Cumulative Incidence Of Venous Thromboembolic Events Research Articles

Venous thromboembolism incidence and association with overall survival in pancreatic cancer: A Finnish nationwide cohort study.

Pancreatic cancer (PC) is associated with a high risk of venous thromboembolic events (VTEs). We investigated the incidence of VTE before and after the diagnosis of PC and its association with overall survival. We identified PC patients diagnosed in 2013-2016 from the Finnish Cancer Registry. Data on healthcare visits and death were collected, along with follow-up data through the end of 2020. We compared patients who underwent radical-intent surgery (RIS) to those who underwent palliative treatment (PT) alone. We identified 4086 PC patients, of whom 343 (8.4%) underwent RIS and 3743 (91.6%) received PT. VTE incidence within 1 year before a PC diagnosis was higher in the PT (4.2%, n = 156) than in the RIS group (0.6%, n = 2; p < 0.001). The cumulative incidence of VTE at 12 and 24 months after a PC diagnosis was 6% (n = 21) and 9% (n = 31), respectively, within the RIS group, and 8% (n = 286) and 8% (n = 304) within the PT group. In the PT group, a VTE within 1 year before a PC diagnosis was independently associated with a worse survival {hazard ratio, HR 1.9 [95% confidence interval (CI) 1.6-2.2]}. In both groups, VTE after a PC diagnosis was associated with a worse survival [RIS group: HR 2.6 (95%CI 1.8-3.7) vs. PT group: HR 2.2 (95%CI 1.9-2.4)]. A VTE within 1 year before a PC diagnosis more often occurred among PT PC patients than among patients who underwent RIS. VTE might serve as a diagnostic clue to detect PC at an earlier stage.

Cell Product Differences on Incidence of Venous Thromboembolism in Patients Treated with CAR T-Cells for Aggressive B-Cell Lymphomas

Introduction Chimeric antigen receptor T (CAR T)-cell therapy has substantial activity in relapsed lymphoid malignancies. However, it is associated with important complications, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Venous thromboembolic events (VTEs) following CAR T-cells have been reported with variable incidence. Risk factors for the development of VTEs following CAR T-cell therapy are largely unknown, including whether the CAR T-cell construct is associated with increased VTEs. Methods We retrospectively evaluated patients treated at our institution who received CAR T-cell therapy for non-Hodgkin lymphoma between May 2018 and January 2022. Baseline characteristics and outcomes were collected. VTEs included deep venous thrombosis and pulmonary embolism. The cumulative incidence (CI) of VTE was calculated with death as competing risk and comparisons between groups were done with Gray test. Univariate comparisons of baseline parameters were performed with Fisher's exact test evaluating the following covariates: age (older or younger than 70 years), LDH and C-reactive protein levels, ECOG performance status, revised IPI, BMI, personal history of VTE, and stage. Due to the low number of VTEs, we did not attempt multivariate modeling based on baseline characteristics. All analyses were performed using R. This study was approved by our Institutional Review Board. Results We identified 95 patients treated with CAR T-cells between May 2018 and January 2022. The majority had diffuse large B-cell lymphoma (DLBCL) (88, 93%). Baseline characteristics are listed in Table 1. Prior history of VTE occurred in 16 patients and 27 received at least one dose of therapeutic or prophylactic anticoagulation post-CAR T infusion prior to developing VTE. Most patients had central venous access during their hospitalization for CAR T cell therapy (n = 91). A total of 56 patients received axicabtagene ciloleucel (58.9%), 30 patients received tisagenlecleucel (31.6%), 5 patients received brexucabtagene autoleucel (5.3%), and 4 received lisocabtagene maraleucel (4.2%). Post-CAR T VTE occurred in 13 patients (14%); median time to VTE (IQR) was 15 days (7-48), with a 100-day cumulative incidence of 12%. All VTEs were DVTs and the majority were PICC line-associated (10, 77%). The incidence of VTE was higher for patients treated with axicabtagene ciloleucel or brexucabtagene autoleucel in contrast to 41BB-containing constructs (16% vs. 3%, p = 0.03) (Figure 1). Among baseline characteristics, a prior history of VTE was associated with increased risk of subsequent VTE (39% vs. 13% without prior VTE, p = 0.04). The 100-day CI of VTE for patients with and without CRS were 15% and 4% (p = 0.09), while the 100-day CI of patients with and without ICANS were 18% and 7% (p = 0.09). Subgroup analysis of patients treated with CD3ζ/CD28 signaling showed that 100-day VTE CI was higher among patients with a prior history of VTE (33% vs. 12%, p = 0.03) and those with BMI of ≥ 30 (38% vs. 11%, p = 0.03). We did not observe an increased incidence of VTE in patients with baseline ECOG performance status ≥ 2, stage III/IV disease, elevated baseline lactate dehydrogenase or C-reactive protein. After a median follow up of 24 months (IQR 13-36), the median progression free survival (PFS) was 7 months (95% CI = 4-12) while the median overall survival (OS) was 14 months (95% CI = 11-19), there were no statistically significant differences in PFS or OS among patients with and without VTE. Conclusions VTEs are an emerging toxicity associated with CAR T cell therapy. We show that increased VTE incidence at 100 days is associated with the use of CD3ζ/CD28 CAR T-cells. This difference may correlate with differing degrees of systemic inflammatory response, as previous reports have detailed higher incidence of high-grade CRS with axicabtagene ciloleucel vs. tisagenlecleucel, and other construct-specific factors may further increase VTE risk in patients with established VTE risk factors (e.g. history of VTE and obesity). We also observed that a large proportion of post CAR T VTEs corresponded to line-associated DVTs. Taken together, these findings may help identify patients at increased risk of VTE after CAR T-cell therapy and potentially guide decisions on surveillance, choice of central access, or prophylactic anticoagulation. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Incidence and Risk Factors for Postoperative Venous Thromboembolic Events in Patients Undergoing Cervical Spine Surgery.

This was a retrospective database study. The objective of this study was to investigate preoperative risk factors and incidence of venous thromboembolic events (VTEs) after cervical spine surgery. VTEs are preventable complications that may occur after spinal procedures. Globally, VTEs account for a major cause of morbidity and mortality. Preoperative risks factors associated with increased VTE incidence after cervical spine surgery have not been well-characterized. Patients undergoing anterior cervical discectomy and fusion (ACDF); posterior cervical fusion (PCF); discectomy; and decompression from 2007 to 2017 were identified using the PearlDiver Database. International Classification of Diseases (ICD) Ninth and 10th Revision codes were used to identify VTEs at 1 week, 1 month, and 3 months postoperative as well as preoperative risk factors. Risk factors with the highest incidence of VTE at 3 months were primary coagulation disorder [ACDF=7.82%, odds ratio (OR)=3.96; decompression=11.24%, OR=3.03], central venous line (ACDF=5.68%, OR=2.11; PCF=12.58%, OR=2.27; decompression=10.17%, OR=2.80) and extremity paralysis (ACDF=6.59%, OR=2.73; PCF=18.80%, OR=2.99; decompression=11.86, OR=3.74). VTE incidence at 3 months for populations with these risks was significant for all surgery types (P<0.001) with the exception of patients with primary coagulation disorder who underwent PCF. Tobacco use had the lowest VTE incidence for all surgery types. The total cumulative incidence of VTEs at 3-month follow-up was 3.10%, with the highest incidence of VTEs occurring within the first postoperative week (0.65% at 1 wk, 0.61% at 1 mo, 0.53% at 3 mo for ACDF; 2.56% at 1 wk, 1.93% at 1 mo, 1.45% at 3 mo for PCF; 1.37% at 1 wk, 0.93% at 1 mo, 0.91% at 3 mo for decompression). Several preoperative risk factors were found to be significant predictors for postoperative VTEs and can be used to suggest those at increased risk as well as decrease the incidence of preventable VTEs after cervical spine surgery. Level III.

Leukocyte Subtypes As Predictors for Venous Thromboembolism in Diffuse Large B-Cell Lymphoma

Introduction: Venous thromboembolic events (VTE) are a frequent complication of patients diagnosed with diffuse large B -cell lymphoma (DLBCL). Development of VTE portends poor prognosis. Previous studies have identified use of anthracyclines, advanced stage at presentation, obesity, and development of neutropenia and anemia after first cycle of chemotherapy as risk factors for VTE. Recent studies suggest leukocyte subpopulations may affect the risk of VTE; elevated neutrophil and monocyte counts have been associated with increased risk of VTE in solid malignancy patients. The role of leukocyte subpopulations in VTE risk in DLBCL patients has not yet been evaluated. We conducted a retrospective study to identify risk factors for VTE and specifically address the role of leukocytes and their subtypes in VTE risk assessment in DLBCL.Methods: We accessed the Stem Cell Transplant and Hematologic Malignancies database of University Hospitals Seidman Cancer Center for DLBCL patients diagnosed between 2000 and 2016. Information collected included demographic characteristics, baseline laboratory and disease information, as well as treatment details. Patient records were reviewed for the presence of VTE, including radiographic confirmation. Progression free survival and overall survival were calculated from time of diagnosis using Kaplan Meier methodology, comparisons were done with log rank. Cumulative incidence of VTE was calculated considering death as competing risk. Univariate Cox regression analysis was conducted for baseline characteristics, risk factors and baseline laboratory parameters. Variables with a univariate p value lower than 0.1 were included in multivariate Cox regression. All analyses were performed using XLSTAT (Addinsoft, NY).Results: A total of 542 patients were included in the study. Baseline characteristics are described in Table 1. At a median follow up of 48 months, 93 patients developed VTE, with 1 and 2 -year cumulative incidence of VTE of 13.5% (95% CI 10.9-16.8) and 20.5% (95% CI 17.3-24.3). In subsequent years, VTE risk increased more modestly, reaching 23.6% at 4 years (95% CI 20.2-27.7). Eighty percent of VTE occurred in patients with active disease. Sixteen percent of VTE were pulmonary embolism (PE), 53% were lower extremity deep vein thrombosis (DVT), and 31% upper extremity DVTs. Approximately 55% of upper extremity DVTs were line - related.On univariate analysis (table 2), the risk factors with statistically significant odds for increased hazard of VTE included previous history of VTE, albumin less than 3 gm/dl, leukocyte count greater than 11,000/mcl, hemoglobin less than 12 gm/dl, absolute neutrophil count (ANC), ANC to absolute lymphocyte ratio (ANC: ALC) higher than 2.5 and presence of bulky disease at the time of diagnosis. In multivariate analysis, BMI > 35, bulky disease and ANC/ALC ratio ≥ 2.5 remained statistically significant risk factors for development of VTE.Presence of VTE at any time after DLBCL diagnosis was also associated with worse overall survival (OS) and progression free survival (PFS) rates. Patients with VTE after diagnosis had an estimated 4 - year OS of 50.6 % (95% CI 39.7-61.6) vs. 71.3% (95% CI 66.9-75.7) in patients without VTE (p<0.0001) (figure 1). Four-year PFS estimates were 37.5% (95 % CI 27.1-48) and 60% (95 % CI 55.3-64.7), respectively (p<0.0001) (figure 2).Conclusion: VTE is a frequent complication in DLBCL patients and is associated with increased mortality and risk of progressive disease. The first 24 months after DLBCL diagnosis appear to be the time of highest VTE risk, likely a consequence of active disease, treatment and other risk factors such as indwelling catheters. Leukocyte subpopulations appear to have a correlation with VTE risk; the ANC: ALC ratio is a measure of systemic inflammatory response, and in DLBCL patients, a ratio above 2.5 is correlated with increased risk of VTE. Incorporation of this laboratory measurement to currently available VTE risk assessment tools may help more precisely identify the at highest risk of VTE. DisclosuresMalek:Takeda: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau; Sanofi: Consultancy, Speakers Bureau. Tomlinson:Foundation Medicine: Consultancy. Caimi:Kite Pharma: Membership on an entity's Board of Directors or advisory committees; ADC Therapeutics: Research Funding; Celgene: Speakers Bureau; Genentech: Membership on an entity's Board of Directors or advisory committees.

Incidence of symptomatic venous thromboembolism in 2372 knee and hip replacement patients after discharge: data from a thromboprophylaxis registry in Montreal, Canada.

BackgroundLow-molecular-weight heparin (LMWH) is a recommended anticoagulant for thromboprophylaxis after major orthopedic surgery. Dabigatran etexilate is an oral anticoagulant recognized as noninferior to LMWH. We aimed to assess the incidence of symptomatic venous thromboembolic events (VTEs) after discharge in patients who underwent joint replacement, using a hospital registry.Patients and methodsPatients who underwent total knee and hip arthroplasty between September 2011 and March 2015 were selected. Subcutaneous enoxaparin (30 mg twice daily) was given during hospitalization. At discharge, patients received either enoxaparin 30 mg twice daily/40 mg once daily or dabigatran 220 mg/150 mg once daily. Patients were seen or called at 2, 6, and 12 weeks after surgery. Outcomes were the number of VTEs, including deep venous thrombosis, pulmonary embolism, and the number of major/minor bleeding events after discharge.ResultsAfter discharge, 1468 patients were prescribed enoxaparin and 904 dabigatran (1396 total knee arthroplasty and 976 total hip arthroplasty patients). Mean age was 66±10 years, and 60% were female. The cumulative incidence of VTEs during the 12-week follow-up was 0.7%. One patient sustained a VTE during the switch window. Seven patients sustained a pulmonary embolism (0.3%). There was no statistical difference between the total knee arthroplasty and total hip arthroplasty groups. The incidence of major and minor bleeding events during follow-up was 0.3% and 30.3%, respectively. These events had a higher incidence in the dabigatran group compared to the enoxaparin group after discharge (p<0.05), but not between knee and hip replacement groups for major bleeding events.ConclusionA pharmaceutical prophylaxis protocol using LMWH and dabigatran during the post-discharge period resulted in low incidences of VTE and equivalence between treatments. However, the increased number of major and minor bleeding events in patients taking dabigatran is of concern regarding the safety and needs to be evaluated using analyses adjusted for risk factors.

Incidence of superficial venous thrombosis in primary care and risk of subsequent venous thromboembolic sequelae: a retrospective cohort study performed with routine healthcare data from the Netherlands

ObjectivesRecent studies in referred populations of patients with superficial venous thrombosis (SVT) report risks of venous thromboembolic (VTE) sequelae (deep vein thrombosis or pulmonary embolism) as high as 25%. Likely,...

MP04-02 LONG TERM INCIDENCE OF VENOUS THROMBOEMBOLIC EVENTS FOLLOWING CYSTECTOMY: A POPULATION-BASED ANALYSIS.

You have accessJournal of UrologyBladder Cancer: Epidemiology & Evaluation I1 Apr 2017MP04-02 LONG TERM INCIDENCE OF VENOUS THROMBOEMBOLIC EVENTS FOLLOWING CYSTECTOMY: A POPULATION-BASED ANALYSIS. Christopher Wallis, Diana Magee, Raj Satkunasivam, and Robert Nam Christopher WallisChristopher Wallis More articles by this author , Diana MageeDiana Magee More articles by this author , Raj SatkunasivamRaj Satkunasivam More articles by this author , and Robert NamRobert Nam More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.140AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Cancer and immobility both contribute to the development of venous thromboembolic events (VTE), including pulmonary embolism and deep vein thrombosis. As such, patients undergoing radical cystectomy for bladder cancer are at elevated risk. We sought to assess the long-term incidence of VTE among all patients undergoing radical cystectomy in the province of Ontario. METHODS We conducted a population-based cohort study to examine the incidence of VTE, a composite of pulmonary embolism and deep vein thrombosis, among all patients treated with radical cystectomy for bladder cancer between 2002 and 2014 in Ontario, Canada. We estimated the cumulative incidence of VTE and used Fine and Grey competing risk survival analysis to assess risk factors for VTE while accounting for the risk of any cause mortality. RESULTS Among 3623 eligible patients, the 10 year cumulative incidence of VTE was 6.68% (Figure). Among those who experienced VTE, the median time from surgery was 216 days (interquartile range 52-677 days; mean 527 days). However, VTE rates peaked much earlier with a mode of 20 days. Neither preoperative (HR 0.68, 95% CI 0.39-1.18) nor postoperative chemotherapy (HR 1.32, 95% CI 0.95-1.84) were significantly associated with VTE incidence. While patients with a prior history of VTE had increased risk of VTE after cystectomy (HR 5.1, 95% CI 2.2-12.0), age, gender, comorbidity score, rurality, diversion type (continent vs ileal conduit), treatment at an academic institution, or year of treatment were not significantly associated with the risk of VTE. CONCLUSIONS Among patients undergoing cystectomy for bladder cancer, the cumulative incidence of VTE continues to rise long after the date of surgery indicating that previous studies may have underestimated these rates, but the highest rates occur at 20 days after surgery. Chemotherapy does not appear to increase the risk of VTE. © 2017FiguresReferencesRelatedDetailsCited byKlaassen Z, Arora K, Goldberg H, Chandrasekar T, Wallis C, Sayyid R, Fleshner N, Finelli A, Kutikov A, Violette P and Kulkarni G (2017) Extended Venous Thromboembolism Prophylaxis after Radical Cystectomy: A Call for Adherence to Current GuidelinesJournal of Urology, VOL. 199, NO. 4, (906-914), Online publication date: 1-Apr-2018. Volume 197Issue 4SApril 2017Page: e28-e29 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Christopher Wallis More articles by this author Diana Magee More articles by this author Raj Satkunasivam More articles by this author Robert Nam More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Long-term incidence of venous thromboembolic events following cystectomy: A population-based analysis.

288 Background: Cancer and immobility both contribute to the development of venous thromboembolic events (VTE), including pulmonary embolism and deep vein thrombosis. As such, patients undergoing radical cystectomy for bladder cancer are at elevated risk. We sought to assess the long-term incidence of VTE among all patients undergoing radical cystectomy in the province of Ontario. Methods: We conducted a population-based cohort study to examine the incidence of VTE, a composite of pulmonary embolism and deep vein thrombosis, among all patients treated with radical cystectomy for bladder cancer between 2002 and 2014 in Ontario, Canada. We estimated the cumulative incidence of VTE and used Fine and Grey competing risk survival analysis to assess risk factors for VTE while accounting for the risk of any cause mortality. Results: Among 3623 eligible patients, the 10 year cumulative incidence of VTE was 6.68% (Table 1). Among those who experienced VTE, the median time from surgery was 216 days (interquartile range 52-677 days; mean 527 days). However, VTE rates peaked much earlier with a mode of 20 days. Neither preoperative (HR 0.68, 95% CI 0.39-1.18) nor postoperative chemotherapy (HR 1.32, 95% CI 0.95-1.84) were significantly associated with VTE incidence. While patients with a prior history of VTE had increased risk of VTE after cystectomy (HR 5.1, 95% CI 2.2-12.0), age, gender, comorbidity score, rurality, diversion type (continent vs ileal conduit), treatment at an academic institution, or year of treatment were not significantly associated with the risk of VTE. Conclusions: Among patients undergoing cystectomy for bladder cancer, the cumulative incidence of VTE continues to rise long after the date of surgery indicating that previous studies may have underestimated these rates, but the highest rates occur at 20 days after surgery. Chemotherapy does not appear to increase the risk of VTE. [Table: see text]

Venous Thromboembolic Events in Diffuse Large B Cell Lymphoma Patients: Risk Factors and Outcomes

Venous thromboembolic events (VTE) are common after the diagnosis of lymphoma. Although various risk factors have been associated with VTE in cancer patients, there is no specific VTE risk prediction score for diffuse large B cell lymphoma (DLBCL) patients. The Khorana score is a prediction-model of VTE in cancer patients receiving chemotherapy that incorporates clinical and laboratory parameters. We evaluated the risk factors for VTE, the effect of VTE on the outcomes of DLBCL patients and the utility of the Khorana score in DLBCL patients.Methods: We searched the Hematologic Malignancies Database of University Hospitals Seidman Cancer Center for newly diagnosed DLBCL patients between 2002 and 2014. Data on patient characteristics including risk factors, disease characteristics, treatment, outcomes and VTE was collected. The Khorana score was calculated using clinical (disease type, body mass index) and laboratory (hemoglobin level, platelet and leukocyte count) parameters. Risk factors identified as having statistical significance on univariate Cox proportional hazards analysis (p <0.05) were selected for multivariate analysis. Cumulative incidence (with death as competing risk) was used to estimate the incidence of VTE. Overall survival (OS) and progression free survival (PFS) were calculated using the Kaplan-Meier method; comparison between groups was done using the log-rank test.Results: Four hundred DLBCL patients were included for analysis. Median age at diagnosis was 63 with 235 patients above the age of 60. Two hundred and thirty seven patients (59.3 %) had advanced stage at diagnosis and 14 patients (3.5%) had a prior history of VTE. Baseline characteristics are listed in Table 1. Sixty percent of patients had a Khorana score of 1 with no risk factors in addition to the diagnosis of lymphoma.At median follow up of 33 months, 70 patients (18%) presented a VTE, with 1-year and 3-year cumulative incidence of 10.1% (95% CI 7.1-13.6) and 14% (95 % CI 10.8-18), respectively. Fifty-seven VTE (81% of all VTEs) were diagnosed in patients with active disease (at diagnosis, relapse or during active therapy). The Khorana score separated DLBCL patients in three VTE risk groups: intermediate (1 point), high (2 points) and very high (3 or more points) with 1 year cumulative incidence of VTE of 6.4%, 11.6% and 22.2%, respectively (p = 0.009) (Figure 1). On univariate analysis, bone involvement by lymphoma, elevated corrected calcium (>12g/dL), increased white cell count (>11,000/mcl), hemoglobin (<10g/dL), monocytosis (>800/mcl) and chromosomal translocations involving MYC presented statistically significant increases in hazard of VTE (Table 2). On multivariate analysis only bone involvement (p=0.017) and anemia (p=0.035) retained statistical significance as risk factors for VTE.Three-year OS for patients presenting with VTE within 1 year of DLBCL diagnosis was 46.7 % (95% CI 30-63.3) vs. 72.3% (95% CI 67.4-77.3) in subjects without early VTE (p=0.05) (Figure 2). Presence of VTE at any time after DLBCL diagnosis was also associated with worse OS rates, with estimated 3-year OS of 52.2 % (95 % CI 39.8-64.7) for subjects experiencing VTE and 74 % (95 % CI 69-79) for those without VTE after DLBCL diagnosis (p<0.0001).Conclusion: Venous thromboembolic events are common after diagnosis of DLBCL and are associated with worsened outcomes. The Khorana score is capable of identifying patient subgroups with increased risk of VTE. Additional parameters associated with aggressive disease and advanced stages could further help in VTE risk stratification for selection of patients who may benefit from antithrombotic prophylaxis. Prospective validation of VTE risk assessments and clinical trials of VTE prevention are needed in this high=risk population. [Display omitted] [Display omitted] [Display omitted] DisclosuresCaimi:Gilead: Consultancy; Novartis: Consultancy; Genentech: Speakers Bureau; Roche: Research Funding.

Antiphopholipid Antibodies and Functional Activated Protein C Resistance in Patients With Breast Cancer During Anthracycline-Based Chemotherapy Administered Through an Intravenous Port-Catheter Device

Venous thromboembolic events (VTEs) are life-threatening complications in patients with cancer and remain the second most common cause of death in hospitalized patients with cancer, after death from cancer itself. Patients with breast cancer, however, are considered to be at relatively low risk of developing VTE. In a cohort of 108 255 patients with breast cancer, the 1and 2-year cumulative incidence of VTE was estimated to be 0.9% and 1.2%, respectively. Both chemotherapy in general and the agent used in particular were found to increase the risk of developing VTE. A systematic screening for thrombosis during anthracycline-based regimens in adjuvant settings revealed a higher VTE (10%) rate when compared to the conventional cyclophosphamide methotrexate fluorouracil therapy (5.4%). The route of application of chemotherapeutic agents represents another high risk factor for the development of VTE. Catheter-related thrombosis (CRT) involves 70% to 80% of all upper extremity thrombotic events and represents about 10% of all cases of VTE in patients with cancer receiving chemotherapy. The role of acquired thrombophilia such as the induction of antiphospholipid antibodies (aPL-abs) and lupus anticoagulant (LAC) in the pathogenesis of VTE in patients with breast cancer has been reported but is still a matter of debate. In a prospective, case-controlled study, we assessed the rate of symptomatic VTE in primary nonmetastatic, patients with breast cancer who received adjuvant anthracycline-based chemotherapy regimens postoperatively via an intravenous port-catheter device (Hickman port, Celsite Access Port venous low-profile composite access ports with titanium chamber, Braun Melsungen AG, Germany). The standard combination administered every 3 weeks and for 6-treatment cycles was as follows: cyclophosphamide 500 mg/m, doxorubicin/epirubicin 15 mg/m, and flurouracil 1000 mg/m. Prior to primary surgery and each of the 6 cycles of chemotherapy, laboratory tests for anticardiolipin antibodies (aCL-ab; immunoglobulin [Ig] G-, IgM-enzyme-linked immunosorbent assay [ELISA] >15 U/mL), LAC (partial thromboplastin time ratio > 1.2), resistance to activated protein C (APC, Coatest; Chromogenix, Molndal, Sweden; APC ratio 500 mg/L) were performed. None of the patients received anticoagulants unless thrombosis was confirmed. Concomitantly, clinical signs for thrombosis were assessed, namely, increasing girth, marked edema, vague pain, and redness in the corresponding upper limb. The collected data were tabulated and analyzed using PSPP-project version 0.7.9, released February 2012. Over a period of 1.5 years, 42 patients with breast cancer (age: 60.6 + 7.5 years) were recruited; 49 age-matched healthy women served as controls (age: 59.0 + 11.2 years; P 1⁄4 .41). In the study period, 7.2% of the patients with breast cancer (n 1⁄4 3) developed symptomatic VTE, which were all localized in the subclavian vein at the side of the port-catheter. All of them occurred after the first chemotherapy cycle and were proven by contrast phlebography. Low-molecular-weight heparin at therapeutic dose was initiated and continued until removal of the device after the sixth cycle of chemotherapy. Symptomatic thrombosis of the pelvic veins, lower extremities, or in other regions was not detected in any of the patients during the

Incidence of venous thromboembolic events (VTE) in multiple myeloma patients receiving lenalidomide (LEN) with and without dexamethasone (DEX).

e18559 Background: LEN showed significant efficacy and was generally well tolerated when combined with DEX in two randomized, double-blind, pivotal phase 3 registration trials in relapsed or refractory multiple myeloma (MM). VTEs have been associated with LEN and DEX combination (LEN+DEX) regimens in patients (pts) who may have other risk factors for VTE. Fewer VTEs have been reported among pts receiving low dose DEX. This study examined the incidence of first VTE and associated risk factors among MM pts receiving LEN and LEN+DEX. Methods: An exploratory, retrospective, claims-based study of pts diagnosed with MM and receiving LEN from Jan 2006 – June 2008 was performed using OptumInsight’s Invision Data Mart Multiplan database. Pts receiving additional MM chemotherapies were excluded. DEX dose level was defined over the first four 28-day cycles of LEN as: low (≤160 mg), medium (&gt;160 mg to &lt;480 mg), or high (≥ 480 mg). Cumulative incidence of first VTE (deep vein thrombosis or pulmonary embolism) within 120 days of initiating LEN treatment was calculated from Kaplan-Meier curves. Risk factors for VTE were examined using hazard ratios (HRs) from a Cox model that included demographics, prior MM therapy, comorbid conditions, DEX dose, and prophylactic use of anti-thrombotics. Results: 643 LEN-treated MM pts were identified (mean age 60 years, 60% male, 13.5% with prior VTE). Cumulative incidence of first VTE at 120 days from first LEN dose was 6.1% overall (95% CI 4.4-8.3%) and 7.2% (5.1-10.2%) in LEN+DEX. VTE risk for LEN without DEX (n=190; 66 with other steroids) was 3.4% (1.5-7.5%). VTE risk by DEX dose level was 5.9% (3.6-9.7%) for low DEX (n=286), 7.5% (3.6-15.1%) for medium DEX (n=99), and 12.3% (6.3-23.1%) for high DEX (n=66). Significant risk factors for VTE were prior VTE (HR=3.9; p&lt;0.001), recent surgery (HR=2.1; p=0.047), renal failure (HR=2.2; p=0.023), and high dose DEX (HR=2.3; p=0.045). Conclusions: Incommunity-based MM pts treated with LEN+DEX, VTE risk increases with the dose of DEX. The exact mechanism by which DEX intensity impacts VTE is not clear. In addition to high dose DEX, other known VTE risk factors were observed.

PL-16 Accounting for death as a competing risk in cancer-associated thrombosis studies

In recent years, clinical investigation in the field of cancer-associated thrombosis has identified a number of potential biomarkers to predict the risk of developing a thrombotic event. Similarly, large randomized clinical trials have demonstrated the benefit of low molecular weight heparins in the treatment as well as prevention of venous thromboembolic events (VTE) in cancer patients. However, the most common statistical methodology to evaluate the occurrence of VTE has been the Kaplan-Meier approach. When used to estimate the cumulative incidence of VTE in cancer studies, the Kaplan-Meier method over-estimates the cumulative incidence function due to failure to account for death as a competing risk for the development of VTE. A more appropriate statistical estimate of cumulative incidence of VTE in cancer studies is the competing risk model. This review describes the theoretical and mathematical basis for estimating the cumulative incidence function by the competing risk model for the analysis of VTE outcomes in cancer-associated thrombosis.

Venous thromboembolism in 9,489 patients with glioma

1538 Background: Venous thromboembolic events (VTE) are a commonly reported complication of brain tumors. The objective of this study was to define the incidence, risk factors, and outcomes associated with VTE in a population-based cohort. Methods: This was a retrospective analysis of all glioma cases diagnosed in California between 1993–1995 and 1997–1999. Glioma cases in the California Cancer Registry were linked to the California Patient Discharge Database to identify incident VTE. Cox models were generated to analyze the association of pre-specified risk factors with VTE or death within one year of the cancer diagnosis. Results: There were 9489 cases: 76% were Caucasians and 56% were men. The 1-year cumulative incidence of VTE was 663 (7%) with an incidence rate during the first year of 11.1 events per 100 person-years. Sixty-six percent of all VTE diagnosed in the first year occurred within 3 months of the cancer diagnosis with a corresponding incidence rate of 21.6 events per 100 person-years. Of 663 first year VTE, 405 (61%) occurred &lt;2 months after an invasive neurosurgical procedure. Glioblastoma multiforme (GBM) was associated with an increased risk of VTE (HR=1.6, CI: 1.3–2.0) compared to other gliomas. The risk of VTE was strongly associated with the number of chronic co-morbidities (HR=4.0, CI: 3.1–5.0 for ≥3 chronic co-morbidities). Asian race was associated with significantly lower risk of VTE (HR=0.3, CI: 0.2–0.6) and female gender conferred a modestly lower risk (HR=0.8, CI: 0.7–0.9). A VTE in the first year was associated with slightly lower risk of death (HR = 0.8; CI: 0.8–0.9), whereas increasing age (HR=6.3, CI: 5.6–7.0 for age≥75), number of co-morbidities (HR=1.9, CI: 1.7–2.0 for ≥3 chronic co-morbidities), and GBM (HR=2.2, CI: 2.0–2.4) or anaplastic astrocytoma (HR=1.5, CI: 1.3–1.7) histology were associated with a higher risk of death within 1 year. Conclusions: In this large glioma cohort, the incidence of symptomatic VTE was very high. Two-thirds of all VTE occurred early after the diagnosis of glioma, and most of these occurred within 2 months of an invasive neurosurgical procedure. The presence of chronic medical co-morbidities and GBM histology were strong predictors of VTE. A diagnosis of VTE was not associated with an increased risk of death within 1 year. No significant financial relationships to disclose.