Pub Date : 2024-08-09DOI: 10.1016/j.lungcan.2024.107920
Virginia Calvo , Emetis Niazmand , Enric Carcereny , Delvys Rodriguez-Abreu , Manuel Cobo , Rafael López-Castro , María Guirado , Carlos Camps , Ana Laura Ortega , Reyes Bernabé , Bartomeu Massutí , Rosario Garcia-Campelo , Edel del Barco , José Luis González-Larriba , Joaquim Bosch-Barrera , Marta Martínez , María Torrente , María-Esther Vidal , Mariano Provencio
Objectives
Lung Cancer (LC) is a multifactorial disease for which the role of genetic susceptibility has become increasingly relevant. Our aim was to use artificial intelligence (AI) to analyze differences between patients with LC based on family history of cancer (FHC).
Materials and methods
From August 2016 to June 2020 clinical information was obtained from Thoracic Tumors Registry (TTR), a nationwide database sponsored by the Spanish Lung Cancer Group. In addition to descriptive statistical analysis, an AI-assisted analysis was performed. The German Technical Information Library supported the merging of data from the electronic medical records and database of the TTR. The results of the AI-assisted analysis were reported using Knowledge Graph, Unified Schema and descriptive and predictive analyses.
Results
Analyses were performed in two phases: first, conventional statistical analysis including 11,684 patients of those 5,806 had FHC. Median overall survival (OS) for the global population was 23 months (CI 95 %: 21.39–24.61) in patients with FHC versus 21 months (CI 95 %: 19.53–22.48) in patients without FHC (NFHC), p < 0.001. The second AI-assisted analysis included 5,788 patients of those 939 had FHC. 58.48 % of women with FHC had LC. 9.53 % of patients had an EGFR or HER2 mutation or ALK translocation and at least one relative with cancer. A family history of LC was associated with an increased risk of smoking-related LC. Non-smokers with a family history of LC were more likely to have an EGFR mutation in NSCLC. In Bayesian network analysis, 55 % of patients with a family history of LC and never-smokers had an EGFR mutation.
Conclusion
In our population, the incidence of LC in patients with a FHC is higher in women and younger patients. FHC is a risk factor and predictor of LC development, especially in people ≤ 50 years. These results were confirmed by conventional statistics and AI-assisted analysis.
{"title":"Family history of cancer and lung cancer: Utility of big data and artificial intelligence for exploring the role of genetic risk","authors":"Virginia Calvo , Emetis Niazmand , Enric Carcereny , Delvys Rodriguez-Abreu , Manuel Cobo , Rafael López-Castro , María Guirado , Carlos Camps , Ana Laura Ortega , Reyes Bernabé , Bartomeu Massutí , Rosario Garcia-Campelo , Edel del Barco , José Luis González-Larriba , Joaquim Bosch-Barrera , Marta Martínez , María Torrente , María-Esther Vidal , Mariano Provencio","doi":"10.1016/j.lungcan.2024.107920","DOIUrl":"10.1016/j.lungcan.2024.107920","url":null,"abstract":"<div><h3>Objectives</h3><p>Lung Cancer (LC) is a multifactorial disease for which the role of genetic susceptibility has become increasingly relevant. Our aim was to use artificial intelligence (AI) to analyze differences between patients with LC based on family history of cancer (FHC).</p></div><div><h3>Materials and methods</h3><p>From August 2016 to June 2020 clinical information was obtained from Thoracic Tumors Registry (TTR), a nationwide database sponsored by the Spanish Lung Cancer Group. In addition to descriptive statistical analysis, an AI-assisted analysis was performed. The German Technical Information Library supported the merging of data from the electronic medical records and database of the TTR. The results of the AI-assisted analysis were reported using Knowledge Graph, Unified Schema and descriptive and predictive analyses.</p></div><div><h3>Results</h3><p>Analyses were performed in two phases: first, conventional statistical analysis including 11,684 patients of those 5,806 had FHC. Median overall survival (OS) for the global population was 23 months (CI 95 %: 21.39–24.61) in patients with FHC versus 21 months (CI 95 %: 19.53–22.48) in patients without FHC (NFHC), p < 0.001. The second AI-assisted analysis included 5,788 patients of those 939 had FHC. 58.48 % of women with FHC had LC. 9.53 % of patients had an EGFR or HER2 mutation or ALK translocation and at least one relative with cancer. A family history of LC was associated with an increased risk of smoking-related LC. Non-smokers with a family history of LC were more likely to have an EGFR mutation in NSCLC. In Bayesian network analysis, 55 % of patients with a family history of LC and never-smokers had an EGFR mutation.</p></div><div><h3>Conclusion</h3><p>In our population, the incidence of LC in patients with a FHC is higher in women and younger patients. FHC is a risk factor and predictor of LC development, especially in people ≤ 50 years. These results were confirmed by conventional statistics and AI-assisted analysis.</p></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"195 ","pages":"Article 107920"},"PeriodicalIF":4.5,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0169500224004549/pdfft?md5=97d1b85b57d7a4c02403157543ffb63f&pid=1-s2.0-S0169500224004549-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141976099","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}
Pub Date : 2024-08-08DOI: 10.1016/j.lungcan.2024.107925
Yao Ding , Shun Lei , Ling Wang , Long Tang , Yue Zhang , Yiran Liao , Xia Deng , Yan Li , Yi Gong , Yongsheng Li
Objective
The reported impact of age on the effectiveness of emerging immunotherapies in patients with advanced non-small cell lung cancer (NSCLC) has been inconsistent in clinical trials, largely due to an underrepresentation of older individuals. This meta-analysis aimed to evaluate the efficacy of immune checkpoint inhibitor (ICI) in older patients with NSCLC.
Materials and methods
The literature up to April 2024 was reviewed to identify articles meeting the criteria for inclusion. Hazard ratios (HRs) for overall survival (OS) across various age groups were examined. The ratio of HR (RHR) was computed and combined for each study.
Results
A preliminary search identified 118 articles, with 13 being phase II or III randomized clinical trials comparing the efficacy of nivolumab, avelumab, ipilimumab, pembrolizumab, atezolizumab, and chemotherapy with or without antiangiogenic therapy. The analysis revealed that the HR for OS was 0.75 (95 % CI: 0.70–0.80, P=0.080) in patients aged under 75 years and 0.87 (95 % CI: 0.74–1.01, P=0.913) in patients aged 75 years and older. The combined RHR for patients aged 75 years and above versus those aged under 75 years was 1.14 (95 % CI: 0.97–1.34, P=0.697). There was no significant difference in OS benefit between patients over 75 years and younger patients (P=0.105). Subgroup analyses indicated that the benefit of OS was consistent across all subgroups and age groups.
Conclusions
Our investigation found no significant differences in the efficacy of immunotherapy for patients with NSCLC aged 75 years and older compared to those under 75 years old. This suggests that the efficacy of immunotherapy against NSCLC is consistent across age groups.
{"title":"Age-related efficacy of immunotherapies in advanced non-small cell lung cancer: a comprehensive meta-analysis","authors":"Yao Ding , Shun Lei , Ling Wang , Long Tang , Yue Zhang , Yiran Liao , Xia Deng , Yan Li , Yi Gong , Yongsheng Li","doi":"10.1016/j.lungcan.2024.107925","DOIUrl":"10.1016/j.lungcan.2024.107925","url":null,"abstract":"<div><h3>Objective</h3><p>The reported impact of age on the effectiveness of emerging immunotherapies in patients with advanced non-small cell lung cancer (NSCLC) has been inconsistent in clinical trials, largely due to an underrepresentation of older individuals. This <em>meta</em>-analysis aimed to evaluate the efficacy of immune checkpoint inhibitor (ICI) in older patients with NSCLC.</p></div><div><h3>Materials and methods</h3><p>The literature up to April 2024 was reviewed to identify articles meeting the criteria for inclusion. Hazard ratios (HRs) for overall survival (OS) across various age groups were examined. The ratio of HR (RHR) was computed and combined for each study.</p></div><div><h3>Results</h3><p>A preliminary search identified 118 articles, with 13 being phase II or III randomized clinical trials comparing the efficacy of nivolumab, avelumab, ipilimumab, pembrolizumab, atezolizumab, and chemotherapy with or without antiangiogenic therapy. The analysis revealed that the HR for OS was 0.75 (95 % CI: 0.70–0.80, <em>P</em>=0.080) in patients aged under 75 years and 0.87 (95 % CI: 0.74–1.01, <em>P</em>=0.913) in patients aged 75 years and older. The combined RHR for patients aged 75 years and above <em>versus</em> those aged under 75 years was 1.14 (95 % CI: 0.97–1.34, <em>P</em>=0.697). There was no significant difference in OS benefit between patients over 75 years and younger patients (<em>P</em>=0.105). Subgroup analyses indicated that the benefit of OS was consistent across all subgroups and age groups.</p></div><div><h3>Conclusions</h3><p>Our investigation found no significant differences in the efficacy of immunotherapy for patients with NSCLC aged 75 years and older compared to those under 75 years old. This suggests that the efficacy of immunotherapy against NSCLC is consistent across age groups.</p></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"195 ","pages":"Article 107925"},"PeriodicalIF":4.5,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141988280","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 : 2024-08-06DOI: 10.1016/j.lungcan.2024.107921
David M. Waterhouse , Sacha Rothschild , Christophe Dooms , Bertrand Mennecier , Farastuk Bozorgmehr , Margarita Majem , Michel H. van den Heuvel , Helena Linardou , Byoung Chul Cho , Rachel Roberts-Thomson , Kentaro Tanaka , Normand Blais , Gustavo Schvartsman , Karin Holmskov Hansen , Izabela Chmielewska , Martin D. Forster , Christina Giannopoulou , Björn Stollenwerk , Cynthia C. Obiozor , Yang Wang , Silvia Novello
Background
In the CodeBreaK 200 phase III, open-label trial, sotorasib significantly improved efficacy versus docetaxel in previously treated KRAS G12C-mutated advanced non-small cell lung cancer (NSCLC). Patient-reported outcomes (PROs) for global health status, physical functioning, dyspnea, and cough favored sotorasib over docetaxel. Here, we report sotorasib’s additional impact on quality of life (QOL).
Methods
In CodeBreaK 200, 345 patients who had progressed after prior therapy received sotorasib (960 mg orally daily) or docetaxel (75 mg/m2 intravenously every 3 weeks). Validated questionnaires captured patients’ perception of their QOL and symptom burden for key secondary and exploratory PRO endpoints, including the European Organisation for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30 (EORTC QLQ-C30) and Quality-of-life Questionnaire Lung Cancer 13 (EORTC QLQ-LC13), question GP5 from the Functional Assessment of Cancer Therapy Tool General Form (FACT-G GP5), PRO-Common Terminology Criteria for Adverse Events (PRO-CTCAE), and 5-level EuroQOL-5 dimensions (EQ-5D-5L) including visual analog scale (EQ-5D VAS). Change from baseline to week 12 was assessed with generalized estimating equations for ordinal outcomes.
Results
Patients receiving sotorasib were less bothered by treatment side effects than those receiving docetaxel (odds ratio [OR] 5.7) and experienced symptoms at lower severity (pain: OR 2.9; aching muscles: OR 4.4; aching joints: OR 4.2; mouth or throat sores: OR 4.3). Further, patients’ symptoms interfered less with usual/daily activities (pain: OR 3.2; aching muscles: OR 3.9; aching joints: OR 10.7). QOL remained stable with sotorasib but worsened with docetaxel (change from baseline in EQ-5D VAS score: 1.5 vs –8.4 at cycle 1 day 5 and 2.2 vs –5.8 at week 12).
Conclusions
Patients receiving sotorasib reported less severe symptoms than those receiving docetaxel. In addition to improving clinical efficacy outcomes, sotorasib maintained QOL versus docetaxel, suggesting sotorasib may be a more tolerable treatment option for patients with pretreated, KRAS G12C-mutated advanced NSCLC.
{"title":"Patient-reported outcomes in CodeBreaK 200: Sotorasib versus docetaxel for previously treated advanced NSCLC with KRAS G12C mutation","authors":"David M. Waterhouse , Sacha Rothschild , Christophe Dooms , Bertrand Mennecier , Farastuk Bozorgmehr , Margarita Majem , Michel H. van den Heuvel , Helena Linardou , Byoung Chul Cho , Rachel Roberts-Thomson , Kentaro Tanaka , Normand Blais , Gustavo Schvartsman , Karin Holmskov Hansen , Izabela Chmielewska , Martin D. Forster , Christina Giannopoulou , Björn Stollenwerk , Cynthia C. Obiozor , Yang Wang , Silvia Novello","doi":"10.1016/j.lungcan.2024.107921","DOIUrl":"10.1016/j.lungcan.2024.107921","url":null,"abstract":"<div><h3>Background</h3><p>In the CodeBreaK 200 phase III, open-label trial, sotorasib significantly improved efficacy versus docetaxel in previously treated <em>KRAS</em> G12C-mutated advanced non-small cell lung cancer (NSCLC). Patient-reported outcomes (PROs) for global health status, physical functioning, dyspnea, and cough favored sotorasib over docetaxel. Here, we report sotorasib’s additional impact on quality of life (QOL).</p></div><div><h3>Methods</h3><p>In CodeBreaK 200, 345 patients who had progressed after prior therapy received sotorasib (960 mg orally daily) or docetaxel (75 mg/m<sup>2</sup> intravenously every 3 weeks). Validated questionnaires captured patients’ perception of their QOL and symptom burden for key secondary and exploratory PRO endpoints, including the European Organisation for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30 (EORTC QLQ-C30) and Quality-of-life Questionnaire Lung Cancer 13 (EORTC QLQ-LC13), question GP5 from the Functional Assessment of Cancer Therapy Tool General Form (FACT-G GP5), PRO-Common Terminology Criteria for Adverse Events (PRO-CTCAE), and 5-level EuroQOL-5 dimensions (EQ-5D-5L) including visual analog scale (EQ-5D VAS). Change from baseline to week 12 was assessed with generalized estimating equations for ordinal outcomes.</p></div><div><h3>Results</h3><p>Patients receiving sotorasib were less bothered by treatment side effects than those receiving docetaxel (odds ratio [OR] 5.7) and experienced symptoms at lower severity (pain: OR 2.9; aching muscles: OR 4.4; aching joints: OR 4.2; mouth or throat sores: OR 4.3). Further, patients’ symptoms interfered less with usual/daily activities (pain: OR 3.2; aching muscles: OR 3.9; aching joints: OR 10.7). QOL remained stable with sotorasib but worsened with docetaxel (change from baseline in EQ-5D VAS score: 1.5 vs –8.4 at cycle 1 day 5 and 2.2 vs –5.8 at week 12).</p></div><div><h3>Conclusions</h3><p>Patients receiving sotorasib reported less severe symptoms than those receiving docetaxel. In addition to improving clinical efficacy outcomes, sotorasib maintained QOL versus docetaxel, suggesting sotorasib may be a more tolerable treatment option for patients with pretreated, <em>KRAS</em> G12C-mutated advanced NSCLC.</p></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"196 ","pages":"Article 107921"},"PeriodicalIF":4.5,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0169500224004550/pdfft?md5=f788b6bd78bf93b5b72d2444d5c9ed96&pid=1-s2.0-S0169500224004550-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142274408","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}
Pub Date : 2024-08-05DOI: 10.1016/j.lungcan.2024.107918
Yiqun Wei , Runmiao Wu , Shuanying Yang , Yanfei Cao , Jing Li , Huihui Ma , Junfang Wu , Jinjin Duan , Shumei Yang
Objectives
Tigger transposable element-derived 1 (TIGD1) expression and its underlying functions and regulatory mechanisms in lung adenocarcinoma (LUAD) remain unknown. Therefore, we intended to explore the expression, potential functions, and regulatory mechanisms of TIGD1 in LUAD.
Materials and methods
TIGD1 expression in LUAD tissues was determined by immunohistochemistry analysis of a tissue microarray. Functional experiments were conducted to determine how TIGD1 affects LUAD tumorigenesis and metastasis. The molecular mechanisms by which TIGD1 induces LUAD progression were determined.
Results
TIGD1 was upregulated in LUAD tissues and was related to lymph node metastases. TIGD1 knockdown suppressed LUAD cell proliferation, migration, and invasion, while promoted cell apoptosis. Furthermore, decreased metastatic nodules were observed in the TIGD1 knockdown mouse metastasis model. Moreover, microarray analysis was performed to determine the potential downstream genes of TIGD1 in LUAD. Hallmark pathway analysis revealed that the downstream genes of TIGD1 were involved in epithelial-mesenchymal transition (EMT). Western blotting confirmed that vimentin and TWIST was downregulated in TIGD1 knockdown cells, while E-cadherin was upregulated. Ingenuity pathway and hallmark pathway analyses revealed that TIGD1 regulated the interleukin-6 signaling pathway and related gene members. Western blotting, quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay indicated that downregulation of TIGD1 decreased interleukin-6 and CXCL1 expression. TIGD1 expression was negatively correlated with immune infiltration in LUAD. The upstream microRNA of TIGD1 was predicted, and subsequent luciferase reporter gene experiments confirmed the interactions between miR-137 and TIGD1. The expression of miR-137 was significantly downregulated in LUAD tissues and miR-137 suppressed the proliferation, migration, and invasion of LUAD cells, partially through negatively regulating the expression of TIGD1.
Conclusion
Our findings suggest that TIGD1, which was regulated by miR-137, contributed to LUAD progression by promoting cell proliferation, migration, invasion, and EMT and suppressing cell apoptosis.
{"title":"MiR-137 mediated high expression of TIGD1 promotes migration, invasion, and suppresses apoptosis of lung adenocarcinoma","authors":"Yiqun Wei , Runmiao Wu , Shuanying Yang , Yanfei Cao , Jing Li , Huihui Ma , Junfang Wu , Jinjin Duan , Shumei Yang","doi":"10.1016/j.lungcan.2024.107918","DOIUrl":"10.1016/j.lungcan.2024.107918","url":null,"abstract":"<div><h3>Objectives</h3><p>Tigger transposable element-derived 1 (TIGD1) expression and its underlying functions and regulatory mechanisms in lung adenocarcinoma (LUAD) remain unknown. Therefore, we intended to explore the expression, potential functions, and regulatory mechanisms of TIGD1 in LUAD.</p></div><div><h3>Materials and methods</h3><p>TIGD1 expression in LUAD tissues was determined by immunohistochemistry analysis of a tissue microarray. Functional experiments were conducted to determine how TIGD1 affects LUAD tumorigenesis and metastasis. The molecular mechanisms by which TIGD1 induces LUAD progression were determined.</p></div><div><h3>Results</h3><p>TIGD1 was upregulated in LUAD tissues and was related to lymph node metastases. TIGD1 knockdown suppressed LUAD cell proliferation, migration, and invasion, while promoted cell apoptosis. Furthermore, decreased metastatic nodules were observed in the TIGD1 knockdown mouse metastasis model. Moreover, microarray analysis was performed to determine the potential downstream genes of TIGD1 in LUAD. Hallmark pathway analysis revealed that the downstream genes of TIGD1 were involved in epithelial-mesenchymal transition (EMT). Western blotting confirmed that vimentin and TWIST was downregulated in TIGD1 knockdown cells, while E-cadherin was upregulated. Ingenuity pathway and hallmark pathway analyses revealed that TIGD1 regulated the interleukin-6 signaling pathway and related gene members. Western blotting, quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay indicated that downregulation of TIGD1 decreased interleukin-6 and CXCL1 expression. TIGD1 expression was negatively correlated with immune infiltration in LUAD. The upstream microRNA of TIGD1 was predicted, and subsequent luciferase reporter gene experiments confirmed the interactions between miR-137 and TIGD1. The expression of miR-137 was significantly downregulated in LUAD tissues and miR-137 suppressed the proliferation, migration, and invasion of LUAD cells, partially through negatively regulating the expression of TIGD1.</p></div><div><h3>Conclusion</h3><p>Our findings suggest that TIGD1, which was regulated by miR-137, contributed to LUAD progression by promoting cell proliferation, migration, invasion, and EMT and suppressing cell apoptosis.</p></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"195 ","pages":"Article 107918"},"PeriodicalIF":4.5,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0169500224004525/pdfft?md5=1e665bf0e5a69be50ea5a3d4465969fc&pid=1-s2.0-S0169500224004525-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142020622","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}
Pub Date : 2024-08-05DOI: 10.1016/j.lungcan.2024.107916
Najmeh Alirezaie , Anne-Laure Chong , Felix K.F. Kommoss , Nelly Sabbaghian , Jose Camacho Valenzuela , Dylan Pelletier , Javad Nadaf , Shailesh B. Kolekar , Pradeesh Sivapalan , Mark G. Evans , Paul S. Thorner , Pierre-Olivier Fiset , Andreas von Deimling , William D. Foulkes
Objective
Pulmonary blastoma is a rare, biphasic, adult-onset lung tumor. In this study, we investigate whether DICER1 pathogenic variants are a feature of pulmonary blastomas through in-depth analysis of the molecular events defining them.
Methods
We performed exome-wide sequencing and DNA methylation profiling of 8 pulmonary blastomas from 6 affected persons.
Results
We identified biallelic somatic DICER1 pathogenic variants in 7 of 8 cases. The remaining case had a solitary missense pathogenic variant in the RNase IIIb domain of DICER1. Six of 8 cases carried a CTNNB1 hotspot variant and 4 of 8 had a somatic pathogenic variant in TP53. Methylation analysis showed that the pulmonary blastomas clustered with other DICER1-mutated tumors and not with other more common types of lung cancer.
Conclusion
We conclude somatic DICER1 pathogenic variants are the major driver of pulmonary blastoma and are likely to act in conjunction with CTNNB1 hotspot variants that are often present.
{"title":"Exomic and epigenomic analysis of pulmonary blastoma","authors":"Najmeh Alirezaie , Anne-Laure Chong , Felix K.F. Kommoss , Nelly Sabbaghian , Jose Camacho Valenzuela , Dylan Pelletier , Javad Nadaf , Shailesh B. Kolekar , Pradeesh Sivapalan , Mark G. Evans , Paul S. Thorner , Pierre-Olivier Fiset , Andreas von Deimling , William D. Foulkes","doi":"10.1016/j.lungcan.2024.107916","DOIUrl":"10.1016/j.lungcan.2024.107916","url":null,"abstract":"<div><h3>Objective</h3><p>Pulmonary blastoma is a rare, biphasic, adult-onset lung tumor. In this study, we investigate whether DICER1 pathogenic variants are a feature of pulmonary blastomas through in-depth analysis of the molecular events defining them.</p></div><div><h3>Methods</h3><p>We performed exome-wide sequencing and DNA methylation profiling of 8 pulmonary blastomas from 6 affected persons.</p></div><div><h3>Results</h3><p>We identified biallelic somatic <em>DICER1</em> pathogenic variants in 7 of 8 cases. The remaining case had a solitary missense pathogenic variant in the RNase IIIb domain of DICER1. Six of 8 cases carried a <em>CTNNB1</em> hotspot variant and 4 of 8 had a somatic pathogenic variant in <em>TP53</em>. Methylation analysis showed that the pulmonary blastomas clustered with other <em>DICER1</em>-mutated tumors and not with other more common types of lung cancer.</p></div><div><h3>Conclusion</h3><p>We conclude somatic <em>DICER1</em> pathogenic variants are the major driver of pulmonary blastoma and are likely to act in conjunction with <em>CTNNB1</em> hotspot variants that are often present.</p></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"195 ","pages":"Article 107916"},"PeriodicalIF":4.5,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141913176","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}
Several patients treated with osimertinib experience progressive disease. The aim was to clarify the mechanisms underlying resistance to osimertinib.
Methods
ELUCIDATOR: A multi-centre, prospective, observational study involved chemotherapy-naive patients with advanced non-small cell lung cancer receiving osimertinib. Mutations in cancer-associated genes, detected via ultrasensitive next-generation sequencing of circulating tumour deoxyribonucleic acid samples, were collected at baseline and after progressive disease detection. These paired plasma samples were compared.
Results
Of 188 patients enrolled (May 2019-January 2021), 178 (119 females [67 %]) median age 74 years, were included. Patients, n = 95 (53 %) had epidermal growth factor receptor exon 19 deletion mutations. Among 115 patients with progressive disease, circulating tumour deoxyribonucleic acid levels of 85 patients were analysed. MET amplification (n = 4), TP53 mutations (n = 4), PIK3CA mutations (n = 3), BRINP3 mutation (n = 2), BRAF mutation (n = 2), APC mutation (n = 1), RET mutation (n = 1) and epidermal growth factor receptor (EGFR) resistance mutation, and C797S (n = 1) were detected. Patients with baseline TP53 mutations, with MET or EGFR amplification had shorter progression-free (PFS) and overall survival. Patients with PIK3CA mutations tended to shorter PFS.
Conclusion
MET amplification and PIK3CA mutation mechanisms underly resistance to osimertinib in patients. Patients with coexisting mutations or amplifications at baseline had shorter PFS and overall survival.
{"title":"Mechanisms of resistance and correlation between pre-treatment co-alterations and p-prognosis to osimertinib in chemo-naïve advanced non-small cell lung cancer","authors":"Akihiro Tamiya , Mitsuo Osuga , Daijiro Harada , Shun-ichi Isa , Yoshihiko Taniguchi , Keiichi Nakamura , Yasuyuki Mizumori , Tsutomu Shinohara , Hidetoshi Yanai , Katsumi Nakatomi , Masahide Oki , Masahide Mori , Tomohito Kuwako , Koji Yamazaki , Atsuhisa Tamura , Masahiko Ando , Yasuhiro Koh","doi":"10.1016/j.lungcan.2024.107917","DOIUrl":"10.1016/j.lungcan.2024.107917","url":null,"abstract":"<div><h3>Background</h3><p>Several patients treated with osimertinib experience progressive disease. The aim was to clarify the mechanisms underlying resistance to osimertinib.</p></div><div><h3>Methods</h3><p>ELUCIDATOR: A multi-centre, prospective, observational study involved chemotherapy-naive patients with advanced non-small cell lung cancer receiving osimertinib. Mutations in cancer-associated genes, detected via ultrasensitive next-generation sequencing of circulating tumour deoxyribonucleic acid samples, were collected at baseline and after progressive disease detection. These paired plasma samples were compared.</p></div><div><h3>Results</h3><p>Of 188 patients enrolled (May 2019-January 2021), 178 (119 females [67 %]) median age 74 years, were included. Patients, n = 95 (53 %) had epidermal growth factor receptor exon 19 deletion mutations. Among 115 patients with progressive disease, circulating tumour deoxyribonucleic acid levels of 85 patients were analysed. <em>MET</em> amplification (n = 4), <em>TP53</em> mutations (n = 4), <em>PIK3CA</em> mutations (n = 3), <em>BRINP3</em> mutation (n = 2), <em>BRAF</em> mutation (n = 2), <em>APC</em> mutation (n = 1), <em>RET</em> mutation (n = 1) and epidermal growth factor receptor (EGFR) resistance mutation, and <em>C797S</em> (n = 1) were detected. Patients with baseline <em>TP53</em> mutations, with <em>MET</em> or <em>EGFR</em> amplification had shorter progression-free (PFS) and overall survival. Patients with <em>PIK3CA</em> mutations tended to shorter PFS.</p></div><div><h3>Conclusion</h3><p><em>MET</em> amplification and <em>PIK3CA</em> mutation mechanisms underly resistance to osimertinib in patients. Patients with coexisting mutations or amplifications at baseline had shorter PFS and overall survival.</p></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"195 ","pages":"Article 107917"},"PeriodicalIF":4.5,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0169500224004513/pdfft?md5=e2dc34b44774c91db765513395ec6f32&pid=1-s2.0-S0169500224004513-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141906924","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}
Pub Date : 2024-08-03DOI: 10.1016/j.lungcan.2024.107919
Jessica R. Bauman , Geoffrey Liu , Isabel Preeshagul , Stephen V. Liu , Barbara Melosky , Devin Abrahami , Benjamin Li , Despina Thomaidou , Kirsten Duncan , Stan Krulewicz , Martin Rupp , Jessica J. Lin
Introduction
With multiple targeted therapies approved for anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC), it is increasingly important to understand outcomes with various sequences of next-generation ALK tyrosine kinase inhibitors (TKIs). We describe contemporary sequencing patterns and treatment effectiveness of first-line (1L) and second-line (2L) treatments in patients who received second-generation ALK TKIs in the 1L treatment of ALK-positive NSCLC in the United States.
Methods
A cohort of adults with ALK-positive advanced NSCLC who initiated treatment with 1L alectinib or brigatinib between June 2017 and April 2021 in the Flatiron Health electronic health record–derived de-identified database were followed through April 2023. Time to treatment discontinuation (TTD) in 1L and 2L, TTD on 1L plus 2L sequential therapy (TTD2), and total time on sequential ALK TKI therapy (including beyond 2L) were evaluated.
Results
Patients (N=273) were followed up for a median duration of 28.9 months. Among patients who discontinued 1L therapy, 22% died after 1L discontinuation (median time from discontinuation to death, 4.0 months) without receiving 2L therapy. Median (95% confidence interval [CI]) TTD was 21.9 (15.2–25.8) and 7.3 (5.3–10.2) months in 1L and 2L, respectively. Median (95% CI) TTD2 was 29.4 (25.1–36.1) months and total time on sequential ALK TKI treatment was 28.0 (23.6–32.9) months.
Conclusions
In this large real-world study, TTD2 and the total time on sequential ALK TKIs was approximately 2.5 years. The high attrition rate from 1L to 2L and the longest clinical benefit observed with 1L therapy support using the drug with the longest 1L effectiveness up front in patients with ALK-positive advanced NSCLC.
{"title":"Real-world treatment sequencing and effectiveness of second- and third-generation ALK tyrosine kinase inhibitors for ALK-positive advanced non-small cell lung cancer","authors":"Jessica R. Bauman , Geoffrey Liu , Isabel Preeshagul , Stephen V. Liu , Barbara Melosky , Devin Abrahami , Benjamin Li , Despina Thomaidou , Kirsten Duncan , Stan Krulewicz , Martin Rupp , Jessica J. Lin","doi":"10.1016/j.lungcan.2024.107919","DOIUrl":"10.1016/j.lungcan.2024.107919","url":null,"abstract":"<div><h3>Introduction</h3><p>With multiple targeted therapies approved for anaplastic lymphoma kinase (<em>ALK</em>)-positive metastatic non-small cell lung cancer (NSCLC), it is increasingly important to understand outcomes with various sequences of next-generation ALK tyrosine kinase inhibitors (TKIs). We describe contemporary sequencing patterns and treatment effectiveness of first-line (1L) and second-line (2L) treatments in patients who received second-generation ALK TKIs in the 1L treatment of <em>ALK</em>-positive NSCLC in the United States.</p></div><div><h3>Methods</h3><p>A cohort of adults with <em>ALK</em>-positive advanced NSCLC who initiated treatment with 1L alectinib or brigatinib between June 2017 and April 2021 in the Flatiron Health electronic health record–derived de-identified database were followed through April 2023. Time to treatment discontinuation (TTD) in 1L and 2L, TTD on 1L plus 2L sequential therapy (TTD2), and total time on sequential ALK TKI therapy (including beyond 2L) were evaluated.</p></div><div><h3>Results</h3><p>Patients (N=273) were followed up for a median duration of 28.9 months. Among patients who discontinued 1L therapy, 22% died after 1L discontinuation (median time from discontinuation to death, 4.0 months) without receiving 2L therapy. Median (95% confidence interval [CI]) TTD was 21.9 (15.2–25.8) and 7.3 (5.3–10.2) months in 1L and 2L, respectively. Median (95% CI) TTD2 was 29.4 (25.1–36.1) months and total time on sequential ALK TKI treatment was 28.0 (23.6–32.9) months.</p></div><div><h3>Conclusions</h3><p>In this large real-world study, TTD2 and the total time on sequential ALK TKIs was approximately 2.5 years. The high attrition rate from 1L to 2L and the longest clinical benefit observed with 1L therapy support using the drug with the longest 1L effectiveness up front in patients with <em>ALK</em>-positive advanced NSCLC.</p></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"195 ","pages":"Article 107919"},"PeriodicalIF":4.5,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0169500224004537/pdfft?md5=2afdf40f65a7de10dc42f9698cd2bb4c&pid=1-s2.0-S0169500224004537-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142083470","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}
Pub Date : 2024-08-01DOI: 10.1016/j.lungcan.2024.107888
Qingfeng Wang , Hongyan Liu , Zhibiao Xu , Li Zhang , Yuyun Liu , Han Gao , Yunru Jiang , Linlin Zhao
Objective
To investigate the effects of pregabalin combined with tramadol/paracetamol on acute pain in patients with CT-guided puncture localization of pulmonary nodules.
Materials and Methods
In this randomized, placebo-controlled and single-center study, 120 patients were allocated randomly to four groups: the control group (Group P), the pregabalin-placebo group (Group BP), the tramadol/paracetamol-placebo group (Group AP), and the pregabalin-tramadol/paracetamol group (Group AB). The primary outcome was the NRS (Numerical Rating Scale) score. Other outcomes included systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), pulse oxygen saturation (SpO2), the incidence of moderate to severe pain, the analgesia recovery ratio, the incidence of adverse drug reactions and patients’ satisfaction.
Results
No significant interaction was detected between the interventions (P = 0.752). The NRS score of the Taking pregabalin group and the Taking tramadol/paracetamol group were significantly lower than those of the Not-taking pregabalin group and the Not-taking tramadol/paracetamol group respectively (P < 0.05). There was significant difference in the NRS scores among the four groups (P < 0.001). The NRS score of Group AB was significantly lower than that of Group P (P < 0.001), Group BP (P < 0.001) and Group AP (P = 0.001). At the same time, the NRS scores of Group BP (P < 0.001) and Group AP (P < 0.001) were significantly lower than those of Group P, but there was no significant difference between Group BP and Group AP (P = 1.000). The SBP, DBP, HR, the incidence of moderate to severe pain and the analgesia recovery ratio of Group AB were significantly lower than those of Group P (P < 0.05), while the SpO2 and the number of people who were very satisfied were significantly higher than those of Group P (P < 0.05). There was no significant difference in the incidence of adverse drug reactions among the four groups (P = 0.272).
Conclusions
The combination or single use of pregabalin and tramadol/paracetamol can effectively relieve the acute pain after localization. Pregabalin combined with tramadol/paracetamol has the best analgesic effect and significantly reduces the hemodynamic fluctuations, with high safety and low incidence of adverse drug reactions, which has a certain clinical popularization and application value.
目的 探讨普瑞巴林联合曲马多/扑热息痛对 CT 引导下穿刺定位肺结节患者急性疼痛的影响。材料和方法在这项随机、安慰剂对照和单中心研究中，120 名患者被随机分配到四组：对照组（P 组）、普瑞巴林-安慰剂组（BP 组）、曲马多/扑热息痛-安慰剂组（AP 组）和普瑞巴林-曲马多/扑热息痛组（AB 组）。主要研究结果为 NRS（数值评定量表）评分。其他结果包括收缩压 (SBP)、舒张压 (DBP)、心率 (HR)、脉搏氧饱和度 (SpO2)、中度至重度疼痛发生率、镇痛恢复比、药物不良反应发生率和患者满意度。服用普瑞巴林组和服用曲马多/扑热息痛组的 NRS 评分分别明显低于未服用普瑞巴林组和未服用曲马多/扑热息痛组（P < 0.05）。四组的 NRS 评分有明显差异（P < 0.001）。AB 组的 NRS 评分明显低于 P 组（P < 0.001）、BP 组（P < 0.001）和 AP 组（P = 0.001）。同时，BP 组（P < 0.001）和 AP 组（P < 0.001）的 NRS 评分明显低于 P 组，但 BP 组和 AP 组之间无明显差异（P = 1.000）。AB 组的 SBP、DBP、HR、中重度疼痛发生率和镇痛恢复比均明显低于 P 组（P < 0.05），而 SpO2 和非常满意人数则明显高于 P 组（P < 0.05）。结论普瑞巴林与曲马多/扑热息痛联合或单用可有效缓解局部麻醉后的急性疼痛。普瑞巴林联合曲马多/扑热息痛镇痛效果最佳，可明显减轻血流动力学波动，安全性高，药物不良反应发生率低，具有一定的临床推广应用价值。
{"title":"Effects of pregabalin combined with tramadol/paracetamol on acute pain in patients with CT-guided puncture localization of pulmonary nodules","authors":"Qingfeng Wang , Hongyan Liu , Zhibiao Xu , Li Zhang , Yuyun Liu , Han Gao , Yunru Jiang , Linlin Zhao","doi":"10.1016/j.lungcan.2024.107888","DOIUrl":"10.1016/j.lungcan.2024.107888","url":null,"abstract":"<div><h3>Objective</h3><p>To investigate the effects of pregabalin combined with tramadol/paracetamol on acute pain in patients with CT-guided puncture localization of pulmonary nodules.</p></div><div><h3>Materials and Methods</h3><p>In this randomized, placebo-controlled and single-center study, 120 patients were allocated randomly to four groups: the control group (Group P), the pregabalin-placebo group (Group BP), the tramadol/paracetamol-placebo group (Group AP), and the pregabalin-tramadol/paracetamol group (Group AB). The primary outcome was the NRS (Numerical Rating Scale) score. Other outcomes included systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), pulse oxygen saturation (SpO<sub>2</sub>), the incidence of moderate to severe pain, the analgesia recovery ratio, the incidence of adverse drug reactions and patients’ satisfaction.</p></div><div><h3>Results</h3><p>No significant interaction was detected between the interventions (<em>P</em> = 0.752). The NRS score of the Taking pregabalin group and the Taking tramadol/paracetamol group were significantly lower than those of the Not-taking pregabalin group and the Not-taking tramadol/paracetamol group respectively (<em>P</em> < 0.05). There was significant difference in the NRS scores among the four groups (<em>P</em> < 0.001). The NRS score of Group AB was significantly lower than that of Group P (<em>P</em> < 0.001), Group BP (<em>P</em> < 0.001) and Group AP (<em>P</em> = 0.001). At the same time, the NRS scores of Group BP (<em>P</em> < 0.001) and Group AP (<em>P</em> < 0.001) were significantly lower than those of Group P, but there was no significant difference between Group BP and Group AP (<em>P</em> = 1.000). The SBP, DBP, HR, the incidence of moderate to severe pain and the analgesia recovery ratio of Group AB were significantly lower than those of Group P (<em>P</em> < 0.05), while the SpO<sub>2</sub> and the number of people who were very satisfied were significantly higher than those of Group P (<em>P</em> < 0.05). There was no significant difference in the incidence of adverse drug reactions among the four groups (<em>P</em> = 0.272).</p></div><div><h3>Conclusions</h3><p>The combination or single use of pregabalin and tramadol/paracetamol can effectively relieve the acute pain after localization. Pregabalin combined with tramadol/paracetamol has the best analgesic effect and significantly reduces the hemodynamic fluctuations, with high safety and low incidence of adverse drug reactions, which has a certain clinical popularization and application value.</p></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"194 ","pages":"Article 107888"},"PeriodicalIF":4.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141716885","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 : 2024-08-01DOI: 10.1016/j.lungcan.2024.107867
Manuel Luis Blanco-Villar , José Expósito-Hernández , Eulalia Navarro-Moreno , José María López Martín , Adrián Aparicio Mota , Felipe Couñago
Background
Lung cancer (LC) remains the leading cause of cancer-related mortality globally, necessitating timely diagnosis and treatment to improve patient outcomes. This study aimed to evaluate the timeliness of care for LC patients at a public hospital in Almería, Spain, assess adherence to guidelines, and explore associations between timeliness and survival.
Methods
A retrospective cohort study was conducted, reviewing medical records of LC patients diagnosed between 2019 and 2021. Quality indicators, adapted from prevailing guidelines, facilitated the assessment of care timeliness, with a focus on diagnostic and treatment wait times. Cox regression modeling was employed to explore survival associations, adjusting for covariates including age, performance status, stage, histology, and treatment modalities.
Results
Of 539 patients included, most (79.84 %) had initial specialist contact within 7 days, and 82.25 % received diagnosis within 30 days. However, delays were observed in treatment initiation, with surgery experiencing the longest median wait time (78 days). Survival analysis showed no significant difference between shorter and longer diagnostic (HR: 0.87, 95 % CI: 0.62–1.24) or treatment intervals (HR: 1.14, 95 % CI: 0.83–1.58). Multivariate analysis identified age, performance status, stage, histology, and treatment as prognostic factors.
Conclusion
This study highlights the importance of timely diagnosis and treatment in improving lung cancer outcomes. Despite achieving diagnostic targets, treatment delays were common, particularly for surgical interventions. These findings underscore the need for enhanced coordination and efficient care pathways to minimize delays, ultimately improving survival rates and quality of life for lung cancer patients. Addressing these issues is crucial for optimizing lung cancer care delivery in the future.
{"title":"Analyzing diagnostic and treatment wait times for lung cancer Patients: Key insights from a provincial registry study","authors":"Manuel Luis Blanco-Villar , José Expósito-Hernández , Eulalia Navarro-Moreno , José María López Martín , Adrián Aparicio Mota , Felipe Couñago","doi":"10.1016/j.lungcan.2024.107867","DOIUrl":"10.1016/j.lungcan.2024.107867","url":null,"abstract":"<div><h3>Background</h3><p>Lung cancer (LC) remains the leading cause of cancer-related mortality globally, necessitating timely diagnosis and treatment to improve patient outcomes. This study aimed to evaluate the timeliness of care for LC patients at a public hospital in Almería, Spain, assess adherence to guidelines, and explore associations between timeliness and survival.</p></div><div><h3>Methods</h3><p>A retrospective cohort study was conducted, reviewing medical records of LC patients diagnosed between 2019 and 2021. Quality indicators, adapted from prevailing guidelines, facilitated the assessment of care timeliness, with a focus on diagnostic and treatment wait times. Cox regression modeling was employed to explore survival associations, adjusting for covariates including age, performance status, stage, histology, and treatment modalities.</p></div><div><h3>Results</h3><p>Of 539 patients included, most (79.84 %) had initial specialist contact within 7 days, and 82.25 % received diagnosis within 30 days. However, delays were observed in treatment initiation, with surgery experiencing the longest median wait time (78 days). Survival analysis showed no significant difference between shorter and longer diagnostic (HR: 0.87, 95 % CI: 0.62–1.24) or treatment intervals (HR: 1.14, 95 % CI: 0.83–1.58). Multivariate analysis identified age, performance status, stage, histology, and treatment as prognostic factors.</p></div><div><h3>Conclusion</h3><p>This study highlights the importance of timely diagnosis and treatment in improving lung cancer outcomes. Despite achieving diagnostic targets, treatment delays were common, particularly for surgical interventions. These findings underscore the need for enhanced coordination and efficient care pathways to minimize delays, ultimately improving survival rates and quality of life for lung cancer patients. Addressing these issues is crucial for optimizing lung cancer care delivery in the future.</p></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"194 ","pages":"Article 107867"},"PeriodicalIF":4.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S016950022400401X/pdfft?md5=a15e9fda74ecb0b7efec9b08d70aed48&pid=1-s2.0-S016950022400401X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141759645","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}
Pub Date : 2024-08-01DOI: 10.1016/j.lungcan.2024.107891
L.H. Douma, P. Baas, C.J. de Gooijer
{"title":"First-line doublet immunotherapy: Game changer or hype for patients with mesothelioma?","authors":"L.H. Douma, P. Baas, C.J. de Gooijer","doi":"10.1016/j.lungcan.2024.107891","DOIUrl":"10.1016/j.lungcan.2024.107891","url":null,"abstract":"","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"194 ","pages":"Article 107891"},"PeriodicalIF":4.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141633912","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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