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.

Inclusion Criteria for the patient group:

• diagnosis of cancer during childhood (diagnosis made between 0 and 16 years of age);
• age at enrollment greater than or equal to 6 years;
• having received anthracycline chemotherapy;
• disease remission for at least 1 year;
• absence of known cardiac disease prior to anthracycline therapy;
• absence of congenital heart disease.

Exclusion Criteria for the patient group:

• disease remission for less than 1 year;
• age less than 6 years at the time of enrollment;
• presence of known comorbidities (cardiopulmonary diseases, neurological diseases, etc.).

Inclusion Criteria for the control group:

• age at the time of enrollment: 6 years or older;
• good health.

Exclusion Criteria for the control group:

• having had oncological diseases;
• having undergone thoracic radiotherapy;
• having undergone anthracycline chemotherapy;
• being under 6 years of age at the time of enrollment;
• having known comorbidities (cardiopulmonary diseases, neurological diseases, etc.).

The patient group will be selected among patients who have undergone anthracycline therapy and are undergoing regular follow-up at the Pediatric Oncology Unit of the Fondazione Policlinico Universitario A. Gemelli in Rome. Information about the tumor, treatments, and cardiac monitoring (echocardiogram) must be available for all patients. The control group will be selected from patients who visit the Pediatric Oncology Unit for a hematological evaluation but who have never undergone anthracycline therapy and have no known cardiac problems. All subjects (patients and controls) will undergo a thorough medical history and a clinical assessment, including a physical examination and measurement of vital signs and anthropometric parameters. Furthermore, all enrolled subjects, both patients and controls, will be required to collect, at a routine blood sampling time, a 6 ml tube for the measurement of biomarkers of endothelial-mesenchymal transition and endothelial activation.