LUNG CANCER

Cancer of the lung, like all cancers, results from an abnormality in the body’s basic unit of life, the cell. Normally, the body maintains a system of checks and balances on cell growth so that cells divide to produce new cells only when needed. Disruption of this system of checks and balances on cell growth results in an uncontrolled division and proliferation of cells that eventually forms a mass known as a tumor.

Tumors can be benign or malignant; when we speak of “cancer,” we refer to those tumors that are considered malignant. Benign tumors can usually be removed and do not spread to other parts of the body. Malignant tumors, on the other hand, grow aggressively and invade other tissues of the body, allowing entry of tumor cells into the bloodstream or lymphatic system which spread the tumor to other sites in the body. This process of spread is termed metastasis; the areas of tumor growth at these distant sites are called metastases. Since lung cancer tends to spread, or metastasize, very early in its course, it is a very life-threatening cancer and one of the most difficult cancers to treat. While lung cancer can spread to any organ in the body, certain organs—particularly the adrenal glands, liver, brain, and bone—are the most common sites for lung cancer metastasis.

Lung cancer, or carcinoma of the lung, is a disease where epithelial (internal lining) tissue in the lung grows out of control. This leads to invasion of adjacent tissue and infiltration beyond the lungs (metastasis). Lung cancer, the most common cause of cancer-related death in men and the second most common in women, is responsible for 1.3 million deaths worldwide annually. The most common symptoms are shortness of breath, cough (including coughing up blood), and weight loss.

The main types of lung cancer are small cell lung cancer and non-small cell lung cancer. This distinction is important because non-small cell lung cancer is sometimes treated with surgery, while small cell cancer is not. Also, small cell lung cancer usually responds better to chemotherapy.

The most important cause of lung cancer is exposure to tobacco smoke. The occurrence of lung cancer in non-smokers, who account for less than 10% of cases, appears to be due to a combination of genetic factors. Radon gas, asbestos, and air pollution may also contribute to the development of lung cancer.

Lung cancer may be seen on chest x-ray and 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. Even with treatment, the overall five-year survival rate is 14%.

The lung is also a very common site for metastasis from tumors in other parts of the body. Tumor metastases are made up of the same type of cells as the original, or primary, tumor. For example, if prostate cancer spreads via the bloodstream to the lungs, it is metastatic prostate cancer in the lung and is not lung cancer.

Lung cancers can arise in any part of the lung, and 90%-95% of cancers of the lung are thought to arise from the epithelial, or lining cells of the larger and smaller airways (bronchi and bronchioles); for this reason, lung cancers are sometimes called bronchogenic carcinomas or bronchogenic cancers. Cancers can also arise from the pleura (the thin layer of tissue that surrounds the lungs), called mesotheliomas, or rarely from supporting tissues within the lungs, for example, blood vessels.

Causes of Lung Cancer

Smoking

The incidence of lung cancer is strongly correlated with cigarette smoking, with about 90% of lung cancers arising as a result of tobacco use. The risk of lung cancer increases with the number of cigarettes smoked over time; doctors refer to this risk in terms of pack-years of smoking history (the number of packs of cigarettes smoked per day multiplied by the number of years smoked). For example, a person who has smoked two packs of cigarettes per day for 10 years has a 20 pack-year smoking history. While the risk of lung cancer is increased with even a 10 pack-year smoking history, those with 30 pack-year histories or more are considered to have the greatest risk for the development of lung cancer. Among those who smoke two or more packs of cigarettes per day, one in seven will die of lung cancer.

Pipe and cigar smoking can also cause lung cancer, although the risk is not as high as with cigarette smoking. While someone who smokes one pack of cigarettes per day has a risk for the development of lung cancer that is 25 times higher than a nonsmoker, pipe and cigar smokers have a risk of lung cancer that is about five times that of a nonsmoker.

Tobacco smoke contains over 4,000 chemical compounds, many of which have been shown to be cancer-causing, or carcinogenic. The two primary carcinogens in tobacco smoke are chemicals known as nitrosamines and polycyclic aromatic hydrocarbons. The risk of developing lung cancer decreases each year following smoking cessation as normal cells grow and replace damaged cells in the lung. In former smokers, the risk of developing lung cancer begins to approach that of a nonsmoker about 15 years after cessation of smoking. For more, please read the Smoking and Quitting Smoking article.

Passive smoking

Passive smoking, or the inhalation of tobacco smoke from other smokers sharing living or working quarters, is also an established risk factor for the development of lung cancer. Research has shown that nonsmokers who reside with a smoker have a 24% increase in risk for developing lung cancer when compared with other nonsmokers. An estimated 3,000 lung cancer deaths occur each year in the U.S. that are attributable to passive smoking.

Asbestos fibers

Asbestos fibers are silicate fibers that can persist for a lifetime in lung tissue following exposure to asbestos. The workplace is a common source of exposure to asbestos fibers, as asbestos was widely used in the past for both thermal and acoustic insulation materials. Today, asbestos use is limited or banned in many countries, including the Unites States. Both lung cancer and mesothelioma (a type of cancer of the pleura or of the lining of the abdominal cavity called the peritoneum) are associated with exposure to asbestos. Cigarette smoking drastically increases the chance of developing an asbestos-related lung cancer in exposed workers. Asbestos workers who do not smoke have a fivefold greater risk of developing lung cancer than nonsmokers, and those asbestos workers who smoke have a risk that is 50 to 90 times greater than nonsmokers.

Radon gas

Radon gas is a natural, chemically inert gas that is a natural decay product of uranium. It decays to form products that emit a type of ionizing radiation. Radon gas is a known cause of lung cancer, with an estimated 12% of lung cancer deaths attributable to radon gas, or 15,000 to 22,000 lung cancer-related deaths annually in the U.S., making radon the second leading cause of lung cancer in the U.S. As with asbestos exposure, concomitant smoking greatly increases the risk of lung cancer with radon exposure. Radon gas can travel up through soil and enter homes through gaps in the foundation, pipes, drains, or other openings. The U.S. Environmental Protection Agency estimates that one out of every 15 homes in the U.S. contains dangerous levels of radon gas. Radon gas is invisible and odorless, but it can be detected with simple test kits.

Familial predisposition

While the majority of lung cancers are associated with tobacco smoking, the fact that not all smokers eventually develop lung cancer suggests that other factors, such as individual genetic susceptibility, may play a role in the causation of lung cancer. Numerous studies have shown that lung cancer is more likely to occur in both smoking and nonsmoking relatives of those who have had lung cancer than in the general population. Recent research has localized a region on the long (q) arm of the human chromosome number 6 that is likely to contain a gene that confers an increased susceptibility to the development of lung cancer in smokers.

Lung diseases

The presence of certain diseases of the lung, notably chronic obstructive pulmonary disease (COPD), is associated with a slightly increased risk (four to six times the risk of a nonsmoker) for the development of lung cancer even after the effects of concomitant cigarette smoking are excluded.

Prior history of lung cancer

Survivors of lung cancer have a greater risk than the general population of developing a second lung cancer. Survivors of non-small cell lung cancers (NSCLCs, see below) have an additive risk of 1%-2% per year for developing a second lung cancer. In survivors of small cell lung cancers (SCLCs), the risk for development of second cancers approaches 6% per year.

Air pollution

Air pollution from vehicles, industry, and power plants can raise the likelihood of developing lung cancer in exposed individuals. Up to 1% of lung cancer deaths are attributable to breathing polluted air, and experts believe that prolonged exposure to highly polluted air can carry a risk similar to that of passive smoking for the development of lung cancer.

Viruses

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

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

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. In lung cancer, these phenomena may include Lambert-Eaton myasthenic syndrome (muscle weakness due to auto-antibodies), hypercalcemia or 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.

Many of the symptoms of lung cancer (bone pain, fever, weight loss) are nonspecific; in the elderly, these may be attributed to comorbid illness. 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. About 10% of people with lung cancer do not have symptoms at diagnosis; these cancers are incidentally found on routine chest x-rays.

Other changes that can sometimes occur with lung cancer may include repeated bouts of pneumonia, changes in the shape of the fingertips, and swollen or enlarged lymph nodes (glands) in the upper chest and lower neck.

These symptoms can happen with other illnesses, too. People with symptoms should talk to their doctor, especially if they smoke, but even if they don’t. Doctors can help find the cause.

When should one consult a doctor?

One should consult a health care provider if they develop the symptoms associated with lung cancer, in particular, if they have

• a new persistent cough or worsening of an existing chronic cough

,

• blood in the sputum,
• persistent bronchitis or repeated respiratory infections

,

• chest pain

,

• unexplained weight loss and/or fatigue

, and/or

• breathing difficulties such as shortness of breath or wheezing.

Diagnosis and Treatment

Picture 1: CT scan showing lung cancer in the left lung

Picture 2: Chest x-ray showing lung cancer in the left lung

A person’s lung cancer diagnosis depends on the type of lung cancer present. The two main types of lung cancer are small cell lung cancer and non-small cell lung cancer. Non-small cell lung cancer is more common than small cell lung cancer. These categories refer to what the cancer cells look like under a microscope.

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 (such as 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.

The extent of disease is referred to as the stage. Information about how big a cancer is or how far it has spread is often used to determine the stage. Doctors use information about stage to plan treatment and to monitor progress.

The differential diagnosis for patients who present with abnormalities on chest x-ray 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.

There are several ways to treat lung cancer. The treatment depends on the type of lung cancer and how far it has spread. Treatments include surgery, chemotherapy, and radiation. People with lung cancer often get more than one kind of treatment.

Surgery
Doctors cut out and remove cancer tissue in an operation.

If investigations confirm lung cancer, CT scan 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 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 a very poor respiratory reserve, as may occur in chronic smokers, surgery may be contraindicated.

Surgery itself has an overall operative death rate of about 4.4%, depending on the patient’s lung function and other risk factors. Surgery is usually only an option in non-small cell lung cancer limited to one lung, up to stage IIIA. This is assessed with medical imaging (computed tomography, positron emission tomography). A sufficient pre-operative 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), 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. Radioactive iodine brachytherapy at the margins of wedge excision may reduce recurrence to that of lobectomy. Chemotherapy
Chemotherapy involves the use of drugs to shrink or kill the cancer. The drugs could be pills or medicines given through an IV (intravenous) tube. Sometimes chemotherapy includes both IV drugs and pills.

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

The combination regimen depends on the tumor type. Non-small cell lung cancer is often treated with cisplatin or carboplatin, in combination with gemcitabine, paclitaxel, docetaxel, etoposide or vinorelbine. Combinations with carboplatin, gemcitabine, paclitaxel, vinorelbine, In small cell lung cancer, cisplatin and etoposide are most commonly used.topotecan and irinotecan are also used.Radiation
Radiation uses high-energy rays (similar to x-rays) to try to kill the cancer cells. The rays are aimed at the part of the body where the cancer is.

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

For both non-small cell lung cancer and small cell lung cancer 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.

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. 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%.These treatments may be provided by different doctors on your medical team. Pulmonologists are doctors that are experts in diseases of the lungs. Surgeons are doctors that perform operations. Medical oncologists are doctors that are experts in cancer and treat cancers with medicines. Radiation oncologists are doctors that treat cancers with radiation.

Prognosis

Prognosis depends on the cell type (histology), stage (degree of spread), and the patient’s performance status. Overall 5 year survival rates vary from 8.9% in developing countries to 15% in the United States.

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

Patients with extensive-stage SCLC have an average five-year survival rate of less than 1%. The For small cell lung carcinoma, prognosis is also poor. The overall five-year survival for patients with SCLC is about 5%.median survival time for limited-stage disease is 20 months, with a five-year survival rate of 20%.

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.

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 playing a similar role in Europe in 2004, followed by Italy and Norway in 2005, Scotland as well as several others in 2006, and England in 2007. New Zealand has also recently banned smoking in public places.

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

dr.rahees.k@live.in