Mesothelioma Treatment

Malignant mesothelioma represents an uncommon disease, most often associated with occupational asbestos exposure, with a steady increase in incidence worldwide. Mesotheliomas are 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 radiotherapy, chemotherapy and radical procedures such as surgery. Palliative measures are also often employed with the primary aim to remove pleural effusions and prevent their recurrence; hence symptoms such as chest pain and dyspnea (in cases of pleural mesothelioma) can be relieved.

Radiotherapy

Radiotherapy is frequently used in order to control local tumor growth; an occasional regression of the disease can be seen, although there is no evidence that radiotherapy alone can affect survival rates. Therefore it is usually used as a part of 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 anterior and posterior fields that encompass the entire part of the chest stricken with disease.

Highly complex intensity-modulated radiation therapy (IMRT) techniques allow more effective sparing of normal tissues, thus providing safer and less toxic treatment with better efficacy. This way higher radiation doses are also delivered to the tumor target. Arc therapy or helical tomotherapy are rotational radiotherapeutic methods that deliver radiation from even more beam angles.

Radiation therapy has a limited role in peritoneal mesothelioma, hence it is not used in most medical centers. The treatment for advanced primary pericardial mesothelioma is usually palliative due to the tumors resistance to radiotherapy and chemotherapy.

Chemotherapy

Monotherapy with single cytotoxic drugs seldom 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 (a multitarget folate pathway inhibitor) in combination with platinum derivatives, and the cisplatin/gemcitabine associations represent a front-line 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 noteworthy promise as targeted therapies, but are yet to reach daily practice.

Chemotherapy has an important role in palliative care of peritoneal mesotheliomas. 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 one quarter of all patients.

Surgery

Main goals of surgery in treating malignant pleural mesothelioma (taking into account the framework of a multimodal approach) is the resection of all macroscopic disease together with the delivery of chemotherapy and radiation. The surgical options available to attain this goal include extrapleural pneumonectomy, pleurectomy/decortication and in some instances surgical pleurodesis via video assisted thoracoscopic surgery.

Some medical centers recommend pleurectomy/decortication as a method of choice for patients with compromised function of the lungs or heart, old age or certain comorbidities, in order to remove the bulk of the tumor while sparing pulmonary function at the same time.

Appropriate knowledge of similarities and differences between all the aforementioned techniques is pivotal in understanding the complex issues surrounding patient selection, adequate diagnosis, staging, preoperative assessment, perioperative management, as well as adjuvant treatment.

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