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Summary Background Clear guidelines for the investigation of occult malignancy after unprovoked venous thromboembolism are not yet available. 18 F-fluorodeoxyglucose ( 18 F-FDG) PET/CT could serve as a comprehensive screening strategy for occult malignancy in this context. We aimed to compare a screening strategy based on 18 F-FDG PET/CT with a limited screening strategy for detection of malignant disease in patients with unprovoked venous thromboembolism. Methods In an open-label, multicentre, randomised study we enrolled patients from four French university hospitals. Patients aged 18 years or older, diagnosed with unprovoked venous thromboembolism (not provoked by a major inherited or acquired risk factor) were invited to participate. Patients were randomly assigned in a 1:1 ratio to a limited screening strategy (physical examination, usual laboratory tests, and basic radiographs) or a screening strategy consisting of the limited strategy plus an 18 F-FDG PET/CT scan. Randomisation was done with a dedicated central web-based randomisation system, in block sizes of six, stratified by centre, and concealed from the investigators. Patients and investigators were not masked to study group assignment. Patients were followed up for 2 years. The primary outcome was the proportion of patients with a cancer diagnosis in each group after the initial screening assessment. Analyses were conducted in modified intention-to-test and per-protocol populations. This trial is completed and registered with ClinicalTrials.gov, number NCT00964275. Findings Between March 3, 2009, and Aug 18, 2012, we enrolled and randomly assigned 399 patients; five withdrew consent, leaving 197 in each group for the modified intention-to-test analysis. After initial screening assessment, cancer was diagnosed in 11 (5·6%) patients in the 18 F-FDG PET/CT group and four (2·0%) patients in the limited screening group (absolute risk difference 3·6%, 95% CI −0·4 to 7·9; p=0·07). At the initial screening assessment, seven (64%) of the 11 cancers diagnosed in the 18 F-FDG PET/CT group were early-stage compared with two of four cancers diagnosed in the limited screening group (p=1·00). One (0·5%) occult malignancy was detected in 186 patients who had negative initial screening in the 18 F-FDG PET/CT group, compared with nine (4·7%) in 193 patients in the limited screening group (absolute risk difference 4·1%, 95% CI 0·8 to 8·4, p=0·01). Overall, five (42%) of the 12 cancers diagnosed in the 18 F-FDG PET/CT group were advanced stage, compared with seven (54%) of the 13 cancers diagnosed in the limited screening group (p=0·70). 16 patients died during follow-up, eight (4·1%) in each group. Two (1·0%) patients in the 18 F-FDG PET/CT group and five (2·5%) in the limited screening group had cancer-related deaths. Interpretation A strategy including limited screening and a 18 F-FDG PET/CT was not associated with a significantly higher rate of cancer diagnosis after unprovoked venous thromboembolism. The risk of subsequent cancer diagnosis was, however, lower in patients who had negative initial screening that included 18 F-FDG PET/CT than in patients who had negative initial limited screening. Whether or not 18 F-FDG PET/CT might be useful in a more selected population of patients with a high risk of cancer remains to be determined. Funding Programme Hospitalier de Recherche Clinique (French Department of Health).

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.

18F-Fluorodesoxyglucose Positron-Emission-Tomography combined with Computed-Tomography (FDG PET/CT) might be an attractive tool for cancer screening in patients with venous thromboembolism (VTE), allowing non-invasive whole-body imaging. One of the frequent criticisms to the use of FDG PET/CT for screening is the potential for false positive results leading to unnecessary/invasive investigations. Our aim was to compare the frequency and invasiveness of additional testing following extensive and limited screening strategies for occult malignancy in patients with unprovoked VTE. We analysed patients included in the MVTEP study, a randomized trial that compared a screening strategy based on FDG-PET/CT with a limited screening strategy for occult malignancy diagnosis in patients with unprovoked VTE. All additional diagnostic procedures following screening were recorded and classified as invasive or non-invasive. A total of 394 patients were analysed. Additional diagnostic procedures realized in patients of each group consisted of 59 tests in patients of the FDG PET/CT group versus 53 tests among the patients from the limited screening group (p=0.65). Overall, 45 (22.8%) patients in the FDG PET/CT group underwent additional diagnostic tests, versus 32 (16.2%) in the limited screening group (absolute risk difference+6.6%, 95% CI -1.3 to +14.4%, p=0.13). Sixteen (8.1%) patients in the FDG PET/CT group underwent invasive procedures, versus 6 (3%) in the limited screening group (absolute risk difference+5.1%, 95% CI +0.5 to +10.0%, p=0.03). We found no statistical difference in the number of additional procedures following each screening strategy. However, a higher number of invasive tests were performed in the FDG PET/CT group.