Early Changes in Cardiovascular Biomarkers with Contemporary Thoracic Radiation Therapy for Breast Cancer, Lung Cancer, and Lymphoma

Abstract

Purpose: We characterized the early changes in cardiovascular biomarkers with contemporary thoracic radiation therapy (RT) and evaluated their associations with radiation dose-volume metrics including mean heart dose (MHD), V5, and V30.

Methods and materials: In a prospective longitudinal study of 87 patients with breast cancer, lung cancer, or mediastinal lymphoma treated with photon or proton thoracic RT, blood samples were obtained pre-RT and after completion of RT (median, 20 days; interquartile range [IQR], 1-35). High-sensitivity cardiac troponin T, N-terminal pro-B-type natriuretic peptide, placental growth factor (PIGF), and growth differentiation factor 15 (GDF-15) were measured. Associations between MHD, V5 and V30, and biomarker levels and associations between echocardiography-derived measures of cardiac function and biomarker levels were assessed in multivariable linear regression models. Analyses were performed according to the following subgroups: (1) breast cancer alone and (2) lung cancer and lymphoma combined.

Results: The median (IQR) estimates of MHD ranged from 1.3 Gy (0.9-2.4) in breast cancer (n = 60) to 6.8 Gy (5.4-10.2) in mediastinal lymphoma (n = 14) and 8.4 Gy (6.7-16.1) in lung cancer (n = 13) patients (P < .001). There were no significant increases in biomarker levels from pre-RT to post-RT in breast cancer. In lung cancer/lymphoma, PIGF increased from a median (IQR) of 20 ng/L (16-26) to 22 ng/L (16-30) (P = .005), and GDF-15 increased from 1171 ng/L (755-2493) to 1887 ng/L (903-3763) (P = .006). MHD, V5, and V30 were significantly associated with post-RT PIGF and GDF-15 levels in multivariable models. Changes in biomarkers were not significantly associated with changes in echocardiography-derived measures of cardiac function.

Conclusion: Contemporary thoracic RT induces acute abnormalities in vascular and inflammatory biomarkers that are associated with radiation dose-volume metrics, particularly in lung cancer and mediastinal lymphoma. Long-term follow-up studies are needed to determine the impact of these changes on the development of overt cardiac disease.

Fig. 1.

Changes in biomarker levels from pre-RT to the completion of RT in breast cancer (A) and lung cancer/mediastinal lymphoma (B). Box plots depict biomarker distributions at each time point; gray lines show individual changes in biomarker levels from pre-RT to the completion of RT. Abbreviations: GDF-15 = growth differentiation factor 15; hs-cTnT = high-sensitivity cardiac troponin T; NT-proBNP = N-terminal B-type natriuretic peptide; PIGF = placental growth factor; RT = radiation therapy.

Fig. 2.

Proportion of patients with potentially clinically significant elevation in biomarker levels from pre-RT to completion of RT in breast cancer (A) and lung cancer/mediastinla lymphoma (B). The height of the bars represents the proportion of patients who developed potentially clinically significant elevations in biomarkers from pre-RT to the completion of RT (i.e., >30% elevation or increase to >14 ng/L for hs-cTnT, and >30% elevation for the other biomarkers). Abbreviations: GDF-15 = growth differention factor 15; hs-cTnT = high sensitivity cardiac troponin T; NT-proBNP = Nterminal B-type natriuretic peptide; PIGF = placental growth factor; RT = radiation therapy.