Journal of Thoracic Oncology最新文献

{"title":"Durvalumab With or Without Tremelimumab in Combination With Chemotherapy in First-Line Metastatic NSCLC: Five-Year Overall Survival Outcomes from the Phase 3 POSEIDON Trial.","authors":"Solange Peters, Byoung Chul Cho, Alexander V Luft, Jorge Alatorre-Alexander, Sarayut Lucien Geater, Konstantin Laktionov, Dmytro Trukhin, Sang-We Kim, Grygorii M Ursol, Maen Hussein, Farah Louise Lim, Cheng-Ta Yang, Luiz Henrique Araujo, Haruhiro Saito, Niels Reinmuth, Caitlin Lowery, Helen Mann, Ross Stewart, Haiyi Jiang, Edward B Garon, Tony Mok, Melissa L Johnson","doi":"10.1016/j.jtho.2024.09.1381","DOIUrl":"https://doi.org/10.1016/j.jtho.2024.09.1381","url":null,"abstract":"<p><strong>Introduction: </strong>The primary analysis (median follow-up 34.9 months across all arms) of the phase 3 POSEIDON study demonstrated a statistically significant overall survival (OS) improvement with first-line tremelimumab plus durvalumab and chemotherapy (T+D+CT) versus CT in patients with EGFR/ALK-wild-type metastatic NSCLC (mNSCLC). D+CT showed a trend for OS improvement versus CT that did not reach statistical significance. This paper reports prespecified OS analyses after longer-term follow-up (median >5 years).</p><p><strong>Methods: </strong>1013 patients were randomized (1:1:1) to T+D+CT, D+CT, or CT, stratified by tumor cell (TC) PD-L1 expression (≥50% vs <50%), disease stage (IVA vs IVB), and histology (squamous vs nonsquamous). Serious adverse events were collected during follow-up.</p><p><strong>Results: </strong>After median follow-up of 63.4 months across all arms, T+D+CT showed sustained OS benefit versus CT (hazard ratio [HR] 0.76, 95% CI: 0.64-0.89; 5-year OS: 15.7% vs 6.8%). OS improvement with D+CT versus CT (HR 0.84, 95% CI: 0.72-1.00; 5-year OS: 13.0%) was consistent with the primary analysis. OS benefit with T+D+CT versus CT remained more pronounced in nonsquamous (HR 0.69, 95% CI: 0.56-0.85) versus squamous (HR 0.85, 95% CI: 0.65-1.10) mNSCLC. OS benefit with T+D+CT versus CT was still evident regardless of PD-L1 expression, including patients with PD-L1 TC <1%, and remained evident in STK11-mutant (nonsquamous), KEAP1-mutant, and KRAS-mutant (nonsquamous) mNSCLC. No new safety signals were identified.</p><p><strong>Conclusions: </strong>After median follow-up of >5 years, T+D+CT showed durable long-term OS benefit versus CT, supporting its use as first-line treatment in mNSCLC, including in patient subgroups with harder-to-treat disease.</p>","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":null,"pages":null},"PeriodicalIF":21.0,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum to \"Treatment response biomarkers: working towards personalised radiotherapy for lung cancer. [Journal of Thoracic Oncology Vol. 19 No. 8: 1164-1185]\".","authors":"Ashley Horne, Ken Harada, Katherine D Brown, Kevin Lee Min Chua, Fiona McDonald, Gareth Price, Paul Martin Putora, Dominic G Rothwell, Corinne Faivre-Finn","doi":"10.1016/j.jtho.2024.08.021","DOIUrl":"https://doi.org/10.1016/j.jtho.2024.08.021","url":null,"abstract":"","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":null,"pages":null},"PeriodicalIF":21.0,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lung Cancer in Finland","authors":"","doi":"10.1016/j.jtho.2024.06.005","DOIUrl":"10.1016/j.jtho.2024.06.005","url":null,"abstract":"","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":null,"pages":null},"PeriodicalIF":21.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142135810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Real-World Assessment of Stage I Lung Cancer Through Electronic Nose Technology","authors":"","doi":"10.1016/j.jtho.2024.05.006","DOIUrl":"10.1016/j.jtho.2024.05.006","url":null,"abstract":"<div><h3>Introduction</h3><p>Electronic nose (E-nose) technology has reported excellent sensitivity and specificity in the setting of lung cancer screening. However, the performance of E-nose specifically for early-stage tumors remains unclear. Therefore, the aim of our study was to assess the diagnostic performance of E-nose technology in clinical stage I lung cancer.</p></div><div><h3>Methods</h3><p><span>This phase IIc trial (NCT04734145) included patients diagnosed with a single greater than or equal to 50% solid stage I nodule. Exhalates were prospectively collected from January 2020 to August 2023. Blinded bioengineers analyzed the exhalates, using E-nose technology to determine the probability of malignancy. Patients were stratified into three risk groups (low-risk, [&lt;0.2]; moderate-risk, [≥0.2–0.7]; high-risk, [≥0.7]). The primary outcome was the diagnostic performance of E-nose versus </span>histopathology (accuracy and F1 score). The secondary outcome was the clinical performance of the E-nose versus clinicoradiological prediction models.</p></div><div><h3>Results</h3><p><span>Based on the predefined cutoff (&lt;0.20), E-nose agreed with histopathologic results in 86% of cases, achieving an F1 score of 92.5%, based on 86 true positives, two false negatives, and 12 false positives (n = 100). E-nose would refer fewer patients with malignant nodules to observation (low-risk: 2 versus 9 and 11, respectively; </span><em>p</em> = 0.028 and <em>p =</em> 0.011) than would the Swensen and Brock models and more patients with malignant nodules to treatment without biopsy (high-risk: 27 versus 19 and 6, respectively; <em>p</em> = 0.057 and <em>p</em> &lt; 0.001).</p></div><div><h3>Conclusions</h3><p>In the setting of clinical stage I lung cancer, E-nose agrees well with histopathology. Accordingly, E-nose technology can be used in addition to imaging or as part of a “multiomics” platform.</p></div>","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":null,"pages":null},"PeriodicalIF":21.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140958276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Suggestions for the predictive factors related to irAES and research methods during dose switching of pembrolizumab treatment in patients with advanced NSCLC","authors":"","doi":"10.1016/j.jtho.2024.05.372","DOIUrl":"10.1016/j.jtho.2024.05.372","url":null,"abstract":"","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":null,"pages":null},"PeriodicalIF":21.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142135737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Histopathological Evidence for a Non-Inflammatory Mechanism in Osimertinib-Induced Myopathy: A Case Report","authors":"","doi":"10.1016/j.jtho.2024.05.373","DOIUrl":"10.1016/j.jtho.2024.05.373","url":null,"abstract":"<div><p>Osimertinib<span><span>, a third-generation EGFR<span><span> tyrosine kinase inhibitor, is the standard of care for patients with advanced NSCLC and EGFR-sensitizing mutations. Both in osimertinib pivotal trials and in the post-marketing phase, asymptomatic creatinine phosphokinase elevation and clinically relevant muscle damage have been reported. However, the mechanisms underlying these conditions remain unclear. Herein, we report the first </span>muscle biopsy description of osimertinib-induced </span></span>myopathy and hypothesize that the mechanisms underpinning muscle toxicity could be driven by hyporegenerative mechanisms and mitochondrial dysfunction with subsequent reduced metabolic endurance, both directly linked to the inhibition of downstream molecular pathways mediated by EGFR in muscle cells.</span></p></div>","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":null,"pages":null},"PeriodicalIF":21.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141442968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The International Association for the Study of Lung Cancer Mesothelioma Staging Project: Proposals for Revisions of the “T” Descriptors in the Forthcoming Ninth Edition of the TNM Classification for Pleural Mesothelioma","authors":"","doi":"10.1016/j.jtho.2024.03.007","DOIUrl":"10.1016/j.jtho.2024.03.007","url":null,"abstract":"<div><h3>Introduction</h3><p><span><span>The primary tumor (T) component in the eighth edition of </span>pleural mesothelioma (PM) staging system is based on pleural involvement and extent of invasion. Quantitative assessment of </span>pleural tumor has been found to be prognostic. We explored quantitative and qualitative metrics to develop recommendations for T descriptors in the upcoming ninth edition of the PM staging system.</p></div><div><h3>Methods</h3><p>The International Association for the Study of Lung Cancer prospectively collected data on patients with PM. Sum of maximum pleural thickness (Psum) was recorded. Optimal combinations of Psum and eighth edition cT descriptors were assessed using recursive binary splitting algorithm, with bootstrap resampling to correct for the adaptive nature of the splitting algorithm, and validated in the eighth edition data. Overall survival (OS) was calculated by the Kaplan-Meier method and differences in OS assessed by the log-rank test.</p></div><div><h3>Results</h3><p>Of 7338 patients submitted, 3598 were eligible for cT analysis<span> and 1790 had Psum measurements. Recursive partitioning identified optimal cutpoints of Psum at 12 and 30 mm, which, in combination with extent of invasion, yielded four prognostic groups for OS. Fmax greater than 5 mm indicated poor prognosis. cT4 category (based on invasion) revealed similar performance to eighth edition. Three eighth edition descriptors were eliminated based on low predictive accuracy. Eighth edition pT descriptors remained valid in ninth edition analyses.</span></p></div><div><h3>Conclusion</h3><p>Given reproducible prognostication by Psum, size criteria will be incorporated into cT1 to T3 categories in the ninth edition. Current cT4 category and all pT descriptors will be maintained, with reclassification of fissural invasion as pT2.</p></div>","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":null,"pages":null},"PeriodicalIF":21.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140194079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Suggestions for Improving the Comprehensive Characterization of Lung Pleomorphic Carcinoma","authors":"","doi":"10.1016/j.jtho.2024.06.016","DOIUrl":"10.1016/j.jtho.2024.06.016","url":null,"abstract":"","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":null,"pages":null},"PeriodicalIF":21.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142135815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Response to the Letter to the Editor: Safety Implications of Switching Pembrolizumab Dosage From 200 mg Every 3 Weeks to 400 mg Every 6 Weeks in Patients With Advanced NSCLC","authors":"","doi":"10.1016/j.jtho.2024.06.017","DOIUrl":"10.1016/j.jtho.2024.06.017","url":null,"abstract":"","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":null,"pages":null},"PeriodicalIF":21.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142135811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tracing Tumor Heterogeneity of Pleomorphic Carcinoma of the Lung","authors":"","doi":"10.1016/j.jtho.2024.04.019","DOIUrl":"10.1016/j.jtho.2024.04.019","url":null,"abstract":"<div><h3>Introduction</h3><p>Pulmonary pleomorphic carcinoma (PPC) is an aggressive and highly heterogeneous NSCLC whose underlying biology is still poorly understood.</p></div><div><h3>Methods</h3><p><span>A total of 42 tumor areas from 20 patients with PPC were microdissected, including 39 primary tumors<span><span> and three metastases, and the histologically distinct components were subjected to </span>whole exome sequencing<span> separately. We further performed in silico analysis of microdissected bulk </span></span></span>RNA sequencing<span> and methylation data of 28 samples from 14 patients with PPC. We validated our findings using immunohistochemistry.</span></p></div><div><h3>Results</h3><p>The epithelial and the sarcomatoid components of PPCs shared a large number of genomic alterations. Most mutations in cancer driver genes were clonal and truncal between the two components of PPCs suggesting a common ancestor. The high number of alterations in the RTK-RAS pathway suggests that it plays an important role in the evolution of PPC. The metastases morphologically and genetically resembled the epithelial or the sarcomatoid components of the tumor.</p><p><span>The transcriptomic and epigenetic profiles of the sarcomatoid components of PPCs with matched squamous-like or adenocarcinoma-like components differed from each other, and they shared more similarities to their matched epithelial components. NCAM1/CD56 was preferentially expressed in the sarcomatoid component of squamous-like PPCs, whereas </span><em>CDH1</em>/E-Cadherin expression was down-regulated in the sarcomatoid component of most PPCs.</p></div><div><h3>Conclusion</h3><p>Lung adenocarcinoma-like PPCs are mainly driven by RTK-RAS signaling, whereas epithelial-mesenchymal transition programs as highlighted by increased <em>NCAM1</em> and decreased <em>CDH1</em> expression govern the epithelial-sarcomatoid transition between the clonally related tumor components. Several alterations in PPCs pinpoint therapeutic opportunities.</p></div>","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":null,"pages":null},"PeriodicalIF":21.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140898924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}