Journal of Thoracic Oncology最新文献

{"title":"Phase II randomized study of maintenance atezolizumab (A) versus atezolizumab + talazoparib (AT) in patients with SLFN11 positive extensive stage small cell lung cancer. S1929.","authors":"Nagla Abdel Karim, Jieling Miao, Karen L Reckamp, Carl M Gay, Lauren A Byers, Ying-Qi Zhao, Mary W Redman, Daniel R Carrizosa, Wei-Lien Wang, William J Petty, Kathan Mehta, Bryan A Faller, Edem S Agamah, Samer S Kasbari, Rajini K Malisetti, Atul Kumar, John Schallenkamp, Krishna C Alluri, Jhanelle E Gray, Karen Kelly","doi":"10.1016/j.jtho.2024.10.021","DOIUrl":"https://doi.org/10.1016/j.jtho.2024.10.021","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate whether the addition of a poly (ADP-ribose) polymerase inhibitor (PARPi) talazoparib to maintenance immune checkpoint inhibitor (ICI) atezolizumab following frontline chemoimmunotherapy improved outcomes in patients with Schlafen 11 (SLFN11)-positive extensive stage small cell lung cancer (ES-SCLC).</p><p><strong>Methods: </strong>Patients with newly diagnosed SLFN11 expressing (H-score ≥ 1, evaluated centrally) ES-SCLC were randomized to maintenance atezolizumab (A) versus atezolizumab plus talazoparib (AT) following frontline chemotherapy plus atezolizumab. The primary objective was to compare progression-free survival (PFS) using a 1-sided 10% level stratified log-rank test. Secondary endpoints included objective response rate (ORR), overall survival (OS), and toxicity. Target sample size was 84 eligible patients.</p><p><strong>Results: </strong>From June 15, 2020 to December 15, 2022, 106 eligible patients were randomized (54 to AT and 52 to A). PFS was improved with AT versus A (hazard ratio [HR], 0.66; 80% confidence interval [CI]: 0.50-0.86; 1-sided P = 0.019) with a median PFS of 2.9 and 2.4 months; OS was not different between groups (HR, 0.98; 80% CI: 0.71-1.36; 1-sided P = 0.47). Grade ≥ 3 non-hematologic treatment-related adverse events (TRAEs) occurred in 17% of patients with AT and 14% of patients with A. Grade ≥ 3 hematological TRAEs were more common in AT (50%) than in A (4%) (P < 0.001).</p><p><strong>Conclusion: </strong>Maintenance AT improved PFS in patients with SLFN11-positive ES-SCLC that did not progress following initial chemo-immunotherapy. Hematologic toxicity, primarily grade 3 anemia, was increased with AT, as expected. Prospective biomarker-selection was demonstrated, paving the way for future evaluation of novel therapies in molecularly defined SCLC populations.</p>","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":null,"pages":null},"PeriodicalIF":21.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142591101","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":"Clinical Utility of Tumor-Naïve Presurgical Circulating Tumor DNA Detection in Early-Stage NSCLC","authors":"","doi":"10.1016/j.jtho.2024.07.002","DOIUrl":"10.1016/j.jtho.2024.07.002","url":null,"abstract":"<div><h3>Objectives</h3><div>The use of tumor-informed circulating tumor DNA (ctDNA) testing in patients with early-stage disease before surgery is limited, mainly owing to restricted tissue access and extended turnaround times. This study aimed to evaluate the clinical value of a tumor-naïve, methylation-based cell-free DNA assay in a large cohort of patients with resected NSCLC.</div></div><div><h3>Method</h3><div>We analyzed presurgical plasma samples from 895 patients with <em>EGFR</em> and anaplastic lymphoma kinase-wild-type, clinical stage I or II NSCLC. The ctDNA status was evaluated for its prognostic significance in relation to tumor volume, metabolic activity, histologic diagnosis, histologic subtypes, and clinical-to-pathologic TNM upstaging.</div></div><div><h3>Results</h3><div>Presurgical ctDNA detection was observed in 55 of 414 patients (13%) with clinical stage I lung adenocarcinoma (LUAD) and was associated with poor recurrence-free survival (2-year recurrence-free survival 69% versus 91%; log-rank <em>p</em> &lt; 0.001), approaching that of clinical stage II LUAD. Presurgical ctDNA detection was not prognostic in patients with clinical stage II LUAD or non-LUAD. Within LUAD, tumor volume and positron emission tomography avidity interacted to predict presurgical ctDNA detection. Moreover, presurgical ctDNA detection was predictive of the postsurgical discovery of International Association for the Study of Lung Cancer grade 3 tumors (<em>p</em> &lt; 0.001) and pathologic TNM upstaging (<em>p</em> &lt; 0.001). Notably, presurgical ctDNA detection strongly correlated with higher programmed death-ligand 1 expression in tumors (positive rates 28% versus 55%, <em>p</em> &lt; 0.001), identifying a subgroup likely to benefit from anti–programmed death-ligand 1 therapies.</div></div><div><h3>Conclusion</h3><div>These findings support the integration of ctDNA testing into routine diagnostic workflows in early-stage NSCLC without the need for tumor tissue profiling. Furthermore, it is clinically useful in identifying patients at high risk who might benefit from innovative treatments, including neoadjuvant immune checkpoint inhibitors.</div></div>","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":null,"pages":null},"PeriodicalIF":21.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141590643","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 Game is Afoot – Seeking Early-Stage Lung Cancer Circulating Tumor DNA","authors":"","doi":"10.1016/j.jtho.2024.08.014","DOIUrl":"10.1016/j.jtho.2024.08.014","url":null,"abstract":"","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":null,"pages":null},"PeriodicalIF":21.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142586239","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":"Comment on “Impact of EML4-ALK Variants and Co-Occurring TP53 Mutations on Duration of First-Line ALK Tyrosine Kinase Inhibitor Treatment and Overall Survival in ALK Fusion-Positive NSCLC: Real-World Outcomes From the GuardantINFORM Database”","authors":"","doi":"10.1016/j.jtho.2024.07.023","DOIUrl":"10.1016/j.jtho.2024.07.023","url":null,"abstract":"","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":null,"pages":null},"PeriodicalIF":21.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142587291","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":"Impact of EML4-ALK Variants and Co-Occurring TP53 Mutations on Duration of First-Line ALK Tyrosine Kinase Inhibitor Treatment and Overall Survival in ALK Fusion-Positive NSCLC: Real-World Outcomes From the GuardantINFORM database","authors":"","doi":"10.1016/j.jtho.2024.07.009","DOIUrl":"10.1016/j.jtho.2024.07.009","url":null,"abstract":"<div><h3>Introduction</h3><div>Tyrosine kinase inhibitors (TKIs) are first-line treatment options for <em>ALK</em>-positive (<em>ALK</em>+) NSCLC. Factors such as variant allele frequencies (VAFs), <em>EML4-ALK</em> fusion variant, and concurrent <em>TP53</em> mutations (<em>TP53</em>mt) in circulating tumor DNA (ctDNA) may affect treatment outcomes. We evaluated their effects on time to discontinuation (TTD) of first-line treatment with next-generation ALK TKIs in a real-world setting.</div></div><div><h3>Methods</h3><div>Adults with advanced or metastatic NSCLC and ctDNA-detected <em>ALK</em> fusion who received first-line next-generation ALK TKI monotherapy were identified in GuardantINFORM. Effects of <em>ALK</em> fusion VAF, <em>EML4-ALK</em> variants, and <em>TP53</em>mt detection on TTD were evaluated.</div></div><div><h3>Results</h3><div>A total of 307 patients with <em>ALK</em> fusion in baseline ctDNA received first-line alectinib (n = 280), brigatinib (n = 15), lorlatinib (n = 9), or ceritinib (n = 3); 150 patients (49%) had <em>ALK-</em>fusion VAF greater than or equal to 1%. Among 232 patients with <em>EML4-ALK</em> fusions (v1, 50%; v3, 36%), <em>TP53</em>mt co-occurred with v1 in 42 (18%) and v3 in 32 (14%). Patients with VAF less than 1% versus greater than or equal to 1% had a median TTD of 32.2 (95% confidence interval [CI]: 20.7–not estimable [NE]) versus 14.7 months (10.4–19.9; hazard ratio [HR] = 1.57 [95% CI: 1.09–2.26]; <em>p =</em> 0.0146). Median TTD was 13.1 (9.5–19.9) versus 27.6 months (17.3–NE) in patients with versus without <em>TP53</em>mt detected (HR = 1.53 [1.07–2.19]; <em>p =</em> 0.0202) and 20.3 (14.4–NE) versus 11.5 months (7.4–31.1) in patients with v1 versus v3 (HR = 1.29 [0.83–2.01]; <em>p =</em> 0.2641). Patients with <em>TP53</em>mt and v3 had a median TTD of 7.4 months (95% CI: 4.2–31.1).</div></div><div><h3>Conclusion</h3><div>High ctDNA VAF, <em>EML4-ALK</em> v3, and <em>TP53</em>mt were associated with early discontinuation of first-line ALK TKIs.</div></div>","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":null,"pages":null},"PeriodicalIF":21.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141633804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tracking Progression of EGFR Mutation Positive NSCLC From Blood: Is This the Prime Time?","authors":"","doi":"10.1016/j.jtho.2024.08.032","DOIUrl":"10.1016/j.jtho.2024.08.032","url":null,"abstract":"","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":null,"pages":null},"PeriodicalIF":21.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142586240","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":"EML4-ALK Variants and Co-Occurring TP53 Mutations in a Real-World Treatment Setting: Do They Matter?","authors":"","doi":"10.1016/j.jtho.2024.09.1378","DOIUrl":"10.1016/j.jtho.2024.09.1378","url":null,"abstract":"","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":null,"pages":null},"PeriodicalIF":21.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142586242","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":"Equipoise Remains a Major Consideration in the Ethical Evaluation of Phase 3 Randomized Controlled Trials Involving Precision Oncology Approaches in NSCLC","authors":"","doi":"10.1016/j.jtho.2024.07.004","DOIUrl":"10.1016/j.jtho.2024.07.004","url":null,"abstract":"","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":null,"pages":null},"PeriodicalIF":21.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142586273","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":"Real-World Acute Toxicity and 90-Day Mortality in Patients With Stage I NSCLC Treated With Stereotactic Body Radiotherapy","authors":"","doi":"10.1016/j.jtho.2024.07.016","DOIUrl":"10.1016/j.jtho.2024.07.016","url":null,"abstract":"<div><h3>Introduction</h3><div>Stereotactic body radiotherapy (SBRT) has firmly established its role in stage I NSCLC. Clinical trial results may not fully apply to real-world scenarios. This study aimed to uncover the real-world incidence of acute toxicity and 90-day mortality in patients with SBRT-treated stage I NSCLC and develop prediction models for these outcomes.</div></div><div><h3>Methods</h3><div>Prospective data from the Dutch Lung Cancer Audit for Radiotherapy (DLCA-R) were collected nationally. Patients with stage I NSCLC (cT1-2aN0M0) treated with SBRT in 2017 to 2021 were included. Acute toxicity was assessed, defined as grade greater than or equal to 2 radiation pneumonitis or grade greater than or equal to 3 non-hematologic toxicity less than or equal to 90 days after SBRT. Prediction models for acute toxicity and 90-day mortality were developed and internally validated.</div></div><div><h3>Results</h3><div>Among 7279 patients, the mean age was 72.5 years, with 21.6% being above 80 years. Most were male (50.7%), had WHO scores 0 to 1 (73.3%), and had cT1a-b tumors (64.6%), predominantly in the upper lobes (65.2%). Acute toxicity was observed in 280 (3.8%) of patients and 90-day mortality in 122 (1.7%). Predictors for acute toxicity included WHO greater than or equal to 2, lower forced expiratory volume in 1 second and diffusion capacity for carbon monoxide, no pathology confirmation, middle or lower lobe tumor location, cT1c-cT2a stage, and higher mean lung dose (c-statistic 0.68). Male sex, WHO greater than or equal to 2, and acute toxicity predicted higher 90-day mortality (c-statistic 0.73).</div></div><div><h3>Conclusions</h3><div>This nationwide study revealed a low rate of acute toxicity and an acceptable 90-day mortality rate in patients with SBRT-treated stage I NSCLC. Notably, advanced age did not increase acute toxicity or mortality risk. Our predictive models, with satisfactory performance, offer valuable tools for identifying high-risk patients.</div></div>","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":null,"pages":null},"PeriodicalIF":21.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141788460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing Acute Toxicity and 90-Day Mortality in Stage I NSCLC: A Real-World Appraisal of Stereotactic Body Radiotherapy Outcomes","authors":"","doi":"10.1016/j.jtho.2024.08.038","DOIUrl":"10.1016/j.jtho.2024.08.038","url":null,"abstract":"","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":null,"pages":null},"PeriodicalIF":21.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142587196","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}