External validation of Cardiac disease, Hypertension, and Logarithmic Left anterior descending coronary artery radiation dose (CHyLL) for predicting major adverse cardiac events after lung cancer radiotherapy.

Abstract

Major adverse cardiac events(MACE) are prevalent in patients with locally advanced-non-small cell lung cancer(LA-NSCLC) following radiotherapy(RT). The CHyLL model, incorporating coronary heart disease(CHD),Hypertension(HTN),Logarithmic LADV15 was developed and internally-validated to predict MACE among LA-NSCLC patients. We sought to externally validate CHyLL to predict MACE in an independent LA-NSCLC cohort. Patients with LA-NSCLC treated with RT were included. CHyLL score was calculated:5.51CHD+1.28HTN+1.48ln(LADV15+1)-1.36CHD*ln(LADV15+1). CHyLL performance in predicting MACE was assessed and compared to mean heart dose(MHD) using Cox-proportional hazard(PH) analyses and Harrel's concordance(C)-indices. MACE and overall survival(OS) among low-vs high-risk groups(CHyLL<5 vs≥5) were compared. In the external validation cohort(N=102), the median age was 71years and 55% were females. Most(n=74,73%), had clinical Stage III disease and 35(34%) underwent surgery. CHyLL demonstrated good MACE prediction with C-index of 0.73(95% Confidence Interval(CI):0.58-0.89), while MHD did not (C-index=0.46 (95% CI:0.30-0.62)). Per CHyLL, 32(31%) and 70(69%) patients were considered low-and high-risk for MACE, respectively. CHyLL consistently identified lower MACE rates in the low-vs high-risk group(log-rank p=0.108):0 vs 8%(12months),5 vs 16%(24months),5 vs 16%(36months),and 5 vs 19%(48months) post-RT. In the pooled internal and external validation cohort(N=303), MACE rates in low-vs high-risk groups were statistically significantly different(log-rank p=0.01):1 vs 6%(12months),3 vs 12%(24months),6 vs 19%(36months),and 6 vs 21%(48months). CHyLL was externally validated and superior to MHD in predicting MACE. CHyLL has the potential to identify high-risk patients who may benefit from cardio-oncology optimization and to estimate personalized LADV15 constraints based on cardiac risk factors and acceptable MACE thresholds.