Early Detection of Radiation-Induced Cardiotoxicity in Patients Receiving Thoracic Radiation

• Published in: International journal of radiation oncology, biology, physics Vol. 120; no. 2; p. S174
• Main Authors: Montalvo, S.K., Lue, B., Kakadiaris, E., Ahn, C., Zhang-Velten, E.R., Aliru, M.L., Lu, W., Westover, K.D., Iyengar, P., Timmerman, R.D., Zaha, V., Vallabhaneni, S., Zhang, K., Chandra, A., Alluri, P.G.
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.10.2024
• ISSN: 0360-3016
• DOI: 10.1016/j.ijrobp.2024.07.2211

Many patients receiving thoracic radiation therapy (TRT) suffer collateral damage to the heart. Thus, radiation-induced cardiotoxicity (RIC) is a competing risk factor for cardiac events and death. Therefore, novel strategies for early detection of RIC at a time point that offers potential for mitigation are urgently needed. Global Longitudinal Strain (GLS), a measure of the relative longitudinal shortening of myocardial fibers during systole, predicts long-term cardiac outcomes in diverse clinical setting. However, the association between TRT and GLS remains poorly defined. We hypothesize that abnormal changes in GLS following TRT predict worse survival outcomes in these patients. We retrospectively reviewed an institutional cohort of patients from 2012-2020 who received TRT with mean heart dose ≥ 5 Gy who had both pre- and post-RT ECHOs with measurable GLS. GLS was defined as abnormal if it was <18% or if there was >15% relative drop from a normal baseline value. Patient demographic data were extracted from electronic medical records. Pre- and post-RT groups were compared with paired statistics, McNeemar's test, and log-rank test via the Kaplan-Meier method. 38 patients with ECHOs at a median of 85 days before and 172 days after RT were included; median follow up was 40.3 weeks (range 4.6 – 534.4). Abnormal GLS was common at baseline (n=12, 31.6%) and more frequent after RT (n=22, 57.9%) OR 10 (95% CI 1.42 – 433.98, p = 0.0117). In contrast, the proportion of patients with abnormal left ventricular ejection fraction (LVEF) <50% was not significantly different after radiation (n=9, 23.6%) when compared to pre-radiation baseline (n=6, 15.8%) (p = 0.25). Patients with abnormal GLS were older (mean age 67.9 vs 60, p = 0.027) and more likely to be men (63.6% vs 18.8%, p = 0.009) compared to patients with a normal GLS, but other clinical characteristics including race, stage, histology, chemotherapy exposure, and RT delivery method were not statistically different. 1-yr and 2-yr overall survival (OS) was significantly worse among patients with abnormal GLS (45% and 32%, respectively) compared to those with normal GLS (75% and 75%, respectively) based on an overall log-rank testing (p = 0.0491). Although there was imbalance in age and sex between the normal and abnormal GLS groups, OS was not significantly different when stratified by age >65 and sex (p = 0.72 and 0.28). We have shown for the first time that abnormal changes in GLS are common after TRT, precede changes in LVEF, and predict worse OS in these patients. Given existing evidence on the effectiveness of GLS-directed cardioprotection therapies in improving cardiac outcomes in cancer patients, early detection of RIC using GLS may enable adoption of mitigation strategies to preserve cardiac function in patients receiving TRT. Prospective studies to validate these hypothesis-generated findings are warranted.