ABSTRACT

Background:People with cancer experience high rates of venous thromboembolism (VTE). Additionally, risk of subsequent cancer is increased in people experiencing their first VTE. The causal mechanisms underlying this association are not completely understood, and it is unknown whether VTE is itself a risk factor for cancer. Methods:We used data from large genome-wide association study meta-analyses to perform bi-directional Mendelian randomisation analyses to estimate causal associations between genetically-proxied lifetime risk of VTE and risk of 18 different cancers. Results:We found no conclusive evidence that genetically-proxied lifetime risk of VTE was causally associated with an increased incidence of cancer, or vice-versa. We observed an association between VTE and pancreatic cancer risk (odds ratio for pancreatic cancer 1.23 (95% confidence interval 1.08 - 1.40) per log-odds increase in risk of VTE, P =0.002). However, sensitivity analyses revealed this association was predominantly driven by a variant proxying non-O blood group, with inadequate evidence from Mendelian randomisation to suggest a causal relationship. Conclusions:These findings do not support the hypothesis that genetically-proxied lifetime risk of VTE is a cause of cancer. Existing observational epidemiological associations between VTE and cancer are therefore more likely to be driven by pathophysiological changes which occur in the setting of active cancer and anti-cancer treatments. Further work is required to explore and synthesise evidence for these mechanisms.

KEY MESSAGES: 1) There is strong observational evidence that active cancer is associated with venous thromboembolism.2) It is currently unknown whether venous thromboembolism is a risk factor for cancer.3) We applied a bi-directional Mendelian randomisation framework to appraise the causal relationships between genetically-proxied risk of venous thromboembolism and 18 different cancers.4) Overall, there was no clear evidence from Mendelian randomisation that lifetime-elevated risk of venous thromboembolism is causally associated with an increased risk of cancer, or visa versa.

PMID:37292802 | PMC:PMC10246038 | DOI:10.1101/2023.05.16.23289792

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PubMed articles on: Cancer & VTE/PE

Stroke Recurrence in Embolic Stroke of Undetermined Source Without Atrial Fibrillation on Invasive Cardiac Monitoring

Heart Lung Circ. 2023 Jun 6:S1443-9506(23)00514-0. doi: 10.1016/j.hlc.2023.05.010. Online ahead of print.

ABSTRACT

BACKGROUND: More than half of patients with embolic stroke of undetermined source (ESUS) suffer from recurrent ischaemic stroke, despite the absence of atrial fibrillation (AF) on invasive cardiac monitoring (ICM). This study investigated the predictors and prognosis of recurrent stroke in ESUS without AF on ICM.

METHOD: This prospective study included patients with ESUS at two tertiary hospitals from 2015 to 2021 who underwent comprehensive neurological imaging, transthoracic echocardiography, and inpatient continuous electrographic monitoring for ≥48 hours prior to ICM for definitive exclusion of AF. Recurrent ischaemic stroke, all-cause mortality, and functional outcome by the modified Rankin scale (mRS) at 3 months were evaluated in patients without AF.

RESULTS: Of 185 consecutive patients with ESUS, AF was not detected in 163 (88%) patients (age 62±12 years, 76% men, 25% prior stroke, median time to ICM insertion 26 [7, 123] days), and stroke recurred in 24 (15%) patients. Stroke recurrences were predominantly ESUS (88%), within the first 2 years (75%), and involved a different vascular territory from qualifying ESUS (58%). Pre-existing cancer was the only independent predictor of recurrent stroke (adjusted hazard ratio [AHR] 5.43, 95% CI 1.43-20.64), recurrent ESUS (AHR 5.67, 95% CI 1.15-21.21), and higher mRS score at 3 months (ß 1.27, 95% CI 0.23-2.42). All-cause mortality occurred in 17 (10%) patients. Adjusting for age, cancer, and mRS category (≥3 vs <3),

CONCLUSIONS: Patients with recurrent ESUS are a high-risk subgroup. Studies elucidating optimal diagnostic and treatment strategies in non-AF-related ESUS are urgently required.

PMID:37291002 | DOI:10.1016/j.hlc.2023.05.010

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PubMed articles on: Cancer & VTE/PE

Congenital hepatic hemangioma: an unusual case report of pulmonary hypertension

BMC Pediatr. 2023 Jun 7;23(1):284. doi: 10.1186/s12887-023-04096-w.

ABSTRACT

BACKGROUND: Pulmonary hypertension (PH) in newborns is a rare but serious condition that often requires immediate intervention and quick diagnosis of the correct etiology to prevent mortality. Congenital hepatic hemangioma (CHH) is an example of an extrathoracic etiology of PH.

CASE PRESENTATION: Herein, we report the case of a newborn with a giant liver hemangioma, who presented with an early onset of PH and was successfully treated with intra-arterial embolization.

CONCLUSIONS: This case illustrates the importance of suspicion and prompt evaluation of CHH and related systemic arteriovenous shunts among infants with unexplained PH.

PMID:37286954 | PMC:PMC10245545 | DOI:10.1186/s12887-023-04096-w

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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.

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

Prognosis of incidental pulmonary embolism vs. symptomatic pulmonary embolism in cancer patients: a single-center retrospective cohort study in China

Thromb J. 2023 Jun 6;21(1):64. doi: 10.1186/s12959-023-00502-6.

ABSTRACT

BACKGROUND: The incidence of incidental pulmonary embolism (IPE) has greatly increased, but its clinical characteristics and outcomes are still controversial. This study aimed to compare the clinical characteristics and outcomes between cancer patients with IPE and patients with symptomatic pulmonary embolism (SPE).

PATIENTS/METHODS: Clinical data of 180 consecutive patients with cancer complicated with pulmonary embolism admitted to Beijing Cancer Hospital from July 2011 to December 2019 were retrospectively collected and analysed. General characteristics, diagnosis time of pulmonary embolism (PE), location of PE, concurrent deep venous thrombosis, anticoagulant treatment, impact of PE on anti-tumor treatment, recurrent venous thromboembolism, rate of bleeding after anticoagulation therapy, survival and risk factors of IPE were compared with SPE.

RESULTS: Of 180 patients, 88 (49%) had IPEs and 92 (51%) had SPEs. Patients with IPE and SPE did not differ in age, sex, tumor type, or tumor stage. Median diagnosis times of IPE and SPE after cancer were 108 (45, 432) days and 90 (7, 383) days, respectively. Compared to SPE, IPE tended to be central (44% versus 26%; P < 0.001), isolated (31.8% versus 0.0%; P < 0.001), and unilateral (67.1% versus 12.8%; P < 0.00). The rate of bleeding after anticoagulation therapy did not differ between IPE and SPE. Patients with IPE had a better prognosis than patients with SPE in terms of 30-, and 90-day mortality, as well as overall survival after diagnosis of PE (median: 314.5 vs. 192.0 days, log-rank P = 0.004) and cancer (median: 630.0 vs. 450.5 days, log-rank P = 0.018). SPE (compared to IPE) was an independent risk factor for poor survival after diagnosis of PE in multivariate analysis (hazard ratio [HR] = 1.564, 95% confidence interval [CI]: 1.008-2.425, p = 0.046).

CONCLUSIONS: IPE accounts for nearly one half of PE cases among Chinese cancer patients. With active anticoagulation treatment, IPE is expected to achieve better survival rates than SPE.

PMID:37280671 | PMC:PMC10245445 | DOI:10.1186/s12959-023-00502-6

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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 | PMC:PMC10242999 | DOI:10.1186/s40364-023-00504-6

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PubMed articles on: Cancer & VTE/PE

Comparison of long-term complications in cancer patients with incidental and acute symptomatic venous thromboembolism

Front Cardiovasc Med. 2023 May 19;10:1118385. doi: 10.3389/fcvm.2023.1118385. eCollection 2023.

ABSTRACT

BACKGROUND: Clinical practice guidelines recommend that patients with incidental venous thromboembolism (VTE) receive the same anticoagulant therapy as those with symptomatic VTE. We aimed to compare the rate of complications between cancer patients with incidental and symptomatic VTE through a long-term follow-up cohort.

METHODS: We performed a post hocanalysis of prospective studies of cancer patients with VTE between 2008 and 2019, with the primary outcome of rates of recurrent VTE and clinically relevant bleeding (CRB) in incidental and symptomatic VTE groups.

RESULTS: In total, 796 patients were included, of which 42.8% had incidental VTE. No significant differences were noted in the rate of recurrent VTE (0.4 per 100 patients/month vs. 0.5 per 100 patients/month; p= 0.313) and in the rate of CRB (0.6 per 100 patients/month vs. 0.5 per 100 patients/month; p= 0.128) between patients with incidental VTE and symptomatic VTE, respectively. At six-month follow-ups, the cumulative incidence of CRB was significantly higher in patients with incidental VTE than that in those with symptomatic VTE (7.9% vs. 4.4%, respectively; OR: 1.8; 95% CI: 1.01-3.2).

CONCLUSION: Cancer patients with incidental VTE had similar rates of CRB and VTE recurrence in long-term follow-up compared with patients with symptomatic VTE. At six-month follow-ups, patients with incidental VTE had a higher cumulative incidence of CRB than those with symptomatic VTE.

PMID:37273873 | PMC:PMC10237269 | DOI:10.3389/fcvm.2023.1118385

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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

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PubMed articles on: Cardio-Oncology

Vernonia amygdalina Ethanol Extract Protects against Doxorubicin-Induced Cardiotoxicity via TGFβ, Cytochrome c, and Apoptosis

Molecules. 2023 May 24;28(11):4305. doi: 10.3390/molecules28114305.