Circulating tumor DNA (ctDNA) has emerged as a promising noninvasive biomarker for monitoring minimal residual disease (MRD) and predicting recurrence in early-stage breast cancer (EBC). Despite growing interest, the prognostic impact of ctDNA detection in this setting remains to be fully elucidated.

Acute myeloid leukemia (AML) is the most common acute leukemia in adults. Approximately 30% of patients present alterations in the FMS-like receptor tyrosine kinase 3 (FLT3) gene, which are associated with poor prognosis. FLT3 inhibitors - midostaurin (first-generation), gilteritinib and quizartinib (second-generation) - have been developed to block FLT3 activation. Given the need of optimizing treatment in FLT3-mutated AML, we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to compare the safety profiles of FLT3 inhibitors. Following the PRISMA statement, we searched Embase, MEDLINE and Cochrane Library. The Cochrane Risk of Bias Tool for RCTs was used for quality assessment. Of 2132 references, seven RCTs, involving 2409 adult patients, met inclusion criteria: quizartinib and midostaurin in two trials each and gilteritinib in three. The most frequently reported adverse events (AEs) were classified under the System Organ Class (SOC) Blood and lymphatic system disorders (N = 5474, 58.4% of them related to FLT3 inhibitors). The most frequently observed non-hematological AEs were gastrointestinal disorders, pyrexia, elevated ALT/AST and headache. FLT3 inhibitors are not associated with a significant increase in the risk of AEs compared to standard treatments. No meaningful differences in AE risk were observed among the three drugs. The only exception was an higher risk of ALT increased with gilteritinib (RR = 2.40, 95% CI: 1.16-4.95). Future studies should stratify safety outcomes by demographic and clinical characteristics and incorporate long-term follow-up for a more comprehensive safety assessment in clinical practice.

IntroductionMachine learning (ML)-based analysis of cell-free DNA (cfDNA) has emerged as a promising strategy for multi-cancer early detection (MCED). However, reported diagnostic performance varies widely across studies, and many estimates are derived from training or enriched cohorts, limiting their relevance to independent validation and real-world settings.MethodsWe conducted a systematic review and diagnostic accuracy meta-analysis of ML-based cfDNA assays for MCED. Four databases (PubMed, Embase, Web of Science, and the Cochrane Library) were searched from inception to February 2, 2025. Only independent validation or testing datasets were included; all training datasets were excluded. Pooled sensitivity, specificity, diagnostic odds ratio (DOR), and summary receiver operating characteristic (SROC) curves were estimated using a bivariate random-effects model. Subgroup analyses and meta-regression were performed to explore sources of heterogeneity.ResultsThirteen studies comprising 23 independent datasets and 14,892 participants were included. The pooled sensitivity was 0.78 (95% CI: 0.66-0.87), and the pooled specificity was 0.96 (95% CI: 0.90-0.98). The summary area under the curve (AUC) was 0.94, with a DOR of 76.6. Substantial between-study heterogeneity was observed (I2 > 90%), with geographic region, sample size, and cfDNA biomarker type identified as major contributing factors.ConclusionML-based cfDNA assays demonstrate consistently high specificity and moderate-to-high sensitivity across independent validation datasets, supporting their potential role in multi-cancer early detection. However, diagnostic performance is highly context dependent and strongly influenced by study design, population characteristics, and analytical choices. These findings highlight the need for large-scale, prospective, population-based validation before widespread clinical implementation.

Colorectal cancer is thought to develop through the stepwise accumulation of somatic mutations. Recent years have seen the publications of several studies greatly advancing our understanding of the molecular events driving the disease. However, individual studies tend to be small and additional insights may be obtained through the combination of data from multiple sources. We performed targeted sequencing of 2172 colorectal cancers from Icelandic patients and combined these data with publicly available mutation calls from 9 515 additional tumours collected from the literature. Analysing microsatellite stable (MSS) and instable (MSI) tumours separately, we find evidence of positive selection of mutations in 112 genes that replicate across multiple studies of patients with diverse demographics. We carried out a meta-analysis of conditional selection, identifying 57 gene pairs where a mutation in one gene influences the selection of the other. We describe many associations with tumour phenotypes, including a strong association between mucinous histology and mutations in the transcription growth factor beta (TGFb) pathway, only in MSS tumours. Our study demonstrates how combining evidence from multiple sources allows for new discoveries in cancer genomics.

Cervical cancer (CC) is one of the most prevalent cancers worldwide. Single nucleotide polymorphisms (SNPs) of the epidermal growth factor receptor (EGFR) and epidermal growth factor (EGF) genes are associated with cancers in diverse populations; However, the roles of these genes in CC are uncertain. Associations between these SNPs and CC risk, as well as the risk of pathological type and clinical stage, were analysed. On thebasis of our data, a cross-cancer meta-analysis was performed to assess the roles of nine SNPs of the EGFR and EGF genes in cancer susceptibility. Finally, SNP‒SNP interactions were analysed in the present study. Our data showed that the potential SNP‒SNP interaction between EGFR and EGF may be associated with CC development in Chinese Han individuals. The meta-analysis indicated that these SNPs in EGFR and EGF may be associated with cancer risk, particularly in Asians. Cross-cancer SNP‒SNP interaction analysis demonstrated that the 9-SNP model exhibited significant synergistic effects in predicting cancer risk.

Early studies indicate that neoadjuvant immune checkpoint inhibitors (ICIs) induce high rates of tumor regression in localized deficient mismatch repair (dMMR) and microsatellite instability-high (MSI-H) gastric and gastroesophageal junction (GEJ) cancers, raising interest in nonoperative management (NOM). Most available data, however, come from small, nonrandomized cohorts. A systematic synthesis was undertaken to better characterize efficacy and safety outcomes.

BRAF V600E-mutated colorectal cancer (CRC) is associated with poor prognosis and resistance to standard chemotherapy. Emerging evidence, including the BEACON trial and subsequent real-world studies, suggests that triple therapy targeting BRAF oncoprotein, epidermal growth factor receptor (EGFR), and MEK improves clinical outcomes.

Lynch syndrome is a hereditary cancer predisposition syndrome caused by germline mutations in the DNA mismatch repair (MMR) genes MSH2, MSH6, MLH1 and PMS2. The objective of this systematic review was to estimate the prevalence of germline mutations in MMR genes among patients with upper tract urothelial carcinoma (UTUC).

Lung cancer exhibits highest incidence among all cancer types worldwide and even after rigorous research and advanced treatment strategies, it constitutes a primary cause of cancer-related mortality. Non-small cell lung cancer is the predominant subtype, constituting the majority of lung cancer cases. Therefore, exploring novel biomarkers is crucial for betterment of diagnostic and therapeutic approaches.

Micronuclei (MN) genotoxicity, linked to chromosomal anomalies, is a key biomarker for carcinogen exposure and cancer susceptibility, with higher frequencies observed in cancer patients. The micronuclei assay, using exfoliated buccal cells, offers a non-invasive method for diagnosing oral lesions caused by tobacco, betel nut, and alcohol. This review aims to systematically review micronuclei frequencies in buccal mucosal cells and assess their potential as genotoxicity markers in oral potentially malignant disorders (OPMD).

Anti-EGFR rechallenge emerged as a potential therapeutic option for patients with chemorefractory metastatic colorectal cancer (mCRC) that maintained a circulating tumor DNA (ctDNA) RAS/BRAF wild type (WT) status. However, its efficacy compared to standard of care (SoC) in randomized controlled trials (RCTs) remains uncertain. In our systematic review and meta-analysis, we investigated the outcomes of anti-EGFR rechallenge versus SoC for patients with pretreated ctDNA RAS/BRAF WT mCRC. This study followed the PRISMA guidelines, and a systematic search of PubMed and ASCO/ESMO meeting abstracts was conducted in October 2025 for relevant RCTs. Pooled odds ratios (OR) for disease control rate (DCR) and objective response rate (ORR), and hazard ratios (HR) for survival outcomes were calculated. We identified three phase II randomized trials with 320 patients. Anti-EGFR rechallenge significantly improved DCR (OR = 3.39, 95 % CI 2.13-5.39), ORR (OR = 5.13, 95 % CI 2.30-11.41) and progression free survival (HR 0.674; 95 % CI, 0.499-0.909; p = 0.009) compared to SoC. No overall survival benefit was detected (HR 0.895; 95 % CI 0.736-1.087; p = 0.263). These findings support the use of anti-EGFR rechallenge strategy aslater-line treatment when tumor shrinkage is a clinical priority. Further evidence from prospective trials is required.

Acromegaly is a rare, insidious disease associated with significant morbidity and mortality usually caused by a growth hormone (GH)-secreting pituitary tumor. Somatic mutations in GNAS are common in these tumors, yet their diagnostic, prognostic, and therapeutic implications are less clear.

Thyroid diseases are common and highly heritable. We performed a meta-analysis of genome-wide association studies from 19 biobanks for five thyroid diseases: thyroid cancer (ThC), benign nodular goiter, Graves' disease, lymphocytic thyroiditis and primary hypothyroidism. We analyzed genetic association data from ~2.9 million genomes and identified 313 known and 570 new independent loci linked to thyroid diseases. We discovered genetic correlations between ThC, benign nodular goiter and autoimmune thyroid diseases (rg = 0.16-0.97). Telomere maintenance genes contributed to benign and malignant thyroid nodular disease risk, whereas cell cycle, DNA repair and damage response genes were associated with ThC. We propose a paradigm that explains genetic predisposition to benign and malignant thyroid nodules. We found polygenic risk score associations with ThC risk of structural disease recurrence, tumor size, multifocality, lymph node metastases and extranodal extension. Polygenic risk scores identified individuals with aggressive ThC in a biobank, creating an opportunity for genetically informed population screening.

Activating epidermal growth factor receptor (EGFR) mutations are key drivers in non-small cell lung cancer (NSCLC) and other solid tumours, predicting responses to tyrosine kinase inhibitors (TKIs). Tumour heterogeneity alongside sampling and technical factors may contribute to discordant EGFR status across biopsies, complicating treatment decisions. However, systematic evidence on prevalence and drivers of discordance remains limited.

To explore the effects of programmed death-ligand 1 (PD-L1) and clinicopathological features on the outcomes of patients with colorectal cancer (CRC), and to predict their prognosis using a meta-analysis.

Lung cancer (LC) patients frequently develop infectious pneumonia, often leading to suspension of anticancer therapy, yet the impact of LC on pneumonia progression remains unclear. This study employed a multidimensional approach to investigate whether LC constitutes a critical factor contributing to pulmonary infection onset and adverse short-term outcomes. Data from two intensive care unit databases were analyzed to assess the association between LC and pneumonia incidence and prognosis from a real-world perspective, with Mendelian randomization (MR) applied to validate causality. Additionally, post-GWAS analyses were conducted to explore comorbidity interaction patterns and potential shared therapeutic targets. Cross-sectional and cohort analyses identified LC as an independent risk factor for infectious pneumonia development and 28-day mortality, findings corroborated by sensitivity analyses across multiple models and datasets. Meta-analysis of MR results demonstrated causal relationships between genetically predicted LC and both pneumonia risk (OR = 1.103, 95% CI: 1.031-1.181, p = 0.004) and short-term mortality (OR = 1.219, 95% CI: 1.100-1.350, p < 0.001), with consistency across histological subtypes. After adjustment for comorbidities including chronic obstructive pulmonary disease (COPD), LC retained independent effects, while a strong LC-COPD genetic correlation was observed. Subgroup and mediation analyses revealed a two-way interplay between LC and COPD in driving pneumonia progression. Drug-target analyses suggested that modulation of the complement and coagulation cascades may benefit pneumonia patients with comorbid LC or COPD, highlighting CFB, SERPINA1, and SERPING1 as key candidates and pointing to monocyte-centered pathways as promising therapeutic directions. These findings indicate that infection-related pulmonary inflammation in LC patients may be partly tumor-driven, challenging routine cessation of anticancer therapy and underscoring the need for comorbidity-oriented treatment strategies.

Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) are widely available and inexpensive agents with proposed antitumor activity, particularly in tumors harboring PIK3CA mutations. This meta-analysis of randomized controlled trials (RCTs) evaluated whether adjuvant NSAID therapy improves outcomes in patients with resected PIK3CA-mutated colorectal cancer (CRC).

Acute lymphoblastic leukemia (ALL) is a hematologic malignancy characterized by malignant transformation of lymphoid precursor cells. ALL prognosis differs considerably, especially between pediatric patients and adult patients, with poor response to therapy in adults. MicroRNAs (miRNAs), small non-coding RNAs that regulate the expression of genes, are possible cancer biomarkers that predict cancer prognosis. This systematic review and meta-analysis evaluates miRNAs as prognostic biomarkers in ALL and extends the findings through ceRNA network and single-cell RNA seq analyses of validated target genes.

Lynch syndrome, caused by germline pathogenic variants in mismatch repair genes, markedly increases risks of endometrial, ovarian, and possibly breast cancer in women. We aimed to establish gene-specific risk profiles for these cancers using a unified multivariate model accounting for correlated outcomes.

HLA-G 14-bp insertion/deletion (I/D) polymorphism has been linked to both cancer susceptibility and various viral infections. This meta-analysis examined the relationship between HLA-G 14-bp I/D polymorphism with different viral infections on patients with or without complications of cancer.