Combining Immunotherapy, Accelerated Radiation and Surgery Bolsters Immune Response Against Mesothelioma, Study Shows

Combining Immunotherapy, Accelerated Radiation and Surgery Bolsters Immune Response Against Mesothelioma, Study Shows

Combining immunotherapy, accelerated radiation and surgery can improve immune system response against malignant pleural mesothelioma, according to a study.

Immunotherapies for solid tumors have become a major focus of cancer research, with promising preliminary results. But the advances have raised the question of what is the best way to integrate the new treatments with standard-of-care therapies.

Studies have indicated that some radiotherapy regimens can bolster immune-system responses to a tumor, although the reason why is not fully understood.

Malignant pleural mesothelioma is commonly treated with chemotherapy, radiation and surgery. Preclinical-trial studies indicate that immunotherapies can help fight this aggressive cancer, although the results have yet to be confirmed in randomized clinical trials.

University of Toronto researchers wanted to see if accelerated radiation could bolster a patient’s immune response to mesothelioma. They also wanted to find the best way to integrate immunotherapy into standard-of-care mesothelioma treatment.

Their study, “In situ vaccination after accelerated hypofractionated radiation and surgery in a mesothelioma mouse model,” was published in the journal of Clinical Cancer Research.

The scientific name for accelerated radiation is accelerated hypofractionated radiation. The idea in accelerated radiation is exactly what the name implies: Give patients doses in a shorter time frame.

An advantage of accelerated radiation is that it generates less long-term damage to healthy tissue surrounding a tumor.

Researchers developed a mouse model of mesothelioma that would mimic the features of patients who had undergone accelerated radiation therapy. After radiation, the team performed surgery on the mice. Then they added immunotherapy to these regimens to see what the outcome would be.

Accelerated radiation triggered an immune response against the tumor cells, researchers discovered. In fact, when it was administered seven days before surgery, it triggered an immune response that was long-lasting.

The response was not seen in mice treated with surgery alone. Nor was it seen in mice treated with surgery and an accelerated-radiation short course 24 hours before surgery.

Another finding was that a combination of immunotherapies and an accelerated radiation short course improved mice’s immune response against cancer cells, compared with an accelerated radiation short course alone. The immunotherapies included Keytruda (pembrolizumab), Yervoy (ipilimumab), and Tecentriq (atezolizumab), which target the PD-1, CTLA-4 and PD-L1 proteins associated with cancer.

The immunotherapy-radiation combo was most effective when the immunotherapy was a CTLA-4 immune checkpoint inhibitor, researchers discovered.

“A specific activation of the immune system against the tumor contributes to the benefit of accelerated, hypofractionated radiation before surgery,” Luis de la Maza and colleagues at the University of Toronto’s Toronto General Research Institute wrote. “Non-ablative hypofractionated radiation combined with surgery provides an opportunity to introduce immune checkpoint blockades in the clinical setting.”

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