Multivariate tools to investigate the spatial contaminant distribution in a highly anthropized area (Gulf of Naples, Italy)

The Gulf of Naples located in a high anthropized coastal area is subjected to an infrastructural intervention for the installation of a submarine power pipeline. In order to evaluate the distribution of contaminants in the seafloor sediments, a preliminary study has been conducted in the area using multivariate techniques. The statistic approach was performed to gain insights on the occurrence of organic and inorganic contaminants within the area, aiming to identify the relevant hot spots. Three geographical sub-areas influenced by different contaminant association were recognized: Torre Annunziata (TA), Capri (CA), and middle offshore (MO). TA and CA resulted marked by a severe contamination pattern due to anthropogenic pressures. In addition, the influence of the depositional basin in governing the contamination trend has been pointed out. The supervised technique PLS_DA resulted to be a powerful tool in addressing the complexity of the huge dataset acquired during the marine survey, highlighting the main trends in the variability of quality indicators, orienting thus the deeper investigations during follow-up monitoring activities

Standardized Index of Shape (DCE-MRI) and Standardized Uptake Value (PET/CT): Two quantitative approaches to discriminate chemo-radiotherapy locally advanced rectal cancer responders under a functional profile.

PURPOSE: To investigate dynamic contrast enhanced-MRI (DCE-MRI) in the preoperative chemo-radiotherapy (CRT) assessment for locally advanced rectal cancer (LARC) compared to18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT). METHODS: 75 consecutive patients with LARC were enrolled in a prospective study. DCE-MRI analysis was performed measuring SIS: linear combination of percentage change (Δ) of maximum signal difference (MSD) and wash-out slope (WOS). 18F-FDG PET/CT analysis was performed using SUV maximum (SUVmax). Tumor regression grade (TRG) were estimated after surgery. Non-parametric tests, receiver operating characteristic were evaluated. RESULTS: 55 patients (TRG1-2) were classified as responders while 20 subjects as non responders. ΔSIS reached sensitivity of 93%, specificity of 80% and accuracy of 89% (cut-off 6%) to differentiate responders by non responders, sensitivity of 93%, specificity of 69% and accuracy of 79% (cut-off 30%) to identify pathological complete response (pCR). Therapy assessment via ΔSUVmax reached sensitivity of 67%, specificity of 75% and accuracy of 70% (cut-off 60%) to differentiate responders by non responders and sensitivity of 80%, specificity of 31% and accuracy of 51% (cut-off 44%) to identify pCR. CONCLUSIONS: CRT response assessment by DCE-MRI analysis shows a higher predictive ability than 18F-FDG PET/CT in LARC patients allowing to better discriminate significant and pCR

18F-FDG PET/CT Is an Early Predictor of Pathologic Tumor Response and Survival to Preoperative Radiochemotherapy with Bevacizumab in High Risk Locally Advanced Rectal Cancer.

There is an unmet need for predictive biomarkers of the clinical benefit of anti-angiogenic drugs.The aim of the present study was to prospectively evaluate the value of FDG-PET/CT performed during and after preoperative radiochemotherapy (CRT) with bevacizumab for the prediction of complete pathologic tumor regression and survival in magnetic resonance imaging (MRI)-defined high-risk locally advanced rectal cancer (LARC) patients Methods: Sixty-one patients treated in a non-randomized phase II study (BRANCH) with concomitant or sequential (4 days before CRT) administration of bevacizumab with preoperative CRT were included. 18F-FDG PET/CT was performed at baseline, 11 days after the beginning of the CRT (early) and before surgery (late). Metabolic changes were compared with pathological complete (TRG1) vs incomplete (TRG2-5) tumor regression, progression-free survival (PFS), cancer specific survival (CSS) and overall survival (OS). Receiver operating characteristic (ROC) curves were calculated for those FDG-PET/CT parameters that significantly correlated with TRG1. Results: Early total lesion glycolysis (TLG-early) and its percent change compared to baseline (ΔTLG-early %) could discriminate TRG1 from TRG2-5. Only ROC analysis of ΔTLG-early % showed an AUC > 0.7 (0.76), with an optimal cutoff at 59.5% (80% sensitivity, 71.4 specificity) for identifying TRG1. Late metabolic assessment could not discriminate between the two groups. After a median follow-up of 98 months (range 77-132) metabolic responders (ΔTLG-early % ≥ 59.5 %) demonstrated a significantly higher 10-year PFS (89.3 vs 63.6 %, P = 0.02) and CSS (92.9 vs 72.6 %, P = 0.04) compared to incomplete metabolic responders . Conclusion: Our results suggest that early metabolic response can act as a surrogate marker of the benefit of antiangiogenic therapy and provide further support for the use of early -FDG-PET/CT evaluation to predict pathological response and survival in the preoperative treatment of patients with LARC. ΔTLG-early% showed the best accuracy in predicting TRG and may be particularly useful in guiding treatment modifying decisions during preoperative CRT based on expected response

A randomized phase 3 study on the optimization of the combination of bevacizumab with FOLFOX/OXXEL in the treatment of patients with metastatic colorectal cancer-OBELICS (Optimization of BEvacizumab scheduLIng within Chemotherapy Scheme).

BACKGROUND: Despite the improvements in diagnosis and treatment, colorectal cancer (CRC) is the second cause of cancer deaths in both sexes. Therefore, research in this field remains of great interest. The approval of bevacizumab, a humanized anti-vascular endothelial growth factor (VEGF) monoclonal antibody, in combination with a fluoropyrimidine-based chemotherapy in the treatment of metastatic CRC has changed the oncology practice in this disease. However, the efficacy of bevacizumab-based treatment, has thus far been rather modest. Efforts are ongoing to understand the better way to combine bevacizumab and chemotherapy, and to identify valid predictive biomarkers of benefit to avoid unnecessary and costly therapy to nonresponder patients. The BRANCH study in high-risk locally advanced rectal cancer patients showed that varying bevacizumab schedule may impact on the feasibility and efficacy of chemo-radiotherapy. METHODS/DESIGN: OBELICS is a multicentre, open-label, randomised phase 3 trial comparing in mCRC patients two treatment arms (1:1): standard concomitant administration of bevacizumab with chemotherapy (mFOLFOX/OXXEL regimen) vs experimental sequential bevacizumab given 4 days before chemotherapy, as first or second treatment line. Primary end point is the objective response rate (ORR) measured according to RECIST criteria. A sample size of 230 patients was calculated allowing reliable assessment in all plausible first-second line case-mix conditions, with a 80% statistical power and 2-sided alpha error of 0.05. Secondary endpoints are progression free-survival (PFS), overall survival (OS), toxicity and quality of life. The evaluation of the potential predictive role of several circulating biomarkers (circulating endothelial cells and progenitors, VEGF and VEGF-R SNPs, cytokines, microRNAs, free circulating DNA) as well as the value of the early [(18)F]-Fluorodeoxyglucose positron emission tomography (FDG-PET) response, are the objectives of the traslational project. DISCUSSION: Overall this study could optimize bevacizumab scheduling in combination with chemotherapy in mCRC patients. Moreover, correlative studies could improve the knowledge of the mechanisms by which bevacizumab enhance chemotherapy effect and could identify early predictors of response. EudraCT Number: 2011-004997-27 TRIAL REGISTRATION: ClinicalTrials.gove number, NCT01718873

Phase 1/2 study of valproic acid and short-course radiotherapy plus capecitabine as preoperative treatment in low-moderate risk rectal cancer-V-shoRT-R3 (Valproic acid--short Radiotherapy--rectum 3rd trial).

BACKGROUND: Locally advanced rectal cancer (LARC) is a heterogeneous group of tumors where a risk-adapted therapeutic strategy is needed. Short-course radiotherapy (SCRT) is a more convenient option for LARC patients than preoperative long-course RT plus capecitabine. Histone-deacetylase inhibitors (HDACi) have shown activity in combination with RT and chemotherapy in the treatment of solid tumors. Valproic acid (VPA) is an anti-epileptic drug with HDACi and anticancer activity. In preclinical studies, our group showed that the addition of HDACi, including VPA, to capecitabine produces synergistic antitumour effects by up-regulating thymidine phosphorylase (TP), the key enzyme converting capecitabine to 5-FU, and by downregulating thymidylate synthase (TS), the 5-FU target. METHODS/DESIGN: Two parallel phase-1 studies will assess the safety of preoperative SCRT (5 fractions each of 5 Gy, on days 1 to 5) combined with (a) capecitabine alone (increasing dose levels: 500-825 mg/m2/bid), on days 1-21, or (b) capecitabine as above plus VPA (oral daily day -14 to 21, with an intra-patient titration for a target serum level of 50-100 microg/ml) followed by surgery 8 weeks after the end of SCRT, in low-moderate risk RC patients. Also, a randomized phase-2 study will be performed to explore whether the addition of VPA and/or capecitabine to preoperative SCRT might increase pathologic complete tumor regression (TRG1) rate. A sample size of 86 patients (21-22/arm) was calculated under the hypothesis that the addition of capecitabine or VPA to SCRT can improve the TRG1 rate from 5% to 20%, with one-sided alpha = 0.10 and 80% power.Several biomarkers will be evaluated comparing normal mucosa with tumor (TP, TS, VEGF, RAD51, XRCC1, Histones/proteins acetylation, HDAC isoforms) and on blood samples (polymorphisms of DPD, TS, XRCC1, GSTP1, RAD51 and XRCC3, circulating endothelial and progenitors cells; PBMCs-Histones/proteins acetylation). Tumor metabolism will be measured by 18FDG-PET at baseline and 15 days after the beginning of SCRT. DISCUSSION: This project aims to improve the efficacy of preoperative treatment of LARC and to decrease the inconvenience and the cost of standard long-course RT. Correlative studies could identify both prognostic and predictive biomarkers and could add new insight in the mechanism of interaction between VPA, capecitabine and RT.EudraCT Number: 2012-002831-28. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT01898104

Virgo gravitational wave detector: Results and perspectives

The Virgo detector reached during the past science run a sensitivity very close to the design one. During the last year the detector has been improved by suspending the main interferometer mirrors with monolithic fibers, with the goal of reducing the thermal noise contribution and testing the new technology. At the same time the design of the next detector improvements are on-going and they will be implemented during the construction of Advanced Virgo

Calibration of the LIGO gravitational wave detectors in the fifth science run

The Laser Interferometer Gravitational Wave Observatory (LIGO) is a network of three detectors built to detect local perturbations in the space–time metric from astrophysical sources. These detectors, two in Hanford, WA and one in Livingston, LA, are power-recycled Fabry-Perot Michelson interferometers. In their fifth science run (S5), between November 2005 and October 2007, these detectors accumulated one year of triple coincident data while operating at their designed sensitivity. In this paper, we describe the calibration of the instruments in the S5 data set, including measurement techniques and uncertainty estimation.United States. National Aeronautics and Space AdministrationCarnegie TrustLeverhulme TrustDavid & Lucile Packard FoundationResearch CorporationAlfred P. Sloan Foundatio