Evaluation of Cardiac and Endothelial Function in Children and Adolescents Treated With Anthracycline

Summary

In recent decades, the survival rate of children with cancer has increased significantly thanks to personalized treatments and the adoption of international therapeutic protocols. However, along with this increase in survival, side effects related to these treatments on various organs and systems have been observed.

Among the most widely used chemotherapeutic agents in pediatric age, anthracyclines play a crucial role in the treatment of various forms of neoplasms (both haematological such as acute lymphoblastic leukemia or lymphomas, and solid tumors such as sarcomas). However, in addition to their excellent antineoplastic effect, they are burdened by the potential for cardiotoxicity. This cardiotoxicity manifests clinically with left ventricular systolic dysfunction and arrhythmias.

At the moment, international guidelines recommend long-term cardiac follow-up evaluations for this group of patients, even after treatment has concluded.The methods used in the cardiac follow-up of patients undergoing anthracycline therapy include echocardiography, cardiac magnetic resonance imaging, tests to assess endothelial function, and measurements of the biomarkers troponin and atrial natriuretic peptide. These methods can assess anthracycline-induced cardiac and endothelial damage once it has already occurred, but they cannot predict its onset nor can they study its pathogenesis.

Furthermore, to date, no information is available regarding the possibility of using "endothelial-mesenchymal transition" biomarkers as predictors of the onset of anthracycline-induced cardiac damage.

This study analyzes these biomarkers as predictive tools for cardiac damage. Specifically, plasma levels of Serpin 3, THBS1, TGFbeta1, HIF1a, extracellular ICAM1, troponin, proBNP, fibrinogen, von Willebrand factor, and endothelin will be measured in patients treated with anthracycline. The concentrations of these biomarkers will be compared with the results of the echocardiogram and with the treatments performed in order to identify any relationships. Furthermore, plasma levels of Serpin 3, THBS1, TGFbeta1, HIF1a, extracellular ICAM1, troponin, proBNP, fibrinogen, von Willebrand factor, and endothelin will also be measured in a population of healthy subjects in order to obtain data on a possible relationship between the biomarkers and the anthracycline therapies performed.

Conditions

• Anthracycline Related Cardiotoxicity in Childhood Cancers
• Chemotherapeutic Toxicity
• Childhood Cancer Survivors

Interventions

DIAGNOSTIC_TEST

Biomarker detection

All patients will be tested for plasma levels of Serpin 3, THBS1, TGFbeta1, HIF1a, extracellular ICAM1, and endothelin. In addition, the study will collect the following anamnestic data: * patient demographics, clinical data (age, sex, presence of comorbidities, medical history), instrumental data (echocardiogram performed), and laboratory data; * data relating to the neoplastic pathology and treatment performed

DIAGNOSTIC_TEST

Biomarker detection

All controls will be tested for plasma levels of Serpin 3, THBS1, TGFbeta1, HIF1a, extracellular ICAM1, and endothelin. In addition, the study will collect information on demographics, clinical data (age, sex, presence of comorbidities, medical history), instrumental data (echocardiogram performed), and laboratory data.

Sponsors & Collaborators

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS

  lead OTHER

Principal Investigators

• Antonio Ruggiero · Fondazione Policlinico Universitario A. Gemelli, IRCCS

Eligibility

Min Age

6 Years

Max Age

35 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2025-11-30

Primary Completion

2027-01-31

Completion

2027-01-31

Countries

• Italy

Study Locations