Pub Date : 2026-01-04DOI: 10.1016/j.lungcan.2025.108905
Monireh Sadat Seyyedsalehi , Massimiliano Cani , Qian Wang , Chitra Thakur , Umberto Malapelle , Chung Yin Kong , Silvia Novello , Paolo Boffetta
Lung cancer (LC) remains the leading cause of cancer-related mortality among women worldwide. Compared to men, LC in women presents distinct epidemiologic, biological, and clinical characteristics. A large proportion of LC cases in women occur in never-smokers, underscoring the important roles of environmental exposures, genetic susceptibility, and hormonal influences in disease pathogenesis. LC in women also displays unique molecular profiles, with a higher prevalence of actionable alterations such as epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements, which inform targeted therapy selection. Despite advances in chemotherapy, targeted agents, and immunotherapy, sex-based differences in treatment efficacy, toxicity, and survivorship persist and remain incompletely understood. Additional barriers, including limited access to LC screening and the underrepresentation of women in clinical trials, further constrain the application of evidence-based interventions for women. This review synthesizes latest evidence on epidemiology, risk factors, molecular features, screening, treatment outcomes, and survivorship challenges in women with LC with a deep focus on novel approaches to overcome current barriers and disparities to improve prevention, early detection, treatment, and long-term survivorship care.
{"title":"Lung cancer in women: current evidence and future research priorities","authors":"Monireh Sadat Seyyedsalehi , Massimiliano Cani , Qian Wang , Chitra Thakur , Umberto Malapelle , Chung Yin Kong , Silvia Novello , Paolo Boffetta","doi":"10.1016/j.lungcan.2025.108905","DOIUrl":"10.1016/j.lungcan.2025.108905","url":null,"abstract":"<div><div>Lung cancer (LC) remains the leading cause of cancer-related mortality among women worldwide. Compared to men, LC in women presents distinct epidemiologic, biological, and clinical characteristics. A large proportion of LC cases in women occur in never-smokers, underscoring the important roles of environmental exposures, genetic susceptibility, and hormonal influences in disease pathogenesis. LC in women also displays unique molecular profiles, with a higher prevalence of actionable alterations such as epidermal growth factor receptor (<em>EGFR</em>) mutations and anaplastic lymphoma kinase (<em>ALK</em>) rearrangements, which inform targeted therapy selection. Despite advances in chemotherapy, targeted agents, and immunotherapy, sex-based differences in treatment efficacy, toxicity, and survivorship persist and remain incompletely understood. Additional barriers, including limited access to LC screening and the underrepresentation of women in clinical trials, further constrain the application of evidence-based interventions for women. This review synthesizes latest evidence on epidemiology, risk factors, molecular features, screening, treatment outcomes, and survivorship challenges in women with LC with a deep focus on novel approaches to overcome current barriers and disparities to improve prevention, early detection, treatment, and long-term survivorship care.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"213 ","pages":"Article 108905"},"PeriodicalIF":4.4,"publicationDate":"2026-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146010182","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}
Pub Date : 2026-01-03DOI: 10.1016/j.lungcan.2025.108893
Kathleen Zwijsen , Ellen Heirwegh , Eline Schillebeeckx , Elly Marcq , Adrian Covaci , Ken Op de Beeck , Jan P. van Meerbeeck , Jo Raskin , Annelies Janssens , Annemiek Snoeckx , Kevin Lamote
Objectives
Pleural mesothelioma (PM) is an aggressive thoracic cancer related to historical exposure to asbestos fibres. Symptoms often appear at an advanced stage, leading to delayed diagnosis and dismal prognosis. Early diagnosis is thus crucial in improving patient outcome. Current biomarker research for early detection focuses on different −omics research fields (genomics, proteomics, transcriptomics, metabolomics and volatomics), however with no clinically useful result. Moreover, currently no screening program is advocated for asymptomatic individuals with an established asbestos exposure. The aim of this review is to summarise the advances in different −omics fields and to pinpoint state-of-the art biomarkers with the highest potential to serve as primary targets in clinical trials for early PM detection or screening.
Methods
A literature search was performed in the databases MEDLINE and Web Of Science. Research articles published before 1 August 2025 were eligible.
Results
In total, 63 articles were included in this review, with specific focus on radiomics, genomics, transcriptomics, epigenomics, proteomics, metabolomics, and volatomics. Several research groups have focused on investigating biomarkers or screening techniques for pleural mesothelioma among individuals with a history of asbestos exposure. Notable approaches include using low-dose Computed Tomography, and determining mesothelin levels and micro-RNAs in blood, and volatile organic compounds in exhaled breath.
Discussion
Single biomarkers like miRNAs, mesothelin, and VOCs show promise, but further validation is needed in larger cohorts with correct control groups. A multi-omics approach, which integrates biomarker panels from various −omics areas, has the potential to enhance diagnostic accuracy.
目的胸膜间皮瘤（PM）是一种与石棉纤维暴露史有关的侵袭性胸部肿瘤。症状往往出现在晚期，导致诊断延误和预后不佳。因此，早期诊断对于改善患者预后至关重要。目前用于早期检测的生物标志物研究主要集中在不同的组学研究领域（基因组学、蛋白质组学、转录组学、代谢组学和挥发组学），但没有临床有用的结果。此外，目前没有筛查方案提倡无症状的个体与石棉暴露。本综述的目的是总结不同组学领域的进展，并确定最有潜力作为早期PM检测或筛查临床试验主要靶点的最先进的生物标志物。方法在MEDLINE和Web Of Science数据库中进行文献检索。在2025年8月1日之前发表的研究论文符合条件。结果本综述共纳入63篇文献，重点关注放射组学、基因组学、转录组学、表观基因组学、蛋白质组学、代谢组学和挥发组学。几个研究小组已经专注于研究有石棉暴露史的个体胸膜间皮瘤的生物标志物或筛选技术。值得注意的方法包括使用低剂量计算机断层扫描，测定血液中的间皮素水平和微rna，以及呼出气体中的挥发性有机化合物。单个生物标志物如mirna、间皮素和VOCs显示出希望，但需要在更大的队列和正确的对照组中进一步验证。多组学方法集成了来自不同组学领域的生物标志物面板，具有提高诊断准确性的潜力。
{"title":"Multi-omic screening for pleural mesothelioma in Asbestos-Exposed Populations: A literature review and Recommendations","authors":"Kathleen Zwijsen , Ellen Heirwegh , Eline Schillebeeckx , Elly Marcq , Adrian Covaci , Ken Op de Beeck , Jan P. van Meerbeeck , Jo Raskin , Annelies Janssens , Annemiek Snoeckx , Kevin Lamote","doi":"10.1016/j.lungcan.2025.108893","DOIUrl":"10.1016/j.lungcan.2025.108893","url":null,"abstract":"<div><h3>Objectives</h3><div>Pleural mesothelioma (PM) is an aggressive thoracic cancer related to historical exposure to asbestos fibres. Symptoms often appear at an advanced stage, leading to delayed diagnosis and dismal prognosis. Early diagnosis is thus crucial in improving patient outcome. Current biomarker research for early detection focuses on different −omics research fields (genomics, proteomics, transcriptomics, metabolomics and volatomics), however with no clinically useful result. Moreover, currently no screening program is advocated for asymptomatic individuals with an established asbestos exposure. The aim of this review is to summarise the advances in different −omics fields and to pinpoint state-of-the art biomarkers with the highest potential to serve as primary targets in clinical trials for early PM detection or screening.</div></div><div><h3>Methods</h3><div>A literature search was performed in the databases MEDLINE and Web Of Science. Research articles published before 1 August 2025 were eligible.</div></div><div><h3>Results</h3><div>In total, 63 articles were included in this review, with specific focus on radiomics, genomics, transcriptomics, epigenomics, proteomics, metabolomics, and volatomics. Several research groups have focused on investigating biomarkers or screening techniques for pleural mesothelioma among individuals with a history of asbestos exposure. Notable approaches include using low-dose Computed Tomography, and determining mesothelin levels and micro-RNAs in blood, and volatile organic compounds in exhaled breath.</div></div><div><h3>Discussion</h3><div>Single biomarkers like miRNAs, mesothelin, and VOCs show promise, but further validation is needed in larger cohorts with correct control groups. A multi-omics approach, which integrates biomarker panels from various −omics areas, has the potential to enhance diagnostic accuracy.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"212 ","pages":"Article 108893"},"PeriodicalIF":4.4,"publicationDate":"2026-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145927314","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}
Pub Date : 2026-01-01DOI: 10.1016/j.lungcan.2025.108875
William J. Phillips , Luna Jia Zhan , Deepro Chowdhury , Jeniszka Gill , Alexander Sun , Rebekah Rittberg , Victor Cohen , Amanda J.W. Gibson , Michael Yan , Daniel Liwski , Saritha Surapaneni , Marie Frederique D’Amours , Fabian P.S. Yu , YongJin Kim , Rana A. Qadeer , David E. Dawe , Jason Agulnik , Vishal Navani , Andrea S. Fung , Stephanie Snow , Sara Moore
{"title":"Corrigendum to “Treatment and outcomes of limited stage small cell lung cancer in the Canadian small cell lung cancer database (CASCADE)” [Lung Cancer 210 (2025) 108840]","authors":"William J. Phillips , Luna Jia Zhan , Deepro Chowdhury , Jeniszka Gill , Alexander Sun , Rebekah Rittberg , Victor Cohen , Amanda J.W. Gibson , Michael Yan , Daniel Liwski , Saritha Surapaneni , Marie Frederique D’Amours , Fabian P.S. Yu , YongJin Kim , Rana A. Qadeer , David E. Dawe , Jason Agulnik , Vishal Navani , Andrea S. Fung , Stephanie Snow , Sara Moore","doi":"10.1016/j.lungcan.2025.108875","DOIUrl":"10.1016/j.lungcan.2025.108875","url":null,"abstract":"","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"211 ","pages":"Article 108875"},"PeriodicalIF":4.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145775021","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}
Pub Date : 2025-12-29DOI: 10.1016/j.lungcan.2025.108891
Deborah Di-Xin Zhou , Sarah J. Lord , Frank Po-Yen Lin , Wendy A. Cooper , Milita Zaheed , Robert John Simes , Thomas John , Chee Khoon Lee
Background
In NSCLC, TP53 mutations are heterogeneous with varied effects on protein synthesis, function and clinical outcomes. We hypothesize that a refined classification of TP53 mutations, beyond binary categorization, could improve prognostication. Furthermore, specific mutations could be associated with enhanced benefit from immune checkpoint inhibitors (ICI) versus chemotherapy. To investigate this, we analyzed data from randomized trials (OAK and POPLAR) which compared atezolizumab to chemotherapy in previously treated advanced driver-negative NSCLC.
Methods
Participants were classified as TP53 mutant or wild-type using baseline plasma, and by coding mutation, and Olivier’s and Poeta’s classification. We performed multivariable Cox regression analyses to evaluate the prognostic significance of TP53 mutations, and interaction tests to assess their predictive value.
Results
Among 762 participants, 49% harbored a TP53 mutation. TP53 mutations based on binary categorization were associated with poorer but not statistically significant OS compared to wild-type (adjusted-HR 1.15; 95 %CI 0.96–1.38; P = .12). However, nonsense mutations classified by coding mutations (adjusted-HR 1.71; 95% CI 1.22–2.39; P = .002), non-missense mutations classified by Olivier’s classification (adjusted-HR 1.33; 95% CI 1.03–1.74; P = .03) and disruptive mutations classified by Poeta’s classification (adjusted-HR 1.33; 95% CI 1.37–1.77; P = .03) were associated with statistically significant poorer OS. TP53 status did not predict differential benefit from ICI versus chemotherapy (interaction P = .45).
Conclusion
In advanced driver-negative NSCLC following progression on first-line chemotherapy, nonsense, non-missense and disruptive mutations of TP53 were strongly associated with inferior OS. These data support utilizing a nuanced classification of TP53 mutations as a stratification factor in future trials, and laboratory reporting to aid prognostication.
背景：在非小细胞肺癌中，TP53突变具有异质性，对蛋白质合成、功能和临床结果的影响各不相同。我们假设TP53突变的精确分类，超越二元分类，可以改善预后。此外，特异性突变可能与免疫检查点抑制剂（ICI）与化疗的获益增强有关。为了研究这一点，我们分析了随机试验（OAK和POPLAR）的数据，这些试验比较了atezolizumab与化疗在先前治疗的晚期驱动阴性NSCLC中的疗效。方法：通过基线血浆、编码突变、Olivier和Poeta分类，将参与者分为TP53突变型和野生型。我们通过多变量Cox回归分析来评估TP53突变的预后意义，并通过相互作用试验来评估其预测价值。结果：在762名参与者中，49%的人携带TP53突变。与野生型相比，基于二元分类的TP53突变与较差的OS相关，但无统计学意义（调整后危险度1.15;95% CI 0.96-1.38; P = 0.12）。然而，编码突变分类的无义突变（校正后危险度1.71,95% CI 1.22-2.39, P = 0.002）、Olivier分类的非错义突变（校正后危险度1.33,95% CI 1.03-1.74, P = 0.03）和Poeta分类的破坏性突变（校正后危险度1.33,95% CI 1.37-1.77, P = 0.03）与较差的OS有统计学意义相关。TP53状态不能预测ICI与化疗的获益差异（相互作用P = 0.45）。结论：在一线化疗进展的晚期驱动阴性NSCLC中，无义、非错义和破坏性TP53突变与不良OS密切相关。这些数据支持在未来的试验中利用TP53突变的细微分类作为分层因素，以及实验室报告来帮助预测。
{"title":"Clinical impact of TP53 classifications in previously treated advanced driver-negative non-small cell lung cancer: A biomarker analysis of the OAK and POPLAR randomized clinical trials","authors":"Deborah Di-Xin Zhou , Sarah J. Lord , Frank Po-Yen Lin , Wendy A. Cooper , Milita Zaheed , Robert John Simes , Thomas John , Chee Khoon Lee","doi":"10.1016/j.lungcan.2025.108891","DOIUrl":"10.1016/j.lungcan.2025.108891","url":null,"abstract":"<div><h3>Background</h3><div>In NSCLC, <em>TP53</em> mutations are heterogeneous with varied effects on protein synthesis, function and clinical outcomes. We hypothesize that a refined classification of <em>TP53</em> mutations, beyond binary categorization, could improve prognostication. Furthermore, specific mutations could be associated with enhanced benefit from immune checkpoint inhibitors (ICI) versus chemotherapy. To investigate this, we analyzed data from randomized trials (OAK and POPLAR) which compared atezolizumab to chemotherapy in previously treated advanced driver-negative NSCLC.</div></div><div><h3>Methods</h3><div>Participants were classified as <em>TP53</em> mutant or wild-type using baseline plasma, and by coding mutation, and Olivier’s and Poeta’s classification. We performed multivariable Cox regression analyses to evaluate the prognostic significance of <em>TP53</em> mutations, and interaction tests to assess their predictive value.</div></div><div><h3>Results</h3><div>Among 762 participants, 49% harbored a <em>TP53</em> mutation. <em>TP53</em> mutations based on binary categorization were associated with poorer but not statistically significant OS compared to wild-type (adjusted-HR 1.15; 95 %CI 0.96–1.38; <em>P</em> = .12). However, nonsense mutations classified by coding mutations (adjusted-HR 1.71; 95% CI 1.22–2.39;<!--> <em>P</em> = .002), non-missense mutations classified by Olivier’s classification (adjusted-HR 1.33; 95% CI 1.03–1.74; <em>P</em> = .03) and disruptive mutations classified by Poeta’s classification (adjusted-HR 1.33; 95% CI 1.37–1.77; <em>P</em> = .03) were associated with statistically significant poorer OS. <em>TP53</em> status did not predict differential benefit from ICI versus chemotherapy (interaction <em>P</em> = .45).</div></div><div><h3>Conclusion</h3><div>In advanced driver-negative NSCLC following progression on first-line chemotherapy, nonsense, non-missense and disruptive mutations of <em>TP53</em> were strongly associated with inferior OS. These data support utilizing a nuanced classification of <em>TP53</em> mutations as a stratification factor in future trials, and laboratory reporting to aid prognostication.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"212 ","pages":"Article 108891"},"PeriodicalIF":4.4,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145918105","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}
Pub Date : 2025-12-29DOI: 10.1016/j.lungcan.2025.108892
Hyun Ae Jung , Jinyeong Lim , Yoon-La Choi , Yeong Jeong Jeon , Junghee Lee , Jong Ho Cho , Yong Soo Choi , Sehhoon Park , Jong-Mu Sun , Jin Seok Ahn , Myung-Ju Ahn , Woong-Yang Park , Hong Kwan Kim , Se-Hoon Lee
Background
APOBEC plays a crucial role in the mutation process and immune response of non-small cell lung cancer (NSCLC). This study evaluated the role of the APOBEC mutation signature in early-stage epidermal growth factor receptor (EGFR) mutant NSCLC. This study aimed to assess the impact of APOBEC enrichment on recurrence-free survival (RFS), post-recurrence tyrosine kinase inhibitor (TKI) progression-free survival (PFS), and post-recurrence survival (PRS).
Methods
We conducted whole-exome sequencing and whole-transcriptome sequencing in 100 patients diagnosed with pathologic stage II-IIIA non-squamous NSCLC.
Results
Among the 100 patients, 18 (18 %) exhibited APOBEC (≥2) enrichment, which did not show a significant association with RFS (P = 0.14). Patients with APOBEC enrichment showed a shorter post-recurrence TKI PFS compared to those without APOBEC enrichment (8.13 months vs. 24.57 months, P = 0.017). In multivariate analysis, poor post-recurrence TKI PFS was associated with the type of EGFR mutation (L858R vs. exon 19 deletion, HR = 1.91, P = 0.04), TP53 mutation (HR = 2.07, P = 0.03), and APOBEC enrichment (≥2 vs. < 2, HR = 2.23, P = 0.02). PRS was 61.10 months and 21.77 months for patients with APOBEC enrichment and patients without APOBEC enrichment, respectively (P = 0.029). In multivariate analysis, poor PRS of EGFR-TKI was associated with the type of EGFR mutation (L858R vs. exon 19 deletion, HR = 2.29, P = 0.04) and APOBEC enrichment (≥2 vs. < 2, HR = 2.71, P = 0.02).
Conclusions
APOBEC enrichment may present at initial diagnosis of early-stage EGFR mutant NSCLC and is associated with poor post-recurrence TKI PFS and PRS rather than RFS.
背景：APOBEC在非小细胞肺癌（NSCLC）的突变过程和免疫应答中起着至关重要的作用。本研究评估了APOBEC突变特征在早期表皮生长因子受体（EGFR）突变型非小细胞肺癌中的作用。本研究旨在评估APOBEC富集对无复发生存（RFS）、复发后酪氨酸激酶抑制剂（TKI）无进展生存（PFS）和复发后生存（PRS）的影响。方法：对100例诊断为病理II-IIIA期非鳞状NSCLC的患者进行全外显子组测序和全转录组测序。结果：100例患者中，18例（18%）出现APOBEC（≥2）富集，与RFS无显著相关性（P = 0.14）。与没有APOBEC富集的患者相比，APOBEC富集的患者复发后TKI PFS较短（8.13个月对24.57个月，P = 0.017）。在多因素分析中，复发后TKI PFS差与EGFR突变类型（L858R vs外显子19缺失，HR = 1.91, P = 0.04）、TP53突变（HR = 2.07, P = 0.03）和APOBEC富集（≥2）相关。结论：早期EGFR突变NSCLC的初始诊断可能存在APOBEC富集，并且与复发后TKI PFS差和PRS相关，而不是与RFS相关。
{"title":"The role of APOBEC in early-stage epidermal growth factor receptor-mutant non-small cell lung cancer","authors":"Hyun Ae Jung , Jinyeong Lim , Yoon-La Choi , Yeong Jeong Jeon , Junghee Lee , Jong Ho Cho , Yong Soo Choi , Sehhoon Park , Jong-Mu Sun , Jin Seok Ahn , Myung-Ju Ahn , Woong-Yang Park , Hong Kwan Kim , Se-Hoon Lee","doi":"10.1016/j.lungcan.2025.108892","DOIUrl":"10.1016/j.lungcan.2025.108892","url":null,"abstract":"<div><h3>Background</h3><div>APOBEC plays a crucial role in the mutation process and immune response of non-small cell lung cancer (NSCLC). This study evaluated the role of the APOBEC mutation signature in early-stage epidermal growth factor receptor (EGFR) mutant NSCLC. This study aimed to assess the impact of APOBEC enrichment on recurrence-free survival (RFS), post-recurrence tyrosine kinase inhibitor (TKI) progression-free survival (PFS), and post-recurrence survival (PRS).</div></div><div><h3>Methods</h3><div>We conducted whole-exome sequencing and whole-transcriptome sequencing in 100 patients diagnosed with pathologic stage II-IIIA non-squamous NSCLC.</div></div><div><h3>Results</h3><div>Among the 100 patients, 18 (18 %) exhibited APOBEC (≥2) enrichment, which did not show a significant association with RFS (<em>P</em> = 0.14). Patients with APOBEC enrichment showed a shorter post-recurrence TKI PFS compared to those without APOBEC enrichment (8.13 months vs. 24.57 months, <em>P</em> = 0.017). In multivariate analysis, poor post-recurrence TKI PFS was associated with the type of EGFR mutation (L858R vs. exon 19 deletion, HR = 1.91, <em>P</em> = 0.04), TP53 mutation (HR = 2.07, <em>P</em> = 0.03), and APOBEC enrichment (≥2 vs. < 2, HR = 2.23, <em>P</em> = 0.02). PRS was 61.10 months and 21.77 months for patients with APOBEC enrichment and patients without APOBEC enrichment, respectively (<em>P</em> = 0.029). In multivariate analysis, poor PRS of EGFR-TKI was associated with the type of EGFR mutation (L858R vs. exon 19 deletion, HR = 2.29, <em>P</em> = 0.04) and APOBEC enrichment (≥2 vs. < 2, HR = 2.71, <em>P</em> = 0.02).</div></div><div><h3>Conclusions</h3><div>APOBEC enrichment may present at initial diagnosis of early-stage <em>EGFR</em> mutant NSCLC and is associated with poor post-recurrence TKI PFS and PRS rather than RFS.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"212 ","pages":"Article 108892"},"PeriodicalIF":4.4,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145878648","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}
Pub Date : 2025-12-26DOI: 10.1016/j.lungcan.2025.108890
Lei Cheng , Dongying Wang , Xueyan Zhang , Baohui Han , Hua Zhong , Wei Nie
Introduction
PIK3CA mutations are oncogenic drivers in 2–4% of non-small cell lung cancers (NSCLC), often co-occurring with other drivers and conferring therapeutic resistance. This report is unique in describing the efficacy of the novel, highly selective PI3Kα inhibitor inavolisib in two heavily pre-treated patients with PIK3CA-mutant NSCLC harboring divergent co-drivers (EGFR and KRAS).
Case presentation
We present a 71-year-old male with EGFR/PIK3CA-mutant adenocarcinoma and brain metastases, and a 54-year-old female with KRAS/PIK3CA-mutant squamous cell carcinoma. Both patients reported rapid symptomatic improvement (hoarseness and shoulder pain, respectively) within two weeks of initiating inavolisib.
Diagnosis, intervention, and outcomes
Both patients received oral inavolisib (6 mg daily). Follow-up imaging after one month revealed significant tumor reduction. Notably, regressing intrapulmonary lesions exhibited tumor cavitation, and the male patient demonstrated a marked regression of central nervous system (CNS) metastases. The treatment was well-tolerated, with only Grade 1 oral mucositis reported.
Conclusion
The primary take-away lesson is that selective PI3Kα inhibition with inavolisib can induce potent systemic and intracranial responses in PIK3CA-mutant NSCLC, regardless of the primary oncogenic co-driver. The observed tumor cavitation suggests a potential anti-angiogenic mechanism, warranting further investigation.
{"title":"Inavolisib for PIK3CA-mutant non-small cell lung cancer: A case report","authors":"Lei Cheng , Dongying Wang , Xueyan Zhang , Baohui Han , Hua Zhong , Wei Nie","doi":"10.1016/j.lungcan.2025.108890","DOIUrl":"10.1016/j.lungcan.2025.108890","url":null,"abstract":"<div><h3>Introduction</h3><div><em>PIK3CA</em> mutations are oncogenic drivers in 2–4% of non-small cell lung cancers (NSCLC), often co-occurring with other drivers and conferring therapeutic resistance. This report is unique in describing the efficacy of the novel, highly selective PI3Kα inhibitor inavolisib in two heavily pre-treated patients with <em>PIK3CA</em>-mutant NSCLC harboring divergent co-drivers (<em>EGFR</em> and <em>KRAS</em>).</div></div><div><h3>Case presentation</h3><div>We present a 71-year-old male with <em>EGFR/PIK3CA</em>-mutant adenocarcinoma and brain metastases, and a 54-year-old female with <em>KRAS/PIK3CA</em>-mutant squamous cell carcinoma. Both patients reported rapid symptomatic improvement (hoarseness and shoulder pain, respectively) within two weeks of initiating inavolisib.</div></div><div><h3>Diagnosis, intervention, and outcomes</h3><div>Both patients received oral inavolisib (6 mg daily). Follow-up imaging after one month revealed significant tumor reduction. Notably, regressing intrapulmonary lesions exhibited tumor cavitation, and the male patient demonstrated a marked regression of central nervous system (CNS) metastases. The treatment was well-tolerated, with only Grade 1 oral mucositis reported.</div></div><div><h3>Conclusion</h3><div>The primary take-away lesson is that selective PI3Kα inhibition with inavolisib can induce potent systemic and intracranial responses in <em>PIK3CA</em>-mutant NSCLC, regardless of the primary oncogenic co-driver. The observed tumor cavitation suggests a potential anti-angiogenic mechanism, warranting further investigation.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"212 ","pages":"Article 108890"},"PeriodicalIF":4.4,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145845517","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}
Pub Date : 2025-12-25DOI: 10.1016/j.lungcan.2025.108889
Mandy Jongbloed , Ronald A.M. Damhuis , Wouter H. Van Geffen , Peter de Boer , Jarno W.J. Huijs , Safiye Dursun , Juliette Degens , Ben E.E.M. van den Borne , Magdolen Youssef-El Soud , Michelle Steens , Cordula Pitz , Dirk K.M. De Ruysscher , Lizza E.L. Hendriks
Currently, guidelines advise local radical treatment (LRT) to all disease sites in addition to systemic therapy in patients with synchronous oligometastatic non-small cell lung cancer (NSCLC). However, the best order of treatments is unknown. This advice is largely based on expert opinion and on studies without immune checkpoint inhibitors (ICI), while an ICI-based regimen is now standard of care first-line treatment for stage IV NSCLC without an actionable genetic alteration (AGA). We conducted a retrospective study to evaluate the order of treatments in patients with synchronous oligometastatic NSCLC without an AGA, with a single extrathoracic metastasis treated with an ICI-based regimen between 2018 and 2022. We evaluated upfront LRT to the metastasis followed by ICI and if indicated LRT to the local disease (Netherlands Cancer Registry: cohort 1, n = 225), and ICI followed by LRT to all disease sites if no progression (regional retrospective series: cohort 2, n = 33). The primary endpoint was overall survival (OS). The median OS for cohort 1 and cohort 2 were 26 and 25 months, respectively, and 3-year OS rates of 45 % and 44 %, respectively. In cohort 1, better survival was seen for those with brain metastasis, good performance status, non-squamous histology and high PD-L1 expression. In cohort 2, better survival was seen for younger age and non-squamous histology. In conclusion, both upfront and delayed LRT combined with an ICI-based treatment can result in long-term survival in this patient population, however the most optimal sequence has yet to determined.
{"title":"Effect of treatment sequencing on outcome of patients with non-small cell lung cancer with a synchronous solitary extrathoracic metastasis","authors":"Mandy Jongbloed , Ronald A.M. Damhuis , Wouter H. Van Geffen , Peter de Boer , Jarno W.J. Huijs , Safiye Dursun , Juliette Degens , Ben E.E.M. van den Borne , Magdolen Youssef-El Soud , Michelle Steens , Cordula Pitz , Dirk K.M. De Ruysscher , Lizza E.L. Hendriks","doi":"10.1016/j.lungcan.2025.108889","DOIUrl":"10.1016/j.lungcan.2025.108889","url":null,"abstract":"<div><div>Currently, guidelines advise local radical treatment (LRT) to all disease sites in addition to systemic therapy in patients with synchronous oligometastatic non-small cell lung cancer (NSCLC). However, the best order of treatments is unknown. This advice is largely based on expert opinion and on studies without immune checkpoint inhibitors (ICI), while an ICI-based regimen is now standard of care first-line treatment for stage IV NSCLC without an actionable genetic alteration (AGA). We conducted a retrospective study to evaluate the order of treatments in patients with synchronous oligometastatic NSCLC without an AGA, with a single extrathoracic metastasis treated with an ICI-based regimen between 2018 and 2022. We evaluated upfront LRT to the metastasis followed by ICI and if indicated LRT to the local disease (Netherlands Cancer Registry: cohort 1, n = 225), and ICI followed by LRT to all disease sites if no progression (regional retrospective series: cohort 2, n = 33). The primary endpoint was overall survival (OS). The median OS for cohort 1 and cohort 2 were 26 and 25 months, respectively, and 3-year OS rates of 45 % and 44 %, respectively. In cohort 1, better survival was seen for those with brain metastasis, good performance status, non-squamous histology and high PD-L1 expression. In cohort 2, better survival was seen for younger age and non-squamous histology. In conclusion, both upfront and delayed LRT combined with an ICI-based treatment can result in long-term survival in this patient population, however the most optimal sequence has yet to determined.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"212 ","pages":"Article 108889"},"PeriodicalIF":4.4,"publicationDate":"2025-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145878633","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}
Pub Date : 2025-12-23DOI: 10.1016/j.lungcan.2025.108886
Dong Woog Yoon , Sumin Shin , Chu Hyun Kim , Yeong Jeong Jeon , Junghee Lee , Seong Yong Park , Yong Soo Choi , Jong Ho Cho , Hong Kwan Kim , Ho Yun Lee
Objectives
We aimed to evaluate the oncologic outcomes of sublobar resection (SLR) compared with lobectomy in patients with radiologically pure-solid stage IA non–small cell lung cancer (NSCLC).
Methods
We retrospectively reviewed 363 patients with clinical stage IA pure-solid NSCLC who underwent curative-intent resection between 2018 and 2020. Patients were divided into SLR (n = 60) and lobectomy (n = 303) groups. Kaplan–Meier analysis was used to estimate overall survival (OS) and recurrence-free survival (RFS), and Cox regression identified prognostic factors. Subgroup analyses were performed for stage IA2 and IA3 patients.
Results
In the overall cohort, the SLR group had significantly worse 5-year OS (75.5 % vs. 93.3 %, p < 0.01) and RFS (58.3 % vs. 77.4 %, p < 0.01) compared with lobectomy. In stage IA2, OS was comparable (87.2 % vs. 91.7 %, p = 0.1), but RFS was inferior after SLR (65.9 % vs. 81.2 %, p = 0.02). In stage IA3, both OS (54.3 % vs. 94.4 %, p < 0.01) and RFS (40.6 % vs. 74.9 %, p < 0.01) were markedly worse after SLR. Segmentectomy showed outcomes similar to lobectomy in IA2 but was inferior in IA3, whereas wedge resection was consistently associated with poor survival.
Conclusions
Lobectomy remains the standard surgical procedure for pure-solid stage IA NSCLC, particularly IA3 disease. Segmentectomy may be considered in carefully selected IA2 patients, while it is advisable to avoid wedge resection. These findings emphasize the importance of selecting the most appropriate patients for SLR and support the need for prospective validation.
目的：比较纯实体期IA期非小细胞肺癌（NSCLC）患者行叶下切除术（SLR）和叶下切除术的肿瘤预后。方法回顾性分析2018年至2020年363例临床期IA型纯实体非小细胞肺癌患者行治愈性切除术。患者分为单叶切除组（n = 60）和肺叶切除组（n = 303）。Kaplan-Meier分析用于估计总生存期（OS）和无复发生存期（RFS）， Cox回归确定预后因素。对IA2期和IA3期患者进行亚组分析。结果在整个队列中，SLR组的5年OS （75.5% vs. 93.3%, p < 0.01）和RFS （58.3% vs. 77.4%, p < 0.01）明显低于肺叶切除术。在IA2期，OS相当（87.2% vs. 91.7%, p = 0.1），但SLR后RFS较差（65.9% vs. 81.2%, p = 0.02）。在IA3期，SLR后OS （54.3% vs. 94.4%, p < 0.01）和RFS （40.6% vs. 74.9%, p < 0.01）均明显恶化。在IA2中，节段切除术的结果与肺叶切除术相似，但在IA3中效果较差，而楔形切除术始终与较差的生存率相关。结论：对于纯固体期IA型非小细胞肺癌，尤其是IA3型非小细胞肺癌，手术切除仍是标准手术方法。在精心挑选的IA2患者中，可以考虑节段切除术，但建议避免楔形切除术。这些发现强调了选择最合适的单反患者的重要性，并支持前瞻性验证的必要性。
{"title":"Is sublobar resection a valid option for radiologically pure-solid clinical stage IA non-small cell lung cancer?: insights from real-world data and current status","authors":"Dong Woog Yoon , Sumin Shin , Chu Hyun Kim , Yeong Jeong Jeon , Junghee Lee , Seong Yong Park , Yong Soo Choi , Jong Ho Cho , Hong Kwan Kim , Ho Yun Lee","doi":"10.1016/j.lungcan.2025.108886","DOIUrl":"10.1016/j.lungcan.2025.108886","url":null,"abstract":"<div><h3>Objectives</h3><div>We aimed to evaluate the oncologic outcomes of sublobar resection (SLR) compared with lobectomy in patients with radiologically pure-solid stage IA non–small cell lung cancer (NSCLC).</div></div><div><h3>Methods</h3><div>We retrospectively reviewed 363 patients with clinical stage IA pure-solid NSCLC who underwent curative-intent resection between 2018 and 2020. Patients were divided into SLR (n = 60) and lobectomy (n = 303) groups. Kaplan–Meier analysis was used to estimate overall survival (OS) and recurrence-free survival (RFS), and Cox regression identified prognostic factors. Subgroup analyses were performed for stage IA2 and IA3 patients.</div></div><div><h3>Results</h3><div>In the overall cohort, the SLR group had significantly worse 5-year OS (75.5 % vs. 93.3 %, p < 0.01) and RFS (58.3 % vs. 77.4 %, p < 0.01) compared with lobectomy. In stage IA2, OS was comparable (87.2 % vs. 91.7 %, p = 0.1), but RFS was inferior after SLR (65.9 % vs. 81.2 %, p = 0.02). In stage IA3, both OS (54.3 % vs. 94.4 %, p < 0.01) and RFS (40.6 % vs. 74.9 %, p < 0.01) were markedly worse after SLR. Segmentectomy showed outcomes similar to lobectomy in IA2 but was inferior in IA3, whereas wedge resection was consistently associated with poor survival.</div></div><div><h3>Conclusions</h3><div>Lobectomy remains the standard surgical procedure for pure-solid stage IA NSCLC, particularly IA3 disease. Segmentectomy may be considered in carefully selected IA2 patients, while it is advisable to avoid wedge resection. These findings emphasize the importance of selecting the most appropriate patients for SLR and support the need for prospective validation.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"212 ","pages":"Article 108886"},"PeriodicalIF":4.4,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145882761","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}
Alectinib has demonstrated significant disease-free survival (DFS) benefits as adjuvant therapy for resected stage IB–IIIA ALK-positive non-small-cell lung cancer (NSCLC) in the ALINA study. This study aimed to assess the cost-effectiveness of introducing adjuvant alectinib into routine clinical practice in France compared with standard adjuvant platinum-based chemotherapy.
Methods
A cohort-based semi-Markov model was developed to simulate long-term health and economic outcomes for patients from the ALINA intention-to-treat population over a 40-year time horizon. Eight mutually exclusive health states were included, capturing DFS, non-metastatic recurrence, metastatic recurrence (first and second line), and death. Clinical inputs were sourced primarily from ALINA, while recurrence treatment patterns, cure assumptions, utilities, and costs reflected French clinical practice and French thoracic oncologists’ opinion. Costs (2024 euros) and outcomes were discounted following French HTA guidelines. Deterministic, probabilistic, and scenario analyses were conducted.
Results
Adjuvant alectinib would yield 17.6 life-years (LYs) and 15.4 quality-adjusted life-years (QALYs) per patient versus 12.4 LYs and 10.4 QALYs with chemotherapy, corresponding to incremental gains of 5.2 LYs and 5.0 QALYs. Total lifetime costs were estimated at €180,561 with alectinib and €237,011 with chemotherapy, resulting in a cost saving of €56,449. Higher upfront treatment costs with alectinib were offset by substantial reductions in recurrence-related expenditures. Across all deterministic, probabilistic, and scenario analyses, alectinib remained both more effective and less costly.
Conclusions
Adjuvant alectinib would provide substantial clinical benefits for patients with resected ALK-positive NSCLC and represent a dominant strategy over platinum-based chemotherapy in the French healthcare setting, improving outcomes while reducing overall costs.
{"title":"Cost-effectiveness of adjuvant alectinib in the treatment of patients with resected stage IB-IIIA ALK-positive non-small lung cancer in France, based on the ALINA study","authors":"Romain Supiot , Alexandre Gherardi , Léopoldine du Manoir de Juaye , Olfa Doghri , Marine Sivignon , Michaël Duruisseaux , Christos Chouaid","doi":"10.1016/j.lungcan.2025.108885","DOIUrl":"10.1016/j.lungcan.2025.108885","url":null,"abstract":"<div><h3>Background and objective</h3><div>Alectinib has demonstrated significant disease-free survival (DFS) benefits as adjuvant therapy for resected stage IB–IIIA ALK-positive non-small-cell lung cancer (NSCLC) in the ALINA study. This study aimed to assess the cost-effectiveness of introducing adjuvant alectinib into routine clinical practice in France compared with standard adjuvant platinum-based chemotherapy.</div></div><div><h3>Methods</h3><div>A cohort-based semi-Markov model was developed to simulate long-term health and economic outcomes for patients from the ALINA intention-to-treat population over a 40-year time horizon. Eight mutually exclusive health states were included, capturing DFS, non-metastatic recurrence, metastatic recurrence (first and second line), and death. Clinical inputs were sourced primarily from ALINA, while recurrence treatment patterns, cure assumptions, utilities, and costs reflected French clinical practice and French thoracic oncologists’ opinion. Costs (2024 euros) and outcomes were discounted following French HTA guidelines. Deterministic, probabilistic, and scenario analyses were conducted.</div></div><div><h3>Results</h3><div>Adjuvant alectinib would yield 17.6 life-years (LYs) and 15.4 quality-adjusted life-years (QALYs) per patient versus 12.4 LYs and 10.4 QALYs with chemotherapy, corresponding to incremental gains of 5.2 LYs and 5.0 QALYs. Total lifetime costs were estimated at €180,561 with alectinib and €237,011 with chemotherapy, resulting in a cost saving of €56,449. Higher upfront treatment costs with alectinib were offset by substantial reductions in recurrence-related expenditures. Across all deterministic, probabilistic, and scenario analyses, alectinib remained both more effective and less costly.</div></div><div><h3>Conclusions</h3><div>Adjuvant alectinib would provide substantial clinical benefits for patients with resected ALK-positive NSCLC and represent a dominant strategy over platinum-based chemotherapy in the French healthcare setting, improving outcomes while reducing overall costs.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"211 ","pages":"Article 108885"},"PeriodicalIF":4.4,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145834227","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}
Pub Date : 2025-12-23DOI: 10.1016/j.lungcan.2025.108887
Susana Hernandez , Esther Conde , Marta Alonso , Daniel Curto , Fatima Duran , Abigail Ast , Javier Torres-Jimenez , Helena Bote-de Cabo , Maria Zurera , Javier Baena , Jon Zugazagoitia , Ricardo Garcia-Lujan , Dolores Isla , Javier De Castro , Luis Paz-Ares , Fernando Lopez-Rios
Background
Non–small cell lung carcinoma (NSCLC) is a leading example of precision oncology, with a growing number of actionable targets. However, long turnaround times (TAT) for biomarker results can delay optimal treatment decisions. We evaluated whether a streamlined workflow could deliver comprehensive molecular reports within 72 h.
Methods
In this prospective cohort study (UTOPIA protocol), 96 patients with early-stage or advanced NSCLC at Hospital Universitario 12 de Octubre underwent molecular tumor board (MTB)-centered triage, automated NGS processing, and integrated data review. TAT was defined (in working days) from MTB triage to electronic report validation. Communication was supported by daily operational huddles and intralaboratory pre-MTB meetings using a standardized checklist.
Results
All 96 NGS reports met the 72-hour TAT target (100%). The NGS failure rate was 1%. Potentially actionable genomic alterations were identified in 45.8% of patients, most frequently EGFR (24%) and KRAS G12C (8.3%). Other targetable alterations included six ALK fusions (6.3%), four MET exon 14 skipping mutations (4.2%), two BRAF V600E mutations (2.1%), and one RET fusion (1%).
Conclusion
An ultrafast biomarker testing workflow for lung cancer, enabled by MTB-driven triage and structured team communication, can reliably generate comprehensive molecular reports within 72 h. This approach may reduce TAT-related treatment delays and support timely biomarker-guided therapy for patients with NSCLC.
{"title":"Optimizing communication for ultrafast lung cancer biomarker testing: the UTOPIA pilot study","authors":"Susana Hernandez , Esther Conde , Marta Alonso , Daniel Curto , Fatima Duran , Abigail Ast , Javier Torres-Jimenez , Helena Bote-de Cabo , Maria Zurera , Javier Baena , Jon Zugazagoitia , Ricardo Garcia-Lujan , Dolores Isla , Javier De Castro , Luis Paz-Ares , Fernando Lopez-Rios","doi":"10.1016/j.lungcan.2025.108887","DOIUrl":"10.1016/j.lungcan.2025.108887","url":null,"abstract":"<div><h3>Background</h3><div>Non–small cell lung carcinoma (NSCLC) is a leading example of precision oncology, with a growing number of actionable targets. However, long turnaround times (TAT) for biomarker results can delay optimal treatment decisions. We evaluated whether a streamlined workflow could deliver comprehensive molecular reports within 72 h.</div></div><div><h3>Methods</h3><div>In this prospective cohort study (UTOPIA protocol), 96 patients with early-stage or advanced NSCLC at Hospital Universitario 12 de Octubre underwent molecular tumor board (MTB)-centered triage, automated NGS processing, and integrated data review. TAT was defined (in working days) from MTB triage to electronic report validation. Communication was supported by daily operational huddles and intralaboratory pre-MTB meetings using a standardized checklist.</div></div><div><h3>Results</h3><div>All 96 NGS reports met the 72-hour TAT target (100%). The NGS failure rate was 1%. Potentially actionable genomic alterations were identified in 45.8% of patients, most frequently <em>EGFR</em> (24%) and <em>KRAS</em> G12C (8.3%). Other targetable alterations included six <em>ALK</em> fusions (6.3%), four <em>MET</em> exon 14 skipping mutations (4.2%), two <em>BRAF</em> V600E mutations (2.1%), and one <em>RET</em> fusion (1%).</div></div><div><h3>Conclusion</h3><div>An ultrafast biomarker testing workflow for lung cancer, enabled by MTB-driven triage and structured team communication, can reliably generate comprehensive molecular reports within 72 h. This approach may reduce TAT-related treatment delays and support timely biomarker-guided therapy for patients with NSCLC.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"211 ","pages":"Article 108887"},"PeriodicalIF":4.4,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145834385","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}
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