International Journal of Cancer最新文献

{"title":"Reassessing the Incidence and Risk Factors of Radiation Pneumonitis in Treatment-Naive EGFR-Mutant NSCLC With Concurrent Third-Generation EGFR-TKI and Thoracic Radiotherapy","authors":"Shuyue Zheng,&nbsp;Wenxiao Jia,&nbsp;Xuquan Jing,&nbsp;Yaru Tian,&nbsp;Feihu Chen,&nbsp;Li Li,&nbsp;Zhijun Guo,&nbsp;Jinming Yu,&nbsp;Hui Zhu","doi":"10.1002/ijc.70630","DOIUrl":"10.1002/ijc.70630","url":null,"abstract":"<div>\u0000 \u0000 <p>This single-center retrospective study evaluated radiation pneumonitis (RP) in 209 treatment-naive EGFR-mutant non-small cell lung cancer (NSCLC) patients receiving first-line third-generation EGFR tyrosine kinase inhibitors (EGFR-TKIs) plus thoracic radiotherapy (TRT), with concurrent defined as any overlap of ≥ 1 day between EGFR-TKI and TRT, at Shandong Cancer Hospital and Institute between January 2019 and September 2024, excluding concurrent chemotherapy and anti-angiogenic therapy. RP was diagnosed by chest computed tomography (CT), clinical symptoms, and irradiated field concordance, while infectious pneumonia and tumor progression were excluded by laboratory tests and serial imaging. Grade ≥ 2 RP occurred in 43.54% of patients (22.01% grade 2, 21.53% grade 3; no grade 4/5 RP), with osimertinib showing the highest rates of grade ≥ 2 and grade 3 RP, followed by aumolertinib and furmonertinib. For grade ≥ 2 RP, patients receiving aumolertinib or furmonertinib had a lower observed risk than those receiving osimertinib, while ipsilateral lung V5 ≥ 35.93% and gross tumor volume (GTV) ≥ 12.62 mL were independent risk factors. For grade 3 RP, an inverse association between smoking history and RP risk was observed, whereas ipsilateral lung V30 ≥ 24.61% and GTV ≥ 14.56 mL were associated with increased risk. Median progression-free survival (PFS) was 26.70 months, with no significant difference among the three TKIs. In this cohort, first-line third-generation EGFR-TKI plus TRT was associated with frequent but generally manageable RP. TKI type, ipsilateral lung V5/V30, and GTV were key predictors of RP, although the dosimetric thresholds and drug-specific differences identified in this cohort require external validation.</p>\u0000 </div>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":"159 11","pages":"2791-2803"},"PeriodicalIF":4.9,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148337009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrating Plasma Proteomics and Polygenic Risk Scores for the Prediction of Lung Cancer Risk","authors":"Fan Yang,&nbsp;Xirui Qiu,&nbsp;Wei Wang,&nbsp;Yifan Wang,&nbsp;Siwei Wang,&nbsp;Jie Wang,&nbsp;Xinru Hu,&nbsp;Yingtian Wang,&nbsp;Fangyi Chen,&nbsp;Haining Qi,&nbsp;Xianglin Zuo,&nbsp;Junru Zhu,&nbsp;Meng Jiang,&nbsp;Rong Yin,&nbsp;Xiaoxiao Wang","doi":"10.1002/ijc.70710","DOIUrl":"10.1002/ijc.70710","url":null,"abstract":"<div>\u0000 \u0000 <p>Multimodal diagnostic strategies and risk stratification are essential for improving early lung cancer detection, clinical outcomes, and personalized interventions. To develop a predictive model for lung cancer incidence by integrating plasma proteomics, genetic factors, and demographic data. We analyzed data from the UK Biobank, which included 47,655 adults without a history of lung cancer at baseline, with 641 incident cases and a median follow-up duration of 13.87 years. COX proportional hazards modeling with SHapley Additive exPlanations (SHAP) sequential feature selection was used to identify significant plasma proteins associated with lung cancer. An XGBoost-based survival model was constructed and evaluated to assess its predictive utility. Proteomic risk score (ProRS), demographic, and Combined risk scores were developed to evaluate their predictive capabilities across genetic risk strata. Among 2911 plasma proteins, we identified 15 significant plasma proteins associated with the development of lung cancer. The XGBoost survival model demonstrated promising predictive performance, achieving a C-statistics of 0.803. Risk stratification revealed that high-risk groups had up to a 101-fold increased risk of lung cancer compared to low-risk groups. We analyzed expression patterns of 15 carcinogenesis-associated proteins during the 15-year period preceding diagnosis. TNR and CLEC3B were identified as the earliest dysregulated proteins, with expression levels consistently downregulated beginning as early as 14 years before diagnosis. GDF15 exhibited sustained and pronounced upregulation throughout the entire 14-year observation window. Integrating plasma proteomics, polygenic risk scores, and demographic factors improves personalized lung cancer risk stratification, offering potential for refined screening strategies.</p>\u0000 </div>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":"159 11","pages":"2835-2849"},"PeriodicalIF":4.9,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148904578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma Protein Biomarkers for Early Detection of Pancreatic Cancer","authors":"Yingsong Lin,&nbsp;Masahiro Nakatochi,&nbsp;Haruki Sasado,&nbsp;Itsuki Kageyama,&nbsp;Sayo Kawai,&nbsp;Taiki Yamaji,&nbsp;Naoki Sasahira,&nbsp;Masato Ozaka,&nbsp;Hiroshi Ishii,&nbsp;Makoto Ueno,&nbsp;Satoshi Kobayashi,&nbsp;Naoto Egawa,&nbsp;Yasushi Adachi,&nbsp;Yuki Obata,&nbsp;Yuki Ohashi,&nbsp;Tae Sasakabe,&nbsp;Asahi Hishida,&nbsp;Shogo Kikuchi","doi":"10.1002/ijc.70637","DOIUrl":"10.1002/ijc.70637","url":null,"abstract":"<div>\u0000 \u0000 <p>Early detection of pancreatic cancer remains challenging, and reliable circulating biomarkers are needed to enable earlier diagnosis and improve clinical outcomes. We conducted a plasma proteomics study using the Olink Explore HT platform to identify novel biomarker candidates for early-stage pancreatic cancer. The study included 42 patients with stage I–II pancreatic cancer and 43 matched controls. Plasma protein levels were quantified using the Olink Proximity Extension Assay, and differential abundance was assessed using Welch's <i>t</i>-test with correction for multiple testing. Diagnostic performance was evaluated using the area under the receiver operating characteristic curve (AUC). Among 5419 proteins analyzed, 982 showed significant differences between cases and controls. Carboxylesterase 3 (CES3) was the most significantly decreased protein, whereas leukocyte immunoglobulin-like receptor B4 (LILRB4) was the most significantly increased protein; both demonstrated excellent diagnostic performance (AUC = 0.91). In addition, pancreatic polypeptide (PPY) showed markedly reduced levels in patients with tumors arising in the head of the pancreas, suggesting anatomical specificity. This comprehensive Olink-based proteomic analysis identifies CES3 and LILRB4 as promising plasma biomarkers for early-stage pancreatic cancer and highlights PPY as informative for tumor localization. These findings provide a valuable resource for biomarker discovery and support further validation of these candidates for noninvasive early detection and risk stratification.</p>\u0000 </div>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":"159 11","pages":"2694-2704"},"PeriodicalIF":4.9,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148443608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic Dysregulation of Somatostatin Receptors (SSTR) 1–5 and Therapeutic Implications in Neuroendocrine and Non-Neuroendocrine Malignancies","authors":"Neeraj Kumari,&nbsp;Pablo Hoffmann,&nbsp;Laura Reichl,&nbsp;Maximilian Schmutz,&nbsp;Nina Fischer,&nbsp;Thi Tuong Vi Dang,&nbsp;Fulvia Ferrazzi,&nbsp;Pascal Johann,&nbsp;Michaela Kuhlen,&nbsp;Constantin Lapa,&nbsp;Rainer Claus","doi":"10.1002/ijc.70635","DOIUrl":"10.1002/ijc.70635","url":null,"abstract":"<p>Somatostatin receptors (SSTR) mediate the antiproliferative, antisecretory, and proapoptotic effects of somatostatin and its synthetic analogs. Their surface expression on neuroendocrine tumor (NET) cells is required for somatostatin analog therapy and radiopharmaceutical therapy (RPT). However, 20%–30% of gastroenteropancreatic NETs and most poorly differentiated neuroendocrine carcinomas show insufficient SSTR expression, limiting therapeutic eligibility. Accumulating evidence indicates that reversible epigenetic mechanisms contribute substantially to SSTR loss, alongside tumor dedifferentiation, lineage-state changes, and clonal evolution with DNA hypermethylation of the <i>SSTR2</i> promoter representing a central event, complemented by chromatin remodeling and non-coding RNA-mediated regulation. Preclinical studies demonstrate that epigenetic therapies, including DNA methyltransferase and histone deacetylase inhibitors, can restore functional SSTR expression. Notably, the first-in-human LANTana trial provides clinical proof-of-concept that epigenetic priming with oral decitabine/cedazuridine can induce SSTR2 re-expression and enable subsequent RPT in receptor-negative tumors. This review synthesizes current knowledge of epigenetic regulation across all five SSTR subtypes (SSTR1–SSTR5), examines receptor silencing in neuroendocrine and non-neuroendocrine malignancies, and critically evaluates the preclinical and clinical evidence supporting therapeutic strategies that target these mechanisms.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":"159 11","pages":"2633-2652"},"PeriodicalIF":4.9,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ijc.70635","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148381299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cancer Planners Forum: Positioning National Cancer Control Plans as Strategic Investments in the Future of Countries","authors":"Zuzanna Tittenbrun,&nbsp;Yannick Romero,&nbsp;Céline Francina,&nbsp;Sonali Johnson","doi":"10.1002/ijc.70643","DOIUrl":"10.1002/ijc.70643","url":null,"abstract":"<div>\u0000 \u0000 <p>National cancer control plans (NCCPs) are essential instruments for guiding comprehensive and coordinated responses to the growing global cancer burden. This special report summarises key insights from the second Cancer Planners Forum, convened by the Union for International Cancer Control (UICC) in May 2026 in collaboration with the World Health Organization, the International Agency for Research on Cancer, the International Atomic Energy Agency and the International Cancer Control Partnership (ICCP). The Forum brought together 120 participants from 54 countries, representing diverse regions, income settings and stages of cancer planning. Discussions highlighted a growing recognition of NCCPs as strategic investments in health systems rather than solely technical planning documents. Key themes included the critical role of robust data systems for priority setting and monitoring, the importance of inclusive stakeholder engagement in strengthening plan ownership and accountability and persistent challenges related to financing and implementation, particularly in low- and middle-income countries. Governance mechanisms, including accountability structures and cross-sectoral coordination, were identified as central to successful implementation. Despite increasing global momentum and a rise in the number of publicly available NCCPs, significant gaps remain between plan development and effective implementation. The Forum underscored the need for strengthened technical assistance in developing resource mobilisation strategies, as well as stronger data systems linked to decision making and continued international collaboration to support countries in translating plans into measurable health outcomes. These findings reinforce the importance of positioning NCCPs as long-term investments in national development and health system strengthening.</p>\u0000 </div>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":"159 11","pages":"2653-2656"},"PeriodicalIF":4.9,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148403012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeted Therapy and Oral Chemotherapy as Maintenance Treatment in Pediatric Very-High-Risk and High-Risk Rhabdomyosarcoma: A Retrospective Study of Efficacy and Safety","authors":"Lei Mao,&nbsp;Yumiao Mai,&nbsp;Suying Lu,&nbsp;Feifei Sun,&nbsp;Juan Wang,&nbsp;Jia Zhu,&nbsp;Junting Huang,&nbsp;Mengjia Song,&nbsp;Yu Zhang,&nbsp;Zijun Zhen,&nbsp;Yanpeng Wu,&nbsp;Xiheng Lin,&nbsp;Cuiping Meng,&nbsp;Yizhuo Zhang,&nbsp;Yi Que","doi":"10.1002/ijc.70624","DOIUrl":"10.1002/ijc.70624","url":null,"abstract":"<div>\u0000 \u0000 <p>Maintenance therapy (MT) and targeted drugs have improved the survival of patients with high-risk rhabdomyosarcoma (RMS) in clinical trials. However, there are limited data concerning targeted drugs and oral chemotherapy for MT in pediatric patients with very-high-risk (VHR) and high-risk (HR) RMS. Here, we evaluated the safety and effectiveness of these regimens and aimed to identify circulating tumor DNA (ct-DNA) markers associated with prognosis. We retrospectively retrieved data for 102 pediatric patients with VHR or HR RMS who underwent MT at Sun Yat-sen University Cancer Center from January 2011 to March 2025 involving targeted drugs plus oral chemotherapy (subgroup 1); targeted drugs (subgroup 2); and oral chemotherapy (subgroup 3). Ct-DNA markers were examined throughout treatment and at follow-up. Subgroups 1 and 2 comprised 14 and seven VHR RMS patients, respectively, and subgroup 3 consisted of 39 VHR and 42 HR RMS patients. With a median follow-up of 32 months, no significant differences among subgroups in duration of remission (<i>p</i> = 0.56) or 2-year event-free survival (<i>p</i> = 0.78) were observed. <i>PAX–FOXO1</i> fusion (<i>p</i> = 0.01), <i>CDK4</i> mutation (<i>p</i> = 0.02), and <i>TP53</i> mutation (<i>p</i> = 0.02) were independently associated with unfavorable duration of remission. No grade 3 or higher treatment-related adverse events were observed. MT with targeted drugs shows comparable efficacy in VHR and HR pediatric RMS patients, with manageable adverse reactions. Longitudinal ct-DNA testing could guide treatment decision-making and prognostic stratification for these patients.</p>\u0000 </div>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":"159 11","pages":"2778-2790"},"PeriodicalIF":4.9,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148337022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systemic Inflammation Mediates the Association Between Plasma Epstein-Barr Virus DNA and Mortality in Metastatic Nasopharyngeal Carcinoma.","authors":"Qin Liu, Zhi-Ming Zeng, Yu-Wen Kuang, Yu-Chen Hua, Chuan-Run Zhang, Meng-Wen Wang, Jie Gong, Jia-Yu Zhou, Ying Deng, Jia-Huan Lu, Shu-Shu Han, Xiang Guo, Wei-Xiong Xia","doi":"10.1002/ijc.70772","DOIUrl":"https://doi.org/10.1002/ijc.70772","url":null,"abstract":"<p><p>We aimed to comprehensively evaluate the associations of a broad panel of systemic inflammation-related biomarkers with overall survival (OS) in metastatic nasopharyngeal carcinoma (mNPC) and to assess whether these signatures mediate the adverse impact of high EBV DNA burden on long-term outcomes. This study included 1847 patients with mNPC treated at Sun Yat-sen University Cancer Center between 2016 and 2022. Multivariable Cox proportional hazards models, restricted cubic spline (RCS) models, and time-dependent receiver operating characteristic (ROC) curve analyses were used to evaluate associations of inflammation-related indices with OS. Exploratory mediation analyses quantified the extent to which biomarkers partially mediated the association between plasma EBV DNA burden and mortality risk. Mean follow-up was 45.4 months; 713 (38.6%) deaths occurred. Plasma EBV DNA showed stable discrimination (AUCs of 0.63, 0.62, and 0.61 for 1-, 3-, and 5-year OS). After full adjustment, CALLY and LCR were protective, whereas CAR, NAR, SIRI, IBI, MLR, NC, PC, GPS, mGPS, and LCS were adverse. CAR, CALLY, LCR, IBI, and NC showed the highest discrimination (1-year AUCs, 0.65-0.66). Mediation analyses indicated that MLR, SIRI, CALLY, and NC accounted for 7.6%-9.6% of the EBV DNA load-mortality association. Elevated pretreatment EBV DNA was associated with a coordinated systemic inflammatory profile and worse OS in mNPC. Selected inflammatory markers statistically accounted for a modest proportion of the observed association between EBV DNA burden and mortality. Integrating EBV DNA with inflammatory profiles may improve risk stratification and guide intensified surveillance, earlier assessment, and risk-adapted therapy.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149101676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Helicobacter pylori Infection and the Risk of Biliary Tract and Pancreatic Cancers: Subsite-Specific Associations in a Japanese Population","authors":"Sayaka Yamamoto,&nbsp;Yuriko N. Koyanagi,&nbsp;Isao Oze,&nbsp;Yuji Iwashita,&nbsp;Yumiko Kasugai,&nbsp;Takahiro Otani,&nbsp;Nobumasa Mizuno,&nbsp;Seiji Natsume,&nbsp;Kazuo Hara,&nbsp;Tetsuya Abe,&nbsp;Yoshiaki Usui,&nbsp;Yukihide Momozawa,&nbsp;Issei Imoto,&nbsp;Hidemi Ito,&nbsp;Keitaro Matsuo","doi":"10.1002/ijc.70652","DOIUrl":"10.1002/ijc.70652","url":null,"abstract":"<div>\u0000 \u0000 <p>Although \u0000 <i>Helicobacter pylori</i>\u0000 (\u0000 <i>H. pylori</i>\u0000 ) infection, a well-established risk factor for gastric cancer, has been implicated as causative in biliary tract cancer (BTC) and pancreatic cancer (PC), the evidence remains inconclusive. Moreover, while germline pathogenic variants may modify the association between \u0000 <i>H. pylori</i>\u0000 infection and gastric cancer risk, their roles in BTC and PC are unclear. We examined these associations while accounting for genetic susceptibility and lifestyle factors. Two case–control studies were conducted, including 116 BTC cases, 417 PC cases, and 3086 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression adjusted for age, sex, study version, carrier status of pathogenic variants, smoking, and alcohol consumption. \u0000 <i>H. pylori</i>\u0000 infection was defined by antibody seropositivity, pepsinogen-based atrophic gastritis (AG), and their combination. Subsite-specific analyses were also performed. No significant association was observed between \u0000 <i>H. pylori</i>\u0000 infection and BTC risk. However, higher \u0000 <i>H. pylori</i>\u0000 antibody titers (per 10 U/mL increase) were positively associated with overall PC risk (OR 1.04, 95% CI: 1.01–1.07). In subsite analyses, AG without detectable antibodies was positively associated with pancreatic head cancer risk (OR 3.04, 95% CI: 1.23–7.54), whereas \u0000 <i>H. pylori</i>\u0000 seropositivity was positively associated with pancreatic body cancer risk (OR 1.75, 95% CI: 1.10–2.77). No interaction between \u0000 <i>H. pylori</i>\u0000 infection and pathogenic variants, smoking, or alcohol consumption was observed for either cancer. These findings suggest that \u0000 <i>H. pylori</i>\u0000 infection may be associated with pancreatic cancer risk in specific anatomical regions, with limited evidence for modification by genetic or lifestyle factors.</p>\u0000 </div>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":"159 11","pages":"2720-2735"},"PeriodicalIF":4.9,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148443543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of Healthcare Utilization Before Diagnosis Between Non-Advanced and Advanced Lung Cancer Patients: A Study Among 72,851 Cases in Germany","authors":"Josephine Küsel-Kanbach,&nbsp;Oliver Riedel,&nbsp;Ulrike Haug","doi":"10.1002/ijc.70682","DOIUrl":"10.1002/ijc.70682","url":null,"abstract":"<p>There is no study from Germany on the association between stage of lung cancer (LC) and patient characteristics. We aimed to compare advanced versus non-advanced LC cases regarding indicators of healthcare utilization. Using claims data covering 20% of the German population, we included LC patients diagnosed between 2013 and 2019. Stratified by stage (advanced vs. non-advanced), we assessed comorbidities, hospitalizations, outpatient physician contacts and utilization of preventive measures before LC diagnosis. Among 72,851 included LC patients, 29% (females) and 28% (males) were classified as non-advanced. For all comorbidities considered and for most other indicators, an inverse association with stage was observed. For example, in males with non-advanced versus advanced LC, the proportions with chronic obstructive pulmonary disease were 37% and 27% (females: 38% vs. 29%), and the proportions with ≥ 1 hospitalization in the 3 years prior LC diagnosis were 70% versus 58% (females: 69% vs. 55%). In conclusion, LC patients with more frequent healthcare utilization before LC diagnosis were more likely to be diagnosed at a non-advanced stage. Regarding future LC screening, the findings underline the importance of developing implementation strategies that ensure the reach of those who use health services less frequently, as these individuals are at higher risk of being diagnosed at an advanced stage if they develop LC.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":"159 11","pages":"2657-2664"},"PeriodicalIF":4.9,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ijc.70682","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148823803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatial Transcriptomic Profiling Reveals a Fibroblast-Associated Extracellular Matrix Niche in KRAS G12C-Mutant Lung Adenocarcinoma Primary Tumors From Patients With Metastasis.","authors":"Honggang Cao, Longyan Chen, Qi Wang, Shoupeng Shao","doi":"10.1002/ijc.70764","DOIUrl":"https://doi.org/10.1002/ijc.70764","url":null,"abstract":"<p><p>KRAS G12C is the most common KRAS alteration in lung adenocarcinoma and has emerging therapeutic relevance. However, the spatial programs within primary tumors that accompany metastasis remain poorly understood. We profiled primary tumor tissues from four patients with KRAS G12C-mutant lung adenocarcinoma, including two without metastasis and two with metastasis, using 10× Visium spatial transcriptomics. Spatial clustering, differential expression, functional enrichment, and Robust Cell Type Decomposition (RCTD)-based deconvolution using a published non-small cell lung cancer (NSCLC) single-cell atlas were performed. Candidate pathway relevance was assessed in The Cancer Genome Atlas (TCGA) KRAS G12C-mutant lung adenocarcinoma cases, and functional validation was performed using fibroblast-tumor co-culture assays. Spatial analysis identified 18 transcriptionally distinct clusters across 14,351 spots. In this exploratory cohort, metastatic-primary tumors showed descriptive expansion of selected spatial domains and reduction of epithelial/alveolar-associated regions. Deconvolution suggested reduced AT2-like signals and increased fibroblast-associated features in metastatic-primary tumors. Stepwise filtering of group-level, compartment-level and cluster-supported genes identified a fibroblast-associated extracellular matrix remodeling module consisting of COL1A1, COL1A2, COL3A1, SPARC, POSTN, and VCAN. In TCGA KRAS G12C-mutant lung cancer, VCAN expression correlated with collagen formation, extracellular matrix degradation, and EMT marker signatures. In vitro, VCAN-overexpressing MRC-5 fibroblasts enhanced H358 invasion without markedly altering short-term proliferation. These exploratory analyses identified a fibroblast-associated extracellular matrix remodeling niche associated with metastatic status in KRAS G12C-mutant lung adenocarcinoma. These preliminary findings support further investigation of primary-tumor stromal reprogramming in larger spatially profiled cohorts and mechanistic models.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149101537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}