Drugs Expert

Lung cancer is a disease of uncontrolled cell growth in tissues of the lung. This growth may lead to metastasis, which is the invasion of adjacent tissue and infiltration beyond the lungs. The vast majority of primary lung cancers are carcinomas of the lung, derived from epithelial cells. Lung cancer, the most common cause of cancer-related death in men and women, is responsible for 1.3 million deaths worldwide annually, as of 2004. The most common symptoms are shortness of breath, coughing (including coughing up blood), and weight loss.

The main types of lung cancer are small cell lung carcinoma and non-small cell lung carcinoma. This distinction is important, because the treatment varies; non-small cell lung carcinoma (NSCLC) is sometimes treated with surgery, while small cell lung carcinoma (SCLC) usually responds better to chemotherapy and radiation. The most common cause of lung cancer is long-term exposure to tobacco smoke. The occurrence of lung cancer in nonsmokers, who account for as many as 15% of cases, is often attributed to a combination of genetic factors, radon gas, asbestos, and air pollution including secondhand smoke.

Lung cancer may be seen on chest radiograph and computed tomography (CT scan). The diagnosis is confirmed with a biopsy. This is usually performed by bronchoscopy or CT-guided biopsy. Treatment and prognosis depend upon the histological type of cancer, the stage (degree of spread), and the patient’s performance status. Possible treatments include surgery, chemotherapy, and radiotherapy. Depending on the stage and treatment, the five-year survival rate is 14%.

What causes Lung Cancer?

Smoking

The incidence of lung cancer is strongly correlated with cigarette smoking, with about 90% of lung cancers arising as a result of tobacco use. The risk of lung cancer increases with the number of cigarettes smoked and the time over which smoking has occurred; doctors refer to this risk in terms of pack-years of smoking history (the number of packs of cigarettes smoked per day multiplied by the number of years smoked). For example, a person who has smoked two packs of cigarettes per day for 10 years has a 20 pack-year smoking history. While the risk of lung cancer is increased with even a 10-pack-year smoking history, those with 30-pack-year histories or more are considered to have the greatest risk for the development of lung cancer. Among those who smoke two or more packs of cigarettes per day, one in seven will die of lung cancer.

Pipe and cigar smoking also can cause lung cancer, although the risk is not as high as with cigarette smoking. Thus, while someone who smokes one pack of cigarettes per day has a risk for the development of lung cancer that is 25 times higher than a nonsmoker, pipe and cigar smokers have a risk of lung cancer that is about five times that of a nonsmoker.

Tobacco smoke contains over 4,000 chemical compounds, many of which have been shown to be cancer-causing or carcinogenic. The two primary carcinogens in tobacco smoke are chemicals known as nitrosamines and polycyclic aromatic hydrocarbons. The risk of developing lung cancer decreases each year following smoking cessation as normal cells grow and replace damaged cells in the lung. In former smokers, the risk of developing lung cancer begins to approach that of a nonsmoker about 15 years after cessation of smoking.

Passive smoking

Passive smoking or the inhalation of tobacco smoke by nonsmokers who share living or working quarters with smokers, also is an established risk factor for the development of lung cancer. Research has shown that nonsmokers who reside with a smoker have a 24% increase in risk for developing lung cancer when compared with nonsmokers who do not reside with a smoker. An estimated 3,000 lung cancer deaths that occur each year in the U.S. are attributable to passive smoking.

Asbestos fibers

Asbestos fibers are silicate fibers that can persist for a lifetime in lung tissue following exposure to asbestos. The workplace is a common source of exposure to asbestos fibers, as asbestos was widely used in the past as both thermal and acoustic insulation. Today, asbestos use is limited or banned in many countries, including the U.S. Both lung cancer and mesothelioma (cancer of the pleura of the lung as well as of the lining of the abdominal cavity called the peritoneum) are associated with exposure to asbestos. Cigarette smoking drastically increases the chance of developing an asbestos-related lung cancer in workers exposed to asbestos. Asbestos workers who do not smoke have a fivefold greater risk of developing lung cancer than nonsmokers, but asbestos workers who smoke have a risk that is 50- to 90-fold greater than nonsmokers.

Radon gas

Radon gas is a natural, chemically inert gas that is a natural decay product of uranium. Uranium decays to form products, including radon, that emit a type of ionizing radiation. Radon gas is a known cause of lung cancer, with an estimated 12% of lung-cancer deaths attributable to radon gas, or about 20,000 lung-cancer-related deaths annually in the U.S., making radon the second leading cause of lung cancer in the U.S. As with asbestos exposure, concomitant smoking greatly increases the risk of lung cancer with radon exposure. Radon gas can travel up through soil and enter homes through gaps in the foundation, pipes, drains, or other openings. The U.S. Environmental Protection Agency estimates that one out of every 15 homes in the U.S. contains dangerous levels of radon gas. Radon gas is invisible and odorless, but it can be detected with simple test kits.

Familial predisposition

While the majority of lung cancers are associated with tobacco smoking, the fact that not all smokers eventually develop lung cancer suggests that other factors, such as individual genetic susceptibility, may play a role in the causation of lung cancer. Numerous studies have shown that lung cancer is more likely to occur in both smoking and non-smoking relatives of those who have had lung cancer than in the general population. Recently, the largest genetic study of lung cancer ever conducted, involving over 10,000 people from 18 countries and led by the International Agency for Research on Cancer (IARC), identified a small region in the genome (DNA) that contains genes that appear to confer an increased susceptibility to lung cancer in smokers. The specific genes, located the q arm of chromosome 15, code for proteins that interact with nicotine and other tobacco toxins (nicotinic acetylcholine receptor genes).

Lung diseases

The presence of certain diseases of the lung, notably chronic obstructive pulmonary disease (COPD), is associated with an increased risk (four- to sixfold the risk of a nonsmoker) for the development of lung cancer even after the effects of concomitant cigarette smoking are excluded.

Prior history of lung cancer

Survivors of lung cancer have a greater risk of developing a second lung cancer than the general population has of developing a first lung cancer. Survivors of non-small cell lung cancers (NSCLCs, see below) have an additive risk of 1%-2% per year for developing a second lung cancer. In survivors of small cell lung cancers (SCLCs, see below), the risk for development of second lung cancers approaches 6% per year.

Air pollution

Air pollution from vehicles, industry, and power plants can raise the likelihood of developing lung cancer in exposed individuals. Up to 1% of lung cancer deaths are attributable to breathing polluted air, and experts believe that prolonged exposure to highly polluted air can carry a risk for the development of lung cancer similar to that of passive smoking.

Classification

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 in nonsmokers. 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 in nonsmokers 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%-10% of lung cancers:

• Bronchial carcinoids account for up to 5% of lung cancers. These tumors are generally small (3-4 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 the Symptoms of Lung Cancer?

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. 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 or CT 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 pain that travels down the outside of the arm (called Pancoast’s syndrome) or paralysis 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, and fatigue. Psychological symptoms such as depression and mood changes are also common.

Diagnosis

Doctors use a wide range of diagnostic procedures and tests to diagnose lung cancer. These include:

• 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, or hives 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.
• A technique called a low-dose helical CT scan (or spiral CT scan) is sometimes used in screening for lung cancers. This procedure requires a special type of CT scanner and has been shown to be an effective tool for the identification of small lung cancers in smokers and former smokers. However, it has not yet been proven whether the use of this technique actually saves lives or lowers the risk of death from lung cancer. The heightened sensitivity of this method is actually one of the sources of its drawbacks, since lung nodules requiring further evaluation will be seen in approximately 20% of people with this technique. Of the nodules identified by low-dose helical screening CTs, 90% are not cancerous but require up to two years of costly and often uncomfortable follow-up and testing. Trials are underway to further determine the utility of spiral CT scans in screening for lung cancer.
• 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.
• 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 one to two 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 thin needle 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%-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 thin needle (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.

Staging

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.

Methods of Treatment

Treatment for lung cancer depends on the cancer’s specific cell type, how far it has spread, and the patient’s performance status. Common treatments include surgery, chemotherapy, and radiation therapy.

Surgery

Gross appearance of the cut surface of a pneumonectomy specimen containing a lung cancer, here a squamous cell carcinoma (the whitish tumor near the bronchi).

If investigations confirm lung cancer, CT scan and often positron emission tomography (PET) are used to determine whether the disease is localized and amenable to surgery or whether it has spread to the point where it cannot be cured surgically.

Blood tests and spirometry (lung function testing) are also necessary to assess whether the patient is well enough to be operated on. If spirometry reveals poor respiratory reserve (often due to chronic obstructive pulmonary disease), surgery may be contraindicated.

Surgery itself has an operative death rate of about 4.4%, depending on the patient’s lung function and other risk factors. Surgery is usually only an option in non-small cell lung carcinoma limited to one lung, up to stage IIIA. This is assessed with medical imaging (computed tomography, positron emission tomography). A sufficient preoperative respiratory reserve must be present to allow adequate lung function after the tissue is removed.

Procedures include wedge resection (removal of part of a lobe), segmentectomy (removal of an anatomic division of a particular lobe of the lung), lobectomy (one lobe), bilobectomy (two lobes), or pneumonectomy (whole lung). In patients with adequate respiratory reserve, lobectomy is the preferred option, as this minimizes the chance of local recurrence. If the patient does not have enough functional lung for this, wedge resection may be performed. Radioactive iodine brachytherapy at the margins of wedge excision may reduce recurrence to that of lobectomy.

Video-assisted thoracoscopic surgery and VATS lobectomy have allowed for minimally invasive approaches to lung cancer surgery that may have the advantages of quicker recovery, shorter hospital stay and diminished hospital costs.

Chemotherapy

Small cell lung carcinoma is treated primarily with chemotherapy and radiation, as surgery has no demonstrable influence on survival. Primary chemotherapy is also given in metastatic non-small cell lung carcinoma.

The combination regimen depends on the tumor type. Non-small cell lung carcinoma is often treated with cisplatin or carboplatin, in combination with gemcitabine, paclitaxel, docetaxel, etoposide, or vinorelbine. In small cell lung carcinoma, cisplatin and etoposide are most commonly used. Combinations with carboplatin, gemcitabine, paclitaxel, vinorelbine, topotecan, and irinotecan are also used. In extensive-stage small-cell lung cancer celecoxib may safely be combined with etoposide, this combination showed improve outcomes.

Adjuvant chemotherapy for NSCLC

Adjuvant chemotherapy refers to the use of chemotherapy after surgery to improve the outcome. During surgery, samples are taken from the lymph nodes. If these samples contain cancer, the patient has stage II or III disease. In this situation, adjuvant chemotherapy may improve survival by up to 15%. Standard practice is to offer platinum-based chemotherapy (including either cisplatin or carboplatin).

Adjuvant chemotherapy for patients with stage IB cancer is controversial, as clinical trials have not clearly demonstrated a survival benefit. Trials of preoperative chemotherapy (neoadjuvant chemotherapy) in resectable non-small cell lung carcinoma have been inconclusive.

Radiotherapy

Radiotherapy is often given together with chemotherapy, and may be used with curative intent in patients with non-small cell lung carcinoma who are not eligible for surgery. This form of high intensity radiotherapy is called radical radiotherapy. A refinement of this technique is continuous hyperfractionated accelerated radiotherapy (CHART), in which a high dose of radiotherapy is given in a short time period. For small cell lung carcinoma cases that are potentially curable, chest radiation is often recommended in addition to chemotherapy. The use of adjuvant thoracic radiotherapy following curative intent surgery for non-small cell lung carcinoma is not well established and is controversial. Benefits, if any, may only be limited to those in whom the tumor has spread to the mediastinal lymph nodes.

For both non-small cell lung carcinoma and small cell lung carcinoma patients, smaller doses of radiation to the chest may be used for symptom control (palliative radiotherapy). Unlike other treatments, it is possible to deliver palliative radiotherapy without confirming the histological diagnosis of lung cancer.

Brachytherapy (localized radiotherapy) may be given directly inside the airway when cancer affects a short section of bronchus. It is used when inoperable lung cancer causes blockage of a large airway.

Patients with limited stage small cell lung carcinoma are usually given prophylactic cranial irradiation (PCI). This is a type of radiotherapy to the brain, used to reduce the risk of metastasis. More recently, PCI has also been shown to be beneficial in those with extensive small cell lung cancer. In patients whose cancer has improved following a course of chemotherapy, PCI has been shown to reduce the cumulative risk of brain metastases within one year from 40.4% to 14.6%.

Recent improvements in targeting and imaging have led to the development of extracranial stereotactic radiation in the treatment of early-stage lung cancer. In this form of radiation therapy, very high doses are delivered in a small number of sessions using stereotactic targeting techniques. Its use is primarily in patients who are not surgical candidates due to medical comorbidities.

Interventional radiology

Radiofrequency ablation should currently be considered an investigational technique in the treatment of bronchogenic carcinoma. It is done by inserting a small heat probe into the tumor to kill the tumor cells.

Targeted therapy

In recent years, various molecular targeted therapies have been developed for the treatment of advanced lung cancer. Gefitinib (Iressa) is one such drug, which targets the tyrosine kinase domain of the epidermal growth factor receptor (EGFR), expressed in many cases of non-small cell lung carcinoma. It was not shown to increase survival, although females, Asians, nonsmokers, and those with bronchioloalveolar carcinoma appear to derive the most benefit from gefitinib.

Erlotinib (Tarceva), another tyrosine kinase inhibitor, has been shown to increase survival in lung cancer patients and has recently been approved by the FDA for second-line treatment of advanced non-small cell lung carcinoma. Similar to gefitinib, it also appeared to work best in females, Asians, nonsmokers, and those with bronchioloalveolar carcinoma, specifically those with specific mutations in EGFR.

The angiogenesis inhibitor bevacizumab, (in combination with paclitaxel and carboplatin), improves the survival of patients with advanced non-small cell lung carcinoma. However, this increases the risk of lung bleeding, particularly in patients with squamous cell carcinoma.

Advances in cytotoxic drugs, pharmacogenetics and targeted drug design show promise. A number of targeted agents are at the early stages of clinical research, such as cyclo-oxygenase-2 inhibitors, the apoptosis promoter exisulind, proteasome inhibitors, bexarotene,  the epidermal growth factor receptor inhibitor cetuximab, and vaccines. Future areas of research include ras proto-oncogene inhibition, phosphoinositide 3-kinase inhibition, histone deacetylase inhibition, and tumor suppressor gene replacement. In a story that was on NBCs Today Show in mid April 2010 called “Discovery of a New Approach For Identifying Smokers at Highest Risk For Developing Lung Cancer”, researchers from the Boston University School of Medicine found a novel gene-expression based approach to define oncogenic pathway signatures, in collaboration with Dr. Andrea Bild at the University of Utar. They have now discovered that the expression of genes belonging to one specific cancer-related pathway P13K, are activated in the cells that line the airway of smokers with Lung Cancer. This gene expression activity in normal cells of the proximal airway, precedes the development of Lung Cancer and may be reversed with a specific chemopreventive agent Myo-Inositol. Myo-Inositol targets this pathway.

Drugs rating:

Prognosis

Prognostic factors in non-small cell lung cancer include presence or absence of pulmonary symptoms, tumor size, cell type (histology), degree of spread (stage) and metastases to multiple lymph nodes, and vascular invasion. For patients with inoperable disease, prognosis is adversely affected by poor performance status and weight loss of more than 10%. Prognostic factors in small-cell lung cancer include performance status, gender, stage of disease, and involvement of the central nervous system or liver at the time of diagnosis.

For non-small cell lung carcinoma (NSCLC), prognosis is generally poor. Following complete surgical resection of stage IA disease, five-year survival is 67%. With stage IB disease, five-year survival is 57%. The five-year survival rate of patients with stage IV NSCLC is about 1%.

For small cell lung carcinoma, prognosis is also generally poor. The overall five-year survival for patients with SCLC is about 5%. Patients with extensive-stage SCLC have an average five-year survival rate of less than 1%. The median survival time for limited-stage disease is 20 months, with a five-year survival rate of 20%.

According to data provided by the National Cancer Institute, the median age of death for cases of lung cancer in the United States is 70 years, and the median age is 71 years.