JTO Clinical and Research Reports最新文献

{"title":"An Uneven Playing Field: Survival Gains in Stage IV NSCLC Across Sociodemographic Strata","authors":"Justin A. Olivera MD, Sara Sakowitz MD, MPH, Mara B. Antonoff MD, FACS","doi":"10.1016/j.jtocrr.2025.100854","DOIUrl":"10.1016/j.jtocrr.2025.100854","url":null,"abstract":"","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 8","pages":"Article 100854"},"PeriodicalIF":3.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144330224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Late Immune-Related Adverse Events After At Least Two Years of Immune Checkpoint Inhibitor Therapy: Incidence and Association With Survival in Patients With Advanced NSCLC","authors":"Omar Elghawy MD,&nbsp;Adam Barsouk MD,&nbsp;Jonathan H. Sussman BS,&nbsp;Benjamin A. Bleiberg MD,&nbsp;Lauren Reed-Guy MD,&nbsp;Christopher D’Avella MD,&nbsp;Aditi Singh MD,&nbsp;Christine Ciunci MD, MSCE,&nbsp;Kyle Robinson MD,&nbsp;John Kosteva MD,&nbsp;Corey Langer MD,&nbsp;Roger B. Cohen MD,&nbsp;Charu Aggarwal MD, MPH,&nbsp;Melina Marmarelis MD, MSCE,&nbsp;Lova Sun MD, MSCE","doi":"10.1016/j.jtocrr.2025.100851","DOIUrl":"10.1016/j.jtocrr.2025.100851","url":null,"abstract":"<div><h3>Background</h3><div>Limited data are available on late immune-related adverse events (IRAEs) in patients with metastatic NSCLC receiving immunotherapy (ICI) beyond 2 years.</div></div><div><h3>Methods</h3><div>A single-institution retrospective analysis including patients who received longer than 2 years of ICI therapy for metastatic NSCLC between 2012 and 2023 was performed. Late IRAEs were defined as those occurring longer than 2 years after initiation of ICI therapy. The association of late IRAE with OS and PFS was assessed using an extended Cox regression with late IRAE modeled as a time-varying covariate.</div></div><div><h3>Results</h3><div>In a cohort of 76 patients who received longer than 2 years of ICI, the median duration of treatment was 41.9 months, and 44 out of 76 (58%) experienced an early IRAE before 2 years. After 2 years on ICI, 38 out of 76 (50%) of patients experienced a late IRAE, many of whom (39%) had no previous early IRAE. Higher rates of late IRAEs were seen in females (<em>p</em> = 0.032), White patients (<em>p</em> = 0.041), and patients with previous grade 2 or higher IRAE (<em>p</em> = 0.020). Late IRAE occurrence was not associated with median progression-free survival or median overall survival.</div></div><div><h3>Conclusions</h3><div>In patients receiving extended-duration ICI beyond 2 years, late IRAEs were common and often occurred in patients without previous history of IRAE. These findings support consideration of ICI discontinuation at 2 years.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 9","pages":"Article 100851"},"PeriodicalIF":3.5,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144725043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Longitudinal Circulating Tumor DNA–Guided Resistance Analysis During Second-Line Osimertinib Treatment","authors":"J.W. Tijmen van der Wel MD ,&nbsp;Merel Jebbink MD ,&nbsp;Vincent van der Noort PhD ,&nbsp;Ferry Lalezari MD, PhD ,&nbsp;Daan van den Broek PhD ,&nbsp;Gerrina Ruiter MD, PhD ,&nbsp;Jacobus A. Burgers MD, PhD ,&nbsp;Paul Baas MD, PhD ,&nbsp;Anne S.R. van Lindert MD ,&nbsp;Eva E. van der Wall MD ,&nbsp;Lisanne E.A. Kastelijn MD, PhD ,&nbsp;Marrit Vermeulen BSc ,&nbsp;Linda J.W. Bosch PhD ,&nbsp;Kim Monkhorst MD, PhD ,&nbsp;Mirjam C. Boelens PhD ,&nbsp;Egbert F. Smit MD, PhD ,&nbsp;Adrianus J. de Langen MD, PhD","doi":"10.1016/j.jtocrr.2025.100853","DOIUrl":"10.1016/j.jtocrr.2025.100853","url":null,"abstract":"<div><h3>Introduction</h3><div>In osimertinib-treated EGFR mutation (EGFRm)–positive NSCLC, resistance inevitably occurs. Early resistance mechanism (RM) detection by circulating tumor DNA (ctDNA) in plasma and consecutive targeted treatment may delay progressive disease (PD). In this multicenter prospective study, we evaluated the detection rate and time interval of RM emergence in plasma ctDNA before radiologic PD.</div></div><div><h3>Methods</h3><div>Patients with EGFRm–positive NSCLC, treated with second- or third-line osimertinib, underwent computed tomography of the thorax and ctDNA analysis (Roche AVENIO expanded panel, research use only [Roche Sequencing Solutions, Roche, Basel, Switzerland]) at baseline and every 8 weeks for response evaluation and EGFRm and RM detection. If MET amplification preceded PD, crizotinib was to be added to osimertinib. Other RMs were monitored but not acted on. After PD, patients underwent a tumor biopsy.</div></div><div><h3>Results</h3><div>Of the 21 evaluable patients, 18 had detectable ctDNA at baseline. In patients with undetectable ctDNA at baseline, ctDNA remained undetectable during treatment. In the 17 out of 18 (94%) patients with detectable ctDNA, PD occurred. In seven out of 21 patients (33%), the EGFRm variant allele frequency increase preceded radiologic PD with a median interval of 9 weeks (range 7–34). In seven out of 21 patients (33%), at least one RM was detected before PD, and the median interval was 14 weeks (range 7–34). Three had one or more RM in ctDNA at baseline. No MET amplification was observed, and treatment with crizotinib was not initiated in any patient. After PD, 16 biopsies were obtained. Five confirmed the RM detected in plasma, five biopsies revealed additional RMs, and six harbored no RM.</div></div><div><h3>Conclusions</h3><div>In 33% of patients treated with second- or third-line osimertinib, RMs in plasma preceded PD by a median of 14 weeks, suggesting an opportunity for early treatment adjustment, potentially extending tyrosine kinase inhibitor treatment duration.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 9","pages":"Article 100853"},"PeriodicalIF":3.5,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144739621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lung Cancer Screening Eligibility, Uptake, and Adherence in Puerto Rico, 2022","authors":"Maira A. Castañeda-Avila PhD, MS ,&nbsp;Eduardo J. Santiago-Rodríguez PhD, MPH ,&nbsp;William Rodríguez-Cintrón MD, MPH ,&nbsp;Coral Olazagasti MD ,&nbsp;Efrén J. Flores MD ,&nbsp;Estelamari Rodríguez MD, MPH ,&nbsp;Ana I. Velázquez Mañana MD, MSc ,&nbsp;Yomayra Otero-Domínguez MD, MS ,&nbsp;Eduardo R. Núñez MD, MS","doi":"10.1016/j.jtocrr.2025.100852","DOIUrl":"10.1016/j.jtocrr.2025.100852","url":null,"abstract":"<div><h3>Importance</h3><div>Lung cancer screening (LCS) with yearly low-dose computed tomography reduces lung cancer mortality, but uptake remains low. Puerto Rico, a U.S. territory, faces significant barriers to LCS implementation, but data on LCS eligibility and use are limited.</div></div><div><h3>Objective</h3><div>This study aimed to estimate the number of individuals eligible for LCS in Puerto Rico and assess the prevalence of LCS use and up-to-date status compared with U.S. Hispanic and non-Hispanic populations.</div></div><div><h3>Design, Setting, and Participants</h3><div>This cross-sectional study analyzed data from the 2022 Behavioral Risk Factor Surveillance System, a population-based telephone survey. Adults eligible for LCS per 2021 U.S. Preventive Services Task Force guidelines (aged 50–80 years, ≥20 pack-year smoking history, current or recent smokers) from Puerto Rico and the United States were included.</div></div><div><h3>Exposures</h3><div>Participants were categorized into three groups: Puerto Rico residents, U.S. Hispanic, and U.S. non-Hispanic populations.</div></div><div><h3>Primary Outcomes and Measures</h3><div>The primary outcomes and measures were self-reported receipt of initial LCS (ever had chest CT for screening) and being up to date with LCS (i.e., chest CT in the past year). Multivariable Poisson models estimated adjusted prevalence ratios for LCS outcomes.</div></div><div><h3>Results</h3><div>After population weighting, 94,955 individuals were eligible for LCS in Puerto Rico, compared with 12.8 million in the U.S., representing 7.9% and 11.9% of their respective populations. The prevalence of self-reported LCS use was 28.4% in Puerto Rico, 27.6% among U.S. Hispanics, and 31.5% among U.S. non-Hispanics. Being up to date with LCS was lower among Puerto Rico residents (9.8%) than among U.S. Hispanics (17.3%) and non-Hispanics (18.1%). Multivariable models found Puerto Rico residents were less likely to be up to date with LCS than were U.S. non-Hispanics (adjusted prevalence ratios, 0.54; 95% CI 0.29–0.99).</div></div><div><h3>Conclusions and Relevance</h3><div>Fewer than 10% of eligible individuals in Puerto Rico self-reported being up to date with LCS, indicating they are almost half as likely to self-report as eligible individuals in the United States, highlighting significant gaps in care. Implementing high-quality LCS in Puerto Rico is critical to reducing lung cancer mortality and providing equitable lung cancer care.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 8","pages":"Article 100852"},"PeriodicalIF":3.0,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144330223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of the Safety, Pharmacokinetics, and Antitumor Activity of Tusamitamab Ravtansine in Patients With Nonsquamous NSCLC With High or Moderate Expression of Carcinoembryonic Antigen-Related Cell Adhesion Molecule 5","authors":"Anas Gazzah MD ,&nbsp;Charles Ricordel MD, PhD ,&nbsp;Antoine Italiano MD, PhD ,&nbsp;Byoung Chul Cho MD, PhD ,&nbsp;Emiliano Calvo MD, PhD ,&nbsp;Dong-Wan Kim MD, PhD ,&nbsp;Carole Helissey MD ,&nbsp;Jin-Soo Kim MD, PhD ,&nbsp;Maria Vieito Villar MD ,&nbsp;Francois Ghiringhelli HDR ,&nbsp;Victor Moreno MD, PhD ,&nbsp;Sophie Cousin MD ,&nbsp;Luis Paz-Ares MD, PhD ,&nbsp;Nathalie Fagniez Pharm D ,&nbsp;Mustapha Chadjaa MD ,&nbsp;Anne-Laure Bauchet DECVP, PhD ,&nbsp;Christine Soufflet MD ,&nbsp;Nina Masson MSc ,&nbsp;Fabrice Barlesi MD, PhD","doi":"10.1016/j.jtocrr.2025.100844","DOIUrl":"10.1016/j.jtocrr.2025.100844","url":null,"abstract":"<div><h3>Introduction</h3><div>Tusamitamab ravtansine is an antibody-drug conjugate targeting cells expressing carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) with a maytansinoid payload, DM4. This phase 1b dose-expansion study (NCT02187848) evaluated its safety, pharmacokinetics, and preliminary antitumor activity in patients with nonsquamous NSCLC (NSq NSCLC).</div></div><div><h3>Methods</h3><div>Patients aged above or equal to 18 years with advanced or metastatic NSq NSCLC, life expectancy more than or equal to 12 weeks, and high (≥2+ intensity in ≥50% of tumor cells) or moderate (≥2+ intensity in 1%–49% of tumor cells) CEACAM5 expression (assessed by immunohistochemistry) received intravenous tusamitamab ravtansine 100 mg/m² every 2 weeks.</div></div><div><h3>Results</h3><div>A total of 64 patients with high and 28 with moderate CEACAM5 expression received a median of 8.0 (1–69) and 4.5 (1–38) treatment cycles, respectively. High expressors had 13 confirmed partial responses and 28 stable diseases (objective response rate, 20.3%; 95% confidence interval [CI]: 12.3%–31.7%, <em>p</em> &lt; 0.0001); median duration of response was 6.7 months, and median time to progression was 3.7 months (95% CI: 2.7–5.1 mo). Moderate expressors had two confirmed partial responses (objective response rate, 7.1%; 95% CI: 2.0%–22.7%, <em>p</em> = 0.4117) and 15 stable diseases.</div><div>Treatment-emergent adverse events (AEs) occurred in 78.3% of patients (72/92), 37.0% (34/92) of patients required dose modifications, and 5.4% (5/92) discontinued treatment. The most common treatment-emergent AEs included asthenia (37.0%), keratitis (29.3%), and dyspnea (23.9%). Corneal AEs occurred in 38.0% (35/92), typically grade 1/2, reversible, and manageable by dose modifications.</div></div><div><h3>Conclusions</h3><div>Tusamitamab ravtansine demonstrated a favorable safety profile, objective responses, and antitumor activity in patients with high CEACAM5-expressing NSq NSCLC.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 10","pages":"Article 100844"},"PeriodicalIF":3.5,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145096129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Parallel Phase II Clinical Trials of Selinexor in Patients With Advanced Thymoma and Thymic Carcinoma","authors":"Chul Kim MD ,&nbsp;Vanya Aggarwal MD ,&nbsp;Gedske Daugaard MD, DMSc ,&nbsp;Tianzhi Tang MD ,&nbsp;Jaeil Ahn PhD ,&nbsp;Benjamin Besse MD, PhD ,&nbsp;Nicolas Girard MD, PhD ,&nbsp;Giuseppe Giaccone MD, PhD ,&nbsp;Peter Meidahl Petersen MD, PhD","doi":"10.1016/j.jtocrr.2025.100848","DOIUrl":"10.1016/j.jtocrr.2025.100848","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction&lt;/h3&gt;&lt;div&gt;Thymic epithelial tumors (TETs) are rare and include thymomas (T) and thymic carcinomas (TC). Effective treatment options are needed for patients with progressive disease after platinum-based chemotherapy. Preclinical studies demonstrated antitumor activity of selinexor, an inhibitor of the nuclear receptor exportin-1 (XPO1/CRM1), supporting the clinical development of XPO1-targeted therapy for the treatment of TETs. To further assess the safety and efficacy of selinexor in TETs, we conducted two coordinated parallel phase II clinical trials.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;This report includes two nearly identical phase II trials, designed to run in parallel, conducted in the United States (NCT03193437) and Europe (Denmark and France; NCT03466827). Analysis was performed on data pooled from both trials. Both trials were nonrandomized, open-label, two-armed phase II trials (arm A: thymoma, arm B: thymic carcinoma) with the same study design. Patients with histologically confirmed, advanced, inoperable TETs who had progressive disease after treatment with at least one platinum-containing chemotherapy regimen were included. In each 4-week cycle, patients received selinexor 60 mg twice weekly for 3 weeks. To improve tolerability, the starting dose was reduced to 40 mg twice weekly during the study. The primary objective was overall response rate (ORR) assessed by Response Evaluation Criteria in Solid Tumors 1.1, with secondary objectives including progression free survival (PFS), overall survival (OS), and adverse events (AEs) assessed per Common Terminology Criteria for Adverse Event version 4.03.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;A total of 31 patients were enrolled between the two trials: 16 with T and 15 with TC. The median age was 57 (range: 41–81) years, with 17 men and 14 women. The median number of previous systemic therapies was 2 (range: 1–9). The starting dose was 60 mg twice weekly for 29 patients (93.5%) and 40 mg twice weekly for two patients (6.5%). There was one complete response in the TC group (ORR 6.7%; 95% confidence interval [CI]: 1.2%–29.8%) and two partial responses (ORR 12.5%; 95% CI: 3.5%–36.0%) in the T group. Stable disease as the best response was observed in 11 patients (68.6%) with T and 12 patients (80%) with TC. The median duration of selinexor therapy was 4.5 (range: 0.1–44.3) months. The most common treatment-related adverse events (TRAEs) were nausea (83.8%), vomiting (45.2%), anemia (41.9%), fatigue (38.7%), and asthenia (38.7%). The most common grade 3 or higher TRAEs were anemia (16.1%), thrombocytopenia (12.9%), and asthenia (12.9%). Furthermore, 20 patients (64.5%) required dose reductions due to AEs and 20 patients (64.5%) required dose interruptions. In the T group, the median PFS was 13.6 months (95% CI: 6.3–44.3), and the median OS was not reached. In the TC group, the median PFS was 7.8 months (95% CI: 4.3–15.5) and the median OS was 15.5 months (95% CI: 13.0–29.9). ","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 9","pages":"Article 100848"},"PeriodicalIF":3.0,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144672261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Phase I Dose-Escalation Clinical Trial of Bronchoscopic Cryoimmunotherapy in Advanced-Stage NSCLC","authors":"Jun-Chieh J. Tsay MD, MS ,&nbsp;Antonio Velez MD ,&nbsp;Destiny Collazo BS ,&nbsp;Isaac Laniado MD ,&nbsp;Jamie Bessich MD ,&nbsp;Vivek Murthy MD ,&nbsp;Andrew DeMaio MD ,&nbsp;Samaan Rafeq MD ,&nbsp;Benjamin Kwok MD ,&nbsp;Fares Darawshy MD ,&nbsp;Ray Pillai MD ,&nbsp;Kendrew Wong MD ,&nbsp;Yonghua Li MD, PhD ,&nbsp;Rosemary Schluger RN ,&nbsp;Alena Lukovnikova BS ,&nbsp;Sofia Roldan BS ,&nbsp;Matt Blaisdell BS ,&nbsp;Fernanda Paz ,&nbsp;Kelsey Krolikowski BS ,&nbsp;Katherine Gershner MD ,&nbsp;Daniel H. Sterman MD","doi":"10.1016/j.jtocrr.2025.100849","DOIUrl":"10.1016/j.jtocrr.2025.100849","url":null,"abstract":"<div><h3>Introduction</h3><div>Outcomes for NSCLC remain suboptimal. Recent data suggest that cryoablation can generate antitumor immune effects. In this first-in-human phase I clinical trial, we investigated the safety and feasibility of bronchoscopic cryoimmunotherapy (BCI) delivered during standard-of-care bronchoscopy and explored associated systemic immune responses.</div></div><div><h3>Methods</h3><div>Subjects with known or suspected advanced-stage NSCLC were recruited. BCI was delivered in dose-escalated freeze-thaw cycles to determine maximum dose tolerance. Feasibility assessment was determined with a pre-set goal of achieving successful BCI in more than or equal to 80% of subjects. Safety was assessed by review of BCI-related complications, including grades 2 to 3 bleeding, pneumothorax requiring intervention, and National Cancer Institute Common Terminology Criteria for Adverse Events grade 3 to 5 adverse events. Pre- and post-BCI blood samples were collected to explore changes in the systemic immune profile.</div></div><div><h3>Results</h3><div>Subjects with predominantly clinical TNM stage 3 or 4 adenocarcinoma or squamous cell carcinoma were enrolled. We reached the maximum dose of 30 seconds with 100% feasibility and no BCI-related adverse events. In peripheral blood analysis, we observed a significant decrease in derived neutrophil-to-lymphocyte ratio in the high-dose BCI group in comparison to the low-dose BCI cohort. We also observed increases in inflammatory cytokines—GM-CSF, IFN-γ, IL-1β, IL-17A, and IL-2—and effector memory T cells post-BCI.</div></div><div><h3>Conclusion</h3><div>BCI is safe and feasible. In addition, we provide preliminary evidence that at higher dose levels there is a systemic immune response consistent with a cytotoxic profile. Further immune analyses will determine the potential of BCI as an adjunctive therapy in combination with immune checkpoint inhibition in NSCLC treatment.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 8","pages":"Article 100849"},"PeriodicalIF":3.0,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144480623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Prospective Exploratory Study of Functional Immunity Assessed by Pretreatment Interferon Gamma Release Assay in Relation to Different Systemic Therapies in Patients With Advanced-Stage NSCLC","authors":"Hsu-Ching Huang MD ,&nbsp;Han-Jhih Chang MS ,&nbsp;Chi-Lu Chiang MD ,&nbsp;Hsin-Yi Huang MS ,&nbsp;Yung-Hung Luo MD ,&nbsp;Yuh-Min Chen MD ,&nbsp;Tsu-Hui Shiao MD ,&nbsp;Chao-Hua Chiu MD","doi":"10.1016/j.jtocrr.2025.100845","DOIUrl":"10.1016/j.jtocrr.2025.100845","url":null,"abstract":"<div><h3>Introduction</h3><div>Predictive markers for chemotherapy and immunotherapy response in advanced NSCLC are limited, and no objective tool exists to assess immune function, which is critical for treatment outcomes. This study prospectively evaluated the interferon gamma (IFN-γ) release assay (IGRA) as a potential predictor of treatment response and a tool for assessing immune function.</div></div><div><h3>Methods</h3><div>We enrolled patients with stage IV NSCLC undergoing first-line chemotherapy, EGFR tyrosine kinase inhibitor (TKI) therapy, or any line of single-agent immunotherapy, alongside stage I controls. Peripheral blood samples were collected pre- and post-treatment for IGRA testing using the QuantiFERON-TB Gold In-Tube (QFT-GIT) kit. Phytohemagglutinin-stimulated IFN-γ (PSIG) responses were measured by both QFT-GIT and in-house enzyme-linked immunosorbent assay, with stage IV patients categorized into high- and low-PSIG response groups based on median pretreatment values.</div></div><div><h3>Results</h3><div>A total of 117 patients were analyzed (32 surgery, 30 EGFR TKI, 25 chemotherapy, 30 immunotherapy). The median PSIG response was significantly higher in stage I patients than stage IV (1420 pg/mL versus 960 pg/mL; <em>p</em> = 0.032). In stage IV, those with driver mutations had higher pretreatment PSIG responses (1278 pg/mL versus 288 pg/mL; <em>p =</em> 0.004). Kaplan–Meier analysis suggested a trend toward longer progression-free and overall survival in the EGFR TKI and immunotherapy groups with higher PSIG responses, though not statistically significant.</div></div><div><h3>Conclusions</h3><div>Patients with advanced-stage NSCLC exhibited reduced lymphocyte function, and patients with driver mutations correlated to less exhausted lymphocyte. IGRA demonstrates potential as a clinical tool for assessing immune function in these patients.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 8","pages":"Article 100845"},"PeriodicalIF":3.0,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144330142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Post-discontinuation Survival in Patients With Advanced NSCLC Receiving Immune Checkpoint Inhibitors: A Pooled Analysis of Prospective Cohort Studies","authors":"Yusuke Inoue MD, PhD ,&nbsp;Yoshihiro Kitahara MD ,&nbsp;Masato Karayama MD, PhD ,&nbsp;Kazuhiro Asada MD, PhD ,&nbsp;Koji Nishimoto MD, PhD ,&nbsp;Shun Matsuura MD, PhD ,&nbsp;Dai Hashimoto MD, PhD ,&nbsp;Masato Fujii MD, PhD ,&nbsp;Takashi Matsui MD, PhD ,&nbsp;Nao Inami MD ,&nbsp;Mikio Toyoshima MD, PhD ,&nbsp;Hiroyuki Matsuda MD, PhD ,&nbsp;Masaki Ikeda MD, PhD ,&nbsp;Mitsuru Niwa MD, PhD ,&nbsp;Yusuke Kaida MD, PhD ,&nbsp;Masaki Sato MD, PhD ,&nbsp;Yasuhiro Ito MD ,&nbsp;Hideki Yasui MD, PhD ,&nbsp;Yuzo Suzuki MD, PhD ,&nbsp;Hironao Hozumi MD, PhD ,&nbsp;Takafumi Suda MD, PhD","doi":"10.1016/j.jtocrr.2025.100847","DOIUrl":"10.1016/j.jtocrr.2025.100847","url":null,"abstract":"<div><h3>Introduction</h3><div>The safety of discontinuing immune checkpoint inhibitors (ICIs) because of a durable response in patients with advanced NSCLC remains uncertain, and post-discontinuation survival outcomes based on the reason for cessation are not well defined.</div></div><div><h3>Methods</h3><div>A pooled analysis was conducted using data from four prospective cohort studies involving 835 patients with advanced NSCLC who discontinued ICIs. Patients were categorized based on discontinuation reasons: durable response; immune-related adverse events (irAEs) (subcategorized by tumor response at discontinuation); non-irAE adverse events; disease progression; and other causes.</div></div><div><h3>Results</h3><div>Disease progression was the most common reason for ICI discontinuation (<em>N</em> = 528 [63.2%]), followed by irAEs (<em>N</em> = 187 [22.4%]) and tumor response (<em>N</em> = 23 [2.8%]). Regarding response status at ICI discontinuation due to irAEs, complete/partial response (CR/PR) was the most frequent (<em>N</em> = 85), followed by stable disease/not evaluable (SD/NE, <em>N</em> = 69) and disease progression (<em>N</em> = 33). After a median post-discontinuation follow-up of 15.8 months (interquartile range, 6.9–23.2), patients who discontinued because of a response had excellent outcomes, with no deaths and only three progression-free survival events. While post-discontinuation overall survival was comparable between the irAE-CR/PR and irAE-SD/NE groups, ICI therapy ≥12 months was associated with improved post-ICI discontinuation survival in the irAE-CR/PR group.</div></div><div><h3>Conclusions</h3><div>Discontinuation of ICIs because of a durable tumor response is rare in real-world settings but represents a feasible strategy for patients with advanced NSCLC. Patients in the irAE-CR/PR group had favorable post-ICI discontinuation survival if they received ICI therapy lasting ≥12 months.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 8","pages":"Article 100847"},"PeriodicalIF":3.0,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144330153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum to ‘Primary Results from IMscin002: A Study to Evaluate Patient Preferences and Perceptions of Health Care Professionals for Atezolizumab Subcutaneous Versus Intravenous for the Treatment of NSCLC’ [JTO Clinical and Research Reports Volume 6 Issue 5 (2025) 100815]","authors":"Federico Cappuzzo MD ,&nbsp;Zanete Zvirbule MD ,&nbsp;Ernesto Korbenfeld MD ,&nbsp;Jaroslaw Kolb-Sielecki MD ,&nbsp;Dolores Isla MD, PhD ,&nbsp;Aleksandra Szczesna MD, PhD ,&nbsp;Amparo Yovanna Castro Sanchez PhD ,&nbsp;Alberto Bustillos MD ,&nbsp;Xiaoyan Liu PhD ,&nbsp;Fiona Young MbChB ,&nbsp;Nadia Tosti PhD ,&nbsp;Marta Freitas Monteiro MSc, PhD ,&nbsp;Margarita Majem MD, PhD","doi":"10.1016/j.jtocrr.2025.100842","DOIUrl":"10.1016/j.jtocrr.2025.100842","url":null,"abstract":"","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 7","pages":"Article 100842"},"PeriodicalIF":3.0,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144203728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}