Adiposity increases the risk of post-menopausal oestrogen receptor (ER)-positive breast cancer. Inflammation, insulin, and insulin-like growth factors and sex-steroid hormones may explain this effect. We performed interventional mediation analysis to estimate the effects of hypothetical interventions targeting these pathways in females with obesity on reducing their excess risk of post-menopausal ER-positive breast cancer relative to females with normal weight.

The mediation analysis included 1260 post-menopausal females (352 with ER-positive breast cancer) from a case-cohort within the Melbourne Collaborative Cohort Study. A Monte Carlo g-computation approach with non-parametric bootstrapping was used to estimate the risk differences (RDs) and 95% confidence intervals (CIs) for interventional direct and indirect effects of hypothetical interventions that shift the joint distribution of inflammation, insulin, and sex-steroid hormone biomarkers in females with obesity to the levels observed in females with normal weight.

The estimated RD for the total effect of obesity relative to normal weight on post-menopausal ER-positive breast cancer was 16.1 (95% CI: 3.3, 30.4) per 1000 females. The RDs for indirect effects through inflammation, insulin, and sex-steroid hormones were 16.4 (95% CI: 4.3, 27.2), -8.4 (95% CI: -23.4, 1.2), and 13.0 (95% CI: 3.3, 23.7) per 1000 females, respectively. The - RD for the direct effect not via any of these three pathways was -5.3 (95% CI: -17.4, 10.6) per 1000 females.

Inflammation and sex-steroid hormones, but not insulin, contributed to the detrimental effect of adiposity on the risk of post-menopausal ER-positive breast cancer. Interventions targeting these pathways may reduce the risk for females with obesity.

The 2021 WHO classification permits diagnosis of glioblastoma in IDH-wildtype diffuse astrocytic tumors with TERT promoter mutation, EGFR amplification, or chromosome 7 gain/10 loss, even without necrosis or microvascular proliferation. The clinical behavior of these molecularly defined glioblastomas (molGBM) remains uncertain.

We retrospectively analyzed patients with molGBM treated at Hannover Medical School between 2017 and 2024. A contemporaneous histologically defined glioblastoma cohort (hisGBM) served as a control group in an approximately 1:3 ratio. MolGBM were stratified by histological grade and additionally compared with IDH-mutant astrocytomas of corresponding grade. Survival was assessed using Kaplan-Meier analysis, Cox regression, and propensity score matching.

Thirty-four patients with molGBM and 103 with hisGBM were included. Compared with hisGBM, molGBM patients were younger (p < 0.001), had higher Karnofsky Performance Status (p < 0.001), and more often presented with seizures (p = 0.006), whereas focal neurological deficits were more frequent in hisGBM. MolGBM showed less contrast enhancement (p < 0.001) and lower Ki-67 indices (p < 0.001). Median overall survival was longer in molGBM (539 vs. 374 days; p = 0.032), but tumor group was not independently associated with survival after adjustment for age and KPS (HR 1.21, 95% CI 0.77-1.90; p = 0.411). In the matched cohort, overall survival did not differ significantly (517 vs. 468 days; p = 0.670). MolGBM had inferior survival to grade-corresponding IDH-mutant astrocytomas (p < 0.001).

MolGBM shows a distinct clinical-radiological phenotype, while its apparent survival advantage over hisGBM is influenced by baseline clinical differences.

Not applicable.

Cancer patients commonly experience declines in quality of life and physical function. The Eastern Cooperative Oncology Group (ECOG) Performance Status Scale is widely used to assess functional status; however, it lacks objective measures of physical fitness. The Senior Fitness Test (SFT) provides a structured and standardized approach to objectively quantify functional abilities. This study aimed to assess functional status in cancer patients using the SFT and to examine its relationship with ECOG performance status. Patients undergoing or having completed anti-cancer treatment were recruited for this study. Multicomponent functional fitness was assessed by a trained exercise scientist using the Senior Fitness Test (SFT), including the 2-min step test, 30-s arm curl, 30-s chair stand, chair sit-and-reach, back scratch and the Timed Up-and-Go Test (TUGT). ECOG performance status was extracted from current medical records or determined by a senior researcher according to official rating guidelines. For each SFT component, individual test results were assigned an age based on normative reference values. Fitness age (FA) was calculated as the mean age across all six SFT measures. A total of n = 30 subjects (f = 15, 61.6 ± 12.1y, 16 during & 14 after therapy) participated in this study. Within the present sample, FA differed significantly from chronological age (+ 8.59 years, 95%-CI: 3.65-13.5, p<0.001) with no differences between therapy stages. Patients defined as limited in their functional status (ECOG 1&2) showed no significant difference between FA and chronological age compared to patients with ECOG stage 0 (p=0.346). The Senior Fitness Test (SFT) is a feasible tool to assess functional status in cancer patients and survivors. Participants exhibited functional deficits equivalent to nearly nine years of age advancement compared with healthy norms, which were not reflected by ECOG performance status and did not differ between patients undergoing treatment and survivors. These findings emphasize the need for objective functional assessments to guide tailored exercise interventions that address long-term limitations and improve quality of life.

Although thyroid cancer has a favorable prognosis, patients experience significant psychological distress from the time of diagnosis. The study aimed to investigate the distress level in patients diagnosed or suspected of thyroid cancer, to characterize the major sources, and to determine the independent predictors of distress.

In this prospective study, patients who had presented to our institution between January 2024 and June 2025 were asked to complete the online questionnaires including the Distress Thermometer (DT) with problem list (PL). Group comparisons between the distress and non-distress groups were performed using Chi-square and t tests. Binary logistic regression analysis was used to identify independent factors associated with distress.

A total of 649 patients were included in analysis. 524 (80.74%) patients were classified in the distress group, while 125 (19.26%) were divided into the non-distress group. The mean DT scores were 7.21 ± 1.91 and 1.40 ± 1.24, respectively. The most frequently reported problems were worry (552, 85.05%), nervousness (498, 76.73%), sadness (433, 66.72%), treatment decisions (414, 63.79%), and fears (404, 62.25%). In multivariable analysis, male sex was independently associated with higher distress, whereas older age, higher education level, and stable employment were associated with lower odds of distress. Practical and emotional problems significantly predicted distress.

Clinically significant distress is highly prevalent at the time of thyroid cancer diagnosis. DT with PL is an efficient screening instrument and could be easily incorporated into practice. Early identification and support for vulnerable patients may help alleviate psychological burden and improve overall care.

AI tools have the potential to enhance personalized clinical care, particularly in radiology. However, their integration into clinical workflows remains complex, especially in pediatric oncology, where early cancer detection is critical. Children with Li-Fraumeni syndrome (LFS), a rare cancer predisposition disorder, undergo regular surveillance whole-body magnetic resonance imaging (wbMRI), which presents an opportunity for AI-assisted tumor detection.

We evaluated the feasibility of an AI-assisted overlay for highlighting tumor-like regions in pediatric surveillance wbMRI and explored how access to the overlay influenced radiologist workflow, candidate-lesion marking behavior, follow-up recommendations, and perceived workload.

We developed a patch-based AI segmentation model trained on augmented 2D slices from 675 surveillance wbMRI volumes of pediatric patients with LFS. The model was designed to highlight regions with high tumor probability. A reader study was conducted with 2 radiologists who independently reviewed wbMRI cases both with and without AI assistance. We measured evaluation time, number and location of reader-marked candidate lesions, type of follow-up recommendation, and subjective feedback using structured questionnaires.

AI assistance altered interpretation workflows for both radiologists, with mixed effects. On average, the time required to evaluate each case increased when using the AI tool for both radiologists. However, one radiologist had an increase in the number of candidate lesion locations selected with the tool, and one had a decrease in the number of candidate lesion locations selected with the tool. Subjective feedback indicated that one of the radiologists reported lower mental demand with the AI tool, while both radiologists reported lower stress with the AI tool. Interrater variability was evident, underscoring the need for personalized calibration of AI tools.

AI-assisted wbMRI interpretation can improve tumor detection in pediatric cancer surveillance by reducing false negatives. However, its influence on workflow efficiency and interradiologist variability highlights the importance of careful implementation. Successful integration requires addressing challenges such as improving the predictive precision of AI models, offering intuitive end-user designs and instructions, and building trust in AI outputs. AI outputs can influence workflow and behavior in reader-specific ways. Clinical translation will require larger, randomized, multireader studies and model refinement to reduce false positives and quantify lesion-level reader performance. This can help ensure better patient outcomes in addition to reduced clinician burnout.

Serous endometrial intraepithelial carcinoma (SEIC) is a rare, non-invasive lesion of the endometrial epithelium, typically characterised by p53 abnormalities. Although regarded as a precursor lesion, recent classification systems increasingly position SEIC within the broader spectrum of serous carcinomas and current guidelines place non-invasive p53-abnormal serous lesions in an uncertain risk category due to limited outcome data. As a result, SEIC is not consistently addressed as a distinct diagnosis, contributing to variation in clinical management. Complete surgical staging, including pelvic and para-aortic lymph node assessment, is frequently performed, yet supporting evidence remains scarce. This study aims to collect longitudinal data to evaluate surgical management strategies in relation to clinical outcomes, survival and quality of life.

This multicentre prospective observational cohort will enrol patients diagnosed with SEIC or equivalent non-invasive serous lesions who provide informed consent. Data will be collected using electronic case report forms (Castor Electronic Data Capture). Baseline clinical, pathological, molecular and treatment data will be collected, including imaging, histopathology, immunohistochemistry and molecular classification when available. Patient-reported outcomes will be assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30), European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Endometrial Cancer Module (EORTC QLQ-EN24) and EuroQol 5-Dimension 5-Level questionnaire (EQ-5D-5L) questionnaires at baseline, 6 months, 2 years and 5 years after diagnosis. The primary outcome is progression-free survival, secondary outcomes include overall survival, health-related quality of life and adverse events. Analyses will be primarily descriptive. Survival outcomes will be estimated using Kaplan-Meier methods, with Cox proportional hazards modelling used to explore predictors of outcome where feasible.

The study will be conducted in accordance with the Declaration of Helsinki and applicable regulations. Ethical approval was obtained at the Erasmus MC (MEC-2025-0368). Results will be disseminated through peer-reviewed publications and scientific meetings.

NCT06677242.

The first therapeutic assessment of locally advanced (LA) head and neck squamous cell carcinomas (HNSCCs) is often performed 10-12 weeks after the end of chemoradiotherapy as a result of the delayed action of radiotherapy. Diagnostic uncertainty between persistent disease and treatment-related changes (oedema, necrosis) can delay confirmation of residual cancer. According to data in the literature, a correlation exists between the detection of circulating tumour DNA (ctDNA) at the end of chemoradiotherapy treatment and residual disease. However, additional data are required before this molecular tool can be used in routine clinical practice. The aim of this clinical trial (NeckTAR-IN) is to assess the usefulness of ctDNA to detect residual disease 3 months after the end of chemoradiotherapy among patients with LA HNSCC.

At M3, objective response (clinical and radiological) will be set against the detection or not of ctDNA in the blood. This is an interventional, multicentre, prospective trial, ancillary to the NeckTAR study. All the patients included in the NeckTAR study are eligible for the NeckTAR-IN study. We expect to enrol 59 patients in this ancillary trial. A blood sample will be taken 1 month and 3 months after the end of chemoradiotherapy. Approval from the ethics committee was granted on 29 August 2025.

The study protocol obtained approval from the French Ethics Committee (N°25.02461.000435). The results will be published in scientific journals and presented at conferences.

NCT07178847.

Natural killer (NK) cell-based immunotherapy is an increasingly important cancer treatment strategy because of its innate cytotoxicity, allogeneic potential, and compatibility with off-the-shelf manufacturing. We analyzed 287 clinical trials identified in the INFORMA database to characterize the global development of NK-cell therapies across phases, regions, indications, combinations, cell sources, product origins, and engineering platforms. Most trials were planned or early-phase, and combination regimens were more frequent than monotherapy. The USA, China, and South Korea led clinical activity. Hematologic malignancies remained the principal testing ground, while lung, colorectal, and other solid tumors reflected broader expansion. Platform-level analysis showed a predominance of allogeneic products and rapid growth of CAR-engineered NK-cell trials after 2020. These findings indicate a transition from proof-of-concept adoptive transfer toward standardized, genetically programmable, off-the-shelf platforms. The principal challenge is shifting from manufacturing feasibility alone to durable biological activity. Future development should align cell engineering, combination partners, translational endpoints, and biomarker-guided patient selection with specific barriers involving persistence, tumor delivery, microenvironmental fitness, and immune escape.

Nearly half of patients with melanoma do not respond to immune checkpoint inhibitors (CPIs) and many develop immune-related adverse events (irAEs), often forcing treatment discontinuation, and underscoring the need to predict and monitor outcomes. Responses may depend on both B cell and T cell activity.

We performed high-dimensional mass cytometry profiling of coexisting peripheral B cell and key T cell states in treatment-naïve patients and healthy individuals, and paired longitudinal samples from CPI-treated patients, with clinical annotations to define immune correlates of outcomes.

CPI-naive patients exhibited reduced CD19+ B cells, reduced B cell (CD21, IL-2, CXCR5) and T cell (CD38, CD27) activation markers, alongside enriched naïve (CD21lo) and double-negative (DN2)-like B cells, CD95+IL-10+plasmablasts, consistent with extrafollicular responses. Concurrently, programmed cell death protein 1 (PD-1)+ and proliferation marker protein-67 (Ki67)+ T cell expansion indicates ongoing activation with features of proliferative exhaustion. Active disease featured increased regulatory CD95 expression on B cells and expanded T follicular helper-like and activated DN (CD4-CD8-) T cells, indicating sustained antigen stimulation. Pretreatment, elevated PD-1+ T cells predicted irAEs, whereas VEGF (vascular endothelial growth factor)+TGF-β (transforming growth factor-β)+ DN T cells were enriched in patients without subsequent toxicity. Pretreatment, plasmablasts, transitional B cells, Forkhead box protein P3 (FoxP3)+ and central memory-like CD8+ T cells correlated with worse overall survival; naïve CD21lo B cells, PD-1+CD8+ T cells and CD4+follicular helper-like T cells predicted shorter event-free survival; CD4+ memory T cells predicted better prognosis, implicating dysregulated differentiation and sustained activation in adverse outcomes. On-treatment, naïve CD21hi B cells, plasmablasts, activated CD8+ and central memory-like CD4+ T cells expanded, indicating de novo humoral responses and cytotoxic T cell invigoration. On-treatment, increased class-switched memory (IgG2+) B and activated T cells predicted improved survival, while persistent naïve and DN B cells were associated with poorer outcomes. Anti-PD-1 monotherapy expanded naïve (CD21hi) B cells and global T cells. Anti-PD-1/anti-LAG-3 (lymphocyte-activation gene 3) combination contracted memory B cells.

Melanoma displays aberrant peripheral B and T cell activation, maturation and exhaustion, prominent in active disease. Treatment-induced class-switched B cells and T cell invigoration predict clinical benefit and naïve/DN B cells signify resistance. Coordinated B and T cell responses, especially recurrent extrafollicular B cell and exhausted/regulatory T cell states emerge as candidate indicators of outcome.

BackgroundCervical cancer significantly impacts sexual and family functioning, yet limited evidence exists on addressing these issues in sub-Saharan Africa.ObjectivesThis study examined the prevalence and associations of sexual and family function among women diagnosed with cervical cancer in Kumasi-Ghana.DesignA concurrent mixed-methods study design.MethodsThis study was conducted at the Komfo Anokye Teaching Hospital from 2020-2021. The quantitative component employed a cross-sectional design using 181 women with histologically confirmed cervical cancer. Sexual functioning was assessed using the Female Sexual Function Index, while family functioning was evaluated using the APGAR Family Functioning Scale. Systematic sampling was used for participant selection. Associations between predictors were examined using Firth penalized logistic regression. Analysis tool was STATA version 16.0. The qualitative component utilized purposive sampling to recruit 15 participants for in-depth interviews. Thematic analysis was performed for qualitative data using NVIVO software version 14.ResultsParticipants had a mean age of 57.5 years (SD=12.85). Almost all (96.1%) women with cervical cancer had sexual dysfunction, despite majority (93.4%) reporting a frequent sexual desire as a relational dimension rather than an indicator of preserved sexual health. Family dysfunction was prevalent, with 65.7% classified as severely dysfunctional families. The study revealed that women with 8-13 children had significantly lower odds of family functioning (AOR = 0.12, 95% CI: 0.01-0.59, p = 0.006). Qualitative findings revealed that, despite higher family dysfunction, meaningful support from spouses and children provided substantial practical and emotional support even as extended family involvement remained limited.ConclusionSexual and family functioning challenges are highly prevalent among Ghanaian women with cervical cancer despite a maintained sexual desire and support from nuclear family. Integration of culturally-appropriate, holistic sexual health counselling and family-centered interventions into routine cervical cancer care is essential for survivorship support in resource-limited settings.