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Small orbit oscillations of the circulating particle beams have been observed immediately following quenches in the LHC’s superconducting main dipole magnets. Magnetic fields generated during the discharge into the quench heaters were identified as the cause. Since the resulting, shielded field inside the beam screen cannot be measured in-situ, the time evolution of the field has to be reconstructed from the measured beam excursions. In this paper, the field-reconstruction method using rotation in normalized phase space and the optimized fitting algorithm are described. The resulting rise times and magnetic field levels are presented for quench events that occurred during regular operation as well as for dedicated beam experiments. Finally, different approaches to model the shielding behavior of the beam screen are discussed.

Overweight is an established risk factor of the colorectal cancer initiation and progression. Aim of this study is to investigate the prognostic role of visceral fat (VAT) in metastatic colorectal cancer (MCRC). We retrospectively analyzed 71 consecutive MCRC patients (2013-2017) at the Oncology Department of CRO Aviano (Italy). VAT area was measured as of cross-sectional area (cm2) at the L3 level divided by the square of the height (m2). A ROC analysis was performed to define a threshold capable to identify distinct prognostic categories of patients according to VAT. Subsequently, the value of VAT in predicting overall survival (OS) was evaluated with uni- and multivariate Cox regression analyses and estimated with Kaplan-Meier curves. Patients’ characteristics before first-line chemotherapy are reported in table 1. Interestingly, 40 pts (56%) had a body mass index (BMI)>25 and 42 (59%) had median VAT of 51.94. LDH level>=480 UI/L was recorded in 12 patients (27%) reflecting the inflammatory response. The optimal cut-off value for VAT was 44. Median OS was 30.97 months. At univariate analysis, older age (HR 2.46, p=0.013), primary tumor resection (HR 0.40, p=0.029), VAT>=44 (HR 2.85, p=0.011) and metastasectomy (HR 0.22, p=0.005), were significantly associated with OS (Table 2 and Figure1). By multivariate analysis, only VAT>=44 (HR2.64; p=0.030) was significantly associated with OS (Table 2). This exploratory study supported the prognostic role of VAT evaluation in patients with MCRC. In particular, high VAT was predictor of worse outcome. Further investigations are needed to confirm these preliminary data.

Cancer patients (CP) typically experiment cachexia and malnutrition due to cancer type and systemic inflammation, that may cause greater treatment toxicities, impacting on prognosis, response to treatment, hospitalization and quality of life. We retrospectively analyzed consecutive data of 190 CP treated from February 2017 to July 2018 at the Anesthesia and Intensive Care Unit of National Cancer Institute, Aviano. At nutritional assessment we evaluated the rate of weight loss (WL) compared to self-reported usual weight (UW) and at 6 and 1 months before the visit, performed by an expert physician and a certified dietitian. We explored the association of WL≥10% with inflammation biomarkers, total protein, albumin, diagnosis and nutritional intervention through chi-squared or Kruskal-Wallis test, as statistically appropriate (Tab.2). Patients’ characteristics were summarized through descriptive analysis (Tab.1). Noteworthy 48% of CP was ≥65 years old, 20% had BMI<18.49; 21% had BMI≥25, 51% of them had a WL≥10%. About 63%, 44% and 13% of patients had a WL≥10% from UW, at 6 months and at 1 month, respectively. Moreover, 57% received oral supplementation after nutritional counseling. Conversely, 31% received artificial nutrition. Interestingly, WL≥10% from UW was associated with neutrophils-to-lymphocytes ratio (P=0.049) (Fig.1), cholesterol level (P=0.016) (Fig.2) and cancer type both from UW (P=0.003) (Fig.3) and at 6 months (P=0.007) before evaluation. A trend was observed with artificial nutrition (P=0.067). Prevention and treatment of cachexia still remain a critical need in CP. Therefore, integrating nutritional supportive care to oncologic treatments is crucial.

After the occurrence and detection of a short circuit to ground in the LHC main dipole circuit, a fast power abort is triggered and the current in the circuit starts decaying semi-exponentially from a maximum value of 11.85 kA to zero, with a time constant of 103 s. If a short to ground occurs, the current flows through the fuse that is present in the grounding subcircuit. Depending on the value of the thermal load, the fuse first enters a pre-arcing region where it starts intermittently blowing up, until the blow-up threshold is reached, after which it definitively blows up. A simulation scheme utilising a common interface between PSpice and Matlab is proposed in order to simulate the blow-up behaviour of the fuse and hence increase the accuracy of the circuit model for short circuits to ground. A parametric analysis of the short circuit to ground parameters is performed and a better understanding of the behaviour of the circuit under different conditions is obtained. The worst-case values of the voltage to ground in the LHC main dipole circuit are identified for both the case where the intermittent behaviour of the fuse is included in the model as well as for the case where the fuse is not modelled and a comparison between the two is given.

An energy of 362 MJ is stored in each of the two LHC proton beams for nominal beam parameters. This will be further increased to about 700 MJ in the future high luminosity LHC (HL-LHC) and uncontrolled beam losses represent a significant hazard for the integrity and safe operation of the machine. In this paper, a number of failure mechanisms that can lead to a fast increase of beam losses are analyzed. Most critical are failures in the magnet protection system, namely the quench heaters and a novel protection system called coupling-loss induced quench (CLIQ). An important outcome is that magnet protection has to be evaluated for its impact on the beam and designed accordingly. In particular, CLIQ, which is to protect the new HL-LHC triplet magnets, constitutes the fastest known failure in the LHC if triggered spuriously. A schematic change of CLIQ to mitigate the hazard is presented. A loss of the beam-beam kick due to the extraction of one beam is another source of beam losses with a fast onset. A significantly stronger impact is expected in the upcoming LHC Run III and HL-LHC as compared to the current LHC, mainly due to the increased bunch intensity. Its criticality and mitigation methods are discussed. It is shown that symmetric quenches in the superconducting magnets for the final focusing triplet can have a significant impact on the beam on short timescales. The impact on the beam due to failures of the beam-beam compensating wires as well as coherent excitations by the transverse beam damper are also discussed.

Introduction/BackgroundPatients (pts) with ovarian cancer experiencing a platinum-sensitive (PS) recurrence are generally re-exposed to platinum agents (PCT). The addition of bevacizumab (BEV) or PARP inhibitors (PARPi) as concomitant and/or maintenance therapy has shown to improve progression free survival (PFS). In the absence of direct comparisons coming from randomized trials (RCTs), we have performed a network meta-analysis to evaluate differences in terms of efficacy between BEV and PARPi in pts with PS recurrent ovarian cancer (rOC), according to BRCA status.MethodologyWe searched PubMed, Embase and Medline for RCTs involving pts with PS rOC treated with BEV (n=3, 1563 pts) or PARPi (n=5, 1839 pts). Only trials with PFS as primary endpoint were included. Analyses have been done pooling pts who had received PARPi in three groups, according to the available data on BRCA genes status: all comers (AC), BRCA mutated pts (BRCAm) and BRCA wild-type pts (BRCAwt). A frequentist approach has been used with R statistical software. To rank the effect size of treatments, surface under the cumulative ranking value (SUCRA) has been applied.ResultsIn AC pts, PARPi improved PFS compared to BEV (hazard ratio [HR]=0.70, 95% CI 0.54–0.91). In BRCAm pts the gain in PFS for PARPi was even higher compared to BEV (HR=0.46, 95% CI 0.36–0.59). In BRCAwt pts the benefit of PARPi over BEV was not statistically significant (HR=0.87, 95% CI 0.63–1.20) but PARPi had the highest likelihood of being ranked as the best treatment in terms of efficacy according to SUCRA (90% and 60%, respectively for PARPi and BEV).ConclusionAccording to indirect comparisons, PARPi performed the best for the treatment of PS rOC, especially in BRCAm pts who had not previously received PARPi. BEV could be still an option in BRCAwt pts.DisclosureFabio Puglisi: Roche, AstraZeneca (honoraria and research founding). No conflict of interest is to be declared for the remaining authors. The authors receive no financial support for this study.

Introduction/BackgroundWomen aged ≥65 represent nearly 50% of ovarian cancer (OC) patients (pts). However, elderly OC pts are less likely to receive optimal treatment. Furthermore, they are significantly under-represented in clinical trials and multidimensional geriatric assessment is still underused. The present study aims to provide an overview of real-life treatment strategies for elderly advanced-OC pts and to investigate clinico-pathological features that could potentially drive choice of first-line treatment.MethodologyA retrospective analysis was conducted on a consecutive series of 45 OC pts aged ≥69 treated with first-line chemotherapy (1L_CT) from 2011 to 2018 at CRO Aviano National Cancer Institute (Italy). Factors associated with treatment choice and rate of adverse events were investigated through Fisher-exact test; differences in progression free survival (PFS) and overall survival (OS) were tested by log-rank test.Results67% of pts received 1L_CT with a standard carboplatin-paclitaxel combination (CPC). Conversely, 33% received a monotherapy (MT) (31% with carboplatin, 2% with paclitaxel). ECOG PS ≥1 was the only factor significantly associated with choice of MT (P=0.021). No differences were observed between CPC and CPC with dose reductions (CPCdr), neither in terms of PFS (HR=1.29 P=0.59) nor OS (HR=1.40 P=0.56). On the other hand, MT was associated with shorter PFS (HR=4.35 P=0.001) and OS (HR=4.48 P=0.005). No differences in treatment discontinuation rate, neutropenia, thrombocytopenia, neuropathy, constipation, diarrhoea and asthenia in CPC, CPCdr and MT were detected (P>0.05).ConclusionThe present study confirms CPC as the standard first-line chemotherapy also in advanced OC elderly pts and suggests that CPCdr is preferable to MT regimens. Notwithstanding the limitations due to the small sample size, the evaluated regimens showed a comparable toxicity profile. Notably, clinical decision-making was mainly driven by PS ECOG highlighting the pivotal role of multidimensional geriatric assessment for pts stratification. Further prospective studies are needed to investigate improved tailored strategies.DisclosureNothing to disclose.

The Protein Structure Prediction (PSP) problem is concerned about the prediction of the native tertiary structure of a protein in respect to its amino acids sequence. PSP is a challenging and computationally open problem. Therefore, several researches and methodologies have been developed for it. In this way, developers are working to integrate frameworks in order to improve their capabilities and make their use more straightforward. This paper presents the application of NSGA-II algorithm using structural and energetic properties of protein. The implementation of this algorithm is based on ProtPred-GROMACS (2PG), an evolutionary framework for PSP. This framework is the integration between ProtPred and GROMACS. Six proteins were used to measure the capacity of ab initio predictions. The results were interesting since in all cases the native-like topology was obtained.