Journal of Thoracic Oncology最新文献

{"title":"Human Immunodeficiency Virus Impairs Immune Responses to Tumor Neoepitopes Without Altering Mutational Profiles in NSCLC","authors":"Baptiste Abbar MD, PhD ,&nbsp;Karim Labreche PhD ,&nbsp;Jacques Cadranel MD, PhD ,&nbsp;Marianne Veyri PhD ,&nbsp;Véronique Morin BS ,&nbsp;Fatou Seck Thiam BS ,&nbsp;Nathalie Desire BS ,&nbsp;Marine Baron MD, PhD ,&nbsp;Erell Guillerm MD ,&nbsp;Alexandre Perrier MD ,&nbsp;Vincent Fallet MD ,&nbsp;Thomas Maitre MD, PhD ,&nbsp;Anthony Canellas MD ,&nbsp;Nadine Tarantino BS ,&nbsp;Oulfata Mze BS ,&nbsp;Assia Samri PhD ,&nbsp;Lisa Dejancourt MS ,&nbsp;Cecilia Nakid-Cordero PhD ,&nbsp;Aurore Vozy MD ,&nbsp;Alberto Picca MD ,&nbsp;Brigitte Autran MD, PhD","doi":"10.1016/j.jtho.2025.02.001","DOIUrl":"10.1016/j.jtho.2025.02.001","url":null,"abstract":"<div><h3>Introduction</h3><div>NSCLC is frequent and associated with poor prognosis among people living with human immunodeficiency virus (PLWHIV); nevertheless, the contributing factors remain unknown.</div></div><div><h3>Methods</h3><div>We prospectively compared the immunogenomic characteristics of 27 NSCLC samples from 15 PLWHIV and 12 immunocompetent patients (ICs). Tumor whole-exome and RNA sequencing, along with a bioinformatics pipeline, allowed analysis of tumor mutational burden, molecular signatures, tumor microenvironment, and prediction of tumor neoepitopes. We conducted ex vivo interferon gamma (IFNγ) enzyme-linked ImmunoSpot assays and intracellular cytokine staining flow cytometry assays to functionally validate our bioinformatic pipeline for neoepitope prediction and to investigate the antitumor immune response.</div></div><div><h3>Results</h3><div>Tumor mutational burden, molecular profiles, number of predicted neoepitopes, and their major histocompatibility complex (MHC) class I/II predicted restriction were similar in both groups. Nevertheless, T-cell responses to neoepitopes, detectable in 4 out of 11 PLWHIV and 5 out of 11 IC, were exclusively directed against MHC class II-restricted neoepitopes in PLWHIV, whereas it was balanced between MHC class I and class II neoepitopes in IC. Intracellular cytokine staining revealed primarily monofunctional responses, mainly mediated by tumor necrosis factor-α–producing CD4 T-cells against MHC class II–restricted neoepitopes, and by CD8 T-cells producing CD107, tumor necrosis factor-α, or IFNγ against MHC class I–restricted neoepitopes. A low CD4 nadir was associated with the lack of neoepitope-specific responses in PLWHIV. Furthermore, PLWHIV tumor microenvironments displayed lower neutrophil proportions and decreased T-cell function markers.</div></div><div><h3>Conclusions</h3><div>Our results indicate that despite similar mutational profiles, HIV infection severely impairs both local and systemic antitumor immune responses in patients with NSCLC, particularly to MHC class I–restricted neoepitopes. These findings support the use of MHC–class I–restricted neoepitope-based immunotherapy in this population.</div></div>","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"20 7","pages":"Pages 897-911"},"PeriodicalIF":21.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143382722","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":"Gut Microbiota in Advanced NSCLC Receiving Chemoimmunotherapy: An Ancillary Biomarker Study From the Phase III Trial JCOG2007 (NIPPON)","authors":"Taiki Hakozaki MD, PhD ,&nbsp;Kentaro Tanaka MD, PhD ,&nbsp;Yoshimasa Shiraishi MD, PhD ,&nbsp;Yuta Sekino MD, PhD ,&nbsp;Noriko Mitome MD ,&nbsp;Yusuke Okuma MD, PhD ,&nbsp;Tomoiki Aiba MD, PhD ,&nbsp;Takahiro Utsumi MD ,&nbsp;Junko Tanizaki MD, PhD ,&nbsp;Koichi Azuma MD, PhD ,&nbsp;Satoshi Hara MD ,&nbsp;Ryo Morita MD, PhD ,&nbsp;Seiji Niho MD, PhD ,&nbsp;Toshihide Yokoyama MD ,&nbsp;Ryo Toyozawa MD ,&nbsp;Hidehito Horinouchi MD, PhD ,&nbsp;Isamu Okamoto MD, PhD ,&nbsp;Yukio Hosomi MD, PhD ,&nbsp;Yuichiro Ohe MD, PhD","doi":"10.1016/j.jtho.2025.02.026","DOIUrl":"10.1016/j.jtho.2025.02.026","url":null,"abstract":"<div><h3>Introduction</h3><div>Immunotherapy has transformed the treatment for NSCLC. Nevertheless, reliable biomarkers for treatment selection remain scarce. Gut microbiota has emerged as a potential biomarker, but its role in chemoimmunotherapy for NSCLC is unclear.</div></div><div><h3>Methods</h3><div>The phase III trial (JCOG2007, NIPPON) compared pembrolizumab plus platinum doublet chemotherapy (PC) with nivolumab and ipilimumab plus platinum doublet chemotherapy (NIC) in treatment-naive patients with advanced NSCLC without driver gene alterations. As an ancillary biomarker study, 270 patients with baseline fecal samples were analyzed for gut microbiota composition from 295 patients enrolled. 16S ribosomal DNA sequencing was performed for the diversity and differential abundance analysis.</div></div><div><h3>Results</h3><div>The beta diversity analysis of the overall cohort (n = 270) revealed distinct microbial structures between the subpopulations defined by whether overall survival (OS) exceeds 12 or 18 months. Subsequent linear discriminant analysis effect size analysis identified specific bacterial genera that differed between the subpopulations, with <em>Fusicatenibacter</em>, <em>Butyricicoccus</em>, and <em>Blautia</em> being enriched in patients with longer OS. Regarding adverse events (AEs), lower microbial alpha diversity and the presence of certain taxa were linked to a higher risk of serious (≥grade 4) AEs. In addition, favorable genera, including <em>Fusicatenibacter</em> and <em>Butyricicoccus</em>, were associated with a lower risk of serious AEs. Last, regimen-specific analysis demonstrated that higher abundance of <em>Fusicatenibacter</em> and <em>Butyricicoccus</em> was linked to better OS in the NIC arm compared with that in the CP arm (hazard ratio for OS = 0.56 and 0.52, respectively). Conversely, the higher abundance of <em>Prevotellaceae</em> NK3B31 was associated with higher mortality risk in the NIC arm (hazard ratio for OS = 2.33).</div></div><div><h3>Conclusions</h3><div>Gut microbiota may serve as a biomarker for chemoimmunotherapy in advanced NSCLC. Differences in microbial diversity and specific bacterial genera were associated with prognosis and serious AEs, with potential regimen-specific effects. These findings support integrating gut microbiota profiling into clinical practice to optimize first-line treatment strategies.</div></div>","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"20 7","pages":"Pages 912-927"},"PeriodicalIF":21.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586178","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":"First-Line Lorlatinib Versus Crizotinib in Asian Patients With Advanced ALK-Positive NSCLC: Five-Year Outcomes From the CROWN Study","authors":"Yi-Long Wu MD ,&nbsp;Hye Ryun Kim MD, PhD ,&nbsp;Ross A. Soo MBBS, PhD ,&nbsp;Qing Zhou MD, PhD ,&nbsp;Hiroaki Akamatsu MD, PhD ,&nbsp;Gee-Chen Chang MD, PhD ,&nbsp;Chao-Hua Chiu MD ,&nbsp;Hidetoshi Hayashi MD, PhD ,&nbsp;Sang-We Kim MD, PhD ,&nbsp;Yasushi Goto MD, PhD ,&nbsp;Terufumi Kato MD ,&nbsp;Jianying Zhou MD ,&nbsp;Victor Ho-Fun Lee MD ,&nbsp;Makoto Nishio MD, PhD ,&nbsp;Baohui Han MD, PhD ,&nbsp;Dong-Wan Kim MD, PhD ,&nbsp;Shun Lu MD ,&nbsp;Anna Polli BS ,&nbsp;Jean-François Martini PhD ,&nbsp;Francesca Toffalorio MD, PhD ,&nbsp;Tony Mok MD","doi":"10.1016/j.jtho.2025.02.021","DOIUrl":"10.1016/j.jtho.2025.02.021","url":null,"abstract":"<div><h3>Introduction</h3><div>Lorlatinib, a third-generation anaplastic lymphoma kinase inhibitor, reported significantly longer progression-free survival (PFS) than crizotinib in the phase 3 CROWN trial (NCT03052608) in patients with previously untreated advanced anaplastic lymphoma kinase–positive NSCLC. Efficacy was similar in the Asian subgroup. We present an updated subgroup analysis in Asian patients after five years of follow-up.</div></div><div><h3>Methods</h3><div>Patients were randomly (1:1) assigned to receive lorlatinib 100 mg once daily (n = 59) or crizotinib 250 mg twice daily (n = 61). This post hoc analysis presents updated investigator-assessed efficacy outcomes, safety, and biomarker analyses.</div></div><div><h3>Results</h3><div>After a median follow-up of 62.4 months for lorlatinib and 55.1 months for crizotinib, median PFS was not reached (NR, 95% confidence interval [CI]: 64.3‒NR) and 9.2 months (95% CI: 7.2‒12.7), respectively (hazard ratio [HR] = 0.22, 95% CI: 0.13‒0.37); the five-year PFS was 63% (95% CI: 49–74) and 7% (95% CI: 2–17). The objective response rate was 81% (95% CI: 69–90) with lorlatinib and 59% (95% CI: 46‒71) with crizotinib. In patients with baseline brain metastases, the intracranial objective response rate was 69% (95% CI: 39‒91) with lorlatinib and 6% (95% CI: &lt;1‒30) with crizotinib. The median time to intracranial progression was NR (95% CI: NR‒NR) and 14.6 months (95% CI: 9.2‒27.4), respectively (HR = 0.01, 95% CI: &lt;0.01‒0.11). Safety profiles were consistent with the entire population.</div></div><div><h3>Conclusions</h3><div>After five years of follow-up, lorlatinib efficacy and safety in the Asian subgroup of CROWN continue to be consistent with those in the overall population, with PFS remaining unreached with lorlatinib.</div></div><div><h3>Trial Registration</h3><div><span><span>ClinicalTrials.gov</span><svg><path></path></svg></span> identifier: NCT03052608</div></div>","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"20 7","pages":"Pages 955-968"},"PeriodicalIF":21.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537422","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":"Cemiplimab Monotherapy for First-Line Treatment of Patients with Advanced NSCLC With PD-L1 Expression of 50% or Higher: Five-Year Outcomes of EMPOWER-Lung 1","authors":"Saadettin Kilickap MD ,&nbsp;Ana Baramidze PhD ,&nbsp;Ahmet Sezer MD ,&nbsp;Mustafa Özgüroğlu MD ,&nbsp;Mahmut Gumus MD ,&nbsp;Igor Bondarenko MD, PhD ,&nbsp;Miranda Gogishvili MD ,&nbsp;Marina Nechaeva MD ,&nbsp;Michael Schenker MD ,&nbsp;Irfan Cicin MD ,&nbsp;Ho Gwo Fuang MD ,&nbsp;Yaroslav Kulyaba MD ,&nbsp;Kasimova Zyuhal MD ,&nbsp;Roxana-Ioana Scheusan MD ,&nbsp;Marina Chiara Garassino MD ,&nbsp;Yuntong Li PhD ,&nbsp;Cong Zhu PhD ,&nbsp;Manika Kaul MD ,&nbsp;Javier Perez PhD ,&nbsp;Frank Seebach MD ,&nbsp;Heather Magnan MD","doi":"10.1016/j.jtho.2025.03.033","DOIUrl":"10.1016/j.jtho.2025.03.033","url":null,"abstract":"<div><h3>Introduction</h3><div>Earlier results from the phase 3 EMPOWER-Lung 1 trial indicated significant survival benefits and a generally acceptable safety profile of first-line cemiplimab monotherapy versus chemotherapy for patients with advanced NSCLC with programmed cell death-ligand 1 (PD-L1) expression in 50% or more tumor cells and no <em>EGFR</em>, <em>ALK,</em> or <em>ROS1</em> aberrations. Here, we report the five-year outcomes.</div></div><div><h3>Methods</h3><div>Patients were randomized 1:1 to cemiplimab 350 mg intravenously every three weeks for two years or the investigator’s choice of chemotherapy. The primary endpoints were overall survival (OS) and progression-free survival.</div></div><div><h3>Results</h3><div>A total of 712 patients were randomized to cemiplimab (n = 357) or chemotherapy (n = 355). The median duration of follow-up was 59.6 months (interquartile range: 55.1–66.7 months) at the data cutoff (January 16, 2024). In patients with verified 50% or higher PD-L1 (n = 565), median OS was 26.1 months for cemiplimab versus 13.3 months for chemotherapy (hazard ratio = 0.59, 95% confidence interval [CI]: 0.48–0.72); the median progression-free survival was 8.1 months versus 5.3 months (hazard ratio = 0.50, 95% confidence interval: 0.41–0.61); and the objective response rate was 46.5% versus 20.6%. The five-year OS probability was 29.0% for cemiplimab and 15.0% for chemotherapy. Improved survival outcomes were observed with both squamous and nonsquamous histology, and increasing activity of cemiplimab was correlated with higher PD-L1 expression, with the highest PD-L1 expression having the best outcome. The safety profile remains consistent with previous results. Grade 3 or higher treatment-related adverse events occurred in 18.3% of patients for cemiplimab and 39.9% for chemotherapy.</div></div><div><h3>Conclusions</h3><div>At five-year follow-up, first-line cemiplimab monotherapy continued to show durable clinical benefits versus chemotherapy in patients with advanced NSCLC with 50% or higher PD-L1. Patients with 90% or higher PD-L1 derived the largest clinical benefits.</div></div>","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"20 7","pages":"Pages 941-954"},"PeriodicalIF":21.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674309","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":"In Response","authors":"Dongchen Xie MD,&nbsp;Wanghong Xu MD, PhD","doi":"10.1016/j.jtho.2025.04.002","DOIUrl":"10.1016/j.jtho.2025.04.002","url":null,"abstract":"","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"20 7","pages":"Pages e90-e91"},"PeriodicalIF":21.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144548364","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 ‘In This Issue’ [Journal of Thoracic Oncology Volume 20 Issue 3 (2025) 241-245]","authors":"","doi":"10.1016/j.jtho.2025.05.002","DOIUrl":"10.1016/j.jtho.2025.05.002","url":null,"abstract":"","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"20 7","pages":"Page 983"},"PeriodicalIF":21.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144549121","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":"First-Line Camrelizumab Versus Placebo Plus Chemotherapy With or Without Radiotherapy for Brain Metastases in NSCLC: The CTONG 2003 Randomized Placebo-Controlled Trial","authors":"Yang-Si Li PhD ,&nbsp;Qitao Yu PhD ,&nbsp;Qing Bu PhD ,&nbsp;Lizhu Lin PhD ,&nbsp;Fangling Ning MD ,&nbsp;Yun Zhao PhD ,&nbsp;Gang Wu PhD ,&nbsp;Gen Lin PhD ,&nbsp;Aimin Zang MD ,&nbsp;Hao Sun PhD ,&nbsp;Jie Huang PhD ,&nbsp;Hai-Yan Tu PhD ,&nbsp;Shenglin Ma PhD ,&nbsp;Chengzhi Zhou PhD ,&nbsp;Anwen Liu PhD ,&nbsp;Cailian Wang PhD ,&nbsp;Yu Yao PhD ,&nbsp;Guang Han PhD ,&nbsp;Jun Zhao PhD ,&nbsp;Qing Zhou PhD ,&nbsp;Yi-Long Wu MD","doi":"10.1016/j.jtho.2025.02.004","DOIUrl":"10.1016/j.jtho.2025.02.004","url":null,"abstract":"<div><h3>Introduction</h3><div>Retrospective studies have indicated the potential benefits of immunotherapy for brain metastases (BMs) in NSCLC. To our knowledge, CTONG 2003 is the first randomized controlled trial to evaluate camrelizumab for untreated BM of NSCLC.</div></div><div><h3>Methods</h3><div>CTONG 2003 is a multicenter, randomized, double-blind, placebo-controlled trial. Treatment-naïve NSCLC with BM, negative for <em>EGFR</em> mutations and <em>ALK</em> fusions, were randomized 1:1 to receive either camrelizumab or placebo, plus platinum-doublet chemotherapy for four to six cycles, followed by maintenance therapy with camrelizumab or placebo with or without pemetrexed for up to 31 cycles. Radiotherapy was administered for BM, if necessary, within 42 days of the first treatment dose. The co-primary endpoints were intracranial progression-free survival (iPFS) and progression-free survival (PFS). The planned enrollment included 200 patients, but recruitment was terminated early because of therapeutic paradigm shifts globally.</div></div><div><h3>Results</h3><div>Between May 28, 2021, and July 21, 2023, 60 patients were randomized, with 32 assigned to the camrelizumab group and 28 to the placebo group. The median iPFS was 12.7 months (95% confidence interval [CI]: 7.1–25.3) for camrelizumab versus 9.9 months (95% CI: 6.3-14.6) for placebo (hazard ratio = 0.45, 95% CI: 0.21–0.96). The median PFS was 9.7 months (95% CI: 6.6–14.0) for camrelizumab versus 6.7 months (95% CI: 4.1–8.6) for placebo (hazard ratio = 0.57, 95% CI: 0.29–1.11). Grade 3 or higher treatment-related adverse events occurred in 65.6% and 46.4% of the respective groups, mainly neutrophil count decrease and anemia.</div></div><div><h3>Conclusions</h3><div>Despite early termination, camrelizumab demonstrated a trend toward improved iPFS and PFS in the BM of NSCLC with an acceptable safety profile.</div></div><div><h3>Trial Registration</h3><div><span><span>ClinicalTrials.gov</span><svg><path></path></svg></span> Identifier: NCT04768075.</div></div>","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"20 7","pages":"Pages 928-940"},"PeriodicalIF":21.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143391093","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: “Decision Trees and Random Forests: Nonlinear and Nonparametric Alternatives to Logistic Regression in Biological Data Analysis”","authors":"Shun Lu MD, PhD,&nbsp;Binbing Yu PhD,&nbsp;Dan Jackson PhD,&nbsp;Fanni Zhang PhD,&nbsp;Yi-Long Wu MD","doi":"10.1016/j.jtho.2025.04.006","DOIUrl":"10.1016/j.jtho.2025.04.006","url":null,"abstract":"","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"20 7","pages":"Pages e85-e86"},"PeriodicalIF":21.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144548360","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 Screening Program Quality Indicators—Review and Recommendations: An International Association for the Study of Lung Cancer Delphi Process Study","authors":"Martin C. Tammemägi DVM, MSc, PhD ,&nbsp;Andrea Borondy-Kitts MS, MPH ,&nbsp;John K. Field PhD ,&nbsp;Claudia I. Henschke MD, PhD ,&nbsp;Anant Mohan MD, PhD ,&nbsp;Anna Kerpel-Fronius MD, PhD ,&nbsp;Luigi Ventura MD ,&nbsp;Dawei Yang MD ,&nbsp;Long Jiang MD, PhD ,&nbsp;Coenraad F.N. Koegelenberg MD, PhD ,&nbsp;Milena Cavic PhD ,&nbsp;Haval Balata MD, PhD ,&nbsp;Lucia Viola MD ,&nbsp;Javier J. Zulueta MD, PhD ,&nbsp;Ricardo Sales dos Santos MD ,&nbsp;Witold Rzyman MD, PhD ,&nbsp;David F. Yankelevitz MD ,&nbsp;Annette McWilliams M.B.B.S. ,&nbsp;Stephen Lam MD ,&nbsp;Ella A. Kazerooni MD, MS ,&nbsp;Rudolf M. Huber MD, PhD","doi":"10.1016/j.jtho.2025.01.019","DOIUrl":"10.1016/j.jtho.2025.01.019","url":null,"abstract":"<div><h3>Introduction</h3><div>Lung cancer screening (LCS) using low-dose-computed tomography reduces lung cancer mortality in high-risk individuals. Evaluating and monitoring LCS programs are important to ensure and improve quality, efficiency, and participant outcomes. There is no agreement on LCS quality indicators (QIs).</div></div><div><h3>Methods</h3><div>Twenty multidisciplinary members of the International Association for the Study of Lung Cancer used a Delphi process to develop consensus QIs. They considered 50 QIs during information/discussion sessions and two anonymous voting rounds. In total, 80% or more voting agree or strongly agree on a five-point Likert scale determined consensus.</div></div><div><h3>Results</h3><div>Twenty essential and six desirable QIs were identified in 10 of 11 LCS pathway domain categories <em>(ENTRY</em>: Proportion eligible who got screened; <em>SMOKING_CESSATION:</em> Proportion of current-smoking individuals offered cessation interventions; <em>IMAGING:</em> Proportion screened requiring clinical diagnostic assessment, scan results distribution, proportion scans requiring early follow-up, proportion baseline or regular scans with actionable additional findings; <em>ADHERENCE</em> to<em>:</em> Annual or regular scans, early interim scans, clinical diagnostic assessment; <em>DIAGNOSTIC:</em> Proportion suspicious-for-lung-cancer scans receiving clinical investigation, undergoing invasive diagnostic procedures; <em>OUTCOMES:</em> Cancer detection rate, stage distribution, interval cancer rate; <em>HARMS:</em> Number and proportion of serious complications after invasive procedures, non-lung cancer diagnoses after invasive procedures or surgery, 30-day mortality after invasive procedure; <em>TREATMENT:</em> Proportion early-stage cancers receiving treatment with curative intent; <em>WAIT_TIMES:</em> Suspicious-for-lung-cancer scan to definitive diagnosis, to curative-intent treatment for individuals with early-stage disease, scan completion to reporting results to primary care provider and participant; <em>EQ</em><em>UITY:</em> Race, sex, and socioeconomic differences in adherence to regular screens, early-stage cancer treatment, offer of smoking cessation interventions, clinical investigation of suspicious-for-lung-cancer screens).</div></div><div><h3>Conclusions</h3><div>A review among panel members provided recommended LCS QIs that should be considered in the development of LCS initiatives.</div></div>","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"20 7","pages":"Pages 871-883"},"PeriodicalIF":21.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047205","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 and Pathologic Phenotyping of mesotheliomas developing in carriers of Germline BAP1 Mutations.","authors":"Michele Carbone, Michael Minaai, Muaiad Kittaneh, Thomas Krausz, Markku M Miettinen, Qiang Pan Hammarström, Lennart Hammarström, Hassan Abolhassani, Ian Pagano, Ronghui Xu, Flavia Novelli, Giovanni Gaudino, Sandra Pastorino, Kavita Y Sarin, Robert T Ripley, Harvey I Pass, David S Schrump, Haining Yang","doi":"10.1016/j.jtho.2025.06.020","DOIUrl":"10.1016/j.jtho.2025.06.020","url":null,"abstract":"<p><strong>Introduction: </strong>Mesothelioma is frequent among carriers of inactivating heterozygous germline BAP1 mutations (BAP1^+/-). We studied whether the natural history and the pathology of mesotheliomas in BAP1^+/- carriers differed from sporadic, not-genetically related, mesotheliomas.</p><p><strong>Methods: </strong>During 1999-2024, we studied 47 families carrying BAP1^+/- transmitted in a Mendelian fashion. We characterized these mutations, collected family history, clinical records, prepared family pedigrees and diagnosed their mesotheliomas.</p><p><strong>Results: </strong>We identified 34 different germline inactivating mutations. Among 238 BAP1^+/- carriers aged 27-81, 84 were diagnosed with mesothelioma (35%), 1/84 had evidence of asbestos exposure. No mesothelioma was recorded among 123 siblings/relatives who did not inherit BAP1^+/- p<0.0001. The 84 BAP1^+/- patients developed mesothelioma at a relatively young age; 45.2% developed multiple cancers. BAP1^+/- patients had a florid, diffuse mesothelial hyperplasia often present in both pleural cavities, peritoneum and pericardium. Thoracoscopy and laparoscopy showed several multi-cavity ∼1-3 mm whitish flat lesions, imaging was usually negative for cancer. Histology revealed epithelioid cells lacking BAP1 nuclear staining arranged in tubulo-papillary and trabecular architectures, focally invading sub-mesothelial adipose tissue. These findings may lead to the diagnosis of stage IV metastatic mesothelioma. However, we found that these tumors remain indolent for years and, at this early stage, patients do not require aggressive therapy. We refer to these tumors as \"Low-grade-germline-mutant-BAP1-associated-mesotheliomas, L-BAM\" to distinguish them from aggressive, therapy-resistant, sporadic mesotheliomas. For the 1/3 of patients who develop lesions visible by imaging, surgery and/or chemotherapy leads to survival of several years, some were cured. Deep invasion by mesothelioma cells with a solid architecture is rare: these cases have poor survival.</p><p><strong>Conclusions: </strong>Compared to sporadic mesotheliomas, mesotheliomas developing in BAP1^+/- carriers are a different disease, biologically, histologically and clinically: these patients require a tailored clinical approach.</p>","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":" ","pages":""},"PeriodicalIF":20.8,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12303596/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528580","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}