MRI-derived extracellular volume as a biomarker of cancer therapy cardiotoxicity: systematic review and meta-analysis

Objectives: MRI-derived extracellular volume (ECV) allows characterization of myocardial changes before the onset of overt pathology, which may be caused by cancer therapy cardiotoxicity. Our purpose was to review studies exploring the role of MRI-derived ECV as an early cardiotoxicity biomarker to guide timely intervention. Materials and methods: In April 2022, we performed a systematic search on EMBASE and PubMed for articles on MRI-derived ECV as a biomarker of cancer therapy cardiotoxicity. Two blinded researchers screened the retrieved articles, including those reporting ECV values at least 3 months from cardiotoxic treatment. Data extraction was performed for each article, including clinical and technical data, and ECV values. Pooled ECV was calculated using the random effects model and compared among different treatment regimens and among those who did or did not experience overt cardiac dysfunction. Meta-regression analyses were conducted to appraise which clinical or technical variables yielded a significant impact on ECV. Results: Overall, 19 studies were included. Study populations ranged from 9 to 236 patients, for a total of 1123 individuals, with an average age ranging from 12.5 to 74 years. Most studies included patients with breast or esophageal cancer, treated with anthracyclines and chest radiotherapy. Pooled ECV was 28.44% (95% confidence interval, CI, 26.85-30.03%) among subjects who had undergone cardiotoxic cancer therapy, versus 25.23% (95%CI 23.31-27.14%) among those who had not (p = .003). Conclusion: A higher ECV in patients who underwent cardiotoxic treatment could imply subclinical changes in the myocardium, present even before overt cardiac pathology is detectable. Clinical relevance statement: The ability to detect subclinical changes in the myocardium displayed by ECV suggests its use as an early biomarker of cancer therapy-related cardiotoxicity. Key points: • Cardiotoxicity is a common adverse effect of cancer therapy; therefore, its prompt detection could improve patient outcomes. • Pooled MRI-derived myocardial extracellular volume was higher in patients who underwent cardiotoxic cancer therapy than in those who did not (28.44% versus 25.23%, p = .003). • MRI-derived myocardial extracellular volume represents a potential early biomarker of cancer therapy cardiotoxicity.