Princess Margaret Cancer Centre in Toronto, Canada, made history with its “SMART” protocol for mesothelioma.

The next version is already in the works. And the next-next one, too.

The mesothelioma researchers, oncologists and surgeons at the cancer centre created SMART a few years ago. The acronym stands for “surgery for mesothelioma after radiation therapy.”

They have deemed the next installment SMARTER, which isn’t a perfectly wrapped acronym. The protocol offers surgeons an option for which surgery to use.

SMART relies solely on the lung-removing extrapleural pneumonectomy (EPP). SMARTER, by comparison, allows for EPP or pleurectomy with decortication (P/D). The latter spares the lung.

“We wanted to make the surgery easier for the patient,” said Dr. John Cho, a specialist at Princess Margaret.

Some U.S. cancer centers — like Michigan Medicine — have incorporated SMART. If you’re interested in this treatment approach, contact our patient advocates. Email and we’ll help you find a cancer center offering SMART for mesothelioma.


The Basis of SMART for Mesothelioma

For decades, doctors thought radiation worked best after surgery. This was especially true for mesothelioma. Doctors could remove visible tumors and direct cancer-killing radioactive beams at the hidden ones.

However, Princess Margaret doctors switched up the order. Radiation beforehand would make surgery easier and prevent patients from undergoing treatment after an invasive surgery.

In the latest results from the cancer centre, doctors found a median survival of 65 months for 19 epithelioid patients with an early stage of mesothelioma. This far exceeds the survival times for most studies involving this asbestos cancer. In fact, it’s the best survival outcome for any group of patients in any lengthy mesothelioma study.

“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.”

The overall survival is around two years, which is promising. Most patients don’t reach two years even after surgery. The general life expectancy after diagnosis is one year, usually due to a late stage when diagnosed.

Extending late-stage patients’ lives is enough reason to believe in SMART.


Why SMARTER Helps?

EPP removes the lung, and not all patients can withstand such an impactful operation. This led the way for SMARTER, which allows for P/D after radiation.

The general protocol is the same, but the details are different.

“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.”

Why? Well, with both lungs still intact, radiation can damage the lung closest to the disease. Heavy radiation damage to a vital organ can be deadly.

“We don’t want to run the risk of the lung being inflamed and damaged due to radiation,” Dr. Cho said.

That’s why EPP is preferred. Doctors remove the lung before its damage can impact survival. For P/D to work, doctors had to change the radiation dosages.

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

Patients are enrolling in SMARTER, but it’s too early to report any findings. The study only began around a year ago, and it’s mostly focusing right now on safety and feasibility over survival. The good news is it’s easier to enroll patients for a P/D study than an EPP one.

“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.”

The study will include four groups. The first involves no dose to the entire lung and a boost on the pleural disease. Then doctors will slowly increase the dose on the entire lung.

“There’s some evidence to suggest there’s an immune system effect to giving high-dose radiation,” Dr. Cho said.

And that, in part, led to the idea of SMARTEST.



Immunotherapy for mesothelioma is now considered a safe and effective treatment. The United States Food and Drug Administration (FDA) approved a drug combination: Opdivo (nivolumab) and Yervoy (ipilimumab) for unresectable mesothelioma.

At Princess Margaret, they’re already wondering how to use immunotherapy in the third evolution of SMART. The combination of radiation and immunotherapy could improve each other individually.

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.

“There is a theory that radiation may partially kill tumors, thus releasing antigens which prime the immune response,” said Dr. Elliot Wakeam, a thoracic surgeon and mesothelioma specialist at Michigan Medicine.

SMARTEST needs more brainstorming — should immunotherapy come before radiation, after it, or after surgery? — but Dr. Cho is confident it’s “definitely going to happen.”

“We’ve just been a bit cautious because we’ve seen people jump on the bandwagon and give these immunotherapy agents and not get the response we’re hoping for,” Dr. Cho said.

Guide Packet Desktop Ad

Want to learn more?

Try Our Free Guide to Fighting Mesothelioma

Get in depth knowledge about your diagnosis & the best treatments.

Learn More
Guide Packet Mobile Ad

    Sources & Author

Picture of Devin Golden

About the Writer, Devin Golden

Devin Golden is the 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.