Lungs cancer

•  Lung cancer is the number-one cause of cancer deaths in both men and women in the U.S. and worldwide.
• Cigarette smoking is the principal risk factor for development of lung cancer.
• Passive exposure to tobacco smoke also can cause lung cancer.
• The two types of lung cancer, which grow and spread differently, are the small cell lung cancers (SCLC) and non-small cell lung cancers (NSCLC).
• The stage of lung cancer refers to the extent to which the cancer has spread in the body.
• Treatment of lung cancer can involve a combination of surgery, chemotherapy, and radiation therapy as well as newer experimental methods.
• The general prognosis of lung cancer is poor, with overall survival rates of about 16% at five years.
• Smoking cessation is the most important measure that can prevent the development of lung cancer.

What is 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 new cells are 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 are referring to those tumors that are malignant. Benign tumors usually can 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 and then 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 after it forms, 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.

How common is lung cancer?

Lung cancer is the most common cause of death due to cancer in both men and women throughout the world. The American Cancer Society estimated that 222,520 new cases of lung cancer in the U.S. will be diagnosed and 157,300 deaths due to lung cancer would occur in 2010. According to the U.S. National Cancer Institute, approximately one out of every 14 men and women in the U.S. will be diagnosed with cancer of the lung at some point in their lifetime.
Lung cancer is predominantly a disease of the elderly; almost 70% of people diagnosed with lung cancer are over 65 years of age, while less than 3% of lung cancers occur in people under 45 years of age.
Lung cancer was not common prior to the 1930s but increased dramatically over the following decades as tobacco smoking increased. In many developing countries, the incidence of lung cancer is beginning to fall following public education about the dangers of cigarette smoking and the introduction of effective smoking-cessation programs. Nevertheless, lung cancer remains among the most common types of cancers in both men and women worldwide. In the U.S., lung cancer has surpassed breast cancer as the most common cause of cancer-related deaths in women.

What causes 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 and the time over which smoking has occurred; 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 also can cause lung cancer, although the risk is not as high as with cigarette smoking. Thus, 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.
Passive smoking
Passive smoking or the inhalation of tobacco smoke by nonsmokers who share living or working quarters with smokers, also is 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 nonsmokers who do not reside with a smoker. An estimated 3,000 lung cancer deaths that occur each year in the U.S. 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 as both thermal and acoustic insulation. Today, asbestos use is limited or banned in many countries, including the U.S. Both lung cancer and mesothelioma (cancer of the pleura of the lung as well as 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 workers exposed to asbestos. Asbestos workers who do not smoke have a fivefold greater risk of developing lung cancer than nonsmokers, but asbestos workers who smoke have a risk that is fifty- to ninetyfold greater than nonsmokers.
Radon gas
Radon gas is a natural, chemically inert gas that is a natural decay product of uranium. Uranium decays to form products, including radon, 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 about 20,000 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. Recently, the largest genetic study of lung cancer ever conducted, involving over 10,000 people from 18 countries and led by the International Agency for Research on Cancer (IARC), identified a small region in the genome (DNA) that contains genes that appear to confer an increased susceptibility to lung cancer in smokers. The specific genes, located the q arm of chromosome 15, code for proteins that interact with nicotine and other tobacco toxins (nicotinic acetylcholine receptor genes).
Lung diseases
The presence of certain diseases of the lung, notably chronic obstructive pulmonary disease (COPD), is associated with an increased risk (four- to sixfold 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 of developing a second lung cancer than the general population has of developing a first 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, see below), the risk for development of second lung 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 for the development of lung cancer similar to that of passive smoking.

 

What are the types of lung cancer?

Lung cancers, also known as bronchogenic carcinomas, are broadly classified into two types: small cell lung cancers (SCLC) and non-small cell lung cancers (NSCLC). This classification is based upon the microscopic appearance of the tumor cells themselves. These two types of cancers grow and spread in different ways and may have different treatment options, so a distinction between these two types is important.
SCLC comprise about 20% of lung cancers and are the most aggressive and rapidly growing of all lung cancers. SCLC are strongly related to cigarette smoking, with only 1% of these tumors occurring in nonsmokers. SCLC metastasize rapidly to many sites within the body and are most often discovered after they have spread extensively. Referring to a specific cell appearance often seen when examining samples of SCLC under the microscope, these cancers are sometimes called oat cell carcinomas.
NSCLC are the most common lung cancers, accounting for about 80% of all lung cancers. NSCLC can be divided into three main types that are named based upon the type of cells found in the tumor:

• Adenocarcinomas are the most commonly seen type of NSCLC in the U.S. and comprise up to 50% of NSCLC. While adenocarcinomas are associated with smoking, like other lung cancers, this type is observed as well in nonsmokers who develop lung cancer. Most adenocarcinomas arise in the outer, or peripheral, areas of the lungs. Bronchioloalveolar carcinoma is a subtype of adenocarcinoma that frequently develops at multiple sites in the lungs and spreads along the preexisting alveolar walls.
• Squamous cell carcinomas were formerly more common than adenocarcinomas; at present, they account for about 30% of NSCLC. Also known as epidermoid carcinomas, squamous cell cancers arise most frequently in the central chest area in the bronchi.
• Large cell carcinomas, sometimes referred to as undifferentiated carcinomas, are the least common type of NSCLC.
• Mixtures of different types of NSCLC are also seen.

Other types of cancers can arise in the lung; these types are much less common than NSCLC and SCLC and together comprise only 5%-10% of lung cancers:

• Bronchial carcinoids account for up to 5% of lung cancers. These tumors are generally small (3 cm-4 cm or less) when diagnosed and occur most commonly in people under 40 years of age. Unrelated to cigarette smoking, carcinoid tumors can metastasize, and a small proportion of these tumors secrete hormone-like substances that may cause specific symptoms related to the hormone being produced. Carcinoids generally grow and spread more slowly than bronchogenic cancers, and many are detected early enough to be amenable to surgical resection.
• Cancers of supporting lung tissue such as smooth muscle, blood vessels, or cells involved in the immune response can rarely occur in the lung.

As discussed previously, metastatic cancers from other primary tumors in the body are often found in the lung. Tumors from anywhere in the body may spread to the lungs either through the bloodstream, through the lymphatic system, or directly from nearby organs. Metastatic tumors are most often multiple, scattered throughout the lung, and concentrated in the peripheral rather than central areas of the lung.

What are lung cancer symptoms and signs?

 

Symptoms of lung cancer are varied depending upon where and how widespread the tumor is. Warning signs of lung cancer are not always present or easy to identify. A person with lung cancer may have the following kinds of symptoms:

• No symptoms: In up to 25% of people who get lung cancer, the cancer is first discovered on a routine chest X-ray or CT scan as a solitary small mass sometimes called a coin lesion, since on a two-dimensional X-ray or CT scan, the round tumor looks like a coin. These patients with small, single masses often report no symptoms at the time the cancer is discovered.
• Symptoms related to the cancer: The growth of the cancer and invasion of lung tissues and surrounding tissue may interfere with breathing, leading to symptoms such as cough, shortness of breath, wheezing, chest pain, and coughing up blood (hemoptysis). If the cancer has invaded nerves, for example, it may cause shoulder pain that travels down the outside of the arm (called Pancoast's syndrome) or paralysis of the vocal cords leading to hoarseness. Invasion of the esophagus may lead to difficulty swallowing (dysphagia). If a large airway is obstructed, collapse of a portion of the lung may occur and cause infections (abscesses, pneumonia) in the obstructed area.
• Symptoms related to metastasis: Lung cancer that has spread to the bones may produce excruciating pain at the sites of bone involvement. Cancer that has spread to the brain may cause a number of neurologic symptoms that may include blurred vision, headaches, seizures, or symptoms of stroke such as weakness or loss of sensation in parts of the body.
• Paraneoplastic symptoms: Lung cancers frequently are accompanied by symptoms that result from production of hormone-like substances by the tumor cells. These paraneoplastic syndromes occur most commonly with SCLC but may be seen with any tumor type. A common paraneoplastic syndrome associated with SCLC is the production of a hormone called adrenocorticotrophic hormone (ACTH) by the cancer cells, leading to oversecretion of the hormone cortisol by the adrenal glands (Cushing's syndrome). The most frequent paraneoplastic syndrome seen with NSCLC is the production of a substance similar to parathyroid hormone, resulting in elevated levels of calcium in the bloodstream.
• Nonspecific symptoms: Nonspecific symptoms seen with many cancers, including lung cancers, include weight loss, weakness, and fatigue. Psychological symptoms such as depression and mood changes are also common.

When should one consult a doctor?
One should consult a health-care provider if he or she develops 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
,
• breathing difficulties such as shortness of breath or wheezing

What is the treatment for lung cancer?

Treatment for lung cancer can involve surgical removal of the cancer, chemotherapy, or radiation therapy, as well as combinations of these treatments. The decision about which treatments will be appropriate for a given individual must take into account the location and extent of the tumor as well as the overall health status of the patient.
As with other cancers, therapy may be prescribed that is intended to be curative (removal or eradication of a cancer) or palliative (measures that are unable to cure a cancer but can reduce pain and suffering). More than one type of therapy may be prescribed. In such cases, the therapy that is added to enhance the effects of the primary therapy is referred to as adjuvant therapy. An example of adjuvant therapy is chemotherapy or radiotherapy administered after surgical removal of a tumor in an attempt to kill any tumor cells that remain following surgery.
Surgery: Surgical removal of the tumor is generally performed for limited-stage (stage I or sometimes stage II) NSCLC and is the treatment of choice for cancer that has not spread beyond the lung. About 10%-35% of lung cancers can be removed surgically, but removal does not always result in a cure, since the tumors may already have spread and can recur at a later time. Among people who have an isolated, slow-growing lung cancer removed, 25%-40% are still alive five years after diagnosis. It is important to note that although a tumor may be anatomically suitable for resection, surgery may not be possible if the person has other serious conditions (such as severe heart or lung disease) that would limit their ability to survive an operation. Surgery is less often performed with SCLC than with NSCLC because these tumors are less likely to be localized to one area that can be removed.
The surgical procedure chosen depends upon the size and location of the tumor. Surgeons must open the chest wall and may perform a wedge resection of the lung (removal of a portion of one lobe), a lobectomy (removal of one lobe), or a pneumonectomy (removal of an entire lung). Sometimes lymph nodes in the region of the lungs also are removed (lymphadenectomy). Surgery for lung cancer is a major surgical procedure that requires general anesthesia, hospitalization, and follow-up care for weeks to months. Following the surgical procedure, patients may experience difficulty breathing, shortness of breath, pain, and weakness. The risks of surgery include complications due to bleeding, infection, and complications of general anesthesia.
Radiation: Radiation therapy may be employed as a treatment for both NSCLC and SCLC. Radiation therapy uses high-energy X-rays or other types of radiation to kill dividing cancer cells. Radiation therapy may be given as curative therapy, palliative therapy (using lower doses of radiation than with curative therapy), or as adjuvant therapy in combination with surgery or chemotherapy. The radiation is either delivered externally, by using a machine that directs radiation toward the cancer, or internally through placement of radioactive substances in sealed containers within the area of the body where the tumor is localized. Brachytherapy is a term used to describe the use of a small pellet of radioactive material placed directly into the cancer or into the airway next to the cancer. This is usually done through a bronchoscope.
Radiation therapy can be given if a person refuses surgery, if a tumor has spread to areas such as the lymph nodes or trachea making surgical removal impossible, or if a person has other conditions that make them too ill to undergo major surgery. Radiation therapy generally only shrinks a tumor or limits its growth when given as a sole therapy, yet in 10%-15% of people it leads to long-term remission and palliation of the cancer. Combining radiation therapy with chemotherapy can further prolong survival when chemotherapy is administered. External radiation therapy can generally be carried out on an outpatient basis, while internal radiation therapy requires a brief hospitalization. A person who has severe lung disease in addition to a lung cancer may not be able to receive radiotherapy to the lung since the radiation can further decrease function of the lungs. A type of external radiation therapy called the "gamma knife" is sometimes used to treat single brain metastases. In this procedure, multiple beams of radiation coming from different directions are focused on the tumor over a few minutes to hours while the head is held in place by a rigid frame. This reduces the dose of radiation that is received by noncancerous tissues.
For external radiation therapy, a process called simulation is necessary prior to treatment. Using CT scans, computers, and precise measurements, simulation maps out the exact location where the radiation will be delivered, called the treatment field or port. This process usually takes 30 minutes to two hours. The external radiation treatment itself generally is done four or five days a week for several weeks.
Radiation therapy does not carry the risks of major surgery, but it can have unpleasant side effects, including fatigue and lack of energy. A reduced white blood cell count (rendering a person more susceptible to infection) and low blood platelet levels (making blood clotting more difficult and resulting in excessive bleeding) also can occur with radiation therapy. If the digestive organs are in the field exposed to radiation, patients may experience nausea, vomiting, or diarrhea. Radiation therapy can irritate the skin in the area that is treated, but this irritation generally improves with time after treatment has ended.
Chemotherapy: Both NSCLC and SCLC may be treated with chemotherapy. Chemotherapy refers to the administration of drugs that stop the growth of cancer cells by killing them or preventing them from dividing. Chemotherapy may be given alone, as an adjuvant to surgical therapy, or in combination with radiotherapy. While a number of chemotherapeutic drugs have been developed, the class of drugs known as the platinum-based drugs have been the most effective in treatment of lung cancers.
Chemotherapy is the treatment of choice for most SCLC, since these tumors are generally widespread in the body when they are diagnosed. Only half of people who have SCLC survive for four months without chemotherapy. With chemotherapy, their survival time is increased up to four- to fivefold. Chemotherapy alone is not particularly effective in treating NSCLC, but when NSCLC has metastasized, it can prolong survival in many cases.
Chemotherapy may be given as pills, as an intravenous infusion, or as a combination of the two. Chemotherapy treatments usually are given in an outpatient setting. A combination of drugs is given in a series of treatments, called cycles, over a period of weeks to months, with breaks in between cycles. Unfortunately, the drugs used in chemotherapy also kill normally dividing cells in the body, resulting in unpleasant side effects. Damage to blood cells can result in increased susceptibility to infections and difficulties with blood clotting (bleeding or bruising easily). Other side effects include fatigue, weight loss, hair loss, nausea, vomiting, diarrhea, and mouth sores. The side effects of chemotherapy vary according to the dosage and combination of drugs used and may also vary from individual to individual. Medications have been developed that can treat or prevent many of the side effects of chemotherapy. The side effects generally disappear during the recovery phase of the treatment or after its completion.
Prophylactic brain radiation: SCLC often spreads to the brain. Sometimes people with SCLC that is responding well to treatment are treated with radiation therapy to the head to treat very early spread to the brain (called micrometastasis) that is not yet detectable with CT or MRI scans and has not yet produced symptoms. Brain radiation therapy can cause short-term memory problems, fatigue, nausea, and other side effects.
Treatment of recurrence: Lung cancer that has returned following treatment with surgery, chemotherapy, and/or radiation therapy is referred to as recurrent or relapsed. If a recurrent cancer is confined to one site in the lung, it may be treated with surgery. Recurrent tumors generally do not respond to the chemotherapeutic drugs that were previously administered. Since platinum-based drugs are generally used in initial chemotherapy of lung cancers, these agents are not useful in most cases of recurrence. A type of chemotherapy referred to as second-line chemotherapy is used to treat recurrent cancers that have previously been treated with chemotherapy, and a number of second-line chemotherapeutic regimens have been proven effective at prolonging survival. People with recurrent lung cancer who are well enough to tolerate therapy also are good candidates for experimental therapies (see below), including clinical trials.
Targeted therapy: The drugs erlotinib (Tarceva) and gefitinib (Iressa) are so-called targeted drugs, which may be used in certain patients with NSCLC who are no longer responding to chemotherapy. Targeted therapy drugs more specifically target cancer cells, resulting in less damage to normal cells than general chemotherapeutic agents. Erlotinib and gefitinib target a protein called the epidermal growth factor receptor (EGFR) that is important in promoting the division of cells. This protein is found at abnormally high levels on the surface of some types of cancer cells, including many cases of non-small cell lung cancer.
Other attempts at targeted therapy include drugs known as antiangiogenesis drugs, which block the development of new blood vessels within a cancer. Without adequate blood vessels to supply oxygen-carrying blood, the cancer cells will die. The antiangiogenic drug bevacizumab (Avastin) has also been found to prolong survival in advanced lung cancer when it is added to the standard chemotherapy regimen. Bevacizumab is given intravenously every two to three weeks. However, since this drug may cause bleeding, it is not appropriate for use in patients who are coughing up blood, if the lung cancer has spread to the brain, or in people who are receiving anticoagulation therapy ("blood thinner" medications). Bevacizumab also is not used in cases of squamous cell cancer because it leads to bleeding from this type of lung cancer.
Cetuximab is an antibody that binds to the epidermal growth factor receptor (EGFR).. In patients with NSCLC whose tumors have been shown to express the EGFR by immunohistochemical analysis, the addition of cetuximab may be considered for some patients.
Photodynamic therapy (PDT): One newer therapy used for different types and stages of lung cancer (as well as some other cancers) is photodynamic therapy. In photodynamic treatment, a photosynthesizing agent (such as a porphyrin, a naturally occurring substance in the body) is injected into the bloodstream a few hours prior to surgery. During this time, the agent is taken up in rapidly growing cells such as cancer cells. A procedure then follows in which the physician applies a certain wavelength of light through a handheld wand directly to the site of the cancer and surrounding tissues. The energy from the light activates the photosensitizing agent, causing the production of a toxin that destroys the tumor cells. PDT has the advantages that it can precisely target the location of the cancer, is less invasive than surgery, and can be repeated at the same site if necessary. The drawbacks of PDT are that it is only useful in treating cancers that can be reached with a light source and is not suitable for treatment of extensive cancers. The U.S. Food and Drug Administration (FDA) has approved the photosensitizing agent called porfimer sodium (Photofrin) for use in PDT to treat or relieve the symptoms of esophageal cancer and non-small cell lung cancer. Further research is ongoing to determine the effectiveness of PDT in other types of lung cancer.
Radiofrequency ablation (RFA): Radiofrequency ablation is being studied as an alternative to surgery, particularly in cases of early stage lung cancer. In this type of treatment, a needle is inserted through the skin into the cancer, usually under guidance by CT scanning. Radiofrequency (electrical) energy is then transmitted to the tip of the needle where it produces heat in the tissues, killing the cancerous tissue and closing small blood vessels that supply the cancer. RFA usually is not painful and has been approved by the U.S. Food and Drug Administration for the treatment of certain cancers, including lung cancers. Studies have shown that this treatment can prolong survival similarly to surgery when used to treat early stages of lung cancer but without the risks of major surgery and the prolonged recovery time associated with major surgical procedures.
Experimental therapies: Since no therapy is currently available that is absolutely effective in treating lung cancer, patients may be offered a number of new therapies that are still in the experimental stage, meaning that doctors do not yet have enough information to decide whether these therapies should become accepted forms of treatment for lung cancer. New drugs or new combinations of drugs are tested in so-called clinical trials, which are studies that evaluate the effectiveness of new medications in comparison with those treatments already in widespread use. Experimental treatments known as immunotherapies are being studied that involve the use of vaccine-related therapies or other therapies that attempt to utilize the body's immune system to fight cancer cells.