Serial Cardiac Magnetic Resonance Imaging (CMR) With Contrast Agents and Biomarker Analysis for the Detection of Cardiotoxicity Under Anthracycline-containing Cancer Therapy

Serial Cardiac Magnetic Resonance Imaging (CMR) With Contrast Agents and Biomarker Analysis for the Detection of Cardiotoxicity Under Anthracycline-containing Cancer Therapy - A Monocentric, Low Interventional Phase IV Pilot Study

The goal of the trial is the early detection of cardiotoxicity in patients treated with anthracycline-based chemotherapy. Current diagnostics, such as troponin T, NT-pro-BNP, electrocardiogram, and echocardiography, are not able to identify early myocardial damage. Therefore, this study aims to identify early myocardial damage by using cardiac magnetic resonance imaging.

The primary endpoint of this study is the change in relaxation times in CMR before, during, and after therapy.

Furthermore, the study analyzes:

• other abnormal results in CMR
• changes in troponin T and NT-pro-BNP
• changes in global longitudinal strain in echocardiography and correlation with results of CMR
• detection of new biomarkers in blood, urine, or stool

The goal of the trial is the early detection of cardiotoxicity in patients treated with anthracycline-based chemotherapy as standard of care therapy. For clarification: Standard anthracycline-based chemotherapy is administered independently of the study and is not the subject of this study, but rather is its basis. No investigational medicinal products are being tested in this clinical trial; instead only diagnostic procedures are being investigated.

Since current diagnostic methods-such as troponin T, NT-proBNP, electrocardiography, and echocardiography-are limited in their ability to detect early myocardial injury, the study aims to identify early myocardial damage using cardiac magnetic resonance imaging (CMR).

Enrolled participants will be stratified into risk groups using the HFA-ICOS score and-depending on the risk category-monitored according to current ESC guidelines using electrocardiography, echocardiography, and serial measurements of troponin T and NT-proBNP.

Preclinical data suggest that anthracyclines may impair myocardial function not only as a result of cumulative dosage over time but also during the early stages of therapy. The investigators therefore evaluate the use of CMR for the early detection of myocardial alterations during anthracycline therapy.

CMR examinations will be scheduled according to the administered cumulative dose of anthracyclines. Following a baseline evaluation prior to the initiation of therapy, the first follow-up CMR examination will be performed after approximately half of the preplanned cumulative anthracycline dose has been administered. A third CMR examination will be conducted after completion of therapy. Twelve months after therapy completion, an end-of-study CMR examination will be performed to assess persistent myocardial changes.

The primary endpoint is the measurement of myocardial relaxation times. Given the early time point of evaluation, additional CMR parameters will also be analyzed, including variations in cardiac morphology, cardiac function, late gadolinium enhancement, and myocardial perfusion.

Currently, both the proportion of participants potentially affected by early myocardial alterations during anthracycline therapy and the underlying pathophysiological mechanisms remain unclear. The study therefore seeks to identify biomarkers or genetic polymorphisms associated with an increased risk of early myocardial injury. For this purpose, blood, urine, and stool samples will be collected for inclusion in a biobank and analyzed for polymorphisms or mutations in genes such as CYBA, RAC2, NCF4, ABCC1, ABCC5, ABCB4, SLC22A17, SLC22A7, SLC28A3, SLC10A2, HAS3, CBR3, RARG, CELF4, and SLC22A3. In addition, anthracycline metabolites and cytokine profiles, such as IL-6 and TNF-α, may be measured.

Inclusion Criteria

- Patients with a recommendation for antineoplastic therapy including at least four administrations of an anthracycline

Exclusion Criteria

• Inability to provide informed consent
• Prior administration of an anthracycline
• Administration of cardiotoxic drugs within the last six months, such as:
• High-dose cyclophosphamide (>1,000 mg/m² or >10 mg/kg)
• HER2 inhibitors
• VEGF inhibitors
• BCR-ABL inhibitors
• BRAF inhibitors
• MEK inhibitors
• Immune checkpoint inhibitors (CTLA-4 inhibitors, PD-1 inhibitors, PD-L1 inhibitors)
• Planned invasive cardiac intervention during the study period
• Cardiac involvement of an underlying disease, e.g. amyloidosis
• Treatment with fewer than four administrations of anthracyclines
• Treatment with a liposomal anthracycline formulation
• Treatment in which anthracyclines are not administered in every chemotherapy cycle
• Thoracic radiation involving the heart prior to anthracycline administration
• Participation in another clinical study concurrently or within the last three months
• Renal impairment with a GFR < 30 ml/min/1.73 m²
• Patients in the perioperative phase of liver transplantation
• Contraindications to cardiac magnetic resonance imaging, such as metallic implants (e.g. cardiac pacemaker)
• Pregnancy or breastfeeding
• Hypersensitivity or intolerance to gadolinium-based contrast agents
• Vulnerable populations (individuals unable to protect their own interests, prisoners)