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.

• Authors: Biniyam G Demissei, Gary Freedman, Steven J Feigenberg, John P Plastaras, Amit Maity, Amanda M Smith, Caitlin McDonald, Karyn Sheline, Charles B Simone 2nd, Lilie L Lin, Joseph R Carver, Peter Liu, Liyong Zhang, Justin E Bekelman, Bonnie Ky
• Journal: International journal of radiation oncology, biology, physics (Int J Radiat Oncol Biol Phys) Vol. 103 Issue 4 Pg. 851-860 (03 15 2019) ISSN: 1879-355X [Electronic] United States
• PMID: 30445173 (Publication Type: Clinical Trial, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018. Published by Elsevier Inc.

Chemical References

• Biomarkers

Topics

• Adult
• Biomarkers (metabolism)
• Breast Neoplasms (radiotherapy)
• Cardiovascular System (physiopathology, radiation effects)
• Female
• Humans
• Lung Neoplasms (radiotherapy)
• Lymphoma (radiotherapy)
• Male
• Middle Aged
• Myocardium (pathology)
• Radiation Injuries (etiology, metabolism, pathology, physiopathology)
• Stroke Volume (radiation effects)
• Thorax
• Time Factors