Durham Reporter

Therapies designed to harness the body's immune system have significantly enhanced survival rates for cancer patients, yet they pose potential risks for those whose cancer has metastasized to the brain. New research from the Duke Cancer Institute, published in JAMA Network Open, highlights a nearly twofold increase in the risk of symptomatic brain inflammation, or radiation necrosis, among these patients when immunotherapy drugs are administered within four weeks of radiosurgery.

"Our findings reveal a previously unreported risk of brain tissue damage in patients who receive dual immune-checkpoint blockade therapies within four weeks of radiosurgery," stated Zachary J. Reitman, M.D., Ph.D., senior author of the study and assistant professor in multiple departments at Duke University School of Medicine. This discovery could lead to improved strategies for deploying these therapies effectively to enhance tumor control while minimizing adverse effects.

The study, involving 288 patients with melanoma and lung cancer, analyzed outcomes concerning the timing of immunotherapy and radiosurgery. Of these, 82 patients received dual immune-checkpoint blockade comprising ipilimumab and nivolumab. Nearly 26% of these patients experienced symptomatic brain inflammation, compared to 12.3% who received a single immunotherapy and 13.7% who received none.

Lead author Eugene J. Vaios, M.D., emphasized that extending the interval between radiosurgery and dual immunotherapy to more than four weeks significantly reduced the risk of brain inflammation. "We found that patients who developed symptomatic brain tissue damage within 12 months of radiosurgery had significantly worse survival," Vaios remarked. Future research is aimed at reducing tissue damage by refining therapy sequencing and developing predictive algorithms.

In addition to Reitman and Vaios, the research involved authors including Rachel F. Shenker, Peter G. Hendrickson, Zihan Wan, Donna Niedzwiecki, among others. Funding for the study was provided by the National Cancer Institute, under the National Institutes of Health.