1/17/26
ABSTRACT
BACKGROUND: Even though antithrombotic therapy has probably little or even negative effects on the well-being of people with cancer during their last year of life, deprescribing antithrombotic therapy at the end of life is rare in practice. It is often continued until death, possibly resulting in excess bleeding, an increased disease burden and higher healthcare costs.
METHODS: The SERENITY consortium comprises researchers and clinicians from eight European countries with specialties in different clinical fields, epidemiology and psychology. SERENITY will use a comprehensive approach combining a realist review, flash mob research, epidemiological studies, and qualitative interviews. The results of these studies will be used in a Delphi process to reach a consensus on the optimal design of the shared decision support tool. Next, the shared decision support tool will be tested in a randomised controlled trial. A targeted implementation and dissemination plan will be developed to enable the use of the SERENITY tool across Europe, as well as its incorporation in clinical guidelines and policies. The entire project is funded by Horizon Europe.
RESULTS: SERENITY will develop an information-driven shared decision support tool that will facilitate treatment decisions regarding the appropriate use of antithrombotic therapy in people with cancer at the end of life.
CONCLUSIONS: We aim to develop an intervention that guides the appropriate use of antithrombotic therapy, prevents bleeding complications, and saves healthcare costs. Hopefully, usage of the tool leads to enhanced empowerment and improved quality of life and treatment satisfaction of people with advanced cancer and their care givers.
PMID:37276718 | DOI:10.1016/j.thromres.2023.05.008
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PubMed articles on: Cardio-Oncology
A Fondazione Italiana Linfomi cohort study of R-COMP vs R-CHOP in older patients with diffuse large B-cell lymphoma
Blood Adv. 2023 Jun 5:bloodadvances.2023009839. doi: 10.1182/bloodadvances.2023009839. Online ahead of print.
ABSTRACT
R-CHOP is the most commonly used regimen worldwide for the upfront treatment of diffuse large B-cell lymphoma (DLBCL). However, it is associated with significant cardiotoxicity, especially in older patients. The R-COMP regimen, with non-pegylated liposomal doxorubicin, may reduce the risk of cardiac events, but its efficacy has never been demonstrated in prospective trials. In this report, we describe the characteristics and outcome of DLBCL patients≥65 years prospectively enrolled in the Elderly Project by the Fondazione Italiana Linfomi and treated with full doses of R-CHOP or R-COMP per local practice. Starting from a dataset of 1163 cases, 383 (55%) were treated with R-CHOP and 308 (45%) with R-COMP. Patients treated with R-COMP were older (median age 76 vs 71 years), less frequently fit at simplified geriatric assessment (61% vs 88%, p<0.001),1, 32% vs 8%, p<0.001).
PMID:37276080 | DOI:10.1182/bloodadvances.2023009839
13:34
PubMed articles on: Cardio-Oncology
Levels of NT‑proBNP in patients with cancer
Oncol Lett. 2023 May 16;26(1):280. doi: 10.3892/ol.2023.13866. eCollection 2023 Jul.
ABSTRACT
At present, it is well known that natriuretic peptides may be produced by cancer cells. Stimulation of N-terminal pro B-type natriuretic peptide (NT-proBNP) synthesis may be a reaction to activity of several proinflammatory cytokines. NT-proBNP is also a marker of myocardial damage during cardiotoxic chemotherapy by anthracyclines. The present study aimed to analyze the association between NT-proBNP and patient/disease characteristics in patients without cardiac symptoms. The present clinical study included 112 patients with cancer who were undergoing anticancer therapy between December 2017 and December 2021. From each patient, peripheral blood was obtained for detection of NT-proBNP before any therapy, after therapy and 1 year after the first sample. NT-proBNP was examined using an immunochemical method. The mean ± SEM value of NT-pro-BNP in the first, second and third sample was 561.0±75.1, 1,565.4±461.1 and 1,940.7±581.1 ng/l. A total of 15 (13.4%), 27 (24.1%) and 25 (30.1%) patients had elevated levels of NT-pro-BNP in the first, second and third sample above the normal value adjusted to age. It was observed that NT-proBNP was increased in older patients and in patients with progressive metastatic disease with poor prognosis. Patients with non-elevated NT-proBNP in the second and third sample had significantly improved OS compared with patients with elevated NT-proBNP [hazard ratio (HR), 0.47; 95% CI, 0.26-0.85; P=0.002 for the second sample; and HR, 0.29; 95% CI, 0.14-0.60; P=0.0000007, for the third sample]. The baseline NT-proBNP value was not prognostic for OS (HR, 0.98; 95% CI, 0.50-1.92; P=0.96). The present results suggest that the level of NT-proBNP was associated with the extent of oncologic disease. Higher levels were associated with progression of metastatic disease and shorter overall survival.
PMID:37274478 | PMC:PMC10236092 | DOI:10.3892/ol.2023.13866
13:34
PubMed articles on: Cardio-Oncology
Radiation-induced circulating microRNAs linked to echocardiography parameters after radiotherapy
Front Oncol. 2023 May 18;13:1150979. doi: 10.3389/fonc.2023.1150979. eCollection 2023.
ABSTRACT
PURPOSE OF REVIEW: To present the randomized controlled trial (RCT) evidence and highlight the areas of uncertainty regarding direct oral anticoagulants (DOAC) for cancer-associated venous thromboembolism (CAT).
RECENT FINDINGS: In the last years, four RCTs have shown that rivaroxaban, edoxaban, and apixaban are at least as effective as low-molecular-weight heparin (LMWH) for the treatment of both incidental and symptomatic CAT. On the other hand, these drugs increase the risk of major gastrointestinal bleeding in patients with cancer at this site. Another two RCTs have demonstrated that apixaban and rivaroxaban also prevent CAT in subjects at intermediate-to-high risk commencing chemotherapy, albeit at the price of higher likelihood of bleeding. By contrast, data are limited about the use DOAC in individuals with intracranial tumors or concomitant thrombocytopenia. It is also possible that some anticancer agents heighten the effects of DOAC via pharmacokinetic interactions, up to making their effectiveness-safety profile unfavorable. Leveraging the results of the aforementioned RCTS, current guidelines recommend DOAC as the anticoagulants of choice for CAT treatment and, in selected cases, prevention. However, the benefit of DOAC is less defined in specific patient subgroups, in which the choice of DOAC over LMWH should be carefully pondered.
PMID:37278934 | DOI:10.1007/s11912-023-01428-y
13:34
PubMed articles on: Cardio-Oncology
Cardiac Mechanical Performance Assessment at Different Levels of Exercise in Childhood Acute Lymphoblastic Leukemia Survivors
J Pediatr Hematol Oncol. 2023 May 16. doi: 10.1097/MPH.0000000000002682. Online ahead of print.
ABSTRACT
BACKGROUND: There is a shortage of relevant studies interested in cardiac mechanical performance. Thus, it is clinically relevant to study the impact of cancer treatments on survivors' cardiac mechanical performance to improve our knowledge. The first objective of this study is to assess survivors' cardiac mechanical performance during a cardiopulmonary exercise test (CPET) using both ventricular-arterial coupling (VAC) and cardiac work efficiency (CWE) from cardiac magnetic resonance (CMR) acquisitions. The second objective is to assess the impact of doxorubicin and dexrazoxane (DEX) treatments.
METHODS: A total of 63 childhood acute lymphoblastic leukemia survivors underwent a CMR at rest on a 3T magnetic resonance imaging system, followed by a CPET on ergocycle. The CircAdapt model was used to study cardiac mechanical performance. At different levels of exercise, arterial elastance, end-systolic elastance, VAC, and CWE were estimated.
RESULTS: We observed significant differences between the different levels of exercise for both VAC (P<0.0001)
CONCLUSIONS: This study reveals that the combination of CPET, CMR acquisitions and CircAdapt model was sensitive enough to observe slight changes in the assessment of VAC and CWE parameters. Our study contributes to improving survivors' follow-up and detection of cardiac problems induced by doxorubicin-related cardiotoxicity.
PMID:37278566 | DOI:10.1097/MPH.0000000000002682
13:34
PubMed articles on: Cardio-Oncology
Late-stage diagnosis of carcinoid heart disease due to lack of access to health care
Cardiooncology. 2023 Jun 5;9(1):28. doi: 10.1186/s40959-023-00176-z.
ABSTRACT
Carcinoid syndrome (CS) is a unique constellation of symptoms caused by release of vasoactive substances from neuroendocrine tumors (Pandit et al., StatPearls, 2022). Neuroendocrine tumors are rare with an annual incidence of 2 in 100,000 people (Ram et al., 46:21-27, 2019). Up to 50% of patients with these tumors will develop carcinoid syndrome, which is characterized by symptoms caused by elevated levels of serotonin and most commonly include fatigue, flushing, wheezing, and non-specific gastrointestinal symptoms such as diarrhea and malabsorption (Pandit et al., StatPearls, 2022) (Fox et.al., 90:1224-1228, 2004). Over time, patients with carcinoid syndrome can develop carcinoid heart disease (CHD). CHD refers to the cardiac complications that occur when the vasoactive substances, such as serotonin, tachykinins, and prostaglandins, secreted from the carcinoid tumors. These complications most commonly include valvular abnormalities, but can also present as coronary artery damage, arrhythmias or direct myocardial injury (Ram et al., 46:21-27, 2019). While CHD is not typically an initial feature of carcinoid syndrome, it does eventually occur in up to 70% of patients with carcinoid tumors (Ram et al., 46:21-27, 2019) (Jin et.al., 146:65-73, 2021) (Macfie et.al., 224:665-669, 2022). CHD is associated with significant morbidity and mortality due to the risk of progressive heart failure (Bober et.al., 14:1179546820968101, 2020). In this case, we describe a 35-year-old Hispanic woman in South Texas with undiagnosed carcinoid syndrome for over 10 years that eventually progressed to severe CHD. In this patient's case, we emphasize how lack of access to healthcare resulted in delay of diagnosis, appropriate treatment, and worsened prognosis in this young patient.
PMID:37277819 | PMC:PMC10240769 | DOI:10.1186/s40959-023-00176-z
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PubMed articles on: Cardio-Oncology
Towards optimal use of antithrombotic therapy of people with cancer at the end of life: A research protocol for the development and implementation of the SERENITY shared decision support tool
Thromb Res. 2023 May 13;228:54-60. doi: 10.1016/j.thromres.2023.05.008. Online ahead of print.
ABSTRACT
BACKGROUND: Clinical informatics tools to integrate data from multiple sources have the potential to catalyze population health management of childhood cancer survivors at high risk for late heart failure through the implementation of previously validated risk calculators.
METHODS: The Oklahoma cohort (n = 365) harnessed data elements from Passport for Care (PFC), and the Duke cohort (n = 274) employed informatics methods to automatically extract chemotherapy exposures from electronic health record (EHR) data for survivors 18 years old and younger at diagnosis. The Childhood Cancer Survivor Study (CCSS) late cardiovascular risk calculator was implemented, and risk groups for heart failure were compared to the Children's Oncology Group (COG) and the International Guidelines Harmonization Group (IGHG) recommendations. Analysis within the Oklahoma cohort assessed disparities in guideline-adherent care.
RESULTS: The Oklahoma and Duke cohorts both observed good overall concordance between the CCSS and COG risk groups for late heart failure, with weighted kappa statistics of .70 and .75, respectively. Low-risk groups showed excellent concordance (kappa > .9). Moderate and high-risk groups showed moderate concordance (kappa .44-.60). In the Oklahoma cohort, adolescents at diagnosis were significantly less likely to receive guideline-adherent echocardiogram surveillance compared with survivors younger than 13 years old at diagnosis (odds ratio [OD] 0.22; 95% confidence interval [CI]: 0.10-0.49).
CONCLUSIONS: Clinical informatics tools represent a feasible approach to leverage discrete treatment-related data elements from PFC or the EHR to successfully implement previously validated late cardiovascular risk prediction models on a population health level. Concordance of CCSS, COG, and IGHG risk groups using real-world data informs current guidelines and identifies inequities in guideline-adherent care.
PMID:37283294 | DOI:10.1002/pbc.30474
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PubMed articles on: Cardio-Oncology
Myocardial bridge in a patient with castration-resistant metastatic prostate cancer treated with enzalutamide
J Oncol Pharm Pract. 2023 Jun 6:10781552231180599. doi: 10.1177/10781552231180599. Online ahead of print.
ABSTRACT
INTRODUCTION: Myocardial bridge is a morphological anomaly of the heart characterised by the presence of a myocardial segment above a coronary artery, which results in a higher risk of cardiovascular events. In patients with prostate cancer treated with androgen receptor-targeted agents, a higher risk of cardiotoxicity was observed.
CASE REPORT: An 88 years old man with metastatic castration-resistant prostate cancer in treatment with enzalutamide, denosumab, and triptorelin presented to our attention complaining dyspnoea and angina pectoris.
MANAGEMENT AND OUTCOME: Blood examinations revealed normal Troponin I levels. Transthoracic echocardiography revealed no signs of acute myocardial ischaemia. The treadmill stress test revealed S-T tract under levelling in V4-V6 with a very slow resolution. Coronary angiography identified a myocardial bridge in the medium tract of the interventricular anterior artery. Due to these findings, ranolazine and simvastatin were started and, after multidisciplinary assessment, we decided to continue the treatment with enzalutamide. At the first follow-up visit echocardiography found out the cardiological reports stability and no therapy changes were performed. During follow-up visit cardiological revaluation showed reports stability and no therapy changes were performed.
DISCUSSION: Due to the high prevalence of prostate cancer in elderly patients at high cardiovascular risk and the increasing use of androgen receptor-targeted agent, a multidisciplinary approach is highly recommended to weigh survival benefits on toxicities. This case report may support the use of androgen receptor-targeted agent in elderly patients with controlled cardiovascular diseases, a population that is often excluded from randomised trials.
PMID:37282514 | DOI:10.1177/10781552231180599
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PubMed articles on: Cardio-Oncology
A Phase II Study of Neoadjuvant PLD/Cyclophosphamide and Sequential nab-Paclitaxel Plus Dual HER2 Blockade in HER2-Positive Breast Cancer
Oncologist. 2023 Jun 5:oyad160. doi: 10.1093/oncolo/oyad160. Online ahead of print.
ABSTRACT
BACKGROUND: Neoadjuvant trastuzumab/pertuzumab (HP) plus chemotherapy for HER2-positive breast cancer (BC) achieved promising efficacy. The additional cardiotoxicity still existed. Brecan study evaluated the efficacy and safety of neoadjuvant pegylated liposomal doxorubicin (PLD)/cyclophosphamide and sequential nab-paclitaxel based on HP (PLD/C/HP-nabP/HP).
PATIENTS AND METHODS: Brecan was a single-arm phase II study. Eligible patients with stages IIA-IIIC HER2-positive BC received 4 cycles of PLD, cyclophosphamide, and HP, followed by 4 cycles of nab-paclitaxel and HP. Definitive surgery was scheduled after 21 days for patients completing treatment or experiencing intolerable toxicity. The primary endpoint was the pathological complete response (pCR).
RESULTS: Between January 2020 and December 2021, 96 patients were enrolled. Ninety-five (99.0%) patients received 8 cycles of neoadjuvant therapy and all underwent surgery with 45 (46.9%) breast-conserving surgery and 51 (53.1%) mastectomy. The pCR was 80.2% (95%CI, 71.2%-87.0%). Four (4.2%) experienced left ventricular insufficiency with an absolute decline in LVEF (43%-49%). No congestive heart failure and ≥grade 3 cardiac toxicity occurred. The objective response rate was 85.4% (95%CI, 77.0%-91.1%), including 57 (59.4%) complete responses and 25 (26.0%) partial responses. The disease control rate was 99.0% (95%CI, 94.3%-99.8%). For overall safety, ≥grade 3 AEs occurred in 30 (31.3%) and mainly included neutropenia (30.2%) and asthenia (8.3%). No treatment-related deaths occurred. Notably, age of >30 (P = 0.01; OR = 5.086; 95%CI, 1.44-17.965) and HER2 IHC 3+ (P = 0.02; OR = 4.398; 95%CI, 1.286-15.002) were independent predictors for superior pCR (ClinicalTrials.gov Identifier NCT05346107).
CONCLUSION: Brecan study demonstrated the encouraging safety and efficacy of neoadjuvant PLD/C/HP-nabP/HP, suggesting a potential therapeutic option in HER2-positive BC.
PMID:37279780 | DOI:10.1093/oncolo/oyad160
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PubMed articles on: Cardio-Oncology
Direct Oral Anticoagulants for Cancer-Associated Venous Thromboembolism
Curr Oncol Rep. 2023 Jun 6. doi: 10.1007/s11912-023-01428-y. 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
13:34
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.
ABSTRACT
Chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the management of aggressive hematologic malignancies. However, its role in patients with lymphoma and cardiac metastasis or cardiomyopathy remains undefined due to potentially life-threatening complications such as ventricular rupture, cardiac tamponade, and circulatory failure. We present a case series of patients with lymphoma and cardiomyopathy or cardiac metastasis managed with chimeric antigen receptor T-cell therapy. (Level of Difficulty: Advanced.).
PMID:37283829 | PMC:PMC10240233 | DOI:10.1016/j.jaccas.2023.101840
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PubMed articles on: Cardio-Oncology
Informatics tools to implement late cardiovascular risk prediction modeling for population management of high-risk childhood cancer survivors
Pediatr Blood Cancer. 2023 Jun 7:e30474. doi: 10.1002/pbc.30474. Online ahead of print.
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
PURPOSE OF REVIEW: To present the randomized controlled trial (RCT) evidence and highlight the areas of uncertainty regarding direct oral anticoagulants (DOAC) for cancer-associated venous thromboembolism (CAT).
RECENT FINDINGS: In the last years, four RCTs have shown that rivaroxaban, edoxaban, and apixaban are at least as effective as low-molecular-weight heparin (LMWH) for the treatment of both incidental and symptomatic CAT. On the other hand, these drugs increase the risk of major gastrointestinal bleeding in patients with cancer at this site. Another two RCTs have demonstrated that apixaban and rivaroxaban also prevent CAT in subjects at intermediate-to-high risk commencing chemotherapy, albeit at the price of higher likelihood of bleeding. By contrast, data are limited about the use DOAC in individuals with intracranial tumors or concomitant thrombocytopenia. It is also possible that some anticancer agents heighten the effects of DOAC via pharmacokinetic interactions, up to making their effectiveness-safety profile unfavorable. Leveraging the results of the aforementioned RCTS, current guidelines recommend DOAC as the anticoagulants of choice for CAT treatment and, in selected cases, prevention. However, the benefit of DOAC is less defined in specific patient subgroups, in which the choice of DOAC over LMWH should be carefully pondered.
PMID:37278934 | DOI:10.1007/s11912-023-01428-y
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PubMed articles on: Cancer & VTE/PE
Pulmonary vein stenosis with pulmonary infarction secondary to primary mediastinal seminoma: a case report
Zhonghua Jie He He Hu Xi Za Zhi. 2023 Jun 12;46(6):592-594. doi: 10.3760/cma.j.cn112147-20221026-00847.
ABSTRACT
Pulmonary vein stenosis is a rare condition that is often underdiagnosed and misdiagnosed. The clinical and radiologic manifestations are unspecific such as cough, hemoptysis and pulmonary lesions and are therefore difficult to distinguished with pneumonia and tuberculosis. The present study is a successful case report of pulmonary vein stenosis and pulmonary infraction secondary to mediastinal seminoma. This case suggested that pulmonary vein stenosis should be considered when a mediastinal mass is accompanied by pulmonary opacites that cannot be explained by common causes such as infection.
PMID:37278174 | DOI:10.3760/cma.j.cn112147-20221026-00847
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PubMed articles on: Cancer & VTE/PE
Risk of Venous Thromboembolism in Multiple Myeloma Patients During the Immediate Peri-Autologous Hematopoietic Cell Transplantation Phase
Clin Appl Thromb Hemost. 2023 Jan-Dec;29:10760296231177678. doi: 10.1177/10760296231177678.
ABSTRACT
Venous thromboembolism (VTE) is a serious complication commonly experienced in cancer patients. Incidence of VTE typically brings poor prognosis as it represents the second most common cause of mortality in cancer patients just after the malignancy itself. Studies suggest that multiple myeloma (MM) is among the malignancies with further enhanced risk of VTE, especially in patients undergoing autologous hematopoietic cell transplantation (AHCT). However, risk factors and preventative approaches remain poorly explored. Here, we explore the incidence of VTE in MM patients undergoing AHCT, while also highlighting risk factors and preventions that may aid in preventing VTE in patients who are at higher risk.
PMID:37277999 | DOI:10.1177/10760296231177678
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PubMed articles on: Cancer & VTE/PE
Cerebral infarction and in-hospital mortality for patients admitted to hospital with intracardiac thrombus: insights from the National Inpatient Sample
J Thromb Thrombolysis. 2023 Jun 5. doi: 10.1007/s11239-023-02824-8. Online ahead of print.
ABSTRACT
The factors associated with cerebral infarction and mortality in patients hospitalized with intracardiac thrombus are unknown. A retrospective cohort study was undertaken of nationally representative hospital admissions in the National Inpatient Sample with a diagnosis of intracardiac thrombus between 2016 to 2019. Multiple logistic regressions were used to define factors associated with cerebral infarction and in-hospital mortality. There were a total of 175,370 admissions for patients with intracardiac thrombus and 10.1% patients had cerebral infarction (n = 17,675). Intracardiac thrombus represented 4.4% of primary diagnosis for admissions while circulatory conditions (65.4%), infection (5.9%), gastrointestinal conditions (4.4%), respiratory conditions (4.4%) and cancer (2.2%) were the other prevalent primary diagnoses. All-cause mortality was higher for patients with cerebral infarction (8.5% vs 4.8%). The five factors most associated with cerebral infarction were nephrotic syndrome (OR 2.67 95%CI 1.05-6.78), other thrombophilia (OR 2.12 95%CI 1.52-2.95), primary thrombophilia (OR 1.99 95%CI 1.52-2.53), previous stroke (OR 1.61 95%CI 1.47-1.75) and hypertension (OR 1.41 95%CI 1.27-1.56). The strongest independent predictors of death were heparin induced thrombocytopenia (OR 2.45 95%CI 150-4.00), acute venous thromboembolism (OR 2.03 95%CI 1.78-2.33, p < 0.001) acute myocardial infarction (OR 1.95 95%CI 1.72-2.22), arterial thrombosis (OR 1.75 95%CI 1.39-2.20) and cancer (OR 1.57 95%CI 1.36-1.81). Patients with intracardiac thrombus are at risk of cerebral infarction and in-hospital mortality. Nephrotic syndrome, thrombophilia, previous stroke, hypertension, and heparin induced thrombocytopenia were associated with cerebral infarction, while acute venous thromboembolism, acute myocardial infarction, and cancer were predictors of mortality.
PMID:37277607 | DOI:10.1007/s11239-023-02824-8
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PubMed articles on: Cancer & VTE/PE
Prognosis of incidental pulmonary embolism vs. symptomatic pulmonary embolism in cancer patients: a single-center retrospective cohort study in China
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PubMed articles on: Cancer & VTE/PE
Correction to: Direct oral anticoagulants for venous thromboembolism in cancer patients: a systematic review and network meta-analysis
Support Care Cancer. 2023 Jun 3;31(6):373. doi: 10.1007/s00520-023-07851-y.
NO ABSTRACT
PMID:37269357 | DOI:10.1007/s00520-023-07851-y
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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 Venous thromboembolism (VTE) is associated with increased morbidity, mortality, and healthcare expenditure. However, the comprehensive utilization of anticoagulation therapy in patients with VTE, especially regarding active cancer, in real-world practice remains unclear. Objective To describe the prescription, persistence, and patterns of anticoagulation therapy among patients with VTE stratified according to active cancer. Methods Using Korean nationwide claims data, we identified an incident, treatment-naïve cohort of patients with VTE from 2013 to 2019 and classified them according to the presence/absence of active cancer. We explored the secular trends, treatment patterns (e.g., discontinuation, interruption, and switch), and persistence of anticoagulation therapy. Results There were 48,504 and 7,255 patients without and with active cancer, respectively. NOACs were the most common anticoagulant in both groups (65.1% and 57.9%, respectively). The prescription of non-vitamin K antagonist oral anticoagulants (NOACs) increased steeply over time, regardless of active cancer, whereas parenteral anticoagulants (PACs) plateaued and warfarin decreased sharply. A heterogeneous pattern was observed between the groups without and with active cancer (3-month persistence was 60.8%, 62.9%, 57.2%, and 3.4%, respectively; 6-month persistence was 42.3%, 33.5%, 25.9%, and 1.2% vs. 9.9%). Median duration of continuous anticoagulant therapy for warfarin, NOAC, and PAC were 183, 147, and 3 days in non-active cancer patients, and 121, 117, and 44 days in active cancer patients. Conclusion Our findings suggest that there were substantial differences in persistence, patterns, and patient characteristics of anticoagulant therapy based on index anticoagulant and active cancer.
PMID:37285903 | DOI:10.1055/a-2107-0815
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Bevacizumab loaded CalliSpheres® bronchial arterial chemoembolization combined with immunotherapy and targeted therapy for advanced lung adenocarcinoma
Front Pharmacol. 2023 May 22;14:1170344. doi: 10.3389/fphar.2023.1170344. eCollection 2023.
ABSTRACT
Background:As a new drug delivery and embolization system, drug-eluted bronchial artery chemoembolization (DEB-BACE) can not only embolize the tumor blood supply artery but also load chemotherapy drugs and slowly release them into the local environment. Bevacizumab (BEV) combined with chemotherapy drugs has attained significant achievements in the first-line treatment of advanced non-squamous non-small cell lung cancer (NSCLC). The role of BEV-loaded DEB-BACE combined with immunotherapy and targeted therapy in patients with lung adenocarcinoma (LUAD) is unclear. This study was designed to evaluate the efficacy and safety of bevacizumab-loaded CalliSpheres® bronchial arterial chemoembolization combined with immunotherapy and targeted therapy in patients with lung adenocarcinoma. Methods:Nine patients with LUAD who received BEV-loaded CalliSpheres® BACE combined with immunotherapy and targeted therapy from 1 Jan 2021 to Dec 2021 were included in this study. The primary endpoint was the disease control rate (DCR) and the objective response rate (ORR). The secondary endpoints were the overall survival rates (OS) at 6 months and 12 months. The tumor response was evaluated according to the mRECIST standard. Safety was assessed by the occurrences of adverse events and the severity of the adverse events. Results:All patients received CalliSpheres® BACE loaded with BEV (200 mg) in combination with immunotherapy and targeted therapy. A total of nine patients received the BACE procedures 20 times, four of them received a third session of BACE, three underwent a second session of DEB-BACE, and two underwent one cycle of DEB-BACE. Partial response and stable disease were found in seven (77.8%), and two (22.2%) patients, respectively, 1 month after the last multimodal treatment. The ORR at 1, 3, 6, and 12 months was 77.8%, 66.7%, 44.4%, and 33.3%, respectively, while the DCR was 100%, 77.8%, 44.4%, and 33.3%, respectively. The OS rates at 6-and 12-month were 77.8% and 66.7%, respectively. There were no serious adverse events. Conclusion:BEV-loaded CalliSpheres® transcatheter bronchial arterial chemoembolization combined with immunotherapy and targeted therapy is a promising and well-tolerated treatment for patients with lung adenocarcinoma.
PMID:37284322 | PMC:PMC10239861 | DOI:10.3389/fphar.2023.1170344
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PubMed articles on: Cancer & VTE/PE
Tissue factor (coagulation factor III): a potential double-edge molecule to be targeted and re-targeted toward cancer
Biomark Res. 2023 Jun 6;11(1):60. doi: 10.1186/s40364-023-00504-6.
ABSTRACT
Tissue factor (TF) is a protein that plays a critical role in blood clotting, but recent research has also shown its involvement in cancer development and progression. Herein, we provide an overview of the structure of TF and its involvement in signaling pathways that promote cancer cell proliferation and survival, such as the PI3K/AKT and MAPK pathways. TF overexpression is associated with increased tumor aggressiveness and poor prognosis in various cancers. The review also explores TF's role in promoting cancer cell metastasis, angiogenesis, and venous thromboembolism (VTE). Of note, various TF-targeted therapies, including monoclonal antibodies, small molecule inhibitors, and immunotherapies have been developed, and preclinical and clinical studies demonstrating the efficacy of these therapies in various cancer types are now being evaluated. The potential for re-targeting TF toward cancer cells using TF-conjugated nanoparticles, which have shown promising results in preclinical studies is another intriguing approach in the path of cancer treatment. Although there are still many challenges, TF could possibly be a potential molecule to be used for further cancer therapy as some TF-targeted therapies like Seagen and Genmab's tisotumab vedotin have gained FDA approval for treatment of cervical cancer. Overall, based on the overviewed studies, this review article provides an in-depth overview of the crucial role that TF plays in cancer development and progression, and emphasizes the potential of TF-targeted and re-targeted therapies as potential approaches for the treatment of cancer.
PMID:37280670 | DOI:10.1186/s40364-023-00504-6
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PubMed articles on: Cancer & VTE/PE
Direct Oral Anticoagulants for Cancer-Associated Venous Thromboembolism
Curr Oncol Rep. 2023 Jun 6. doi: 10.1007/s11912-023-01428-y. 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
Direct Oral Anticoagulants for Cancer-Associated Venous Thromboembolism
Curr Oncol Rep. 2023 Jun 6. doi: 10.1007/s11912-023-01428-y. Online ahead of print.
ABSTRACT
PURPOSE OF REVIEW: To present the randomized controlled trial (RCT) evidence and highlight the areas of uncertainty regarding direct oral anticoagulants (DOAC) for cancer-associated venous thromboembolism (CAT).
RECENT FINDINGS: In the last years, four RCTs have shown that rivaroxaban, edoxaban, and apixaban are at least as effective as low-molecular-weight heparin (LMWH) for the treatment of both incidental and symptomatic CAT. On the other hand, these drugs increase the risk of major gastrointestinal bleeding in patients with cancer at this site. Another two RCTs have demonstrated that apixaban and rivaroxaban also prevent CAT in subjects at intermediate-to-high risk commencing chemotherapy, albeit at the price of higher likelihood of bleeding. By contrast, data are limited about the use DOAC in individuals with intracranial tumors or concomitant thrombocytopenia. It is also possible that some anticancer agents heighten the effects of DOAC via pharmacokinetic interactions, up to making their effectiveness-safety profile unfavorable. Leveraging the results of the aforementioned RCTS, current guidelines recommend DOAC as the anticoagulants of choice for CAT treatment and, in selected cases, prevention. However, the benefit of DOAC is less defined in specific patient subgroups, in which the choice of DOAC over LMWH should be carefully pondered.
PMID:37278934 | DOI:10.1007/s11912-023-01428-y
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Dynamic Patterns and Persistence of Anticoagulation Therapy in Patients with Venous Thromboembolism in South Korea: A Nationwide Cohort Study
Thromb Haemost. 2023 Jun 7. doi: 10.1055/a-2107-0815. Online ahead of print.
ABSTRACT
INTRODUCTION: Myocardial bridge is a morphological anomaly of the heart characterised by the presence of a myocardial segment above a coronary artery, which results in a higher risk of cardiovascular events. In patients with prostate cancer treated with androgen receptor-targeted agents, a higher risk of cardiotoxicity was observed.
CASE REPORT: An 88 years old man with metastatic castration-resistant prostate cancer in treatment with enzalutamide, denosumab, and triptorelin presented to our attention complaining dyspnoea and angina pectoris.
MANAGEMENT AND OUTCOME: Blood examinations revealed normal Troponin I levels. Transthoracic echocardiography revealed no signs of acute myocardial ischaemia. The treadmill stress test revealed S-T tract under levelling in V4-V6 with a very slow resolution. Coronary angiography identified a myocardial bridge in the medium tract of the interventricular anterior artery. Due to these findings, ranolazine and simvastatin were started and, after multidisciplinary assessment, we decided to continue the treatment with enzalutamide. At the first follow-up visit echocardiography found out the cardiological reports stability and no therapy changes were performed. During follow-up visit cardiological revaluation showed reports stability and no therapy changes were performed.
DISCUSSION: Due to the high prevalence of prostate cancer in elderly patients at high cardiovascular risk and the increasing use of androgen receptor-targeted agent, a multidisciplinary approach is highly recommended to weigh survival benefits on toxicities. This case report may support the use of androgen receptor-targeted agent in elderly patients with controlled cardiovascular diseases, a population that is often excluded from randomised trials.
PMID:37282514 | DOI:10.1177/10781552231180599
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PubMed articles on: Cardio-Oncology
A Phase II Study of Neoadjuvant PLD/Cyclophosphamide and Sequential nab-Paclitaxel Plus Dual HER2 Blockade in HER2-Positive Breast Cancer
Oncologist. 2023 Jun 5:oyad160. doi: 10.1093/oncolo/oyad160. Online ahead of print.
ABSTRACT
BACKGROUND: Neoadjuvant trastuzumab/pertuzumab (HP) plus chemotherapy for HER2-positive breast cancer (BC) achieved promising efficacy. The additional cardiotoxicity still existed. Brecan study evaluated the efficacy and safety of neoadjuvant pegylated liposomal doxorubicin (PLD)/cyclophosphamide and sequential nab-paclitaxel based on HP (PLD/C/HP-nabP/HP).
PATIENTS AND METHODS: Brecan was a single-arm phase II study. Eligible patients with stages IIA-IIIC HER2-positive BC received 4 cycles of PLD, cyclophosphamide, and HP, followed by 4 cycles of nab-paclitaxel and HP. Definitive surgery was scheduled after 21 days for patients completing treatment or experiencing intolerable toxicity. The primary endpoint was the pathological complete response (pCR).
RESULTS: Between January 2020 and December 2021, 96 patients were enrolled. Ninety-five (99.0%) patients received 8 cycles of neoadjuvant therapy and all underwent surgery with 45 (46.9%) breast-conserving surgery and 51 (53.1%) mastectomy. The pCR was 80.2% (95%CI, 71.2%-87.0%). Four (4.2%) experienced left ventricular insufficiency with an absolute decline in LVEF (43%-49%). No congestive heart failure and ≥grade 3 cardiac toxicity occurred. The objective response rate was 85.4% (95%CI, 77.0%-91.1%), including 57 (59.4%) complete responses and 25 (26.0%) partial responses. The disease control rate was 99.0% (95%CI, 94.3%-99.8%). For overall safety, ≥grade 3 AEs occurred in 30 (31.3%) and mainly included neutropenia (30.2%) and asthenia (8.3%). No treatment-related deaths occurred. Notably, age of >30 (P = 0.01; OR = 5.086; 95%CI, 1.44-17.965) and HER2 IHC 3+ (P = 0.02; OR = 4.398; 95%CI, 1.286-15.002) were independent predictors for superior pCR (ClinicalTrials.gov Identifier NCT05346107).
CONCLUSION: Brecan study demonstrated the encouraging safety and efficacy of neoadjuvant PLD/C/HP-nabP/HP, suggesting a potential therapeutic option in HER2-positive BC.
PMID:37279780 | DOI:10.1093/oncolo/oyad160
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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
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.
ABSTRACT
Chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the management of aggressive hematologic malignancies. However, its role in patients with lymphoma and cardiac metastasis or cardiomyopathy remains undefined due to potentially life-threatening complications such as ventricular rupture, cardiac tamponade, and circulatory failure. We present a case series of patients with lymphoma and cardiomyopathy or cardiac metastasis managed with chimeric antigen receptor T-cell therapy. (Level of Difficulty: Advanced.).
PMID:37283829 | PMC:PMC10240233 | DOI:10.1016/j.jaccas.2023.101840
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PubMed articles on: Cardio-Oncology
Informatics tools to implement late cardiovascular risk prediction modeling for population management of high-risk childhood cancer survivors
Pediatr Blood Cancer. 2023 Jun 7:e30474. doi: 10.1002/pbc.30474. Online ahead of print.
ABSTRACT
BACKGROUND: Clinical informatics tools to integrate data from multiple sources have the potential to catalyze population health management of childhood cancer survivors at high risk for late heart failure through the implementation of previously validated risk calculators.
METHODS: The Oklahoma cohort (n = 365) harnessed data elements from Passport for Care (PFC), and the Duke cohort (n = 274) employed informatics methods to automatically extract chemotherapy exposures from electronic health record (EHR) data for survivors 18 years old and younger at diagnosis. The Childhood Cancer Survivor Study (CCSS) late cardiovascular risk calculator was implemented, and risk groups for heart failure were compared to the Children's Oncology Group (COG) and the International Guidelines Harmonization Group (IGHG) recommendations. Analysis within the Oklahoma cohort assessed disparities in guideline-adherent care.
RESULTS: The Oklahoma and Duke cohorts both observed good overall concordance between the CCSS and COG risk groups for late heart failure, with weighted kappa statistics of .70 and .75, respectively. Low-risk groups showed excellent concordance (kappa > .9). Moderate and high-risk groups showed moderate concordance (kappa .44-.60). In the Oklahoma cohort, adolescents at diagnosis were significantly less likely to receive guideline-adherent echocardiogram surveillance compared with survivors younger than 13 years old at diagnosis (odds ratio [OD] 0.22; 95% confidence interval [CI]: 0.10-0.49).
CONCLUSIONS: Clinical informatics tools represent a feasible approach to leverage discrete treatment-related data elements from PFC or the EHR to successfully implement previously validated late cardiovascular risk prediction models on a population health level. Concordance of CCSS, COG, and IGHG risk groups using real-world data informs current guidelines and identifies inequities in guideline-adherent care.
PMID:37283294 | DOI:10.1002/pbc.30474
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PubMed articles on: Cardio-Oncology
Myocardial bridge in a patient with castration-resistant metastatic prostate cancer treated with enzalutamide
J Oncol Pharm Pract. 2023 Jun 6:10781552231180599. doi: 10.1177/10781552231180599. Online ahead of print.
ABSTRACT
Venous thromboembolism (VTE) is a serious complication commonly experienced in cancer patients. Incidence of VTE typically brings poor prognosis as it represents the second most common cause of mortality in cancer patients just after the malignancy itself. Studies suggest that multiple myeloma (MM) is among the malignancies with further enhanced risk of VTE, especially in patients undergoing autologous hematopoietic cell transplantation (AHCT). However, risk factors and preventative approaches remain poorly explored. Here, we explore the incidence of VTE in MM patients undergoing AHCT, while also highlighting risk factors and preventions that may aid in preventing VTE in patients who are at higher risk.
PMID:37277999 | DOI:10.1177/10760296231177678
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PubMed articles on: Cancer & VTE/PE
Pulmonary embolism in United States emergency departments, 2010-2018
Sci Rep. 2023 Jun 5;13(1):9070. doi: 10.1038/s41598-023-36123-2.
ABSTRACT
Little is known about pulmonary embolism (PE) in the United States emergency department (ED). This study aimed to describe the disease burden (visit rate and hospitalization) of PE in the ED and to investigate factors associated with its burden. Data were obtained from the National Hospital Ambulatory Medical Care Survey (NHAMCS) from 2010 to 2018. Adult ED visits with PE were identified using the International Classification of Diseases codes. Analyses used descriptive statistics and multivariable logistic regression accounting for the NHAMCS's complex survey design. Over the 9-year study period, there were an estimated 1,500,000 ED visits for PE, and the proportion of PE visits in the entire ED population increased from 0.1% in 2010-2012 to 0.2% in 2017-2018 (P for trend = 0.002). The mean age was 57 years, and 40% were men. Older age, obesity, history of cancer, and history of venous thromboembolism were independently associated with a higher proportion of PE, whereas the Midwest region was associated with a lower proportion of PE. The utilization of chest computed tomography (CT) scan appeared stable, which was performed in approximately 43% of the visits. About 66% of PE visits were hospitalized, and the trend remained stable. Male sex, arrival during the morning shift, and higher triage levels were independently associated with a higher hospitalization rate, whereas the fall and winter months were independently associated with a lower hospitalization rate. Approximately 8.8% of PE patients were discharged with direct-acting oral anticoagulants. The ED visits for PE continued to increase despite the stable trend in CT use, suggesting a combination of prevalent and incident PE cases in the ED. Hospitalization for PE remains common practice. Some patients are disproportionately affected by PE, and certain patient and hospital factors are associated with hospitalization decisions.
PMID:37277498 | PMC:PMC10241783 | DOI:10.1038/s41598-023-36123-2
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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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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
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
Tissue factor (TF) is a protein that plays a critical role in blood clotting, but recent research has also shown its involvement in cancer development and progression. Herein, we provide an overview of the structure of TF and its involvement in signaling pathways that promote cancer cell proliferation and survival, such as the PI3K/AKT and MAPK pathways. TF overexpression is associated with increased tumor aggressiveness and poor prognosis in various cancers. The review also explores TF's role in promoting cancer cell metastasis, angiogenesis, and venous thromboembolism (VTE). Of note, various TF-targeted therapies, including monoclonal antibodies, small molecule inhibitors, and immunotherapies have been developed, and preclinical and clinical studies demonstrating the efficacy of these therapies in various cancer types are now being evaluated. The potential for re-targeting TF toward cancer cells using TF-conjugated nanoparticles, which have shown promising results in preclinical studies is another intriguing approach in the path of cancer treatment. Although there are still many challenges, TF could possibly be a potential molecule to be used for further cancer therapy as some TF-targeted therapies like Seagen and Genmab's tisotumab vedotin have gained FDA approval for treatment of cervical cancer. Overall, based on the overviewed studies, this review article provides an in-depth overview of the crucial role that TF plays in cancer development and progression, and emphasizes the potential of TF-targeted and re-targeted therapies as potential approaches for the treatment of cancer.
PMID:37280670 | DOI:10.1186/s40364-023-00504-6
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PubMed articles on: Cancer & VTE/PE
Direct Oral Anticoagulants for Cancer-Associated Venous Thromboembolism
Curr Oncol Rep. 2023 Jun 6. doi: 10.1007/s11912-023-01428-y. Online ahead of print.
ABSTRACT
PURPOSE OF REVIEW: To present the randomized controlled trial (RCT) evidence and highlight the areas of uncertainty regarding direct oral anticoagulants (DOAC) for cancer-associated venous thromboembolism (CAT).
RECENT FINDINGS: In the last years, four RCTs have shown that rivaroxaban, edoxaban, and apixaban are at least as effective as low-molecular-weight heparin (LMWH) for the treatment of both incidental and symptomatic CAT. On the other hand, these drugs increase the risk of major gastrointestinal bleeding in patients with cancer at this site. Another two RCTs have demonstrated that apixaban and rivaroxaban also prevent CAT in subjects at intermediate-to-high risk commencing chemotherapy, albeit at the price of higher likelihood of bleeding. By contrast, data are limited about the use DOAC in individuals with intracranial tumors or concomitant thrombocytopenia. It is also possible that some anticancer agents heighten the effects of DOAC via pharmacokinetic interactions, up to making their effectiveness-safety profile unfavorable. Leveraging the results of the aforementioned RCTS, current guidelines recommend DOAC as the anticoagulants of choice for CAT treatment and, in selected cases, prevention. However, the benefit of DOAC is less defined in specific patient subgroups, in which the choice of DOAC over LMWH should be carefully pondered.
PMID:37278934 | DOI:10.1007/s11912-023-01428-y
07:09
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PubMed articles on: Cancer & VTE/PE
Pulmonary vein stenosis with pulmonary infarction secondary to primary mediastinal seminoma: a case report
Zhonghua Jie He He Hu Xi Za Zhi. 2023 Jun 12;46(6):592-594. doi: 10.3760/cma.j.cn112147-20221026-00847.
ABSTRACT
Pulmonary vein stenosis is a rare condition that is often underdiagnosed and misdiagnosed. The clinical and radiologic manifestations are unspecific such as cough, hemoptysis and pulmonary lesions and are therefore difficult to distinguished with pneumonia and tuberculosis. The present study is a successful case report of pulmonary vein stenosis and pulmonary infraction secondary to mediastinal seminoma. This case suggested that pulmonary vein stenosis should be considered when a mediastinal mass is accompanied by pulmonary opacites that cannot be explained by common causes such as infection.
PMID:37278174 | DOI:10.3760/cma.j.cn112147-20221026-00847
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PubMed articles on: Cancer & VTE/PE
Risk of Venous Thromboembolism in Multiple Myeloma Patients During the Immediate Peri-Autologous Hematopoietic Cell Transplantation Phase
Clin Appl Thromb Hemost. 2023 Jan-Dec;29:10760296231177678. doi: 10.1177/10760296231177678.
ABSTRACT
Background Venous thromboembolism (VTE) is associated with increased morbidity, mortality, and healthcare expenditure. However, the comprehensive utilization of anticoagulation therapy in patients with VTE, especially regarding active cancer, in real-world practice remains unclear. Objective To describe the prescription, persistence, and patterns of anticoagulation therapy among patients with VTE stratified according to active cancer. Methods Using Korean nationwide claims data, we identified an incident, treatment-naïve cohort of patients with VTE from 2013 to 2019 and classified them according to the presence/absence of active cancer. We explored the secular trends, treatment patterns (e.g., discontinuation, interruption, and switch), and persistence of anticoagulation therapy. Results There were 48,504 and 7,255 patients without and with active cancer, respectively. NOACs were the most common anticoagulant in both groups (65.1% and 57.9%, respectively). The prescription of non-vitamin K antagonist oral anticoagulants (NOACs) increased steeply over time, regardless of active cancer, whereas parenteral anticoagulants (PACs) plateaued and warfarin decreased sharply. A heterogeneous pattern was observed between the groups without and with active cancer (3-month persistence was 60.8%, 62.9%, 57.2%, and 3.4%, respectively; 6-month persistence was 42.3%, 33.5%, 25.9%, and 1.2% vs. 9.9%). Median duration of continuous anticoagulant therapy for warfarin, NOAC, and PAC were 183, 147, and 3 days in non-active cancer patients, and 121, 117, and 44 days in active cancer patients. Conclusion Our findings suggest that there were substantial differences in persistence, patterns, and patient characteristics of anticoagulant therapy based on index anticoagulant and active cancer.
PMID:37285903 | DOI:10.1055/a-2107-0815
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PubMed articles on: Cancer & VTE/PE
Bevacizumab loaded CalliSpheres® bronchial arterial chemoembolization combined with immunotherapy and targeted therapy for advanced lung adenocarcinoma
Front Pharmacol. 2023 May 22;14:1170344. doi: 10.3389/fphar.2023.1170344. eCollection 2023.
ABSTRACT
Background:As a new drug delivery and embolization system, drug-eluted bronchial artery chemoembolization (DEB-BACE) can not only embolize the tumor blood supply artery but also load chemotherapy drugs and slowly release them into the local environment. Bevacizumab (BEV) combined with chemotherapy drugs has attained significant achievements in the first-line treatment of advanced non-squamous non-small cell lung cancer (NSCLC). The role of BEV-loaded DEB-BACE combined with immunotherapy and targeted therapy in patients with lung adenocarcinoma (LUAD) is unclear. This study was designed to evaluate the efficacy and safety of bevacizumab-loaded CalliSpheres® bronchial arterial chemoembolization combined with immunotherapy and targeted therapy in patients with lung adenocarcinoma. Methods:Nine patients with LUAD who received BEV-loaded CalliSpheres® BACE combined with immunotherapy and targeted therapy from 1 Jan 2021 to Dec 2021 were included in this study. The primary endpoint was the disease control rate (DCR) and the objective response rate (ORR). The secondary endpoints were the overall survival rates (OS) at 6 months and 12 months. The tumor response was evaluated according to the mRECIST standard. Safety was assessed by the occurrences of adverse events and the severity of the adverse events. Results:All patients received CalliSpheres® BACE loaded with BEV (200 mg) in combination with immunotherapy and targeted therapy. A total of nine patients received the BACE procedures 20 times, four of them received a third session of BACE, three underwent a second session of DEB-BACE, and two underwent one cycle of DEB-BACE. Partial response and stable disease were found in seven (77.8%), and two (22.2%) patients, respectively, 1 month after the last multimodal treatment. The ORR at 1, 3, 6, and 12 months was 77.8%, 66.7%, 44.4%, and 33.3%, respectively, while the DCR was 100%, 77.8%, 44.4%, and 33.3%, respectively. The OS rates at 6-and 12-month were 77.8% and 66.7%, respectively. There were no serious adverse events. Conclusion:BEV-loaded CalliSpheres® transcatheter bronchial arterial chemoembolization combined with immunotherapy and targeted therapy is a promising and well-tolerated treatment for patients with lung adenocarcinoma.
PMID:37284322 | PMC:PMC10239861 | DOI:10.3389/fphar.2023.1170344
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PubMed articles on: Cancer & VTE/PE
Tissue factor (coagulation factor III): a potential double-edge molecule to be targeted and re-targeted toward cancer
Biomark Res. 2023 Jun 6;11(1):60. doi: 10.1186/s40364-023-00504-6.
ABSTRACT
BACKGROUND: There is a shortage of relevant studies interested in cardiac mechanical performance. Thus, it is clinically relevant to study the impact of cancer treatments on survivors' cardiac mechanical performance to improve our knowledge. The first objective of this study is to assess survivors' cardiac mechanical performance during a cardiopulmonary exercise test (CPET) using both ventricular-arterial coupling (VAC) and cardiac work efficiency (CWE) from cardiac magnetic resonance (CMR) acquisitions. The second objective is to assess the impact of doxorubicin and dexrazoxane (DEX) treatments.
METHODS: A total of 63 childhood acute lymphoblastic leukemia survivors underwent a CMR at rest on a 3T magnetic resonance imaging system, followed by a CPET on ergocycle. The CircAdapt model was used to study cardiac mechanical performance. At different levels of exercise, arterial elastance, end-systolic elastance, VAC, and CWE were estimated.
RESULTS: We observed significant differences between the different levels of exercise for both VAC (P<0.0001)
CONCLUSIONS: This study reveals that the combination of CPET, CMR acquisitions and CircAdapt model was sensitive enough to observe slight changes in the assessment of VAC and CWE parameters. Our study contributes to improving survivors' follow-up and detection of cardiac problems induced by doxorubicin-related cardiotoxicity.
PMID:37278566 | DOI:10.1097/MPH.0000000000002682
05:33
PubMed articles on: Cardio-Oncology
Radiation-induced circulating microRNAs linked to echocardiography parameters after radiotherapy
Front Oncol. 2023 May 18;13:1150979. doi: 10.3389/fonc.2023.1150979. eCollection 2023.
ABSTRACT
INTRODUCTION: Patients treated with radiotherapy to the chest region are at risk of cardiac sequelae, however, identification of those with greatest risk of complications remains difficult. Here, we sought to determine whether short-term changes in circulating miRNA expression are related to measures of cardiac dysfunction in follow-up.
MATERIALS AND METHODS: Two parallel patient cohorts were enrolled and followed up for 3 years after completion of RT to treat left-sided breast cancer. In the primary group (N=28) we used a a panel of 752 miRNAs to identify miRNAs associated with radiation and cardiac indices at follow up. In the second, independent cohort (N=56) we validated those candidate miRNAs with a targeted qPCR panel. In both cohorts. serum samples were collected before RT, 24h after the last dose and 1 month after RT; cardiac echocardiography was performed 2.5-3 year after RT.
RESULTS: Seven miRNAs in the primary group showed marked changes in serum miRNAs immediately after RT compared to baseline and associations with cardiopulmonary dose-volume histogram metrics. Among those miRNAs: miR-15b-5p, miR-22-3p, miR-424-5p and miR-451a were confirmed to show significant decrease of expression 24 hours post-RT in the validation cohort. Moreover, miR-29c, miR-451 and miR-424 were correlated with the end-diastolic diameter of the left ventricle, which was also confirmed in multivariable analysis adjusting for RT-associated factors.
CONCLUSION: We identified a subset of circulating miRNAs predictive for cardiac function impairment in patients treated for left-sided breast cancer, although longer clinical observation could determine if these can be used to predict major clinical endpoints.
PMID:37274244 | PMC:PMC10232985 | DOI:10.3389/fonc.2023.1150979
05:33
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PubMed articles on: Cardio-Oncology
Monocyte-to-lymphocyte ratio as predictor of cancer therapy-related cardiotoxicity in patients with breast cancer: a pilot cohort study
Breast Cancer Res Treat. 2023 Jun 5. doi: 10.1007/s10549-023-06979-z. Online ahead of print.
ABSTRACT
BACKGROUND: Elevated pre-treatment baseline inflammation has been associated with cancer therapy-related cardiac dysfunction (CTRCD) in patients with breast cancer. Monocyte-to-lymphocyte ratio (MLR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio and systemic immune-inflammation index (NLR × platelets) have emerged in clinical context as markers of disease-related inflammation.
OBJECTIVES: To evaluate development of CTRCD according to pre-treatment blood inflammatory biomarkers in patients with breast cancer.
METHODS: Pilot cohort study including consecutive female patients ≥ 18 years with HER2-positive early breast cancer who consulted at the institution's breast oncology outpatient clinic between march/2019 and march/2022. CTRCD: absolute reduction in LVEF > 10% to below 53% (2D-echocardiogram). Survival analysis was performed using Kaplan-Meier curves, compared by the log-rank test, and discrimination ability was evaluated through AUC-ROC.
RESULTS: Forty-nine patients (53.3 ± 13.3 y) were included and followed-up for a median of 13.2 months. CTRCD was observed in 6 (12.2%) patients. Patients with high blood inflammatory biomarkers had lower CTRCD-free survival (P < 0.050 for all). MLR showed statistically significant AUC (0.802; P = 0.017). CTRCD was observed in 27.8% of patients with high MLR versus 3.2% with low MLR (P = 0.020); negative predictive value was 96.8% (95%CI 83.3-99.4%).
CONCLUSION: In patients with breast cancer, elevated pre-treatment inflammatory markers were associated with increased risk of cardiotoxicity. Among these markers, MLR had good discriminatory performance and high negative predictive value. The incorporation of MLR might improve risk evaluation and selection of patients for follow-up during cancer therapy.
PMID:37273150 | DOI:10.1007/s10549-023-06979-z
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07:09
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PubMed articles on: Cancer & VTE/PE
Dynamic Patterns and Persistence of Anticoagulation Therapy in Patients with Venous Thromboembolism in South Korea: A Nationwide Cohort Study
Thromb Haemost. 2023 Jun 7. doi: 10.1055/a-2107-0815. Online ahead of print.
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