Concurrent Administration of Immune Checkpoint Inhibitors and Stereotactic Radiosurgery is Not Associated with an Increased Risk of Radiation Necrosis: An International Multicenter Study of 657 Patients

Purpose/Objective(s) Stereotactic radiosurgery (SRS) and immune checkpoint inhibitors (ICI) are highly effective treatments for brain metastases (BrM), particularly when these therapies are administered concurrently. However, there are limited data reporting the risk of radiation necrosis (RN) in this setting. Materials/Methods Patients with BrM from primary non-small cell lung cancer, renal cell carcinoma, or melanoma treated with SRS and ICI were considered. Recursive partitioning analysis (RPA) was utilized for model development, and a loop of potential models was analyzed, with the highest-fidelity model selected. Results Six hundred fifty-seven patients with 4,182 BrM across 11 international institutions were analyzed. Rates of RN and symptomatic RN (SRN) for all patients were 10% and 6.8%, respectively. The highest-fidelity models consistently identified V12 Gy as the dominant variable predictive of RN. Three risk groups were identified using V12 Gy: (1) < 12 cm3; (2) 20 cm3 ≤ V12 Gy ≥ 12 cm3; (3) > 20 cm3. Odds ratios for RN and SRN with cases of V12 Gy ≥ 12 cm3 compared with < 12 cm3 were 3.05 (p < 0.001) and 3.72 (p < 0.001), respectively. Rates of RN and SRN are presented in the table below. Concurrent ICI use rates were equivalent among these resulting groups, and the addition of concurrent ICI use did not improve the model's fidelity. Using RPA, 80% of the highest-fidelity models failed to incorporate concurrent ICI as a predictive variable. Even after exclusion of V12 Gy as a candidate variable, concurrent ICI remained unused in 85% of the highest-fidelity models. These models yielded 94% accuracy for the validation set and 92% accuracy for the test set. Conclusion Utilization of SRS and ICI results in a low risk of RN and SRN. This risk is not increased when ICI and SRS are administered concurrently. Therefore, ICI can safely be administered within 4-weeks of SRS. In patients receiving SRS and ICI, three risk groups based on V12 Gy were identified, which clinicians may consider to further reduce rates of RN.