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Written By: Devin Golden

SMART for Mesothelioma

Surgery for Mesothelioma After Radiation Therapy (SMART) is a multimodal approach to mesothelioma treatment. It uses aggressive regimens of radiation therapy to stop the growth the tumors and shrink the cancer prior to aggressive surgery, which removes a massive chunk of the tumor.

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Important Facts About SMART for Mesothelioma

  • SMART began at Princess Margaret Cancer Centre in Toronto, Canada. It’s offered at Michigan Medicine and is growing in popularity.
  • SMART uses large doses of radiation before aggressive surgery.
  • Studies report survival rates of more than three years for SMART. People with epithelioid mesothelioma have the best prognosis.
  • Extrapleural pneumonectomy is the surgery for SMART, but doctors are looking into whether pleurectomy with decortication is a better option. Specialists also may add immunotherapy to the approach.

What Is SMART?

SMART is a groundbreaking protocol for mesothelioma treatment. It administers radiation therapy before surgery. Oftentimes, doctors use radiation after surgery.

SMART began as a clinical trial at Princess Margaret Cancer Centre in Toronto, Canada led by Dr. Marc de Perrot. Other specialists incorporated their variations of SMART at different U.S. hospitals following favorable results.

Most doctors suggest mesothelioma surgery as the first-line treatment. Chemotherapy and radiation are often “adjuvant” treatments.

In SMART, radiation therapy is a “neoadjuvant” treatment since it occurs before surgery. Doctors believe radiation before surgery prevents “recurrence” of the disease. Recurrence means the cancer has returned.

Process for SMART

SMART begins with a one-week “course” of radiotherapy. This process involves five daily fractions of radiation throughout the week.

Surgery occurs a few days after radiation ends. According to the MedStar Washington Hospital Center’s website, EPP takes around three hours to complete, possibly longer.

The University of California San Francisco website states EPP requires two weeks of recovery in the hospital. Following discharge, patients need 6-8 more weeks of outpatient recovery.

After surgery and full recovery, patients may start adjuvant chemotherapy around three months after surgery. This step often depends on whether tumors reached the lymph nodes. Patients will receive 4-6 cycles of chemotherapy, and each cycle takes around three weeks.

How to Receive Mesothelioma SMART Treatment

People with pleural mesothelioma may wonder how to get SMART for their cancer. You should follow these three steps:

1

Learn more about SMART. You can read about survival rates for patients and what the approach entails.

2

Look for a cancer center (hospital) offering SMART for mesothelioma. While the concept began in Canada, it’s offered at a few cancer centers in the United States through clinical trials.

3

Contact a patient advocate. This step is important to connecting with a cancer center with SMART for mesothelioma. Patient advocates will coordinate an initial consultation for free.

SMART Surgery Types

SMART treats pleural mesothelioma, which accounts for around 80% of all mesothelioma cases. This cancer forms near the lungs, in a thin lining called the pleura.

SMART uses extrapleural pneumonectomy (EPP) after radiation. Doctors remove the nearby lung (ipsilateral lung), along with the:

  • Pleura
  • Part or all of the diaphragm
  • Lining around the heart

Doctors remove the lung within days after radiation ends. Dr. John Cho, of Princess Margaret, said they “don’t want to run the risk of leaving in a lung that’s inflamed and damaged due to radiation.”

Some doctors believe in pleurectomy with decortication (P/D) as an option. This surgery is less taxing for patients since it leaves both lungs intact. P/D for mesothelioma is part of the SMARTER evolution of the SMART protocol.

SMART Radiation Therapy Types

SMART uses a radiation therapy called “intensity-modulated radiation therapy.” This is shortened to the abbreviation IMRT.

IMRT sends highly focused radiation beams at the target. It’s an advancement from photon radiation (external beam radiation) as it decreases the damage to healthy tissue. IMRT still can affect the lung tissue and can cause pneumonitis (lung tissue inflammation and scarring).

Another option is proton beam radiation, which further reduces damage to healthy tissue. Dr. Cho said using proton radiation might not work. The method takes too much time due to the beam’s narrow radius.

“It’d be too challenging since the patient is breathing the entire time and the lung is moving,” he said.

Dr. Cho said an option is to use both IMRT and proton radiation. The former covers most of the lung and proton radiation is targeted just for just the part of the lungs with a noticeable chunk of tumors.

Survival Rates for SMART

SMART has impressive mesothelioma survival rates, possibly some of the best.

Doctors at Princess Margaret found that 72% of select patients survived for three years. The median life expectancy for epithelioid mesothelioma cases was 51 months (4 years, 3 months).

For all patients, the survival for SMART was 24.4 months. The general survival time for mesothelioma is around one year.

In 2021, doctors reported median survival of 65 months (5 years, 5 months) for 19 patients with epithelioid mesothelioma. All 19 also had an early stage diagnosis that hadn’t reached lymph nodes.

“I went back to double-check the numbers because I couldn’t believe it at first,” Dr. Cho said. “I thought we made a mistake.”

Side Effects of SMART

Princess Margaret researched the side effects of SMART for mesothelioma. Doctors found a recurrence rate of 63%.

Nearly half of patients experienced mild or severe complications within 30 days after EPP. One patient died from grade 5 pneumonia.

Other side effects include pneumonitis (lung tissue inflammation), lung scarring (fibrosis), breathing issues, fatigue and damage to skin. These occur due to radiation therapy.

EPP also can cause side effects, such as:

  • Internal bleeding
  • Respiratory failure
  • Pneumonia
  • Infection
  • Internal bleeding
  • Blood clots
  • Pulmonary edema
  • Cardiac issues

SMARTER Protocol for Mesothelioma

SMARTER is the evolution of SMART. It allows doctors to use P/D surgery instead of EPP, which requires a high level of physical fitness. More patients can enroll in SMARTER than SMART because more qualify based on health.

“We primarily use EPP, but we also do P/D as well,” said Dr. Elliot Wakeam, of Toronto General Hospital. “We can do both. I would tailor it to the patient. If you’re a young and fit patient, EPP gives you better disease clearance.”

SMARTER is still in the early stages of clinical trials and research. There’s no survival data available yet for SMARTER.

“Most patients are getting pleurectomy with decortication because it’s easier for them to tolerate,” Dr. Cho said, noting the fitness bar for EPP is higher, leading to fewer eligible patients. “Our population size is bigger with SMARTER for P/D.”

He added that the protocol must change. With both lungs still intact, radiation can damage the lung closest to the disease. Heavy radiation damage to a vital organ can be deadly. For P/D to work, doctors had to change the radiation dosages.

“The short answer is no,” Dr. Cho said. “We don’t believe we can directly apply what we’re doing with SMART to pleurectomy with decortication.

“We separated the lung into two buckets: the entire lung and the pleural disease. We dial (the radiation) up where the disease is and dial it down for the entire lung.”

SMARTEST Protocol for Mesothelioma

SMARTEST follows SMARTER in the evolution of SMART. SMARTEST would implement immunotherapy into the protocol.

Dr. Cho and other doctors believe immunotherapy — specifically checkpoint inhibitors like Keytruda and Opdivo — enhances radiation therapy. Likewise, radiation makes immunotherapy work faster.

“There is a theory that radiation may partially kill tumors, thus releasing antigens which prime the immune response,” said Dr. Wakeam, who worked at Princess Margaret and brought SMART to Michigan Medicine (he since moved to Toronto General Hospital). “Immunotherapy can help increase the response.”

Essentially, the sum of the two will be greater than each individual part on its own.

“We have more evidence that immunotherapy and radiation together may have a synergistic effect,” said Dr. Charles Simone, a radiation specialist and chief medical officer of the New York Proton Center.

SMARTEST Clinical Trial Begins at Princess Margaret Cancer Center in Toronto

A clinical trial for SMARTEST started at University Health Network in Toronto, Ontario, Canada. University Health Network includes the Princess Margaret Cancer Center. The trial opened May 19, 2022 and is now accepting patients.

The SMARTEST trial is a phase 2 study with up to 30 participants. Anyone who wants to join must be a candidate for aggressive mesothelioma surgery: either pleurectomy/decortication or extrapleural pneumonectomy.

Following surgery, patients receive the immunotherapy drugs tremelimumab and durvalumab for mesothelioma. Tremelimumab and durvalumab are immune checkpoint inhibitors. These immunotherapies block certain cancerous proteins that subdue the immune system.

Tremelimumab is a blockade for CTLA-4 and B7, two proteins that connect and help mesothelioma tumors hide from the immune system’s T cells. Durvalumab keeps PD-1 and PD-L1 apart. These two proteins also block the T cells’ activity.

SMARTEST is a multimodal therapy approach to mesothelioma. The order of radiation first, surgery second, and immunotherapy third is innovative and the first of its kind.

The SMARTEST trial is for people eligible for surgery, so you should ask your doctor about this option.

We at Mesothelioma Guide can also help you enroll in a specific clinical trial. This study is taking place at Princess Margaret Cancer Centre in Toronto, Ontario, Canada. If you do not want to travel to Toronto, then you might have to wait until the study expands to U.S. cancer centers.

Doctors and Cancer Centers Offering SMART

Princess Margaret Cancer Centre in Toronto is where SMART started. It’s the most famous hospital offering the approach.

Dr. Wakeam brought SMART for mesothelioma to Michigan Medicine. He joined the hospital in2019 and started the protocol soon after.

Dr. Cho stressed the importance of going to a respected cancer center. He said SMART requires experienced surgeons to perform either EPP or P/D.

“It seems that there’s a steep learning curve to get the technique down,” Dr. Cho said.

Other doctors and cancer centers offer SMART or a version of SMART for mesothelioma. Contact our patient advocates to learn more about options close to you.

Sources & Author

    1. Surgery for malignant pleural mesothelioma after radiotherapy (SMART): final results from a single-centre, phase 2 trial. The Lancelet. Retrieved from: https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(20)30606-9/fulltext. Accessed: 01/13/2021.
    2. A feasibility study evaluating Surgery for Mesothelioma After Radiation Therapy: the “SMART” approach for resectable malignant pleural mesothelioma. Journal of Thoracic Oncology. Retrieved from:
      https://www.ncbi.nlm.nih.gov/pubmed/24445595. Accessed: 04/28/2020.
    3. Radiation before surgery more than doubles mesothelioma survival: UHN study. University Health Network. Retrieved from:
      https://www.uhn.ca/corporate/News/PressReleases/Pages/radiation_before_-surgery_doubles_mesothelioma_survival.aspx. Accessed: 04/28/2020.
    4. Extrapleural Pneumonectomy. University of California San Francisco Department of Surgery. Retrieved from: https://surgery.ucsf.edu/conditions–procedures/extrapleural-pneumonectomy.aspx. Accessed: 02/16/2021.
    5. Extrapleural Pneumonectomy. Medstar Washington Hospital Center. Retrieved from: https://www.medstarwashington.org/our-services/thoracic-surgery/treatments/extrapleural-pneumonectomy/. Accessed: 02/16/2021.
    6. SMARTEST Trial. Clinicaltrials.gov. Retrieved from: https://clinicaltrials.gov/ct2/show/NCT05380713. Accessed: 06/28/2022.
Devin Golden

About the Writer, Devin Golden

Devin Golden is a content writer for Mesothelioma Guide. He produces mesothelioma-related content on various mediums, including the Mesothelioma Guide website and social media channels. Devin's objective is to translate complex information regarding mesothelioma into informative, easily absorbable content to help patients and their loved ones.