Original Investigation
Cardiac Radiation Dose, Cardiac Disease, and Mortality in Patients With Lung Cancer

https://doi.org/10.1016/j.jacc.2019.03.500Get rights and content
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Abstract

Background

Radiotherapy-associated cardiac toxicity studies in patients with locally advanced non–small cell lung cancer (NSCLC) have been limited by small sample size and nonvalidated cardiac endpoints.

Objectives

The purpose of this analysis was to ascertain whether cardiac radiation dose is a predictor of major adverse cardiac events (MACE) and all-cause mortality (ACM).

Methods

This retrospective analysis included 748 consecutive locally advanced NSCLC patients treated with thoracic radiotherapy. Fine and Gray and Cox regressions were used to identify predictors for MACE and ACM, adjusting for lung cancer and cardiovascular prognostic factors, including pre-existing coronary heart disease (CHD).

Results

After a median follow-up of 20.4 months, 77 patients developed ≥1 MACE (2-year cumulative incidence, 5.8%; 95% confidence interval [CI]: 4.3% to 7.7%), and 533 died. Mean radiation dose delivered to the heart (mean heart dose) was associated with a significantly increased risk of MACE (adjusted hazard ratio [HR]: 1.05/Gy; 95% CI: 1.02 to 1.08/Gy; p < 0.001) and ACM (adjusted HR: 1.02/Gy; 95% CI: 1.00 to 1.03/Gy; p = 0.007). Mean heart dose (≥10 Gy vs. <10 Gy) was associated with a significantly increased risk of ACM in CHD-negative patients (178 vs. 118 deaths; HR: 1.34; 95% CI: 1.06 to 1.69; p = 0.014) with 2-year estimates of 52.2% (95% CI: 46.1% to 58.5%) versus 40.0% (95% CI: 33.5% to 47.4%); but not among CHD-positive patients (112 vs. 82 deaths; HR: 0.94; 95% CI: 0.70 to 1.25; p = 0.66) with 2-year estimates of 54.6% (95% CI: 46.8% to 62.7%) versus 50.8% (95% CI: 41.5% to 60.9%), respectively (p for interaction = 0.028).

Conclusions

Despite the competing risk of cancer-specific death in locally advanced NSCLC patients, cardiac radiation dose exposure is a modifiable cardiac risk factor for MACE and ACM, supporting the need for early recognition and treatment of cardiovascular events and more stringent avoidance of high cardiac radiotherapy dose.

Key Words

cardiac toxicity
cardiotoxicity
non–small cell lung cancer
NSCLC
radiotherapy

Abbreviations and Acronyms

ACM
all-cause mortality
CHD
coronary heart disease
CTCAE
common terminology criteria for adverse event
CVD
cardiovascular disease
MACE
major adverse cardiac events
MHD
mean heart dose
NSCLC
non–small cell lung cancer

Cited by (0)

Dr. Williams has received research grants from Varian Medical Systems. Dr. Nguyen has received consulting fees from Blue Earth, Ferring, Janssen, Astellas, Cota, Nanobiotix, Genome DX, Augmenix, Boston Scientific, Dendreon, and Bayer; and has received grants (to institution) from Janssen and Astellas. Dr. Nohria has received a research grant (to institution) from Amgen; and has served as a consultant for Takeda Oncology. Dr. Hoffmann has received research grants (to institution) from Medimmune, Kowa, and HeartFlow Inc. Dr. Aerts has received consulting fees from Sphera and Genospace. Dr. Mak has served on the Scientific Advisory Board of AstraZeneca; and has received an honorarium from NewRT. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

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