Search Results (8,911)

A circulating tumor DNA (ctDNA) assay is an emerging non-invasive diagnostic approach providing real-time insights into the heterogeneous tumor molecular landscape of advanced prostate cancer, overcoming the limitations of traditional tissue biopsies and PSA. Detection methods include droplet digital PCR, next-generation sequencing, and new epigenomic and fragmentomic strategies (investigational) designed to improve sensitivity in cases of low ctDNA shedding. While ctDNA’s role in localized prostate cancer is limited, it offers significant prognostic value in metastatic cases, where high ctDNA levels correlate with shorter survival. Additionally, longitudinal ctDNA monitoring can predict treatment response and identify emerging resistance mechanisms, including androgen receptor alterations associated with androgen receptor pathway inhibitor therapy and BRCA reversion mutations linked to PARP inhibitors. Importantly, liquid biopsy enables genomic characterization to inform treatment decision-making, particularly in clinical scenarios where tissue biopsy is challenging, such as bone-only disease. However, the widespread clinical implementation of ctDNA analysis is hindered by several analytical challenges, including low sensitivity in localized disease and low disease burden, and the risk of false positives due to clonal hematopoiesis. Furthermore, greater efforts are required to standardize pre-analytical workflows and post-analytical data interpretation and reporting across institutions. This review aims to summarize the evolving role of cfDNA technologies in localized and advanced prostate cancer, highlighting their prognostic and predictive value and their role in uncovering mechanisms of treatment resistance. Full article

Background: Early external validation studies demonstrated the robust and consistent predictive performance of the International IgA Nephropathy Prediction Tool (IIgAN-PT) across diverse ethnic populations. However, emerging evidence suggests that, in contemporary cohorts of patients with IgA nephropathy, the IIgAN-PT increasingly tends to overestimate the risk of adverse renal outcomes. Subclassification of segmental glomerulosclerosis (S lesions) in the Oxford Classification system (MEST-C) could identify high-risk IgAN patients, with evidence that different S subclassifications respond differently to treatment. Our study aimed to evaluate the predictive performance of the IIgAN-PT in a contemporary Chinese external validation cohort and to optimize its prognostic accuracy by incorporating the most severe and prevalent pathological subclassification of S lesions, NOS⁺Adh⁺, into the original model. Methods: A total of 746 Chinese patients were included with biopsy-proven IgAN in this study. Major adverse kidney events (MAKEs) were defined as death from any cause, initiation of renal replacement therapy, or a 50% decline in eGFR. This study evaluated the discrimination and model fit of three predictive models. The performance of the original and modified IIgAN-PT models was compared and evaluated through reclassification, survival analysis, calibration, decision curve analyses and subgroup analyses. Results: In the study cohort, the median follow-up duration was 4.2 years, during which 77 patients experienced MAKEs. The discriminative ability of the three original models was relatively limited. In contrast, the modified IIgAN-PT incorporating the NOS⁺Adh⁺ subtype of S subclassification demonstrated improved global performance for predicting 5-year risk, achieving a C-index of 0.808 (95% CI, 0.756–0.861). Kaplan–Meier survival curves showed clear risk stratification, particularly between low- and intermediate-risk categories. Reclassification analyses (continuous NRI and IDI) and decision curve analysis further supported enhanced predictive performance, while calibration curves corrected the original model’s risk overestimation. The modified model maintained stable performance across clinically relevant subgroups, including patients with hypertension, proteinuria, or receiving immunosuppression. Conclusions: This study further confirms the independent and clinically relevant prognostic value of the S pathological subclassification. The modified IIgAN-PT model, incorporating the NOS⁺Adh⁺ subtype of S subclassification, demonstrated consistent performance in individualized risk assessment for patients with IgA nephropathy. Full article

Background: Stroke is the most common neurological disorder in adults and a leading cause of mortality and disability. Intracerebral hemorrhage (ICH), although less frequent than ischemic stroke, is associated with higher morbidity and mortality and often requires ICU admission. Predicting mortality remains challenging due to disease heterogeneity. Objectives: This study evaluated the prognostic value of the modified Nutrition Risk in Critically Ill (mNUTRIC) and Controlling Nutritional Status (CONUT) scores, along with conventional severity scores (GCS, APACHE II, SOFA), in ICU patients with ICH. Methods: This retrospective cohort study included 347 ICU patients with ICH admitted between January 2019 and June 2025. Patients were stratified by survival status and nutritional and conventional severity scores were analyzed. Subgroup analysis was performed in patients with GCS ≤ 12 and APACHE II ≥ 17 (n = 96). Multivariate logistic regression and receiver operating characteristic (ROC) analyses assessed predictive performance. Results: ICU mortality was 24.2%. Deceased patients had lower GCS and higher APACHE II, SOFA, mNUTRIC, and CONUT scores (p < 0.001). Subgroup analysis showed higher mortality in patients with elevated mNUTRIC and CONUT scores (p = 0.038 and p = 0.005). Multivariate analysis identified GCS (OR = 0.675, p < 0.001) and CONUT (OR = 1.174, p = 0.040) as independent predictors; mNUTRIC was not significant. ROC analysis demonstrated good discrimination (AUC 0.818 for mNUTRIC and 0.81 for CONUT), with mNUTRIC being more specific and CONUT more sensitive. Optimal cut-off values were >3 for mNUTRIC and >4 for CONUT. Conclusions: Both mNUTRIC and CONUT scores are associated with mortality in ICU patients with ICH, with CONUT showing independent prognostic value. Their combined use may aid clinical decision-making. Full article

Background and Objectives: Metastatic renal cell carcinoma (mRCC) remains a lethal disease despite advances with immune checkpoint inhibitors such as nivolumab. However, a substantial proportion of patients exhibit primary resistance or early progression, highlighting the need for reliable and easily accessible prognostic biomarkers. The C-reactive protein–albumin–lymphocyte (CALLY) index is a novel immunonutritional biomarker integrating systemic inflammation, nutritional status, and immune competence. Materials and Methods: In this retrospective single-center study, 91 patients with mRCC treated with nivolumab were analyzed. Patients were stratified into low and high CALLY index groups based on a receiver operating characteristic-derived cut-off (0.322). Survival outcomes were assessed using Kaplan–Meier analysis and Cox regression models. Results: Patients with a low CALLY index demonstrated significantly shorter progression-free survival (4.5 vs. 13.5 months, p < 0.001) and overall survival (9.1 vs. 25.5 months, p = 0.003). Multivariate analysis confirmed the CALLY index as an independent prognostic factor for both progression-free survival (HR: 2.63, p = 0.002) and overall survival (HR: 1.88, p = 0.035). Conclusions: The CALLY index is a simple, cost-effective, and reproducible biomarker that independently predicts survival in nivolumab-treated mRCC. It may serve as a practical tool for risk stratification and personalized treatment planning in the immunotherapy era. Full article

Background/Objectives: Integrating multi-omics data for cancer prognosis remains a challenging problem in bioinformatics because molecular profiles are high-dimensional, heterogeneous, and structured by incomplete biological relationships. Pathway databases provide biologically meaningful prior knowledge for modeling gene-level associations, but the sparsity and local incompleteness of pathway-derived networks often limit the performance of graph-based survival models. This study aimed to develop a pathway-guided framework for improving multi-omics survival prediction and identifying biologically relevant prognostic signals. Methods: We proposed PANA-Surv, a pathway-guided adaptive neighborhood augmentation framework for multi-omics cancer survival analysis. In this framework, KEGG pathways were used to construct gene graphs, and gene-level multi-omics profiles were encoded as node features. A conditional variational autoencoder module (PANA-VAE) was designed to enhance local representations through neighborhood reconstruction and adaptive weighting. The augmented features were then integrated into a graph convolutional survival model optimized with the Cox partial likelihood. Results: PANA-Surv was evaluated on 10 cancer cohorts from The Cancer Genome Atlas (TCGA). The proposed method achieved the highest mean concordance index (C-index) among all compared models and significantly outperformed Cox-EN, DeepSurv, GraphSurv, and LAGProg (all p < 0.01). Ablation analyses showed that both neighborhood reconstruction and adaptive weighting contributed to the observed performance gains, and KEGG-guided graph construction was more effective than alternative graph construction strategies. In a breast cancer (BRCA) case study, PANA-Surv identified 18 prognostic genes, including 12 genes supported by previous studies and 6 potentially novel candidates. Conclusions: These findings indicate that the integration of pathway prior knowledge with adaptive local feature enhancement can improve multi-omics survival modeling and support the identification of biologically relevant prognostic signals associated with cancer outcomes. Full article

Background: Persistent lymph node metastases after neoadjuvant radiochemotherapy (RCT) for locally advanced rectal cancer indicate poor response to treatment. This study evaluated the long-term prognosis of patients with residual nodal disease following neoadjuvant RCT and total mesorectal excision (TME) in comparison with patients who underwent upfront TME without adjuvant radiotherapy. Methods: Consecutive patients with rectal adenocarcinoma and histopathologically confirmed lymph node metastases after TME were identified from the prospectively maintained database of the colorectal unit at Dresden-Friedrichstadt General Hospital. Patients with distant metastases, in-hospital mortality, or postoperative radiotherapy were excluded. The two groups were comprehensively compared regarding patient-, tumor-, and treatment-related characteristics. Cumulative local recurrence, time to recurrence, cancer-specific survival, and overall survival were analyzed using the Kaplan–Meier method. Results: Between 1996 and 2021, 155 eligible patients were identified, including 101 patients in the RCT group and 54 in the upfront surgery group. Baseline characteristics were largely comparable, except for a higher median age (70.5 vs. 64 years, p < 0.001) and a higher proportion of lymphovascular invasion (36.0% vs. 15.2%, p = 0.004) in the upfront surgery group. Ten-year local recurrence rates were similar between groups (21.0% [95% CI: 10.4–31.6] vs. 20.8% [95% CI: 8.5–33.1], p = 0.609). No significant differences were observed in time to recurrence or cancer-specific survival. Overall survival was lower in the upfront surgery group, most likely reflecting the substantially higher age of these patients. Conclusions: Despite more intensive treatment, patients with a persistent ypN-positive category have outcomes no better than untreated patients with node-positive disease after TME, indicating a biologically high-risk subgroup. Non-response is therefore a sign of a negative selection. These patients may lose the opportunity for optimal local tumor control during prolonged neoadjuvant treatment, underscoring the urgent need for reliable predictive markers to identify non-responders and guide individualized treatment strategies. Full article

Background: Although immune checkpoint inhibitors (ICIs) have improved survival in advanced melanoma, predicting individual responses remains challenging; thus, practical and inexpensive biomarkers are needed. In this study, we investigated the prognostic value of the neutrophil percentage–albumin ratio (NPAR) in patients with advanced melanoma receiving ICI therapy. Methods: Fifty patients treated in our clinic were included, with a mean age of 53.3 years and 66% being male. Visceral metastases were present in 76% of the cohort. Through conducting Receiver Operating Characteristic (ROC) analysis, we determined an NPAR cut-off value of 1.81, with patients categorized into low (<1.81, n = 27)- and high (≥1.81, n = 23)-NPAR groups. The progression-free survival (PFS) and overall survival (OS) were evaluated using Kaplan–Meier and Cox regression analyses. Results: High NPAR (≥1.81) significantly shortened both PFS and OS. In the univariate analysis, high NPAR emerged as a strong risk factor for PFS (HR: 2.68, p = 0.002) and OS (HR: 3.70, p < 0.001), while multivariate analysis confirmed NPAR as an independent negative prognostic factor for PFS (HR: 2.45, p = 0.006) and OS (HR: 2.82, p = 0.003), regardless of clinical variables. Additionally, visceral metastasis was an independent negative predictor of survival. Conclusions: Pre-treatment NPAR levels may be an independent and potential predictor of survival in advanced melanoma patients receiving ICIs. This easily calculable ratio could provide a practical guide for risk stratification. Full article

Background/Objectives: Breast cancer (BC) is a highly prevalent neoplasm worldwide. Despite the wide range of therapeutic options currently available, it remains the leading cause of cancer-related mortality among women. Capecitabine, a prodrug of 5-fluorouracil (5-FU), is widely used in the treatment of advanced BC. However, despite its efficacy, capecitabine exhibits considerable interindividual variability in therapeutic response. This study aimed to evaluate the effect of single-nucleotide polymorphisms (SNPs) in genes involved in capecitabine bioactivation on progression-free survival (PFS) in patients with BC. Methods: An ambispective cohort study was conducted. Four relevant SNPs in the CES1, CDA, and TYMP genes were analyzed in 85 Caucasian patients with BC using real-time polymerase chain reaction (PCR) with TaqMan^® probes. Results: A significant association was observed between shorter PFS and the GA genotype of the CES1 rs71647871 SNP (p = 0.010; HR = 7.46; 95% CI = 1.24–122.52), as well as with the TT genotype of the CDA rs602950 SNP (p = 0.009; HR = 3.50; 95% CI = 1.36–9.03). Conclusions: These findings suggest that CES1 rs71647871 and CDA rs602950 may serve as predictive biomarkers of capecitabine effectiveness in patients with BC. Further studies involving larger cohorts are needed to validate these findings and generate additional evidence to support their potential implementation in clinical practice. Full article

Background/Objectives: Survival rates after pediatric liver transplantation have improved substantially over recent decades, yet the psychiatric consequences for recipients remain a concern that warrants closer attention. We sought to map the psychiatric symptom burden across multiple domains in this population and to determine which symptom clusters carry the greatest impact on health-related quality of life (HRQOL). Materials and Methods: Fifty liver transplant recipients between the ages of 8 and 18 were enrolled at a single center. Children and their parents completed four psychiatric measures—the CBCL, CDI, SCARED, and CRIES-13—alongside the parent-proxy PedsQL to capture HRQOL across physical, emotional, social, and school functioning domains. Correlations between instruments were calculated, and linear regression was used to determine which psychiatric variables independently predicted PedsQL Total scores. Results: Across all psychiatric measures, higher symptom scores were associated with lower HRQOL, with school functioning recording the lowest absolute PedsQL domain score, while emotional functioning demonstrated the strongest and most consistent inverse correlations with all psychiatric symptom measures across instruments. CBCL Total (r = −0.607), SCARED Total (r = −0.557), and CRIES-13 Total (r = −0.548) scores all correlated meaningfully with overall HRQOL. When entered into multivariable analysis, anxiety symptoms measured by the SCARED (β = −0.295, p = 0.032) and post-traumatic stress symptoms measured by the CRIES-13 (β = −0.400, p = 0.004) stood out as the two independent predictors of worse PedsQL Total scores. Conclusions: Even in medically stable recipients, anxiety and post-traumatic stress symptoms were independently associated with lower daily functioning scores and overall quality of life. These findings suggest that routine psychosocial screening and trauma-informed approaches may warrant integration into post-transplant care protocols, and that prospective, adequately powered studies are needed to confirm and extend these associations. Full article

Background and Objectives: Positron emission tomography with 18F-FDG (PET-CT) provides a quantitative measure of tumor metabolic activity through the maximum standardized uptake value (SUVmax) of lung tumors—a measure of metabolic activity that may have prognostic value in non-small cell lung cancer (NSCLC). This study evaluated whether preoperative tumor SUVmax predicts outcomes in resected NSCLC. Materials and Methods: This single-center retrospective study included 209 consecutive patients with resected NSCLC who had preoperative FDG PET-CT. SUVmax of the primary tumor was recorded, and patients were stratified into low- and high-SUVmax groups to evaluate survival outcomes. Results: Median age was 62 years and 77% were male. Histologic subtypes were adenocarcinoma (44%), squamous carcinoma (43%), and others (13%), with stage I–III distribution of 39.7%, 33.5%, and 26.8%, respectively. SUVmax demonstrated moderate discrimination for mortality (AUC = 0.652), with an optimal cutoff of 11.14. Patients with SUVmax ≥ 11.14 had significantly worse OS and DFS. However, on multivariate analysis, SUVmax was not an independent predictor of outcomes, while extracapsular invasion (OS) and adjuvant chemotherapy (DFS) remained significant. Conclusions: In this cohort of resected NSCLC, high preoperative SUVmax (≥11.14) was associated with more advanced tumor stage and worse OS/DFS but was not an independent prognostic factor after accounting for other variables. Tumor invasiveness and use of adjuvant therapy were stronger outcome predictors. Preoperative SUVmax may help identify high-risk patients when considered alongside established clinicopathologic factors. Full article

Background: Human epidermal growth factor receptor 2 (HER2) alterations have been implicated as mechanisms of resistance to anti-epidermal growth factor receptor (anti-EGFR) therapy in metastatic colorectal cancer (mCRC). We aimed to evaluate the predictive and prognostic significance of HER2 expression in patients with RAS wild-type mCRC in a real-world setting. Methods: We conducted a multicenter retrospective cohort study across ten oncology centers in Turkey, including patients with RAS wild-type mCRC treated between 2015 and 2022. Clinical outcomes, including progression-free survival (PFS) and overall survival (OS), were compared between HER2-positive and HER2-negative groups. Multivariable Cox proportional hazards models were used to identify independent predictors of survival outcomes. Results: Among 204 patients, 28 (13.7%) were HER2-positive. Baseline characteristics were generally comparable; however, HER2-positive patients showed a trend toward higher-grade tumors and were significantly less likely to receive anti-EGFR therapy. HER2-positive patients had significantly shorter PFS compared to HER2-negative patients (median 10 vs. 13 months; p = 0.006). In multivariable analysis, HER2 positivity remained an independent predictor of shorter PFS (HR 1.76, 95% CI 1.01–3.07; p = 0.045). In the subgroup of 144 patients receiving anti-EGFR therapy, HER2-positive patients also demonstrated significantly shorter PFS (median 9.0 vs. 14.0 months; p = 0.023). No significant differences in OS were observed between groups. Conclusions: HER2 positivity is associated with reduced response to anti-EGFR therapy and independently predicts shorter PFS in patients with RAS wild-type mCRC. These findings further support the role of HER2 as a clinically relevant biomarker in RAS wild-type mCRC, particularly in predicting response to anti-EGFR therapy, while highlighting the need for optimized patient selection strategies in the era of HER2-targeted treatments. Full article

Purpose: Prostate cancer is one of the most common malignancies in men, yet current prognostic methods remain suboptimal. Emerging evidence indicates that microRNAs (miRNAs) play critical roles in prostate cancer progression. This study aimed to identify miRNAs associated with adverse clinical outcomes by comparing miRNA expression profiles between prostate tumors with unfavorable versus favorable prognostic features. Materials and Methods: High-throughput next-generation sequencing (NGS) was used to analyze miRNA expression in formalin-fixed, paraffin-embedded prostate cancer tissue samples. Patients were classified into favorable or unfavorable prognosis groups based on risk stratification scores, Gleason grade group, and biochemical recurrence. Differentially expressed miRNAs were identified using a fold-change threshold ≥2 and a false discovery rate (FDR) <0.05. Predicted target genes and pathway analyses were conducted to generate candidate regulatory hypotheses rather than confirm mechanistic relationships. Results: Several miRNAs were differentially expressed according to prognostic category. miR-206 was significantly downregulated in high-risk tumors compared with low-risk tumors. High-Gleason-grade tumors showed reduced expression of miR-7704 and miR-4454, while miR-25-3p and let-7f-5p were upregulated. In patients with early biochemical recurrence, miR-7704 and miR-10400-5p were downregulated relative to those with prolonged recurrence-free survival. Target prediction analysis identified CPEB3, HAND1, PTAR1, and SPRYD4 as shared candidate targets, with CPEB3 emerging as a prioritized candidate supported by consistency in external datasets rather than a confirmed molecular target. Conclusions: Distinct miRNA expression patterns correlate with prostate cancer aggressiveness and clinical outcomes. miR-206, miR-7704, miR-4454, miR-25-3p, and let-7f-5p represent candidate prognostic biomarkers. Their shared target CPEB3 should be interpreted as a prioritized candidate for future investigation. Given the very small sample size and the lack of qRT-PCR and functional validation, these findings should be considered preliminary and hypothesis-generating, requiring validation in larger independent cohorts and experimental studies. Full article

Dental implant therapy demonstrates high long-term survival; however, biological, behavioral, and technical complications remain prevalent. The objective of this project report was to introduce GF-Predictability for Dental Implants (GF-PreDImp), a novel, comprehensive pre-surgical multidimensional scoring proposal designed to quantify implant success predictability through a structured, evidence-based system. The model integrates six domains, Biological, Behavioral, Hard tissue, Soft tissue, Implant, and Prosthetic, assessing variables into a 100-point composite index. The domains evaluate systemic conditions (20 pts), behavioral habits (20 pts), hard-tissue anatomy (20 pts), soft-tissue characteristics (15 pts), implant parameters (15 pts), and prosthetic/surgical factors (10 pts). The final GF-PreDImp score categorizes predictability into five levels: excellent (≥85), good (70–84), moderate to guarded (55–69), guarded to high risk (40–54), and poor (<40). The tool generates dynamic visual outputs, including radar charts, enabling rapid clinical interpretation. While GF-PreDImp provides a framework for individualized risk stratification, it currently serves as a design proposal. Its implementation can improve clinical decision-making and enhance long-term implant outcomes. Further clinical assessments must be done to confirm the findings in future studies. Full article

Melanoma adjuvant therapy has substantially improved recurrence-free and distant metastasis-free survival in patients with resected high-risk disease, and more recently, these advances have extended to earlier stages. However, important unmet needs remain, including the management of stage IIIA disease, the optimal treatment strategy after relapse on adjuvant therapy, and the identification of biomarkers capable of refining patient selection. This review summarizes recent advances and unresolved questions in the adjuvant and neoadjuvant treatment of melanoma. We discuss novel systemic strategies, including immune checkpoint inhibitor combinations and personalized neoantigen mRNA vaccines, together with the expanding role of neoadjuvant approaches. We also examine prognostic and predictive tools—such as clinicopathologic models, circulating tumor DNA, serum biomarkers, tumor microenvironment features, and gene expression profiling—that may help better define recurrence risk and therapeutic benefit. Current evidence suggests that although modern therapies have changed the natural history of resected melanoma, a substantial proportion of patients are still overtreated or undertreated when treatment decisions are based on stage alone. Future progress will depend on integrating biological risk stratification with clinical staging and optimizing treatment sequencing across adjuvant and neoadjuvant settings. Full article

Background/Objectives: Metabolic syndrome (MetS) affects more than 1.5 billion adults worldwide and is present in 37–70% of STEMI patients. Its ten-year prognostic value after primary PCI—particularly for heart failure, which is rarely examined as a primary endpoint—remains incompletely characterized. Methods: In total, 506 STEMI patients treated with primary PCI (December 2009–June 2010) were followed for ten years. MetS was defined at admission using AHA/NHLBI criteria. Co-primary endpoints were all-cause mortality, MACE, and hospitalization for heart failure. Multivariable Cox regression was adjusted for sex, age, LVEF, previous MI, Killip class, and multivessel disease. Four ML models were evaluated by 10-fold stratified cross-validation with SHAP-based feature, with a Fine–Gray subdistribution-hazard sensitivity analysis for heart failure. Feature attribution used TreeSHAP on XGBoost and permutation importance on a Random Survival Forest. Results: MetS(+) patients were older, more frequently female, and had higher SYNTAX scores (all p < 0.05). MetS was present in 216 patients (42.7%). It did not independently predict mortality (HR 1.09, p = 0.66) but did predict MACE (HR 1.47, p = 0.028) and heart failure hospitalization (cause-specific HR 2.86, 95% CI 1.57–5.22; Fine–Gray HR 2.61, 95% CI 1.44–4.75; both p ≤ 0.002). The null mortality finding coincided with differential statin discontinuation and a selective obesity paradox: in non-obese patients, MetS doubled mortality (42.9% vs. 21.1%, p = 0.008), while in obese patients, the effect disappeared (26.5% vs. 23.2%, p = 0.529). Two independent ML frameworks ranked the cumulative number of MetS criteria—rather than the binary diagnosis—among the leading individual-level features for heart failure prediction (Random Survival Forest c-index 0.843). Conclusions: In primary PCI-treated STEMI survivors, MetS independently predicts ten-year MACE and heart failure but not mortality. The number of MetS criteria at baseline, rather than the binary classification, was more strongly associated with heart failure risk; whether prospective modification of individual components reduces this risk requires dedicated interventional studies. The lean MetS-positive phenotype may represent a candidate subgroup warranting further investigation. Full article