Catheter-based therapy for intermediate or high-risk pulmonary embolism is associated with lower in-hospital mortality in patients with cancer: Insights from the National Inpatient Sample.

BACKGROUND: Pulmonary embolism (PE) is a common complication among patients with cancer and is a significant contributor to morbidity and mortality. Catheter-based therapies (CBT), including catheter-directed thrombolysis (CDT) and mechanical thrombectomy, have been developed and are used in patients with intermediate or high-risk PE. However, there is a paucity of data on outcomes in patients with cancer as most clinical studies exclude this group of patients. AIMS: To characterize outcomes of patients with cancer admitted with intermediate or high-risk PE treated with CBT compared with no CBT. METHODS: Patients with an admission diagnosis of intermediate or high-risk PE and a history of cancer from October 2015 to December 2018 were identified using the National Inpatient Sample. Outcomes of interest were in-hospital death or cardiac arrest (CA) and major bleeding. Inverse probability treatment weighting (IPTW) was utilized to compare outcomes between patients treated with and without CBT. Variables that remained unbalanced after IPTW were adjusted using multivariable logistic regression. RESULTS: A total of 2084 unweighted admissions (10,420 weighted) for intermediate or high-risk PE and cancer were included, of which 136 (6.5%) were treated with CBT. After IPTW, CBT was associated with lower death or CA (aOR 0.54, 95% CI 0.46-0.64) but higher major bleeding (aOR 1.41, 95% CI 1.21-1.65). After stratifying by PE risk type, patients treated with CBT had lower risk of death or CA in both intermediate (aOR 0.52, 95% CI 0.36-0.75) and high-risk PE (aOR 0.48, 95% CI 0.33-0.53). However, patients with CBT were associated with increased risk of major bleeding in intermediate-risk PE (aOR 2.12, 95% CI 1.67-2.69) but not in those with high-risk PE (aOR 0.84, 95% CI 0.66-1.07). CONCLUSIONS: Among patients with cancer hospitalized with intermediate or high-risk PE, treatment with CBT was associated with lower risk of in-hospital death or CA but higher risk of bleeding. Prospective studies and inclusion of patients with cancer in randomized trials are warranted to confirm our findings.

Optimal authoritative risk assessment score of Cancer-associated venous thromboembolism for hospitalized medical patients with lung Cancer.

BACKGROUND: Cancer-associated venous thromboembolism (VTE) is common in patients with primary lung cancer. It has been understudied which authoritative risk assessment score of cancer-associated VTE is optimal for the assessment of VTE development in hospitalized medical patients with lung cancer. METHODS: Patients with lung cancer who had undergone computed tomography pulmonary angiography (CTPA), compression ultrasonography (CUS) of lower and upper extremities, and/or planar ventilation/perfusion (V/Q) scan to confirm the presence or absence of VTE during a medical hospitalization were retrospectively reviewed. Based on the actual prevalence of VTE among all patients, the possibility of VTE were reassessed with the Khorana score, the PROTECHT score, the CONKO score, the ONKOTEV score, the COMPASS-CAT score, and the CATS/MICA score, to compare their assessment accuracy for VTE development. RESULTS: A total of 1263 patients with lung cancer were incorporated into the final analysis. With respect to assessment efficiency for VTE occurrence, the scores with adjusted agreement from highest to lowest were the ONKOTEV score (78.6%), the PROTECHT score (73.4%), the CONKO score (72.1%), the COMPASS-CAT score (71.7%), the Khorana score (70.9%), and the CATS/MICA score (60.3%). The ONKOTEV score had the highest Youden index which was 0.68, followed by the PROTECHT score (0.58), the COMPASS-CAT score (0.56), the CONKO score (0.55), the Khorana score (0.53), and the CATS/MICA score (0.23). CONCLUSIONS: Among the Khorana score, the PROTECHT score, the CONKO score, the ONKOTEV score, the COMPASS-CAT score, and the CATS/MICA score which are approved by authoritative guidelines, the ONKOTEV score is optimal for the assessment of VTE development in hospitalized medical patients with lung cancer.

Practical considerations for the use of direct oral anticoagulants in oncology patients.

Oncology patients are at a high risk of experiencing venous thromboembolism. Historically, venous thromboembolisms in cancer patients have been managed with low-molecular-weight heparin on the basis of the CLOT trial published in 2003. However, recent prospective data provide evidence for safe and effective direct oral anticoagulant use in this population. The purpose of this review article is to evaluate the current body of literature surrounding direct oral anticoagulant use in the oncology population and to highlight key practical considerations when prescribing these agents for patients with cancer.

Rivaroxaban versus Apixaban for Treatment of Cancer-Associated Venous Thromboembolism in Patients at Lower Risk of Bleeding.

This retrospective study, utilizing U.S. electronic health record (EHR) data from January 2013 to December 2020, sought to assess whether rivaroxaban and apixaban had similar effectiveness and safety in the treatment of cancer-associated venous thromboembolism (VTE) in patients with a cancer type not associated with a high risk of bleeding. We included adults diagnosed with active cancer, excluding esophageal, gastric, unresected colorectal, bladder, noncerebral central nervous system cancers and leukemia, who experienced VTE and received a therapeutic VTE dose of rivaroxaban or apixaban on day 7 post-VTE, and were active in the EHR ≥12 months prior to the VTE. Primary outcome was the composite of recurrent VTE or any bleed resulting in hospitalization at 3 months. Secondary outcomes included recurrent VTE, any bleed resulting in hospitalization, any critical organ bleed, and composites of these outcomes at 3 and 6 months. Inverse probability of treatment-weighted Cox regression was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). We included 1,344 apixaban and 1,093 rivaroxaban patients. At 3 months, rivaroxaban was found to have similar hazard to apixaban for developing recurrent VTE or any bleed resulting in hospitalization (HR: 0.87; 95% CI: 0.60-1.27). No differences were observed between cohorts for this outcome at 6 months (HR: 1.00; 95% CI: 0.71-1.40) or for any other outcome at 3 or 6 months. In conclusion, patients receiving rivaroxaban or apixaban showed similar risks of the composite of recurrent VTE or any bleed resulting in hospitalization in patients with cancer-associated VTE. This study was registered at www.clinicaltrials.gov as #NCT05461807. Key Points Rivaroxaban and apixaban have similar effectiveness and safety for treatment of cancer-associated VTE through 6 months.Clinicians should therefore consider patient preference and adherence when choosing the optimal anticoagulant.

Risk Factor Analysis of Venous Thromboembolism in Cancer: A National Inpatient Sample Study.

Objective In this study, we aimed to explore the association of demographic characteristics and comorbidities with the risk of venous thromboembolism (VTE) in cancer inpatients, as well as to delineate the mortality risk in cancer inpatients with VTE. Methods We conducted a retrospective cohort analysis based on the National Inpatient Sample (NIS) 2012-2014, involving 339,395 inpatients with a primary diagnosis of cancer subdivided into cohorts without VTE (n=331,695) and with VTE (n=7,700). We used a binomial logistic regression model to evaluate the odds ratio (OR) of demographics, comorbidities, and in-hospital mortality rate with respect to cancer inpatients with VTE. Results A higher proportion of cancer inpatients with VTE were 36-50 years in age (83.1%), male (50%), and of black (19.3%) and Hispanic ethnicity (17.2%) compared to the non-VTE cohort. The prevalence of comorbidities was higher in the VTE cohort, including HIV/AIDS, congestive heart failure (CHF), chronic pulmonary disease, diabetes, hypertension, and obesity. CHF demonstrated the highest risk of association with VTE (OR: 2.68, 95% CI: 2.30-3.12), followed by hypertension (OR: 1.23, 95% CI: 1.16-1.29), diabetes (OR: 1.16, 95% CI: 1.07-1.26), and chronic pulmonary disease (OR: 1.13, 95% CI: 1.05-1.22). Conversely, valvular diseases, obesity, and drug abuse were not significantly associated with VTE in cancer inpatients. The in-hospital mortality rate was higher in cancer inpatients with VTE (12% vs. 2.1%), thereby increasing the in-hospital mortality risk (OR: 3.87, 95% CI: 3.58-4.18). Conclusion VTE risk was significantly higher in cancer patients with comorbid CHF, hypertension, diabetes, and chronic pulmonary disease. The risk of all-cause in-hospital mortality was increased by four times in cancer inpatients with VTE.

Anticoagulant Therapy for Cancer-Associated Venous Thromboembolism after Cancer Remission.

Objectives: To examine the outcomes of anticoagulant therapy for patients with venous thromboembolism (VTE) with active cancer and the outcomes after cancer remission with and without anticoagulant therapy. Materials and Methods: Of the 338 patients with cancer-associated VTE who received anticoagulant therapy, we evaluated therapeutic outcomes over 1 year for 112 patients whose cancers were in remission (cancer remission group) and 226 patients who continued cancer treatment (continued cancer treatment group). Further, the cancer remission group was divided into 89 and 23 patients who completed (completion of anticoagulation group) and continued (continued anticoagulation group) anticoagulant therapy, respectively. Treatment outcomes after completing anticoagulant therapy were compared between these two groups. The follow-up period was 1 year, and the endpoints were all-cause death, VTE recurrence, and bleeding events. Results: The event-free survival rates were 99.1% and 42.9% in the cancer remission and continued cancer treatment groups, respectively. For treatment outcomes after the completion of anticoagulant therapy, the event-free survival rates were 98.9% and 87% in the completion of anticoagulation and continued anticoagulation groups, respectively (log rank, P=0.005). Conclusion: When cancer is in remission, recurrence is low even if anticoagulant therapy is terminated after a certain period.

Blocking podoplanin inhibits platelet activation and decreases cancer-associated venous thrombosis.

BACKGROUND: Patients with cancer are at a high risk of venous thromboembolism (VTE), studies have shown that high expression of podoplanin (PDPN) in tumors is associated with increased risk of VTE. METHODS: Two human malignant cell lines (NCI-H226 and C8161) expressing high levels of PDPN were selected to explore the role of platelet in cancer-associated venous thrombosis in vitro and in vivo. Immunohistochemical staining using anti-PDPN antibody was performed in the pulmonary carcinoma patients. RESULTS: Both NCI-H226 and C8161 cells expressing high PDPN triggered platelet activation via CLEC-2 in vitro, which was abrogated by an anti-PDPN antibody SZ-168. Furthermore, the in vivo study revealed that injection of CHO-PDPN or C8161 in two mouse model of venous thrombosis activated platelets, increased platelet counts and enhanced thrombosis. More importantly, PDPN-enhanced thrombosis was reduced in mice treated with SZ168. A total of 63.3% tumor specimens stained positive for PDPN. High PDPN expression was associated with an increased risk of VTE and poor prognosis. CONCLUSIONS: PDPN expression in tumors induced platelet activation and was related to a high risk of VTE via platelet activation. SZ168 inhibited PDPN-induced platelet activation in vitro and decreased the incidence of VTE in mice.

Healthcare costs of patients with cancer stratified by Khorana score risk levels.

AIMS: Patients with cancer are at high risk of venous thromboembolism (VTE), which entails a high economic burden. The risk of cancer-associated VTE can be assessed using the Khorana score (KS), a validated VTE risk prediction algorithm. This study compared healthcare costs associated with different KS in a population of patients newly diagnosed with cancer. METHODS: The Optum Clinformatics DataMart database (01/01/2012-09/30/2017) was used to select adult patients with ≥1 hospitalization or ≥2 outpatient claims with a cancer diagnosis (index date) initiated on systemic therapy or radiation therapy. Patients were classified in mutually exclusive cohorts based on KS (i.e. KS = 0, 1, 2 or ≥3). The observation period spanned from index to the earliest among the end of data availability, death, end of insurance coverage, or 12 months. RESULTS: In total 6,194 patients (KS = 0: 2,488; KS = 1: 2,125; KS = 2: 1,074; KS ≥ 3: 507) were included. On average, patients were aged 68 years, 48-52% were female, and the Quan-Charlson comorbidity index ranged between 1.1 and 1.4. Over the observation period, all-cause total healthcare costs per patient per month (PPPM) were $8,826 (KS = 0), $11,598 (KS = 1), $14,028 (KS = 2), and $16,211 (KS ≥ 3). Using the KS = 0 cohort as a reference, adjusted PPPM costs were $2,506, $4,775, and $6,452 higher in the KS = 1, KS = 2, and KS ≥ 3 cohorts, respectively. Hospitalization and outpatient costs were the main drivers of these differences. Similar results were found for VTE-related costs, which represented 4-11% of the total all-cause cost difference between KS cohorts. LIMITATIONS: Residual confounders; results may not be generalized to patients with other insurance plans or those who received treatments other than systemic therapy or radiation therapy. CONCLUSIONS: This real-world analysis found that cancer patients at higher risk of VTE (based on KS) incurred significantly greater all-cause and VTE-related healthcare costs compared with cancer patients at lower risk of VTE.

The role of podoplanin in cancer-associated thrombosis.

Venous thromboembolism (VTE) is a frequent and life-threatening complication in patients with cancer. The underlying mechanisms of cancer-associated VTE are still not completely understood. However, emerging studies indicate that the mechanisms differ across tumor types. A recent study revealed that in patients with brain tumors, podoplanin overexpression is strongly correlated with intratumoral thrombotic vessels, hypercoagulability and increased VTE risk. In vitro experiments demonstrated that platelet aggregation induced by human glioblastoma cells was highly podoplanin-dependent. Podoplanin is a transmembrane glycoprotein with the ability to induce platelet activation via the platelet-receptor CLEC-2. Moreover, podoplanin is a lymphatic endothelial marker and exhibits substantial functions during embryonic development. It is variously upregulated by many cancers including primary brain tumors and linked to malignant progression and poor survival. In vivo studies have indicated that the podoplanin-CLEC-2 axis might be mechanistically involved in the development of venous thrombosis. In this review, we discuss the role of podoplanin in promoting cancer-associated VTE. Since podoplanin is associated with VTE risk in brain tumor patients, it could be a useful biomarker to identify patients at very high VTE risk. Those patients may benefit from primary thromboprophylaxis. In addition, the podoplanin-CLEC-2 axis might serve as an attractive target for new therapies against cancer-associated VTE.

Low-molecular-weight heparins for cancer-associated thrombosis: Adherence to clinical practice guidelines and patient perception in TROPIQUE, a 409-patient prospective observational study.

PURPOSE: Data on long-term treatment with low-molecular-weight heparins (LMWH) in cancer patients treated for venous thromboembolism are scarce. Study objectives were to document the long-term clinical use of LMWH and patient perception in this setting. METHODS: Adult cancer patients receiving antineoplastic treatment or palliative care and LMWH for cancer associated venous thromboembolism (CAT) were eligible to participate in this prospective observational study. Main outcome was adherence to clinical practice guidelines based on recommended LMWH treatment doses for at least 3months in the absence of severe renal insufficiency. Patients' perception of the treatment was assessed in an ancillary study using the Perception Anticoagulant Treatment Questionnaire (PACT-Q). RESULTS: Among 409 included cancer patients aged 65±12.1years, overall adherence to practice guidelines as defined in the protocol was 55.3% (226 patients). However, 98.0% of patients received a prescription for 3months or more and mean LMWH treatment duration for VTE was 6.27±0.15months which meets guidelines recommendations. Main patients' expectations scored on a 1-5 scale were blood clots prevention (mean 3.94±0.75), symptom relief (mean 3.98±1.04) and ease of use (mean 4.22±0.9). LMWH treatment appeared convenient (global score 79.7±17.1 on a 0 to 100 scale) and 69.1% of patients were satisfied or very satisfied. CONCLUSION: Despite incomplete strict adherence to guidelines, treatment duration with LMWH was adequate showing substantial progress in the management of CAT patients. Patients expectations were high while treatment was perceived convenient with a high degree of satisfaction.