Patients with acute myeloid leukemia (AML) with FMS-like tyrosine kinase 3 (FLT3) mutations have a poor prognosis, even after hematopoietic stem cell transplantation (HSCT). Targeted maintenance therapy with gilteritinib is now recommended post-HSCT in de novo measurable residual disease-positive FLT3mut+ AML patients. However, the benefits of post-HSCT gilteritinib maintenance in relapsed and refractory (R/R) disease are less clear. A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines to collate and describe the body of evidence (from inception of databases to April 29, 2024) assessing the clinical outcomes of gilteritinib post-HSCT therapy in patients with R/R FLT3mut+ AML. Eight studies (2 randomized controlled; 6 observational) reporting clinical outcomes in a total of 134 adult patients with FLT3mut+ AML were included in the narrative synthesis. Six were single-arm studies, and 2 included a comparator group without maintenance therapy after transplantation. From time of HSCT, 1- and 2-year overall survival (OS) rates ranged from 72.3 % to 100 % (n = 55) and 55.8 % to 60.0 % (n = 41), respectively, and 1- and 2-year relapse-free survival (RFS) rates were 46.7 %-100.0 % (n = 27) and 46.7 %-80.0 % (n = 13), respectively. Comparative data suggest that gilteritinib as post-HSCT maintenance therapy may improve clinical outcomes of patients with R/R FLT3mut+ AML versus no gilteritinib maintenance. However, no definite conclusions can be drawn from the limited clinical data available in this setting. Further well-designed studies with uniformity in defining OS and RFS are required to provide further insight into this strategy for the high-risk R/R FLT3mut+ AML population.

In the present study, a systematic revision in the Medline was conducted to determine the somatic mutation in gangliogliomas.

Pseudo-Richter transformation (pseudo-RT) is a rare and recently recognized phenomenon characterized by a transient large B-cell proliferation occurring shortly after interruption of Bruton tyrosine kinase inhibitor (BTKi) therapy in chronic lymphocytic leukemia (CLL). Although it closely mimics true Richter transformation (RT) clinically and histologically, pseudo-RT follows a distinct and reversible course, and its recognition is essential to avoid misdiagnosis and inappropriate treatment.

Early-stage breast cancer (BC) shows heterogeneous recurrence risk. Circulating tumor DNA (ctDNA) is promising non-invasive biomarker for minimal residual disease and recurrence prediction, though prognostic performance varies by assay and context.

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.

Rhabdomyosarcoma (RMS) is a predominantly paediatric cancer that is classified by the presence or absence of a PAX-FOXO1 fusion gene, which is associated with a worse prognosis. Previous classification was based on histology, alveolar RMS (ARMS) or embryonal RMS (ERMS). In other paediatric cancers, fusion gene status has been shown to associate with differences in the tumour microenvironment (TME). However, comprehensive understanding of the TME in RMS and how it may differ between subtypes is lacking. This systematic review aimed to identify differences in the TME between fusion-positive RMS and fusion-negative RMS, to better understand how the fusion gene drives malignancy. The Web of Science, MEDLINE (Ovid), and EMBASE (Ovid) were searched to identify relevant studies investigating the TME in RMS. A total of 17 studies met the inclusion criteria and were included in the review, but only three studies specified fusion status in their sample data. Nine studies investigated the extracellular matrix and stroma, and another nine investigated the immune microenvironment. Significant differences in CD163+ macrophages, matrix metalloproteinases and stromal platelet-derived growth factor receptors-α/β were observed between ARMS and ERMS. Regarding fusion status, there were differences in the prevalence of T cell dysfunction, NECTIN-3 expression, and genes related to PD-1 signalling and interferon (IFN) response. This review highlights a need for further research of the TME in each fusion subtype. This will improve our understanding of how the fusion gene drives malignancy and ultimately aids in the development of novel treatment strategies.

BACKGROUND: Immunocompromised individuals exhibit an increased risk of malignancies attributable to impaired immune surveillance and increased susceptibility to oncogenic infections, resulting in distinct responses to immunotherapy. The intricacies of infection-related cancer risks and the feasibility and efficacy of immunotherapy in these patients remain inadequately understood. METHODS: A comprehensive search of PubMed, Web of Science, EMBASE, Medline, and Cochrane Library was conducted up to Nov 10, 2024. A random-effects model was pre-specified as the primary analytical method to account for anticipated clinical and methodological heterogeneity among the included studies. Heterogeneity was quantified using the I2 statistic. Tumor mutational burdens (TMBs) were assessed for Spearman correlation with standardized incidence ratios (SIRs). RESULTS: This systematic review included 151 studies, comprising 74 in solid organ transplant (SOT), 15 in hematopoietic stem cell transplant (HSCT), and 62 in people living with HIV (PLHIV). The analysis encompassed 2,418,274 SOT recipients, 117,264 HSCT recipients, and 5,762,641 PLHIV, covering 17 infection-related cancers. Excluding nasopharyngeal cancer, 16 cancers showed higher SIRs in SOT recipients and PLHIV compared to the general population. A statistically significant correlation was observed between TMBs and SIRs in SOT recipients (Spearman’s ρ = 0.85, P = 0.002), with consistent findings across key subgroups (kidney [Spearman’s ρ = 0.92, P < 0.001], liver [Spearman’s ρ = 0.91 (P < 0.001)], heart and/or lung [Spearman’s ρ = 0.74, P = 0.023]), and PLHIV (Spearman’s ρ = 0.89, P = 0.002), whereas no significant association was detected in HSCT recipients (Spearman’s ρ = 0.15, P = 0.805). CONCLUSION: These findings suggest that TMBs from infections or immunosuppression may contribute to cancer risk, emphasizing the potential of immune checkpoint inhibitors despite rejection risks. Personalized cancer surveillance and tailored therapies are essential for immunosuppressed populations. TRIAL REGISTRATION: PROSPERO protocol ID CRD42024594181.

NBN is a putative ovarian cancer susceptibility gene. The association between a pathogenic variant in NBN and ovarian cancer is not well established. We aimed to estimate the ovarian cancer risk in unselected women with an NBN pathogenic variant.

The nasal cavities and sinuses are the site of many tumoral entities, which are increasingly well described, especially since the advent of molecular biology. The present systematic review collates the current state of knowledge on six new entities described in the 2017 and 2022 versions of the WHO classification of sinonasal tumors: DEK::AFF2 rearranged squamous cell carcinoma, HPV-associated multiphenotypic sinonasal carcinoma, NUT carcinoma, SMARCB1-deficient and SMARCA4-deficient carcinoma, biphenotypic sinonasal sarcoma, and adamantinoma-like Ewing sarcoma. A systematic literature search was performed on PubMed. The inclusion criteria focused on English-language articles precisely describing the histologic, immunohistochemical, molecular, clinical and prognostic characteristics of these entities. It is essential to be able to identify these entities, as they have distinct profiles in terms of progression and prognosis compared to other sinonasal tumors. The present study exhaustively describes their clinical and pathologic characteristics.

BACKGROUND: BRCA1/2-carriers—who account for 5–10% of breast cancer (BC) cases—face markedly elevated lifetime risks of BC. Among those diagnosed with primary breast cancer (PBC), these carriers confront a cumulative contralateral breast cancer (CBC) risk of 40% within 10 years—alongside poorer overall survival (OS) and breast cancer–specific survival (BCSS). Whether contralateral risk-reducing mastectomy (CRRM) can improve OS, BCSS, and reduce CBC risk in this high-risk group remains unresolved. PATIENTS AND METHODS: We conducted a systematic review and meta-analysis of cohort studies (PROSPERO:CRD420251024265). PubMed, Embase, Cochrane Library were searched through June 2025. Studies enrolled BRCA1/2-carriers with PBC, compared CRRM versus Non-CRRM, and reported OS, BCSS, or CBC risk. We pooled hazard ratio (HR) and risk ratio (RR) for these outcomes. Heterogeneity was quantified by I2. RESULTS: This meta‐analysis included nine cohort studies, encompassing BRCA1/2-carriers with PBC. In the OS analysis, including 3138 patients in the CRRM group versus 2,592 in the Non-CRRM group, CRRM presented a substantial survival benefit (HR 0.638; P < 0.001). BCSS (567 CRRM and 623 Non-CRRM patients), likewise demonstrated an advantage for the CRRM group (HR 0.601; P = 0.005). CBC risk, evaluated in 637 CRRM and 976 Non-CRRM patients, was reduced by 91% (RR 0.090; P < 0.001), reflecting an absolute risk reduction of 188 CBC events per 1000. CONCLUSION: CRRM confers substantial oncologic benefits, improving OS and BCSS and reducing CBC risk in BRCA1/2 carriers with PBC, and should be considered for this high-risk population, informing guideline recommendations.

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.

Cellular senescence is a stress-induced cell-cycle arrest that constrains expansion of ultraviolet-damaged keratinocytes yet can remodel the microenvironment. This systematic review evaluated histological and genetic or epigenetic senescence markers in actinic keratosis (AK), cutaneous squamous cell carcinoma (cSCC), and basal cell carcinoma (BCC). PubMed, Scopus, and Web of Science were searched (January 2005-May 2025); 34 human studies were included. AK showed an early senescent signature with frequent cyclin-dependent kinase inhibitor p21 (p21CIP1) expression (82.1%) and DNA damage signaling, including phosphorylated histone H2AX (gamma-H2AX) positivity (77%). In invasive cSCC, p21CIP1 fell to 43.9% and tumor suppressor p53 immunoreactivity often declined, whereas cyclin-dependent kinase inhibitor p16 (p16INK4a) commonly accumulated without arrest, including cytoplasmic staining at invasion fronts. Reported escape pathways involved c-Jun N-terminal kinase 2 activity and long noncoding RNA PVT1-dependent repression of p21. Telomerase reverse transcriptase (TERT) promoter mutations were prevalent in cSCC (about 50%) and BCC (up to 78%) but uncommon in AK, consistent with late telomerase activation. Study heterogeneity, variable antibody scoring, and limited assessment of senescence-associated beta-galactosidase and secretory mediators restricted cross-study comparability. Standardized, spatially resolved profiling may refine risk stratification and support senescence-targeted prevention and therapy in keratinocyte cancers.

Gastric cancer is one of the most prevalent malignant tumors worldwide. Sporadic gastric cancer accounts for more than 80% of all gastric cancer cases, and its pronounced heterogeneity underlies the substantial variability in clinical outcomes and the complexity of treatment strategies. The breast cancer gene 1 (BRCA1) and breast cancer gene 2 (BRCA2) are core regulators of the DNA damage homologous recombination repair (HRR) pathway, and their pathogenic mutations are closely associated with hereditary breast and ovarian cancer syndrome. Recent evidence has shown that BRCA1/2 mutations also exist in some sporadic gastric cancer patients and may profoundly affect tumor biological behavior, clinical prognosis, and treatment response. This article systematically reviews the latest research progress on BRCA1/2 mutations in sporadic gastric cancer, focusing on their incidence and molecular characteristics, their impact on patients' postoperative prognosis, and their potential value as novel biomarkers for guiding individualized therapy, thereby providing a theoretical basis for clinical risk stratification and tailored treatment strategies.

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).

The detection of actionable DNA biomarkers in liquid biopsies is essential for advancing precision oncology. While conventional techniques such as PCR and NGS are highly accurate, their high cost, complexity, and slow turnaround time limit widespread clinical applications. Electrochemical biosensors present a promising alternative through their portability, affordability, and rapid analysis capabilities.

A distinct subpopulation of tumour cells, known as breast cancer stem cells (BCSCs), plays a critical role in driving poor therapeutic outcomes due to its high proliferative capacity, metastatic potential and resistance to treatment. MicroRNAs (miRNAs) have emerged as a promising focus of research owing to their stability and ability to modulate tumour biology. However, the role of miRNAs in regulating BCSC characteristics remains insufficiently understood. This systematic review aims to synthesise evidence from in vitro and in vivo studies to evaluate the potential of miRNA-based strategies in targeting BCSCs to suppress their proliferation, metastasis potential, and treatment resistance.

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).

To evaluate the diagnostic, prognostic, and recurrence-related roles of microRNAs (miRNAs) in meningioma based on expression profiles across different biological samples. This systematic review was conducted in accordance with Cochrane Collaboration and PRISMA guidelines. A search was performed in PubMed, Scopus, Web of Science, and Google Scholar without language restrictions. Cohort and case–control studies assessing miRNA expression in tumor tissue, serum, or cerebrospinal fluid from patients with histologically confirmed meningioma were included. Risk of bias was evaluated using the Newcastle–Ottawa Scale. Bioinformatic pathway enrichment analyses were conducted for recurrently miRNAs. Twenty-three studies involving 1615 participants were included, of whom 1461 had meningiomas (WHO grades 1–3). Overall, 153 miRNAs were evaluated, including 90 upregulated, 45 downregulated, and 18 without significant differential expression. miR-21, miR-34a, and members of the miR-181 family were consistently associated with tumor grade and progression. Tumor recurrence was most frequently linked to miR-224-5p, miR-331-5p, miR-29c-3p, and miR-219-5p. Circulating miRNAs, particularly miR-497 and miR-219, demonstrated diagnostic potential in serum and cerebrospinal fluid. Pathway analyses highlighted enrichment in metabolic and signaling pathways, including sphingolipid, sulfur, and fatty acid metabolism. This review identifies miR-21, miR-224-5p, miR-331-5p, miR-29c-3p, and circulating miR-497 and miR-219 as the most promising miRNA biomarkers for meningioma diagnosis, grading, and recurrence monitoring. Despite methodological heterogeneity, the consistency of these findings across independent studies supports their translational potential. Nonetheless, large, standardized studies with independent validation cohorts are required prior to clinical implementation.

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.