Malignant Mesothelioma

WHAT IS MALIGNANT MESOTHELIOMA?

Malignant mesothelioma, a rare form of cancer, is a disease in which cancer (malignant) cells are found in the sac lining the chest (the pleura) or abdomen (the peritoneum).

A history of asbestos exposure is reported in about 70% to 80% of all cases of mesothelioma. Most people with malignant mesothelioma have worked on jobs where they breathed asbestos.



HOW TO DETECT MALIGNANT MESOTHELIOMA?

A person who has shortness of breath, pain in the chest, or pain or swelling in the abdomen should be suggested to have malignant mesothelioma and be received an x-ray of the chest or abdomen.

Thoracoscopy and peritoneoscopy are very helpful for the diagnosis of malignant mesothelioma. Biopsies which are usually done during the thoracoscopy or peritoneoscopy are gold-standard test.

Stage Information

A proposed staging system based upon thoracic surgery principles and clinical data is shown below.

Stage I: Disease confined within the capsule of the parietal pleura: ipsilateral pleura, lung, pericardium, and diaphragm.
Stage II: All of stage I with positive intrathoracic (N1 or N2) lymph nodes.
Stage III: Local extension of disease into the following: chest wall or mediastinum; heart or through the diaphragm, peritoneum; with or without extrathoracic or contralateral (N3) lymph node involvement.
Stage IV: Distant metastatic disease.


HOW TO TREAT MALIGNANT MESOTHELIOMA?

Localized Malignant Mesothelioma (Stage I)

Standard treatment options

Solitary mesotheliomas: Surgical resection en bloc including contiguous structures to ensure wide disease-free margins. Sessile polypoid lesions should be treated with surgical resection to ensure maximal potential for cure.
Intracavitary mesothelioma:
Palliative surgery (pleurectomy and decortication) with or without postoperative radiation therapy. Pleurectomy and decortication can provide palliative relief from symptomatic effusions, discomfort caused by tumor burden, and pain caused by invasive tumor. Operative mortality from pleurectomy/decortication is less than 2%.
Extrapleural pneumonectomy.
Palliative radiation therapy. The use of radiation therapy in pleural mesothelioma has been shown to alleviate pain in the majority of patients treated.
Chemotherapy. The most studied agent is doxorubicin, which has produced partial responses in approximately 15% to 20% of patients studied. Some combination chemotherapy regimens have been reported to have higher response rates in small trials. However the toxicity reported is also higher and there is no evidence that combination regimens result in longer survival or longer control of symptoms.
Intracavitary chemotherapy following resection.
Advanced Malignant Mesothelioma (Stages II, III, and IV)

Standard treatment options:

Symptomatic treatment to include drainage of effusions, chest tube pleurodesis, or thoracoscopic pleurodesis.
Palliative surgical resection in selected patients.
Palliative radiation therapy.
Single-agent chemotherapy. Partial responses have been reported with doxorubicin, epirubicin, mitomycin, cyclophosphamide, cisplatin, carboplatin, and ifosfamide.
Intracavitary therapy. Intrapleural or intraperitoneal administration of chemotherapeutic agents (e.g., cisplatin, mitomycin, and cytarabine) has been reported to produce transient reduction in the size of tumor masses and temporary control of effusions in small clinical studies.
Combination chemotherapy: The combination of pemetrexed and cisplatin may be used.
Recurrent Malignant Mesothelioma

Treatment of recurrent mesothelioma usually utilizes procedures and/or agents not previously employed in the initial treatment attempt. No standard treatment approaches have been proven to improve survival or control symptoms for a prolonged period of time. These patients should be considered candidates for clinical trials of new biologicals, chemotherapeutic agents, or physical approaches.

A trial compared pemetrexed (500 mg/m2) and cisplatin (75 mg/m2 on day 1) with cisplatin alone (75 mg/m2 on day 1 intravenously every 21 days). A total of 456 patients were enrolled: 226 patients received pemetrexed plus cisplatin and 222 patients received cisplatin alone; 8 patients did not receive therapy. After 117 patients had enrolled, folic acid and vitamin B12 were added to reduce toxic effects. Folic acid (350-1,000 μg orally) was given daily, beginning 1 to 3 weeks before the first chemotherapy dose and continuing daily until 1 to 3 weeks after treatment ended. A vitamin B12 injection (1,000 μg intramuscularly) was administered 1 to 3 weeks before the first chemotherapy dose and was repeated approximately every 9 weeks until treatment ended. Dexamethasone (4 mg) or an equivalent corticosteroid was administered orally twice daily for skin rash prophylaxis to all patients 1 day before, on the day of, and 1 day after each pemetrexed dose. The results showed that the median survivals were 12.1 versus 9.3 months, respectively (P=0.020). Median time to progression was significantly longer in the pemetrexed plus cisplatin arm (5.7 months vs 3.9 months, P=0.001). This superiority in the combination arm was also demonstrated in the vitamin supplemented subgroup. The median survivals were 13.3 and 10.0 months in the combination group and cisplatin alone group, respectively (P=0.051). The principal adverse effects of the pemetrexed plus cisplatin regimen were myelosuppression, fatigue, nausea, vomiting, and dyspnea. Most grade 3 to 4 adverse effects were significantly reduced by vitamin supplementation without any decrease in efficacy.



HOW TO ESTIMATE THE PROGNOSIS OF MALIGNANT MESOTHELIOMA?

Patients with stage I disease have a significantly better prognosis than those with more advanced stages. However, because of the relative rarity of this disease, exact survival information based upon stage is limited.Median survival for malignant local pleural disease has been reported as 16 months and extensive disease as 5 months. Prognosis in this disease is difficult to assess consistently because there is great variability in the time before diagnosis and the rate of disease progression. Various surgical procedures may be possible in selected patients, providing long-term survival without cure. In large retrospective series of pleural mesothelioma patients, important prognostic factors were found to be stage, age, performance status, and histology. For patients treated with aggressive surgical approaches, factors associated with improved long-term survival include epithelial histology, negative lymph nodes, and negative surgical margins. For those patients treated with aggressive surgical approaches, nodal status is an important prognostic factor. In some instances the tumor grows through the diaphragm making the site of origin difficult to assess. Cautious interpretation of treatment results in this disease is imperative because of the selection differences among series. Effusions, both pleural and peritoneal, represent major symptomatic problems for at least two thirds of the patients.