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Malignant mesothelioma 2008

Friday, August 1, 2008

Source: Current Opinion in Pulmonary Medicine

An article has recently been appeared in the journal Current Opinion in Pulmonary Medicine that reviews the latest knowledge that medical science has developed regarding malignant mesothelioma. “Malignant Mesothelioma 2008” was written by a number of mesothelioma specialists at the New York University of School of Medicine, one of whom was Harvey I. Pass, an internationally-recognized expert on mesothelioma. The following piece is a summary of the literature review provided in that article. While we normally cover the latest individual studies and clinical trials, we want to take the opportunity to review the latest information regarding the diagnosis and treatment of pleural mesothelioma.

Introduction to Mesothelioma

Mesothelioma is diagnosed in 2500–3000 people per year in the United States and is directly responsible for 15,000–20,000 yearly deaths worldwide. It has been known for almost a century that asbestos is the major cause of the disease, but there is some data to suggest that a DNA virus known as SV40 may also play a co-causative role in some cases. SV40 is a controversial topic in mesothelioma research because it has been shown to cause the disease in hamsters, and a subset of human cases also shows evidence of SV40 infiltration, but its etiological significance in humans has not been confirmed. The authors conclude that the virus can be considered a cofactor at best.

Mesothelioma Histology

As is well known in mesothelioma studies, there are three histological subtypes of the disease, meaning there are differences among the cell types in which the malignancy arises. The most common form of the disease is epithelial mesothelioma, which arises in epithelial cells and is diagnosed in more than 50% of all cases. The other categorical subtype of the disease is known as sarcomatoid mesothelioma, which arises in mainly in sarcoma cells. The third major mesothelioma subtype is known as mixed mesothelioma or biphasic mesothelioma and this form of the disease has a mixed distribution of the other two cell types.

The diagnostic identification of the histological subtype is important because each of the various forms affects a patient’s prognosis differently. While mesothelioma is known for its resistance to treatment and is presently without cure, different forms of the disease do respond better than others to treatment. All other factors being equal, epithelial mesothelioma is associated with the best prognosis, while sarcomatoid mesothelioma is associated with the worst. The mixed type’s prognostic indications depend on the overall distribution of the individual cell types.

Mesothelioma Diagnosis

Improving the diagnostic abilities of physicians is one of the most important advances that can be made in mesothelioma research. A number of studies have shown that early diagnosis is associated with longer survival, so it is clearly in the patient’s best interest to receive the diagnosis as early as possible.

The authors describe a number of techniques that can be used for diagnostic purposes. Immunohistochemical staining is a technique where tissue samples are treated for the presence of particular antibodies and positive values are seen through a dye-based reaction to the treatment. Mesothelioma is often misdiagnosed in its earlier stages, so the development of IHC-based testing has been helpful to differentiate it from other forms of cancer. Mesothelioma “stains” for a number of specific markers, so their presence in a tissue sample is indicative of a positive mesothelioma diagnosis.

Another diagnostic front that is being investigated refers to tumor markers, which are antibodies secreted into the blood stream or proteins found within tissue samples that can conclusively determine a mesothelioma diagnosis. Two of the most promising markers are osteopontin (OPN) and mesothelin (SMRP).

Imaging techniques are very important in the diagnosis of mesothelioma and in tracking one’s progress during treatment. Chest x-ray is the standard first technique for the presentation of any pulmonary or thoracic issue, but it does not have high enough resolution for the purposes of mesothelioma diagnosis. CT is the current standard for mesothelioma diagnosis, with MRI being used to answer questions CT is unable to. PET is being increasingly utilized to diagnose distant metastases, while integrated CT/PET is being explored to enhance the accuracy of staging the disease. The authors also write that FDG-PET is being used to monitor tumor response to treatment.

Other important diagnostic tools includes thoracentesis, thoracoscopy and video-assisted thorascopic surgery (VATS) and open pleural biopsy.

Mesothelioma Prognosis

The authors state that most people with mesothelioma will die of local complications to the disease and not because of metastatic spread. The tumor mass grows and continues to encapsulate the lung until it can no longer function. However, as some of the multimodal treatment techniques become more effective at local control of the disease, the occurrence of death due to distant metastases is growing in proportion.

The most important prognostic factor for the disease is performance status at time of diagnosis. Patients with PS of 0 have been shown to have the best prognosis. Other important factors include histology, gender and a number of other lab findings. For example, epithelial histology functions as an indicator of good prognosis and non-epithelial histology as an indicator of worse prognosis, while male gender is an indicator of worse prognosis over female gender.

Treatment Options

Mesothelioma is notoriously-resistant to curative treatments and median survival for most patients is under 16 months from diagnosis. There have been some recent improvements in the efficacy of the available treatments and innovative physicians are actively exploring new techniques and trying to advance on the current ones. In many cases, a patient will only be treated with supportive, or otherwise palliative, options because their diagnosis was only given after the disease had advanced to a later stage where curative surgery was not an option. For these patients, minimally-invasive surgeries may be offered to palliate symptoms, and chemotherapy may be given to extend life.

Patients who are eligible for radical surgery have the best chances to extend survival. There are two major surgical techniques used for radical surgery: pleurectomy-decortication (P/D) and extrapleural pneumonectomy (EPP). During a P/D, both the parietal and the visceral pleura will be removed, and possibly the diaphragm and pericardium, while EPP will feature the removal of the entire affected lung, along with the parietal pleura and possibly the diaphragm and pericardium. Both procedures are highly invasive operations, but EPP is clearly the more radical of the two.

Studies have revealed that the trimodal treatment of the disease, i.e., using surgery, chemotherapy and radiation in combination, is the most effective option to extend life for patients who are candidates for it. However, there are serious questions regarding the order in which the procedures should be deployed and if this order affects overall survival time. Until the studies that are looking into these questions are completed, we will not the answer, but the dedication these physicians bring to mesothelioma treatment is clear.

The authors also describe a number of other treatment options that have been proposed for mesothelioma treatments. Some of them included intrapleural photodynamic therapy, hyperthermic perfusion of the pleura, and immunotherapy.

The chemotherapy combination of pemetrexed and cisplatin is the chemo standard of care for the treatment of the disease.

Conclusion

As this article makes clear, there is much that still needs to be learned about malignant mesothelioma. Even as treatments have improved in recent years, the disease remains without a cure and because of that, innovative physicians and scientists continue to investigate the disease and inquire into its secrets. Mesothelioma treatments have not replicated the same advancements that treatments for other cancers have experienced during the last ten years, but there is hope that the improving efficacy of the current therapies will continue.

Labels: mesothelioma

posted by Belluck & Fox at 4:30 PM
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