medwireNews: Combining dual immune checkpoint inhibitors (ICIs) with radiosurgery for the treatment of brain metastases is associated with an elevated risk for symptomatic radionecrosis, indicates a database analysis.
“This finding is consistent with reports of increased symptomatic radionecrosis following concurrent antibody-drug conjugate therapy and radiosurgery,” write the investigators in a research letter to JAMA Network Open.
They explain that “[r]adionecrosis, a delayed form of brain injury after radiosurgery, is a serious neuro-oncologic challenge with significant patient morbidity and mortality,” the risk for which could be exacerbated by immunotherapy as it “may prime the tumor microenvironment and amplify radiation-induced immune responses.”
For this study, the team collated data from an institutional database on 288 patients (53% men, median age 64 years) with non-small-cell lung cancer or melanoma and brain metastases who underwent radiosurgery between January 2014 and August 2022. Twenty-eight percent of the patients received dual ICIs, 45% received a single ICI, and 27% received no ICIs.
A total of 51 (18%) of participants developed symptomatic radionecrosis over a median follow-up of 58.8 months, of which just over half (53%) of the cases were confirmed by pathologic assessment.
The 24-month cumulative incidence of symptomatic radionecrosis was higher among patients who received dual ICIs than those who received single or no ICIs, at 21.8% versus 13.5% and 13.7%, respectively.
The increased incidence appeared to be driven by concurrent use of dual immunotherapy – defined as treatment given in the 4 weeks before or after radiosurgery – with a 24-month cumulative incidence of 25.9% versus 12.3% with concurrent single immunotherapy.
By contrast, the incidence was not higher when dual ICIs were given sequentially.
After adjusting for various patient and treatment factors, dual checkpoint inhibition was found to be the only factor that was significantly associated with an increased risk for symptomatic radionecrosis, at a hazard ratio of 2.4.
Finally, Zachary Reitman (Duke Cancer Institute, Durham, North Carolina, USA) and co-authors found that survival within a year of radiosurgery was significantly worse for people who did versus did not develop radionecrosis, at respective medians of 6.9 and 46.0 months.
They therefore say that “[w]hen clinically feasible, clinicians should consider delaying radiosurgery by 4 weeks or offer fractionated radiosurgery in patients receiving dual-immune checkpoint blockade.”
The researchers acknowledge the limitations of the study, such as its nonrandomized and retrospective nature, and conclude that “[o]ngoing trials (including NRG-BN013, ABC-X, HYPOGRYPHE) are needed to validate these findings.”
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