Lung Cancer最新文献

{"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 ,&nbsp;Junyi He ,&nbsp;Yalan Wang ,&nbsp;Yuwen Yang ,&nbsp;Lin Zhang ,&nbsp;Mengting Shi ,&nbsp;Jiaqing Liu ,&nbsp;Dongcheng Sun ,&nbsp;Zhehai Wang ,&nbsp;Jian Fang ,&nbsp;Qitao Yu ,&nbsp;Baohui Han ,&nbsp;Shundong Cang ,&nbsp;Gongyan Chen ,&nbsp;Xiaodong Mei ,&nbsp;Zhixiong Yang ,&nbsp;Yan Huang ,&nbsp;Wenfeng Fang ,&nbsp;Yunpeng Yang ,&nbsp;Yuanyuan Zhao ,&nbsp;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 ,&nbsp;Michiko Ueki ,&nbsp;Momoko Morishita ,&nbsp;Hiroaki Ikushima ,&nbsp;Hideaki Isago ,&nbsp;Kousuke Watanabe ,&nbsp;Katsutoshi Oda ,&nbsp;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 &lt; 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 &lt; 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}

{"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 ,&nbsp;Guangjian Yang ,&nbsp;Yaning Yang ,&nbsp;Shuyang Zhang ,&nbsp;Yan Wang ,&nbsp;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}

{"title":"Diagnostic and prognostic relevance of inflammatory markers in surgically treated thymic epithelial tumors: An international multicenter study","authors":"Evelyn Megyesfalvi ,&nbsp;Aron Ghimessy ,&nbsp;Jonas Bauer ,&nbsp;Orsolya Pipek ,&nbsp;Kevin Saghi ,&nbsp;Aron Gellert ,&nbsp;Janos Fillinger ,&nbsp;Ozlem Okumus ,&nbsp;Vivien Teglas ,&nbsp;Erna Ganofszky ,&nbsp;Krisztina Bogos ,&nbsp;Ferenc Renyi-Vamos ,&nbsp;Zsolt Megyesfalvi ,&nbsp;Clemens Aigner ,&nbsp;Balazs Hegedus ,&nbsp;Balazs Dome ,&nbsp;Bernhard Moser","doi":"10.1016/j.lungcan.2025.108111","DOIUrl":"10.1016/j.lungcan.2025.108111","url":null,"abstract":"<div><h3>Background</h3><div>Complementary prognostic markers are needed in thymic epithelial tumors (TETs) to aid patient stratification and determine the most appropriate follow-up strategies. This study aimed to assess the diagnostic and prognostic relevance of blood-based inflammatory markers in a large cohort of surgically treated TET patients.</div></div><div><h3>Material and Methods</h3><div>A total of 743 TET patients who underwent surgical resection between 1999–2021 were included in this multicenter study. Inflammatory markers were recorded from the most recent preoperative blood cell count prior to surgery. Measured variables were rescaled and harmonized to obtain comparable values across the participating centers.</div></div><div><h3>Results</h3><div>Preoperative CRP was significantly higher in TET patients with increased tumor size (vs. those with T1 tumors, p = 0.035). Likewise, neutrophil-to-lymphocyte ratio (NLR) (p = 0.002) and platelet-to-lymphocyte ratio (PLR) (p &lt; 0.001) were both significantly higher in thymic carcinomas than in thymomas. Notably, increased NLR and PLR were mainly attributed to significantly decreased lymphocyte levels in thymic carcinoma patients. Concerning survival outcomes, we found that elevated PLR and fibrinogen influenced overall survival (OS) (p = 0.002 and p = 0.018, respectively) and cause-specific survival (CSS) (p = 0.002 and p = 0.009, respectively) independently of other variables in our multivariate models, and they constituted negative prognosticators in TETs. Elevated CRP had an independent negative impact only on OS. Although elevated NLR was linked with impaired prognosis in our univariate model (p = 0.008), its independent prognostic significance could not be validated.</div></div><div><h3>Conclusions</h3><div>Using the so-far largest cohort of surgically treated TET patients, our study demonstrates that CRP, PLR, and NLR have diagnostic significance in TETs, while elevated PLR and fibrinogen constitute independent negative prognosticators for OS and CSS. Accordingly, the current multicenter study offers additional guidance in developing personalized surveillance protocols in thymoma and thymic carcinoma.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"200 ","pages":"Article 108111"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143075013","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":"Rearranged during transfection (RET) lung cancer – Update on targeted therapies","authors":"W.J. Mullally ,&nbsp;C.G. O’Leary ,&nbsp;K.J. O’Byrne","doi":"10.1016/j.lungcan.2025.108083","DOIUrl":"10.1016/j.lungcan.2025.108083","url":null,"abstract":"<div><div>The enhanced comprehension of the molecular pathways underpinning oncogenesis in non-small cell lung cancer (NSCLC) has led to the advancement of personalized treatment for individuals with actionable mutations using targeted therapies. The rearranged during transfection <em>(RET)</em> proto-oncogene, is critical in the embryonic development of various tissues, including renal, neural, and neuroendocrine tissue. <em>RET</em> fusions have been observed in approximately 1–2% of NSCLC cases. Targeted therapies for NSCLC with <em>RET</em> alterations have progressed significantly over the past decade. While multikinase inhibitors (MKIs) faced limitations in efficacy and tolerability, the introduction of selective RET inhibitors (SRIs) such as selpercatininb and pralsetinib has transformed patient outcomes, resulting in deep and durable responses. Ongoing clinical trials are exploring their potential benefits in the neoadjuvant and adjuvant setting. Early phase clinical trials endeavor to demonstrate next-generation selective RET inhibitors can effectively overcome SRI resistance mechanisms, offer improved safety profiles, and enhance patient outcomes.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"200 ","pages":"Article 108083"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008213","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}

{"title":"Adherence to community-based lung cancer screening in the Yorkshire Lung Screening Trial","authors":"Sarah Q. Ahmad ,&nbsp;Francesca Pesola ,&nbsp;Philip A.J. Crosbie ,&nbsp;Rhian Gabe ,&nbsp;Neil Hancock ,&nbsp;Martyn P.T. Kennedy ,&nbsp;Catriona Marshall ,&nbsp;Samantha L. Quaife ,&nbsp;Suzanne Rogerson ,&nbsp;Irene Simmonds ,&nbsp;Matthew E.J. Callister","doi":"10.1016/j.lungcan.2025.108086","DOIUrl":"10.1016/j.lungcan.2025.108086","url":null,"abstract":"<div><h3>Introduction</h3><div>Lung cancer screening saves lives by detecting cancers early, but continued adherence to screening rounds is required for participants to experience the maximum clinical benefit. Here we describe factors associated with screening adherence in the Yorkshire Lung Screening Trial.</div></div><div><h3>Methods</h3><div>All eligible individuals following baseline (prevalent) screening were invited for a biennial incident screen in a community setting. Participants were contacted by phone (up to two attempts) to arrange an appointment or sent a pre-arranged appointment letter if non-contactable. Characteristics of attenders versus non-attenders were compared using univariate and multivariable models.</div></div><div><h3>Results</h3><div>Of 6,650 individuals who attended baseline screening, 5,975 were eligible for the second round. The mean age of those eligible was 70.5 years, 45.2 % were female, 31.7 % were from the most socio-economically deprived quintile and 33.9 % reported current smoking at the time of the baseline scan. Of these, 5,184 (86.8 %) attended their second screen and 791 (13.2 %) did not. Factors associated with lower attendance following multivariable analysis were socio-economic deprivation (OR 0.78, 95 % CI 0.60–1.02, most versus least deprived quintile) and current smoking (OR 0.57, 95 % CI 0.48–0.66, current versus previously quit). Sex, age, and ethnicity were not associated with attendance. Attendance was more likely in people who had an indeterminate (OR 2.10, 95 % CI 1.61–2.73; n = 871) or positive (OR 3.16, 95 % CI 0.98–10.19; n = 60) baseline scan compared to a negative baseline scan.</div></div><div><h3>Discussion</h3><div>Adherence was good overall but lower adherence amongst people who currently smoke and those from deprived populations is a concern due to their greater risk of lung cancer death. Further research is needed into interventions that increase adherence in these high-risk populations.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"200 ","pages":"Article 108086"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066407","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":"Comprehensive molecular profiling of squamous non-small cell lung cancer reveals high incidence of actionable genomic alterations among patients with no history of smoking","authors":"Joshua E. Reuss ,&nbsp;Jacob Zaemes ,&nbsp;Nishant Gandhi ,&nbsp;Phillip Walker ,&nbsp;Sandip P. Patel ,&nbsp;Joanne Xiu ,&nbsp;Charu Aggarwal ,&nbsp;Ari Vanderwalde ,&nbsp;Suresh S. Ramalingam ,&nbsp;Balazs Halmos ,&nbsp;Stephen V. Liu","doi":"10.1016/j.lungcan.2025.108101","DOIUrl":"10.1016/j.lungcan.2025.108101","url":null,"abstract":"<div><h3>Background</h3><div>Next-generation sequencing (NGS) to detect actionable genomic driver alterations (AGAs) is critical to appropriate management of non-small cell lung cancer (NSCLC), but is inconsistently performed for squamous NSCLC (sqNSCLC). Molecular characterization of sqNSCLC by smoking status has not been well-reported. We analyzed a large cohort of sqNSCLC utilizing NGS to elucidate molecular differences in sqNSCLC by smoking status.</div></div><div><h3>Methods</h3><div>sqNSCLC was profiled by NGS using a 592 gene panel. Smoking status was obtained from medical records. Genomic alterations, mutation burden, PD-L1 immunohistochemistry, gene set enrichment analyses (GSEA), immune-cell infiltration, and clinical outcomes were compared between never- and ever-smokers. Fisher’s exact, Mann-Whitney U or t-tests were used, where appropriate. Statistical significance was defined as p &lt; 0.05 with q &lt; 0.05 or FDR &lt; 0.25, where appropriate.</div></div><div><h3>Results</h3><div>2,891 patients with sqNSCLC were included, of which 2862 (98%) were ever-smokers and 63 (2%) were never-smokers. AGAs were detected in 22.2% (14/63) of never-smokers and 2.4% (69/2828) of ever-smokers. Never-smokers had a significantly higher prevalence of actionable <em>MET</em> and <em>EGFR</em> mutations compared to ever-smokers (9.5% vs 0.4% and 7.9% vs 0.4%, respectively), though actionable alterations were detected in both cohorts. GSEA revealed significantly enriched expression of interferon-α, interferon-γ and IL-6/JAK/STAT pathways in never-smokers.</div></div><div><h3>Conclusion</h3><div>A high frequency of AGAs were detected in never-smokers with sqNSCLC, with significantly increased prevalence of actionable <em>EGFR</em> and <em>MET</em> alterations compared to ever-smokers. Our findings indicate that, analogous to the diagnostic algorithm for non-squamous NSCLC, NGS testing to inform frontline treatment decision-making is critical for never-smokers with sqNSCLC.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"200 ","pages":"Article 108101"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143101905","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}

{"title":"First-line osimertinib compared to earlier generation TKIs in advanced EGFR-mutant NSCLC: A real-world survival analysis","authors":"Igor Gomez-Randulfe ,&nbsp;Lauren A. Scanlon ,&nbsp;Mathew Carter ,&nbsp;Laura Moliner ,&nbsp;Emine Cil ,&nbsp;Raffaele Califano ,&nbsp;Yvonne Summers ,&nbsp;Fiona Blackhall ,&nbsp;Colin R Lindsay ,&nbsp;Jacob Lewis ,&nbsp;Fabio Gomes","doi":"10.1016/j.lungcan.2025.108084","DOIUrl":"10.1016/j.lungcan.2025.108084","url":null,"abstract":"<div><h3>Objectives</h3><div>This study aimed to compare the overall survival (OS) of patients with advanced EGFR-mutant NSCLC treated with first-line osimertinib versus earlier-generation EGFR tyrosine kinase inhibitors (TKIs) in a real-world setting. Secondary endpoint included OS in patients with uncommon EGFR mutations. Exploratory aim focused on the impact of TKIs sequencing strategies.</div></div><div><h3>Methods</h3><div>We conducted a retrospective cohort study of patients diagnosed with advanced EGFR-mutant NSCLC who started first-line treatment with either osimertinib or another EGFR TKI (afatinib, erlotinib, or gefitinib) at The Christie (Manchester, UK) from January 2014 to May 2023. Data were extracted from electronic health records, and survival outcomes were analysed using Kaplan-Meier estimates and Cox proportional hazards models.</div></div><div><h3>Results</h3><div>We identified 119 patients treated with first-line osimertinib and 217 with other EGFR TKIs. In the whole population, median age was 69 years (IQR 59.8–77) and 67.3 % of the patients had an ECOG 0–1. With a median follow-up of 73.2 months (95 % CI 66.2–115.7) and 30.6 months (95 % CI 26.0–38.4) in the earlier-generation TKIs and the osimertinib groups, respectively, the median OS was comparable (16.6 vs 16.9 months; HR = 1, p = 0.97). Patients with uncommon EGFR mutations (n = 48; 14.3 %) had poorer survival compared to those with common mutations (HR = 1.664, p = 0.002). Amongst patients who received two treatment lines, those who received osimertinib after another TKI had a shorter OS than those who received osimertinib first-line followed by another line of therapy (HR = 2.062, p = 0.022).</div></div><div><h3>Conclusion</h3><div>First-line osimertinib showed comparable OS to earlier-generation EGFR TKIs for advanced EGFR-mutant NSCLC. Patients with uncommon EGFR mutations had a poorer survival. Further research is warranted to optimize treatment for patients with uncommon EGFR mutations and to explore the cost-effectiveness of different sequencing approaches.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"200 ","pages":"Article 108084"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008185","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}

{"title":"Histological and genetic features and therapeutic responses of lung cancers explored via the global analysis of their metabolome profile","authors":"Daisuke Narita ,&nbsp;Eiji Hishinuma ,&nbsp;Risa Ebina-Shibuya ,&nbsp;Eisaku Miyauchi ,&nbsp;Naomi Matsukawa ,&nbsp;Ikuko N. Motoike ,&nbsp;Kengo Kinoshita ,&nbsp;Seizo Koshiba ,&nbsp;Yoko Tsukita ,&nbsp;Hirotsugu Notsuda ,&nbsp;Nozomu Kimura ,&nbsp;Ryota Saito ,&nbsp;Koji Murakami ,&nbsp;Naoya Fujino ,&nbsp;Tomohiro Ichikawa ,&nbsp;Mitsuhiro Yamada ,&nbsp;Tsutomu Tamada ,&nbsp;Hisatoshi Sugiura","doi":"10.1016/j.lungcan.2025.108082","DOIUrl":"10.1016/j.lungcan.2025.108082","url":null,"abstract":"<div><h3>Background</h3><div>Lung cancer is the deadliest disease globally, with more than 120,000 diagnosed cases and more than 75,000 deaths annually in Japan. Several treatment options for advanced lung cancer are available, and the discovery of biomarkers will be useful for personalized medicine. Using metabolome analysis, we aimed to identify biomarkers for diagnosis and treatment response by examining the changes in metabolites associated with lung cancer progression.</div></div><div><h3>Methods</h3><div>Plasma samples from patients with recurrent or metastatic non-small cell lung carcinomas diagnosed at Tohoku University Hospital between 2019 and 2024 were used in this study. Metabolomic analysis was performed using the Biocrates Life Sciences MxP Quant 500 kit. Multivariate, principal component, and orthogonal partial least squares discriminant analyses were performed.</div></div><div><h3>Results</h3><div>The triglyceride and phosphatidylcholine concentrations were higher in the patients with early than in those with advanced lung adenocarcinomas. However, the cholesterol ester concentrations were higher for the patients with advanced lung cancer. The concentrations of hexosylceramide were higher in patients with early lung adenocarcinoma than in those with squamous cell carcinoma. Relative to <em>epidermal growth factor receptor</em> (<em>EGFR</em>)-mutation negative cases, the <em>EGFR</em>-mutation positive cases showed marked differences between the ceramide and triglyceride concentrations. For the best therapeutic effect of EGFR-TKI treatment, the hexosylceramide (HexCer) (d18:1/24:0), ceramide (Cer) (d18:2/22:0), and ceramide (Cer) (d18:2/24:0) concentrations were higher for the stable and progressive disease groups. The concentrations of phosphatidylcholine (PC) ae C42:2, sphingomyelin (SM) C24:1, and lysophosphatidylcholine (lysoPC) a C18:2 were higher in the partial response group treated with immune checkpoint inhibitors and chemotherapy.</div></div><div><h3>Conclusion</h3><div>Metabolomic analysis may be useful for the diagnosis and treatment of lung cancer and may provide clues for new therapeutic strategies. PC ae C42:2, SM C24:1, and lysoPC a C18:2 can serve as predictive biomarkers for monitoring the therapeutic effects of the combination of immune checkpoint inhibitors and chemotherapy.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"200 ","pages":"Article 108082"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066598","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":"Comparative analysis of first-line treatment in NSCLC including unresectable stage III (IIIB/IIIC) and stage IV with low PD-L1 expression: Clinical trial eligible versus ineligible patients","authors":"Tae Hata ,&nbsp;Tadaaki Yamada ,&nbsp;Yasuhiro Goto ,&nbsp;Akihiko Amano ,&nbsp;Yoshiki Negi ,&nbsp;Satoshi Watanabe ,&nbsp;Naoki Furuya ,&nbsp;Tomohiro Oba ,&nbsp;Tatsuki Ikoma ,&nbsp;Akira Nakao ,&nbsp;Keiko Tanimura ,&nbsp;Hirokazu Taniguchi ,&nbsp;Akihiro Yoshimura ,&nbsp;Tomoya Fukui ,&nbsp;Daiki Murata ,&nbsp;Kyoichi Kaira ,&nbsp;Shinsuke Shiotsu ,&nbsp;Makoto Hibino ,&nbsp;Asuka Okada ,&nbsp;Yusuke Chihara ,&nbsp;Koichi Takayama","doi":"10.1016/j.lungcan.2025.108104","DOIUrl":"10.1016/j.lungcan.2025.108104","url":null,"abstract":"<div><h3>Background</h3><div>Clinical trial eligible patients with advanced non-small cell lung cancer (aNSCLC) and low programmed cell death ligand 1 (PD-L1) expression achieve greater benefit from immune checkpoint inhibitor (ICI) combination chemotherapy (ICI-Chemo) compared with Chemo alone. We examined whether patients ineligible for clinical trials may benefit from ICI-Chemo.</div></div><div><h3>Methods</h3><div>This multicenter retrospective cohort study enrolled patients with aNSCLC, including unresectable Stage III (IIIB/IIIC) and IV disease with a PD-L1 tumor proportion score of 1–49% treated with ICI-Chemo or Chemo as first-line therapy from 2018 to 2023 in Japan. Treatment outcome and safety of ICI-Chemo versus Chemo groups in trial-eligible and trial-ineligible patients was compared based on criteria from previous phase III clinical trials.</div></div><div><h3>Results</h3><div>Overall, 728 patients were analyzed: 333 trial-eligible and 395 ineligible patients. The median overall survival was 25.1 months in the ICI-Chemo group and 18.5 months in the Chemo group for eligible patients (HR 0.73, 95 %CI: 0.54–0.97) and was 18.2 months in the ICI-Chemo group and 14.9 months in the Chemo group for ineligible patients (HR 0.75, 95 %CI: 0.59–0.95). Median progression-free survival was longer with ICI-Chemo in both groups. For ineligible patients, performance status (PS) ≥ 2 and squamous cell carcinoma (SqCC) were clinical factors associated with worse survival prognosis, and survival outcomes with ICI-Chemo and Chemo were comparable. The ineligible group had no increase in severe adverse events compared to the eligible group.</div></div><div><h3>Conclusions</h3><div>This study suggests a possible clinical benefit of receiving ICI-Chemo for trial-ineligible patients with low PD-L1 expression, excluding those with PS ≥ 2 or SqCC.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"200 ","pages":"Article 108104"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143075011","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}