Luis Posado-Domínguez, Alejandro Olivares-Hernández, Daniel Morchón-Araujo, Luis Figuero-Perez, Lorena Bellido-Hernández, Laura Corvo-Felix, Jonnathan Roldan-Ruiz, Iñigo San Miguel, Emilio Fonseca-Sanchez, Edel Del Barco-Morillo
{"title":"化疗-免疫治疗对转移性肺腺癌患者TTF-1生物标志物阴性预后的影响:一项回顾性队列研究","authors":"Luis Posado-Domínguez, Alejandro Olivares-Hernández, Daniel Morchón-Araujo, Luis Figuero-Perez, Lorena Bellido-Hernández, Laura Corvo-Felix, Jonnathan Roldan-Ruiz, Iñigo San Miguel, Emilio Fonseca-Sanchez, Edel Del Barco-Morillo","doi":"10.21037/tlcr-2025-65","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The prognostic significance of TTF-1 expression in advanced lung adenocarcinoma may be an important factor in optimizing treatment strategies. This study aimed to evaluate the impact of TTF-1 negativity on overall survival (OS) and progression-free survival (PFS) in stage IV lung adenocarcinoma patients with low PD-L1 expression treated with platinum-pemetrexed-pembrolizumab.</p><p><strong>Methods: </strong>We conducted a retrospective analysis of 155 patients with stage IV lung adenocarcinoma and PD-L1 expression <50%. We stratified patients according to TTF-1 expression. The primary survival analysis focused on 64 patients who received first-line platinum-pemetrexed chemotherapy in combination with pembrolizumab. We evaluated OS and PFS using Kaplan-Meier curves and multivariate Cox regression.</p><p><strong>Results: </strong>Among patients treated with platinum-pemetrexed-pembrolizumab, TTF-1-negative patients showed significantly shorter OS and numerically shorter PFS compared to TTF-1-positive patients. Median OS was 13 months for TTF-1-negative patients and 21 months for TTF-1-positive patients (P=0.01). Median PFS was 10 <i>vs.</i> 13 months, respectively (P=0.11). In the overall cohort, TTF-1 negativity was independently associated with a 2.3-fold increased risk of mortality (hazard ratio =2.288, 95% confidence interval: 1.073-4.879, P=0.03).</p><p><strong>Conclusions: </strong>TTF-1 negativity is an independent adverse prognostic factor in patients with stage IV lung adenocarcinoma and low PD-L1 expression. The observed differences in survival suggest that platinum-pemetrexed-pembrolizumab may be less effective for TTF-1-negative patients, and that alternative strategies should be explored in this high-risk subgroup.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 7","pages":"2494-2508"},"PeriodicalIF":3.5000,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12337030/pdf/","citationCount":"0","resultStr":"{\"title\":\"Prognostic impact of negative TTF-1 biomarker in metastatic lung adenocarcinoma treated with chemo-immunotherapy: a retrospective cohort study.\",\"authors\":\"Luis Posado-Domínguez, Alejandro Olivares-Hernández, Daniel Morchón-Araujo, Luis Figuero-Perez, Lorena Bellido-Hernández, Laura Corvo-Felix, Jonnathan Roldan-Ruiz, Iñigo San Miguel, Emilio Fonseca-Sanchez, Edel Del Barco-Morillo\",\"doi\":\"10.21037/tlcr-2025-65\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>The prognostic significance of TTF-1 expression in advanced lung adenocarcinoma may be an important factor in optimizing treatment strategies. This study aimed to evaluate the impact of TTF-1 negativity on overall survival (OS) and progression-free survival (PFS) in stage IV lung adenocarcinoma patients with low PD-L1 expression treated with platinum-pemetrexed-pembrolizumab.</p><p><strong>Methods: </strong>We conducted a retrospective analysis of 155 patients with stage IV lung adenocarcinoma and PD-L1 expression <50%. We stratified patients according to TTF-1 expression. The primary survival analysis focused on 64 patients who received first-line platinum-pemetrexed chemotherapy in combination with pembrolizumab. We evaluated OS and PFS using Kaplan-Meier curves and multivariate Cox regression.</p><p><strong>Results: </strong>Among patients treated with platinum-pemetrexed-pembrolizumab, TTF-1-negative patients showed significantly shorter OS and numerically shorter PFS compared to TTF-1-positive patients. Median OS was 13 months for TTF-1-negative patients and 21 months for TTF-1-positive patients (P=0.01). Median PFS was 10 <i>vs.</i> 13 months, respectively (P=0.11). In the overall cohort, TTF-1 negativity was independently associated with a 2.3-fold increased risk of mortality (hazard ratio =2.288, 95% confidence interval: 1.073-4.879, P=0.03).</p><p><strong>Conclusions: </strong>TTF-1 negativity is an independent adverse prognostic factor in patients with stage IV lung adenocarcinoma and low PD-L1 expression. The observed differences in survival suggest that platinum-pemetrexed-pembrolizumab may be less effective for TTF-1-negative patients, and that alternative strategies should be explored in this high-risk subgroup.</p>\",\"PeriodicalId\":23271,\"journal\":{\"name\":\"Translational lung cancer research\",\"volume\":\"14 7\",\"pages\":\"2494-2508\"},\"PeriodicalIF\":3.5000,\"publicationDate\":\"2025-07-31\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12337030/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Translational lung cancer research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.21037/tlcr-2025-65\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/7/18 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Translational lung cancer research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.21037/tlcr-2025-65","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/7/18 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
Prognostic impact of negative TTF-1 biomarker in metastatic lung adenocarcinoma treated with chemo-immunotherapy: a retrospective cohort study.
Background: The prognostic significance of TTF-1 expression in advanced lung adenocarcinoma may be an important factor in optimizing treatment strategies. This study aimed to evaluate the impact of TTF-1 negativity on overall survival (OS) and progression-free survival (PFS) in stage IV lung adenocarcinoma patients with low PD-L1 expression treated with platinum-pemetrexed-pembrolizumab.
Methods: We conducted a retrospective analysis of 155 patients with stage IV lung adenocarcinoma and PD-L1 expression <50%. We stratified patients according to TTF-1 expression. The primary survival analysis focused on 64 patients who received first-line platinum-pemetrexed chemotherapy in combination with pembrolizumab. We evaluated OS and PFS using Kaplan-Meier curves and multivariate Cox regression.
Results: Among patients treated with platinum-pemetrexed-pembrolizumab, TTF-1-negative patients showed significantly shorter OS and numerically shorter PFS compared to TTF-1-positive patients. Median OS was 13 months for TTF-1-negative patients and 21 months for TTF-1-positive patients (P=0.01). Median PFS was 10 vs. 13 months, respectively (P=0.11). In the overall cohort, TTF-1 negativity was independently associated with a 2.3-fold increased risk of mortality (hazard ratio =2.288, 95% confidence interval: 1.073-4.879, P=0.03).
Conclusions: TTF-1 negativity is an independent adverse prognostic factor in patients with stage IV lung adenocarcinoma and low PD-L1 expression. The observed differences in survival suggest that platinum-pemetrexed-pembrolizumab may be less effective for TTF-1-negative patients, and that alternative strategies should be explored in this high-risk subgroup.
期刊介绍:
Translational Lung Cancer Research(TLCR, Transl Lung Cancer Res, Print ISSN 2218-6751; Online ISSN 2226-4477) is an international, peer-reviewed, open-access journal, which was founded in March 2012. TLCR is indexed by PubMed/PubMed Central and the Chemical Abstracts Service (CAS) Databases. It is published quarterly the first year, and published bimonthly since February 2013. It provides practical up-to-date information on prevention, early detection, diagnosis, and treatment of lung cancer. Specific areas of its interest include, but not limited to, multimodality therapy, markers, imaging, tumor biology, pathology, chemoprevention, and technical advances related to lung cancer.