The medical community is investigating every possible avenue for fighting mesothelioma. All combinations are in play.
Surgery with chemotherapy is the most common pairing for this fast-spreading cancer. Adding radiation is the most proven combination. Researchers are investigating whether immunotherapy and chemotherapy work together. Also on the docket is whether immunotherapy and virotherapy can improve survival.
Up until now, this treatment tag team hasn’t been the focus of experimental studies. Clinical trials have mostly focused on immunotherapy and radiation separately, with other standard methods.
But in the coming years, this may change.
“As immunotherapy is coming more in favor, that may make radiation more in favor,” said Dr. Charles Simone, the chief medical officer of the New York Proton Center. “We have more evidence that immunotherapy and radiation together may have a synergistic effect.”
An Untested Treatment Pairing
“Everything works in theory, right?”
Those were the words of one mesothelioma specialist and thoracic surgeon who is wary of most experimental treatment approaches. Immunotherapy and radiation could be another example.
Immunotherapy with radiation is a novel idea, but it also makes sense from a biological standpoint. The immune system responds when something goes awry in the body. When something is present that shouldn’t be.
Viruses and other toxins elicit an immune system response. Cancers like mesothelioma should flip the switch for the immune system.
However, cancers like mesothelioma have proteins that deceive the immune system’s detection system. Think of it like a robber who evades the motion sensors inside a building. The mesothelioma tumors can grow and replicate freely, without much resistance from the immune system’s T-cells.
Immunotherapy (explicitly checkpoint inhibitor drugs) is the medical community’s answer to this dilemma. Drugs such as pembrolizumab and nivolumab cause the robber to activate the motion sensors. The T-cells and other immune system agents target the mesothelioma cells when they come across them.
But how can we inspire the T-cells to swarm to the tumor locations faster? That’s where radiation factors in.
“Immunotherapy ramps up the body’s chances of fighting cancer,” Dr. Simone said. “Radiation can inflame the body where the cancer exists, and then the immune system responds to that (inflammation).”
Radiation also can kill tumors and release cancerous proteins, which serve as a fingerprint for the immune system to match with other cells.
“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. “Immunotherapy can help increase the response.
“That’s the idea anyway. It’s a theory.”
Implementing Immunotherapy Into Multimodal Protocols
Michigan Medicine utilizes the SMART protocol for pleural mesothelioma. This method was conceptualized by Dr. Marc de Perrot at Princess Margaret Cancer Center in Toronto, where Dr. Wakeam adopted it as his go-to multimodal therapy regimen for pleural mesothelioma.
Now at Michigan Medicine, Dr. Wakeam champions SMART. The acronym stands for “surgery for mesothelioma after radiation therapy.” Patients undergo five sessions of radiation before curative surgery. The radiotherapy stops tumor growth and kills cells on the margins, making bulk removal of the disease easier during surgery.
Immunotherapy with radiation could double the tumor-killing effect.
Dr. Harvey Pass, a cardiothoracic surgeon at New York University’s Langone Medical Center, is one of the top mesothelioma specialists in the world. In the May 2020 edition of the Journal of Thoracic and Cardiovascular Surgery, he gave written applause to the SMART protocol.
He went further, though, suggesting it could be the avenue for introducing immunotherapy with radiation.
“Checkpoint inhibition will ‘take the brakes off’ of the inhibitory effect of immune cytotoxicity,” Dr. Pass wrote, “… however, studies have shown that you can get more ‘bang for your buck’ when you add other therapies to the checkpoint inhibitors. Early studies reveal that the chance for greater than 90% tumor kill, as well as long-term progression-free survival and overall survival, increase remarkably with combination therapy.”
Combination therapy pairing radiation and immunotherapy — whether before or after surgery, or with chemotherapy as well — could be the potion to permanently stop mesothelioma, or at least slow it down. Survival rates of a few months would turn into multiple years.
At least, that’s the theory.
Show Sources & Author
- Commentary: Not only SMART clinically, but translationally. Journal of Thoracic and Cardiovascular Surgery. Retrieved from:
https://www.jtcvs.org/article/S0022-5223(19)32114-2/pdf. Accessed: 06/16/2020.