Prognostic significance of VEGF after twenty-year follow-up in a randomized trial of fenretinide in non-muscle-invasive bladder cancer

Non-muscle-invasive bladder cancer (NMIBC) may progress to muscle-invasive disease, but no effective preventive treatments are available. In addition, no reliable prognostic biomarkers have been identified. We assessed the long-term effect of the oral retinoid fenretinide and the prognostic value of circulating VEGF levels. We updated through the Tumor Registry the vital status of 99 patients with resected Ta/T1 bladder tumors who were recruited in a randomized trial of 2 years of fenretinide or no treatment in 1993-1994. Serum VEGF levels measured at baseline and 12 months were available in a subgroup of 62 patients. After a median of 20.5 years, 54 subjects died, 35 of any cancer and 14 of bladder cancer. Neither overall survival (OS), nor cancer survival (CS) or bladder cancer survival (BCS) was affected by fenretinide (log-rank P 65 0.2). DNA aneuploidy in bladder washing was associated with shorter OS (P =0.02), CS (P =0.05), and BCS (P = 0.09). Subjects with baseline VEGF levels in the top quintile ( 65350 pg/mL) had a significantly shorter OS (P =0.01), CS (P = 0.02), and BCS (P= 0.008). The trend across quintiles of VEGF was significant for BCS (P =0.007). Multivariate analyses showed that, in addition to smoking status, VEGF level in the top quintile was an independent prognostic factor for OS (HR =2.7; 95% CI, 1.1-6.5), CS (HR = 3.3; 95% CI, 1.1-9.4) and BCS (HR =8.9; 95% CI,1.3-61). Fenretinide did not affect the long-term outcome of patients with NMIBC. High serum VEGF level was a significant predictor of overall and cancer death and may help to identify high-risk subjects who may benefit from a preventive therapy. Cancer Prev Res; 9(6); 437-44

A case series of low dose bevacizumab and chemotherapy in heavily pretreated patients with epithelial ovarian cancer

Abstract Background The addition of bevacizumab to standard chemotherapy prolongs progression free survival in the first line treatment of epithelial ovarian cancer (EOC), but its cost/effectiveness is debated. We assessed the safety and activity of a lower dose of bevacizumab in pretreated advanced stage EOC. Methods We treated 15 patients, mostly with platinum resistant EOC, who had received a median of four prior cytotoxic regimens, with bevacizumab 5–7.5 mg/kg q21 days in combination with either carboplatin (n = 8), oral cyclofosfamide (n = 5) or weekly paclitaxel (n = 2). Bevacizumab was administered until disease progression. Tumor response was assessed by CA125 and fusion 18 F-FDG PET/contrast enhanced CT. Results The median number of bevacizumab cycles was 21 (range 3–59). The median baseline CA125 was 272 U/ml and decreased to 15.2 U/ml at nadir. Tumor response was 4 complete response (CR) (26.7%) and 7 partial response (PR) (46.7%) by chemotherapy (CT), with an overall response rate of 73.4% (95% CI, 51.0 – 95.8) according to Response Evaluation Criteria In Solid Tumors (RECIST), and 6 CR (40%) and 4 PR (26.7%) by PET, for an overall metabolic response rate of 67% (95%CI, 42.8 – 90.6) according to PET Response Criteria in Solid Tumors (PERCIST). Median progression free survival (PFS) was 21 months and median overall survival (OS) was 24 months. Grade 3 adverse events related to bevacizumab were hypertension (n = 2), proteinuria (n = 1) and epistaxis (n = 5). Treatment was delayed in five patients for nasal bleeding or uncontrolled hypertension. Conclusions Low-dose bevacizumab and chemotherapy was well tolerated and active in a heavily pretreated population of advanced EOC. Further studies should assess the activity of low dose bevacizumab in EOC.</p

Multidifferential study of identified charged hadron distributions in ZZ-tagged jets in proton-proton collisions at s=\sqrt{s}=13 TeV

Jet fragmentation functions are measured for the first time in proton-proton collisions for charged pions, kaons, and protons within jets recoiling against a $Z$ boson. The charged-hadron distributions are studied longitudinally and transversely to the jet direction for jets with transverse momentum 20 $< p_{\textrm{T}} < 100$ GeV and in the pseudorapidity range $2.5 < \eta < 4$. The data sample was collected with the LHCb experiment at a center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 1.64 fb$^{-1}$. Triple differential distributions as a function of the hadron longitudinal momentum fraction, hadron transverse momentum, and jet transverse momentum are also measured for the first time. This helps constrain transverse-momentum-dependent fragmentation functions. Differences in the shapes and magnitudes of the measured distributions for the different hadron species provide insights into the hadronization process for jets predominantly initiated by light quarks.Comment: All figures and tables, along with machine-readable versions and any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-013.html (LHCb public pages

Study of the B−→Λc+Λˉc−K−B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-} decay

The decay $B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-}$ is studied in proton-proton collisions at a center-of-mass energy of $\sqrt{s}=13$ TeV using data corresponding to an integrated luminosity of 5 $\mathrm{fb}^{-1}$ collected by the LHCb experiment. In the $\Lambda_{c}^+ K^{-}$ system, the $\Xi_{c}(2930)^{0}$ state observed at the BaBar and Belle experiments is resolved into two narrower states, $\Xi_{c}(2923)^{0}$ and $\Xi_{c}(2939)^{0}$, whose masses and widths are measured to be $$m(\Xi_{c}(2923)^{0}) = 2924.5 \pm 0.4 \pm 1.1 \,\mathrm{MeV}, \\ m(\Xi_{c}(2939)^{0}) = 2938.5 \pm 0.9 \pm 2.3 \,\mathrm{MeV}, \\ \Gamma(\Xi_{c}(2923)^{0}) = \phantom{000}4.8 \pm 0.9 \pm 1.5 \,\mathrm{MeV},\\ \Gamma(\Xi_{c}(2939)^{0}) = \phantom{00}11.0 \pm 1.9 \pm 7.5 \,\mathrm{MeV},$$ where the first uncertainties are statistical and the second systematic. The results are consistent with a previous LHCb measurement using a prompt $\Lambda_{c}^{+} K^{-}$ sample. Evidence of a new $\Xi_{c}(2880)^{0}$ state is found with a local significance of $3.8\,\sigma$, whose mass and width are measured to be $2881.8 \pm 3.1 \pm 8.5\,\mathrm{MeV}$ and $12.4 \pm 5.3 \pm 5.8 \,\mathrm{MeV}$, respectively. In addition, evidence of a new decay mode $\Xi_{c}(2790)^{0} \to \Lambda_{c}^{+} K^{-}$ is found with a significance of $3.7\,\sigma$. The relative branching fraction of $B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-}$ with respect to the $B^{-} \to D^{+} D^{-} K^{-}$ decay is measured to be $2.36 \pm 0.11 \pm 0.22 \pm 0.25$, where the first uncertainty is statistical, the second systematic and the third originates from the branching fractions of charm hadron decays.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-028.html (LHCb public pages

Measurement of the ratios of branching fractions R(D∗)\mathcal{R}(D^{*}) and R(D0)\mathcal{R}(D^{0})

The ratios of branching fractions $\mathcal{R}(D^{*})\equiv\mathcal{B}(\bar{B}\to D^{*}\tau^{-}\bar{\nu}_{\tau})/\mathcal{B}(\bar{B}\to D^{*}\mu^{-}\bar{\nu}_{\mu})$ and $\mathcal{R}(D^{0})\equiv\mathcal{B}(B^{-}\to D^{0}\tau^{-}\bar{\nu}_{\tau})/\mathcal{B}(B^{-}\to D^{0}\mu^{-}\bar{\nu}_{\mu})$ are measured, assuming isospin symmetry, using a sample of proton-proton collision data corresponding to 3.0 fb${ }^{-1}$ of integrated luminosity recorded by the LHCb experiment during 2011 and 2012. The tau lepton is identified in the decay mode $\tau^{-}\to\mu^{-}\nu_{\tau}\bar{\nu}_{\mu}$. The measured values are $\mathcal{R}(D^{*})=0.281\pm0.018\pm0.024$ and $\mathcal{R}(D^{0})=0.441\pm0.060\pm0.066$, where the first uncertainty is statistical and the second is systematic. The correlation between these measurements is $\rho=-0.43$. Results are consistent with the current average of these quantities and are at a combined 1.9 standard deviations from the predictions based on lepton flavor universality in the Standard Model.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-039.html (LHCb public pages

The Critical Role of the Clinical Research Coordinator for Clinical Trials: A Survey in Oncology

Introduction Access to innovative medicine requires proper evidence from clinical trials with the growing demand of qualified and experienced personnel. The clinical research coordinator (CRC) plays an important role in the conduction of research activities and provides a strong support to the research team. In Italy, this role is not recognized at any institutional level and its professional outline is still indefinite. Several national associations (Associazione Italiana di Oncologia Medica, Collegio Italiano dei Primari Oncologi Medici Ospedalieri, Gruppo Italiano Data Manager) are committed to promoting the enhancement and recognition of the professional status of CRCs, underlining their role as fundamental. Methods A web survey, proposed by the AIOM CRC Working Group, was submitted to 319 Italian oncology sites with items focusing on the organization of sites, the research activities, the staff composition, and the presence of coordinators and the multidisciplinary team. Results A total of 115 sites (35.9%) responded to the web survey. Clinical studies were carried out at 88.7% of the investigated sites, and coordinators were on staff at 75.5% of the active investigational sites. Interestingly, there was a direct association between the number of clinical studies and the number of coordinators, whose contribution to the research activities is believed to be essential for trial conduct in 82.4% of cases. Most sites retain that the quality of clinical research has absolutely improved (83.3%) after the implementation of a coordinator as member of the team. Conclusions Given the constant growth of the number of clinical trials performed at Italian oncology sites, the CRC proves to be an essential component of the research team. However, there is an urgent need to institute the professional role alongside the need to standardize the training of coordinators to establish the minimum requirements enhanced by qualifying courses

Gender moderates the relationship between attachment insecurities and emotion dysregulation

none9noThe relation between attachment styles and emotion regulation is well documented, and emotion dysregulation is considered characteristic of individuals with insecure attachment styles. Although gender differences in emotion regulation have often been reported, it is not clear whether the association between attachment styles and aspects of emotion dysregulation may vary across gender. A sample of 229 newlywed couples completed the Experiences in Close Relationship– Revised scale and the Difficulties in Emotion Regulation Scale. First, we confirmed previous evidence on the association between attachment insecurities and emotion dysregulation. Indeed, attachment anxiety and avoidance were both related to emotional nonacceptance and lack of emotional clarity. Moreover, attachment anxiety was associated with difficulties in impulse control and limited access to effective emotion regulation strategies, whereas attachment avoidance was uniquely related to lack of emotional awareness. Finally, gender was found to moderate the association that both attachment anxiety and attachment avoidance had with difficulties in pursuing desired goals when experiencing negative emotions. Specifically, among women (but not men), attachment anxiety was associated with greater difficulties in engaging in goal-directed behavior when distressed. Conversely, the association between attachment avoidance and difficulties in pursuing desired goals when distressed was positive for men and negative for women.Velotti, P; D’Aguanno, M; De Campora, G; Di Francescantonio, S; Garofalo, C; Giromini, L; Petrocchi, C; Terrasi, M; Zavattini, GcVelotti, Patrizia; D’Aguanno, M; De Campora, G; Di Francescantonio, S; Garofalo, C; Giromini, L; Petrocchi, C; Terrasi, M; Zavattini, G