Coronary artery calcium score on standard of care oncologic CT scans for the prediction of adverse cardiovascular events in patients with non-small cell lung cancer treated with concurrent chemoradiotherapy

Abstract

IntroductionChemoradiotherapy (CRT) has been associated with increased incidence of cardiovascular (CV) adverse events (CVAE). Coronary artery calcium scoring (CAC) has shown to predict coronary events beyond the traditional CV risk factors. This study examines whether CAC, measured on standard of care, non-contrast chest CT (NCCT) imaging, predicts the development of CVAE in patients with non-small cell lung cancer (NSCLC) treated with CRT.MethodsPatients with NSCLC treated with CRT at MD Anderson Cancer Center from 7/2009 until 4/2014 and who had at least one NCCT scan within 6 months from their first CRT were identified. CAC scoring was performed on NCCT scans by an expert cardiologist and a cardiac radiologist following the 2016 SCCT/STR guidelines. CVAE were graded based on the most recent Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. CVAE were also grouped into (i) coronary/vascular events, (ii) arrhythmias, or (iii) heart failure. All CVAE were adjudicated by a board-certified cardiologist.ResultsOut of a total of 193 patients, 45% were female and 91% Caucasian. Mean age was 64 ± 9 years and mean BMI 28 ± 6 kg/m2. Of 193 patients, 74% had CAC >0 Agatston units (AU), 49% CAC ≥100 AU and 36% CAC ≥300 AU. Twenty-nine patients (15%) developed a grade ≥2 CVAE during a median follow-up of 24.3 months (IQR: 10.9–51.7). Of those, 11 (38%) were coronary/vascular events. In the multivariate cox regression analysis, controlling for mean heart dose and pre-existing CV disease, higher CAC score was independently associated with development of a grade ≥2 CVAE [HR: 1.04 (per 100 AU), 95% CI: 1.01–1.08, p = 0.022] and with worse overall survival (OS; CAC ≥100 vs. <100 AU, HR: 1.64, 95% CI: 1.11–2.44, p = 0.013). In a sub-analysis evaluating the type of the CVAE, it was the coronary/vascular events that were significantly associated with higher baseline CAC (median: 676 AU vs. 73 AU, p = 0.035).DiscussionCardiovascular adverse events are frequent in patients with NSCLC treated with CRT. CAC calculated on “standard of care” NCCT can predict the development of CVAEs and specifically coronary/vascular events, as well as OS, independently from other traditional risk factors and radiation mean heart dose.Clinical trial registration[https://clinicaltrials.gov/ct2/show/NCT00915005], identifier [NCT00915005].

Does coronary artery calcium score have an impact on overall survival for locally advanced non-small cell lung cancer treated with definitive radiotherapy

“…5-year overall survival was 25% (95% CI 22-29) (Figure 2). Median survival differed between the CACs groups (univariable pvalue 0.49); in CACs 0, median survival was 28 months (95% CI [23][24][25][26][27][28][29][30][31][32][33][34][35][36], while in CACs 1-99, 32 months (26-40), and decreasing median survival in CACs 100-399 and CACs ≥400, with a median survival of respectively 24 months (95% CI 17-29) and 20 months (95% CI [16][17][18][19][20][21][22][23][24][25][26]. Kaplan-Meier survival estimates for the overall survival grouped by CACs are shown in Figure 2.…”

“…To match a recent study [18], the analysis was repeated with CACs divided into two groups: CACs < 100 and ≥100. The entire analysis was also performed in two additional unplanned analyses: 1) without forcing the CAC into the model and 2) excluding patients with mean tumor dose below 60 Gy.…”

“…Traditional risk factors for cardiac diseases, such as hypertension, diabetes, and dyslipidemia [17], are rarely systematically collected in patients with LA-NSCLC, so there is a need for a prognostic marker that can identify LA-NSCLC patients at an increased risk of cardiac disease, in need of cardiac risk factor optimization before radiotherapy treatment. The role of CACs as a prognostic marker for overall survival in LA-NSCLC patients has previously only been tested in a few small studies suggesting an impact of CACs on overall survival [18,19].…”

Early Cardio-Oncology Intervention in Thoracic Radiotherapy: Results of the Cardiac Aggressive Risk Mitigation (CARMA) Pilot Study

“…Furthermore, our study demonstrated how readily available CV risk markers, such as the presence of CAC on RT planning CTs and/or LAD radiation dose exposure, can capture additional at-risk patients for CV events. Baseline CAC on RT planning CT scans has been associated with increased risk of major cardiac events in patients with breast 27,28 and lung cancer 9,[29][30][31] , yet CAC assessment prior to initiation of cancer treatment is not routinely performed. Similarly, evidence suggests that cardiac substructure radiation dose exposure, particularly to the left coronary arteries, is a better predictor of MACE compared to whole heart dose (i.e., mean heart dose) and warrants inclusion into the global CV risk assessment of patients receiving cardiotoxic cancer therapies 6, [10][11][12][13] We further characterized the prevalence of CHIP at baseline and after completion of RT.…”

Multimodality imaging in cardio-oncology: the added value of CMR and CCTA

“…A baseline Calcium Score quantification on a non-contrast ECG-gated chest CT performed during the cancer staging phase is strongly suggested according to the strong evidence correlation between coronary calcification and increased risk for a major adverse cardiac event. 94 …”