ABSTRACT

BACKGROUND: Histologically assessed liver fibrosis stage has prognostic significance in patients with non-alcoholic fatty liver disease (NAFLD) and is accepted as a surrogate endpoint in clinical trials for non-cirrhotic NAFLD. Our aim was to compare the prognostic performance of non-invasive tests with liver histology in patients with NAFLD.

METHODS: This was an individual participant data meta-analysis of the prognostic performance of histologically assessed fibrosis stage (F0-4), liver stiffness measured by vibration-controlled transient elastography (LSM-VCTE), fibrosis-4 index (FIB-4), and NAFLD fibrosis score (NFS) in patients with NAFLD. The literature was searched for a previously published systematic review on the diagnostic accuracy of imaging and simple non-invasive tests and updated to Jan 12, 2022 for this study. Studies were identified through PubMed/MEDLINE, EMBASE, and CENTRAL, and authors were contacted for individual participant data, including outcome data, with a minimum of 12 months of follow-up. The primary outcome was a composite endpoint of all-cause mortality, hepatocellular carcinoma, liver transplantation, or cirrhosis complications (ie, ascites, variceal bleeding, hepatic encephalopathy, or progression to a MELD score ≥15). We calculated aggregated survival curves for trichotomised groups and compared them using stratified log-rank tests (histology: F0-2 vs F3 vs F4; LSM: <10<20<1·32·67; NFS: <-1·4550·676), calculated areas under the time-dependent receiver operating characteristic curves (tAUC), and performed Cox proportional-hazards regression to adjust for confounding. This study was registered with PROSPERO, CRD42022312226.

FINDINGS: Of 65 eligible studies, we included data on 2518 patients with biopsy-proven NAFLD from 25 studies (1126 [44·7%] were female, median age was 54 years [IQR 44-63), and 1161 [46·1%] had type 2 diabetes). After a median follow-up of 57 months [IQR 33-91], the composite endpoint was observed in 145 (5·8%) patients. Stratified log-rank tests showed significant differences between the trichotomised patient groups (p<0·0001

INTERPRETATION: Simple non-invasive tests performed as well as histologically assessed fibrosis in predicting clinical outcomes in patients with NAFLD and could be considered as alternatives to liver biopsy in some cases.

FUNDING: Innovative Medicines Initiative 2.

PMID:37290471 | DOI:10.1016/S2468-1253(23)00141-3

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PubMed articles on: Cardio-Oncology

The Efficacy of Multi-Leaf Collimator in the Reduction of Cardiac and Coronary Artery Dose in Left-Sided Breast Cancer Radiotherapy

Adv Biomed Res. 2023 Apr 25;12:89. doi: 10.4103/abr.abr_342_21. eCollection 2023.

ABSTRACT

BACKGROUND: Multi-leaf collimator (MLC) is one of the efficient and cost-effective methods for protecting sensitive tissues around the target. This study aimed to evaluate the protective effect of MLC on the protection of sensitive organs in patients with left breast cancer.

MATERIALS AND METHODS: This study was performed on computed tomography (CT) scans of 45 patients with left breast cancer. Two treatment plans were completed for each patient. Only the heart and left lung were considered organs at risk in the first treatment plan, and in the second treatment plan, the left anterior descending artery (LAD) was also considered the organ at risk. It was covered as much as possible by the MLC. Dosimetric results of tumor and organ at risk (OARs) were extracted from the dose-volume histogram and compared.

RESULTS: The results showed that more LAD coverage by MLC leads to a significant reduction in the mean dose of OARs (P-value <0.05).5 (volume received the dose of 5 Gy) and V20 for the lung, V10, V25, and V30 for LAD, and V5, V20, V25, and V30 for the heart also decreased significantly (P-value

CONCLUSIONS: In general, better protection of LAD, heart, and lungs can be achieved by maximal shielding organs at risk by MLC in radiation therapy for patients with left breast cancer.

PMID:37288034 | PMC:PMC10241641 | DOI:10.4103/abr.abr_342_21

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PubMed articles on: Cardio-Oncology

Feasibility of Aerobic Exercise Training to Mitigate Cardiotoxicity of Breast Cancer Therapy: A Systematic Review and Meta-Analysis

Clin Breast Cancer. 2023 May 3:S1526-8209(23)00094-0. doi: 10.1016/j.clbc.2023.04.010. Online ahead of print.

ABSTRACT

BACKGROUND: Current anticancer treatments for breast cancer (BC) may cause cardiotoxicity. This study aimed to investigate the effectiveness of aerobic exercise in mitigating cardiotoxicity caused by BC therapy.

MATERIALS AND METHODS: PubMed, Embase, Cochrane Library, Web of Science, and the Physiotherapy Evidence Database were searched until February 7, 2023. Clinical trials investigating the effectiveness of exercise training, including aerobic exercise, in BC patients receiving treatments that could cause cardiotoxicity were eligible. Outcome measures included cardiorespiratory fitness (CRF) (peak oxygen consumption, VO2peak), left ventricular ejection fraction, and peak oxygen pulse. Intergroup differences were determined by standard mean differences (SMD) and 95% confidence intervals (CIs). Trial sequential analysis (TSA) was utilized to ensure whether the current evidence was conclusive.

RESULTS: Sixteen trials involving 876 participants were included. Aerobic exercise significantly improved CRF measured by VO2peak in mL/kg/min (SMD 1.79, 95% CI 0.99-2.59) when compared to usual care. This result was confirmed through TSA. Subgroup analyses revealed that aerobic exercise given during BC therapy significantly improved VO2peak (SMD 1.84, 95% CI 0.74-2.94). Exercise prescriptions at a frequency of up to 3 times per week, an intensity of moderate to vigorous, and a >30-minute session length also improved VO2peak.

CONCLUSION: Aerobic exercise is effective in improving CRF when compared to usual care. Exercise performed up to 3 times per week, at a moderate-to-vigorous intensity, and having a session length >30 minutes is considered effective. Future high-quality research is needed to determine the effectiveness of exercise intervention in preventing cardiotoxicity caused by BC therapy.

PMID:37286435 | DOI:10.1016/j.clbc.2023.04.010

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PubMed articles on: Cardio-Oncology

Nebivolol versus placebo in patients undergoing anthracyclines (CONTROL Trial): rationale and study design

J Cardiovasc Med (Hagerstown). 2023 Jul 1;24(7):469-474. doi: 10.2459/JCM.0000000000001491.

ABSTRACT

AIMS: Anthracyclines are the chemotherapeutic agents most frequently associated with cardiotoxicity, while remaining widely used. Different neurohormonal blockers have been tested as a primary prevention strategy to prevent or attenuate the onset of cardiotoxicity, with mixed results. However, prior studies were often limited by a nonblinded design and an assessment of cardiac function based only on echocardiographic imaging. Moreover, on the basis of an improved mechanistic understanding of anthracycline cardiotoxicity mechanisms, new therapeutic strategies have been proposed. Among cardioprotective drugs, nebivolol might be able to prevent the cardiotoxic effects of anthracyclines, through its protective properties towards the myocardium, endothelium, and cardiac mitochondria. This study aims to evaluate the cardioprotective effects of the beta blocker nebivolol in a prospective, placebo-controlled, superiority randomized trial in patients with breast cancer or diffuse large B cell lymphoma (DLBCL) who have a normal cardiac function and will receive anthracyclines as part of their first-line chemotherapy programme.

METHODS: The CONTROL trial is a randomized, placebo-controlled, double-blinded, superiority trial. Patients with breast cancer or a DLBCL, with a normal cardiac function as assessed by echocardiography, scheduled for treatment with anthracyclines as part of their first-line chemotherapy programme will be randomized 1 : 1 to nebivolol 5 mg once daily (o.d.) or placebo. Patients will be examined with cardiological assessment, echocardiography and cardiac biomarkers at baseline, 1 month, 6 months and 12 months. A cardiac magnetic resonance (CMR) assessment will be performed at baseline and at 12 months. The primary end point is defined as left ventricular ejection fraction reduction assessed by CMR at 12 months of follow-up.

CONCLUSION: The CONTROL trial is designed to provide evidence to assess the cardioprotective role of nebivolol in patients undergoing chemotherapy with anthracyclines.

CLINICAL TRIAL REGISTRATION: The study is registered in the EudraCT registry (number: 2017-004618-24) and in the ClinicalTrials.gov registry (identifier: NCT05728632).

PMID:37285278 | DOI:10.2459/JCM.0000000000001491

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PubMed articles on: Cardio-Oncology

Investigation of cardioprotective effect of lercanidipine on doxorubicin-induced cardiotoxicity

Naunyn Schmiedebergs Arch Pharmacol. 2023 Jun 7. doi: 10.1007/s00210-023-02566-7. Online ahead of print.

ABSTRACT

Although doxorubicin (DOX) is an effective anti-neoplastic drug for many types of cancer, particularly dose-related cardiotoxicity limits the use of the drug. In this study, it was aimed to investigate the protective effect of lercanidipine (LRD) against DOX-induced cardiotoxicity. In our study, 40 Wistar albino female rats were randomly divided into 5 groups as control, DOX, LRD 0.5 (DOX + 0.5 mg/kg LRD), LRD 1 (DOX + 1 mg/kg LRD), and LRD 2 (DOX + 2 mg/kg LRD). At the end of the experiment, the rats were sacrificed, and their blood, heart, and endothelial tissues were examined biochemically, histopathologically, immunohistochemically, and genetically. According to our findings, necrosis, tumor necrosis factor alpha activity, vascular endothelial growth factor activity, and oxidative stress were increased in the heart tissues of the DOX group. In addition, DOX treatment caused the deteriorations in biochemical parameters, and levels of autophagy-related proteins, Atg5, Beclin1, and LC3-I/II were detected. Significant dose-related improvements in these findings were observed with LRD treatment. Besides, Atg5, LC3-I/II, and Beclin1 levels evaluated by western blot revealed that LRD exerts a tissue protective effect by regulating autophagy in endothelial tissue. LRD treatment, which is a new-generation calcium channel blocker, showed antioxidant, anti-inflammatory, and anti-apoptotic properties in heart and endothelial tissue in a dose-dependent manner and also showed protective activity by regulating autophagy in endothelial tissue. With studies evaluating these mechanisms in more detail, the protective effects of LRD will be revealed more clearly.

PMID:37284897 | DOI:10.1007/s00210-023-02566-7

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PubMed articles on: Cardio-Oncology

Impact of Volumetric Dosimetry on the Projected Cost of Radiation-Related Late Effects Screening After Childhood Cancer: A Real-World Cohort Analysis

Oncologist. 2023 Jun 7:oyad136. doi: 10.1093/oncolo/oyad136. Online ahead of print.

ABSTRACT

BACKGROUND: Screening guidelines for childhood cancer survivors treated with radiation currently rely on broad anatomic irradiated regions (IR) to determine risk for late effects. However, contemporary radiotherapy techniques use volumetric dosimetry (VD) to define organ-specific exposure, which supports more specific screening recommendations that could be less costly.

PATIENTS AND METHODS: This was a cross-sectional study of 132 patients treated with irradiation at Children's Hospital Los Angeles from 2000 to 2016. For 5 key organs (cochlea, breast, heart, lung, and colon), radiation exposure was determined retrospectively using both IR and VD methods. Under each method, Children's Oncology Group Long-Term Follow-Up Guidelines were used to identify organs flagged for screening and recommended screening tests. Projected screening costs incurred under each method were computed through age 65 using insurance claims data.

RESULTS: Median age at the end of treatment was 10.6 years (range, 1.4-20.4). Brain tumor was the most common diagnosis (45%) and head/brain the most common irradiated region (61%). For all 5 organs, use of VD rather than IR resulted in fewer recommended screening tests. This led to average cumulative estimated savings of $3769 (P = .099), with significant savings in patients with CNS tumors (P = .012). Among patients with savings, average savings were $9620 per patient (P = .016) and significantly more likely for females than males (P = .027).

CONCLUSION: Use of VD to enhance precision of guideline-based screening for radiation-related late effects permits fewer recommended screening tests and generates cost-savings.

PMID:37284853 | DOI:10.1093/oncolo/oyad136

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PubMed articles on: Cardio-Oncology

CAR-T Therapy in Lymphoma Patients With Coexisting Cardiomyopathy or Cardiac Lymphomatous Involvement

JACC Case Rep. 2023 Apr 21;15:101840. doi: 10.1016/j.jaccas.2023.101840. eCollection 2023 Jun 7.