Natural Progression of Left Ventricular Function following Anthracyclines without Cardioprotective Therapy: A Systematic Review and Meta-Analysis

Abstract

Background: Anthracyclines form the backbone of many systemic chemotherapy regimens but are accompanied by dose-limiting cardiotoxicity. We elucidate the progression and severity of cardiac function over time, in the absence of cardioprotection, which less is known about. Methods: This PRISMA-guideline-adherent review was registered on PROSPERO (CRD42022373496). Results: 26 studies met the eligibility criteria including a total of 910 patients. The overall reduction in post-anthracycline pooled mean left ventricular ejection fraction (LVEF) in placebo arms of the included randomised-controlled trials was 4.5% (95% CI, 2.6 to 6.4). The trend in LVEF showed a progressive decline until approximately 180 days, after which there was no significant change. Those receiving a cumulative anthracycline dose of 300 mg/m2 experienced a more profound reduction. The overall pooled risk of a 10% absolute decline in LVEF from baseline, or a decline to an LVEF below 50%, was 17% (95% CI: 11 to 24; I2 = 71%). Sensitivity analyses of baseline LVEF and trastuzumab treatment status did not yield significant differences. Conclusion: While the mean LVEF decline in patients without cardioprotective therapy was clinically small, a vulnerable subset experienced significant impairment. Further research to best identify those who benefit most from cardioprotective therapies when receiving anthracyclines is required.

Atorvastatin for Anthracycline-Associated Cardiac Dysfunction

“…This decline in LVEF is similar to that reported in other single and multicenter studies and this magnitude of decline has been reported to lead to an increased risk of subsequent development of clinical heart failure. 26 The present study also highlights the impact of end-point selection in studies among patients at risk of cardiac dysfunction with cancer therapies. The primary end point in STOP-CA was the proportion in each study group with a 10% or greater decline in LVEF.…”

“…The risk of cardiac dysfunction with anthracyclines is dose dependent, 24 higher in patients at elevated cardiovascular risk, 15 and related to the cancer type; thus, the rate of cardiac dysfunction is lower among patients with breast cancer compared with patients with lymphoma. 25,26 This difference in risk of anthracyclineassociated cardiac dysfunction between the 2 study cohorts is reflected in the rate of the primary end point. When applying similar criteria (an LVEF reduction of 10%), 11% of participants in the previous study developed cardiac dysfunction compared with 21% in our study.…”

“…In the previous study, the dose of anthracyclines was lower, the cohort was younger, and breast cancer was the indication in 85%, with the remaining 15% of that population being treated for lymphoma. The risk of cardiac dysfunction with anthracyclines is dose dependent, higher in patients at elevated cardiovascular risk, and related to the cancer type; thus, the rate of cardiac dysfunction is lower among patients with breast cancer compared with patients with lymphoma . This difference in risk of anthracycline-associated cardiac dysfunction between the 2 study cohorts is reflected in the rate of the primary end point.…”

Lifetime Burden of Psychological Symptoms, Disorders, and Suicide Due to Cancer in Childhood, Adolescent, and Young Adult Years

“…This may stem from various dimensions, including the fear of death and pain from disease and treatment. Separate studies have suggested that childhood cancer survivors may be at an increased risk of not only physical complications related to cancer and its treatment but also psychological disorders …”

“…5 This may stem from various dimensions, including the fear of death and pain from disease and treatment. Separate studies have suggested that childhood cancer survivors may be at an increased risk of not only physical complications related to cancer and its treatment [6][7][8][9] but also psychological disorders. 10 Various studies highlighted varying trajectories of psychological issues in childhood, adolescent, and young adults with cancer (CYACs), including both actively treated patients and survivors in remission, with findings ranging from inconclusive to significantly reduced or increased risks compared with age-matched comparators.…”