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The association between breast cancer diagnosis and treatment and the risk of incident ischemic stroke remains unclear. We investigated ischemic stroke risk among breast cancer survivors and evaluated associations by age, follow-up duration, and type of cancer treatment. We conducted a nationwide, retrospective, matched cohort study using the Korean National Health Insurance Service database. Women aged 18 years and older with newly diagnosed breast cancer who underwent breast cancer surgery between January 2010 and December 2016 and had no prior stroke were identified. Each was matched 1:3 by birth year to cancer-free women. The primary outcome was first ischemic stroke, defined as hospitalization with International Classification of Disease, Tenth Revision codes I63/I64 plus inpatient brain CT or MRI. Subdistribution hazard ratios (sHRs) and 95% CIs were estimated using Fine-Gray models that accounted for death as a competing risk and adjusted for sociodemographic factors and cardiovascular and non-CV comorbidities. We analyzed 107,606 breast cancer surgery survivors (mean age, 50.0 years) and 322,818 matched cancer-free women. Over a mean 7.2-year follow-up, ischemic stroke occurred in 1,155 survivors (1.07%). Stroke risk was elevated shortly after breast cancer diagnosis (1-year sHR 1.59; 95% CI 1.34-1.89; 3-year sHR 1.17; 95% CI 1.05-1.30) compared with cancer-free women, with stronger associations at 3 and 6 months after diagnosis across all age groups. Over the long term, survivors had a slightly lower risk of stroke (sHR 0.94; 95% CI 0.88-1.00), and in a 1-year landmark analysis including only event-free individuals, the risk was lower (sHR 0.87, 95% CI 0.81-0.93). Among survivors, anthracycline use (sHR 1.25) and combined tamoxifen-aromatase inhibitor therapy (sHR 1.49) were associated with increased risk of stroke, whereas radiation therapy was associated with decreased risk (sHR 0.84). These associations attenuated and became nonsignificant beyond 1 year. Stroke risk was also higher among survivors with low income, hypertension, diabetes, or current smoking. The association between breast cancer and ischemic stroke risk is time dependent, with a short-term increase after diagnosis and treatment followed by a gradual decline over time. These findings highlight the need for proactive stroke risk management, including early CV assessment and ongoing monitoring for thromboembolic events during survivorship.
Altered amino acid metabolism is a feature of gastric cancer. Type 2 diabetes (T2D), a prevalent metabolic comorbidity, may affect circulating amino acid profiles; this study aimed to quantify its impact. A validated targeted LC-MS/MS assay profiled 22 serum amino acids in 156 participants, including gastric cancer patients with and without type 2 diabetes and controls. Adjusted models showed that many observed differences were attributable to type 2 diabetes and body mass index. Type 2 diabetes was associated with lower ornithine (β =  -1.16; q = 0.0019) and interacted with gastric cancer for arginine (β_int =  -1.10; q = 0.0044) and phenylalanine (β_int =  +1.05; q = 0.0112). After adjustment, only valine, taurine, and total amino acids remained lower in gastric cancer. Body mass index was inversely associated with glutamine and positively associated with glutamate. Covariate-adjusted analysis distinguishes cancer-related from comorbidity-driven alterations and identifies type 2 diabetes as a key modifier of amino acid metabolism. Metabolic covariates should be considered when interpreting amino acid alterations in advanced gastric cancer biomarker studies. However, the findings should be interpreted in light of the predominantly advanced-stage gastric cancer cohort and require validation in larger prospective studies. This study investigated whether serum amino acid profiles observed in gastric cancer are influenced by metabolic comorbidities such as type 2 diabetes (T2D). A targeted LC–MS/MS method was used to quantify serum amino acids in gastric cancer patients and controls with or without T2D. The results showed that amino acids related to the urea cycle and nitrogen metabolism, particularly arginine, phenylalanine, and ornithine, were strongly affected by the combined presence of gastric cancer and T2D. These findings suggest that metabolic comorbidities should be carefully considered when interpreting amino acid alterations associated with gastric cancer.
The timely diagnosis and referral of children with cancer have been identified as a priority for pediatric oncology. Despite the prominence of timely detection educational interventions, scant data exist on the approach and efficacy of these trainings. For this scoping review, PubMed, Web of Science, Scopus, and SciELO were searched to identify studies reporting on educational interventions for the timely detection of pediatric patients with cancer. Our search yielded 5,682 studies, and 29 met the inclusion criteria. These studies captured experiences from 20 countries. Interventions were most frequently conducted in person (12 of 29, 41.4%), with varying formats including workshops (10 of 29, 34.5%), multiday courses (5 of 29, 17.2%), and lectures (4 of 29, 13.7%). Seven studies (24.1%) reported the use of supplementary materials such as job aids, posters, or flyers. Interventions focused on increasing recognition of the signs and symptoms of childhood cancers (25 of 29, 86.2%), whereas some addressed referral practices (11 of 29, 37.9%). Audiences were varied, but included physicians (23 of 29, 79.3%) most often. Most studies (28 of 29, 96.6%) evaluated the impact or outcomes of their educational interventions. Most studies assessing the impact reported the number of participants trained (23 of 29, 79.3%). Knowledge assessment was conducted immediately in 11 studies (37.9%). Additional outcomes included the number of patient referrals (9 of 29, 31.0%), the number of new childhood cancer cases (4 of 29, 13.8%), time to diagnosis (4 of 29, 13.7%), and the stage distribution of cancers at diagnosis (6 of 29, 20.7%). Our review highlights the potential of educational interventions to improve provider knowledge and referral practices in childhood cancer diagnosis. Yet, current interventions vary widely in scope, content, and outcome measures. Further research is needed to address methodological limitations and ensure that greater awareness yields meaningful improvements in pediatric cancer outcomes worldwide.
BackgroundGynecological cancers are among the leading causes of cancer-related deaths, which makes it important to focus on the end-of-life (EOL) quality and its improvement among gynecological cancer patients. Several indirect indicators have been developed to assess poor EOL quality among gynecological cancer patients, and these indicators can be used to assess EOL quality across different settings.Objectives(1) To assess the EOL quality and its improvement; and (2) to assess the EOL care and its changes among gynecological cancer patients at Oulu University Hospital by quality care measures.DesignWe conducted a retrospective study, comparing 2 cohorts. Patient data were obtained from the records of Oulu University Hospital.Setting/SubjectsWe compared 2 cohorts of gynecological cancer patients who died between 1.1.2018 and 30.6.2020 (Cohort 1) and between 1.1.2021 and 30.6.2023 (Cohort 2).ResultsIn the latter cohort (Cohort 2), more patients were referred to palliative care (81% vs 94%, respectively). Additionally, there was a significant decrease in the proportion of patients receiving chemotherapy during the last 3 months of life in Cohort 2 (44% vs 25%). The time between the EOL discussion and death was longer in Cohort 2 (median 57 vs 125 days, respectively).ConclusionBased on these indicators, the EOL quality of patients with gynecological cancer at Oulu University Hospital may have improved in recent years. However, there remains room for improvement, particularly in the earlier initiation of palliative care.
Altered immune states at the time of cancer diagnosis remain insufficiently characterized. Although circulating immune biomarkers offer a promising, non-invasive way of analysing systemic tumour-host interactions, their potential remains poorly defined. Here, we present an integrated multi-omics analysis of peripheral blood mononuclear cells from treatment-naïve cancer patients, minimizing confounding by therapy-induced immune changes, combining immune phenotyping (flow cytometry, FC), multiplex cytokine profiling, and single-cell RNA sequencing (scRNA-seq). Compared with healthy donors, patients exhibited widespread immune dysregulation, including expansion of FOXP3+ regulatory T cells, depletion of CD16+CD11b+ monocytes and CD56^dim^ Natural killer (NK) cells, and elevated plasma IL-6 and IL-4 levels. scRNA-seq identified cancer-associated immune signatures, notably consistent upregulation of THBS1 and CH25H, indicative of systemic imprinting by tumour-derived cues. We further developed machine learning-guided models integrating single-cell multi-omics data (sc-FC and scRNA-seq) to characterize cancer-associated immune patterning and cancer type-related signal structure, while providing biologically interpretable feature attribution across modalities. The models achieved robust classification performance within the cohort and revealed modality-spanning features linked to immune state alterations. Together, these findings establish a framework for immune-based, multi-omics profiling of peripheral blood and provide a resource for discovering circulating cancer-associated immune signatures. This supports future development of immune-based diagnostics and disease monitoring approaches.
To identify the active components of Yiguanjian Decoction (YGJ) and elucidate their molecular actions against thyroid cancer. The TCMSP, TCMID, and BATMAN-TCM databases were used to screen the bioactive components in YGJ and their therapeutic targets. Subsequently, thyroid cancer-related targets were compiled from Drugbank, DisGeNET, and OMIM. Protein-protein interaction (PPI) networks were generated from the STRING database, and functional enrichment analyses (GO/KEGG) were conducted via Metascape and DAVID. Molecular docking simulations were performed to evaluate binding affinities between key compounds and targets. Finally, in vitro and in vivo experiments were carried out to validate YGJ's anti-cancer effects, including suppression of thyroid cancer cell proliferation and migration and induction of apoptosis. The systematic screening identified 69 bioactive compounds in YGJ and 358 corresponding therapeutic targets. Cytoscape's Network Analyzer revealed 10 hub targets (AKT1, FOS, JUN, MAPK1, MAPK14, MAPK3, MYC, RELA, SRC, and TP53) with top centrality scores in the PPI network. Functional enrichment analyses revealed that YGJ's anti-thyroid cancer activity involved 3 major pathways, including MAPK, Toll-like receptor, and T cell receptor signaling (all P<0.001). In vitro experiments demonstrated that YGJ effectively inhibited 8505C and TPC-1 cell proliferation and migration by downregulating key oncogenic regulators (p-ERK, NF-κB, c-MYC). In vivo xenograft studies further confirmed that YGJ significantly reduced tumor volume and weight in BALB/c mice, suppressed Ki67 expression, and showed no obvious toxicity to major organs. Molecular docking further identified essential hydrogen bonding and hydrophobic interactions for stabilizing ligand-target complexes. This study comprehensively reveals YGJ's pharmacological properties against thyroid cancer, identifying its core targets and multi-pathway mechanisms.
Obesity is the largest risk factor for endometrial cancer. Body Mass Index (BMI) does not fully capture obesity's metabolic and inflammatory complexity. Adipocyte hypertrophy and crown-like structures reflect adipose tissue dysfunction and obesity-associated chronic inflammation. We aimed to investigate adipocyte size and crown-like structures in visceral adipose tissue, and explore their associations with adipose tissue distribution, obesity-related comorbidities, and tumor characteristics in women with endometrial cancer. In this retrospective study, ninety endometrial cancer patients treated at a tertiary hospital between 2012 and 2022 are included. Preoperative computed tomography scans were analyzed using a validated deep learning algorithm to quantify visceral and subcutaneous adipose tissue areas and hepatic steatosis. Omental biopsies (n = 73) were examined for adipocyte size and presence of crown-like structures. Ninety patients were included, 87.8% with high-grade endometrial cancer. Adipocyte size correlated with adipose tissue compartments, particularly visceral adipose tissue (r = 0.60, p<.01), and was associated with higher age (p<.01), diabetes mellitus (p=.03), cardiovascular disease (p<.01), and hepatic steatosis (p≤.01). Crown-like structures were present in 48% of cases with omentum available (n = 73) and independently associated with diabetes mellitus (p≤.01), but not with BMI or adipose tissue areas. Adipocyte size and CLS were unrelated to tumor characteristics. Our findings emphasize that AT dysfunction, may link obesity with endometrial cancer. Future studies should further explore how these inflammatory and endocrine alterations in AT affect the tumor microenvironment and influence EC biology.
Antibody-drug conjugates (ADCs) target surface proteins on cancer cells, leading to internalization and delivery of a drug payload, thereby enhancing selectivity and minimizing toxicity. ADCs against TROP2 (Sacituzumab govitecan) or HER2 (T-DXd) have demonstrated efficacy in metastatic breast cancer, yet paradoxically, outside of HER2-amplified breast cancers, expression levels of these breast cancer-enriched epitopes in tumor biopsies have not been strongly correlated with clinical response. We undertook serial quantitative imaging of circulating tumor cells (CTCs) in a prospective cohort of 35 patients treated with either of these ADCs. At the single-cell level, expression of TROP2 and HER2 within individual patients is highly heterogeneous in both CTCs and paired tumor biopsies. Measurement of these epitopes on CTCs immediately prior to ADC therapy does not predict depth of clinical response. However, absence of CTCs or >80% reduction in CTC numbers after three weeks of treatment (CTCLow) predicts durable response, compared with CTCHigh cases (TROP2: HR 5.15, P = 0.012; HER2: HR 6.01, P < 0.001). Targeted epitopes are not commonly downregulated on CTCs at the time of acquired clinical resistance, and switching between TROP2- and HER2-targeting ADCs sharing similar payloads infrequently leads to second-line response. Thus, while CTC burden is correlated with response to these ADCs, the level of TROP2 or HER2 expression is poorly predictive. These findings point to sensitivity to the drug payload as a potential driver of clinical response to currently approved ADCs in breast cancer.
DNA2 coordinates essential maintenance processes, including cell-cycle progression; however, its aberrant activity has been implicated in cancer cell survival under oncogene-induced replication stress. To date, no comprehensive pan-cancer investigation of DNA2 has been conducted. Employing TCGA cohorts and complementary public databases, we executed the first pan-cancer multi-omics study of DNA2, examining transcriptomic, genomic variations, survival, immune infiltration, single-cell functional states, protein-protein interaction enrichment, and pharmacogenomic drug-response data across tumor profiles. DNA2 was considerably overexpressed in 17 tumors compared with matching normal tissues. In endometrial cancer, the highest frequency of genetic changes (~ 7%) was observed. Univariable analyses of survival showed that elevated DNA2 expression was related to worse overall survival in malignancies, including adrenocortical carcinoma (HR = 17.06) and mesothelioma (HR = 2.67). Single-cell omics revealed a tumor-specific correlation between DNA2 expression and functional annotations that encompass DNA damage, angiogenesis, and proliferation. Moreover, DNA2 expression was consistently positively associated with regulatory T-cell subtypes, but negatively related with NK cells, and cytotoxic T cells in multiple tumors as per immune landscape profiling. According to the pharmacogenomic analysis from GDSC2 dataset, tumor cells that express higher DNA2 are more sensitive to Tozasertib, and Daporinad. DNA2 is at the core of several interrelated modules, including flap processing, telomerase extension, and cell-cycle progression, according to the enrichment study. These findings have suggested DNA2 as a therapeutic vulnerability in cancer, a context-dependent biomarker with implications for treatment response, prognosis, and immunity.
Macroautophagy (autophagy) enables cellular stress adaptation by degrading damaged components; ULK1, a serine/threonine kinase, initiates this process in response to nutrient and energy cues. While autophagy is well studied, few investigations have directly tested ULK1 in cancer progression. Emerging functional data across numerous cancers indicate that ULK1 can promote or restrain malignant behavior through both autophagy-dependent and autophagy-independent mechanisms, modulating mitochondrial quality, anoikis escape, invasion, therapy adaptation, and immune visibility. Pharmacology has advanced from early ULK1/2 inhibitors to structure-guided and machine learning-derived inhibitors with improved potency and selectivity. The first clinical agent, DCC-3116, demonstrates on-target engagement with acceptable tolerability and is being evaluated in combinations where therapy induces autophagy. Here, we review ULK1 as a regulator of cancer progression, synthesizing pan-cancer clinical and functional evidence alongside the evolving pharmacology of ULK1 modulation to define the settings in which its targeted inhibition may be most effectively translated.
JAMA Senior Editor Derek C. Angus, MD, MPH, spoke with Kimmie Ng, MD, MPH, director of the Young-Onset Colorectal Cancer Center at Dana-Farber Cancer Institute, and Ilana Richman, MD, MHS, an assistant professor at the Yale School of Medicine, about the rise in early-onset cancer among younger individuals for Healthy Dialogue.
Modern risk-adapted management of thyroid cancer involves risk stratification as an active, dynamic process that begins with the detection of a thyroid nodule and continues throughout the clinical course of diagnosis, active surveillance or treatment, and follow-up. Rooted in clinicopathological staging, which can be further refined with the molecular risk characterization of the tumor, initial management plans are developed and modified over time on the basis of the natural history of the disease and the response to therapy. We present a clinical framework for therapeutic decision making that can be used to compare, contrast, and illustrate the relative risks, benefits, and patient preferences that are integral to the development of a personalized management plan. We examine examples of therapeutic decision making in active surveillance of low-risk papillary thyroid cancer, minimalist therapeutic management options for low- and intermediate-risk thyroid cancer, and systemic therapies for advanced thyroid cancer, showing how the therapeutic decision-making framework can be used to achieve informed consensus and management recommendations.
The converging trends of a global increase in the incidence of colorectal cancer (CRC) and the prevalence of obesity suggest that surgery for CRC in patients with excess body weight (EBW) will become an increasingly common clinical entity. We aimed to evaluate the effect of EBW, defined as being overweight or obese, on short-term perioperative outcomes following minimally invasive rectal cancer surgery (MIRCS). The review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, EMBASE, Web of Science, and the Cochrane Library were searched for relevant studies. Only comparative studies comparing MIRCS in patients with vs without EBW were included. Studies evaluating open rectal cancer surgery were excluded. This review was prospectively registered on PROSPERO (CRD42024591252). Twenty-six retrospective cohort studies involving 7172 patients were analysed. Patients with EBW had greater rates of open conversion (risk ratio (RR) 1.64, 95% CI 1.19-2.26), longer operative durations (mean difference (MD) 20.81 min, 95% CI 13.31-28.30), increased postoperative morbidity (RR 1.13, 95% CI 1.03-1.24), and higher readmission rates (RR 1.31, 95% CI 1.04-1.66) compared to patients without EBW undergoing MIRCS. No significant differences were found for length of hospital stay, intraoperative blood loss, surgical site infection, anastomotic leakage, gastrointestinal recovery, mortality, circumferential resection margin positivity, or lymph node harvest. Our review indicates a moderate increase in technical complexity and perioperative risk among patients with EBW undergoing MIRCS. These findings underscore the need for careful preoperative risk stratification and optimisation in this higher-risk patient cohort.
Positive margins occur in 12% to 30% of breast-conserving surgeries and are associated with increased local recurrence risks. Accurate and efficient intraoperative margin assessment, therefore, remains an unmet clinical need. To evaluate the success rate of intraoperative specimen positron emission tomography (PET)-computed tomography (CT) imaging in addressing positive margins in patients with invasive ductal carcinoma. This was an interventional, multicenter, nonrandomized clinical trial that recruited patients from June 2022 to March 2025. Patients were followed up 2 weeks after surgery. Six European breast cancer centers participated and integrated specimen PET-CT imaging into their routine surgical flow. The analysis included eligible patients with early-stage breast cancer scheduled for breast-conserving surgery. Patients received an intravenous injection of low-dose 18F-fluorodeoxyglucose (FDG; 0.8 MBq/kg). After tumor excision, the specimen was imaged intraoperatively using a dedicated specimen PET-CT scanner. Surgeons interpreted PET-CT images intraoperatively, and additional tissue was excised when margins were deemed suspicious to achieve final negative margins. The primary outcome was the success rate of specimen PET-CT in addressing positive margins for the invasive component in patients undergoing breast-conserving surgery for invasive ductal carcinoma. Secondary outcomes included success rates in other breast cancer subtypes, final positive margin rates, reoperation rates, and diagnostic performance using histopathology as the reference standard. The analysis cohort consisted of 148 female patients with a median (IQR) age of 65 (53-73) years and a median (IQR) preoperative tumor size of 17 (12-22) mm. For the invasive component of invasive ductal carcinoma, success rates increased from 83.3% (70 of 84 patients) without intraoperative margin assessment (IMA) to 86.9% (73 of 84 patients) with routine margin assessment and to 95.2% (80 of 84 patients) with specimen PET-CT (P < .001 vs no IMA). Across all study groups, success rates improved from 76.4% (113 of 148 patients) without IMA to 81.8% (121 of 148 patients) with routine margin assessment techniques and to 91.9% (136 of 148 patients) with specimen PET-CT (P < .001 vs no IMA; P = .009 vs standard-of-care IMA). Study findings show that specimen PET-CT imaging was associated with an improvement in the assessment of positive margins for invasive component in patients undergoing conserving surgery for early breast cancer. The use of this integrated approach might lead to a substantial reduction of re-excision rates after breast-conserving surgery. ClinicalTrials.gov Identifier: NCT04999917.
Thrombosis remains a major cause of morbidity and mortality in patients with cancer. Existing risk models fail to reliably predict venous thromboembolism (VTE), underscoring the need for more accurate predictive models. In this study, we conducted a high-throughput proteomic analysis of 1105 plasma proteins in peripheral blood samples from patients with newly diagnosed lung or gastric cancer who were prospectively monitored for VTE development. Using a Bayesian probabilistic machine learning approach, we developed a predictive model incorporating 11 protein biomarkers and five clinical parameters (age, sex, history of VTE, body mass index, and hemoglobin), which outperformed the standardly used Khorana prediction score [c statistic 0.84 (0.79 to 0.90) as compared with 0.36 (0.27 to 0.45)]. Orthogonal validation in an external placebo cohort from a phase 3 trial confirmed the model's predictive power. Further investigation into the mechanistic role of CD200 receptor 1 (CD200R1), an immune checkpoint receptor known to limit leukocyte inflammatory response that contributed strongly to the model, showed that reduced concentrations in plasma correlated with higher D-dimer concentrations and thrombosis risk. CD200R1-deficient mice were characterized by features of a prothrombotic state, with elevated thrombin-antithrombin complexes, increased interleukin-17A (IL-17A), and endothelial inflammation. Administration of anti-IL-17A antibodies to CD200R1-deficient mice normalized thrombin-antithrombin complexes in vivo, and a meta-analysis of human COVID-19 studies showed reduced pulmonary thromboembolism in those on anti-IL-17A antibodies. These findings highlight the utility of plasma proteomics to improve prediction of thrombosis in patients with cancer and to identify unanticipated mechanistic insights and therapeutic targets in thrombo-inflammatory disease.
Advanced head and neck squamous cell carcinoma (HNSCC) carries a poor prognosis, particularly in resource-limited settings with restricted access to targeted or immune therapies. We evaluated whether adding triple oral metronomic chemotherapy (OMCT; erlotinib, celecoxib, methotrexate) to paclitaxel-carboplatin (PC) improves overall survival (OS) in patients with platinum-sensitive, unresectable advanced HNSCC. This was a single-center, investigator-initiated, prospective, randomized, open-label, phase III superiority trial conducted at a tertiary cancer center in North India. A total of 238 adults with histologically confirmed, unresectable advanced HNSCC eligible for palliative platinum-based chemotherapy were randomly assigned 1:1 after stratification by tumor site and Eastern Cooperative Oncology Group (ECOG) performance status. Arm A received PC plus OMCT; Arm B received PC alone. The primary end point was OS. Secondary end points included progression-free survival (PFS), quality of life (QoL; European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 and Functional Assessment of Cancer Therapy-Head & Neck), and safety. Among 238 patients (119 per arm), the median age was 47 years; 97.8% were male, and 78% had ECOG performance status (PS) 0-1. The median OS was 10 months (95% CI, 8.3 to 11.7) with PC + OMCT versus 5 months (95% CI, 3.9 to 6.1) with PC alone (hazard ratio [HR], 0.54 [95% CI, 0.41 to 0.72]; P < .001). The median PFS was 6 months versus 2 months, respectively (HR, 0.38 [95% CI, 0.28 to 0.50]; P < .001). QoL analyses demonstrated clinically meaningful preservation across multiple domains in the PC + OMCT arm. Grade ≥3 toxicities did not increase with the addition of OMCT. In platinum-sensitive advanced HNSCC, the addition of triple OMCT to PC significantly improved OS and PFS with acceptable toxicity. PC + OMCT represents a feasible and cost-conscious first-line option in resource-constrained settings.
Combining CDK 4/6 inhibitors with endocrine therapy (ET) extends progression-free survival (PFS) and overall survival (OS) in hormone receptor (HR) positive, human epidermal growth factor receptor-2 (HER2) negative metastatic breast cancer. We aimed to explore the relationship between metabolic tumor volume (MTV), total lesion glycolysis (TLG), and PFS/OS in these patients. MTV and TLG were measured from baseline 18 F-fluorodeoxyglucose (18-FDG) positron emission tomography/computed tomography (PET/CT) of 87 HR-positive/HER2-negative metastatic breast cancer patients and their effects on survival were analyzed using Kaplan-Meier methods. The median OS was 42.0 months for patients with MTV < 121.7 cm³ and 24.6 months with ≥ 121.7 cm3 (p = 0.001). The median OS was 40.3 months for patients with TLG < 732.4 g and 24.6 months with ≥ 732.4 g (p = 0.006). The median OS for patients with an ECOG score of 0 was 53.6 months, while for those with an ECOG score of 1-2, it was 26.4 months (p = 0.005). Age ≥ 60 years (HR = 5.11, p = 0.002) and ECOG score > 0 (HR = 3.38, p = 0.011) are independent predictors of PFS. Baseline 18 F-FDG PET/CT may provide prognostic insights in HR+/HER2- metastatic breast cancer. High MTV and TLG are associated with poorer OS in univariate analyses but not in multivariable analyses. ECOG score > 0 and age ≥ 60 years are independent predictors of PFS.
BackgroundUltra-radical cytoreductive surgery is frequently performed for patients with advanced ovarian cancer (OC). However, anastomotic leakage (AL) is a serious complication of such surgeries and the risk factors remain unclear. This study identified early postoperative C-reactive protein (CRP) and albumin were the strongest predictors of leakage.MethodsThis multicenter retrospective study involved 305 patients with ovarian cancer who underwent primary anastomosis following enterectomy, spanning January 2018 to June 2023. Comprehensive clinical and demographic data were used to develop predictive models. Feature selection was performed using LASSO and univariate logistic regression. Machine learning algorithms were subsequently applied, with model interpretability assessed using SHapley Additive explanations (SHAP).ResultsThe study revealed an AL prevalence of 14.1%, with 46.5% of affected patients requiring reoperation. Five predictors were identified, including postoperative CRP, serum albumin levels, Eastern Cooperative Oncology Group score, N stage, and blood urea nitrogen. The Lasso-Logistic model demonstrated the best predictive performance with an area under the curve of 0.828 (0.119). SHAP analysis highlighted early postoperative CRP, albumin, and N stage as major contributing factors. Economic analysis revealed a significant correlation between AL and hospital stay, hospital costs, and time to chemotherapy.DiscussionEarly postoperative inflammatory and nutritional biomarkers, particularly CRP and albumin, demonstrated significant predictive value for anastomotic leakage, providing an early warning for risk stratification and intervention. The investigation also bolstered the evidence supporting the restrictive surgical scope approach advocated in clinical guidelines.
Gastric cancer (GC) remains a major cause of cancer-related mortality worldwide, highlighting the need for reliable prognostic biomarkers. Although chemokines critically regulate the tumor microenvironment (TME), their integrated prognostic value and mechanistic roles in GC remain unclear. We aimed to develop a chemokine-based prognostic signature and elucidate its underlying cellular basis. Transcriptomic data from TCGA and GEO cohorts were integrated to construct and validate a prognostic model using least absolute shrinkage and selection operator (LASSO) Cox regression based on six differentially expressed chemokines. Associations between the risk score and TME characteristics, tumor mutation burden (TMB), and drug sensitivity were evaluated. Single-cell RNA sequencing (scRNA-seq) was performed to determine the cellular origin and functional role of the key chemokine CXCL8. A six-chemokine signature stratified patients into high- and low-risk groups with significantly different overall survival (OS; p = 0.003) and progression-free survival (PFS; p < 0.001). The risk score was an independent prognostic factor, and the corresponding nomogram demonstrated good predictive performance (C-index = 0.680). The high-risk group exhibited elevated TMB and reduced chemosensitivity. scRNA-seq analysis identified macrophages as the principal source of CXCL8. These CXCL8-high macrophages displayed a pro-tumorigenic phenotype and functioned as key communication hubs within the TME, particularly through SPP1 signaling. This chemokine-based signature provides clinically relevant prognostic stratification in GC and implicates the CXCL8-macrophage axis as a potential therapeutic target.
Validating polygenic risk scores (PRSs) as a breast cancer (BC) risk stratification tool in high-risk clinical settings is essential for potential clinical implementation. To evaluate the performance of African-ancestry PRSs for overall BC and triple-negative BC (TNBC) in an independent African American cohort at elevated familial risk. This case-control study was conducted among women with self-reported African ancestry in a clinical hereditary cancer genetic testing setting who had negative results for pathogenic or likely pathogenic variants in known BC-associated genes between 2016 to 2024. Analyses were performed from September 2025 to April 2026. Six African-ancestry PRSs and a European-ancestry PRS (PRS-313). Performance of the PRSs was measured with covariate-adjusted area under the receiver operating characteristic curve (AUC) and adjusted odds ratio (OR) per 1 SD from logistic regression adjusting for age, top 10 genetic principal components, and family history. This study included 31 522 women (mean [SD] age, 47.1 [13.3] years): 12 067 women with BC (2311 with TNBC) and 19 455 women unaffected by BC. Women unaffected by BC were younger at testing than women with BC at diagnosis (mean [SD] age, 42.1 [11.7] years vs 55.2 [11.8] years) and were more likely to report a first- and second-degree family history of BC than women with BC (14 524 women [74.7%] vs 6483 women [53.7%]). For overall BC, PRS-313 showed an AUC of 0.567 (95% CI, 0.560-0.574) and an OR of 1.28 (95% CI, 1.25-1.31) per 1 SD of individuals unaffected by BC. In comparison, the African overall BC models 1 (2 324 063-variant model) and 2 (175 173-variant model) performed better, with AUCs of 0.588 (95% CI, 0.580-0.595) and 0.584 (95% CI, 0.576-0.591) and ORs of 1.39 (95% CI, 1.35-1.43) and 1.37 (95% CI, 1.34-1.41) per 1 SD of individuals unaffected by BC, respectively. Importantly, for TNBC, one 162-variant PRS consistently outperformed all other models, with an AUC of 0.609 (95% CI, 0.596-0.622) and an OR of 1.47 (95% CI, 1.40-1.55) per 1 SD of individuals unaffected by BC. In this clinically ascertained case-control study of self-reported Black or African American women, the PRSs demonstrated good performance among women with a strong family history of BC, reflecting populations in whom early PRS testing is most relevant. The high accuracy of the 162-variant TNBC PRS supported its potential as a cost-effective risk assessment tool to promote equitable care.