This meta-analysis aimed to assess the prognostic value of circulating tumor DNA (ctDNA) in predicting progression-free survival (PFS) and overall survival (OS) of advanced non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs), thereby providing evidence-based support for clinical decision-making.

Background Early onset pancreatic cancer (EOPC), defined for the primary analysis as pancreatic ductal adenocarcinoma (PDAC) diagnosed before the age of 50 years, is an increasingly recognised clinical and epidemiological entity. Because published studies use heterogeneous age thresholds, the present review prespecified <50 years as the main definition and interpreted studies using other cutoffs in sensitivity or narrative analyses. Methods We systematically searched PubMed, EMBASE, and the Cochrane Library for studies published between January 1990 and December 2024 that reported outcomes specific to EOPC. Search terms were reformatted with standard quotation marks and included "pancreatic cancer", "pancreatic adenocarcinoma", "pancreatic ductal adenocarcinoma", "early onset", "young onset", "young adult", "age < 50", "age less than 50", and "premature". Meta-analytic procedures and epidemiological interpretation were re-reviewed with statistical/epidemiological input. Results 40 studies encompassing more than 285,000 patients were included. Global incident EOPC cases increased from 24,480 (1990) to 42,254 (2021), representing a 72·6% rise. Age-standardised prevalence rate increased by 17·0% (1·65 per 100,000 in 2021). EOPC patients have a 3·08% per year increase in the youngest age group (20-29 years) over 2010-2021. Germline pathogenic variants were identified in 17·3% of EOPC patients (vs 6·4% in older cohorts; OR 2·41, 95% CI 1·87-3·11). EOPC patients were more likely to receive treatment (OR 2·95, 95% CI 2·54-3·43; I2 = 13%) and showed modestly improved overall survival (pooled HR 0·89, 95% CI 0·80-0·99; I2 = 16%) compared with average or late onset disease. Conclusions EOPC is an increasingly recognised and clinically challenging subset of PDAC. The substantial hereditary and potentially actionable molecular burden supports universal germline testing and comprehensive tumour genomic profiling, particularly in younger patients and in KRAS wild-type disease. PARP inhibitors should be described as improving progression-free survival or disease-control outcomes in selected BRCA-mutated metastatic PDAC rather than as having established a statistically significant overall survival benefit.

Cerebral cavernous malformations (CCMs) are vascular lesions characterized by blood-brain barrier instability and a propensity for recurrent hemorrhage. While RhoA-ROCK signaling dysregulation is the canonical driver of pathogenesis, vitamin D has emerged as a potential molecular modifier. This systematic review synthesizes clinical, genetic, and preclinical evidence to evaluate the biological role of vitamin D and its receptor signaling pathways in CCM pathogenesis.

To systematically evaluate the diagnostic performance of miRNA panels for endometrial cancer.

Non-Hodgkin lymphoma (NHL) has been associated with IL-10 single-nucleotide polymorphisms (SNPs), although findings remain inconsistent. This meta-analysis aims to investigate the association between key IL-10 SNPs (rs1800871, rs1800872, rs1800890, and rs1800896) with NHL. A systematic search of multiple databases was conducted to get relevant articles. The study included 53,864 cases and 60,448 controls from 41 studies. Pooled ORs with 95% CIs were calculated for each SNP, along with a heterogeneity test and publication bias analysis. The SNP rs1800890 showed modest but significant associations with NHL risk in codominant 1 (OR = 1.12, p < 0.001), codominant 2 (OR = 1.06, p = 0.006), and recessive models (OR = 1.08, p = 0.002); rs1800896 showed weak significant associations with NHL risk in dominant (OR = 1.08, p = 0.001) and codominant 2 models (OR = 1.07, p = 0.006). Subgroup analysis based on ethnicity revealed a nominally significant protective association in Caucasians for rs1800871 in the allelic model (OR = 0.87, p = 0.038).

Cervical cancer is a multifactorial disease like any other human cancer. Among these factors, genetic polymorphisms of Glutathione S-Transferase Mu1 (GSTM1) have been incriminated, but the studies results remain controversial. The objective of this meta-analysis was to study the influence of GSTM1 polymorphisms on the occurrence of cervical cancer and to explore interactions between genes and human papillomavirus (HPV) infection and exposure to tobacco smoke. A meta-analysis was conducted on studies published up to June 12, 2025, from six databases: ScienceDirect, Embase, Scopus, PubMed, Google Scholar, Web of Science. Eligible studies included all case-control investigations that assessed the association between GSTM1 polymorphisms and the risk of cervical cancer. Odds ratios and confidence intervals from the studies were used to estimate the combined effect size. Statistical analyses were conducted using both the DerSimonian and Laird random-effects model and Mantel and Haenszel fixed-effect model with a 95% confidence interval. Subgroup analyses were performed to identify potential sources of variability. A significant association was observed between the GSTM1-null and an increased risk of Cervical Cancer (ORCC=1.47, Pz=0.011) and Squamous Intraepithelial Lesions (ORSIL=1.42, Pz=0.035) compared with the GSTM1-present. The included studies showed high heterogeneity. Overall, carriers of the GSTM1-null had a higher likelihood of developing Cervical Cancer compared to carriers of the GSTM1-present. In subgroup analyses, an increased risk associated with the GSTM1-null was found among Asian populations (ORCC=1.54, Pz=0.002) and according to sample type, in blood DNA extracts (ORCC=1.27, Pz=0.052). Furthermore, the GSTM1-null was associated with increased risk in HPV+ women (ORCC=4.88, Pz=0.005) and in women exposed to tobacco smoke (ORCC=1.35, Pz=0.033). According to histological type, GSTM1-null was also associated with the development of Squamous Cell Carcinoma (ORSCC=1.52, Pz=0.020). in conclusion, GSTM1-nullwere associated with an increased risk of cervical cancer in women, especially in HPV+ women and those exposed to tobacco smoke.

To assess the efficacy and safety of first-line programmed-death 1 (PD-1)/programmed-death ligand 1 (PD-L1) inhibitors + chemotherapy for driver-gene negative advanced non-squamous non-small cell lung cancer (NSCLC).

Glioblastoma (GBM) is the most aggressive and biologically heterogeneous tumor of the central nervous system, associated with dismal prognosis and frequent recurrence. Amplification of the epidermal growth factor receptor (EGFR) and EGFRvIII mutation are common alterations, yet their prognostic significance remains unclear. This systematic review evaluated whether clinical evidence supports a predictive association between EGFR amplification or EGFRvIII mutation and response to EGFR-targeted therapy in adults with recurrent GBM.

To evaluate the plasma-based methylated Septin9 (mSEPT9) diagnostic accuracy for gastric cancer (GC) and analyze its performance across different subgroups.

Relapse remains the leading cause of treatment failure following hematopoietic cell transplantation (HCT) for hematologic malignancies. Circulating tumor DNA (ctDNA) has emerged as a promising minimally invasive biomarker for measurable residual disease (MRD) assessment and early relapse detection; however, the prognostic significance of ctDNA in the post-transplant setting has not been comprehensively synthesized. We conducted a systematic review and meta-analysis in accordance with PRISMA guidelines and registered the protocol in PROSPERO (CRD420261392100). PubMed, Embase, Web of Science, EBSCO, Cochrane CENTRAL, and supplementary sources were searched through November 2025. Eligible studies evaluated tumor-specific ctDNA or tumor-informed/tumor-associated cfDNA in patients undergoing allogeneic or autologous HCT for hematologic malignancies. Random-effects meta-analyses were performed for relapse/progression, overall survival (OS), and relapse-free/progression-free survival (RFS/PFS). Studies evaluating total cfDNA quantity, methylation-based cfDNA profiling, cfRNA, or chimerism-only monitoring were synthesized narratively. Ten observational cohort studies comprising 883 patients met inclusion criteria. Across acute leukemias, lymphomas, multiple myeloma, and myelodysplastic syndromes, ctDNA/cfDNA positivity was consistently associated with adverse outcomes. The pooled hazard ratio (HR) for relapse or disease progression was 12.57 (95% CI: 4.59-34.46; p < 0.001), while pooled HRs were 7.45 (95% CI: 4.11-13.48; p < 0.001) for OS and 4.46 (95% CI: 2.22-8.97; p < 0.001) for RFS/PFS. Although statistical heterogeneity was low, interpretation was limited by the relatively small number of studies contributing to each pooled endpoint. Narrative evidence additionally suggested that broader circulating nucleic acid approaches may provide complementary information regarding graft-versus-host disease, infection, and other post-transplant complications. Tumor-specific ctDNA positivity is consistently associated with increased relapse risk and inferior survival outcomes following HCT. These findings support further investigation of ctDNA-based MRD monitoring as a promising non-invasive biomarker for post-transplant molecular surveillance and risk stratification. However, prospective multicenter validation studies, assay standardization, and ctDNA-guided interventional trials remain necessary before routine clinical implementation can be recommended.

Bladder cancer is a molecularly heterogeneous malignancy in which biomarker-driven therapies increasingly shape clinical management. Fibroblast growth factor receptor 3 (FGFR3) alterations and nectin-4 expression are key therapeutic targets, yet their integrated biological and clinical relevance remains unclear. A systematic search of PubMed, Scopus, and Cochrane Central was conducted from database inception to 22 February 2026 (PROSPERO: CRD420261309413). Studies reporting the prevalence of FGFR3 alterations and/or nectin-4 expression in bladder cancer were included. Proportions were pooled using a random-effects model with restricted maximum likelihood and Freeman-Tukey transformation. Heterogeneity was assessed with I2 and Cochran's Q. Fourteen studies (three randomized and 11 observational), including 3955 patients (mean age: 67.34 years), were analyzed. The pooled prevalence of FGFR3 alterations was 52% (95% CI: 23.33-80.12; I2 = 99%), while that of nectin-4 expression was 78% (95% CI: 64.23-89.81; I2 = 91%). FGFR3 prevalence varied significantly by disease stage, study design, and region, with higher rates in advanced/metastatic disease and randomized trials (p < 0.05). Nectin-4 expression was generally high across included studies, although interpretation was limited by the small number of studies and assay variability. Sensitivity analyses showed the stability of estimates; however, interpretation is limited by substantial heterogeneity. The observed prevalence estimates are strongly influenced by study design, biomarker selection, and assay variability, limiting their interpretation as true biological prevalence. These results should, therefore, be interpreted cautiously and viewed as descriptive rather than definitive estimates. Separate analyses of biomarker-enriched trials and unselected cohorts are necessary to obtain clinically meaningful estimates.

Dysregulated microRNA (miR) expression has emerged as a potential prognostic tool in head and neck squamous cell carcinoma (HNSCC), but the clinical value of miR-34a remains unclear. This systematic review, meta-analysis, and trial sequential analysis (TSA) evaluated the association between tumor tissue miR-34a expression and survival outcomes in HNSCC. Following a protocol registered in PROSPERO (n. CRD420251238772), PubMed/MEDLINE, Scopus, ScienceDirect, CENTRAL, Google Scholar, and grey literature sources were searched for studies reporting overall survival (OS) or disease-free survival (DFS) stratified by miR-34a expression in HNSCC or its subsites. Hazard ratios (HRs) were extracted directly or reconstructed from Kaplan-Meier (KM) curves using the Tierney method, supported by a dedicated Python application (KM2HR). Four retrospective studies, corresponding to six study/site-specific cohorts and 318 patients, met the inclusion criteria. For OS (four cohorts), the fixed-effects model yielded a pooled HR of 2.25 (95% CI 1.48-3.41) for low versus high miR-34a expression, indicating worse survival in the low-expression group. However, the random-effects model attenuated the association (HR 1.32, 95% CI 0.32-5.54), with substantial heterogeneity (I2 ≈ 77%). For DFS (two studies), the fixed-effects model suggested poorer outcomes with low miR-34a (HR 2.92, 95% CI 1.24-6.88), whereas the random-effects model reversed the direction of effect with extremely wide confidence intervals (HR 0.19, 95% CI ≈ 0.00-129.34; I2 = 91%). TSA for OS (accrued information size 225 patients; estimated power ≈66%) crossed the monitoring boundary but did not reach the a priori information size, supporting only a tentative signal. A bioinformatic exploration of the TCGA HNSCC cohort (n = 522) showed a non-significant trend towards worse OS with low miR-34a (HR 1.24, 95% CI 0.93-1.65) and was excluded from pooling. Overall, low tumor miR-34a expression appears to be associated with poorer OS, but the evidence is limited by retrospective design, small sample size, and marked heterogeneity. miR-34a is a promising biomarker for prognostic stratification in HNSCC, yet larger, prospective, site-specific studies with standardized assays, pre-defined cut-offs, and appropriate adjustment for HPV status and clinical covariates are required before clinical implementation can be recommended.

Tumour agnostic therapies represent a paradigm shift in oncology. BRAF inhibitors have demonstrated efficacy in melanoma. However, their role in non-melanomatous cancers was originally contentious. This systematic review aims to evaluate the safety and efficacy of BRAF-targeted therapies, both as monotherapy and in combination with other targeted therapies, in BRAF-mutated, non-melanomatous tumours.

We evaluated the diagnostic accuracy of circulating cell-free DNA (cfDNA) and circulating tumor DNA (ctDNA) compared to tissue biopsy in breast cancer across three assay modalities.

TERT promoter (TERTp) mutations shape glioma prognosis and therapy, yet tissue testing can be limited by sampling error and surgical inaccessibility. MRI-based radiomics offers a non-invasive alternative. This study aimed to quantify the diagnostic accuracy of pre-operative MRI radiomics for predicting TERTp status and compare radiomics-only, clinical-only, and combined models.We conducted a PRISMA-DTA-conformant, PROSPERO-registered systematic review and meta-analysis. PubMed, Embase, Web of Science, and Scopus were searched to 13 October 2025. Eligible studies evaluated MRI-derived radiomics models and reported accuracy on non-training data against a molecular reference standard. Risk of bias was appraised with QUADAS-AI. Bivariate random-effects models pooled sensitivity, specificity, and AUC, prioritizing external test performance when available. Fourteen retrospective studies including 2,863 patients were eligible for systematic review; 13 studies were included in the quantitative meta-analysis. MRI-only radiomics models demonstrated pooled sensitivity of 0.76 (95% CI, 0.66-0.84), specificity of 0.70 (95% CI, 0.63-0.77), and AUC of 0.79 (95% CI, 0.75-0.82), indicating moderate discriminative performance with substantial heterogeneity. Deeks' funnel plot asymmetry test was not significant (p = 0.78). Clinical-only models yielded pooled sensitivity of 0.73 (95% CI, 0.61-0.82), specificity of 0.57 (95% CI, 0.34-0.77), and AUC of 0.73 (95% CI, 0.69-0.77). Combined radiomics-clinical models showed numerically higher pooled performance, with sensitivity of 0.78 (95% CI, 0.70-0.85), specificity of 0.76 (95% CI, 0.67-0.84), and AUC of 0.82 (95% CI, 0.79-0.85), although this finding should be interpreted descriptively rather than as definitive evidence of superiority. Subgroup analyses suggested that classifier type, validation strategy, and feature-extraction software may contribute to performance variability. Sensitivity analysis showed that the overall findings remained broadly stable after excluding the influential study. Pre-operative MRI-based radiomics shows moderate accuracy for predicting TERTp mutation status in glioma. Combined radiomics-clinical models achieved numerically higher performance, but current evidence remains limited by retrospective designs, internal validation, and methodological heterogeneity. These models should be considered adjunctive rather than replacement tools, and prospective multicenter external validation with standardized workflows is required before clinical implementation.

Molecular Tumor Boards (MTBs) bring together multidisciplinary experts to translate genomic data into clinical decisions in oncology, however, their overall clinical impact remains unclear. The aim of this systematic review is to assess the clinical impact of MTB-recommended therapies on patients with cancer outcomes.

Urothelial carcinoma (UC) is a significant global health challenge with heterogeneous clinical presentations from nonmuscle-invasive to metastatic disease. Circulating tumor DNA (ctDNA) has emerged as promising noninvasive biomarker for risk classification, treatment monitoring and recurrence detection. Systematic searches of PubMed identified 390 articles; 61 met inclusion criteria for plasma ctDNA analysis in UC. Independent dual screening, Joanna Briggs Institute assessment, and stratification by disease stage (nonmuscle-invasive bladder cancer [NMIBC], muscle-invasive bladder cancer [MIBC], metastatic urothelial carcinoma [mUC], and upper tract urothelial carcinoma [UTUC]) were performed. Simple pooled detection rates were calculated. ctDNA detection rates increased with disease advancement: NMIBC (53.2%), MIBC (47.6%), mUC (85.9%), and UTUC (50.5%). TERT promoter mutations predominated, followed by genomic alterations in TP53. Assays varied widely across studies with next-generation sequencing (22.4%) being most common. In NMIBC, ctDNA enabled risk stratification and recurrence detection. In MIBC, IMvigor010 demonstrated patients with positive ctDNA had worse overall survival (OS) (hazard ratio, 6.3); IMvigor011 showed that patients with negative ctDNA managed without adjuvant therapy had excellent outcomes (98% OS at 18 months). Post-surgical monitoring achieved 94%-100% sensitivity for recurrence with 96- to 131-day lead times. In mUC, KEYNOTE-361 showed ctDNA reductions at 6 weeks predicted improved OS (p < 10-4), whereas fibroblast growth factor receptor 3 mutations tracked resistance. Preoperative ctDNA fraction >2% in UTUC predicted worse OS (p < 10-3). ctDNA is a critical precision oncology tool in UC management, with TERT mutations as the predominant alteration. Stage-tailored strategies are emerging, including risk assessment in NMIBC, refining adjuvant decisions in MIBC, and treatment monitoring in mUC. Integration of ctDNA-guided approaches should proceed alongside prospective validation to ensure safe and effective adoption.

The purpose of this meta-analysis study is to provide evidence for the clinical utility of TP53 mutations in circulating tumor DNA (ctDNA) as a prognostic biomarker.

Triple-negative breast cancer (TNBC) is associated with high recurrence and mortality. Liquid biopsy biomarkers, such as circulating tumor DNA (ctDNA), cell-free DNA (cfDNA), and microRNAs (miRNAs), offer noninvasive tools for monitoring TNBC.

Menin inhibitors (MI) are promising targeted therapies for acute myeloid leukemia (AML), particularly in NPM1-mutated and KMT2A-rearranged disease. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of MI-based therapy in adults with relapsed/refractory AML. A search of six databases through January 2026 identified 14 studies including 784 treated patients. Among response-evaluable cohorts (k = 22; n = 579), the pooled overall response rate (ORR) was 54.6% (95% CI 46.4-62.6; I2=63.5%). The pooled complete response (CR) rate was 29.3%, and CR+CRh was 28.5%. Combination therapy with MI plus hypomethylating agent and venetoclax produced higher CR (43.3% vs 19.5%; p = 0.002) and CR+CRh rates (48.6% vs 25.8%; p = 0.007) than monotherapy. Common adverse events included LFT elevation (38.7%), febrile neutropenia (33.6%), and diarrhea (28.8%). Differentiation syndrome occurred in 14.6%, and treatment-related mortality in 5.0%. MI-based therapy demonstrates meaningful activity in heavily pretreated AML, with deeper responses observed using combination strategies.