Treatment with immunotherapy and radiation has been shown to not increase the risk of radiation necrosis for patients with non-small cell lung cancer who have brain metastases, according to research.

In particular, immune checkpoint inhibitors (ICIs) alongside stereotactic radiotherapy (SRS), a type of immunotherapy and radiation, respectively, do not increase the risk of radiation necrosis in this patient population. However, researchers have identified a relationship between the volume of the brain area being targeted by radiation and radiation necrosis.

A retrospective study conducted through the International Radiosurgery Research Foundation, findings of which were published in the Journal of Neuro-Oncology, included 395 patients with 2,540 brain metastases treated with single fraction SRS and ICI, with a median patient age of 67 years old and a median follow-up of 14.2 months.

“The risk of any grade radiation necrosis and symptomatic radiation necrosis following single fraction stereotactic radiosurgery and immune checkpoint inhibition for non-small cell lung cancer brain metastases increases as V12 Gy exceeds 10 cm3,” said senior study author Dr. Manmeet S. Ahluwalia, chief of medical oncology, chief scientific officer, deputy director and Fernandez Family Foundation Endowed Chair in Cancer Research at Miami Cancer Institute, part of Baptist Health South Florida, in a news release.

These findings are consistent with the position taken by the authors of a prior study published in the Journal of Applied Clinical Medical Physics, stating that “multiple studies have shown a strong correlation between V12 and incidence of radiation necrosis.”

“Concurrent immune checkpoint inhibition and stereotactic radiosurgery do not appear to increase this risk,” Ahluwalia stated. “Instead, radiosurgical planning techniques should aim to minimize V12 Gy. In addition, the study suggests that treatment with immune checkpoint inhibitors can continue when radiation necrosis occurs.”

Stereotactic radiosurgery “delivers a large, precise radiation dose to the tumor area in a single session,” and may be used for some tumors in parts of the patient’s brain or spinal cord that can’t be treated with surgery or when a patient isn’t healthy enough for surgery, and radiation necrosis is a rare but possible side effect of radiation therapy where a mass of dead tissue forms at the tumor site in the months or years following treatment, as explained by the American Cancer Society.

Approximately 80% of brain metastases originate from cases of non-small cell lung cancer, study authors wrote. According to the American Lung Association, approximately 25% of patients with lung cancer will have a brain metastasis at the time they receive their diagnosis, and there is a lifetime brain metastasis risk of approximately 50%, although the commonality of brain metastases varies by cancer type and the presence of certain biomarkers within the cancer.

Among all patients in the Journal of Neuro-Oncology study, at one year the cumulative incidence of any-grade and symptomatic radiation necrosis was 4.8% and 3.8%, respectively. Any-grade radiation necrosis occurred in 3.8% of patients who received concurrent immune checkpoint inhibition and stereotactic radiosurgery versus 5.3% of patients who didn’t, and the rates for symptomatic radiation necrosis were 3.8% and 3.6% for the concurrent and non-concurrent treatment patient cohorts, respectively.