Clinical lung cancer最新文献

{"title":"Effects of Sex on Mortality in Patients With Lung Cancer: A Multiple Mediation Analysis of The Boston Lung Cancer Study","authors":"Adriana Araceli Rodriguez Alvarez ,&nbsp;Yuming Sun ,&nbsp;Yi Li ,&nbsp;David C. Christiani","doi":"10.1016/j.cllc.2025.09.007","DOIUrl":"10.1016/j.cllc.2025.09.007","url":null,"abstract":"<div><h3>Objective</h3><div>Identify the specific variables that can explain the sex difference in lung cancer mortality.</div></div><div><h3>Material and Methods</h3><div>This retrospective cohort study analyzed data from the Boston Lung Cancer Study (1992-2022). We employed descriptive statistics, Wilcoxon rank-sum test, and Pearson’s Chi-square test to compare demographic and clinical variables by sex. Kaplan–Meier survival curves and Cox proportional hazards models were used to evaluate survival differences. Mediation analysis was conducted to investigate causal pathways through which sex influences mortality, incorporating cancer stage, smoking status, and treatment modalities.</div></div><div><h3>Results</h3><div>Among 7642 patients, 53.7% were women. Men were older, had heavier smoking histories, and more frequently received chemotherapy and radiotherapy, whereas women underwent more surgeries. Median survival was significantly longer for women (4.54 vs. 2.59 years), with a 29% reduced hazard of lung cancer–related death (HR: 0.71; 95% CI, 0.66-0.75; <em>P</em> &lt; .0001). Approximately 32% of this survival difference was mediated by early-stage diagnosis, surgical intervention, and smoking history.</div></div><div><h3>Conclusion</h3><div>Women exhibited a survival advantage, of which only about one-third was explained by earlier diagnosis and higher surgical intervention rates. The remaining two-thirds of the mortality difference remains unexplained. Addressing these modifiable factors may reduce sex inequalities in lung cancer outcomes.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"27 2","pages":"Pages 201-209.e3"},"PeriodicalIF":3.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145354015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revisiting AI Model Interpretability in Lung Cancer Screening: Challenges in Balancing Predictive Performance and Reliability","authors":"Souichi Oka ,&nbsp;Yoshiyasu Takefuji","doi":"10.1016/j.cllc.2025.09.005","DOIUrl":"10.1016/j.cllc.2025.09.005","url":null,"abstract":"","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"27 2","pages":"Pages 197-198"},"PeriodicalIF":3.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145279101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of Neratinib-Based Therapy in ERBB2-Mutant Lung Adenocarcinomas: Findings From 2 International Phase 2 Studies","authors":"Bob T. Li ,&nbsp;Leena Gandhi ,&nbsp;Vignesh Ravichandran ,&nbsp;Benjamin Besse ,&nbsp;Julien Mazières ,&nbsp;Geoffrey I. Shapiro ,&nbsp;Valentina Boni ,&nbsp;Saiama N. Waqar ,&nbsp;Haeseong Park ,&nbsp;David I. Quinn ,&nbsp;Alejandro Martinez ,&nbsp;Salomon M. Stemmer ,&nbsp;Alexis B. Cortot ,&nbsp;Fabrice Barlesi ,&nbsp;Elisabeth Quoix ,&nbsp;Mark E. Burkard ,&nbsp;S. Duygu Selcuklu ,&nbsp;Casey Hunt ,&nbsp;Mark T.A. Donoghue ,&nbsp;Mark G. Kris ,&nbsp;Pasi A. Jänne","doi":"10.1016/j.cllc.2025.09.009","DOIUrl":"10.1016/j.cllc.2025.09.009","url":null,"abstract":"<div><h3>Background</h3><div><em>ERBB2</em> mutations are oncogenic drivers in 2% to 4% of lung cancers and potentially actionable using HER2 tyrosine kinase inhibitors.</div></div><div><h3>Patients and Methods</h3><div>Patients with advanced <em>ERBB2</em>-mutant lung cancer entered 2 phase 2 studies (PUMA-NER-4201 [4201]; PUMA-NER-5201 [SUMMIT]). Patients received neratinib (monotherapy 4201; monotherapy SUMMIT), or neratinib with weekly temsirolimus (combination 4201), or trastuzumab every 3 weeks (combination SUMMIT). Protocol-defined endpoints common to both studies were analyzed. Exploratory genomic analyses were conducted. ClinicalTrials.gov: NCT01827267; NCT01953926.</div></div><div><h3>Results</h3><div>Sixty patients in 4201 (neratinib, <em>n</em> = 17; neratinib plus temsirolimus, <em>n</em> = 43) and 78 in SUMMIT (neratinib, <em>n</em> = 26; neratinib plus trastuzumab, <em>n</em> = 52) received study treatment. Objective response rates were 0% (95% confidence interval [CI], 0.0-19.5; 4201) and 3.8% (95% CI, 0.1-19.6; SUMMIT) with neratinib, 14.0% (95% CI, 5.3-27.9) with neratinib plus temsirolimus, and 9.6% (95% CI, 3.2-21.0) with neratinib plus trastuzumab. Five patients whose tumors harbored <em>ERBB2</em> exon 20 insertion, L755P and D769Y missense mutations, and a novel <em>ERBB2-SHC1</em> fusion had responses ≥ 1 year (neratinib monotherapy, <em>n</em> = 1; SUMMIT; neratinib plus temsirolimus, <em>n</em> = 2; neratinib plus trastuzumab, <em>n</em> = 2). Grade ≥ 3 treatment-related adverse events occurred in 23.5% (4201) and 34.6% (SUMMIT) of neratinib-treated patients, 37.2% of patients treated with neratinib plus temsirolimus, and 48.1% of patients treated with neratinib plus trastuzumab.</div></div><div><h3>Conclusion</h3><div>Single-agent neratinib has limited activity in <em>ERBB2</em>-mutated lung cancers. Combinations with temsirolimus or trastuzumab did not markedly improve overall outcomes, producing durable responses in a limited subset of patients.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"27 2","pages":"Pages 214-226.e5"},"PeriodicalIF":3.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145451181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Randomized Phase II Trial of Hypo-fractionated Intensity-Modulated Radiation Therapy (IMRT) Utilizing 2.5 Gy/Fraction Versus Standard- Fractionated IMRT, Concurrent With Carboplatin/Paclitaxel and Followed by Consolidation Durvalumab, for Subjects With Stage III Non-Small Cell Lung Cancer","authors":"Krishna Reddy,&nbsp;Fen Wang,&nbsp;Ying Cao,&nbsp;Gregory N. Gan","doi":"10.1016/j.cllc.2025.12.004","DOIUrl":"10.1016/j.cllc.2025.12.004","url":null,"abstract":"<div><h3>Background</h3><div>Locoregional control remains suboptimal for patients with stage III non-small cell lung cancer (NSCLC) who receive standard-of-care concurrent chemoradiation, with standard-fractionated radiation treatment (RT) delivered at 2 Gy/fraction. Hypo-fractionated RT is effectively used as a standard-of-care treatment option in several different cancers and allows escalation of the biological effective dose (BED) to the tumor, without increasing the overall treatment time. In NSCLC, hypo-fractionated RT regimens have been investigated in early phase trials and found to be feasible if performed with careful attention to the dose received by adjacent critical structures.</div></div><div><h3>Methods</h3><div>The study is a randomized, phase II clinical trial designed to evaluate the feasibility, toxicity and efficacy of hypo-fractionated RT to 62.5 Gy in 25 fractions (2.5 Gy/fraction) in stage III NSCLC subjects, compared to the current standard-of care 6-week RT regimen (2 Gy/fraction), with concurrent systemic chemotherapy and consolidation immunotherapy. Our primary objective is to compare locoregional control between hypo-fractionated RT versus standard fractionated RT. Secondary objectives include comparing acute and late toxicities, progression free survival, overall survival, and quality of life.</div></div><div><h3>Conclusions</h3><div>This study will assess the safety and feasibility of hypo-fractionated RT at 2.5 Gy/fraction with concurrent chemotherapy and consolidation immunotherapy and is the first prospective, randomized clinical trial, to our knowledge, to compare the efficacy of hypo-fractionated RT versus standard-fractionated RT for patients with stage III non-small cell lung cancer.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"27 2","pages":"Pages 98-105"},"PeriodicalIF":3.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146185046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thoracic Radiotherapy and Radiation Time Would Affect the Efficacy of Advanced Non-Small Cell Lung Cancer for Patients Who Responded to TKIs Treatment","authors":"Ma Jinbo,&nbsp;Li Cheng,&nbsp;Wang Xiao,&nbsp;Zhang Pengfei,&nbsp;Ma Xiaoyan,&nbsp;Kan Hongxing,&nbsp;Zhang Wei","doi":"10.1016/j.cllc.2025.12.009","DOIUrl":"10.1016/j.cllc.2025.12.009","url":null,"abstract":"<div><h3>Purpose</h3><div>This trial aimed to investigate the difference in treatment efficacy of thoracic radiotherapy before and after thoracic progression during treatment with EGFR-TKI to determine the optimal timing of consolidation thoracic radiotherapy.</div></div><div><h3>Materials and Methods</h3><div>815 patients with histologically confirmed advanced NSCLC with EGFR mutation received 1-3 generation EGFR-TKIs or EGFR-TKIs treatment plus thoracic radiotherapy from May 2017 to May 2020.. For patients who received thoracic radiotherapy, 196 received thoracic radiotherapy before thoracic progression, and 244 patients received thoracic radiotherapy after thoracic progression. Kaplan-Meier analysis and log-rank test were used to compare survival differences for radiotherapy sequences.</div></div><div><h3>Results</h3><div>There was a significant statistical difference in the median OS[mOS: 31.8 vs 18.4 months, HR=0.60(0.479, 0.952), P=0.000] and PFS[mPFS: 22.6 vs 14.0 months, HR=0.60(0.485, 0.736), P=0.000] between TKIs plus radiotherapy group and TKIs group. For patients who received thoracic radiotherapy, 5-year OS rates were 43.6% and 28.2% in the pre-progression and post-progression groups, respectively (HR=0.67, P=0.047). The median OS was 33.7 months (22.10-38.1) and 27.8 months (19.16-27.90) for the two groups, respectively. 5-year progression-free survival rates were 71.8% and 54.5% in the pre-progression group and post-progression group, respectively (HR=0.73,P=0.043). The median PFS was 27.4 months (23.48-31.25) and 19.2 months (15.94-22.53) for the two groups, respectively.</div></div><div><h3>Conclusion</h3><div>It indicated that advanced stage NSCLC with positive EGFR mutation had better long-term survival if patients underwent thoracic radiotherapy before thoracic progression in the TKIs treatment.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"27 2","pages":"Pages 126-134"},"PeriodicalIF":3.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147303040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TIGOS Trial: A Randomized, Double-Blind, Phase III Trial of Atigotatug and Nivolumab Fixed-Dose Combination With Chemotherapy Versus Atezolizumab With Chemotherapy as First-Line Therapy in Patients With Extensive-Stage Small Cell Lung Cancer","authors":"Luis G. Paz-Ares ,&nbsp;Kenneth John O'Byrne ,&nbsp;Melissa L. Johnson ,&nbsp;Martin Reck ,&nbsp;Nicolas Girard ,&nbsp;Hidetoshi Hayashi ,&nbsp;Caicun Zhou ,&nbsp;Vishwanath Suresh Gharpure ,&nbsp;Radhika Pisupati ,&nbsp;Misena Pacius ,&nbsp;Neal E. Ready","doi":"10.1016/j.cllc.2026.01.009","DOIUrl":"10.1016/j.cllc.2026.01.009","url":null,"abstract":"<div><h3>Introduction</h3><div>Extensive-stage small cell lung cancer (ES-SCLC) is an aggressive malignancy with limited treatment options and poor outcomes. Despite the addition of antiprogrammed death ligand 1 inhibitors to platinum-etoposide chemotherapy, median overall survival (OS) remains &lt; 1 year.</div></div><div><h3>Patients and Methods</h3><div>TIGOS (CA245-0001; NCT06646276) is an ongoing randomized, double-blind, multicenter phase III study evaluating a fixed-dose combination (FDC) of atigotatug and nivolumab (BMS-986489) plus carboplatin-etoposide chemotherapy compared with atezolizumab plus carboplatin-etoposide chemotherapy as first-line treatment for patients with ES-SCLC. Atigotatug is a monoclonal antibody acting as a tumor-targeted innate immune inducer that binds fucosyl-monosialoganglioside-1, which is expressed on ≤ 90% of SCLC tumor cells and minimally in normal tissues. Nivolumab, an antiprogrammed death-1 antibody, restores T-cell activity and promotes adaptive antitumor immunity. Together, these agents act through distinct but complementary immune mechanisms to enhance tumor cell killing.</div><div>Approximately 530 adults (age ≥ 18 years) with histologically or cytologically confirmed ES-SCLC, ≥ 1 measurable extracranial lesion per RECIST v1.1, and an Eastern Cooperative Oncology Group performance status of 0-1 will be randomized 1:1 to receive either atigotatug and nivolumab FDC or atezolizumab in combination with carboplatin plus etoposide until progression, toxicity, or withdrawal.</div><div>The primary endpoint is OS. The key secondary endpoint (statistically analyzed) is time to definitive deterioration; other secondary endpoints include progression-free survival, objective response, duration of response, and safety.</div></div><div><h3>Conclusion</h3><div>Recruitment is ongoing at 182 sites across 26 countries with an estimated primary completion date of April 2028, with study completion in September 2031.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"27 2","pages":"Pages 140-145"},"PeriodicalIF":3.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147316550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patient-Relevant Outcomes From the Phase III MARIPOSA-2 Trial: Amivantamab-Chemotherapy Versus Chemotherapy in EGFR-Mutant Advanced Non-Small-Cell Lung Cancer Following Disease Progression on Osimertinib","authors":"Pascale Tomasini ,&nbsp;Oscar Juan-Vidal ,&nbsp;Raffaele Califano ,&nbsp;Chien-Chung Lin ,&nbsp;Pauline Hulo ,&nbsp;Christophe Dooms ,&nbsp;Jian Fang ,&nbsp;Ana Blasco ,&nbsp;Dariusz Kowalski ,&nbsp;Jorge Salinas ,&nbsp;Govind Babu ,&nbsp;Tho Lye Mun ,&nbsp;Alessandra Bearz ,&nbsp;Veerle Surmont ,&nbsp;Clarissa Baldotto ,&nbsp;Richu Sharma ,&nbsp;Oscar Arrieta ,&nbsp;Katarzyna Stencel ,&nbsp;Cynthia Card ,&nbsp;Alona Zer ,&nbsp;Enriqueta Felip","doi":"10.1016/j.cllc.2025.12.005","DOIUrl":"10.1016/j.cllc.2025.12.005","url":null,"abstract":"<div><h3>Objective</h3><div>The MARIPOSA-2 study demonstrated improved progression-free survival with amivantamab and chemotherapy compared with chemotherapy alone in patients with EGFR-mutated locally advanced or metastatic non-small-cell lung cancer (NSCLC) with disease progression on or after treatment with osimertinib. This publication describes the results of patient-reported outcomes (PROs) measures and time to symptomatic progression (TTSP) for 2 treatment arms.</div></div><div><h3>Methods</h3><div>PRO instruments included the European Organization for Research and Treatment of Cancer Quality of Life (QoL) Questionnaire Core 30 (EORTC QLQ-C30), Patient-Reported Outcomes Measurement Information System Physical Function Short Form 8c, and the NSCLC Symptom Assessment Questionnaire. Changes from baseline were analyzed using mixed-effects models for repeated measures. Treatment comparisons were based on least-squares means. The hazard ratio for TTSP was estimated using a stratified Cox regression model with <em>P</em> value derived from a stratified log-rank test.</div></div><div><h3>Results</h3><div>Patients received amivantamab-chemotherapy (n = 131) or chemotherapy alone (n = 263). PRO scores were stable over time with little or no group differences in least-squares mean change from baseline. At 6 months postbaseline, 55.1% of patients in the amivantamab-chemotherapy arm reported improved or stable EORTC QLQ-C30 global health status/QoL scores compared with 29.1% in the chemotherapy arm. TTSP was prolonged for the amivantamab-chemotherapy treatment group versus chemotherapy alone (hazard ratio [HR] [95% CI], 0.73 [0.55-0.96]; nominal <em>P</em>  = .0259).</div></div><div><h3>Conclusion</h3><div>PRO results indicate that the clinical benefits of adding amivantamab to chemotherapy were achieved without compromising health-related QoL. Amivantamab-chemotherapy prolonged TTSP versus chemotherapy alone.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"27 2","pages":"Pages 38-47"},"PeriodicalIF":3.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145975193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Limited-Stage Small-Cell Lung Cancer With Severe Paraneoplastic Limbic Encephalitis Successfully Treated With Chemoradiotherapy Followed by Immune Checkpoint Inhibitor Maintenance Therapy: A Case Report","authors":"Daisuke Morinaga ,&nbsp;Hidenori Kitai ,&nbsp;Hanko Sato ,&nbsp;Doppo Fukui ,&nbsp;Wataru Harabayashi ,&nbsp;Yukiko Yoshida ,&nbsp;Shotaro Ito ,&nbsp;Yuta Takashima ,&nbsp;Megumi Furuta ,&nbsp;Akihiko Kudo ,&nbsp;Shintaro Fujii ,&nbsp;Hisashi Uwatoko ,&nbsp;Hiroaki Yaguchi ,&nbsp;Keiko Tanaka ,&nbsp;Ichiro Yabe ,&nbsp;Jun Sakakibara-Konishi ,&nbsp;Satoshi Konno","doi":"10.1016/j.cllc.2026.01.011","DOIUrl":"10.1016/j.cllc.2026.01.011","url":null,"abstract":"<div><div><ul><li><span>•</span><span><div>Tissue-based assays can reveal neuronal antibody reactivity and support the diagnosis of autoimmune or paraneoplastic encephalitis, especially when standard serum and cerebrospinal fluid antibody panels are negative.</div></span></li><li><span>•</span><span><div>In limited-stage small-cell lung cancer with paraneoplastic limbic encephalitis, immune checkpoint inhibitors can be a feasible option when both tumor regression and neurological stabilization are achieved following concurrent chemoradiotherapy.</div></span></li></ul></div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"27 2","pages":"Pages 121-125"},"PeriodicalIF":3.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147269976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Institution-Specific Hypofractionated Radiation Therapy Regimen in the Treatment of Central and Ultracentral Non-small Cell Lung Cancer","authors":"M. Judy Lubas ,&nbsp;Albi Vata ,&nbsp;Jordan Fredette ,&nbsp;Martin J. Edelman ,&nbsp;Sameera Kumar","doi":"10.1016/j.cllc.2025.08.018","DOIUrl":"10.1016/j.cllc.2025.08.018","url":null,"abstract":"<div><h3>Purpose/Objectives</h3><div>While stereotactic body radiation therapy (SBRT) or hypofractionated radiation therapy (HFRT) is routinely used to treat inoperable early-stage non-small lung cancer (esNSCLC) patients with peripheral tumors, SBRT or HFRT for central (cenT) and ultracentral tumors (UCT) remains controversial. To treat patients with tumors located within 0-2 cm of critical mediastinal structures (CMSTs), we employ an institution specific hypofractionated radiation regimen (isHFRT) with a biologically effective dose (BED) of 98.59 using 17 fractions to a dose of 6987 cGy.</div></div><div><h3>Methods</h3><div>We conducted a single-institution retrospective review of patients with esNSCLC treated with this isHFRT between 2011 and 2020, evaluating both tumor control rates and rates of treatment related toxicity.</div></div><div><h3>Results</h3><div>Of the 31 patients evaluated, 61.3% of patients had UCTs while 38.7% had cenTs. At 1- and 3 years, local control (LC) was noted to be 93.5% and 86.8% respectively. 1-year overall survival (OS) was 74.2% for all comers, 75.0% for patients with cenTs and 73.7% for patients with UCTs (<em>p</em> = 0.70). 3-year OS was 20.8%. Only 22.6% of patients who expired at 1-year experienced disease progression. At 12 months, adverse event free survival (AEFS) was 67.7%. While 25.8% (<em>n</em> = 8) of patients experienced a Grade 2 (G2) or greater toxicity, no patient experienced a G2 or greater cardiotoxicity. Only 1 patient (3.3%) experienced a Grade 5 toxicity (fatal hemoptysis 12-months following treatment). Review of the case demonstrated that the maximum tracheobronchial tree dose had been exceeded.</div></div><div><h3>Conclusions</h3><div>Our isHFRT for patients with esNSCLC proves a safe and effective treatment for medically inoperable esNSCLC patients with cenTs and UCTs with comparable rates of toxicity when compared to prior studies.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"27 2","pages":"Pages 169-176.e2"},"PeriodicalIF":3.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145181852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Refining High-Risk EGFR-Mutant Lung Cancer Patients: The Role of Adjusted Variant Allele Frequency in First-Line Osimertinib Therapy","authors":"Marta Brambilla ,&nbsp;Francesca Barbetta ,&nbsp;Giuseppe Nardo ,&nbsp;Luca Agnelli ,&nbsp;Giorgia Di Liberti ,&nbsp;Paolo Ambrosini ,&nbsp;Chiara Cavalli ,&nbsp;Adele Busico ,&nbsp;Iolanda Capone ,&nbsp;Daniele Lorenzini ,&nbsp;Filippo de Braud ,&nbsp;Giancarlo Pruneri","doi":"10.1016/j.cllc.2025.08.014","DOIUrl":"10.1016/j.cllc.2025.08.014","url":null,"abstract":"<div><div>Next-Generation Sequencing (NGS) has an increasing role in patients with advanced non–small-cell lung cancer (aNSCLC) and, in parallel, the use of targeted therapy dramatically improves the outcome of those with actionable alterations. In this scenario, the possible prognostic significance of some features provided by NGS testing and, among these, of Variant Allele Frequency (VAF), is still unclear. Herein, we report a real-world single-center prospective cohort of 88 consecutive patients with aNSCLC profiled by NGS and harboring a classic EGFR mutation, who were treated with the standard first-line tyrosine kinase inhibitor osimertinib. A subset of patients with shorter progression-free survival (PFS) was characterized by extremely high VAF/tumor cellularity, &gt;1.7 adjusted VAF (aVAF). Median PFS was 5.3 months shorter in the high aVAF cohort; a similar trend was observed in overall survival too. No significant association between aVAF and <em>TP53</em> mutations, Tumor Mutational Burden or other clinical, pathological or molecular features was found. Our findings suggest that NGS could improve the traditional binary classification of <em>EGFR</em> mutations in aNSCLC, highlighting a correlation between high EGFR mutations aVAF and worse outcome.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"27 2","pages":"Pages 146-150.e2"},"PeriodicalIF":3.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145112139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}