Everything About Lung Cancer

Lung Cancer : Risk Factors

The risk factors for smoking include:

• Smoking (especially cigarettes, pipes, cigars)
• Smoking is, by far, the leading risk factor for lung cancer. In 2004, the United States Surgeon General released a report addressing the harmful effects of smoking on health (The Health Consequences of Smoking: A Report of the Surgeon General). Included in the report were the following statements:
  • "The evidence is sufficient to infer a causal relationship between smoking and lung cancer."
  • "Smoking causes genetic changes in cells of the lung that ultimately lead to the development of lung cancer."
  • "Although characteristics of cigarettes have changed during the last 50 years and yields of tar and nicotine have declined substantially...the risk of lung cancer in smokers has not declined."
  There are more than 60 molecules in cigarette smoke that are thought to be carcinogenic in humans or laboratory animals. Two carcinogens highly associated with lung cancer are benzo[a]pyrene and N-nitrosamine NNK. These molecules bind to DNA and proteins, forming adducts. The presence of adducts increases the chance of DNA mutation and interferes with the proper function of proteins. The presence of adducts is directly related to smoking status. Studies show that the level of adducts drops when a person quits smoking.
• Secondhand smoke and air pollution
• Second-Hand Smoke
  Exposure to second-hand smoke also greatly increases risk of lung cancer. In 2006, the Surgeon General released a report addressing the harmful effects of second-hand smoke on health (The Health Consequences of Involuntary Exposure to Tobacco Smoke: A Report of the Surgeon General). According to the report, second-hand smoke contains over 50 cancer-causing chemicals and can lead to many health problems, including lung cancer. The effects of second-hand smoke are especially harmful to the developing lungs of infants and children.
• Family history
• Radon
• Radon
  Radon is a naturally occuring, colorless, oderless gas. Exposure to radon is one of the leading risk factors for lung cancer, possibly contributing to 10% of all lung cancer cases. The mechanism by which radon leads to cancer is still unclear. Laboratory studies with radon have shown cellular damage that appears comparable to the damage caused by tobacco smoke, suggesting a similar mechanism of action. The production of reactive oxygen intermediates that can cause DNA damage is a likely event in mutagenic process caused by radon.
• Asbestos
• Asbestos
  Asbestos is a naturally occurring mineral that was frequently used in commercial construction throughout the 1950's and 1960's. The long, thin fibers of asbestos are fragile and have a tendancy to break down into dust particles. Asbestos particles are easily inhaled into the lungs, where they cause damage to lung tissue that can lead to lung cancer.
  Individuals who are exposed to asbestos and tobacco smoke are at a significantly increased risk of lung cancer. Studies suggest that asbestos particles may help deliver concentrated tobacco carcinogens to cells lining the lungs. However the exact mechanism by which asbestos, alone or in combination with tobacco smoke, leads to lung cancer is still uncertain.
• Metals like chromium, cadmium, arsenic
• Chronic lung diseases such as tuberculosis
• Chronic Lung Diseases
  Chronic lung diseases such as asbestosis (scarring of lung tissue caused by asbestos), asthma, chronic bronchitis, emphysema, pneumonia, and tuberculosis have been suggested to increase risk of lung cancer. All of these diseases damage lung tissue and can result in scar tissue on the lungs.
  As often is the case, it is difficult to distinguish between a relationship or correlation and causation or an actual cause. As an example: the increased incidence of lung cancer in individuals with a history of chronic bronchitis (or emphysema) may be due to a genetic predisposition that increases susceptibility to both the bronchitis (or emphysema) AND cancer. In this instance, the first disease does not CAUSE the second.
  On the other hand, the chronic diseases may aid in the accumulation of harmful toxins in the lungs, resulting in cell/tissue damage and CAUSING an increase in cancer. Further studies are needed to clearly determine if the observed correlation is actually a causative one.
  Exposure to certain workplace chemicals such as asbestos, coal gas, chromium, nickel, arsenic, vinyl chloride, and mustard gas increases the risk of lung cancer.

The relative effects of these and other risk factors in any given case of cancer is variable and very difficult to determine with accuracy at this time. Some of these and other risk factors are discussed below.

Family History of Lung Cancer
It is possible to inherit defective genes that lead to the development of a familial form of a particular cancer type. For example, certain genes influence a person's ability to metabolize some of the carcinogenic chemicals in cigarette smoke. An individual with inherited susceptibility that chooses to smoke may be at an increased the risk of developing lung cancer compared to other smokers.

Risk is higher if an immediate family member has been diagnosed with lung cancer. The more closely related an individual is to someone with lung cancer, the more likely they are to share the genes that increased the risk of the affected individual. Risk also increases with the number of relatives affected.

Lung Cancer : Symptoms

Symptoms and Signs of Lung Cancer

Cigarette smoking causes lung damage even in the absence of cancer. The symptoms associated with lung damage are cough and shortness of breath. There may be occasions when there is production of blood stained sputum even when there is no cancer. Lung infections are also common in persons with lung damage. Dilatation of the air Spaces, or emphysema, is reported to be an especially common complication of smoking in Chinese. Lung cancer usually develops in the presence of lung damage. The symptoms and signs of lung cancer may be indistinguishable from lung damage caused by cigarette smoking. Occasionally, lung cancer is diagnosed incidentally when a pre-employment or routine chest x-ray is performed.

There areowing symptoms associated with advanced stage lung cancer. A physician should be consulted if they persist. It is important to note, however, that these symptoms may be caused by factors unrelated to cancer.

 no symptoms associated with early stage lung cancer. The American Cancer Society lists the foll

However, that these symptoms may be caused by factors unrelated to cancer:

• Persistent cough
• Sputum streaked with blood
• Chest pain
• Voice change
• Recurrent pneumonia or bronchitis

• Loss of appetite
• Shortness of breath
• Weight loss
• Wheezing

• Facial swelling
• Fever
• Hoarseness or changing voice
• Swallowing difficulty
• Weakness

Lung Cancer : Detection and Diagnosis

Detection
Despite ongoing investigation into screening technology, research shows that lung cancer death rates have not improved. At the time they are diagnosed, the majority of lung cancers have progressed to an advanced state. Lung cancer screening is not currently routine practice. The disease is sometimes caught in its early stages by tests that are performed for other reasons. The most common methods of lung cancer detection include:

• chest x-ray
• chest CT (computer tomography) scan,
• Computed Tomography (CT)
  History
  The CT scan was first used clinically in the 1960's, but it wasn't until the late 1970's to early 1980's that medical use of CT was widespread. In 1979 two scientists, Godfrey Hounsfield and Allan Cormack, shared the Nobel Prize for their work developing the CT scanner. CT is also called Computerized Axial Tomography or CAT.⁽¹⁾
  How CT works
  A CT scanner uses x-rays in the same way as a conventional x-ray but instead of taking one image a CT scanner takes multiple images, or slices. A computer program gathers all the images and compiles them to create a three dimensional image of the internal structures being examined.
  Below is a list of the information included in this section:
  • CT Equipment
  • The CT Exam
  • Contrast Media for CT Exams
    
  • CT Imaging Results
• bronchoscopy (insertion of a tube into the bronchi), 
• Bronchoscopy
  Bronchoscopy is the use of a flexible or rigid tube to examine the airways.  Bronchoscopy is used to detect and diagnose lung cancer.  It is also used to remove airway blockages (i.e. food), to treat bleeding, to deliver radiation to cancerous areas (brachytherapy) and to take small tissue samples (biopsies).  Flexible bronchscopes are used when possible because they offer a better view for the physician and are less uncomfortable for the patient.   The patient does not need to be under general anesthesia. Rigid bronchoscopy requires that the patient be under general anesthesia. Newer methods utilize fluorescent imaging techniques to better visualize the tissues. Using blue light instead of white light allows the detection of early cancers.
• sputum cytology (examination of cells in the phlegm).

• Sputum Samples

  Sputum is a thick mixture of saliva, mucus and other material that can be brought up from the throat and air passages leading to the lungs. Sputum contains cells and DNA and can be examined for abnormalities, including some that indicate the presence of lung cancer. Although it is not a very sensitive test, examination of cells in sputum is still used to detect lung cancer. In part because of the poor sensitivity of the test, routine screening for lung cancer via sputum samples is not recommended.
  Recent advances have improved the test considerably. The ThinPrep® preparation technique has been shown to provide additional sensitivity.Research is now being performed to assess the value of looking at fluorescence in body fluids to detect cancer and to look for the presence of genetic defects and specific genes that could indicate the presence of cancer.

Diagnosis

Diagnostic Tests

Any persistent cough or change in the nature of the cough, the appearance of blood-stained sputum, or unexplained breathlessness should prompt a person to seek medical advice. Often chest x-rays are important in the first diagnosis of lung cancer. Sputum may be sent for testing for cancer cells or infections, such as tuberculosis which is not uncommon in Singapore.
If the suspicion of cancer is high, a bronchoscopy may be arranged. In this examination, a fiber-optic tube about 7 millimeter in diameter, is introduced through the nose and into the lung under light-sedation and local anaesthesia. You will be able to breath normally during the procedure which lasts 15 to 30 minutes. Small pieces of tissue can be painlessly removed for further examination to diagnose cancer. Some management decisions in lung cancer (especially pertaining to targeted therapies), require specific genetic tests to be done on cancer cells from your biopsy sample.
Once cancer is diagnosed, computerised tomography (CT) scans of the chest and liver may be performed to determine if the cancer has spread to other organs, such as the liver or adrenal gland, which is just above the kidneys on both sides. Occasionally, bone scans and CT of the brain are also required.
A lung function test, which involves blowing into a large cylinder,may be performed preoperatively to determine the lung function prior to any surgery discussions.

Lung Cancer : The Pathology Report and Staging

The Pathology Report

If there is suspicion that a patient may have lung cancer, a sample of tissue (biopsy) may be taken for examination. After a biopsy is taken, the physician who performed the biopsy sends the specimen to a pathologist. The pathologist examines the specimen at both the macroscopic (visible with the naked eye) and microscopic (requiring magnification) levels and then sends a pathology report to the physician. The report contains information about the tissue's appearance, cellular make up, and state of disease or normalcy. For more information about pathology reports, refer to the Diagnosis & Detection section.

Staging

Staging a cancer is a way of describing the extent of the disease. One of the most common methods used for cancer staging is called the T/N/M system, which assigns a degree of severity based on the size, location, and spread of cancer in the body. Staging of non-small cell lung cancer (NSCLC) follows the TNM criteria. Details of this system can be found in the Diagnosis and Detection section.

Because small cell lung cancer (SCLC) is often diagnosed at a more advanced state, the T/N/M system is not used. Instead small cell lung cancer is usually staged using the Veterans Administration Lung Study Group System, a 2-stage system based on location of the cancer. Most small cell lung cancers are diagnosed in the extensive-stage.

• Limited-stage: The cancer is located in only one lung and lymph nodes on the same side of the body
• Extensive-stage: The cancer has spread to the other lung and/or other regions of the body

Lung Cancer : Tumor Biology

Genetic changes that occur in cancer include mutation of key regulatory genes, changes in protein products, and changes in the amount of product produced by genes (gene expression). As changes accumulate, cells become more abnormal and cancer progresses. Details of genetic change associated with cancer can be found in the Mutation section. There are over 100 genes known to be associated with the development of lung cancer. Some of the most frequently altered genes are listed below and discussed on the following pages:

• Ras
• Myc
• Rb
• TP53
• Epidermal Growth Factor Receptor (EGFR)

Ras

Ras is an oncogene that is altered in up to 30% of non small cell lung cancers (NSCLC). The ras protein is involved in transmitting signals through the cell that drive the cell into the division process.

Myc

The Myc family of oncogenes that are expressed abnormally in many types of cancer, including lung cancer. The myc protein acts as atranscription factor to regulate the expression of several genes. . Myc protein expression is altered in up to 80% of small cell lung cancers (SCLC).

Rb

The retinoblastoma gene (Rb) is a tumor suppressor altered in up to 90% of small cell lung cancers (SCLC).  The Rb protein interacts with transcription factors to indirectly control cell division.

TP53

TP53 (or P53) is a tumor suppressor gene altered in up to 50% of non small cell lung cancers (NSCLC) and 80% of small cell lung cancers (SCLC). The p53 protein interacts with DNA and other proteins to play an important role in the regulation cell growth and division, as well as programmed cell death, or apoptosis.

Epidermal Growth Factor Receptor

EGFR (epidermal growth factor receptor), also known as erbB1 and HER1, is a gene that encodes for a tyrosine kinase located in the cell membrane of epithelial cells. The EGFR protein is involved in response to growth factors and, under the right conditions, can stimulate epithelial cell division. Overexpression of the EGFR protein occurs in approximately 60-85% of squamous cell carcinomas and 50% of large cell and adenocarcinomas. Overexpression of EGFR is seen only infrequently (0-5%) in small cell lung cancer (SCLC). 

Currently, there are two types of therapies directed against EGFR. Monoclonal antibodies bind to the region of EGFR located outside the cell, preventing other (activating) molecules from binding. Tyrosine kinase inhibitors, on the other hand, bind to the section of EGFR located inside the cell, interfering with the activities of the receptor normally induced by the binding of an activator.

Lung Cancer : Treatment

As our focus is on the biology of the cancers and their treatments, we do not give detailed treatment guidelines. Instead, we link to organizations in the U.S. that generate the treatment guidelines.

The National Comprehensive Cancer Network (NCCN) lists the following treatments for lung cancer:

• Surgery
• Radiation Therapy
• Chemotherapy

There are two main types of lung cancer, small cell lung cancer and non-small cell lung cancer. The diagnosis is based on what the pathologist (specialist who looks at tissues under the microscope) sees on microscopic examination of the tissue removed and after special staining tests have been performed on the tissue.

Small cell lung cancer is more rapidly growing and spreads earlier to other organs than non-small cell lung cancer. About 10% of all lung cancers are small cell lung cancer. Non-small cell lung cancer grows slower than small cell lung cancer and tends to be confined to the lung for a longer period of time.

Treatment of Non-small cell Lung Cancer

Small cell lung cancer tends to spread early to other organs, such as liver, bone and brain. Therapy involves early chemotherapy. If the cancer has not spread beyond the confines of one lung, chemotherapy combined with radiotherapy has been shown to have better results than just chemotherapy alone.

Chemotherapy is given over 4 to 6 months. There is usually mild nausea or vomiting, complete hair loss, lethargy or tiredness, and loss of appetite. The exact choice of medicines will depend on the person's general health and other medical problems.

Prognosis of Lung Cancer

Prognosis means the probable outcome of an illness based upon all the relevant facts of the case. All findings from clinical examination and x-ray investigations and pathology reports are important and must be considered together to decide what the progress of an individual case of lung cancer may be. From this, the appropriate course of treatment can be decided and put into action. The treatment strategy will vary from person to person.

The doctor looks for the following features:

• The size of the lung cancer is important. The larger the cancer, the more likely the cancer will be inoperable.
• Which of the neighbouring lymph glands were involved? Were all the involved lymph glands removed at surgery? Which other sites in the body are involved with cancer?
• Did the pathologist see high risk features such as small cell lung cancer? Small cell lung cancer is a rapidly growing cancer. Very often, the cancer has spread to many other organs at the time of diagnosis. Were other organs involved?
• If the person has other underlying medical problems, surgery may not be possible even if the cancer was small and considered to be early stage. Lung cancer commonly develops in smokers who have lung damage from their many years of smoking. Smoking also increases a person's risk of heart disease and stroke, which may mean that surgery will be high risk.