European Journal of Cancer最新文献_第7页

Combination of predicted sensitivity to endocrine therapy (SET2,3 index) and the recurrence score® in node-positive breast cancer: Independent validation in the PACS-01 trial 淋巴结阳性乳腺癌预测内分泌治疗敏感性（set2,3指数）和复发评分®的结合：PACS-01试验的独立验证

IF 7.1 1区医学 Q1 ONCOLOGY

European Journal of Cancer

Pub Date : 2025-12-01 DOI: 10.1016/j.ejca.2025.116152

Frédérique Penault-Llorca , Amelie Lusque , Thomas Filleron , Kevin Tran , Lili Du , Rick Baehner , Florence Dalenc , Magali Lacroix-Triki , Thomas Bachelot , Fabrice Andre , Pascal Boucher , Jérôme Lemonnier , W. Fraser Symmans

Aim

To independently confirm whether the combination of sensitivity to endocrine therapy (SET2,3) index and Recurrence Score® (RS) improves prognostic assessment for patients with hormone receptor-positive (HR+) lymph node-positive (LN+) breast cancer. Secondly, to evaluate SET_ER/PR index, the component of SET2,3 that measures endocrine transcriptional activity.

Methods

HR+ tumor samples from the PACS-01 trial were tested for RS and SET2,3 index. Pre-defined cut points defined high-risk if RS > 25 or SET2,3 < 2.10. The primary analysis assessed 8-year distant recurrence-free interval (DRFI) in patients who received endocrine therapy (ET). Hazard ratios were calculated with 95 % confidence interval (HR, 95 %CI) from multivariable Cox proportional hazards models, with two-sided tests and nominal significance at p < 0.05.

Results

RS and SET2,3 results were available from 659 patients including 490 who received ET. Primary multivariable analysis showed that SET2,3 status added significant prognostic information to RS status (SET2,3: HR 0.29, 95 %CI 0.18–0.47; RS: HR 2.62, 1.62–4.25). SET2,3 and RS status were discordant in 27 % of patients. Among those, DRFI rate at 8 years was 22 % higher in patients with high SET2,3 despite high-risk RS (80.5 % versus 58.5 %), and 17.2 % lower with low SET2,3 despite low-risk RS (77.3 % versus 94.5 %). The SET_ER/PR index predicted the ET effect on DRFI (P_interaction <0.001) and added prognostic information to RS in ET subset (SET_ER/PR: HR 0.58, 95 %CI 0.36–0.91).

Conclusion

SET2,3 improved prognostic assessment by RS, with its SET_ER/PR index component adding significant endocrine-predictive information to RS in the patients who received ET.

Trial Registration

PACS-01

目的：独立证实联合内分泌治疗敏感性（set2,3）指数和复发评分（RS）是否能改善激素受体阳性（HR+）淋巴结阳性（LN+）乳腺癌患者的预后评估。其次，评估SET2、3中衡量内分泌转录活性的组成部分SETER/PR指数。方法：对PACS-01试验HR+ 肿瘤标本进行RS和set2,3指数检测。如果RS > 25或set2,3 ，则预定义的切点定义为高风险。结果：来自659例患者的RS和set2,3结果，其中490例接受ET治疗。主要多变量分析显示，set2,3状态为RS状态提供了显著的预后信息（set2,3: HR 0.29, 95 %CI 0.18-0.47; RS: HR 2.62, 1.62-4.25）。27. %的患者SET2、3和RS状态不一致。其中，高SET2,3的患者8年DRFI率比高危RS高22. %(80.5 %比58.5% %)，低SET2,3的患者8年DRFI率比低风险RS低17.2% %（77.3% %比94.5 %）。SETER/PR指数预测ET对DRFI的影响（p - interaction ER/PR: HR 0.58, 95 %CI 0.36-0.91）。结论：set2,3改善了RS的预后评估，其SETER/PR指数成分为接受et患者的RS提供了重要的内分泌预测信息。

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引用次数: 0

Successful treatment of durvalumab-induced psoriasis in an HBV-positive lung cancer patient with Risankizumab: A novel case report 瑞尚单抗成功治疗durvalumab诱导的hbv阳性肺癌患者牛皮癣：一个新的病例报告。

IF 7.1 1区医学 Q1 ONCOLOGY

European Journal of Cancer

Pub Date : 2025-12-01 DOI: 10.1016/j.ejca.2025.116156

Davide Fattore, Francesca Futura Bernardi, Gianluca Esposito, Matteo Megna

引用次数: 0

Garsorasib in patients with KRAS G12C-mutated non-small-cell lung cancer: A pooled analysis of phase 1/2 study Garsorasib治疗KRAS g12c突变的非小细胞肺癌：1/2期研究的汇总分析

IF 7.1 1区医学 Q1 ONCOLOGY

European Journal of Cancer

Pub Date : 2025-11-29 DOI: 10.1016/j.ejca.2025.116153

Zhengbo Song , Ziming Li , Yiping Zhang , Pingli Wang , Liyan Jiang , Yanqiu Zhao , Jianying Zhou , Xicheng Wang , Wu Zhuang , Jianhua Shi , Dingzhi Huang , Xiaomin Dang , Shundong Cang , Yi Gong , Shi Jin , Weiwei Li , Xiaorong Dong , Junping Zhang , Mingfang Zhao , Xiangjiao Meng , Shun Lu

Introduction

Garsorasib, a KRAS G12C inhibitor, has previously demonstrated its efficacy and safety in patients with KRAS G12C-mutated non-small-cell lung cancer (NSCLC). Here, we present long-term follow-up data from a pooled analysis of the phase 1/2 study.

Methods

This multicenter, open-label phase 1/2 study enrolled patients with KRAS G12C-mutated, locally advanced or metastatic NSCLC. The primary endpoints for phase 1 were safety and tolerability and for phase 2 objective response rate (ORR) by a blinded independent review committee per RECIST version 1.1. Data was pooled from patients who received garsorasib 600 mg twice daily.

Results

This pooled dataset included 189 patients (N = 66 in phase 1 and N = 123 in phase 2). The median pooled follow-up time was 13.0 months (IQR: 6.7–17.5). The objective response rate was 48.1 % (95 %CI: 40.8–55.5), and disease control rate was 87.8 % (95 %CI: 82.3–92.1). The median duration of response was 12.45 months (95 % CI: 8.31, 14.49), the median progression-free survival was 9.07 months (95 %CI: 7.39–9.76), and the median overall survival was 14.19 months (95 %CI: 13.08–17.54). Treatment-related adverse events of any grade occurred in 96.3 % of patients, with grade ≥ 3 in 49.2 % of patients. No new safety findings were observed, and most of the adverse events were controllable.

Conclusion

This pooled analysis confirmed the robust efficacy and manageable safety of garsorasib in KRAS G12C-mutated NSCLC.

ClinicalTrials.gov Identifier

NCT05383898

Garsorasib是一种KRAS G12C抑制剂，此前已证明其对KRAS G12C突变的非小细胞肺癌（NSCLC）患者的有效性和安全性。在这里，我们提供了来自1/2期研究的汇总分析的长期随访数据。方法：这项多中心、开放标签的1/2期研究纳入了KRAS g12c突变、局部晚期或转移性非小细胞肺癌患者。第一阶段的主要终点是安全性和耐受性，第二阶段的客观缓解率（ORR）由一个盲法独立审查委员会根据RECIST 1.1版进行评估。数据来自每天两次接受garsorasib 600 mg的患者。结果：该合并数据集包括189例患者（N = 66在一期，N = 123在二期）。中位合并随访时间为13.0个月（IQR: 6.7-17.5）。客观有效率为48.1 %(95 %CI: 40.8 ~ 55.5)，疾病控制率为87.8 %（95 %CI: 82.3 ~ 92.1）。中位缓解持续时间为12.45个月（95 %CI: 8.31, 14.49），中位无进展生存期为9.07个月（95 %CI: 7.39-9.76），中位总生存期为14.19个月（95 %CI: 13.08-17.54）。96.3 %的患者发生任何级别的治疗相关不良事件，49.2% %的患者发生≥ 3级的不良事件。没有观察到新的安全性发现，大多数不良事件是可控的。结论：本汇总分析证实了garsorasib治疗KRAS g12c突变的NSCLC的强大疗效和可管理的安全性。临床试验：政府标识符：NCT05383898。

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引用次数: 0

Quantitative spatial profiling of PD-1/PD-L1 and TIGIT/CD155 interaction indicates poor survival outcome and resistance to adjuvant chemotherapy in pancreatic adenosquamous carcinoma PD-1/PD-L1和TIGIT/CD155相互作用的定量空间分析表明，胰腺腺鳞癌患者的生存预后较差，对辅助化疗有耐药性。

IF 7.1 1区医学 Q1 ONCOLOGY

European Journal of Cancer

Pub Date : 2025-11-29 DOI: 10.1016/j.ejca.2025.116159

Xianlong Chen , Shanyue Sun , Shuofeng Li , Shuangni Yu , Jie Chen , Xinyuan Chen , Xiaohua Shi , Zhiyong Liang

Background

Pancreatic adenosquamous carcinoma (PASC) is a rare, highly aggressive pancreatic cancer. Its therapeutic response varies, presumably due to tumor microenvironment (TME) complexity.

Methods

We investigated whether using multiparameter algorithms to measure key immunosuppressive mechanisms in the TME could identify strong predictors of survival and response to adjuvant chemotherapy (ACT). Pre-treatment tumor tissues from 120 patients with PASC were stained using multiplexed quantitative immunofluorescence (training cohort: 92 patients; validation cohort: 28 patients). Novel Automated Quantitative Analysis (AQUA) algorithms were used for spatial profiling of biomarker-positive cells. Biomarker co-localization was determined in pathologist-selected tumor regions. The impact of certain biomarker signatures, including TIGIT/CD155 co-expression and PD-1/PD-L1 interaction scores, on survival outcomes and response to ACT was determined.

Results

In the training cohort, PD-1/PD-L1 colocalization scores were significantly associated with advanced AJCC stage and perineural invasion. A TME with high PD-1/PD-L1 and TIGIT/CD155 co-localization scores represented a unique subtype, characterized by decreased cytotoxic T cell and increased suppressive immune checkpoint molecule levels. High PD-1/PD-L1 and TIGIT/CD155 co-localization scores were independent indicators of worse survival outcomes. Additionally, patients with low TIGIT/CD155 colocalization scores were more likely to benefit from ACT. These findings were reproducible in the external validation cohort.

Conclusions

Quantitative spatial profiling of the PD-1/PD-L1 and TIGIT/CD155 suppression pathways using novel AQUA algorithms could help predict patient outcomes and ACT responses reliably, guiding development of more effective personalized management for PASC.

背景：胰腺腺鳞癌（PASC）是一种罕见的、高度侵袭性的胰腺癌。其治疗反应各不相同，可能是由于肿瘤微环境（TME）的复杂性。方法：我们研究了使用多参数算法来测量TME中关键的免疫抑制机制是否可以识别出生存和对辅助化疗（ACT）反应的强预测因子。120例PASC患者的治疗前肿瘤组织采用多重定量免疫荧光染色（训练组92例，验证组28例）。新的自动定量分析（AQUA）算法用于生物标志物阳性细胞的空间分析。在病理选择的肿瘤区域确定生物标志物共定位。确定了某些生物标志物特征，包括TIGIT/CD155共表达和PD-1/PD-L1相互作用评分，对生存结果和对ACT的反应的影响。结果：在训练队列中，PD-1/PD-L1共定位评分与晚期AJCC分期和神经周围侵犯显著相关。具有高PD-1/PD-L1和TIGIT/CD155共定位评分的TME代表了一种独特的亚型，其特征是细胞毒性T细胞减少和抑制性免疫检查点分子水平增加。高PD-1/PD-L1和TIGIT/CD155共定位评分是较差生存结果的独立指标。此外，TIGIT/CD155共定位评分较低的患者更有可能从ACT中获益。这些发现在外部验证队列中是可重复的。结论：使用新型AQUA算法对PD-1/PD-L1和TIGIT/CD155抑制通路进行定量空间分析，有助于可靠地预测患者预后和ACT反应，指导PASC更有效个性化管理的发展。

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引用次数: 0

A scalable natural language processing framework for drug repurposing in chemotherapy-induced adverse events from clinical narrative records 一个可扩展的自然语言处理框架，用于从临床叙述记录中对化疗引起的不良事件进行药物再利用

IF 7.1 1区医学 Q1 ONCOLOGY

European Journal of Cancer

Pub Date : 2025-11-29 DOI: 10.1016/j.ejca.2025.116157

Masami Tsuchiya , Mari Inoue , Yoshimasa Kawazoe , Kiminori Shimamoto , Tomohisa Seki , Shungo Imai , Hayato Kizaki , Emiko Shinohara , Shuntaro Yada , Shoko Wakamiya , Eiji Aramaki , Satoko Hori

Background

Preventing chemotherapy-related adverse events (AEs) remains an unmet clinical challenge. Preclinical studies have suggested protective effects of several existing agents, but translation into human evidence has been limited. We aimed to establish proof of concept (PoC) for drug repurposing by applying a natural language processing (NLP)-based framework to electronic health record (EHR) narratives, thereby bridging preclinical findings with clinical validation.

Methods

We retrospectively analyzed 56,326 patients with cancer treated at the University of Tokyo Hospital (2004–2023). A transformer-based NLP model extracted symptomatic AEs from clinical notes. Candidate preventive drugs identified from preclinical evidence were assessed using propensity score matching and Cox proportional hazards models. We evaluated angiotensin II receptor blockers (ARBs) for fluoropyrimidine-induced oral mucositis and ramelteon for platinum-induced peripheral neuropathy, with laxatives serving as a negative control.

Results

NLP demonstrated high accuracy (precision 0.81–0.83; recall 0.95–0.97). After matching, ARB co-administration was significantly associated with reduced mucositis incidence (hazard ratio [HR] 0.58, 95 % confidence interval [CI] 0.44–0.77; P < 0.001), representing a clinical PoC consistent with mechanistic preclinical data. Ramelteon showed an exploratory protective signal against neuropathy (HR 0.60, 95 % CI:0.38–0.93; P = 0.024). No preventive association was observed for laxatives.

Conclusions

This study introduces a scalable NLP-epidemiology framework for non-invasive, real-world validation of drug repurposing candidates. The ARB finding provides human-level PoC evidence supporting prospective clinical testing, while the ramelteon signal warrants further exploration. Our approach demonstrates how EHR narratives can operationalize translational research, prioritizing safe, accessible agents for improving the tolerability of cancer treatment.

背景：预防化疗相关不良事件（ae）仍然是一个未解决的临床挑战。临床前研究表明，几种现有药物具有保护作用，但转化为人类证据的效果有限。我们的目标是通过将基于自然语言处理（NLP）的框架应用于电子健康记录（EHR）叙述，从而建立药物再利用的概念验证（PoC），从而将临床前发现与临床验证联系起来。方法回顾性分析2004-2023年在东京大学医院接受治疗的56,326例癌症患者。基于变压器的NLP模型从临床记录中提取症状性ae。从临床前证据中确定的候选预防药物使用倾向评分匹配和Cox比例风险模型进行评估。我们评估了血管紧张素II受体阻滞剂（ARBs）治疗氟嘧啶诱导的口腔黏膜炎和拉美替宁治疗铂诱导的周围神经病变，泻药作为阴性对照。结果snlp具有较高的准确度（精密度0.81 ~ 0.83，召回率0.95 ~ 0.97）。匹配后，ARB联合给药与降低黏膜炎发生率显著相关（风险比[HR] 0.58, 95 %可信区间[CI] 0.44-0.77; P <； 0.001），表明临床PoC与临床前机制数据一致。Ramelteon显示出探索性的神经病变保护信号（HR 0.60, 95 % CI: 0.38-0.93; P = 0.024）。没有观察到泻药的预防作用。本研究引入了一个可扩展的nlp -流行病学框架，用于对药物再利用候选药物进行无创、真实的验证。ARB的发现为人类水平的PoC提供了支持前瞻性临床试验的证据，而ramelteon信号值得进一步探索。我们的方法展示了电子病历叙述如何能够使转化研究操作化，优先考虑安全、可获得的药物，以提高癌症治疗的耐受性。

{"title":"A scalable natural language processing framework for drug repurposing in chemotherapy-induced adverse events from clinical narrative records","authors":"Masami Tsuchiya , Mari Inoue , Yoshimasa Kawazoe , Kiminori Shimamoto , Tomohisa Seki , Shungo Imai , Hayato Kizaki , Emiko Shinohara , Shuntaro Yada , Shoko Wakamiya , Eiji Aramaki , Satoko Hori","doi":"10.1016/j.ejca.2025.116157","DOIUrl":"10.1016/j.ejca.2025.116157","url":null,"abstract":"<div><h3>Background</h3><div>Preventing chemotherapy-related adverse events (AEs) remains an unmet clinical challenge. Preclinical studies have suggested protective effects of several existing agents, but translation into human evidence has been limited. We aimed to establish proof of concept (PoC) for drug repurposing by applying a natural language processing (NLP)-based framework to electronic health record (EHR) narratives, thereby bridging preclinical findings with clinical validation.</div></div><div><h3>Methods</h3><div>We retrospectively analyzed 56,326 patients with cancer treated at the University of Tokyo Hospital (2004–2023). A transformer-based NLP model extracted symptomatic AEs from clinical notes. Candidate preventive drugs identified from preclinical evidence were assessed using propensity score matching and Cox proportional hazards models. We evaluated angiotensin II receptor blockers (ARBs) for fluoropyrimidine-induced oral mucositis and ramelteon for platinum-induced peripheral neuropathy, with laxatives serving as a negative control.</div></div><div><h3>Results</h3><div>NLP demonstrated high accuracy (precision 0.81–0.83; recall 0.95–0.97). After matching, ARB co-administration was significantly associated with reduced mucositis incidence (hazard ratio [HR] 0.58, 95 % confidence interval [CI] 0.44–0.77; <em>P</em> < 0.001), representing a clinical PoC consistent with mechanistic preclinical data. Ramelteon showed an exploratory protective signal against neuropathy (HR 0.60, 95 % CI:0.38–0.93; <em>P</em> = 0.024). No preventive association was observed for laxatives.</div></div><div><h3>Conclusions</h3><div>This study introduces a scalable NLP-epidemiology framework for non-invasive, real-world validation of drug repurposing candidates. The ARB finding provides human-level PoC evidence supporting prospective clinical testing, while the ramelteon signal warrants further exploration. Our approach demonstrates how EHR narratives can operationalize translational research, prioritizing safe, accessible agents for improving the tolerability of cancer treatment.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"232 ","pages":"Article 116157"},"PeriodicalIF":7.1,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145681552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Trends in organ preservation in rectal cancer management: A population-based study in the Netherlands 直肠癌管理中器官保存的趋势：荷兰一项基于人群的研究。

IF 7.1 1区医学 Q1 ONCOLOGY

European Journal of Cancer

Pub Date : 2025-11-29 DOI: 10.1016/j.ejca.2025.116154

A. Darai , S. de Vries , G.L. Beets , I.D. Nagtegaal , A.C. Couwenberg , L.M.G. Moons , F.N. van Erning , P.A.J. Vissers , J.H.W. de Wilt , B.A. Grotenhuis

Introduction

This population-based study aims to provide an overview of organ preservation (OP) trends in rectal cancer treatment in the Netherlands.

Materials and methods

Data from patients with non-metastatic stage I–III rectal cancer, diagnosed between 2009–2023 and recorded in the Netherlands Cancer Registry (NCR), were analysed. Trends in treatment patterns and OP rates were assessed across different therapeutic modalities and time periods. OP was defined as the avoidance of radical TME surgery during primary treatment.

Results

Treatment strategies for 44 579 patients with stage I–III rectal cancer were analysed, of whom 12 407 (26.3 %) underwent primary TME-surgery. Primary local excision (LE) was performed in 7 132 (16.0 %) patients, increasing from 236 (8.6 %) patients in 2009–573 (25.3 %) in 2023. Among LE patients, 5 957 (83.5 %) achieved OP, while 1 175 (16.5 %) underwent additional TME resection. Initial treatment with (chemo)radiation was administered to 25,040 (53.2 %) patients, resulting in OP for 4 885 (19.5 %) patients: 4 337 treated with (chemo)radiation alone. After (chemo)radiation, 20 139 (80.4 %) underwent TME, of whom 2 014 (10.0 %) had ypT0N0 and 1 222 (6.1 %) had ypT1N0 tumours. There was an increasing trend in OP after (chemo)radiation from 6.6 % in 2009–44.9 % in 2023. Overall, OP rates for rectal cancer patients increased from 9.6 % in 2009–40.9 % in 2023.

Discussion

This study highlights a paradigm shift in primary rectal cancer treatment in the Netherlands, driven by the gradual implementation of organ-preserving strategies. In 2023, more than 40 % of rectal cancer patients reached OP.

引言：这项基于人群的研究旨在概述荷兰直肠癌治疗中的器官保存（OP）趋势。材料和方法：对2009-2023年间诊断并记录在荷兰癌症登记处（NCR）的非转移性I-III期直肠癌患者的数据进行分析。在不同的治疗方式和时间段评估治疗模式和OP率的趋势。OP定义为在初始治疗期间避免根治性TME手术。结果：分析了44579例I-III期直肠癌患者的治疗策略，其中12407例（26.3 %）接受了原发性tme手术。7 132例（16.0 %）患者进行了原发性局部切除（LE）， 2009年为236例（8.6 %），2023年为573例（25.3 %）。在LE患者中，5 957例（83.5 %）实现了手术，而1 175例（16.5 %）接受了额外的TME切除术。对25,040例（53.2 %）患者进行初始（化疗）放疗，其中4 885例（19.5 %）患者发生OP， 4 337例患者单独（化疗）放疗。化疗后，20139例（80.4 %）行TME，其中2014例（10.0 %）为ypT0N0肿瘤，1222例（6.1 %）为ypT1N0肿瘤。化疗后OP有上升趋势，从2009年的6.6 %上升到2023年的44.9 %。总体而言，直肠癌患者的OP率从2009年的9.6 %增加到2023年的40.9 %。讨论：这项研究强调了荷兰原发性直肠癌治疗的范式转变，由器官保存策略的逐步实施推动。2023年，超过40% %的直肠癌患者达到了OP。

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引用次数: 0

Progression-free survival as a surrogate for overall survival in gastro-esophageal cancer trials with immunotherapy: A meta-analysis 免疫治疗胃食管癌试验的无进展生存期替代总生存期：一项荟萃分析

IF 7.1 1区医学 Q1 ONCOLOGY

European Journal of Cancer

Pub Date : 2025-11-29 DOI: 10.1016/j.ejca.2025.116155

Alberto Giovanni Leone , Fausto Petrelli , Samuel J. Klempner , Elizabeth C. Smyth , Raghav Sundar , Florian Lordick , Sylvie Lorenzen , Micheal Masetti , Radka Obermannova , Maria Alsina , Yelena Y. Janjigian , Filippo Pietrantonio

Background

Immune checkpoint inhibitors (ICIs)-based regimens are the first-line standard of care for most patients with advanced gastroesophageal adenocarcinoma (GEA) and esophageal squamous cell carcinoma (ESCC). The efficacy of these treatments often depend on PD-L1 expression levels.

Overall survival (OS) has traditionally been the primary endpoint for evaluating treatment efficacy. Through a meta-analysis, we investigated whether progression-free survival (PFS) is a valid surrogate for OS in the ICIs-era, overall and across different PD-L1 subgroups.

Methods

A systematic literature review was conducted to identify eligible randomized controlled trials (RCTs) published by 30/06/2025. Trial-level surrogacy of PFS for OS was assessed using Spearman rank correlation coefficient (R) and weighted linear regression, calculating the coefficient of determination (R²).

Results

Eighteen eligible RCTs were evaluated. Regarding GEA, the correlation between treatment effects on PFS and on OS was moderate in the overall population (R=0.82; R²=0.52) and in the CPS≥ 1 subgroup (R=0.81; R²=0.66), moderate yet non-significant in the CPS< 1 subgroup (R=0.67; R²=0.51), and strong in the CPS≥ 5 subgroup (R=0.77; R²=0.85). In ESCC, the correlation in the overall population was weak (R=0.64; R²=0.47). No improvement of the correlation was found in the subgroup of patients with CPS≥ 10 (R=0.33; R²=0.16) or TPS≥ 1 % (R=0.40, R²=0.005).

Conclusions

While the correlation between treatment effects on PFS and OS was weak in ESCC, it was moderate in PD-L1-low GEA, and good in PD-L1-high GEA. Therefore, PFS is an adequate co-primary endpoint in future trials investigating novel ICIs—based regimens in GEA, especially if the analyses are pre-planned in PD-L1-high subgroups.

背景：基于免疫检查点抑制剂（ICIs）的方案是大多数晚期胃食管腺癌（GEA）和食管鳞状细胞癌（ESCC）患者的一线护理标准。这些治疗的效果往往取决于PD-L1的表达水平。总生存期（OS）历来是评估治疗疗效的主要终点。通过荟萃分析，我们调查了在icis时代，总体上和不同PD-L1亚组中，无进展生存期（PFS）是否是OS的有效替代指标。方法：对2025年6月30日发表的符合条件的随机对照试验（rct）进行系统文献综述。采用Spearman秩相关系数(R)和加权线性回归评估PFS对OS的试验级替代作用，计算决定系数（R2）。结果：共评估了18项符合条件的随机对照试验。对于GEA，治疗效果对PFS和OS的相关性在总体人群中为中等（R=0.82, R2=0.52），在CPS≥ 1亚组中为中等（R=0.81, R2=0.66），在CPS≥ 5亚组中为中等但不显著（R= 0.51），在CPS≥ 5亚组中为较强（R=0.77, R2=0.85）。在ESCC中，总体人群的相关性较弱（R=0.64; R2=0.47）。在CPS≥ 10 （R=0.33; R2=0.16）或TPS≥ 1 % （R=0.40, R2=0.005）的患者亚组中，相关性未见改善。结论：ESCC患者PFS与OS的相关性较弱，pd - l1低GEA组相关性中等，pd - l1高GEA组相关性较好。因此，PFS是未来研究新的基于icis的GEA方案的试验中适当的共同主要终点，特别是如果分析是预先计划在pd - l1高亚组中进行的。

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引用次数: 0

Prediction of HER2 changes post-neoadjuvant therapy based on fusion of ultrasound radiomics and clinicopathological features empowered by explainable AI: A multicenter study 一项多中心研究：基于超声放射组学和可解释AI的临床病理特征融合预测新辅助治疗后HER2变化

IF 7.1 1区医学 Q1 ONCOLOGY

European Journal of Cancer

Pub Date : 2025-11-29 DOI: 10.1016/j.ejca.2025.116158

Yuqi Yan , Xinzheng Xue , Jiayu Xie , Jian Liu , Lin Sui , Tian Jiang , Zhiyan Jin , Di Ou , Zhirui Chuan , Mingjie Jin , Yang Zhang , Vicky Yang Wang , Xiaomao Luo , Shihao Xu , Dong Xu

Background

Dynamic HER2 expression changes during neoadjuvant therapy (NAT) challenge precision oncology. Current biopsy-dependent evaluation inadequately meets clinical needs for dynamic monitoring. We developed a non-invasive predictive model integrating pretreatment ultrasound radiomics and clinicopathological parameters to forecast post-NAT HER2 status evolution in breast cancer.

Methods

In this multicenter retrospective study (January 2017–May 2023), 655 patients with paired pre- and post-NAT HER2 assessments were enrolled from three institutions. Pretreatment ultrasound images underwent manual tumor segmentation and radiomic feature extraction. Clinicopathological parameters, including baseline HER2 status and NAT regimen, were retrospectively collected. An Ultrasound Image Clinical Feature Fusion (UICFF) framework incorporating attention-guided multimodal feature selection was developed for HER2 transition prediction. Model performance was compared with six classical and two unimodal baselines. Survival outcomes were evaluated using Kaplan–Meier analysis.

Results

Dynamic HER2 alterations occurred in 29.7 %, 34.6 %, and 25.5 % of the training, internal, and external cohorts, respectively. The multimodal UICFF achieved superior discrimination (AUC_internal = 0.811; AUC_external = 0.823), outperforming radiomics-only and clinicopathological-only models (external ΔAUCs: +0.193 and +0.125, respectively). SHapley Additive exPlanations analysis identified age, menopausal status, Ki-67 index, and wavelet-based texture features as dominant predictors. Younger age and larger tumor size were positively associated with HER2 dynamics. Dynamic HER2 changes correlated with improved pathological response to HER2 blockade (58.6 % vs. 38.1 %) but showed no independent effect on 5-year event-free survival.

Conclusions

The interpretable UICFF framework enables individualized, pretreatment prediction of HER2 evolution in patients undergoing NAT, providing a clinically actionable and noninvasive alternative to repeated biopsies.

背景：新辅助治疗（NAT）过程中HER2表达的动态变化对精准肿瘤学提出了挑战。目前依赖活检的评估不足以满足临床动态监测的需要。我们开发了一种非侵入性预测模型，结合预处理超声放射组学和临床病理参数来预测nat后乳腺癌HER2状态的演变。方法在这项多中心回顾性研究（2017年1月- 2023年5月）中，来自三个机构的655名患者进行了配对的nat前和nat后HER2评估。预处理超声图像进行人工肿瘤分割和放射学特征提取。回顾性收集临床病理参数，包括基线HER2状态和NAT方案。超声图像临床特征融合（UICFF）框架结合注意引导的多模态特征选择被开发用于HER2转移预测。将模型性能与6条经典基线和2条单峰基线进行比较。使用Kaplan-Meier分析评估生存结果。结果在培训组、内部组和外部组中，动态HER2改变发生率分别为29.7% %、34.6% %和25.5% %。多模态UICFF取得了较好的鉴别效果（AUC_internal = 0.811; AUC_external = 0.823），优于单纯放射组学模型和单纯临床病理模型（分别为ΔAUCs: +0.193和+0.125）。SHapley加性解释分析发现，年龄、绝经状态、Ki-67指数和基于小波的纹理特征是主要的预测因素。年龄小、肿瘤大小大与HER2动态呈正相关。动态HER2变化与HER2阻断后病理反应的改善相关（58.6 % vs. 38.1 %），但对5年无事件生存无独立影响。结论：可解释的UICFF框架可实现NAT患者HER2演变的个体化预处理预测，为重复活检提供了一种临床可操作且无创的替代方法。

{"title":"Prediction of HER2 changes post-neoadjuvant therapy based on fusion of ultrasound radiomics and clinicopathological features empowered by explainable AI: A multicenter study","authors":"Yuqi Yan , Xinzheng Xue , Jiayu Xie , Jian Liu , Lin Sui , Tian Jiang , Zhiyan Jin , Di Ou , Zhirui Chuan , Mingjie Jin , Yang Zhang , Vicky Yang Wang , Xiaomao Luo , Shihao Xu , Dong Xu","doi":"10.1016/j.ejca.2025.116158","DOIUrl":"10.1016/j.ejca.2025.116158","url":null,"abstract":"<div><h3>Background</h3><div>Dynamic HER2 expression changes during neoadjuvant therapy (NAT) challenge precision oncology. Current biopsy-dependent evaluation inadequately meets clinical needs for dynamic monitoring. We developed a non-invasive predictive model integrating pretreatment ultrasound radiomics and clinicopathological parameters to forecast post-NAT HER2 status evolution in breast cancer.</div></div><div><h3>Methods</h3><div>In this multicenter retrospective study (January 2017–May 2023), 655 patients with paired pre- and post-NAT HER2 assessments were enrolled from three institutions. Pretreatment ultrasound images underwent manual tumor segmentation and radiomic feature extraction. Clinicopathological parameters, including baseline HER2 status and NAT regimen, were retrospectively collected. An Ultrasound Image Clinical Feature Fusion (UICFF) framework incorporating attention-guided multimodal feature selection was developed for HER2 transition prediction. Model performance was compared with six classical and two unimodal baselines. Survival outcomes were evaluated using Kaplan–Meier analysis.</div></div><div><h3>Results</h3><div>Dynamic HER2 alterations occurred in 29.7 %, 34.6 %, and 25.5 % of the training, internal, and external cohorts, respectively. The multimodal UICFF achieved superior discrimination (AUC_internal = 0.811; AUC_external = 0.823), outperforming radiomics-only and clinicopathological-only models (external ΔAUCs: +0.193 and +0.125, respectively). SHapley Additive exPlanations analysis identified age, menopausal status, Ki-67 index, and wavelet-based texture features as dominant predictors. Younger age and larger tumor size were positively associated with HER2 dynamics. Dynamic HER2 changes correlated with improved pathological response to HER2 blockade (58.6 % vs. 38.1 %) but showed no independent effect on 5-year event-free survival.</div></div><div><h3>Conclusions</h3><div>The interpretable UICFF framework enables individualized, pretreatment prediction of HER2 evolution in patients undergoing NAT, providing a clinically actionable and noninvasive alternative to repeated biopsies.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"232 ","pages":"Article 116158"},"PeriodicalIF":7.1,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145681554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Characteristics and quality of life of nine-year survivors with metastatic melanoma treated with pembrolizumab beyond second-line therapy 经派姆单抗治疗的9年转移性黑色素瘤患者的特点和生活质量

IF 7.1 1区医学 Q1 ONCOLOGY

European Journal of Cancer

Pub Date : 2025-11-29 DOI: 10.1016/j.ejca.2025.116149

S. Dugas-Breit , A. Forschner , M. Erdmann , R. Gutzmer , K.C. Kähler , I. Holst , A. Brekner , C. Franklin , A. Sindrilaru , L. Zimmer , L. Heinzerling , J. Utikal , F. Meier , A. Bender , C. Berking , C. Garbe , M. Weichenthal , D. Schadendorf , A. Hauschild , M. Gschnell , J.C. Hassel

Background

Immune checkpoint blockers have improved survival in metastatic melanoma. Long-term quality of life (QoL) and sequelae from immune-related adverse events (irAE) are therefore of increasing importance. This study reports long-term outcomes from a real-world cohort of patients with stage IV melanoma treated with pembrolizumab after progression on ipilimumab and, if indicated, BRAF/MEK inhibition.

Methods

Survival of patients who started treatment with pembrolizumab within the German Expanded Access Program (EAP) were evaluated in Cancer centers that included ≥ 10 patients. For survivors, baseline characteristics, best response and irAEs were assessed retrospectively. In addition, in a cross-sectional approach patients were interviewed for persisting symptoms and QoL (WHO-5, EORTC QLQ-C30).

Results

Of 325 treated patients, 55 (17 %) survived after a median follow-up of 9.1 years. At treatment start, survivors had a median age of 60 years; 60 % were male; 40 % BRAF-mutated; 66 % stage M1c/d. Overall response rate was 89 %, including 69 % complete responses. Progression occurred in 22 (40 %). As of May 2024, 46 (84 %) were disease-free, 7 (13 %) had controlled disease, and 2 (4 %) progressed. IrAEs occurred in 39 (71 %), with 15 (27 %) grade 3/4. Persisting symptoms were reported by 19 (35 %), mainly endocrine insufficiencies, vitiligo, and fatigue. Median WHO-5 score was 76 %, and mean QLQ-C30 global health 70.1. Survivors with prior irAEs had significantly lower QoL (WHO-5, p = 0.026) and social functioning (QLQ-C30, p = 0.046). Of 21 survivors < 65 years (38 %), 11 (20 %) were employed at follow-up.

Conclusion

Pembrolizumab induced long-term survival in a real-world pretreated melanoma cohort. Despite persisting symptoms in one third, QoL, when measured by standard instruments, was good for most survivors nearly a decade after treatment.

免疫检查点阻断剂提高了转移性黑色素瘤的生存率。因此，长期生活质量（QoL）和免疫相关不良事件（irAE）的后遗症变得越来越重要。这项研究报告了一组现实世界IV期黑色素瘤患者的长期结果，这些患者在伊匹单抗进展后接受派姆单抗治疗，如果有指示，则接受BRAF/MEK抑制。方法在癌症中心评估在德国扩展准入计划（EAP）中开始使用pembrolizumab治疗的患者的生存率，包括≥ 10例患者。对于幸存者，回顾性评估基线特征、最佳反应和irae。此外，采用横断面方法对患者进行持续症状和生活质量的访谈（WHO-5, EORTC QLQ-C30）。结果在325例接受治疗的患者中，55例（17. %）在中位随访9.1年后存活。在治疗开始时，幸存者的中位年龄为60岁；60 %为男性；40 % BRAF-mutated;66 %分期M1c/d。总有效率为89 %，包括69 %的完整应答。22例发生进展（40 %）。截至2024年5月，46例（84 %）无病，7例（13 %）病情得到控制，2例（4 %）病情进展。IrAEs发生39例（71 %），其中15例（27 %）为3/4级。19例（35% %）出现持续症状，主要是内分泌不足、白癜风和疲劳。WHO-5评分中位数为76 %，QLQ-C30全球健康平均值为70.1。既往有irae的幸存者的生活质量（WHO-5, p = 0.026）和社会功能（QLQ-C30, p = 0.046）显著降低。在21名幸存者中（ 65岁）（38 %），11名（20 %）接受随访。结论：pembrolizumab在现实世界预处理黑色素瘤队列中诱导长期生存。尽管三分之一的患者持续出现症状，但用标准仪器测量，大多数幸存者在治疗后近十年的生活质量都很好。

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引用次数: 0

Corrigendum to “Epithelial head and neck cancer survival in Europe: Geographical variation, time trends and long term survival” Eur J Cancer 229 (October) (2025) 115692 “欧洲上皮性头颈癌生存率：地理差异、时间趋势和长期生存率”Eur J cancer 229（10月）（2025）115692的勘误

IF 7.1 1区医学 Q1 ONCOLOGY

European Journal of Cancer

Pub Date : 2025-11-29 DOI: 10.1016/j.ejca.2025.116147

G. Gatta , S. Luttmann , A. Trama , S. Rossi , J. Galceran , K. Innos , M. Guevara , L. Licitra , D. Bennet , D. Redondo-Sánchez , R. Capocaccia

引用次数: 0