The effect of coronary artery calcifications and radiotherapy on the risk of coronary artery disease

The effect of coronary artery calcifications and radiotherapy on the risk of coronary artery disease in high-risk breast cancer patients in the DBCG RT-Nation cohort

Refsgaard L, Holm Milo ML, Buhl ES, Jensen JM, Maae E, Berg M, Jensen I, Nielsen MH, Lorenzen EL, Thorsen LBJ, Korreman SS, Offersen BV.

Radiother Oncol. 2025

Background and purpose: Radiotherapy improves outcomes for breast cancer. However, prior studies have correlated the risk of coronary artery disease (CAD) to the mean heart dose (MHD), mean dose to the left anterior descending artery (LAD_mean) and the left ventricle V5Gy (LV5). Other studies showed an increased risk of CAD for patients with pronounced coronary artery calcification (CAC) at the time of radiotherapy.

Materials and methods: This cohort study included 3355 high-risk breast cancer patients treated in Western Denmark (2008-2016). The planning CT scans, treatment plans, and dose distributions were analyzed. Coronary artery calcification (CAC) was measured using the Agatston score. Agatston score is a semi-automated tool to calculate a score based on the extent of CAC detected by an unenhanced low-dose CT scan. The score allows for early risk stratification as patients with a high Agatston score (in the literature regarded as >160) have an increased risk for a major adverse cardiac event.

We examined the dose-response relationship between MHD, LV5 and LAD_mean and CAD, and the effect of CAC presence at radiotherapy. Secondary analysis assessed overall survival.

Results: Of 3355 patients, 45 (1.2 %) developed CAD during follow-up. Agatston score was a strong predictor of CAD risk with a hazard ratio of 9.51(CI95:5.16-17.53) for Agatston score ≥ 100 versus Agatston score < 100 and a 6.7 % difference in absolute cumulative CAD risk at ten years (7.7 % vs 1 %). For AS < 100 (97 % of patients) CAD risk increased with MHD, hazard ratio 1.25 (CI95:1.01-1.56) per Gy. For Agatston score ≥ 100, CAD risk was driven by CAC rather than radiation dose. CAC was associated with poorer overall survival. Median MHD for the whole cohort was 1.25 Gy (IQR:1.01-1.56).

Conclusion: Agatston score from planning CT-scans predicted CAD risk and overall survival in breast cancer patients receiving radiotherapy. The MHD remained the strongest predictor in patients with low CAC. For patients with high CAC, the high baseline risk from CAC was a stronger risk factor than the dose-related risk.