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Randomized Controlled Trial of Acceptance and Commitment Therapy for Fatigue Interference With Functioning in Metastatic Breast Cancer

PURPOSE Fatigue is a highly prevalent and disabling symptom for patients with metastatic breast cancer (MBC). Evidence-based interventions for managing fatigue in advanced cancer populations are lacking. This phase II randomized controlled trial tested the effect of acceptance and commitment therapy (ACT) on fatigue interference with functioning in patients with MBC. METHODS Eligible patients were women with stage IV breast cancer who had moderate to severe fatigue interference. Patients completed a baseline assessment that included self-report measures of fatigue interference with activities, mood, and cognition (primary outcome) and sleep interference with functioning, engagement in daily activities, and quality of life (QOL; secondary outcomes). Then patients were randomly assigned to six weekly telephone-delivered sessions of either ACT (n = 116) or education/support (n = 120). Follow-up assessments occurred at 2 weeks, 3 months, and 6 months postintervention (means, 9.69, 20.51, and 33.59 weeks postbaseline, respectively). RESULTS Linear mixed model analyses showed that compared with patients in the education/support condition, patients in the ACT condition reported significantly less fatigue interference ( P = .018). These results were significant at 2 weeks and 6 months postintervention. ACT's effect on sleep interference was not statistically significant after the Sidak adjustment for multiple comparisons ( P = .037). ACT patients showed a steady decline in sleep interference, a trend that was not found for education/support patients. Engagement in daily activities and QOL did not significantly differ between study groups, except for functional QOL ( P = .006). Compared with education/support patients, ACT patients showed significantly better functional QOL at 2 weeks and 6 months postintervention. CONCLUSION Results suggest that a brief, telephone-delivered ACT intervention can reduce fatigue interference with functioning in patients with MBC.

A novel MRI contrast agent NaGdF4@PEG–CLS@MMP-13 NPs for detecting articular cartilage injury

Cyclin-Dependent Kinase 4/6 Inhibition as a Novel Therapy for Peritoneal Mucinous Carcinomatosis With GNAS Mutations

PURPOSE Mucinous neoplasms of the gastrointestinal tract are characterized by a propensity for metastasis to the peritoneum, resulting in peritoneal mucinous carcinomatosis (PMC). A subset of these tumors, most often originating in the appendix, harbor mutations in the GNAS oncogene. While the natural history of GNAS -mutant PMC varies, patient outcomes are generally poor, as is response to cytotoxic chemotherapy. The purpose of this study was to evaluate the clinical efficacy of single-agent palbociclib, a cyclin-dependent kinase (CDK)4/6 inhibitor, in patients with GNAS -mutant PMC. PATIENTS AND METHODS We enrolled 16 patients with PMC in a single-arm personalized cancer therapy trial. For all patients, tumor tissue and/or circulating tumor DNA genomic profiling using next-generation sequencing and, when possible, PD-L1 expression, tumor mutational burden, and microsatellite instability status was assessed. Twelve of 16 patients had previous disease progression on at least one previous line of chemotherapy. The primary tumor was appendix in 13 patients, unknown in two patients, and pancreas in one patient. Eleven cases were classified as low grade, and five as high grade. RESULTS In 13 of 16 patients, we observed a decrease in carcinoembryonic antigen (CEA), and in six patients, the CEA declined by >50%. As measured by clinical and modified peritoneal RECIST criteria, 50% of evaluable patients had stable disease after 12 months of palbociclib. At a median follow-up of 17.6 months, median survival has not been reached. Clinical response to CDK4/6 inhibition was mirrored in tumors with GNAS mutation and mucinous histology using an ex vivo preclinical platform. CONCLUSION CDK4/6 inhibition with palbociclib had clinical activity in PMC characterized by mutations in GNAS that was superior to that previously reported with cytotoxic chemotherapy. CDK4/6 inhibition is a novel therapeutic strategy worthy of further evaluation in this subgroup of gastrointestinal neoplasms.

Study on hydration mechanism and ratio optimization of slag powder modified high-water material

Second MEK Inhibitor Shows Promise in Neurofibromatosis Type 1 With Symptomatic Plexiform Neurofibromas Signaling Hope for Other RASopathies

Author Correction: Sex disparities in outcomes among hospitalizations for heart failure

Germline and Somatic Genomic Testing for Metastatic Prostate Cancer: ASCO Guideline

ASCO Guidelines provide recommendations with comprehensive review and analyses of the relevant literature for each recommendation, following the guideline development process as outlined in the ASCO Guidelines Methodology Manual . ASCO Guidelines follow the ASCO Conflict of Interest Policy for Clinical Practice Guidelines . Clinical Practice Guidelines and other guidance (“Guidance”) provided by ASCO is not a comprehensive or definitive guide to treatment options. It is intended for voluntary use by clinicians and should be used in conjunction with independent professional judgment. Guidance may not be applicable to all patients, interventions, diseases or stages of diseases. Guidance is based on review and analysis of relevant literature, and is not intended as a statement of the standard of care. ASCO does not endorse third-party drugs, devices, services, or therapies and assumes no responsibility for any harm arising from or related to the use of this information. See complete disclaimer in Appendix 1 and 2 (online only) for more . PURPOSE To evaluate evidence on germline and somatic genomic testing for patients with metastatic prostate cancer and provide recommendations. METHODS A systematic review by a multidisciplinary panel with patient representation was conducted. The PubMed database was searched from January 2018 to May 2024. Articles were selected for inclusion if they reported on patients with metastatic prostate cancer who received a germline or somatic genomic test and/or made comparisons between those tests, reported detection rates, prognostic information, or treatment implications. RESULTS A total of 1,713 papers were identified in the literature search. After applying the eligibility criteria, 14 remained: eight systematic reviews and six clinical trials. RECOMMENDATIONS Patients with metastatic prostate cancer should undergo both germline and somatic DNA sequencing using panel-based assays. These tests can guide the use of poly(ADP-ribose) polymerase inhibitors, which have a survival benefit in metastatic castration-resistant prostate cancer. In addition, germline testing may have screening implications for additional cancers for patients and cascade testing implications for family members. The data supporting when to perform repeat testing and optimal tissue type to use (eg, primary tumor v metastatic biopsy versus circulating tumor DNA [ctDNA] testing) are more limited, but this panel recommends considering retesting in patients whose results were previously negative or uninformative, and to consider either a metastatic biopsy or ctDNA when a significant change in clinical status occurs. Next-generation genomic sequencing findings that are associated with prognostic only (and not predictive) value should not be used to guide treatment outside of a clinical trial. Additional information is available at www.asco.org/genitourinary-cancer-guidelines .

Gender-differences in imaging phenotypes of osteoarthritis in the osteoarthritis initiative

Abstract In osteoarthritis (OA) research it is increasingly recognized that stratification according to disease phenotypes is essential for optimizing treatment regimens. Gender-specific differences in clinical OA manifestations have been identified, and this analysis aimed to assess whether these differences extend to imaging phenotypes. From the Osteoarthritis Initiative database 2523 participants (1409 women and 1114 men) with completed 3T MRI and whole-organ magnetic resonance imaging scores (WORMS) of the right knee at baseline were included. Imaging phenotypes were assigned based on modified Rapid OsteoArthritis MRI Eligibility Score: the inflammatory, meniscus-cartilage, and bone phenotype. Logistic regression was performed to investigate the effect of gender on phenotype, independent of BMI, race, Kellgren & Lawrence (KL) grade and level of physical activity. Female gender was independently associated with lower odds for the meniscus-cartilage (OR 0.61, 95%CI 0.47–0.80, p < 0.001) but not for the inflammatory (OR 1.04, 95%CI 0.89–1.24, p = 0.697) or the subchondral bone phenotype (OR 1.13, 95%CI 0.95–1.36, p = 0.166). This difference highlights an opportunity for future refinements to better accommodate gender/sex differences in disease trajectories while investigating different treatment regimes in knee OA.

Second Primary Cancer Risks After Breast Cancer in <i>BRCA1</i> and <i>BRCA2</i> Pathogenic Variant Carriers

PURPOSE Second primary cancer (SPC) risks after breast cancer (BC) in BRCA1/BRCA2 pathogenic variant (PV) carriers are uncertain. We estimated relative and absolute risks using a novel linkage of genetic testing data to population-scale National Disease Registration Service and Hospital Episode Statistics electronic health records. METHODS We followed 25,811 females and 480 males diagnosed with BC and tested for germline BRCA1/BRCA2 PVs in NHS Clinical Genetics centers in England between 1995 and 2019 until SPC diagnosis, death, migration, contralateral breast/ovarian surgery plus 1 year, or the 31st of December 2020. We estimated standardized incidence ratios (SIRs) using English population incidences, hazard ratios (HRs) comparing carriers to noncarriers using Cox regression, and Kaplan-Meier 10-year cumulative risks. RESULTS There were 1,840 BRCA1 and 1,750 BRCA2 female PV carriers. Compared with population incidences, BRCA1 carriers had elevated contralateral BC (CBC; SIR, 15.6 [95% CI, 11.8 to 20.2]), ovarian (SIR, 44.0 [95% CI, 31.4 to 59.9]), combined nonbreast/ovarian (SIR, 2.18 [95% CI, 1.59 to 2.92]), colorectal (SIR, 4.80 [95% CI, 2.62 to 8.05]), and endometrial (SIR, 2.92 [95% CI, 1.07 to 6.35]) SPC risks. BRCA2 carriers had elevated CBC (SIR, 7.70 [95% CI, 5.45 to 10.6]), ovarian (SIR, 16.8 [95% CI, 10.3 to 26.0]), pancreatic (SIR, 5.42 [95% CI, 2.09 to 12.5]), and combined nonbreast/ovarian (SIR, 1.68 [95% CI, 1.24 to 2.23]) SPC risks. Compared with females without BRCA1/BRCA2 PVs on testing, BRCA1 carriers had elevated CBC (HR, 3.60 [95% CI, 2.65 to 4.90]), ovarian (HR, 33.0 [95% CI, 19.1 to 57.1]), combined nonbreast/ovarian (HR, 1.45 [95% CI, 1.05 to 2.01]), and colorectal (HR, 2.93 [95% CI, 1.53 to 5.62]) SPC risks. BRCA2 carriers had elevated CBC (HR, 2.40 [95% CI, 1.70 to 3.40]), ovarian (HR, 12.0 [95% CI, 6.70 to 21.5]), and pancreatic (HR, 3.56 [95% CI, 1.34 to 9.48]) SPC risks. Ten-year cumulative CBC, ovarian, and combined nonbreast/ovarian cancer risks were 16%/6.3%/7.8% ( BRCA1 carriers), 12%/3.0%/6.2% ( BRCA2 carriers), and 3.6%/0.4%/4.9% (noncarriers). Male BRCA2 carriers had higher CBC (HR, 13.1 [95% CI, 1.19 to 146]) and prostate (HR, 5.61 [95% CI, 1.96 to 16.0]) SPC risks than noncarriers. CONCLUSION Survivors of BC carrying BRCA1 and BRCA2 PVs are at high SPC risk. They may benefit from enhanced surveillance and risk-reduction measures.

Factors affecting visual outcome in patients with toxic optic neuropathy caused by ethambutol

Gourmet cockatoos like to fancy up their food

Reply to: Significance of Up-Front Stereotactic Radiosurgery for Non–Small Cell Lung Cancer Patients With Brain Metastases in the Era of New Generation Tyrosine Kinase Inhibitors

Author Correction: Potential shared mechanisms in atopic dermatitis and type 2 diabetes identified via transcriptomic and machine learning approaches

ALK Tyrosine Kinase Inhibitors Induced Weight Gain: More Refined Definition of Weight Gain, Glucagon-Like Peptide-1 Agonist Treatment, and Therapeutic Drug Monitoring of <i>ALK+</i> Non–Small Cell Lung Cancer?

Utilizing non-invasive biomarkers for early and accurate differentiation of uncomplicated and complicated acute appendicitis: a retrospective cohort analysis

Reply to: Comment on the Definition and Interpretation of Complete Mesocolic Excision in the RELARC Trial

METTL3 promotes the progression of non-alcoholic fatty liver disease by mediating m6A methylation of FAS

Body Weight Gain Associated With Alectinib in Patients With ALK+ Non–Small Cell Lung Cancer: Pooled Analysis of Individual Patient Data From Four Prospective Clinical Trials

PURPOSE Weight gain is a known adverse event (AE) of alectinib. This study evaluates the progression of actual weight gain over time and explores its association with baseline characteristics. METHODS A pooled analysis of individual patient data from four clinical trials (ALEX, J-ALEX, ALUR, and ML29453) was conducted. Actual weight gain was calculated as the percent change from baseline. A linear mixed model estimated weight change over time and associations between clinical characteristics and weight change. RESULTS Follow-up weights were available for three trials (J-ALEX, ALUR, and ML29453) and missing for ALEX. In total, 2,622 weights were recorded in the first year (N = 302). At baseline, 13.6% of the Japanese population were underweight and 5.0% in the Western population. Actual weight gain of any grade was substantially higher than reported AE rates (49% v 5%), with 18% experiencing ≥10% weight gain (from median 55.6 kg to 64.1 kg). Time on alectinib was positively associated with weight change (β = .37; 95% CI, 0.24 to 0.51; P &lt; .001), corresponding to an average increase of 4.4% over 1 year. Baseline BMI was not associated with weight change in J-ALEX (β = –.090 [95% CI, –0.19 to 0.012]; P = .092) and ALUR/ML29453 (β = –.016 [95% CI, –0.077 to 0.044]; P = .59). Baseline albumin was positively associated with weight change in ALUR/ML29453 (β = .084 [95% CI, 0.027 to 0.14]; P = .0045), although not considered a clinically meaningful predictor. CONCLUSION Weight gain is under-reported as AE in trials. Actual weights showed ≥10% weight gain in 18% of patients. Clinicians should be aware of this AE, emphasizing the importance of timely identification and monitoring weight. Identifying predictors for weight gain remains challenging.

Reliability and validity of a self-developed virtual reality-based test battery for assessing motor skills in sports performance

Abstract Athletes must master various motor skills for success in their sports. To assess performance and identify areas of improvement, effective sports-motoric tests are essential. Key abilities such as reaction time, jumping, and complex movement coordination are critical. Virtual reality (VR) offers a practical, traditional equipment-free tool for assessment, though new VR-based tests must be evaluated first. We evaluated a self-developed test battery to measure reaction time (drop-bar test), jumping ability (jump and reach test), and parkour execution involving multiple complex motor tasks (with/without a virtual opponent). 32 participants completed these tests twice in real environment (RE) and VR (pre- and post-test). Intraclass correlation coefficients showed high reliability for reaction time in RE (0.858) and VR (0.888), with moderate significant correlations between them (r = .445), suggesting validity. The jump and reach test showed even better reliability (RE: 0.944, VR: 0.886) with strong correlations between RE and VR (r = .838). The parkour test showed lower reliability (x̄ 0.770), particularly for one task, with significant differences between the conditions indicating different behavior in VR. However, the addition of a virtual opponent eliminated these differences. VR appears to be a promising alternative to traditional testing methods, revealing comparable values across conditions.

Cost-Effectiveness of Total Neoadjuvant Therapy With Selective Nonoperative Management for Locally Advanced Rectal Cancer: Analysis of Data From the Organ Preservation for Rectal Adenocarcinoma Trial

PURPOSE The clinical efficacy of total neoadjuvant therapy (TNT) followed by selective nonoperative management (NOM) for locally advanced rectal cancer (LARC) was examined in the Organ Preservation for Rectal Adenocarcinoma (OPRA) trial. We investigated the cost and quality-of-life implications of adopting this treatment approach. METHODS We analyzed clinical, cost, and quality-of-life outcomes for TNT with selective NOM in comparison with chemoradiotherapy (CRT)-surgery-adjuvant chemotherapy (standard of care [SOC]) using data from OPRA, prospective cohorts, and published studies. Cost-effectiveness was evaluated over varying willingness-to-pay thresholds, and sensitivity analyses evaluated cost-effectiveness for different surgical contexts and SOC variants as well as a 10-year time horizon. RESULTS SOC was dominated by TNT with selective NOM in the base case analysis. TNT in which CRT was followed by consolidation chemotherapy (CNCT) was the least costly at $89,712 in Medicare proportionate US dollars (MP$), followed by TNT in which induction chemotherapy was followed by CRT (INCT) at MP$90,259 and SOC at MP$98,755. INCT was the preferred strategy, with 4.56 quality-adjusted life years, followed by CNCT at 4.42 and SOC at 4.29. TNT with selective NOM dominated SOC in all sensitivity analyses except when SOC omitted adjuvant chemotherapy without an impact on disease-free survival. CNCT was more cost effective than SOC when the proportion of patients entering NOM after TNT was ≥22% or ≥43%, for SOC with and without adjuvant therapy, both well below the rates seen in OPRA. CONCLUSION TNT with selective NOM is cost effective. The cost-effectiveness of CNCT with NOM relative to SOC is dependent on CNCT being made available to a sufficiently large proportion of patients with LARC. Additional analyses are needed to validate these findings from a societal perspective and in the context of other emerging treatment paradigms for LARC.