Cardiotoxicity is a serious adverse effect that can occur in women undergoing treatment for breast cancer. Identifying patients who will develop cardiotoxicity remains challenging.
To identify, ...describe, and evaluate all prognostic models developed to predict cardiotoxicity following treatment in women with breast cancer.
This systematic review searched the Medline, Embase, and Cochrane databases up to September 22, 2021, to include studies developing or validating a prediction model for cardiotoxicity in women with breast cancer. The Prediction Model Risk of Bias Assessment Tool (PROBAST) was used to assess both the risk of bias and the applicability of the prediction modeling studies. Transparency reporting was assessed with the Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis (TRIPOD) tool.
After screening 590 publications, we identified 7 prognostic model studies for this review. Six were model development studies and 1 was an external validation study. Outcomes included occurrence of cardiac dysfunction (echocardiographic parameters), heart failure, and composite clinical outcomes. Model discrimination, measured by the area under receiver operating curves or C statistic, ranged from 0.70 (95% IC, 0.62-0.77) to 0.87 (95% IC, 0.77-0.96). The most common predictors identified in final prediction models included age, baseline left ventricular ejection fraction, hypertension, and diabetes. Four of the developed models were deemed to be at high risk of bias due to analysis concerns, particularly for sample size, handling of missing data, and not presenting appropriate performance statistics. None of the included studies examined the clinical utility of the developed model. All studies met more than 80% of the items in TRIPOD checklist.
In this systematic review of the 6 predictive models identified, only 1 had undergone external validation. Most of the studies were assessed as being at high overall risk of bias. Application of the reporting guidelines may help future research and improve the reproducibility and applicability of prediction models for cardiotoxicity following breast cancer treatment.
In patients treated with cardiotoxic chemotherapies, the presence of cardiovascular risk factors and previous cardiac disease have been strongly correlated to the onset of cardiotoxicity. The ...influence of overweight and obesity as risk factors in the development of treatment-related cardiotoxicity in breast cancer (BC) was recently suggested. However, due to meta-analysis design, it was not possible to take into account associated cardiac risk factors or other classic risk factors for anthracycline (antineoplastic antibiotic) and trastuzumab (monoclonal antibody) cardiotoxicity.
Using prospective data collected from 2012-2014 in the French national multicenter prospective CANTO (CANcer TOxicities) study of 26 French cancer centers, we aimed to examine the association of body mass index (BMI) and cardiotoxicity (defined as a reduction in left ventricular ejection fraction LVEF > 10 percentage points from baseline to LVEF < 50%). In total, 929 patients with stage I-III BC (mean age 52 ± 11 years, mean BMI 25.6 ± 5.1 kg/m2, 42% with 1 or more cardiovascular risk factors) treated with anthracycline (86% epirubicin, 7% doxorubicin) and/or trastuzumab (36%), with LVEF measurement at baseline and at least 1 assessment post-chemotherapy were eligible in this interim analysis. We analyzed associations between BMI and cardiotoxicity using multivariate logistic regression. At baseline, nearly 50% of the study population was overweight or obese. During a mean follow-up of 22 ± 2 months following treatment completion, cardiotoxicity occurred in 29 patients (3.2%). The obese group was more prone to cardiotoxicity than the normal-weight group (9/171 versus 8/466; p = 0.01). In multivariate analysis, obesity (odds ratio OR 3.02; 95% CI 1.10-8.25; p = 0.03) and administration of trastuzumab (OR 12.12; 95% CI 3.6-40.4; p < 0.001) were independently associated with cardiotoxicity. Selection bias and relatively short follow-up are potential limitations of this national multicenter observational cohort.
In BC patients, obesity appears to be associated with an important increase in risk-related cardiotoxicity (CANTO, ClinicalTrials.gov registry ID: NCT01993498).
ClinicalTrials.gov NCT01993498.
Importance: Cardiotoxicity is a serious adverse effect that can occur in women undergoing treatment for breast cancer. Identifying patients who will develop cardiotoxicity remains ...challenging.Objective: To identify, describe, and evaluate all prognostic models developed to predict cardiotoxicity following treatment in women with breast cancer.Evidence review: This systematic review searched the Medline, Embase, and Cochrane databases up to September 22, 2021, to include studies developing or validating a prediction model for cardiotoxicity in women with breast cancer. The Prediction Model Risk of Bias Assessment Tool (PROBAST) was used to assess both the risk of bias and the applicability of the prediction modeling studies. Transparency reporting was assessed with the Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis (TRIPOD) tool.Findings: After screening 590 publications, we identified 7 prognostic model studies for this review. Six were model development studies and 1 was an external validation study. Outcomes included occurrence of cardiac dysfunction (echocardiographic parameters), heart failure, and composite clinical outcomes. Model discrimination, measured by the area under receiver operating curves or C statistic, ranged from 0.70 (95% IC, 0.62-0.77) to 0.87 (95% IC, 0.77-0.96). The most common predictors identified in final prediction models included age, baseline left ventricular ejection fraction, hypertension, and diabetes. Four of the developed models were deemed to be at high risk of bias due to analysis concerns, particularly for sample size, handling of missing data, and not presenting appropriate performance statistics. None of the included studies examined the clinical utility of the developed model. All studies met more than 80% of the items in TRIPOD checklist.Conclusions and relevance: In this systematic review of the 6 predictive models identified, only 1 had undergone external validation. Most of the studies were assessed as being at high overall risk of bias. Application of the reporting guidelines may help future research and improve the reproducibility and applicability of prediction models for cardiotoxicity following breast cancer treatment.
The WHO Unity Studies initiative engaged low‐ and middle‐income countries in the implementation of standardised SARS‐CoV‐2 sero‐epidemiological investigation protocols and timely sharing of ...comparable results for evidence‐based action. To gain a deeper understanding of the methodological challenges faced when conducting seroprevalence studies in the African region, we conducted unstructured interviews with key study teams in five countries. We discuss the challenges identified: participant recruitment and retention, sampling, sample and data management, data analysis and presentation. Potential solutions to aid future implementation include preparedness actions such as the development of new tools, robust planning and practice.
To date, an estimated 10% of children eligible for antiretroviral treatment (ART) receive it, and the frequency of retention in programs is unknown. We evaluated the 2-year risks of death and loss to ...follow-up (LTFU) of children after ART initiation in a multicenter study in sub-Saharan Africa.
Pooled analysis of routine individual data from 16 participating clinics produced overall Kaplan-Meier estimates of the probabilities of death or LTFU after ART initiation. Risk factors analysis used Weibull regression, accounting for between-cohort heterogeneity.
The median age of 2405 children at ART initiation was 4.9 years (12%, younger than 12 months), 52% were male, 70% had severe immunodeficiency, and 59% started ART with a nonnucleoside reverse transcriptase inhibitor. The 2-year risk of death after ART initiation was 6.9% (95% confidence interval CI: 5.9 to 8.1), independently associated with baseline severe anemia (adjusted hazard ratio aHR: 4.10 CI: 2.36 to 7.13), immunodeficiency (adjusted aHR: 2.95 CI: 1.49 to 5.82), and severe clinical status (adjusted aHR: 3.64 CI: 1.95 to 6.81); the 2-year risk of LTFU was 10.3% (CI: 8.9 to 11.9), higher in children with severe clinical status.
Once on treatment, the 2-year risk of death is low but the LTFU risk is substantial. ART is still mainly initiated at advanced disease stage in African children, reinforcing the need for early HIV diagnosis, early initiation of ART, and procedures to increase program retention.
BACKGROUND AND PURPOSE: Recent studies demonstrated the benefit of mechanical thrombectomy (MT) plus intravenous tissue-type plasminogen activator (IV-tPA) (MT-IV-tPA) in acute ischemic stroke. This ...study aimed to estimate the cost-utility of MT-IV-tPA compared with IV-tPA alone from the perspective of the French National Health Insurance. METHODS: We developed a decision tree for the first 3 months after stroke onset and a Markov model until 10 years post-stroke. The health states of the Markov model were according to the modified Rankin Scale (mRS): independent (mRS=0-2), dependent (mRS=3-5), dead (mRS=6). Recurrent stroke was the fourth health stage of our model. We conducted systematic literature reviews and meta-analyses to estimate the cost and utility of each health state, and the transition probabilities between health states. A microcosting study was conducted to estimate the cost of MT. We estimated the incremental cost-effectiveness ratio of MT-IV-tPA and conducted a probabilistic analysis in order to estimate the probability that MT-IV-tPA is cost-effective compared to IV-tPA, the expected value of perfect information (EVPI), and the expected value of partial perfect information (EVPPI), given the uncertainty surrounding the value of our model's parameters. RESULTS: The total mean (standard deviation (SD) cost of MT was euro6708.9 (2357.0). The incremental cost-effectiveness ratio (ICER) of the strategy using IV-tPA combined to MT costs was euro14,715 per QALY gained as compared to a strategy using IV-tPA alone. The probabilistic analysis showed that the probability of MT-IV-TPA being cost-effective was 85.4% at threshold willingness-to-pay of euro30,000 per QALY gained, reaching 98% at euro50,000 per QALY gained. CONCLUSION: Although there is no universally accepted willingness-to-pay threshold in France, our analysis suggest that MT combined to IV-tPA can be considered a cost-effective treatment compared with IV-tPA alone.
PDF
