Prospective Exploratory Analysis of Cardiac Biomarkers and Electrocardiogram Abnormalities in Patients Receiving Thoracic Radiation Therapy with High-Dose Heart Exposure

Abstract

Introduction Acute effects of incidental cardiac irradiation in patients treated for thoracic cancer are not well characterized. We evaluated longitudinal changes in cardiac biomarkers for patients undergoing conformal radiation therapy (RT) with thoracic malignancies with high-dose cardiac exposure. Methods Twenty-five patients enrolled in a prospective trial (February 2009–December 2012) received ≥45 Gy to the thorax, with pretreatment estimates of ≥20 Gy to the heart. Chemotherapy was allowed except for doxorubicin or fluorouracil. Electrocardiographic (ECG), troponin-I (TnI), and brain natriuretic peptide (BNP) measurements were obtained before RT, within 24 hours of the first fraction, at the end of RT, and at first follow-up (1–2 months). These biomarkers were quantified at specific times and changes from baseline were evaluated with paired t tests. Results The median heart dose was 25.9 Gy (range 10.1–35.1 Gy). After the first RT fraction, no changes were noted in ECG or median Tnl or BNP levels; at the end of RT, two patients had elevated TnI and BNP, but neither difference was statistically significant. At first follow-up, TnI had returned to normal but the median BNP remained elevated (P=0.042). BNP did not increase over time in the 18 patients who received only RT. Twelve patients experienced acute ECG changes during RT, which resolved in seven patients by the next measurement. No patients experienced clinically significant RT-related events. Conclusion Increases in BNP and ECG changes were observed during high doses of radiation to the heart. The findings of this pilot study warrant further investigation and validation.

Heart dosimetric analysis of three types of cardiac toxicity in patients treated on dose-escalation trials for Stage III non-small-cell lung cancer

“…41 Another trial evaluated patients receiving ≥20 Gy to the heart and showed that almost half experienced electrocardiographic changes during RT, but again, none were significant. 42 More studies are clearly needed on this topic.…”

Late Effects of Total-Body Gamma Irradiation on Cardiac Structure and Function in Male Rhesus Macaques

“…In a study of 30 patients undergoing thoracic radiotherapy with chemotherapy, no significant elevations in troponin, nt-proBNP or creatine kinase-myocardial band (CK-MB) were observed after radiotherapy ( 58 ). However, recent studies suggest BNP may be useful as an acute marker of early radiotherapy-related cardiovascular impairment in left-sided breast cancer patients ( 59 ), and in patients receiving thoracic radiotherapy with high-dose heart exposure ( 59 , 60 ). Nevertheless, the majority of patients receiving greater than 20 Gy to the heart during thoracic radiotherapy did not exhibit increased levels of troponin I ( 60 ).…”

“…However, recent studies suggest BNP may be useful as an acute marker of early radiotherapy-related cardiovascular impairment in left-sided breast cancer patients ( 59 ), and in patients receiving thoracic radiotherapy with high-dose heart exposure ( 59 , 60 ). Nevertheless, the majority of patients receiving greater than 20 Gy to the heart during thoracic radiotherapy did not exhibit increased levels of troponin I ( 60 ). The follow-up times in the above studies were shorter than those in the current study.…”

Clinical characteristics and dose-volume histogram parameters associated with the development of pleural effusions in non-small cell lung cancer patients treated with chemoradiation therapy

“…Even though proximal tumors received lower doses of radiation to the left ventricle, they also demonstrated cardiac dysfunction before CRT completion. Furthermore, Gomez et al studied esophageal cancer patients and found that brain natriuretic peptide, which is released in response to excessive stretching of heart muscle cells, increased from pre-treatment values at the end of CRT and first follow-up period [21]. Shirai et al reported 35% of esophageal cancer patients who were treated with RT developed PlEf and correlated the occurrence of PlEf to HV 5 –HV 60 , LV 50, LV 60 , and MHD.…”