Therapy Combination Carries Risk for Cancer Patients with Brain Metastases
Contact
DURHAM, N.C. – Therapies that unleash the immune system to fight tumors have greatly extended the lives of people with many types of cancer.
But there are reports that patients with melanoma and lung cancer whose disease has spread to the brain may experience serious inflammatory reactions after receiving immunotherapy drugs concurrently with radiation.
In a study appearing April 9 in JAMA Network Open, researchers at the Duke Center for Brain and Spine Metastasis report a nearly two-fold increase in the risk of symptomatic brain inflammation, termed radiation necrosis, among patients with brain metastases receiving the immunotherapies within four weeks of a form of targeted radiation therapy called 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,” said senior author Zachary J. Reitman, M.D., Ph.D., assistant professor in the departments of Radiation Oncology, Neurosurgery and Pathology at Duke University School of Medicine. “Identifying this risk can potentially lead to more effective use of these therapies to maximize tumor control and reduce adverse effects.”
Reitman and colleagues in the Duke Cancer Institute -- including lead author Eugene J. Vaios, M.D., assistant professor of Radiation Oncology – analyzed outcomes from 288 melanoma and lung cancer patients at Duke. Eighty-two patients were treated with dual immune-checkpoint blockade of ipilimumab plus nivolumab; 129 received only a single immunotherapy drug; and 77 received no immunotherapy. All underwent radiosurgery.
Of the patients who received the dual immune-checkpoint blockade concurrently with radiosurgery, 25.9% developed symptomatic inflammation and damage to tissue in their brains. In contrast, 12.3% of patients who received only one immunotherapy and radiosurgery, and 13.7% of patients who received no immunotherapy, experienced similar injury.
Vaios said the researchers also found that the rates of symptomatic inflammation were significantly reduced when the interval between radiosurgery and dual immune-checkpoint blockade exceeded four weeks (e.g., sequential therapy). With sequential therapy, this risk became comparable to treatment with one immunotherapy or no immunotherapy.
That could improve the odds of survival after radiosurgery.
“We found that patients who developed symptomatic brain tissue damage within 12 months of radiosurgery had significantly worse survival,” Vaios said. “In future studies, we hope to identify a way to reduce tissue damage, perhaps by better sequencing therapies and by developing predictive algorithms to better quantify risk, guide treatment selection, and appropriately counsel patients.”
In addition to Vaios and Reitman, study authors include Rachel F. Shenker, Peter G. Hendrickson, Zihan Wan, Donna Niedzwiecki, David Carpenter, Warren Floyd, Sebastian Winter, Helen A. Shih, Jorg Dietrich, Chunhao Wang, April K.S. Salama, Jeffrey M. Clarke, Karen Allen, Paul Sperduto, Trey Mullikin, John P. Kirkpatrick, and Scott Floyd.
The study received funding support from the National Cancer Institute, which is part of the National Institutes of Health (5R38-CA245204, 1K38CA292995-01, K08-CA2560450).