Assessment of eligibility criteria in renal cell carcinoma trials evaluating systemic therapy.

OBJECTIVES: To characterise the restrictiveness of eligibility criteria in contemporary renal cell carcinoma (RCC) trials, using recommendations from the American Society of Clinical Oncology (ASCO)-Friends of Cancer Research (FCR) initiative. METHODS: vPhase I-III trials assessing systemic therapies in patients with RCC starting between 30 June 2012 and 30 June 2022 were identified. Eligibility criteria regarding brain metastases, prior or concurrent malignancies, hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, and human immunodeficiency virus (HIV) infection were identified and stratified into three groups: exclusion, conditional inclusion, and not reported. Descriptive statistics were used to determine the frequency of eligibility criteria. Fisher's exact test or chi-square test were used to calculate their associations with certain trial characteristics. RESULTS: A total of 423 RCC trials were initially identified of which 112 (26.5%) had sufficient accessible information. Exclusion of patients with HIV infection, HBV/HCV infection, brain metastases, and prior or concurrent malignancies were reported in 74.1%, 53.6%, 33.0%, and 8.0% of trials, respectively. In the context of HIV and HBV/HCV infection, patients were largely excluded from trials evaluating immunotherapy (94.4% and 77.8%, respectively). In addition, brain metastases were excluded in trials assessing targeted therapy (36.4%), combined therapy (33.3%), and immunotherapy (22.2%). Exclusion of patients with prior or concurrent malignancies was less frequently reported, accounting for 9.1%, 8.3%, and 5.6% targeted therapy, combined therapy and immunotherapy trials, respectively. CONCLUSION: A substantial proportion of RCC trials utilise restrictive eligibility criteria, excluding patients with fairly prevalent comorbidities. Implementing the ASCO-FCR recommendations will ensure resulting data are more inclusive and aligned with patient populations in the real-world.

Cue-Reactive Phenomenology Mediates the Relationship Between Positive Schizotypy and Cue-Reactive Urge to Gamble in Poker-Machine Gamblers.

Although ubiquitous in numerous nightlife cultures, poker-machines present a high risk for problematic use and addiction. Previous research has demonstrated that gambling cues (e.g., flashing lights) can activate gambling urges in poker-machine gamblers. However, the processes that contribute to the maintenance of cue-reactive urges to gamble remain unclear. Consequently, the present study explored whether positive schizotypy predicted gambling urge, and whether cue-reactive altered state of awareness, cue-reactive altered time sense, and cue-reactive absorption mediated this relationship. Seventy adults aged between 19 and 68 (M = 48.86, SD = 12.82) participated in an online cue-reactivity experiment. Participants first completed the Problem Gambling Severity Index and the Unusual Experiences subscale of the Short Oxford-Liverpool Inventory of Feelings and Experiences. Subsequently, at three time points (i.e., baseline, directly after a neutral cue, and directly after a gambling cue) participants completed the Altered State of Awareness, Altered Time Sense, and Absorption subscales of the Phenomenology of Consciousness Inventory and a visual analogue scale measuring cue-reactive urge to gamble. It was found that positive schizotypy was significantly positively correlated with cue-reactive urge to gamble. Additionally, cue-reactive altered state of awareness, cue-reactive altered time sense, and cue-reactive absorption mediated this relationship. The theoretical, clinical and practical implications are discussed.

Distress and psychosocial support seeking: A comparison of rural and metropolitan oncology patient experiences.

INTRODUCTION: Prevalence of distress in cancer patients is established at approximately 50%, yet uptake of psychosocial support is minimal. OBJECTIVE: This study aimed to understand why clinically distressed oncology patients choose not to access psychosocial support, including whether this differs by geographic location. It also aimed to determine the proportion of rural and metropolitan patients experiencing clinical levels of distress, and of these, the proportion who do not wish to access support. DESIGN: The study used a cross-sectional design. Two hundred and ninety-eight Australian cancer patients completed an online survey, including the Distress Thermometer and open-ended questions about reasons for declining support. Descriptive statistics and content analysis were used to analyse the data. FINDINGS: More than half (56%) of participants reported experiencing clinically significant levels of distress. Of these, almost half (47%) declined psychosocial support. Content analysis of reasons for declining psychosocial support resulted in six main concepts: I don't need support; I'm using personal resources to cope; negative perceptions and attitudes; life doesn't stop for cancer; I'm focussed on fighting cancer; and systemic barriers. Rural cancer patients most often indicated using personal resources to cope, while metropolitan participants most commonly indicated not needing support. A range of subconcepts were also identified. Perceiving distress as manageable or transient was almost exclusively reported by metropolitan participants, while stigma was almost exclusively reported by rural participants. DISCUSSION: The findings provided greater depth of insight into reasons cancer patients decline psychosocial support and identified several qualitative differences in the reasons provided by metropolitan and rural patients. Recommendations are provided for clinicians, in particular for clinicians who work with rural cancer patients and their supporters. CONCLUSION: These findings can inform equitable resourcing of psychosocial support in rural areas and the adaptation of psychosocial interventions to be more flexible and responsive to individual needs. This may help increase patient uptake of support, particularly in rural areas.

Real-World Outcomes of Latinx Versus Non-Latinx Patients Treated With First-Line Immunotherapy for Metastatic Renal-Cell Carcinoma.

BACKGROUND: There are limited data regarding the impact of ethnicity among patients receiving immune checkpoint inhibitors. We evaluated real-world outcomes between Latinx and non-Latinx patients with metastatic renal-cell carcinoma (mRCC) treated with first-line nivolumab/ipilimumab within 2 different healthcare settings. METHODS: We performed a retrospective analysis of patients with mRCC who received nivolumab/ipilimumab within the Los Angeles County Department of Health Services (LAC-DHS), a safety-net healthcare system, and the City of Hope Comprehensive Cancer Center (COH), a tertiary oncology center, between January 1, 2015 and December 31, 2021. Progression-free survival (PFS) and overall survival (OS) were determined using the Kaplan-Meier method and covariates were adjusted using multivariate Cox proportional hazards regression. RESULTS: Of 94 patients, 40 patients (43%) were Latinx while the remainder were non-Latinx (44 pts [46%] White, 7 pts [7%] Asian, and 3 pts [3%] Other). Fifty (53%) and 44 (47%) patients received their care at COH and LAC-DHS, respectively. Most Latinx patients (95%) were treated at LAC-DHS, and most non-Latinx patients (89%) were treated at COH. Pooled analysis by ethnicity demonstrated significantly shorter PFS in Latinx versus non-Latinx patients (10.1 vs. 25.2 months, hazard ratios [HR] 3.61, 95% CI 1.96-6.66, P ≤ .01). Multivariate analysis revealed a HR of 3.41 (95% CI 1.31-8.84; P = .01). At a median follow-up of 11.0 months, the median OS was not reached in either arm at the time of data cutoff. CONCLUSION: Latinx patients with mRCC had a shorter PFS treated with frontline nivolumab/ipilimumab compared to their non-Latinx counterparts. No difference was observed in OS although these data were immature. Larger studies are needed to further interrogate the social and economic determinants of ethnicity on clinical outcomes in mRCC.

Twelve-Month Follow-up of the Immune Response After COVID-19 Vaccination in Patients with Genitourinary Cancers: A Prospective Cohort Analysis.

BACKGROUND: Vaccinations against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have had a transformative impact on morbidity and mortality. However, the long-term impact of vaccination on patients with genitourinary cancers is currently unknown. MATERIALS AND METHODS: This study aimed to assess seroconversion rates in patients with genitourinary cancers receiving COVID-19 vaccination. Patients with prostate cancer, renal cell carcinoma, or urothelial cancer who had not been vaccinated for COVID-19 were included. Blood samples were obtained at baseline and after 2, 6, and 12 months of one dose of an FDA-approved COVID-19 vaccine. Antibody titer analysis was performed using the SCoV-2 Detect IgG ELISA assay, and the results were reported as immune status ratio (ISR). A paired t-test was used for comparison of ISR values between timepoints. In addition, T-cell receptor (TCR) sequencing was performed to assess for differences in TCR repertoire 2 months after vaccination. RESULTS: Out of 133 patients enrolled, 98 baseline blood samples were collected. At 2-, 6-, and 12-month time points 98, 70, and 50 samples were collected, respectively. Median age was 67 (IQR, 62-75), with the majority of patients diagnosed with prostate (55.1%) or renal cell carcinoma (41.8%). Compared to baseline (0.24 [95% CI, 0.19-0.31]) a significant increase in the geometric mean ISR values was observed at the 2-month timepoint (5.59 [4.76-6.55]) (P < .001). However, at the 6-month timepoint, a significant decrease in the ISR values was observed (4.66 [95% CI, 4.04-5.38]; P < .0001). Notably, at the 12-month timepoint, the addition of a booster dose resulted in an absolute increase in the ISR values compared to those who did not receive a booster dose (P = .04). CONCLUSIONS: Only a minority of patients with genitourinary cancers did not ultimately achieve satisfactory seroconversion after receiving commercial COVID-19 vaccination. Cancer type or treatment rendered did not appear to affect the immune response mounted after vaccination.

Systemic Therapy for Chondrosarcoma.

OPINION STATEMENT: Clinical trial enrollment should be actively encouraged in all patients diagnosed with advanced, surgically unresectable chondrosarcoma (CS) due to the lack of consensus treatment recommendations. In the absence of an appropriate clinical trial, treatments are determined based on histologic subtype of CS with consideration given to targetable mutations (i.e., IDH1). Conventional CS is inherently resistant to cytotoxic chemotherapy and patients may benefit from antiangiogenic therapy including off-label use of pazopanib. Individuals harboring an IDH1 mutation may derive clinical benefit from ivosidenib, an IDH1 inhibitor. Upon progression and with functional status permitting, alternative options include mTOR inhibitors (sirolimus, temsirolimus) or other tyrosine kinase inhibitors (dasatinib), though no clear sequencing data exists. For dedifferentiated CS, conventional chemotherapies with osteosarcoma-like regimens are upfront options although prospective data is limited with minimal overall benefit. Alternative treatment options include immunotherapy with pembrolizumab or ivosidenib in IDH1-mutant, dedifferentiated CS, but questionable efficacy was observed in small sample sizes with either approach. In mesenchymal CS, treatment with Ewing sarcoma-like chemotherapy regimens may be considered, although data supporting its use is even more limited given its rarity.

Cue-Reactive Imagery Mediates the Relationships of Reward Responsiveness with Both Cue-Reactive Urge to Gamble and Positive Affect in Poker-Machine Gamblers.

Previous research has demonstrated that gambling cues (e.g., flashing lights on poker-machines) can trigger an urge to gamble in poker-machine gamblers. However, the psychological mechanisms that promote the urge to gamble remain poorly understood. The present study explored whether reward responsiveness predicted urge to gamble and positive affect, and whether cue-reactive rationality, volitional control and imagery mediated these relationships. Ninety-three (45% male and 55% female) Australian regular poker-machine gamblers aged between 18 and 77 participated in an online cue-reactivity experiment. Participants initially completed the Problem Gambling Severity Index and Reward Responsiveness scale. Subsequently, at three time points (i.e., baseline, directly after a neutral cue and directly after a gambling cue) participants completed the rationality, volitional control and imagery subscales of the Phenomenology of Consciousness Inventory and two visual analogue scales that measured urge to gamble and positive affect. Analyses indicated that gambling cues triggered statistically significant increases in both urge to gamble and positive affect and these variables were statistically significantly positively correlated with reward responsiveness. Furthermore, only cue-reactive imagery mediated the relationships between reward responsiveness and the two outcome variables (i.e., cue-reactive urge to gamble and positive affect). These findings highlight the potential importance of targeting reward responsiveness and cue-reactive mental imagery in the context of exposure therapies for poker-machine problem gamblers.

The relationship between early maladaptive schemas and interpersonal problems: A meta-analytic review.

Early maladaptive schemas (EMSs) have been hypothesized to be associated with interpersonal problems. Furthermore, a stronger contention is that EMSs impact negatively on, or cause, interpersonal problems. The aims of this meta-analysis were (a) to assess the strength of the association between EMSs and interpersonal problems, (b) clarify which EMSs are most strongly associated with interpersonal problems, (c) examine any possible moderators on the relationship between EMSs and interpersonal problems, and (d) examine whether any empirical evidence exists supporting a causal relationship between EMSs and interpersonal problems. A comprehensive systematic literature search and meta-analysis were conducted using the PRISMA guidelines for systematic reviews. A total of 49 empirical studies were reviewed investigating EMSs and interpersonal problems. EMSs were found to have a moderate positive association with interpersonal problems with different EMSs having small to moderate effect sizes. To date, there has been limited evidence supporting a causal effect of EMSs on interpersonal problems. Possible limitations and avenues for future research were discussed.

Trait Mindfulness, Problem-Gambling Severity, Altered State of Awareness and Urge to Gamble in Poker-Machine Gamblers.

In Australia, poker-machine gamblers represent a disproportionate number of problem gamblers. To cultivate a greater understanding of the psychological mechanisms involved in poker-machine gambling, a repeated measures cue-reactivity protocol was administered. A community sample of 38 poker-machine gamblers was assessed for problem-gambling severity and trait mindfulness. Participants were also assessed regarding altered state of awareness (ASA) and urge to gamble at baseline, following a neutral cue, and following a gambling cue. Results indicated that: (a) urge to gamble significantly increased from neutral cue to gambling cue, while controlling for baseline urge; (b) cue-reactive ASA did not significantly mediate the relationship between problem-gambling severity and cue-reactive urge (from neutral cue to gambling cue); (c) trait mindfulness was significantly negatively associated with both problem-gambling severity and cue-reactive urge (i.e., from neutral cue to gambling cue, while controlling for baseline urge); and (d) trait mindfulness did not significantly moderate the effect of problem-gambling severity on cue-reactive urge (from neutral cue to gambling cue). This is the first study to demonstrate a negative association between trait mindfulness and cue-reactive urge to gamble in a population of poker-machine gamblers. Thus, this association merits further evaluation both in relation to poker-machine gambling and other gambling modalities.

Cue-Reactive Rationality, Visual Imagery and Volitional Control Predict Cue-Reactive Urge to Gamble in Poker-Machine Gamblers.

Poker-machine gamblers have been demonstrated to report increases in the urge to gamble following exposure to salient gambling cues. However, the processes which contribute to this urge to gamble remain to be understood. The present study aimed to investigate whether changes in the conscious experience of visual imagery, rationality and volitional control (over one's thoughts, images and attention) predicted changes in the urge to gamble following exposure to a gambling cue. Thirty-one regular poker-machine gamblers who reported at least low levels of problem gambling on the Problem Gambling Severity Index (PGSI), were recruited to complete an online cue-reactivity experiment. Participants completed the PGSI, the visual imagery, rationality and volitional control subscales of the Phenomenology of Consciousness Inventory (PCI), and a visual analogue scale (VAS) assessing urge to gamble. Participants completed the PCI subscales and VAS at baseline, following a neutral video cue and following a gambling video cue. Urge to gamble was found to significantly increase from neutral cue to gambling cue (while controlling for baseline urge) and this increase was predicted by PGSI score. After accounting for the effects of problem-gambling severity, cue-reactive visual imagery, rationality and volitional control significantly improved the prediction of cue-reactive urge to gamble. The small sample size and limited participant characteristic data restricts the generalizability of the findings. Nevertheless, this is the first study to demonstrate that changes in the subjective experience of visual imagery, volitional control and rationality predict changes in the urge to gamble from neutral to gambling cue. The results suggest that visual imagery, rationality and volitional control may play an important role in the experience of the urge to gamble in poker-machine gamblers.

Cue-Reactive Altered State of Consciousness Mediates the Relationship Between Problem-Gambling Severity and Cue-Reactive Urge in Poker-Machine Gamblers.

In order to enhance our understanding of the nature of poker-machine problem-gambling, a community sample of 37 poker-machine gamblers (M age = 32 years, M PGSI = 5; PGSI = Problem Gambling Severity Index) were assessed for urge to gamble (responses on a visual analogue scale) and altered state of consciousness (assessed by the Altered State of Awareness dimension of the Phenomenology of Consciousness Inventory) at baseline, after a neutral cue, and after a gambling cue. It was found that (a) problem-gambling severity (PGSI score) predicted increase in urge (from neutral cue to gambling cue, controlling for baseline; sr (2) = .19, p = .006) and increase in altered state of consciousness (from neutral cue to gambling cue, controlling for baseline; sr (2) = .57, p < .001), and (b) increase in altered state of consciousness (from neutral cue to gambling cue) mediated the relationship between problem-gambling severity and increase in urge (from neutral cue to gambling cue; κ(2) = .40, 99 % CI [.08, .71]). These findings suggest that cue-reactive altered state of consciousness is an important component of cue-reactive urge in poker-machine problem-gamblers.

Development and validation of the Informal Supporter Readiness Inventory (ISRI).

OBJECTIVE: This article outlines the development and validation of the Informal Supporter Readiness Inventory (ISRI), based on the model developed by the present authors in (Davies, 2023). This scale assesses the readiness of informal supporters to intervene or provide support in situations of intimate partner violence (IPV). METHODS: The research followed a three-phased procedure of item development, scale development, and scale evaluation; adhering to best practice guidelines for psychometric development and validation. This process provided empirical substantiation for the domains of the Model of Informal Supporter Readiness (Davies, 2023). RESULTS: The 57-item ISRI incorporates four primary factors: normative, individual, goodman-emotional, and situational-assessment. These factors demonstrated robust internal consistency and factor structures. Additionally, the ISRI evidenced strong test-retest reliability, and both convergent and divergent validity. Although aligning closely with the Model of Informal Supporter Readiness, the scale revealed a nuanced bifurcation of situational factors into situational-emotional and situational-assessment. DISCUSSION: The ISRI offers an important advancement in IPV research by highlighting the multifaceted nature of informal supporter intervention. The findings have several implications, from tailoring individualised supportive interventions to strengthening support networks and empowering survivors. The present study's findings underscore the potential of adopting a social network-oriented approach to interventions in IPV scenarios. Applications for research and practice are discussed.

The Extended Social Network-Oriented Support Model for Intimate Partner Violence Survivors.

Intimate partner violence (IPV) transcends cultural, social and economic boundaries, affecting countless individuals globally. Recovery for IPV survivors is supported by their social networks, yet the readiness of these networks is often poorly understood. This perspective paper proposes an extension to existing network-oriented IPV support models by integrating a focus on the readiness and well-being of informal supporters towards the goal of enhancing IPV survivor recovery through effective networks. This paper presents the extended social network-oriented support model, incorporating the Informal Supporter Readiness Inventory. This tool assesses the readiness of informal supporters, incorporating factors, such as normative and individual beliefs about IPV, and context-specific factors, to enable identification and targeted assistance where needed. Additionally, the proposed model emphasises the importance of supporting the well-being of informal supporters, who frequently endure elevated levels of stress, anxiety and depression. By integrating these elements, the extended social network-oriented support model is designed to help professional supporters foster resilient and sustainable support networks for IPV survivors, with potential applicability across various healthcare disciplines. The extended model underscores the necessity of assessing and fostering both the readiness and well-being of informal supporters to enhance the recovery journey for IPV survivors.

Barriers to Clinical Trial Implementation Among Community Care Centers.

Importance: While an overwhelming majority of patients diagnosed with cancer express willingness to participate in clinical trials, only a fraction will enroll onto a research protocol. Objective: To identify critical barriers to trial enrollment to translate findings into actionable practice changes that increase cancer clinical trial enrollment. Design, Setting, and Participants: This survey study included designated site contacts at oncology practices with teams who were highly involved with the Association of Community Cancer Centers (ACCC) Community Oncology Research Institute (ACORI) clinical trials activities, all American Society of Clinical Oncology (ASCO)-ACCC collaboration pilot sites, and/or sites providing care to at least 25% African American and Hispanic residents. To determine participation trends among health care practices in oncology-focused research, identify barriers to clinical trial implementation and operation, and establish unmet needs for cancer clinics interested in trial participation, a 34-question survey was designed. Survey questions were defined within 3 categories: cancer center demographic characteristics, clinical trial characteristics, and referral practices. The survey was distributed through email and was open from June 20 through October 5, 2022. Main Outcomes and Measures: Participation in and barriers to conducting oncology trials in different community oncology settings. Results: The survey was distributed to 100 cancer centers, with completion by 58 centers (58%) across 25 states. Fifty-two centers (88%) reported that they conduct therapeutic clinical trials, of which 33 (63%) were from urban settings, 11 (21%) were from suburban settings, and 8 (15%) were from rural settings. Only 25% of rural practices (2 of 8) offered phase 1 trials, compared with 67% of urban practices (22 of 33) (P = .01). Respondents noted challenges in conducting research, including patient recruitment (27 respondents [52%]), limited staffing (27 [52%]), and nonrelevant trials for their patient population (25 [48%]). Among sites not offering therapeutic trials, barriers to research conduct included limited infrastructure, funding, and staffing. Most centers (46 of 58 [79%]) referred patients to outside centers for clinical trial enrollment, particularly in the context of late-stage disease and/or disease progression. Only 17 of these sites (37%) had established protocols for patient follow-up subsequent to outside referral. Conclusions and Relevance: In this national survey study of barriers to clinical trial implementation, most sites offered therapeutic trials, but there were significant disparities in trial availability across care settings. Furthermore, fundamental deficiencies in trial support infrastructure limited research activity, including within programs currently conducting research as well as at sites interested in future clinical research opportunities. These results identify crucial unmet needs for oncology clinics to effectively offer clinical trials to patients seeking care.

A systematic review of informal supporters of intimate partner violence survivors: the intimate partner violence model of informal supporter readiness.

Background: Intimate partner violence (IPV) is a serious public health issue that consists of physical, sexual, and psychological violence perpetrated by a current or former partner. Informal supporters (e.g., family and friends) of survivors are more often witness to IPV or are the first people a survivor will disclose abuse to and are more able to provide consistent ongoing support than professional services. Therefore, greater understanding of informal supporters is warranted to aid in reducing the risks experienced by survivors. This systematic review aimed to: (1) identify factors associated with either an increase or decrease in helping behaviour toward a survivor, (2), identify the most effective self-care strategies employed by informal supporters, and (3) consider the current theoretical approaches used to understand informal supporters help-giving behavioural intention. Methods: A systematic literature search was conducted following the PRISMA guidelines. The search included English language articles published between 2005 and 2021 in the databases Psych Articles, Scopus, Proquest Social Services Abstracts, and Ebscohost. Studies were included if the primary research aims explored the motivators and inhibitors of helping intention or self-care strategies of adult social network members of adult IPV survivors. Two reviewers independently screened all identified articles for inclusion suitability. Results: One hundred and twenty articles were subjected to full text screening resulting in 31 articles being identified as meeting inclusion criteria. Synthesis of the findings identified the following three key areas associated with help-giving behavioural intentions: normative factors, individual factors, and situational factors. There were no articles identified that considered self-care of informal supporters. Of the 31 articles, 22 had a theoretical underpinning. None of the utilised theories explained all three of the identified factors of help-giving behavioural intention. Conclusion: These results are integrated into a proposed Intimate Partner Violence Model of Informal Supporter Readiness (IPV-MISR), incorporating the identified factors associated with help-giving behavioural intention. This model provides a framework for conceptualising the readiness of an informal supporter to provide adequate support to IPV survivors. The model extends existing theoretical standpoints and has utility in both practice and research.

Bioinformatic Analysis of Recurrent Genomic Alterations and Corresponding Pathway Alterations in Ewing Sarcoma.

Ewing Sarcoma (ES) is an aggressive, mesenchymal malignancy associated with a poor prognosis in the recurrent or metastatic setting with an estimated overall survival (OS) of <30% at 5 years. ES is characterized by a balanced, reciprocal chromosomal translocation involving the EWSR1 RNA-binding protein and ETS transcription factor gene (EWS-FLI being the most common). Interestingly, murine ES models have failed to produce tumors phenotypically representative of ES. Genomic alterations (GA) in ES are infrequent and may work synergistically with EWS-ETS translocations to promote oncogenesis. Aberrations in fibroblast growth factor receptor (FGFR4), a receptor tyrosine kinase (RTK) have been shown to contribute to carcinogenesis. Mouse embryonic fibroblasts (MEFs) derived from knock-in strain of homologous Fgfr4G385R mice display a transformed phenotype with enhanced TGF-induced mammary carcinogenesis. The association between the FGFRG388R SNV in high-grade soft tissue sarcomas has previously been demonstrated conferring a statistically significant association with poorer OS. How the FGFR4G388R SNV specifically relates to ES has not previously been delineated. To further define the genomic landscape and corresponding pathway alterations in ES, comprehensive genomic profiling (CGP) was performed on the tumors of 189 ES patients. The FGFR4G388R SNV was identified in a significant proportion of the evaluable cases (n = 97, 51%). In line with previous analyses, TP53 (n = 36, 19%), CDK2NA/B (n = 33, 17%), and STAG2 (n = 22, 11.6%) represented the most frequent alterations in our cohort. Co-occurrence of CDK2NA and STAG2 alterations was observed (n = 5, 3%). Notably, we identified a higher proportion of TP53 mutations than previously observed. The most frequent pathway alterations affected MAPK (n = 89, 24% of pathological samples), HRR (n = 75, 25%), Notch1 (n = 69, 23%), Histone/Chromatin remodeling (n = 57, 24%), and PI3K (n = 64, 20%). These findings help to further elucidate the genomic landscape of ES with a novel investigation of the FGFR4G388R SNV revealing frequent aberration.

Assessing the relationship between early maladaptive schemas and interpersonal problems using interpersonal scenarios depicting rejection.

BACKGROUND: Early maladaptive schemas (EMSs) have been theorised to contribute to reoccurring interpersonal problems. This study developed a novel experimental paradigm that aimed to assess if EMSs moderate the impact of interpersonal situations on interpersonal responses by manipulating the degree of rejection in a series of interpersonal vignettes depicting acceptance, ambiguous rejection and rejection. METHOD: In a sample of 158 first-year psychology students (27.2% male; 72.2% female; 0.6% other) participant responses to interpersonal scenarios were measured including degree of perceived rejection, emotional distress, conviction in varying cognitive appraisals consistent with attribution theory and behavioural responses to scenarios. Qualitative data was analysed using inductive content analysis and statistical analyses were conducted using multi-level mixed effect linear and logistic regression models using the software Jamovi. RESULTS: People reporting higher EMSs reported increased emotional distress (F(1, 156) = 24.85, p < .001), perceptions of rejection (F(1, 156) = 34.33, p < .001), self-blame (F(1, 156) = 53.25, p < .001), other-blame (F(1, 156) = 13.16, p < .001) and more intentional (F(1, 156) = 9.24, p = .003), stable (F(1, 156) = 25.22, p < .001) and global (F(1, 156) = 19.55, p < .001) attributions but no differences in reported behavioural responses. The results also supported that EMSs moderate the relationship between interpersonal rejection and perceptions of rejection (F(2, 1252) = 18.43, p < .001), emotional distress (F(2, 1252) = 12.64, p < .001) and self-blame (F(2, 1252) = 14.00, p < .001). CONCLUSION: Together these findings suggest that people with EMSs experience increased distress and select negative cognitions in situations where there are higher levels of rejection but that distress and negative cognitions are generally higher in people with EMSs irrespective of the situation.

Managing Metastatic Renal Cell Carcinoma after Progression on Immunotherapy.

Treatment of metastatic renal cell carcinoma (mRCC) after first-line immune checkpoint inhibitors (ICIs) lacks standardization, with limited evidence from small trials and retrospective data. Vascular endothelial growth factor receptor (VEGFR) inhibition through tyrosine kinase inhibitors (TKIs) is the most widely adopted second-line treatment. Encouraging results have been seen with VEGFR-TKIs in the second-line after exposure to an ICI-based combination, achieving a response rate of 30%, and 75% of patients achieving disease control. Rechallenge with ICI alone seems safe but has limited clinical benefit. Promising regimens with combination therapies and novel drugs are being evaluated in phase 3 trials.

Role of immunotherapy in chondrosarcoma: A case report and review of the literature.

Chondrosarcomas (CSs) consist of a heterogenous group of primary bone cancers arising from malignant cells which produce cartilaginous matrix. As the second most common primary bone cancer, CS are often resistant to systemic chemotherapy due to poor vascularization, slow proliferation, and expression of multidrug-resistant pumps. Immune checkpoint inhibitors have transformed the field of oncology and are now designated as frontline therapy for many solid tumor cancers. Several studies have demonstrated increased expression of programed cell death 1 (PD-1) and PD-L1 in CS tissue in vitro, which has led to the development of multiple clinical trials for immunotherapy in patients with aggressive CS. In this review, we highlight the ongoing investigation into the role for immunotherapy in CS. We also report the case of a 44-year-old female with a history of stage IV primary CS of the right shoulder who underwent radical resection with recurrence and demonstrated a spectacular sustained response to pembrolizumab at our center. Our review highlights the need for further studies investigating the role of immunotherapy in the treatment of aggressive bone sarcomas that are resistant to standard surgical resection, chemotherapy, and radiation treatment.

Chondrosarcoma is a cancer of the cells that make cartilage and is often removed surgically. However, when the cancer spreads to other organs such as the lungs or are in areas unreachable by surgeons, there are not many effective treatments. While targeted treatments are in development, many of them have unclear effectiveness. A new and rapidly growing area of cancer treatment is known as immunotherapy, which uses the body's own immune system to kill cancer cells. In this review, we discuss trials in using immunotherapy against aggressive forms of chondrosarcoma. We also present the case of a patient where an immunotherapy agent called pembrolizumab was highly effective in preventing disease progression.

Stereotactic Body Radiation Therapy for Oligoprogressive and Oligorecurrent Non-Small-Cell Lung Cancer.

BACKGROUND AND PURPOSE: The role of stereotactic body radiation therapy (SBRT) in oligoprogressive non-small-cell lung cancer (NSCLC) is controversial. We evaluated whether SBRT in a subset of patients with oligoprogressive or oligorecurrent NSCLC offers a durable response, obviating the need to change systemic therapy. METHODS: A retrospective analysis of 168 NSCLC patients who underwent SBRT for oligoprogressive or oligorecurrent disease was performed. Oligoprogression was defined as progression in ≤5 lesions during or after systemic therapy following an initial complete or partial response. Oligorecurrence was defined as progression while off systemic therapy. Progression-free survival (PFS), overall survival (OS) and time to next treatment or death (TNT-D) were estimated. RESULTS: Median age was 68 years. Sixty-seven percent of patients were on systemic therapy at the time of progression. Progression at the primary site was present in 31% of the patients. The number of sites of metastatic progression was 0 to 2 in 76% and 3 to 5 in 24% of the patients. Two-year OS and PFS were 56% (95%CI 46%-64%) and 14% (95%CI 8%-21%), respectively. Median TNT-D was 9 months (95%CI 6-11). No grade 4 or 5 toxicity was seen. In multivariable analysis, patients with 3 to 5 sites of metastatic progression had worse OS (HR 2.6, 95%CI 1.5-4.3, P < .001) and shorter TNT-D (HR 1.7, 95%CI 1.1-2.5, P = .01) than those with 0 to 2 sites. CONCLUSION: SBRT is a safe and viable treatment option for oligoprogressive and oligorecurrent NSCLC. Patients with 0 to 2 sites had better OS and longer TNT-D compared to those with 3 to 5 lesions.