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.

Background: A diagnosis of cancer and treatment may constitute a highly traumatic period for paediatric cancer patients (PYACPs). However, no review has comprehensively analysed how the mental health of PYACPs is acutely affected and the longitudinal course. Methods: This systematic review followed PRISMA guidelines. Comprehensive searches of databases were conducted to identify studies of depression, anxiety and post-traumatic stress symptoms in PYACPs. Random effects meta-analyses were used for the primary analysis. Results: From 4898 records, 13 studies were included. Acutely after diagnosis, depressive and anxiety symptoms were significantly elevated in PYACPs. Depressive symptoms only significantly decreased after 12 months (standardised mean difference, SMD = −0.88; 95% CI: −0.92, −0.84). This downward trajectory persisted to 18 months (SMD = −1.862; 95% CI: −1.29, −1.09). Anxiety symptoms similarly only decreased after 12 (SMD = −0.34; 95% CI: −0.42, −0.27) up to 18 months (SMD = −0.49; 95% CI: −0.60, −0.39) after the cancer diagnosis. Post-traumatic stress symptoms showed protracted elevations throughout follow-up. Overall, significant predictors of poorer psychological outcomes included unhealthy family functioning, concomitant depression or anxiety, poor cancer prognosis or experiencing cancer and treatment-related side effects. Conclusions: While depression and anxiety may improve over time with a favourable environment, post-traumatic stress may have a protracted course. Timely identification and psycho-oncological intervention are critical.

ImportanceA cancer diagnosis and treatment may result in highly traumatic periods with lasting psychological consequences for children, adolescent, and young adult patients with cancer (CYACs). Early identification and management may prevent long-term psychological morbidity and suicide.ObjectiveTo analyze risk, severity, and risk factors for depression, anxiety, psychotic disorders, and suicide in CYACs and noncancer comparators.Data SourcesLiterature search of PubMed, MEDLINE, Embase, PsycINFO, CINAHL, and PubMed Central from January 1, 2000, to November 18, 2022.Study SelectionFull-length articles in peer-reviewed journals that measured and reported risk and/or severity of depression, anxiety, psychotic disorders, and suicide mortality in CYACs and a noncancer comparator group.Data Extraction and SynthesisPreferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines were followed with prospective PROSPERO registration.Main Outcomes and MeasuresRisk ratios (RRs) were used for dichotomous outcomes, and standardized mean differences (SMDs) were used for continuous outcomes. SMDs were defined as follows: 0.2, small; 0.5, medium; and 0.8, large. Sources of heterogeneity and risk factors were investigated using sensitivity, subgroup, and meta-regression analyses.ResultsFrom 7319 records, 52 studies were included. Meta-analyses revealed that CYACs were at increased lifetime risk of severe symptoms or a disorder of depression (RR, 1.57; 95% CI, 1.29-1.92), anxiety (RR, 1.29; 95% CI, 1.14-1.47), and psychotic disorders (RR, 1.56; 95% CI, 1.36-1.80) relative to both matched controls and their siblings. Overall suicide mortality was not significantly elevated (RR, 1.63; 95% CI, 0.78-3.40). The mean severity of depression was found to be elevated in CYACs receiving treatment (SMD, 0.44; 95% CI, 0.13-0.74) and long-term survivors (SMD, 0.18; 95% CI, 0.02-0.33). The mean severity of anxiety was found to be elevated only during treatment (SMD, 0.16; 95% CI, 0.03-0.20).Conclusions and RelevanceFindings of this systematic review and meta-analysis suggest that CYACs may experience lasting psychological burden long into survivorship. Timely identification, preventive efforts, and psycho-oncological intervention for psychological comorbidity are recommended.

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