti, G (June 2006). "Proteasome inhibitors in lung cancer". Critical Reviews in Oncology/Haematology 58 (3): 177–189. doi:10.1016/j.critrevonc.2005.12.001. PMID 16427303.
  108. ^ Dragnev, KH; Petty WJ, Shah SJ et al. (March 2007). "A proof-of-principle clinical trial of bexarotene in patients with non-small cell lung cancer". Clinical Cancer Research (American Association for Cancer Research) 13 (6): 1794–1800. doi:10.1158/1078-0432.CCR-06-1836. PMID 17363535.
  109. ^ Albright, C; Garst J (July 2007). "Vaccine therapy in non-small cell lung cancer". Current Oncology Reports 9 (4): 241–246. doi:10.1007/s11912-007-0029-9. PMID 17588347.
  110. ^ Sun, S; Schiller JH, Spinola M, Minna JD (October 2007). "New molecularly targeted therapies for lung cancer". Journal of Clinical Investigation (American Society for Clinical Investigation) 117 (10): 2740–2750. doi:10.1172/JCI31809. PMID 17909619. http://www.jci.org/cgi/content/full/117/10/2740.
  111. ^ "Non-Small Cell Lung Cancer Treatment". PDQ for Health Professionals. National Cancer Institute. http://www.cancer.gov/cancertopics/pdq/treatment/non-small-cell-lung/HealthProfessional/page2. Retrieved on 2008-11-22.
  112. ^ "-Small Cell Lung Cancer Treatment". PDQ for Health Professionals. National Cancer Institute. http://www.cancer.gov/cancertopics/pdq/treatment/small-cell-lung/healthprofessional. Retrieved on 2008-11-22.
  113. ^ Mountain, CF (1997). "Revisions in the international system for staging lung cancer" (PDF). Chest (American College of Chest Physicians) 111: 1710–1717. doi:10.1378/chest.111.6.1710. PMID 9187198. http://www.chestjournal.org/cgi/reprint/111/6/1710.
  114. ^ "Cancer Statistics Review 1975-2002 - Search". Surveillance Epidemiology and End Results (SEER). http://seer.cancer.gov/cgi-bin/csr/1975_2002/search.pl#results. Retrieved on 2007-11-18.
  115. ^ "Commonly diagnosed cancers worldwide". Cancer Research UK. April 2005. http://info.cancerresearchuk.org/cancerstats/geographic/world/commoncancers/. Retrieved on 2008-01-11.
  116. ^ 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. PMID 18818225. http://tobaccocontrol.bmj.com/cgi/content/full/17/5/313.
  117. ^ Parent, ME; Rousseau MC, Boffetta P et al. (January 2007). "Exposure to diesel and gasoline engine emissions and the risk of lung cancer". American Journal of Epidemiology 165 (1): 53–62. doi:10.1093/aje/kwj343. PMID 17062632.
  118. ^ "Gender in lung cancer and smoking research" (PDF). World Health Organization. 2004. http://www.who.int/gender/documents/en/lungcancerlow.pdf. Retrieved on 2007-05-26.
  119. ^ Liu, BQ; Peto R, Chen ZM et al. (1998-11-21). "Emerging tobacco hazards in China: 1. Retrospective proportional mortality study of one million deaths". British Medical Journal 317 (7170): 1411–1422. PMID 9822393. http://www.bmj.com/cgi/content/full/317/7170/1411.
  120. ^ Behera, D; Balamugesh T (2004). "Lung cancer in India" (PDF). Indian Journal of Chest Diseases and Allied Sciences 46 (4): 269–281. PMID 15515828. http://www.vpci.org.in/upload/Journals/pic130.pdf#page=27.
  121. ^ Mohr, SB; Garland CF, Gorham ED et al. (2008). "Could ultraviolet B irradiance and vitamin D be associated with lower incidence rates of lung cancer?". Journal of Epidemiology and Community Health 62 (1): 69–74. doi:10.1136/jech.2006.052571. PMID 18079336.
  122. ^ a b Chen, F; Bina WF, Cole P (April 2007). "Declining incidence rate of lung adenocarcinoma in the United States". Chest 131 (4): 1000–1005. PMID 17426202. http://www.chestjournal.org/cgi/content/full/131/4/1000.
  123. ^ 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. PMID 9126499. http://ije.oxfordjournals.org/cgi/reprint/26/1/14.
  124. ^ Morgagni, Giovanni Battista (1761). De sedibus et causis morborum per anatomen indagatis. http://books.google.ca/books?id=A3IFAAAAQAAJ&printsec=frontcover&dq=editions:0gslDCsk4Fm2hLne.
  125. ^ Bayle, Gaspard-Laurent (1810) (in French). Recherches sur la phtisie pulmonaire. Paris.
  126. ^ 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. http://toxsci.oxfordjournals.org/cgi/content/full/64/1/4.
  127. ^ Adler, I (1912). Primary Malignant Growths of the Lungs and Bronchi. New York: Longmans, Green, and Company. OCLC 14783544. , 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.
  128. ^ Grannis, FW. "History of cigarette smoking and lung cancer". smokinglungs.com. http://www.smokinglungs.com/cighist.htm. Retrieved on 2007-08-06.
  129. ^ Proctor, R (2000). The Nazi War on Cancer. Princeton University Press. pp. 173–246. ISBN 0-691-00196-0.
  130. ^ Doll, R; Hill AB (November 1956). "Lung cancer and other causes of death in relation to smoking; a second report on the mortality of British doctors". British Medical Journal 2 (5001): 1071–1081. PMID 13364389.
  131. ^ US Department of Health Education and Welfare (1964) (PDF), Smoking and health: report of the advisory committee to the Surgeon General of the Public Health Service, Washington, DC: US Government Printing Office, http://profiles.nlm.nih.gov/NN/B/B/M/Q/_/nnbbmq.pdf
  132. ^ Pirozynski, M (December 2006). "100 years of Lung Cancer". Respiratory Medicine 100 (12): 2073–2084. doi:10.1016/j.rmed.2006.09.002. PMID 17056245.
  133. ^ Greaves, M (2000). Cancer: the Evolutionary Legacy. Oxford University Press. pp. 196–197. ISBN 0-19-262835-6.
  134. ^ Horn, L; Johnson DH (July 2008). "Evarts A. Graham and the first pneumonectomy for lung cancer". Journal of Clinical Oncology 26 (19): 3268–3275. PMID 18591561. http://jco.ascopubs.org/cgi/pdf_extract/26/19/3268.
  135. ^ Edwards, AT (1946). "Carcinoma of the bronchus". Thorax 1 (1): 1–25.
  136. ^ Kabela, M (1956). "[Experience with radical irradiation of bronchial cancer]" (in German). Ceskoslovenská Onkológia 3 (2): 109–115. PMID 13383622.
  137. ^ 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.
  138. ^ 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.
  139. ^ 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.
Source : http://en.wikipedia.org/wiki/Lung_cancer
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