Search Results (8,234)

Background: Acute myeloid leukemia (AML) is biologically heterogeneous and associated with poor outcomes. Although oxidative stress contributes to AML pathogenesis, the prognostic value of related biomarkers remains uncertain. Objective: This study aimed to evaluate associations between oxidative stress-related biomarkers and prognosis in adults with AML, focusing on overall survival (OS), complete remission (CR), relapse, relapse-free survival (RFS), event-free survival (EFS), and early mortality. Methods: This PRISMA-compliant systematic review was registered in PROSPERO (CRD420261364956). MEDLINE/PubMed, Scopus, Cochrane Library, Science Citation Index, ClinicalTrials.gov, and WHO ICTRP were searched from January 2015 through 31 July 2026. Eligible studies included adults with AML, oxidative stress-related biomarkers measured in biological samples, and extractable prognostic data. Risk of bias was assessed using QUIPS and certainty of evidence using GRADE. Results: Thirteen of 537 records met the inclusion criteria; 203 supplementary reports yielded no additional studies. Investigated biomarkers included ROS-related phenotypes, antioxidant and redox-regulatory genes, glutathione metabolism, iron/inflammation-related markers, and oxidative DNA damage indicators. Adverse outcomes were associated with ROS-related phenotypes, combined ROS/aldehyde dehydrogenase activity, GPX3, GSTP1, ferritin, gamma-glutamyl transpeptidase-to-albumin ratio, SOD1, and glutathione-related metabolic profiles. Conclusions: These biomarkers may have prognostic value, particularly for OS, but heterogeneity limits clinical application. Standardized validation and integration into applicable risk models are required. Full article

Background: Lung adenocarcinoma (LUAD) is the most common subtype of non-small-cell lung cancer and is one of the leading causes of cancer-related deaths globally. Despite current developments, reliable biomarkers for effective diagnosis, prognosis, and patient stratification are still lacking. Methods: We analyzed publicly available TCGA-LUAD and GEO datasets using integrative bioinformatics approaches, including differential gene expression, weighted gene co-expression network analysis (WGCNA), survival modeling, mutation profiling, immune cell infiltration scores, machine learning, and bulk-RNA and single-cell RNA sequencing. Results: A total of 5581 deregulated genes were identified, with the turquoise module (298 genes) showing strong correlation with LUAD (Corr = −0.79, p < 2.2 × 10⁻³⁰⁸). The integration of two analyses yielded 281 overlapping genes, out of which nine candidates (ANO2, CHIAP2, CPED1, DNASE1L3, GSTM5, HTR3C, PRKCE, SLC14A1, and WNT3A) were selected via LASSO Cox regression to build a prognostic risk model. High-risk patients have significantly worse survival (log-rank p = 0.0027). CPED1 exhibited the highest mutation frequency, with 41% of TCGA-LUAD samples harboring mutations. Among all CPED1 mutation events, missense mutations were the most common (47%). GSEA and KEGG analysis revealed significant enrichment of pathways such as nucleocytoplasmic transport, oxidative phosphorylation, protein processing in the endoplasmic reticulum, ribosome, and ribosome biogenesis in high-risk patients. Immune infiltration analysis indicated differences in immune cell infiltration scores between high- and low-immune-score groups, with M1 macrophages showing strong statistical correlation with aDC, monocytes, and CD4⁺ naïve T cells. Machine learning confirmed that the combined Enet+PLS model predicted CPED1 as a core predictor, and CPED1 was successfully validated in independent GEO datasets (GSE43458 and GSE31210), showing strong diagnostic accuracy (AUCs up to 0.98). Finally, single-cell RNA sequencing revealed that CPED1 was mostly expressed in fibroblasts and myeloid cells, with CPED1 significantly downregulated in LUAD compared with normal samples. Conclusions: This study integrates multi-omics and machine learning to highlight CPED1 as a promising candidate biomarker, with potential diagnostic and prognostic relevance in LUAD. The nine-gene risk signature stratified patients by survival outcomes in the TCGA cohort. Genomic and immune analyses revealed features associated with the high-immune-score group. As the study is entirely computational and the prognostic model lacks external survival validation, these findings should be regarded as preliminary and hypothesis-generating, requiring future independent validation and functional studies to confirm the biological significance and clinical utility of CPED1 and related genes. Full article

Background/Objectives: Elevated intracranial pressure (ICP) drives secondary brain injury and poor outcome. The pressure reactivity index (PRx), the reference marker of cerebral autoregulation, requires high-frequency waveforms unavailable in many centers. We examined whether routinely charted hourly ICP and cerebral perfusion pressure (CPP) can stratify prognosis without the PRx. Methods: In a retrospective cohort of 990 adults with invasive ICP monitoring at a tertiary neurosurgical ICU (a predominantly non-traumatic case mix), we derived from hourly ICP the mean, variability (within-patient standard deviation), and peak burden (time above 22 mmHg), and from CPP the low-perfusion burden (time below 60 mmHg). Each metric (per 1 SD) was related to 28-day mortality and poor neurological outcome (Glasgow Outcome Scale 1–3), adjusted for age, sex, APACHE II, GCS, diagnosis, and mean ICP, with incremental value and sensitivity analyses. Results: In total, 86 of 990 patients died within 28 days. ICP variability was associated with both mortality and poor neurological outcome and, unlike peak burden, remained independent after adjustment for mean ICP. Peak burden lost significance once mean and variability were known. For CPP, hypoperfusion burden, but not CPP variability, was associated with mortality. CPP variability did not survive joint modeling with ICP variability. Excess risk was confined to low CPP, with no harm at high CPP. ICP variability added incremental value beyond a clinical model, robust to sensitivity analyses. Conclusions: Routinely available ICP variability and CPP hypoperfusion burden carry prognostic information beyond mean pressure. ICP variability predicted both outcomes, whereas hypoperfusion burden predicted mortality. These summaries may offer a pragmatic alternative where the PRx is unavailable, pending validation. Full article

Background/Objectives: Advanced endometrial cancer (FIGO III–IV) is characterised by poor prognosis and a heterogeneous biological profile, and molecular classification enables treatment personalisation by identifying subtypes with distinct therapeutic targets. We aimed to characterise the molecular and histopathological features of FIGO III–IV cases in a Polish multicentre cohort and to discuss the resulting treatment implications. Methods: This retrospective multicentre study included 915 consecutive patients with endometrial cancer operated on between April 2022 and May 2025 at three oncology centres in south-eastern Poland. Molecular subtyping (POLEmut, p53abn, dMMR/MSI-H, NSMP) was performed using immunohistochemistry (IHC) and next-generation sequencing (NGS). FIGO stage was assigned according to the FIGO 2009 classification. Results: Among 888 patients with a known molecular subtype, FIGO III–IV cases accounted for 15.9% (n = 141). The p53abn subtype predominated (35.5%), followed by dMMR/MSI-H (26.2%), NSMP (24.1%), and POLEmut (5.7%). The proportion of p53abn increased with stage (I–II vs. III–IV, p < 0.001), whereas dMMR/MSI-H remained stable regardless of stage (p = 0.83). POLEmut was absent in FIGO IV (0/16; 95% CI 0.0–19.4%), which should be regarded as an exploratory observation requiring prospective validation. Conclusions: The molecular profile of advanced endometrial cancer may inform treatment strategy; the therapeutic implications presented here are descriptive and hypothesis-generating, as the study did not include survival data. The dMMR/MSI-H subtype identifies patients who may benefit from immunotherapy in accordance with current clinical indications, supporting routine MMR testing regardless of disease stage. Conversely, p53abn tumours point to the need for a more intensive treatment strategy, in line with current guidelines. The absence of POLEmut in FIGO IV is an exploratory observation requiring prospective validation. Treatment de-escalation in POLEmut FIGO IIIC remains subject to further clinical validation and requires individualised assessment after complete staging. Full article

Background: Artificial intelligence-derived parameters hold substantial promise as indicators for tumor prognosis prediction and treatment guidance. However, existing studies have not sufficiently addressed the application of these parameters across different cancer types. Methods: We employed a deep learning algorithm to conduct a multi-cancer analysis for disease-free survival (MC-DFS) prediction using 8856 cases with associated whole-slide images and clinical data. The training cohort consisted of 7392 cases from the TCGA set (24 cancer types), and the independent external validation cohort comprised 1464 cases from the CPTAC and General Hospital sets (9 cancer types). A nomogram prediction signature for disease-free survival (NOMO) was developed by integrating the MC-DFS, tumor stage, and patient age. The prognostic model’s performance was validated in an independent cohort. Results: In the training and validation cohorts, the MC-DFS model achieved area under the curve (AUC) values of 0.750 and 0.682, respectively. It effectively differentiated patients with poorer disease-free survival, with hazard ratios of 4.823 (95% CI: 4.343–5.356, p < 0.0001) in the training cohort and 2.092 (95% CI: 1.472–2.971, p < 0.0001) in the validation cohort. Each cancer subtype’s analysis confirmed the model’s robust performance. Additionally, using nomogram analysis, we developed a multi-model prediction signature for disease-free survival across multiple cancer types based on MC-DFS and the clinicopathologic features in the training cohort. This enhanced model offers more precise risk stratification for stage I malignancies and complements the existing tumor staging systems by identifying high-risk patients. Conclusions: The newly developed MC-DFS shows marked improvements in prognostic predictions across multiple cancer types. With further validations across multiple centers, this nomogram prediction system could become a valuable practical tool for managing various cancers. Full article

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and a leading cause of cancer-related mortality worldwide. Despite advances in diagnosis and therapy, the prognosis for advanced HCC remains poor due to late-stage diagnosis, high recurrence rates, therapeutic resistance, and pronounced molecular heterogeneity. HCC development is driven by complex somatic gene alterations, epigenetic reprogramming, dysregulated signaling pathways, metabolic changes, and an immunosuppressive tumor microenvironment. Molecular profiling studies have identified key oncogenic pathways involved in HCC progression, including MAPK/ERK (mitogen-activated protein kinase/extracellular signal-regulated kinase), Wnt/β-catenin, PI3K/AKT/mTOR (Phosphoinositide 3-kinase/Protein Kinase B/mechanistic Target of Rapamycin), Hippo-YAP/TAZ, (Yes-associated protein/transcriptional co-activator with PDZ-binding motif) cell cycle regulators, and p53-mediated tumor suppression. These pathways coordinate critical cellular processes such as proliferation, survival, metabolism, invasion, and genomic stability. Emerging mechanisms, including cancer stem cell plasticity, immune evasion, epigenetic dysregulation, and steroid receptor coactivator (SRC)-dependent transcriptional regulation, further contribute to tumor progression and therapeutic resistance. Additionally, recent bioinformatic analyses suggest a potential role for progesterone-mediated oocyte maturation pathways in HCC, although their functional relevance remains unclear. A thorough understanding of these interconnected mechanisms could lead to novel therapeutic targets and the development of more effective, personalized treatment strategies for HCC. This review discusses key signaling pathways and emerging mechanisms in HCC and their roles in disease development and treatment. Full article

Background: Randomized trials support sublobar resection for selected small peripheral lung cancers, but real-world outcomes may vary by procedure type, nodal assessment, and pathological risk. Methods: We performed a two-stage real-world analysis. Stage 1 included 22,864 patients with lung adenocarcinoma ≤3 cm from a node-assessed N0M0 SEER cohort. Stage 2 included 872 patients with node-negative lung adenocarcinoma from a multi-institutional, single-center-dominant clinicopathological cohort. The primary endpoint was disease-free survival (DFS). Results: In SEER, sublobar resection was associated with higher all-cause mortality (HR 1.31, 95% CI 1.23–1.38) and lung cancer-specific death (HR 1.38, 95% CI 1.27–1.51). Procedure-specific estimates were smaller for segmentectomy than for wedge resection and were attenuated after adjustment for examined lymph-node count. In the clinicopathological cohort, the primary postoperative model showed a higher DFS hazard with sublobar resection (HR 1.75, 95% CI 1.08–2.83), with a similar estimate after overlap weighting (HR 1.75, 95% CI 1.08–2.85). However, the association was not statistically clear after propensity-score matching (HR 1.41, 95% CI 0.76–2.63), 60-month restriction (HR 1.09, 95% CI 0.58–2.03), or restriction to a comparable-follow-up cohort (HR 1.57, 95% CI 0.88–2.78). The proportional-hazards assumption for DFS was violated, and late estimates were based on sparse risk sets and were unstable. The recurrence association was predominantly locoregional, and increasing Core-HRPF burden was associated with progressively worse prognosis. Conclusions: Real-world sublobar resection is a heterogeneous exposure. Observed outcome associations varied by procedure type, nodal assessment, analytical specification, and follow-up horizon and should not be interpreted as evidence that sublobar resection is intrinsically inferior to lobectomy. Full article

Background: Eukaryotic translation elongation factor 1 alpha 1 (EEF1A1) primarily participates in protein synthesis by binding aminoacyl-tRNA complexes to facilitate peptide chain elongation on ribosomes. Its expression and functional roles exhibit significant heterogeneity across various malignancies, exerting dual regulatory effects as both an oncogene and a tumor suppressor. This study aims to investigate the potential prognostic value and tumor-suppressive role of EEF1A1 in kidney renal clear cell carcinoma (KIRC). Methods: We analyzed the differential expression of EEF1A1 in KIRC and its correlation with patient prognosis based on the TCGA, GEO, and HPA databases. The STRING and GEPIA databases were utilized to perform functional enrichment analysis of its interacting proteins and co-expressed genes. The xCell algorithm was employed to assess the correlation between EEF1A1 and immune cell infiltration, immune checkpoints, and immunomodulatory molecules. Furthermore, drug sensitivity analysis was conducted to evaluate its clinical application potential. Finally, the expression of EEF1A1 in 786-0 and A498 cell lines was validated via qRT-PCR and Western blotting. Furthermore, CCK-8, wound healing, and Transwell migration/invasion assays were performed to evaluate cell proliferation, migration, and invasion, respectively. Results: EEF1A1 may function as a negative regulator of malignant behaviors in KIRC tissues and cell lines, and its expression level was closely associated with clinicopathological features and prognosis of patients. GO, KEGG, and GSEA enrichment analyses revealed that low EEF1A1 expression is closely linked to immunosuppressive pathways. Further immunological analysis confirmed significant correlations between EEF1A1 and various immune cell infiltrates, immune checkpoints, tumor-infiltrating lymphocytes, and immunomodulatory molecules. Moreover, cells with high EEF1A1 expression exhibited increased sensitivity to anti-tumor drugs, with expression levels negatively correlated with inhibitory activity (IC50). Finally, overexpression of EEF1A1 significantly inhibited the proliferation, migration, and invasion of clear cell renal cell carcinoma cells. Conclusions: EEF1A1 serves as a potential prognostic biomarker in KIRC and is associated with clinical progression, immune-related characteristics, metabolic pathways, and drug sensitivity. Functional validation further supports its role in regulating malignant phenotypes of KIRC cells. Full article

Uterine leiomyosarcoma (uLMS) is a rare but highly aggressive mesenchymal malignancy of smooth-muscle origin that represents a significant therapeutic challenge due to its poor prognosis and limited treatment options. Despite advances in molecular characterization, diagnosis remains difficult, and systemic therapies have shown limited success, contributing to a high recurrence rate and poor survival. Recent proteomic investigations have provided new insights into uLMS biology by exploring the global protein expression patterns that define malignant transformation and progression. Using high-resolution mass spectrometry (MS)-based techniques, quantitative proteomics, and integrated multi-omics approaches, researchers have begun to identify dysregulated proteins, signaling pathways, and post-translational modifications (PTMs) linked to tumor metabolism, extracellular matrix (ECM) remodeling, cell-cycle regulation, and chemoresistance. These studies have also uncovered candidate biomarkers that may improve the discrimination of uLMS from benign leiomyoma and have proposed novel therapeutic targets associated with metabolic reprogramming, kinase activation and tumor microenvironment (TME) modulation. This review summarizes recent advancements in uLMS proteomics, discusses their methodological underpinnings, highlights key molecular mechanisms and biomarkers, and explores their translational potential. Finally, we outline current limitations and future directions toward clinical implementation of proteomic findings in precision oncology for uLMS patients. Full article

Triple-negative breast cancer (TNBC) is a subtype associated with poor prognosis and low survival rates, largely due to limited treatment options. In recent years, histone deacetylase (HDAC) inhibitors have emerged as promising anti-cancer candidates due to their attractive epigenetic properties and distinct mechanisms of action but have shown limited success in solid tumors. Here, we explore ribitoborate along with HDAC inhibitors for potential use as a treatment for TNBC. Experiments were performed on the TNBC cell line MDA-MB-231. The results of the study revealed that ribitoborate and romidepsin showed synergistic responses leading to significant arrest of cell proliferation (80%) (p < 0.01) as well as migration inhibition. These effects were associated with downregulation of c-Myc, survivin, Bcl-2, and cyclin D1, as well as upregulation of p53 and p21 proteins; notably the changes were significantly greater with the combined treatment than with either ribitoborate or romidepsin alone. Romidepsin and ribitoborate combined treatment time-dependently increased cell death of MDA-MB-231 cells with greater efficiency than romidepsin alone. Cell death by apoptosis was supported by the upregulation of H3k9 and H3k27 acetylation with decreasing proliferation. These results suggest the great potential of the drug combination for treatment of TNBC. The underlying molecular mechanisms for synergy could be further explored for potential development of new combined therapy for breast cancer. Full article

Background: Colorectal cancer is the third most commonly diagnosed cancer in the world. Liver metastases are frequent, adversely affecting patient prognosis. We compared progression-free survival and overall survival in colorectal cancer patients with liver metastasis treated with surgical resection or stereotactic body radiotherapy. No previous study had shown superiority of one treatment option over the other. Methods: We conducted a retrospective cohort study of 40 colorectal cancer patients with liver metastasis treated with surgical resection or stereotactic body radiotherapy at the Hebrew University-Hadassah Medical Center. Patient demographics, tumor characteristics, treatment details, and survival outcomes were analyzed. Kaplan–Meier curves and log-rank tests were used for survival analysis. Results: The median overall survival for the entire cohort was 44 months (95% CI 29–59 months). In patients treated with surgical resection, the median overall survival was 51 months (95% CI: 36–67 months), while in patients treated with stereotactic body radiotherapy the median overall survival was 32 months (95% CI: 21–43 months), a non-statistically significant result (p = 0.306). The number of lobes involved did not significantly impact overall survival (p = 0.214). Additionally, it did not significantly affect progression-free survival (p = 0.41). Liver metastases located in the left lobe led to considerably worse progression-free survival compared to other regions involved, specifically in the patients who underwent surgery. Conclusions: Our findings underscore the importance of personalized treatment strategies tailored to the distinct characteristics of colorectal cancer patients with liver metastasis. Currently, surgical resection remains the standard of care. Further research is warranted to address the possibility of extending SBRT to first-line treatment in selected unresectable patients. Full article

Background: Doxorubicin (DOX) is widely used in breast cancer treatment; however, therapeutic resistance and an immunosuppressive tumor microenvironment remain major obstacles to effective therapy. Immunogenic cell death (ICD) contributes to chemotherapy-induced antitumor immunity, but the molecular regulators linking DOX response, ICD-related signaling, and immune infiltration in breast cancer remain incompletely understood. This study aimed to identify and experimentally validate HSP90AA1 as a potential regulator of DOX response and ICD-associated immune remodeling in breast cancer. Methods: ICD-related genes were analyzed using public breast cancer transcriptomic datasets to construct prognostic models and evaluate their associations with survival, immune infiltration, immune checkpoint expression, and HLA-related molecules. HSP90AA1 was selected as a candidate gene for further validation. HSP90AA1 expression was examined in breast cancer tissues and cell lines. HSP90AA1 knockdown was performed in breast cancer cells, followed by DOX treatment. Western blotting was used to detect apoptosis-related proteins, ICD-related markers, and immune-associated molecules, including cleaved-caspase-3, BAX, BCL-2, CALR, HMGB1, p-eIF2α/eIF2α, and PD-L1. In vivo, a 4T1 syngeneic breast cancer mouse model was established to assess the effects of HSP90AA1 knockdown combined with DOX on tumor growth and tumor immune-related protein expression. Results: Bioinformatic analyses showed that ICD-related molecular patterns were associated with prognosis and immune microenvironment features in breast cancer. HSP90AA1 was upregulated in breast cancer and associated with unfavorable survival, supporting its potential relevance as an ICD-related prognostic candidate. In vitro, HSP90AA1 knockdown enhanced DOX-induced apoptotic responses, as indicated by increased cleaved-caspase-3 and BAX expression and decreased BCL-2 expression. HSP90AA1 knockdown also strengthened DOX-induced ICD-related molecular changes, including increased CALR, HMGB1, and p-eIF2α/eIF2α levels, accompanied by altered PD-L1 expression. In vivo, Hsp90aa1 knockdown combined with DOX resulted in a greater reduction in terminal tumor burden than DOX treatment alone. Tumor tissues from the combination group showed increased CALR, HMGB1, CD8A, and GZMB expression, together with altered PD-L1 expression. Tumor tissues from the combination group showed increased CALR, HMGB1, CD8A, and GZMB expression, together with altered PD-L1 expression, indicating ICD-related and immune-associated molecular changes. Conclusions: This study identifies HSP90AA1 as a potential ICD-related regulator of DOX response in breast cancer. HSP90AA1 knockdown may enhance the response to DOX by promoting apoptotic responses and ICD-related molecular changes, together with immune-related tumor microenvironment remodeling. These findings provide experimental evidence supporting HSP90AA1 as a potential therapeutic target for improving chemotherapy response in breast cancer. Full article

Background and Objectives: Metastatic pancreatic adenocarcinoma is related to poor prognosis and is frequently accompanied by malnutrition, inflammation, and immune dysregulation. The Controlling Nutritional Status (CONUT) score is a composite laboratory-based index that may reflect aspects of nutritional and immune status. This study aimed to evaluate the association between pretreatment CONUT score and overall survival (OS) in patients with metastatic pancreatic adenocarcinoma receiving first-line systemic chemotherapy. Materials and Methods: In this retrospective analysis, a total of 156 patients diagnosed with metastatic pancreatic adenocarcinoma between January 2017 and July 2024 and treated with first-line systemic chemotherapy were included. Based on the conventional CONUT classification, patients were categorized a priori into normal-CONUT (scores 0–1) and elevated-CONUT (scores ≥ 2) groups, with CONUT additionally evaluated as a continuous score. OS was estimated using the Kaplan–Meier method. Univariable and multivariable Cox regression analyses were performed to evaluate the association between the CONUT score, selected clinical factors, and overall survival. Results: The cohort demonstrated a median OS of 9.1 months (95% CI: 6.6–11.6). OS was significantly better among individuals classified in normal CONUT group relative to elevated CONUT group (14.1 vs. 6.5 months, respectively, p <0.001). Higher continuous CONUT scores were also associated with shorter OS (HR 1.23 (1.14–1.32), p < 0.001). In multivariable analysis, an elevated CONUT score (HR, 2.40 (1.63–3.52); p <0.001), liver metastases (HR 1.99 (1.31–3.02); p = 0.001), and the presence of comorbidity (HR, 1.88 (1.28–2.75); p = 0.001) remained significantly associated with shorter OS. Conclusions: An elevated pretreatment CONUT score was associated with shorter overall survival in this selected chemotherapy-treated cohort. As a readily available laboratory-based index, CONUT may provide additional prognostic information; however, prospective studies are needed to determine whether it adds value beyond established clinical factors. Full article

Background/Objectives: Advanced gastroesophageal adenocarcinoma (GEA) carries a poor prognosis, with median overall survival of 13–20 months despite standard chemotherapy. Since trastuzumab’s approval, biomarker-driven precision therapies have expanded rapidly. This review comprehensively summarises current and emerging targeted agents across the key molecular targets driving advanced GEA. Methods: A comprehensive literature review was conducted using PubMed, Google Scholar and Cochrane Library in accordance with PRISMA guidelines, searching English-language human studies published between February and July 2026, supplemented by updates during editing to reflect current standards. Results: HER2-directed therapy has progressed from trastuzumab through dual blockade, immunotherapy combinations, next-generation ADCs (notably trastuzumab deruxtecan) and bispecific antibodies such as zanidatamab, which has now overtaken trastuzumab in the first-line setting. CLDN18.2-targeted zolbetuximab has demonstrated survival benefit in biomarker-selected patients, with newer ADCs, BiTEs and the first approved solid-tumour CAR-T therapy (satricabtagene autoleucel) extending this target further. VEGFR2 inhibition with ramucirumab remains a cornerstone in later lines, while novel VEGF/PD-1(L1) bispecifics are under investigation. FGFR2b-targeted bemarituzumab showed early promise that weakened on phase 3 confirmation, and MET/EGFR-directed agents, including savolitinib and amivantamab, require stringent biomarker selection to demonstrate benefit amid tumour heterogeneity. Conclusions: Novel targeted agents, particularly to HER2 and CLDN18.2, have demonstrated survival benefit despite ongoing challenges. Other lines are more investigational. Full article

Background/Objectives: Uterine adenosarcoma is a rare uterine malignancy with limited evidence on prognostic factors and long-term outcomes. We aimed to evaluate clinicopathological characteristics, treatment patterns, oncologic outcomes, and prognostic factors associated with disease-free survival (DFS) and overall survival (OS) in patients with uterine adenosarcoma. Methods: This multicenter retrospective cohort study included 43 patients with histopathologically confirmed uterine adenosarcoma who underwent primary surgery at seven tertiary referral centers in Türkiye between 2016 and 2026. Clinicopathological features, treatment modalities, recurrence patterns, and survival outcomes were assessed. Survival was analyzed using Kaplan–Meier and log-rank methods, and multivariable Cox proportional hazards regression was performed to identify independent prognostic factors. Results: The mean age at diagnosis was 59.1 ± 10.8 years, and 83.7% of patients were postmenopausal. Pelvic pain (62.8%) and abnormal uterine bleeding (60.5%) were the most common presenting symptoms. Most patients (79.1%) underwent laparotomy, and 79.1% had stage I disease. Sarcomatous overgrowth (SO) was present in 44.1% and lymphovascular space invasion (LVSI) in 18.6%. During a median follow-up of 72 months, 34.9% experienced recurrence, most commonly in the pelvis. The five-year DFS and OS rates were 59.9% and 80.4%, respectively. SO was independently associated with DFS (HR 4.41, 95% CI 1.21–16.08; p = 0.025) and OS (HR 10.23, 95% CI 1.16–89.80; p = 0.036), while LVSI was independently associated with OS (HR 11.17, 95% CI 1.34–93.14; p = 0.026). Conclusions: Uterine adenosarcoma showed favorable long-term survival but substantial recurrence risk. SO and LVSI may have potential prognostic relevance and could contribute to postoperative risk assessment and individualized follow-up. Full article