Patients with melanoma and lung cancer who have brain metastases may experience severe inflammatory reactions after receipt of immunotherapy drugs combined with radiation therapy, according to a recent study published by Vaios et al in JAMA Network Open.
Study Methods and Results
In this study, researchers analyzed the outcomes of 288 patients with melanoma and lung cancer—82 of whom were treated with dual immune checkpoint blockade of ipilimumab plus nivolumab, 129 of whom received a single immunotherapy drug, and 77 of whom received no immunotherapy. All patients underwent radiosurgery.
The researchers reported a nearly twofold increase in the risk of radiation necrosis among patients with brain metastases receiving the immunotherapies within 4 weeks of radiosurgery. Among the patients who received the dual immune checkpoint blockade concurrently with radiosurgery, 25.9% developed symptomatic inflammation and damage to the tissue in their brains. In contrast, 12.3% of the patients who received just one immunotherapy and radiosurgery as well as 13.7% of those who received no immunotherapy experienced similar injury.
The rates of radiation necrosis were significantly reduced when the interval between radiosurgery and dual immune checkpoint blockade exceeded 4 weeks. For instance, with sequential therapy, this risk became comparable to that of treatment with one immunotherapy or no immunotherapy.
Conclusions
“Our findings reveal a previously unreported risk of brain tissue damage in patients who receive dual immune checkpoint blockade therapies within 4 weeks of radiosurgery,” detailed senior study author Zachary J. Reitman, MD, PhD, Assistant Professor in the Department of Radiation Oncology, Neurology, and Pathology at the 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,” he added.
The researchers hope the results of their study may help to improve the rate of survival after radiosurgery. “We found that patients who developed symptomatic brain tissue damage within 12 months of radiosurgery had significantly worse survival,” underscored lead study author Eugene J. Vaios, MD, MBA, Assistant Professor of Radiation Oncology at the Duke Cancer Institute. “In future studies, we [plan] 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,” he concluded.
Disclosure: The research in this study was supported by the National Cancer Institute of the National Institutes of Health. For full disclosures of the study authors, visit jamanetwork.com.
