Lung CancerPub Date : 2025-02-01DOI: 10.1016/j.lungcan.2024.108062
Yucheng Dong , Guangjian Yang , Yaning Yang , Shuyang Zhang , Yan Wang , Haiyan Xu
{"title":"Dynamic characterization of circulating tumor DNA in HER2-altered advanced non-small cell lung cancer treated with pyrotinib and apatinib: Exploratory biomarker analysis from PATHER2 study","authors":"Yucheng Dong , Guangjian Yang , Yaning Yang , Shuyang Zhang , Yan Wang , Haiyan Xu","doi":"10.1016/j.lungcan.2024.108062","DOIUrl":"10.1016/j.lungcan.2024.108062","url":null,"abstract":"<div><h3>Background</h3><div><em>HER2</em> mutations are critical drivers of non-small cell lung cancer (NSCLC), affecting 2 %–3 % of patients and often leads to poor prognosis and limited response to conventional therapies. This study investigates the genomic characteristics and prognostic relevance of dynamic circulating tumor DNA (ctDNA) monitoring in advanced NSCLC patients with <em>HER2</em> mutations treated with pyrotinib and apatinib.</div></div><div><h3>Methods</h3><div>The PATHER2 study included 33 advanced NSCLC patients harboring <em>HER2</em> mutations or amplification, who received combination therapy of pyrotinib and apatinib. Among them, 27 patients had baseline blood samples available for analysis. Baseline blood samples (n = 27), follow-up samples after one treatment cycle (n = 13), and samples upon disease progression (n = 18) were collected. ctDNA was extracted and sequenced using a 556-gene panel.</div></div><div><h3>Results</h3><div>At baseline, <em>HER2</em> mutations were detected in 21 of 27 patients through ctDNA, and 19 showed consistent results between tissue and blood sample testing. Patients with <em>TP53</em> and <em>DNMT3A</em> alterations at baseline had significantly shorter progression-free survival (PFS). Dynamic ctDNA monitoring revealed that patients without detectable <em>HER2</em> mutations after one treatment cycle had longer PFS and a trend toward longer overall survival (OS) compared to those with persistent <em>HER2</em> mutations. The newly emerged mutations after resistance were infrequently found in <em>HER2</em>, instead primarily enriched in the chromatin remodeling pathway.</div></div><div><h3>Conclusion</h3><div>ctDNA holds significant value in guiding the treatment of patients with <em>HER2</em> mutations. Baseline <em>TP53</em> and <em>DNMT3A</em> alterations, along with persistent <em>HER2</em> mutations after initial treatment, are associated with poorer prognosis. The primary mechanism of resistance to pyrotinib and apatinib in these patients may be attributed to chromatin remodeling rather than on-target alterations.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"200 ","pages":"Article 108062"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008226","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}
Lung CancerPub Date : 2025-02-01DOI: 10.1016/j.lungcan.2025.108108
Tingting Liu , Junyi He , Yalan Wang , Yuwen Yang , Lin Zhang , Mengting Shi , Jiaqing Liu , Dongcheng Sun , Zhehai Wang , Jian Fang , Qitao Yu , Baohui Han , Shundong Cang , Gongyan Chen , Xiaodong Mei , Zhixiong Yang , Yan Huang , Wenfeng Fang , Yunpeng Yang , Yuanyuan Zhao , Li Zhang
{"title":"Health-related quality of life and symptoms in patients with previously untreated, locally advanced or metastatic non-squamous non-small cell lung cancer treated with sintilimab or placebo plus pemetrexed and platinum (ORIENT-11): A randomized, double-blind, phase 3 trial","authors":"Tingting Liu , Junyi He , Yalan Wang , Yuwen Yang , Lin Zhang , Mengting Shi , Jiaqing Liu , Dongcheng Sun , Zhehai Wang , Jian Fang , Qitao Yu , Baohui Han , Shundong Cang , Gongyan Chen , Xiaodong Mei , Zhixiong Yang , Yan Huang , Wenfeng Fang , Yunpeng Yang , Yuanyuan Zhao , Li Zhang","doi":"10.1016/j.lungcan.2025.108108","DOIUrl":"10.1016/j.lungcan.2025.108108","url":null,"abstract":"<div><h3>Background</h3><div>In the phase 3 ORIENT-11 study, sintilimab plus pemetrexed-platinum provided statistically significant longer overall survival and progression-free survival versus placebo plus pemetrexed-platinum as first-line treatment in patients with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC). Here, we report the patient-reported outcomes (PRO) analysis findings in ORIENT-11.</div></div><div><h3>Methods</h3><div>PROs were measured using the European Organization for Research and Treatment of Cancer Quality of Life of Cancer Patients Questionnaire Core 30 items (EORTC QLQ-C30) and the Lung Cancer Symptom Scale (LCSS) questionnaire. PRO endpoints included evaluation of least square (LS) mean changes from baseline to week 12 (platinum-containing treatment) and week 21 (maintenance treatment), time to true deterioration (TTD), and overall improvement or stability rate for QLQ-C30 and LCSS scales. PRO scores in two groups were compared using the Mann–Whitney test. Least squares (LS) mean changes from baseline to week 12, week 21, and other time points were assessed with mixed-effect model repeated measures analysis. TTD was calculated using the Kaplan-Meier method and compared with the Cox proportional hazards model between groups.</div></div><div><h3>Results</h3><div>252 (94.7 %) patients in the sintilimab-combination group and 123 (93.9 %) patients in the placebo-combination group had a baseline and at least one postbaseline PRO assessment. Change from baseline to week 12 or 21 favored the sintilimab-combination group on QLQ-C30 global health status/quality of life (GHS/QoL), most function and symptoms scales, and most LCSS scales. Notably, the QLQ-C30 pain score change gradually deteriorated in the placebo-combination group with increased treatment. At the same time, it improved in the sintilimab-combination group significantly from 6 weeks later, with the improvement sustained in subsequent courses of treatment. Sintilimab plus chemotherapy significantly delayed the TTD in most QLQ-C30 and LCSS scales compared with placebo plus chemotherapy, and the overall improvement or stability rates were higher in the former.</div></div><div><h3>Conclusions</h3><div>The addition of sintilimab to chemotherapy maintained or improved health-related quality of life and symptoms compared with chemotherapy. Along with the previous efficacy and safety results, these data support the addition of sintilimab to standard chemotherapy as first-line therapy in locally advanced or metastatic non-squamous NSCLC.</div><div><strong>Clinical trial registration</strong>: NCT03607539.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"200 ","pages":"Article 108108"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Clinical utility of comprehensive genomic profiling in non-small cell lung cancer: An analysis of a nation-wide database","authors":"Koki Fujii , Michiko Ueki , Momoko Morishita , Hiroaki Ikushima , Hideaki Isago , Kousuke Watanabe , Katsutoshi Oda , Hidenori Kage","doi":"10.1016/j.lungcan.2025.108099","DOIUrl":"10.1016/j.lungcan.2025.108099","url":null,"abstract":"<div><h3>Background</h3><div>Molecular testing is recommended to patients with advanced non-small cell lung cancer (NSCLC) because those who receive targeted therapy have better prognosis than patients who don’t. However, recent studies have raised concerns that first-line companion diagnostic testing at diagnosis may have lower detection rates than previously reported. Therefore, we sought to determine the utility of comprehensive genomic profiling (CGP) tests in NSCLC by analyzing a nation-wide database.</div></div><div><h3>Methods</h3><div>We searched the Center for Cancer Genomics and Advanced Therapeutics database and downloaded clinical and genomic data from 3,240 lung cancer cases registered from June 2019 to August 2023. Patients undergoing tissue tests and plasma tests were analyzed separately. NSCLC with previously known driver mutations and those without were further analyzed separately. All 3,240 lung cancer patients were analyzed for the presence of germline findings.</div></div><div><h3>Results</h3><div>We found that 25 % of patients who had negative companion diagnostic results tested positive for driver oncogene mutations with indications for approved inhibitors when they underwent tissue CGP tests. Tissue CGP tests had lower detection rates for gene fusions compared with gene mutations (93 % for mutations and 73 % for fusions, p < 0.001), and plasma CGP tests had lower detection rates for both mutations and fusions compared with tissue testing (69 % for mutations and 37 % for fusions, p < 0.001). Finally, presumed germline pathogenic variants were detected in 3.9–5.3 % of NSCLC patients.</div></div><div><h3>Conclusion</h3><div>NSCLC patients who tested negative for companion diagnostic tests benefited from CGP tests, especially with tissue-based panels. CGP tests detect germline findings in NSCLC patients at rates similar to previous reports.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"200 ","pages":"Article 108099"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lung CancerPub Date : 2025-02-01DOI: 10.1016/j.lungcan.2025.108180
Knight Sean , Blake Andrew , Eyre Heather , Kirkham Sara , Hussell Tracy , Cartmell Sarah , Finegan Katherine , Hodgetts Ryan , Evison Matthew
{"title":"70 Trial protocol and update for the DREM study","authors":"Knight Sean , Blake Andrew , Eyre Heather , Kirkham Sara , Hussell Tracy , Cartmell Sarah , Finegan Katherine , Hodgetts Ryan , Evison Matthew","doi":"10.1016/j.lungcan.2025.108180","DOIUrl":"10.1016/j.lungcan.2025.108180","url":null,"abstract":"","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"200 ","pages":"Article 108180"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143508496","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}
Lung CancerPub Date : 2025-02-01DOI: 10.1016/j.lungcan.2025.108136
Scott Deborah , Geldart Tom , Kirtley Daisy , Noble Mark , Harle Amelie , Bayne Mike , Gorf Lauren
{"title":"25 ctDNA testing and application in non-small cell lung cancer - a review of regional practice in Dorset","authors":"Scott Deborah , Geldart Tom , Kirtley Daisy , Noble Mark , Harle Amelie , Bayne Mike , Gorf Lauren","doi":"10.1016/j.lungcan.2025.108136","DOIUrl":"10.1016/j.lungcan.2025.108136","url":null,"abstract":"","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"200 ","pages":"Article 108136"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143508667","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}
Lung CancerPub Date : 2025-02-01DOI: 10.1016/j.lungcan.2025.108171
Thorley Richard , Pearce Catharine , Breen David , Daneshvar Cyrus , Hassan Maged
{"title":"61 Achieving and maintaining competence as a physician in focused neck ultrasound and cervical lymph node sampling","authors":"Thorley Richard , Pearce Catharine , Breen David , Daneshvar Cyrus , Hassan Maged","doi":"10.1016/j.lungcan.2025.108171","DOIUrl":"10.1016/j.lungcan.2025.108171","url":null,"abstract":"","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"200 ","pages":"Article 108171"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143510329","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}
Lung CancerPub Date : 2025-02-01DOI: 10.1016/j.lungcan.2025.108154
Wong Hoi-Ting , Yap Eugene Ming Yang , Dhunnookchand Ryan , Orhan Orhan , Newsom-Davis Tom , Davies Alice , Wiseman Dexter
{"title":"44 Seeing beyond the scan: Evaluating the impact of preoperative EBUS-TBNA on NSCLC staging","authors":"Wong Hoi-Ting , Yap Eugene Ming Yang , Dhunnookchand Ryan , Orhan Orhan , Newsom-Davis Tom , Davies Alice , Wiseman Dexter","doi":"10.1016/j.lungcan.2025.108154","DOIUrl":"10.1016/j.lungcan.2025.108154","url":null,"abstract":"","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"200 ","pages":"Article 108154"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143511228","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}
Lung CancerPub Date : 2025-02-01DOI: 10.1016/j.lungcan.2025.108177
Navani Neal , Sharman Anna , Evison Matthew , Shepherd Paula , Shah Riyaz , Moore David
{"title":"67 Achieving equitable, timely and comprehensive biomarker testing in NSCLC","authors":"Navani Neal , Sharman Anna , Evison Matthew , Shepherd Paula , Shah Riyaz , Moore David","doi":"10.1016/j.lungcan.2025.108177","DOIUrl":"10.1016/j.lungcan.2025.108177","url":null,"abstract":"","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"200 ","pages":"Article 108177"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143511280","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}