Clinical Medicine Insights-Oncology最新文献

{"title":"Cost-Effectiveness of Tarlatamab in the Second-Line Treatment of Refractory Small Cell Lung Cancer From a US Perspective.","authors":"Hanrui Zheng, Feng Wen, Bin Wu","doi":"10.1177/11795549261441335","DOIUrl":"https://doi.org/10.1177/11795549261441335","url":null,"abstract":"<p><strong>Background: </strong>Compared with chemotherapy, tarlatamab significantly prolonged overall survival in patients with extensive-stage small cell lung cancer (ES-SCLC) whose disease progressed during or after platinum-based chemotherapy. The aim of this study was to evaluate the cost-effectiveness of tarlatamab versus chemotherapy as a second-line treatment for ES-SCLC from the perspective of the US health care system.</p><p><strong>Methods: </strong>A partitioned survival model was constructed to simulate disease progression on the basis of the DeLLphi-304 trial results. A 28-day cycle length and a 10-year time horizon were adopted for the model. Direct medical costs and health utility estimates were extracted from previously published studies and publicly available databases. The model outputs included the total and incremental costs and quality-adjusted life years (QALYs). The primary outcome was the incremental cost-effectiveness ratio (ICER). The willingness-to-pay (WTP) thresholds were set at $150 000/QALY and $200 000/QALY for the United States. One-way sensitivity analysis and probabilistic sensitivity analyses were performed to evaluate the robustness of the model outcomes.</p><p><strong>Results: </strong>At an incremental cost of $203 332.28, tarlatamab yielded an additional 0.29 QALYs compared with chemotherapy. This resulted in an ICER of $701 145.79/QALY, which substantially exceeded the WTP thresholds. The cost of tarlatamab emerged as a major influential parameter in the sensitivity analyses, demonstrating its substantial impact on cost-effectiveness outcomes. Sensitivity and scenario analyses confirmed the robustness of the cost-effectiveness results.</p><p><strong>Conclusion: </strong>At WTP thresholds of $150 000/QALY and $200 000/QALY, tarlatamab was not considered a cost-effective option at the current price compared with chemotherapy for the treatment of recurrent ESCLC from the US payer perspective.</p>","PeriodicalId":48591,"journal":{"name":"Clinical Medicine Insights-Oncology","volume":"20 ","pages":"11795549261441335"},"PeriodicalIF":1.9,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13125839/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147822324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transarterial Chemoembolization Combined With Lenvatinib in the Treatment of Intermediate-Stage Hepatocellular Carcinoma With Hypovascular Nodules: A Retrospective Cohort Study.","authors":"Jun Yang, Fei Shi, Nan Jiang, Shen Zhang, Yu Yin, Bin Yu, Wencong Feng, Hongao Chu, Caifang Ni","doi":"10.1177/11795549261441338","DOIUrl":"https://doi.org/10.1177/11795549261441338","url":null,"abstract":"<p><strong>Background: </strong>To compare the efficacy and safety of transarterial chemoembolization (TACE) combined with lenvatinib vs TACE alone in intermediate-stage hepatocellular carcinoma (HCC) patients with hypovascular nodules.</p><p><strong>Methods: </strong>This retrospective study analyzed the clinical data of intermediate-stage HCC patients with hypovascular nodules who underwent TACE. Patients were categorized into the TACE-Lenv combination group and the TACE monotherapy group according to their receipt of lenvatinib therapy. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), progression of hypovascular nodules, and treatment-related adverse events were recorded and analyzed.</p><p><strong>Results: </strong>The study enrolled 75 patients, with 40 allocated to the TACE-Lenv group and 35 to the TACE group. The combination therapy group demonstrated significantly higher ORR and DCR (92.5% vs 74.3%, <i>P</i> = .032; 97.5% vs 82.9%, <i>P</i> = .030) compared with TACE monotherapy. The TACE-Lenv group exhibited significantly prolonged median OS and PFS (41.1 vs 19.7 months, <i>P</i> < .001; 20.2 vs 9.9 months, <i>P</i> < .001). In addition, compared with the TACE group, the TACE-Lenv group extended the median time to nodule progression (37.0 vs 16.5 months, <i>P</i> < .001). After propensity score matching, significant differences remained in the aforementioned outcomes between the 2 groups. No significant differences were observed in liver function parameters or the incidence of grade 3 to 4 AEs between the 2 groups after treatment.</p><p><strong>Conclusions: </strong>The combination therapy of TACE and lenvatinib demonstrated excellent clinical efficacy in intermediate-stage HCC with hypovascular nodules and may therefore emerge as a preferred treatment option for this specific patient population.</p>","PeriodicalId":48591,"journal":{"name":"Clinical Medicine Insights-Oncology","volume":"20 ","pages":"11795549261441338"},"PeriodicalIF":1.9,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13111896/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147786367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Patient Experience of Cancer-Related Cachexia: Implications for Patient-Reported Outcomes Measures.","authors":"Magdalena Harrington, Susan Martin, Oyebimpe Olayinka-Amao, Jarjieh Fang, Euan McLeod, Ira Jacobs","doi":"10.1177/11795549261430229","DOIUrl":"https://doi.org/10.1177/11795549261430229","url":null,"abstract":"<p><strong>Background: </strong>Understanding the patient experience, including symptoms and impacts, of cancer-related cachexia is an important step in developing and validating patient-reported outcome measures that can support the subsequent development of new treatments. The Functional Assessment of Anorexia-Cachexia Therapy-5-item anorexia-related symptoms scale (FAACT-5IASS) is an outcome measure that may be suitable for the assessment of cachexia in patients with cancer. The objective of this analysis was to better understand the patient experience of cachexia based on qualitative interviews with patients.</p><p><strong>Methods: </strong>Concept elicitation interviews were conducted with patients with cancer and cachexia to understand key symptoms and their impacts. Outputs from the interviews were also used to confirm the relevance and content validity of the FAACT-5IASS for characterizing the identified cachexic symptoms.</p><p><strong>Results: </strong>Patients (N = 20) with non-small-cell lung (n = 8), pancreatic (n = 5), or colorectal (n = 7) cancer participated in interviews. Patients identified lack of appetite, nausea (and vomiting when describing nausea), and fatigue as key symptoms, although nausea and vomiting were primarily attributed to chemotherapy rather than specific to cachexia. These symptoms were reported as the most bothersome with negative impacts on appearance, physical function, social activities, and moods/emotions. Post-hoc analysis of the interviews supported the relevance of 4 out of 5 concepts in the FAACT-5IASS (having good appetite, satiety, food tasting unpleasant, and interest in food when eating).</p><p><strong>Conclusions: </strong>This qualitative research identified the importance of assessing key symptoms and impacts of cachexia using patient-reported measures that are conceptually relevant.</p>","PeriodicalId":48591,"journal":{"name":"Clinical Medicine Insights-Oncology","volume":"20 ","pages":"11795549261430229"},"PeriodicalIF":1.9,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13110313/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147786416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Symptom Burden and Healthcare Resource Use in Patients With Claudin 18.2-Positive, HER2-Negative, Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma: A Retrospective Review.","authors":"Matheus Sewastjanow-Silva, Mok Oh, Lawrence Chang, Arijit Ganguli, Jane E Rogers, Rebecca E Waters, Ernesto Rosa Vicentini, Kohei Yamashita, Todor I Totev, Eric Q Wu, Hongbo Yang, Kenneth Iwata, Jaffer A Ajani","doi":"10.1177/11795549261430041","DOIUrl":"10.1177/11795549261430041","url":null,"abstract":"<p><strong>Background: </strong>Control of disease-related symptoms is a goal of chemotherapy for patients with locally advanced (LA) unresectable or metastatic gastric/gastroesophageal junction (mG/GEJ) adenocarcinoma. This study describes disease-related symptoms and healthcare resource utilization (HRU) in this population.</p><p><strong>Methods: </strong>A retrospective review of adult patients with claudin 18.2-positive (CLDN18.2+), human epidermal growth factor receptor 2-negative (HER2-), LA unresectable or mG/GEJ adenocarcinoma was performed. Outcomes were assessed from the index date (date of diagnosis) through the follow-up end date (earliest of first-line treatment discontinuation, last follow-up visit, death, or 1 year after index date).</p><p><strong>Results: </strong>Sixty-two patients were included in the analysis (mean age, 61.3 years; 54.8% male; 88.7% White; 67.7% had gastric primary tumors; 75.8% had peritoneal metastases; 98.4% received first-line treatment [mean time from diagnosis to treatment initiation, 37.0 days]). All patients reported ⩾1 disease-related symptom (mean = 7.2) at the index date. The most common symptoms at the index date were weight loss (74.2%), abdominal pain/stomach pain (66.1%), anemia/weakness (61.3%), poor appetite (56.5%), and epigastric pain (50.0%). Of the 21 patients evaluated at the 6-month follow-up, 95.2% reported ⩾1 disease-related symptom. The greatest changes were seen for weight loss (0.0% at 6 months vs 74.2% at the index date), epigastric pain (9.5% vs 50.0%), poor appetite (23.8% vs 56.5%), reflux (4.8% vs 35.5%), early satiety (0.0% vs 29.0%), and abdominal pain/stomach pain (38.1% vs 66.1%). A mean of 3.4 outpatient visits per patient per month was reported (mean follow-up, 6.5 months), 21.0% of patients had an inpatient admission, and 35.5% had an emergency department visit.</p><p><strong>Conclusions: </strong>This study demonstrates substantial disease-related symptom burden and high HRU for patients with CLDN18.2+, HER2-, LA unresectable or mG/GEJ adenocarcinoma.</p>","PeriodicalId":48591,"journal":{"name":"Clinical Medicine Insights-Oncology","volume":"20 ","pages":"11795549261430041"},"PeriodicalIF":1.9,"publicationDate":"2026-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13033856/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147595706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Osimertinib for Patients With EGFR-Mutated Non-Small Cell Lung Cancer: Current Evidence.","authors":"Xiumei Tang, Yanmei Chen, Yuan Zhu, Yuan Liu, Weimin Li, Wenzhao Wang, Zhoufeng Wang","doi":"10.1177/11795549261434260","DOIUrl":"10.1177/11795549261434260","url":null,"abstract":"<p><strong>Background: </strong>Osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, has demonstrated efficacy across multiple treatment lines for patients with EGFR-mutated non-small cell lung cancer (NSCLC). However, the optimal treatment sequence and comparative effectiveness vs alternative therapies remain unclear.</p><p><strong>Methods: </strong>A systematic review and meta-analysis was conducted following the PRISMA 2020 guidelines. Embase, Medline (via Ovid), PubMed, Cochrane Central Register of Controlled Trials, Web of Science, and Google Scholar were searched from inception to May 31, 2025. Clinical trials comparing osimertinib with other treatments (placebo, EGFR-tyrosine kinase inhibitors [TKIs], chemotherapy, targeted therapy) in patients with EGFR-mutated NSCLC were included. Primary outcomes included objective response rate (ORR), median progression-free survival (mPFS), disease control rate (DCR), overall survival (OS), and adverse events. Subgroup analyses were performed by treatment line and comparator type. Risk of bias was assessed using the Cochrane RoB 2 tool. Statistical analysis was performed using R version 4.5.0 with random-effects models for high heterogeneity (I²> 50%).</p><p><strong>Results: </strong>Sixteen studies encompassing 4931 patients were included. Osimertinib demonstrated significantly superior ORR compared to control treatments (relative risk [RR] = 1.59, 95% confidence interval [CI] = 1.16 to 2.17, <i>P</i> < .001), exceeding the minimal clinically important difference threshold. The mPFS benefit was substantial (standardized mean difference [SMD] = 4.53 months, 95% CI = 1.23 to 7.82, <i>P</i> < .0001), with greater improvements observed in first-line therapy (SMD = 3.25, 95% CI = 0.52 to 5.97) vs second-line treatment (SMD = 7.61, 95% CI = -10.08 to 25.30). The DCR was significantly improved (RR = 1.26, 95% CI = 1.05 to 1.52, <i>P</i> < .0001). The OS showed modest but consistent improvement (SMD = 0.18, 95% CI = 0.11 to 0.26, <i>P</i> < .0001) with no heterogeneity (I²= 0%). Osimertinib was most effective vs chemotherapy and showed consistent benefits vs first-generation TKIs. Adverse events included increased upper respiratory tract infections, skin toxicities, and QT prolongation, while nausea and alopecia were reduced.</p><p><strong>Conclusions: </strong>Osimertinib demonstrates superior efficacy across multiple endpoints in patients with EGFR-mutated NSCLC, with benefits observed in both first-line and second-line settings. The treatment provides clinically meaningful benefits with a manageable safety profile, supporting its use as a preferred therapeutic option across different treatment sequences.</p>","PeriodicalId":48591,"journal":{"name":"Clinical Medicine Insights-Oncology","volume":"20 ","pages":"11795549261434260"},"PeriodicalIF":1.9,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13031757/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147576038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retrospective Analysis of the Clinical Efficacy, Safety, and Influencing Factors of Drug-Eluting Bead Transarterial Chemoembolization for Unresectable Hepatic Malignancies.","authors":"Li Liu, Yuling Sheng, Xianxian Liang, Tao Yang, Li Dong, Dazhi Gao, Bo Chen, Tantan Xu, Min Ai, Husheng Shan, Jinjing Tang, Longjiang Zhang, Donghong Shi, Xiaoli Zhu","doi":"10.1177/11795549261434259","DOIUrl":"10.1177/11795549261434259","url":null,"abstract":"<p><strong>Background: </strong>Transarterial chemoembolization (TACE) is an established therapeutic modality for malignant hepatic tumors. This study assessed the clinical efficacy, adverse events, and factors associated with treatment outcomes of drug-eluting bead transarterial chemoembolization (DEB-TACE) in the treatment of hepatic malignancies.</p><p><strong>Methods: </strong>Clinical data were collected from 94 patients with hepatic malignancies who underwent DEB-TACE. Treatment response was assessed in accordance with the modified Response Evaluation Criteria in Solid Tumors (mRECIST). Postoperative complications and relevant hematological parameters were analyzed by reviewing clinical symptoms and laboratory/examination findings. Logistic regression analysis was used to identify factors associated with treatment outcomes.</p><p><strong>Results: </strong>Median follow-up duration was 29.0 months (range: 3.0-51.0 months). Treatment response assessment post-DEB-TACE revealed that 2 patients (2.1%) achieved a complete response (CR), 53 (56.4%) achieved a partial response (PR), 27 (28.7%) had stable disease (SD), and 12 (12.8%) developed progressive disease (PD). The overall objective response rate (ORR) was 58.5%, and the disease control rate (DCR) was 87.2%. Median progression-free survival (PFS) was 5.0 months (95% confidence interval [CI]: 3.7-6.3 months), and median overall survival (OS) was 15.0 months (95% CI: 7.6-22.4 months). Multivariate logistic regression analysis demonstrated that hematological parameters-including D-dimer levels, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and C-reactive protein (CRP) levels-were associated with patient prognosis and survival outcomes.</p><p><strong>Conclusions: </strong>Drug-eluting bead transarterial chemoembolization is an effective treatment for various liver malignancies, associated with few manageable postoperative complications. In addition, d-dimer, the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), and C-reactive protein (CRP) levels may predict DEB-TACE efficacy.</p>","PeriodicalId":48591,"journal":{"name":"Clinical Medicine Insights-Oncology","volume":"20 ","pages":"11795549261434259"},"PeriodicalIF":1.9,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13018707/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147576049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stage Migration and Validity of the International Federation of Gynecology and Obstetrics (FIGO) 2018 Staging System for Cervical Cancer: A Retrospective Cohort Study From a Tertiary Cancer Center in Nepal.","authors":"Simit Sapkota, Subhas Pandit, Jeebana Bhandari, Abish Adhikari, Sunil Shrestha, Anjani Kumar Jha","doi":"10.1177/11795549261434986","DOIUrl":"10.1177/11795549261434986","url":null,"abstract":"<p><strong>Introduction: </strong>Cervical cancer remains a major public health concern in low- and middle-income countries, including Nepal. The International Federation of Gynecology and Obstetrics (FIGO) 2018 staging system for cervical cancer introduced stage IIIC for tumors with lymph node metastasis, reflecting the prognostic significance of nodal involvement. This study aimed to evaluate stage migration from FIGO 2009 to FIGO 2018 and to validate the prognostic performance of the revised staging system in locally advanced cervical cancer.</p><p><strong>Methods: </strong>In this retrospective cohort study, we consecutively included 155 patients with histologically confirmed cervical cancer treated with definitive radiotherapy or chemo-radiotherapy at Kathmandu Cancer Center between August 2016 and June 2019. Patients were initially staged according to the FIGO 2009 criteria and retrospectively restaged according to the FIGO 2018 criteria. Recurrence patterns were documented, and overall survival (OS) and disease-free survival were estimated using the Kaplan-Meier method with log-rank tests for group comparisons. All patient identifiers were removed, and the study conformed to the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guidelines. Ethical approval was obtained from the Nepal Health Research Council (approval number: 655/2020P), and the requirement for written informed consent was waived.</p><p><strong>Results: </strong>Under FIGO 2009, most patients were classified as stage IIB (47.7%) and IIIB (36.7%), whereas under FIGO 2018, this led to 34.2% in stage IIB and 31% in stage IIIC1. Stage migration occurred in 38.7% of patients, predominantly from IIIB (58.3%) and IIB (35.4%) to IIIC1. Both staging systems demonstrated decreased OS with advanced stages; however, stage IIIC1 patients had better OS than stage IIIB patients under the FIGO 2018 staging, likely reflecting heterogeneity in tumor extent and treatment factors. Five-year OS rates were not significantly different between the 2 staging systems. Recurrence was observed in 29.2% of patients, with distant metastasis being the most common pattern.</p><p><strong>Conclusions: </strong>The FIGO 2018 staging system results in substantial stage migration and highlights heterogeneity among node-positive (stage IIIC1) patients. Consideration of tumor extent and nodal burden is important for accurate prognostication. These findings support the need for further studies to refine the staging system and improve its prognostic precision in cervical cancer.</p>","PeriodicalId":48591,"journal":{"name":"Clinical Medicine Insights-Oncology","volume":"20 ","pages":"11795549261434986"},"PeriodicalIF":1.9,"publicationDate":"2026-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13009913/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147515997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proposing an Optimized Prediction Model for Pancreatic Cancer Based on Mendelian Randomization Analysis of Fibrinogen Levels and Urinary Protein Excretion Rate.","authors":"Qian Wu, Mengqing Sun, Yan Lin, Shujin Lin, Ting Lin, Xiao Han, Xianlin Han","doi":"10.1177/11795549251392490","DOIUrl":"10.1177/11795549251392490","url":null,"abstract":"<p><strong>Background: </strong>An ongoing debate exists on the relationship between fibrinogen levels, urinary albumin excretion (UAE), and pancreatic ductal adenocarcinoma (PDAC), as demonstrated by clinical data of patients with benign and malignant pancreatic tumors.</p><p><strong>Methods: </strong>FinnGen and EMBL-EBI provided data on single-nucleotide polymorphisms associated with fibrinogen levels, UAE, and PDAC. To examine exposure-outcome relationships, weighted median, MR-Egger, and inverse variance weighted methods were employed. Heterogeneity and horizontal pleiotropy were evaluated using Cochran's Q test and MR-Egger intercept analysis, respectively. The robustness of the Mendelian randomization (MR) analysis results was assessed using a leave-one-out sensitivity analysis. Clinical information, including sex, age, tumor location, pathological diagnosis, UAE level, fibrinogen level, and serum carbohydrate antigen 19-9 (CA19-9) level, was collected from patients with pancreatic malignant tumors at Peking Union Medical College Hospital from 2019 to 2024.</p><p><strong>Results: </strong>Fibrinogen levels and PDAC exhibited a strong positive causal association according to MR analysis (95% confidence interval [CI]: 1.630 to 8.753; <i>P</i> = .004). The UAE and PDAC exhibited a substantial beneficial causal association (95% CI: 0.055 to 3.831; <i>P</i> = .044) in the intercept analysis, and Cochran's Q test did not show horizontal pleiotropy or heterogeneity (<i>P</i> > .05). Sensitivity analysis demonstrated the robustness of the findings. The inclusion of both fibrinogen and UAE levels increased the prediction rate for pancreatic malignancy by 6.36%. Genetic variations at SLC22A4 (rs12777) and FMO4 (rs1227104) may influence systemic inflammation, fibrinogen production, renal/metabolic homeostasis, and immunometabolic reprogramming, thereby shaping the tumor microenvironment and contributing to PDAC development.</p><p><strong>Conclusion: </strong>This study demonstrated the potential of fibrinogen levels and UAE as biomarkers of pancreatic malignancy through MR and clinical data validation. These metrics significantly improved the prediction of pancreatic cancer when used in combination with CA19-9 levels. In addition, this study proposes a mechanism for fibrinogen levels and UAE in PDAC involving SLC22A4 and FMO4.</p>","PeriodicalId":48591,"journal":{"name":"Clinical Medicine Insights-Oncology","volume":"20 ","pages":"11795549251392490"},"PeriodicalIF":1.9,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13010017/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147515880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PD-1/PD-L1-CXCR3 Coexpression and CXCR3 on Intermediate Monocytes Predict Fibrosis, Leukemic Transformation, and Survival in Egyptian Philadelphia-Negative Myeloproliferative Neoplasms.","authors":"Dalia E Sherief, Rawan Ahmed Elmezien, Nahla Nosair, Amira Aa Othman, Emad Sadaka, Rasha Elgamal","doi":"10.1177/11795549261431360","DOIUrl":"10.1177/11795549261431360","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Despite established prognostic scores, predicting disease progression in myeloproliferative neoplasms (MPNs) remains challenging, and the role of specific immune cell subsets-particularly the PD-1/PD-L1 axis-in mediating fibrosis and transformation is poorly characterized. This study aimed to investigate the prognostic utility of novel immune-inflammatory biomarkers, including PD-1/PD-L1 coexpression with C-X-C chemokine receptor type 3 (CXCR3), CXCR3 expression on monocyte subsets, and systemic indices (systemic immune-inflammation index [SII], systemic inflammation response index [SIRI]), for predicting fibrosis grade, leukemic transformation, and survival outcomes in patients with Philadelphia-negative MPNs.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;In a prospective case-control study, including 90 Egyptian patients with Philadelphia-negative MPNs and 90 matched controls, we quantified PD-1/PD-L1 coexpression with CXCR3 and CXCR3 expression on monocyte subsets by flow cytometry. Validation employed targeted next-generation sequencing (NGS) in the full cohort, complemented by focused mechanistic validation using bulk RNA sequencing (n = 20 primary myelofibrosis [PMF], n = 10 controls), single-cell RNA sequencing (n = 10 PMF, n = 5 controls), and targeted serum cytokine profiling (IL-6 and TGF-β; n = 90 MPN, n = 90 controls). Diagnostic/prognostic performance used receiver operating characteristic (ROC) curves, decision curve analysis, logistic/Cox regression, random forest/gradient boosting, and external validation in an independent Egyptian cohort (n = 30). Patient-reported outcomes were assessed with the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;PD-1/CXCR3 and PD-L1/CXCR3 were elevated in patients (&lt;i&gt;P&lt;/i&gt; &lt; .001). PD-L1/CXCR3 demonstrated high discrimination between advanced (grade 4) and grade 3 fibrosis (area under the curve [AUC] 0.975; cut-off &gt;40%; sensitivity 92.9%; specificity 90%). In an exploratory analysis, reduced CXCR3 on intermediate monocytes was associated with leukemic transformation (AUC 0.876; cut-off ⩽ 12%) with high negative predictive value (98.4%). Higher PD-L1/CXCR3 correlated with worse fatigue (&lt;i&gt;r&lt;/i&gt; = 0.58, &lt;i&gt;P&lt;/i&gt; &lt; .001) and pruritus (&lt;i&gt;r&lt;/i&gt; = 0.45, &lt;i&gt;P&lt;/i&gt; = .002) on MPN-SAF and was an independent predictor of poorer survival. A biomarker-enhanced prognostic score (incorporating high PD-L1/CXCR3, low CXCR3/intermediate, age, and Dynamic International Prognostic Scoring System) outperformed DIPSS/DIPSS-Plus/MIPSS70 (AUC 0.85; bootstrap AUC 0.84) and showed promising initial validation in an external cohort (AUC 0.82). Single-cell RNA sequencing revealed a CXCR3-low intermediate monocyte population enriched for profibrotic/inflammatory signatures; targeted cytokine analysis indicated higher IL-6/TGF-β in checkpoint-high states.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;PD-1&lt;sup&gt;+&lt;/sup&gt;CXCR3&lt;sup&gt;+&lt;/sup&gt;/PD-L1&lt;sup&gt;+&lt;/sup&gt;CXCR3&lt;sup&gt;+&lt;/sup&gt; coe","PeriodicalId":48591,"journal":{"name":"Clinical Medicine Insights-Oncology","volume":"20 ","pages":"11795549261431360"},"PeriodicalIF":1.9,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13010026/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147515908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Clinicopathology and Simplified Molecular Marker-Based Risk Stratification Model for Predicting 3-Year Recurrence in Endometrial Cancer.","authors":"Juntao Zhang, Yichuan Zhou, Yuzhen Huang, Xiaoyan Qin, Hua Yang, Chunrun Yang, Jianbin Guo","doi":"10.1177/11795549261428372","DOIUrl":"https://doi.org/10.1177/11795549261428372","url":null,"abstract":"<p><strong>Background: </strong>The integration of clinicopathological parameters and molecular biomarkers holds significant prognostic value for endometrial carcinoma (EC) recurrence assessment. The purpose of this study is to combine clinical pathological parameters with simple molecular features to predict 3-year recurrence of EC.</p><p><strong>Methods: </strong>Based on a retrospective cohort with 136 patients assessing recurrence risk within 3 years postoperatively, we developed PM-TERR (clinicopathology and simplified molecular markers-based EC tailored 3-year recurrence risk). All patients were randomly assigned to the training set (96 patients) and the test set (40 patients). The nomogram comprised 4 input variables (Stage, Grade, Pathology Type, and P53 status) for calculating a PM-TERR score.</p><p><strong>Results: </strong>Kaplan-Meier analysis demonstrated a significant association between PM-TERR scores and disease-free survival (DFS) in both the training and test sets (both <i>P</i> < .001). The PM-TERR model outperformed the ESMO stratification in predicting DFS. The likelihood value of the PM-TERR model increased by 6.88 in the training set, and by 2.20 in the test set, both sets <i>P</i> < .05. Time-dependent ROC analysis further confirmed the PM-TERR enhanced predictive accuracy, with consistently higher AUC values across all time points than ESMO in both cohorts.</p><p><strong>Conclusion: </strong>In summary, the PM-TERR model integrates stage, grade, histology, and p53 status to predict 3-year recurrence risk. This retrospective, single-center study demonstrates its potential utility; however, future prospective, multi-center validation is required to confirm its robustness and clinical applicability before broader implementation.</p>","PeriodicalId":48591,"journal":{"name":"Clinical Medicine Insights-Oncology","volume":"20 ","pages":"11795549261428372"},"PeriodicalIF":1.9,"publicationDate":"2026-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12957589/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147366685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}