Effect of Cardiac Radiation Doses on Survival in Treatment of Stage III Non-Small Cell Lung Cancer Patients

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Radiotherapy-induced cardiac toxicity and mortality studies data are based on breast cancer and lymphoma trials. The survival of on non-small cell lung cancer (NSCLC) patients increases as new chemotherapy agents and modern radiotherapy (RT) techniques are applied. Studies investigating the effect of heart radiation doses on survival are insufficient. In this study, the main purpose is to determine whether cardiac radiation dose is a predictive factor on overall survival (OS) in stage III NSCLC patients. A total of 167 patients with stage III NSCLC who received definitive chemoradiotherapy at our center between April 2014 and October 2019 were retrospectively evaluated. Heart and left anterior descending artery (LAD) targets were determined according to the Radiotherapy Oncology Group (RTOG) 1106 study. Heart doses were measured at 5 Gy intervals from 5 Gy (V5) to 70 Gy receiving volumes (V70). Minimum, maximum and mean doses for heart and LAD were examined. The presence of coronary artery disease (CAD) was recorded before RT. Cox regression analysis was performed using the backward likelihood ratio method for risk assessment on survival and statistical significance was considered as p <0.05 values The median follow-up duration was median 15 months (2-55). It was observed that 40 Gy (V40) (p = 0.038), 45 Gy (V45) (p = 0.038), 50 Gy V50 (p = 0.038) and 55 Gy V55 (p = 0.038) receiving volumes respectively were effective on survival. Dose-volume threshold values in percentage were calculated by ROC analysis. Threshold values were determined as 18% for V40, 14% for V45, 10% for V50 and 8% for V55. In the univariate analysis, advanced age (p = 0.002), heart V40≤ 18% (p = 0.026) and heart V45 ≤ 14% (p = 0.012) were statistically significant on OS. For one- and two-year cumulative OS in patients with heart doses of V40≤ 18% and V45≤ 14%, were 77% and 48%, whereas for patients with heart doses V40> 18% and V45> 14% were 66% and 38%, respectively. The mean heart dose was 17.56 Gy (0.17-53) and the mean LAD dose was 11.08 Gy (0.17-46). There was no statistically significant effect of both heart and LAD mean doses on OS. At the time of diagnosis, 38 (29%) patients had CAD. There was no statistically significant difference between patients with and without CAD in terms of OS and heart doses. Predictive factors affecting OS in multivariate Cox regression analysis were found as advanced age (HR = 1.05, 95% CI = 1.03-1.07, p <0 0.01), V40≤ 18% (HR = 1.53, 95% CI = 1.03-2.27, p = 0 037) and V45≤ 14% (HR = 1.58, 95% CI = 1.06-2.35, p = 0 024). Despite the risk of cancer-specific death in locally advanced NSCLC patients, exposure to a high dose of cardiac radiation is a modifiable cardiac risk factor for OS. In our study, advanced age, V40>18%, and V45 >14% were shown to have a negative predictive effect on survival.