Symptomatic Radiation Necrosis Linked To Immunotherapy Use During Brain Metastases Radiation

medwireNews: Treating brain metastases with an immune checkpoint inhibitor alongside stereotactic radiotherapy may increase the likelihood of symptomatic radiation necrosis, suggests research published in JAMA Oncology.

The study of patients with newly diagnosed brain metastases from melanoma, non-small-cell lung cancer or renal cell carcinoma included 115 individuals given ipilimumab, pembrolizumab or nivolumab for a median of 14.3 weeks alongside stereotactic radiation. Their outcome was compared with that of 365 patients who received radiotherapy alone.

Symptomatic radiation necrosis was defined as an enlarging lesion causing neurological symptoms that was confirmed as necrosis on surgical resection or showed changes consistent with necrosis on imaging, explain Ayal Aizer, from Brigham and Women’s Hospital in Boston, Massachusetts, USA, and co-authors.

This outcome was reported for 23 of the immunotherapy-treated patients and 25 of the controls, giving a significant hazard ratio (HR) for symptomatic radiation necrosis of 2.56 with immunotherapy after adjusting for tumour histology, they report.

Further analysis showed that the association between symptomatic radiation necrosis and receipt of immunotherapy was especially pronounced in patients with melanoma, with a HR of 4.02 versus no immunotherapy. For melanoma patients, use of ipilimumab gave a significant HR of 4.70, while receipt of pembrolizumab or nivolumab gave a HR of 3.57, although this did not reach statistical significance.

“Given the strong association between immunotherapy and symptomatic radiation necrosis that we observed, utilization of immunotherapy as monotherapy for treatment of brain metastases has appeal,” Ayal Aizer et al write. 

“However, intracranial response rates to immune-checkpoint monotherapy in patients with brain metastases are generally low, although concurrent ipilimumab plus nivolumab in melanoma has promise,” they comment. 

The authors conclude: “Prospective studies are needed to better characterize the risks and benefits of combining brain-directed stereotactic radiation with immunotherapy in this population.”

Reference

Martin AM, Cagney DN, Catalano PJ, et al. Immunotherapy and symptomatic radiation necrosis in patients with brain metastases treated with stereotactic radiation. JAMA Oncol; Advance online publication 11 January 2018. doi:10.1001/jamaoncol.2017.3993