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, certainorgans - particularly the adrenal glands, liver, brain, andbone - are the most common sites for lung cancer metastasis.
The lung also is 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 (primary) tumor. For example, ifprostate cancer spreads via the bloodstream to the lungs, it is metastatic prostate cancer in the lung and is not lung cancer.
The principal function of the lungs is to exchange gases between the air we breathe and the blood. Through the lung, carbon dioxide is removed from the bloodstream and oxygen from inspired air enters the bloodstream. The right lung has three lobes, while the left lung is divided into two lobes and a small structure called the lingula that is the equivalent of the middle lobe on the right.
The major airways entering the lungs are the bronchi, which arise from the trachea. The bronchi branch into progressively smaller airways called bronchioles that end in tiny sacs known as alveoli where gas exchange occurs. The lungs and chest wall are covered with a thin layer of tissue called the pleura.
Lung cancers can arise in any part of the lung, but 90%-95% of cancers of the lung are thought to arise from the epithelial cells, the cells lining the larger and smaller airways (bronchi and bronchioles); for this reason, lung cancers are sometimes called bronchogenic cancers or bronchogenic carcinomas. Carcinoma is another term for cancer.
Cancers also can arise from the pleura (called mesotheliomas) or rarely from supporting tissues within the lungs, for example, the blood vessels.
The most common cause of lung cancer is smoking.
Smoking causes lung cancer because there are substances within tobacco that are known to cause cancer. These substances are known as carcinogens (which means "cancer-causing agents"), and it is these carcinogens that cause the actual damage to the cells in the lungs. A cell that is damaged may become cancerous over a period of time.
One cannot predict which smoker is at greater risk of developing lung cancer.
In general, though, a smoker's chances of developing cancer depends on:
- The age that the person began smoking.
- How long the person has smoked.
- How many cigarettes per day the person smokes.
Passive smoking - breathing in someone else's smoke - may also increase the risk for developing lung cancer.
There are other causes of lung cancer not related to smoking. People who smoke and who also are exposed to these other causes have an even higher risk for lung cancer.
These other causes include:
- Exposure to cancer-causing agents through a person's job. This includes exposure to asbestos, either in the mining or construction industries. Inhaled asbestos particles may remain in the lungs, damaging lung cells. It also includes exposure to certain industrial substances like coal products, vinyl chloride, nickel chromate, arsenic, and exposure to some organic chemicals like chloromethyl ethers.
- Exposure to radiation, either through one's occupation or for medical reasons, such as repeated x-rays, though this is quite uncommon.
- Radon gas, which occurs naturally in rocks and soil in certain areas, may cause lung damage and may eventually result in lung cancer if it seeps into your home. The presence of radon in the home can be measured using an inexpensive kit that can be purchased at department or hardware stores.
Research suggests that some people are more at risk for developing cancer if their body is not as easily able to deal with certain cancer-causing chemicals. This inability to neutralize cancer-causing chemicals is believed to be inherited.
Researchers also believe that in some people, when they come into contact with certain cancer-causing agents, their immune system, instead of neutralizing them, will actually make these agents more aggressive within the body. Such people, therefore, would be more sensitive to tobacco smoke and chemicals known to cause 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.
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 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 experiencenausea, 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.
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.
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.
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.