Lung Cancer最新文献_第6页

External evaluation of the Manchester score in a contemporary SCLC cohort 当代SCLC队列中曼彻斯特评分的外部评价。

IF 4.4 2区医学 Q1 ONCOLOGY

Lung Cancer

Pub Date : 2025-12-23 DOI: 10.1016/j.lungcan.2025.108884

Charlie Cunniffe , Matthew Sperrin , Gerard Walls , Fiona Blackhall , Gareth Price

Objectives

The Manchester Score, a prognostic model developed in 1987, was used to stratify patients with Small Cell Lung Cancer (SCLC) by mortality risk, including stage, performance status, and three blood tests as risk factors. Many tools have since been developed for this purpose, but few have seen clinical use, with lack of robust external validation frequently cited as a barrier. In this study we apply a robust and pragmatic external validation approach to the Manchester Score to understand if it remains valid in an unselected modern patient cohort.

Methods

SCLC patients treated in an academic centre between 2013 and 2022 (N = 1783) were included in the validation cohort. Discrimination was assessed using Kaplan-Meier curves, AUC, and Harrell’s C-index for the Manchester score and its underlying Cox model. Three levels of Cox model updating were used to address missing baseline hazard data: recalibration, recalibration with rescaling, and model refitting. Calibration was then evaluated with optimism adjustment at 6-, 12-, and 24-months post-diagnosis.

Results

The Manchester score shows good discrimination in the modern patient cohort. There is clear separation between risk groups in the Kaplan-Meier curves, with AUC = 0.75 and C-index = 0.68 for the Manchester Score and (AUC = 0.79, C-index = 0.70) for the underlying Cox model. Median survival in the ‘good’ prognostic group (meeting < 2/5 risk criteria) has increased compared to that from 1987. All model updating methods reported good calibration, with recalibration alone providing the best observed-to-expected ratio at 6 months (1.012 [0.978,1.045]).

Conclusion

The original Manchester Score prognostic groups remain discriminative of survival, and when updated can predict survival probability at multiple timepoints.

目的：曼彻斯特评分是1987年开发的一种预后模型，用于根据死亡风险对小细胞肺癌（SCLC）患者进行分层，包括分期、表现状态和三种血液检查作为危险因素。此后，为此目的开发了许多工具，但很少有临床应用，缺乏可靠的外部验证经常被认为是一个障碍。在这项研究中，我们应用了一个强大的和务实的外部验证方法来曼彻斯特评分，以了解它是否仍然有效，在一个未选择的现代患者队列。方法：将2013年至2022年间在某学术中心接受治疗的SCLC患者（N = 1783）纳入验证队列。使用Kaplan-Meier曲线、AUC和Harrell的曼彻斯特评分c指数及其基础Cox模型来评估歧视。三个级别的Cox模型更新被用来解决缺失的基线危险数据：重新校准、重新校准和重新调整模型。然后在诊断后6个月、12个月和24个月用乐观调整对校准进行评估。结果：曼彻斯特评分在现代患者队列中具有良好的辨别性。Kaplan-Meier曲线中风险组之间存在明显的分离，Manchester Score的AUC = 0.75, C-index = 0.68，基础Cox模型的AUC = 0.79, C-index = 0.70。结论：最初的曼彻斯特评分预后组仍然具有判别生存的能力，更新后可以预测多个时间点的生存概率。

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引用次数: 0

Tarlatamab in routine clinical care: How much safety is enough? 塔拉他单抗在常规临床护理中的应用：多少安全性才足够？

IF 4.4 2区医学 Q1 ONCOLOGY

Lung Cancer

Pub Date : 2025-12-23 DOI: 10.1016/j.lungcan.2025.108888

Ernest Nadal , Jordi Bruna

引用次数: 0

Locoregional therapies in advanced and recurrent pleural mesothelioma: A systematic review 晚期和复发胸膜间皮瘤的局部治疗：一项系统综述

IF 4.4 2区医学 Q1 ONCOLOGY

Lung Cancer

Pub Date : 2025-12-17 DOI: 10.1016/j.lungcan.2025.108877

Paolo Ambrosini , Thierry Berghmans , Mario Occhipinti , Valérie Durieux , Paul Van Schil , Arnaud Scherpereel , Andrea Riccardo Filippi , Mariana Brandão

Background

Locoregional therapies, including radiotherapy, surgery and other ablative techniques, are occasionally used as strategies to manage oligorecurrent or oligoprogressive pleural mesothelioma. Yet, their real-world utilization, safety and efficacy remain poorly defined.

Methods

We conducted a systematic review in accordance with PRISMA guidelines. A search was conducted in MEDLINE, Scopus, Academic Search Premier and ProQuest Central up to June 2025 for retrospective and prospective studies of surgical cytoreduction, radiotherapy, or other local interventions in oligorecurrent or oligoprogressive pleural mesothelioma. Data on patient demographics, treatment protocols, local control (LC), progression-free survival (PFS), overall survival (OS) and toxicity were extracted and synthesized descriptively.

Results

A total of 22 studies, all retrospective, encompassing 234 patients, were included. Radiotherapy series (n = 142 patients) reported one-year LC rates ranging from 73.5 to 100 %, a median PFS of 5.1–8.0 months, a median OS of 26.9–38.0 months and grade 3–4 toxicities in ≤ 13 % of patients. Surgical series of oligorecurrences (n = 67 patients) demonstrated OS ranging from 14.5 to 44.6 months, with rare long-term survivors after distant resections. A single series of percutaneous cryoablation (n = 24 patients) achieved a 90.8 % local recurrence free-survival rate at one year with minimal toxicity; a single radiofrequency ablation case yielded a 24-month PFS.

Conclusions

Retrospective evidence suggests that locoregional interventions can achieve long-term local control and acceptable safety in selected pleural mesothelioma patients with oligorecurrent or oligoprogressive disease. Prospective trials are warranted to establish optimal patient selection and strategies integrating these approaches into standard care.

背景局部治疗，包括放疗、手术和其他消融技术，偶尔被用作治疗少复发或少进展胸膜间皮瘤的策略。然而，它们在现实世界中的应用、安全性和有效性仍不明确。方法按照PRISMA指南进行系统评价。截至2025年6月，MEDLINE、Scopus、Academic search Premier和ProQuest Central进行了一项关于手术细胞减少、放疗或其他局部干预治疗少复发或少进展胸膜间皮瘤的回顾性和前瞻性研究。提取并描述性地合成了患者人口统计学、治疗方案、局部控制（LC）、无进展生存（PFS）、总生存（OS）和毒性的数据。结果共纳入22项研究，均为回顾性研究，纳入234例患者。放疗系列（n = 142例）报告一年LC率为73.5%至100%，中位PFS为5.1-8.0个月，中位OS为26.9-38.0个月，≤13%的患者毒性为3-4级。手术系列的少复发（n = 67例）显示了14.5至44.6个月的OS，在远处切除后很少有长期存活。单一系列经皮冷冻消融（n = 24例）在一年内获得90.8%的局部无复发生存率，毒性最小；一个射频消融病例获得了24个月的PFS。结论回顾性证据表明，局部干预可以实现长期的局部控制和可接受的安全性，在选定的胸膜间皮瘤患者少复发或少进展。有必要进行前瞻性试验，以建立最佳的患者选择和策略，将这些方法整合到标准护理中。

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引用次数: 0

Neighborhood matters: Predicting lung cancer screening adherence with explainable AI 邻里关系：用可解释的人工智能预测肺癌筛查依从性。

IF 4.4 2区医学 Q1 ONCOLOGY

Lung Cancer

Pub Date : 2025-12-17 DOI: 10.1016/j.lungcan.2025.108882

Kun-Han Lu , Yi Xiao , Aamna Akhtar , Jazma Tapia , Calvin P. Tribby , Peter Vien , Naj Boucher , Termisha Pete , David M. Kadar , Viviana Rosales , Cherry Lee , WingYin Lau , Sophia Yueng , Jonjon Macalintal , Jiue-An Yang , Marta Jankowska , Chi Wah Wong , Loretta Erhunmwunsee

Background

This study builds a predictive model for lung cancer screening (LCS) adherence using social determinants of health (SDOH) data in high-risk populations. By identifying key factors influencing non-adherence, we seek to improve risk stratification for individuals less likely to complete annual LCS follow-up scans within 15-months.

Methods

We recruited 188 minoritized individuals meeting high-risk smoking pack year criteria who underwent their first low-dose computed tomography (LDCT) scan between 2017 and 2021 at four clinical centers in Los Angeles County. Participants completed an IRB-approved survey assessing demographics, tobacco use, social needs, discrimination, and lung cancer risk perception. Residential address at time of first LDCT was geocoded to match with neighborhood-level SDOH metrics. The data were split into training (N = 145) and testing cohorts (N = 43) by whether individuals received their initial LDCT by June 30, 2021. Electronic medical records were checked for LDCT follow-up within 15 months of initial LCS. Those who underwent the subsequent LDCT within 15 months of the initial LCS were considered adherent. We trained an XGBoost classifier with hyperparameter tuning and performed SHapley Additive exPlanations (SHAP) analysis to interpret model predictions.

Results

The cohort included 69 (37 %) Asian/Pacific Islander, 53 (28 %) Black/African American, and 49 (26 %) Hispanic/Latino participants. The LCS non-adherence rate was 66 %. The XGBoost classifier achieved an AUROC of 0.81 and AUPRC of 0.90, with prediction performance of accuracy = 0.79, recall = 0.78, specificity = 0.81, positive predictive value = 0.88, and negative predictive value = 0.68. SHAP analysis indicated that neighborhood-level SDOH factors, such as school proficiency and poverty levels, were more predictive of non-adherence than individual-level factors like smoking status.

Conclusions

This machine learning approach accurately predicted LCS non-adherence using individual- and neighborhood-level SDOH factors. These findings emphasize the relevance of community-level characteristics in informing LCS adherence interventions and may support the development of regionally tailored strategies to improve adherence in high-risk populations.

背景：本研究利用健康社会决定因素（SDOH）数据在高危人群中建立了肺癌筛查（LCS）依从性的预测模型。通过确定影响不依从性的关键因素，我们寻求改善不太可能在15个月内完成年度LCS随访扫描的个体的风险分层。方法：我们招募了188名符合高危吸烟包年标准的少数族裔个体，他们于2017年至2021年在洛杉矶县的四个临床中心接受了第一次低剂量计算机断层扫描（LDCT）扫描。参与者完成了一项irb批准的调查，评估人口统计学、烟草使用、社会需求、歧视和肺癌风险认知。第一次LDCT时的住宅地址进行地理编码，以匹配邻居级别的SDOH指标。根据个人是否在2021年6月30日之前接受了首次LDCT，将数据分为训练组（N = 145）和测试组（N = 43）。在初始LCS的15个月内检查LDCT随访的电子医疗记录。在初始LCS后15个月内接受后续LDCT的患者被认为是依从性的。我们用超参数调优训练了一个XGBoost分类器，并执行SHapley加性解释（SHAP）分析来解释模型预测。结果：该队列包括69名（37%）亚洲/太平洋岛民，53名（28%）黑人/非裔美国人，49名（26%）西班牙裔/拉丁裔参与者。LCS不遵守率为66%。XGBoost分类器AUROC为0.81，AUPRC为0.90，预测准确率为0.79，召回率为0.78，特异性为0.81，阳性预测值为0.88，阴性预测值为0.68。SHAP分析表明，社区水平的SDOH因素（如学校水平和贫困水平）比个人水平的因素（如吸烟状况）更能预测不依从性。结论：该机器学习方法使用个体和社区水平的SDOH因素准确预测LCS不依从性。这些研究结果强调了社区层面特征与LCS依从性干预措施的相关性，并可能支持制定适合区域的策略，以提高高风险人群的依从性。

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引用次数: 0

Neoadjuvant immunotherapy plus chemotherapy in locally advanced stage III NSCLC patients undergoing definitive chemo-radiotherapy---a real‑world multicenter retrospective study 新辅助免疫治疗加化疗在局部晚期III期NSCLC患者接受明确的化疗-放疗-一个真实世界的多中心回顾性研究

IF 4.4 2区医学 Q1 ONCOLOGY

Lung Cancer

Pub Date : 2025-12-17 DOI: 10.1016/j.lungcan.2025.108883

Guoyin Li , Chaoyuan Liu , Pan Xi , Liangxue Hou , Yaoxiong Xia , YunXiang Qi , Wenyan Pan , Wei Bai , Xiaoyan Li , Hao Zhou , Pengyi Li , Zewen Song , Huiyun Zhao , Xuewen Liu

Background

The optimal integration of immunotherapy with definitive chemoradiotherapy (CRT) for unresectable stage III non-small cell lung cancer (NSCLC) remains an area of active investigation. While consolidation immunotherapy is standard, the efficacy and safety of a neoadjuvant approach are not yet established by phase III trials. This real-world study compares outcomes between neoadjuvant immuno-chemotherapy followed by CRT (NEO) and CRT followed by adjuvant immunotherapy (ADJ, the PACIFIC regimen).

Methods

In this multicenter retrospective analysis, we reviewed data from patients with stage III NSCLC who received radical thoracic radiotherapy and peri-radiotherapy immunotherapy between January 2020 and December 2023. Patients were classified into NEO (n = 321) or ADJ (n = 142) groups. Primary endpoints were progression-free survival (PFS) and overall survival (OS). Secondary endpoints included treatment patterns, recurrence modes, and incidence of pneumonitis. Propensity score matching (PSM) and robust statistical analyses were used to minimize confounding.

Results

The median PFS was significantly longer in the NEO group than in the ADJ group (25.0 months vs. 16.3 months; HR = 0.57, 95 % CI: 0.43–0.74; p < 0.001). Median OS was not reached (NR) in the NEO group compared to 41.1 months in the ADJ group (HR = 0.54, 95 % CI: 0.37–0.78; p = 0.001). The survival benefit for the NEO group remained consistent after PSM and multivariable adjustment. The objective response rate to neoadjuvant therapy was 68.4 %. Patterns of recurrence were similar between groups, with distant metastasis being the most common site of first progression. The incidence of grade ≥2 radiation pneumonitis was comparable (31.8 % NEO vs. 30.8 % ADJ, p = 0.925), though a non-significant trend towards higher grade ≥3 radiation pneumonitis was observed in the NEO group (14.0 % vs. 7.5 %, p = 0.071). Rates of checkpoint inhibitor pneumonitis were low and similar between groups.

Conclusion

In this large real-world cohort, a treatment sequence incorporating neoadjuvant immuno-chemotherapy prior to definitive CRT was associated with significantly improved PFS and OS compared to the standard adjuvant immunotherapy approach, without a definitive increase in severe pneumonitis. These findings support the further investigation of neoadjuvant immunotherapy strategies in phase III randomized trials for stage III NSCLC.

背景：对于不可切除的III期非小细胞肺癌（NSCLC），免疫治疗与放化疗（CRT）的最佳结合仍然是一个积极研究的领域。虽然巩固免疫治疗是标准的，但新辅助方法的有效性和安全性尚未通过III期试验确定。这项现实世界的研究比较了新辅助免疫化疗后CRT （NEO）和CRT后辅助免疫治疗（ADJ， PACIFIC方案）的结果。方法在这项多中心回顾性分析中，我们回顾了2020年1月至2023年12月期间接受根治性胸部放疗和放疗期免疫治疗的III期NSCLC患者的数据。患者分为NEO组（n = 321）和ADJ组（n = 142）。主要终点为无进展生存期（PFS）和总生存期（OS）。次要终点包括治疗方式、复发方式和肺炎发病率。倾向评分匹配（PSM）和稳健的统计分析，以尽量减少混淆。结果NEO组的中位PFS明显长于ADJ组（25.0个月比16.3个月；HR = 0.57, 95% CI: 0.43-0.74; p < 0.001）。NEO组未达到中位生存期（NR），而ADJ组为41.1个月（HR = 0.54, 95% CI: 0.37-0.78; p = 0.001）。经PSM和多变量调整后，NEO组的生存获益保持一致。新辅助治疗的客观有效率为68.4%。两组之间的复发模式相似，远处转移是最常见的首次进展部位。≥2级放射性肺炎的发生率相当（NEO组为31.8%，ADJ为30.8%,p = 0.925），但在NEO组中观察到更高级别≥3级放射性肺炎的无显著趋势（14.0%,p = 0.071）。检查点抑制剂肺炎的发生率在两组之间很低且相似。结论：在这个庞大的现实世界队列中，与标准辅助免疫治疗方法相比，在最终CRT之前结合新辅助免疫化疗的治疗序列与显著改善的PFS和OS相关，而没有明显增加严重肺炎的发生率。这些发现支持在III期非小细胞肺癌的III期随机试验中进一步研究新辅助免疫治疗策略。

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引用次数: 0

A pathomics model for predicting response to chemo-immunotherapy in lung squamous cell carcinoma: A multicenter study 预测肺鳞状细胞癌化疗免疫治疗反应的病理模型：一项多中心研究

IF 4.4 2区医学 Q1 ONCOLOGY

Lung Cancer

Pub Date : 2025-12-16 DOI: 10.1016/j.lungcan.2025.108881

Dongying Wang , Shuai Mu , Minghui Zhang , Guangyu Tao , Shuyuan Wang , Yinchen Shen , Guanxi Xiao , Xueyan Zhang , Baohui Han , Lei Cheng , Hua Zhong , Wei Nie

Background

The identification of lung squamous cell carcinoma (LUSC) patients who may benefit from first-line chemo-immunotherapy (CIT) remains a challenge. This study aimed to develop a pathomics model to predict the T cell-inflamed gene-expression profile (GEP) status and validate its utility in identifying patients who derive survival benefit from CIT.

Methods

The pathomics model was developed using whole-slide images and RNA-sequencing data from The Cancer Genome Atlas (TCGA) LUSC cohort (n = 334) to predict the GEP status and generate a pathomics score (PS). The predictive value of PS was validated in a prospective, multicenter trial (AK105-302, n = 267) by assessing its interaction with treatment (CIT vs. chemotherapy) for progression-free survival (PFS) and overall survival (OS). Two additional independent cohorts (n = 82 and n = 50) were used for external validation.

Results

The pathomics model accurately predicted GEP status, achieving area under the curve (AUC) values of 0.80 and 0.71 in the TCGA training and validation sets, respectively. In the AK105-302 cohort, significant interactions were identified between PS and treatment modalities for both PFS (interaction p = 0.011) and OS (interaction p < 0.001). Patients with high PS who received CIT exhibited significantly prolonged PFS (hazard ratio [HR]: 0.31, 95 % confidence interval [CI]: 0.21–0.48, p < 0.001) and OS (HR: 0.30, 95 % CI: 0.18–0.50, p < 0.001) compared to high PS patients receiving chemotherapy. However, this survival benefit was not observed in the low-PS patients. These findings were corroborated in two independent clinical cohorts. Furthermore, biological assessments revealed a significant association between high PS and an immune-hot tumor microenvironment.

Conclusion

We developed a GEP-based pathomics model that provides a practical, cost-effective strategy to identify patients most likely to derive superior survival benefit from first-line CIT over chemotherapy alone.

背景：鉴别可能受益于一线化学免疫治疗（CIT）的肺鳞状细胞癌（LUSC）患者仍然是一个挑战。本研究旨在建立一种病理模型来预测T细胞炎症基因表达谱（GEP）状态，并验证其在识别从cit中获得生存益处的患者中的应用。方法利用来自癌症基因组图谱（TCGA） LUSC队列（n = 334）的全切片图像和rna测序数据建立病理模型，预测GEP状态并生成病理评分（PS）。一项前瞻性多中心试验（AK105-302, n = 267）通过评估其与治疗（CIT vs.化疗）对无进展生存期（PFS）和总生存期（OS）的相互作用，验证了PS的预测价值。另外两个独立队列（n = 82和n = 50）用于外部验证。结果病理模型准确预测GEP状态，TCGA训练集和验证集的曲线下面积（AUC）分别为0.80和0.71。在AK105-302队列中，在PFS（相互作用p = 0.011）和OS（相互作用p <； 0.001）中，发现PS和治疗方式之间存在显著的相互作用。与接受化疗的高PS患者相比，接受CIT的高PS患者表现出明显延长的PFS（风险比[HR]: 0.31, 95%可信区间[CI]: 0.21-0.48, p < 0.001）和OS （HR: 0.30, 95% CI: 0.18-0.50, p < 0.001）。然而，在低ps患者中没有观察到这种生存获益。这些发现在两个独立的临床队列中得到了证实。此外，生物学评估显示高PS与免疫热肿瘤微环境之间存在显著关联。结论：我们开发了一种基于gep的病理模型，该模型提供了一种实用的、具有成本效益的策略，以确定最有可能从一线CIT中获得优于单独化疗的生存获益的患者。

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引用次数: 0

Identifying eligible patients for the Australian national lung cancer screening program in primary care: A cross-sectional study using clinical decision support systems and evaluating PLCOm2012 data quality 确定澳大利亚国家初级保健肺癌筛查项目的合格患者：一项使用临床决策支持系统和评估PLCOm2012数据质量的横断面研究

IF 4.4 2区医学 Q1 ONCOLOGY

Lung Cancer

Pub Date : 2025-12-14 DOI: 10.1016/j.lungcan.2025.108880

Lucas De Mendonça , Shakira Onwuka , Sarah York , Javiera Martinez-Gutierrez , Jon Emery , Christine Paul , Jo-Anne Manski-Nankervis , Nicole M. Rankin

Primary care is pivotal in identifying eligible participants for Australia’s National Lung Cancer Screening Program (NLCSP). Clinical Decision Support Systems (CDSS) can assist by flagging potentially eligible individuals using Electronic Medical Record (EMR) data. We developed a CDSS to identify people aged 50–70 who currently or formerly smoked cigarettes (with an unknown quit date or cessation within the past 10 years) for use in Australian general practice EMRs. This study aimed to: (1) assess the algorithm’s accuracy in identifying eligible patients, (2) estimate NLCSP eligibility based on audited EMR smoking data, and (3) evaluate EMR data quality for applying the PLCO_m2012 risk prediction tool.

A cross-sectional EMR audit was conducted across five Victorian general practices. Of 4,186 records flagged by the CDSS, 1,315 (31.4 %) were manually audited. The algorithm correctly identified all patients according to its rules (age and smoking status). Pack-year could be calculated for 226 patients (17.2 %), with 91 (6.9 %) meeting NLCSP eligibility. Eligibility was higher among people who currently smoke (9.2 %) than those who formerly smoked (3.6 %). A subset of 933 records was assessed for PLCOm2012 variables, revealing substantial data gaps (% missing): education level (100 %), ethnicity (58 %), BMI (57 %), and daily cigarette consumption (33 %).

CDSS algorithms can identify potential NLCSP participants, but confirmation of smoking history remains essential due to sub-optimal smoking data quality. Significant data limitations currently hinder PLCO_m2012 implementation via CDSS in general practice EMRs.

初级保健在确定澳大利亚国家肺癌筛查计划（NLCSP）的合格参与者方面至关重要。临床决策支持系统（CDSS）可以通过使用电子病历（EMR）数据标记潜在的合格个人来提供帮助。我们开发了一个CDSS来识别50-70岁目前或曾经吸烟的人（戒烟日期未知或在过去10年内戒烟），用于澳大利亚全科医生的电子病历。本研究旨在：(1)评估算法识别合格患者的准确性；(2)基于审计的EMR吸烟数据估计NLCSP的资格；(3)评估应用PLCOm2012风险预测工具的EMR数据质量。横断面电子病历审计进行了五个维多利亚一般做法。在CDSS标记的4186条记录中，1315条（31.4%）是手工审计的。该算法根据其规则（年龄和吸烟状况）正确识别所有患者。226例患者（17.2%）可以计算出包年，其中91例（6.9%）符合NLCSP资格。目前吸烟者（9.2%）比以前吸烟者（3.6%）的适格性更高。对933份记录的PLCOm2012变量进行了评估，发现了大量的数据缺口（缺失%）：教育水平（100%）、种族（58%）、BMI（57%）和每日香烟消费（33%）。CDSS算法可以识别潜在的NLCSP参与者，但由于吸烟数据质量不理想，确认吸烟史仍然是必要的。目前，严重的数据限制阻碍了PLCOm2012通过CDSS在常规emr中实施。

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引用次数: 0

Multiomic analysis of treatment-naïve NSCLC before the era of neoadjuvant immunotherapy reveals contrasting immune phenotypes in stage IIIA: node-dominant (T1N2) exhibiting hot versus tumor-dominant (T4N0) cold features 新辅助免疫治疗时代之前treatment-naïve NSCLC的多组学分析揭示了IIIA期的不同免疫表型：淋巴结优势（T1N2）表现为热特征与肿瘤优势（T4N0）表现为冷特征

IF 4.4 2区医学 Q1 ONCOLOGY

Lung Cancer

Pub Date : 2025-12-13 DOI: 10.1016/j.lungcan.2025.108879

Duk Ki Kim , Yooyoung Chong , Min-Kyung Yeo , Da Hyun Kang , Joo-Eun Lee , Hyun-Yi Kim , Min-Woong Kang , Chaeuk Chung

Background

Non-small cell lung cancer (NSCLC) exhibits substantial heterogeneity in its tumor immune microenvironment, which critically influences therapeutic outcomes. Recently, immune checkpoint inhibitors (ICIs) have been increasingly incorporated not only in metastatic settings but also into neoadjuvant, adjuvant, and perioperative treatments. Pathologic complete remission (pCR) following neoadjuvant immunotherapy is strongly associated with reduced recurrence and favorable survival outcomes. However, reliable biomarkers for predicting preoperative immunotherapy response remain limited. The dichotomy between “hot” and “cold” tumors provides a useful framework to explain differential immunotherapy responsiveness, yet how these immune phenotypes manifest across specific tumor stages remains poorly defined.

Methods

We performed integrative analyses combining bulk RNA sequencing and immunohistochemistry (IHC) on tumor specimens from patients with stage T1N2 and T4N0 NSCLC. Frozen samples were used for RNA sequencing and formalin-fixed paraffin-embedded (FFPE) tissues for IHC, obtained from surgeries performed between 2009 and 2018—prior to the widespread introduction of immunotherapy. Differentially expressed genes (DEGs) were identified, and Gene Ontology (GO) enrichment analyses were conducted to characterize biological pathways. Immune cell infiltration and spatial distribution were assessed by IHC staining for CD3⁺, CD4⁺, CD8⁺, CD56⁺, FOXP3⁺, CD68⁺, and CD163⁺ markers. Statistical analyses were performed using the Mann–Whitney U test.

Results

Transcriptomic and histologic analyses revealed distinct molecular and immune profiles between T1N2 and T4N0 tumors. T1N2 tumors were enriched for immune activation pathways and displayed dense, evenly distributed infiltration of CD3⁺, CD4⁺, and CD8⁺ T cells. In contrast, T4N0 tumors showed upregulation of extracellular matrix organization and adhesion-related pathways, accompanied by reduced intratumoral CD4⁺ and CD8⁺ T-cell density, accumulation of FOXP3⁺ regulatory T cells, and increased CD163⁺ M2 macrophages, consistent with an immune-excluded phenotype.

Conclusion

Our integrative multiomic analysis delineates node-dominant (T1N2) NSCLC as “hot” tumors with active immune engagement, whereas tumor-dominant (T4N0) NSCLC exhibit “cold” features characterized by stromal remodeling, immune exclusion, and immunosuppression. These findings suggest that the balance between tumor invasiveness and nodal spread may shape immune contexture and potentially modulate responsiveness to neoadjuvant immunotherapy, highlighting the clinical value of immune landscape profiling in personalized NSCLC treatment.

背景：非小细胞肺癌（NSCLC）的肿瘤免疫微环境具有很大的异质性，这对治疗结果有重要影响。最近，免疫检查点抑制剂（ICIs）不仅越来越多地应用于转移性肿瘤，而且还应用于新辅助、辅助和围手术期治疗。新辅助免疫治疗后的病理完全缓解（pCR）与减少复发和有利的生存结果密切相关。然而，预测术前免疫治疗反应的可靠生物标志物仍然有限。“热”和“冷”肿瘤之间的二分法提供了一个有用的框架来解释不同的免疫治疗反应性，然而这些免疫表型如何在特定的肿瘤阶段表现出来仍然不清楚。方法对T1N2期和T4N0期非小细胞肺癌患者的肿瘤标本进行大量RNA测序和免疫组化（IHC）综合分析。冷冻样本用于RNA测序和福尔马林固定石蜡包埋（FFPE）组织用于免疫组化，这些样本来自于2009年至2018年间进行的手术——在广泛引入免疫疗法之前。鉴定差异表达基因（DEGs），并进行基因本体（GO）富集分析以表征生物学途径。免疫组化染色检测免疫细胞CD3+、CD4+、CD8+、CD56+、FOXP3+、CD68+、CD163+标志物的浸润及空间分布。采用Mann-Whitney U检验进行统计分析。结果转录组学和组织学分析显示T1N2和T4N0肿瘤具有不同的分子和免疫特征。T1N2肿瘤免疫激活途径丰富，CD3+、CD4+、CD8+ T细胞浸润密集、分布均匀。相反，T4N0肿瘤表现出细胞外基质组织和黏附相关通路的上调，并伴有瘤内CD4+和CD8+ T细胞密度的降低，FOXP3+调节性T细胞的积累，CD163+ M2巨噬细胞的增加，符合免疫排斥表型。我们的综合多组学分析表明，淋巴结显性（T1N2）非小细胞肺癌是具有主动免疫参与的“热”肿瘤，而肿瘤显性（T4N0）非小细胞肺癌表现出以基质重塑、免疫排斥和免疫抑制为特征的“冷”特征。这些发现表明，肿瘤侵袭性和淋巴结扩散之间的平衡可能塑造免疫环境，并可能调节对新辅助免疫治疗的反应性，突出了免疫景观分析在个性化非小细胞肺癌治疗中的临床价值。

{"title":"Multiomic analysis of treatment-naïve NSCLC before the era of neoadjuvant immunotherapy reveals contrasting immune phenotypes in stage IIIA: node-dominant (T1N2) exhibiting hot versus tumor-dominant (T4N0) cold features","authors":"Duk Ki Kim , Yooyoung Chong , Min-Kyung Yeo , Da Hyun Kang , Joo-Eun Lee , Hyun-Yi Kim , Min-Woong Kang , Chaeuk Chung","doi":"10.1016/j.lungcan.2025.108879","DOIUrl":"10.1016/j.lungcan.2025.108879","url":null,"abstract":"<div><h3>Background</h3><div>Non-small cell lung cancer (NSCLC) exhibits substantial heterogeneity in its tumor immune microenvironment, which critically influences therapeutic outcomes. Recently, immune checkpoint inhibitors (ICIs) have been increasingly incorporated not only in metastatic settings but also into neoadjuvant, adjuvant, and perioperative treatments. Pathologic complete remission (pCR) following neoadjuvant immunotherapy is strongly associated with reduced recurrence and favorable survival outcomes. However, reliable biomarkers for predicting preoperative immunotherapy response remain limited. The dichotomy between “hot” and “cold” tumors provides a useful framework to explain differential immunotherapy responsiveness, yet how these immune phenotypes manifest across specific tumor stages remains poorly defined.</div></div><div><h3>Methods</h3><div>We performed integrative analyses combining bulk RNA sequencing and immunohistochemistry (IHC) on tumor specimens from patients with stage T1N2 and T4N0 NSCLC. Frozen samples were used for RNA sequencing and formalin-fixed paraffin-embedded (FFPE) tissues for IHC, obtained from surgeries performed between 2009 and 2018—prior to the widespread introduction of immunotherapy. Differentially expressed genes (DEGs) were identified, and Gene Ontology (GO) enrichment analyses were conducted to characterize biological pathways. Immune cell infiltration and spatial distribution were assessed by IHC staining for CD3<sup>+</sup>, CD4<sup>+</sup>, CD8<sup>+</sup>, CD56<sup>+</sup>, FOXP3<sup>+</sup>, CD68<sup>+</sup>, and CD163<sup>+</sup> markers. Statistical analyses were performed using the Mann–Whitney <em>U</em> test.</div></div><div><h3>Results</h3><div>Transcriptomic and histologic analyses revealed distinct molecular and immune profiles between T1N2 and T4N0 tumors. T1N2 tumors were enriched for immune activation pathways and displayed dense, evenly distributed infiltration of CD3<sup>+</sup>, CD4<sup>+</sup>, and CD8<sup>+</sup> T cells. In contrast, T4N0 tumors showed upregulation of extracellular matrix organization and adhesion-related pathways, accompanied by reduced intratumoral CD4<sup>+</sup> and CD8<sup>+</sup> T-cell density, accumulation of FOXP3<sup>+</sup> regulatory T cells, and increased CD163<sup>+</sup> M2 macrophages, consistent with an immune-excluded phenotype.</div></div><div><h3>Conclusion</h3><div>Our integrative multiomic analysis delineates node-dominant (T1N2) NSCLC as “hot” tumors with active immune engagement, whereas tumor-dominant (T4N0) NSCLC exhibit “cold” features characterized by stromal remodeling, immune exclusion, and immunosuppression. These findings suggest that the balance between tumor invasiveness and nodal spread may shape immune contexture and potentially modulate responsiveness to neoadjuvant immunotherapy, highlighting the clinical value of immune landscape profiling in personalized NSCLC treatment.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"211 ","pages":"Article 108879"},"PeriodicalIF":4.4,"publicationDate":"2025-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145797437","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}

引用次数: 0

Prognostic comparison of lymph node metastasis subtypes in lung adenocarcinoma: clinical implications of intranodal metastasis versus extranodal extension for optimizing R classification 肺腺癌淋巴结转移亚型的预后比较：结内转移与结外转移对优化R分级的临床意义。

IF 4.4 2区医学 Q1 ONCOLOGY

Lung Cancer

Pub Date : 2025-12-11 DOI: 10.1016/j.lungcan.2025.108876

Jia-Yong Wu , Guo-Zhong Liang , Tian-Qing Chen , Hai-Ping Qiu , Cai-Biao Huang , Xiao-Ping Xie

Background

Lung adenocarcinoma (LUAD) prognosis is strongly influenced by lymph node (LN) status. While extranodal extension (ENE) is a recognized negative prognostic factor, the International Association for the Study of Lung Cancer (IASLC) has proposed reclassifying ENE from R0 (complete resection) to R1 (incomplete resection). The prognostic significance of intranodal metastasis (INM) remains less defined. This study aims to compare the prognosis of LUAD patients with INM versus ENE to inform potential refinements to the R classification system.

Methods

This retrospective study enrolled 357 patients with pT1-3N0-1M0 LUAD who underwent lobectomy with systematic lymph node dissection between 2015 and 2021. Patients were stratified into three groups based on postoperative pathology: no LN metastasis (N0, n = 180), INM (n = 124), and ENE (n = 53). Overall survival (OS) and disease-free survival (DFS) were compared using Kaplan-Meier and Cox regression analyses.

Results

Among 177N1-stage patients, no significant difference in OS or DFS was observed between the INM and ENE groups (p > 0.05). However, both the INM and ENE groups showed significantly worse OS and DFS compared to the N0 group (p < 0.05). Multivariate analysis confirmed LN metastasis as an independent adverse prognostic factor for both DFS (HR = 2.95, 95 % CI: 1.32–6.61, P = 0.008) and OS (HR = 3.11, 95 % CI: 1.52–6.38, P = 0.002). Patients with nodal metastasis also had a significantly higher risk of recurrence.

Conclusion

In N1-stage LUAD, the prognosis of patients with INM is comparable to that of patients with ENE, with both groups exhibiting significantly poorer outcomes than node-negative patients. These findings suggest that the presence of nodal metastasis, regardless of extracapsular extension, may represent occult residual disease. We propose that INM, alongside ENE, should be considered for classification as incomplete resection (R1) to better guide adjuvant therapy strategies.

背景：肺腺癌（LUAD）的预后受淋巴结（LN）状态的强烈影响。虽然结外延伸（ENE）是公认的不良预后因素，但国际肺癌研究协会（IASLC）已提议将ENE从R0（完全切除）重新分类为R1（不完全切除）。结内转移（INM）的预后意义仍不明确。本研究旨在比较INM和ENE LUAD患者的预后，为R分类系统的潜在改进提供信息。方法：本回顾性研究纳入了357例2015年至2021年间接受肺叶切除术并系统性淋巴结清扫的pT1-3N0-1M0 LUAD患者。根据术后病理情况将患者分为3组：无LN转移（n = 180）、INM （n = 124）和ENE （n = 53）。采用Kaplan-Meier和Cox回归分析比较总生存期（OS）和无病生存期（DFS）。结果：177n1期患者中，INM组与ENE组OS、DFS比较差异无统计学意义（p < 0.05）。然而，INM组和ENE组的OS和DFS均较N0组明显差(p)。结论：在n1期LUAD中，INM患者的预后与ENE患者相当，两组预后均明显差于淋巴结阴性患者。这些发现提示淋巴结转移的存在，无论囊外延伸，都可能代表隐匿性残留疾病。我们建议INM和ENE应考虑归类为不完全切除（R1），以更好地指导辅助治疗策略。

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引用次数: 0

Global patterns and trends in mesothelioma incidence: A retrospective cross-sectional study 间皮瘤发病率的全球模式和趋势：一项回顾性横断面研究。

IF 4.4 2区医学 Q1 ONCOLOGY

Lung Cancer

Pub Date : 2025-12-11 DOI: 10.1016/j.lungcan.2025.108878

Leiwen Fu , Ke Liu , Yang Liu , Yanxiao Gao , Bingyi Wang , Yuxian Sun , Wei Shu , Yujia Ning , Minyi Zhang , Jian Du , Liang Li

Background

Mesothelioma is a rare and aggressive malignancy primarily caused by asbestos exposure; it predominantly affects older adults with a history of occupational contact.

Methods

This population-based study used the GLOBOCAN 2022 database to estimate mesothelioma incidence and mortality across 185 countries in 2022. Long-term trends were assessed using the Cancer Incidence in Five Continents (CI5) Volume XII and CI5 plus databases. Age-standardised incidence rates (ASIRs) were calculated, and Joinpoint regression analysis was employed to assess trends in mesothelioma ASIRs by estimating the average annual percentage change (AAPC).

Results

In 2022, there were an estimated 30,633 new mesothelioma cases globally, with an ASIR of 0.28 per 100,000. Europe bore the highest burden, accounting for 48.1% of global cases and 48.4% of deaths. A significant positive correlation was observed between the ASIR or age-standardised mortality rate (ASMR) and the Human Development Index. From 2003 to 2017, while mesothelioma incidence decreased in many regions, significant increases were observed among male in Croatia (AAPC: 2.5, 95% CI: 0.3 to 4.8), the Republic of Korea (2.5, 1.2 to 3.7), and Slovenia (1.2, 0.1 to 2.2), as well as in female in Canada (4.5, 1.3 to 7.9). Mesothelioma incidence declined significantly in males in Australia, Belarus, Germany, Israel, the Netherlands, New Zealand, Norway, Turkey, the UK, and in the White population of the USA, as well as in females in Belarus, Germany, and Turkey.

Conclusion

Mesothelioma remains a significant global health challenge, characterised by notable geographic and socioeconomic disparities. Sustained public health efforts are required to eliminate asbestos exposure and reduce disease burden, particularly in regions with rising incidence.

背景：间皮瘤是一种罕见的侵袭性恶性肿瘤，主要由石棉暴露引起；它主要影响有职业接触史的老年人。方法：这项基于人群的研究使用GLOBOCAN 2022数据库来估计2022年185个国家的间皮瘤发病率和死亡率。使用五大洲癌症发病率（CI5）第十二卷和CI5 plus数据库评估长期趋势。计算年龄标准化发病率（asir），并通过估计平均年百分比变化（AAPC）采用Joinpoint回归分析来评估间皮瘤asir的趋势。结果：2022年，全球估计有30,633例间皮瘤新发病例，ASIR为0.28 / 10万。欧洲的负担最重，占全球病例的48.1%，死亡人数的48.4%。在ASIR或年龄标准化死亡率（ASMR）与人类发展指数之间观察到显著的正相关。从2003年到2017年，虽然许多地区的间皮瘤发病率下降，但克罗地亚（AAPC: 2.5, 95% CI: 0.3至4.8）、韩国（2.5,1.2至3.7）和斯洛文尼亚（1.2,0.1至2.2）的男性以及加拿大的女性（4.5,1.3至7.9）的间皮瘤发病率显著增加。间皮瘤发病率在澳大利亚、白俄罗斯、德国、以色列、荷兰、新西兰、挪威、土耳其、英国和美国白人人群中的男性以及白俄罗斯、德国和土耳其的女性中显著下降。结论：间皮瘤仍然是一个重大的全球健康挑战，其特征是显著的地理和社会经济差异。需要持续的公共卫生努力，以消除石棉接触和减轻疾病负担，特别是在发病率上升的区域。

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引用次数: 0