ALBERT

Description: Introduction: Patients with pancreatic cancer are at very high risk of venous thromboembolism (VTE). While the etiology of the prothrombotic state of these patients is not fully understood, emerging evidence suggests a causal role for circulating tumor-derived, tissue factor bearing microparticles (TFMP). We aim to assess whether a new, practical TFMP coagulant activity assay – the fibrin generation test (FGT) – is able to identify pancreatic cancer patients at the highest risk of VTE as they would benefit most from pharmaceutical thromboprophylaxis. Methods: In this ongoing prospective cohort study, patients with pancreatic cancer who have recently started neoadjuvant or palliative chemotherapy are enrolled after informed consent. Exclusion criteria are VTE within 3 months prior to inclusion and current anticoagulant use. Within 30 minutes from standardized blood withdrawal, the FGT is performed on fresh, essentially cell-free, citrated plasma. The time to fibrin formation is measured by optical densitometry after incubation of the samples with either saline or anti-factor VIIa, both in duplicate. The prolongation in the time to fibrin formation in the presence of anti-factor VIIa compared to saline reflects the contribution of the TFMP to coagulation. A predefined cut-off of 13% was used to indicate high TFMP coagulant activity. The primary outcome is objectively confirmed symptomatic or asymptomatic deep vein thrombosis (DVT) or pulmonary embolism (PE) during 6 months follow-up. We use multiple imputation techniques to avoid bias from excluding patients in whom the FGT result is unavailable due to non-adherence to the standardized blood withdrawal. We perform competing risk regression analysis to deal with death as competing event for the occurrence of VTE. Results: At present, 88 patients with pancreatic cancer have been enrolled. Baseline characteristics and follow-up data are presented in the Table. The TFMP coagulant activity as assessed with the FGT was high in 43 patients (48.9%). Fourteen percent (6/43) of patients with a high FGT result developed VTE, as compared to 2.6% (1/39) in patients with a low FGT result (OR 6.0; 95%CI 0.74-48.99). In the multivariate competing risk model including sex, age, tumor extent, and histology the adjusted OR was 6.04 (95%CI 0.75-48.8). Conclusion: Our preliminary results suggest that the FGT, a practical TFMP coagulant activity assay, has predictive value for VTE in patients with pancreatic cancer. Although the number of events at present is too low to draw definite conclusions, the FGT is a promising biomarker that could easily be implemented in clinical practice. If these results will be confirmed, the FGT may be used as a risk stratification tool to identify pancreatic cancer patients at high-risk for VTE and install thrombosis prophylaxis in these patients. Table. Baseline characteristics and follow-up data Characteristic All patients (N=88) Median age, years (IQR) 62.6 (55.1-68.0) Mean BMI, kg/m2 (SD) 26.3 (20) Male 49 (55.7%) Performance status WHO 0 50 (56.8%) WHO 1 32 (36.4%) WHO 2 6 (6.8%) Antiplatelet therapy 12 (13.6%) Cancer details Extent Local disease 36 (40.9%) Resectable 2 (2.3%) Borderline resectable 8 (9.1%) Irresectable 26 (29.5%) Distant metastasis 52 (59.1%) Recurrent cancer 8 (9.1%) Adenocarcinoma 80 (90.9%) Median time from cancer diagnosis to inclusion, days (IQR) 70 (47-103.5) Chemotherapy Gemcitabin 68 (77%) Neoadjuvant chemotherapy 10 (11.4%) Median time from start chemotherapy to inclusion, days (IQR) 14 (7-45) Median FGT, % (IQR) 14.9 (0-42.9) FGT result unavailable 6 (6.8%) Median follow-up, days (IQR) 123 (4-180) Follow-up status Withdrawn alive 57 (64.8%) Death 24 (27.3%) DVT or PE 7 (8.0%) Disclosures No relevant conflicts of interest to declare.

Description: INTRODUCTION Clinically unsuspected pulmonary embolism (UPE) is frequently diagnosed in cancer patients undergoing routine computed tomography scans for staging purposes or treatment response evaluation. The reported incidence of UPE ranges from 1% to 5%, and is likely to increase further with the improvements of imaging techniques. Current guidelines suggest that UPE should receive similar initial and long-term anticoagulant treatment as for symptomatic PE. However, direct evidence is scarce. Selected subgroups of cancer patients with UPE such as those with subsegmental UPE may be treated conservatively by withholding anticoagulation as subsegmental PE seems to have a more benign course than more proximal PE. AIM The aim of this study is to evaluate the current treatment approaches for UPE and to assess their efficacy and safety in a large prospective cohort of cancer patients. MATERIAL AND METHODS This is a prospective, observational, multicenter, international study in cancer patients with UPE. Adult patients with UPE are consecutively included in the study. Patients already treated with anticoagulant therapy and patients with a life expectancy of less than 3 months are not eligible for participation. All patients will be followed for 12 months after diagnosis. The outcome variables (recurrent VTE, bleeding and mortality) will be recorded at 3, 6 and 12 months of follow-up. All outcomes will be adjudicated by a central independent adjudication committee. To enable sufficient power for a comparison of VTE recurrence rate between patients with (sub)segmental PE and those with central and/or lobar PE, a sample size of 610 patients was calculated based on an assumed overall recurrent VTE rate of 13% and an odds of 3:1 of (sub)segmental PE versus central PE. RESULTS From April 2012 to June 2014 a total of 123 cancer patients with UPE were enrolled, of whom 71 (57.8%) had lobar or central PE. 116 patients (94.3%) were treated and 83.6% of them received low molecular weight heparin (LMWH) as the initial and long-term treatment. The baseline characteristics are depicted in Table 1. The incidence of VTE recurrence, bleeding and mortality at 3 months of follow-up are 4.9%, 8.5% and 11%, respectively. At 6 months these rates are 4.9%, 18%, and 18.1% and at 12 months of follow-up 4.9%, 18% and 43.1%, respectively. Follow-up and central adjudication are being completed and an update of this ongoing project will be presented. CONCLUSIONS The results from this study will give insight in the current treatment strategies in cancer patients with UPE. Important prospective data on the outcome of UPE in terms of recurrent VTE, bleeding and mortality in cancer patients will be generated, especially regarding the outcome of (sub)segmental UPE. These distally located PE may have a more benign course compared with lobar and/or central PE thus requiring no or short anticoagulant treatment. This will be tested in subsequent randomized trials. Baseline characteristics of cancer patients with UPE. Table 1 Table 1. SD = standard deviation; LMWH = low-molecular weight heparin; UFH = unfractionated heparin Disclosures No relevant conflicts of interest to declare.

Description: Abstract 391 Introduction Traditionally, the focus of VTE diagnostic is on deep vein thrombosis (DVT) of the leg and pulmonary embolism. Until recently, upper extremity DVT (UEDVT) was regarded as an uncommon and relatively benign presentation of venous thromboembolism; however, the more widespread use of central venous catheters has caused a significant increase in its incidence. Moreover, recent data indicate that 10–25% of these patients may have pulmonary embolism. Therefore, effective and safe diagnostic strategies are needed. The use of an algorithm combining a clinical decision score, D-dimer and ultrasonography is well-established for suspected lower limb DVT, but has not been evaluated in suspected UEDVT. This diagnostic management study assessed the safety and feasibility of a new diagnostic algorithm in patients with clinically suspected UEDVT. Methods In- and outpatients with suspected UEDVT were recruited from January 2010 until July 2012 in 17 hospitals in Europe and the United States. To confirm an acceptable failure rate of excluding UEDVT (upper 95% confidence interval below 3%), approximately 400 patients needed to be included. Main exclusion criteria were previous UEDVT and the use of therapeutic doses of anticoagulants. Informed consent was obtained from all participants. The algorithm consisted of the sequential application of the Constans' clinical decision score (Constans et al, Thromb Haemost 2008), D-dimer testing and compression ultrasonography. Patients were first categorized as UEDVT likely or unlikely by the Constans' score. In the patients with an unlikely score and a normal D-dimer, UEDVT was considered excluded and no further testing was done. All other patients underwent compression ultrasonography, which first assessed the deep veins for the presence of UEDVT and then the superficial veins for the presence of superficial vein thrombosis (SVT). Ultrasonography was repeated in case of an indeterminate ultrasonography result, or in patients with a high probability score, abnormal D-dimer and a normal ultrasonography. The primary outcome was the 3-month incidence of symptomatic UEDVT and pulmonary embolism in patients with a diagnostic work-up excluding both UEDVT and SVT. Results The study population comprised of 356 consecutive patients with suspected UEDVT. The algorithm was feasible and completed in 96% (Figure). Of the 356 patients, 181 had a low probability score and D-dimer was measured. In 78 patients (22%) a normal D-dimer combined with a low probability score excluded UEDVT without any imaging, and these patients all had an uneventful 3 month follow up. An abnormal D-dimer test result was found in 100 patients, who underwent ultrasonography. In 3 patients, D-dimer measurement was not done, and these patients received ultrasonography right away. Of all patients with a low probability score, 15 patients had UEDVT, 24 patients had SVT, while thrombosis (both deep and superficial) was excluded in 141 patients. One remaining patient died of progressive cancer before ultrasonography could be done. All 175 patients with a high probability score underwent compression ultrasonography right away, which was repeated if indicated. Of these patients with a high probability score, 82 had UEDVT and 22 had SVT. In 71 patients, thrombosis was excluded, including 11 patients in whom the protocol was not followed completely. To summarize, of the 356 included patients, 97 patients had UEDVT (27%), 46 had SVT (13%) and in 212 patients the algorithm excluded UEDVT and SVT (60%). Of all patients in whom the algorithm excluded UEDVT and SVT, one patient developed UEDVT during follow-up for an overall failure rate of 0.47% (95%CI: 0.0–2.6%). Final results of the definitive study population of 407 patients will be presented. Conclusions A new diagnostic algorithm which combines a clinical decision score, D-dimer and ultrasonography can safely and effectively exclude venous thrombosis of the upper extremity. This approach is attractive as it is simple, quick and non-invasive, and very similar to the well established algorithm for suspected DVT of the leg which could facilitate its implementation in clinical practice. Disclosures: No relevant conflicts of interest to declare.