Identification of Risk of Cardiovascular Disease by Automatic Quantification of Coronary Artery Calcifications on Radiotherapy Planning CT Scans in Patients With Breast Cancer

Abstract

IMPORTANCE Cardiovascular disease (CVD) is common in patients treated for breast cancer, especially in patients treated with systemic treatment and radiotherapy and in those with preexisting CVD risk factors. Coronary artery calcium (CAC), a strong independent CVD risk factor, can be automatically quantified on radiotherapy planning computed tomography (CT) scans and may help identify patients at increased CVD risk.OBJECTIVE To evaluate the association of CAC with CVD and coronary artery disease (CAD) in patients with breast cancer. DESIGN, SETTING, AND PARTICIPANTSIn this multicenter cohort study of 15 915 patients with breast cancer receiving radiotherapy between 2005 and 2016 who were followed until December 31, 2018, age, calendar year, and treatment-adjusted Cox proportional hazard models were used to evaluate the association of CAC with CVD and CAD.EXPOSURES Overall CAC scores were automatically extracted from planning CT scans using a deep learning algorithm. Patients were classified into Agatston risk categories (0, 1-10, 11-100, 101-399, >400 units). MAIN OUTCOMES AND MEASURESOccurrence of fatal and nonfatal CVD and CAD were obtained from national registries. RESULTSOf the 15 915 participants included in this study, the mean (SD) age at CT scan was 59.0 (11.2; range, 22-95) years, and 15 879 (99.8%) were women. Seventy percent (n = 11 179) had no CAC. Coronary artery calcium scores of 1 to 10, 11 to 100, 101 to 400, and greater than 400 were present in 10.0% (n = 1584), 11.5% (n = 1825), 5.2% (n = 830), and 3.1% (n = 497) respectively. After a median follow-up of 51.2 months, CVD risks increased from 5.2% in patients with no CAC to 28.2% in patients with CAC scores higher than 400. After adjustment, CVD risk increased with higher CAC score (hazard ratio [HR] CAC = 1-10 = 1.1; 95% CI, 0.9-1.4; HR CAC = 11-100 = 1.8; 95% CI, 1.5-2.1; HR CAC = 101-400 = 2.1; 95% CI, 1.7-2.6; and HR CAC>400 = 3.4; 95% CI, 2.8-4.2). Coronary artery calcium was particularly strongly associated with CAD (HR CAC>400 = 7.8; 95% CI, 5.5-11.2). The association between CAC and CVD was strongest in patients treated with anthracyclines (HR CAC>400 = 5.8; 95% CI, 3.0-11.4) and patients who received a radiation boost (HR CAC>400 = 6.1; 95% CI, 3.8-9.7).CONCLUSIONS AND RELEVANCE This cohort study found that coronary artery calcium on breast cancer radiotherapy planning CT scan results was associated with CVD, especially CAD. Automated CAC scoring on radiotherapy planning CT scans may be used as a fast and low-cost tool to identify patients with breast cancer at increased risk of CVD, allowing implementing CVD risk-mitigating strategies with the aim to reduce the risk of CVD burden after breast cancer.

An overview of radiation-induced heart disease

“…A multicenter cohort study evaluated the correlation between coronary artery calcium (CAC) and CAD. They found that CAC on breast cancer RT planning CT scan results was associated with CVD, especially CAD, particularly in CAC score > 400 [54]. Treatment of radiation-induced CAD with common revascularization techniques is challenging, as those patients usually have more complex anatomy and disease complexity, scarred and fibrotic grafts and higher rates of postoperative complications, such as poor healing, infections and bleeding, and higher mortality as compared to CAD from other causes [18,19].…”

“…Radiation doses above 30 Gy reportedly increased RIHD by three and a half folds [18,56]. Some of the studies about radiation-related risk factors are summarized in Table 1 [47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62][63][64].…”

Cardiac Computed Tomography in Cardio-Oncology

“…Furthermore, emerging data suggest that breast arterial calcification on mammography correlates with CAC, allowing for identification of atherosclerosis and subsequent ASCVD risk ( 34 ). Recently, the BRAGATSTON clinical trial evaluated if automated quantification of CAC on RT planning chest CTs was useful for CVD risk prediction ( 35 , 36 ). The investigators found that automated CAC scoring results might be used as a fast and low-cost tool to identify patients with breast cancer at increased CVD risk ( 36 ).…”

“…Recently, the BRAGATSTON clinical trial evaluated if automated quantification of CAC on RT planning chest CTs was useful for CVD risk prediction ( 35 , 36 ). The investigators found that automated CAC scoring results might be used as a fast and low-cost tool to identify patients with breast cancer at increased CVD risk ( 36 ).…”

Automated coronary artery calcium scoring in patients with breast cancer to assess the risk of heart disease following adjuvant radiation therapy

“…According to recent findings from Western studies on patients with breast cancer, the CAC score has shown to be predictive in the development of ACE in breast cancer patients [ 15 , 18 ]. However, the value of the CAC score needs to be confirmed and validated in other geographic areas as cardiac diseases have a multifactorial etiology, including race- and patient-specific factors.…”