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Nov 23, 2007

Cancer-Classification-02

Adult cancers

In the U.S. and other developed countries, cancer is presently responsible for about 25% of all deaths. On a yearly basis, 0.5% of the population is diagnosed with cancer. The statistics below are for adults in the United States, and may vary substantially in other countries:

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Cancer-Classification-01

Nomenclature

The following closely related terms may be used to designate abnormal growths:

  • Neoplasm: a scientific term which refers to an abnormal proliferation of genetically altered cells.
  • Malignant neoplasm: synonymous with cancer.
  • Tumor: broadly defined, can be any swelling or mass. However, the vast majority of entities referred to as 'tumors' in common usage are in fact neoplasms. Specifically, a tumor is a solid neoplasm; some neoplasms, such as cancers of the blood, are not solid.
  • Benign tumor: a tumor (solid neoplasm) that has self-limiting growth and does not invade other tissues nor metastasize. Usually not cancerous.
  • Pre-malignancy or pre-cancer: A non-invasive neoplasm that may not form an obvious mass or lesion but has the potential to progress to cancer if left untreated. These lesions are, in order of increasing potential for cancer, atypia, dysplasia and carcinoma in situ.
  • Transformation: the concept that an indolent or minimally aggressive neoplasm can transition to a state of more malignant behavior over time. Example: Richter's transformation.

Cancers are classified by the type of cell that resembles the tumor and, therefore, the tissue presumed to be the origin of the tumor. Examples of general categories include:

  • Carcinoma: Malignant tumors derived from epithelial cells. This group represents the most common cancers, including the common forms of breast, prostate, lung and colon cancer.
  • Sarcoma: Malignant tumors derived from connective tissue, or mesenchymal cells.
  • Lymphoma and leukemia: Malignancies derived from hematopoetic (blood-forming) cells
  • Germ cell tumor: Tumors derived from totipotent cells. In adults most often found in the testicle and ovary; in fetuses, babies, and young children most often found on the body midline, particularly at the tip of the tailbone; in horses most often found at the poll (base of the skull).
  • Blastic tumor: A tumor (usually malignant) which resembles an immature or embryonic tissue. Many of these tumors are most common in children.

Malignant tumors are usually named using the Latin or Greek root of the organ of origin as a prefix and the above category name as the suffix. For instance, a malignant tumor of the liver is called hepatocarcinoma; a malignant tumor of the fat cells is called liposarcoma. For common cancers, the English organ name is used. For instance, the most common type of breast cancer is called ductal carcinoma of the breast or mammary ductal carcinoma. Here, the adjective ductal refers to the appearance of the cancer under the microscope, resembling normal breast ducts.

Benign tumors are named using -oma as a suffix with the organ name as the root. For instance, a benign tumor of the smooth muscle of the uterus is called leiomyoma (the common name of this frequent tumor is fibroid). However, some cancers also use this prefix for historical reasons, examples being melanoma and seminoma.

Cancer-The Deadly Crab

Cancer is a group of diseases in which cells are aggressive (grow and divide without respect to normal limits), invasive (invade and destroy adjacent tissues), and/or metastatic (spread to other locations in the body). These three malignant properties of cancers differentiate them from benign tumors, which are self-limited in their growth and do not invade or metastasize (although some benign tumor types are capable of becoming malignant). Cancer may affect people at all ages, even fetuses, but risk for the more common varieties tends to increase with age. Cancer causes about 13% of all deaths. Apart from humans, forms of cancer may affect other animals and plants.

Nearly all cancers are caused by abnormalities in the genetic material of the transformed cells. These abnormalities may be due to the effects of carcinogens, such as tobacco smoke, radiation, chemicals, or infectious agents. Other cancer-promoting genetic abnormalities may be randomly acquired through errors in DNA replication, or are inherited, and thus present in all cells from birth. Complex interactions between carcinogens and the host genome may explain why only some develop cancer after exposure to a known carcinogen. New aspects of the genetics of cancer pathogenesis, such as DNA methylation, and microRNAs are increasingly being recognized as important.

Genetic abnormalities found in cancer typically affect two general classes of genes. Cancer-promoting oncogenes are often activated in cancer cells, giving those cells new properties, such as hyperactive growth and division, protection against programmed cell death, loss of respect for normal tissue boundaries, and the ability to become established in diverse tissue environments. Tumor suppressor genes are often inactivated in cancer cells, resulting in the loss of normal functions in those cells, such as accurate DNA replication, control over the cell cycle, orientation and adhesion within tissues, and interaction with protective cells of the immune system.

Cancer is usually classified according to the tissue from which the cancerous cells originate, as well as the normal cell type they most resemble. These are location and histology, respectively. A definitive diagnosis usually requires the histologic examination of a tissue biopsy specimen by a pathologist, although the initial indication of malignancy can be symptoms or radiographic imaging abnormalities. Most cancers can be treated and some cured, depending on the specific type, location, and stage. Once diagnosed, cancer is usually treated with a combination of surgery, chemotherapy and radiotherapy. As research develops, treatments are becoming more specific for different varieties of cancer. There has been significant progress in the development of targeted therapy drugs that act specifically on detectable molecular abnormalities in certain tumors, and which minimize damage to normal cells. The prognosis of cancer patients is most influenced by the type of cancer, as well as the stage, or extent of the disease. In addition, histologic grading and the presence of specific molecular markers can also be useful in establishing prognosis, as well as in determining individual treatments.

Nov 15, 2007

Vinflunine Improves Response and Survival in Mesothelioma

Source: CancerPage.com

A study on the benefits of vinflunine for the treatment of mesothelioma was published in the Journal of Clinical Oncology on October 20. Vinflunine is a microtubule inhibitor that is being studied for its therapeutic effects on a number of different cancers. This particular study was looking at the effects of vinflunine as a first line therapy against malignant pleural mesothelioma and the initial results were positive.

The study sampled a population of 67 patients with pleural mesothelioma. Overall, patients showed a response rate of 13.8% and most maintained upon (60%) or improved (13.8%) their performance status. The median progression-free survival was 3.2 months and the median overall survival was 10.8 months. 1-year survival rate was 36.9%.

Because of the positive results exhibited during the study, the authors have concluded that vinflunine merits further research. They suggest vinflunine may be beneficial to patients with disease progression after Alimta/cisplatin treatment and feel combination therapy with cisplatin itself should also be studied.

Oct 23, 2007

Treatment for Mesothelioma -Treatment Centers

There are a number of medical centers in the U.S. and elsewhere that specialize in one or more types of mesothelioma treatment. Some of the experts at these medical centers include:

This is by no means a complete list of mesothelioma surgeons or doctors. There may well be other specialists closer to where you live, and you should always speak with your doctor about referrals.

Treatment for Mesothelioma -Shark Cartilage and cancer

According to I. William Lane, author of "Sharks Don't Get Cancer" and a leading proponent of shark cartilage as an effective cancer treatment, ingestion of shark cartilage inhibits angiogenesis. In lay terms, what this means is that cartilage apparently reduces the creation of a network of blood vessels around a tumor, and therefore prevents it from growing or spreading.

A number of websites (including those owned by William Lane and his son, Andrew Lane) and health food stores sell shark cartilage pills and claim that they are effective cancer (and/or arthritis) therapies.

Potential consumers, however, should be aware that the effectiveness of shark cartilage has not been demonstrated scientifically. They should also know that although I. William Lane is popularly known as "Dr. Lane", he has a Ph.D. in agricultural biochemistry rather than a M.D. Also, he was a vice-president at W.R. Grace, which is an important defendant in many asbestos cancer lawsuits.

Potential consumers should also be aware that, in December 1999, the U.S. Department of Justice filed a lawsuit against Lane Labs-USA and Andrew Lane (its president and the son of I. William Lane) in the U.S District Court for the District of New Jersey. The FDA sought to stop them from marketing shark cartilage with claims that it is an effective cancer therapy.

Cartilage is a type of tissue found in the skeleton. Interestingly, the skeletons of sharks are almost entirely cartiliginous and, as far as we know, the cancer rate in sharks for certain types of tumors appears to be low. Shark and bovine cartilage, and possibly other types, contain angiogenic inhibitors - compounds that halt the creation of blood vessels. This combination of facts means that shark and other types of cartilage are of considerable interest to medical researchers.

However there is, at this time, no clinical evidence that swallowing powdered shark cartilage is an effective cancer treatment or that it inhibits angiogenesis. The cartilage is digested by the body's gastric system, rather than absorbed (with its antiangiogenic inhibitors) into the bloodstream.

Although there are several antiangiogenesis clinical trials in progress they are all in very early stages of testing. These drugs are not administered orally.

Before anyone with mesothelioma takes shark cartilage he/she should discuss this matter with his/her treating physician. There are a number of reasons to do this, including the need to ensure that he/she obtains only clinical-grade cartilage and the possibility of side-effects.

Further Resources

Treatment for Mesothelioma -Unconventional therapies

number of mesothelioma treatments are outside the mainstream of both established and experimental therapies. As lawyers, not doctors, we are not qualified to judge the value of such unconventional or unproven treatments. In our experience, most doctors disapprove of these treatments, and there is no clear, non-anecdotal evidence of the success of any of these treatments. However, we believe you have the right to all the information available so that you can discuss all possibilities with your physician and make an informed decision about your options.

Antineoplastons:

Dr. Stanislaw Burzynski has been working on antineoplastons as a treatment for cancer since 1967. Antineoplastons are naturally occurring peptides which Dr. Burzynski claims can "reprogram" cancerous cells to behave like "normal" cells again. The success of antineoplaston treatments has been highly controversial, however. The American Cancer Society reports that they have no reliable evidence of the objective benefits of antineoplastons. Dr. Burzynski was also charged in 1995 with fraud and violation of Federal Drug Administration regulations. The Burzynski Research Institute is currently conducting clinical trials of antineoplastons.

Further Information:

* British Columbia Cancer Agency: Unconventional Therapies - Antineoplastons
* National Cancer Institute: Fact Sheet on Antineoplastons
* Report of the Office of Technology Assessment: Unconventional Cancer Treatments - Antineoplastons
* Burzynski Research Institute: Clinical Trials Home Page
* Green, S. Antineoplastons: An Unproved Cancer Therapy. JAMA 267(21):2924-2928 June 3, 1992
* Burzynski, S. Antineoplastons: The Controversy Continues (Letter to the Editor). JAMA 269(4):475, JAN 27, 1993

Cancell (also called Entelev or Cantron):

Cancell is a chemical mixture which is intended to deprive cancerous cells of their ability to get energy. Developed by chemist James Sheridan, proponents claim that Cancell has successfully treated people and animals for cancer for over 30 years without serious side effects. However, supporters of Cancell also recommend avoiding certain vitamins and claim that chemotherapy negates the effect of Cancell. The National Cancer Institute has found no evidence of a biological effect. The American Cancer Society strongly urges against using Cancell as a treatment method.

Further Information:

* National Cancer Institute: Fact Sheet on Cancell
* British Columbia Cancer Agency: Unconventional Therapies - Cancell / Entelev
* Cancell Home Page

Foreign Clinics:

There are numerous clinics, usually located outside of the United States, which claim to use innovative and allegedly successful techniques to cure cancer. Most of these clinics are expensive, and none of them have proven to be effective.

Further Information:

* National Cancer Institute report: "Questionable cancer practices in Tijuana and other Mexican border clinics"

Immuno-Augmentive Therapy (IAT) Centre, Freeport, Grand Bahama Island:

Treatment at the IAT Centre consists of the daily administration of a specially-prepared blood serum which is claimed to boost the immune system and reverse the cancer process.

Lawrence Burton (he has a Ph.D. rather than an M.D.) developed the treatment and is its main advocate. It is disallowed in most of the United States, and the FDA imposed an import ban in 1986. In 1985 the clinic was closed by the Bahamian government due to evidence of HIV, bacterial and hepatitis-B contamination in IAT products. It was reopened the next year when IAT acquired HIV-testing equipment, but since the products are not tested regularly by an independent laboratory, the current risk of biologic contamination is not known.

The benefits of immuno-augmentative therapy remain unverified, although there are numerous testimonials to its effectiveness. In fact, no independent clinical trial of IAT's products has ever been performed, despite direct attempts by the NCI and the Office of Technology Assessment. The American Cancer Society advises against immuno-augmentative therapy. In addition to significant treatment fees, patients must pay for room and board.

Further Information

* British Columbia Cancer Agency: Unconventional Therapies - Immuno-augmentative Therapy
* Report of the Office of Technology Assessment: Unconventional Cancer Treatments - Immuno-augmentative Therapy

American Biologics-Mexico SA Medical Center, Tijuana, Mexico:

The first mesothelioma patient to be treated at this clinic was the actor, Steve McQueen. Since then, there have been anecdotal reports of the success of their treatment , but no conclusive evidence. Treatment consists of an "individualized approach" to "metabolic therapy", consisting of diet, vitamins, exercise, and other techniques. They claim to "control" cancer and numerous other diseases rather than "cure" them. The AB-Mexico clinic is associated with the Bradford Research Institute.

Further Information:

* Report of the Office of Technology Assessment: Unconventional Cancer Treatments - Biologics
* National Cancer Institute: Fact Sheet on Laetrile / Amygdalin
* British Columbia Cancer Agency: Unconventional Therapies - Laetrile / Amygdalin
* American Biologics Medical Center

Gerson Therapy: Center for Integrative Medicine at Centro Hospitalario Internacional Pacifico (CHIPSA), and Hospital Meridian de Playas de Tijuana, Mexico:

There are two clinics in Tijuana, Mexico, which provide treatment based on Gerson Therapy: the Center for Integrative Medicine at Centro Hospitalario Internacional Pacifico (CHIPSA) and Hospital Meridian de Playas de Tijuana. The therapy was developed by Dr. Max Gerson in 1945, and his daughter, Charlotte Gerson Strauss, has continued the therapy since his death in 1959.

Using diet (fresh, raw juices consumed continuously for 13 hours a day ), enemas (including coffee enemas) and other therapies, the Gerson Therapy clinics claim to detoxify the body and restore its natural cancer-fighting abilities.

According to the National Cancer Institute, Dr. Gerson's methods were reviewed and no convincing evidence of effectiveness against cancer was found. No other independent studies have found that Gerson Therapy is effective against cancer. Until 1989, the dietary regimen included raw calf liver juice, and the use of this juice was associated with several infections due to contamination. Coffee enemas have also been associated with serious side effects such as fluid and electrolyte abnormalities.

CHIPSA combines Gerson Therapy with treatment methods devised by Dr. Josef Issels. They call it Issels-Gerson Combination Therapy.

Further Information:

* National Cancer Institute: Fact Sheet on Gerson Therapy
* British Columbia Cancer Agency: Unconventional Therapies - Gerson Therapy
* Report of the Office of Technology Assessment: Unconventional Cancer Treatments - Dietary Treatments
* CHIPSA
* Gerson Institute and Cancer Curing Society
* The Issels Treatment
The Issels Foundation

Alivizatos Greek Cancer Cure:

The Greek Cancer Cure was developed thirty years ago by a microbiologist, Dr. Hariton-Tzannis Alivizatos. His treatment consisted of a blood test which supposedly diagnosed the location and extent of the cancer, followed by injections of a serum which were meant to boost the immune system and "dissolve" the tumor. Before his death in 1991, Dr. Alivizatos had his license to practice medicine revoked by the Greek government several times due to his use of the serum. He never responded to the National Cancer Institute and American Cancer Society's request for information on his treatment. He never published his results or allowed an independent review of his claims. When a Seattle doctor posing as a patient discovered that the serum was a mixture of niacin (a B-vitamin) and water, his clinic was closed by the Greek government.

Today, some North American clinics claim to offer the same treatment which is marketed under the names METBAL and Cellbal. The FDA has banned the importation of METBAL.

Information on Treatments

British Columbia Cancer Agency: Unconventional Therapies - Greek Cancer Cure

Quackwatch: Alivizatos Greek Cancer Cure
Further Resources

* National Cancer Institute: Fact Sheet on Unconventional Methods of Cancer Treatment
* Quackwatch: Message on "Alternative" Treatments
* Questionable Cancer Therapies
* Questionable Cancer Therapy: Shark Cartilage

Treatment for Mesothelioma -Angiogenesis Therapy

Cancer cells, like other cells in the human body, rely for their growth on a rich supply of blood. They must be surrounded by an effective network of capillaries and larger blood vessels that nourish the cells. The medical term for the process of developing this network is angiogenesis.

In fact, fast-growing cancers are highly efficient at promoting angiogenesis. They produce angiogenesis promoters that create capillaries and a network of blood vessels around the tumor. The tumor is nourished with an increasing supply of oxygen-rich blood, and it grows and spreads (or metastasizes).

Understanding that angiogenesis is fundamental to the process of how tumors grow and metastasize, medical researchers started to investigate how they could slow down, stop, or reduce angiogenesis. If they could do this, they reckoned, they could starve the tumor to death - or at least slow its growth significantly. The National Cancer Institute has created an illustrated teaching tool to better understand how angiogenesis works.

A number of antiangiogenesis drugs, also called angiogenesis inhibitors or angiogenic inhibitors, have been developed. When administered to laboratory animals with tumors, they have caused the tumors to shrink or even disappear. Endostatin, combrestatin, angiostatin, thrombospondin, and vascular endothelial growth inhibitor (VEGI) are among these experimental drugs. See also: "Moving beyond chemotherapy: novel cytostatic agents for malignant mesothelioma," by H.L. Kindler in Lung Cancer August 2004; 45 Suppl. 1:S125-S127.

A few of these drugs are now being tested on humans. One of them, combrestatin, destroys the lining of blood vessels around tumors. Another, endostatin, acts by impeding the growth of new blood vessels around the tumors. For endostatin there have been some promising developments. Harvard's Dana-Farber Cancer Institute released an updated report on Phase 1 trials of the angiogenic inhibitor and says it exhibits virtually no toxicity even at high doses, while shrinking tumors in two of 28 advanced cancer patients and slowing disease progression in four others for more than six months.

This area of cancer research holds promise for the treatment of mesothelioma tumors, but it is very much in the early and experimental stages.

There are some anti-angiogenesis clinical trials and they can be located by searching the National Cancer Institute's clinical trials database. Most of the research is centered in Boston where the original angiogenesis research was performed by Dr. Judah Folkman's team at Children's Hospital. In early 2001, the NOVA program on PBS aired the story of Judah Folkman's scientific voyage in a program entitled "The Cancer Warrior" (aired 2/27/01). Link to a recent NOVA interview with Dr. Folkman or read FAQ about anti-angiogenesis. There has been criticism about Dr. Folkman's claims when scientists could not replicate the results that endostatin shrinks tumors by cutting off their blood supply.

Other medical centers where antiangiogenic tests are being performed include Brigham and Women's Hospital, Dana-Farber Cancer Institute and Massachusetts General Hospital in Boston, the University of Wisconsin Comprehensive Cancer Center, and the University of Texas M.D. Anderson Cancer Center in Houston.

Further Resources

  • Angiogenesis Inhibitors in the Treatment of Cancer: An Interview with Lee S. Rosen, MD by Eric Sabo American Society of Clinical Oncology 39th Annual Meeting May 31, 2003 - June 3, 2003; Chicago, Illinois
  • Anti-angiogenesis: The Challenges Ahead by Sara M. Mariani, MD, PhD Highlights From the 2003 Annual Meeting of the American Association for Cancer Research; April 5-9, 2003; Toronto, Ontario, Canada.
  • Unfulfilled Promise of Endostatin in a Gene Therapy-Xenotransplant Model of Human Acute Lymphocytic Leukemia, Molecular Therapy, V5 (4): 352-359; April 2002, Wolfgang Eisterer, Xiaoyan Jiang, Thomas Bachelot, Robert Pawliuk, Carolina Abramovich, Philippe Leboulch, Donna Hogge and Connie Eaves (abstract found at www.sciencedirect.com)

Treatment for Mesothelioma -Immunotherapy including gene therapy

Immunotherapy, also referred to as biological therapy, is based on the theory that it is possible to mobilize the body's own immune defenses against cancerous cells. Another name often applies to this therapy, biological response modifiers (BRMs), and is described in overview article on the subject.

For an up-to-date scientific discussion about immunotherapy, Science Magazine published a special issue on the topic of immunotherapy (see www.sciencemag.org to find articles from the issue July 9, 2004; vol. 305). There were also some positive results from immunotherapy treatment of malignant mesothelioma patients in a recent French study (see: "Malignant mesothelioma. Medical oncology: standards, new trends, trials - the French experience;" Lung Cancer. 2004 V 45 suppl. 1:S129-31).

Gene Therapy:

This a new treatment which is currently in clinical trials. Using an adenovirus for delivery, a "suicide gene" is inserted directly into the tumor. This gene makes the cells sensitive to a normally ineffective drug, such as glanciclovir. Treatment with the drug then destroys those cells that are rapidly dividing - which are the cancer cells - leaving the healthy cells unharmed.

In theory, this approach allows treatment to target the tumor specifically, as opposed to treatments such as chemotherapy which also kill healthy cells. (See: "Gene Therapy in Cancer Patients," by E.A. Armandola, PhD; Medscape General Medicine 4(4), 2002).

Gene therapy for mesothelioma is being researched at the University of Pennsylvania, with Dr. Steven Albelda as the principal investigator. This treatment is not without risk, as became apparent in the death of Jesse Gelsinger, a University of Pennsylvania gene therapy trial participant. (Note that Mr. Gelsinger was not a participant in the mesothelioma trial.)

For a more recent assessment of gene therapy, see "Genetic Therapy for Pleural Malignancies," from the Conference Report from the 7th Annual Meeting of the American Society of Gene Therapy (2004).

Cytokines - Interferons (IFN) and Interleukins (IL):

Cytokines are small proteins that occur naturally in the human body. They are similar to hormones and have specific effects on the behavior of other cells.

In 1976 Dr. Robert Gallo (later head of the National Cancer Institute, and famous for his work on HIV) isolated a cytokine protein molecule called interleukin-2 (IL2) which is capable of stimulating the growth of immune system cells called T-cells. T-cells are sometimes called "killer cells" because they search out malignant or virally infected cells and kill them. Using IL2 as a treatment for pleural mesothelioma is still in the experimental stages, but researchers hope that injecting IL2 intrapleurally will promote a significant anti-tumor response.

Interferons are also naturally occuring cytokine proteins, but they inhibit the growth of malignant cells as well as enhance the immune system. Like interleukins, these immune system promoters are being tested to see if they help increase the body's response to what is often an extremely resistant malignancy, mesothelioma.

Search for clinical trials using Interferon for mesothelioma, on the NCI web site.

Further Resources

Treatment for Mesothelioma -Photodynamic therapy

Photodynamic therapy (PDT) is a treatment method often used in combination with other treatments, such as drugs or surgery. PDT uses light to kill cancerous cells. Photodynamic therapy is still in an experimental stage for treatment of mesothelioma.

Initially, the patient receives a photosensitizer which collects in cancerous cells but not in healthy cells. (A photosensitizer is a drug which makes malignant cells vulnerable (sensitive) to light of specific wavelengths.) After the cells have been sensitized, fiberoptic cables are placed in the body (usually through open-chest surgery) in order to focus light of just the right frequency on the tumor. This causes the photosensitizer to produce a toxic oxygen molecule which kills the cell.

See also article, "Intraoperative Photodynamic Therapy after pleuropneumonectomy in patients with malignant pleural mesothelioma," by H. Schouwink et al, Chest, 2001;120:1167-1174 and response to article (Chest, 2002;122:1866-1867).

Further Resources

Treatment for mesothelioma-Multimodal Treatment

Doctors specializing in mesothelioma treatment frequently adopt a multimodal approach: they treat a patient with a combination of therapies. Due to the relative lack of effectiveness of single-modality treatment in affecting patient survival, the multimodal combination of treatments holds more promise for survival of malignant mesothelioma patients. For an over view of single-mode and multimodal treatment regimens, see the abstract of "Treatment of Malignant Mesothelioma" by M.T. Jaklitsch, S.C. Grondin, and D.J. Sugarbaker and published in the World Journal of Surgery in 2001.

The December 1999 issue of the medical journal, Chest, published a clinical case presentation that illustrates a fairly typical multimodal treatment. The patient was a 52-year-old man with an early diagnosis of Stage I pleural mesothelioma. Doctors performed a pleurectomy (i.e. surgery) and then delivered intrapleural doses of chemotherapy drugs. Then he received additional localized radiation and chemotherapy. Two years after the surgery he did not show evidence of the tumor.

The author concluded that "Aggressive trimodality therapy for mesothelioma is presented as a successful treatment option." (R. Buono - "Mesothelioma Clinical Presentation", Chest 1999; 116:444S-445S).

In recent years, there has been some progress made in the management of malignant mesothelioma, particularly in the area of combination of agents and treatment methods used. More details can be found in this interview with mesothelioma medical expert, Dr. Nicholas Vogelzang: "New Directions for the Treatment of Mesothelioma: An Expert Interview" (Oncology 6(1), 2003).

The following discussion of mesothelioma treatments is organized into separate sections (surgery, photodynamic therapy, radiation, etc.) so that each component of a combination of treatments (multimodality therapy) can be better understood.

Treatment for mesothelioma-Chemotherapy

Traditional Chemotherapy:

This traditional approach uses special anti-cancer (cytotoxic) medicines and chemicals to try to kill the malignant cells. Often, it is offered as an additional therapy alongside radical surgery and/or in combination with radiation therapy or immunotherapy, particularly when the cancer has spread beyond an operable area. Many drugs have been tried; however all have met with only limited success against malignant mesothelioma.

The chemotherapeutic agents can be administered either systemically (in the blood stream) or intrapleurally (in the pleural cavity itself.) These cytotoxic drugs are very potent and can have many severe side effects which you should discuss with your doctor.

Further Resources

Treatment for mesothelioma-Radiation

For patients with localized disease, and who can tolerate a radical surgery, radiation is often given post-operatively as a consolidative treatment. The entire hemi-thorax is treated with radiation therapy, often given simultaneously with chemotherapy. This approach of using surgery followed by radiation with chemotherapy has been pioneered by the thoracic oncology team at Brigham & Women's Hospital in Boston. [7] Delivering radiation and chemotherapy after a radical surgery has led to extended life expectancy in selected patient populations with some patients surviving more than 5 years. As part of a curative approach to mesothelioma, radiotherapy is also commonly applied to the sites of chest drain insertion, in order to prevent growth of the tumor along the track in the chest wall.

Although mesothelioma is generally resistant to curative treatment with radiotherapy alone, palliative treatment regimens are sometimes used to relieve symptoms arising from tumor growth, such as obstruction of a major blood vessel. Radiation therapy when given alone with curative intent has never been shown to improve survival from mesothelioma. The necessary radiation dose to treat mesothelioma that has not been surgically removed would be very toxic

Treatment for Mesothelioma -Surgery

There are two main types of surgical treatment for pleural mesothelioma: extra-pleural pneumonectomy (EPP) and pleurectomy/decortication.

EPP involves the removal of the pleura, diaphragm, pericardium, and the whole lung involved with the tumor. Pleurectomy/decortication involves the removal of the pleura without removing the entire lung.

Which treatment is recommended depends on many factors, including the stage of the tumor. (The NCI has a detailed description of mesothelioma stages.) However, it is unclear if EPP provides significantly greater benefits than pleurectomy/decortication, and indeed if either is significantly more effective than non-surgical options.

A recent study followed about 400 mesothelioma patients who, between 1983 and 1998, had pleurectomy/decortication, or extra-pleural pneumonectomy (EPP), or thoracotomy. The results indicate that no one type of surgery was more effective than another in extending the survival rate. Rather, other factors seemed to determine how long people survived. These factors included the stage and cell type of the tumor, the gender of the patient, and the type of treatment(s) given together with the surgery. Click here for the text of this study.

Surgery can provide symptomatic relief and sometimes the bulk of the tumor can be removed. Surgery is often used in combination with other treatments (known as multi-modal treatments), but its value is very limited if the tumor is near any vital organs.

Both EPP and pleurectomy/decortication are complex surgeries, not performed frequently by most surgeons. They require referral to centers dedicated to such treatments. Many of these centers also specialize in other forms of mesothelioma treatment, either alone or in combination (multi-modal therapy.) You should discuss referrals with your doctor. See also: "The effect of extent of local resection on patients on patterns of disease progression in malignant pleural mesothelioma," by D.J. Stewart, et al in Ann. Thorac Surg., July 2004; 78(1):245-252.

Further Resources

Treatment

Treatment of MM using conventional therapies has not proved successful and patients have a median survival time of 6 - 12 months after presentation. The clinical behaviour of the malignancy is affected by several factors including the continuous mesothelial surface of the pleural cavity which favours local metastasis via exfoliated cells, invasion to underlying tissue and other organs within the pleural cavity, and the extremely long latency period between asbestos exposure and development of the disease.

Environmental Exposure

Incidence of mesothelioma had been found to be higher in populations living near Naturally Occurring Asbestos (NOA)

Asbestos In residential areas

Many building materials used in both public and domestic premises prior to the banning of asbestos may contain asbestos. Those performing renovation works or diy activities may expose themselves to asbestos dust. In the UK use of Chrysotile asbestos was banned at the end of 1999. Brown and blue asbestos was banned in the UK around 1985. Buildings built or renovated prior to these dates may contain asbestos materials.

Paraoccupational secondary Exposure

Family members and others living with asbestos workers have an increased risk of developing mesothelioma, and possibly other asbestos related diseases. This risk may be the result of exposure to asbestos dust brought home on the clothing and hair of asbestos workers. To reduce the chance of exposing family members to asbestos fibres, asbestos workers are usually required to shower and change their clothing before leaving the workplace.

Occupational Exposure

Exposure to asbestos fibres has been recognised as an occupational health hazard since the early 1900s. Several epidemiological studies have associated exposure to asbestos with the development of lesions such as asbestos bodies in the sputum, pleural plaques, diffuse pleural thickening, asbestosis, carcinoma of the lung and larynx, gastrointestinal tumours, and diffuse mesothelioma of the pleura and peritoneum.

The documented presence of asbestos fibres in water supplies and food products has fostered concerns about the possible impact of long-term and, as yet, unknown exposure of the general population to these fibres. Although many authorities consider brief or transient exposure to asbestos fibres as inconsequential and an unlikely risk factor, some epidemiologists claim that there is no risk threshold. Cases of mesothelioma have been found in people whose only exposure was breathing the air through ventilation systems. Other cases had very minimal (3 months or less) direct exposure.

Commercial asbestos mining at Wittenoom, Western Australia, occurred between 1945 and 1966. A cohort study of miners employed at the mine reported that while no deaths occurred within the first 10 years after crocidolite exposure, 85 deaths attributable to mesothelioma had occurred by 1985. By 1994, 539 reported deaths due to mesothelioma had been reported in Western Australia

Exposure

Asbestos was known in antiquity, but it wasn't mined and widely used commercially until the late 1800s. Its use greatly increased during World War II. Since the early 1940s, millions of American workers have been exposed to asbestos dust. Initially, the risks associated with asbestos exposure were not publicly known. However, an increased risk of developing mesothelioma was later found among shipyard workers, people who work in asbestos mines and mills, producers of asbestos products, workers in the heating and construction industries, and other tradespeople. Today, the U.S. Occupational Safety and Health Administration (OSHA) sets limits for acceptable levels of asbestos exposure in the workplace, and created guidelines for engineering controls and respirators, protective clothing, exposure monitoring, hygiene facilities and practices, warning signs, labeling, recordkeeping, and medical exams. By contrast, the British Government's Health and Safety Executive (HSE) states formally that any threshold for mesothelioma must be at a very low level and it is widely agreed that if any such threshold does exist at all, then it cannot currently be quantified. For practical purposes, therefore, HSE does not assume that any such threshold exists. People who work with asbestos wear personal protective equipment to lower their risk of exposure.

Risk Factors

Working with asbestos is the major risk factor for mesothelioma. A history of asbestos exposure exists in almost all cases. However, mesothelioma has been reported in some individuals without any known exposure to asbestos. In rare cases, mesothelioma has also been associated with irradiation, intrapleural thorium dioxide (Thorotrast), and inhalation of other fibrous silicates, such as erionite.

Asbestos is the name of a group of minerals that occur naturally as masses of strong, flexible fibers that can be separated into thin threads and woven. Asbestos has been widely used in many industrial products, including cement, brake linings, roof shingles, flooring products, textiles, and insulation. If tiny asbestos particles float in the air, especially during the manufacturing process, they may be inhaled or swallowed, and can cause serious health problems. In addition to mesothelioma, exposure to asbestos increases the risk of lung cancer, asbestosis (a noncancerous, chronic lung ailment), and other cancers, such as those of the larynx and kidney.

The combination of smoking and asbestos exposure significantly increases a person's risk of developing cancer of the airways (lung cancer, bronchial carcinoma). The Kent brand of cigarettes used asbestos in its filters for the first few years of production in the 1950s and some cases of mesothelioma have resulted. Smoking modern cigarettes does not appear to increase the risk of mesothelioma.

Some studies suggest that simian virus 40 (SV40) may act as a cofactor in the development of mesothelioma.

Incidence

Although reported incidence rates have increased in the past 20 years, mesothelioma is still a relatively rare cancer. The incidence is approximately one per 1,000,000. For comparison, populations with high levels of smoking can have a lung cancer incidence of over 1,000 per 1,000,000. Incidence of malignant mesothelioma currently ranges from about 7 to 40 per 1,000,000 in industrialized Western nations, depending on the amount of asbestos exposure of the populations during the past several decades.[5] It has been estimated that incidence may have peaked at 15 per 1,000,000 in the United States in 2004. Incidence is expected to continue increasing in other parts of the world. Mesothelioma occurs more often in men than in women and risk increases with age, but this disease can appear in either men or women at any age. Approximately one fifth to one third of all mesotheliomas are peritoneal.

Between 1940 and 1979, approximately 27.5 million people were occupationally exposed to asbestos in the United States [4]. Between 1973 and 1984, there has been a threefold increase in the diagnosis of pleural mesothelioma in Caucasian males. From 1980 to the late 1990s, the death rate from mesothelioma in the USA increased from 2,000 per year to 3,000, with men four times more likely to acquire it than women. These rates may not be accurate, since it is possible that many cases of mesothelioma are misdiagnosed as adenocarcinoma of the lung, which is difficult to differentiate from mesothelioma.

Screening and staging

Screening

There is no universally agreed protocol for screening people who have been exposed to asbestos. However some research indicates that the serum osteopontin level might be useful in screening asbestos-exposed people for mesothelioma. The level of soluble mesothelin-related protein is elevated in the serum of about 75% of patients at diagnosis and it has been suggested that it may be useful for screening.

Staging

Mesothelioma is described as localized if the cancer is found only on the membrane surface where it originated. It is classified as advanced if it has spread beyond the original membrane surface to other parts of the body, such as the lymph nodes, lungs, chest wall, or abdominal organs

Diagnosis

The National Cancer Institute's definition of screening for cancer is the examination or testing of people for early signs of certain type of cancer even though they have no symptons - this is the best way to achieve a diagnosis as early as possible. Early detection and diagnosis is particularly important for people with historical exposure to asbestos due to the latency period (up to 30 years) before which symptoms of malignant mesothelioma cancer may become apparent.

Early Signs of Mesothelioma Aid Diagnosis:

Recognizing early symptoms of malignant mesothelioma may aid in diagnosis. Symptoms include difficulty in breathing (dyspnea) and/or chest pains, fever, nausea or anemia; other signals are hoarseness, difficulty swallowing (dysphagia), or coughing up blood (hemoptysis). For many suffering from pleural mesothelioma, there may be pain in the chest or lower back. Those people with peritoneal mesothelioma may experience an expanding waist size or abdominal pain resulting from the growth of cancer cells in the abdomen.

Since many of these symptoms are also caused by less serious illnesses, it can be difficult to recognize asbestos-related diseases in the early stages. Due to this difficulty of early diagnosis of asbestos cancer and mesothelioma, the best way to determine your health risk is to consult a doctor for an initial examination, which may include a pulmonary function test (PFT) and x-rays.

Screening Methods to Identify Asbestos-Related Disease:

After a preliminary physical examination, the doctor may need to look inside your chest cavity with a thorascope for accurate diagnosis. During this thoracoscopy procedure, a cut will be made in your chest and a small piece of tissue (biopsy) may removed for examination. While you may feel some pressure, there is usually no pain.

Another special tool that may be used is the peritoneoscope, which allows for examination inside your abdomen. This instrument is inserted into an opening made in the abdomen, and a biopsy specimen may also be taken.

If the presence of fluid is indicated by either of these procedures, the doctor may drain it by inserting a needle into the affected area. Removal of chest fluid is called thoracentesis; removal of abdominal fluid is call paracentesis.

Other screening methods for diagnosis of asbestos-related disease include various imaging tests. In addition to X-rays, methods include magnetic resonance imaging (MRI) or positron emission tomography (PET). A more recent and promising screening method is the computed tomography (CT) scan.

Computed Tomagraphy / CT Scan:

Computed tomagraphy, or spiral CT scan, is a special radiographic technique that produces a clear cross-sectional image that allows a radiologist to see distinct aspects of the lung or pleura that are not readily apparent from the standard X-ray image. Recent studies (CHEST 2002;122:15-20 and MAYO CLIN PROC 2002;77:329-333) support the use of annual chest computed tomography (CT scans) exams as a valuable screening tool for people with a high risk of developing lung cancer, including mesothelioma cancer. There does appear to be conflicting assessment as to the cost-effectiveness of CT screening. A 2003 study by Johns Hopkins raises this concern about the cost-effectiveness of CT scans and states, "There is a downside to this, including high costs and possible harm to individuals who may unnecessarily get invasive procedures if the scan detects a benign lung nodule." A more recent study in Chest, 2003:124:614-621 comes to a different conclusion: "A baseline low-dose CT scan for lung cancer screening is potentially highly cost-effective and compares favorably to the cost-effectiveness ratios of other screening programs."

Further Resources

Signs & Symptoms of Mesothelioma

Symptoms of mesothelioma may not appear until 20 to 50 years after exposure to asbestos. Shortness of breath, cough, and pain in the chest due to an accumulation of fluid in the pleural space are often symptoms of pleural mesothelioma.

Symptoms of peritoneal mesothelioma include weight loss and cachexia, abdominal swelling and pain due to ascites (a buildup of fluid in the abdominal cavity). Other symptoms of peritoneal mesothelioma may include bowel obstruction, blood clotting abnormalities, anemia, and fever. If the cancer has spread beyond the mesothelium to other parts of the body, symptoms may include pain, trouble swallowing, or swelling of the neck or face.

These symptoms may be caused by mesothelioma or by other, less serious conditions.

Mesothelioma that affects the pleura can cause these signs and symptoms:

  • chest wall pain
  • pleural effusion, or fluid surrounding the lung
  • shortness of breath
  • fatigue or anemia
  • wheezing, hoarseness, or cough
  • blood in the sputum (fluid) coughed up

In severe cases, the person may have many tumor masses. The individual may develop a pneumothorax, or collapse of the lung. The disease may metastasize, or spread, to other parts of the body.

Tumors that affect the abdominal cavity often do not cause symptoms until they are at a late stage. Symptoms include:

  • abdominal pain
  • ascites, or an abnormal buildup of fluid in the abdomen
  • a mass in the abdomen
  • problems with bowel function
  • weight loss

In severe cases of the disease, the following signs and symptoms may be present:

A mesothelioma does not usually spread to the bone, brain, or adrenal glands. Pleural tumors are usually found only on one side of the lungs.

What is mesothelioma

Mesothelioma is a form of cancer that is almost always caused by previous exposure to asbestos. In this disease, malignant cells develop in the mesothelium, a protective lining that covers most of the body's internal organs. Its most common site is the pleura (outer lining of the lungs and chest cavity), but it may also occur in the peritoneum (the lining of the abdominal cavity) or the pericardium (a sac that surrounds the heart).

Most people who develop mesothelioma have worked on jobs where they inhaled asbestos particles, or have been exposed to asbestos dust and fibre in other ways, such as by washing the clothes of a family member who worked with asbestos, or by home renovation using asbestos cement products. Unlike lung cancer, there is no association between mesothelioma and smoking