Incidence and Outcomes Associated with Distal Deep Vein Thrombosis in 760,344 Patients with 13 Common Malignancies

Abstract Introduction: The epidemiology of isolated distal deep-vein-thrombosis (d-DVT) in the calf among cancer patients is not well defined, particularly the incidence and effect on development of recurrent VTE (rVTE) and overall survival. Methods: We used the California Cancer Registry (CCR), linked with the California Patient Discharge Database (PDD) and the Emergency Department Database (ED), which were linked to the CCR vital statistics file. Excluding patients with a prior diagnosis of VTE, we identified 760,344 first primary cancer patients diagnosed in 2005-2014 with one of the 13 most common, invasive cancers (breast, prostate, lung and bronchus, colorectal, lymphoma, urinary bladder, uterus, kidney, pancreas, stomach, ovary, myeloma, and brain). Patients with an incident cancer-associated thrombosis (CAT) diagnosis were identified if in the PDD or ED databases there was a specific ICD-9-CM code for: pulmonary embolism (PE, 415.11, 415.13. 415.19, 673.20, 673.21, 673.23, 673.24), proximal DVT (p-DVT, 451.11, 451.19, 451.81, 453.2, 453.41), distal DVT (d-DVT, 453.42), or unspecified leg DVT (nos-DVT, 453.40, 453.8 (principal diagnosis only)) or pregnancy related leg VTE (671.31, 671.33, 671.42, 671.44). The VTE location was assigned in a hierarchical fashion: PE (+/- DVT) then p-DVT, then d-DVT alone. Recurrent VTE was defined as a subsequent PDD admission with a specific ICD-9-CM VTE code in: 1) a principal diagnosis of VTE, 2) principal diagnosis of cancer and second position VTE code, or 3) secondary position of a hospital acquired VTE code. Incidence and outcomes associated with d-DVT were analyzed by cancer type. The 24-month cumulative incidence function (CIF) of first-time CAT adjusts for the competing risk of death. Multivariable Cox proportional hazards regression models were used to identify factors associated with rVTE, adjusting for the competing risk of death. The association of incident CAT location with overall survival was analyzed using multivariable Cox regression models, using CAT as a time-dependent covariate. Model covariates included sex, race/ethnicity, age at diagnosis, incident CAT location, neighborhood socioeconomic status, type of health insurance at cancer diagnosis or initial treatment, cancer stage, and initial cancer treatment (chemotherapy, radiation, and surgery); we report adjusted hazard ratios (HR) and 95% confidence intervals (CI). Results: Incident CAT occurred in 39,044 patients in our study (5.1%); 59.1% had PE (+/- DVT), 21.9% p-DVT, 12.1% d-DVT and 7.0% nos-DVT. Among incident CAT patients, 9.2% (n=3,587) had a rVTE, with 64.7% as PE (+/-DVT), 21.8% as p-DVT, 7.0% as d-DVT and 6.5% as nos-DVT. Among patients with incident d-DVT, 46.8% of rVTE events presented as PE, 26.1% as p-DVT and 17.8% as d-DVT. The 2-year CIF of incident d-DVT by cancer type and stage is shown in the Figure. The CIF of myeloma and brain cancers were 1.10% and 1.50%, respectively. In multivariable models assessing the impact of incident CAT location on risk of rVTE, the risk for recurrence was similar for an incident d-DVT and p-DVT for all cancers types. The risk for rVTE was similar between those with d-DVT and PE for all cancers except prostate, stomach, and ovarian, where incident d-DVT had a 50% reduced risk of rVTE compared to PE. In multivariable models considering the impact of incident CAT location on survival (Table), d-DVT was associated with worse survival among all cancer types compared to those with no CAT, with a HR that ranged from 1.55 (CI: 1.26-1.89) for myeloma to HR=4.86 (CI: 4.28-5.53) for prostate cancer. When we compared survival of incident d-DVT to p-DVT for each type of cancer, survival was similar, except for patients with colorectal [HR=0.80 (CI: 0.71-0.90)], bladder [HR=0.76, (CI: 0.63-0.91)], uterus [HR=0.75, (CI: 0.63-0.91)], kidney [HR= 0.74 (CI: 0.59-0.92)], and myeloma [HR=0.64,( CI: 0.50-0.81)] where d-DVT was associated with improved survival. Conclusions: Isolated distal DVT cases made up only a small percentage of all diagnosed incident CAT events for all cancer types analyzed, with the 2-year cumulative incidence ranging from 0.5% - 2.0% for stage 4 patients. Subsequent rVTE events in these patients were principally PE or p-DVT (73%). D-DVT was not a significant predictor of rVTE. A diagnosis of incident d-DVT was strongly associated with worse survival, and for most cancers, survival was similar among patients with an incident p-DVT or PE. Disclosures No relevant conflicts of interest to declare.

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Frequency, demographics and risk (according to tumour type or site) of cancer-associated thrombosis among patients seen at outpatient DVT clinics

Thrombosis and Haemostasis ◽

10.1160/th09-06-0397 ◽

2010 ◽

Vol 103 (02) ◽

pp. 338-343 ◽

Cited By ~ 42

Author(s):

Shankaranarayana Paneesha ◽

Aidan McManus ◽

Roopen Arya ◽

Nicholas Scriven ◽

Timothy Farren ◽

...

Keyword(s):

Cancer Patients ◽

Similar Rate ◽

Cancer Type ◽

Tumour Site ◽

Vein Thrombosis ◽

Patients With Cancer ◽

Skin Cancers ◽

Cancer Types ◽

Cancer Associated Thrombosis ◽

Deep Vein

SummaryVenous thromboembolism (VTE) is a clinically important complication for both hospitalised and ambulatory cancer patients. In the current study, the frequency, demographics and risk (according to tumour site) of VTE were examined among patients seen at outpatient DVT (deep-vein thrombosis) clinics. Of 10,015 VTE cases, 1,361 were diagnosed with cancer, for an overall rate of cancer-associated VTE of 13.6% in this outpatient population. Patients with cancer-associated VTE were significantly older than cancer-free VTE cases (66.4 ± 12.7 vs. 58.8 ± 18.5 years; p<0.0001). The frequency of cancer-associated VTE peaked earlier among females than males, occurring in the sixth (137/639, 21.4% vs. 98/851, 11.3%; p<0.001) and seventh decades (213/980, 21.7% vs. 197/1096, 18%; p=0.036). VTE was described most frequently in common cancers – breast, prostate, colorectal and lung (56.1% of cases). The risk of VTE varied widely across 17 cancer types. Calculating odds ratios (OR) to assess the effect size of cancer type on VTE risk, the highest odds were observed for patients with pancreatic cancer (OR 9.65, 95% confidence interval [CI] (5.51–16.91). Tumours of the head and neck had higher odds than previously reported (OR 8.24, 95% CI 5.06–13.42). Reduced risk estimates were observed for skin cancers (melanoma and non-melanoma: OR 0.89, 95% CI 0.42–1.87; OR 0.74, 95% CI, 0.32–1.69, respectively). We conclude that outpatients have a similar rate of cancer-associated VTE as VTE patient populations previously reported, that cancer-associated VTE occurs in an older age group and earlier in females and that outpatients exhibit distinct tumour site-specific risk from that described among hospitalised cancer patients.

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Performance of the Wells score in predicting deep vein thrombosis in medical and surgical hospitalized patients with or without thromboprophylaxis: The R-WITT study

Vascular Medicine ◽

10.1177/1358863x21994672 ◽

2021 ◽

pp. 1358863X2199467

Author(s):

Jean-Eudes Trihan ◽

Michael Adam ◽

Sara Jidal ◽

Isabelle Aichoun ◽

Sarah Coudray ◽

...

Keyword(s):

Deep Vein Thrombosis ◽

Risk Stratification ◽

Hospitalized Patients ◽

Operating Characteristics ◽

Vein Thrombosis ◽

Ultrasound Study ◽

Wells Score ◽

Deep Vein ◽

The Impact ◽

Test Probability

The Wells score had shown weak performance to determine pre-test probability of deep vein thrombosis (DVT) for inpatients. So, we evaluated the impact of thromboprophylaxis on the utility of the Wells score for risk stratification of inpatients with suspected DVT. This bicentric cross-sectional study from February 1, 2018 to January 31, 2019 included consecutive medical and surgical inpatients who underwent lower limb ultrasound study for suspected DVT. Wells score clinical predictors were assessed by both ordering and vascular physicians within 24 h after clinical suspicion of DVT. Primary outcome was the Wells score’s accuracy for pre-test risk stratification of suspected DVT, accounting for anticoagulation (AC) treatment (thromboprophylaxis for ⩾ 72 hours or long-term anticoagulation). We compared prevalence of proximal DVT among the low, moderate and high pre-test probability groups. The discrimination accuracy was defined as area under the receiver operating characteristics (ROC) curve. Of the 415 included patients, 30 (7.2%) had proximal DVT. Prevalence of proximal DVT was lower than expected in all pre-test probability groups. The prevalence in low, moderate and high pre-test probability groups was 0.0%, 3.1% and 8.2% ( p = 0.22) and 1.7%, 4.2% and 25.8% ( p < 0.001) for inpatients with or without AC, respectively. Area under ROC curves for discriminatory accuracy of the Wells score, for risk of proximal DVT with or without AC, was 0.72 and 0.88, respectively. The Wells score performed poorly for discrimination of risk for proximal DVT in hospitalized patients with AC but performed reasonably well among patients without AC; and showed low inter-rater reliability between physicians. ClinicalTrials.gov Identifier: NCT03784937.

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How I treat cancer-associated venous thromboembolism

Blood ◽

10.1182/blood-2018-08-835595 ◽

2019 ◽

Vol 133 (4) ◽

pp. 291-298 ◽

Cited By ~ 16

Author(s):

Noémie Kraaijpoel ◽

Marc Carrier

Keyword(s):

Venous Thromboembolism ◽

Cancer Staging ◽

Cancer Type ◽

Related Factors ◽

Vein Thrombosis ◽

Patients With Cancer ◽

Treatment Response Evaluation ◽

Related Risk ◽

Deep Vein ◽

Underlying Risk

Abstract Venous thromboembolism (VTE), which includes deep vein thrombosis and pulmonary embolism, is a common complication of cancer and is associated with significant morbidity and mortality. Several cancer-related risk factors contribute to the development of VTE including cancer type and stage, chemotherapy, surgery, and patient-related factors such as advanced age and immobilization. Patients with cancer frequently undergo diagnostic imaging scans for cancer staging and treatment response evaluation, which is increasing the underlying risk of VTE detection. The management of cancer-associated VTE is challenging. Over the years, important advances have been made and, recently, randomized controlled trials have been published helping clinicians’ management of this patient population. In this review, we will discuss common cancer-associated VTE scenarios and critically review available evidence to guide treatment decisions.

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The Future of Phlebology in Europe

Phlebology The Journal of Venous Disease ◽

10.1177/0268355514527046 ◽

2014 ◽

Vol 29 (1_suppl) ◽

pp. 181-185 ◽

Cited By ~ 1

Author(s):

Brahman Dharmarajah ◽

Tristan RA Lane ◽

Hayley M Moore ◽

HA Martino Neumann ◽

Eberhard Rabe ◽

...

Keyword(s):

Cost Effective ◽

Research Strategy ◽

Clinical Severity ◽

Venous Disease ◽

Vein Thrombosis ◽

Venous Diseases ◽

Thrombus Removal ◽

Deep Vein ◽

The Impact

Background Worldwide superficial and deep venous diseases are common and associated with significant individual and socioeconomic morbidity. Increasing burden of venous disease requires Phlebology to define itself as an independent specialty representing not only patients but the multidisciplinary physicians involved in venous care. Methods & Results In this article the scope of venous disease in Europe and subsequent future governance for treatment in the region is discussed. Superficial venous disease is common with 26.9-68.6% of European populations reported to have C2-C6 disease according to the CEAP (Clinical severity, Aetiology, Anatomy and Pathophysiology) scoring system. However, a significant disparity is observed in the treatment of superficial venous disease across Europe. Post thrombotic syndrome (PTS) after deep vein thrombosis (DVT) contributes to the increasing burden of deep venous disease. Aggressive thrombus removal for acute ileofemoral DVT provides a cost-effective 14.4% risk reduction in the development of PTS. Additionally, deep venous lesions requiring endovascular intervention are being increasingly performed to prevent recurrent thrombosis. The European College of Phlebology (ECoP) has been formed to provide a responsible body for the care of the European patient with venous disease. The role of the ECoP includes unifying European member states through standardised guideline production, identification of research strategy and provision of training and accreditation of physicians. Conclusion Creation of a European venous disease specific speciality will provide a patient centred approach through understanding of the impact of disease in the region and delivery of high quality diagnostics and treatment from an appropriately certified Phlebologist.

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Abstract 512: Predictors of Mortality in Cancer-Associated Calf Deep Vein Thrombosis

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.37.suppl_1.512 ◽

2017 ◽

Vol 37 (suppl_1) ◽

Author(s):

Juan P Salazar Adum ◽

Luis Diaz-Quintero ◽

Harry E Fuentes ◽

Alfonso Tafur ◽

Benjamin Lind ◽

...

Keyword(s):

Deep Vein Thrombosis ◽

Mortality Prediction ◽

Categorical Variables ◽

Mortality Data ◽

Cancer Type ◽

Continuous Variables ◽

Filter Placement ◽

Predictors Of Mortality ◽

Vein Thrombosis ◽

Deep Vein

Background: Venous thromboembolism (VTE) is a leading cause of mortality in cancer patients. The outcomes of patients with cancer-associated calf deep vein thrombosis (CDVT), including mortality data, are less understood compared with proximal thrombosis. Aim: To characterize predictors of mortality among cancer-associated CDVT patients. Methods: Single institution inception cohort of cancer-associated CDVT patients who presented with thrombosis distal to popliteal level confirmed objectively by ultrasound, computed tomography or VQ scan were independently reviewed. Active cancer was defined as metastatic disease or use of chemotherapy at diagnosis. The Khorana risk score (KRS) suggested for DVT and mortality prediction in cancer was abstracted based on laboratory tests and cancer type at diagnosis. Institutional review board approval was obtained prior to the analysis. Categorical variables are expressed as percentages and continuous variables as median (interquartile range). SPSS software version 22 was used and Chi-square, Mann–Whitney U and Cox proportional hazard were applied. Results: One hundred nine patients (Men=44 (40%), Age>65=89 (82%), BMI>30=25 (23%), Smoker=59 (54%)) were included. The majority had a low or intermediate KRS (30%-64% respectively). Forty-seven percent died during a median follow-up time of 2.5 years (0.5-3.1). After multivariate analysis, the predictors of mortality were found to be: smoking (Hazard Ratio 2.3; 95%CI 1.2-4.7), metastasis (HR 5.8; 95%CI 2.9-11.7), gastrointestinal cancer (HR 3.9; 95%CI 1.8-8.5), and lung cancer (HR 4.1 95%CI 1.7-10.3). VTE specific variables not associated with mortality included: bilateral CDVT, concomitant pulmonary embolism, multiple vein involvement, filter placement, or a surgery-associated event. Conclusion: Cancer-specific variables and smoking predicted mortality among CDVT patients in this cohort. Neither the KRS nor VTE specific characteristics were predictive of death. A larger study is necessary to further explore these findings.

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Toxicity, response, and survival in older adults with metastatic melanoma treated with checkpoint inhibitors.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.9544 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 9544-9544

Author(s):

Nienke A De Glas ◽

Esther Bastiaannet ◽

Frederiek van den Bos ◽

Simon Mooijaart ◽

Astrid Aplonia Maria Van Der Veldt ◽

...

Keyword(s):

Older Adults ◽

Overall Survival ◽

Metastatic Melanoma ◽

Older Patients ◽

Regression Models ◽

Checkpoint Inhibitors ◽

Performance Status ◽

Toxicity Response ◽

Grade 3 ◽

The Impact

9544 Background: Checkpoint inhibitors have strongly improved survival of patients with metastatic melanoma. Trials suggest no differences in outcomes between older and younger patients, but only relatively young patients with a good performance status were included in these trials. The aim of this study was to describe treatment patterns and outcomes of older adults with metastatic melanoma, and to identify predictors of outcome. Methods: We included all patients aged ≥65 years with metastatic melanoma between 2013 and 2020 from the Dutch Melanoma Treatment registry (DMTR), in which detailed information on patients, treatments and outcomes is available. We assessed predictors of grade ≥3 toxicity and 6-months response using logistic regression models, and melanoma-specific and overall survival using Cox regression models. Additionally, we described reasons for hospital admissions and treatment discontinuation. Results: A total of 2216 patients were included. Grade ≥3 toxicity did not increase with age, comorbidity or WHO performance status, in patients treated with monotherapy (anti-PD1 or ipilimumab) or combination treatment. However, patients aged ≥75 were admitted more frequently and discontinued treatment due to toxicity more often. Six months-response rates were similar to previous randomized trials (40.3% and 43.6% in patients aged 65-75 and ≥75 respectively for anti-PD1 treatment) and were not affected by age or comorbidity. Melanoma-specific survival was not affected by age or comorbidity, but age, comorbidity and WHO performance status were associated with overall survival in multivariate analyses. Conclusions: Toxicity, response and melanoma-specific survival were not associated with age or comorbidity status. Treatment with immunotherapy should therefore not be omitted solely based on age or comorbidity. However, the impact of grade I-II toxicity in older patients deserves further study as older patients discontinue treatment more frequently and receive less treatment cycles.[Table: see text]

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Use of Electronic Health Record Simulation to Understand the Accuracy of Intern Progress Notes

Journal of Graduate Medical Education ◽

10.4300/jgme-d-15-00201.1 ◽

2016 ◽

Vol 8 (2) ◽

pp. 237-240 ◽

Cited By ~ 10

Author(s):

Christopher A. March ◽

Gretchen Scholl ◽

Renee K. Dversdal ◽

Matthew Richards ◽

Leah M. Wilson ◽

...

Keyword(s):

Thrombosis Prophylaxis ◽

Medical Problems ◽

Vein Thrombosis ◽

Patterns Of Use ◽

Progress Notes ◽

Deep Vein Thrombosis Prophylaxis ◽

Electronic Health ◽

Deep Vein ◽

The Impact

ABSTRACT With the widespread adoption of electronic health records (EHRs), there is a growing awareness of problems in EHR training for new users and subsequent problems with the quality of information present in EHR-generated progress notes. By standardizing the case, simulation allows for the discovery of EHR patterns of use as well as a modality to aid in EHR training.Background To develop a high-fidelity EHR training exercise for internal medicine interns to understand patterns of EHR utilization in the generation of daily progress notes.Objective Three months after beginning their internship, 32 interns participated in an EHR simulation designed to assess patterns in note writing and generation. Each intern was given a simulated chart and instructed to create a daily progress note. Notes were graded for use of copy-paste, macros, and accuracy of presented data.Methods A total of 31 out of 32 interns (97%) completed the exercise. There was wide variance in use of macros to populate data, with multiple macro types used for the same data category. Three-quarters of notes contained either copy-paste elements or the elimination of active medical problems from the prior days' notes. This was associated with a significant number of quality issues, including failure to recognize a lack of deep vein thrombosis prophylaxis, medications stopped on admission, and issues in prior discharge summary.Results Interns displayed wide variation in the process of creating progress notes. Additional studies are being conducted to determine the impact EHR-based simulation has on standardization of note content.Conclusions

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Incidence of Upper Extremity Deep Vein Thrombosis in Acute Leukemia and Effect on Mortality

TH Open ◽

10.1055/s-0040-1718883 ◽

2020 ◽

Vol 04 (04) ◽

pp. e309-e317

Author(s):

Christina Poh ◽

Ann Brunson ◽

Theresa Keegan ◽

Ted Wun ◽

Anjlee Mahajan

Keyword(s):

Deep Vein Thrombosis ◽

Acute Leukemia ◽

Upper Extremity ◽

Lymphoblastic Leukemia ◽

Cox Proportional Hazards ◽

High Risk Population ◽

Vein Thrombosis ◽

Increased Risk ◽

Deep Vein ◽

The Impact

AbstractThe cumulative incidence, risk factors, rate of subsequent venous thromboembolism (VTE) and bleeding and impact on mortality of isolated upper extremity deep vein thrombosis (UE DVT) in acute leukemia are not well-described. The California Cancer Registry, used to identify treated patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) diagnosed between 2009 and 2014, was linked with the statewide hospitalization database to determine cumulative incidences of UE DVT and subsequent VTE and bleeding after UE DVT diagnosis. Cox proportional hazards regression models were used to assess the association of UE DVT on the risk of subsequent pulmonary embolism (PE) or lower extremity deep vein thrombosis (LE DVT) and subsequent bleeding, and the impact of UE DVT on mortality. There were 5,072 patients identified: 3,252 had AML and 1,820 had ALL. Three- and 12-month cumulative incidences of UE DVT were 4.8% (95% confidence interval [CI]: 4.1–5.6) and 6.6% (95% CI: 5.8–7.5) for AML and 4.1% (95% CI: 3.2–5.1) and 5.9% (95% CI: 4.9–7.1) for ALL, respectively. Twelve-month cumulative incidences of subsequent VTE after an incident UE DVT diagnosis were 5.3% for AML and 12.2% for ALL. Twelve-month cumulative incidences of subsequent bleeding after an incident UE DVT diagnosis were 15.4% for AML and 21.1% for ALL. UE DVT was associated with an increased risk of subsequent bleeding for both AML (hazard ratio [HR]: 2.07; 95% CI: 1.60–2.68) and ALL (HR: 1.62; 95% CI: 1.02–2.57) but was not an independent risk factor for subsequent PE or LE DVT for either leukemia subtype. Isolated incident UE DVT was associated with increased leukemia-specific mortality for AML (HR: 1.42; 95% CI: 1.16–1.73) and ALL (HR: 1.80; 95% CI: 1.31–2.47). UE DVT is a relatively common complication among patients with AML and ALL and has a significant impact on bleeding and mortality. Further research is needed to determine appropriate therapy for this high-risk population.

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Microsatellite instability status differentially associates with intratumoral immune microenvironment in human cancers

Briefings in Bioinformatics ◽

10.1093/bib/bbaa180 ◽

2020 ◽

Author(s):

Peng Zhang ◽

Mingyue Liu ◽

Ya Cui ◽

Pan Zheng ◽

Yang Liu

Keyword(s):

Colorectal Cancer ◽

Microsatellite Instability ◽

Therapeutic Response ◽

In Silico Analysis ◽

Cancer Type ◽

Clinical Responses ◽

Stomach Adenocarcinoma ◽

Immune Contexture ◽

Cancer Types ◽

The Impact

Abstract Based on clinical outcomes in colorectal cancer, high microsatellite instability (MSI-H) has recently been approved by the Food and Drug Administration (FDA) as a genetic test to select patients for immunotherapy targeting PD-1 and/or CTLA-4 without limitation to cancer type. However, it is unclear whether the MSI-H would broadly alter the tumor microenvironment to confer the therapeutic response of different cancer types to immunotherapy. To fill in this gap, we performed an in silico analysis of tumor immunity among different MSI statuses in five cancer types. We found that consistent with clinical responses to immunotherapy, MSI-H and non-MSI-H samples from colorectal cancer (COAD-READ) exhibited distinct infiltration levels and immune phenotypes. Surprisingly, the immunological difference between MSI-H and non-MSI-H samples was diminished in stomach adenocarcinoma and esophageal carcinoma (STAD-ESCA) and completely disappeared in uterine corpus endometrial carcinoma (UCEC). Regardless of cancer types, the abundance of tumor-infiltrating immune cells, rather than MSI status, strongly associated with the clinical outcome. Since preexisting antitumor immune response in the tumor (hot cancer) is accepted as a prerequisite to the therapeutic response to anti-PD-1/CTLA-4 immunotherapy, our data demonstrate that the impact of MSI varied on immune contexture will lead to the further evaluation of predictive immunotherapy responsiveness based on the universal biomarker of MSI status.

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