Incidence, predictors and prognostic significance of thromboembolic disease in patients with advanced ALKrearranged non-small cell lung cancer To the Editor: Thromboembolic disease is fairly common in patients with lung cancer [1-3]. This incidence seems to be higher in patients with lung adenocarcinomas [4], with approximately 15% of those with advanced stage disease developing venous thromboembolisms (VTE) during the whole course of their disease [5-7]. Pulmonary adenocarcinomas are a heterogeneous group of diseases that can be stratified according to the presence of major oncogenic driver alterations. Anaplastic lymphoma kinase (ALK) rearrangements are detected in approximately 4% of these cases [8]. Isolated reports have suggested that patients bearing ALK-rearranged tumours might have a higher than expected incidence of thromboembolisms [9, 10]. In the present study, we have analysed the incidence, predictors and prognostic significance of thromboembolic events in a large, multi-institutional and homogeneous cohort of advanced stage patients with ALK-rearranged lung cancers from Spain and Portugal. Our primary objective was to estimate the incidence of thromboembolic events and their association with overall survival in these patients. A centralised institutional ethics committee approval at the 12 de Octubre University Hospital valid for all Spanish centres, and an institutional ethics committee approval at the Portuguese Institute of Oncology of Porto, were obtained before the study was initiated. We retrospectively selected all consecutive patients diagnosed with advanced stage (stages III and IV) ALK fusion positive non-small cell lung cancers (NSCLCs) between January 2012 and December 2016. Data were contributed by 29 Medical Centres from Spain and one from Portugal. ALK positivity was determined according to local standard protocols in each institution. We excluded patients with neuroendocrine tumours and patients on therapeutic doses of anticoagulants prior to advanced stage cancer diagnosis. We defined a thromboembolic event as any venous or arterial thromboembolism, documented by imaging studies, that occurred at the time or after advanced stage cancer diagnosis. In addition to thromboembolic events, collected during the whole patients' follow-up period, we collected baseline information (within 1 month of advanced stage cancer diagnosis) of several clinical and analytical variables of interest. We included 241 ALK-rearranged NSCLCs in this study. The median age was 56 years (range 17-84 years). Half of the patients were never smokers (52%), and most had stage IV pulmonary adenocarcinomas (n=204, 85%). Baseline brain and liver metastasis were detected in 22% and 25% of the patients, respectively. 17 patients (7%) and 185 patients (77%) had high and intermediate Khorana risk scores (KRS) [11] respectively. The median follow-up of our study population was 19 months (range 0-59 months), and 127 (53%) of the patients died. The median follow-up of alive patients was 30 months (range 4-49 months). The est...

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Phosphoinositide 3'-kinase (PI3K) is a key component of both chronic active and tonic B-cell receptor-signalling pathways. As such, PI3K inhibitors have emerged as promising therapeutic agents for diverse lymphoid malignancies, particularly chronic lymphocytic leukaemia. Multiple in vitro experiments and clinical trials have shown efficacy of these agents across all prognostic subgroups with a favourable toxicity profile. Moreover, in vitro studies suggest that combinations with monoclonal antibodies and/or other immune strategies could enhance the effect of PI3K inhibition.

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BackgroundPatients with venous thromboembolism (VTE) secondary to transient risk factors may develop VTE recurrences after discontinuing anticoagulation. Identifying at‐risk patients could help to guide the duration of therapy.MethodsWe used the RIETE database to assess the prognostic value of d‐dimer testing after discontinuing anticoagulation to identify patients at increased risk for recurrences. Transient risk factors were classified as major (postoperative) or minor (pregnancy, oestrogen use, immobilization or recent travel).ResultsIn December 2018, 1655 VTE patients with transient risk factors (major 460, minor 1195) underwent d‐dimer measurements after discontinuing anticoagulation. Amongst patients with major risk factors, the recurrence rate was 5.74 (95% CI: 3.19–9.57) events per 100 patient‐years in those with raised d‐dimer levels and 2.68 (95% CI: 1.45–4.56) in those with normal levels. Amongst patients with minor risk factors, the rates were 7.79 (95% CI: 5.71–10.4) and 3.34 (95% CI: 2.39–4.53), respectively. Patients with major risk factors and raised d‐dimer levels (n = 171) had a nonsignificantly higher rate of recurrences (hazard ratio [HR]: 2.14; 95% CI: 0.96–4.79) than those with normal levels. Patients with minor risk factors and raised d‐dimer levels (n = 382) had a higher rate of recurrences (HR: 2.34; 95% CI: 1.51–3.63) than those with normal levels. On multivariate analysis, raised d‐dimers (HR: 1.74; 95% CI: 1.09–2.77) were associated with an increased risk for recurrences in patients with minor risk factors, not in those with major risk factors.ConclusionsPatients with raised d‐dimer levels after discontinuing anticoagulant therapy for VTE provoked by a minor transient risk factor were at an increased risk for recurrences.