ABSTRACT
Cancer-associated venous thromboembolism (VTE) is associated with high VTE recurrence and bleeding. We included all randomized clinical trials that evaluated the efficacy and safety of various anticoagulants in cancer-associated VTE. Trial-level data were extracted from 13 trials. Aggregate odds ratios (ORs) were calculated using direct and network meta-analysis. The primary outcome was VTE (pulmonary embolism and/or deep vein thrombosis) recurrence. Secondary outcomes were major bleeding and all-cause mortality. We identified 13 trials with 4869 patient-years of follow-up (6595 total patients; mean age 62.4 ± 12.2; 50.4 % female; 17.7 % hematological malignancies). The most common cancer type was colorectal and 48 % had metastatic cancer at baseline. Compared to vitamin-K-antagonists (VKAs), non-vitamin-K-antagonist-oral-anticoagulants (NOACs) were associated with significantly reduced VTE recurrence (OR, 0.58; 95 % CI, 0.40-0.83) and reduced major bleeding risks (OR, 0.56; 95 % CI, 0.35-0.91). However, no differences were observed in the subgroup analysis of patients with active cancer. Although NOACs were associated with reduced VTE recurrence compared with low-molecular-weight-heparin (LMWHs) (OR, 0.46; 95 % CI, 0.25- 0.85), there was a significant increased major bleeding in high-quality trials. LMWHs were associated with significantly reduced VTE recurrence compared with VKAs (OR, 0.52; 95 % CI, 0.39-0.71) and similar bleeding risks. Conclusions: Among patients with cancer-associated VTE, NOACs were associated with significantly reduced VTE recurrence and bleeding compared with VKAs, however, with similar outcomes in the active cancer population. NOACs were associated with reduced VTE recurrence but higher bleeding risks compared with LMWHs. LMWHs were associated with significantly reduced VTE recurrence and similar bleeding compared with VKAs.
PMID:32540780 | DOI:10.1016/j.critrevonc.2020.103005
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PubMed articles on: Cardio-Oncology
Cardio-Oncology in Brazil: The Dimensions of a New Era in the Care of Patients
Hajjar LA and Mathias C. JACC CardioOncol 2020.
NO ABSTRACT
PMID:32548595 | PMC:PMC7243784 | DOI:10.1016/j.jaccao.2020.05.004
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PubMed articles on: Cancer & VTE/PE
Vascular effects of cancer treatments
Campia U. Vasc Med 2020.
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
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Reprogramming of tumor-associated macrophages by targeting β-catenin/FOSL2/ARID5A signaling: A potential treatment of lung cancer
Sarode P, et al. Sci Adv 2020.
ABSTRACT
Tumor-associated macrophages (TAMs) influence lung tumor development by inducing immunosuppression. Transcriptome analysis of TAMs isolated from human lung tumor tissues revealed an up-regulation of the Wnt/β-catenin pathway. These findings were reproduced in a newly developed in vitro "trained" TAM model. Pharmacological and macrophage-specific genetic ablation of β-catenin reprogrammed M2-like TAMs to M1-like TAMs both in vitro and in various in vivo models, which was linked with the suppression of primary and metastatic lung tumor growth. An in-depth analysis of the underlying signaling events revealed that β-catenin-mediated transcriptional activation of FOS-like antigen 2 (FOSL2) and repression of the AT-rich interaction domain 5A (ARID5A) drive gene regulatory switch from M1-like TAMs to M2-like TAMs. Moreover, we found that high expressions of β-catenin and FOSL2 correlated with poor prognosis in patients with lung cancer. In conclusion, β-catenin drives a transcriptional switch in the lung tumor microenvironment, thereby promoting tumor progression and metastasis.
PMID:32548260 | PMC:PMC7274802 | DOI:10.1126/sciadv.aaz6105
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PubMed articles on: Cardio-Oncology
Risk of Prevalent Asthma among Children Affected by Inflammatory Bowel Disease: A Population-Based Birth Cohort Study
Barbiellini Amidei C, et al. Int J Environ Res Public Health 2020.
ABSTRACT
Literature on the risk of asthma among children with inflammatory bowel disease (IBD) is limited and has reported discording results. To the best of our knowledge, no previous study has evaluated the association between asthma and childhood onset IBD, focusing on pediatric IBD with onset between 10 and 17 years, early-onset IBD (EO-IBD) between 0 and 9 years, and very early-onset IBD (VEO-IBD) between 0 and 5 years, all conditions characterized by different clinical progressions. A nested matched case-control design on a longitudinal cohort of 213,515 newborns was adopted. Conditional binomial regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI) of asthma among children with IBD compared with controls. We found 162 children with IBD and 1620 controls. Overall, childhood onset IBD was associated with increased risks of being affected by asthma (OR: 1.49 95% CI 1.05-2.12), although a significant risk was only present among males (OR: 1.60 95% CI 1.02-2.51). Children with Crohn's disease and ulcerative colitis had similarly increased risks, although they failed to attain statistical significance. Risks of asthma based on age at IBD onset were inversely related to age, with the lowest non-significant risks for pediatric IBD and EO-IBD, while children affected by VEO-IBD had the highest risk of asthma (OR: 2.75 95% CI 1.26-6.02). Our study suggests the presence of a higher prevalence of asthma among both male children with IBD and children with VEO-IBD. It could be advisable to pay greater attention to possible respiratory symptoms among these categories at higher risk.
PMID:32549223 | DOI:10.3390/ijerph17124255
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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
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PubMed articles on: Cardio-Oncology
Cardiovascular disease and asymptomatic childhood cancer survivors: Current clinical practice
Bottinor WJ, et al. Cancer Med 2020.
ABSTRACT
BACKGROUND: It is poorly understood how cardiovascular screening in asymptomatic childhood cancer survivors (CCS) is applied to and impacts clinical care.
OBJECTIVES: To describe the current role of cardiovascular screening in the clinical care of asymptomatic CCS.
METHODS: At 50 pediatric academic medical centers, a childhood cancer survivorship clinic director, pediatric cardiologist, and adult cardiologist with a focus on CCS were identified and invited to participate in a survey. Surveys were managed electronically. Categorical data were analyzed using nonparametric methods.
RESULTS: Of the 95 (63%) respondents, 39% were survivorship practitioners, and 61% were cardiologists. Eighty-eight percent of survivorship practitioners reported that greater than half of CCS received cardiovascular screening. CCS followed by adult cardiology were more likely to be seen by a cardio-oncologist. Those followed by pediatric cardiology were more likely to be seen by a heart failure/transplant specialist. Common reasons for referral to cardiology were abnormal cardiovascular imaging or concerns a CCS was at high risk for cardiovascular disease. Ninety-two percent of cardiologists initiated angiotensin converting enzyme inhibitor or angiotensin receptor blocker therapy for mild systolic dysfunction. Adult cardiologists initiated beta-blocker therapy for less severe systolic dysfunction compared to pediatric cardiologists (P < .001). Pediatric cardiologists initiated mineralocorticoid therapy for less severe systolic dysfunction compared to adult cardiologists (P = .025). Practitioners (93%) support a multi-institutional collaboration to standardize cardiovascular care for CCS.
CONCLUSIONS: While there is much common ground in the clinical approach to CCS, heterogeneity is evident. This highlights the need for cohesive, multi-institutional, standardized approaches to cardiovascular management in CCS.
PMID:32558321 | DOI:10.1002/cam4.3190
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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
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PubMed articles on: Cancer & VTE/PE
Cancer-associated venous thromboembolism: Treatment and prevention with rivaroxaban
Bauersachs R, et al. Res Pract Thromb Haemost 2020 - Review.
ABSTRACT
Cancer-associated venous thromboembolism (VTE) is a frequent, potentially life-threatening event that complicates cancer management. Anticoagulants are the cornerstone of therapy for the treatment and prevention of cancer-associated thrombosis (CAT); factor Xa-inhibiting direct oral anticoagulants (DOACs; apixaban, edoxaban, and rivaroxaban), which have long been recommended for the treatment of VTE in patients without cancer, have been investigated in this setting. The first randomized comparisons of DOACs against low-molecular-weight heparin for the treatment of CAT indicated that DOACs are efficacious in this setting, with findings reflected in recent updates to published guidance on CAT treatment. However, the higher risk of bleeding events (particularly in the gastrointestinal tract) with DOACs highlights the need for appropriate patient selection. Further insights will be gained from additional studies that are ongoing or awaiting publication. The efficacy and safety of DOAC thromboprophylaxis in ambulatory patients with cancer at a high risk of VTE have also been assessed in placebo-controlled randomized controlled trials of apixaban and rivaroxaban. Both studies showed efficacy benefits with DOACs, but both studies also showed a nonsignificant increase in major bleeding events while on treatment. This review summarizes the evidence base for rivaroxaban use in CAT, the patient profile potentially most suited to DOAC use, and ongoing controversies under investigation. We also describe ongoing studies from the CALLISTO (Cancer Associated thrombosis-expLoring soLutions for patients through Treatment and Prevention with RivarOxaban) program, which comprises several randomized clinical trials and real-world evidence studies, including investigator-initiated research.
PMID:32548552 | PMC:PMC7292665 | DOI:10.1002/rth2.12327
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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
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PubMed articles on: Cancer & VTE/PE
microRNAs and Markers of Neutrophil Activation as Predictors of Early Incidental Post-Surgical Pulmonary Embolism in Patients with Intracranial Tumors
Oto J, et al. Cancers (Basel) 2020.
ABSTRACT
Venous thromboembolism (VTE) is a common complication of cancer that severely increases morbidity and mortality. Patients with intracranial tumors are more likely to develop VTE than patients with cancers at other sites. Conversely, limited tools exist to identify patients with high thrombotic risk. Upon activation, neutrophils release their content through different mechanisms triggering thrombosis. We explored the ability of microRNAs (miRNAs) and plasma markers of neutrophil activation measured before surgery to predict the risk of early post-surgical pulmonary embolism (PE) in glioma and meningioma patients. We recruited and prospectively followed 50 patients with glioma and 50 with meningioma, 34% of whom in each group developed an early objectively-diagnosed post-surgical PE. We measured miRNA expression and neutrophil markers (cell-free DNA, nucleosomes, calprotectin and myeloperoxidase) before surgery. In glioma patients, we adjusted and validated a predictive model for post-surgical PE with 6 miRNAs: miR-363-3p, miR-93-3p, miR-22-5p, miR-451a, miR-222-3p and miR-140-3p (AUC = 0.78; 95% Confidence Interval (CI) [0.63, 0.94]) and another with cfDNA and myeloperoxidase as predictors (AUC = 0.71; 95%CI [0.52, 0.90]). Furthermore, we combined both types of markers and obtained a model with myeloperoxidase and miR-140-3p as predictors (AUC = 0.79; 95%CI [0.64, 0.94]). In meningioma patients we fitted and validated a predictive model with 6 miRNAs: miR-29a-3p, miR-660-5p, miR-331-3p, miR-126-5p, miR-23a-3p and miR-23b-3p (AUC = 0.69; 95%CI [0.52, 0.87]). All our models outperformed the Khorana score. This is the first study that analyzes the capability of plasma miRNAs and neutrophil activation markers to predict early post-surgical PE in glioma and meningioma patients. The estimation of the thrombotic risk before surgery may promote a tailored thromboprophylaxis in a selected group of high-risk patients, in order to minimize the incidence of PE and avoid bleedings.
PMID:32545233 | DOI:10.3390/cancers12061536
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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
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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
Thymic carcinoma typically exhibits more clinically aggressive behavior and portends a worse prognosis as compared to thymoma. Venous thromboembolism is a significant cause of morbidity and mortality in oncologic patients. Traditionally, the standard-of-care management of cancer-associated venous thromboembolism has been therapeutic anticoagulation with low molecular weight heparins; however, with the advent of direct oral anticoagulants, there is an ongoing paradigm shift to transition to these novel agents in an attempt to attenuate cancer-associated venous thromboembolism events. We describe an exceedingly rare case of metastatic thymic carcinoma-associated right atrial thrombus with high-risk embolic features, which subsequently underwent near-complete dissolution with rivaroxaban after 3 months.
PMID:32551115 | PMC:PMC7278298 | DOI:10.1177/2050313X20927596
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PubMed articles on: Cancer & VTE/PE
An International Survey on the Use of Thromboprophylaxis in Urological Surgery
Violette PD, et al. Eur Urol Focus 2020.
ABSTRACT
BACKGROUND: The use of perioperative thromboprophylaxis in urological surgery is common but not standardized.
OBJECTIVE: To characterize international practice variation in thromboprophylaxis use in urological surgery.
DESIGN, SETTING, AND PARTICIPANTS: We conducted a scenario-based survey addressing the use of mechanical and pharmacological thromboprophylaxis in urological cancer procedures (radical cystectomy [RC], radical prostatectomy [RP], and radical nephrectomy [RN]) among practicing urologists in Canada, Finland, and Japan. The survey presented patient profiles reflecting a spectrum of risk for venous thromboembolism; the respondents described their clinical practice.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The proportion of respondents who routinely used (1) mechanical, (2) pharmacological, and (3) extended pharmacological prophylaxis was stratified by procedure. A logistic regression identified characteristics associated with thromboprophylaxis use.
RESULTS AND LIMITATIONS: Of 1051 urologists contacted, 570 (54%) participated in the survey. Japanese urologists were less likely to prescribe pharmacological prophylaxis than Canadian or Finnish urologists (p < 0.001 for all procedures). Canadian and Finnish urologists exhibited large variation for extended pharmacological prophylaxis for RP and RN. Finnish urologists were most likely to prescribe extended prophylaxis versus Canadian and Japanese urologists (RC 98%, 84%, and 26%; Open RP 25%, 8%, and 3%; robotic RP 11%, 9%, and 0%; and RN 43%, 7%, and 1%, respectively; p < 0.001 for each procedure). Less variation was found regarding the prescription of mechanical prophylaxis, which was most commonly used until ambulation or discharge. The length of hospital stay was longer in Japan and may bias estimates of extended prophylaxis in Japan.
CONCLUSIONS: We found large variation in clinical practice regarding pharmacological thromboprophylaxis within and between countries. Knowledge translation of evidence-based guidelines may reduce problematic international variation in practice.
PATIENT SUMMARY: Use of medications to decrease blood clots after urological cancer surgery differs within and between countries. Closer adherence to urology guidelines addressing the prevention of blood clots may decrease this variation and improve patient outcomes.
PMID:32561453 | DOI:10.1016/j.euf.2020.05.015
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PubMed articles on: Cancer & VTE/PE
Pressurized intraperitoneal aerosol chemotherapy (PIPAC) for unresectable peritoneal metastasis from gastric cancer
Alyami M, et al. Eur J Surg Oncol 2020.
ABSTRACT
BACKGROUND: PIPAC is a recent approach with promising results for patients with peritoneal metastasis (PM). We aimed to evaluate survival and postoperative outcome of patients with unresectable PM from gastric origin treated with chemotherapy and PIPAC.
METHODS: A retrospective analysis of a prospective maintained PIPAC database was queried for all patients diagnosed with unresectable PM from gastric cancer who underwent PIPAC before 2018. PIPAC with Cisplatin 7.5 mg/m2 and doxorubicin 1.5 mg/m2 were given for 30 min at 6-week intervals. Outcome criteria were overall survival and adverse events according to (CTCAE) version4.0.
RESULTS: One hundred Sixty-three PIPAC were done in 42 consecutive patients. Twenty-two (52%) of the patients were female. Signet-ring cells were observed in 33/42 patients (78.6%). At the first PIPAC, median age was 51.5 years (32-74). Median PCI was 17 (1-39). Twenty (47.6%) patients underwent more than 2 lines of pre-PIPAC chemotherapy. All patients had systemic chemotherapy alternating with PIPAC. Median consecutive PIPAC procedures were 3 (1-12). Overall and major complications (CTCAE - III, IV) occurred in 10 (6.1%) and 5 procedures (3.1%), respectively. Two patients (4.7%) died within 30 days of a PIPAC procedure, one related to small bowel obstruction and a pulmonary embolism for the other. Overall Survival was 19.1 months. Six (14.3%) patients became resectable during treatment and underwent curative intent CRS and HIPEC.
CONCLUSIONS: PIPAC with low-dose cisplatin and doxorubicin is safe and feasible in association with systemic chemotherapy for gastric PM. Survival data are encouraging and justify further clinical studies in this indication.
PMID:32561204 | DOI:10.1016/j.ejso.2020.05.021
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PubMed articles on: Cardio-Oncology
Vascular Damage - Coronary Artery Disease
Cadeddu Dessalvi C, et al. J Cardiovasc Echogr 2020 -
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