TYPES OF LUNG CANCER
There are important differences between lung cancer that started in the lungs and lung cancer that has spread to the lung.  This section is about primary lung cancer - cancer that started in the lungs. There are several different types of primary lung cancer. These are divided into two main types:

• Small cell lung cancer  
• Non-small cell lung cancer

There is another rare type of cancer called mesothelioma that affects the covering of the lung (the pleura).  It is often caused by exposure to asbestos. It is very different to lung cancer.   

Small cell lung cancer
Small cell lung cancer is so called because the cancer cells are small cells that are mostly filled with the nucleus (the control centre of cells).  Small cell lung cancer often spreads quite early on. 

Non-small cell lung cancer
There are four types of non-small cell lung cancer. These are grouped together because they behave in a similar way and respond to treatment differently to small cell lung cancer. The four types are:

• Squamous cell carcinoma  
• Adenocarcinoma  
• Large cell carcinoma
• Epidermoid carcinoma

Occasionally it is not possible to work out which type of non small cell lung cancer you have. If the cells in the biopsy are very undeveloped, it just may not be possible to tell.

Squamous cell cancer is the commonest type of lung cancer. It develops from the cells that line the airways.  The incidence of squamous cell cancer is going down in the UK.

Adenocarcinoma also develops from the cells that line the airways. But it develops from a particular type of cell that produces mucus (phlegm).  The incidence of adenocarcinoma is increasing and it may soon become more common in the UK than squamous cell lung cancer. 

Large cell lung cancer is called this because the cells look large and rounded when they are looked at under a microscope.

Epidermoid carcinomas are most common among men and the elderly. It starts in one of the larger breathing tubes and usually does not grow or spread as quickly as other types of lung cancer.

How does epidermoid carcinoma develop?
Non-small cell lung cancer is usually associated with a history of smoking, passive smoking or radon exposure. More than 87 percent of lung cancers are caused directly by smoking, while some of the remainder is caused by environmental exposure to tobacco smoke. Other risk factors for lung cancer include a family or personal history of lung cancer and exposure to cancer-causing agents in the workplace or the environment. Asbestos workers are about seven times more likely to die of lung cancer compared to the general population. Exposure to asbestos fibres is an important risk factor for lung cancer. Asbestos workers who smoke have a 50 to 90 times greater chance of getting lung cancer than that of the population in general. Radon, a radioactive gas that occurs when uranium breaks down naturally, cannot be seen, tasted, or smelled. It can become more concentrated indoors and may pose a cancer risk. Studies from populated areas in parts of the United States built over soil with natural uranium deposits have found that the risk of lung cancer may be doubled or even tripled after one has lived in a radon-contaminated residence for an extended period of time. However, when compared to the lung cancer risk associated with tobacco, the radon risk cited in the example above is very small.

What are the symptoms of epidermoid carcinoma?
Although some cancers do not have any symptoms at first, this type of cancer is diagnosed because of complaints such as a persistent cough, coughing up of blood, shortness of breath or wheezing, unexplained weight loss or loss of appetite, fatigue, difficulty swallowing, pain in the chest, shoulder or arm, recurrent pneumonia in the same place, bone pain, hoarseness, headaches, confusion or seizures and swelling of the face, neck or upper extremities.

Cancer that has spread to the lungs
Secondary cancer is cancer that has spread from somewhere else in the body.  There are quite a few different cancers that can spread to the lungs, including breast cancer and bowel cancer. 

It is important to know what you are dealing with so that you can find the right information.  The choice of cancer treatment depends on where the cancer started.  When cancer spreads to the lung from the breast, the cells are breast cancer cells, not lung cancer cells.  So they respond to breast cancer treatments.   And cancer that has spread from the bowel should respond to bowel cancer treatments.

Mesothelioma     see website: www.mesothelioma.uk.com
Mesothelioma is a cancer occurring in the lining of the lungs, chest and abdomen. The only known cause of mesothelioma is exposure to asbestos products. The risk of developing mesothelioma varies, depending on duration and intensity of exposure.

Malignant mesothelioma affecting the lungs and chest cavity is referred to as "pleural mesothelioma". When the disease affects the abdominal cavity, it is referred to as "peritoneal mesothelioma". A more detailed discussion of both types of malignant mesothelioma appears later in this book.

Mesothelioma generally begins in the lungs and spreads to the abdominal lining. The prognosis worsens when the abdominal lining becomes affected. In most cases, death is the result of the invasive nature of the tumour on heart and/or lungs.

Asbestos exposure is generally a common factor uniting mesothelioma victims.

Patients are generally male (over 80%).

Typical symptoms include chest pain, shortness of breath, coughing, weight loss, and sexual dysfunction. In later stages of the disease process, patients may experience deformation of the chest wall and abdominal masses that may or may not obstruct the bowel.

There is as yet no known cure for malignant mesothelioma. The prognosis depends on various factors, including the size and stage of the tumour, the extent of the tumour, the cell type, and whether or not the tumour responds to treatment. The individual mesothelioma victims age and state of underlying health, as well as their state of mind and motivation to survive the disease likewise may play a role in a favourable prognosis.

Although there is no standard treatment protocol for mesothelioma, numerous treatment options are available for those diagnosed with the disease. Early diagnosis typically results in a greater range of available treatment options. Treatments include:

• traditional chemotherapy
• radiation therapy
• surgery
• experimental therapies and drugs
• complementary medicine and therapies
• lifestyle modifications

Traditional Chemotherapy
In traditional chemotherapy, special anti-cancer (cytotoxic) medicines and chemicals are administered, with the goal of killing the malignant cells. Chemotherapy is frequently one facet of a regimen including radical surgery, radiation therapy and/or immunotherapy. Chemotherapy may also be used in situations where the cancer has spread to the extent that surgery is no longer a viable option.

Many drugs have been tried; however all have met with only limited success against malignant mesothelioma. The response rate to single agent chemotherapy is typically less than 20%; use of drug combinations yields little difference in result. There is therefore no standard of systemic chemotherapy for the treatment of mesothelioma.

The chemotherapeutic agents can be administered either systemically (in the blood stream) or intra-pleurally (in the pleural cavity itself.) These cytotoxic drugs are very potent. Because they cannot differentiate healthy cells from cancerous ones, they often have many severe side effects.

Radiation Therapy (Radiotherapy)
Radiation therapy involves the localized use of high-dose radiation (like x-rays) on malignant tumours. Typically, radiation therapy not used on its own, but rather, in conjunction with other therapies such as surgical resection and chemotherapy. In many instances, the potential benefit that may be gained from radiation is outweighed by side effects, including radiation pneumonitis, myelitis, hepatitis and myocarditis, which may significantly diminish the patients quality of life. Radiation can also be used for palliative (pain-relieving) purposes--to reduce the tumours size, thereby helping to relieve symptoms like pain and shortness of breath.

Factors that can limit the application of radiation as a treatment method include the volume of the tumour and how near it is to vital organs. Compared to other types of lung cancer in terms of how it responds to radiation, mesothelioma is not as sensitive to radiation as small cell carcinoma of the lung, but may be more responsive to radiation treatment than non-small cell lung cancer.

Exploratory surgery
Exploratory surgery of the chest (thoracoscopy or thoracotomy), can be a valuable tool in early diagnosis of mesothelioma. If the disease is detected early, the patient has more treatment options to consider, including the potential for aggressive surgery.

During an exploratory procedure, doctors may also drain built-up fluid from pleural effusions. Drainage may help to alleviate shortness of breath, but is regarded as essentially a palliative measure. Drainage may not be effective, however, where the patient has a bulky tumour in the pleural space or where a thick visceral pleural peel of tumour confines the lung.

Surgical treatments
Extra-pleural pneumonectomy (EPP) EPP is regarded as radical surgery. It is a major surgical procedure, involving removal of the pleura, diaphragm, pericardium, portions of the phrenic nerve, and the whole lung affected by the tumour.

To increase the rate of survival, EPP must be followed by adjuvant therapy (chemotherapy and/or radiation), and it carries a significant risk (greater than 15%) of death during or shortly after surgery. Its application is therefore typically confined to a minority of patients who are in Stage I of the disease and who are otherwise medically fit to undergo major surgery.

Pleurectomy/decortication Pleurectomy/decortication involves the removal of the pleura÷essentially, surgically stripping the pleura and pericardium from the apex of the lung to the diaphragm--but without removing the entire lung. This procedure offers the best option for locally controlling pleural fluid. The Cause of death is much less than with EPP (under 3%). Pleurectomy is regarded as more effective than talc pleurodesis in reducing the recurrence of pleural effusion associated with mesothelioma.

Pleurecotomy is best used in patients who are managing their disease generally and have good expansion in their lungs, but who have experienced rapid and symptomatic fluid build-up. Pleurectomy may also be a more suitable treatment method for mesothelioma sufferers in later stages of the disease than the more radical and risky EPP, as well as for older mesothelioma sufferers.

Surgery can remove the bulk of the tumour and provide symptomatic relief÷but it is not a viable option if the tumour is near vital organs. Both EPP and pleurectomy/decortication are complex surgeries, not performed frequently by most surgeons, and require referral to centres dedicated to such treatment. Many of these centres also specialize in other forms of mesothelioma treatment, alone or in combination (multi-modal therapy.)

Which type of surgery is recommended depends on many factors, including the stage of the tumour. Notably, in at least one study, researchers found that the size of the tumour prior to surgery was a good predictor of surgical outcome and overall survival.

Mesothelioma sufferers should evaluate all options carefully, since no one procedure has been comprehensively shown to have distinct advantages over another. Further, surgery has not been shown to offer significant advantages over non-surgical options.

Experimental drugs
Onconase Onconase, made by pharmaceutical company Alfacell, has shown a survival benefit to sufferers of malignant mesothelioma in a study, the results of which were released in March 1999. The study showed a 34.3% one-year survival rate and 21.1% two-year survival rate to patients with inoperable malignant mesothelioma. Another study of Onconase is expected to compare its results with those of doxorubicin, a standard chemotherapy drug.

Onconase is an enzyme derived from purified frog eggs. The enzyme degrades RNA, which is used by cells to produce protein and energy.

The successful study discussed above monitored 105 mesothelioma patients, all of whom received weekly infusions of Onconase until their cancers failed to respond to the drug. Of these patients, 39% demonstrated either reduction of tumour size or stabilization of the disease, as measured by CT scan. Of this 39%, the mean survival time was over 17 months; 61% of that group survived for a year, and 31.7% survived two years. Even among those with the negative prognostic indicator of abdominal involvement, there was a mean survival rate of 12 months, a 1-year survival rate of 48% and a 2-year survival rate of 35.6%.

One unexplained, but potentially positive finding of the study is that patients with abdominal involvement typically a sign that the disease is worsening actually had a better outcome than those without abdominal involvement in the disease process.

Patients in this study generally tolerated the drug well, with only five dropping out of the study due to side effects. Typically experienced side effects were kidney problems, swelling of the extremities and rashes.

A 1996 study of Onconase effects on mesothelioma yielded similar results. In that study, 20 patients with malignant mesothelioma were treated with the drug. Three patients demonstrated partial responses that is, they showed a greater than 50% reduction in the size of their tumours. Ten patients showed stabilization of the progress of their mesothelioma which had been progressing prior to use of Onconase.

Lovastatin Lovastatin, a drug that is typically tolerated well by users, and that has been widely used in the treatment of high cholesterol, has shown positive results in inhibiting mesothelial cell growth. This drug has not yet been subjected to clinical trials, however.

Endostatin and angiostatin Another promising treatment regimen involves endostatin and angiostatin, substances that inhibit the growth of the blood vessels that feed cancerous tumours. Cancers like mesothelioma (as well as breast cancer, melanoma, and kidney cancer) typically need many blood vessels to grow. Use of endostatin and angiostatin inhibits the growth of the blood vessels that feed the tumour, thereby slowing or inhibiting the disease process.

Immunotherapy Immunotherapy is based on the theory that the body's own immune defences can be mobilized to fight against cancerous cells. Several experimental treatments seek to enhance the immune system's ability to combat malignant mesothelioma. These include gene therapy and the use of cytokine proteins such as interferons and interleukin-2. These treatments are being tested both alone and in combination with other treatments such as chemotherapy.

Gene therapy Gene therapy changes the genetic machinery of the cancer cells. The cells are initially infected with "suicide genes," delivered to them by adenoviruses (viruses that cause colds and herpes). The viruses used for gene therapy are disabled and packed with an enzyme, which turns into a poison and cripples the cell's genetic machinery thereby stopping the rapid division of the cancer cells and thus inhibiting rapid growth of the mesothelial tumour. This therapy, which has been successfully used for sufferers of both mesothelioma and brain cancer, may require surgery as well as careful monitoring.

Notably, gene therapy may be better suited to mesothelioma patients than other cancer sufferers. For example, mesothelioma patients are able to tolerate higher doses of the adenoviruses than brain cancer sufferers, and this therapy has not adversely affected the small number of mesothelioma sufferers upon whom it has been implemented. There is no evidence, however, that this therapy reduced the size of mesothelial tumours. Rather, its effect appears to be retardation of tumour growth.

Gene therapy allows for treatment that specifically targets only the tumour. In fact, researchers are studying a vaccine that could be injected directly into the tumour. The specificity of gene therapy in identifying and destroying cancer cells may make it a more attractive option than conventional chemotherapy which can indiscriminately kill healthy cells along with cancerous ones.

Cytokines, Interferons and Interleukins Cytokines are small proteins that are similar to hormones. They have specific effects on the behaviour of other cells. Interleuken-2 (IL2), which was initially identified in 1976 and has been used in treatment of AIDS, is one such protein. IL2 stimulates the growth of T-cells. T-cells are a type of immune system cell, sometimes referred to as "killer cells" because they search out and destroy malignant or virally infected cells. Using IL2 as a treatment for pleural mesothelioma is still in the experimental stages, but researchers hope that injecting IL2 intra-pleurally will prove to promote a significant anti-tumour response.

To date, however, IL2 and interferon-gamma (IFN-gamma), a similar substance, have produced limited results and substantial adverse effects. IFN-gamma did produce good results when used in a study of 89 patients with early stage mesothelioma. Over 46 months of treatment, there was an overall response rate of 20%. Nine percent of those had complete responses, and an additional ten percent experienced at least a 50% reduction in the size of their tumours. In this study, patients who entered during Stage I of their disease fared the best, reporting a response rate of 45%.

Another immunotherapy agent, IFN-alpha-2a, was found have some limited efficacy, one complete response and three partial responses in a group of 25 patients who received the agent subcutaneously. IFN-alpha-2a did not produce significant side effects in that study.

Finally, significant regression of mesothelioma has been reported from direct injection of the immunotherapy agent GM-CSF into the tumour on a regular basis.

Photodynamic therapy Photodynamic therapy uses light to kill cancerous cells. The patient receives a photosensitizing drug-- which targets cancer cells and renders them vulnerable to light of specific wavelengths. After the drug has sensitized the cancerous cells, fibreoptic cables are placed in the body (usually through open-chest surgery). The fibreoptic cables direct light of a precisely adjusted frequency onto the tumour. This causes the photosensitizing drug to produce a toxic oxygen molecule, which kills the cancer cell.

Patients who undergo this type of therapy often do so following surgery and chemotherapy.

Although this treatment is still in a very experimental stage for the treatment of mesothelioma, it has shown promising results in the treatment of other cancers.

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