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Differences in gene expression levels between the primary tumors (PTs) and matched regional lymph nodal metastases (LNs) in patients with totally excised non-small cell lung cancer (NSCLC) were explored. Microdissected formalin-fixed paraffin-embedded (FFPE) samples from (PT) and their matched infiltrated LNs, from 239 patients [183 (with matched PT and LNs samples)-case and 56 PT only samples-control cohorts] were analyzed for BRCA1, ERCC1, RAP80, PKM2, RRM1, RRM2, TS, TSP1, and TXR1 mRNA expression by quantitative real-time polymerase-chain reaction (PCR). Moderately positive correlation between the expression of each gene in the PT and the matched LNs was observed. Concordance rates between the PT and the LNs were: BRCA1 (67.7%), ERCC1 (68.4%), PKM2 (63.4%), RAP80 (68.8%), RRM1 (70.9%), RRM2 (69%), TS (72.9%), TSP1 (69.8%), TXR1 (63.7%). Expression levels and their differences were correlated with Relapse-Free Survival (RFS) and Overall Survival (OS). High BRCA1 PT in patients with squamous histology was associated with increased OS (p = 0.036). High TSP1 PT levels were shown to be the only independent prognostic factor for OS and RFS (p = 0.023 and p = 0.007). PKM2 low levels in both PT and matched LNs were associated with better OS irrespective of the underlying histology (p = 0.031). RRM1 discordant levels between PT and matched LNs were associated with worse OS in squamous tumors (p = 0.019) compared to patients with both low expression in PT and LN.TXR1 high levels in both PT and matched LNs were associated with better OS in patients with squamous tumors (p = 0.007).These findings indicate that there is different gene expression between PT and matched LNs which may affect the outcome in early NSCLC and therefore PT’s molecular biology should not be the sole determinant for prognostication.

Radiotracer imaging studies for a small field, high resolution ∞-Camera system and a clinical system for Positron Emission Tomography (PET) by means of GATE (GEANT4 Application for Tomographic Emission) simulations are presented in this work. In a validation phase, which preceded the main study, experimentally obtained results for planar images with the existing ∞-Camera system were directly compared to simulated data. A simple phantom structure, consisting of four parallel capillaries filled with 99mTc water solution, was imaged by the γ-Camera system for several phantom-collimator distances and the measured and Monte-Carlo calculated spatial projections were compared. The major objective of this validation study was the optimal description of the most important components, the hexagonal, parallel-hole Pb-collimator and the pixelated CsI scintillation crystal of the γ-imaging system in terms of GATE components. In the main study, a GATE simulation setup for this ∞-Camera detector is used and Monte-Carlo data are accumulated for simple geometrical phantoms with different monophotonic radiotracer energies and relative intensities. In parallel, a commercially available cylindrical shaped PET scanner ring, consisting of 32 sectors with 4 x 6 x 6 LSO scintillation crystals, has been constructed in the GATE environment. Simulation data are obtained for the most usual positron emitters (18F, 11C and 15O) and for several phantom geometries. The spatial resolution of both systems and their overall performance is presented and discussed in this study.

Background PRMT5 is an enzyme that methylates arginines in proteins important for tumor growth and development. GSK3326595 is a potent and selective PRMT5 inhibitor that demonstrates efficacy in multiple tumor models. METEOR-1 is a phase I study to assess the safety, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy of GSK3326595 in adults with solid tumors. Methods Eligible participants (pts) were >18 years with advanced or metastatic solid tumors. Pts were enrolled in a modified toxicity probability interval design. Safety, tolerability, PK, PD, and efficacy data were used to identify the recommended phase 2 dose (RP2D). Results Fifty-four pts with a median age of 60 (range 21 – 81) received at least one dose of drug. The most common tumor types were adenoid cystic carcinoma (ACC; n = 14 [26%]), colorectal cancer (n = 9 [17%]), and breast cancer (n = 3 [6%]). Dosing proceeded from 12.5 mg to 600 mg once daily (QD), and from 50 mg to 200 mg twice daily. Median time on treatment was 1.8 months (range 1 day to 18.7 months). Overall, 48 pts (89%) experienced at least one adverse event (AE) that was deemed treatment-related. The most common related AEs were fatigue (n = 21 [39%]), anemia (n = 17 [31%]), nausea (n = 17 [31%]), alopecia (n = 15 [28%]), and dysgeusia (n = 14 [26%]). Grade 3/4 related AEs included anemia (n = 8 [15%]), thrombocytopenia, neutropenia, and fatigue (each n = 4 [7%]). There were no Grade 5 related AEs. Twenty-two pts (41%) had ≥1 dose reduction. GSK3326595 Cmax and AUC were dose-dependent after single and repeat dosing. PD analyses showed robust target engagement, as measured by dimethylated arginine in plasma and tumor samples. Clinical activity was observed in several tumor types, with partial responses in patients with HPV+ cervical cancer (1 response/1 subject) and ACC (3 responses/14 subjects). Durable stable disease was achieved in bladder cancer and other tumors. 400 mg QD was selected as the RP2D. Conclusions This is the first study evaluating a PRMT5 inhibitor. Overall, AEs were common but manageable. Patients with multiple tumor types responded to therapy. Part 2 of the study is open for subjects with predefined solid tumors and non-Hodgkin’s lymphoma. Clinical trial identification NCT02783300. Legal entity responsible for the study GlaxoSmithKline. Funding GlaxoSmithKline. Disclosure L.L. Siu: Advisory / Consultancy: Merck (compensated), Pfizer (compensated), Celgene (compensated), AstraZeneca/Medimmune (compensated), Morphosys (compensated), Roche (compensated), GeneSeeq (compensated), Loxo (compensated), Oncorus (compensated), Symphogen (compensated), Seattle Geneti; Research grant / Funding (institution): Novartis, Bristol-Myers Squibb, Pfizer, Boerhinger-Ingelheim, GlaxoSmithKline, Roche/Genentech, Karyopharm, AstraZeneca/Medimmune, Merck, Celgene, Astellas, Bayer, Abbvie, Amgen, Symphogen, Intensity Therapeutics, Mirati, Shattucks; Shareholder / Stockholder / Stock options, Spouse: agios. D.W. Rasco: Research grant / Funding (institution): gsk. S. Postel Vinay: Research grant / Funding (institution): Boehringer Ingelheim, Roche and Merck KGaA; Advisory / Consultancy: Merck KGaA; Travel / Accommodation / Expenses: AstraZeneca; Leadership role, Principal/sub-investigator of clinical trials: Aduro Biotech, Agios Pharmaceuticals, Amgen, Argen-X Bvba, Arno Therapeutics, Astex Pharmaceuticals, AstraZeneca, Aveo, Bayer Healthcare Ag, Bbb Technologies Bv, Beigene, Bioalliance Pharma, Biontech Ag, Blueprint Medicines, Boehringer Ingelheim, Bristol. P. Martin Romano: Research grant / Funding (institution): AstraZeneca, BMS, Boehringer Ingelheim, Janssen Cilag, Merck, Novartis, Pfizer, Roche, Sanofi; Non-remunerated activity/ies, Drug supplied: AstraZeneca, Bayer, BMS, Boringher Ingelheim, Johnson & Johnson, Lilly, Medimmune, Merck, NH TherAGuiX, Pfizer, Roche; Non-remunerated activity/ies, Courses, trainings for: AstraZeneca, Roche. J.L. Egger: Shareholder / Stockholder / Stock options, Full / Part-time employment: GlaxoSmithKline. S.A. Gorman: Shareholder / Stockholder / Stock options, Full / Part-time employment: GlaxoSmithKline. R. Parasrampuria: Full / Part-time employment: GlaxoSmithKline. K. Wang: Shareholder / Stockholder / Stock options, Full / Part-time employment: GlaxoSmithKline. B.E. Kremer: Shareholder / Stockholder / Stock options, Full / Part-time employment: GlaxoSmithKline. M.M. Gounder: Research grant / Funding (institution): GlaxoSmithKline; Honoraria (self): Epizyme, Tracon, Amgen, Daiichi Sankyo, Springwork Therapeutics, Bayer, Karyopharm. All other authors have declared no conflicts of interest.

The Single Photon Emission Computed Tomography (SPECT) using simple γ - radiotracers has been established as a standard technique in the physiological and functional nuclear imaging. On the other hand, accurate reconstruction of abnormalities inside biological tissues based on the detected temperature distribution obtained at the surface of the skin presents a major challenge in emission thermography. The present work focuses on the experimental study with these modalities using appropriately constructed 99 Tc and thermal phantoms. Special emphasis was given to the relationship between the physical characteristics, such as the location and the emission power of an embedded heat source inside an absorbing medium and the measured temperature distribution by means of infrared imaging. Those thermal phantoms were studied at temperature 35 0 − 40 0 C, which corresponds to mammal’s core temperature. The obtained planar information was further analyzed to reconstruct the tomographic images, and from them, the final 3D image of the phantoms. The reconstruction procedure was performed with iterative algorithms based on MLEM and accelerated ART techniques. In order to investigate scattering and absorption effects, the same reconstruction procedure has been applied to optical (fluorescence) tomography with appropriately constructed phantoms. Recon- structions results are presented in this study for different phantom depth locations and heat generation rates.

Cancer patients receiving chemotherapy are at increased risk of venous thromboembolism (VTE). The presence of cancer and anticoagulant use are risk factors for bleeding, yet data on bleeding risk are limited in these patients. This analysis evaluated the risk of major bleeding in cancer patients receiving chemotherapy using a US claims database. This retrospective cohort study used the MarketScan® databases, a nationwide database containing data from about 100 payers and covering > 30 million patients annually. Adult cancer patients receiving chemotherapy within 6 months of cancer diagnosis between January 2004 and December 2010 were included. Cancers of interest were: lung, colon/rectum, pancreas, bladder, stomach, and ovary. The index date was the first date of chemotherapy. Patients were followed until the earliest of: 1) first diagnosis of major bleeding; 2) termination of enrolment in the health plan; 3) end of study. The primary outcome was the first occurrence of major bleeding, based on selected ICD-9-CM/CPT codes, following chemotherapy initiation. Of 74,575 patients identified, exclusion of those with prior history of bleeding at baseline (∼5%) resulted in 70,822 patients included in the analysis. Mean age was 62 years, 37% were ≥ 65 years, and 52% were male. Average time of follow up and chemotherapy were 14.3 and 8.6 months, respectively; 6% had a history of VTE within 6 months prior to the index date. Major bleeding occurred in 5.8% of patients and the incidence rate for all cancers combined was 4.9 per 100 person-year (PY) and 10.5, 9.3, 6.2, 4.3, 3.6, and 3.3/100 PY for pancreatic, stomach, lung, bladder, colon/rectum, and ovarian cancer, respectively. Approximately 14% of patients (N = 10,456) developed VTE after chemotherapy initiation (> half in the first 3 months of chemotherapy treatment). Of these, 7.8% experienced major bleeding with incidence rates ranging from 5.9-17.7/100 PY after VTE. Major bleeding incidence in cancer patients receiving chemotherapy varies by cancer type with the highest rates in patients with upper gastrointestinal cancer. Compared to the overall cohort, major bleeding risk was higher in cancer patients who developed VTE. Disclosure J.H. Zong: Employee of Sanofi. L. Eckert: Employee of Sanofi. L. Zhang: Employee of Sanofi. W.S. Dai: Employee of Sanofi. A.T. Cohen: Consult: Astellas, AZ, Bayer, BI, BMS, Daiichi, GSK, JJ ResFund: AZ, Bayer, BI, BMS, Daiichi, GSK, JJ BoardSpeakerAdvis comm: Bayer, BI, BMS, Daiichi, GSK, J&J, Mitsubishi, Pfizer, Sanofi. All other authors have declared no conflicts of interest.

Introduction Venous thromboembolism (VTE) is one of the leading cause of death for cancer pts, with an incidence of 1 event per 110-120 patients, mainly within the first year from diagnosis. Cancer pts with VTE show a 2.2-fold increase in mortality and lung cancer is the second tumor type with the highest incidence of VTE. Considering that chemotherapy is associated with a 6 times increased risk of VTE and that biological agents, especially antiangiogenetic compounds, cause an additional risk, the aim of the study is to evaluate, with a radiological retrospective evaluation, the real incidence of PE in selected cohorts of advanced NSCLC patients and the impact of PE on survival. Materials and methods This retrospective monocentric study enrolled 141 advanced NSCLC pts, diagnosed between June 2007 and June 2008 (cohort 1), and between January 2010 and December 2010 (cohort 2). Pts were mostly men, with a median age of 63 years, performance status of 0 and a prevalence of comorbidities predisposing to VTE of 42.0% and 70.0% in first and second cohort, respectively. 74.1% and 43.3% of pts received biological agents in first and second cohort; 39.5% and 21.7% antiangiogenetic agents. Results Retrospective review of 460 contrast-enhanced multidetector computed tomography studies showed a prevalence of PE of 13.6% in the first cohort and of 15.0% in the second one. Survival analysis didn't show any statistically significant differences in terms of OS and TTP in the first cohort. In the second cohort, Kaplan Meier curves showed a significantly difference in terms of TTP in favor of pts who never developed PE, p-value = 0.003. Similar results were observed considering as stratification factors the use of biological agents, p-value = 0.007, and of antiangiogenic agents, p-value = 0.010. Conclusion The higher incidence of PE in the second cohort, despite a lower exposure to biological and antiangiogenic agents, could be related to a greater thrombogenic action of these drugs, but also a higher prevalence of comorbidities predisposing to VTE. Descriptive analysis was confirmed by survival data, underlining the need of further studies to clarify the role of predisposing factors for PE. Disclosure All authors have declared no conflicts of interest.

Background Non Small Cell Lung Cancer (NSCLC) diagnosis and treatment is a highly complex process, requiring managerial skills merged with clinical knowledge and experience. Integrated Care Pathways (ICP) might be a good strategy to overview and improve patient's management. The aim of our study was to review our NSCLC patient's ICP in order to provide evidence of clinical or organizational inappropriateness. Methods We retrospectively reviewed the electronic medical records of 169 NSCLC patients who had had a first access at the Oncology Department of the University Hospital Santa Maria della Misericordia (Udine, Italy) during 2010. The ICP mapping and few quality indicators had already been settled by a previous study on the 2008 population and were integrated with new uptodate indicators selected from scientific literature and discussed at the weekly MDT. Results 146 patients were considered eligible; median age was 67 years old. Patients were mainly males (65%), had adenocarcinoma histology and advanced disease at the time of diagnosis (52.7%). Distant from benchmark were the percentage of diagnostic bronchoscopic procedures (60.7 vs 80-85%), the number of surgical candidates who underwent mediastinoscopy for positive PET for mediastinal nodes (0 vs 100%), median time from diagnosis to surgery and to chemotherapy (58.5 vs 21 and 34 vs 21 days; p Conclusion Our analysis has highlighted a good adherence to current national and intenational guidelines and scientific literature as far as medical oncology treatment and pathological diagnosis are concerned. There is still room for improvement, most of all regarding the pre-surgical procedures and timing for surgery. The ICP study has proven to be a feasible ad efficacious methodology to point out the patient's health management. Disclosure All authors have declared no conflicts of interest.

The authors have conducted a small-scale study attempting to learn the nature of some high school pupils' understanding of the mole concept.