ABSTRACT

PURPOSE OF REVIEW: Patients with cancer are at high risk for thrombotic events, mainly deep vein thrombosis and pulmonary embolism. Low-molecular-weight heparins (LMWHs) and direct oral anticoagulants (DOACs) are among the current treatment options for cancer-associated thrombosis (CAT). We assessed real world data (RWD) regarding treatment patterns of CAT from 1 September 2018 to 31 January 2020.

RECENT FINDINGS: RWD showed that LMWHs were the most common initial anticoagulation treatment for CAT. Based on these data DOACs had a lower risk of recurrent venous thromboembolism compared with LMWHs and warfarin. However, the selection bias and the small number of patients in these studies might explain this difference and these limitations should be taken into consideration. Moreover, there was no statistical difference regarding adverse events during anticoagulant treatment between LMWHs and DOACs with the limitations of RWD. As far as the duration of the treatment is concerned, the adherence ranged from 100% to 67.3% at 6 months.

SUMMARY: The current review of RWD illustrates that LMWHs and DOACs are used for the treatment of CAT. LMWHs are most commonly used for the initial management of CAT. Data regarding recurrence of CAT, adverse events, compliance and duration of anticoagulant treatment should be analyzed with caution as RWD are observational studies with many limitations. Further research is needed to elucidate the best algorithm for the management of CAT.

PMID:32541315 | DOI:10.1097/CCO.0000000000000646

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PubMed articles on: Cancer & VTE/PE

Anticoagulants for the treatment of venous thromboembolism in patients with cancer: A comprehensive systematic review, pairwise and network meta-analysis

Sidahmed S, et al. Crit Rev Oncol Hematol 2020 - Review.

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

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.