TY - JOUR
T1 - Incident Atrial Fibrillation and Survival Outcomes in Esophageal Cancer following Radiotherapy
AU - Miller, Eric D.
AU - Wu, Trudy
AU - McKinley, Grant
AU - Slivnick, Jeremy
AU - Guha, Avirup
AU - Mo, Xiaokui
AU - Prasad, Rahul
AU - Yildiz, Vedat
AU - Diaz, Dayssy
AU - Merritt, Robert E.
AU - Perry, Kyle A.
AU - Jin, Ning
AU - Hodge, Dinah
AU - Poliner, Michael
AU - Chen, Sunnia
AU - Gambril, John
AU - Stock, James
AU - Wilbur, Jameson
AU - Pierre-Charles, Jovan
AU - Ghazi, Sanam M.
AU - Williams, Terence M.
AU - Bazan, Jose G.
AU - Addison, Daniel
N1 - Publisher Copyright:
© 2023 Elsevier Inc.
PY - 2024/1/1
Y1 - 2024/1/1
N2 - Purpose: Radiation therapy (RT) associates with long-term cardiotoxicity. In preclinical models, RT exposure induces early cardiotoxic arrhythmias including atrial fibrillation (AF). Yet, whether this occurs in patients is unknown. Methods and Materials: Leveraging a large cohort of consecutive patients with esophageal cancer treated with thoracic RT from 2007 to 2019, we assessed incidence and outcomes of incident AF. Secondary outcomes included major adverse cardiovascular events (MACE), defined as AF, heart failure, ventricular arrhythmias, and sudden death, by cardiac RT dose. We also assessed the relationship between AF development and progression-free and overall survival. Observed incident AF rates were compared with Framingham predicted rates, and absolute excess risks were estimated. Multivariate regression was used to define the relationship between clinical and RT measures, and outcomes. Differences in outcomes, by AF status, were also evaluated via 30-day landmark analysis. Furthermore, we assessed the effect of cardiac substructure RT dose (eg, left atrium, LA) on the risk of post RT-related outcomes. Results: Overall, from 238 RT treated patients with esophageal cancer, 21.4% developed incident AF, and 33% developed MACE with the majority (84%) of events occurring ≤2 years of RT initiation (median time to AF, 4.1 months). Cumulative incidence of AF and MACE at 1 year was 19.5%, and 25.7%, respectively; translating into an observed incident AF rate of 824 per 10,000 person-years, compared with the Framingham predicted rate of 92 (relative risk, 8.96; P < .001, absolute excess risk 732). Increasing LA dose strongly associated with incident AF (P = .001); and those with AF saw worse disease progression (hazard ratio, 1.54; P = .03). In multivariate models, outside of traditional cancer-related factors, increasing RT dose to the LA remained associated with worse overall survival. Conclusions: Among patients with esophageal cancer, radiation therapy increases AF risk, and associates with worse long-term outcomes.
AB - Purpose: Radiation therapy (RT) associates with long-term cardiotoxicity. In preclinical models, RT exposure induces early cardiotoxic arrhythmias including atrial fibrillation (AF). Yet, whether this occurs in patients is unknown. Methods and Materials: Leveraging a large cohort of consecutive patients with esophageal cancer treated with thoracic RT from 2007 to 2019, we assessed incidence and outcomes of incident AF. Secondary outcomes included major adverse cardiovascular events (MACE), defined as AF, heart failure, ventricular arrhythmias, and sudden death, by cardiac RT dose. We also assessed the relationship between AF development and progression-free and overall survival. Observed incident AF rates were compared with Framingham predicted rates, and absolute excess risks were estimated. Multivariate regression was used to define the relationship between clinical and RT measures, and outcomes. Differences in outcomes, by AF status, were also evaluated via 30-day landmark analysis. Furthermore, we assessed the effect of cardiac substructure RT dose (eg, left atrium, LA) on the risk of post RT-related outcomes. Results: Overall, from 238 RT treated patients with esophageal cancer, 21.4% developed incident AF, and 33% developed MACE with the majority (84%) of events occurring ≤2 years of RT initiation (median time to AF, 4.1 months). Cumulative incidence of AF and MACE at 1 year was 19.5%, and 25.7%, respectively; translating into an observed incident AF rate of 824 per 10,000 person-years, compared with the Framingham predicted rate of 92 (relative risk, 8.96; P < .001, absolute excess risk 732). Increasing LA dose strongly associated with incident AF (P = .001); and those with AF saw worse disease progression (hazard ratio, 1.54; P = .03). In multivariate models, outside of traditional cancer-related factors, increasing RT dose to the LA remained associated with worse overall survival. Conclusions: Among patients with esophageal cancer, radiation therapy increases AF risk, and associates with worse long-term outcomes.
UR - http://www.scopus.com/inward/record.url?scp=85171201494&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85171201494&partnerID=8YFLogxK
U2 - 10.1016/j.ijrobp.2023.08.011
DO - 10.1016/j.ijrobp.2023.08.011
M3 - Article
C2 - 37574171
AN - SCOPUS:85171201494
SN - 0360-3016
VL - 118
SP - 124
EP - 136
JO - International Journal of Radiation Oncology Biology Physics
JF - International Journal of Radiation Oncology Biology Physics
IS - 1
ER -
