What Is Lung Cancer?
Lung cancer is the uncontrolled growth of abnormal cells in one or both lungs. These abnormal cells do not carry out the functions of normal lung cells and do not develop into healthy lung tissue. As they grow, the abnormal cells can form tumors and interfere with the functioning of the lung, which provides oxygen to the body via the blood.
The Genetic Basis of Lung Cancer
All cells in the body contain the genetic material called deoxyribonucleic acid (DNA). Every time a mature cell divides into two new cells, its DNA is exactly duplicated. The cells are copies of the original cell, identical in every way. In this way our bodies continually replenish themselves. Old cells die off and the next generation replaces them.
A cancer begins with an error, or mutation, in a cell’s DNA. DNA mutations can be caused by the normal aging process or through environmental factors, such as cigarette smoke, breathing in asbestos fibers, and to exposure to radon gas.
Researchers have found that it takes a series of mutations to create a lung cancer cell. Before becoming fully cancerous, cells can be precancerous, in that they have some mutations but still function normally as lung cells. When a cell with a genetic mutation divides, it passes along its abnormal genes to the two new cells, which then divide into four cells with errors in their DNA and so on. With each new mutation, the lung tissue cell becomes more mutated and may not be as effective in carrying out its function as a lung cell. At a later stage of disease, some cells may travel away from the original tumor and start growing in other parts of the body. This process is call metastasis and the new distant sites are referred to as metastases.
Primary Versus Secondary Lung Cancer
Primary lung cancer starts in the lungs. The cancer cells are abnormal lung cells. Sometimes, people will have cancer travel from another part of their body or metastasize to their lungs. This is called secondary lung cancer because the lungs are a secondary site compared to the original primary location of the cancer. So, for example, breast cancer cells which have traveled to the lung are not lung cancer but rather metastatic breast cancer, and will require treatment prescribed for breast cancer rather than lung cancer.
Symptoms of Lung Cancer
It’s important to report any unusual physical feelings to your doctor. Often, these unusual feelings can be attributed to other causes, such as bronchitis. But a doctor should check anything that is unusual or worrisome. The signs and symptoms of lung cancer can take years to develop and they may not appear until the disease is advanced.
Symptoms of lung cancer that are in the chest:
- Coughing, especially if it persists or becomes intense
- Pain in the chest, shoulder, or back unrelated to pain from coughing
- A change in color or volume of sputum
- Shortness of breath
- Changes in the voice or being hoarse
- Harsh sounds with each breath (stridor)
- Recurrent lung problems, such as bronchitis or pneumonia
- Coughing up phlegm or mucus, especially if it is tinged with blood
- Coughing up blood
If the original lung cancer has spread, a person may feel symptoms in other places in the body. Common places for lung cancer to spread include other parts of the lungs, lymph nodes, bones, brain, liver, and adrenal glands.
Symptoms of lung cancer that may occur elsewhere in the body:
- Loss of appetite or unexplained weight loss
- Muscle wasting (also known as cachexia)
- Headaches, bone or joint pain
- Bone fractures not related to accidental injury
- Neurological symptoms, such as unsteady gait or memory loss
- Neck or facial swelling
- General weakness
- Blood clots
Diagnosing Lung Cancer
If lung cancer is suspected as a result of a screening procedure, a small piece of tissue from the lung must be examined under a microscope to look for cancer cells. Called a biopsy, this procedure can be performed in different ways. In some cases, the doctor passes a needle through the skin into the lungs to remove a small piece of tissue; this procedure is often called a needle biopsy.
In other cases, a biopsy may be done during a bronchoscopy. To perform a bronchoscopy, the doctor inserts a small tube through the mouth or nose and into the lungs. The tube, which has a light on the end, allows the doctor to see inside the lungs and to remove a small tissue sample.
When a person is diagnosed with lung cancer, looking at biopsied cells under the microscope also helps doctors determine the type of lung cancer. It is important to know the specific type because this information helps doctors recommend the best treatment.
Types and Staging of Lung Cancer
There are two major types of lung cancer, non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Staging lung cancer is based on whether the cancer is local or has spread from the lungs to the lymph nodes or other organs. Because the lungs are large, tumors can grow in them for a long time before they are found. Even when symptoms—such as coughing and fatigue—do occur, people think they are due to other causes. For this reason, early-stage lung cancer (stages I and II) is difficult to detect. Most people with lung cancer are diagnosed at stages III and IV.
Non-Small Cell Lung Cancer
Non-small cell lung cancer accounts for about 85 percent of lung cancers. Among them are these types of tumors:
- Adenocarcinoma is the most common form of lung cancer in the United States among both men and women.
- Squamous cell carcinoma (which is also called epidermoid carcinoma) forms in the lining of the bronchial tubes.
- Large cell carcinomas refer to non-small cell lung cancers that are neither adenocarcinomas nor epidermoid cancers.
STAGES OF NON-SMALL CELL LUNG CANCER
Stage I: The cancer is located only in the lungs and has not spread to any lymph nodes.
Stage II: The cancer is in the lung and nearby lymph nodes.
Stage III: Cancer is found in the lung and in the lymph nodes in the middle of the chest, also described as locally advanced disease. Stage III has two subtypes:
- If the cancer has spread only to lymph nodes on the same side of the chest where the cancer started, it is called stage IIIA.
- If the cancer has spread to the lymph nodes on the opposite side of the chest, or above the collar bone, it is called stage IIIB.
Stage IV: This is the most advanced stage of lung cancer, and is also described as advanced disease. This is when the cancer has spread to both lungs, to fluid in the area around the lungs, or to another part of the body, such as the liver or other organs.
Small Cell Lung Cancer
Small cell lung cancer accounts for the remaining 15 percent of lung cancers in the United States. Small cell lung cancer results from smoking even more so than non-small cell lung cancer, and grows more rapidly and spreads to other parts of the body earlier than non-small cell lung cancer. It is also more responsive to chemotherapy.
Stages of Small Cell Lung Cancer
Limited stage: In this stage, cancer is found on one side of the chest, involving just one part of the lung and nearby lymph nodes.
Extensive stage: In this stage, cancer has spread to other regions of the chest or other parts of the body.
More recently, the American Joint Commission on Cancer implemented a more detailed staging system in which the stages of small cell lung cancer are described using Roman numerals and letters (for example, Stage IIA). This is the same method that is used for non-small cell lung cancer in describing the growth and spread of the cancer.
Non-Small Cell Lung Cancer Treatment
Surgery, radiation, chemotherapy, and targeted treatments—alone or in combination—are used to treat lung cancer. Each of these types of treatments may cause different side effects.
Most stage I and stage II non-small cell lung cancers are treated with surgery to remove the tumor. For this procedure, a surgeon removes the lobe, or section, of the lung containing the tumor.
Some surgeons use video-assisted thoracoscopic surgery (VATS). For this procedure, the surgeon makes a small incision, or cut, in the chest and inserts a tube called a thoracoscope. The thoracoscope has a light and a tiny camera connected to a video monitor so that the surgeon can see inside the chest. A lung lobe can then be removed through the scope, without making a large incision in the chest.
Chemotherapy and Radiation
For people with non-small cell lung tumors that can be surgically removed, evidence suggests that chemotherapy after surgery, known as “adjuvant chemotherapy,” may help prevent the cancer from returning. This is particularly true for patients with stage II and IIIA disease. Questions remain about whether adjuvant chemotherapy applies to other patients and how much they benefit.
For people with stage III lung cancer that cannot be removed surgically, doctors typically recommend chemotherapy in combination with definitive (high-dose) radiation treatments. In stage IV lung cancer, chemotherapy is typically the main treatment. In stage IV patients, radiation is used only for palliation of symptoms.
The chemotherapy treatment plan for lung cancer often consists of a combination of drugs. Among the drugs most commonly used are cisplatin (Platinol) or carboplatin (Paraplatin) plus docetaxel (Taxotere), gemcitabine (Gemzar), paclitaxel (Taxol and others), vinorelbine (Navelbine and others), or pemetrexed (Alimta).
There are times when these treatments may not work. Or, after these drugs work for a while, the lung cancer may come back. In such cases, doctors often prescribe a second course of drug treatment referred to as second-line chemotherapy.
Recently, the concept of maintenance chemotherapy has been tested in clinical trials, either as a switch to another drug before the cancer progresses; or to continue one of the drugs used initially for a longer period of time. Both of these strategies have shown advantages in selected patients.
Chemotherapy Before Other Treatments (Neoadjuvant Treatment)
Receiving chemotherapy before radiation or surgery may help people with lung cancer by shrinking the tumor enough to make it easier to remove with surgery, increasing the effectiveness of radiation and destroying hidden cancer cells at the earliest possible time.
If a tumor doesn’t shrink with chemotherapy, the medication can be stopped right away, allowing the doctor to try a different treatment. In addition, research shows that people with lung cancer are much more able to cope with the side effects of chemotherapy when it is given before surgery.
Sometimes, a short trial period of treatment with the drug shrinks the tumor before surgery. If that is the case, then continued treatment with the same drug after surgery is more likely to benefit the patient. Because many lung cancer specialists around the world are giving chemotherapy to their patients before surgery, patients should discuss it with their doctor.
One of the most exciting developments in lung cancer medicine is the introduction of targeted treatments. Unlike chemotherapy drugs, which cannot tell the difference between normal cells and cancer cells, targeted therapies are designed specifically to attack cancer cells by attaching to or blocking targets that appear on the surfaces of those cells. People who have advanced lung cancer with certain molecular biomarkers may receive treatment with a targeted drug alone or in combination with chemotherapy. These treatments for lung cancer include:
Erlotinib (Tarceva) A targeted treatment called erlotinib has been shown to benefit some people with non-small cell lung cancer. This drug blocks a specific kind of receptor on the cell surface—the epidermal growth factor receptor (EGFR). Receptors such as EGFR act as doorways by allowing substances in that they can encourage a cancer cell to grow and spread. Lung cancer cells that have a mutation on the EGFR are likely to respond to treatment with erlotinib instead of chemotherapy. For patients who have received chemotherapy, and are in need of additional treatment, erlotinib can be used even without the presence of the mutation.
Bevacizumab (Avastin) Just like normal tissues, tumors need a blood supply to survive. Blood vessels grow in several ways. One way is through the presence of a substance called vascular endothelial growth factor (VEGF). This substance stimulates blood vessels to penetrate tumors and supply oxygen, minerals, and other nutrients to feed the tumor. When tumors spread throughout the body, they release VEGF to create new blood vessels.
Bevacizumab works by stopping VEGF from stimulating the growth of new blood vessels. (Because normal tissues have an established blood supply, they are not affected by the drug.) When combined with chemotherapy, bevacizumab has been shown to improve survival in people with certain types of non-small lung cancer, such as adenocarcinoma and large cell carcinoma.
Crizotinib (Xalkori) is a newly available treatment that has shown benefits for people with advanced non–small cell lung cancer who have the ALK biomarker. Mutations in the way cells program ALK result in changes to the way it functions, leading to increased tumor cell growth. Crizotinib works by blocking ALK and stopping the growth of the tumor.
Chemotherapy and Radiation Therapy
For people with small cell lung cancer, regardless of stage, chemotherapy is an essential part of treatment. Radiation treatment may be used as well depending on the stage of cancer.
For people with limited-stage small cell lung cancer, combination chemotherapy plus radiation therapy given at the same time is the recommended treatment. The most commonly used initial chemotherapy regimen is etoposide (Toposar or Vepesid) plus cisplatin (Platinol), known as EP.
For people with extensive-stage small cell lung cancer, chemotherapy alone using the EP regimen is the standard treatment. However, another regimen that may be used is carboplatin (Paraplatin) plus irinotecan (Camptosar)
Radiation therapy of the brain may be used before or after chemotherapy for some people whose cancer has spread to the brain.
Preventive Radiation Therapy to the Brain
In more than half of the people with small cell lung cancer, the cancer also spreads to the brain. For people whose lung cancer has responded to chemotherapy, doctors may prescribe radiation therapy to the brain to help prevent the cancer from spreading to the brain. This procedure is known as prophylactic cranial irradiation (PCI). This can benefit patient with both limited-stage and extensive-stage small cell lung cancers.
A very small percentage of people who have limited-stage small cell lung cancer and no lymph node tumors may benefit from surgery, after which adjuvant chemotherapy is given.