Journal of Thoracic Oncology最新文献

{"title":"A Response to the Letter to the Editor: Can High-Dose Furmonertinib Effectively Address Unmet Needs in EGFR-Mutated NSCLC With Leptomeningeal Metastases?","authors":"Sen Yang MD, Haiyang Chen MD, Qiming Wang MD","doi":"10.1016/j.jtho.2025.03.047","DOIUrl":"10.1016/j.jtho.2025.03.047","url":null,"abstract":"","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"20 7","pages":"Pages e81-e83"},"PeriodicalIF":21.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144549075","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":"PD-L1–Overexpressing NSCLC: Overcoming All-Comer Approach and Network Effect to Weather the “Winter” of Cancer Immunotherapy","authors":"Fabio Salomone MD , Antonio Nuccio MD , Roberto Ferrara MD, PhD","doi":"10.1016/j.jtho.2025.04.012","DOIUrl":"10.1016/j.jtho.2025.04.012","url":null,"abstract":"","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"20 7","pages":"Pages 834-838"},"PeriodicalIF":21.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144549176","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 Norway","authors":"Odd Terje Brustugun MD, PhD , Bjørn Henning Grønberg MD, PhD , Marianne Aanerud MD, PhD , Erna-Elise Paulsen MD, PhD , Lars Fjellbirkeland MD, PhD","doi":"10.1016/j.jtho.2025.03.046","DOIUrl":"10.1016/j.jtho.2025.03.046","url":null,"abstract":"","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"20 7","pages":"Pages 839-846"},"PeriodicalIF":21.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144549166","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":"Beyond Programmed Death-Ligand 1: Gut Microbiome Composition as a Biomarker For First-Line Chemoimmunotherapy in Advanced NSCLC","authors":"Prodromos Koutoukoglou MD, MSc , Giannis Mountzios ΜD, MSc, PhD","doi":"10.1016/j.jtho.2025.04.011","DOIUrl":"10.1016/j.jtho.2025.04.011","url":null,"abstract":"","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"20 7","pages":"Pages 831-833"},"PeriodicalIF":21.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144549175","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 ‘Tobacco News Update—From the IASLC Tobacco Control Committee’ [Journal of Thoracic Oncology Volume 20, Issue 3 (2025) 246-248]","authors":"","doi":"10.1016/j.jtho.2025.05.003","DOIUrl":"10.1016/j.jtho.2025.05.003","url":null,"abstract":"","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"20 7","pages":"Page 984"},"PeriodicalIF":21.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144549122","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":"Re-Evaluating the Overall Survival Advantage of Segmentectomy: A Missing Perspective on Age","authors":"Arif Hakan Önder MD","doi":"10.1016/j.jtho.2025.02.017","DOIUrl":"10.1016/j.jtho.2025.02.017","url":null,"abstract":"","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"20 7","pages":"Pages e79-e80"},"PeriodicalIF":21.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144549170","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":"Lurbinectedin Plus Pembrolizumab in Relapsed SCLC: The Phase I/II LUPER Study","authors":"Antonio Calles MD, MSc ,&nbsp;Alejandro Navarro MD ,&nbsp;Bernard Gaston Doger de Speville Uribe PhD ,&nbsp;Enric Álvarez Colomé PhD, MSc ,&nbsp;María de Miguel MD, PhD ,&nbsp;Rosa Álvarez MD ,&nbsp;Marta Arregui MD ,&nbsp;Víctor Moreno PhD ,&nbsp;Pedro Rocha MD, PhD, MSc ,&nbsp;Emiliano Calvo PhD ,&nbsp;Jorge Ramon-Patino PhD ,&nbsp;Elena Corral de la Fuente MD ,&nbsp;Daniel Alcalá-López PhD ,&nbsp;Olga Boix PhD ,&nbsp;Melissa Fernández-Pinto MSc ,&nbsp;Jose Rodríguez-Morató PhD ,&nbsp;Ramón Palmero MD ,&nbsp;Ernest Nadal MD, PhD ,&nbsp;Maria Jove MD, PhD ,&nbsp;Enriqueta Felip MD, PhD","doi":"10.1016/j.jtho.2025.02.005","DOIUrl":"10.1016/j.jtho.2025.02.005","url":null,"abstract":"<div><h3>Introduction</h3><div>SCLC has limited second-line treatment options after chemotherapy. We assessed the efficacy and safety of lurbinectedin combined with pembrolizumab in relapsed SCLC patients who had not received prior immunotherapy, aiming to prevent early progression and achieve sustained responses.</div></div><div><h3>Methods</h3><div>The LUPER trial (NCT04358237) is a phase I/II, single-arm, open-label, multicenter study. Phase I established the recommended phase II dose. The primary endpoint of phase II was the investigator-confirmed objective response rate. Secondary endpoints included duration of response, progression-free survival (PFS), overall survival (OS), and safety. Patients were categorized as platinum-sensitive (chemotherapy-free interval ≥ 90 d) or platinum-resistant (&lt;90 d).</div></div><div><h3>Results</h3><div>The recommended phase II dose was 3.2 mg/m² lurbinectedin and 200 mg pembrolizumab IV every three weeks. Phase II included 28 patients, 50% of whom were platinum-resistant. The objective response rate was 46.4% (95% confidence interval: 27.5–66.1, <em>p</em> &lt; 0.001), including three complete responses, with two complete metabolic responses post-treatment completion at 35 cycles. The median duration of response was 7.8 months, with 40% of patients maintaining responses for 12 months or longer. The median PFS was 4.6 months, and the median OS was 10.5 months. Platinum-sensitive patients had significantly better PFS (8.0 versus 2.8 mo, <em>p</em> = 0.012) and numerically superior OS (15.7 versus 7.1 mo, <em>p</em> = 0.058). Grade 3 or higher treatment-related adverse events occurred in 71.4% of patients, with transient neutropenia being the most common. Immune-related adverse events were consistent with prior pembrolizumab studies.</div></div><div><h3>Conclusions</h3><div>Lurbinectedin plus pembrolizumab reported promising efficacy in relapsed SCLC, particularly for platinum-sensitive patients, with a known and manageable safety profile. These results support further exploration of this combination in SCLC treatment.</div></div>","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"20 7","pages":"Pages 969-982"},"PeriodicalIF":21.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143408997","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":"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}