Liquid biopsy-based genomic risk score to predict neurologic death in non-small cell lung cancer patients

Biomarkers that predict neurologic death may allow for personalization of therapy for high-risk brain metastases patients.

Patients with NSCLC who underwent comprehensive genomic profiling were identified in an institutional database. Neurologic death was determined by medical record review. Proportional hazards regression models considering non-neurologic death as a competing risk were used to identify mutations statistically associated with the occurrence of neurologic death (p < 0.1) and to create a risk scoring system for neurologic death. A competing risk proportional hazards regression model with non-neurologic death as a competing risk was used to assess the association between the risk score and neurologic death, and to calculate hazard ratios predicting neurologic death between risk groups.

307 patients were included in the primary analysis and 213 in a cohort of patients with brain metastases. Risk scores were constructed in both populations. Patients with higher risk scores had an increased risk of neurologic death when compared to those in the low-risk group, with respective HRs of 3.76 for the entire cohort and 2.87 for the brain metastasis cohort per unit increase in the risk score. When dividing the risk score into three groups, the cumulative incidence of neurologic death in high, moderate, and low risk groups was 49.0%, 20.3% and 0% for the entire cohort and 52.4%, 30.4%, and 0% in the brain metastasis cohort.

Development of a genomic signature to predict neurologic death via non-invasive liquid biopsy appears feasible in NSCLC patients.