Immune checkpoint blockade (ICB) produces durable tumor control in a subset of patients, yet resistance is usually interpreted through tumor-intrinsic lesions or suppression within the tumor microenvironment (TME). We propose that ICB resistance can also be organized as failure of a multiscale antitumor immune circuit comprising local immune execution, regional immune education in tumor-draining lymph nodes (TDLNs), and systemic immune calibration by the host. In this model, “hierarchical” denotes nested functional dependence rather than one-way anatomical control: local killing depends probabilistically on antigen visibility, access, and a renewable supply of tumor-reactive cells; nodal priming depends on competent dendritic-cell licensing and host immune fitness; and reciprocal feedback can propagate or repair failure across compartments. We first define the canonical CD8-dominant substrate that ICB can amplify, including cross-presentation, costimulation, progenitor-exhausted T-cell maintenance, trafficking, and target-cell recognition, while retaining alternative CD4, natural killer, intratumoral antigen-presenting-cell, and tertiary lymphoid routes. We then evaluate local, regional, and systemic resistance mechanisms, four directional feedback axes, and context-dependent patterns in pancreatic cancer, melanoma, non-small-cell lung cancer, microsatellite-stable colorectal cancer, hepatocellular carcinoma, and prostate cancer. Evidence from animal perturbation, human spatial and clonal studies, and clinical trials supports individual circuit components but remains heterogeneous. Randomized perioperative regimens demonstrate disease- and setting-specific benefit, whereas negative randomized results and mixed or limiting early-phase signals across innate agonism, stromal or metabolic targeting, radiotherapy combinations, and systemic conditioning constrain therapeutic extrapolation. We therefore present compartment-resolved biomarkers and adaptive trial designs as research hypotheses, not a validated classifier or standard-care algorithm. The framework will be useful only if prespecified multiscale measurements improve prediction beyond tumor-only models and if mechanism-matched interventions produce the expected pharmacodynamic repair before clinical benefit is attributed to the circuit.
Numerous case reports regarding adult multisystem Langerhans cell histiocytosis (MS-LCH) have been published, yet the vast majority only describe single-organ involvement. Cases presenting sequential multi-organ lesions, clinical manifestations mimicking idiopathic hypophysitis and refractory gastritis, accompanied by long-term missed diagnosis and delayed definitive confirmation remain extremely rare. This article reports a 44-year-old female patient with delayed-diagnosed multisystem LCH. Her initial symptom was isolated central diabetes insipidus, which was misdiagnosed as infundibulohypophysitis. Subsequently, she developed intractable gastrointestinal discomfort accompanied by unexplained 10 kg weight loss. The definitive diagnosis was established nearly 10 months after symptom onset until a subcutaneous frontal skull mass emerged. Pathological diagnosis was obtained via surgical resection. The patient received cytarabine induction chemotherapy followed by salvage therapy combining TCD regimen and denosumab, achieving sustained partial remission of systemic lesions. Targeted next-generation sequencing identified a grade II somatic MAP2K1 mutation without the common BRAF V600E hotspot mutation, providing definitive molecular evidence for long-term maintenance targeted therapy with MEK inhibitors. This case is intended to deepen clinicians’ recognition on the diagnostic and therapeutic strategies of adult LCH, facilitate early confirmed diagnosis and timely clinical intervention to reduce related complications, and further explore its underlying pathogenesis as well as individualized management regimens.
BackgroundWith the accelerating aging of the population, the number of elderly patients with lung cancer continues to increase. Although surgery remains an important treatment modality for lung cancer, early recurrence (ER) is still a major factor affecting long-term survival in elderly patients.PurposeThis study aimed to integrate peripheral blood T-lymphocyte subset indicators with clinicopathological characteristics to develop and externally validate a machine learning-based prediction model for ER in elderly patients with lung cancer.MethodsThis study was designed as a multicenter retrospective cohort study. ER was defined as local recurrence or distant metastasis within 2 years after surgery. A total of 23 candidate predictors were included, and dual feature selection was performed using the Boruta algorithm and LASSO regression, followed by a systematic comparison of 14 machine learning algorithms and 7 ensemble optimization strategies. Model performance was evaluated using the area under the receiver operating characteristic curve (AUROC), area under the precision-recall curve (AUPRC), calibration curve, Brier score, and decision curve analysis. SHAP was used to interpret the optimal model.ResultsA total of 893 elderly patients with lung cancer were included in this study. After dual feature selection, five predictors were ultimately retained: tumor stage, total T-lymphocyte percentage, body mass index (BMI), Karnofsky performance scale (KPS), and suppressor/cytotoxic T-lymphocyte percentage. After ensemble optimization, SMOTE-Stacking achieved the best performance in internal validation. In external validation, among the four models belonging to the statistically equivalent top-performing tier, Soft Voting Ensemble (SV) demonstrated the most robust performance. SHAP analysis indicated that tumor stage and total T-lymphocyte percentage were the two core drivers of model prediction, both exhibiting clear nonlinear threshold effects.ConclusionER in elderly patients with lung cancer results from the combined effects of tumor burden, host functional status, and T-lymphocyte immune imbalance. A machine learning model integrating peripheral blood T-lymphocyte subsets has noninvasive and clinically translational potential and may provide evidence for ER risk stratification, individualized follow-up, and early intervention decision-making in elderly patients with lung cancer.
The rising incidence and detection rate of thyroid cancer have led to a concomitant increase in the number of thyroidectomy procedures performed annually. Among the postoperative complications, recurrent laryngeal nerve injury (RLNI) remains a major factor affecting patients’ quality of life. In pursuit of precision therapeutic strategies and reduced nerve injury rates,clinicians have shown growing interest in the recurrent laryngeal nerve(RLN). In recent years, high-frequency ultrasound (HFUS) has been increasingly incorporated into the perioperative management of thyroidectomy. This study is the first to address RLN management during the perioperative period for thyroid cancer. The ultrasonographic characteristics of the RLN are systematically reviewed, with particular emphasis on the clinical utility of HFUS in preoperative screening, intraoperative monitoring, and postoperative follow-up. We also discuss the inherent limitations of this technique and outline future directions. Despite these promising advances, significant challenges persist in ensuring the accuracy and standardization of ultrasonographic examinations across diverse patient populations. In conclusion, this review highlights the transformative potential of HFUS in optimizing perioperative neural monitoring and functional evaluation for thyroid cancer. However, it also notes that ultrasound cannot currently replace laryngoscopy or intraoperative nerve monitoring (IONM), though it serves as a valuable complementary tool with clear clinical utility.
PurposeBreast cancer is the most common malignancy among women worldwide. A notable subset of patients presents with de-novo stage IV breast cancer at initial diagnosis, meaning metastatic lesions are already present. These patients typically receive primary systemic therapy aimed at palliative care, with locoregional treatment remaining controversial. Although numerous retrospective studies have suggested that resection of the primary tumor may improve survival, prospective randomized trials have not demonstrated a clear benefit, and routine surgical intervention is not generally advocated. This paper aims to review and discuss the research progress regarding locoregional surgical treatment for de-novo stage IV breast cancer.MethodologyRecent retrospective and prospective studies on locoregional surgery for de-novo stage IV breast cancer were searched, with a focus on prospective randomized controlled trials (RCTs). The collected evidence was reviewed to evaluate the role of local surgery in this patient population.ResultsMost retrospective studies and meta-analyses report that primary breast surgery is associated with improved prognosis when stage IV disease is first diagnosed. However, significant selection bias exists in these data. Women who undergo surgery tend to be younger, have smaller primary tumors, fewer comorbidities, and lower metastatic burden—particularly fewer visceral metastases. They are also more likely to receive higher-quality overall care. These factors suggest that surgeons preferentially select patients with a better expected prognosis for surgery. In contrast, prospective randomized trials have consistently failed to demonstrate that locoregional surgery provides additional survival benefits beyond systemic therapy alone. Consequently, routine locoregional surgical treatment is not recommended for most patients with de-novo stage IV breast cancer. Nevertheless, a notable exception exists for patients with bone-only metastases.ConclusionAlthough retrospective analyses support a survival advantage from locoregional surgery in de-novo stage IV breast cancer, prospective RCTs have not confirmed a benefit for the general patient population. However, locoregional surgery does appear to offer survival benefits for patients with bone-only metastases. Further prospective clinical trial data are certainly needed to better define the value of locoregional surgery in de-novo stage IV breast cancer.
IntroductionRadiation-induced rectovaginal fistula (RI-RVF) is a severe late complication of pelvic radiotherapy, arising predominantly after treatment for gynaecological malignancy and characterised by fibrosis, ischaemia, impaired healing and poor quality of life. No universally accepted treatment standard exists.MethodsA structured narrative review searched PubMed and Google Scholar (January 2020–July 2026), with earlier landmark studies identified through reference-list screening; it was not conducted or reported as a systematic review. Eight reviewers screened records singly rather than in duplicate, with uncertain cases resolved by consensus with two senior supervisors. Predefined outcome domains beyond anatomical closure were extracted, including stoma-free survival, continence, low anterior resection syndrome, sexual function, pelvic pain and patient-reported quality of life. Seventy publications were cited, of which 26 constitute the clinical evidence base; the remaining 44 provided anatomical, radiotherapeutic, methodological or background context.ResultsFaecal diversion is an appropriate initial, bridging or palliative intervention rather than a universal first-line treatment; spontaneous closure after diversion alone is uncommon (6/50; 12%), and colostomy and ileostomy carry distinct complication profiles. The Martius flap is applied mainly to low fistulas with small defects; the quoted 1.5 cm threshold reflects selection criteria in published series rather than a validated cut-off, and larger defects have been repaired successfully. Gracilis interposition is used for complex or recurrent fistulas, although supporting meta-analytic data derive from heterogeneous perineal fistula cohorts in which only approximately 18% of patients had received radiotherapy. Delayed coloanal anastomosis was associated with fewer anastomotic complications than immediate anastomosis in low rectal cancer meta-analyses, though not consistently across endpoints; this evidence does not derive from RI-RVF populations. Functional and patient-reported outcomes were reported inconsistently, with non-comparable instruments. Evidence for stromal vascular fraction is confined to case reports and small series.ConclusionsThe overall certainty of the available evidence is low. Martius flap reconstruction, graciloplasty and delayed coloanal anastomosis are established options, but reported efficacy must be interpreted against the heterogeneity and indirectness of the available evidence. Stromal vascular fraction remains experimental. Prospective studies should redefine success beyond anatomical closure to include stoma-free survival, functional recovery and patient-reported quality of life.
PurposeThe COVID-19 pandemic led to delays in elective procedures and a reduction in oncological resections worldwide, potentially affecting the prognosis of cancer patients. This study assessed changes in surgical volume, tumor stage distribution, and postoperative overall survival across the pre-pandemic, pandemic, and post-pandemic periods within a regional network comprising one tertiary referral center and two peripheral hospitals.MethodsThis retrospective multicenter observational study included oncological surgical procedures performed in three surgical departments in Halle (Saale) between August 1, 2017, and April 30, 2025. The data were stratified into pre-pandemic, pandemic, and post-pandemic periods. Study outcomes included surgical volume, tumor stage distribution, and postoperative overall survival. Survival analyses were performed in a patient-based cohort using the first eligible procedure as the index operation and assessed at predefined postoperative time points.ResultsA total of 2871 oncological surgical procedures were analyzed across pre-pandemic (n=952), pandemic (n=940), and post-pandemic (n=979) periods. Monthly surgical volume fluctuated across the observation period, reaching its lowest value in April 2020 and December 2021 (n = 20) and its highest value in January 2021 (n = 40). Among patients included in the survival analysis, the proportion of UICC stage IV was higher during the pandemic (26.8%) than in the pre-pandemic (23.9%) or post-pandemic (24.2%) periods. Kaplan–Meier analysis showed a trend toward shorter postoperative overall survival during the pandemic period (log-rank p = 0.066). In multivariable Cox regression adjusted for age, sex, tumor stage, and resection site, the pre-pandemic cohort was associated with a lower hazard of death than the pandemic cohort (HR 0.78, 95% CI 0.65-0.93; p = 0.005).ConclusionChanges in oncological surgical volume were observed across the study periods. During the pandemic period, a higher proportion of advanced tumor stages at presentation and a trend toward shorter postoperative overall survival were observed. After adjustment for baseline characteristics, the pre-pandemic cohort showed a lower mortality hazard than the pandemic cohort. These findings support the importance of resilient healthcare infrastructures for continuous, guideline-concordant oncological care.
Chemotherapy-induced thrombocytopenia (CIT) is a clinically significant complication of systemic anticancer therapy. Although CIT is commonly classified as nadir CIT or persistent CIT based on the timing and pattern of platelet recovery, prolonged thrombocytopenia after chemotherapy discontinuation remains poorly characterized. We report a retrospective case series of five patients with solid tumors who developed prolonged thrombocytopenia after chemotherapy discontinuation. Despite conventional supportive measures, platelet counts (PCs) failed to recover adequately; all patients subsequently received long-term thrombopoietin receptor agonist (TPO-RA) therapy to maintain PCs. TPO-RA supportive treatment was maintained for 7 to 22 months. Bone marrow (BM) examinations consistently demonstrated reduced or absent megakaryocytes, whereas overall hematopoietic activity ranged from relatively preserved to hypoplastic. At last follow-up, all patients were alive. No bleeding or thrombotic events were observed after discontinuation of anticancer therapy, and no clinically apparent TPO-RA-related adverse events were documented during treatment. One patient resumed anticancer therapy while receiving TPO-RA support, whereas the remaining four received no further anticancer treatment. This case series characterizes an understudied pattern of prolonged impairment of platelet recovery after chemotherapy that may require sustained thrombopoietic support. Larger prospective longitudinal studies are needed to clarify the underlying heterogeneity and identify patients most likely to require prolonged TPO-RA therapy.
ObjectiveTo explore the application value of habitat imaging based on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for differentiating luminal and non-luminal subtypes of breast cancer (BC).MethodsRetrospective data from 396 BC patients across two centers were collected. The data from Center 1 were split into a training set of 220 patients and an internal validation set of 56 patients, while Center 2 provided an external test set of 120 patients. Multivariable analysis was performed to identify independent risk factors for developing the clinical model. K-means algorithm was used to perform clustering on DCE-MRI. After feature extraction and selection, eight machine learning algorithms were utilized to build traditional radiomics model, habitat model, and clinical model. A stacking fusion strategy was employed to integrate the traditional radiomics model, habitat model, and clinical model for identifying luminal and non-luminal subtypes patients. Model performance was evaluated using receiver operating characteristic (ROC) curves, calibration curve and decision curve analysis (DCA). Shapley Additive Explanations (SHAP) was performed for model interpretability.ResultsFor the discrimination of breast cancer luminal and non-luminal subtypes, the stacking model yielded the largest area under the curve value (AUC = 0.840), followed by the habitat model and the conventional radiomics model (AUC = 0.830, AUC = 0.805, respectively), all of which were significantly better than the clinical model (p < 0.05, respectively). Calibration curves showed good calibration of the stacking model, and decision curves confirmed its favorable net clinical benefit. SHAP revealed habitat-LGBM in the stacking model with their contribution being particularly prominent.ConclusionHabitat imaging exhibits promising potential to differentiate luminal and non-luminal breast cancer subtypes. The stacking model integrating habitat-LGBM, traditional radiomics-LGBM and clinical-XGBoost may provide favorable predictive performance.
BackgroundCancer-associated fibroblasts (CAFs) can modify ovarian cancer-cell behavior through paracrine signals, but the contribution of CAF-derived Gremlin-1 remains incompletely defined.MethodsWe compared stage IV and stage I ovarian-cancer transcriptomes in GSE9891, performed functional-enrichment analyses of differentially expressed genes, and interrogated CSIOVDB and KM Plotter for GREM1 expression patterns, clinicopathologic associations, EMT-score correlation, and survival outcomes. We also measured GREM1 mRNA in a small cohort of normal, benign and malignant ovarian tissues. In vitro, SKOV3 and A2780 cells were exposed to rGremlin-1, and GREM1 expression was manipulated by overexpression or knockdown in commercial fibroblasts marketed as CAFs (hereafter ‘CAFs’) under co-culture conditions. Cell viability, invasion, migration, apoptosis, EMT markers and, in SKOV3 cells, FGFR1/MEK/ERK phosphorylation were assessed.ResultsGSE9891 DEGs were enriched in ECM-related processes. CSIOVDB associated higher GREM1 expression with tumor stroma, peritoneal metastasis, advanced stage, higher grade, a mesenchymal subtype, and EMT score. In a small exploratory tissue cohort, GREM1 expression showed a numerical increase in benign and malignant ovarian tumors relative to normal tissue, consistent in direction with the CSIOVDB findings, but this pattern was not statistically significant and should be interpreted as descriptive rather than confirmatory. rGremlin-1 exposure altered invasion, migration, EMT markers, and apoptosis, while the SKOV3 CCK-8 response was biphasic. CAF GREM1 gain- and loss-of-function produced opposing changes in several co-culture phenotypes, although some responses were cell-line or time dependent. In SKOV3 cells, OE GREM1 CAFs were associated with higher p-FGFR1/FGFR1, p-MEK1/2/MEK1/2 and p-ERK1/2/ERK1/2 ratios; shGREM1 reduced the p-ERK1/2/ERK1/2 ratio, whereas the p-FGFR1/FGFR1 and p-MEK1/2/MEK1/2 contrasts were not significant.ConclusionCAF GREM1 expression was associated with selected phenotypes in SKOV3 and A2780 cells under the tested in vitro conditions. FGFR1/MEK/ERK phosphorylation patterns in SKOV3 cells suggested a candidate signaling link. Further validation in independently characterized CAF models and additional ovarian-cancer systems is needed.
ObjectiveThis study aimed to characterize the tumor response rate, progression-free survival (PFS), and overall survival (OS) among patients with HR-positive, HER2-negative metastatic breast cancer receiving CDK4/6 inhibitors plus endocrine therapy at Ho Chi Minh City Oncology Hospital. Secondary objectives included identifying clinical factors associated with survival outcomes and characterizing treatment-related toxicities.Materials and methodsWe conducted a retrospective cohort study enrolling 107 patients who received first-line ribociclib or palbociclib in combination with an aromatase inhibitor or fulvestrant at Ho Chi Minh City Oncology Hospital between March 1, 2021, and April 1, 2023.ResultsThe median follow-up duration was 29 months. The median PFS was 28.0 months. The Kaplan–Meier-estimated PFS rates at 12 and 24 months were 66.4% (95% CI, 56.6%–74.4%) and 54.1% (95% CI, 44.2%–63.0%), respectively. The median OS was not reached; corresponding OS rates at 12 and 24 months were 88.8% and 87.8%, respectively. On multivariate Cox regression analysis, ER and PR expression levels emerged as independent prognostic determinants of PFS. Grade 3–4 neutropenia was observed in 58.8% of patients; all events were managed through dose interruption or reduction, and no cases of febrile neutropenia were documented.ConclusionCDK4/6 inhibitors (ribociclib or palbociclib) combined with endocrine therapy demonstrated favorable efficacy and tolerability in Vietnamese patients with HR-positive, HER2-negative metastatic breast cancer. Treatment outcomes and safety profiles were consistent with those reported in pivotal clinical trials and real-world studies. These findings should be interpreted in light of the retrospective single-center design, modest sample size, non-randomized treatment allocation, and immature OS data.
Rationale and objectivesBone metastasis (BM) is pivotal in prostate cancer (PCa) management. This study developed a multimodal model integrating MRI-derived deep features from the prostate gland (PG) and periprostatic adipose tissue (PPAT) with clinical variables for BM risk assessment.MethodsRetrospectively, 464 patients were recruited and randomly divided into training and internal test cohorts at a ratio of 7:3. Deep features were extracted from PG and PPAT regions on T2-weighted MRI using a pretrained ResNet-50 as a fixed feature extractor. Clinical, PG, and PPAT component models were developed using patient-level cross-validation. Their out-of-fold probabilities were integrated by a logistic-regression meta-learner to construct the Deep feature-based PG-PPAT-Clinical (DPPC) model. Model performance was evaluated using ROC-AUC, average precision, calibration analysis, decision-curve analysis, and SHAP analysis.ResultsThe DPPC model achieved ROC-AUCs of 0.922 (95% CI, 0.887–0.954) in the training cohort and 0.928 (95% CI, 0.864–0.978) in the internal test cohort. Its ROC-AUC was significantly higher than that of the Clinical model in the training cohort and the PPAT model in the internal test cohort, whereas the remaining pairwise differences were not statistically significant. At a probability threshold of 0.5, the internal-test sensitivity and specificity were 65.1% and 95.9%, respectively. The observed BM rates were 87.5% in the high-risk group and 13.9% in the low-risk group.ConclusionBy synergizing deep learning signatures from PG and PPAT with clinical factors, the DPPC model demonstrates promising performance for BM risk stratification, and external validation and further calibration assessment are required.
BackgroundAlthough central nervous system leukemia (CNSL) is a recognized complication of acute leukemia, myelodysplastic neoplasms (MDS) complicated by CNSL are exceedingly rare, particularly after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Previous studies have largely focused on chronic myelomonocytic leukemia with central nervous system (CNS) involvement. Here, we describe the first comprehensively documented case of isolated CNS infiltration after allo-HSCT in a patient with MDS.Case presentationA patient with high-risk MDS with increased blasts-2, harboring IDH1 and TP53 mutations, a complex karyotype, and a very high Molecular International Prognostic Scoring System score underwent unrelated allo-HSCT. On day +19 post-transplantation, the patient developed a severe, unexplained headache. Cerebrospinal fluid (CSF) analysis by flow cytometry revealed blasts largely immunophenotypically consistent with those in the bone marrow at initial diagnosis, while concurrent bone marrow assessment confirmed remission. CSF blasts were cleared following triple intrathecal therapy (IT). To date, the patient remains in remission on azacitidine maintenance therapy, with an overall survival of 14 months from diagnosis.ConclusionAlthough CNSL is exceptionally rare in patients with MDS, this case demonstrates that isolated CNS infiltration may occur after allo-HSCT. Our findings emphasize that CNS involvement should be considered in the differential diagnosis of patients with MDS presenting with neurological manifestations, even without marrow relapse. Furthermore, this case highlights the critical role of CSF flow cytometry in establishing the diagnosis when conventional CSF studies are inconclusive.
IntroductionRadiation dose de-escalation for human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) has been actively investigated to reduce long-term toxicity. Following the recent failure of randomized non-inferiority trials, the real-world adoption and outcomes of de-escalated radiation remain unclear. We evaluated contemporary patterns of dose de-escalation and associated overall survival (OS) in a national cohort.MethodsThe National Cancer Database was queried for patients diagnosed from 2018–2022 with p16-positive OPSCC meeting NRG-HN005 eligibility criteria (cT1–2N1 or cT3N0–1) treated with definitive external beam radiation therapy without primary surgery. Dose-de-escalated radiation therapy (DDRT) was defined as 50.0–65.9 Gy; standard-dose radiation therapy (SDRT) as ≥66.0 Gy. Multivariable logistic regression identified predictors of DDRT. OS was estimated using Kaplan–Meier methods with log-rank testing and 2-month landmark analysis.ResultsAmong 14,869 patients, 1,119 (7.5%) received DDRT. DDRT was more frequently delivered at academic centers (50.3% vs 40.0%, p<0.001). On multivariable analysis, academic facility type (Odds Ratio: 1.76, 95% Confidence Interval 1.31-2.43, p<0.001), more recent year of diagnosis, and geographic region were independently associated with DDRT. Three-year OS was inferior with DDRT compared with SDRT (82.1% vs 88.9%, p<0.001). Among patients receiving first-course chemotherapy, DDRT remained associated with worse OS (82.5% vs. 89.8%, p<0.001). No significant difference was observed among patients not receiving chemotherapy; however, this subgroup was small and likely underpowered to detect a meaningful difference. Landmark analysis yielded consistent findings.ConclusionRadiation dose de-escalation remains infrequent in contemporary U.S. practice but is more commonly delivered at academic centers. In this population-based analysis, de-escalation was associated with inferior overall survival, aligning with recent randomized evidence. Reduced-dose radiation should remain investigational pending biomarker-guided selection strategies.
ObjectiveGastric carcinoma (GC) is a leading cause of cancer-related mortality, often driven by epigenetic dysregulation. This study investigates the role of Retinoblastoma-binding protein 2 (RBP2), a chromatin-associated transcriptional regulator frequently overexpressed in GC. We specifically focus on elucidating how RBP2 functions as a transcriptional regulator within the autophagy-angiogenesis network and its impact on disease progression.MethodsThe regulatory axis was dissected using integrated approaches, including transcriptomic profiling, cellular and molecular biology assays, and in vivo animal models. Clinical specimen analysis was performed to correlate RBP2 expression with autophagy and angiogenesis markers. Functional validation involved gain- and loss-of-function experiments to delineate the signaling circuitry linking RBP2 to BECN1 and VEGFA.ResultsWe discovered that RBP2 drives GC progression by establishing an autophagy-angiogenesis positive feedback loop. RBP2 transcriptionally regulates BECN1 through promoter-dependent mechanisms supported by dual-luciferase reporter and ChIP-qPCR assays, thereby inducing protective autophagy. This autophagy enhances VEGFA secretion, which upregulates RBP2 via the inactivation of the JNK/p53/miR-212 axis, thereby relieving post-transcriptional repression. This self-reinforcing circuit facilitates sustained gastric carcinogenesis.ConclusionOur findings support a novel “RBP2-BECN1 -VEGFA-JNK/p53/miR-212-RBP2” regulatory axis that links epigenetic regulation to autophagic survival and angiogenic signaling. This study elucidates a key mechanism underlying GC pathogenesis and suggests potential targets for combinatorial therapeutic strategies.
BackgroundBrain tumors – both primary and metastatic – are a leading cause of mortality and disability among cancer patients. For patients with cancer, physical exercise has proven effective in the management of multiple cancer- and treatment-related symptoms. However, the benefits of physical exercise have been understudied in patients with a brain tumor diagnosis.MethodsWe systematically reviewed the literature on physical exercise interventions in patients with brain tumors. A systematic search of PubMed and the Cochrane Library was conducted up to December 2025 following PRISMA guidelines. Studies were screened according to predefined inclusion and exclusion criteria, and data were extracted using a structured approach. Study quality and level of evidence were assessed using the Oxford Centre for Evidence-Based Medicine (CEBM) Levels of Evidence, and risk of bias was evaluated using the Cochrane Risk of Bias 2 (RoB 2) tool for randomized controlled trials (RCT) and Risk Of Bias in Non-randomized Studies of Interventions (ROBINS -I) for non-randomized studies. Results were synthesized descriptively.ResultsThirty-one studies (23 clinical trials, 4 observational studies, 2 qualitative analyses, 1 case report and 1 case study) met inclusion criteria and were synthesized descriptively to accommodate for the heterogeneity of study designs and recorded outcomes. Brain tumor patients were able to participate in aerobic, strength training, mixed (aerobic + strength), yoga and balance exercise interventions, and the findings suggest potential improvements in physical and cognitive function as well as quality of life. Adverse events reported were rare and consistent with exercise-related adverse events reported for individuals without cancer.ConclusionsThe available literature suggests the feasibility and overall safety of physical exercise in brain tumor patients although evidence of clinical effectiveness remains preliminary. The majority of findings are based on structured intervention studies, and broader applicability remains to be determined due to the limited evidence available. The high risk of bias noted in most studies, as well as their generally small sample sizes and diversity of exercise interventions studied, highlight the need for larger prospective clinical trials to determine clinical effectiveness and inform the design of exercise guidelines for brain tumor patients.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/view/CRD420251111272, identifier CRD420251111272.
IntroductionExisting research has linked increased patient participation in oncology care to greater patient satisfaction, enhanced quality of life, and improved healthcare utilization among patients with cancer. Yet, current measures of patient engagement and similar constructs do not reflect the unique experiences of patients with metastatic breast cancer; they also have limitations in terms of modality, cost, and potential for integration into clinical care. To address this, we sought to develop a new measure of participatory care in metastatic breast cancer care, referred to as the Capacity, Opportunity, and Resources in Metastatic Breast Cancer (CORe-MBC) that could be easily used in clinical care.MethodsA comprehensive pool of candidate items for CORe-MBC was created with input from MBC patients, oncologists, and experts in measure development. Items were tested among 130 English-speaking patients with MBC recruited from a large academic oncology center; participants also completed validated measures of health activation, self-efficacy, satisfaction with care, and social support (e.g., emotional, informational, and tangible). Psychometric testing included exploratory factor analyses, using oblique rotations to evaluate factor structure, and parallel analysis to test for dimensionality.ResultsPatients’ ages ranged from 34 to 90 years. The majority (82%) identified as White, one-third (34%) had less than a college degree, and almost all (99%) were female. Candidate items loaded onto three factors (all factor loadings >.5), reflecting the domains of capacity, opportunity, and resources. A total of 10 items were selected for the final measure. Items demonstrated high internal consistency (α = 0.83). Domains of capacity, opportunity, and resources demonstrated moderate to high construct validity with comparable measures of patient activation (r = 0.56, p <.0001) and self-efficacy (r = 0.31–0.40, p < 0.0005), and multiple measures of satisfaction with healthcare (r = 0.42–0.55, p <.0001), and social support (r = 0.52–0.75, p <.0001), respectively.ConclusionThe CORe-MBC measure appears to be psychometrically valid and reliable. Additional studies are ongoing to further validate use of the tool among diverse populations and within a variety of oncology practices, with the goal of providing clinicians with actionable insights to tailor and improve care.
PurposeTo develop and validate a multiparametric MRI (mpMRI)-based radiomics model incorporating features from both the tumor lesion and periprostatic adipose tissue (PPAT) for predicting synchronous bone metastasis (BM) in patients with newly diagnosed prostate cancer (PCa).MethodsThis retrospective study enrolled 237 patients with histologically confirmed PCa who underwent prostate mpMRI between January 2021 and December 2024. Patients were randomly allocated to a training cohort (n = 165) and a validation cohort (n = 72) in a 7:3 ratio. Univariate and multivariate logistic regression analyses identified independent clinical predictors of BM. Radiomics features were extracted from tumor lesions and PPAT on T2-weighted imaging (T2WI), fat-suppressed T2-weighted imaging (T2WI-FS), and apparent diffusion coefficient (ADC) maps. Separate radiomics models were constructed for intratumoral, PPAT, and combined (intratumoral + PPAT) features. A combined clinical-radiomics model was established by integrating the radiomics score (Rad-score) with independent clinical predictors. Model performance was evaluated using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA).ResultsMultivariate analysis identified clinical T stage (OR = 5.00, 95% CI: 1.65–16.70; p = 0.006) and Ki-67 expression (OR = 4.61, 95% CI: 1.63–14.10; p = 0.005) as independent predictors of BM. The intratumoral radiomics model achieved AUCs of 0.928 (training) and 0.835 (validation). The PPAT radiomics model achieved AUCs of 0.859 (training) and 0.842 (validation). The combined radiomics model (intratumoral + PPAT) yielded AUCs of 0.955 (95% CI: 0.927–0.982) and 0.850 (95% CI: 0.745–0.954) in the training and validation cohorts, respectively. The combined clinical-radiomics model demonstrated AUCs of 0.960 (95% CI: 0.934–0.986) and 0.873 (95% CI: 0.785–0.960), respectively. DCA indicated favorable clinical net benefit across a wide range of threshold probabilities.ConclusionThe combined model integrating PPAT and tumor radiomics features with clinical predictors demonstrated robust discriminative ability for predicting BM in newly diagnosed PCa. This non-invasive model may provide complementary risk stratification beyond conventional clinical assessment by identifying patients with potentially aggressive disease characteristics and supporting individualized clinical decision-making.
BackgroundCervical nodal metastasis critically influences prognosis in oral squamous cell carcinoma (OSCC), yet current staging does not quantify the degree of metastatic replacement within lymph nodes. This study evaluated morphometric index Node Deposit Size Index (NDSI) to assess their association with pathological aggressiveness and survival.MethodsAn ambispective cohort of 104 surgically treated, node-positive OSCC patients was analysed. Maximum metastatic deposit diameter and lymph node diameter were measured on routine H&E slides. NDSI correlated with clinicopathological variables, extranodal extension (ENE), lymph node density (LND), and survival using non-parametric tests, Spearman correlation, Kaplan–Meier analysis, and ROC curves.ResultsENE-positive nodes demonstrated higher NDSI than ENE-negative nodes (86.9% vs 43.8%; p < 0.001). NDSI increased across pathological nodal stage (pN), from 31.9% in pN1 to 87.8% in pN3b (p < 0.001), and across overall stage, reaching 87.9% in Stage IVB (p < 0.001). Higher NDSI was associated with lymphovascular invasion (LVI) (72.0% vs 45.4%; p < 0.001) and perineural invasion (69.5% vs 50.7%; p = 0.024). NDSI correlated with LND (Spearman ρ=0.43, p < 0.001). ROC analysis identified an NDSI cutoff of 73.3% for predicting ENE (AUC = 0.854; not internally validated) and a cutoff of 60% for predicting 1-year mortality (AUC = 0.708; not internally validated). On multivariable linear regression (R² = 0.524), LVI and pN (pN2a, pN2b, and pN3b) were independently associated with higher NDSI, whereas the remaining clinicopathological variables were not independently significant.ConclusionNDSI correlate with adverse pathology and early mortality. However, the association between NDSI and ENE is not fully independent of pathological N-stage, and reproducibility, independent prognostic value, and cutoff stability require external validation before clinical use.
ObjectiveTo investigate the association between surgical timing and neurological recovery and survival in patients with complete or incomplete paralysis due to metastatic spinal cord compression, and to develop a nomogram for predicting marked neurological recovery.MethodsA total of 302 patients who underwent surgical decompression for spinal metastasis-induced paralysis between 2019 and 2023 were retrospectively analyzed. Patients were divided into four groups based on the time from paralysis onset to surgery: <24h, 24–72h, 72h–1w, and >1w. The primary outcome was marked neurological recovery (improvement to AIS D/E). Survival outcomes were also assessed. Multivariable Firth penalized logistic regression and Cox proportional hazards regression were performed. A nomogram was constructed and validated using bootstrap resampling (C-index, calibration curve, ROC curve, and decision curve analysis).ResultsEarlier surgery was strongly associated with better neurological recovery. Compared with the <24h group, the odds ratios for marked recovery were 0.69 (24–72h, p=0.361), 0.34 (72h–1w, p=0.019), and 0.17 (>1w, p<0.001). Delayed surgery was associated with significantly increased mortality risk: hazard ratios were 1.87 (72h–1w, p=0.026) and 4.44 (>1w, p<0.001). Preoperative AIS grade C (OR=6.86, p<0.001), higher ESCC grade (grade 2 vs. 1C: OR=0.14; grade 3 vs. 1C: OR=0.28), and flaccid muscle tone (OR=0.23, p<0.001) were independent predictors of recovery. The nomogram showed excellent discrimination with a bootstrap-corrected C-index of 0.873 and an AUC of 0.888 (95% CI: 0.852–0.925). Decision curve analysis confirmed its clinical utility.ConclusionEarly surgery (within 1 week, ideally <24h) was associated with better neurological recovery and longer survival in patients with spinal metastasis-induced paralysis. However, given the retrospective design and the absence of key oncological covariates—including performance status, systemic disease burden, and visceral metastases—the survival association should be interpreted with caution and does not imply causality. Preoperative AIS grade C was associated with better recovery, while higher ESCC grade (grade 2 vs. 1C: OR=0.14; grade 3 vs. 1C: OR=0.28) was associated with lower odds of recovery, indicating that patients with less severe cord compression (ESCC grade 1C) had better outcomes. Flaccid muscle tone predicted poorer outcomes. The proposed nomogram provides a preliminary tool for individualized prediction of marked neurological recovery, pending external validation.
