Biomarkers' ability to predict cardiac toxicity in oncological patients undergoing to antineoplastic treatment: 5-year follow-up
Authors: Papa M.D , Lupi M.D , Piazzani M.D , Gheza M.D , Fioretti M.D , Simoncini M.D , Madureri M.D , Sigala M.D , Nodari S 
Published: November 2020

Abstract

Background
It is known that anticancer treatment can cause adverse cardiovascular (CV) events, influencing patients' survival and quality of life regardless of their cancer prognosis; today there are no defined protocols for the early identification of cardiotoxicity (CTX).

Purpose
To evaluate the ability of biomarkers, cardiac TnI and NT-proBNP, to predict CTX induced by antineoplastic therapy.

Methods
We have enrolled women with non-metastatic breast cancer who had to start a treatment with Anthracycline (ANT), in the patients (pts) with HER2+ cancer, Trastuzumab (TRZ) could also be introduced. The presence of a known heart disease, a previous mediastinal irradiation and a previous treatment with ANT, were the main exclusion criteria. All pts underwent complete cardiological evaluation (ECG, Echo) before the beginning of the therapy (T0), after each ANT cycle and every 3 months up to 1 year of follow-up after the end of therapy with ANT. During each visit, a venous sampling was performed for the determination of biomarkers. We collected the data of the routine cardiological visits carried out by the pts in the following 5 years.

Results
179pts finished the follow-up,7pts (21%) were hypertensive, 9pts (5%) diabetic, 32pts (18%) dyslipidemics. 53pts (30%) (“TnI+ group”) showed a significant increase in TnI (&gt;0.04ng/mL) or less than this cut-off but persistently &gt;0.015ng/mL in at least 2 measurements; comparing the LVEF of the two groups detected at 1 year follow-up it was observed a significant difference: 60±6.5% in the “TnI+ group” and 63±4.1% in the “TnI− group” (p=0.005); a tendency to significance was observed from the comparison between LVEF measured at baseline compared to that of 1-year follow-up in the “TnI+ group” (62±4.2% vs 60±6.5%, p=0.06); furthermore 7 patients of the “TnI+ group” developed LV systolic dysfunction (according to the definition of the CREC) early in the first year of follow-up (vs 1 pts of the “TnI− group”, p=0.001), with recovery after the introduction of specific cardiology therapy. 76/179 pts (43%) showed NT-proBNP values ≥125 ng/L in at least two consecutive determinations (“NT-proBNP+ group”), in this group 25% of the pts had more than 3 CV risk factors, compared to 11% in the “NT-proBNP− group” (p=0.011), 3/8 pts that showed LV systolic dysfunction were included in the “NT-proBNP+ group”.

Conclusion(s)
In a homogeneous group of patients with a low CV risk profile, anticancer treatment with low doses of ANT and with TRZ can induce significant changes in plasma TnI levels that can be correlated with early alterations in LV systolic function, but not with major CV events after 5 years. Significant increases in NT-proBNP have also been reported, but there has been no significant correlation with the progressive development of LV dysfunction and HF. The combination of individual clinical risk factors and biomarkers, especially TnI, in a predictive model could allow early identification of CTX.

Funding Acknowledgement
Type of funding source: None