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Page Updated: July 02, 2022

The SMART Protocol for Pleural Mesothelioma

Elliot Wakeam, M.D Page Medically Reviewed and Edited by Elliot Wakeam, M.D

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Fact Checked

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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We make every attempt to keep our information accurate and up-to-date.

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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.

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Treating Pleural Mesothelioma

Pleural mesothelioma occurs most often in people exposed to asbestos for long periods, 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.

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, which 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 to minimize complications and maximize the patient’s 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 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 safe enough for patients to continue further study. With positive results, the study has expanded and now includes more patients and additional treatment strategies, including immunotherapy.

Benefits of SMART

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 significant improvement compared to other treatments. However, it is important to note that these promising results only occurred in patients with epithelial mesothelioma, the least aggressive cell type. There are other benefits of the SMART protocol:

  • The intensity-modulated radiation therapy used to treat patients in the SMART protocol helps sterilize and manage tumors’ edges 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.
  • 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.
  • One additional advantage for patients is that the therapy is complete within 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 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 to use less aggressive surgical procedures to reduce risks and complications in clinical trials.
  • In the ongoing clinical trials for the SMARTER protocol, patients receive radiation doses three times over 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]
  • In a recent study of the SMART protocol, researchers recorded major improvements in survival time for mesothelioma patients. It included 96 patients with a median survival time of 65.9 months. This was the first study in which that statistic exceeded five years.[8]

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, improve the outcomes for all mesothelioma patients.

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Page Medically Reviewed and Edited by Elliot Wakeam, M.D

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.

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References
  1. Waqas, A., Linkov, F., Landsittel, D.P., Silverstein, J.C., Bashara, W., Gaudioso, C., Feldman, M.D., Pass, H.I., Melamed, J., Freidberg, J.S., and Becich, M.J. (2018). Factors Influencing Malignant Mesothelioma Survival: A Retrospective Review of the National Mesothelioma Virtual Bank Cohort. F1000 Research. 7, 1184.
    Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6198263/
  2. Mayo Clinic. (2019, January 15). Mesothelioma. Symptoms and Causes.
    Retrieved from: https://www.mayoclinic.org/diseases-conditions/mesothelioma/symptoms-causes/syc-20375022
  3. Scherpereel, A. (2017, January). Malignant Pleural Mesthelioma: New Treatments, New Hopes? European Respiratory Journal. 49, DOI: 10.1183/13993003.00319-2017.
    Retrieved from: https://erj.ersjournals.com/content/49/3/1700319
  4. Duranti, L., Pardolesi, A., Bertolaccini, L., Tavecchio, L., Scanagatta, P., Rolli, L., and Pastorino, U. (2019, March). Extra-Pleural Pneumonectomy. J. Thorac. Dis. 11(3), 1022-1030.
    Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6462700/
  5. De Perrot, M., Felt, R., Leighl, N.B. Hope, A., Waddell, T.K., Keshavjee, S., and Cho. J. (2016, February). Accelerated Hemithoracic Radiation Followed by Extrapleural Pneumonectomy for Malignant Pleural Mesothelioma. J. Thorac. Cardov. Sur. 151(2), 468-75.
    Retrieved from: https://www.sciencedirect.com/science/article/pii/S0022522315019868
  6. De la Maza, L., Wu, M., Wu, L., Yun, H., Zhao, Y., Cattral, M., McCart, A., Cho, J., and DePerrot, M. (2017). In Situ Vaccination after Accelerated Hypofrationated Radiation and Surgery in a Mesothelioma Mouse Model. Clinical Cancer Research. DOI: 10.1158/1078-0432.CCR-17-0438.
    Retrieved from: https://clincancerres.aacrjournals.org/content/early/2017/06/10/1078-0432.CCR-17-0438
  7. University Health Network, Toronto. (2021, October 6). A Feasibility Study Evaluating Surgery for Mesothelioma After Radiation Therapy Using Extensive Pleural Resection (SMARTER).
    Retrieved from: https://clinicaltrials.gov/ct2/show/NCT04028570
  8. Cho, B.C.J., Donahoe, L., Bradbury, P.A., Leighl, N., Keshavjee, S., Hope, A., Pal, P., Cabanero, M., Czarnecka, K., McRae, K., Tsao, M., and de Perrot, M. (2021, January 12). Surgery for Malignant Pleural Mesothelioma after Radiotherapy (SMART): Final Results from a Single-Centre, Phase 2 Trial. The Lancet Oncology. 22(2), P190-P197.
    Retrieved from: https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(20)30606-9/fulltext
View All References

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