The SMART Protocol for Pleural Mesothelioma
Page Medically Reviewed and Edited by Elliot Wakeam, M.D This page has been fact checked by a Medical Doctor who specializes in mesothelioma. Sources of information are listed at the bottom of the article.
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Survival after a mesothelioma diagnosis is just fifteen months on average, and multi-modal treatments provide the best chance to extend that life expectancy.[1][2] To improve the odds, researchers are working on the SMART (surgery for mesothelioma after radiation therapy) protocol for shorter, safer treatments with better outcomes.
Treating Pleural Mesothelioma
Pleural mesothelioma occurs most often in people who were exposed to asbestos for long periods of time, usually in the workplace. The fibers of this mineral can become lodged in tissues of the lungs and pleura, causing damage and cancer in some people. Pleural mesothelioma is cancer in the pleural tissue that surrounds the lungs.
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This type of cancer is often diagnosed in later stages, and it is aggressive, making it difficult to treat. Prognosis is often poor. The standard approach for treatment is multi-modal, meaning some combination of chemotherapy, radiation therapy, and surgery.[3]
Resectable mesothelioma, cancers that can be removed surgically, may respond to an aggressive type of surgery known as an extrapleural pneumonectomy (EPP) that removes one lung and its surrounding tissue. There are serious risks though. Potential complications include acute respiratory distress syndrome, respiratory failure, atrial arrhythmia, pulmonary embolism, and respiratory infections, among others.[4]
Surgery can be successful at extending a mesothelioma patient’s life. It can also lead to remission, but the risks of such extensive surgery are serious, especially when combined with other treatments such as chemotherapy. Researchers are trying to find a way to deliver this treatment in a way that minimizes complications and maximizes patient quality of life and survival.
The SMART Protocol
Researchers developed the SMART protocol for treating pleural mesothelioma after seeing positive results in patients who received radiation therapy after undergoing an EPP. The SMART protocol uses radiation first, followed by EPP.[5]
The radiation therapy is delivered five times in the course of a week. The patient then undergoes an EPP within two weeks of the completion of radiation therapy. Some patients receive adjuvant chemotherapy as well, but most do not need it.
In phase I and phase II trials of this protocol, the procedure proved to be safe enough for patients to continue with further study. With positive results, the study has expanded and now includes more patients and additional treatment strategies including immunotherapy.
Benefits of SMART
The intensity-modulated radiation therapy used to treat patients in the SMART protocol helps to sterilize and manage the edges of tumors before surgery. Traditionally, surgery for pleural mesothelioma is preceded by chemotherapy to shrink tumors, but this takes a long time and causes many side effects. The accelerated radiation therapy over a shorter period of time helps patients get into treatment sooner. It is also more convenient for patients, with a more compact treatment period.
The most obvious benefit of the SMART protocol as measured in clinical trials is the improved survival times. The results of the trials showed a median overall survival time of fifty-one months and a medical disease-free survival time of forty-seven months.[5] This is a major improvement compared to other treatments. It is important to note, however, that these promising results were only seen in patients with epithelial mesothelioma, the least aggressive cell type. One other advantage for patients is that the therapy is all complete within a matter of two to three weeks rather than many months.
New Developments in the SMART Protocol
While the SMART protocol has shown promise and positive results in many patients, there is room for improvement. Researchers developing better treatments for pleural mesothelioma are expanding on the protocol in order to see better results and fewer complications and risks.
One study, using mice, investigated the use of immunotherapy treatments following the SMART protocol. The idea arose from the fact that high-dose radiation may stimulate the patient’s immune system. The protocol, the researchers thought, might be a good opportunity to include an immune checkpoint blockade. More study is needed to determine if this procedure could work in human patients.[6]
The same researchers who developed the SMART protocol have adapted it to the SMARTER protocol. This stands for surgery for mesothelioma after radiation therapy using extensive pleural resection. The basic protocol is the same, but the researchers are attempting in clinical trials to use less aggressive surgical procedures to reduce risks and complications.
In the ongoing clinical trials for the SMARTER protocol, patients receive radiation doses three times over the course of a week, followed by surgery. Some patients may receive the EPP surgery, but others are undergoing a less radical procedure, a pleurectomy/decortication, which removes less tissue. The researchers hope to find an ideal radiation dose that is effective but limits damage to healthy tissue.[7]
Treating pleural mesothelioma is a challenge for many reasons. Most patients have a poor prognosis, and even those who may see good results must go through difficult, uncomfortable procedures that put them at risk of serious complications. New developments in treatment, like the SMART and SMARTER protocols serve to improve the outcomes for all mesothelioma patients.
Page Medically Reviewed and Edited by Elliot Wakeam, M.D
Elliot Wakeam, M.D. is a board-certified surgeon who has been recognized for his role in helping to develop the SMART protocol, meaning “surgery for mesothelioma after radiation therapy.” He also focuses on healthcare delivery; strategies for surgeons to help patients recover post-surgery; and new approaches for surgical cancer treatment. Dr. Wakeam earned a Masters of Public Health at Harvard School of Public Health, followed by his medical degree from Jefferson Medical College, where he graduated magna cum laude. Dr. Wakeam is affiliated with numerous renowned medical associations, including the American Association of Thoracic Surgery, the Canadian Association of Thoracic Surgery, and the American College of Surgeons. He is currently an assistant professor in thoracic surgery at the University of Michigan Health System.