ABSTRACT
Chemotherapy, alone or in association with radiation therapy, has represented the cornerstone of cancer treatment for decades. However, in the last several years, an unprecedented progress in the understanding of cancer biology and the discovery of novel therapeutic targets have led to a paradigm shift in the management of patients with neoplastic diseases. The introduction of tyrosine kinase inhibitors, vascular endothelial growth factor pathway inhibitors, immunomodulatory agents, proteasome inhibitors, immune checkpoint inhibitors, and chimeric antigen receptor T cells, among others, has been associated with prolonged survival in many forms of cancer. A common feature of both chemotherapy and novel cancer treatments is the frequent occurrence of vascular toxicity, mainly mediated by injury to the endothelium. While the mechanisms may vary between agents, the clinical manifestations may overlap and range from hypertension, vasospastic and thrombotic arterial events (myocardial ischemia and infarction, peripheral ischemia, and limb gangrene), venous thromboembolism (deep vein thrombosis and pulmonary embolism) to capillary leak syndrome. Therefore, the effective management of patients with cancer requires a multidisciplinary team approach in which oncologist and cardiovascular medicine specialists work together to prevent, detect, and minimize acute vascular toxicity and long-term consequences of cancer therapy.
PMID:32539632 | DOI:10.1177/1358863X20914978
03:11
PubMed articles on: Cardio-Oncology
Left-Ventricular Function After 3 Months of Sacubitril-Valsartan in Acute Decompensated Heart Failure
Mirić D, et al. J Cardiovasc Transl Res 2020.
ABSTRACT
There is limited data on the effect of sacubitril-valsartan on the echocardiographic parameters in acute decompensated heart failure (ADHF). We prospectively enrolled 68 consecutive patients with ADHF who received sacubitril-valsartan (N = 34, S/V group) or angiotensin inhibition-based therapy (N = 34, ACEi/ARB group). Two-dimensional echocardiography with speckle tracking (2D-STE) was performed at baseline and after 3 months of treatment. Changes in 2D-STE parameters, including global longitudinal strain (GLS), were compared between the groups by t test and ANCOVA. Baseline characteristics were similar between the groups. Following 3 months of treatment, LVEF and GLS significantly improved in the S/V group (mean LVEF from 27 to 34.5% and GLS from - 6.6 to - 9.4%) but not in ACEi/ARB group. The improvement in LVEF and GLS was more prominent in patients with non-ischemic cardiomyopathy. In patients with ADHF 3-month treatment with sacubitril-valsartan, compared to guideline directed medical therapy without sacubitril, improves LVEF and GLS. Graphical Abstract A typical change in GLS in a patient with acute decompensated heart failure after 3 months of sacubitril-valsartan.
PMID:32557158 | DOI:10.1007/s12265-020-10041-4
03:11
PubMed articles on: Cancer & VTE/PE
Effect of chemotherapy and longitudinal analysis of circulating extracellular vesicle tissue factor activity in patients with pancreatic and colorectal cancer
Kasthuri RS, et al. Res Pract Thromb Haemost 2020.
ABSTRACT
INTRODUCTION: We conducted a longitudinal study in patients with pancreatic and colorectal cancer. We determined the effect of chemotherapy on extracellular vesicle tissue factor (EVTF) activity and the association of plasma EVTF activity with venous thromboembolism (VTE) and survival.
MATERIAL AND METHODS: We enrolled 13 patients with pancreatic and 22 patients with colorectal cancer. Plasma samples were collected during the 85-day study period. Patients were followed for 3 months after the study period. We recorded symptomatic VTE during the study period (3 months) or asymptomatic deep vein thrombosis detected by ultrasound at day 85. We measured EVTF activity before and after chemotherapy.
RESULTS AND CONCLUSIONS: In the pancreatic cancer group, 2 patients had elevated levels of EVTF activity. One of these patients developed symptomatic VTE and died, and the second patient did not have a VTE but died. Chemotherapy decreased EVTF activity in 2 pancreatic patients with high levels. In the colorectal cancer group, 4 patients developed VTE, but EVTF activity was not elevated in any patient and no patient died. We observed a borderline significant correlation between EVTF activity and D-dimer in the patients with pancreatic but not colorectal cancer. In this small descriptive study, 2 patients with pancreatic cancer had an elevated level of EVTF activity. Both patients died during the study period, and one had a VTE. Chemotherapy decreased EVTF activity in these patients. In contrast, elevated levels of EVTF activity were not observed in patients with colorectal cancer with or without VTE.
PMID:32548563 | PMC:PMC7292676 | DOI:10.1002/rth2.12317
03:11
PubMed articles on: Cardio-Oncology
A clinician's guide for developing a prediction model: a case study using real-world data of patients with castration-resistant prostate cancer
Veen KM, et al. J Cancer Res Clin Oncol 2020 - Review.
ABSTRACT
PURPOSE: With the increasing interest in treatment decision-making based on risk prediction models, it is essential for clinicians to understand the steps in developing and interpreting such models.
METHODS: A retrospective registry of 20 Dutch hospitals with data on patients treated for castration-resistant prostate cancer was used to guide clinicians through the steps of developing a prediction model. The model of choice was the Cox proportional hazard model.
RESULTS: Using the exemplary dataset several essential steps in prediction modelling are discussed including: coding of predictors, missing values, interaction, model specification and performance. An advanced method for appropriate selection of main effects, e.g. Least Absolute Shrinkage and Selection Operator (LASSO) regression, is described. Furthermore, the assumptions of Cox proportional hazard model are discussed, and how to handle violations of the proportional hazard assumption using time-varying coefficients.
CONCLUSION: This study provides a comprehensive detailed guide to bridge the gap between the statistician and clinician, based on a large dataset of real-world patients treated for castration-resistant prostate cancer.
PMID:32556680 | DOI:10.1007/s00432-020-03286-8
03:12
PubMed articles on: Cancer & VTE/PE
Efficacy and safety of direct oral anticoagulants versus low molecular weight heparin for cancer related venous thromboembolism: A meta-analysis of randomized trials
Elbadawi A, et al. Eur Heart J Cardiovasc Pharmacother 2020.
ABSTRACT
AIMS: To examine the efficacy and safety of direct oral anticoagulants (DOAC) versus low molecular weight heparin (LMWH) in patients with cancer-related venous thrombo-embolism (VTE).
METHODS AND RESULTS: An electronic search of MEDLINE, SCOPUS and COCHRANE without language restrictions was performed through April 2020 for randomized controlled trials that compared the effects of DOACs versus LMWH on patients with cancer-related VTE. Summary estimates were reported using random effects model. The main efficacy outcome was VTE recurrence while the main safety outcome was major bleeding events. The final analysis included 4 randomized trials with a total of 2,907 patients. The weighted mean follow-up was 6.1 months. Compared with LMWH, DOACs were associated with lower risk of VTE recurrence (5.7% vs. 9.1%, risk ratio [RR] 0.62; 95% confidence interval [CI] 0.44 to 0.87; P = 0.01), driven by lower deep venous thrombosis (P = 0.02). There was no difference between DOACs and LMWH in major bleeding events (4.8% vs. 3.6%, RR 1.33; 95% CI 0.84 to 2.11; P = 0.23). The incidence of all-cause mortality was similar (RR 0.99; 95% CI 0.84 to 1.16; P = 0.91). Subgroup analysis suggested no differences according to the type of DOAC in recurrent VTE or major bleeding (Pinteraction= 0.53 and Pinteraction= 0.11, respectively).
CONCLUSION: Among patients with cancer-related VTE, DOACs were associated with lower risk of VTE recurrence and similar risk of major bleeding compared with LMWH. Future studies examining the subset of cancer patients who drive the most benefit are encouraged.
PMID:32556105 | DOI:10.1093/ehjcvp/pvaa067
03:12
PubMed articles on: Cardio-Oncology
Echocardiography and biomarkers for the diagnosis of cardiotoxicity
Berliner D, et al. Herz 2020 - Review.
ABSTRACT
As a result of better treatment options for malignant cancer, the cardiovascular side effects of such therapies have increasingly come into focus in recent years. The new cardiological subspecialty of oncocardiology is developing strategies to prevent and/or detect those effects early in order to treat them in a timely and adequate manner. The diagnosis of cardiotoxic effects is based mainly on imaging and specific biomarkers. Echocardiography has become the main imaging technique due to its wide availability. In addition to quantitative determination of left ventricular function using two-dimensional methods, three-dimensional methods offer better precision and less variability in the detection of cardiac dysfunction. Furthermore, the analysis of the global longitudinal strain (GLS) reveals even subtle changes in left ventricular function and thus detects very early damage before left ventricular ejection fraction drops. Various biomarkers have been tested recently for their potential to detect cardiotoxicity. Cardiac troponins are currently the best investigated biomarkers and certainly have the highest impact. Due to contradicting results, the importance of natriuretic peptides has not yet been conclusively clarified. Results for myeloperoxidase are promising, as are the results for circulating microRNAs, which still mainly derive from experimental data. In this context, further studies still need to show the value of these in everyday clinical practice.
PMID:32564096 | DOI:10.1007/s00059-020-04957-5
03:12
PubMed articles on: Cancer & VTE/PE
Risk factors for pediatric cerebral sinovenous thrombosis: A case-control study with case validation
Sellers A, et al. Thromb Res 2020.
ABSTRACT
INTRODUCTION: Cerebral sinovenous thrombosis (CSVT) represents the second most common type of venous thromboembolism (VTE) in children. Current literature includes limited evidence on risk factors for CSVT, particularly in the pediatric population. We sought to determine risk factors for CSVT in pediatric patients through a single-institutional case-control study. In addition, we evaluated thrombophilias, treatments and outcomes in CSVT among cases.
METHODS: A case-control study was performed at Johns Hopkins All Children's Hospital on patients admitted from March 31, 2006 through April 1, 2018. Cases were identified using diagnostic codes and confirmed based on electronic health record (EHR) and neuroimaging review. Controls were matched in a 2:1 fashion accounting for the month and year of admission.
RESULTS: A total of 60 CSVT cases and 120 controls were identified. Median (range) age was 4.8 years (0-21.3 years) for cases and 5.6 years (0-20.0 years) for controls. Factors putatively associated with CSVT in unadjusted analyses were: corticosteroid use, presence of a central venous catheter, mechanical ventilation, systemic infection, head/neck infection, head/neck trauma, and chronic inflammatory disease. In the multivariable model, head/neck infection (OR: 13.8, 95% CI: 4.87-38.7; P < 0.01), head/neck trauma (OR: 12.7, 95% CI: 2.88-56.2; P < 0.01), and mechanical ventilation (OR: 9.32, 95% CI: 2.35-36.9; P = 0.01) remained independent, statistically-significant risk factors. 61% of patients were subacutely treated with anticoagulants and of those, only two developed relevant bleeding after initiation of therapy.
CONCLUSIONS: This single-institutional case-control study reveals that head/neck infection, head/neck trauma, and mechanical ventilation are independent risk factors for pediatric CSVT. These findings will be further investigated via a cooperative registry of pediatric hospital-acquired VTE, by which a risk model for pediatric CSVT will be developed and validated, in order to inform future preventive strategies in at-risk pediatric patients.
PMID:32554256 | DOI:10.1016/j.thromres.2020.06.013
03:12
PubMed articles on: Cardio-Oncology
Cardiac MRI Myocardial Functional and Tissue Characterization Detects Early Cardiac Dysfunction in a Mouse Model of Chemotherapy-Induced Cardiotoxicity
Naresh NK, et al. NMR Biomed 2020.
ABSTRACT
BACKGROUND: Doxorubicin and doxorubicin-trastuzumab combination chemotherapy have been associated with cardiotoxicity that eventually leads to heart failure and may limit dose-effective cancer treatment. Current diagnostic strategies rely on decreased ejection fraction (EF) to diagnose cardiotoxicity.
PURPOSE: The aim of this study is to explore the potential of cardiac MR (CMR) imaging to identify imaging biomarkers in a mouse model of chemotherapy-induced cardiotoxicity.
METHODS: A cumulative dose of 25 mg/kg doxorubicin was administered over three weeks using subcutaneous pellets (n = 9, Dox). Another group (n = 9) received same dose of Dox and a total of 10 mg/kg trastuzumab (DT). Mice were imaged at baseline, 5/6 weeks and 10 weeks post-treatment on a 7T MRI system. The protocol included short-axis cine MRI covering the left ventricle (LV) and mid-ventricular short-axis tissue phase mapping (TPM), pre- and post-contrast T1 mapping, T2 mapping and Displacement Encoding with Stimulated Echoes (DENSE) strain encoded MRI. EF, peak myocardial velocities, native T1, T2, extracellular volume (ECV), and myocardial strain were quantified. N = 7 mice were sacrificed for histopathologic assessment of apoptosis at 5/6 weeks.
RESULTS: Global peak systolic longitudinal velocity was reduced at 5/6 weeks in Dox (0.6 ± 0.3 vs 0.9 ± 0.3, p = 0.02). In the Dox group, native T1 was reduced at 5/6 weeks (1.3 ± 0.2 ms vs 1.6 ± 0.2 ms, p = 0.02), and relatively normalized at week 10 (1.4 ± 0.1 ms vs 1.6 ± 0.2 ms, p > 0.99). There was no change in EF and other MRI parameters and histopathologic results demonstrated minimal apoptosis in all mice (~1-2 apoptotic cell/high power field), suggesting early-stage cardiotoxicity.
CONCLUSIONS: In a mouse model of chemotherapy-induced cardiotoxicity using doxorubicin and trastuzumab, advanced CMR shows promise in identifying treatment-related decrease in myocardial velocity and native T1 prior to the onset of cardiomyocyte apoptosis and reduction of EF.
PMID:32567177 | DOI:10.1002/nbm.4327
03:12
PubMed articles on: Cancer & VTE/PE
Direct oral anticoagulants compared to low-molecular-weight heparin for the treatment of cancer-associated thrombosis: Updated systematic review and meta-analysis of randomized controlled trials
Moik F, et al. Res Pract Thromb Haemost 2020.
ABSTRACT
BACKGROUND: Low-molecular-weight-heparins (LMWHs) have been established for the treatment of cancer-associated venous thromboembolism (VTE). Recently published randomized controlled trials (RCTs) have compared direct oral anticoagulants (DOACs) with LMWHs. The aim of this systematic review and meta-analysis was to evaluate efficacy and safety of DOACs versus LMWHs and update the evidence for treatment of VTE in cancer.
METHODS: Biomedical databases were screened for RCTs evaluating DOACs for cancer-associated VTE. Primary efficacy and safety outcomes of this meta-analysis were recurrent VTE and major bleeding at 6 months. Secondary outcomes comprised clinically relevant nonmajor bleeding (CRNMB), major gastrointestinal (GI) and genitourinary bleeding, mortality, fatal bleeding/pulmonary embolism, and treatment discontinuation rate. We performed prespecified subgroup analyses. Pooled relative risk (RR) and 95% confidence intervals (CIs) were obtained by the Mantel-Haenszel method within a random-effect model.
RESULTS: We screened 759 articles and included 4 RCTs (n = 2894). DOACs significantly reduced recurrent VTEs compared to LMWHs (5.2% vs 8.2%; RR, 0.62 [95% CI, 0.43-0.91]), but were associated with a nonsignificant increase in major bleedings (4.3% vs 3.3%; RR, 1.31 [95% CI, 0.83-2.08]) and a significant increase in CRNMB (10.4% vs 6.4%; RR, 1.65 [95% CI, 1.19-2.28]). Mortality risks were comparable between groups (RR, 0.99 [95% CI, 0.83-1.18]). Preterm treatment discontinuation was less common with DOACs (RR, 0.88 [95% CI, 0.81-0.96]). Major bleeding was more frequent in patients with GI cancer treated with DOACs (RR, 2.30 [95% CI, 1.08-4.88]).
CONCLUSION: In patients with cancer-associated VTE, DOACs are more effective in preventing recurrent VTE compared to LMWH. However, risk of bleeding is increased with DOACs, especially in patients with GI cancer.
PMID:32548553 | PMC:PMC7292654 | DOI:10.1002/rth2.12359
03:12
PubMed articles on: Cancer & VTE/PE
Dissolution of metastatic thymic carcinoma-associated right atrial thrombus with rivaroxaban
Nimblette C, et al. SAGE Open Med Case Rep 2020.
ABSTRACT
Comments
Post a Comment
اكتب تعليق حول الموضوع