BackgroundMolecular profiling with next-generation sequencing (NGS) can improve breast-cancer (BC) diagnostics, prognostication, and treatment selection. Despite this potential, tumor genomic testing has been insufficiently studied and implemented in Ukraine. This exploratory study aimed to identify and clinically analyze variants in tumor suppressor genes, oncogenes, as well as genes involved in epigenetic regulation and cellular signaling pathways, in tumor tissue samples from Ukrainian BC patients using NGS assessing a 50-gene targeted panel.MethodsThis was a retrospective cross-sectional study. Tumor tissue from 57 consecutively enrolled women with newly diagnosed, histologically confirmed BC was analyzed using the Ion AmpliSeq™ Cancer Hotspot Panel v2 (50 genes). Variants were filtered by stringent quality criteria and classified according to ACMG and AMP/ASCO/CAP. Group comparisons were evaluated using Fisher's exact and nonparametric tests; correlations were evaluated using Spearman's test.ResultsVariants were detected in 32 of 57 (56.1%) tumors across eight genes. The highest number of variants were detected in TP53 gene (15; 48.38%), followed by PIK3CA gene (5; 16.12%). The most recurrent single variant was PIK3CA c.3140A>G (H1047R) (11/57; 19.3%). Carriers of PIK3CA variants tended to be older and more often had ER/PR-positive, Luminal A tumors, and lower Ki-67 index. TP53 alterations tended to occur in ER-negative and triple-negative tumors, although these trends did not reach statistical significance in this cohort.ConclusionsThis study provides an initial NGS-based characterization of variants in Ukrainian BC and supports previously reported associations of PIK3CA and TP53 with clinicopathological phenotypes. Our findings should be considered exploratory and hypothesis-generating, and may support future studies on genomic profiling for patient stratification and trial enrollment in settings with limited local genomic data.

BackgroundCervical cancer is the leading cause of cancer-related mortality among women in Uganda, with national screening coverage critically low at 20.6%. The disease is largely preventable through early detection, yet client-level and health-system failures conspire to suppress uptake.ObjectivesTo integrate client and provider perspectives to construct a comprehensive explanatory model of barriers to cervical cancer screening uptake in Hoima district, rural Uganda.DesignA convergent mixed-methods design, with quantitative and qualitative data collected concurrently across 20 health facilities and integrated through systematic triangulation.MethodsThe quantitative component recruited 400 women aged 20-60 years through systematic random sampling, analysed using binary logistic regression. The qualitative component recruited 30 health workers for key informant interviews, analysed using Braun and Clarke's thematic analysis framework. Reporting conforms to STROBE and COREQ guidelines.ResultsOnly 3.0% of women (n = 12/400) reported ever undergoing screening. Three significant determinants of uptake were identified: awareness of screening importance (AOR = 7.34, 95% CI: 2.41-22.37, p = 0.021); unmarried marital status (AOR = 8.69, 95% CI: 1.85-40.82, p = 0.006); and student occupation (AOR = 6.92, 95% CI: 1.51-31.81, p < 0.05). Wide confidence intervals reflect the small number of screened women. Qualitative analysis identified five supply-side themes: extreme centralisation of services; near-universal lack of trained personnel (96.7% untrained); absence of essential equipment; variable health worker knowledge; and workload-related resistance to expansion. Triangulation revealed strong convergence: the supply-side training deficit directly explains the demand-side knowledge gap. Apparent dissonance around cost was resolved by recognising that indirect access costs represent the true financial barrier for rural women.ConclusionLow screening uptake reflects a self-reinforcing cycle of structural weakness and uninformed community demand. Effective intervention requires simultaneously strengthening health system capacity and stimulating demand through targeted health education via preferred channels, notably radio and churches.

Background: Short-course radiotherapy (SCRT)-based total neoadjuvant therapy (TNT) is used for locally advanced rectal cancer (LARC). However, the pathological complete response (pCR) rate still hovers around 30%. Radiotherapy and immune checkpoint inhibitors have been shown to exert synergistic anticancer effects. This phase II randomized clinical trial aimed to evaluate the efficacy and safety of SCRT followed by capecitabine plus oxaliplatin (CAPOX) and tislelizumab versus SCRT followed by CAPOX alone in LARC. Methods: Patients initially diagnosed with clinical tumor stage 1 to 2, with node involvement and no distant metastasis (cT_1-2N₊M₀) or clinical tumor stage 3 to 4, with any node status and no distant metastasis (cT_3-4N_anyM₀) rectal adenocarcinoma were randomly assigned to receive SCRT (25 Gy in 5 fractions [25 Gy/5F]), followed by 4 cycles of CAPOX combined with tislelizumab (SCRT-TNT-ICI) or CAPOX alone (SCRT-TNT). After total mesorectal excision, 2 cycles of postoperative chemotherapy were administered according to the patient's preference. The primary end point was the pCR rate, and secondary end points included major pathological response (tumor regression grade 0 or 1), 3-year progression-free survival, 3-year overall survival, and adverse events. Results: Between September 2021 and March 2024, 118 patients were randomized, of whom 111 started the allocated treatment, with 53 and 58 in SCRT-TNT-ICI and SCRT-TNT groups, respectively. Of those, 89 patients had surgical resection, including 45 in the SCRT-TNT-ICI group and 44 in the SCRT-TNT group. The pCR rate was 45.3% (95% confidence interval [CI], 31.5% to 59.8%) in the SCRT-TNT-ICI group compared to 27.6% (95% CI, 16.6% to 40.8%) in the SCRT-TNT group (odds ratio = 2.17; 95% CI, 0.99 to 4.79; P = 0.052). The major pathological response rates were 50.9% (95% CI, 36.6% to 65.2%) and 31.0% (95% CI, 19.5% to 44.6%), respectively (odds ratio = 2.31; 95% CI, 1.06 to 5.01; P = 0.033). During the neoadjuvant treatment period, the incidence of grade 3 to 4 adverse events was comparable between the SCRT-TNT-ICI and SCRT-TNT groups, with anemia being the most common in both groups. Conclusion: This phase II study provides preliminary evidence of promising tumor regression with SCRT-TNT combined with tislelizumab in LARC, warranting further validation in phase III trials. Trial registration: This trial was registered at clinicaltrials.gov (Identifier: NCT05086627).

Emerging evidence indicates impaired endometrial receptivity may contribute to reduced embryo implantation and poorer pregnancy outcomes in Polycystic ovary syndrome (PCOS) patients, though exact mechanisms are not yet fully elucidated.

To explore the impact of low-grade systemic inflammation on endometrial dysfunction in women with PCOS, and to assess the relationship between inflammatory markers, endocrine and metabolic factors, and their link to endometrial receptivity.

A retrospective analysis was conducted involving 180 infertile women with PCOS recruited from the gynecology department between January 2023 and June 2025 as the case group. The control group consisted of 180 women with regular menstrual cycles and no PCOS features, who experienced infertility due to male or tubal factors during the same period. Clinical data and metabolic/endocrine parameters, including the LH/FSH ratio, estradiol (E2), testosterone (T), and HOMA-IR, were collected. Serum levels of pro-inflammatory (IL-1β, IL-6, TNF-α) and anti-inflammatory (IL-4, IL-10) cytokines were quantified using ELISA. During the mid-luteal phase, transvaginal 3D ultrasound was used to assess endometrial thickness, pattern, and blood flow indices (VI, FI, VFI), as well as uterine artery Doppler parameters (PI, RI). Between-group differences were analyzed, along with correlations among inflammatory markers, metabolic profiles, and endometrial characteristics.

Compared to controls, the PCOS group had significantly higher BMI, LH/FSH ratio, T, and HOMA-IR (P<0.001). They showed increased pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) and reduced anti-inflammatory cytokines (IL-4, IL-10) (P<0.001). Endometrial blood flow patterns were poorer, and uterine artery PI and RI were higher in the PCOS group (P<0.001), while endometrial thickness, VI, FI, and VFI did not differ significantly (P>0.05). Within PCOS group, pro-inflammatory cytokines correlated positively with BMI, LH/FSH ratio, T, HOMA-IR, and uterine artery PI and RI (r=0.44-0.58, P<0.001), whereas anti-inflammatory cytokines correlated negatively with these measures (r=-0.43 to -0.63, P<0.001). No significant correlations were observed with endometrial thickness or vascularization indices.

Patients with PCOS exhibit state of low-grade systemic inflammation, characterized by elevated pro-inflammatory cytokines and reduced anti-inflammatory cytokines, which is closely associated with insulin resistance and hyperandrogenemia. This inflammatory state may contribute to development of endometrial dysfunction by increasing uterine artery blood flow resistance.

The modest neoadjuvant response in early-stage HR+/HER2- breast cancer necessitates novel treatment intensification strategies. While radiotherapy can enhance systemic efficacy via immune modulation, the optimal fractionation for integration with immunochemotherapy remains unknown. This multicenter phase II study aims to evaluate the feasibility, safety, and preliminary efficacy of Toripalimab combined with chemotherapy and tumor-directed radiotherapy, specifically investigating three distinct fractionation schedules.

This prospective, multicenter, three-cohort exploratory study enrolls treatment-naïve patients with early-stage HR+/HER2- breast cancer. Participants receive neoadjuvant Toripalimab plus chemotherapy alongside image-guided radiotherapy restricted to the primary tumor. Cohorts are differentiated by fractionation regimen: Arm 1 (8 Gy × 3 fractions, total 24 Gy); Arm 2 (16 Gy single fraction); Arm 3 (0.5 Gy twice daily for 8 cycles, cumulative 8 Gy). A total of 45 patients (15 per cohort) will be enrolled. The primary endpoint is pathological complete response (pCR). Secondary endpoints include objective response rate, recurrence, survival outcomes (OS, EFS, DMFS, IDFS, IBTR), and safety.

This exploratory study will provide feasibility, tolerability, and preliminary efficacy data for a novel multimodal neoadjuvant strategy combining different radiotherapy fractionation patterns with immunotherapy and chemotherapy. Given the descriptive analytical framework, findings are expected to be hypothesis generating and will inform the selection of radiotherapy schedules for future larger-scale randomized trials aimed at improving outcomes in HR+/HER2- breast cancer.

http://www.chictr.org.cn, identifier NCT06639672.

Liver metastases are associated with systemic immune tolerance and primary resistance to immune checkpoint inhibitors (ICIs) by establishing complex physical and metabolic barriers within the tumor immune microenvironment (TIME). We developed a non-invasive macroscopic fractal dynamics framework to map these microenvironmental barriers across scales, aiming to predict ICI efficacy in colorectal cancer liver metastases (CRLM) and lung squamous cell carcinoma (SCC).

This single-center, retrospective, proof-of-concept cohort study consecutively enrolled 472 patients with CRLM or SCC liver metastases. Patients were divided into a training cohort (n=400, 2019-2024) and an independent validation cohort (n=72, 2025). Vascular fractal acceleration (A_fd ) and metabolic fractal dimension (D_f ) were extracted from contrast-enhanced magnetic resonance imaging (CE-MRI) and ¹⁸F-FDG PET, respectively. To eliminate baseline histological confounding, macroscopic fractal probes were Z-score normalized strictly within their respective histological cohorts. Cross-scale validation utilized digital pathology and platelet-poor plasma (PPP) cytokine profiling. An extreme gradient boosting (XGBoost) model was explicitly trained to predict a composite "High TIME Barrier" phenotype-defined by restricted CD8⁺ infiltration and low PD-L1 expression-to generate the Immuno-Radiomics Joint Score (IRJS). An exploratory survival analysis was subsequently conducted to evaluate its association with progression-free survival (PFS) among the 185 patients receiving ICI therapy. We evaluated early dynamic drift (ΔA_fd ) at week 3 for its utility in tracking physical barrier remodeling.

CRLM and SCC displayed distinct fractal trajectories indicative of metabolic and physical barriers, respectively. High A_fd correlated with dense fibrovascular stroma and severe spatial exclusion of CD8⁺ T cells. High D_f corresponded to severe hypoxia, CD163-enriched macrophage infiltration, and systemic immune exhaustion, characterized by elevated circulating TGF-β and exhausted IFN-γ. The IRJS demonstrated strong diagnostic performance for the High TIME barrier phenotype (temporal validation AUC: 0.912). In the ICI sub-cohort, multivariable Cox regression confirmed that an increase in the continuous baseline IRJS was a robust, independent risk factor associated with primary ICI resistance and shorter PFS.

Macroscopic fractal dynamics offer a non-invasive, cross-scale method to evaluate the "physical-metabolic" dual microenvironmental barriers in liver metastases. The combined IRJS and dynamic ΔA_fd tracking system show potential as exploratory, non-invasive surrogates to identify the systemic immune exhaustion phenotype. Pending external multi-center validation, these tools may generate hypotheses for associating macroscopic spatial barriers with primary ICI resistance and informing multidisciplinary interventions.

Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer incidence and mortality worldwide. In recent years, immune checkpoint inhibitors (ICIs), particularly those targeting the programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) axis, have significantly improved survival outcomes in a subset of patients. However, the magnitude and durability of clinical benefit vary considerably according to PD-L1 expression, treatment setting, histological subtype, oncogenic driver status, and whether ICIs are administered as monotherapy or in combination regimens. A substantial proportion of patients therefore exhibit either primary resistance or acquired resistance after an initial response. This review systematically summarizes the key mechanisms underlying immune resistance in lung cancer. These include defects in antigen presentation, such as abnormalities in major histocompatibility complex class I (MHC-I), transporter associated with antigen processing 2 (TAP2), and β2-microglobulin (B2M), as well as dysregulation of the interferon-γ/Janus kinase-signal transducer and activator of transcription (IFN-γ/JAK-STAT) signaling pathway. Tumors frequently exhibit an immune-excluded or 'cold' phenotype, which further limits immune recognition and reduces responsiveness to immunotherapy. This review summarizes immune resistance in NSCLC through a framework that distinguishes primary resistance from acquired resistance. Primary resistance reflects failure of immune activation at treatment initiation, usually due to pre-existing tumor-intrinsic or microenvironmental barriers, including impaired antigen presentation, defective IFN-γ/JAK-STAT signaling, low tumor immunogenicity, immune-cold or immune-excluded phenotypes, and suppressive TME states. In contrast, acquired resistance reflects adaptive tumor and immune ecosystem evolution under therapeutic pressure, leading to neoantigen loss, HLA or B2M alterations, compensatory checkpoint activation, progressive T cell exhaustion, TME remodeling, and epigenetic stabilization of immune escape. We further discuss mechanism-based biomarkers, translational correlates, and rational therapeutic strategies for overcoming resistance.

This study aimed to evaluate the prognostic value of the estimated dose of radiation to immune cells (EDRIC) and the radiotherapy-related nadir lymphocyte count (RT-NLC), and to establish a risk stratification model for predicting outcomes in patients with unresectable stage III non-small cell lung cancer (NSCLC) treated with definitive chemoradiotherapy (CRT) and immunotherapy.

We retrospectively analyzed 136 patients treated between May 2019 and November 2023. EDRIC and RT-NLC were dichotomized at median values. Survival analysis was performed using Kaplan-Meier and Cox regression. High-risk patients were defined as having EDRIC ≥ 6.75 Gy and RT-NLC < 0.54×10⁹/L.

EDRIC inversely correlated with RT-NLC (r = -0.38, P < 0.001). Lower EDRIC was associated with significantly improved median overall survival (OS: 49.7 vs. 38.1 months, P = 0.015), progression-free survival (PFS: 29.7 vs. 17.3 months, P = 0.006), locoregional relapse-free survival (LRFS: 32.4 vs. 19.8 months, P = 0.004), and distant metastasis-free survival (DMFS: 44.8 vs. 24.0 months, P = 0.001). On multivariable analysis, low EDRIC independently predicted improved OS (HR = 0.51), PFS (HR = 0.56), LRFS (HR = 0.53), and DMFS (HR = 0.42). High RT-NLC group was significantly prolonged median DMFS (44.8 vs 26.8 months, P = 0.012). High-risk patients demonstrated inferior survival (P < 0.05) but derived significant benefit from consolidation immunotherapy, with improved OS (HR = 0.37, P = 0.041), PFS (HR = 0.44, P = 0.034), and DMFS (HR = 0.33, P = 0.011).

EDRIC and RT-NLC are significant prognostic biomarkers in unresectable stage III NSCLC. A risk model integrating these parameters effectively identifies high-risk patients who obtain substantial survival benefit, particularly in distant metastasis control, from consolidation immunotherapy, supporting personalized treatment strategies. Prospective validation is warranted.

Oral squamous cell carcinoma (OSCC) is the predominant histological subtype of oral cavity cancers, with a 5-year survival rate of approximately 50%. The tumour microenvironment, particularly macrophage infiltration and polarization, plays a critical role in tumour progression and patient prognosis. Models describing macrophages as either M1 (pro-inflammatory) or M2 (anti-inflammatory) are increasingly recognized as oversimplified, given the functional heterogeneity and plasticity of tumour-associated macrophages (TAMs). This study aims to evaluate the expression of macrophage markers CD68, CD163, CD11c, and CD115 in OSCC compared to normal oral mucosa (NOM), to assess their diagnostic and prognostic value.

A cross-sectional study of 179 tissue samples (111 OSCC, 68 controls) analysed macrophage markers (CD68, CD163, CD11c, CD115) via real-time qPCR. Statistical tests included Mann-Whitney U, ROC analysis for diagnostic utility, Spearman's ρ for correlations, and assessments of associations with prognosis and recurrence. Cut-offs for gene overexpression were based on ROC results and evaluated clinically.

All four markers showed significantly higher expression in OSCC compared to NOM (p < 0.001 for CD68, CD163, CD11c; p = 0.001 for CD115). ROC analyses demonstrated diagnostic AUCs of 0.69 (CD68), 0.78 (CD163), 0.81 (CD11c), and 0.66 (CD115), indicating poor, fair and good discriminative capacity, respectively. Overexpression of the genes defined by COP was significantly associated with malignancy (p < 0.01). Elevated CD68 and CD163 levels correlated with higher tumour grading (G2/G3), while increased CD11c expression was linked to nodal metastasis (p = 0.04). Strong positive correlations existed between CD115 and the other markers (ρ > 0.61, p < 0.001), supporting a model of macrophage heterogeneity and plasticity. Concurrent upregulation of pro-inflammatory (CD11c) and M2-associated (CD163) markers suggests a complex, dynamic TAM landscape rather than a simple M1/M2 dichotomy.

Altered RNA expression of the macrophage cell surface markers CD115, CD68, CD163 and CD11c in OSCC, and their respective association with tumour grading, N-status and perineural sheath infiltration, may serve as a basis for future single-cell sequencing or immunohistological - multiplex immunofluorescence - studies. Further investigation of these markers could lead to promising insights into the modulation of the tumour immune microenvironment.

This meta-analysis compared chimeric antigen receptor T-cell (CAR-T) therapy and bispecific antibodies (BsAbs) for relapsed/refractory B-cell non-Hodgkin lymphoma (R/R B-NHL), focusing on efficacy and safety. We analyzed 59 phase I/II trials involving 2,914 patients. CAR-T achieved higher ORR (72% [95% CI 67-77%] vs. 50% [38-62%]) and CR (54% [49-59%] vs. 33% [23-46%]) than BsAbs. However, it was associated with higher rates of grade ≥3 CRS (8% [6-11%] vs. 4% [3-7%]), ICANS (12% [9-16%] vs. 6% [2-18%]), and neurotoxicity (8% [6-10%] vs. 6% [2-13%]). Among CAR-T constructs, dual-targeting products (CD19/20 and CD19/22) showed higher efficacy with more varied toxicity profiles; among BsAbs, CD3×CD20 had a more favorable safety profile relative to CD3×CD19. These results suggest CAR-T may be preferable when deep remission is the priority, whereas BsAbs could be a better fit for frail patients or those seeking outpatient care with lower toxicity risks. Treatment selection should be tailored to patient characteristics, including age, tumor burden, and comorbidities. Together, these results provide a comprehensive, evidence-based framework to guide individualized treatment and sequencing in clinical practice.