Finding ferritin footprints in 5-fluorouracil-induced cardiotoxicity

Fluoropyrimidines, including 5-fluorouracil (5-FU), used in the treatment of patients with gastrointestinal malignancies, are associated with cardiotoxicity. Although the mechanism of this cardiotoxicity remains unknown, rat models treated with 5-FU have higher iron concentrations in myocardial tissue compared to controls. As a result, we sought to examine whether ferritin could be a clinical biomarker of cardiotoxicity among patients receiving 5-FU-based chemotherapy. We conducted a retrospective chart review on adult patients receiving 5-FU-based intravenous chemotherapy at a single academic center from June 2022 to 2024. Potential cardiotoxicity was defined by obstructive coronary artery disease, new wall motion abnormalities on transthoracic echocardiography (TTE), left ventricular ejection fraction decrease ≥10% from pre-treatment TTE, coronary vasospasm, pericardial effusion, or incident heart failure. Of our 93 patients, those with ferritin ≥ 100 ng/mL were nearly 5 times as likely to exhibit potential cardiotoxicity (adjusted odds ratio [aOR] 4.7, confidence interval [CI] 1.0-23.5) (Fig. 1A). Similarly, patients with ferritin ≥ 100 ng/mL were approximately 3 times as likely to experience treatment failure (aOR 3.2, CI 1.1-9.7). Based on the apparent relationship between ferritin ≥100 ng/mL, cardiotoxicity, and treatment outcomes, we encourage oncologists to routinely obtain iron studies in addition to pre- and post-treatment TTE among patients receiving 5-FU.