Introduction: The ROS1 gene rearrangement has become an important biomarker in NSCLC. The College of American Pathologists/International Association for the Study of Lung Cancer/Association for Molecular Pathology testing guidelines support the use of ROS1 immunohistochemistry (IHC) as a screening test, followed by confirmation with fluorescence in situ hybridization (FISH) or a molecular test in all positive results. We have evaluated a novel anti-ROS1 IHC antibody (SP384) in a large multicenter series to obtain real-world data.

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High resolution LC-MS untargeted lipidomics using data independent acquisition (DIA) has the potential to increase lipidome coverage, as it enables the continuous and unbiased acquisition of all eluting ions. However, the loss of the link between the precursor and the product ions combined with the high dimensionality of DIA data sets hinder accurate feature annotation. Here, we present LipidMS, an R package aimed to confidently identify lipid species in untargeted LC-DIA-MS. To this end, LipidMS combines a coelution score, which links precursor and fragment ions with fragmentation and intensity rules. Depending on the MS evidence reached by the identification function survey, LipidMS provides three levels of structural annotations: (i) “subclass level”, e.g., PG(34:1); (ii) “fatty acyl level”, e.g., PG(16:0_18:1); and (iii) “fatty acyl position level”, e.g., PG­(16:0/18:1). The comparison of LipidMS with freely available data dependent acquisition (DDA) and DIA identification tools showed that LipidMS provides significantly more accurate and structural informative lipid identifications. Finally, to exemplify the utility of LipidMS, we investigated the lipidomic serum profile of patients diagnosed with nonalcoholic steatohepatitis (NASH), which is the progressive form of nonalcoholic fatty liver disease, a disorder underlying a strong lipid dysregulation. As previously published, a significant decrease in lysophosphatidylcholines, phosphatidylcholines and cholesterol esters and an increase in phosphatidylethanolamines were observed in NASH patients. Remarkably, LipidMS allowed the identification of a new set of lipids that may be used for NASH diagnosis. Altogether, LipidMS has been validated as a tool to assist lipid identification in the LC-DIA-MS untargeted analysis of complex biological samples.

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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...