Lung Carcinoid Tumor. What is cancer?

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1 What is cancer? Lung Carcinoid Tumor The body is made up of hundreds of millions of living cells. Normal body cells grow, divide, and die in an orderly fashion. During the early years of a person's life, normal cells divide faster to allow the person to grow. After the person becomes an adult, most cells divide only to replace worn-out or dying cells or to repair injuries. Cancer begins when cells in a part of the body start to grow out of control. There are many kinds of cancer, but they all start because of out-of-control growth of abnormal cells. Cancer cell growth is different from normal cell growth. Instead of dying, cancer cells continue to grow and form new, abnormal cells. Cancer cells can also invade (grow into) other tissues, something that normal cells cannot do. Growing out of control and invading other tissues are what makes a cell a cancer cell. Cells become cancer cells because of damage to DNA. DNA is in every cell and directs all its actions. In a normal cell, when DNA gets damaged the cell either repairs the damage or the cell dies. In cancer cells, the damaged DNA is not repaired, but the cell doesn't die like it should. Instead, this cell goes on making new cells that the body does not need. These new cells will all have the same damaged DNA as the first cell does. People can inherit damaged DNA, but most DNA damage is caused by mistakes that happen while the normal cell is reproducing or by something in our environment. Sometimes the cause of the DNA damage is something obvious, like cigarette smoking. But often no clear cause is found. In most cases the cancer cells form a tumor. Some cancers, like leukemia, rarely form tumors. Instead, these cancer cells involve the blood and blood-forming organs and circulate through other tissues where they grow. Cancer cells often travel to other parts of the body, where they begin to grow and form new tumors that replace normal tissue. This process is called metastasis. It happens when the cancer cells get into the bloodstream or lymph vessels of our body.

2 No matter where a cancer may spread, it is always named for the place where it started. For example, breast cancer that has spread to the liver is still called breast cancer, not liver cancer. Likewise, prostate cancer that has spread to the bone is metastatic prostate cancer, not bone cancer. Different types of cancer can behave very differently. For example, lung cancer and breast cancer are very different diseases. They grow at different rates and respond to different treatments. That is why people with cancer need treatment that is aimed at their particular kind of cancer. Not all tumors are cancerous. Tumors that aren't cancer are called benign. Benign tumors can cause problems -- they can grow very large and press on healthy organs and tissues. But they cannot grow into (invade) other tissues. Because they can't invade, they also can't spread to other parts of the body (metastasize). These tumors are almost never life threatening. What are lung carcinoid tumors? Lung carcinoid tumors are an uncommon type of tumor that starts in the lungs. They tend to grow slower than other types of lung cancers. They are made up of special kinds of cells called neuroendocrine cells. To understand lung carcinoid tumors, it helps to know something about the normal structure and function of the lungs, as well as the neuroendocrine system. The lungs The lungs are 2 sponge-like organs in your chest cavity. Your right lung has 3 sections, called lobes. The left lung has 2 lobes. It is smaller because the heart takes up more room on that side of the body. The lungs bring air in and out, taking in oxygen and getting rid of carbon dioxide gas, a waste product of the body. When you breathe in, air enters through your mouth and nose and goes into your lungs through the trachea (windpipe). The trachea divides into tubes called the bronchi (singular, bronchus), which divide into smaller branches called the bronchioles. At the end of the bronchioles are tiny air sacs known as alveoli.

3 A thin lining called the pleura surrounds the lungs. The pleura protects your lungs and helps them slide back and forth as they expand and contract during breathing. The chest cavity is called the pleural cavity. The diffuse neuroendocrine system Carcinoid tumors start from cells of the diffuse neuroendocrine system. This system is made up of cells that are like nerve cells in certain ways and like hormone-making endocrine cells in other ways. These cells do not form an actual organ like the adrenal or thyroid glands. Instead, they are scattered throughout the body in organs like the lungs, stomach, and intestines. Neuroendocrine cells make hormones like adrenaline and adrenaline-like substances. In the lungs, this may help control air flow and blood flow and may help control the growth of other types of lung cells. Neuroendocrine cells may detect decreased oxygen or increased carbon dioxide in the air we breathe and then release chemical messages to help the lungs adjust to these changes. People who live at higher altitudes have more lung neuroendocrine cells, probably because there is less oxygen in the air they breathe. Types of lung neuroendocrine tumors Like most cells in your body, lung neuroendocrine cells sometimes go through certain changes that cause them to grow too much and form tumors. These are known as neuroendocrine tumors or neuroendocrine cancers. Neuroendocrine tumors can develop anywhere in the body. Neuroendocrine tumors that begin in the digestive tract, another common site for these tumors, are discussed in a separate American Cancer Society document, Gastrointestinal Carcinoid Tumors.

4 This document discusses only neuroendocrine tumors that start in the lungs. There are 4 types of neuroendocrine lung tumors: Small cell lung cancer Large cell neuroendocrine carcinoma Atypical carcinoid tumor Typical carcinoid tumor Small cell lung cancer Small cell lung cancer (SCLC) is one of the fastest growing and spreading of all cancers. It is discussed in a separate American Cancer Society document, Lung Cancer (Small Cell). Large cell neuroendocrine carcinoma Large cell neuroendocrine carcinoma (LCNEC) is a rare cancer that, except for the size of the cells forming the cancer, is very similar to SCLC in its prognosis (outlook) and in how patients are treated. Typical and atypical carcinoid tumors The other 2 types of lung neuroendocrine tumors are carcinoids. The rest of this document will only cover these 2 types of tumors. Carcinoid tumors Carcinoid tumors start from cells of the diffuse neuroendocrine system. Typical and atypical carcinoid tumors look different under the microscope. Typical carcinoids grow slowly and only rarely spread beyond the lungs. About 9 out of 10 lung carcinoids are typical carcinoids. Atypical carcinoids grow a little faster and are somewhat more likely to spread to other organs. Seen under a microscope, they have more cells in the process of dividing and look more like a fast-growing tumor. They are much less common than typical carcinoids. Carcinoids are sometimes also classified by where they form in the lung. Central carcinoids form in the walls of large airways (bronchi) near the center of the lungs. Most lung carcinoid tumors are central carcinoids, and nearly all of these are also typical carcinoids. Peripheral carcinoids develop in the narrower airways toward the edges of the lungs. Most peripheral carcinoids are also typical carcinoids.

5 This distinction is important because the tumor's location affects which symptoms a patient may have (see the section "How are lung carcinoid tumors diagnosed? ) and may also affect how the tumor is treated. What are the key statistics about lung carcinoid tumors? About 1% to 2% of all lung cancers are carcinoids. This means there are about 4,500 newly diagnosed lung carcinoid tumors in the United States each year. Carcinoid tumors are actually more common in the digestive tract than in the lungs. Only about 3 out of 10 carcinoid tumors start in the lungs. Lung carcinoids are more common in whites than in African Americans, Asian Americans, or Hispanics/Latinos. They are also more common in women. In contrast with other types of lung cancer, carcinoids tend to be diagnosed in people who are slightly younger. The average age at diagnosis is around 60 years. Information on survival rates for lung carcinoids can be found in the section, "How are lung carcinoid tumors staged?" What are the risk factors for lung carcinoid tumors? A risk factor is anything that affects your chance of getting a disease such as cancer. Different cancers have different risk factors. For example, strong sunlight is a risk factor for skin cancer, and smoking is a risk factor for cancers of the lung, larynx (voice box), mouth, throat, esophagus, kidneys, bladder, and several other organs. But risk factors don't tell us everything. Having a known risk factor, or even several risk factors, does not mean that you will get the disease. And many people who get the disease may not have had any known risk factors. Not much is known about why lung carcinoid tumors develop in some people but not in others. Tobacco smoke Typical lung carcinoid tumors do not seem to be linked with smoking or with any known chemicals in the environment or workplace. But some studies have found that atypical lung carcinoids may be more common in people who smoke. Gender Carcinoids occur more often in women than in men. The reasons for this are not known.

6 Race/ethnicity Lung carcinoids are more common in whites than in African Americans, Asian Americans, or Hispanics/Latinos. Age These tumors are usually found in people about 60 years old, which is slightly younger than the average age for other types of lung cancer. But carcinoids can occur in people of almost any age. Although it is rare, lung carcinoid tumors are sometimes even found in children. Multiple endocrine neoplasia type 1 People with multiple endocrine neoplasia type 1 (MEN1, an inherited syndrome) are at high risk for tumors in the pancreas and in the pituitary and parathyroid glands. They also seem to be at increased risk for lung carcinoid tumors. Family history Most people with lung carcinoid tumors do not have a family history of this type of cancer, but a tendency to develop lung carcinoid tumors can be inherited. In rare cases, several family members have been diagnosed with this cancer. But because this cancer is so uncommon, the risk is still low. Do we know what causes lung carcinoid tumors? Very little is known about what causes lung carcinoid tumors. Researchers have learned a lot about how certain risk factors like cancer-causing chemicals or radiation can cause changes in lung cells that lead to carcinomas, the more common type of lung cancer. But these factors are not thought to play a large role in the development of lung carcinoid tumors. Carcinoid tumors probably develop from tiny clusters of neuroendocrine cells in the lung airways called carcinoid tumorlets. Tumorlets are sometimes found unexpectedly in lung biopsies done to treat or diagnose other conditions. Under the microscope, tumorlets resemble carcinoid tumors, except that they are much smaller -- less than 5 mm (¼ inch) across. Most tumorlets never grow any bigger, but some may eventually become carcinoid tumors. Researchers still do not understand how carcinoid tumorlets develop from lung neuroendocrine cells or why tumorlets sometimes grow to become carcinoid tumors.

7 Can lung carcinoid tumors be prevented? Because we do not yet know what causes most lung carcinoid tumors, it is not possible to know how to prevent them. Smoking has been linked with an increased risk of atypical carcinoids, so quitting (or not starting) might reduce a person's risk. Can lung carcinoid tumors be found early? Lung carcinoid tumors are not common, and there are no widely recommended screening tests for these tumors in most people. (Screening is testing for cancer in people without any symptoms.) People with multiple endocrine neoplasia type 1 (MEN1) are at increased risk for these tumors, and some doctors recommend they have computed tomography (CT) scans of the chest every 3 years starting when they are age 20. Because carcinoid tumors usually grow and spread slowly, most are found at an early or localized stage. Many patients with peripheral carcinoid tumors or with small central carcinoid tumors have no symptoms. Carcinoids that do not cause symptoms often are found on a chest x-ray done during a routine exam or when looking into unrelated medical problems, such as some heart diseases. How are lung carcinoid tumors diagnosed? Certain signs and symptoms might suggest that a person may have a lung carcinoid tumor, but tests are needed to confirm the diagnosis. Signs and symptoms About 2 out of 3 people with carcinoid tumors will have signs or symptoms that will lead to the diagnosis of the disease. But because carcinoids tend to grow slowly, they may not cause symptoms for several years in some people, or they may be found by medical tests done for other reasons. Central carcinoid tumors These tumors start in the large bronchial tubes leading into the lung. People with these tumors may have a cough or cough up bloody sputum, or they may have wheezing symptoms like asthma. Other possible symptoms include shortness of breath and chest pain, especially when taking deep breaths. Large carcinoids can cause partial or complete blockage of a large air passage, leading to a lung infection called post-obstructive pneumonia. Sometimes a doctor may suspect a tumor only after treatment with antibiotics fails to cure the pneumonia.

8 Peripheral carcinoids These tumors start in the smaller airways toward the outer edges of the lungs. They rarely cause any symptoms unless there are so many of them they interfere with breathing. Usually they are found as a spot on a chest x-ray taken for an unrelated problem. Symptoms caused by hormones produced by the tumor Some carcinoid tumors can produce hormone-like substances that are released into the bloodstream. Lung carcinoids do this far less often than gastrointestinal carcinoid tumors. Carcinoid syndrome: Rarely, lung carcinoid tumors release enough hormone-like substances into the bloodstream to cause symptoms. This results in the carcinoid syndrome. Symptoms include facial flushing (redness and warm feeling), severe diarrhea, wheezing, and fast heartbeat. Many patients find that stress, heavy exercise, and drinking alcohol may make these symptoms worse. Over a long time, these hormone-like substances can damage heart valves, causing shortness of breath, weakness, and a heart murmur (an abnormal heart sound). Cushing syndrome: In rare cases, lung carcinoid tumors may produce ACTH. This substance causes the adrenal glands to make too much cortisol and other hormones. This can cause weight gain, weakness, high blood sugar (or even diabetes), and increased body and facial hair. Although the symptoms and signs above may be caused by lung carcinoid tumors, they can also be caused by other conditions. Still, if you have any of these problems, it's important to see your doctor right away so the cause can be found and treated, if needed. Medical history and physical exam If you have any signs or symptoms that suggest you might have a lung carcinoid tumor, your doctor will want to take a complete medical history, including your family history, to check for symptoms and possible risk factors. You will also be asked about your general health. A physical exam provides information about your general health, possible signs of lung carcinoid tumor, and other health problems. During your physical exam, your doctor will pay close attention to your chest and lungs. If symptoms and/or the results of the physical exam suggest a lung carcinoid tumor might be present, more involved tests probably will be done. These might include imaging tests, lab tests, and other procedures. Imaging tests Imaging tests use x-rays, radioactive particles, or other means to create pictures of the inside of your body. Imaging tests may be done for a number of reasons, including to

9 help find a suspicious area that might be cancerous, to learn how far cancer may have spread, and to help determine if treatment has been effective. Chest x-ray A chest x-ray may be the first imaging test a doctor orders if he or she suspects a lung problem. It might be able to show if there is a tumor in the lung. However, some carcinoids that are small or are in places where they are covered by other organs in the chest may not show up on a chest x-ray. If your doctor is still suspicious or if a vague abnormality appears on the chest x-ray, a CT scan may be ordered. Computed tomography (CT) scan The CT scan is an x-ray procedure that produces detailed cross-sectional images of your body. Instead of taking one picture, like a regular x-ray, a CT scanner takes many pictures as it rotates around you while you are lying on a narrow platform. A computer then combines these into images of slices of the part of your body that is being studied. Before the scan, you may be asked to drink a contrast solution and/or get an intravenous (IV) injection of a contrast dye that helps better outline abnormal areas in the body. You may need an IV line through which the contrast dye is injected. The injection can cause some flushing (redness and warm feeling). Some people are allergic and get hives or, rarely, more serious reactions like trouble breathing and low blood pressure. Be sure to tell the doctor if you have ever had a reaction to any contrast material used for x-rays. You need to lie still on a platform while the scan is being done. During the test, the platform moves in and out of the scanner, a ring-shaped machine that completely surrounds it. You might feel a bit confined by the ring you have to lie in while the pictures are being taken. CT scans can have several uses: CT scans of the chest can spot very small lung tumors and help determine the exact location and extent of the tumors. CT scans can be helpful in staging a cancer (determining the extent of its spread). For example, CT scans of the abdomen can show if the cancer has spread to the liver or other organs. This can help to determine if surgery is a good treatment option. CT scans can also be used to guide a biopsy needle precisely into a suspected tumor or metastasis. For this procedure, called a CT-guided needle biopsy, the patient remains on the CT scanning table, while a radiologist advances a biopsy needle through the skin and toward the location of the mass. CT scans are repeated until the needle is within the mass. A biopsy sample is then removed and looked at under a microscope.

10 Radionuclide scans Scans using small amounts of radioactivity and special cameras may be helpful in looking for carcinoid tumors. They can help determine the extent of the tumor, as well as help locate it if doctors aren't sure where it is in the body. Somatostatin receptor scintigraphy: The most commonly used scan is somatostatin receptor scintigraphy (SRS), also known as the OctreoScan. It uses octreotide bound to radioactive indium-111. Octreotide is a hormone-like substance that attaches to carcinoid cells. A small amount of this substance is injected into a vein. It travels through the blood and is attracted to carcinoid tumors. About 4 hours after the injection, a special camera can be used to show where the radioactivity has collected in the body. More scans may be done in the following few days as well. I-131 MIBG: This test is used less often. It uses a chemical called MIBG to which radioactive iodine (I-131) is attached. This substance is injected into a vein, and the body is scanned several hours or days later with a special camera to look for areas that picked up the radioactivity. These would most likely be carcinoid tumors, although other kinds of neuroendocrine tumors will also pick up this chemical. Positron emission tomography (PET): A PET scan is another imaging test that uses low levels of radioactivity to look for tumors. For most diseases, PET scans use a form of radiolabeled glucose (sugar) to find tumors. This type of PET scan is not very useful in finding carcinoid tumors. PET scanning for carcinoid tumors usually uses a radioactive form of 5-hydroxytryptophan, a chemical that is taken up and used by carcinoid cells. A special camera can detect the radioactivity. The usefulness of this test for lung carcinoid tumors is still being studied. This special type of PET scan is not available in every hospital. Biopsy Even if an imaging test such as a chest x-ray or CT scan finds a mass, it is often hard for doctors to tell if the mass is a carcinoid tumor, another type of lung cancer, or an area of infection. In many cases, the only way to know for sure is to remove cells from the tumor and look at them under a microscope. This procedure is called a biopsy. There are several ways to take a sample from a lung tumor. Bronchoscopic biopsy This approach is used to view and sample tumors of large airways, such as central carcinoids. The doctor passes a long, thin, flexible, fiber-optic tube called a bronchoscope down the throat, through the windpipe, and into the lungs to look at the lining of the lung's main airways. You will be sedated for this. If a tumor is found, the doctor can take a small sample of the tumor through the tube. The doctor can also take a brushing sample through the bronchoscope by wiping a tiny brush over the surface of the tumor. Brushing samples are sometimes a helpful addition to the bronchial biopsy, but they are not as helpful in diagnosing carcinoids as they are with lung carcinomas.

11 An advantage of this type of biopsy is that no surgical incision or hospital stay is needed, and you are ready to return home within hours. A disadvantage is that this type of biopsy may not always be able to remove enough of a sample to be certain the tumor is a carcinoid. But with recent advances in the lab testing of lung tumors, doctors can usually make an accurate diagnosis even with very small samples. Bleeding from a carcinoid tumor after a biopsy is rare but it can be a serious problem. If bleeding becomes a problem, doctors can inject drugs through the bronchoscope into the tumor to narrow its blood vessels, or they can seal off the bleeding vessels with a laser aimed through the bronchoscope. Needle biopsies Tumors that are not near the large airways are often sampled by needle biopsy. A long, hollow needle is passed through the skin in the chest between the ribs and into the lung. CT scan images are used to guide the needle into the tumor so that a small sample can be removed and looked at under the microscope. This procedure is also done without a surgical incision or overnight hospital stay. A possible complication of this approach is the buildup of air between the lung and the chest wall, which is known as a pneumothorax. In some cases this can lead to the collapse of part of a lung, causing shortness of breath. If this happens, it can be treated by temporarily placing a suction tube through the skin and into the chest, which will reexpand the lung. Surgical biopsies In some cases, neither a bronchoscopic biopsy nor a needle biopsy will remove enough tissue to identify the type of tumor, and your doctor may need to do surgery to get a biopsy sample. Different types of operations may be used. Thoracotomy: For a thoracotomy, the surgeon makes an incision in the chest wall between the ribs to get to the lungs and to the space between the lungs and the chest wall. In some cases if the doctor strongly suspects a carcinoid or some other type of lung cancer, they may do a thoracotomy and remove the entire tumor without first doing a biopsy. Thoracoscopy: This procedure is less invasive than a thoracotomy. It is also used to look at the space between the lungs and the chest wall. Most often it is done in the operating room while you are under general anesthesia (in a deep sleep). The doctor inserts a thin, lighted scope with a small video camera on the end through a small cut made in the chest wall to look at the space between the lungs and the chest wall. (Sometimes more than one cut is made.) Using this scope, the doctor can see potential areas of cancer and remove small pieces of tissue to look at under the microscope. Thoracoscopy can also be used to sample lymph nodes and fluid and find out whether a tumor is growing into nearby tissues or organs.

12 Mediastinoscopy: If imaging tests such as a CT scan suggest that the cancer may have spread to the lymph nodes between the lungs, the doctor may do a procedure called a mediastinoscopy. This is done in an operating room while you are under general anesthesia (in a deep sleep). A small cut is made in the front of the neck above the breastbone (sternum) and a thin, hollow, lighted tube is inserted behind the sternum. Special instruments can be passed through this tube to take tissue samples from the lymph nodes along the windpipe and the major bronchial tube areas. Blood and urine tests Because carcinoid tumors can secrete hormone-like chemicals into the blood, the tumor can sometimes be detected by simple blood or urine tests. This is especially true if you have symptoms of the carcinoid syndrome, which is caused by excessive levels of these substances in the blood. Serotonin is a substance made by some carcinoid tumors, and probably causes some of the symptoms. It is broken down by the body into 5-hydroxyindoleacetic acid (5-HIAA), which is released into the urine. A commonly used test to look for carcinoid syndrome measures the levels of 5-HIAA in a urine sample collected over 24 hours. Measuring the serotonin levels in the blood or urine may also give useful information. These tests can help diagnose some carcinoid tumors, but they are not always accurate. Some other medical conditions, as well as foods and medicines, can affect the results, and some carcinoid tumors may not release enough of these substances to give a positive test result. Other tests commonly used to look for carcinoids can include blood tests for chromogranin A (CgA), neuron-specific enolase (NSE), cortisol, and substance P. Depending on where the tumor might be located and on the patient's symptoms, doctors may do other blood tests as well. Abnormal lab test results are not as likely to be seen with lung carcinoid tumors as they are with carcinoid tumors that start elsewhere in the body. Pulmonary function tests Pulmonary function tests (PFTs) are often done after a lung carcinoid diagnosis to see how well your lungs are working. This is especially important if surgery is an option in treating the cancer. Because surgery will remove part or all of the lung, it's important to know how well the lungs are working beforehand. These tests can give the surgeon an idea of whether surgery is a good option, and if so, how much lung can safely be removed. There are a few different types of PFTs, but they all basically have you breathe in and out through a tube that is connected to different machines.

13 How are lung carcinoid tumors staged? Staging is a process of finding out how far a cancer has spread. Your treatment and prognosis (the outlook for chances of survival) depend, to a large extent, on the cancer's stage. Staging is based on the results of the physical exam, biopsies, and imaging tests (CT scan, PET scan, etc.), which are described in the section, "How are lung carcinoid tumors diagnosed?" The staging system for lung carcinoid tumors is the same one used to stage non-small cell lung cancer -- the American Joint Committee on Cancer (AJCC) TNM staging system. The TNM system describes 3 key pieces of information: T indicates the size of the main (primary) tumor and whether it has grown into nearby areas. N describes how much the cancer has spread to nearby (regional) lymph nodes. Lymph nodes are small bean-shaped collections of immune system cells that are important in fighting infections. M indicates whether the cancer has spread (metastasized) to other organs of the body. (The most common site is the liver.) Numbers or letters appear after T, N, and M to provide more details about each of these factors. The numbers 0 through 4 indicate increasing severity. The letter X means cannot be assessed because the information is not available. T categories TX: The main (primary) tumor can't be assessed, or cancer cells were seen on sputum cytology but no tumor can be found. T0: There is no evidence of a primary tumor. Tis: The cancer is found only in the top layers of cells lining the air passages. It has not invaded into deeper lung tissues. This stage is also known as carcinoma in situ. T1: The tumor is no larger than 3 cm (slightly less than 1¼ inches) across, has not reached the membranes that surround the lungs (visceral pleura), and does not affect the main branches of the bronchi. T1a: A T1 tumor that is 2 cm (about 4/5 of an inch) or less across. T1b: A T1 tumor that is larger than 2 cm but not larger than 3 cm across. T2: The tumor has 1 or more of the following features: It is between 3 cm and 7 cm across (larger than 3 cm but not larger than 7 cm). If the tumor is 5 cm or less across (but still larger than 3 cm), it is called T2a. If the tumor is larger than 5 cm across (but not larger than 7 cm), it is called T2b.

14 It involves a main bronchus, but is not closer than 2 cm (about ¾ inch) to the carina (the point where the windpipe splits into the left and right main bronchi). It has grown into the membranes that surround the lungs (visceral pleura). The tumor partially clogs the airways, but this has not caused the entire lung to collapse or develop pneumonia. T3: The tumor has 1 or more of the following features: It is larger than 7 cm across. It has grown into the chest wall, the breathing muscle that separates the chest from the abdomen (diaphragm), the membranes surrounding the space between the two lungs (mediastinal pleura), or membranes of the sac surrounding the heart (parietal pericardium). It invades a main bronchus and is closer than 2 cm (about ¾ inch) to the carina, but it does not involve the carina itself. It has grown into the airways enough to cause an entire lung to collapse or to cause pneumonia in the entire lung. Two or more separate tumor nodules are present in the same lobe of a lung T4: The cancer has 1 or more of the following features: A tumor of any size has grown into the space behind the chest bone and in front of the heart (mediastinum), the heart, the large blood vessels near the heart (such as the aorta), the windpipe, the esophagus (tube connecting the throat to the stomach), the backbone, or the carina. Two or more separate tumor nodules are present in different lobes of the same lung. N categories NX: Nearby lymph nodes cannot be assessed. N0: There is no spread to nearby lymph nodes. N1: The cancer has spread to lymph nodes within the lung and/or around the area where the bronchus enters the lung (hilar lymph nodes). Affected lymph nodes are on the same side as the primary tumor(s). N2: The cancer has spread to lymph nodes around the carina (the point where the windpipe splits into the left and right bronchi) or in the space behind the breastbone and in front of the heart (mediastinum). Affected lymph nodes are on the same side as the primary tumor. N3: The cancer has spread to lymph nodes near the collarbone on either side, and/or spread to hilar or mediastinal lymph nodes on the side opposite the primary tumor.

15 M categories M0: No spread to distant organs or areas. This includes other lobes of the lungs, lymph nodes further away than those mentioned in the N stages above, and other organs or tissues such as the liver, bones, or brain. M1: The cancer has spread to 1 or more distant sites. This can be to another lobe of the lung, to distant lymph nodes, or to other organs. M1a: Any of the following: The cancer has spread to the other lung. Cancer cells are found in the fluid around the lung (called a malignant pleural effusion). Cancer cells are found in the fluid around the heart (called a malignant pericardial effusion). M1b: The cancer has spread to distant organs or lymph nodes. Stage grouping for lung cancer and lung carcinoid Once the T, N, and M categories have been assigned, this information is combined (stage grouping) to assign an overall stage of 0, I, II, III, or IV. Some stages are subdivided into A and B. The stages identify tumors that have a similar prognosis and so they are treated in a similar way. Patients with lower stage numbers tend to have a better prognosis. Occult cancer TX, N0, M0: Cancer cells are seen in a sample of sputum or other lung fluids, but the location of the cancer can't be determined. Stage 0 Tis, N0, M0: The cancer is found only in the top layers of cells lining the air passages. It has not invaded deeper into other lung tissues and has not spread to lymph nodes or distant sites. Stage IA T1, N0, M0: The cancer is no larger than 3 cm across, has not reached the membranes that surround the lungs, and does not affect the main branches of the bronchi. It has not spread to lymph nodes or distant sites. Stage IB T2a, N0, M0: The cancer has 1 or more of the following features:

16 The main tumor is between 3 and 5 cm across (larger than 3 cm but not larger than 5 cm). The tumor involves a main bronchus, but is not within 2 cm of the carina. The tumor has grown into the visceral pleura (the membranes surrounding the lungs). The cancer is partially clogging the airways. The cancer has not spread to lymph nodes or distant sites. Stage IIA Three main combinations of categories make up this stage. T1, N1, M0: The cancer is no larger than 3 cm across, has not grown into the membranes that surround the lungs, and does not affect the main branches of the bronchi. It has spread to lymph nodes within the lung and/or around the area where the bronchus enters the lung (hilar lymph nodes). These lymph nodes are on the same side as the cancer. It has not spread to distant sites. OR T2a, N1, M0: The cancer has 1 or more of the following features: The main tumor is between 3 and 5 cm across (larger than 3 cm but not larger than 5 cm). The tumor involves a main bronchus, but is not within 2 cm of the carina. The tumor has grown into the visceral pleura (the membranes surrounding the lungs). The cancer is partially clogging the airways. It has also spread to lymph nodes within the lung and/or around the area where the bronchus enters the lung (hilar lymph nodes). These lymph nodes are on the same side as the cancer. It has not spread to distant sites. OR T2b, N0, M0: The cancer has 1 or more of the following features: The main tumor is between 5 and 7 cm across (larger than 5 cm but not larger than 7 cm). The tumor involves a main bronchus, but is not within 2 cm of the carina. The tumor has grown into the visceral pleura (the membranes surrounding the lungs). The cancer is partially clogging the airways. The cancer has not spread to lymph nodes or distant sites.

17 Stage IIB Two combinations of categories make up this stage. T2b, N1, M0: The cancer has 1 or more of the following features: The main tumor is between 5 and 7 cm across (larger than 5 cm but not larger than 7 cm). The tumor involves a main bronchus, but is not within 2 cm of the carina. The tumor has grown into the visceral pleura (the membranes surrounding the lungs). The cancer is partially clogging the airways. It has also spread to lymph nodes within the lung and/or around the area where the bronchus enters the lung (hilar lymph nodes). These lymph nodes are on the same side as the cancer. It has not spread to distant sites. OR T3, N0, M0: The main tumor has 1 or more of the following features: It is larger than 7 cm across. It has grown into the chest wall, the breathing muscle that separates the chest from the abdomen (diaphragm), the membranes surrounding the space between the lungs (mediastinal pleura), or membranes of the sac surrounding the heart (parietal pericardium). It invades a main bronchus and is closer than 2 cm (about ¾ inch) to the carina, but it does not involve the carina itself. It has grown into the airways enough to cause an entire lung to collapse or to cause pneumonia in the entire lung. Two or more separate tumor nodules are present in the same lobe of a lung. The cancer has not spread to lymph nodes or distant sites. Stage IIIA Three main combinations of categories make up this stage. T1 to T3, N2, M0: The tumor can be any size or have any of the following features The tumor involves a main bronchus without growing into the carina. The tumor has grown into the visceral pleura (the membranes surrounding the lungs). The cancer is partially clogging the airways.

18 It has grown into the airways enough to cause an entire lung to collapse or to cause pneumonia in the entire lung. It has grown into the chest wall, the breathing muscle that separates the chest from the abdomen (diaphragm), the membranes surrounding the space between the two lungs (mediastinal pleura), or membranes of the sac surrounding the heart (parietal pericardium). Two or more separate tumor nodules are present in the same lobe of a lung. The cancer has also spread to lymph nodes around the carina (the point where the windpipe splits into the left and right bronchi) or in the space behind the breastbone and in front of the heart (mediastinum). These lymph nodes are on the same side as the main lung tumor. The cancer has not spread to distant sites. OR T3, N1, M0: The tumor has 1 or more of the following features: It is larger than 7 cm across. It has grown into the chest wall, the breathing muscle that separates the chest from the abdomen (diaphragm), the membranes surrounding the space between the two lungs (mediastinal pleura), or membranes of the sac surrounding the heart (parietal pericardium). It invades a main bronchus and is closer than 2 cm to the carina, but it does not involve the carina itself. Two or more separate tumor nodules are present in the same lobe of a lung. It has grown into the airways enough to cause an entire lung to collapse or to cause pneumonia in the entire lung. It has also spread to lymph nodes within the lung and/or around the area where the bronchus enters the lung (hilar lymph nodes). These lymph nodes are on the same side as the cancer. It has not spread to distant sites. OR T4, N0 or N1, M0: The cancer has 1 or more of the following features: A tumor of any size has grown into the space behind the chest bone and in front of the heart (mediastinum), the heart, the large blood vessels near the heart (such as the aorta), the windpipe, the esophagus (tube connecting the throat to the stomach), the backbone, or the carina. Two or more separate tumor nodules are present in different lobes of the same lung. It may also have spread to lymph nodes within the lung and/or around the area where the bronchus enters the lung (hilar lymph nodes). Any affected lymph nodes are on the same side as the cancer. It has not spread to distant sites.

19 Stage IIIB Two combinations of categories make up this stage. Any T, N3, M0: The cancer can be of any size. It may or may not have grown into nearby structures or caused pneumonia or lung collapse. It has spread to lymph nodes near the collarbone on either side, and/or has spread to hilar or mediastinal lymph nodes on the side opposite the primary tumor. The cancer has not spread to distant sites. OR T4, N2, M0: The cancer has 1 or more of the following features: A tumor of any size has grown into the space behind the chest bone and in front of the heart (mediastinum), the heart, the large blood vessels near the heart (such as the aorta), the windpipe, the esophagus (tube connecting the throat to the stomach), the backbone, or the carina. Two or more separate tumor nodules are present in different lobes of the same lung. The cancer has also spread to lymph nodes around the carina (the point where the windpipe splits into the left and right bronchi) or in the space behind the breastbone and in front of the heart (mediastinum). Affected lymph nodes are on the same side as the main lung tumor. It has not spread to distant sites. Stage IV Two combinations of categories make up this stage. Any T, any N, M1a: The cancer can be any size and may or may not have grown into nearby structures or reached nearby lymph nodes. In addition, any of the following is true: The cancer has spread to the other lung. Cancer cells are found in the fluid around the lung (called a malignant pleural effusion). Cancer cells are found in the fluid around the heart (called a malignant pericardial effusion). OR Any T, any N, M1b: The cancer can be any size and may or may not have grown into nearby structures or reached nearby lymph nodes. It has spread to distant sites, such as another organ. Survival rates for lung carcinoid tumors Survival rates are a way for doctors to discuss and compare the prognosis (outlook) for patients, usually based on the stage of the cancer or other traits. For example, the 5-year

20 survival rate refers to the percentage of patients who live at least 5 years after being diagnosed (although many patients live much longer than this). Overall, the 5-year survival rate for patients with typical lung carcinoids is around 85% to 90%, and the 5-year survival rate for patients with atypical lung carcinoids is around 50% to 60%. These ranges reflect different survival rates quoted by several medical journal articles. Because these cancers are not common, it is hard to find accurate survival rates based on the TNM stage of the cancer. But as a general rule, survival rates are likely to be higher than those listed above for people with a lung carcinoid that is still localized (confined to the area where it started), while the rates are likely to be lower for those with cancers that have metastasized. Even with typical carcinoids that appear to have been treated successfully, in a small number of cases the cancer can recur many years later, which is why doctors often advise close follow-up for at least 10 years. There are some important points to keep in mind when looking at survival rates such as the numbers above. These numbers are derived from patients treated at least several years ago. Improvements in treatment since then mean that the survival rates for people now being diagnosed with these cancers may be higher. Survival statistics can sometimes be useful as a general guide, but they may not accurately represent any one person's prognosis. A number of factors other than the type and extent of the cancer may also affect outlook, including a person's general health and the response of the cancer to treatment. Your doctor is likely to be a good source as to whether the numbers above may apply to you, as he or she is familiar with the aspects of your particular situation. How are lung carcinoid tumors treated? This information represents the views of the doctors and nurses serving on the American Cancer Society's Cancer Information Database Editorial Board. These views are based on their interpretation of studies published in medical journals, as well as their own professional experience. The treatment information in this document is not official policy of the Society and is not intended as medical advice to replace the expertise and judgment of your cancer care team. It is intended to help you and your family make informed decisions, together with your doctor. Your doctor may have reasons for suggesting a treatment plan different from these general treatment options. Don't hesitate to ask him or her questions about your treatment options.

21 Making treatment decisions The first part of this section describes the various types of treatments used for lung carcinoids. This is followed by a description of the most common approaches used based on the extent of the disease. After the tumor is found and staged, your cancer care team will discuss your treatment options with you. The main factors in selecting a treatment for lung carcinoid tumors are the size and location of the tumor, whether it has spread to lymph nodes or other organs, and if you have any other serious medical conditions. Selecting a treatment plan is an important decision, and you should take the time to think about all of your choices. Seeking a second opinion is often a good idea. A second opinion may provide more information and help you feel more confident about the treatment plan you choose. Surgery Surgery is the main treatment for lung carcinoid tumors whenever possible. Most lung carcinoid tumors are cured by surgery alone. The type of surgery will depend on a number of factors, including the size and location of the tumor and whether you have any other lung problems or serious diseases. Thoracic and cardiothoracic surgeons are likely to have the most experience with these operations. Several types of surgery are used to treat people with lung carcinoid tumors. Surgeons usually have to remove some normal lung tissue along with the tumor, but they try not to remove any more normal tissue than they need to. These operations require general anesthesia (where you are in a deep sleep) and may also require surgical incision between the ribs in the chest (thoracotomy). You will generally need to spend 5 to 7 days in the hospital after the surgery. Sleeve resection To treat central carcinoids of a large airway, the surgeon may do a sleeve resection. If you think of the large airway with a tumor as similar to the sleeve of a shirt with a stain an inch or 2 above the wrist, the sleeve resection would be like cutting across the sleeve above and below the stain and sewing the cuff back onto the shortened sleeve. Wedge resection For small carcinoids found at the edges of the lungs away from the large airways, the surgeon may remove a wedge-shaped piece of the lung in an operation called a wedge resection or segmental resection.

22 Lobectomy If it is not possible to do a sleeve or wedge resection because of the size or location of the tumor, the surgeon will usually do a lobectomy, in which an entire lobe of the lung is removed. In some cases 2 lobes may be removed (bilobectomy). Pneumonectomy In rare cases where the cancer is in many spots or is in a place that makes it hard to remove, it may be necessary to remove the entire left or right lung in an operation called a pneumonectomy. With any of these operations, lymph nodes near the lungs are usually removed to look for possible spread of the cancer. This is important because about 10% of typical carcinoids and 30% to 50% of atypical carcinoids will have spread to lymph nodes by the time they are diagnosed. If these nodes are not removed, it might increase the risk of the carcinoid tumor spreading even farther, to other organs. If this happens, you may no longer be able to be cured by surgery. Removing the lymph nodes also provides some indication of your risk of having the cancer come back. Video-assisted thoracic surgery (VATS) This is a less invasive procedure for treating some cancers in the lungs. During this operation, a thin telescopic tube with a tiny video camera on the end is placed through a small hole in the chest to help the surgeon see the chest cavity. One or two other small holes are created in the skin, and long instruments passed though these holes are used to remove the tumor. Because only small incisions are needed, there is a little less pain after the surgery. Another advantage of this surgery is a shorter hospital stay -- usually around 4 to 5 days. Most experts recommend that only tumors smaller than 4 to 5 cm (about 2 inches) across be treated with this method. This would apply to most carcinoids. The cure rate after this surgery seems to be the same as using older techniques. It is important, though, that the surgeon performing this procedure be experienced since it requires a great deal of technical skill. Possible side effects of surgery Possible complications depend on the extent of the surgery and the person's health beforehand. Serious complications can include excessive bleeding, wound infections, and pneumonia. Because the surgeon must spread the ribs to get to the lung in patients undergoing a thoracotomy, the incision will hurt for some time after surgery. Your activity will be limited for at least a month or two. If your lungs are in good condition (other than the presence of the cancer) you can usually return to normal activities after a lobe or even an entire lung has been removed. If

23 you also have non-cancerous diseases such as emphysema or chronic bronchitis (which are common among heavy smokers), you may become short of breath with activities after surgery. Surgery to relieve symptoms from lung carcinoid tumors If you can't have major surgery because of reduced lung function or other serious medical problems, or if the cancer is widespread, other types of surgery may be used to relieve some symptoms. For example, if the tumor is blocking airways and it might lead to pneumonia or shortness of breath, removing most of the tumor through a bronchoscope or vaporizing most of it with a laser can be helpful. These treatments, called palliative procedures, can relieve symptoms, but they cannot cure the cancer and are recommended only if you cannot have surgery to completely remove the tumor. If you are treated with these procedures you may also get radiation therapy (see the section Radiation therapy ). Sometimes fluid can build up in the chest cavity (outside of the lungs) and interfere with breathing. To remove the fluid and keep it from coming back, doctors sometimes perform a procedure called pleurodesis. A small cut is made in the skin of the chest wall, and a hollow tube is placed into the chest to remove the fluid. Either talc or a drug such as doxycycline or a chemotherapy drug is then instilled into the chest cavity. This causes the linings of the lung (visceral pleura) and chest wall (parietal pleural) to stick together, sealing the space and preventing further fluid buildup. The tube is generally left in for a day or two to drain any new fluid that might collect. For more general information about surgery, please see the separate American Cancer Society document, Surgery. Chemotherapy Chemotherapy is the use of anti-cancer drugs that are injected into a vein or taken by mouth. These drugs enter the bloodstream and reach all areas of the body, making this treatment useful for some types of lung cancer that have spread or metastasized to organs beyond the lungs. Unfortunately, carcinoid tumors usually do not respond very well to chemotherapy. Chemotherapy is mainly used for carcinoid tumors that have spread to other organs, are causing severe symptoms, and have not responded to other medicines. In some cases it may be given after surgery Because chemotherapy does not always shrink carcinoid tumors, it is important to ask your doctors if your chances of benefit outweigh the side effects you may have. Some of the chemotherapy drugs that may be used for advanced lung carcinoids include: Streptozotocin Etoposide (VP-16)