Cancer Res Treat [JOURNAL]
Sun
200 papers
Response to Neoadjuvant Systemic Therapy May Serve as an Indicator for Omitting Post-BCS Radiation Therapy in Women with Early-Stage Breast Cancer.
Li C, Wang Y, Liu M … +5 more , Sun S, Jia Y, Qu J, Zhang S, Du C
Cancer Res Treat · 2025 Sep · PMID 40935677 · Publisher ↗
PURPOSE: To avoid unnecessary toxicities and optimize the allocation of healthcare resources, it is crucial to adequately select patients with extremely low recurrence risk to downgrade or eliminate radiation therapy. MA...
PURPOSE: To avoid unnecessary toxicities and optimize the allocation of healthcare resources, it is crucial to adequately select patients with extremely low recurrence risk to downgrade or eliminate radiation therapy. MATERIALS AND METHODS: From the SEER database, clinical data of 7,291 female patients with early-stage breast cancer who underwent neoadjuvant systemic therapy (NST) and breast-conserving surgery (BCS) were collected for this study. The patients were stratified by their response to NST, and the long-term survival, and risk of recurrence were assessed using Cox regression analysis and Fine-gray competing risk models for those with and without post-BCS RT, respectively. RESULTS: Our results showed that female with early-stage breast cancer who achieved complete response (CR) to NST, omitting post-BCS RT achieved the same OS and DFS as those who received the post-BCS RT, and the omission did not increase the risk of recurrence or BCSD. For patients who did not achieve CR to NST, five clinical indicators (including age, N stage, grade, response to NST, and molecular subtype) were employed to construct a nomogram for clinical prediction of the risk of recurrence. The validated results affirmed our model's ability to accurately discriminate high- and low-risk patients and its promising clinical application value. CONCLUSION: Post-BCS RT can be omitted for women with early-stage breast cancer who achieved CR to NST. For those who failed to achieve CR to NST, a nomogram was constructed for clinicians to decide whether to omit post-BCS RT or not based on the individualized assessment.
Risk-Stratified Management of ADC drug-Related Neutropenia: Integrating Clinical Trial Meta-Summary and Existing Guideline Principles.
Chen Z, Zhao K, Jiang J … +1 more , Yang L
Cancer Res Treat · 2025 Sep · PMID 40935676 · Publisher ↗
PURPOSE: Anti-tumor drugs have developed rapidly in recent years. Antibody-drug conjugates (ADCs), as a novel class of targeted biologics, demonstrate significant survival benefits but inevitably cause treatment-related...
PURPOSE: Anti-tumor drugs have developed rapidly in recent years. Antibody-drug conjugates (ADCs), as a novel class of targeted biologics, demonstrate significant survival benefits but inevitably cause treatment-related toxicities, with hematologic toxicity-particularly severe neutropenia (grade ≥3)-representing the most prevalent and clinically consequential adverse effect. Currently, no standardized ADC-specific neutropenia management guidelines exist, resulting in fragmented prevention strategies where clinical practice relies on extrapolation from chemotherapy protocols and reactive approaches (e.g., post-onset growth factor support). This study aims to address this gap by proposing a structured preventive framework for ADC-induced neutropenia. MATERIALS AND METHODS: We conducted a systematic meta-summary of neutropenia data from clinical trials involving ADCs. This evidence was integrated with established principles from chemotherapy-induced neutropenia guidelines and expert consensus. The analysis focused on drug-specific risk profiles, patient-related factors, and evidence-based interventional strategies. RESULTS: We developed a risk-adapted preventive strategy centered on a "planning for a rainy day" approach. The framework incorporates: (1) risk stratification based on the specific ADC drug and patient factors; (2) primary prophylaxis with long-acting granulocyte colony-stimulating factor (G-CSF) for high-risk patients; (3) secondary prevention strategies for subsequent treatment cycles; and (4) dynamic monitoring of absolute neutrophil counts (ANC) around days 5-7 post-infusion. CONCLUSION: Shifting from a reactive to a proactive, personalized prevention paradigm can potentially reduce the incidence of severe neutropenia, subsequent treatment interruptions, and infection-related mortality. This framework provides actionable guidance for standardizing ADC toxicity management and underscores the importance of prioritizing hematologic safety in future ADC development.
Genomic Profiling Identified a Mutational Signature Related to Female in Non-Smoking Lung Adenocarcinoma.
Zhuang J, Yang Y, Chen X … +4 more , Zheng G, Shen X, He F, Xie B
Cancer Res Treat · 2025 Sep · PMID 40935675 · Publisher ↗
PURPOSE: Our aim was to illustrate mutational characteristic in non-smoking lung adenocarcinoma (LUAD) and to explore its relationship with clinical factors. MATERIALS AND METHODS: We included 86 non-smokers with LUAD an...
PURPOSE: Our aim was to illustrate mutational characteristic in non-smoking lung adenocarcinoma (LUAD) and to explore its relationship with clinical factors. MATERIALS AND METHODS: We included 86 non-smokers with LUAD and downloaded the clinical information, whole exon sequencing (WES), and RNA sequencing (RNA-seq) data from cBioPortal and TCGA website. NMF algorithm, "SomaticSignatures", and "DeconstructSigs" were used to re-construct and infer new mutational signature. The similarity between COSMIC and re-constructed mutational signature was measured by cosine similarity. The enrichment status of signaling pathways was derived by GSEA. "pRRophetic" package was used to predict the sensitivity of adjuvant drug for cancer treatments. RESULTS: The most frequent driver genes in non-smoking LUAD were EGFR (59% in cBioPortal cohort, 68% in Fujian non-smoking LUAD cohort). We identified three new mutation signatures of LUAD in non-smokers and identified S2 as the most enriched signature in these non-smokers with LUAD. In cBioPortal and Fujian non-smoking LUAD cohort, the proportion of S2 was higher in females (p<0.05) and patients with TMB (p<0.01). Similar results were observed in non-smoking TCGA-LUAD cohort (Pfemale=0.0013, PTMB<0.001). OXIDATIVE_PHOSPHORYLATION signaling pathway were most enriched in S2-enriched group (NES= 1.63). S2-enriched group had higher mutation rate of EGFR (p=0.003) and more drug sensitivity to metformin (p=0.035). CONCLUSION: We identified a new mutational signature (S2) which is most enriched in LUAD in non-smokers and related to female and low-TMB. S2 mutational signature may help revealed female-related mutagenesis mechanisms and develop strategies for therapeutic of never-smoker lung adenocarcinoma.
Cytokine-Primed MSCs Enhance Antitumor Immunity-Associated Gene Expression Without Promoting AML Cell Growth.
Lee NH, Kim B, Yoo KH
Cancer Res Treat · 2025 Sep · PMID 40935674 · Publisher ↗
PURPOSE: Mesenchymal stromal cells (MSCs), while regarded as promising immunomodulatory tools, have raised concerns in recent studies for their potential to promote tumor growth or facilitate immune evasion. These risks...
PURPOSE: Mesenchymal stromal cells (MSCs), while regarded as promising immunomodulatory tools, have raised concerns in recent studies for their potential to promote tumor growth or facilitate immune evasion. These risks are particularly relevant in hematologic malignancies, where MSCs have been used to mitigate graft-versus-host disease or support hematopoietic engraftment. This study aimed to evaluate the effects of cytokine-primed MSCs on acute myeloid leukemia (AML) cells, with a focus on both safety and immunomodulatory efficacy. MATERIALS AND METHODS: Wharton's jelly-derived MSCs were primed with interferon-gamma (IFN-γ), interleukin-6, lipopolysaccharide, and tumor necrosis factor-alpha, followed by co-cultured with AML cell lines. AML cell viability was measured by CCK-8 assay. RNA sequencing and qPCR were performed to assess gene expression profiles under each priming condition. RESULTS: Cytokine priming MSC did not result in significant changes in AML cell viability (p > 0.05), supporting the safety of this approach. Meanwhile, IFN-γ priming significantly upregulated genes involved in immune modulation and apoptosis, including IDO1, TNFSF10, ICAM1, and chemokines CXCL9, CXCL10, and CXCL11. CONCLUSION: Cytokine priming, particularly with IFN-γ, enhanced the immunomodulatory gene expression of MSCs without promoting AML cell proliferation. Although direct cytotoxic effects were not observed in co-culture experiments, the absence of increased leukemic cell growth under any priming condition supports the biological safety of this approach. These findings provide a strong foundation for further in vivo studies to assess the therapeutic applicability of primed MSCs in hematologic malignancies while ensuring oncologic safety.
H3K18la Facilitates TRA2A-Mediated Alternative Splicing of STIL, Suppressing Ferroptosis and Cisplatin Treatment Sensitivity in Ovarian Cancer.
Gao M, Wang S, Huang Z … +2 more , Wang T, Yu Y
Cancer Res Treat · 2025 Sep · PMID 40907573 · Publisher ↗
PURPOSE: Ovarian cancer (OC) is a common and highly lethal malignant tumor in women. Due to its hidden early symptoms, most patients are diagnosed at an advanced stage, and the tumor often develops resistance to chemothe...
PURPOSE: Ovarian cancer (OC) is a common and highly lethal malignant tumor in women. Due to its hidden early symptoms, most patients are diagnosed at an advanced stage, and the tumor often develops resistance to chemotherapy, making treatment challenging. Elucidating the mechanisms of OC development and identifying new therapeutic targets, are crucial for improving treatment outcomes. MATERIALS AND METHODS: We used bioinformatics analysis combined with qRT-PCR, WB, and IHC to study TRA2A expression and histone lactylation in OC samples. CCK8, clone formation, EdU, and Transwell experiments were used to assess OC cells proliferation. RT-PCR analyzed TRA2A-mediated alternative splicing. And the nude mouse xenograft model was constructed to validate TRA2A's molecular function in vivo. RESULTS: This study reveals a novel mechanism by which OC cells evade ferroptosis through the TRA2A-STIL signaling axis. Specifically, H3K18la is significantly enriched at the promoter region of the TRA2A gene, activating its transcription and upregulating expression. The upregulated TRA2A protein, functioning as a key splicing factor, specifically regulates alternative splicing (AS) of the STIL mRNA. This promotes expression of the STIL-L isoform, which inhibits ferroptosis in OC cells by modulating iron metabolism. Furthermore, targeted knockdown of TRA2A combined with cisplatin treatment significantly enhanced the therapeutic efficacy against OC. Consequently, targeting TRA2A-mediated AS represents a promising novel therapeutic target for OC. CONCLUSION: This study uncovers for the first time a novel mechanism by which OC cells evade ferroptosis via an H3K18la-modified TRA2A-STIL signaling axis, thereby establishing a promising new therapeutic target for OC treatment.
Deep Learning-Based Multimodal Prediction of NAC Response in LARC by Integrating MRI and Proteomics.
Li Y, Ding J, Du F … +5 more , Wang Z, Liu Z, Liu Y, Zhou Y, Zhang Q
Cancer Res Treat · 2025 Sep · PMID 40907572 · Publisher ↗
PURPOSE: 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 provid...
PURPOSE: 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. MATERIALS AND METHODS: 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). RESULTS: 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). CONCLUSION: 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.
Prognostic Role of SOCS1 Mutations in Diffuse Large B-Cell Lymphoma.
Zhang XY, Xing TY, Hua W … +12 more , Li Y, Kong YL, Pan BH, Zhang XY, Wu JZ, Shen HR, Yin H, Wang L, Li JY, Gao R, Liang JH, Xu W
Cancer Res Treat · 2025 Sep · PMID 40907571 · Publisher ↗
PURPOSE: This study investigates the prognostic impact of SOCS1 mutations in diffuse large B-cell lymphoma (DLBCL) and explores the underlying biological mechanisms, focusing on immune regulation and cellular metabolism....
PURPOSE: This study investigates the prognostic impact of SOCS1 mutations in diffuse large B-cell lymphoma (DLBCL) and explores the underlying biological mechanisms, focusing on immune regulation and cellular metabolism. MATERIALS AND METHODS: We included 2,590 DLBCL patients from 7 publicly databases (integrated cohort) and 202 additional DLBCL cases from our institution (JSPH cohort). Next-generation sequencing (NGS) was used to detect SOCS1 mutations in DLBCL patients. We analyzed the association between these mutations and overall survival (OS) and progression-free survival (PFS). Additionally, we examined how SOCS1 mutations might influence immune responses, cellular metabolism, and signaling pathways, particularly in the ST2 subtypes of DLBCL. RESULTS: In the integrated cohort, 15.1% of patients carried SOCS1 mutations, with 12.3% of these mutations located in the SOCS-BOX domain. SOCS1 mutations were found to be more frequent in the GCB and ST2 subtypes of DLBCL. In the integrated cohort, patients with SOCS1 mutations had significantly better OS (p=0.015) and PFS (p=0.007). Mutations located in the SOCS-BOX domain were associated with even better OS (p=0.015) and PFS (p=0.012). In the JSPH cohort, transcriptomic analyses indicated enhanced interferon signaling, immune activation, and downregulation of metabolic pathways in SOCS1-mut cases, especially within the ST2 subtype. These alterations may contribute to a more favorable tumor microenvironment and improved clinical outcomes. CONCLUSION: SOCS1 mutations, particularly those in the SOCS-BOX domain, are associated with improved prognosis in DLBCL. By promoting immune activation and inhibiting cellular metabolism, these mutations may not only serve as prognostic biomarkers but also provide insights into potential therapeutic avenues.
Long-Term Prognostic Value and Analytical Parameters of the Next-Generation Sequencing-Based Multigene Assay in Hormone Receptor-Positive, HER2-Negative Breast Cancer.
Kim H, Koh J, Lee H … +15 more , Gong G, Oh S, Lee J, Chang HE, Choi Y, Kang E, Ryu JM, Shin DS, Lee SB, Lee HJ, Kim HK, Shin HC, Han W, Lee HB, Park KU
Cancer Res Treat · 2025 Sep · PMID 40907570 · Publisher ↗
PURPOSE: 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 decentr...
PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.
Healthy Behaviors and All-cause Mortality among Korean Gastric Cancer Survivors.
Won D, Lee J, Cho S … +3 more , Baek JY, Lee HJ, Shin A
Cancer Res Treat · 2025 Sep · PMID 40907569 · Publisher ↗
PURPOSE: The incidence, prevalence and survival rates of gastric cancer are high, and the prognostic effects of healthy behaviors among survivors have not been well investigated. Therefore, We aimed to assess the effects...
PURPOSE: The incidence, prevalence and survival rates of gastric cancer are high, and the prognostic effects of healthy behaviors among survivors have not been well investigated. Therefore, We aimed to assess the effects of postdiagnosis healthy behaviors and behavior changes after gastric cancer diagnosis on all-cause mortality. MATERIALS AND METHODS: As a population-based retrospective cohort study, we used a cancer public library sample DB of gastric cancer patients between 2012 and 2019. Information from regular health check-up examinations were used to investigate their anthropometric measures, physical activities, alcohol consumption, and smoking status before and after cancer diagnosis. Hazard ratios (HRs) for all-cause deaths with 95% confidence intervals (CIs) were estimated via the Cox proportional hazards model. RESULTS: We analyzed 9,717 gastric cancer patients and 5,929 of those as a subgroup to assess the effects of behavior changes. Reduced mortality was shown among cancer patients who met the recommended criteria after the cancer diagnosis for physical activity (adjusted HR = 0.67 [95% CI=0.49-0.93], mean frequencies of moderate to vigorous physical activity per week: ≥5 days vs. 0 days) and smoking cessation (0.77 [0.61-0.97], smoking status: never-smokers vs. current smokers). Participants who reported enhancement in behaviors had significantly lower mortality than the others who reported no or limited changes in physical activity (0.73 [0.55-0.96]) and smoking status (0.56 [0.38-0.83]). CONCLUSION: The current study highlights the advantages of physical activity and smoking cessation in reducing mortality, and these benefits are even greater when patients improve their behavior after cancer diagnosis.
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.
Yun WG, Chae YS, Han Y … +7 more , Cho YJ, Jung HS, Kwon W, Park JS, Kim H, Lee KB, Jang JY
Cancer Res Treat · 2025 Aug · PMID 40878434 · Publisher ↗
PURPOSE: 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 unclea...
PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.
Genomic Insights into Innate Resistance in Early-Stage EGFR-Mutant Non-Small Cell Lung Cancer: A Comprehensive Analysis of Next-Generation Sequencing Data.
Seong H, Kim SH, Kim MH … +3 more , Kim A, Song JS, Eom JS
Cancer Res Treat · 2025 Aug · PMID 40878433 · Publisher ↗
PURPOSE: 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...
PURPOSE: 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). MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.
Impact of Pre-admission Central Nervous System Medication Use on Delirium in Hospitalized Patients with Advanced Cancer: A Multicenter, Prospective, Observational Study in Korea.
Geum MJ, Yoo SH, Lee SW … +4 more , Hong M, Jung EH, Kim YJ, Kang B
Cancer Res Treat · 2025 Aug · PMID 40878432 · Publisher ↗
PURPOSE: 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. MATERIALS AND METHODS:...
PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSION: 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.
Nomograms Integrating Body Composition Metrics Predict Total Pathologic Complete Remission after Neoadjuvant Systemic Therapy for Breast Cancer.
Ding J, Gong Y, Wang J … +8 more , Wang Y, Yao H, Sheng X, Wang M, Shen D, Li J, Zha X, Xu L
Cancer Res Treat · 2025 Aug · PMID 40842075 · Publisher ↗
PURPOSE: 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 exh...
PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.
Preferential Sensitivity of the EGFR L858M/L861R Mutation to Second-Generation EGFR Tyrosine Kinase Inhibitors in Non-small Cell Lung Cancer.
Lee C, Kim S, Kim S … +6 more , Park T, Kim M, Keam B, Kim TM, Kim DW, Youk J
Cancer Res Treat · 2025 Aug · PMID 40842074 · Publisher ↗
PURPOSE: 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 potent...
PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.
Risk Stratification in T4 or N3 Nasopharyngeal Carcinoma.
Guo LF, Zhu LC, Yu YF … +3 more , Lu ZZ, Lin Q, Wu SG
Cancer Res Treat · 2025 Aug · PMID 40808534 · Publisher ↗
PURPOSE: To investigate the prognostic heterogeneity among stage III nasopharyngeal carcinoma (NPC) patients according to the 9th edition of the American Joint Committee on Cancer (AJCC)/Union for International Cancer Co...
PURPOSE: To investigate the prognostic heterogeneity among stage III nasopharyngeal carcinoma (NPC) patients according to the 9th edition of the American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) staging system to identify potential subgroups requiring tailored therapeutic strategies. MATERIALS AND METHODS: We retrospectively included stage III patients (T1-3N3 or T4N0-3) who were diagnosed with NPC between January 2015 and December 2021 according to the 9th edition of the AJCC/UICC staging system. Kaplan-Meier method and multivariable Cox regression analyses were used for statistical analysis. RESULTS: We included 309 patients in this study. A total of 92/309 (29.8%) patients developed locoregional recurrence and/or distant metastasis with a median follow-up of 52.9 months. Those with T4N3 disease had significantly lower distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS) but comparable locoregional relapse-free survival (LRFS) to those with T1-3N3 and T4N0-2 disease. Those with T4N3 disease had comparable LRFS but had significantly lower 5-year DMFS (78.7% vs. 44.7%, p<0.001), PFS (65.7% vs. 27.6%, p<0.001), and OS (77.1% vs. 45.9%, p<0.001) compared to those with stage T4N0-2 and T1-3N3 diseases. Similar results were confirmed using the multivariate analysis. CONCLUSION: Our study demonstrates the prognostic heterogeneity of stage III disease within the 9th edition NPC staging system. T4N3 category should be considered separately and treated as a distinct entity regardless of the staging editions.
Effectiveness of Radiotherapy for Hepatocellular Carcinoma with Lymph Node Metastasis: A Meta-Analysis.
Hwang S, Hur S, Yoon WS … +2 more , Park S, Rim CH
Cancer Res Treat · 2025 Aug · PMID 40808533 · Publisher ↗
PURPOSE: Lymph node metastasis (LNM) of hepatocellular carcinoma (HCC) carries a poor prognosis; however, no standard treatment has been established. Radiotherapy (RT) has demonstrated favorable tumor response, with the...
PURPOSE: Lymph node metastasis (LNM) of hepatocellular carcinoma (HCC) carries a poor prognosis; however, no standard treatment has been established. Radiotherapy (RT) has demonstrated favorable tumor response, with the advantage of being less affected by anatomical hindrances. MATERIALS AND METHODS: Databases were searched up to April 2024. The inclusion criteria were: (1) ≥5 patients with HCC LNM, (2) studies that performed external RT, and (3) reporting survival or response rate (RR). The main effect measures are pooled 1- and 2-year overall survival (OS) rates, response rate (RR) and grade ≥3 complications. RESULTS: Twelve studies involving 825 patients were included. The pooled 1-year OS rate and 2-year OS rate were 49.3% (95% confidence interval [CI]: 39.2%-59.4%) and 24.5% (95% CI: 17.0%-34.0%), respectively. The median OS ranged from 5.8 to 29.7 months, with a median value of 9.7 months. In one study, 14.7% of patients were prescribed an immunoagent. In other studies, some patients received sorafenib, but no specific systemic therapy was performed for the majority. The pooled RR was 75.1% (95% CI: 66.9%-81.8%). The pooled RR of high dose and low dose groups was 83.8% (95% CI: 76.3-89.3) vs. 55.6% (95% CI: 44.4-66.3), respectively (p<0.001). The pooled rate of grade ≥3 gastrointestinal toxicity was 3.7% (95% CI: 2.1%-6.6%). CONCLUSION: RT is an effective and feasible palliative option for HCC LNM. Further researches of combined treatment with novel systemic agents are necessary.
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.
Lee JH, Kim N, Kim JH … +26 more , Oh HJ, Kim Y, Choi Y, Jo H, Lee HK, Choi J, Jun YK, Yoon H, Shin CM, Park YS, Lee DH, Lee HS, Kang SH, Park YS, Ahn SH, Suh YS, Park DJ, Kim HH, Kim JW, Kim JW, Lee KW, Chang W, Lee YJ, Lee KH, Kim YH, Ahn S
Cancer Res Treat · 2025 Aug · PMID 40808532 · Publisher ↗
PURPOSE: 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 clinicopat...
PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSION: 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.
Clinicopathological Significance of Tumor-Infiltrating T Lymphocytes and Macrophages in Primary Large B-Cell Lymphoma of Immune-Privileged Sites.
Kim J, Kim D, Cho H … +2 more , Yoon DH, Go H
Cancer Res Treat · 2025 Aug · PMID 40808531 · Publisher ↗
PURPOSE: 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), originat...
PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.
Efficacy and Safety of Lenvatinib Plus Everolimus in Metastatic Renal Cell Carcinoma After Immune Checkpoint and VEGFR Tyrosine Kinase Inhibitors Treatment.
Lee SH, Park I, Yoon S … +1 more , Lee JL
Cancer Res Treat · 2025 Aug · PMID 40808530 · Publisher ↗
PURPOSE: 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 inhibi...
PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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%. CONCLUSION: 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.
DNA Damage and Nuclear Anaplasia Induced by Trastuzumab Deruxtecan in Cancer Cells with Variable HER2 Expression and Homologous Recombination Deficiency Status.
Kim SH, Park Y, Min A … +10 more , Park HY, Kim YJ, Ham S, Koh J, Kim S, Lee DW, Ryu HS, Kim JS, Lee KH, Im SA
Cancer Res Treat · 2026 Apr · PMID 40776560 · Full text
PURPOSE: Human epidermal growth factor receptor 2 (HER2) is amplified or overexpressed in various malignancies, including breast and gastric cancers, and is associated with poor prognosis. Although HER2-targeted therapie...
PURPOSE: Human epidermal growth factor receptor 2 (HER2) is amplified or overexpressed in various malignancies, including breast and gastric cancers, and is associated with poor prognosis. Although HER2-targeted therapies, such as trastuzumab, improve outcomes in HER2-positive tumors, resistance often develops, and HER2-low tumors remain largely untargeted. Trastuzumab deruxtecan (T-DXd; DS-8201a) is a HER2-targeted antibody-drug conjugate with potent activity in HER2-positive and HER2-low tumors. This study evaluates its antitumor mechanisms and efficacy in HER2-positive, HER2-low, and homologous recombination deficiency (HRD)-associated models. MATERIALS AND METHODS: Effects of T-DXd were assessed in cancer cell lines with diverse HER2 expression and HRD status. In vivo efficacy was evaluated using a xenograft model derived from HER2-low SNU-601 gastric cancer cells. RESULTS: T-DXd reduced HER2 phosphorylation and downstream signaling (AKT, ERK) in HER2-positive cells. It induced DNA damage accumulation, as evidenced by increased γH2AX and p-Chk1 expression, and triggered apoptosis through cleaved poly(ADP-ribose) polymerase and caspase-3 activation, confirmed by annexin V staining. Similar effects were observed in HER2-low cells, with greater sensitivity in HRD cells. In xenografts, T-DXd reduced tumor volume by up to 80% at 4 mg/kg and 10 mg/kg. Histological analyses showed decreased Ki-67 and increased apoptosis. Furthermore, T-DXd induced G2/M cell cycle arrest and nuclear anaplasia, suggesting disruption of chromosomal stability as a potential antitumor mechanism. No significant toxicity, including body weight loss, was observed. CONCLUSION: These findings highlight T-DXd's effectiveness in HER2-low and HRD tumors, supporting its broader clinical application, including strategies targeting DNA damage repair pathways.
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