Small series have suggested that Fluorodesoxyglucose Positron-Emission-Tomography with Computed-Tomography (FDG-PET/CT) is feasible to screen for cancer in patients with unprovoked venous ...thromboembolism (VTE), but without validation in a large population. The aim was to assess diagnostic accuracy indices of FDG-PET/CT for occult cancer diagnosis in patients with unprovoked VTE.
We analysed patients from the FDG-PET/CT group of a randomized trial that compared a screening strategy based on FDG-PET/CT with a limited screening strategy for occult malignancy detection in patients with unprovoked VTE. FDG-PET/CT was interpreted as positive for cancer, as negative or as equivocal. Patients were considered as having cancer on the basis of screening results, or of any test performed during a two-years follow-up period. We ran two sets of analysis, considering patients with equivocal FDG-PET/CT as positive, then as negative for malignancy.
Between March 2009, and August 2012, 172 patients were included. FDG-PET/CT was interpreted as positive for malignancy in 10 patients (5.8%), as equivocal in 23 patients (13.4%) and as negative in 139 patients (80.8%). Malignancy was diagnosed in 7/10 (70.0%), 2/23 (8.7%) and 1/139 (0.7%) patients, respectively. Grouping positive and equivocal results, sensitivity and specificity were 90% (95%CI 60% to 98%) and 85% (95%CI 79% to 90%), respectively. Grouping negative and equivocal results, sensitivity and specificity were 70% (95%CI 40% to 89%) and 98% (95%CI 95% to 99%), respectively.
FDG-PET/CT showed good accuracy for occult cancer screening in patients with unprovoked VTE. Remaining challenges include the need to define specific interpretation criteria in this dedicated population.
Recent data on lower-limb superficial-vein thrombosis (SVT) may substantially impact its clinical management. Particularly, the clear confirmation that SVT is closely linked to deep-vein thrombosis ...(DVT) or pulmonary embolism (PE) highlights the potential severity of the disease. DVT or PE is diagnosed in 20–30% of SVT patients. Moreover, clinically relevant symptomatic thromboembolic events complicate isolated SVT (without concomitant DVT or PE at diagnosis) in 4–8% of patients. For the first time, an anticoagulant treatment, once-daily 2.5 mg fondaparinux for 45 days, was demonstrated to be effective and safe for preventing these symptomatic thromboembolic events in patients with lower-limb isolated SVT in the randomized, placebo-controlled CALISTO study. More recent data from another randomized trial support these findings. New recommendations on the management of SVT patients, including complete ultrasonography examination of the legs and, in patients with isolated SVT, prescription of once-daily 2.5 mg fondaparinux subcutaneously for 45 days on top of symptomatic treatments, may be proposed, wherever the cost of fondaparinux is acceptable. Superficial-vein thrombosis (SVT) of the lower limbs has long been regarded as a benign, self-limiting disease, expected to resolve spontaneously and rapidly, and requiring only symptomatic treatments 1,2 . However, the perception of this disease is now changing with the recent publication of data indicating its potential severity 3 and showing for the first time the benefit of a therapeutic strategy based on the administration of an anticoagulant treatment 4 . The overall management of this frequent disease therefore needs to be reconsidered.
Abstract
Cancer-associated thrombosis (CT) carries a high, heterogeneous, and poorly predicted likelihood of mortality. Thus, we aimed to define predictors of 30-day mortality in 10,025 patients with ...CT. In a randomly selected derivation cohort, we used recursive partitioning analysis to detect variables that select for a risk of mortality within 30 days. In a validation cohort, we evaluated our results using Cochran–Armitage test. The most common types of cancer were lung (16%), breast (14%), and colorectal (14%); median age was 69 years (range, 14–101); most had metastatic disease (63%); 13% of patients died within 30 days. In the derivation cohort (
n
= 6,660), a white blood cell (WBC) count in the highest quartile predicted early mortality (odds ratio, 7.8; 95% confidence interval CI, 4.6–13.1); and the presence of metastatic disease, pulmonary embolism (PE), and immobility defined the risk of those with normal WBC count. We defined death risk according four sequential questions: (1) Does the patient have an elevated WBC count? (Yes, group D). (2) If no, does the patient have metastasis? (No, group A). (3) If yes, is the patient immobile? (Yes, group D). (4) If no, does the patient have a PE? (Yes, group C; no, group B). In the validation cohort (
n
= 3,365), the 30-day risk of death was 2.9% in group A (95% CI, 1.9–4.3), compared with 25% in group D (95% CI, 22.5–27.5), and there was a rate escalation between groups (
p
for trend < 0.01). In conclusion, with four sequential questions, the risk of death in CT can be easily stratified. An elevated WBC count at baseline predicted 30-day mortality better than metastases, PE, or immobility.
•Renal recovery is frequent in patient with acute PE, and occurs after the first week.•A quarter of AKI patients does not fully recover a normal renal function after PE•Treatment, care and decisions ...should consider AKI in patients with acute PE
Risk stratification is recommended for patients with pulmonary embolism (PE), and usually starts with the assessment of the hemodynamic status and the simplified Pulmonary Embolism Severity Index ...(sPESI). The influence of acute kidney injury (AKI) on the prognostic stratification has not been evaluated according to the “Kidney Disease: Improving Global Outcomes” (KDIGO). AKI was computed according to the KDIGO definition in patients with acute PE in the RIETE (Registro Informatizado Enfermedad TromboEmbolica) registry. Patients with hemodynamic instability were considered high-risk. Normotensive patients were stratified according to the sPESI score (low-risk: sPESI = 0; intermediate-risk: sPESI > 0). The primary outcome was all-cause 30-day mortality. Secondary outcomes were major bleeding and VTE recurrences during the same period. Among 30,532 patients with PE, 1108 (3.6%) were classified to be at high-risk, 10,577 (34.6%) at low-risk, and the remaining 18,847 (61.8%) at intermediate-risk of adverse events. At baseline, 7879 (26%) had AKI. Overall, 1543 of 30,532 patients (5.1%) died within the first 30 days. The presence of AKI was associated with increased mortality rates in all subgroups of patients: in those at low-risk it increased from 0.46 to 3%, in intermediate-risk from 5.4 to 10%, and in high-risk patients from 9.4 to 18%. The presence of AKI was also associated with an increased risk of major bleeding in all subgroups. The addition of the AKI status to the sPESI score improved the prediction of the 30-day mortality and may be particularly helpful for decisions such as identification of low-risk patient for home discharge.
The need to accurately identify cancer outpatients at high risk of thrombotic complications is still unmet. In a prospective, multicenter cohort study (ONCOlogie et Chambres ImPlantables ONCOCIP), ...consecutive adult patients with a solid tumor and implanted port underwent 12-month follow-up. Our primary objective was to identify risk factors for (1) catheter-related thrombosis, defined as ipsilateral symptomatic upper-limb deep-vein thrombosis with or without pulmonary embolism, and (2) venous thromboembolism other than catheter-related, defined as any symptomatic superficial- or deep-vein thrombosis (other than catheter-related) or pulmonary embolism, and incidental pulmonary embolism. All events were objectively confirmed and centrally adjudicated. Rate assessments integrated competing risk of death. Overall, 3032 patients were included (median age: 63 years; women: 58%). The most frequent cancer locations were breast (33.7%), lung (18.5%), and colorectal (15.6%), cancer being metastatic in 43.2% of patients. Most patients (97.1%) received chemotherapy. By 12 months, 48 (1.6%) patients had been lost to follow-up and 656 (24.6%) had died; 3.8% (n = 111) of patients had experienced catheter-related thrombosis, and 9.6% (n = 276) venous thromboembolism other than catheter-related. By multivariate analysis, use of cephalic vein for catheter insertion predicted catheter-related thrombosis, whereas ongoing antiplatelet therapy was protective; risk factors for venous thromboembolism other than catheter-related were advanced age, previous venous thromboembolism, cancer site, and low hemoglobin level or increased leukocyte count before chemotherapy. In conclusion, this large prospective cohort study showed a high rate of venous thromboembolism in patients with a solid tumor and implanted port. Risk factors for catheter-related thrombosis differed from those for venous thromboembolism not catheter-related. This trial was registered at www.clinicaltrials.gov as #NCT02025894.
•The incidence of venous thromboembolism is high in patients with a solid tumor and implanted port in the real-life practice setting.•The risk factors for catheter-related thrombosis differ from those for venous thromboembolism unrelated to the catheter.
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Unprovoked venous thromboembolism (VTE) may be the first manifestation of an undiagnosed cancer. We assessed the cost-effectiveness of 18F-Fluorodesoxyglucose Positron Emission/Computed Tomography ...(FDG PET/CT) plus limited screening and limited screening strategies in patients with unprovoked VTE from the perspectives of the Ontario (Canada) and French health care systems.
We conducted a cost-effectiveness analysis based on a published randomized controlled trial of 394 patients aged 18 years or older who were diagnosed with unprovoked VTE. We obtained data with respect to efficacy and health care utilization from the published trial. The primary measure of effectiveness was the number of avoided cases of delayed cancer diagnosis and the secondary measure of effectiveness was the quality adjusted life year (QALY) at the end of the study in each group. We used generalized linear models to estimate incremental cost-effectiveness ratios (ICER) while controlling for patient demographic and clinical characteristics. Results were presented as the incremental cost to avoid one case of delayed cancer diagnosis and the incremental cost per QALY gained. The 95% confidence intervals (CIs) were estimated using bootstrap re-sampling procedures with 5000 iterations.
Compared to a limited screening strategy, the ICER of limited strategy plus FDG PET/CT scan was C$ 26,840.19 (95% CI: C$ 24,046.51; C$ 34,581.53) per one avoided case of delayed cancer diagnosis from the Ontario health system perspective and €16,370.45 (95% CI: € 9904.48; € 39,578.91) per one avoided case of delayed cancer diagnosis from the French health system perspective. The probabilities that addition of FDG PET/CT to limited screening is cost-effective rose with increasing willingness to pay values. Compared with the limited screening, the extensive screening was associated with C$ 3412.85 per QALY gained (95% CI: 1463.89; −13,935.88) from the Ontario health system perspective and €2162.83 per QALY gained (95% CI 958.78; −10,544.42) from the French health system perspective.
Addition of a FDG PET/CT for occult cancer diagnosis was associated with better health outcomes (fewer cases of delayed cancer diagnosis and greater QALYs) and a higher cost from the perspective of publicly funded health care systems; the cost-effectiveness results are however highly uncertain.
•VTE can occur as the first manifestation of an occult malignancy.•Extensive screening based on FDG PET/CT is more expensive than limited screening alone.•FDG PET/CT missed significantly less occult cancers than limited screening alone.•Cancer screening using FDG PET/CT in patients with unprovoked VTE might be economically attractive.
Venous thromboembolism (VTE) can occur as the first manifestation of an underlying occult malignancy. It remains unclear whether or not a better selection of high risk patients might lead to more ...efficient occult cancer screening strategies.
Our aim was to assess the predictors of occult malignancy diagnosis in patients with unprovoked VTE.
Univariate analyses were performed to assess the effect of candidate predictors on occult cancer detection in patients enrolled in a prospective, multicenter, randomized, controlled study (MVTEP study) whose primary aim was to compare a limited screening strategy with a strategy combining limited screening and FDG PET/CT in patients with unprovoked VTE. This trial is completed and registered with ClinicalTrials.gov, number NCT00964275.
Between March 3, 2009, and August 18, 2012, 399 patients were included. Five patients withdrew consent and refused the use of their data, and no VTE was confirmed in 2 patients who were excluded from this analysis. A total of 25 (6.4%) out of the 392 analysed patients received a new diagnosis of malignancyduring the 2-years follow-up. Age≥50years (p=0.01), male gender (p=0.04), leukocytes count (p=0.01), and platelets count (p=0.03) were associated with occult cancer detection. Patients with leukocytosis or thrombocytosis had a risk of cancer way above 10%. Previous VTE and smoker status (combining previous and current smokers) were not associated with occult cancer diagnosis (p>0.05).
Demographic characteristics (age and sex), and laboratory tests (high platelets and leukocytes counts) may be associated with cancer detection in patients withunprovoked VTE.
•Venous thromboembolism can occur as the first manifestation of an occult malignancy.•Selecting “high risk” patients might lead to more efficient occult cancer screening strategies.•Age≥50 y, male sex, high platelets and leukocytes counts may be associated with cancer detection.•Previous VTE and smoker status were not associated with occult cancer diagnosis.
Purpose Small series have suggested that Fluorodesoxyglucose Positron-Emission-Tomography with Computed-Tomography (FDG-PET/CT) is feasible to screen for cancer in patients with unprovoked venous ...thromboembolism (VTE), but without validation in a large population. The aim was to assess diagnostic accuracy indices of FDG-PET/CT for occult cancer diagnosis in patients with unprovoked VTE. Materials and methods We analysed patients from the FDG-PET/CT group of a randomized trial that compared a screening strategy based on FDG-PET/CT with a limited screening strategy for occult malignancy detection in patients with unprovoked VTE. FDG-PET/CT was interpreted as positive for cancer, as negative or as equivocal. Patients were considered as having cancer on the basis of screening results, or of any test performed during a two-years follow-up period. We ran two sets of analysis, considering patients with equivocal FDG-PET/CT as positive, then as negative for malignancy. Results Between March 2009, and August 2012, 172 patients were included. FDG-PET/CT was interpreted as positive for malignancy in 10 patients (5.8%), as equivocal in 23 patients (13.4%) and as negative in 139 patients (80.8%). Malignancy was diagnosed in 7/10 (70.0%), 2/23 (8.7%) and 1/139 (0.7%) patients, respectively. Grouping positive and equivocal results, sensitivity and specificity were 90% (95%CI 60% to 98%) and 85% (95%CI 79% to 90%), respectively. Grouping negative and equivocal results, sensitivity and specificity were 70% (95%CI 40% to 89%) and 98% (95%CI 95% to 99%), respectively. Conclusion FDG-PET/CT showed good accuracy for occult cancer screening in patients with unprovoked VTE. Remaining challenges include the need to define specific interpretation criteria in this dedicated population.
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