Evolving Role of Radiation Therapy in the Treatment of Mesothelioma

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Malignant mesothelioma typically affects the lungs, but sometimes affects the peritoneum, testes, or pericardium.
Malignant mesothelioma typically affects the lungs, but sometimes affects the peritoneum, testes, or pericardium.

The optimal palliative, adjuvant, and neoadjuvant roles for radiation therapy in the treatment of malignant mesothelioma are not yet completely established, but the American Society of Clinical Oncology (ASCO) has released an evidence-based clinical guideline that makes several recommendations.

Approximately 3000 new cases of malignant mesothelioma, an aggressive cancer of the lining of internal organs, are diagnosed in the United States each year. The vast majority involve lung pleura and are associated with asbestos inhalation.1 Less frequently, mesothelioma occurs in the peritoneum, testes, or pericardium.1 Most patients are white, male, and older than 65 years.1

Mesothelioma is a dismal diagnosis. There is no known cure.1,2 The FDA last approved a new drug regimen for its treatment — pemetrexed plus cisplatin — back in 2004.3 Diagnosis is usually made after patients begin to experience symptoms such as chest pain or shortness of breath.1 It is often accompanied by pleural effusion, an accumulation of fluid between the pleural layers that encompass the lungs. The diagnostic gold standard is thoracoscopy and endoscopic biopsy for confirmatory histologic analysis following detection of abnormalities on chest radiography.1

Incidence rates climbed through the 1970s, 1980s, and 1990s; however, following reductions in occupational exposures to asbestos, rates appear to have plateaued.1 Regulatory efforts to reduce workplace exposures began in the 1970s, but overall incidence rates did not decline for several decades because of the long latency period between exposure and carcinogenesis.1

Few Options, Limited Evidence

Treatment options include surgery, chemotherapy (usually a platinum-based chemotherapy plus pemetrexed), and less frequently, radiotherapy. Cisplatin plus pemetrexed is the first-line standard of care and no validated second-line treatment is available.2 Adding bevacizumab, an anti-VEGF therapy, to cisplatin has been proposed as a new treatment regimen and immunotherapies are under investigation as possible second-line options after disease progression following chemotherapy.2

Evidence-based management of mesothelioma can be challenging because patient populations for participation in clinical trials are relatively small. Ashton and colleagues reported in a systematic review of radiotherapy in mesothelioma that of 249 published papers reviewed, only 2 were high-quality, randomized clinical trials.4

Evidence that chemotherapy might prolong survival times, perhaps by as much as 7 months, and that a second line of chemotherapy or thalidomide might offer additional, modest survival benefits is limited.1,5 According to a recent analysis of data from 1625 patients in the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database, the median overall survival time was 1 year among patients who received any chemotherapy for mesothelioma and 4 months for those not receiving chemotherapy (range, 1 to 69 months for both groups).1 Sixteen percent of patients foregoing chemotherapy altogether survived 1 year, compared with 48% of patients undergoing any chemotherapy.1 However, the SEER-Medicare study authors cautioned that patient or disease characteristics could have confounded their retrospective database analysis.

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