Assessment of the onset of radiation-induced cardiac damage after radiotherapy of breast cancer patients

Abstract

Objectives: The study aimed to evaluate the dose delivered to the heart during radiotherapy of left-sided and right-sided breast cancer (BC) patients, correlate the dose and laterality of radiotherapy to the possible cardiac damage and evaluate whether Left-ventricular Ejection Fraction (LVEF), Troponin-I (TnI), Creatinine Kinase (CK), Creatine Kinase-MB Relative Index (CK-MBRI) or Lactic Dehydrogenase (LDH) could be used to detect the possible onset of radiotherapy-related cardiotoxicity. Subjects and methods: 80 females were assigned as; 30 left-sided BC patients, 30 right-sided BC patients and 20 healthy females. Patients were treated by radical mastectomy followed by FAC-based chemotherapy and radiotherapy. CT-based 3D-planning was used to generate cardiac dose-volume histograms to assess mean dose received by the heart. Echocardiography was done to all patients before and 1 year after completing radiotherapy. In serum, TnI and CK-MB concentration and CK and LDH activities were determined before and 1 year after radiotherapy. Results: In left-sided patients, mean dose delivered to the heart was significantly higher in left-sided patients with significant association with total radiotherapy dose in left-but not right-sided patients. LVEF before and after radiotherapy were statistically different only in left-sided patients. LVEF one year after radiotherapy dropped 20% or more (DLVEF) in 6 patients, all were left-sided. Using cutoff values 0.08 ng/mL for TnI and 1.4 for CK-MBRI; 11 left-sided patients had abnormal TnI and CK-MBRI vs 5 right-sided patients, the 6 patients identified with DLVEF ! 20 were all among them. Conclusion: the mean dose delivered to the heart is significantly higher in left-sided patients, and it was correlated to the total radiotherapy dose. One year after radiotherapy, DLVEF is possibly good marker of cardiotoxicity onset, however, the persistent elevation of both TnI and CK-MBRI could identify both patients with cardiotoxicity and patients that are thought to be in subclinical phase of cardiac damage.

Role of Cardiac Biomarkers in Cancer Patients

“…Six of these patients had a one-year drop in EF of 20% or more. TnI and creatine kinase MBRI isoenzyme values were more frequently above threshold in left breast treated patients, and the six patients with an EF drop ≥ 20% were all among those with altered biomarkers and treated on the left side [60].…”

“…Cancers 2021, 13, x 13 of 27 were more frequently above threshold in left breast treated patients, and the six patients with an EF drop ≥ 20% were all among those with altered biomarkers and treated on the left side [60].…”

Biomarkers for the detection of apparent and subclinical cancer therapy-related cardiotoxicity

“…Several studies examined the role of early use of cardiac injury biomarkers in radiotherapy. Although there is evidence that left chest radiotherapy can induce increased high-sensitive troponin and creatine kinase MB (CK-MB), a convincing association between radiation-induced troponin activation and LV systolic or diastolic dysfunction has not been forwarded so far (85)(86)(87). Only limited data is available on the role of BNP in radiation-associated cardiotoxicity.…”

The Significance of Elevated Lactate Dehydrogenase and Creatine Kinase Activities as Prognostic Biomarkers for the Mortality in Patients with Terminal Cancers

“…The extracellular LDH had applied to distinguish cellular damage caused by e.g. ischemia, after ingestion of certain drugs, and from chemotherapy or radiotherapy [3,4] .The intracellular creatine-kinase (CK) enzyme catalyses reversible phosphate transport from creatine-phosphate to the ADP; yielding ATP & creatine [5] . Rresearches exhibited that CK action increased in gastrointestinal malignancy owing to over-synthesis and release of the CK-BB after tumor necrosis [6] .…”