Meta-Analysis of Association Between Mediastinal Radiotherapy and Long-Term Heart Failure

Abstract

This investigation sought to identify and quantify any increased risk of long-term heart failure (HF) after thoracic radiotherapy (RT) for cancer and identify any population covariates that corresponded with increased risk. Electronic databases were systematically searched for studies reporting relative risk, odds ratio, and hazard ratio (HR) for symptomatic HF more than 5 years after RT administration. Clinical characteristics, study design, univariable effect sizes, and associated 95% CIs were extracted. Univariable effect size was pooled and computed in a meta-analysis using random-effects model weighted by inverse variance. Six studies (45,669 patients) with weighted median follow-up duration of 13.9 years were included, each data-linkage study that reported HRs for HF. Pooled HR for long-term HF was significant (HR 1.83 [1.09 to 3.08], p = 0.022), with significant between-study heterogeneity (Q 43.38, df = 5, p <0.001, I² 88.47%). Statistical significance was lost when excluding studies of malignancies other than breast cancer or hematological malignancies and excluding studies with Newcastle-Ottawa scores <8, but the direction of effect and magnitude remained approximately the same. Subgroup and meta-regression analyses demonstrated that study differences in age at time of RT administration and duration of follow-up explained approximately 80% of observed heterogeneity. Earlier publication date was associated with increased HF risk. Other variables, including female proportion, proportion of adjuvant chemotherapy use, and sample size did not significantly impact the conclusions. In conclusion, RT approximately doubled the long-term risk of HF. This finding was associated with younger age at time of RT and longer follow-up duration, which explained approximately 80% of interstudy heterogeneity.