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3 Treatment of Mesothelioma

Malignant mesothelioma represents a rare disease, most often associated with occupational asbestos exposure, with a steady increase in incidence worldwide. Mesothelioma is almost universally considered a fatal malignancy, and until recently the treatment options were limited and often ineffective.

Current treatment modalities for malignant mesothelioma can be classified into radiation therapy, chemotherapy and radical procedures such as surgery. Palliative measures are also often employed with the primary target to remove pleural effusions and prevent their return; hence the symptoms such as chest pain and dyspnea (in the cases of pleural mesothelioma) can be relieved.

Radiotherapy

Radiation therapy is frequently used in order to control local tumor growth; an occasional regression of the disease can be considered, although there is no evidence that radiotherapy alone can affect survival rates. Therefore it is commonly used as a part of the multimodal approach, most often combined with surgery.

When administering radiotherapy as an adjuvant therapy after surgical extrapleural pneumonectomy or pleurectomy /decortication, patients are usually treated with conventional radiation techniques using the anterior and posterior fields covering the entire part of the chest stricken with the disease.

The highly complex intensity modulation (IMRT) techniques of radiotherapy allow for a more efficient saving of normal tissues, a safer and less toxic treatment, thus providing better efficiency. Higher doses of this radiation are also delivered to the tumor target. Arco therapy or helical tomotherapy is the rotating radiotherapeutic methods that deliver radiation from even more beam angles.

Radiotherapy has a limited role in peritoneal mesothelioma, hence it is not used in most medical centers. Treatment for advanced primary pericardial mesothelioma is generally palliative because of the resistance of tumors to radiotherapy and chemotherapy.

Chemotherapy

Monotherapy with single cytotoxic drugs rarely gives a significant result in the treatment of malignant pleural mesothelioma, but combination regimens with novel drugs and standard molecules are showing better clinical responses and benefits. According to the results of Phase II / III studies, pemetrexed (an inhibitor to several target languages of the folate pathway) in combination with platinum derivatives, and cisplatin/gemcitabine associations represent a frontline chemotherapy.

Vinorelbine as a single agent and combination of mitomycin C, vinblastine and cisplatin have also been validated as a good symptom relief approach with acceptable toxicity. Histone deacetylase inhibitors and antiangiogenic agents also show remarkable promise as targeted therapies but are still to achieve daily practice.

Chemotherapy has an important role in the palliative care of mesothelioma peritoneal. It can be administered systemically or directly into the abdomen, with continuous hyperthermic peritoneal perfusion showing the best response rate of 84.6%. The most studied agent is cisplatin with proven activity in a quarter of all patients.

Surgery

The main goals of surgery in treating malignant pleural mesothelioma (which takes into account the structure of a multimodal approach) are the resection of all macroscopic disease along with delivery of chemotherapy and radiation. Surgical options available to achieve this goal include extrapleural pneumonectomy, pleurectomy / descortication and in some cases surgical pleurodesis through thoracoscopic assisted video surgery.

Some medical centers recommend pleurectomy / descortication as a method of choice for patients with compromised lung or heart function, advanced age or certain comorbidities, in order to remove the tumor volume while sparing lung function at the same time.

Proper knowledge of the similarities and differences between all of the above mentioned techniques is pivotal in understanding the complex issues surrounding patient selection, adequate diagnosis, the platform, preoperative evaluation, perioperative management, as well as adjuvant treatment.

Cytoreductive surgery followed by intraperitoneal hyperthermic perfusion represents a standard approach for resectable peritoneal mesothelioma. Pericardiectomy may be attempted for pericardial mesothelioma, but the procedure is often unsuccessful because the pericardium may be dense adherent to the myocardium.
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