Takahiro Haeno, Kazuko Sakai, Shuji Minamoto, Daiki Nakatsu, Marco A. De Velasco, Shinya Rai, Hirokazu Tanaka, Itaru Matsumura, Kazuto Nishio
Background
Intratumor heterogeneity (ITH), characterized by the coexistence of genetically distinct subclones within a tumor, has been associated with adverse clinical outcomes in various cancers. However, the clinical and biological implications of ITH in diffuse large B-cell lymphoma (DLBCL) are still incompletely understood.
Materials & Methods
In this study, we applied a SNP-array–based approach to assess the clonal complexity in formalin-fixed, paraffin-embedded tumor specimens obtained from newly diagnosed patients with advanced-stage DLBCL (n = 74) by calculating the clonal composition (CC) number.
Rseults
Patients with Poly-CC tumors (CC ≥ 1), which accounted for 79.7% of the cases, had a 5-year event-free survival rate of 38.9%, compared with 69.1% in those with Mono-CC tumors (CC = 0) (Log-rank p = 0.0520). This association reached statistical significance in the activated B-cell (ABC) subtype (n = 35, Log-rank p = 0.0450) but not in the germinal center B-cell (GCB) subtype (n = 30, Log-rank p = 0.910). Gene set enrichment analysis revealed upregulation of cell cycle–related pathways in Poly-CC tumors, consistent with the significantly higher Ki-67 positivity rate than in Mono-CC tumors, as confirmed by immunohistochemistry (p = 0.00227). Within the ABC subtype, Poly-CC (Poly-ABC) tumors exhibited more differentiated transcriptional states and enrichment of IRF4-associated gene signatures as compared with Mono-CC (Mono-ABC) tumors. Conversely, IFN-γ and IFN-α response pathways and the IL-6/JAK-STAT3 signaling pathway were markedly suppressed in the Poly-ABC tumors. Furthermore, Poly-ABC tumors carried a significantly higher number of pathogenic mutations as compared with Mono-ABC tumors (p = 0.0147).
Conclusion
These results suggest that clonal complexity captures tumor-intrinsic features and biological diversity in DLBCL, especially in the ABC subtype, offering novel insights into the disease pathogenesis.
背景：肿瘤内异质性（ITH），以肿瘤内基因不同的亚克隆共存为特征，与各种癌症的不良临床结果有关。然而，ITH在弥漫性大b细胞淋巴瘤（DLBCL）中的临床和生物学意义尚不完全清楚。材料与方法：在本研究中，我们采用基于snp阵列的方法，通过计算克隆组成（CC）数来评估来自新诊断的晚期DLBCL患者（n = 74）的福尔马林固定石蜡包埋肿瘤标本的克隆复杂性。结果：多癌（CC≥1）患者的5年无事件生存率为38.9%，占病例的79.7%，而单核癌（CC = 0）患者的5年无事件生存率为69.1% （Log-rank p = 0.0520）。这种相关性在活化b细胞（ABC）亚型（n = 35, Log-rank p = 0.0450）中有统计学意义，而在生发中心b细胞（GCB）亚型（n = 30, Log-rank p = 0.910）中无统计学意义。基因集富集分析显示Poly-CC肿瘤中细胞周期相关通路上调，免疫组化证实Ki-67阳性率明显高于Mono-CC肿瘤（p = 0.00227）。在ABC亚型中，与Mono-CC （Mono-ABC）肿瘤相比，Poly-CC （Poly-ABC）肿瘤表现出更多分化的转录状态和irf4相关基因特征的富集。相反，IFN-γ和IFN-α反应通路以及IL-6/JAK-STAT3信号通路在Poly-ABC肿瘤中明显抑制。此外，与单abc肿瘤相比，Poly-ABC肿瘤携带的致病突变数量显著增加（p = 0.0147）。结论：这些结果表明，克隆复杂性捕获了DLBCL（尤其是ABC亚型）的肿瘤固有特征和生物多样性，为该疾病的发病机制提供了新的见解。
{"title":"Clonal Complexity Defines Distinct Tumor-Intrinsic Biology and Prognosis in Diffuse Large B-Cell Lymphoma","authors":"Takahiro Haeno, Kazuko Sakai, Shuji Minamoto, Daiki Nakatsu, Marco A. De Velasco, Shinya Rai, Hirokazu Tanaka, Itaru Matsumura, Kazuto Nishio","doi":"10.1002/cam4.71597","DOIUrl":"10.1002/cam4.71597","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Intratumor heterogeneity (ITH), characterized by the coexistence of genetically distinct subclones within a tumor, has been associated with adverse clinical outcomes in various cancers. However, the clinical and biological implications of ITH in diffuse large B-cell lymphoma (DLBCL) are still incompletely understood.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials & Methods</h3>\u0000 \u0000 <p>In this study, we applied a SNP-array–based approach to assess the clonal complexity in formalin-fixed, paraffin-embedded tumor specimens obtained from newly diagnosed patients with advanced-stage DLBCL (<i>n</i> = 74) by calculating the clonal composition (CC) number.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Rseults</h3>\u0000 \u0000 <p>Patients with Poly-CC tumors (CC ≥ 1), which accounted for 79.7% of the cases, had a 5-year event-free survival rate of 38.9%, compared with 69.1% in those with Mono-CC tumors (CC = 0) (Log-rank p = 0.0520). This association reached statistical significance in the activated B-cell (ABC) subtype (<i>n</i> = 35, Log-rank <i>p</i> = 0.0450) but not in the germinal center B-cell (GCB) subtype (<i>n</i> = 30, Log-rank p = 0.910). Gene set enrichment analysis revealed upregulation of cell cycle–related pathways in Poly-CC tumors, consistent with the significantly higher Ki-67 positivity rate than in Mono-CC tumors, as confirmed by immunohistochemistry (<i>p</i> = 0.00227). Within the ABC subtype, Poly-CC (Poly-ABC) tumors exhibited more differentiated transcriptional states and enrichment of IRF4-associated gene signatures as compared with Mono-CC (Mono-ABC) tumors. Conversely, IFN-γ and IFN-α response pathways and the IL-6/JAK-STAT3 signaling pathway were markedly suppressed in the Poly-ABC tumors. Furthermore, Poly-ABC tumors carried a significantly higher number of pathogenic mutations as compared with Mono-ABC tumors (<i>p</i> = 0.0147).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These results suggest that clonal complexity captures tumor-intrinsic features and biological diversity in DLBCL, especially in the ABC subtype, offering novel insights into the disease pathogenesis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"15 2","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12863995/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146103202","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}
Lauren Struszczak, Jean-Philippe Walhin, James Betts, Dylan Thompson, Mark Beresford, James E Turner
<p><strong>Background: </strong>This randomised, controlled non-inferiority trial investigated whether 8 weeks of remotely-supported exercise training changes cardiorespiratory fitness, functional fitness and body composition by a magnitude that is not meaningfully inferior to changes caused by partly-supervised exercise training.</p><p><strong>Methods: </strong>Thirty female breast cancer survivors (57 ± 6 years, <math> <semantics> <mrow><mover><mi>V</mi> <mo>̇</mo></mover> <msub><mi>O</mi> <mn>2</mn></msub> <mi>max</mi></mrow> <annotation>$$ dot{mathrm{V}}{mathrm{O}}_2max $$</annotation></semantics> </math> 28.9 ± 6.1 mL·kg<sup>-1</sup>·min<sup>-1</sup>, BMI 25.3 ± 3.3 kg·m<sup>-2</sup>) were randomised to 8 weeks of partly-supervised (n = 15) or remotely-supported (n = 15) exercise training. The partly-supervised group undertook two supervised and one unsupervised session per week, progressing from 55% to 70% <math> <semantics> <mrow><mover><mi>V</mi> <mo>̇</mo></mover> <msub><mi>O</mi> <mn>2</mn></msub> <mi>max</mi></mrow> <annotation>$$ dot{mathrm{V}}{mathrm{O}}_2max $$</annotation></semantics> </math> and 35-50 min. The remotely-supported group were prescribed the same total duration of exercise per week (progressing from 105 to 150 min). Intensity was prescribed using heart rate targets corresponding to 55%-70% <math> <semantics> <mrow><mover><mi>V</mi> <mo>̇</mo></mover> <msub><mi>O</mi> <mn>2</mn></msub> <mi>max</mi></mrow> <annotation>$$ dot{mathrm{V}}{mathrm{O}}_2max $$</annotation></semantics> </math> . <math> <semantics> <mrow><mover><mi>V</mi> <mo>̇</mo></mover> <msub><mi>O</mi> <mn>2</mn></msub> <mi>max</mi></mrow> <annotation>$$ dot{mathrm{V}}{mathrm{O}}_2max $$</annotation></semantics> </math> , functional fitness, body composition and blood pressure were assessed pre- and post-intervention.</p><p><strong>Results: </strong>Adherence was higher in the partly-supervised group (87% ± 7%) versus the remotely-supported group (64% ± 25%; p = 0.01). The remotely-supported group exhibited changes in timed up and go (difference to partly-supervised; 95% CI -0.8 to 0.4 s) and percentage body fat (difference to partly-supervised; 95% CI -0.6 to 0.5 kg·m<sup>-2</sup>) that were non-inferior to the partly-supervised group. It was inconclusive whether changes among the remotely-supported group for <math> <semantics> <mrow><mover><mi>V</mi> <mo>̇</mo></mover> <msub><mi>O</mi> <mn>2</mn></msub> <mi>max</mi></mrow> <annotation>$$ dot{mathrm{V}}{mathrm{O}}_2max $$</annotation></semantics> </math> (difference to partly-supervised; 95% CI -3.3 to 1.1 mL·kg<sup>-1</sup>·min<sup>-1</sup>), blood pressure (difference to partly-supervised; 95% CI systolic; -3 to 12 mmHg, diastolic; -5 to 6 mmHg), 6 min walk (difference to partly-supervised; 95% CI -54.0 to 0.4 m), or sit to stand (difference to partly-supervised; 95% CI -3 to 2 repetitions), were non-inferior to the partly-supervised group.</p><p><strong>Conclusion: </strong>Remotely-supported exercise
背景：这项随机对照非劣效性试验调查了8周远程支持运动训练是否在一定程度上改变了心肺健康、功能健康和身体成分，其改变程度并不明显低于部分监督运动训练引起的变化。方法：30名女性乳腺癌幸存者（57±6岁，vo2 max $$ dot{mathrm{V}}{mathrm{O}}_2max $$ 28.9±6.1 mL·kg-1·min-1, BMI 25.3±3.3 kg·m-2）随机分为8周部分监督（n = 15）或远程支持（n = 15）运动训练。部分监督组每周进行两次监督和一次无监督的会议，从55次开始% to 70% V ̇ O 2 max $$ dot{mathrm{V}}{mathrm{O}}_2max $$ and 35-50 min. The remotely-supported group were prescribed the same total duration of exercise per week (progressing from 105 to 150 min). Intensity was prescribed using heart rate targets corresponding to 55%-70% V ̇ O 2 max $$ dot{mathrm{V}}{mathrm{O}}_2max $$ . V ̇ O 2 max $$ dot{mathrm{V}}{mathrm{O}}_2max $$ , functional fitness, body composition and blood pressure were assessed pre- and post-intervention.Results: Adherence was higher in the partly-supervised group (87% ± 7%) versus the remotely-supported group (64% ± 25%; p = 0.01). The remotely-supported group exhibited changes in timed up and go (difference to partly-supervised; 95% CI -0.8 to 0.4 s) and percentage body fat (difference to partly-supervised; 95% CI -0.6 to 0.5 kg·m-2) that were non-inferior to the partly-supervised group. It was inconclusive whether changes among the remotely-supported group for V ̇ O 2 max $$ dot{mathrm{V}}{mathrm{O}}_2max $$ (difference to partly-supervised; 95% CI -3.3 to 1.1 mL·kg-1·min-1), blood pressure (difference to partly-supervised; 95% CI systolic; -3 to 12 mmHg, diastolic; -5 to 6 mmHg), 6 min walk (difference to partly-supervised; 95% CI -54.0 to 0.4 m), or sit to stand (difference to partly-supervised; 95% CI -3 to 2 repetitions), were non-inferior to the partly-supervised group.Conclusion: Remotely-supported exercise might be an alternative to partly-supervised exercise regarding functional fitness (assessed by timed up and go) and body composition (assessed by percentage body fat). It remains inconclusive whether remotely-supported exercise is an alternative regarding V ̇ O 2 max $$ dot{mathrm{V}}{mathrm{O}}_2max $$ , blood pressure and other functional fitness measurements (6-min walk, sit to stand).Trials registration: NCT06376578 (20/11/2020).
{"title":"Cardiorespiratory Fitness, Functional Fitness and Body Composition Among Breast Cancer Survivors With 8 Weeks of Exercise Training: A Randomised, Controlled Non-Inferiority Trial Comparing Remotely-Supported and Partly-Supervised Interventions.","authors":"Lauren Struszczak, Jean-Philippe Walhin, James Betts, Dylan Thompson, Mark Beresford, James E Turner","doi":"10.1002/cam4.71608","DOIUrl":"https://doi.org/10.1002/cam4.71608","url":null,"abstract":"<p><strong>Background: </strong>This randomised, controlled non-inferiority trial investigated whether 8 weeks of remotely-supported exercise training changes cardiorespiratory fitness, functional fitness and body composition by a magnitude that is not meaningfully inferior to changes caused by partly-supervised exercise training.</p><p><strong>Methods: </strong>Thirty female breast cancer survivors (57 ± 6 years, <math> <semantics> <mrow><mover><mi>V</mi> <mo>̇</mo></mover> <msub><mi>O</mi> <mn>2</mn></msub> <mi>max</mi></mrow> <annotation>$$ dot{mathrm{V}}{mathrm{O}}_2max $$</annotation></semantics> </math> 28.9 ± 6.1 mL·kg<sup>-1</sup>·min<sup>-1</sup>, BMI 25.3 ± 3.3 kg·m<sup>-2</sup>) were randomised to 8 weeks of partly-supervised (n = 15) or remotely-supported (n = 15) exercise training. The partly-supervised group undertook two supervised and one unsupervised session per week, progressing from 55% to 70% <math> <semantics> <mrow><mover><mi>V</mi> <mo>̇</mo></mover> <msub><mi>O</mi> <mn>2</mn></msub> <mi>max</mi></mrow> <annotation>$$ dot{mathrm{V}}{mathrm{O}}_2max $$</annotation></semantics> </math> and 35-50 min. The remotely-supported group were prescribed the same total duration of exercise per week (progressing from 105 to 150 min). Intensity was prescribed using heart rate targets corresponding to 55%-70% <math> <semantics> <mrow><mover><mi>V</mi> <mo>̇</mo></mover> <msub><mi>O</mi> <mn>2</mn></msub> <mi>max</mi></mrow> <annotation>$$ dot{mathrm{V}}{mathrm{O}}_2max $$</annotation></semantics> </math> . <math> <semantics> <mrow><mover><mi>V</mi> <mo>̇</mo></mover> <msub><mi>O</mi> <mn>2</mn></msub> <mi>max</mi></mrow> <annotation>$$ dot{mathrm{V}}{mathrm{O}}_2max $$</annotation></semantics> </math> , functional fitness, body composition and blood pressure were assessed pre- and post-intervention.</p><p><strong>Results: </strong>Adherence was higher in the partly-supervised group (87% ± 7%) versus the remotely-supported group (64% ± 25%; p = 0.01). The remotely-supported group exhibited changes in timed up and go (difference to partly-supervised; 95% CI -0.8 to 0.4 s) and percentage body fat (difference to partly-supervised; 95% CI -0.6 to 0.5 kg·m<sup>-2</sup>) that were non-inferior to the partly-supervised group. It was inconclusive whether changes among the remotely-supported group for <math> <semantics> <mrow><mover><mi>V</mi> <mo>̇</mo></mover> <msub><mi>O</mi> <mn>2</mn></msub> <mi>max</mi></mrow> <annotation>$$ dot{mathrm{V}}{mathrm{O}}_2max $$</annotation></semantics> </math> (difference to partly-supervised; 95% CI -3.3 to 1.1 mL·kg<sup>-1</sup>·min<sup>-1</sup>), blood pressure (difference to partly-supervised; 95% CI systolic; -3 to 12 mmHg, diastolic; -5 to 6 mmHg), 6 min walk (difference to partly-supervised; 95% CI -54.0 to 0.4 m), or sit to stand (difference to partly-supervised; 95% CI -3 to 2 repetitions), were non-inferior to the partly-supervised group.</p><p><strong>Conclusion: </strong>Remotely-supported exercise ","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"15 2","pages":"e71608"},"PeriodicalIF":3.1,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146140469","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}
Background: Dose exposure to supraventricular cardiac conduction system doses has been reported to be associated with distinct arrhythmia classes after thoracic radiotherapy, but its impact in esophageal squamous cell carcinoma (ESCC) remains unknown.
Materials and methods: Locally advanced ESCC treated with neoadjuvant chemoradiotherapy (nCRT) were included. The primary endpoint was grade ≥ 3 adverse cardiac arrhythmia events. Prediction performance was evaluated through time-dependent receiver operating characteristic curves, and competing risk frameworks were implemented to quantify the cumulative incidence of distinct cardiac arrhythmia.
Results: Of 358 patients, 84.9% were men, with a median age of 66 years (range: 39-79 years). A total of 60 (16.8%) patients experienced at least 1 grade ≥ 3 arrhythmia, with a median time to first arrhythmia of 13 months (95% CI: 12-15 months). The 2-year cumulative incidences of distinct cardiac arrhythmia were 8.89% for AF, 2.96% for atrial flutter, and 5.12% for other SVT. Baseline coronary heart disease was a risk factor for all types of arrhythmia (p < 0.05). After adjusting for baseline cardiovascular risk factors, Heart Dmax (sHR 3.69, p = 0.0024) was associated with AF, Heart volume receiving 5 Gy with atrial flutter (sHR: 9.35, p = 0.0077), and Heart volume receiving 40 Gy (sHR 5.72, p = 0.00078) with other SVT.
Conclusion: Grade ≥ 3 cardiac arrhythmia associated with thoracic radiation occurs in 16.7% of ESCC patients undergoing nCRT within a median time of 13 months. The radiation dose exposure of the supraventricular cardiac conduction system is not associated with increased cardiac arrhythmia. Specific arrhythmia subtypes exhibited differential associations with distinct dose-volume parameters of whole heart irradiation.
背景：据报道，暴露于室上心脏传导系统剂量与胸部放疗后不同类型的心律失常有关，但其对食管鳞状细胞癌（ESCC）的影响尚不清楚。材料和方法：采用新辅助放化疗（nCRT）治疗局部晚期ESCC。主要终点为≥3级不良心律失常事件。通过时间相关的受试者工作特征曲线评估预测效果，并实施竞争风险框架来量化不同心律失常的累积发生率。结果：358例患者中，84.9%为男性，中位年龄66岁（范围：39-79岁）。共有60例（16.8%）患者经历了至少1次≥3级心律失常，到首次心律失常的中位时间为13个月（95% CI: 12-15个月）。AF的2年累计明显心律失常发生率为8.89%，心房扑动发生率为2.96%，其他室间性心动过速发生率为5.12%。基线冠心病是所有类型心律失常的危险因素(pmax （sHR 3.69, p = 0.0024）与房颤相关，心脏容量接受5 Gy时伴有心房扑动（sHR: 9.35, p = 0.0077），心脏容量接受40 Gy时伴有其他SVT （sHR 5.72, p = 0.00078）。结论：接受nCRT治疗的ESCC患者中，有16.7%的患者在13个月内发生了胸椎放射相关的≥3级心律失常。室上心脏传导系统的辐射剂量暴露与心律失常的增加无关。特定的心律失常亚型与全心照射不同的剂量-体积参数表现出不同的相关性。
{"title":"Whole Heart Dose Parameters Predict Severe Arrhythmias After Neoadjuvant Chemoradiotherapy for Esophageal Squamous Cell Cancer: A Competing Risk Analysis of 358 Patients.","authors":"Wei-Xiang Qi, Haiping Zhang, Xunmei Yang, Shuyan Li, Mengdi Wang, Biao Yu, Linlin Chen, Gang Cai, Cheng Xu, Jiayi Chen, Shengguang Zhao","doi":"10.1002/cam4.71610","DOIUrl":"https://doi.org/10.1002/cam4.71610","url":null,"abstract":"<p><strong>Background: </strong>Dose exposure to supraventricular cardiac conduction system doses has been reported to be associated with distinct arrhythmia classes after thoracic radiotherapy, but its impact in esophageal squamous cell carcinoma (ESCC) remains unknown.</p><p><strong>Materials and methods: </strong>Locally advanced ESCC treated with neoadjuvant chemoradiotherapy (nCRT) were included. The primary endpoint was grade ≥ 3 adverse cardiac arrhythmia events. Prediction performance was evaluated through time-dependent receiver operating characteristic curves, and competing risk frameworks were implemented to quantify the cumulative incidence of distinct cardiac arrhythmia.</p><p><strong>Results: </strong>Of 358 patients, 84.9% were men, with a median age of 66 years (range: 39-79 years). A total of 60 (16.8%) patients experienced at least 1 grade ≥ 3 arrhythmia, with a median time to first arrhythmia of 13 months (95% CI: 12-15 months). The 2-year cumulative incidences of distinct cardiac arrhythmia were 8.89% for AF, 2.96% for atrial flutter, and 5.12% for other SVT. Baseline coronary heart disease was a risk factor for all types of arrhythmia (p < 0.05). After adjusting for baseline cardiovascular risk factors, Heart D<sub>max</sub> (sHR 3.69, p = 0.0024) was associated with AF, Heart volume receiving 5 Gy with atrial flutter (sHR: 9.35, p = 0.0077), and Heart volume receiving 40 Gy (sHR 5.72, p = 0.00078) with other SVT.</p><p><strong>Conclusion: </strong>Grade ≥ 3 cardiac arrhythmia associated with thoracic radiation occurs in 16.7% of ESCC patients undergoing nCRT within a median time of 13 months. The radiation dose exposure of the supraventricular cardiac conduction system is not associated with increased cardiac arrhythmia. Specific arrhythmia subtypes exhibited differential associations with distinct dose-volume parameters of whole heart irradiation.</p>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"15 2","pages":"e71610"},"PeriodicalIF":3.1,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146140492","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}
Junyu Yan, Min Hao, Tong Wang, Qi Yang, Congcong Jia, Wenju Niu, Yan Tan, Hui Zhang, Hongyan Cao, Guoqiang Yang
Background
Gliomas are the most common primary brain tumors, exhibiting significant phenotypic variability even within the same grade. Identifying glioma subtypes through non-invasive methods could improve patient management.
Methods
In this study, we applied hierarchical multi-kernel learning to identify glioma phenotypic subtypes using MRI data (T1CE and T2FLAIR) from the First Hospital of Shanxi Medical University (FHSXMU) and Shanxi Provincial People's Hospital (SPPH) (n = 246). We further validated our findings using an independent dataset of similar tumor characteristics from The Cancer Genome Atlas/The Cancer Imaging Archive (TCGA/TCIA) (n = 144). Additionally, we analyzed pathway activity across glioma subtypes from the TCGA/TCIA dataset and employed five machine learning models, namely kernel partial least squares with the genetic algorithm (GA-KPLS), random forest, the least absolute shrinkage and selection operator, K-Nearest Neighbor, and Naïve Bayes, to predict isocitrate dehydrogenase (IDH) genotype from the FHSXMU/SPPH dataset.
Results
We identified 2 glioma phenotypic subtypes, high-risk and low-risk groups. These groups showed significant differences in overall survival (p < 0.05) and were associated with distinct signaling pathways. The JAK–STAT and TGF-β pathways were activated in the high-risk group, while the Hypoxia and p53 pathways were activated in the low-risk group. Among the machine learning models, the GA-KPLS model demonstrated the highest predictive performance for the IDH genotype, achieving an area under the curve of 0.819.
Conclusion
Our study provides a non-invasive method to identify glioma phenotypic subtypes, reveal distinct signaling pathways, and define therapeutically homogeneous patient subgroups that could guide targeted therapy.
{"title":"Identification of Glioma Phenotypic Subtypes From Multimodal MRI Data Using Hierarchical Multi-Kernel Learning","authors":"Junyu Yan, Min Hao, Tong Wang, Qi Yang, Congcong Jia, Wenju Niu, Yan Tan, Hui Zhang, Hongyan Cao, Guoqiang Yang","doi":"10.1002/cam4.71572","DOIUrl":"10.1002/cam4.71572","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Gliomas are the most common primary brain tumors, exhibiting significant phenotypic variability even within the same grade. Identifying glioma subtypes through non-invasive methods could improve patient management.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this study, we applied hierarchical multi-kernel learning to identify glioma phenotypic subtypes using MRI data (T1CE and T2FLAIR) from the First Hospital of Shanxi Medical University (FHSXMU) and Shanxi Provincial People's Hospital (SPPH) (<i>n</i> = 246). We further validated our findings using an independent dataset of similar tumor characteristics from The Cancer Genome Atlas/The Cancer Imaging Archive (TCGA/TCIA) (<i>n</i> = 144). Additionally, we analyzed pathway activity across glioma subtypes from the TCGA/TCIA dataset and employed five machine learning models, namely kernel partial least squares with the genetic algorithm (GA-KPLS), random forest, the least absolute shrinkage and selection operator, K-Nearest Neighbor, and Naïve Bayes, to predict isocitrate dehydrogenase (IDH) genotype from the FHSXMU/SPPH dataset.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We identified 2 glioma phenotypic subtypes, high-risk and low-risk groups. These groups showed significant differences in overall survival (<i>p</i> < 0.05) and were associated with distinct signaling pathways. The JAK–STAT and TGF-β pathways were activated in the high-risk group, while the Hypoxia and p53 pathways were activated in the low-risk group. Among the machine learning models, the GA-KPLS model demonstrated the highest predictive performance for the IDH genotype, achieving an area under the curve of 0.819.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our study provides a non-invasive method to identify glioma phenotypic subtypes, reveal distinct signaling pathways, and define therapeutically homogeneous patient subgroups that could guide targeted therapy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"15 2","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12861564/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146100074","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}
Bixue Huang, Yun Li, Ruihua Fang, Kexing Lv, Zhangfeng Wang, Xiaolin Zhu, Lin Chen, Wenbin Lei
Background
To evaluate the effect of bilateral elective node dissection on the prognosis of patients with T3N0M0 glottic carcinoma.
Methods
This retrospective cohort study enrolled two cohorts: patients screened from the Surveillance, Epidemiology, and End Results (SEER) database of the National Cancer Institute, and those treated at the First Affiliated Hospital of Sun Yat-sen University. Patients screened from the SEER database were divided into untreated, radiotherapy (RT), surgery, and concurrent systemic therapy (ST)/RT groups. Patients from our center were divided into unilateral and bilateral groups based on lymph node dissection. Propensity score-matching (PSM) was applied to eliminate baseline variations. Kaplan–Meier analysis was used to assess different treatment method effects.
Results
This study retrieved 2027 and 133 patients from the SEER database and our center, respectively, from 2014 to 2022. After PSM, overall survival (OS) and cancer-specific survival (CSS) improved in the ST/RT (both p < 0.001) and surgery (both p < 0.001) groups versus the RT group, with no differences between groups (OS, p = 0.45; CSS, p = 0.84). Patients who underwent elective node dissection (END) had better OS (p = 0.025) and CSS (p < 0.001) than those without END. No significant difference was observed in OS (p = 0.110) between the END and ST/RT groups; however, the END group showed significant improvement in CSS (p = 0.007). Patients who underwent bilateral neck dissection had better progression-free survival than the unilateral group after PSM (p = 0.024).
Conclusion
Surgery combined with bilateral node dissection can bring better survival prognosis for patients with T3N0M0 glottic carcinoma.
{"title":"Bilateral Neck Dissection Effectively Improves Prognosis of Patients With T3N0M0 Glottic Carcinoma","authors":"Bixue Huang, Yun Li, Ruihua Fang, Kexing Lv, Zhangfeng Wang, Xiaolin Zhu, Lin Chen, Wenbin Lei","doi":"10.1002/cam4.71593","DOIUrl":"10.1002/cam4.71593","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>To evaluate the effect of bilateral elective node dissection on the prognosis of patients with T3N0M0 glottic carcinoma.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This retrospective cohort study enrolled two cohorts: patients screened from the Surveillance, Epidemiology, and End Results (SEER) database of the National Cancer Institute, and those treated at the First Affiliated Hospital of Sun Yat-sen University. Patients screened from the SEER database were divided into untreated, radiotherapy (RT), surgery, and concurrent systemic therapy (ST)/RT groups. Patients from our center were divided into unilateral and bilateral groups based on lymph node dissection. Propensity score-matching (PSM) was applied to eliminate baseline variations. Kaplan–Meier analysis was used to assess different treatment method effects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>This study retrieved 2027 and 133 patients from the SEER database and our center, respectively, from 2014 to 2022. After PSM, overall survival (OS) and cancer-specific survival (CSS) improved in the ST/RT (both <i>p</i> < 0.001) and surgery (both <i>p</i> < 0.001) groups versus the RT group, with no differences between groups (OS, <i>p</i> = 0.45; CSS, <i>p</i> = 0.84). Patients who underwent elective node dissection (END) had better OS (<i>p</i> = 0.025) and CSS (<i>p</i> < 0.001) than those without END. No significant difference was observed in OS (<i>p</i> = 0.110) between the END and ST/RT groups; however, the END group showed significant improvement in CSS (<i>p</i> = 0.007). Patients who underwent bilateral neck dissection had better progression-free survival than the unilateral group after PSM (<i>p</i> = 0.024).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Surgery combined with bilateral node dissection can bring better survival prognosis for patients with T3N0M0 glottic carcinoma.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"15 2","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12861563/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146100039","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}
Louis Jansen, Lisa Nachtsheim, Sofia Kourou, Philipp Wolber, Kariem Sharaf, Kevin Hansen, Sami Shabli, Julia van de Loo, Alexander Quaas, Christoph Arolt, Marianne Engels, Lena Hieggelke, Luc G T Morris, Jens Peter Klussmann, Marcel Mayer
Introduction: Salivary gland lesions (SGL) are a rare and heterogeneous group of benign and malignant masses. Fine-needle aspiration cytology (FNAC), guided by the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC), offers a minimally invasive method for early differentiation of SGL. The purpose of this study was to evaluate the cost-effectiveness of FNAC in diagnosing major SGL within the MSRSGC framework.
Methods: Three decision tree models were created based on probabilities from real-world and literature data. Real-world data was derived from the previously published largest single-center study evaluating FNAC performance of SGL to date. Costs were determined from German and American fee catalogs. Multiple Monte Carlo simulations were run to assess the cost-effectiveness of performing FNAC within the MSRSGC framework under different conditions for both health care systems.
Results: Using decision analysis, FNAC followed by surgery, if indicated, was less costly than upfront surgery. The cost reduction through FNAC was over 30% for all models. Cost reduction per case through FNAC followed by surgery, if indicated, compared to upfront surgery ranged between $5606 and $13,096 in the US model (average costs for upfront surgery: $17,472) and between 2465€ and 5337€ in the German model (average costs for upfront surgery: 8018€). When enhancing the German model with real world data, the cost reduction ranged between 2478€ and 5954€ (average costs for upfront surgery: 7988€).
Conclusion: In this model based on MSRSGC estimates and real-world data, FNAC followed by surgery, if indicated, proved to be a more cost-efficient approach to diagnosing SGL than upfront surgery. Thus, patients and healthcare systems benefit from high-output centers that guarantee expert cytopathological diagnosis.
{"title":"Cost-Effectiveness Analysis of the Milan System for Reporting Salivary Gland Cytopathology in Fine-Needle Aspiration Cytology of Salivary Gland Lesions.","authors":"Louis Jansen, Lisa Nachtsheim, Sofia Kourou, Philipp Wolber, Kariem Sharaf, Kevin Hansen, Sami Shabli, Julia van de Loo, Alexander Quaas, Christoph Arolt, Marianne Engels, Lena Hieggelke, Luc G T Morris, Jens Peter Klussmann, Marcel Mayer","doi":"10.1002/cam4.71579","DOIUrl":"https://doi.org/10.1002/cam4.71579","url":null,"abstract":"<p><strong>Introduction: </strong>Salivary gland lesions (SGL) are a rare and heterogeneous group of benign and malignant masses. Fine-needle aspiration cytology (FNAC), guided by the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC), offers a minimally invasive method for early differentiation of SGL. The purpose of this study was to evaluate the cost-effectiveness of FNAC in diagnosing major SGL within the MSRSGC framework.</p><p><strong>Methods: </strong>Three decision tree models were created based on probabilities from real-world and literature data. Real-world data was derived from the previously published largest single-center study evaluating FNAC performance of SGL to date. Costs were determined from German and American fee catalogs. Multiple Monte Carlo simulations were run to assess the cost-effectiveness of performing FNAC within the MSRSGC framework under different conditions for both health care systems.</p><p><strong>Results: </strong>Using decision analysis, FNAC followed by surgery, if indicated, was less costly than upfront surgery. The cost reduction through FNAC was over 30% for all models. Cost reduction per case through FNAC followed by surgery, if indicated, compared to upfront surgery ranged between $5606 and $13,096 in the US model (average costs for upfront surgery: $17,472) and between 2465€ and 5337€ in the German model (average costs for upfront surgery: 8018€). When enhancing the German model with real world data, the cost reduction ranged between 2478€ and 5954€ (average costs for upfront surgery: 7988€).</p><p><strong>Conclusion: </strong>In this model based on MSRSGC estimates and real-world data, FNAC followed by surgery, if indicated, proved to be a more cost-efficient approach to diagnosing SGL than upfront surgery. Thus, patients and healthcare systems benefit from high-output centers that guarantee expert cytopathological diagnosis.</p>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"15 2","pages":"e71579"},"PeriodicalIF":3.1,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146140521","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}
Zhu You, Tianqi Zhang, Li Dai, Jie Wen, Mingyang Liu, Tengda Zhao, Guozhu Yin, Yihua Wu, Shizhou Zhang
Objectives: To assess the effectiveness and safety of cryoablation for oral mucosal melanoma (OMM) and explore its underlying mechanisms to provide insights for precision treatment of OMM.
Materials and methods: Patients diagnosed with OMM were divided into a cryoablation group and a noncryoablation therapy group. We compared the therapeutic outcomes of these groups and investigated the effects of cryoablation on glycometabolism, the immune microenvironment, and cell death modalities in the OMM.
Results: The study included 32 OMM patients, with 18 in the cryoablation group and 14 in the noncryoablation therapy group. Cryoablation demonstrated high safety and effectiveness, with a postoperative survival rate of 72.22% (13/18). The median overall survival was 85.5 months (95% CI: 57.3-113.6) in the cryoablation group and 72.4 months (95% CI: 51.36-93.4) in the non-cryoablation group. Significant changes in the immune microenvironment, including increased infiltration of CD4+, CD8+, and CD66+ cells and elevated expression of PD-1, PD-L1+, and CTLA4+ immune checkpoints, were observed postcryoablation. Conversely, FOXP3+ and CD19+ cell densities significantly decreased. Additionally, the expression levels of GLUT-1, HIF-1α, and PK-M2 were notably reduced. The primary antitumor effect of cryoablation is attributed to apoptosis.
Conclusion: Cryoablation is an effective treatment for OMM, and its antitumor effects are potentially linked to the modulation of the immune microenvironment, alteration of glucose metabolism, and induction of apoptosis.
{"title":"Effectiveness and Mechanism of Cryoablation in the Treatment of Oral Mucosal Melanoma.","authors":"Zhu You, Tianqi Zhang, Li Dai, Jie Wen, Mingyang Liu, Tengda Zhao, Guozhu Yin, Yihua Wu, Shizhou Zhang","doi":"10.1002/cam4.71577","DOIUrl":"10.1002/cam4.71577","url":null,"abstract":"<p><strong>Objectives: </strong>To assess the effectiveness and safety of cryoablation for oral mucosal melanoma (OMM) and explore its underlying mechanisms to provide insights for precision treatment of OMM.</p><p><strong>Materials and methods: </strong>Patients diagnosed with OMM were divided into a cryoablation group and a noncryoablation therapy group. We compared the therapeutic outcomes of these groups and investigated the effects of cryoablation on glycometabolism, the immune microenvironment, and cell death modalities in the OMM.</p><p><strong>Results: </strong>The study included 32 OMM patients, with 18 in the cryoablation group and 14 in the noncryoablation therapy group. Cryoablation demonstrated high safety and effectiveness, with a postoperative survival rate of 72.22% (13/18). The median overall survival was 85.5 months (95% CI: 57.3-113.6) in the cryoablation group and 72.4 months (95% CI: 51.36-93.4) in the non-cryoablation group. Significant changes in the immune microenvironment, including increased infiltration of CD4+, CD8+, and CD66+ cells and elevated expression of PD-1, PD-L1+, and CTLA4+ immune checkpoints, were observed postcryoablation. Conversely, FOXP3+ and CD19+ cell densities significantly decreased. Additionally, the expression levels of GLUT-1, HIF-1α, and PK-M2 were notably reduced. The primary antitumor effect of cryoablation is attributed to apoptosis.</p><p><strong>Conclusion: </strong>Cryoablation is an effective treatment for OMM, and its antitumor effects are potentially linked to the modulation of the immune microenvironment, alteration of glucose metabolism, and induction of apoptosis.</p>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"15 2","pages":"e71577"},"PeriodicalIF":3.1,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12881701/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146130492","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}
Koji Fujita, Kei Takuma, Mai Nakahara, Hironobu Suto, Asahiro Morishita, Takashi Himoto, Keiichi Okano, Hideki Kobara
Objectives: Progression of hepatocellular carcinoma (HCC) and cardiovascular thrombosis (CVT) has a bidirectional causal relationship. CVT complications will increase in patients with HCC due to etiology shift from viral hepatitis to metabolic dysfunction-related steatohepatitis.
Aim: This study aimed to evaluate the clinical impact of CVT, focusing on patients with HCC treated after transarterial chemoembolization.
Methods: A retrospective cohort study enrolled 402 patients including 79 patients with CVT in a single university hospital. Cox proportional hazard model analysis was performed to identify independent prognostic factors. After adjusting for baseline characteristics by propensity score matching, the survival impact of the CVT complication was evaluated using the Kaplan-Meier curve.
Results: A multivariate analysis determined that CVT complication was an independent risk factor for overall deaths in patients with HCC (HR = 1.751, IQR 1.203-2.548, p < 0.05). Propensity score matching generated a pair of 54-patient cohorts. The median survival time of patients with CVT (1106 days) shortened to half compared to those without CVT (2707 days, HR = 2.298, IQR: 1.399-4.169, p = 0.0020). While recurrence-free survival was not significantly different (p > 0.05), post-recurrence survival was shorter in patients with CVT (2150 days vs. 1008 days, HR = 1.945, IQR: 1.150-3.740, p = 0.0188).
Conclusions: Assuming that the expected life expectancy is only half that of uncomplicated cases of CVT, CVT might be a major prognostic factor in patients with HCC, following tumor burden and functional hepatic reserve.
目的：肝细胞癌（HCC）的进展与心血管血栓形成（CVT）存在双向因果关系。由于病因从病毒性肝炎转变为代谢功能障碍相关的脂肪性肝炎，HCC患者的CVT并发症将增加。目的：本研究旨在评估CVT的临床影响，重点关注经动脉化疗栓塞治疗的HCC患者。方法：回顾性队列研究纳入402例患者，其中79例为CVT。采用Cox比例风险模型分析确定独立预后因素。通过倾向评分匹配调整基线特征后，使用Kaplan-Meier曲线评估CVT并发症对生存的影响。结果：多因素分析确定CVT并发症是HCC患者总死亡的独立危险因素（HR = 1.751, IQR = 1.203 ~ 2.548, p 0.05）， CVT患者复发后生存时间较短（2150天比1008天，HR = 1.945, IQR: 1.150 ~ 3.740, p = 0.0188）。结论：假设预期寿命仅为无并发症CVT患者的一半，CVT可能是HCC患者预后的主要因素，仅次于肿瘤负荷和肝脏功能储备。
{"title":"The Clinical Impact of Cardiovascular Thrombosis on Overall Survival in Patients With Hepatocellular Carcinoma After Transarterial Chemoembolization.","authors":"Koji Fujita, Kei Takuma, Mai Nakahara, Hironobu Suto, Asahiro Morishita, Takashi Himoto, Keiichi Okano, Hideki Kobara","doi":"10.1002/cam4.71594","DOIUrl":"https://doi.org/10.1002/cam4.71594","url":null,"abstract":"<p><strong>Objectives: </strong>Progression of hepatocellular carcinoma (HCC) and cardiovascular thrombosis (CVT) has a bidirectional causal relationship. CVT complications will increase in patients with HCC due to etiology shift from viral hepatitis to metabolic dysfunction-related steatohepatitis.</p><p><strong>Aim: </strong>This study aimed to evaluate the clinical impact of CVT, focusing on patients with HCC treated after transarterial chemoembolization.</p><p><strong>Methods: </strong>A retrospective cohort study enrolled 402 patients including 79 patients with CVT in a single university hospital. Cox proportional hazard model analysis was performed to identify independent prognostic factors. After adjusting for baseline characteristics by propensity score matching, the survival impact of the CVT complication was evaluated using the Kaplan-Meier curve.</p><p><strong>Results: </strong>A multivariate analysis determined that CVT complication was an independent risk factor for overall deaths in patients with HCC (HR = 1.751, IQR 1.203-2.548, p < 0.05). Propensity score matching generated a pair of 54-patient cohorts. The median survival time of patients with CVT (1106 days) shortened to half compared to those without CVT (2707 days, HR = 2.298, IQR: 1.399-4.169, p = 0.0020). While recurrence-free survival was not significantly different (p > 0.05), post-recurrence survival was shorter in patients with CVT (2150 days vs. 1008 days, HR = 1.945, IQR: 1.150-3.740, p = 0.0188).</p><p><strong>Conclusions: </strong>Assuming that the expected life expectancy is only half that of uncomplicated cases of CVT, CVT might be a major prognostic factor in patients with HCC, following tumor burden and functional hepatic reserve.</p>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"15 2","pages":"e71594"},"PeriodicalIF":3.1,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146140550","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}
Background: Platinum-based two-agent chemotherapy combined with immunotherapy is now the first-line standard of care for extensive-stage small cell lung cancer (ES-SCLC). Further studies are needed to determine whether continuing immunotherapy (IO) can provide benefit in patients whose disease has progressed after first-line treatment. Therefore, we conducted a retrospective study to evaluate the efficacy of continuing IO in patients.
Methods: The study retrospectively collected clinical data of ES-SCLC patients as progressive disease (PD) after receiving first-line treatment with PD-1/PD-L1 inhibitors. According to whether to continue immunotherapy or not, patients were divided into the continuing IO group and the control group. The differences in progression-free survival (PFS2, defined as time from progression on first-line treatment to progression on second-line treatment) and overall survival (OS) between the two groups were compared.
Result: As a result, a total of 489 patients from three cancer centers were enrolled in this study, of which 298 patients were included in the continuing IO group and 191 patients were included in the control group. By analysis, it was found that continuing IO could prolong OS (median: 18.82 months vs. 16.43 months, p = 0.008) and PFS2 (median: 4.13 months vs. 3.77 months, p = 0.04) compared to the control group. In subgroup analyses, continuing immunotherapy led to prolonged survival in patients with an initial efficacy evaluation of the complete response (CR) or partial response (PR). And there was also no difference in survival between the PD-L1 inhibitor group and the PD-1 inhibitor group in the comparison of different ICIs types.
Conclusions: Continuation of immunotherapy after standard first-line immunotherapy plus chemotherapy can improve survival in patients with ES-SCLC.
{"title":"Continuing Immunotherapy Beyond Progression Prolongs the Survival of Patients With Extensive-Stage Small-Cell Lung Cancer: A Multicenter Retrospective Analysis.","authors":"Zhuoran Sun, Yaru Tian, Shuangqing Lu, Jiling Niu, Qingfen Dong, Hui Zhu","doi":"10.1002/cam4.71607","DOIUrl":"https://doi.org/10.1002/cam4.71607","url":null,"abstract":"<p><strong>Background: </strong>Platinum-based two-agent chemotherapy combined with immunotherapy is now the first-line standard of care for extensive-stage small cell lung cancer (ES-SCLC). Further studies are needed to determine whether continuing immunotherapy (IO) can provide benefit in patients whose disease has progressed after first-line treatment. Therefore, we conducted a retrospective study to evaluate the efficacy of continuing IO in patients.</p><p><strong>Methods: </strong>The study retrospectively collected clinical data of ES-SCLC patients as progressive disease (PD) after receiving first-line treatment with PD-1/PD-L1 inhibitors. According to whether to continue immunotherapy or not, patients were divided into the continuing IO group and the control group. The differences in progression-free survival (PFS2, defined as time from progression on first-line treatment to progression on second-line treatment) and overall survival (OS) between the two groups were compared.</p><p><strong>Result: </strong>As a result, a total of 489 patients from three cancer centers were enrolled in this study, of which 298 patients were included in the continuing IO group and 191 patients were included in the control group. By analysis, it was found that continuing IO could prolong OS (median: 18.82 months vs. 16.43 months, p = 0.008) and PFS2 (median: 4.13 months vs. 3.77 months, p = 0.04) compared to the control group. In subgroup analyses, continuing immunotherapy led to prolonged survival in patients with an initial efficacy evaluation of the complete response (CR) or partial response (PR). And there was also no difference in survival between the PD-L1 inhibitor group and the PD-1 inhibitor group in the comparison of different ICIs types.</p><p><strong>Conclusions: </strong>Continuation of immunotherapy after standard first-line immunotherapy plus chemotherapy can improve survival in patients with ES-SCLC.</p>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"15 2","pages":"e71607"},"PeriodicalIF":3.1,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146140489","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}
Huan Zhang, Chenchen Wang, Ju Zhang, Xiaojing Zhu, Jumei Yin, Nuo Yao, Qimeng Pang, Zhihua Liu, Dawei Wu, Zheyi Han, Lei Shang, Yongquan Shi
Background: Coffee consumption has been strongly associated with gastrointestinal cancers, but the relationship is controversial. This study seeks to assess their correlation under different dietary backgrounds considering the substantial impact of the food matrix on the effects of bioactive compounds in coffee.
Methods: We selected 29,422 adults from 2001 to 2018 National Health and Nutrition Examination Survey (NHANES), categorizing their dietary backgrounds based on food groups and dietary patterns for the study.
Results: The results showed that the incidence of gastrointestinal cancers was 6.25‰, and the incidence was higher in participants consuming coffee (p < 0.001). The adjusted ORs (95% CI) for gastrointestinal cancers risk by coffee consumption with specific dietary habits were 0.820 (0.814-0.826) for a low-salt diet, 0.703 (0.695-0.710) for drinking tea, and 0.581 (0.576-0.586) for high vegetable intake. Factor analyses identified three dietary patterns, and participants who scored higher in the "Western Pattern" and "Balanced Pattern" had a reduced risk of gastrointestinal cancers after consuming coffee, with ORs (95% CIs) of 0.753 (0.746-0.760) and 0.963 (0.954-0.972), respectively. In contrast, coffee consumption linked to higher gastrointestinal cancer risk in participants scoring high on "Vegetarian pattern" with an OR (95% CI) of 1.707 (1.692-1.721).
Conclusions: The anti-neoplastic effects of coffee on gastrointestinal cancer are related to dietary background. Based on the findings of this study, we recommend that individuals with dietary patterns classified as "Western" or "Balanced" consume coffee, as it may help reduce the risk of gastrointestinal cancer. Conversely, vegetarians may not experience the same benefits from coffee consumption.
{"title":"Anti-Neoplastic Effects of Coffee on Gastrointestinal Cancer as Influenced by the Dietary Background: A Cross-Sectional Study Based on NHANES 2001-2018.","authors":"Huan Zhang, Chenchen Wang, Ju Zhang, Xiaojing Zhu, Jumei Yin, Nuo Yao, Qimeng Pang, Zhihua Liu, Dawei Wu, Zheyi Han, Lei Shang, Yongquan Shi","doi":"10.1002/cam4.71612","DOIUrl":"10.1002/cam4.71612","url":null,"abstract":"<p><strong>Background: </strong>Coffee consumption has been strongly associated with gastrointestinal cancers, but the relationship is controversial. This study seeks to assess their correlation under different dietary backgrounds considering the substantial impact of the food matrix on the effects of bioactive compounds in coffee.</p><p><strong>Methods: </strong>We selected 29,422 adults from 2001 to 2018 National Health and Nutrition Examination Survey (NHANES), categorizing their dietary backgrounds based on food groups and dietary patterns for the study.</p><p><strong>Results: </strong>The results showed that the incidence of gastrointestinal cancers was 6.25‰, and the incidence was higher in participants consuming coffee (p < 0.001). The adjusted ORs (95% CI) for gastrointestinal cancers risk by coffee consumption with specific dietary habits were 0.820 (0.814-0.826) for a low-salt diet, 0.703 (0.695-0.710) for drinking tea, and 0.581 (0.576-0.586) for high vegetable intake. Factor analyses identified three dietary patterns, and participants who scored higher in the \"Western Pattern\" and \"Balanced Pattern\" had a reduced risk of gastrointestinal cancers after consuming coffee, with ORs (95% CIs) of 0.753 (0.746-0.760) and 0.963 (0.954-0.972), respectively. In contrast, coffee consumption linked to higher gastrointestinal cancer risk in participants scoring high on \"Vegetarian pattern\" with an OR (95% CI) of 1.707 (1.692-1.721).</p><p><strong>Conclusions: </strong>The anti-neoplastic effects of coffee on gastrointestinal cancer are related to dietary background. Based on the findings of this study, we recommend that individuals with dietary patterns classified as \"Western\" or \"Balanced\" consume coffee, as it may help reduce the risk of gastrointestinal cancer. Conversely, vegetarians may not experience the same benefits from coffee consumption.</p>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"15 2","pages":"e71612"},"PeriodicalIF":3.1,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12880880/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146130474","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}
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