Relevance of Molecular Profiling in Patients With Low-Grade Endometrial Cancer

Molecular Profiling; Endometrial CancerPerfil molecular; Càncer d'endometriPerfil molecular; Cáncer de endometrioImportance Patients with low-grade (ie, grade 1-2) endometrial cancer (EC) are characterized by their favorable prognosis compared with patients with high-grade (ie, grade 3) EC. With the implementation of molecular profiling, the prognostic relevance of tumor grading might lose attention. As most patients present with low-grade EC and have an excellent outcome, the value of molecular profiling for these patients is unclear. Objective To determine the association of molecular profiling with outcomes among patients with low-grade EC. Design, Setting, and Participants This retrospective cohort study included a multicenter international European cohort of patients diagnosed with EC between 1994 and 2018, with a median follow-up of 5.9 years. Molecular subgroups were determined by next-generation sequencing using single-molecule molecular inversion probes and by immunohistochemistry. Subsequently, tumors were classified as polymerase epsilon (POLE)-altered, microsatellite instable (MSI), tumor protein p53 (TP53)-altered, or no specific molecular profile (NSMP). Patients diagnosed with any histological subtypes and FIGO (International Federation of Gynecology and Obstetrics) stages of EC were included, but patients with early-stage EC (FIGO I-II) were only included if they had known lymph node status. Data were analyzed February 20 to June 16, 2022. Exposures Molecular testing of the 4 molecular subgroups. Main Outcomes and Measures The main outcome was disease-specific survival (DSS) within the molecular subgroups. Results A total of 393 patients with EC were included, with a median (range) age of 64.0 (31.0-86.0) years and median (range) body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) of 29.1 (18.0-58.3). Most patients presented with early-stage (290 patients [73.8%]) and low-grade (209 patients [53.2%]) disease. Of all patients, 33 (8.4%) had POLE-altered EC, 78 (19.8%) had MSI EC, 72 (18.3%) had TP53-altered EC, and 210 (53.4%) had NSMP EC. Across all molecular subgroups, patients with low-grade EC had superior 5-year DSS compared with those with high-grade EC, varying between 90% to 100% vs 41% to 90% (P < .001). Multivariable analysis in the entire cohort including age, tumor grade, FIGO stage, lymphovascular space invasion, and the molecular subgroups as covariates found that only high-grade (hazard ratio [HR], 4.29; 95% CI, 2.15-8.53; P < .001), TP53-altered (HR, 1.76; 95% CI, 1.04-2.95; P = .03), and FIGO stage III or IV (HR, 4.26; 95% CI, 2.50-7.26; P < .001) disease were independently associated with reduced DSS. Conclusions and Relevance This cohort study found that patients with low-grade EC had an excellent prognosis independent of molecular subgroup. These findings do not support routine molecular profiling in patients with low-grade EC, and they demonstrate the importance of primary diagnostic tumor grading and selective profiling in low-grade EC to increase cost-effectiveness

Virtual Reality Aggression Prevention Therapy (VRAPT) versus Waiting List Control for Forensic Psychiatric Inpatients:A Multicenter Randomized Controlled Trial

Many forensic psychiatric inpatients have difficulties regulating aggressive behavior. Evidence of effective aggression treatments is limited. We designed and investigated the effectiveness of a transdiagnostic application of a virtual reality aggression prevention training (VRAPT). In this randomized controlled trial at four Dutch forensic psychiatric centers, 128 inpatients with aggressive behavior were randomly assigned to VRAPT (N = 64) or waiting list control group (N = 64). VRAPT consisted of 16 one-hour individual treatment sessions twice a week. Assessments were done at baseline, post-treatment and at 3-month follow-up. Primary outcome measures were aggressive behavior observed by staff and self-reported aggressive behavior. Analysis was by intention to treat. This trial was registered in the Dutch Trial Register (NTR, TC = 6340). Participants were included between 1 March 2017, and 31 December 2018. Compared to waiting list, VRAPT did not significantly decrease in self-reported or observed aggressive behavior (primary outcomes). Hostility, anger control, and non-planning impulsiveness improved significantly in the VRAPT group compared to the control group at post-treatment. Improvements were not maintained at 3-month follow-up. Results suggest that VRAPT does not decrease aggressive behavior in forensic inpatients. However, there are indications that VRAPT temporarily influences anger control skills, impulsivity and hostility

General Survey of Polarization Observables in Deuteron Electrodisintegration

Polarization observables in inclusive and exclusive electrodisintegration of the deuteron using a polarized beam and an oriented target are systematically surveyed using the standard nonrelativistic framework of nuclear theory but with leading order relativistic contributions included. The structure functions and the asymmetries corresponding to the various nucleon polarization components are studied in a variety of kinematic regions with respect to their sensitivity to realistic $NN$-potential models, to subnuclear degrees of freedom in terms of meson exchange currents, isobar configurations and to relativistic effects in different kinematical regions, serving as a benchmark for a test of present standard nuclear theory with effective degrees of freedom.Comment: 56 pages, 32 figures, revtex

Covariant description of inelastic electron--deuteron scattering:predictions of the relativistic impulse approximation

Using the covariant spectator theory and the transversity formalism, the unpolarized, coincidence cross section for deuteron electrodisintegration, $d(e,e'p)n$, is studied. The relativistic kinematics are reviewed, and simple theoretical formulae for the relativistic impulse approximation (RIA) are derived and discussed. Numerical predictions for the scattering in the high $Q^2$ region obtained from the RIA and five other approximations are presented and compared. We conclude that measurements of the unpolarized coincidence cross section and the asymmetry $A_\phi$, to an accuracy that will distinguish between different theoretical models, is feasible over most of the wide kinematic range accessible at Jefferson Lab.Comment: 54 pages and 24 figure

Immunohistochemical biomarkers are prognostic relevant in addition to the ESMO-ESGO-ESTRO risk classification in endometrial cancer

Endometrial carcinoma; Immunohistochemistry; OutcomeCarcinoma de endometrio; Inmunohistoquímica; ResultadoCarcinoma d'endometri; Immunohistoquímica; ResultatObjective Pre-operative immunohistochemical (IHC) biomarkers are not incorporated in endometrial cancer (EC) risk classification. We aim to investigate the added prognostic relevance of IHC biomarkers to the ESMO-ESGO-ESTRO risk classification and lymph node (LN) status in EC. Methods Retrospective multicenter study within the European Network for Individualized Treatment of Endometrial Cancer (ENITEC), analyzing pre-operative IHC expression of p53, L1 cell-adhesion molecule (L1CAM), estrogen receptor (ER) and progesterone receptor (PR), and relate to ESMO-ESGO-ESTRO risk groups, LN status and outcome. Results A total of 763 EC patients were included with a median follow-up of 5.5-years. Abnormal IHC expression was present for p53 in 112 (14.7%), L1CAM in 79 (10.4%), ER- in 76 (10.0%), and PR- in 138 (18.1%) patients. Abnormal expression of p53/L1CAM/ER/PR was significantly related with higher risk classification groups, and combined associated with the worst outcome within the ‘high and advanced/metastatic’ risk group. In multivariate analysis p53-abn, ER/PR- and ESMO-ESGO-ESTRO ‘high and advanced/metastatic’ were independently associated with reduced disease-specific survival (DSS). Patients with abnormal IHC expression and lymph node metastasis (LNM) had the worst outcome. Patients with LNM and normal IHC expression had comparable outcome with patients without LNM and abnormal IHC expression. Conclusion The use of pre-operative IHC biomarkers has important prognostic relevance in addition to the ESMO-ESGO-ESTRO risk classification and in addition to LN status. For daily clinical practice, p53/L1CAM/ER/PR expression could serve as indicator for surgical staging and refine selective adjuvant treatment by incorporation into the ESMO-ESGO-ESTRO risk classification

Inclusive Electron Scattering from Nuclei at x≃1x \simeq 1

The inclusive A(e,e') cross section for $x \simeq 1$ was measured on $^2$H, C, Fe, and Au for momentum transfers $Q^2$ from 1-7 (GeV/c)$^2$. The scaling behavior of the data was examined in the region of transition from y-scaling to x-scaling. Throughout this transitional region, the data exhibit $\xi$-scaling, reminiscent of the Bloom-Gilman duality seen in free nucleon scattering.Comment: 4 pages, RevTeX; 4 figures (postscript in .tar.Z file

Relativistic effects and two-body currents in 2H(e⃗,e′p)n^{2}H(\vec{e},e^{\prime}p)n using out-of-plane detection

Measurements of the ${^2}H(\vec{e},e^{\prime}p)n$ reaction were performed using an 800-MeV polarized electron beam at the MIT-Bates Linear Accelerator and with the out-of-plane magnetic spectrometers (OOPS). The longitudinal-transverse, $f_{LT}$ and $f_{LT}^{\prime}$, and the transverse-transverse, $f_{TT}$, interference responses at a missing momentum of 210 MeV/c were simultaneously extracted in the dip region at Q$^2$=0.15 (GeV/c)$^2$. On comparison to models of deuteron electrodisintegration, the data clearly reveal strong effects of relativity and final-state interactions, and the importance of the two-body meson-exchange currents and isobar configurations. We demonstrate that these effects can be disentangled and studied by extracting the interference response functions using the novel out-of-plane technique.Comment: 4 pages, 4 figures, and submitted to PRL for publicatio

Tensor Analyzing Powers for Quasi-Elastic Electron Scattering from Deuterium

We report on a first measurement of tensor analyzing powers in quasi-elastic electron-deuteron scattering at an average three-momentum transfer of 1.7 fm$^{-1}$. Data sensitive to the spin-dependent nucleon density in the deuteron were obtained for missing momenta up to 150 MeV/$c$ with a tensor polarized $^2$H target internal to an electron storage ring. The data are well described by a calculation that includes the effects of final-state interaction, meson-exchange and isobar currents, and leading-order relativistic contributions.Comment: 4 pages, 3 figure