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Background First-line pembrolizumab monotherapy improves overall and progression-free survival in patients with untreated metastatic non-small-cell lung cancer with a programmed death ligand 1 (PD-L1) tumour proportion score (TPS) of 50% or greater. We investigated overall survival after treatment with pembrolizumab monotherapy in patients with a PD-L1 TPS of 1% or greater. Methods This randomised, open-label, phase 3 study was done in 213 medical centres in 32 countries. Eligible patients were adults (≥18 years) with previously untreated locally advanced or metastatic non-small-cell lung cancer without a sensitising EGFR mutation or ALK translocation and with an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1, life expectancy 3 months or longer, and a PD-L1 TPS of 1% or greater. Randomisation was computer generated, accessed via an interactive voice-response and integrated web-response system, and stratified by region of enrolment (east Asia vs rest of world), ECOG performance status score (0 vs 1), histology (squamous vs non-squamous), and PD-L1 TPS (≥50% vs 1-49%). Enrolled patients were randomly assigned 1:1 in blocks of four per stratum to receive pembrolizumab 200 mg every 3 weeks for up to 35 cycles or the investigator's choice of platinum-based chemotherapy for four to six cycles. Primary endpoints were overall survival in patients with a TPS of 50% or greater, 20% or greater, and 1% or greater (one-sided significance thresholds, p=0·0122, p=0·0120, and p=0·0124, respectively) in the intention-to-treat population, assessed sequentially if the previous findings were significant. This study is registered at ClinicalTrials.gov, number NCT02220894. Findings From Dec 19, 2014, to March 6, 2017, 1274 patients (902 men, 372 women, median age 63 years [IQR 57-69]) with a PD-L1 TPS of 1% or greater were allocated to pembrolizumab (n=637) or chemotherapy (n=637) and included in the intention-to-treat population. 599 (47%) had a TPS of 50% or greater and 818 patients (64%) had a TPS of 20% or greater. As of Feb 26, 2018, median follow-up was 12·8 months. Overall survival was significantly longer in the pembrolizumab group than in the chemotherapy group in all three TPS populations (≥50% hazard ratio 0·69, 95% CI 0·56-0·85, p=0·0003; ≥20% 0·77, 0·64-0·92, p=0·0020, and ≥1% 0·81, 0·71-0·93, p=0·0018). The median surival values by TPS population were 20·0 months (95% CI 15·4-24·9) for pembrolizumab versus 12·2 months (10·4-14·2) for chemotherapy, 17·7 months (15·3-22·1) versus 13·0 months (11·6-15·3), and 16·7 months (13·9-19·7) versus 12·1 months (11·3-13·3), respectively. Treatment-related adverse events of grade 3 or worse occurred in 113 (18%) of 636 treated patients in the pembrolizumab group and in 252 (41%) of 615 in the chemotherapy group and led to death in 13 (2%) and 14 (2%) patients, respectively. Interpretation The benefit-to-risk profile suggests that pembrolizumab monotherapy can be extended as first-line therapy to patients with locally advanced or metastatic non-small-cell lung cancer without sensitising EGFR or ALK alterations and with low PD-L1 TPS. Funding Merck Sharp & Dohme.

Objective: Evaluate impact after 223 Ra therapy and 18 F-NaF (sodium fluoride) PET/CT in the selection and evaluation of response in patients treated with 223 Ra in six different solid tumors. Material and Methods: Twenty patients with metastatic castration-resistant prostate cancer (mCRPC), seven metastatic castration-sensitive prostate cancer (mCSPC), three osteosarcoma, two breast cancer, two non-small cell lung cancer (NSCLC), one chondrosarcoma, one chordoma and one patient lung neuroendocrine carcinoma. Three groups of study were defined according total skeletal tumor-burden obtained by 18 F-NaF PET/CT, group 1 3000cm 3 VOI´s. A semi-quantitative comparison was performed measuring the SUVmax values of VOIs values in all bone metastases in each patient previous to receive the first cycle of 223 Ra, after 3 and 6 cycles. Results: 30 patients non-progress disease was documented after 24±4 weeks. 8 patients progress disease was presented after three cycles of 223 Ra, two patients with osteosarcoma, four patients with mCRPC, one patient with chondrosarcoma and one patient with NSCLC. Group 1 patients showed better response rates compared to group 3 (p

Human copper transporter 1 (hCtr1) is the main transporter of copper which has been involved as an essential cofactor in biological processes and mechanisms of action for cisplatin and its analogues. Although expression of hCtr1 is present in all tissues that require copper, several studies have showed that levels of expression are highly variable between normal and neoplastic tissues. We evaluated the potential diagnostic of the

Bipartite graphs visualization shows different characteristics to general graphs visualization. The data model structure associated with bipartite graphs suggests a spatial distribution consists of two groups of elements separated physically but linked by relations. This article presents a quick review of some of the most common methods of bipartite graphs visualization and shows some simple alternatives to implement these methods. In addition, a new method for bipartite graphs visualization, called Sierra, is proposed. This method allows a quick and simple determination of the degree (number of links) of each node in the graph. Also, the method facilitates the identification of grouping between elements as the relationships that could exist between independent groups.