Non-Small Cell Lung Cancer

Non-small cell lung cancer is a disease in which malignant (cancer) cells form in the tissues of the lung.

The lungs are a pair of cone-shaped breathing organs in the chest. The lungs bring oxygen into the body as you breathe in. They release carbon dioxide, a waste product of the body’s cells, as you breathe out. Each lung has sections called lobes. The left lung has two lobes. The right lung is slightly larger and has three lobes. Two tubes called bronchi lead from the trachea (windpipe) to the right and left lungs. The bronchi are sometimes also involved in lung cancer. Tiny air sacs called alveoli and small tubes called bronchioles make up the inside of the lungs.

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Anatomy of the respiratory system, showing the trachea and both lungs and their lobes and airways. Lymph nodes and the diaphragm are also shown. Oxygen is inhaled into the lungs and passes through the thin membranes of the alveoli and into the bloodstream (see inset).A thin membrane called the pleura covers the outside of each lung and lines the inside wall of the chest cavity. This creates a sac called the pleural cavity. The pleural cavity normally contains a small amount of fluid that helps the lungs move smoothly in the chest when you breathe.

There are two main types of lung cancer: non-small cell lung cancer and small cell lung cancer.

There are several types of non-small cell lung cancer.

Each type of non-small cell lung cancer has different kinds of cancer cells. The cancer cells of each type grow and spread in different ways. The types of non-small cell lung cancer are named for the kinds of cells found in the cancer and how the cells look under a microscope:

  • Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells that look like fish scales. This is also called epidermoid carcinoma.
  • Large cell carcinoma: Cancer that may begin in several types of large cells.
  • Adenocarcinoma: Cancer that begins in the cells that line the alveoli and make substances such as mucus.

Other less common types of non-small cell lung cancer are: pleomorphic, carcinoid tumor, salivary gland carcinoma, and unclassified carcinoma.

Smoking can increase the risk of developing non-small cell lung cancer.

Smoking cigarettes or cigars is the most common cause of lung cancer. The more years a person smokes, the greater the risk. If a person has stopped smoking, the risk becomes lower as the years pass, but is never completely gone.

Anything that increases a person's chance of developing a disease is called a risk factor. Having a risk factor does not mean that you will get cancer; not having risk factors doesn’t mean that you will not get cancer. People who think they may be at risk should discuss this with their doctor. Risk factors for lung cancer include the following:

  • Smoking cigarettes or cigars, now or in the past.
  • Being exposed to second-hand smoke.
  • Being treated with radiation therapy to the breast or chest.
  • Being exposed to asbestos, radon, chromium, arsenic, soot, or tar.
  • Living where there is air pollution.

When smoking is combined with other risk factors, the risk of developing lung cancer is increased.

Possible signs of non-small cell lung cancer include a cough that doesn't go away and shortness of breath.

Sometimes lung cancer does not cause any symptoms and is found during a routine chest x-ray. Symptoms may be caused by lung cancer or by other conditions. A doctor should be consulted if any of the following problems occur:

  • A cough that doesn’t go away.
  • Trouble breathing.
  • Chest discomfort.
  • Wheezing.
  • Streaks of blood in sputum (mucus coughed up from the lungs).
  • Hoarseness.
  • Loss of appetite.
  • Weight loss for no known reason.
  • Feeling very tired.

Tests that examine the lungs are used to detect (find), diagnose, and stage non-small cell lung cancer.

Tests and procedures to detect, diagnose, and stage non-small cell lung cancer are often done at the same time. The following tests and procedures may be used:

  • Physical exam and history: An exam of the body to check general signs of health, including checking for signs of disease, such as lumps or anything else that seems unusual. A history of the patient’s health habits, including smoking, and past jobs, illnesses, and treatments will also be taken.
  • Chest x-ray: An x-ray of the organs and bones inside the chest. An x-ray is a type of energy beam that can go through the body and onto film, making a picture of areas inside the body.

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X-ray of the chest. X-rays are used to take pictures of organs and bones of the chest. X-rays pass through the patient onto film.

  • CT scan (CAT scan): A procedure that makes a series of detailed pictures of areas inside the body, such as the chest, taken from different angles. The pictures are made by a computer linked to an x-ray machine. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography.
  • PET scan (positron emission tomography scan): A procedure to find malignant tumor cells in the body. A small amount of radioactive glucose (sugar) is injected into a vein. The PET scanner rotates around the body and makes a picture of where glucose is being used in the body. Malignant tumor cells show up brighter in the picture because they are more active and take up more glucose than normal cells do.

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PET (positron emission tomography) scan. The patient lies on a table that slides through the PET machine. The head rest and white strap help the patient lie still. A small amount of radioactive glucose (sugar) is injected into the patient's vein, and a scanner makes a picture of where the glucose is being used in the body. Cancer cells show up brighter in the picture because they take up more glucose than normal cells do.

  • Sputum cytology: A procedure in which a pathologist views a sample of sputum (mucus coughed up from the lungs) under a microscope, to check for cancer cells.
  • Fine-needle aspiration (FNA) biopsy of the lung: The removal of tissue or fluid from the lung using a thin needle. A CT scan, ultrasound, or other imaging procedure is used to locate the abnormal tissue or fluid in the lung. A small incision may be made in the skin where the biopsy needle is inserted into the abnormal tissue or fluid. A sample is removed with the needle and sent to the laboratory. A pathologist then views the sample under a microscope to look for cancer cells. A chest x-ray is done after the procedure to make sure no air is leaking from the lung into the chest.

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Lung biopsy. The patient lies on a table that slides through the computed tomography (CT) machine which takes x-ray pictures of the inside of the body. The x-ray pictures help the doctor see where the abnormal tissue is in the lung. A biopsy needle is inserted through the chest wall and into the area of abnormal lung tissue. A small piece of tissue is removed through the needle and checked under the microscope for signs of cancer.

  • Bronchoscopy: A procedure to look inside the trachea and large airways in the lung for abnormal areas. A bronchoscope is inserted through the nose or mouth into the trachea and lungs. A bronchoscope is a thin, tube-like instrument with a light and a lens for viewing. It may also have a tool to remove tissue samples, which are checked under a microscope for signs of cancer.

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Bronchoscopy. A bronchoscope is inserted through the mouth, trachea, and major bronchi into the lung, to look for abnormal areas. A bronchoscope is a thin, tube-like instrument with a light and a lens for viewing. It may also have a cutting tool. Tissue samples may be taken to be checked under a microscope for signs of disease.

  • Thoracoscopy: A surgical procedure to look at the organs inside the chest to check for abnormal areas. An incision (cut) is made between two ribs, and a thoracoscope is inserted into the chest. A thoracoscope is a thin, tube-like instrument with a light and a lens for viewing. It may also have a tool to remove tissue or lymph node samples, which are checked under a microscope for signs of cancer. In some cases, this procedure is used to remove part of the esophagus or lung. If certain tissues, organs, or lymph nodes can’t be reached, a thoracotomy may be done. In this procedure, a larger incision is made between the ribs and the chest is opened.
  • Thoracentesis: The removal of fluid from the space between the lining of the chest and the lung, using a needle. A pathologist views the fluid under a microscope to look for cancer cells.

Certain factors affect prognosis (chance of recovery) and treatment options.

The prognosis (chance of recovery) and treatment options depend on the following:

  • The stage of the cancer (the size of the tumor and whether it is in the lung only or has spread to other places in the body).
  • The type of lung cancer.
  • Whether there are symptoms such as coughing or trouble breathing.
  • The patient’s general health.

For most patients with non-small cell lung cancer, current treatments do not cure the cancer.

After lung cancer has been diagnosed, tests are done to find out if cancer cells have spread within the lungs or to other parts of the body.

The process used to find out if cancer has spread within the lungs or to other parts of the body is called staging. The information gathered from the staging process determines the stage of the disease. It is important to know the stage in order to plan treatment. Some of the tests used to diagnose non-small cell lung cancer are also used to stage the disease. (See the General Information section.) Other tests and procedures that may be used in the staging process include the following:

  • Laboratory tests: Medical procedures that test samples of tissue, blood, urine, or other substances in the body. These tests help to diagnose disease, plan and check treatment, or monitor the disease over time.
  • MRI (magnetic resonance imaging): A procedure that uses a magnet, radio waves, and a computer to make a series of detailed pictures of areas inside the body, such as the brain. This procedure is also called nuclear magnetic resonance imaging (NMRI).
  • Radionuclide bone scan: A procedure to check if there are rapidly dividing cells, such as cancer cells, in the bone. A very small amount of radioactive material is injected into a vein and travels through the bloodstream. The radioactive material collects in the bones and is detected by a scanner.
  • Endoscopic ultrasound (EUS): A procedure in which an endoscope is inserted into the body. An endoscope is a thin, tube-like instrument with a light and a lens for viewing. A probe at the end of the endoscope is used to bounce high-energy sound waves (ultrasound) off internal tissues or organs and make echoes. The echoes form a picture of body tissues called a sonogram. This procedure is also called endosonography. EUS may be used to guide fine needle aspiration (FNA) biopsy of the lung, lymph nodes, or other areas.

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Endoscopic ultrasound-guided fine-needle aspiration biopsy. An endoscope that has an ultrasound probe and a biopsy needle is inserted through the mouth and into the esophagus. The probe bounces sound waves off body tissues to make echoes that form a sonogram (computer picture) of the lymph nodes near the esophagus. The sonogram helps the doctor see where to place the biopsy needle to remove tissue from the lymph nodes. This tissue is checked under a microscope for signs of cancer.

  • Lymph node biopsy: The removal of all or part of a lymph node. A pathologist views the tissue under a microscope to look for cancer cells.
  • Mediastinoscopy: A surgical procedure to look at the organs, tissues, and lymph nodes between the lungs for abnormal areas. An incision (cut) is made at the top of the breastbone and a mediastinoscope is inserted into the chest. A mediastinoscope is a thin, tube-like instrument with a light and a lens for viewing. It may also have a tool to remove tissue or lymph node samples, which are checked under a microscope for signs of cancer.

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Mediastinoscopy. A mediastinoscope is inserted into the chest through an incision above the breastbone to look for abnormal areas between the lungs. A mediastinoscope is a thin, tube-like instrument with a light and a lens for viewing. It may also have a cutting tool. Tissue samples may be taken from lymph nodes on the right side of the chest and checked under a microscope for signs of cancer. In an anterior mediastinotomy (Chamberlain procedure), the incision is made beside the breastbone to remove tissue samples from the lymph nodes on the left side of the chest.

  • Anterior mediastinotomy: A surgical procedure to look at the organs and tissues between the lungs and between the breastbone and heart for abnormal areas. An incision (cut) is made next to the breastbone and a mediastinoscope is inserted into the chest. A mediastinoscope is a thin, tube-like instrument with a light and a lens for viewing. It may also have a tool to remove tissue or lymph node samples, which are checked under a microscope for signs of cancer. This is also called the Chamberlain procedure.

There are three ways that cancer spreads in the body.

The three ways that cancer spreads in the body are:

  • Through tissue. Cancer invades the surrounding normal tissue.
  • Through the lymph system. Cancer invades the lymph system and travels through the lymph vessels to other places in the body.
  • Through the blood. Cancer invades the veins and capillaries and travels through the blood to other places in the body.

When cancer cells break away from the primary (original) tumor and travel through the lymph or blood to other places in the body, another (secondary) tumor may form. This process is called metastasis. The secondary (metastatic) tumor is the same type of cancer as the primary tumor. For example, if breast cancer spreads to the bones, the cancer cells in the bones are actually breast cancer cells. The disease is metastatic breast cancer, not bone cancer.

The following stages are used for non-small cell lung cancer:

Occult (hidden) Stage

In the occult (hidden) stage, cancer cells are found in sputum (mucus coughed up from the lungs), but no tumor can be found in the lung by imaging or bronchoscopy, or the primary tumor is too small to be checked.

Stage 0 (Carcinoma in Situ)

In Stage 0, abnormal cells are found in the innermost lining of the lung. These abnormal cells may become cancer and spread into nearby normal tissue. Stage 0 is also called carcinoma in situ.

Stage I

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Stage I non-small cell lung cancer. In stage IA, cancer is in the lung only. In Stage IB, the cancer may do one or more of the following: (a) grow larger in the lung, (b) spread to the main bronchus of the lung, (c) spread to the innermost layer of the pleura that covers the lungs.

In stage I, cancer has formed. Stage I is divided into stages IA and IB:

  • Stage IA: The tumor is in the lung only and is 3 centimeters or smaller.
  • Stage IB: One or more of the following is true:
    • The tumor is larger than 3 centimeters.
    • Cancer has spread to the main bronchus of the lung, and is at least 2 centimeters from the carina (where the trachea joins the bronchi).
    • Cancer has spread to the innermost layer of the membrane that covers the lungs.
    • The tumor partly blocks the bronchus or bronchioles and part of the lung has collapsed or developed pneumonitis (inflammation of the lung).

Stage II

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Stage II non-small cell lung cancer. In stage IIA, cancer has spread to lymph nodes on the same side of the chest as the cancer. In stage IIB, cancer is either the same as in stage IB and has also spread to lymph nodes on the same side of the chest; or cancer has not spread to lymph nodes but has spread to one or more of the following: (a) the chest wall, (b) the diaphragm, (c) the pleura between the lungs, (d) the membrane around the heart, and/or (e) the main bronchus.

Stage II is divided into stages IIA and IIB:

  • Stage IIA: The tumor is 3 centimeters or smaller and cancer has spread to nearby lymph nodes on the same side of the chest as the tumor.
  • Stage IIB:
    • Cancer has spread to nearby lymph nodes on the same side of the chest as the tumor and one or more of the following is true:
      • The tumor is larger than 3 centimeters.
      • Cancer has spread to the main bronchus of the lung and is 2 centimeters or more from the carina (where the trachea joins the bronchi).
      • Cancer has spread to the innermost layer of the membrane that covers the lungs.
      • The tumor partly blocks the bronchus or bronchioles and part of the lung has collapsed or developed pneumonitis (inflammation of the lung).
    • Cancer has not spread to lymph nodes and one or more of the following is true:
      • The tumor may be any size and cancer has spread to the chest wall, or the diaphragm, or the pleura between the lungs, or membranes surrounding the heart.
      • Cancer has spread to the main bronchus of the lung and is no more than 2 centimeters from the carina (where the trachea meets the bronchi), but has not spread to the trachea.
      • Cancer blocks the bronchus or bronchioles and the whole lung has collapsed or developed pneumonitis (inflammation of the lung).

Stage IIIA

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Stage IIIA non-small cell lung cancer. The cancer has spread to the lymph nodes on the same side of the chest as the cancer. It may also spread to one or more of the following: (a) the main bronchus, (b) the chest wall, (c) the diaphragm, (d) the pleura between the lungs, and/or (e) the pericardium (membrane around the heart).

In stage IIIA, cancer has spread to lymph nodes on the same side of the chest as the tumor. Also:

  • The tumor may be any size.
  • Cancer may have spread to the main bronchus, the chest wall, the diaphragm, the pleura around the lungs, or the membrane around the heart, but has not spread to the trachea.
  • Part or all of the lung may have collapsed or developed pneumonitis (inflammation of the lung).

Stage IIIB

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Stage IIIB non-small cell lung cancer. The cancer has spread to (a) lymph nodes above the collarbone or lymph nodes on the opposite side of the chest from the cancer, and/or it may also spread to one or more of the following: (b) the heart, (c) the inferior vena cava and the aorta, (d) the chest wall, (e) the diaphragm, (f) the trachea, and (g) the sternum or esophagus. Cancer may also spread to the fluid between the pleura (thin layers of tissue lining the lungs and chest cavity).

In stage IIIB, the tumor may be any size and has spread:

  • To lymph nodes above the collarbone or in the opposite side of the chest from the tumor; and/or
  • To any of the following:
    • Heart.
    • Major blood vessels that lead to or from the heart.
    • Chest wall.
    • Diaphragm.
    • Trachea.
    • Esophagus.
    • Sternum (chest bone) or backbone.
    • More than one place in the same lobe of the lung.
    • The fluid of the pleural cavity surrounding the lung.

Stage IV

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Stage IV non-small cell lung cancer. The cancer has spread to another lobe of the same lung, to the other lung, and/or to one or more other parts of the body.

In stage IV, cancer may have spread to lymph nodes and has spread to another lobe of the lungs or to other parts of the body, such as the brain, liver, adrenal glands, kidneys, or bone.

Recurrent Non-Small Cell Lung Cancer

Recurrent non-small cell lung cancer is cancer that has recurred (come back) after it has been treated. The cancer may come back in the brain, lung, or other parts of the body.

There are different types of treatment for patients with non-small cell lung cancer.

Different types of treatments are available for patients with non-small cell lung cancer. Some treatments are standard (the currently used treatment), and some are being tested in clinical trials. A treatment clinical trial is a research study meant to help improve current treatments or obtain information on new treatments for patients with cancer. When clinical trials show that a new treatment is better than the standard treatment, the new treatment may become the standard treatment. Patients may want to think about taking part in a clinical trial. Some clinical trials are open only to patients who have not started treatment.

Six types of standard treatment are used:

Surgery

Four types of surgery are used:

  • Wedge resection: Surgery to remove a tumor and some of the normal tissue around it. When a slightly larger amount of tissue is taken, it is called a segmental resection.

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Wedge resection of the lung. Part of the lung lobe containing the cancer and a small amount of healthy tissue around it is removed.

  • Lobectomy: Surgery to remove a whole lobe (section) of the lung.
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Lobectomy. A lobe of the lung is removed.

  • Pneumonectomy: Surgery to remove one whole lung.

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Pneumonectomy. The whole lung is removed.

  • Sleeve resection: Surgery to remove part of the bronchus.

Radiation therapy

Radiation therapy is a cancer treatment that uses high-energy x-rays or other types of radiation to kill cancer cells or keep them from growing. There are two types of radiation therapy. External radiation therapy uses a machine outside the body to send radiation toward the cancer. Internal radiation therapy uses a radioactive substance sealed in needles, seeds, wires, or catheters that are placed directly into or near the cancer.

Radiosurgery is a method of delivering radiation directly to the tumor with little damage to healthy tissue. It does not involve surgery and may be used to treat certain tumors in patients who cannot have surgery.

The way the radiation therapy is given depends on the type and stage of the cancer being treated.

Chemotherapy

Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. When chemotherapy is taken by mouth or injected into a vein or muscle, the drugs enter the bloodstream and can reach cancer cells throughout the body (systemic chemotherapy). When chemotherapy is placed directly into the spinal column, an organ, or a body cavity such as the abdomen, the drugs mainly affect cancer cells in those areas (regional chemotherapy). The way the chemotherapy is given depends on the type and stage of the cancer being treated.

Laser therapy

Laser therapy is a cancer treatment that uses a laser beam (a narrow beam of intense light) to kill cancer cells.

Photodynamic therapy (PDT)

Photodynamic therapy (PDT) is a cancer treatment that uses a drug and a certain type of laser light to kill cancer cells. A drug that is not active until it is exposed to light is injected into a vein. The drug collects more in cancer cells than in normal cells. Fiberoptic tubes are then used to carry the laser light to the cancer cells, where the drug becomes active and kills the cells. Photodynamic therapy causes little damage to healthy tissue. It is used mainly to treat tumors on or just under the skin or in the lining of internal organs.

Watchful waiting

Watchful waiting is closely monitoring a patient’s condition without giving any treatment until symptoms appear or change. This may be done in certain rare cases of non-small cell lung cancer.

New types of treatment are being tested in clinical trials.

This summary section describes treatments that are being studied in clinical trials. It may not mention every new treatment being studied.

Chemoprevention

Chemoprevention is the use of drugs, vitamins, or other substances to reduce the risk of developing cancer or to reduce the risk cancer will recur (come back).

Biologic therapy

Biologic therapy is a treatment that uses the patient's immune system to fight cancer. Substances made by the body or made in a laboratory are used to boost, direct, or restore the body's natural defenses against cancer. This type of cancer treatment is also called biotherapy or immunotherapy.

New combinations

New combinations of treatments are being studied in clinical trials.

Patients may want to think about taking part in a clinical trial.

For some patients, taking part in a clinical trial may be the best treatment choice. Clinical trials are part of the cancer research process. Clinical trials are done to find out if new cancer treatments are safe and effective or better than the standard treatment.

Many of today's standard treatments for cancer are based on earlier clinical trials. Patients who take part in a clinical trial may receive the standard treatment or be among the first to receive a new treatment.

Patients who take part in clinical trials also help improve the way cancer will be treated in the future. Even when clinical trials do not lead to effective new treatments, they often answer important questions and help move research forward.

Patients can enter clinical trials before, during, or after starting their cancer treatment.

Some clinical trials only include patients who have not yet received treatment. Other trials test treatments for patients whose cancer has not gotten better. There are also clinical trials that test new ways to stop cancer from recurring (coming back) or reduce the side effects of cancer treatment.

Follow-up tests may be needed.

Some of the tests that were done to diagnose the cancer or to find out the stage of the cancer may be repeated. Some tests will be repeated in order to see how well the treatment is working. Decisions about whether to continue, change, or stop treatment may be based on the results of these tests. This is sometimes called re-staging.

Some of the tests will continue to be done from time to time after treatment has ended. The results of these tests can show if your condition has changed or if the cancer has recurred (come back). These tests are sometimes called follow-up tests or check-ups.

Treatment Options by Stage

Occult Non-Small Cell Lung Cancer
Stage 0 (Carcinoma in Situ)
Stage I Non-Small Cell Lung Cancer
Stage II Non-Small Cell Lung Cancer
Stage IIIA and Stage IIIB Non-Small Cell Lung Cancer
Stage IV Non-Small Cell Lung Cancer

Occult Non-Small Cell Lung Cancer

Treatment of occult non-small cell lung cancer depends on where the cancer has spread. It can usually be cured by surgery.

Stage 0 (Carcinoma in Situ)

Treatment of Stage 0 may include the following:

  • Surgery (wedge resection or segmental resection).
  • Photodynamic therapy using an endoscope.

Stage I Non-Small Cell Lung Cancer

Treatment of stage I non-small cell lung cancer may include the following:

  • Surgery (wedge resection, segmental resection, or lobectomy).
  • External radiation therapy (for patients who cannot have surgery or choose not to have surgery).
  • Surgery followed by chemotherapy.
  • A clinical trial of photodynamic therapy using an endoscope.
  • A clinical trial of surgery followed by chemoprevention.

Stage II Non-Small Cell Lung Cancer

Treatment of stage II non-small cell lung cancer may include the following:

  • Surgery (wedge resection, segmental resection, lobectomy, or pneumonectomy).
  • External radiation therapy (for patients who cannot have surgery or choose not to have surgery).
  • Surgery followed by chemotherapy, with or without other treatments.
  • A clinical trial of external radiation therapy following surgery.

Stage IIIA and Stage IIIB Non-Small Cell Lung Cancer

Treatment of stage IIIA non-small cell lung cancer may include the following:

  • Surgery with or without radiation therapy.
  • External radiation therapy alone.
  • Chemotherapy combined with other treatments.
  • A clinical trial of new ways of giving radiation therapy and chemotherapy.
  • A clinical trial of new combinations of treatments.

Treatment of stage IIIB non-small cell lung cancer may include the following:

  • External radiation therapy alone.
  • Chemotherapy combined with external radiation therapy.
  • Chemotherapy combined with external radiation therapy, followed by surgery.
  • Chemotherapy alone.
  • A clinical trial of new ways of giving radiation therapy.
  • A clinical trial of new combinations of treatments.

Stage IV Non-Small Cell Lung Cancer

Treatment of stage IV non-small cell lung cancer may include the following:

  • Watchful waiting.
  • External radiation therapy as palliative therapy, to relieve pain and other symptoms and improve the quality of life.
  • Chemotherapy.
  • Laser therapy and/or internal radiation therapy.
  • A clinical trial of chemotherapy with or without biologic therapy.

Treatment Options for Recurrent Non-Small Cell Lung Cancer

Treatment of recurrent non-small cell lung cancer may include the following:

  • External radiation therapy as palliative therapy, to relieve pain and other symptoms and improve the quality of life.
  • Chemotherapy alone.
  • Surgery (for some patients who have a very small amount of cancer that has spread to the brain).
  • Laser therapy or internal radiation therapy.
  • Radiosurgery (for certain patients who cannot have standard surgery).

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