Heart dose and coronary artery calcification in patients receiving thoracic irradiation for lung cancer

Abstract

Background: Thoracic irradiation (TIR) is associated with an increased risk of coronary artery disease (CAD) and coronary-related death. Lung cancer patients receive considerable doses of TIR, making them a high-risk population that may benefit from post-therapy surveillance. Coronary artery calcium (CAC) is a known biomarker of CAD development and may serve as a useful indicator of disease progression in this population. We hypothesized greater CAC progression in lung cancer patients subjected to higher whole heart radiation doses. Methods: CAC progression (pre-and >2 years post-TIR) from chest CT scans of lung cancer patients were evaluated. A 2:1 matched control population was established controlling for age, gender, race, and CT scan interval. Vessel-specific CAC presence, progression, and extension in pre-and post-interval CT studies was evaluated by two blinded reviewers using the ordinal method. Dosimetric treatment files were restored and contours of the whole heart and proximal left anterior descending artery (LAD) were created within existing plans to compute radiation doses (Pinnacle Treatment Planning Software). Binary logistic regression analysis identified factors predictive for CAC development. Multiple logistic regression analysis with hierarchal method was used to assess covariates. Results: Thirty-five patients and 65 controls (50% female) were evaluated; mean age 57 years, mean follow-up post-radiation 4.9±2.2 years. Average mean and maximum left anterior descending coronary artery (LAD) radiation doses were 19.9 Gy (95% CI, 14.1-25.7) and 30.7 Gy (95% CI, 23.8-37.5), respectively; 91.6% inter-observer variability. There was greater incidence of coronary calcification in irradiated patients (48.6% vs. 24.6%; P=0.01). In interval CT scans, a greater proportion of radiated patients demonstrated new coronary calcification (P=0.007) and extension within the LAD (P=0.003). Radiation exposure was the only independent predictor of new calcification (OR 3.1; 95% CI: 1.09-9.2). Conclusions:We identified both an increase in the development and progression of CAC in lung cancer patients receiving TIR. Future studies utilizing alternative cancer populations and larger sample sizes are necessary to further correlate radiographic and dosimetric observations to cardiovascular events.

Long-term prognostic significance of history of cancer and atrial fibrillation in coronary artery disease

“…A report from Korea revealed an increased risk of de novo malignancy after percutaneous coronary intervention (PCI) compared to age- and sex-matched control patients who had not undergone PCI [8] . Of note, the study showed that the risk for lung and hematologic cancers was higher than that for other types of cancer [7] . Conversely, in patients with established cancer, the treatment for malignancy may have adverse effects on the genesis and progression of CAD [13] .…”

“…A recent meta -analysis showed that patients with cancer had a 1.5-fold increased risk of developing AF compared to those without cancer [4] . Additionally, cancer survivors have been found to have an increased risk of developing CAD [6] , [7] . Moreover, a previous study found a bidirectional association between the presence of CAD and an increased risk of death in patients with cancer [8] .…”

Common Pathophysiology in Cancer, Atrial Fibrillation, Atherosclerosis, and Thrombosis

“…Although pre-existing factors may affect the risk for developing CAD and cancer, in patients with established cancer, the treatment for their malignancy may also have adverse effects on the genesis and progression of CAD. Radiation, which is used in the treatment of various types of cancers, has been shown to increase the risk for ischemic heart disease ( 102 , 103 , 104 ). In one study, patients who received thoracic radiation for lung cancer had progression in coronary artery calcium, a known predictor of CAD, compared with those who did not ( 103 ).…”

“…Radiation, which is used in the treatment of various types of cancers, has been shown to increase the risk for ischemic heart disease ( 102 , 103 , 104 ). In one study, patients who received thoracic radiation for lung cancer had progression in coronary artery calcium, a known predictor of CAD, compared with those who did not ( 103 ). Various classes of cytotoxic chemotherapy have been known to cause cardiotoxicity, cardiomyopathy, and vascular toxicity, which may contribute to increased atherosclerotic risk ( 105 ).…”

Cardiac Computed Tomography in Cardio-Oncology

“…Several small single-center studies suggest that baseline CAC might help identify subclinical ASCVD and predict CV events in these patients ( 45 , 46 , 47 ). Although there are limited data, there may be a role for CAC surveillance in these patients as it may demonstrate ASCVD disease progression related to RT ( 43 , 48 ) ( Figure 2 ). Cardiac CT has the ability to characterize atherosclerotic plaques and show features related to vulnerability; however, there are no data yet regarding the relationship of baseline plaque vulnerability, RT exposure, and outcomes.…”