Misplaced Pages

Revision as of 22:51, 7 May 2007

Lung cancer
Specialty	Oncology, pulmonology

Lung cancer is the malignant transformation and expansion of lung tissue, and is the most lethal of all cancers worldwide, responsible for 1.2 million deaths annually. It is caused predominantly by cigarette smoking, and predominantly affects men, with it being the leading cause of death of men between the ages of 40 and 65. With increased smoking among women, it is now occuring in women but it is less common. While some people who have never smoked do still get lung cancer, this appears to be due to a combination of genetic factors and exposure to secondhand smoke.

Current research indicates that the factor with the greatest impact on risk of lung cancer is long-term exposure to inhaled carcinogens. The most common means of such exposure is air pollution and tobacco smoke.

Treatment and prognosis depend upon the histological type of cancer, the stage (degree of spread), and the patient's performance status. Treatments include surgery, chemotherapy, and radiotherapy.

Signs and symptoms

Symptoms that suggest lung cancer include:

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

If the cancer grows into the lumen it may obstruct the airway, 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. In lung cancer, this may be Lambert-Eaton myasthenic syndrome (muscle weakness due to auto-antibodies), hypercalcemia and 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 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.

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 bone, such as the spine (causing back pain and occasionally spinal cord compression), the liver and the brain.

Diagnosis

Performing a chest X-ray 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 (infection) and pleural effusion. If there are no X-ray findings but the suspicion is high (e.g. a heavy smoker with blood-stained sputum), bronchoscopy and/or a CT scan may provide the necessary information. In any case, bronchoscopy or CT-guided biopsy is often necessary to identify the tumor type.

If investigations have confirmed lung cancer, scan results and often positron emission tomography (PET) are used to determine whether the disease is localised and amenable to surgery or whether it has spread to the point it cannot be cured surgically. PET is not useful as screening, as not all malignancies are positive on PET scan (such as bronchoalveolar carcinoma), and lung infections may be positive on PET Scan.

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 a very poor respiratory reserve, as may occur in chronic smokers, surgery may be contraindicated.

Types

There are two main types of lung cancer categorized by the size and appearance of the malignant cells seen by a histopathologist under a microscope: non-small cell (80%) and small-cell (roughly 20%) lung cancer. This classification although based on simple pathomorphological criteria has very important implications for clinical management and prognosis of the disease.

Non-small cell lung cancer

For non-small cell lung cancer (NSCLC), prognosis is poor. For advanced NSCLC, average survival is 6 months for untreated patients, and 9 months for patients treated with chemotherapy. The 5-year survival rate of patients with NSCLC is 60 to 70% for patients with stage I disease and zero for patients with stage IV disease.

The NSCLCs are grouped together because their prognosis and management is roughly identical. When it cannot be subtyped, it is frequently coded to 8046/3. The subtypes are:

• Squamous cell carcinoma, accounting for 29% of lung cancers, also starts in the larger bronchi but grows slower. This means that the size of these tumours varies on diagnosis.
• Adenocarcinoma is the most common subtype of NSCLC, accounting for 32% of lung cancers. It is a form which starts near the gas-exchanging surface of the lung. Most cases of the adenocarcinoma are associated with smoking. However, among non-smokers and in particular female non-smokers, adenocarcinoma is the most common form of lung cancer. A subtype of adenocarcinoma, the bronchioalveolar carcinoma, is more common in female non-smokers and may have different responses to treatment.
• Large cell carcinoma is a fast-growing form, accounting for 9% of lung cancers, that grows near the surface of the lung.

Small cell lung cancer

For Small cell carcinoma (SCLC), prognosis is also poor. The overall five-year survival for patients with SCLC is about 5%. 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%.

• SCLC (also called "oat cell carcinoma") is the less common form of lung cancer. It tends to start in the larger breathing tubes and grows rapidly becoming quite large. The oncogene most commonly involved is L-myc. The "oat" cell contains dense neurosecretory granules which give this an endocrine/paraneoplastic syndrome association. It is initially more sensitive to chemotherapy, but ultimately carries a worse prognosis and is often metastatic at presentation. This type of lung cancer is strongly associated with smoking.

Other types

• Carcinoid
• Adenoid cystic carcinoma
• Cylindroma
• Mucoepidermoid carcinoma

Metastatic

The lung is a common place for metastasis from tumors in other parts of the body. These cancers, however, are identified by the site of origin, i.e., a breast cancer metastasis to the lung is still known as breast cancer. The adrenal glands, liver, brain, and bone are the most common sites of metastasis from primary lung cancer itself.

Causes

Exposure to carcinogens, such as those present in air pollution and tobacco smoke, immediately causes cumulative changes to the tissue lining the bronchi of the lungs (the bronchial mucous membrane) and more tissue gets damaged until a tumour develops.

There are four major causes of lung cancer (and cancer in general):

• Carcinogens such as those in cigarette smoke
• Radiation exposure
• Genetic susceptibility
• Viral infection

The role of smoking

Smoking, particularly of cigarettes, is by far the main contributor to lung cancer, which at least in theory makes it one of the easiest diseases to prevent. In the United States, smoking is estimated to account for 87% of lung cancer cases (90% in men and 79% in women), and in the UK for 90%. Cigarette smoke contains 19 known carcinogens including radioisotopes from the radon decay sequence, nitrosamine, and benzopyrene. Additionally, nicotine appears to depress the immune response to malignant growths in exposed tissue. The length of time a person continues to smoke as well as the amount smoked increases the person's chances of developing lung cancer. If a person stops smoking, these chances steadily decrease as damage to the lungs is repaired and contaminant particles are gradually vacated. More recent work has shown that, across the developed world, almost 90% of lung cancer deaths are caused by smoking. In addition, there is evidence that lung cancer in never-smokers has a better prognosis than in smokers, and that patients who smoke at the time of diagnosis have shorter survival than those who have quit. Passive smoking—the inhalation of smoke from another's smoking— is claimed to be a cause of lung cancer in non-smokers. Studies from the USA (1986, 1992, 1997, 2001, 2003), Europe (1998), the UK (1998,), and Australia (1997) have consistently shown a significant increase in relative risk among those exposed to passive smoke.

The EPA in 1993 claimed that about 3,000 lung cancer-related deaths a year were caused by passive smoking. However, since this report was based on a study that was alleged to be heavily biased and was ruled by a federal judge to be "unscientific", the EPA report was declared null and void by a federal judge in 1998(,).

The extensive attempts made by Philip Morris to delay the release of the 1997 IARC study, to affect the wording of its conclusions, to neutralise its negative results for their business, and to counteract its impact on public and policymakers' opinion have been documented by Ong & Glantz in The Lancet journal. Their work was based on 32 million pages of documents made public as part of the settlement of the 1998 legal case of State of Minnesota and Blue Cross/Blue Shield of Minnesota vs Philip Morris Inc, et al. and available at Philip Morris' own website.

Recent investigation of sidestream smoke suggests it is more dangerous than direct smoke inhalation.

Asbestos

Asbestos can cause a variety of lung diseases. It increases the risk of developing lung cancer. There is a synergistic effect between tobacco smoking and asbestos in the formation of lung cancer.

Asbestos can also cause cancer of the pleura, called mesothelioma (which is distinct from lung cancer).

Radon gas

Radon is a colorless and odourless gas generated by the breakdown of radioactive radium, which in turn is the decay product of uranium, found in the earth's crust. Radon exposure is the second major cause of lung cancer after smoking. The radiation decay products ionize genetic material, causing mutations that sometimes turn cancerous. 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. In the US, the EPA estimates that one in 15 homes has radon levels above the recommended guideline of 4 pCi/L (150 Bq/m). Iowa has the highest average radon concentrations in the United States. Studies performed by R. William Field, Daniel J. Steck, Charles F. Lynch, Brian J. Smith and colleagues at the University of Iowa have demonstrated a 50% increased lung cancer risk with prolonged radon exposure at the EPA's action level of 4 pCi/L () . Recent pooled epidemiologic radon studies by Dan Krewski et al. (2005; 2006) and Sarah Darby et al. (2005) have also shown an increased lung cancer risk from radon below the U.S. EPA's action level of 4 pCi/L.

Radon causes lung cancer because it causes arbitrary damage to the chromosomes and DNA molecules contained in the nucleus of the cell.

Genetics and viruses

Oncogenes are genes that are believed make people more susceptible to cancer. Proto-oncogenes are believed to turn into oncogenes when exposed to particular carcinogens. Viruses are also suspected of causing cancer in humans, as this link has already been proven in animals. Genetic susceptibility and viral infection are not of major importance in lung cancer, but they may influence pathogenesis.

Lung cancer staging

Lung cancer staging is an important part of the assessment of prognosis and potential treatment for lung cancer.

See non-small cell lung cancer staging.

Epidemiology

The population segment most likely to develop lung cancer is the over-fifties who also 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 for men and women. In the US, 175,000 new cases are expected in 2006: 90,700 in men and 80,000 in women. Although the rate of men dying from lung cancer is declining in western countries, it is actually increasing for women due to the increased takeup of smoking by this group. Among lifetime non-smokers, men who have never smoked have higher age-standardized lung cancer death rates than women. Of the 80,000 women who are diagnosed with lung cancer in 2006, approximately 70,000 are expected to die from it.

Lung cancer was extremely rare prior to the advent of cigarette smoking. In 1878, malignant lung tumors made up only 1% of all cancers seen at autopsy; this had risen to 10-15% by the early 1900s. Case reports in the medical literature numbered only 374 worldwide in 1912. The British Doctors Study, published in the 1950s, first offered solid epidemiological evidence on the link between lung cancer and smoking.

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 non-smokers to others' tobacco smoke. Emissions from automobiles, factories and power plants also pose potential risks.

In the Second World and Third World, smoking-related lung cancer is rising rapidly in incidence. Countries such as China are expected to see a marked increase in lung cancer cases as smoking is exceedingly common and other causes of death (such as infections) are becoming less common, revealing an "iceberg" of pulmonary neoplasms. Cheap tobacco products and heavy advertising are seen by health campaigners as a major problem in these countries.

Prevention

Primary prevention

Prevention is the most cost-effective means of fighting lung cancer on the national and global scales. 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 fight to prevent lung cancer, and smoking cessation is the most important preventative tool in this process.

Policy interventions to decrease passive smoking (e.g. in restaurants and workplaces) have become more common in various Western countries, with California taking a lead in banning smoking in public establishments in 1998, Ireland playing a similar role in Europe in 2004, followed by Italy and Norway in 2005 and Scotland as well as several others in 2006. New Zealand has also recently banned smoking in public places. (See Smoking ban).

Only the Asian state of Bhutan has a complete smoking ban (since 2005). In many countries pressure groups are campaigning for similar bans. Arguments cited against such bans is criminalisation of smoking, increased risk of smuggling and the risk that such a ban cannot be enforced.

Screening and secondary prevention

Regular chest radiography and sputum examination programs were not effective in reducing mortality from lung cancer. Earlier studies (Mayo Lung Project and Czechoslovakia lung cancer screening study, combining over 17,000 smokers) showed earlier detection of lung cancer was possible but mortality was not improved. Simply detecting a tumor at an earlier stage may not necessarily yield improved mortality. For example, plain radiography resulted in increased time from diagnosis of cancer until death and those cancers being detected by screening tended to be earlier stages. However, these patients continued to die at the same rate as those who are not screened. At present, no professional or specialty organization advocates screening for lung cancer outside of clinical trials.

A computed tomography (CT) scan can uncover tumors not yet visible on an X-ray. CT scanning is now being actively evaluated as a screening tool for lung cancer in high risk patients, and it is showing promising results. The USA-based National Cancer Institute is currently completing a randomized trial comparing CT scans with chest radiographs. Several single-institution trials are ongoing around the world.

The International Early Lung Cancer Action Project published the results of CT screening on over 31,000 high-risk patients in late 2006 in the New England Journal of Medicine. In this study 85% of the 484 detected lung cancers were stage I and thus highly treatable. Mathematically these stage I patients would have an expected 10-year survival of 88%. However, there was no randomization of patients (all received CT scans and there was no comparison group receiving only x-rays) and the patients were not actually followed out to 10 years post detection (the median followup was 40 months).

In contrast, a March 2007 study in JAMA found no benefit. 3,200 current or former smokers were screened for 4 years and offered 3 or 4 CT scans. Lung cancer diagnoses were 3 times as high, and surgeries were 10 times as high, as predicted by a model, but there were no significant differences between observed and expected numbers of advanced cancers or deaths.

Randomized controlled studies are underway in this area to see if decreased long-term mortality can be directly observed from CT screening.

It should be noted that screening studies have only been done in high risk populations, such as smokers and workers with occupational exposure to certain substances. This is important when one considers that repeated radiation exposure from screening could actually induce carcinogenesis in a small percentage of screened subjects, so this risk should be mitigated by a (relatively) high prevalence of lung cancer in the population being screened.

References

1. National Lung Cancer Partnership: Lung Cancer in American Women
2. Gorlova OY, Weng SF, Zhang Y, Amos CI, Spitz MR. Aggregation of cancer among relatives of never-smoking lung cancer patients. Int J Cancer. 2007 Feb 15;121(1):2865-2872 PMID 17304511
3. Sasco AJ, Secretan MB, Straif K. Tobacco smoking and cancer: a brief review of recent epidemiological evidence. Lung Cancer. 2004 Aug;45 Suppl 2:S3-9. PMID 15552776
4. Hackshaw AK, Law MR, Wald NJ. The accumulated evidence on lung cancer and environmental tobacco smoke. BMJ. 1997 Oct 18;315(7114):980-8. PMID 9365295
5. ^ "Lung Carcinoma: Tumors of the Lungs: Merck Manual Professional Edition, Online edition". Retrieved March 19. {{cite web}}: Check date values in: |accessdate= (help); Unknown parameter |accessyear= ignored (|access-date= suggested) (help)
6. ^ Harrison's Principle's of Internal Medicine. 2005. p. 506. doi:10.1036/0071402357. {{cite book}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
7. Dr. C. Everett Koop. "Smoking and smokeless tobacco". Retrieved July 15. {{cite web}}: Check date values in: |accessdate= (help); Unknown parameter |accessyear= ignored (|access-date= suggested) (help)
8. Peto R, R (1994). Mortality from smoking in developed countries 1950–2000: Indirect estimates from National Vital Statistics. Oxford: Oxford University Press. ISBN 0-19-262535-7. {{cite book}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
9. Nordquist LT, Simon GR, Cantor A, Alberts WM, Bepler G. Improved survival in never-smokers vs current smokers with primary adenocarcinoma of the lung. Chest. 2004 Aug;126(2):347-51. PMID 15302716
10. Tammemagi CM, Neslund-Dudas C, Simoff M, Kvale P. Smoking and lung cancer survival: the role of comorbidity and treatment. Chest. 2004 Jan;125(1):27-37. PMID 14718417
11. US Department of Health and Human Services., The health consequences of involuntary smoking: report of the Surgeon General (DHHS Pub No (PHS) 87–8398), DHHS, Washington, DC (1986). PMID 3097495
12. National Research Council., Environmental tobacco smoke: measuring exposures and assessing health effects, NRC, Washington, DC (1986).
13. US Environmental Protection Agency., Respiratory health effects of passive smoking: lung cancer and other disorders, EPA, Washington, DC (1992).
14. California Environmental Protection Agency., Health effects of exposure to environmental tobacco smoke, California EPA, Sacramento (1997). PMID 9583639.
15. Centers for Disease Control and Prevention (CDC). State-specific prevalence of current cigarette smoking among adults, and policies and attitudes about secondhand smoke--United States, 2000. MMWR Morb Mortal Wkly Rep. 2001 Dec 14;50(49):1101-6. PMID 11794619
16. Alberg AJ, Samet JM. Epidemiology of lung cancer. Chest. 2003 Jan;123(1 Suppl):21S-49S. PMID 12527563
17. In: P Boffetta, A Agudo and W Ahrens et al., Editors, Multicenter case-control study of exposure to environmental tobacco smoke and lung cancer in Europe, J Natl Cancer Inst 90 (1998), pp. 1440–1450.
18. Scientific Committee on Tobacco and Health., Report of the Scientific Committee on Tobacco and Health, Department of Health, London (1998)
19. Hackshaw AK. Lung cancer and passive smoking. Stat Methods Med Res. 1998 Jun;7(2):119-36. PMID 9654638
20. National Health and Medical Research Council., The health effects of passive smoking, Australian Government Publishing Service, Canberra (1997).
21. NY Times "Judge Voids Study Linking Cancer to Secondhand Smoke"
22. PBS: "SMOKE SCREEN?"
23. Ong, E.K. "Tobacco industry efforts subverting International Agency for Research on Cancer's second-hand smoke study". Lancet (355(9211)). 2000: 1253–9. PMID 10770318. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
24. pmdocs.com
25. Schick S, Glantz S. Philip Morris toxicological experiments with fresh sidestream smoke: more toxic than mainstream smoke. Tob Control. 2005 Dec;14(6):396-404. PMID 16319363
26. Hammond, E.C. "Asbestos exposure, cigarette smoking and death rates". Ann N Y Acad Sci (330). 1979: 473. PMID 294198. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
27. Lung Cancer in the United States: Facts from National Lung Cancer Partnership new cases of lung cancer in the US
28. New survey finds most women don't know much about lung cancer even though it's the leading cancer killer of women in the U.S from National Lung Cancer Partnership News
29. Witschi H. A short history of lung cancer. Toxicol Sci. 2001 Nov;64(1):4-6. PMID 11606795
30. Adler I. Primary malignant growths of the lungs and bronchi. New York: Longmans, Green, and Company; 1912., cited in Spiro SG, Silvestri GA. One hundred years of lung cancer. Am J Respir Crit Care Med. 2005 Sep 1;172(5):523-9. PMID 15961694
31. Screening for lung cancer, The Cochrane Database of Systematic Reviews 2007
32. Henschke CI, et al, Survival of patients with stage I lung cancer detected on CT screening. N Engl J Med. 2006 Oct 26;355(17):1763-71. PMID 17065637
33. Peter B. Bach, et al., Computed Tomography Screening and Lung Cancer Outcomes, JAMA. 2007;297:953-961. (March 7, 2007)

External links

• Informative video about Lung Cancer
• Lung Cancer Resources Page at the National Cancer Institute.
• Tobacco Smoke and Involuntary Smoking, Summary of Data Reported and Evaluation 2004 by the IARC.
• Lung Cancer Articles & Information Stop Smoking Articles & Information
• RadiologyInfo - The radiology information resource for patients with lung cancer

• Pulmonology
• Types of cancer