Cancer Research and Treatment最新文献

{"title":"Deep Learning-Based Multimodal Prediction of NAC Response in LARC by Integrating MRI and Proteomics.","authors":"Yan Li, Jiaxuan Ding, Fenqi Du, Zhongxing Wang, Zeyuan Liu, Yanlong Liu, Yang Zhou, Qiuju Zhang","doi":"10.4143/crt.2025.707","DOIUrl":"https://doi.org/10.4143/crt.2025.707","url":null,"abstract":"<p><strong>Purpose: </strong>Locally advanced rectal cancer (LARC) exhibits significant heterogeneity in response to neoadjuvant chemotherapy (NAC), with poor responders facing delayed treatment and unnecessary toxicity. Although MRI provides spatial pathophysiological information and proteomics reveals molecular mechanisms, current single-modal approaches cannot integrate these complementary perspectives, resulting in limited predictive accuracy and biological insight.</p><p><strong>Materials and methods: </strong>This retrospective study developed a multimodal deep learning framework using a cohort of 274 LARC patients treated with NAC (2012-2021). Graph neural networks analyzed proteomic profiles from FFPE tissues, incorporating KEGG/GO pathways and PPI networks, while a spatially enhanced 3D ResNet152 processed T2WI. A LightGBM classifier integrated both modalities with clinical features using zero-imputation for missing data. Model performance was assessed through AUC-ROC, decision curve analysis, and interpretability techniques (SHAP and Grad-CAM).</p><p><strong>Results: </strong>The integrated model achieved superior NAC response prediction (test AUC 0.828, sensitivity 0.875, specificity 0.750), significantly outperforming single-modal approaches (MRI ΔAUC +0.109; proteomics ΔAUC +0.125). SHAP analysis revealed MRI-derived features contributed 57.7% of predictive power, primarily through peritumoral stromal heterogeneity quantification. Proteomics identified 10 key chemoresistance proteins, including CYBA, GUSB, ATP6AP2, DYNC1I2, DAD1, ACOX1, COPG1, FBP1, DHRS7, and SSR3. Decision curve analysis confirmed clinical utility across threshold probabilities (0-0.75).</p><p><strong>Conclusion: </strong>Our study established a novel MRI-proteomics integration framework for NAC response prediction, with MRI defining spatial resistance patterns and proteomics deciphering molecular drivers, enabling early organ preservation strategies. The zero-imputation design ensured deplorability in diverse clinical settings.</p>","PeriodicalId":49094,"journal":{"name":"Cancer Research and Treatment","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145001788","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":"Long-Term Prognostic Value and Analytical Parameters of the Next-Generation Sequencing-Based Multigene Assay in Hormone Receptor-Positive, HER2-Negative Breast Cancer.","authors":"Hyunji Kim, Jiwon Koh, Hyunwoo Lee, Gyungyub Gong, Sujin Oh, Jiyoung Lee, Ho Eun Chang, Yunhee Choi, Eunhye Kang, Jai Min Ryu, Dong Seung Shin, Sae Byul Lee, Hee Jin Lee, Hong-Kyu Kim, Hee-Chul Shin, Wonshik Han, Han-Byoel Lee, Kyoung Un Park","doi":"10.4143/crt.2025.701","DOIUrl":"https://doi.org/10.4143/crt.2025.701","url":null,"abstract":"<p><strong>Purpose: </strong>In hormone receptor (HR)-positive, HER2-negative early breast cancer, gene expression testing facilitates treatment decisions. A next-generation sequencing (NGS)-based assay was developed to address test decentralization and underrepresentation of younger/premenopausal patients. We aimed to validate the long-term prognostic value of the NGS-based assay and analyze its quality control (QC) parameters.</p><p><strong>Materials and methods: </strong>We analyzed samples from 265 patients with breast cancer with at least 10 years of follow-up. We evaluated the long-term prognostic ability of the NGS-based assay according to the risk groups for distant recurrence, as determined by the Decision Index (DI), and the performance of the QC parameters used for the experimental process.</p><p><strong>Results: </strong>Among 265 participants, 60.4% were ≤50 years old, and 39 (14.7%) experienced distant recurrence within 10 years. In the DI-stratified low- and high-risk groups (n=186; 70.2% and n=79; 29.8%), 10-year distant metastasis-free survival rates were 96.1% (95% CI 92.1-98.1) and 79.3% (95% CI 68.4-86.8), respectively. In patients aged ≤50 years, the high-risk group had a hazard ratio of 5.89 (95% CI 2.84-12.20). Analyses including 106 samples that failed the stringent QC criteria showed inferior prognostic value, wherein DV200 and cDNA concentrations were the most crucial parameters.</p><p><strong>Conclusion: </strong>We validated the prognostic ability of an NGS-based assay to stratify HR-positive/HER2-negative breast cancers and predict the risk of distant recurrence, and confirmed the requirement for stringent QC criteria to ensure its prognostic ability.</p>","PeriodicalId":49094,"journal":{"name":"Cancer Research and Treatment","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145001749","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":"Impact of Pre-admission Central Nervous System Medication Use on Delirium in Hospitalized Patients with Advanced Cancer: A Multicenter, Prospective, Observational Study in Korea.","authors":"Min Jung Geum, Shin Hye Yoo, Si Won Lee, Moonki Hong, Eun Hee Jung, Yu Jung Kim, Beodeul Kang","doi":"10.4143/crt.2025.460","DOIUrl":"https://doi.org/10.4143/crt.2025.460","url":null,"abstract":"<p><strong>Purpose: </strong>This study investigated the impact of pre-admission central nervous system (CNS) medication use on delirium incidence, duration, and survival in hospitalized patients with advanced cancer.</p><p><strong>Materials and methods: </strong>In this multicenter prospective study across four tertiary hospitals in South Korea, adults with advanced cancer were enrolled and categorized based on their use of CNS medications within 90 days preceding admission. Associations between pre-admission CNS medication use and outcomes (delirium incidence, delirium duration, and overall survival) were assessed using multivariable regression and Cox proportional hazards models.</p><p><strong>Results: </strong>Of the 190 patients enrolled, 140 had used CNS medications prior to admission. Delirium occurred in 22.1% of the patients with CNS medication use versus 14.0% of those without (adjusted odds ratio [aOR]: 2.53, 95% confidence interval [CI]: 0.95-7.60; not significant). Opioid (aOR: 2.48, 95% CI: 1.01-6.61) and antidepressant (aOR: 5.58, 95% CI: 1.22-27.35) use were significantly associated with increased delirium risk. Use of three or more CNS medication classes was associated with a markedly high risk (aOR: 11.15, 95% CI: 2.13-64.17). Delirium duration did not differ significantly between groups. Patients with pre-admission CNS medication exposure exhibited shorter overall survival (adjusted hazard ratio [aHR]: 1.45, 95% CI: 1.01-2.09). Prior opioid use was also associated with increased mortality (aHR: 1.45, 95% CI: 1.03-2.05).</p><p><strong>Conclusion: </strong>Pre-admission exposure to CNS medication, particularly opioids and antidepressants, was associated with an increased risk of delirium in patients with advanced cancer. A thorough medication history review upon admission is crucial to identifying high-risk patients and implementing early preventive interventions.</p>","PeriodicalId":49094,"journal":{"name":"Cancer Research and Treatment","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144976004","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":"Concept of Depth of Invasion can Improve Staging Performance in Patients with Resected Distal Cholangiocarcinoma: Validation of the American Joint Committee on Cancer Staging System.","authors":"Won-Gun Yun, Yoon Soo Chae, Youngmin Han, Young Jae Cho, Hye-Sol Jung, Wooil Kwon, Joon Seong Park, Haeryoung Kim, Kyoung Bun Lee, Jin-Young Jang","doi":"10.4143/crt.2025.406","DOIUrl":"https://doi.org/10.4143/crt.2025.406","url":null,"abstract":"<p><strong>Purpose: </strong>The American Joint Committee on Cancer (AJCC) staging system for distal cholangiocarcinoma (dCC) has evolved significantly. However, the prognostic correlation of the newly proposed staging system remains unclear. Therefore, we aimed to compare the staging performance between AJCC 7th and 8th editions for dCC.</p><p><strong>Materials and methods: </strong>We reviewed pathological slides of consecutive patients who underwent resection for dCC between 2000 and 2022. According to the AJCC 8th edition, depth of invasion was defined as the distance from the basement membrane of adjacent normal or dysplastic epithelium to the deepest tumor invasion. We analyzed changes in the T category from the AJCC 7th to 8th edition and assessed overall survival and recurrence based on these staging systems.</p><p><strong>Results: </strong>Among 428 patients, application of the 8th edition resulted in down-staging of 272 (63.6%) patients and up-staging of only 13 (3.0%). Lymph node metastases were identified in 150 (35.1%) patients, with 29 (6.8%) having ≥ 4 metastatic nodes. The C-indices for overall survival and recurrence are 0.557 and 0.569 for the T stage of the AJCC 7th edition, and 0.606 and 0.631 for that of the AJCC 8th edition (95% confidence interval for delta: 0.005-0.092 for survival, 0.023-0.100 for recurrence). Additionally, the T category of the 8th edition correlated more strongly with lymph node metastases than that of the 7th edition.</p><p><strong>Conclusion: </strong>In dCC, the T category of the AJCC 8th edition demonstrates improved prognostic correlation and better alignment with lymph node metastases compared to that of the 7th edition.</p>","PeriodicalId":49094,"journal":{"name":"Cancer Research and Treatment","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144975950","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":"Genomic Insights into Innate Resistance in Early-Stage EGFR-Mutant Non-Small Cell Lung Cancer: A Comprehensive Analysis of Next-Generation Sequencing Data.","authors":"Hayoung Seong, Soo Han Kim, Mi-Hyun Kim, Ahrong Kim, Ju Sun Song, Jung Seop Eom","doi":"10.4143/crt.2025.114","DOIUrl":"https://doi.org/10.4143/crt.2025.114","url":null,"abstract":"<p><strong>Purpose: </strong>Comprehensive genomic profiling of early-stage non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations remains limited. This study aimed to investigate genomic profiles of early- and advanced-stage EGFR-mutant NSCLC and identify potential innate resistance mechanisms to EGFR-tyrosine kinase inhibitors (TKIs) using targeted next-generation sequencing (NGS).</p><p><strong>Materials and methods: </strong>This retrospective observational study analyzed genomic profiles of patients with early-stage (IA-IIIA) and advanced-stage (IIIB-IV) EGFR-mutant NSCLC from the Lung Cancer NGS registry. Targeted NGS was performed to assess concurrent genetic alterations (GAs), tumor mutational burden (TMB), and variant allele frequency (VAF) of EGFR mutations.</p><p><strong>Results: </strong>Overall, 160 patients (100 early-stage and 60 advanced-stage) were analyzed. The proportion of patients with concurrent GAs was not significantly different between stages (82.0% vs. 91.7%, p=0.092). Median TMB was 3.8 mutations/Mb in both stages, with no significant difference (p=0.206). However, the median VAF of EGFR mutations was significantly lower in early-stage compared to that in advanced-stage (19.3% vs. 29.6%, p=0.002). While TMB remained unchanged with disease progression (P = 0.192), VAF of EGFR mutations increased significantly (p<0.001). Moreover, the frequencies of concurrent single nucleotide variants and copy number variants were significantly lower in early-stage NSCLC.</p><p><strong>Conclusion: </strong>Genomic heterogeneity in EGFR-mutant NSCLC arises early in tumorigenesis. The comparable TMB and lower VAF of EGFR mutations in early-stage disease suggest that innate resistance to EGFR-TKIs may be driven by concurrent GAs, supporting the consideration of combination therapies even in early-stage EGFR-mutant NSCLC.</p>","PeriodicalId":49094,"journal":{"name":"Cancer Research and Treatment","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144975973","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":"Preferential Sensitivity of the EGFR L858M/L861R Mutation to Second-Generation EGFR Tyrosine Kinase Inhibitors in Non-small Cell Lung Cancer.","authors":"Chaelin Lee, Sheehyun Kim, Soyeon Kim, Taekeun Park, Miso Kim, Bhumsuk Keam, Tae Min Kim, Dong-Wan Kim, Jeonghwan Youk","doi":"10.4143/crt.2025.279","DOIUrl":"https://doi.org/10.4143/crt.2025.279","url":null,"abstract":"<p><strong>Purpose: </strong>Non-small cell lung cancer (NSCLC) frequently harbors targetable EGFR mutations. However, rare variants such as EGFR L858M or L861R remain poorly characterized. This study aimed to elucidate the oncogenic potential and EGFR tyrosine kinase inhibitors (TKIs) sensitivity of the EGFR L858M/L861R mutation to inform personalized treatment strategies.</p><p><strong>Materials and methods: </strong>Tumor samples from a NSCLC patient were analyzed using targeted panel sequencing and confirmed with the FoundationOne Liquid CDx assay. EGFR-mutant constructs, including L858M, L858R, L861R, L861Q, L858M/L861R, and L858R/L861Q, were generated and transduced into various cell lines. Cell viability, immunoblot, and soft agar colony formation assays were conducted to assess the oncogenicity and drug sensitivity, while computational protein modeling and docking simulations evaluated the drug-binding affinities of EGFR TKIs.</p><p><strong>Results: </strong>Ba/F3 cells expressing the EGFR L858M/L861R mutation exhibited robust IL-3-independent proliferation accompanied by markedly increased EGFR phosphorylation, while NIH-3T3 cells showed anchorage-independent colony formation. Compared to other mutations, cells expressing EGFR L858M/L861R mutation were less sensitive to first-generation EGFR TKIs (gefitinib, erlotinib) and third-generation EGFR TKIs (osimertinib, lazertinib), whereas second-generation EGFR TKIs (afatinib, poziotinib) demonstrated potent inhibitory effects. Computational modeling revealed a narrower drug-binding efficiency of first-generation inhibitors.</p><p><strong>Conclusion: </strong>The EGFR L858M/L861R mutation drives strong oncogenic signaling and exhibits preferential sensitivity to second-generation EGFR TKIs. These findings underscore the importance of accurate molecular diagnosis for guiding effective, personalized therapeutic strategies in NSCLC.</p>","PeriodicalId":49094,"journal":{"name":"Cancer Research and Treatment","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144975986","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":"Nomograms Integrating Body Composition Metrics Predict Total Pathologic Complete Remission after Neoadjuvant Systemic Therapy for Breast Cancer.","authors":"Jingjing Ding, Yichun Gong, Jue Wang, Yuanyuan Wang, Hao Yao, Xingye Sheng, Mingyu Wang, Danni Shen, Junhan Li, Xiaoming Zha, Lu Xu","doi":"10.4143/crt.2025.456","DOIUrl":"https://doi.org/10.4143/crt.2025.456","url":null,"abstract":"<p><strong>Purpose: </strong>Neoadjuvant systemic therapy (NST) is a systemic treatment for locally advanced or initially unresectable breast cancer before surgery. Patients achieved total pathological complete response (tpCR) after NST exhibited significantly better overall prognosis than patients with non-pCR.</p><p><strong>Materials and methods: </strong>This study collected baseline indicators, body composition indicators and tpCR results of breast cancer patients at the First Affiliated Hospital of Nanjing Medical University. Patients were divided into training set and validation set in a ratio of 7:3. Univariate and multivariate logistic regression analyses were performed, and the probability of tpCR was predicted by constructing nomograms based on the results of the multivariate logistic regression analysis.</p><p><strong>Results: </strong>The study included 500 patients between 2014 and 2022 with breast cancer who underwent NST. The training set and validation set consist of 350 and 150 patients respectively. Patients with progesterone receptor-negative status (p < 0.001), HER2 receptor-positive status (p < 0.001), large body surface area (p=0.091), low skeletal muscle index (p=0.008), and high skeletal muscle density (p < 0.004) were more likely to achieve tpCR. Patients with American Joint Committee on Cancer (AJCC) T-stage 4 (p=0.126), AJCC N-stage 1 (p=0.026) were less likely to achieve tpCR.</p><p><strong>Conclusion: </strong>Existing tpCR prediction models mostly focus on tumor biological characteristics and ignore the effect of body compositions. This study constructed a nomogram to predict tpCR in patients with breast cancer undergoing NST based on baseline and body composition indicators. This nomogram can help assess efficacy and optimize treatment strategies, thus improving the overall prognosis of patients.</p>","PeriodicalId":49094,"journal":{"name":"Cancer Research and Treatment","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144976036","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":"Clinicopathological Significance of Tumor-Infiltrating T Lymphocytes and Macrophages in Primary Large B-Cell Lymphoma of Immune-Privileged Sites.","authors":"Jinseong Kim, Deokhoon Kim, Hyungwoo Cho, Dok-Hyun Yoon, Heounjeong Go","doi":"10.4143/crt.2025.641","DOIUrl":"https://doi.org/10.4143/crt.2025.641","url":null,"abstract":"<p><strong>Purpose: </strong>Immune-privileged large B-cell lymphomas (IP-LBCLs), comprising primary central nervous system lymphoma (PCNS-LBCL), primary vitreoretinal lymphoma (PVR-LBCL), and primary testicular lymphoma (PT-LBCL), originate in sites with limited immune surveillance. Owing to their rarity, the prognostic implications of the tumor microenvironment in IP-LBCLs remain unclear, warranting further investigation.</p><p><strong>Materials and methods: </strong>This study evaluated 109 IP-LBCL cases (PCNS-LBCL, n=87; PT-LBCL, n=22; six cases of PVR-LBCL excluded) using multiplex immunohistochemistry on tissue microarrays, along with clinicopathological analysis. Immune cell infiltration, tumor major histocompatibility complex (MHC) class I, and programmed death ligand-1 (PD-L1) expression, and their associations with clinical outcomes, were evaluated.</p><p><strong>Results: </strong>PT-LBCL demonstrated higher infiltration of all tumor-infiltrating T lymphocyte (TIL) subsets than PCNS-LBCL (all p<0.05). Elevated CD4⁺ and CD8⁺ T-cell levels correlated with prolonged progression-free survival (PFS) (both p<0.05). M1 macrophage infiltration was associated with improved PFS (p=0.005) and independently predicted a favorable prognosis (hazard ratio = 0.49, p=0.041). Loss of MHC class I expression was more frequent in PT-LBCL than in PCNS-LBCL (77.3% vs. 9.2%; p<0.001). TIL infiltration predicted improved PFS only when the tumor MHC class I was preserved. Moreover, programmed death protein-1 (PD-1)⁺ TILs and tumor PD-L1 expression were associated with prognosis in conjunction with various clinicopathological variables.</p><p><strong>Conclusion: </strong>These findings highlight the favorable prognostic role of TILs and M1 macrophages, and underscore the complex immune-tumor interactions in IP-LBCLs, despite their origin in immune-privileged sites.</p>","PeriodicalId":49094,"journal":{"name":"Cancer Research and Treatment","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144849446","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":"Clinicopathological Factors Influencing PD-L1 Expression and The Effect of Immune Checkpoint Inhibitors on Survival Outcomes in Patients with Gastric Cancer Depending on Sex in a Tertiary Hospital in South Korea.","authors":"Jeong Hwan Lee, Nayoung Kim, Ji-Hyun Kim, Hyeon Jeong Oh, Yeejin Kim, Yonghoon Choi, Hyemin Jo, Ho-Kyoung Lee, Jinju Choi, Yu Kyung Jun, Hyuk Yoon, Cheol Min Shin, Young Soo Park, Dong Ho Lee, Hye Seung Lee, So Hyun Kang, Young Suk Park, Sang-Hoon Ahn, Yun-Suhk Suh, Do Joong Park, Hyung Ho Kim, Ji-Won Kim, Jin Won Kim, Keun-Wook Lee, Won Chang, Yoon Jin Lee, Kyoung Ho Lee, Young Hoon Kim, Soyeon Ahn","doi":"10.4143/crt.2025.126","DOIUrl":"https://doi.org/10.4143/crt.2025.126","url":null,"abstract":"<p><strong>Purpose: </strong>Programmed cell death ligand-1 (PD-L1) negatively regulates T-cell activation, and exhibits sex-based differences in expression and immune responses. This study investigated sex-related differences in clinicopathological factors influencing PD-L1 expression and the effect of immune checkpoint inhibitors (ICIs) on survival in gastric cancer (GC) patients in South Korea.</p><p><strong>Materials and methods: </strong>We analyzed a prospective cohort of 468 GC patients who underwent PD-L1 immunohistochemistry. Age, tumor characteristics, molecular features, and survival outcomes were compared by sex. Multivariate analyses, including Cox proportional hazards modeling with an interaction term for sex, were performed.</p><p><strong>Results: </strong>Among 468 patients, 280 (59.8%) were PD-L1 positive. In the overall cohort, PD-L1 positivity was significantly associated with Epstein-BarrVirus (EBV) infection (odd ratio [OR]=7.46, p<0.001), antral location of GC (OR=1.84, p=0.027), and macrosatellite instability-High (MSI-H) (OR=5.04, p=0.027). Diffuse-type histology was inversely associated (OR=0.22, p=0.041). In males, EBV (OR=36.27) and antral location (OR=2.38) were significant. In females, only MSI-H was significant (OR=11.63). ICI-containing therapy significantly improved survival in males (p=0.012) but not in females (p=0.415). Cox regression showed a survival benefit from ICIs (HR=0.70, p=0.080), with a borderline-significant interaction by sex (p=0.073).</p><p><strong>Conclusion: </strong>PD-L1 expression and therapeutic efficacy of ICIs differ by sex in GC. EBV infection and antral tumor location were independent factors in males, while MSI-H status was significant in females. These findings highlights the importance of sex-based immunobiology in tailoring GC treatment strategies.</p>","PeriodicalId":49094,"journal":{"name":"Cancer Research and Treatment","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144849445","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":"Efficacy and Safety of Lenvatinib Plus Everolimus in Metastatic Renal Cell Carcinoma After Immune Checkpoint and VEGFR Tyrosine Kinase Inhibitors Treatment.","authors":"So Heun Lee, Inkeun Park, Shinkyo Yoon, Jae Lyun Lee","doi":"10.4143/crt.2025.628","DOIUrl":"https://doi.org/10.4143/crt.2025.628","url":null,"abstract":"<p><strong>Purpose: </strong>Real-world data on the efficacy and safety of lenvatinib plus everolimus in metastatic renal cell carcinoma (RCC) after failure of immune checkpoint inhibitors (ICIs) and/or VEGFR-targeted tyrosine kinase inhibitors (TKIs) remain limited.</p><p><strong>Materials and methods: </strong>This single-center retrospective study included patients with metastatic RCC treated with lenvatinib plus everolimus as second-line or later therapy at Asan Medical Center, Korea, between September 2017 and June 2024. Data on dose adjustments, treatment response, survival, and adverse events were collected from electronic medical records. Primary endpoints were objective response rate (ORR) and progression-free survival (PFS); secondary endpoints included overall survival (OS), time to progression (TTP), adverse events, and prognostic factors.</p><p><strong>Results: </strong>A total of 83 patients were included, predominantly with clear cell histology (90.4%). The median number of prior therapies was four (range, 1-7), with 80.7% receiving the combination as fourth-line or beyond. All had prior anti-angiogenic TKI exposure, 86.7% had received ICIs, and 37.3% had prior mTOR inhibitor therapy. The ORR was 40.0%, with disease control at 81.3%. Median PFS and OS were 5.4 months (95% CI, 4.4-6.8) and 8.5 months (95% CI, 6.3-12.1), respectively. Efficacy was consistent across key subgroups. During the treatment, lenvatinib dose reductions were required in 55.4% of patients, and 26.5% experienced treatment interruptions. Grade ≥3 proteinuria occurred in 22.9%.</p><p><strong>Conclusion: </strong>Lenvatinib plus everolimus demonstrated promising efficacy in heavily pretreated patients with metastatic RCC, including those previously exposed to VEGFR-targeted TKIs and/or ICIs. Further studies are warranted to optimize treatment strategies in this patient population.</p>","PeriodicalId":49094,"journal":{"name":"Cancer Research and Treatment","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144849448","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}