Serum proteomic test in advanced non-squamous non-small cell lung cancer treated in first line with standard chemotherapy

Background:VeriStrat is a blood-based proteomic test with predictive and prognostic significance in second-line treatments for non-small cell lung cancer (NSCLC). This trial was designed to investigate the role of VeriStrat in first-line treatment of advanced NSCLC with standard chemotherapy. Here we present the results for 76 non-squamous patients treated with a combination of carboplatin or cisplatin with pemetrexed.Methods:The test-assigned classifications of VeriStrat Good or VeriStrat Poor to samples collected at baseline. The primary end point was progression-free survival (PFS); secondary end points included overall survival (OS) and objective response. Exploratory analyses of end points separately in carboplatin/pemetrexed and cisplatin/pemetrexed subgroups were also conducted.Results:Patients classified as VeriStrat Good had longer PFS and OS than VeriStrat Poor: 6.5 vs 1.6 months and 10.8 vs 3.4 months, respectively; the corresponding hazard ratios (HRs) were 0.36 (P<0.0001) and 0.26 (P<0.0001); they were also more likely to achieve objective response. Prognostic significance of VeriStrat was confirmed in multivariate analysis. Significant differences in OS and PFS between Veristrat classifications were also found when treatment subgroups were analysed separately.Conclusions:The trial demonstrated clinical utility of VeriStrat as a prognostic test for standard first-line chemotherapy of non-squamous advanced NSCLC

Circulating cell-free DNA and circulating tumor cells as prognostic and predictive biomarkers in advanced non-small cell lung cancer patients treated with first-line chemotherapy

Cell-free DNA (cfDNA) and circulating tumor cells (CTCs) are promising prognostic and predictive biomarkers in non-small cell lung cancer (NSCLC). In this study, we examined the prognostic role of cfDNA and CTCs, in separate and joint analyses, in NSCLC patients receiving first line chemotherapy. Seventy-three patients with advanced NSCLC were enrolled in this study. CfDNA and CTC were analyzed at baseline and after two cycles of chemotherapy. Plasma cfDNA quantification was performed by quantitative PCR (qPCR) whereas CTCs were isolated by the ScreenCell Cyto (ScreenCell, Paris, France) device and enumerated according to malignant features. Patients with baseline cfDNA higher than the median value (96.3 hTERT copy number) had a significantly worse overall survival (OS) and double the risk of death (hazard ratio (HR): 2.14; 95% confidence limits (CL) = 1.24\u20133.68; p-value = 0.006). Conversely, an inverse relationship between CTC median baseline number (6 CTC/3 mL of blood) and OS was observed. In addition, we found that in patients reporting stable disease (SD), the baseline cfDNA and CTCs were able to discriminate patients at high risk of poor survival. cfDNA demonstrated a more reliable biomarker than CTCs in the overall population. In the subgroup of SD patients, both biomarkers identified patients at high risk of poor prognosis who might deserve additional/alternative therapeutic interventions

lung cancer predisposition in women with previous breast cancer identified by whole exome sequencing

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Pooled Analysis of Clinical Outcome of Patients with Chemorefractory Metastatic Colorectal Cancer Treated within Phase I/II Clinical Studies Based on Individual Biomarkers of Susceptibility : a Single-Institution Experience

BACKGROUND: Patients with metastatic colorectal cancer (mCRC) refractory to standard therapies have a poor prognosis. In this setting, recruitment into clinical trials is warranted, and studies driven by selection according to individual tumor molecular characteristics are expected to provide added value. OBJECTIVE: We retrospectively analyzed data from patients with mCRC refractory to or following failure of standard therapies who were enrolled into phase I/II clinical studies at the Niguarda Cancer Center based on the presence of a specific molecular profile expected to represent the target of susceptibility to the experimental drug(s). PATIENTS AND METHODS: From June 2011 to May 2016, 2044 patients with mCRC underwent molecular screening. Eighty patients (3.9%) were enrolled in ad hoc studies; the median age was 60 years (range 36-86) and the median number of previous treatment lines was five (range 2-8). Molecular characteristics exploited within these studies were MGMT promoter hypermethylation (48.7%), HER2 amplification (28.8%), BRAF V600E mutation (20%), and novel gene fusions involving ALK or NTRK (2.5%). RESULTS: One patient (1%) had RECIST (Response Evaluation Criteria In Solid Tumors) complete response (CR), 13 patients (16.5%) experienced a partial response (PR), and 28 (35%) stable disease (SD). Median progression-free survival (PFS) was 2.8 months (range 2.63-3.83), with 24% of patients displaying PFS >5 months. Median growth modulation index (GMI) was 0.85 (range 0-15.61) and 32.5% of patients had GMI >1.33. KRAS exon 2 mutations were found in 38.5% of patients, and among the 78 patients with known KRAS status, those with wild-type tumors had longer PFS than those with mutated tumors (3.80 [95% CI 2.80-5.03] vs. 2.13 months [95% CI 1.77-2.87], respectively, p = 0.001). Median overall survival (OS) was 7.83 months (range 7.17-9.33) for all patients, and patients with KRAS wild-type tumors had longer OS than those with mutated tumors (7.83 [95% CI 7.33-10.80] vs. 7.18 months [95% CI 5.63-9.33], respectively, p = 0.06). CONCLUSIONS: This single-institution retrospective study indicates that in a heavily pretreated population approximately 4% of mCRC tumors display a potential actionable molecular context suitable for therapeutic intervention. Application of molecular selection is challenging but improves clinical outcome even in later lines of treatment

Polymer/rock interactions in polymer treatments for water-cut control

In this paper we study the adsorption of polymers bearing differently charged groups onto solid surfaces of siliceous nature. By means of static adsorption tests we show that the adsorption is dominated by the electrostatic interactions between the polymer molecules and the solid surface. We also show that both lithology and brine composition can strongly influence the adsorption behavior; such effects must be therefore carefully assessed before applying these treatments in the field

Superconducting parameters of lead in Al/Formvar/Pb tunnel junctions

The functions Δ(ω), α2(ω) F(ω) and Z(ω) and the parameters λ, , μ* of Pb are calculated by analysing the tunnel characteristics of Al/Formvar/Pb junctions. The results, in comparison with those obtained on Al/AlxOy/Pb tunnel junctions, seem to exclude the direct influence of the Formvar on the electron-phonon interaction function via the transfer of vibrational structures in the explored energy range. All the observed modifications (the lowering of the amplitude of the phononic peaks of the Pb and the variation of their ratio, the reduction of λ, the negative value of μ*) are connected with the particular structure of the insulator-superconductor interface. This interpretation is supported by the data of the ESCA analysis of the tunnel structure.Les fonctions Δ(ω), α2(ω) F(ω), Z(ω), et les paramètres λ, , μ* du Pb ont été évalués à partir de l'analyse directe des caractéristiques tunnel de jonctions Al/Formvar/Pb. Les résultats, comparés avec ceux obtenus dans le cas de jonctions tunnel Al/Alx,O y/Pb, semblent exclure une influence directe du Formvar sur la fonction interaction electron-phonon, dans l'intervalle d'énergie exploré, via un transfert de ses fréquences propres vibrationnelles sur l'électrode supraconductrice. Toutes les modifications observées (diminution de l'amplitude des pics dans la densité d'états des phonons du Pb et modification du rapport relatif, diminution du λ et le signe négatif de μ*) sont corrélées à la structure particulière de l'interface isolantsupraconducteur. Cette interprétation est confirmée par l'analyse ESCA de la jonction

Polymer adsorption at the brine/rock interface : the role of electrostatic interactions and wettability

Injection of polymers that selectively reduce the water permeability can be used to control water production from oil or gas wells. Because this method relies on the adsorption of a polymer layer onto the rock surface, a deeper understanding of the relevant polymer/rock interactions is of primary importance in order to develop reliable chemical selection rules for field applications. In this paper we study the role of electrostatic interactions and wettability in the adsorption of water-soluble polymers (bearing differently charged groups) onto solid surfaces of siliceous nature. By means of static adsorption tests, we show that the adsorption is dominated by the electrostatic interactions between the polymer molecules and the solid surface. We also show that lithology, brine composition and wettability are critical parameters that can influence the adsorption behavior at a brine/rock interface

Pore-scale mechanism for selective permeability reduction by polymer injection

In this paper we discuss a pore-scale picture of the mechanism underlying the selective permeability reduction caused by the adsorption of a polymer layer in a water wet porous medium. Our analysis is based on the use of physically representative model of the porous medium, which allows us to estimate directly the expected permeability reduction. Comparison of model predictions with coreflood experimental data has revealed that the selectivity in permeability reduction cannot be explained if the polymer layer is modeled as a rigid, impenetrable layer. This result is consistent with the suggestion that swelling-shrinking phenomena of the adsorbed polymer later is responsible for the selectivity in the permeability modification induced by these treatments