SMART Protocol for Mesothelioma Adds Immunotherapy

Research & Clinical Trials
Reading Time: 3 mins
Publication Date: 07/06/2017
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How to Cite’s Article


Povtak, T. (2020, October 16). SMART Protocol for Mesothelioma Adds Immunotherapy. Retrieved October 5, 2022, from


Povtak, Tim. "SMART Protocol for Mesothelioma Adds Immunotherapy.", 16 Oct 2020,


Povtak, Tim. "SMART Protocol for Mesothelioma Adds Immunotherapy." Last modified October 16, 2020.

Scientist with Petri dishes

The innovative SMART protocol for treating pleural mesothelioma cancer is on the verge of getting smarter.

Doctors at the Princess Margaret Cancer Center in Toronto — where the SMART approach was first used — are designing a new protocol that will incorporate immunotherapy into the high-dose radiation/aggressive surgery mix that has been so successful.

It will be known as SMART v2.0, the acronym for an improved version of Surgery for Mesothelioma After Radiation Therapy.

“We’re still getting a grip on all the different potential interactions,” Dr. John Cho of the cancer center’s clinical research unit told “We’re deciding the details but with a strong interest in including these new, exciting immunotherapy insights.”

The original SMART protocol for mesothelioma involves accelerated hypofractionated radiation, preceding the aggressive extrapleural pneumonectomy (EPP) surgery.

Most mesothelioma specialty centers in the U.S. with a multimodal approach first use chemotherapy, followed by surgery, and conclude with a lower dose of radiation if necessary.

The reverse-order approach from Toronto resulted in a 66 percent, three-year survival rate among patients with the epithelial subtype of mesothelioma and no lymph node involvement, almost double the normal rate in the U.S.

That study, presented at the annual America Association for Thoracic Surgery meeting, reported a median overall survival and disease-free survival at 51 and 47 months, respectively.

“We believe this approach is making a difference. We’ve been doing it a lot, and it works,” Cho said. “When you have an aggressive tumor [like mesothelioma], you need management that will match it aggressively.”

Adding Immunotherapy Will Improve Treatment

Several factors, including the belief that high-dose radiation alone activates a patient’s own immune system against the cancer, sparked the move to add immunotherapy to the treatment mix.

Researchers in Toronto also recently published results from a mouse-model study, involving the addition of different immunotherapy drugs combined with the high dose radiation, in the journal Clinical Cancer Research. The study showed increased efficacy with various combinations.

Ipilimumab (Yervoy), atexolizumab (Tecentriq) and pembrolizumab (Keytruda) were among the immunotherapy drugs tested. All have shown effectiveness in clinical trials involving other cancers.

“The ultimate goal, of course, is to translate this type of lab research into the clinic,” Cho said. “These immunotherapy agents are very specific and only work in certain circumstance. Predicting the behavior is very complex.”

SMART Protocol Remains Controversial

Cho estimates that it will be 6-12 months before a new clinical protocol with immunotherapy is started.

Despite its impressive results, not all researchers and doctors embrace the SMART approach. The reason: It’s an aggressive treatment.

The high level of radiation before surgery eliminates the option of leaving the lung intact. The EPP is designed to remove the entire lung, the lining around it and parts of the diaphragm.

In some instances, though, a surgeon will change course, and do less, once the chest is opened. The radiation eliminates that option. There is no turning back once the SMART procedure begins. It requires close coordination between the radiologist and surgical staff.

According to previous studies, 80-85 percent of the patients in the U.S. who begin an EPP actually have the entire lung removed. The SMART approach requires a much-stricter patient selection process.

“A specific activation of the immune system against the tumor contributes to the benefit of accelerated hypofractionated radiation before surgery,” authors of the latest study wrote. “In conclusion, we demonstrated the importance of the immune system in the benefit of clinical protocols using…radiation followed by surgery.”

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