Coronary Artery Calcifications and Cardiac Risk After Radiation Therapy for Stage III Lung Cancer

Abstract

Purpose: Heart dose and heart disease increase the risk for cardiac toxicity associated with radiation therapy. We hypothesized that computed tomography (CT) coronary calcifications are associated with cardiac toxicity and may help ascertain baseline heart disease.

Methods and materials: We analyzed the cumulative incidence of cardiac events in patients with stage III non-small cell lung cancer receiving median 74 Gy on prospective dose-escalation trials. Events were defined as symptomatic effusion, pericarditis, unstable angina, infarction, significant arrhythmia, and/or heart failure. Coronary calcifications were delineated on simulation CTs using radiation software program (130 HU threshold). Calcifications were defined as "none," "low," and "high," with median volume dividing low and high.

Results: Of 109 patients, 26 had cardiac events at median 26 months (range, 1-84 months) after radiation therapy. Median follow-up in surviving patients was 8.8 years (range, 2.3-17.3). On simulation CTs, 64 patients (59%) had coronary calcifications with median volume 0.2 cm³ (range, 0.01-8.3). Only 16 patients (15%) had baseline coronary artery disease. Cardiac events occurred in 7% (3 of 45), 29% (9 of 31), and 42% (14 of 33) of patients with no, low, and high calcifications, respectively. Calcification burden was associated with cardiac toxicity on univariate (low vs none: hazard ratio [HR] 5.0, P = .015; high vs none: HR 8.1, P < .001) and multivariate analyses (low vs none: HR 7.0, P = .005, high vs none: HR 10.6, P < .001, heart mean dose: HR 1.1/Gy, P < .001). Four-year competing risk-adjusted event rates for no, low, and high calcifications were 4%, 23%, and 34%, respectively.

Conclusions: The presence of coronary calcifications is a cardiac risk factor that can identify high-risk patients for medical referral and help guide clinicians before potentially cardiotoxic cancer treatments.

Figure 1.

Examples of patients (A-C) with cardiac toxicity who had no known cardiac history, but calcifications detected on radiation planning simulation CT (images on left, calcifications delineated in automated fashion shown in red) or diagnostic CT (images on right, calcifications delineated manually shown in blue)

Figure 2.

Cumulative incidence of competing risk-adjusted symptomatic cardiac events in patients divided based on calcification burden (A), heart mean dose for all patients (B), and heart mean dose for patients with calcifications (C).

Figure 3.

Estimated 4-year competing risk-adjusted symptomatic cardiac event rate in patients grouped into 9 unique bins by both calcification burden (No, Low, High calcs) and mean heart dose (<10 Gy, 10-20 Gy, ≥20 Gy).