Management of pulmonary embolism in patients with cancer

ESC CardioMed ◽  
2018 ◽  
pp. 2790-2794
Author(s):  
Cihan Ay ◽  
Florian Posch
Keyword(s):  
Pulmonary Embolism ◽  
Standard Of Care ◽  
Bleeding Risk ◽  
Current Standard ◽  
Gastrointestinal Malignancies ◽  
Patients With Cancer ◽  
Function Impairment ◽  
Colorectal Cancer Patients ◽  
High Index Of Suspicion

Pulmonary embolism (PE) is a frequent complication in patients with cancer. Clinicians have to maintain a high index of suspicion to reduce the large proportion of PEs that remain undiagnosed in the cancer population. Thrombolysis is not a standard treatment for haemodynamically unstable patients with cancer-associated PE because the risk of haemorrhage can be excessive. Anticoagulation with a low-molecular-weight heparin (LMWH) or a non-vitamin K antagonist oral anticoagulant (NOAC) for at least 6 months is the current standard of care for the treatment of cancer-associated PE. Due to signals of an increased bleeding risk as compared to LMWH, NOACs should be administered cautiously in patients with luminal gastrointestinal malignancies such as oesophagogastric or colorectal cancer. Patients with active malignancy and ongoing cancer therapy appear to be the strongest candidates for long-term anticoagulation beyond 6 months. Guidance statements facilitate the management of challenging patients with brain metastases, unsuspected PE, thrombocytopenia, kidney function impairment, and recurrent PE.

Management of pulmonary embolism in patients with cancer

ESC CardioMed ◽  
2018 ◽  
pp. 2790-2794
Author(s):  
Cihan Ay ◽  
Florian Posch
Keyword(s):  
Pulmonary Embolism ◽  
Vitamin K ◽  
Meta Analysis ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Standard Of Care ◽  
Current Standard ◽  
Patients With Cancer ◽  
High Index Of Suspicion ◽  
Excessive Anticoagulation

Pulmonary embolism (PE) is a frequent complication in patients with cancer. Clinicians have to maintain a high index of suspicion to reduce the large proportion of PEs that remain undiagnosed in the cancer population. Thrombolysis is not a standard treatment for haemodynamically unstable patients with cancer-associated PE because the risk of haemorrhage can be excessive. Anticoagulation with a low-molecular-weight heparin (LMWH) for at least 6 months is the current standard of care for the treatment of cancer-associated PE, while vitamin K antagonists are a reasonable second choice for patients with contraindications against LMWH or a strong preference towards an oral agent. Although an indirect network meta-analysis suggests that non-vitamin K-dependent oral anticoagulants may be comparably efficacious and safe as LMWH for treating PE in cancer patients, these agents cannot be recommended as a standard first-line treatment at this time because a head-to-head comparison to the standard of care has not yet been reported. Anticoagulation beyond 6 months is an emerging concept; however, the patient population that may benefit from this intervention still needs to be defined. Guidance statements facilitate the management of challenging patients with brain metastases, unsuspected PE, thrombocytopenia, and recurrent PE.

scholarly journals Economic Analysis of Rivaroxaban for the Treatment and Long-Term Prevention of Venous Thromboembolism in Portugal

2014 ◽  
Vol 27 (5) ◽  
pp. 615 ◽  
Author(s):  
Isabel Fonseca Santos ◽  
Sónia Pereira ◽  
Euan McLeod ◽  
Anne-Laure Guillermin ◽  
Ismini Chatzitheofilou
Keyword(s):  
Pulmonary Embolism ◽  
Venous Thromboembolism ◽  
Standard Of Care ◽  
Quality Adjusted Life Years ◽  
Vein Thrombosis ◽  
Scenario Analyses ◽  
Life Years ◽  
Deep Vein ◽  
Quality Adjusted Life

<p><strong>Introduction:</strong> Venous thromboembolism is a burden on healthcare systems. The aim of this analysis was to project the long-term costs and outcomes for rivaroxaban compared to standard of care (enoxaparin/warfarin) in Portugal for the treatment and secondary prevention of venous thromboembolism.<br /><strong>Material and Methods:</strong> A Markov model was developed using event rates extracted from the EINSTEIN trials supplemented with literature-based estimates of longer-term outcomes. Core outcomes included per patient costs and quality-adjusted life years reported separately per treatment arm and incrementally, as well as cost per quality-adjusted life years gained. The deep vein thrombosis and pulmonary embolism indications were analysed separately. The analyses were conducted from the Portuguese societal perspective and over a 5-year time horizon. Costs and outcomes were discounted at a 5% annual rate. Several scenario analyses were undertaken to explore the impact on results of varying key modeling assumptions.<br /><strong>Results:</strong> Rivaroxaban treatment was associated with cost-savings for the treatment of deep vein thrombosis and was both cost-saving and more effective for the treatment of pulmonary embolism, compared with enoxaparin/warfarin.<br /><strong>Discussion:</strong> The results of the sensitivity and scenario analyses further supported that rivaroxaban is a cost-effective alternative to standard of care treatment. The use of an expert panel to derive some input values and the lack of Portuguese specific utilities were the main limitations.<br /><strong>Conclusion:</strong> Rivaroxaban represents an efficient alternative to using enoxaparin/warfarin in Portugal, as it’s associated with lower costs (for both indications) and greater quality adjusted life years (for the pulmonary embolism indication).</p><p><br /><strong>Keywords: </strong>Venous Thrombosis; Pulmonary Embolism; Rivaroxaban; Venous Thromboembolism.</p>

scholarly journals The Yin and the Yang of Treatment for Chronic Hepatitis B—When to Start, When to Stop Nucleos(t)ide Analogue Therapy

Viruses ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 934 ◽  
Author(s):  
Samuel Hall ◽  
Jessica Howell ◽  
Kumar Visvanathan ◽  
Alexander Thompson
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
Antiviral Agents ◽  
Standard Of Care ◽  
Current Standard ◽  
Hbsag Loss ◽  
Personalised Treatment ◽  
Treat All

Over 257 million individuals worldwide are chronically infected with the Hepatitis B Virus (HBV). Nucleos(t)ide analogues (NAs) are the first-line treatment option for most patients. Entecavir (ETV) and tenofovir disoproxil fumarate (TDF) are both potent, safe antiviral agents, have a high barrier to resistance, and are now off patent. They effectively suppress HBV replication to reduce the risk of cirrhosis, liver failure, and hepatocellular carcinoma (HCC). Treatment is continued long-term in most patients, as NA therapy rarely induces HBsAg loss or functional cure. Two diverging paradigms in the treatment of chronic hepatitis B have recently emerged. First, the public health focussed “treat-all” strategy, advocating for early and lifelong antiviral therapy to minimise the risk of HCC as well as the risk of HBV transmission. In LMICs, this strategy may be cost saving compared to monitoring off treatment. Second, the concept of “stopping” NA therapy in patients with HBeAg-negative disease after long-term viral suppression, a personalised treatment strategy aiming for long-term immune control and even HBsAg loss off treatment. In this manuscript, we will briefly review the current standard of care approach to the management of hepatitis B, before discussing emerging evidence to support both the “treat-all” strategy, as well as the “stop” strategy, and how they may both have a role in the management of patients with chronic hepatitis B.

scholarly journals Radiotherapy in the treatment of gastrointestinal stromal tumor

Rare Tumors ◽  
2011 ◽  
Vol 3 (4) ◽  
pp. 111-113 ◽  
Author(s):  
Christin A. Knowlton ◽  
Luther W. Brady ◽  
Rebecca C. Heintzelman
Keyword(s):  
Kinase Inhibitor ◽  
Standard Of Care ◽  
High Rate ◽  
Viable Option ◽  
Current Standard ◽  
Mesenchymal Tumors ◽  
Palliative Setting ◽  
Term Response

Gastrointestinal stromal tumors (GISTs) are uncommon mesenchymal tumors of the gastrointestinal tract. Up to one-third of GISTs are malignant with a high rate of metastasis. Surgical resection is the mainstay of care for patients with resectable disease. Imatinib mesylate, a selective tyrosine kinase inhibitor, is the current standard of care for GISTs that cannot be completely resected or in cases of metastatic GIST. Although often overlooked, radiation therapy is a viable option for select patients with GIST. We report the case of a patient with unresectable GIST who was treated with local radiotherapy and achieved long-term response. We also present a review of the literature regarding the use of radiotherapy in the treatment of GIST. GIST has been shown to be a radiosensitive tumor. Radiotherapy can offer long-term local control and should be considered in the adjuvant or palliative setting. The role of radiotherapy delivered concurrently with imatinib in the treatment of GIST may warrant further investigation.

scholarly journals Curcumin in Autoimmune and Rheumatic Diseases

Nutrients ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 1004 ◽  
Author(s):  
Melissa Yang ◽  
Umair Akbar ◽  
Chandra Mohan
Keyword(s):  
Type 2 Diabetes ◽  
Ulcerative Colitis ◽  
Clinical Trials ◽  
Therapeutic Agent ◽  
Standard Of Care ◽  
Cohort Size ◽  
Lipid Levels ◽  
Current Standard

Over recent decades, many clinical trials on curcumin supplementation have been conducted on various autoimmune diseases including osteoarthritis, type 2 diabetes, and ulcerative colitis patients. This review attempts to summarize the highlights from these clinical trials. The efficacy of curcumin either alone or in conjunction with existing treatment was evaluated. Sixteen clinical trials have been conducted in osteoarthritis, 14 of which yielded significant improvements in multiple disease parameters. Eight trials have been conducted in type 2 diabetes, all yielding significant improvement in clinical or laboratory outcomes. Three trials were in ulcerative colitis, two of which yielded significant improvement in at least one clinical outcome. Additionally, two clinical trials on rheumatoid arthritis, one clinical trial on lupus nephritis, and two clinical trials on multiple sclerosis resulted in inconclusive results. Longer duration, larger cohort size, and multiple dosage arm trials are warranted to establish the long term benefits of curcumin supplementation. Multiple mechanisms of action of curcumin on these diseases have been researched, including the modulation of the eicosanoid pathway towards a more anti-inflammatory pathway, and the modulation of serum lipid levels towards a favorable profile. Overall, curcumin supplementation emerges as an effective therapeutic agent with minimal-to-no side effects, which can be added in conjunction to current standard of care.

scholarly journals Targeted Therapy as a Potential De-Escalation Strategy in Locally Advanced HPV-Associated Oropharyngeal Cancer: A Literature Review

2021 ◽  
Vol 11 ◽  
Author(s):  
Lennox Chitsike ◽  
Penelope J. Duerksen-Hughes
Keyword(s):  
Targeted Therapy ◽  
Targeted Therapies ◽  
Locally Advanced ◽  
Standard Of Care ◽  
Therapeutic Index ◽  
Clinical Validation ◽  
Current Standard ◽  
Ongoing Research ◽  
Molecular Features

The treatment landscape of locally advanced HPV-oropharyngeal squamous cell carcinoma (OPSCC) is undergoing transformation. This is because the high cures rates observed in OPSCC are paired with severe treatment-related, long-term toxicities. These significant adverse effects have led some to conclude that the current standard of care is over-treating patients, and that de-intensifying the regimens may achieve comparable survival outcomes with lower toxicities. Consequently, several de-escalation approaches involving locally advanced OPSCC are underway. These include the reduction of dosage and volume of intensive cytotoxic regimens, as well as elimination of invasive surgical procedures. Such de-intensifying treatments have the potential to achieve efficacy and concurrently alleviate morbidity. Targeted therapies, given their overall safer toxicity profiles, also make excellent candidates for de-escalation, either alone or alongside standard treatments. However, their role in these endeavors is currently limited, because few targeted therapies are currently in clinical use for head and neck cancers. Unfortunately, cetuximab, the only FDA-approved targeted therapy, has shown inferior outcomes when paired with radiation as compared to cisplatin, the standard radio-sensitizer, in recent de-escalation trials. These findings indicate the need for a better understanding of OPSCC biology in the design of rational therapeutic strategies and the development of novel, OPSCC-targeted therapies that are safe and can improve the therapeutic index of standard therapies. In this review, we summarize ongoing research on mechanism-based inhibitors in OPSCC, beginning with the salient molecular features that modulate tumorigenic processes and response, then exploring pharmacological inhibition and pre-clinical validation studies of candidate targeted agents, and finally, summarizing the progression of those candidates in the clinic.

scholarly journals Tenecteplase in Pulmonary Embolism Patients: A Meta-Analysis and Systematic Review

2021 ◽  
Author(s):  
Zhu Zhang ◽  
Linfeng Xi ◽  
Shuai Zhang ◽  
Yunxia Zhang ◽  
Guohui Fan ◽  
...  
Keyword(s):  
Pulmonary Embolism ◽  
High Risk ◽  
Meta Analysis ◽  
Random Effect ◽  
Random Effect Model ◽  
Bleeding Risk ◽  
Effect Model ◽  
High Bleeding Risk

Abstract OBJECTIVE: To assess the efficacy and safety of tenecteplase in patients with pulmonary embolism (PE). METHODS: We completed the literature search on May 31, 2021 using PubMed, EMBASE and the Web of Science. Analyses were conducted according to PE risk stratification, study design and duration of follow-up. The pooled risk ratios (RRs) and its 95% confident intervals (CIs) for death and major bleeding were calculated using a random-effect model.RESULTS: A total of six studies, with four randomized controlled trials (RCTs) and two cohort studies, were included in this study out of the 160 studies retrieved. For patients with high-risk PE, tenecteplase increased 30-day survival rate (16% vs 6%; P=0.005) and did not increase the incidence of bleeding (6% vs 5%; P=0.73). For patients with intermediate-risk PE, four RCTs suggested that tenecteplase reduced right ventricular insufficiency at 24h early in the onset and the incidence of hemodynamic failure without affecting mortality in a short/long-term [<30 days RR=0.83, 95% CI (0.47, 1.46);≥30 days RR=1.04, 95% CI (0.88, 1.22)]. However, tenecteplase was associated with high bleeding risk [<30 days RR=1.79, 95% CI (1.61, 2.00); ≥30 days RR=1.28, 95% CI (0.62, 2.64)].CONCLUSIONS: Tenecteplase may represent a promising candidate for patients with intermediate/high risk PE. Furthermore, tenecteplase may be preferable in the COVID-19 pandemic due to its all-at-once administration.

scholarly journals Short- and long-term mortality after pulmonary embolism in patients with and without cancer

2018 ◽  
Vol 23 (3) ◽  
pp. 261-266 ◽  
Author(s):  
Ghazi Alotaibi ◽  
Cynthia Wu ◽  
Ambikaipakan Senthilselvan ◽  
Michael Sean McMurtry
Keyword(s):  
Pulmonary Embolism ◽  
Short Term ◽  
Term Survival ◽  
Patients With Cancer ◽  
Risk Of Death ◽  
All Cause Mortality ◽  
Short And Long Term ◽  
Incident Cases ◽  
Long Term Mortality

Pulmonary embolism (PE) is a major cause of mortality and morbidity. It is known that the risk of death varies by provoking factors; however, it is unknown if the risk of death persists beyond the initial diagnosis among patients with cancer-associated and non-cancer provoked patients. In this study, we aimed to investigate the effect of cancer on overall, short- and long-term mortality in a cohort of consecutive incident PE patients. Using administrative databases, we identified all incident cases of PE between 2004 and 2012 in Alberta, Canada. Cases were stratified by provoking factors (i.e. unprovoked, provoked, and cancer-associated). A multivariate Cox survival model was used to estimate the hazard ratios of short- and long-term death. We identified 8641 patients with PE, among which 42.2% were unprovoked, 37.9% were provoked and 19.9% were cancer-associated. The 1-year and 5-year survival probabilities were 60% (95% CI: 57–64%) and 39% (95% CI: 36–43%) in patients with cancer-associated PE, 93% (95% CI: 92–94%) and 80% (95% CI: 78–81%) in provoked PE, and 94% (95% CI: 93–95%) and 85% (95% CI: 83–87%) in unprovoked PE, respectively. Compared to patients with unprovoked events, both short-term and long-term survival in patients with cancer-associated PE have a higher observed risk of all-cause mortality in all age groups ( p<0.001). In contrast, patients with provoked events had a similar short- and long-term all-cause mortality. While PE has a significant mortality in all risk groups, patients with cancer have a higher risk of short-term mortality compared to patients with unprovoked PE.

scholarly journals Penetrance of hypertrophic cardiomyopathy and outcome in sarcomeric mutation carriers

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Lorenzini ◽  
G Norrish ◽  
E Field ◽  
J.P Ochoa ◽  
M Cicerchia ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Gene Mutations ◽  
Standard Of Care ◽  
Current Standard ◽  
Mutation Carriers ◽  
Disease Penetrance ◽  
Long Term Follow Up ◽  
Few Data

Abstract Background Predictive genetic screening of the first degree relatives of patients with hypertrophic cardiomyopathy (HCM) caused by sarcomere protein (SP) gene mutations is current standard of care, but there are few data on long-term outcomes in mutation carriers without HCM. Purpose To establish the role of sex and genotype in HCM penetrance as well as the rate of major adverse clinical events in SP mutation carriers and following the diagnosis of HCM. Methods Retrospective analysis of consecutive adult and paediatric SP mutation carriers identified during family screening and who did not fulfill diagnostic criteria for HCM at first evaluation. Results 321 individuals from 170 families [median age first evaluation 15.2 years (IQR 7.3–32.6); 153 (47.7%) males] were evaluated. Causal SP genes were: MYBPC3 (n=133 (41.4%)), MYH7 (n=77 (24.0%)), TNNI3 (n=51 (15.9%)), TNNT2 (n=40 (12.5%)), TPM1 (n=9 (2.8%)), MYL2 (n=6 (1.9%)), and ACTC1 (n=1 (0.3%)); 4 (1.3%) carried multiple mutations. After a median follow up of 7.4 years (IQR 2.5–12.7), 89 (27.7%) patients developed HCM. Disease penetrance at the age of 50 years was 47% (95% CI 38%-56%). One hundred and fifty three (47.7%) individuals underwent cardiac magnetic resonance (CMR) imaging; among those diagnosed with HCM, 22/89 (24.7%) fulfilled criteria on CMR but not echocardiography. In a multivariable model adjusted for genotype, follow up duration and evaluation with CMR, independent predictors of HCM development were male sex (HR 3.11; CI 1.82–5.32) and abnormal ECG (HR 7.87; CI 4.43–13.97). Patients with MYH7 and multiple mutations were more likely to develop HCM than those with MYBPC3 mutations (HR 2.03; CI 1.04–3.96 and HR 10.13; CI 1.40–72.92, respectively). Disease penetrance was lowest in carriers of TNNI3 mutations (HR 0.13; CI 0.03–0.48). There were no major adverse events in individuals without HCM. Following the diagnosis of HCM, the combined rate of all-cause death, appropriate defibrillator shock or resuscitated cardiac arrest was 1.1%/year [median follow up 4.0 years (IQR 2.1–8.9)]. Conclusions Approximately 50% of SP mutation carriers develop HCM by the age of 50 and become prone to disease complications during long-term follow-up. Sex, MYH7 mutations and the presence of an abnormal ECG are associated with a higher risk of disease development. CMR should be employed systematically in long-term screening. HCM penetrance by sex Funding Acknowledgement Type of funding source: None

scholarly journals PDTM-44. ROLE OF ONC-206 IN REGULATING MEDULLOBLASTOMA TUMOR PROGRESSION

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi196-vi197
Author(s):  
Anshu Malhotra ◽  
Jingbo Liu ◽  
Tobey MacDonald
Keyword(s):  
Cell Lines ◽  
Small Molecule ◽  
Standard Of Care ◽  
Clinical Results ◽  
Current Standard ◽  
Survival Pathways ◽  
Cognitive Deficiencies ◽  
G Protein Coupled

Abstract Medulloblastoma (MB) is the most common malignant brain tumor in children. Of the four different sub-groups, the Sonic Hedgehog (SHH) subgroup accounts for about 30% of human MBs. The current standard of care (resection, cranio-spinal irradiation, and chemotherapy) for MB is typically ineffective for SHH MB in non-infants and those with metastatic disease. Survivors are frequently beset with long-term side effects including cognitive deficiencies and a severely impaired quality of life. Taken together, there is a critical need for novel targeted therapies for SHH MB. Recently, promising preclinical and clinical results have been obtained in a variety of cancers treated with a small molecule antagonist, ONC-201, which acts against DRD2, a G-protein coupled receptor that is widely expressed in MBs and regulates pro-survival pathways in tumors. In the present study we report the activity of ONC-201 and another DRD2 antagonist, ONC-206, which binds DRD2 with increased affinity. We tested three different MB cell lines with varied levels of DRD2 expression against these drugs, and consistently observed increased cell death at lower doses of ONC-206 compared to ONC-201. Following literature reports about the mechanism of action of ONC-201, we also evaluated the role of ClpP gene in MB cell lines. ClpP is a mitochondrial protease that has been shown to directly bind ONC 201. We observed a decrease in the expression of this gene after treatment of MB cell lines with ONC-206. Current studies are focusing on exploring the mechanism by which ONC-206 affects MB growth and metastasis. Dissecting this mechanism will be pivotal in predicting the role of this small molecule as a pre-clinical therapeutic for MB treatment.

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