Lung cancer

Lung cancer is a malignant tumour of the lungs. Most commonly it is bronchogenic carcinoma (about 90%). Lung cancer is the most lethal malignant tumour worldwide, causing up to 3 million deaths annually.

The most important risk factor for lung cancer is smoking.

Treatment and prognosis depend upon the histological type of cancer and the stage (degree of spread). Possible treatment modalities include surgery, chemotherapy) and/or radiotherapy.

Signs and symptoms

Common symptoms that suggest lung cancer include:

dyspnea (shortness of breath)
hemoptysis (coughing up blood)
chronic cough
wheezing
chest pain
cachexia (weight loss), fatigue and loss of appetite
dysphonia (hoarse voice)
clubbing of the fingernails

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 seek medical attention.

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. 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 categorised by the size and appearance of the malignant cells seen by a histopathologist under a microscope: small-cell (roughly 20%) and non-small cell (80%) 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

The non-small cell lung cancers (NSCLC) are grouped together because their prognosis and management is roughly identical. The subtypes are:

Epidermoid carcinoma (or Squamous cell carcinoma) also starts in the larger breathing tubes but grows slower meaning that the size of these tumours varies when on diagnosis.
Adenocarcinoma (or for slower growing forms alveolar cell cancer) is a form which starts near the gas-exchanging surface of the lung. It is less closely associated with smoking.
Large cell carcinoma is a fast-growing form that grows near the surface of the lung.

Small cell lung cancer

Small cell carcinoma (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 more sensitive to chemotherapy, but carries a worse prognosis and is often metastatic at presentation.

Other types

See the article carcinoid

Up to 10% of lung tumours do not fall under the NSCLC/SCLC division. The main representatives in this group are carcinoid. Rarer lung tumours include cylindroma and mucoepidermoid carcinoma.

Causes

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Cancer death rates in the United States.

Exposure to carcinogens, such as those present in 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, actually, 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 believed to be by far the main cause of lung cancer, which at least in theory makes it one of the easiest diseases to prevent. An estimated 80% of lung cancers result from smoking due to the hundreds of known carcinogens—such as polynuclear aromatic hydrocarbons—present in cigarette smoke. The length of time a person continues to smoke as well as the amount smoked increases the person's chances of contracting lung cancer. If a person stops smoking, these chances steadily decrease as the lung damage is repaired.

Passive smoking—the inhalation of smoke from another's smoking—has recently been identified as a much larger cause of lung cancer in non-smokers than previously believed. The US Environmental Protection Agency (EPA) in 1993 concluded that about 3,000 lung cancer-related deaths a year were caused by passive smoking, though the true extent is still contested by scientists.

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.

Radioactivity

Radon is a colorless and odorless gas generated by the breakdown of radioactive radium, which in turn is the decayed product of uranium, found in the earth's crust. Radon exposure is the second major cause of lung cancer after smoking. The radiation ionizes 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 standard.

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.

Treatment

Treatment for lung cancer depends on the cancer's specific form, how far it has spread, and other factors such as the patient's age and general medical state. Common treatments include surgery, chemotherapy, and radiation therapy.

Surgery

Surgery is only an option in NSCLC and if the disease is limited to one lobe and has not spread beyond its confines. This is assessed with medical imaging (CT, PET). Furthermore, as stated, a sufficient respiratory reserve needs to be present to allow for the removal of large amounts of lung tissue. Procedures performed are lobectomy (removal of one lobe), bilobectomy (two lobes) and pneumectomy (removal of a whole lung).

After surgery, adjuvant chemotherapy is usually recommended to decrease the risk of recurrence. Five-year prognosis is often as good as 70% in limited disease with clear resection margins.

Chemotherapy

Small-cell lung cancer is treated primarily with chemotherapy, as surgery has no demonstrable influence on survival. Primary chemotherapy is also given in metastatic NSCLC.

The combination regimens depend on the tumour type:

NSCLC: cisplatin or carboplatin, in combination with gemcitabine, paclitaxel, docetaxel, etoposide or vinorelbine
SCLC: cisplatin or carboplatin, in combination etoposide or ifosfamide; combinations with gemcitabine, paclitaxel, vinorelbine, topotecan and irinotecan are being studied

Radiotherapy

Radiotherapy is often given together with chemotherapy, and may be used with curative intent in patients who are not elegible for surgery. A radiation dose of 40 Gy in many fractions is commonly used with curative intent, and smaller doses (20 Gy) may be used for symptom control where metastatic disease compresses vital structures.

Interventional radiology

Radiofrequency ablation is increasing in popularity for this condition as it is nontoxic and causes very little pain. It seems especially effective when combined with chemotherapy as it catches the cells inside a tumor—the ones difficult to get with chemotherapy due to reduced blood supply to the inside of the tumor. It is done by inserting a small heat probe into the tumor to cook the tumor cells. The body then disposes of the cooked cells through its normal eliminative processes.

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 epidermal growth factor receptor (EGF-R) which is expressed in many cases of NSCLC. however despite an exciting start it was not shown to increase survival, although younger females without a smoking history appear to be deriving most benefit from gefitinib.

A newer drug called erlotinib (Tarceva®) has been shown to increase survival in lung cancer patients and has recently been approved by the FDA for second-line treatment of advanced non-small cell lung cancer.[1] (http://medicineworld.org/cancer/lead/tarceva-approved.html)

Treatment of non-small cell lung cancer is evolving and the next few years could present exciting developments and new targeted therapies for lung cancer.

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. It is expected that 2001 will have seen 169,500 new cases of lung cancer in the US; 90,700 in men and 78,000 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.

The British Doctors Study, published in the 1950s, first offered solid 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 recognised as a risk factor for lung cancer, leading to policy interventions to decrease undesired exposure of non-smokers to others' tobacco smoke.

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 probably 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 New York City taking a lead in banning smoking in public establishments in March 2003, and Ireland playing a similar role in Europe in 2004.

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. A cynical view taken by many campaigners is that losses in excise would harm government revenue.

Screening and secondary prevention

Because prognosis depends heavily on early detection there have been several attempts at secondary prevention. Regular chest radiography and sputum examination programs were not effective in early detection of this cancer and did not result in a reduction of mortality.

Computerized tomography (CT) scanning is now being actively evaluated as a screening tool for lung cancer, and it is showing promising results. The National Cancer Institute (USA) is currently completing a randomized trial comparing CT scans with chest radiographs. Several single-institution trials are ongoing around the world. A large group of investigators (the International Early Lung Cancer Action Project) are currently collating the results of 26,000 screen-detected lung cancers and are showing excellent preliminary survivals with these patients. More work is needed in this area.

External links

Lung Cancer Resources Page (http://www.nci.nih.gov/cancerinfo/types/lung) at the National Cancer Institute.
Lungs Online - Lung Cancer (http://www.lungsonline.com/lung_cancer.html)
Tobacco Smoke and Involuntary Smoking, Summary of Data Reported and Evaluation 2004 (http://www-cie.iarc.fr/htdocs/indexes/vol83index.html) by the IARC.
A summary of the previous report (http://www.greenfacts.org/tobacco/) by the industry lobbying group GreenFacts.

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