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Individuals with dark personality traits are more prone to burnout, but this was not yet investigated in academia. Perfectionistic self-presentation (PSPS), an interpersonal expression of perfectionism, could be an explaining factor. Therefore, we investigated the relationship between the dark triad (Machiavellianism, vulnerable and grandiose narcissism, and psychopathy) and academic burnout, and whether the PSPS total score and its dimensions (perfectionistic self-promotion, nondisplay of imperfection, and nondisclosure of imperfection) mediates this. We expected that higher dark triad traits would be associated with higher academic burnout and that this would be explained by higher PSPS. Hypotheses included expectations for each PSPS dimension as well. Questionnaires were completed by 304 bachelor/master students (Mage = 22.81 years). Mediations were performed for each dark triad trait with total PSPS and each of its dimensions separately as mediator, and academic burnout as dependent variable. Total PSPS and almost all of its dimensions positively and significantly mediated the relation between Machiavellianism as well as psychopathy and academic burnout (small effect sizes). In contrast, only the PSPS dimension nondisplay of imperfection was a significant, positive mediator of the relation between grandiose narcissism and academic burnout (medium effect size). The other mediations with grandiose or vulnerable narcissism were non-significant. Future research should investigate this further, for instance by using the standard dark triad scales. Finally, this study offers insights for interventions and prevention of academic burnout by highlighting the unique impact of each dark triad trait. For example, those high on Machiavellianism may benefit from tools to deal with cynicism and perfectionism, ultimately lowering the risk for academic burnout.

Few theoretical and empirical works have described impostor phenomenon (IP) and no study explored impostorism from a dark perspective. We adopted a person-centered approach to identify clusters of impostors based on scores on the IP, perfectionistic self-presentation and the Dark Triad using a sample of 306 university students (Mage = 22.82). The latent profile analysis suggested a 6-cluster solution, which was further compared in terms of psychopathology symptoms (i.e., burnout, generalized anxiety, and fear of failure) by means of (M)ANOVAs. Our results indicated that impostorism relies on a self-presentation strategy. Moreover, individuals scoring high on IP experienced enhanced levels of psychopathology symptoms. Looking at IP from a continuum perspective might improve our understanding about what makes someone suffer from impostorism.

Radiation therapy (RT) has long been fundamental for the curative treatment of breast cancer. While substantial progress has been made in the anatomical and technological precision of RT delivery, and some approaches to de-escalate or omit RT based on clinicopathologic features have been successful, there remain substantial opportunities to refine individualised RT based on tumour biology.A major area of clinical and research interest is to ascertain the individualised risk of loco-regional recurrence to direct treatment decisions regarding escalation and de-escalation of RT. Patient-tailored treatment with RT is considerably lagging behind compared with the massive progress made in the field of personalised medicine that currently mainly applies to decisions on the use of systemic therapy or targeted agents.Herein we review select literature surrounding the use of tumour genomic biomarkers and biomarkers of the immune system, including tumour infiltrating lymphocytes (TILs), within the management of breast cancer, specifically as they relate to progress in moving toward analytically validated and clinically tested biomarkers utilized in RT.

Abstract Purpose / objective This study compares the dosimetric plans of three distinct boost modalities in cervical cancer (CC): intracavitary (IC) with tandem/ovoids brachytherapy (BT), IC + interstitial (IS) BT, and Stereotactic-Body-Radiotherapy (SBRT). The aim is to determine the dosimetric impact in terms of target coverage and organ at risk (OAR) doses. Materials and methods 24 consecutive IC + IS BT boost treatment plans were retrospectively identified. For each plan included, two additional plans were created: IC-BT and SBRT. Importantly, no planning target volume (PTV) or planning (organ at) risk volume (PRV) margins were generated, therefore all structures were identical for any boost modality. Two different normalizations were performed: (1) Normalization to the target: prescription of 7.1 Gy to the D90% (defined as the minimum dose covering 90%) of the high-risk clinical target volume (HR-CTV); (2) Normalization to the OARs. HR-CTV coverage and OARs sparing were compared. The equivalent doses in 2 Gy fractions (EQD2) of EBRT and BT for CTV-HR and OARs were calculated using the linear-quadratic model with α/β of 10 (EQD210) and 3 (EQD23), respectively Results A total of 72 plans were investigated. In the first normalization, the mean EQD23−D2cc (defined as the minimal dose of the 2 cc) of OAR was significantly higher in the IC-BT plans, and the bladder D2cc hard constraint could not be reached. IC + IS BT leads to a 1 Gy mean absolute decrease of bladder EQD23-D2cc (relative dose: -19%), allowing to reach the hard constraint. SBRT (without PTV) delivers the lowest EQD23-D2cc to the OAR. In the second normalization, IC-BT provides a significantly lower dose to the EQD210-D90% (6.62 Gy) and cannot achieve the coverage goal. SBRT (without PTV) yields the highest dose to the D90% of HR-CTV and a significantly lower EQD210-D50% and D30%. Conclusion The key dosimetric benefit of BT over SBRT without PTV is a significantly higher D50% and D30% in the HR-CTV, which increases the local and conformal dose to the target. IC + IS BT vs. IC-BT provides significantly better target coverage and a lower dose to the OARs, making it the preferred boost modality in CC.

Background Luminal B breast cancer (BC) presents a worse prognosis when compared with luminal A BC and exhibits a lower sensitivity to chemotherapy and a lower immunogenicity in contrast to non-luminal BC subtypes. The Neo-CheckRay clinical trial investigates the use of stereotactic body radiation therapy (SBRT) directed to the primary tumor in combination with the adenosine pathway inhibitor oleclumab to improve the response to neo-adjuvant immuno-chemotherapy in luminal B BC. The trial consists of a safety run-in followed by a randomized phase II trial. Here, we present the results of the first-in-human safety run-in.Methods The safety run-in was an open-label, single-arm trial in which six patients with early-stage luminal B BC received the following neo-adjuvant regimen: paclitaxel q1w×12 → doxorubicin/cyclophosphamide q2w×4; durvalumab (anti-programmed cell death receptor ligand 1 (PD-L1)) q4w×5; oleclumab (anti-CD73) q2w×4 → q4w×3 and 3×8 Gy SBRT to the primary tumor at week 5. Surgery must be performed 2–6 weeks after primary systemic treatment and adjuvant therapy was given per local guidelines, RT boost to the tumor bed was not allowed. Key inclusion criteria were: luminal BC, Ki67≥15% or histological grade 3, MammaPrint high risk, tumor size≥1.5 cm. Primary tumor tissue samples were collected at three timepoints: baseline, 1 week after SBRT and at surgery. Tumor-infiltrating lymphocytes, PD-L1 and CD73 were evaluated at each timepoint, and residual cancer burden (RCB) was calculated at surgery.Results Six patients were included between November 2019 and March 2020. Median age was 53 years, range 37–69. All patients received SBRT and underwent surgery 2–4 weeks after the last treatment. After a median follow-up time of 2 years after surgery, one grade 3 adverse event (AE) was reported: pericarditis with rapid resolution under corticosteroids. No grade 4–5 AE were documented. Overall cosmetical breast evaluation after surgery was ‘excellent’ in four patients and ‘good’ in two patients. RCB results were 2/6 RCB 0; 2/6 RCB 1; 1/6 RCB 2 and 1/6 RCB 3.Conclusions This novel treatment combination was considered safe and is worth further investigation in a randomized phase II trial.Trial registration number NCT03875573.

Abstract Recent progress in immunobiology has led the way to successful host immunity enhancement against breast cancer. In triple-negative breast cancer, the combination of cancer immunotherapy based on PD-1/PD-L1 immune checkpoint inhibitors with chemotherapy was effective both in advanced and early setting phase 3 clinical trials. These encouraging results lead to the first approvals of immune checkpoint inhibitors in triple-negative breast cancer and thus offer new therapeutic possibilities in aggressive tumors and hard-to-treat populations. Furthermore, several ongoing trials are investigating combining immunotherapies involving immune checkpoint inhibitors with conventional therapies and as well as with other immunotherapeutic strategies such as cancer vaccines, CAR-T cells, bispecific antibodies, and oncolytic viruses in all breast cancer subtypes. This review provides an overview of immunotherapies currently under clinical development and updated key results from clinical trials. Finally, we discuss the challenges to the successful implementation of immune treatment in managing breast cancer and their implications for the design of future clinical trials.

Psychopathic traits are often investigated within the individual, while most traits come to expression within the interpersonal context. Low social communion might even be an important overlooked core feature of psychopathy. This raises the question how psychopathic (i.e., Grandiose-Manipulative, Callous-Unemotional, and Irresponsible-Impulsive) traits affect the tendency to show prosocial behavior, and whether peer problems explain this relationship. Besides, the effects of gender on these subrelations are explored. In total, 541 community adolescents and emerging adults (26.4 % men; 16–25 years old, Mage = 21.7, SDage = 2.50) completed questionnaires, measuring psychopathic traits, prosocial behavior, and peer problems. The relationship between psychopathic traits and prosocial behavior was investigated with three separate moderated mediation regression analyses (for Grandiose-Manipulative, Callous-Unemotional, and Impulsive-Irresponsible traits separately) including peer problems as mediator and gender as moderator. Significant direct negative effects of Grandiose-Manipulative and Callous-Unemotional traits on prosocial behavior were found, though not for Impulsive-Irresponsible traits. Peer problems did not mediate this relation and gender was no moderator. The significant moderation effect indicated that only for women a significant direct positive effect of Callous-Unemotional traits on peer problems was found, but not for men nor other psychopathic traits. More gender differences were found with men (vs. women) scoring significantly higher on all three psychopathic traits and lower on prosocial behavior. Implications of psychopathic traits within the interpersonal context are discussed and future research could further investigate how this relationship can be explained, for example by including different types of measures and other potential mediators (e.g., empathy).

Since the publication of the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), identity impairment has become a diagnostic criterion for all personality disorders. The current study examined the occurrence of identity dimensions, clinically relevant identity impairments and personality pathology, and associations between these constructs in 92 forensic patients and 139 healthy controls. Patients showed higher levels of almost all identity dimensions, identity impairments, personality disorders, and almost all maladaptive personality traits than controls. Various identity dimensions were associated with consolidated identity as well as identity impairments in both groups. Both patients and controls with high ruminative exploration and identity malfunctioning showed more personality pathology. Different associations between identity functioning and particularly antisocial and borderline personality disorder showed to be stronger in patients than in controls. Our results highlight the importance of identity impairment as a crucial criterion to assess and treat personality pathology in forensic patients. [ABSTRACT FROM AUTHOR]

Abstract Background Although systematic research on narcissism has been conducted for over 100 years, researchers have only recently started to distinguish between grandiose and vulnerable narcissism in relation to criminal behavior. In addition, there is some evidence suggesting that identity integration and self-control may underlie this association. Therefore, the present study aimed to develop a theory-driven hypothetical model that investigates the complex associations between grandiose and vulnerable narcissism, identity integration, self-control, and criminal behavior using structural equation modeling (SEM). Methods The total sample (N = 222) included 65 (29.3%) individuals convicted of criminal behavior and 157 (70.7%) participants from the community, with a mean age of 37.71 years (SD = 13.25). Criminal behavior was a grouping variable used as a categorical outcome, whereas self-report questionnaires were used to assess grandiose and vulnerable narcissism, self-control, and identity integration. Results The overall SEM model yielded good fit indices. Grandiose narcissism negatively predicted criminal behavior above and beyond the influence of identity integration and self-control. In contrast, vulnerable narcissism did not have a direct significant effect on criminal behavior, but it was indirectly and positively associated with criminal behavior via identity integration and self-control. Moreover, grandiose narcissism was positively, whereas vulnerable narcissism was negatively associated with identity integration. However, identity integration did not have a direct significant effect on criminal behavior, but it was indirectly and negatively associated with criminal behavior via self-control. Finally, self-control was, in turn, negatively related to criminal behavior. Conclusions We propose that both subtypes of narcissism should be carefully considered in clinical assessment and current intervention practices.

Abstract Our recently developed prone crawl position (PCP) for radiotherapy of breast cancer patients with lymphatic involvement showed promising preliminary data and it is being optimized for clinical use. An important aspect in this process is making new, position specific delineation guidelines to ensure delineation (for treatment planning) is uniform across different centers. The existing ESTRO and PROCAB guidelines for supine position (SP) were adapted for PCP. Nine volunteers were MRI scanned in both SP and PCP. Lymph node regions were delineated in SP using the existing ESTRO and PROCAB guidelines and were then translated to PCP, based on the observed changes in reference structure position. Nine PCP patient CT scans were used to verify if the new reference structures were consistently identified and easily applicable on different patient CT scans. Based on these data, a team of specialists in anatomy, CT- and MRI radiology and radiation oncology postulated the final guidelines. By taking the ESTRO and PROCAB guidelines for SP into account and by using a relatively big number of datasets, these new PCP specific guidelines incorporate anatomical variability between patients. The guidelines are easily and consistently applicable, even for people with limited previous experience with delineations in PCP.

Abstract Background Residual breast cancer after neo-adjuvant chemotherapy (NACT) predicts disease outcome and is a surrogate for survival in aggressive breast cancer (BC) subtypes. Pathological complete response (pCR) rate, however, is lower for luminal B BC in comparison to the triple negative (TNBC) and HER2+ subtypes. The addition of immune checkpoint blockade (ICB) to NACT has the potential to increase pCR rate but is hampered by the lower immunogenicity of luminal B BC. Novel strategies are needed to stimulate the immune response and increase the response rate to ICB in luminal B BC. Methods The Neo-CheckRay trial is a randomized phase II trial investigating the impact of stereotactic body radiation therapy (SBRT) to the primary breast tumor in combination with an anti-CD73 (oleclumab) to increase response to anti PD-L1 (durvalumab) and NACT. The trial is designed as a three-arm study: NACT + SBRT +/− durvalumab +/− oleclumab. The result at surgery will be evaluated using the residual cancer burden (RCB) index as the primary endpoint. Six patients will be included in a safety run-in, followed by a randomized phase II trial that will include 136 evaluable patients in 3 arms. Inclusion is limited to luminal B breast cancers that are MammaPrint genomic high risk. Discussion combination of ICB with chemotherapy in luminal B BC might benefit from immune priming agents to increase the response rate. As none have been identified so far, this phase II trial will evaluate SBRT and oleclumab as potential immune priming candidates. Trial registration trial registered on ClinicalTrials.gov ( NCT03875573 ) on March 14th, 2019.

Purpose/ObjectiveDeep Inspiration Breath Hold (DIBH) is now considered as the standard of care for many breast cancer patients. However, there are still uncertainties about the dose given to the heart, and it is unknown if patients may improve voluntary DIBH depth by gaining experience during treatment. In this study, we will examine the interfractional three-dimensional (3D) heart displacement throughout voluntary DIBH (vDIBH) radiotherapy by means of daily cone-beam computed tomography (CBCT).Material and methodsTwo hundred twenty-five unique CBCTs from 15 patients treated in 15 fractions were analyzed. During CBCT, a vDIBH was conducted without any visual feedback. Patients performed their DIBH freely after receiving explanations and training. After daily CBCT matching to the chest wall (CW), surface-guided radiation therapy (SGRT) tracked DIBH depth to ensure that the CW position was the same as the daily acquired CBCT. The CBCTs were retrospectively registered to the DIBH planning-CT to calculate daily changes in heart displacement relative to the CW.ResultsThe mean displacement of the heart during DIBH treatment relative to the DIBH planning-CT was as follows: 1.1 mm to the right, interquartile range (IQR) 8.0; 0.5 mm superiorly, IQR 4.8; and 0 mm posteriorly, IQR 6.4. The Spearman correlation coefficients (rs) were -0.15 (p=0.025), 0.04 (p=0.549), and 0.03 (p=0.612) for the X, Y, and Z directions, respectively. The differences in median heart displacement were significant: Friedmann rank sum test p=0.031 and pairwise comparison using the Wilcoxon rank-sum test were p=0.008 for X and Y; p=0.33 for X and Z; and p=0.07 for Y and Z. The total median heart motion was δtot median= 7.26 mm, IQR= 6.86 mm.ConclusionDuring DIBH, clinicians must be aware of the wide range of intra- and inter-individual heart position variations. The inter-individual heterogeneity shown in our study should be investigated further in order to avoid unexpected cardiac overexposure and to develop a more accurate heart dose-volume model.

Abstract Background To improve split-VMAT technique by optimizing treatment delivery time for deep-inspiration breath hold (DIBH) radiotherapy in left-sided breast cancer patients, when automatic beam-interruption devices are not available. Methods Ten consecutive patients were treated with an eight partial arcs (8paVMAT) plan, standard of care in our center. A four partial arcs (4paVMAT) plan was also created and actual LINAC outputs were measured, to evaluate whether there was a dosimetric difference between both techniques and potential impact on the delivered dose. Subsequently, ten other patients were consecutively treated with a 4paVMAT plan to compare the actual treatment delivery time between both techniques. The prescribed dose was 40.05 Gy/15 fractions on the PTV breast (breast or thoracic wall), lymph nodes (LN) and intramammary lymph node chain (IMN). Treatment delivery time, PTVs coverage, conformity index (CI), organs at risk (OAR) dose, monitor units (MU), and gamma index were compared. Results Both split-VMAT techniques resulted in similar dose coverage for the PTV Breast and LN, and similar CI. For PTV IMN we observed a 5% increased coverage for the volume receiving ≥ 36 Gy with 4paVMAT, with an identical volume receiving ≥ 32 Gy. There was no difference for the OAR sparing, with the exception of the contralateral organs: there was a 0.6 Gy decrease for contralateral breast mean (p ≤ 0.01) and 1% decrease for the volume of right lung receiving ≥ 5 Gy (p = 0.024). Overall, these results indicate a modest clinical benefit of using 4paVMAT in comparison to 8paVMAT. An increase in the number of MU per arc was observed for the 4paVMAT technique, as expected, while the total number of MU remained comparable for both techniques. All the plans were measured with the Delta4 phantom and passed the gamma index criteria with no significant differences. Finally, the main difference was seen for the treatment delivery time: there was a significant decrease from 8.9 to 5.4 min for the 4paVMAT plans (p

The long-term changes of dynamic risk and protective factors have rarely been studied in forensic psychiatric patients. We utilized a latent growth curve analysis to investigate trajectories of risk and protective factors over time in all 722 male forensic psychiatric patients who were unconditionally released between 2004 and 2014 from any of 12 Dutch forensic psychiatric centers (FPCs). The study covered the period from juridical observation until unconditional release. Moreover, we investigated whether these trajectories differ between patients depending on their psychiatric diagnosis namely substance use disorders (SUD), psychotic disorders, and cluster B personality disorders (PDs). In addition, we also investigated whether SUD may influence changes in risk and protective factors in a group of psychotic and cluster B PDs patients, respectively. Overall, findings suggest that all changes in dynamic risk and protective factors could be depicted by two phases of patients' stay in the FPCs. Specifically, most changes on dynamic risk and protective factors occurred at the beginning of treatment, that is, from the time of juridical assessment up to the time of unguided leave. Moreover, the moment of unguided leave could be considered the ‘turning point’ in the treatment of offenders. We also found that SUD and psychotic patients changed the most in the first phase of their stay, while cluster B PDs patients changed the most in the second phase. However, SUD did not modify changes in risk and protective factors in psychotic and cluster B PDs patients. These findings may help improve offender treatment and crime prevention strategies.

Abstract Background Immunotherapeutic approaches have revolutionized oncological practice but are less evaluated in gynecological malignancies. PD-1/PD-L1 blockade in gynecological cancers showed objective responses in 13–17% of patients. This could be due to immunosuppressive effects exerted by gynecological tumors on the microenvironment and an altered tumor vasculature. In other malignancies, combining checkpoint blockade with radiation delivers benefit that is believed to be due to the abscopal effect. Addition of immune modulation agents has also shown to enhance immune checkpoint blockade efficacy. Therefore we designed a regimen consisting of PD-1 blockade combined with radiation, and different immune/environmental-targeting compounds: repurposed drugs, metronomic chemotherapy and a food supplement. We hypothesize that these will synergistically modulate the tumor microenvironment and induce and sustain an anti-tumor immune response, resulting in tumor regression. Methods PRIMMO is a multi-center, open-label, non-randomized, 3-cohort phase 2 study with safety run-in in patients with recurrent/refractory cervical carcinoma, endometrial carcinoma or uterine sarcoma. Treatment consists of daily intake of vitamin D, lansoprazole, aspirin, cyclophosphamide and curcumin, starting 2 weeks before the first pembrolizumab dose. Pembrolizumab is administered 3-weekly for a total of 6 cycles. Radiation (3 × 8 Gy) is given on days 1, 3 and 5 of the first pembrolizumab dose. The safety run-in consists of 6 patients. In total, 18 and 25 evaluable patients for cervical and endometrial carcinoma respectively are foreseen to enroll. No sample size is determined for uterine sarcoma due to its rarity. The primary objective is objective response rate at week 26 according to immune-related response criteria. Secondary objectives include safety, objective response rate at week 26 according to RECIST v1.1, best overall response, progression-free survival, overall survival and quality of life. Exploratory, translational research aims to evaluate immune biomarkers, extracellular vesicles, cell death biomarkers and the gut microbiome. Discussion In this study, a combination of PD-1 blockade, radiation and immune/environmental-targeting compounds is tested, aiming to tackle the tumor microenvironment and induce anti-tumor immunity. Translational research is performed to discover biomarkers related to the mode of action of the combination. Trial registration EU Clinical Trials Register: EudraCT 2016-001569-97, registered on 19-6-2017. Clinicaltrials.gov: NCT03192059, registered on 19-6-2017.

Forensic healthcare workers deal with patients with severe psychiatric and behavioral problems that put them at an increased risk of developing work-related stress and burnout. Working with this target group of patients during the Coronavirus disease 2019 (Covid-19) pandemic with far-reaching restrictive measures can negatively affect the psychological well-being of forensic workers. Research suggests that resilience can buffer workplace stress and contribute positively to psychological well-being. However, research on resilience, psychological well-being and work-related stress among forensic healthcare workers is still lacking. Therefore, in this study, we investigated the interrelations between psychological well-being and resilience on the one hand and work-related stress and Covid-19 fear-related symptoms on the other hand. Self-report data were obtained from 318 healthcare workers (73.9% women) working in three Forensic Psychiatric Centers (M age = 44.20, SD = 14.31) and are in direct contact with forensic patients. The data were analyzed using network analysis. Consistent with previous research, the results showed that workplace stress and fear associated with the Covid-19 pandemic can be detrimental to workers' psychological well-being, while resilience can serve as a protective factor against being personally attacked or threatened by patients at the workplace. Last but not least, we identified highly central symptoms, namely tremors due to the fear of the coronavirus and anxiety when other people coughing, which would be the best candidates for future treatment targets. This knowledge can help clinicians optimize interventions to reduce workplace stress and fear due to the pandemic. Future studies should aim to replicate our findings in a larger and more representative sample of forensic healthcare workers.