Radt-07 Impact of Keap1/Nfe2l2 Variants on Local Control in NSCLC Brain Metastases Treated With Stereotactic Radiosurgery

The Kelch-like ECH-associated protein 1 (KEAP1)/nuclear factor erythroid 2-like 2 (NFE2L2) reactive oxygen species processing pathway may be a useful biomarker of clinical radioresistance in localized non-small cell lung cancer (NSCLC). It is unknown whether KEAP1/NFE2L2 variants impact the response of brain metastases from NSCLC to radiotherapy. Here, we tested whether KEAP1/NFE2L2 variants associate with rates of local control in patients with NSCLC brain metastases undergoing stereotactic radiosurgery (SRS). We hypothesize KEAP1/NFE2L2 pathogenic variants (PV) are associated with decreased local control (LC) and increased time to intracranial progression (ICP). 541 patients undergoing SRS for NSCLC brain metastases at a single institution were retrospectively identified; n=269 underwent clinical next generation sequencing. Kaplan-Meier analyses were calculated for LC and ICP; results across variant status were compared using the log-rank test. Comparisons were performed for variant versus no mutation, and by variant type (PV and variant of unknown significance (VUS)). At 12 months, LC was 90.8% (95% CI, 79.2-96.1%) among patients with variants, compared to 90.6% (84.4-94.4%) in patients without. There was no significant difference in median time to ICP between patients with variants (5.1 months; 95% CI, 3.3-9.5 months) compared to those without (7.2 months; 95% CI, 5.7-9.5 months). 12-month LC was 92.15±5.33% in PV, 89.43±5.89% in VUS, and 90.6±2.46% in patients without mutations. LC and ICP displayed a non-significant trend for differences when KEAP1/NFE2L2 PV and VUS were compared. Overall, KEAP1/NFE2L2 variant status did not demonstrate a statistically significant difference in LC or ICP after SRS for brain metastases in this cohort. On the basis of these data, KEAP1/NFE2L2 variant status should not impact clinical management of NSCLC brain metastasis patients. Larger cohorts are needed to examine KEAP1/NFE2L2 status association with outcomes among NSCLC brain metastasis patients. Thus, the impact of KEAP1/NFE2L2 mutations may differ in the localized versus metastatic setting.