TY - JOUR
T1 - Identification of Risk of Cardiovascular Disease by Automatic Quantification of Coronary Artery Calcifications on Radiotherapy Planning CT Scans in Patients with Breast Cancer
AU - Gal, Roxanne
AU - Van Velzen, Sanne G.M.
AU - Hooning, Maartje J.
AU - Emaus, Marleen J.
AU - Van Der Leij, Femke
AU - Gregorowitsch, Madelijn L.
AU - Blezer, Erwin L.A.
AU - Gernaat, Sofie A.M.
AU - Lessmann, Nikolas
AU - Sattler, Margriet G.A.
AU - Leiner, Tim
AU - De Jong, Pim A.
AU - Teske, Arco J.
AU - Verloop, Janneke
AU - Penninkhof, Joan J.
AU - Vaartjes, Ilonca
AU - Meijer, Hanneke
AU - Van Tol-Geerdink, Julia J.
AU - Pignol, Jean Philippe
AU - Van Den Bongard, Desirée H.J.G.
AU - Išgum, Ivana
AU - Verkooijen, Helena M.
N1 - Funding Information:
Funding/Support: This study was funded by the Dutch Cancer Society (grant number UU 2015-7947).
Funding Information:
reported receiving grants from the Dutch Cancer Society, Pie Medical Imaging, the Dutch Technology Foundation (with participation of Pie Medical Imaging) and the Netherlands Organisation for Health Research and Development (with participation of Pie Medical Imaging), receiving fees for lectures from Philips Healthcare and Bayer Healthcare, being shareholder of Quantib-U BV, and a patent with royalties planned. Prof de Jong reported receiving research support from Philips Healthcare. Dr Penninkhof reported receiving grants from Elekta AB and Accuray, Inc. Dr Isgum reported receiving grants from the Dutch Cancer Society, Pie Medical Imaging, the Dutch Technology Foundation (with participation of Philips Healthcare), and the Netherlands Organisation for Health Research and Development, and reported being cofounder of and shareholder in Quantib-U BV. Dr Verkooijen reported receiving research grants from Elekta AB. No other conflicts of interest that could have influenced the work in this article were reported.
Publisher Copyright:
© 2021 American Medical Association. All rights reserved.
PY - 2021/7/1
Y1 - 2021/7/1
N2 - 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 Participants: In this multicenter cohort study of 15915 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 Measures: Occurrence of fatal and nonfatal CVD and CAD were obtained from national registries. Results: Of the 15915 participants included in this study, the mean (SD) age at CT scan was 59.0 (11.2; range, 22-95) years, and 15879 (99.8%) were women. Seventy percent (n = 11179) 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; HRCAC = 11-100= 1.8; 95% CI, 1.5-2.1; HRCAC = 101-400= 2.1; 95% CI, 1.7-2.6; and HRCAC>400= 3.4; 95% CI, 2.8-4.2). Coronary artery calcium was particularly strongly associated with CAD (HRCAC>400= 7.8; 95% CI, 5.5-11.2). The association between CAC and CVD was strongest in patients treated with anthracyclines (HRCAC>400= 5.8; 95% CI, 3.0-11.4) and patients who received a radiation boost (HRCAC>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. Trial Registration: ClinicalTrials.gov Identifier: NCT03206333.
AB - 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 Participants: In this multicenter cohort study of 15915 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 Measures: Occurrence of fatal and nonfatal CVD and CAD were obtained from national registries. Results: Of the 15915 participants included in this study, the mean (SD) age at CT scan was 59.0 (11.2; range, 22-95) years, and 15879 (99.8%) were women. Seventy percent (n = 11179) 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; HRCAC = 11-100= 1.8; 95% CI, 1.5-2.1; HRCAC = 101-400= 2.1; 95% CI, 1.7-2.6; and HRCAC>400= 3.4; 95% CI, 2.8-4.2). Coronary artery calcium was particularly strongly associated with CAD (HRCAC>400= 7.8; 95% CI, 5.5-11.2). The association between CAC and CVD was strongest in patients treated with anthracyclines (HRCAC>400= 5.8; 95% CI, 3.0-11.4) and patients who received a radiation boost (HRCAC>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. Trial Registration: ClinicalTrials.gov Identifier: NCT03206333.
KW - Breast Neoplasms/diagnostic imaging
KW - Cardiovascular Diseases/diagnostic imaging
KW - Cohort Studies
KW - Coronary Artery Disease/complications
KW - Female
KW - Humans
KW - Risk Factors
KW - Tomography, X-Ray Computed/methods
UR - http://www.scopus.com/inward/record.url?scp=85105858822&partnerID=8YFLogxK
U2 - 10.1001/jamaoncol.2021.1144
DO - 10.1001/jamaoncol.2021.1144
M3 - Article
C2 - 33956083
AN - SCOPUS:85105858822
SN - 2374-2437
VL - 7
SP - 1024
EP - 1032
JO - JAMA Oncology
JF - JAMA Oncology
IS - 7
ER -