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. A total of 43 ROS1 FISH-positive and 193 ROS1 FISH-negative NSCLC samples were studied. All specimens were screened by using two antibodies (clone D4D6 from Cell Signaling Technology and clone SP384 from Ventana Medical Systems), and the different interpretation criteria were compared with break-apart FISH (Vysis). FISH-positive samples were also analyzed with next-generation sequencing (Oncomine Dx Target Test Panel, Thermo Fisher Scientific). An H-score of 150 or higher or the presence of at least 70% of tumor cells with an intensity of staining of 2+ or higher by the SP384 clone was the optimal cutoff value (both with 93% sensitivity and 100% specificity). The D4D6 clone showed similar results, with an H-score of at least 100 (91% sensitivity and 100% specificity). ROS1 expression in normal lung was more frequent with use of the SP384 clone (p < 0.0001). The ezrin gene (EZR)-ROS1 variant was associated with membranous staining and an isolated green signal FISH pattern (p = 0.001 and p = 0.017, respectively). The new SP384 ROS1 IHC clone showed excellent sensitivity without compromising specificity, so it is another excellent analytical option for the proposed testing algorithm.

Background: Recently, immunotherapy has changed the standard of treatment in non-small cell lung cancer (NSCLC). Outside clinical trials, data of real life is lacking. This is an observational study that represents the real world experience with nivolumab in pretreated NSCLC. Methods: Eligibility criteria included, histologically confirmed NSCLC, stage IIIB and IV, evaluable disease and at least one prior therapy. Patients received nivolumab until progressive disease (PD) or unacceptable toxicity. The main aim of the study was to report the efficacy and safety profile of Nivolumab in pretreated patients with advanced NSCLC of our everyday clinical practice. The secondary aim was to perform subgroup analysis by clinical features. Results: From August of 2015 to January of 2017, 188 patients were enrolled. The patients demographics were: median age 58 years, 144 male; 17 never smoker and 171 former/current smoker; 112 adenocarcinoma, 66 squamous-cell carcinoma and 10 not otherwise specified (NOS); 61 stage IIIB and 127 stage IV; 15 performance status (PS) 0, 154 PS 1 and 19 PS 2; 5 epidermal growth factor receptor (EGFR) and 1 anaplastic lymphoma kinase (ALK); 42 with central nervous system (CNS) metastases; and 71 received 2 or more prior therapy lines. Of the 188 patients enrolled, 25 (13.3%) were not evaluated, 3 (1.6%) had complete response (CR), 45 (23.9%) partial response (PR), 48 (25.5%) disease stabilization (DS) and 67 (35.6%) PD. The median of progression-free survival (PFS) was 4.83 months (95% CI, 3.6–5.9) and overall survival (OS) was 12.85 months (95% CI, 9.07–16.62). The subgroup analysis revealed statistical significance in OS for patients with CNS metastases 14.8 months (95% CI, 11.5–17.3) vs. 5.09 months (95% CI, 0.3–9.8) and also PS 0 [not reached (NR)] vs. PS 1 11.7 months vs. PS 2 3.4 months (95% CI, 2.3–4.4). The safety profile was in accordance with the literature data. Conclusions: This study represents the real word experience with nivolumab and the results are consistent with previously reported in clinical trials. PS 2 and the presence of CNS metastases are associated with poor prognosis.

To analyze GDF15 and MMP7 serum levels as diagnostic biomarkers in gastric cancer (GC) patients. The prognostic value of GDF15 and MMP7 serum levels in combination with miR-200c blood expression was also analyzed. Fifty-two GC and 23 control samples were included. GDF15 and MMP7 proved to be powerful tools for GC diagnosis. Increased levels of GDF15 and MMP7 were associated with shorter progression-free survival and overall survival in univariate analysis. In multivariate analysis, the combination of high levels of GDF15, MMP7 and miR-200c was an independent predictor for death (p = 0.033). GDF15 and MMP7 serum levels have diagnostic value for GC. The combination marker formed by GDF15, MMP7 and miR-200c is indicative of adverse evolution in GC patients.

The lung immune prognostic index (LIPI) has been proposed as a new categorical blood-based biomarker to select advanced non-small cell lung cancer (NSCLC) patients for anti-programmed cell death-1 (PD-1) or programmed death ligand 1 (PD-L1) therapy. In this study, we investigate for the first time to the best of our knowledge the prognostic and predictive utility of the LIPI in a multicenter nivolumab monotherapy-based cohort. We retrospectively analyzed the influence of the baseline LIPI on overall survival (OS), progression-free survival (PFS), disease control rate (DCR), and overall response rate (ORR) among 153 patients of a cohort of 188 advanced NSCLC patients treated with nivolumab in the second line of therapy or beyond. Worse LIPI was significantly associated with shorter OS in univariate [hazard ratio (HR) =3.12, 95% confidence interval (CI), 2.12–4.60; P<0.0001] and multivariate (HR =3.67, 95% CI, 1.96–6.86; P<0.0001) analyses. Worse LIPI was associated with shorter PFS (HR =1.45, 95% CI, 1.05–2.03; P=0.03), but this correlation did not reach statistical significance in multivariate analysis (HR =1.49, 95% CI, 0.94–2.38; P=0.09). Worse LIPI was associated with lower DCR in univariate [odds ratio (OR) =0.41, 95% CI, 0.24–0.70; P=0.001] and multivariate (OR =0.44, 95% CI, 0.25–0.78; P=0.005) analyses. This study confirms the utility of the LIPI in prognostication and disease control prediction in advanced NSCLC patients treated with nivolumab in the second line of therapy or beyond.