LUNG CANCER
Hippocrates said: “There are 2 dimensions in the medical profession”
a. treating sick people, and b. looking for the reasons why they are taken sick.
Lung cancer is currently the third most common cancer in the Western World, ranking behind prostate and breast cancers. Lung cancer is the leading cause of cancer death in many countries in both men and women, AND is one of the most preventable kinds of cancer, as at least four out of five cases are associated with cigarette smoking.
Schematic illustration of a lung cancer located in the right upper lobe of the lung.
Why is it then so difficult to reduce its incidence when prevention measures are available?
In 1912, Adler described 374 then known cases of lung cancer from the world literature. Lung cancer is now the commonest cancer type (21%) in males in the United States of America (USA) and in the European Union (EU). In 1985, the incidence of lung cancer among women in the
Lung cancer surpassed stomach cancer in the early 1980s as the world’s most common malignancy in men and women combined.
Highest incidence in EU:
Men in
Women in the
Lowest incidence in the EU:
Incidence per 100.000 of population per year
Maoris in
American blacks in San Francisco Bay Area 107 males, 36 females
Inhabitants of
African population 1 males, < 1 females
1. Cigarette smoking: smokers have a 10 –25 times higher risk when compared to non-smokers.
Janerich et al suggested that 20% of all lung cancers ion-smokers are the result of passive smoking at home during childhood and young adulthood.
2. People exposed to air pollution in urban centres have a 2 x higher risk of developing lung cancer than people living in rural areas.
3. Chronic obstructive lung diseases (COPD) lead to cancer proneness of the squamous cell type, superimposed on the effect of smoking. Scar tissue may lead to the development of adenocarcinomas; lung cysts and idiopathic lung fibrosis are associated with a higher incidence of adenocarcinoma and bronchoalveolar cell carcinoma.
4. Exposure to asbestos, glass-wool and ceramic fibres increases the risk for lung cancer.
5. Genetic factors (see next slide).
6. It is suggested that dietary factors may also play a role. Ethanol is associated with an increased incidence, while dietary consumption of lettuce, broccoli and black tea may be associated with decreased incidence.
3. Genetic factors:
The enzyme system aryl-hydrocarbon-hydroxylase (AHH) plays an important role in the conversion of weak carcinogens in cigarette-smoke into active carcinogens. McLemore et al showed a strong association between active smoking and the expression of the gene CYP1A1 iormal lung tissue. The product of this gene, a cytochrome P4501A1-dependent monooxygenase, converts the weak carcinogens in cigarette smoke into procarcinogens.
Sellers et al described in a study of 337 families that the incidence of lung cancer in smoking males who have a specific gene is higher (42%) than in male smokers without the specific gene (27%), in non-smoking gene-positive carriers (27%), and ion-smoking gene-negative carriers (4%).
According to other studies, smokers with enzyme P-45011D6 on chromosome 22 have a higher risk of developing lung cancer.
Further development could lead to appropriate investigations to be carried out specifically on people most likely to develop the disease.
Causes of lung cancer:
80% are associated with long term tobacco smoking;
10% are associated with long term exposure to occupational carcinogens;
Passive smoking is responsible for 1%;
Radon is responsible for 5%;
4% due to unknown causes.
Histological distribution of cancer in The Netherlands.
Squamous cell cancer 50%
Large cell undifferentiated lung cancer 10%,
Small cell undifferentiated lung cancer 20%,
Adenocarcinoma 20%, Others 1%
Origin and characteristics:
Squamous cell carcinoma originates in central bronchi, is the most common type of lung cancer in men and in smokers, is the easiest to detect early, tends to be most curable if found early, and spreads relatively slowly.
Adenocarcinoma originates in small bronchi or smaller bronchioles, is the commonest type in women and nonsmokers, often spreads to lymph glands and chest wall, and manifests itself usually late.
Large-cell carcinoma originates in outer parts of the lungs, and is the least common form of the nonsmall-cell lung cancers.
Small-cell lung cancer originates in central bronchi, is the most aggressive form of lung cancer and spreads quickly (often before symptoms appear) to the liver, bone and brain.
This picture was downloaded from the Internet, via Search On health: SnapHealthMedical ConditionsCancerLung CancerLung Cancer Fact Sheet.ht
In the age group 35-75 years, squamous cell carcinoma is the most frequent type of lung cancer in males, wheras adenocarcinoma is the most frequent of lung cancer in females. Large cell cancer is the less frequent type in both sexes. In men below 60 years, adenocarcinoma is relatively common.
A malignant transformation within a lung cell is thought to follow activation of proto-oncogens and/ or impaired activity of tumor-suppressor genes. Proto-oncogens regulate the normal growth and devolopment within a particular cell. The expression of proto-oncogens is normally under tight control. When malignant transformation occurs, this tight control is lost and proto-oncogens are activated through several pathways. ErbB-1 and myc are proto-oncogens. P53 on chromosome 17 is a tumor-suppressor gene.Malignant transformation occurs in one clone of cells. These cells differentiate further along one or more cell lines, leading to the various histological types (sometimes mixed types) of lung cancer.
Small cell lung cancer:
classical cell line (70%) with well-defined neuroendocrine features, a low colony-forming efficiency, and highly responsive to chemo- and radiotherapy;
variant cell line (30%), with loss of neuroendocrine features, a high colony-forming efficiency, poorly responsive to chemo- and radiotherapy, and morphologically resembling the large cell undifferentiated large cancer type. This type is associated with overexpression of the c-myc oncogene.
Evolution of small cell lung cancer from classical to variant type may occur as a natural event, be induced by therapy or as a result of genetic developments and interaction between myc-oncogenes and Harvey-ras oncogenes.
NSCLC can differentiate into:
Squamous cell lung cancer
Non-squamous cell tumors without neuroendocrine features (80%);
Non-squamous cell tumors with neuroendocrine cell features (20%).
The recogntion of neuroendocrine features within this subgroup is important in that this group NE-NSCLC
(neuroendocrine non-small cell lung cancer) should probably be treated with post-operative adjuvant chemotherapy.
Additional factors:
1. Selection of high risk individuals:
a. COPD, a smoking history of 40 pack years or more; b. Patients with a curative resection of early stage NSCLC (non-small cell lung cancer); c. Patients with limited stage SCLC (small cell lung cancer) who achieve complete remission after chemotherapy; d. Patients with a family history of cancer
2. Computer assisted morphologic assessment of sputum and bronchial samples.
3. Immunocytochemical technique using monoclonal antibodies directed at lung cancer antigens in sputum samples.
4. Genetic marker analyses: myc and ras oncogens, loss of tumor suppressor genes (Rb, p16, p53)
5. Fluorescence bronchoscopy for detecting early invasive cancers and in situ cancers not visible by standard techniques.
http://www.medscape.com/medscape/features/question/1998/04.98/q354.html
CT scan
PET scan
What are the types of lung cancer?
Lung cancers, also known as bronchogenic carcinomas, are broadly classified into two types: small cell lung cancers (SCLC) and non-small cell lung cancers (NSCLC). This classification is based upon the microscopic appearance of the tumor cells themselves. These two types of cancers grow and spread in different ways and may have different treatment options, so a distinction between these two types is important.
SCLC comprise about 20% of lung cancers and are the most aggressive and rapidly growing of all lung cancers. SCLC are strongly related to cigarette smoking, with only 1% of these tumors occurring ionsmokers. SCLC metastasize rapidly to many sites within the body and are most often discovered after they have spread extensively. Referring to a specific cell appearance often seen when examining samples of SCLC under the microscope, these cancers are sometimes called oat cell carcinomas.
NSCLC are the most common lung cancers, accounting for about 80% of all lung cancers. NSCLC can be divided into three main types that are named based upon the type of cells found in the tumor:
· Adenocarcinomas are the most commonly seen type of NSCLC in the U.S. and comprise up to 50% of NSCLC. While adenocarcinomas are associated with smoking, like other lung cancers, this type is observed as well ionsmokers who develop lung cancer. Most adenocarcinomas arise in the outer, or peripheral, areas of the lungs.
· Bronchioloalveolar carcinoma is a subtype of adenocarcinoma that frequently develops at multiple sites in the lungs and spreads along the preexisting alveolar walls.
· Squamous cell carcinomas were formerly more common than adenocarcinomas; at present, they account for about 30% of NSCLC. Also known as epidermoid carcinomas, squamous cell cancers arise most frequently in the central chest area in the bronchi.
· Large cell carcinomas, sometimes referred to as undifferentiated carcinomas, are the least common type of NSCLC.
· Mixtures of different types of NSCLC are also seen.
Other types of cancers can arise in the lung; these types are much less common than NSCLC and SCLC and together comprise only 5% to 10% of lung cancers:
· Bronchial carcinoids account for up to 5% of lung cancers. These tumors are generally small (3 cm to 4 cm or less) when diagnosed and occur most commonly in people under 40 years of age. Unrelated to cigarette smoking, carcinoid tumors can metastasize, and a small proportion of these tumors secrete hormone-like substances that may cause specific symptoms related to the hormone being produced. Carcinoids generally grow and spread more slowly than bronchogenic cancers, and many are detected early enough to be amenable to surgical resection.
· Cancers of supporting lung tissue such as smooth muscle, blood vessels, or cells involved in the immune response can rarely occur in the lung.
As discussed previously, metastatic cancers from other primary tumors in the body are often found in the lung. Tumors from anywhere in the body may spread to the lungs either through the bloodstream, through the lymphatic system, or directly from nearby organs. Metastatic tumors are most often multiple, scattered throughout the lung, and concentrated in the peripheral rather than central areas of the lung.
What are lung cancer symptoms and signs?
Symptoms of lung cancer are varied depending upon where and how widespread the tumor is. Warning signs of lung cancer are not always present or easy to identify. Lung cancer may not cause pain or even any symptoms at all in some cases. A person with lung cancer may have the following kinds of symptoms:
· No symptoms: In up to 25% of people who get lung cancer, the cancer is first discovered on a routine chest X-ray orCT scan as a solitary small mass sometimes called a coin lesion, since on a two-dimensional X-ray or CT scan, the round tumor looks like a coin. These patients with small, single masses often report no symptoms at the time the cancer is discovered.
· Symptoms related to the cancer:The growth of the cancer and invasion of lung tissues and surrounding tissue may interfere with breathing, leading to symptoms such as cough, shortness of breath, wheezing, chest pain, and coughing up blood (hemoptysis). If the cancer has invaded nerves, for example, it may cause shoulder painthat travels down the outside of the arm (called Pancoast syndrome) orparalysis of the vocal cords leading to hoarseness. Invasion of the esophagus may lead to difficulty swallowing (dysphagia). If a large airway is obstructed, collapse of a portion of the lung may occur and cause infections (abscesses, pneumonia) in the obstructed area.
· Symptoms related to metastasis: Lung cancer that has spread to the bones may produce excruciating pain at the sites of bone involvement. Cancer that has spread to the brain may cause a number of neurologic symptoms that may include blurred vision, headaches, seizures, or symptoms of stroke such as weakness or loss of sensation in parts of the body.
· Paraneoplastic symptoms: Lung cancers frequently are accompanied by symptoms that result from production of hormone-like substances by the tumor cells. These paraneoplastic syndromes occur most commonly with SCLC but may be seen with any tumor type. A common paraneoplastic syndrome associated with SCLC is the production of a hormone called adrenocorticotrophic hormone (ACTH) by the cancer cells, leading to oversecretion of the hormone cortisol by the adrenal glands (Cushing’s syndrome). The most frequent paraneoplastic syndrome seen with NSCLC is the production of a substance similar to parathyroid hormone, resulting in elevated levels of calcium in the bloodstream.
· Nonspecific symptoms: Nonspecific symptoms seen with many cancers, including lung cancers, include weight loss, weakness, andfatigue. Psychological symptoms such as depression and mood changes are also common.
When should one consult a doctor?
One should consult a health care professional if he or she develops the symptoms associated with lung cancer, in particular, if they have
· a new persistent cough or worsening of an existing chronic cough
· blood in the sputum
· persistent bronchitis or repeated respiratory infections
· chest pain
· unexplained weight loss and/or fatigue
· breathing difficulties such as shortness of breath or wheezing
How is lung cancer diagnosed?
Doctors use a wide range of diagnostic procedures and tests to diagnose lung cancer. These include the following:
· The history and physical examination may reveal the presence of symptoms or signs that are suspicious for lung cancer. In addition to asking about symptoms and risk factors for cancer development such as smoking, doctors may detect signs of breathing difficulties, airway obstruction, or infections in the lungs. Cyanosis, a bluish color of the skin and the mucous membranes due to insufficient oxygen in the blood, suggests compromised function due to chronic disease of the lung. Likewise, changes in the tissue of the nail beds, known as clubbing, also may indicate chronic lung disease.
· The chest X-ray is the most common first diagnostic step when any new symptoms of lung cancer are present. The chest X-ray procedure often involves a view from the back to the front of the chest as well as a view from the side. Like any X-ray procedure, chest X-rays expose the patient briefly to a small amount of radiation. Chest X-rays may reveal suspicious areas in the lungs but are unable to determine if these areas are cancerous. In particular, calcified nodules in the lungs or benign tumors called hamartomas may be identified on a chest X-ray and mimic lung cancer.
· CT (computerized tomography, computerized axial tomography, or CAT) scans may be performed on the chest, abdomen, and/or brain to examine for both metastatic and lung tumors. A CT scan of the chest may be ordered when X-rays do not show an abnormality or do not yield sufficient information about the extent or location of a tumor. CT scans are X-ray procedures that combine multiple images with the aid of a computer to generate cross-sectional views of the body. The images are taken by a large donut-shaped X-ray machine at different angles around the body. One advantage of CT scans is that they are more sensitive than standard chest X-rays in the detection of lung nodules, that is, they will demonstrate more nodules. Sometimes intravenous contrast material is given prior to the scan to help delineate the organs and their positions. A CT scan exposes the patient to a minimal amount of radiation. The most common side effect is an adverse reaction to intravenous contrast material that may have been given prior to the procedure. This may result in itching, a rash, orhives that generally disappear rather quickly. Severe anaphylactic reactions (life-threatening allergic reactions with breathing difficulties) to contrast material are rare. CT scans of the abdomen may identify metastatic cancer in the liver or adrenal glands, and CT scans of the head may be ordered to reveal the presence and extent of metastatic cancer in the brain.
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This picture is a chest x-ray of a person with a lung mass. This is a front view, where the lungs are the two dark areas and the heart and other structures are visible in the middle of the chest. The x-ray shows a mass in the right upper lung, indicated with the arrow.
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This chest x-ray shows adenocarcinoma of the lung. There is a rounded light spot in the right upper lung at the level of the second rib. The light spot has irregular and poorly defined borders and is not uniform in density. Diseases that may cause this type of x-ray result would be tuberculous or fungal granuloma, and malignant or benign tumors.
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This is a chest x-ray showing a mass in the right lower lung near heart.
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This is a chest x-ray (CXR) of a nodule in the right lung.
A CXR in a patient with central cancer of the right lung. Notice the white mass in the middle portion of the right lung
· A technique called a low-dose helical CT scan (or spiral CT scan) is recommended for use annually in current and former smokers between ages 55 and 80 with at least a 30 pack year history of cigarette smoking who have smoked cigarettes within the past 15 years per the USPSTF recommendations. The technique appears to increase the likelihood of detection of smaller, earlier, and more curable lung cancers. Three years of low-dose CT scanning in this group reduced the risk of lung cancer death by 20%. Use of models and rules for analyzing the results of these tests are decreasing the need for testing to evaluate detected nodules when the likelihood is high the nodule is not cancerous.
· Magnetic resonance imaging (MRI) scans may be appropriate when precise detail about a tumor’s location is required. The MRI technique uses magnetism, radio waves, and a computer to produce images of body structures. As with CT scanning, the patient is placed on a moveable bed which is inserted into the MRI scanner. There are no known side effects of MRI scanning, and there is no exposure to radiation. The image and resolution produced by MRI is quite detailed and can detect tiny changes of structures within the body. People with heart pacemakers, metal implants, artificial heart valves, and other surgically implanted structures cannot be scanned with an MRI because of the risk that the magnet may move the metal parts of these structures.
· Positron emission tomography (PET) scanning is a specialized imaging technique that uses short-lived radioactive drugs to produce three-dimensional colored images of those substances in the tissues within the body. While CT scans and MRI scans look at anatomical structures, PET scans measure metabolic activity and the function of tissues. PET scans can determine whether a tumor tissue is actively growing and can aid in determining the type of cells within a particular tumor. In PET scanning, the patient receives a short half-lived radioactive drug, receiving approximately the amount of radiation exposure as two chest X-rays. The drug accumulates in certain tissues more than others, depending on the drug that is injected. The drug discharges particles known as positrons from whatever tissues take them up. As the positrons encounter electrons within the body, a reaction producing gamma rays occurs. A scanner records these gamma rays and maps the area where the radioactive drug has accumulated. For example, combining glucose (a common energy source in the body) with a radioactive substance will show where glucose is rapidly being used, for example, in a growing tumor. PET scanning may also be integrated with CT scanning in a technique known as PET-CT scanning. Integrated PET-CT has been shown to improve the accuracy of staging (see below) over PET scanning alone.
· Bone scans are used to create images of bones on a computer screen or on film. Doctors may order a bone scan to determine whether a lung cancer has metastasized to the bones. In a bone scan, a small amount of radioactive material is injected into the bloodstream and collects in the bones, especially in abnormal areas such as those involved by metastatic tumors. The radioactive material is detected by a scanner, and the image of the bones is recorded on a special film for permanent viewing.
· Sputum cytology: The diagnosis of lung cancer always requires confirmation of malignant cells by a pathologist, even when symptoms and X-ray studies are suspicious for lung cancer. The simplest method to establish the diagnosis is the examination of sputum under a microscope. If a tumor is centrally located and has invaded the airways, this procedure, known as a sputum cytology examination, may allow visualization of tumor cells for diagnosis. This is the most risk-free and inexpensive tissue diagnostic procedure, but its value is limited since tumor cells will not always be present in sputum even if a cancer is present. Also, noncancerous cells may occasionally undergo changes in reaction to inflammation or injury that makes them look like cancer cells.
· Bronchoscopy: Examination of the airways by bronchoscopy (visualizing the airways through a thin, fiberoptic probe inserted through the nose or mouth) may reveal areas of tumor that can be sampled (biopsied) for diagnosis by a pathologist. A tumor in the central areas of the lung or arising from the larger airways is accessible to sampling using this technique. Bronchoscopy may be performed using a rigid or a flexible fiberoptic bronchoscope and can be performed in a same-day outpatient bronchoscopy suite, an operating room, or on a hospital ward. The procedure can be uncomfortable, and it requires sedation or anesthesia. While bronchoscopy is relatively safe, it must be carried out by a lung specialist (pulmonologist or surgeon) experienced in the procedure. When a tumor is visualized and adequately sampled, an accurate cancer diagnosis usually is possible. Some patients may cough up dark-brown blood for 1 to 2 days after the procedure. More serious but rare complications include a greater amount of bleeding, decreased levels of oxygen in the blood, and heart arrhythmias as well as complications from sedative medications and anesthesia.
· Needle biopsy: Fine needle aspiration (FNA) through the skin, most commonly performed with radiological imaging for guidance, may be useful in retrieving cells for diagnosis from tumor nodules in the lungs. Needle biopsies are particularly useful when the lung tumor is peripherally located in the lung and not accessible to sampling by bronchoscopy. A small amount of local anesthetic is given prior to insertion of a thieedle through the chest wall into the abnormal area in the lung. Cells are suctioned into the syringe and are examined under the microscope for tumor cells. This procedure is generally accurate when the tissue from the affected area is adequately sampled, but in some cases, adjacent or uninvolved areas of the lung may be mistakenly sampled. A small risk (3% to 5%) of an air leak from the lungs (called a pneumothorax, which can easily be treated) accompanies the procedure.
· Thoracentesis: Sometimes lung cancers involve the lining tissue of the lungs (pleura) and lead to an accumulation of fluid in the space between the lungs and chest wall (called a pleural effusion). Aspiration of a sample of this fluid with a thieedle (thoracentesis) may reveal the cancer cells and establish the diagnosis. As with the needle biopsy, a small risk of a pneumothorax is associated with this procedure.
· Major surgical procedures: If none of the aforementioned methods yields a diagnosis, surgical methods must be employed to obtain tumor tissue for diagnosis. These can include mediastinoscopy (examining the chest cavity between the lungs through a surgically inserted probe with biopsy of tumor masses or lymph nodes that may contain metastases) or thoracotomy (surgical opening of the chest wall for removal or biopsy of a tumor). With a thoracotomy, it is rare to be able to completely remove a lung cancer, and both mediastinoscopy and thoracotomy carry the risks of major surgical procedures (complications such as bleeding, infection, and risks from anesthesia and medications). These procedures are performed in an operating room, and the patient must be hospitalized.
· Blood tests: While routine blood tests alone cannot diagnose lung cancer, they may reveal biochemical or metabolic abnormalities in the body that accompany cancer. For example, elevated levels of calcium or of the enzyme alkaline phosphatase may accompany cancer that is metastatic to the bones. Likewise, elevated levels of certain enzymes normally present within liver cells, including aspartate aminotransferase (AST or SGOT) and alanine aminotransferase (ALT or SGPT), signal liver damage, possibly through the presence of tumor metastatic to the liver. One current focus of research in the area of lung cancer is the development of a blood test to aid in the diagnosis of lung cancer. Researchers have preliminary data that has identified specific proteins, or biomarkers, that are in the blood and may signal that lung cancer is present in someone with a suspicious area seen on a chest X-ray or other imaging study.
What is staging of lung cancer?
The stage of a cancer is a measure of the extent to which a cancer has spread in the body. Staging involves evaluation of a cancer’s size and its penetration into surrounding tissue as well as the presence or absence of metastases in the lymph nodes or other organs. Staging is important for determining how a particular cancer should be treated, since lung-cancer therapies are geared toward specific stages. Staging of a cancer also is critical in estimating the prognosis of a given patient, with higher-stage cancers generally having a worse prognosis than lower-stage cancers.
Doctors may use several tests to accurately stage a lung cancer, including laboratory (blood chemistry) tests, X-rays, CT scans, bone scans, MRI scans, and PET scans. Abnormal blood chemistry tests may signal the presence of metastases in bone or liver, and radiological procedures can document the size of a cancer as well as its spread.
NSCLC are assigned a stage from I to IV in order of severity:
· In stage I, the cancer is confined to the lung.
· In stages II and III, the cancer is confined to the chest (with larger and more invasive tumors classified as stage III).
· Stage IV cancer has spread from the chest to other parts of the body.
SCLC are staged using a two-tiered system:
· Limited-stage (LS) SCLC refers to cancer that is confined to its area of origin in the chest.
· In extensive-stage (ES) SCLC, the cancer has spread beyond the chest to other parts of the body.
What is the treatment for lung cancer?
Treatment for lung cancer can involve surgical removal of the cancer, chemotherapy, or radiation therapy, as well as combinations of these treatments. The decision about which treatments will be appropriate for a given individual must take into account the location and extent of the tumor as well as the overall health status of the patient.
As with other cancers, therapy may be prescribed that is intended to be curative (removal or eradication of a cancer) or palliative (measures that are unable to cure a cancer but can reduce pain and suffering). More than one type of therapy may be prescribed. In such cases, the therapy that is added to enhance the effects of the primary therapy is referred to as adjuvant therapy. An example of adjuvant therapy is chemotherapy or radiotherapy administered after surgical removal of a tumor in an attempt to kill any tumor cells that remain following surgery.
Surgery: Surgical removal of the tumor is generally performed for limited-stage (stage I or sometimes stage II) NSCLC and is the treatment of choice for cancer that has not spread beyond the lung. About 10% to 35% of lung cancers can be removed surgically, but removal does not always result in a cure, since the tumors may already have spread and can recur at a later time. Among people who have an isolated, slow-growing lung cancer removed, 25% to 40% are still alive 5 years after diagnosis. It is important to note that although a tumor may be anatomically suitable for resection, surgery may not be possible if the person has other serious conditions (such as severe heart or lung disease) that would limit their ability to survive an operation. Surgery is less often performed with SCLC than with NSCLC because these tumors are less likely to be localized to one area that can be removed.
The surgical procedure chosen depends upon the size and location of the tumor. Surgeons must open the chest wall and may perform a wedge resection of the lung (removal of a portion of one lobe), a lobectomy (removal of one lobe), or a pneumonectomy (removal of an entire lung). Sometimes lymph nodes in the region of the lungs also are removed (lymphadenectomy). Surgery for lung cancer is a major surgical procedure that requires general anesthesia, hospitalization, and follow-up care for weeks to months. Following the surgical procedure, patients may experience difficulty breathing, shortness of breath, pain, and weakness. The risks of surgery include complications due to bleeding, infection, and complications of general anesthesia.
Radiation: Radiation therapy may be employed as a treatment for both NSCLC and SCLC. Radiation therapy uses high-energy X-rays or other types of radiation to kill dividing cancer cells. Radiation therapy may be given as curative therapy, palliative therapy (using lower doses of radiation than with curative therapy), or as adjuvant therapy in combination with surgery or chemotherapy. The radiation is either delivered externally, by using a machine that directs radiation toward the cancer, or internally through placement of radioactive substances in sealed containers within the area of the body where the tumor is localized. Brachytherapy is a term used to describe the use of a small pellet of radioactive material placed directly into the cancer or into the airway next to the cancer. This is usually done through a bronchoscope.
Radiation therapy can be given if a person refuses surgery, if a tumor has spread to areas such as the lymph nodes or trachea making surgical removal impossible, or if a person has other conditions that make them too ill to undergo major surgery. Radiation therapy generally only shrinks a tumor or limits its growth when given as a sole therapy, yet in 10% to 15% of people it leads to long-term remission and palliation of the cancer. Combining radiation therapy with chemotherapy can further prolong survival when chemotherapy is administered. External radiation therapy can generally be carried out on an outpatient basis, while internal radiation therapy requires a brief hospitalization. A person who has severe lung disease in addition to a lung cancer may not be able to receive radiotherapy to the lung since the radiation can further decrease function of the lungs. A type of external radiation therapy called the “gamma knife” is sometimes used to treat single brain metastases. In this procedure, multiple beams of radiation coming from different directions are focused on the tumor over a few minutes to hours while the head is held in place by a rigid frame. This reduces the dose of radiation that is received by noncancerous tissues.
For external radiation therapy, a process called simulation is necessary prior to treatment. Using CT scans, computers, and precise measurements, simulation maps out the exact location where the radiation will be delivered, called the treatment field or port. This process usually takes 30 minutes to 2 hours. The external radiation treatment itself generally is done 4 or 5 days a week for several weeks.
Radiation therapy does not carry the risks of major surgery, but it can have unpleasant side effects, including fatigue and lack of energy. A reduced white blood cell count (rendering a person more susceptible to infection) and low blood platelet levels (making blood clotting more difficult and resulting in excessive bleeding) also can occur with radiation therapy. If the digestive organs are in the field exposed to radiation, patients may experience nausea, vomiting, or diarrhea. Radiation therapy can irritate the skin in the area that is treated, but this irritation generally improves with time after treatment has ended.
Chemotherapy: Both NSCLC and SCLC may be treated with chemotherapy. Chemotherapy refers to the administration of drugs that stop the growth of cancer cells by killing them or preventing them from dividing. Chemotherapy may be given alone, as an adjuvant to surgical therapy, or in combination with radiotherapy. While a number of chemotherapeutic drugs have been developed, the class of drugs known as the platinum-based drugs have been the most effective in treatment of lung cancers.
Chemotherapy is the treatment of choice for most SCLC, since these tumors are generally widespread in the body when they are diagnosed. Only half of people who have SCLC survive for 4 months without chemotherapy. With chemotherapy, their survival time is increased up to four- to fivefold. Chemotherapy alone is not particularly effective in treating NSCLC, but when NSCLC has metastasized, it can prolong survival in many cases.
Chemotherapy may be given as pills, as an intravenous infusion, or as a combination of the two. Chemotherapy treatments usually are given in an outpatient setting. A combination of drugs is given in a series of treatments, called cycles, over a period of weeks to months, with breaks in between cycles. Unfortunately, the drugs used in chemotherapy also kill normally dividing cells in the body, resulting in unpleasant side effects. Damage to blood cells can result in increased susceptibility to infections and difficulties with blood clotting (bleeding or bruising easily). Other side effects include fatigue, weight loss, hair loss, nausea, vomiting, diarrhea, and mouth sores. The side effects of chemotherapy vary according to the dosage and combination of drugs used and may also vary from individual to individual. Medications have been developed that can treat or prevent many of the side effects of chemotherapy. The side effects generally disappear during the recovery phase of the treatment or after its completion.
Prophylactic brain radiation: SCLC often spreads to the brain. Sometimes people with SCLC that is responding well to treatment are treated with radiation therapy to the head to treat very early spread to the brain (called micrometastasis) that is not yet detectable with CT or MRI scans and has not yet produced symptoms. Brain radiation therapy can cause short-term memory problems, fatigue, nausea, and other side effects.
Treatment of recurrence: Lung cancer that has returned following treatment with surgery, chemotherapy, and/or radiation therapy is referred to as recurrent or relapsed. If a recurrent cancer is confined to one site in the lung, it may be treated with surgery. Recurrent tumors generally do not respond to the chemotherapeutic drugs that were previously administered. Since platinum-based drugs are generally used in initial chemotherapy of lung cancers, these agents are not useful in most cases of recurrence. A type of chemotherapy referred to as second-line chemotherapy is used to treat recurrent cancers that have previously been treated with chemotherapy, and a number of second-line chemotherapeutic regimens have been proven effective at prolonging survival. People with recurrent lung cancer who are well enough to tolerate therapy also are good candidates for experimental therapies (see below), including clinical trials.
Targeted therapy: The drugs erlotinib (Tarceva) and gefitinib (Iressa) are so-called targeted drugs, which may be used in certain patients with NSCLC who are no longer responding to chemotherapy. Targeted therapy drugs more specifically target cancer cells, resulting in less damage to normal cells than general chemotherapeutic agents. Erlotinib and gefitinib target a protein called the epidermal growth factor receptor (EGFR) that is important in promoting the division of cells. This protein is found at abnormally high levels on the surface of some types of cancer cells, including many cases of non-small cell lung cancer.
Other attempts at targeted therapy include drugs known as antiangiogenesis drugs, which block the development of new blood vessels within a cancer. Without adequate blood vessels to supply oxygen-carrying blood, the cancer cells will die. The antiangiogenic drug bevacizumab (Avastin) has also been found to prolong survival in advanced lung cancer when it is added to the standard chemotherapy regimen. Bevacizumab is given intravenously every 2 to 3 weeks. However, since this drug may cause bleeding, it is not appropriate for use in patients who are coughing up blood, if the lung cancer has spread to the brain, or in people who are receiving anticoagulation therapy (“blood thinner” medications). Bevacizumab also is not used in cases of squamous cell cancer because it leads to bleeding from this type of lung cancer.
Cetuximab is an antibody that binds to the epidermal growth factor receptor (EGFR). In patients with NSCLC whose tumors have been shown to express the EGFR by immunohistochemical analysis, the addition of cetuximab may be considered for some patients.
Photodynamic therapy (PDT): One newer therapy used for different types and stages of lung cancer (as well as some other cancers) is photodynamic therapy. In photodynamic treatment, a photosynthesizing agent (such as a porphyrin, a naturally occurring substance in the body) is injected into the bloodstream a few hours prior to surgery. During this time, the agent is taken up in rapidly growing cells such as cancer cells. A procedure then follows in which the physician applies a certain wavelength of light through a handheld wand directly to the site of the cancer and surrounding tissues. The energy from the light activates the photosensitizing agent, causing the production of a toxin that destroys the tumor cells. PDT has the advantages that it can precisely target the location of the cancer, is less invasive than surgery, and can be repeated at the same site if necessary. The drawbacks of PDT are that it is only useful in treating cancers that can be reached with a light source and is not suitable for treatment of extensive cancers. The U.S. Food and Drug Administration (FDA) has approved the photosensitizing agent called porfimer sodium (Photofrin) for use in PDT to treat or relieve the symptoms of esophageal cancer and non-small cell lung cancer. Further research is ongoing to determine the effectiveness of PDT in other types of lung cancer.
Radiofrequency ablation (RFA): Radiofrequency ablation is being studied as an alternative to surgery, particularly in cases of early stage lung cancer. In this type of treatment, a needle is inserted through the skin into the cancer, usually under guidance by CT scanning. Radiofrequency (electrical) energy is then transmitted to the tip of the needle where it produces heat in the tissues, killing the cancerous tissue and closing small blood vessels that supply the cancer. RFA usually is not painful and has been approved by the U.S. Food and Drug Administration for the treatment of certain cancers, including lung cancers. Studies have shown that this treatment can prolong survival similarly to surgery when used to treat early stages of lung cancer but without the risks of major surgery and the prolonged recovery time associated with major surgical procedures.
Experimental therapies: Since no therapy is currently available that is absolutely effective in treating lung cancer, patients may be offered a number of new therapies that are still in the experimental stage, meaning that doctors do not yet have enough information to decide whether these therapies should become accepted forms of treatment for lung cancer. New drugs or new combinations of drugs are tested in so-called clinical trials, which are studies that evaluate the effectiveness of new medications in comparison with those treatments already in widespread use. Experimental treatments known as immunotherapies are being studied that involve the use of vaccine-related therapies or other therapies that attempt to utilize the body’s immune system to fight cancer cells. Vaccine therapies against lung cancer are another area in which research is ongoing. In 2010, a treatment vaccine for advanced prostate cancer gained approval by the FDA, and lung cancer treatment vaccines are also being studied in clinical trials.
Medically Reviewed by a Doctor on 12/3/2013
What is the prognosis (outcome) of lung cancer?
The prognosis of lung cancer refers to the chance for cure or prolongation of life (survival) and is dependent upon where the cancer is located, the size of the cancer, the presence of symptoms, the type of lung cancer, and the overall health status of the patient.
SCLC has the most aggressive growth of all lung cancers, with a median survival time of only 2 to 4 months after diagnosis when untreated. (That is, by 2 to 4 months, half of all patients have died.) However, SCLC is also the type of lung cancer most responsive to radiation therapy and chemotherapy. Because SCLC spreads rapidly and is usually disseminated at the time of diagnosis, methods such as surgical removal or localized radiation therapy are less effective in treating this type of lung cancer. When chemotherapy is used alone or in combination with other methods, survival time can be prolonged four- to fivefold; however, of all patients with SCLC, only 5% to 10% are still alive 5 years after diagnosis. Most of those who survive have limited-stage SCLC.
In non-small cell lung cancer (NSCLC), the most important prognostic factor is the stage (extent of spread) of the tumor at the time of diagnosis. Results of standard treatment are generally poor in all but the smallest of cancers that can be surgically removed. However, in stage I cancers that can be completely removed surgically, 5-year survival approaches 75%. Radiation therapy can produce a cure in a small minority of patients with NSCLC and leads to relief of symptoms in most patients. In advanced-stage disease, chemotherapy offers modest improvements in survival although rates of overall survival are poor.
The overall prognosis for lung cancer is poor when compared with some other cancers. Survival rates for lung cancer are generally lower than those for most cancers, with an overall 5-year survival rate for lung cancer of about 17% compared to 67% for colon cancer, 90% for breast cancer, 81% for bladder cancer, and over 99% for prostate cancer.
How can lung cancer be prevented?
Cessation of smoking and eliminating exposure to tobacco smoke is the most important measure that can prevent lung cancer. Many products, such as nicotine gum, nicotine sprays, or nicotine inhalers, may be helpful to people trying to quit smoking. Minimizing exposure to passive smoking also is an effective preventive measure. Using a home radon test kit can identify and allow correction of increased radon levels in the home. Methods that allow early detection of cancers, such as the helical low-dose CT scan, also may be of value in the identification of small cancers that can be cured by surgical resection and prevented from becoming widespread, incurable, metastatic cancer.
Medically Reviewed by a Doctor
Mediastinal Tumor
What are mediastinal tumors?
The mediastinum is divided into three sections:
Mediastinal tumors are benign or cancerous growths that form in the area of the chest that separates the lungs. This area, called the mediastinum, is surrounded by the breastbone in front, the spine in back, and the lungs on each side. The mediastinum contains the heart, aorta, esophagus, thymus and trachea.
· The anterior (front)
· The middle
· The posterior (back)
Mediastinum tumors are mostly made of reproductive (germ) cells or develop in thymic, neurogenic (nerve), lymphatic or mesenchymal (soft) tissue.
Who is affected by mediastinal tumors?
In general, mediastinal tumors are rare. Mediastinal tumors are usually diagnosed in patients aged 30 to 50 years, but they can develop at any age and form from any tissue that exists in or passes through the chest cavity.
The location of tumors within the mediastinum varies according to the age of the patient. In children, tumors are commonly found in the posterior (back) mediastinum. These mediastinal tumors often begin in the nerves and are typically benign (noncancerous).
In adults, most mediastinal tumors occur in the anterior (front) mediastinum and are generally malignant (cancerous) lymphomas or thymomas.
Is a mediastinal tumor serious?
Due to their location in the mediastinum, mediastinal tumors (both benign and malignant) that are left untreated can cause serious complications including invading the heart, pericardium (the lining around the heart), and great vessels (the aorta and vena cava). Tumors located in the posterior (back) mediastinum can cause compression of the spinal cord.
What causes mediastinal tumors?
There are several types of mediastinal tumors, with their causes linked to where they form in the mediastinum.
Anterior (front) mediastinum
· Germ cell – The majority of germ cell neoplasms (60 to 70%) are benign and are found in both males and females.
· Lymphoma – Malignant tumors that include both Hodgkin’s disease and non Hodgkin’s lymphoma.
· Thymoma and thymic cyst – The most common cause of a thymic mass, the majority of thymomas are benign lesions that are contained within a fibrous capsule. However, about 30% of these may be more aggressive and become invasive through the fibrous capsule.
· Thyroid mass mediastinal – Usually a benign growth, such as a goiter, these can occasionally be cancerous.
Middle mediastinum
· Bronchogenic cyst – A benign growth with respiratory origins.
· Lymphadenopathy mediastinal – An enlargement of the lymph nodes.
· Pericardial cyst – A benign growth that results from an “out-pouching” of the pericardium (the heart’s lining).
· Thyroid mass mediastinal – Usually a benign growth, such as a goiter. These types of tumors can occasionally be cancerous.
· Tracheal tumors – These include tracheal neoplasms and non-euplastic masses, such as tracheobronchopathia osteochondroplastica (benign tumors).
· Vascular abnormalities including aortic aneurysm and aortic dissection.
Posterior (back) mediastinum
· Extramedullary haematopoiesis – A rare cause of masses that form from bone marrow expansion and are associated with severe anemia.
· Lymphadenopathy mediastinal – An enlargement of the lymph nodes.
· Neuroenteric cyst mediastinal – A rare growth, which involves both neural and gastrointestinal elements.
· Neurogenic neoplasm mediastinal – The most common cause of posterior mediastinal tumors, these are classified as nerve sheath neoplasms, ganglion cell neoplasms, and paraganglionic cell neoplasms. Approximately 70% of neurogenic neoplasms are benign. Oesophageal abnormalities including achalasia oesophageal, oesophageal neoplasm and hiatal hernia. Paravertebral abnormalities including infectious, malignant and traumatic abnormalities of the thoracic spine. Thyroid mass mediastinal – Usually a benign growth, such as a goiter, which can occasionally be cancerous. Vascular abnormalities – Includes aortic aneurysms.
What are the symptoms of a mediastinal tumor?
Almost 40% of people who have mediastinal tumors experience no symptoms. Most of the growths are often discovered on a chest x-ray that is performed for another reason. When symptoms are present they are often a result of the compression of surrounding structures, such as the spinal cord, heart or the pericardium (the heart’s lining), and may include:
· Cough
· Shortness of breath
· Chest pain
· Fever
· Chills
· Night sweats
· Coughing up blood
· Hoarseness
· Unexplained weight loss
· Lymphadenopathy (swollen or tender lymph nodes)
· Wheezing
· Stridor (a high-pitched, noisy respiration, which can be a sign of respiratory obstruction, especially in the trachea or larynx)
How is a mediastinal tumor diagnosed?
The tests most commonly used to diagnose and evaluate a mediastinal tumor include:
· Chest x-ray
· Computed tomography (CT) scan of the chest or CT-guided needle biopsy
· Magnetic resonance imaging (MRI) of the chest
· Mediastinoscopy with biopsy (Performed under general anesthesia, this examination of the chest cavity uses a lighted tube inserted through a small incision under the chest bone; a sample of tissue is taken to determine if cancer is present. Mediastinoscopy with biopsy allows doctors to accurately diagnose 80 to 90% of mediastinal tumors, and 95 to 100% of anterior mediastinal tumors.)
How are mediastinal tumors treated?
The treatment used for mediastinal tumors depends on the type of tumor and its location:
· Thymic cancers require surgery, followed by radiation or chemotherapy. Types of surgery include thoracoscopy (a minimally invasive approach), mediastinoscopy (minimally invasive) and thoracotomy (a procedure performed through an incision in the chest).
· Lymphomas are recommended to be treated with chemotherapy followed by radiation.
· Neurogenic tumors found in the posterior (back) mediastinum are treated surgically.
What are the benefits of minimally invasive surgery to treat mediastinal tumors?
As compared with traditional surgery, patients who undergo minimally invasive surgery, such as video-assisted thoracoscopy (VATS) mediastinoscopy, experience:
· Decreased postoperative pain
· Shorter hospital stay
· More rapid recovery and return to work
Other possible benefits include reduced risk of infection and less bleeding.
What are the risks of minimally invasive surgery to treat mediastinal tumors?
There are complications of radiation, chemotherapy and surgical treatment of mediastinal tumors. Your health care team will discuss the possible risks and potential benefits of each treatment option with you.
The possible complications of minimally invasive surgical treatment include:
· Damage to the surrounding area, which may include the heart, pericardium (the heart’s lining) or spinal cord. Pleural effusion (a collection of fluid between the thin layers of tissue lining the lung and the wall of the chest cavity, or pleura)
· Postoperative drainage
· Postoperative infection or bleeding
Your health care team will provide specific instructions to prepare you for each treatment or procedure. They will also provide specific instructions for your recovery and return to work, including guidelines for activity, driving, incision care and diet.
What Are Mediastinal Tumors?
Neoplasms are abnormal growths of tissue that can occur in almost any area of the body. They are also called tumors. They are most commonly linked with cancer. Tumors can develop in the mediastinum.
The mediastinum is the area in the middle of the chest that lies between the sternum(breastbone) and the spinal column. It contains vital organs including the heart,esophagus, and trachea. Tumors that develop in this area are called mediastinal tumors. These tumors are very rare.
Mediastinal tumors can develop in one of three areas of the mediastinum: the anterior(front), the middle, or the posterior (back). The position of the tumor in the mediastinum typically depends on the age of the patient.
Children are more likely to develop these tumors in the back of the mediastinum. They are often benign (non-cancerous). Adults are more likely to develop them in the front of the mediastinum. These tumors are typically malignant (cancerous). Adults that develop these types of tumors are usually between the ages of 30 and 50.
· Neoplasms are abnormal growths of tissue that can occur in almost any area of the body. They are also called tumors. They are most commonly linked with cancer. Tumors can develop in the mediastinum.
The mediastinum is the area in the middle of the chest that lies between the sternum(breastbone) and the spinal column. It contains vital organs including the heart,esophagus, and trachea. Tumors that develop in this area are called mediastinal tumors. These tumors are very rare.
Mediastinal tumors can develop in one of three areas of the mediastinum: the anterior(front), the middle, or the posterior (back). The position of the tumor in the mediastinum typically depends on the age of the patient.
Children are more likely to develop these tumors in the back of the mediastinum. They are often benign (non-cancerous). Adults are more likely to develop them in the front of the mediastinum. These tumors are typically malignant (cancerous). Adults that develop these types of tumors are usually between the ages of 30 and 50.
· What Causes Mediastinal Tumors?
There are a number of different types of mediastinal tumors. The cause of these tumors is directly linked with where they form in the mediastinum.
In the front of the mediastinum, tumors can be caused by:
· lymphoma, including Hodgkin’s disease and non-Hodgkin’s lymphoma
· thymoma and thymic cyst—a tumor of the thymus
· thyroid mass mediastinal—generally a benign growth, but can sometimes be cancerous
In the middle of the mediastinum, tumors can be caused by:
· bronchogenic cyst—a benign growth that starts in the respiratory system
· lymphadenopathy mediastinal, or enlargement of the lymph nodes
· pericardial cyst—a benign growth on the heart lining
· thyroid mass mediastinal
· tracheal tumors—usually benign growths
· vascular complications, such as swelling of the aorta
In the back of the mediastinum, tumors can be caused by:
· extramedullary haematopoiesis—rare growths that start in the bone marrow and are related to severe anemia
· lymphadenopathy mediastinal
· neuroenteric cyst mediastinal—a rare growth involving both the nerves and the gastrointestinal system
· neurogenic neoplasm mediastinal—the most common case of posterior mediastinal tumors, they are cancerous cells of the nerves. According to the Cleveland Clinic Foundation, about 70 percent of these are benign (Cleveland Clinic).
Tumors that form in the mediastinum are known as primary tumors. Sometimes mediastinal tumors will develop because cancer from another part of the body has spread. The spread of cancer from one area of the body to another is known asmetastasis. Mediastinal tumors that develop because of metastasis are known as asecondary tumor.
Symptoms of A Mediastinal Tumors
If you have a mediastinal tumor, you may not have any symptoms. Tumors are typically discovered during a chest X-ray performed to diagnose another health condition.
If symptoms develop, it is often because the tumor is pushing on surrounding organs. Symptoms can include:
· cough
· shortness of breath
· chest pain
· fever/chills
· night sweats
· coughing up blood
· unexplained weight loss
· respiratory blockage
· hoarseness
Tumors are typically discovered during a chest X-ray performed to diagnose another health condition. If symptoms develop, it is often because the tumor is pushing on surrounding organs.
Symptoms can include:
· cough
· shortness of breath
· chest pain
· fever/chills
· night sweats
· coughing up blood
· unexplained weight loss
· respiratory blockage
· hoarseness
How Are Mediastinal Tumors Diagnosed?
If you have symptoms of a mediastinal tumor, your doctor will order additional tests to confirm your diagnosis. These tests may include:
· a chest X-ray
· a CT scan of the chest
· an MRI of the chest
· a mediastinoscopy with biopsy
Mediastinoscopy with biopsy is used to collect cells from the mediastinum. During this test, you will be given anesthesia. Your doctor will make a small incision (cut) under the breastbone. A sample of tissue will be removed. The sample will be analyzed to see if cancer is present. This procedure will help your doctor accurately diagnose the type of tumor you have.
How Are Mediastinal Tumors Treated?
Treatment for mediastinal tumors will depend on their location.
Surgery is often used first to remove the tumor. Once the tumor is removed, chemotherapy and/or radiationtherapy are used to destroy remaining cancer cells.
Both benign and malignant tumors require treatment. Non-cancerous tumors can grow and impact organ function. Cancerous tumors can spread to other areas of the body.
The specific type of treatment that you receive will be determined by your doctor.
What Complications Are Associated with Mediastinal Tumors?
If left untreated, mediastinal tumors can cause serious health complications. As tumors grow, they will push against surrounding organs and tissues. Tumors that invade the heart or the vessels of the heart can cause death.
Tumors may also invade the spinal column. This may result in compression of the spinal cord.
Treatment for this condition typically involves chemotherapy and radiation. Both treatments can have serious side effects, such as:
· changes in appetite
· bleeding problems
· anemia
· constipation
· diarrhea
· fatigue
· hair loss
· infection
· nausea/vomiting
· pain
· swelling
Radiation therapy may have similar side effects. Radiation may also cause changes in the skin, including:
· dryness
· itching
· peeling
· blistering
The Long-Term Outlook for Patients With Mediastinal Tumors
The outlook for patients with mediastinal tumors depends on the location of the tumor. Long-term outlook also depends on if the tumor is primary or secondary. Talk to your doctor to get more accurate information about your prognosis.
THYMOMAS
Thymomas are malignant tumors that arise in the thymus gland, typically in the anterior mediastinum. Although considered malignant, most thymomas grow slowly and tend to spread only locally, by “seeding” cells into surrounding tissues and spaces such as the pleural space (the space surrounding each lung). There is therefore often a very good chance of curing thymomas by either surgery alone or surgery followed by radiation. We often proceed to remove these localized tumors without even the need for a preliminary biopsy.
More difficult thymic tumors that consist of frank carcinoma cells, and other thymic tumors that appear to invade surrounding structures on preoperative radiographic studies, are often best treated by administering preoperative chemotherapy or chemotherapy and radiation before surgical removal. These cases are discussed at our multidisciplinary Thoracic Tumor Board which consists of specialists from oncology, radiation oncology, radiology, and pathology in addition to thoracic surgeons. Here, the optimal treatment plan can be designed with the combined input from all the appropriate experts. These tumors require a preoperative needle biopsy or surgical biopsy to confirm the diagnosis before giving preoperative therapies. Surgery is then generally carried out if it is felt to be possible and there has been at least some shrinkage in response to the preoperative treatment.
The most common surgical incision through which to remove a thymoma is a median sternotomy. This is a vertical incision through the breast bone that provides excellent exposure of the anterior mediastinum. Since no chest wall muscles are cut with this incision, postoperative pain is modest, and recovery is not prolonged. Smaller thymomas may be treated with VATS (video-assisted thoracoscopic surgery – see Lung Cancer section of this website) thymectomy, but this is an emerging area that we are moving into cautiously, with patient-safety at the forefront of our minds. We are also among the most experienced centers in transcervical thymectomy for myasthenia gravis, but we believe this approach should be reserved primarily for patients without thymoma – it should certainly not be used for more than the smallest thymomas (less than 2 cm in size) given the risk of spillage of tumor cells.
There are several staging systems for thymoma, but the most widely used are the Masaoka system and the World Health Organization (WHO) system. The Masaoka system is based on degree of invasion of the capsule around the tumor and of surrounding structures; the WHO system is based upon the appearance of the cells that make up the tumor under the microscope. Combining the two systems allows us to provide the best estimate of prognosis for each individual tumor, as well as allowing us to recommend when preoperative and postoperative treatments might be advantageous.
Masaoka System
|
I |
Completely encapsulated tumor, without tumor invasion into the capsule |
|
II |
Tumor invasion into fatty/thymic tissue surrounding the tumor or microscopic invasion into the capsule |
|
III |
Tumor invasion into organs surrounding the thymus |
|
IVA |
Tumor implants in the pleura or pericardium (the linings of the lungs or heart) |
|
IVB |
Spread to lymph nodes or via bloodstream to distant organs |
World Health Organization (WHO) System
A
AB
B1, B2, B3
C Thymic Carcinoma
Cure rates for Masaoka stage I tumors are 90-95%; stage II 85-90%; stage III 50-70%; stage IV 20-50%. WHO type A and AB tumors within each of these Masaoka stages appear to have cure rates at the higher end of the range, while those with type B tumors will fall at the lower end of the cure range. Type C tumors – thymic carcinoma—have the worst prognosis.
Stage-based Therapy for Thymomas is as follows:
|
Stage I |
Surgical resection alone |
|
Stage II |
Surgical resection, sometimes followed by radiation |
|
Stage III |
Chemotherapy or chemoradiation followed by surgical resection; or surgical resection followed by radiation or chemoradiation |
|
Stage IV |
Chemoradiation followed in some cases by by surgical resection |
Myasthenia gravis is a disease of the junctions where nerves that control muscle function meet the muscles themselves (the neuromuscular junction). In myasthenia gravis patients, antibodies form within the neuromuscular junction that make the transmission of nerve impulses from nerve to muscle less efficient. This creates a variety of problems which may include weakness of the peripheral muscles (usually worsening with repetitive contraction of the muscles), droopy eyelids (ptosis), double vision, and swallowing or breathing difficulties.
Drug therapy, which usually is initiated with pyridostigmine (mestinon) alone, often helps these symptoms of myasthenia gravis. Other, immunosuppressive drugs, such as prednisone or azathioprine, are added in some cases.
Surgical removal of the thymus gland (thymectomy) has had a role in the management of patients with thymoma for over 70 years. Although it has never been studied versus medical therapy in a randomized trial (where patients are “randomized” to either have surgery or have no surgery), many non-randomized studies suggest that the operation is beneficial. While very few patients have a complete remission of the disease without thymectomy, 30-40% of patients will have a complete remission after surgery.
At Stanford, we are able to perform thymectomy for most myasthenia gravis patients through a single, 5 cm long incision at the base of the neck. This operation, called transcervical thymectomy can be performed with very little risk or discomfort. Patients return home the day of surgery or the following day, and they generally return to their usual activities within a week. The alternative procedure – thymectomy through a median sternotomy – has a substantially increased complication rate in patients with myasthenia gravis, who are susceptible to lung and other complications due to their muscle weakness.
Before coming to Stanford, Division Chief Dr. Joseph Shrager published the world’s largest series of extended transcervical thymectomy. This study demonstrated that the operation provides very similar remission rates to those achieved by thymectomy by median sternotomy, with far less complications and faster recovery. We are among the centers that has the greatest experience with this operation, and we are pleased to be able to offer it to myasthenia gravis patients in the greater San Francisco Bay Area as well as those from around the country.
A variety of types of lymphomas (tumors of the lymphatic, or lymph node, system) may arise primarily in the mediastinum. The most common of these is Hodgkin’s Lymphoma and B-cell Lymphomas. These are most often located in the anterior mediastinum, but they may also involve the middle mediastinum.
The treatment of lymphoma is primarily chemotherapy and/or radiation therapy and not surgical removal. However, prompt and accurate pathologic diagnosis by surgical biopsy is the essence of successful therapy, and Stanford surgeons are experienced in all of the techniques available to biopsy mediastinal masses. These minimally invasive procedures may include anterior mediastinotomy (Chamberlain Procedure), mediastinoscopy, and occasionally video-assisted thorascopic surgery (VATS). The availability at Stanford of the video mediastinoscope – useful from either the cervical or anterior approaches – permits accurate tissue sampling with minimal morbidity. Stanford’s world-renowned lymphoma oncologists can then plan the appropriate therapy.
Nearly all tumors that occur in the posterior mediastinum are benign. These tumors are thus ideally suited to minimally invasive, video-assisted thoracoscopic surgical (VATS) approaches(see Lung Cancer section of this website). This approach can be used to resect all but the largest neurogenic tumors, bronchogenic cysts, and foregut duplication cysts. VATS permits far less discomfort and faster recovery than the traditional approach via thoracotomy, which requires a larger skin incision, more cutting of muscle, and spreading the ribs.
Neurogenic Tumors of the Mediastinum
Background
Several tumors of neurogenic origin can occur in the mediastinum. Tumors that occur in this area of the chest can present in many different ways clinically and can produce many different pathologic processes. An understanding of the embryology of this area and of the anatomic relationships of the normal structures within the mediastinum is essential in the proper determination of the exact nature of a mass or tumor located in this area.
History of the Procedure. Although the entire field of surgery is an ancient one, successful surgical procedures within the thorax are a relatively recent advancement. Until the era when the airway and ventilation could be controlled artificially, the mediastinum, like other parts of the thorax, was deemed a dangerous area to approach.
A few surgeons in the late 1800s and early 1900s attempted and described surgical approaches to the mediastinum. In 1888, Nassiloff first showed that the esophagus was accessible using a posterior approach. In this time frame, with no ability to manage the airway or to ventilate safely, such a surgical approach had to remain completely extrapleural because perforation of the pleura would result in a fatal pneumothorax.
In 1893, Bastinelli described the removal of an anterior mediastinal dermoid cyst. The procedure required resection of the manubrium, but the patient recovered.
In 1897, Milton wrote extensively on mediastinal surgery using the median sternotomy approach. He tried this approach first on human cadavers, finding that median sternotomy gave him excellent access to the mediastinum. He then used the same approach to explore the mediastinum of a live goat. Although he did enter the pleural cavity of the animal, he was able to perform a tracheostomy and give artificial respiration through it. This support enabled him to successfully explore the mediastinum and allowed the animal to have an uneventful recovery. Milton then described a human case in which he resected most of a tuberculous sternum plus 2 large tuberculous lymph nodes from the mediastinum, successfully avoiding the pleural spaces. This patient did well.
In 1940, Heuer published a monograph on mediastinal tumors. Most of the cases referenced in it were from the 1920s and 1930s, and, in spite of Milton’s previously described work, no reference was made to the use of median sternotomy as an acceptable surgical approach to the mediastinum.
Heuer noted that at that time dermoid cysts and teratomas were the most commonly found tumors of the mediastinum. He also described successful removal of neurogenic tumors from the posterior mediastinum and described several types of thymic tumors.
In 1939, Alfred Blalock reported the first case in which symptoms of myasthenia gravis were completely relieved by removal of a thymic tumor, thus initiating a surgical option in the treatment of that disease.[1]
In 1995, video-assisted removal of neurogenic tumors was reported in combination with microneurosurgical techniques.
Recently, isolated reports of robotic resection of neurogenic tumors have also been reported.[2]
Problem. Any discussion of masses and tumors of the mediastinum requires delineation of the boundaries of that area. When defining the location of specific mediastinal masses, the portion of the thorax defined as the mediastinum extends from the posterior aspect of the sternum to the anterior surface of the vertebral bodies and includes the paravertebral sulci. The mediastinum is limited bilaterally by the mediastinal parietal pleura and extends from the diaphragm inferiorly to the level of the thoracic inlet superiorly.[3]
Because some mediastinal tumors and other masses are most often found in particular mediastinal locations, many authors have artificially subdivided the area for better descriptive localization of specific lesions. Most commonly, the mediastinum is subdivided into 3 spaces or compartments (ie, anterior, middle, posterior) when discussing the location or origin of specific masses or neoplasms. The anterior compartment extends from the posterior surface of the sternum to the anterior surface of the pericardium and great vessels. The middle compartment, or middle mediastinum, is located between the posterior limit of the anterior compartment and the anterior longitudinal spinal ligament. The posterior mediastinum is the area posterior to the heart and trachea and includes the paravertebral sulci.
Common anterior mediastinal tumors include thymomas, lymphomas, germ cell tumors, and mesenchymal tumors. Benign conditions include goiters and lymphangiomas. Most anterior mediastinal tumors are thymomas.
While neoplasms of the middle mediastinum are most commonly of lymphatic origin, neurogenic tumors also may occasionally occur in this area. Another significant group of masses identified in this compartment is cystic structures associated with a developmental abnormality of the primitive foregut or the precursors of the pericardium or pleura.[4]
Neurogenic tumors are, by far, the most commoeoplasm of the posterior mediastinum. Tumors originating from lymphatic, vascular, or mesenchymal tissues can also be found in this compartment.
Epidemiology
Frequency. A review of collected series reveals that many mediastinal neoplasms and masses vary in incidence and presentation depending on patient age. Specific types of mediastinal tumors characteristically occur in specific areas within the mediastinum.
Historically, in adults, the most common type of mediastinal tumor or cyst found is the neurogenic tumor (21%), followed by thymic tumors (19%), lymphomas (13%), and germ cell tumors (10%). Foregut and pericardial cysts are the next most frequently occurring abnormality within this group. More recent data from several large series indicate that thymomas have become the most common mediastinal tumor. Some series also indicate that mediastinal lymphoma has passed neurogenic tumors in frequency.
In children and infants, neurogenic tumors are the most commonly occurring tumor or cyst, followed by foregut cysts, germ cell tumors, lymphomas, lymphangiomas and angiomas, tumors of the thymus, and pericardial cysts.
In adults, only approximately 1-2% of neurogenic tumors are malignant. In patients younger than 20 years or older than 40 years, approximately one third of mediastinal tumors are malignant, while in patients aged 20-40 years, roughly half are malignant. Benign lesions generally occur in individuals aged 20-50 years and occur slightly more frequently in women than in men.
Approximately two thirds of mediastinal tumors and cysts are symptomatic in the pediatric population, while only approximately one third produce symptoms in adults. The higher incidence of symptoms in the pediatric population is most likely related to the fact that a mediastinal mass, even a small one, is more likely to have a compressive effect on the small, flexible airway structures of a child.
When considering all age groups, nearly 55% of patients with benign mediastinal masses are asymptomatic at presentation, compared to only approximately 15% of those in whom masses are found to be malignant.
Neurogenic tumors make up approximately 21% of all adult mediastinal tumors and 35% of all pediatric mediastinal tumors. Neurogenic tumors are the most common posterior mediastinal mass. Neurogenic tumors make up roughly 20% of all mediastinal tumors.
Almost all neurogenic tumors in adult patients are of nerve sheath origin, these being neurilemomas and neurofibromas.
Approximately 90% of pheochromocytomas occur in the adrenal medulla, and only approximately 2% of pheochromocytomas occur in the chest.
Roughly 10% of pheochromocytomas are associated with one of a variety of familial syndromes, the most noted of which are the multiple endocrine neoplasia syndromes. One interesting syndrome specifically associated with multiple extraadrenal pheochromocytomas is the Carney triad, in which these neoplasms occur in association with pulmonary hamartomas and gastric leiomyosarcomas. However, this syndrome does not appear to be familial.
Etiology. Neurogenic tumors of the mediastinum arise from cells of the nerve sheath, paraganglionic tissue, and autonomic ganglia, all of which originate embryonically from the neural crest. Several tissues, including neural tissue, neural sheath tissue, and associated fibrous connective tissue of mesodermal origin, can be the source of these neoplasms.
Pathophysiology.
Tumors and cysts of the mediastinum can produce abnormal effects at both systemic and local levels.
Local pathophysiology. Because of the malleable nature and small size of the pediatric airway and other normal mediastinal structures, benign tumors and cysts can produce abnormal local effects. These effects are more evident in children than in adults. Compression or obstruction of portions of the airway, the esophagus, or the right heart and great veins by an enlarging tumor or cyst can easily occur and can result in a number of symptoms. Infection can occur primarily within some of these mediastinal lesions, particularly those of a cystic nature, or can occur secondarily in nearby structures, such as the lungs, as a result of local compression or obstruction.
Malignant mediastinal tumors can cause all of the same local effects as those associated with benign lesions but, in addition, can produce abnormalities by invasion of local structures. Local structures most commonly subject to invasion by malignant tumors include the tracheobronchial tree and lungs, esophagus, superior vena cava, pleura and chest wall, and any adjacent intrathoracic nerves. Pathophysiologic changes that can be produced by invasion of specific structures are obstructive pneumonia and hemoptysis; dysphagia; superior vena cava syndrome; pleural effusion; and various neurologic abnormalities such as vocal cord paralysis, Horner syndrome, paraplegia, diaphragmatic paralysis, and pain in the distribution of specific sensory nerves.
Systemic pathophysiology. Certain mediastinal tumors can produce systemic abnormalities. Many of these manifestations are related to bioactive substances produced by specific neoplasms.
Tumors developing from autonomic nerve cells can produce several vasoactive substances. The most common of these is neuroblastoma, which produces excess amounts of the catecholamines, epinephrine, and norepinephrine. Ganglioneuroma and ganglioneuroblastoma can produce these substances but do so less often. Autonomic nerve tumors are also capable of producing excess amounts of vasoactive intestinal peptide. Neuroblastomas are thought to produce abnormal antibodies that are responsible for some unusual neurologic manifestations in some children with the tumor.
Some neurosarcomas have been associated with the production of an insulinlike substance that, in turn, can produce hypoglycemia.
Presentation.
Many mediastinal tumors and cysts produce no symptoms and are found incidentally during chest radiographs or other imaging studies of the thorax performed for another reason. Symptoms are present in approximately one third of adult patients with a mediastinal tumor or cyst but are seen more commonly in the pediatric population, in which nearly two thirds present with some symptoms. In adults, asymptomatic masses are more likely to be benign.
Symptoms associated with the respiratory tract predominate in pediatric patients because airway compression is more likely. This occurs because of the significant malleability of the airway structures and the small size of the chest cavity in infants and children. Symptoms most often observed include persistent cough, dyspnea, and stridor. If the location and size of the mass produces partial or complete obstruction, obstructive pneumonia can also occur. Infectious symptomatology, and even signs of sepsis, can occur if a mediastinal cyst becomes infected.
Constitutional symptoms, such as weight loss, fever, malaise, and vague chest pain, commonly occur with malignant tumors in pediatric patients.
Symptoms associated with compression of some portion of the respiratory tract can be produced by benign lesions in adults, but this occurs much less commonly than in children. Infectious symptoms or sepsis from infection of a mediastinal cyst can occur in adults, although this is also very unlikely in persons in this age group. However, malignant lesions are more likely to produce signs and symptoms of obstruction, compression, or both because they invade or transfix normal mediastinal structures.
Clinical findings associated with these malignant properties include cough, dyspnea, stridor, dysphagia, and even more dramatic findings such as superior vena cava syndrome. Invasion of the chest wall or pleura by a malignant neoplasm can produce persistent pleural effusions and a significant amount of local pain. Invasion of nearby nerves within the thorax can produce local and referred pain and a variety of other findings such as hoarseness from recurrent nerve paralysis, diaphragmatic paralysis from phrenic nerve paralysis, Horner syndrome from autonomic nerve invasion, and even motor paralysis from direct spinal cord involvement. Pain in the shoulder or upper extremity can occur from invasion of the ipsilateral brachial plexus. Systemic findings such as weight loss, fever, and malaise also occur.
In von Recklinghausen disease or neurofibromatosis, an inheritable disease, the individual may develop multiple tumors, generally neurofibromas.
Functioning mediastinal pheochromocytomas produce an excess of circulating catecholamines. The hallmark clinical finding in individuals with these neoplasms is hypertension. The hypertension may be persistent, paroxysmal, or persistent with paroxysmal episodes. Hypertensive crises may occur and may be triggered or exacerbated by anesthesia, trauma, and the onset of labor. The hypertension found in these individuals may be termed malignant and most often is resistant to any standard antihypertensive therapy. It certainly may lead to the usual complications of long-standing or severe hypertension such as stroke, cardiac failure, or renal function abnormalities.
In some patients, paroxysmal episodes can be accompanied by other symptoms, which include headaches, diaphoresis, anxiety, chest pain, palpitations, and pallor. Some patients also have an associated tachycardia.
Marked vasoconstriction from the excessive catecholamine discharge associated with these neoplasms creates a severely volume-contracted state in these individuals. This, in turn, produces the appearance of an elevated hematocrit value.
Indications
Treatment selection for a given mediastinal tumor or cyst depends on the diagnosis of the lesion being investigated.[5] Surgical resection is the primary treatment of choice in a large percentage of cases of neurogenic tumors.
Surgical resection is the treatment of choice for tumors originating from nerve sheath tissue, including neurilemoma, neurofibroma, and neurogenic sarcoma. Complete resection of the more malignant forms of these tumors may not be possible, and additional treatment modalities may be required.
Primary resection is the treatment of choice for neurogenic tumors of paraganglionic origin, which include paraganglionoma, chemodectomas, and mediastinal pheochromocytoma. Approximately 10% of pheochromocytomas are malignant and may not be entirely resectable. Some, even though benign, may be incompletely resected because of their location and increased vascularity. Preoperative treatment including alpha and beta blockade to prevent malignant hypertension during dissection is critical to excision of these tumors.
Peripheral neuroectodermal tumors (PNET), otherwise known as Askin tumors, are rare tumors occurring in the posterior sulcus or chest wall of adolescent and young adult patients. They are believed to develop from intercostal nerve tissue. Standard therapy includes en bloc resection, with accompanying radiotherapy and chemotherapy if complete resection is not possible.
Treatment varies for neurogenic tumors originating from autonomic nervous tissues. Ganglioneuroma, the most mature and benign form of autonomic nerve tumor, is treated by surgical resection. Neuroblastoma and ganglioneuroblastoma identified at an early stage of disease also may be treated with primary resection. Advanced stages of these diseases are treated primarily with chemotherapy, and surgical resection is rarely indicated.
Relevant Anatomy
When defining the location of specific mediastinal masses, the portion of the thorax defined as the mediastinum extends from the posterior aspect of the sternum to the anterior surface of the vertebral bodies and includes the paravertebral sulci. It is limited bilaterally by the mediastinal parietal pleura and extends from the diaphragm inferiorly to the level of the thoracic inlet superiorly.
Traditionally, the mediastinum is artificially subdivided into 3 compartments for better descriptive localization of specific lesions. When the location or origin of specific masses or neoplasms is discussed, the compartments or spaces are most commonly defined as anterior, middle, and posterior.
The anterior compartment extends from the posterior surface of the sternum to the anterior surface of the pericardium and great vessels. The anterior compartment normally contains the thymus gland, adipose tissue, and lymph nodes.
The middle compartment, or middle mediastinum, is located between the posterior limit of the anterior compartment and the anterior longitudinal spinal ligament. This area contains the heart, pericardium, ascending and transverse portions of the aorta, brachiocephalic vessels, main pulmonary arteries and veins, superior and inferior vena cavae, trachea and mainstem bronchi, numerous lymph nodes, and various neural structures such as the phrenic nerves. A small percentage of neurogenic tumors occur in the middle mediastinal compartment.
The posterior mediastinum is the area posterior to the heart and trachea and includes the paravertebral sulci. It contains the descending thoracic aorta and ligamentum arteriosum, esophagus, thoracic duct, azygos vein, and numerous neural structures (including autonomic ganglion and nerves, lymph nodes, and adipose tissue). Almost all tumors of neurogenic origin occupy this portion of the mediastinum.
Contraindications
Surgical removal is not indicated as primary treatment for some specific mediastinal tumors and cysts. Advanced stages of neuroblastoma and ganglioneuroblastoma are the tumors of neurogenic origin for which surgical resection is not considered as primary treatment.
Outcome and Prognosis
Prognosis after resection of a mediastinal tumor varies widely depending on the type of lesion resected.
After resection of mediastinal cysts and benign tumors, the prognosis is generally excellent. This group of tumors includes such neoplasms as thymolipomas, benign teratomas, benigeurilemomas and neurofibromas, ganglioneuromas, benign paragangliomas, benign mesenchymal tumors (eg, fibromas, angiomas, lymphangiomas), ectopic benign thyroid tissue and tumors, and parathyroid adenomas.
Prognosis after treatment of malignant mediastinal tumors depends on the type of lesion, its biological behavior, and the extent of the disease present.
Neuroblastoma
Survival numbers in pediatric patients with neuroblastoma have been studied in depth and analyzed with reference to a number of clinical and biological prognostic factors. This analysis is beyond the scope of this text. However, intrathoracic neuroblastomas generally have a more favorable outcome than extrathoracic types. The overall survival rate for thoracic neuroblastomas is greater than 70% at 5 years and greater than 60% at 10 years.
Ganglioneuroblastoma
These tumors are generally less aggressive than neuroblastomas. They are evaluated using the same prognostic and staging criteria as neuroblastoma. Ganglioneuroblastomas have a better prognosis because a large percentage of them manifest as an asymptomatic solitary mass and can be completely resected in many cases.
Neuroblastomas and ganglioneuroblastomas are extremely rare but much more aggressive in adults. Neuroblastoma exhibits wide local and distant spread and is rapidly fatal, while ganglioneuroblastoma may, in some cases, be treated with surgical resection.
Askin or peripheral neuroectodermal tumor
These are very rare but very aggressive tumors. Survival is commonly less than 1 year, and long-term survival, even with aggressive therapy, is rare.
Malignant nerve sheath tumors
Malignant schwannomas occurring in patients with von Recklinghausen disease have a poorer prognosis than do those that occur in the absence of that disease.
The long-term survival rate after resection approaches 50% for this neoplasm; however, individuals with associated von Recklinghausen disease have a high incidence of local or distant recurrence within 2 years.
Malignant mediastinal paragangliomas and pheochromocytomas
Extraadrenal pheochromocytomas are rare but have a higher malignant potential than their adrenal counterparts. Malignancy can occur in as many as 10% of these tumors. These tumors are commonly aggressive locally, and metastases may occur even after a long disease-free period following resection.
Prepared by Prof. Igor Y. Galaychuk, MD
02.2014
