Translational lung cancer research最新文献

{"title":"Bioelectrical impedance-derived body composition and systemic therapy outcomes in non-small cell lung cancer.","authors":"Xin Zheng, Rui Gao, Boao Jiang, Yihai Wei, Jingwen Diao, Bo Cheng, Jianfu Li, Jingting Su, Yuejiao Su, Wenhai Fu, Peiling Chen, Xianzhe Fan, Wenhua Liang, Ying Deng","doi":"10.21037/tlcr-2026-0718","DOIUrl":"https://doi.org/10.21037/tlcr-2026-0718","url":null,"abstract":"<p><strong>Background: </strong>Body mass index (BMI) cannot distinguish skeletal muscle from adipose tissue or capture fat distribution in non-small cell lung cancer (NSCLC). We explored whether bioelectrical impedance analysis (BIA)-assessed body composition was associated with systemic therapy outcomes.</p><p><strong>Methods: </strong>Consecutive adults with confirmed NSCLC who underwent pretreatment multifrequency BIA between March 2023 and March 2025 were retrospectively included. Analyses were performed by treatment context, including stage I surgical patients and stage II-IV patients receiving immune checkpoint inhibitor (ICI)- or epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI)-based systemic therapy. Body-composition parameters were compared by clinical stage and <i>EGFR</i> mutation status using analysis of covariance (ANCOVA). Progression-free survival (PFS) was analyzed using Kaplan-Meier methods and Cox proportional hazards models. Objective response rate (ORR) was evaluated using logistic regression. Joint analyses were performed according to skeletal muscle index (SMI) and visceral fat index (VFI), and longitudinal body-composition changes during immunotherapy were also assessed.</p><p><strong>Results: </strong>Among 473 screened patients, 369 were included, comprising 126 with stage I disease and 243 with stage II-IV disease. After predefined exclusions, outcome cohorts included 125 ICI-treated and 43 EGFR-TKI-treated patients. In cross-sectional analyses, adiposity-related parameters were nominally lower in stage II-IV disease than in stage I disease, but these differences did not remain significant after false discovery rate (FDR) correction; no body-composition parameter differed significantly by <i>EGFR</i> mutation status. Among 94 men included in the primary ICI PFS analysis, high SMI was associated with longer PFS [adjusted hazard ratio (HR), 0.49; 95% confidence interval (CI): 0.25-0.97], whereas high VFI was associated with shorter PFS (adjusted HR, 2.11; 95% CI: 1.09-4.07). High SMI was also associated with higher ORR among these men [adjusted odds ratio (OR), 3.04; 95% CI: 1.20-7.72]. The combined SMI/VFI phenotype further stratified PFS, with low SMI/high VFI identifying the least favorable subgroup. In an exploratory longitudinal analysis, a >10% decrease in trunk fat mass was associated with shorter PFS. No clear associations between body-composition parameters and PFS were observed in the small EGFR-TKI cohort.</p><p><strong>Conclusions: </strong>BIA-assessed skeletal muscle reserve and visceral adiposity were associated with outcomes during ICI-based therapy in men with NSCLC. Higher SMI and lower VFI identified a more favorable clinical profile. Prospective validation is warranted to define the role of BIA-based body-composition assessment in host-related risk stratification during systemic therapy.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"15 9","pages":"282"},"PeriodicalIF":3.4,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657894/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149184436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interpretable deep learning and radiomics for predicting the occurrence of brain metastases following prophylactic brain irradiation in small cell lung cancer.","authors":"Xingtong Zhang, Lei Zhao, Jie Wang, Xuerou Zhang, Xilong Liang, Wenwei Cao, Ying Huang, Yunhua Xu","doi":"10.21037/tlcr-2026-0708","DOIUrl":"https://doi.org/10.21037/tlcr-2026-0708","url":null,"abstract":"<p><strong>Background: </strong>Brain metastasis remains an important clinical concern in patients with small cell lung cancer (SCLC), even after prophylactic cranial irradiation (PCI). Accurate identification of patients at high risk of brain metastasis after PCI may facilitate individualized surveillance and management. This study developed a fusion model based on two-and-a-half-dimensional (2.5D) multi-channel deep learning features, clinical features, and radiomics features to predict whether patients with SCLC will develop brain metastases following PCI.</p><p><strong>Methods: </strong>This retrospective study included 185 patients with SCLC who underwent PCI and randomly divided them into a training set (N=148) and a testing set (N=37). A 2.5D multi-channel convolutional neural network (CNN) model was constructed based on multi-planar regions of interest (ROI) derived from CT images to extract 2.5D deep learning features. Based on the largest cross-section and three-dimensional (3D) volume of the tumor ROI, two-dimensional (2D) and 3D deep learning features were extracted, respectively. Subsequently, features from different dimensions were fused with clinical features and traditional omics features to construct the 2D_clinic_Rad, 2.5D_clinic_Rad, and 3D_clinic_Rad models, respectively. The performance differences between the 3D models and the clinical and traditional radiomics models were then compared.</p><p><strong>Results: </strong>The 2.5D_clinic_Rad fusion model demonstrated the best performance in predicting brain metastases, achieving an area under the curve (AUC) of 0.841 on the test set, outperforming clinical models, traditional radiomics models, and 2D and 3D deep learning fusion models. Analysis of decision curves and calibration curves indicated that the 2.5D_clinic_Rad model demonstrated the highest clinical net benefit and the best calibration consistency compared to other models.</p><p><strong>Conclusions: </strong>The fusion model based on 2.5D_clinic_Rad can effectively predict the risk of brain metastasis in patients with SCLC following whole-brain prophylactic irradiation.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"15 9","pages":"281"},"PeriodicalIF":3.4,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657897/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149184613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unlocking the central nervous system sanctuary in <i>EGFR</i>-mutant non-small cell lung cancer: molecular insights and therapeutic signals from amivantamab-lazertinib in leptomeningeal disease.","authors":"Elvire Pons-Tostivint, Manon Robert, Chloé Sauzay","doi":"10.21037/tlcr-2026-0920","DOIUrl":"https://doi.org/10.21037/tlcr-2026-0920","url":null,"abstract":"","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"15 9","pages":"294"},"PeriodicalIF":3.4,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657878/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149183989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of osimertinib combined with anlotinib in EGFR-mutant non-squamous non-small cell lung cancer with gradual progression after first-line osimertinib therapy: a single-center retrospective cohort study.","authors":"Li Hao, Haiyang Yu, Yong Wang, Yueyin Pan, Xinghua Han","doi":"10.21037/tlcr-2026-0785","DOIUrl":"https://doi.org/10.21037/tlcr-2026-0785","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), has substantially improved clinical outcomes in patients with &lt;i&gt;EGFR&lt;/i&gt;-mutant non-squamous non-small cell lung cancer (NSCLC). Nevertheless, acquired resistance inevitably develops, leading to disease progression in the majority of patients. Preclinical and clinical evidence suggests that anlotinib, a multi-targeted anti-angiogenic TKI, may overcome osimertinib resistance. This study aimed to evaluate the efficacy and safety of continued osimertinib in combination with anlotinib in patients with &lt;i&gt;EGFR&lt;/i&gt;-mutant non-squamous NSCLC who developed gradual progression following first-line osimertinib therapy.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This retrospective study enrolled patients with unresectable stage III or IV &lt;i&gt;EGFR&lt;/i&gt;-mutant non-squamous NSCLC who received first-line osimertinib therapy at The First Affiliated Hospital of University of Science and Technology of China between January 2021 and December 2024. Eligible patients developed gradual progression after first-line osimertinib therapy. Subsequently, patients received combination therapy with osimertinib (80 mg orally once daily) plus anlotinib (10 mg orally on days 1-14 of every 3-week cycle). The primary endpoint was progression-free survival (PFS). Secondary endpoints included PFS rates at 6 and 12 months, objective response rate (ORR), disease control rate (DCR), overall survival (OS), OS rates at 12 and 24 months, and safety profile.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;A total of 52 patients were enrolled. The median age was 66 years. 40(76.9%) had an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-1, 16 (30.8%) presented with brain metastases, 23 (44.2%) harbored exon 19 deletions, and 29 (55.8%) had L858R mutations. Molecular testing was performed in 12 patients after gradual progression. As of September 6, 2025, the median follow-up was 34.8 months, 48 PFS events were recorded and 22 patients died. The ORR was 7.7% (4/52), and the DCR was 86.5% (45/52). The median PFS (mPFS) was 9.9 months [95% confidence interval (CI): 4.2-12.1], with PFS rates of 61.5% at 6 months and 40.4% at 12 months. The median OS was not reached. OS rates were 86.3% at 12 months and 62.4% at 24 months. The exploratory multivariate COX analysis revealed that ECOG PS [hazard ratio (HR): 3.115, 95% CI: 1.111-7.706, P&lt;0.001] and brain metastasis (HR: 2.242, 95% CI: 1.341-7.842, P=0.009) were associated with mPFS. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 9.6% (5/52) of patients. The most frequently observed AEs were diarrhea (42.3%, 22/52), hypertension (34.6%, 18/52), proteinuria (30.8%, 16/52), decreased appetite (28.8%, 15/52), and weight loss (28.8%, 15/52).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;In this retrospective cohort focusing on the specific pattern of gradual progression following first-line osimertinib therapy, continued o","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"15 9","pages":"285"},"PeriodicalIF":3.4,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657886/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149184439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma proteomic profiles associated with low-dose computed tomography findings and incident lung cancer: a prospective pilot study.","authors":"Antti Tikkanen, Sanna Iivanainen, Milla E K Luukkainen, Jussi P Koivunen","doi":"10.21037/tlcr-2026-0646","DOIUrl":"https://doi.org/10.21037/tlcr-2026-0646","url":null,"abstract":"<p><strong>Background: </strong>Plasma proteins may reflect tumor-host biology, but their relationships with low-dose computed tomography (LDCT) findings and incident lung cancer remain uncertain. Although LDCT screening has improved survival, challenges remain in risk stratification and interpretation of screening findings. The aim of the present study was to investigate associations between plasma proteomic profiles, LDCT findings and incident lung cancer, and to explore their potential for lung cancer risk stratification.</p><p><strong>Methods: </strong>In this prospective study, baseline plasma proteomic profiles and LDCT radiographic findings (baseline and follow-up) were analyzed in 193 participants with significant smoking history. A targeted panel of 92 proteins was used to evaluate associations with LDCT classifications and incident lung cancer. Five participants with non-lung malignancies were excluded, leaving 188 participants, including six incident lung cancer cases. Exploratory prediction models for lung cancer were developed using machine learning approaches.</p><p><strong>Results: </strong>Individuals with positive LDCT findings showed overexpression of multiple plasma proteins compared with those with indeterminate or negative findings; participants who developed lung cancer also showed differential protein expression compared with participants without cancer. While individual protein odds ratio (OR) estimates were imprecise, a seven-protein machine learning model, consisting of TNFRSF9, FGF2, CCL20, CD4, MMP12, CXCL11, and CD40 demonstrated an area under the curve (AUC) of 0.915 [95% confidence interval (CI): 0.829-1.000] in predicting lung cancer. Proteomic profiling revealed associations of lung cancer with pathways, such as TNFα and IL6-JAK-STAT3 signaling, commonly linked to early carcinogenic processes.</p><p><strong>Conclusions: </strong>Plasma proteomic profiling may provide complementary, biologically informative signals alongside LDCT in lung cancer screening. By integrating circulating biomarkers with imaging, this approach enables investigation of early disease biology in a pre-diagnostic setting, providing insights into systemic alterations that may precede clinically apparent cancer. While these findings are hypothesis-generating and do not establish the clinical utility of plasma proteomics in LDCT screening, these findings justify the need to evaluate this approach for additional risk stratification in LDCT lung cancer screening. Larger independent studies are required to determine whether plasma proteomics can improve risk stratification beyond LDCT and thereby reduce unnecessary follow-up examinations.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"15 9","pages":"273"},"PeriodicalIF":3.4,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657898/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149184526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retrospective real-world associations between <i>EGFR</i> alterations and furmonertinib outcomes in advanced non-small cell lung cancer.","authors":"Yameng Cui, Shaozhang Zhou, Zheng Liu, Qichuan Wang, Liuchun Wang, Yanhong Shang, Jinghao Jia, Hongjiang Yu, Jiangyan Zhang, Zihui An, Zhansheng Jiang, Junli Cao","doi":"10.21037/tlcr-2026-1103","DOIUrl":"https://doi.org/10.21037/tlcr-2026-1103","url":null,"abstract":"<p><strong>Background: </strong>Furmonertinib, a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), has shown promising efficacy in <i>EGFR</i>-mutant non-small cell lung cancer (NSCLC). This real-world study aimed to explore efficacy differences among <i>EGFR</i> mutation subtypes and the influence of concomitant genetic alterations on furmonertinib.</p><p><strong>Methods: </strong>This retrospective multicenter real-world study enrolled patients with unresectable stage IIIB/C-IV <i>EGFR</i>-mutant NSCLC who received furmonertinib (80 milligrams per day). Main eligibility criteria included advanced <i>EGFR</i>-mutant NSCLC, measurable lesions, and available next-generation sequencing (NGS) molecular data. Patients were recruited from five Chinese medical centers. Progression-free survival (PFS) was defined as time from furmonertinib initiation to disease progression or any-cause death; overall survival (OS) was defined as time from furmonertinib initiation to any-cause death or last follow-up. Baseline clinical and NGS-detected molecular data were collected. Survival endpoints included objective response rate (ORR), disease control rates (DCRs), PFS and OS. Kaplan-Meier and Cox proportional-hazards models were applied to evaluate prognostic associations, reporting hazard ratios (HR) with 95% confidence intervals (CIs) alongside exact P values.</p><p><strong>Results: </strong>A total of 139 patients were included, among whom 64 harbored <i>EGFR</i> exon 19 deletion and 74 harbored L858R mutation. <i>TP53</i> mutations were detected in 64.4% (58/90) of the tested patients. There were 136 patients profiled for additional concurrent driver alterations. Among 131 evaluable patients, ORR was 69.5% and the DCR was 97.7%. Median PFS of the entire cohort was 623 days (approximately 20.8 months); median OS was not reached. Compared with L858R, <i>EGFR</i> exon19 deletion was associated with longer PFS (adjusted HR =1.77, 95% CI: 1.09-2.87, P=0.02). After adjusting for age, disease stage, and <i>EGFR</i> mutation subtype, multiple gene mutations were associated with poorer PFS (HR =4.03, 95% CI: 1.98-8.19, P<0.001) and OS (HR =3.25, 95% CI: 1.07-9.86, P=0.04). No significant prognostic association was observed for <i>TP53</i> co-mutation.</p><p><strong>Conclusions: </strong>This retrospective real-world cohort suggests that <i>EGFR</i> subtypes and multiple concurrent genomic alterations are associated with survival outcomes under furmonertinib treatment.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"15 9","pages":"287"},"PeriodicalIF":3.4,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657901/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149184547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multimodal digital assessment of early recovery after chest tube omission in early-stage lung cancer patients undergoing wedge resection: a post hoc analysis of a prospective cohort.","authors":"Yang Chen, Runchen Wang, Youfang Li, Menghan He, Kaishen Chen, Xiaoqing Lan, Taimin Zhu, Hengrui Liang, Wei Wang, Jianxing He, Wenwei Guo, Zhexue Hao","doi":"10.21037/tlcr-2026-0758","DOIUrl":"https://doi.org/10.21037/tlcr-2026-0758","url":null,"abstract":"<p><strong>Background: </strong>Given the limited surgical trauma associated with wedge resection, the clinical impact of routine chest tube drainage may be more apparent in early postoperative recovery than in safety outcomes alone. We used a multimodal digital platform integrating wearable monitoring and electronic patient-reported outcomes (ePROs) to compare recovery after wedge resection with and without chest tube placement.</p><p><strong>Methods: </strong>This study was a post hoc secondary analysis of prospectively collected data from a registered single-center observational cohort (NCT06118229). We included 98 patients from the parent cohort who had M0 primary lung cancer, underwent wedge resection, and had evaluable perioperative clinical and digital data; 54 were managed without chest tube placement and 44 with routine drainage. Propensity score matching yielded 34 matched pairs.</p><p><strong>Results: </strong>Compared with the chest tube group, the no chest tube group had a shorter postoperative hospital stay (2.51±1.11 <i>vs.</i> 3.14±1.03 days; P=0.02). Differences were most apparent in patient-reported recovery on postoperative day 2, with lower pain scores (2.79±2.11 <i>vs.</i> 4.08±2.07; P=0.03), less restless sleep (1.98±1.86 <i>vs.</i> 3.49±2.32; P=0.01), and less drowsiness (2.07±1.35 <i>vs.</i> 3.08±1.70; P=0.02). Wearable-derived physiologic trajectories were largely similar, although oxygen saturation on postoperative day 1 was higher in the no chest tube group (97.22%±1.64% <i>vs.</i> 96.05%±1.56%; P=0.003).</p><p><strong>Conclusions: </strong>After wedge resection, omission of routine chest tube drainage was associated with a more favorable early patient-reported recovery, whereas physiologic differences were modest. Multimodal digital assessment may offer a practical and patient-centered approach to postoperative monitoring after minimally invasive thoracic surgery.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"15 9","pages":"279"},"PeriodicalIF":3.4,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657899/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149184587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A modified cryobiopsy specimen retrieval method using a thin bronchoscope and small guide sheath for the diagnosis of peripheral pulmonary lesions.","authors":"Yuki Takigawa, Kenichiro Kudo, Ken Sato, Mayu Goda, Keisuke Shiraha, Takeru Ichikawa, Shoichiro Matsumoto, Suzuka Matsuoka, Sho Mitsumune, Jun Nishimura, Hiromi Watanabe, Keiichi Fujiwara","doi":"10.21037/tlcr-2026-0855","DOIUrl":"https://doi.org/10.21037/tlcr-2026-0855","url":null,"abstract":"<p><strong>Background: </strong>Retrieval of 1.1-mm ultrathin cryobiopsy specimens through a large guide sheath (GS) enables specimen collection without removal of the therapeutic bronchoscope and GS; however, this approach remains limited to selected patients because therapeutic bronchoscopes have restricted access to the peripheral bronchi. To expand the applicability of cryobiopsy to more peripheral pulmonary lesions (PPLs), we applied a modified cryobiopsy specimen retrieval approach, termed the ultrathin CRYObiopsy specimen with Guide sheath en bloc RetrievAl THrough a bronchoscoPe channel (CRYO-GRATHP) method using a thin bronchoscope. This study evaluated the efficacy and safety of this procedure.</p><p><strong>Methods: </strong>We retrospectively analyzed patients with PPLs who underwent bronchoscopic cryobiopsy using the CRYO-GRATHP method at Okayama Medical Center between April 2023 and March 2026. Lesions were localized using an endobronchial ultrasound with a small GS and a thin bronchoscope, followed by small forceps biopsy and ultrathin cryobiopsy using a 1.1-mm cryoprobe. The primary endpoint was diagnostic yield, and the secondary endpoints included safety, procedure duration, specimen size, sampling success by freezing time, and biomarker testing success.</p><p><strong>Results: </strong>A total of 28 patients were included. All patients underwent additional cryobiopsy because rapid on-site cytological evaluation of small forceps biopsy specimens was negative. The median target lesion size was 17 mm, and most lesions were in the upper lobes (79%). The overall diagnostic yield was 75.0%, and a specific diagnosis was achieved in 77.3% of upper-lobe lesions. The median specimen size was 3.73 mm² for cryobiopsy and 1.00 mm² for forceps biopsy (P<0.001). Regarding safety, bleeding was limited to grade 0-2 in all cases, with no grade ≥3 bleeding, and no pneumothorax was observed. Nineteen (68%) procedures were performed without endotracheal intubation.</p><p><strong>Conclusions: </strong>In this pilot study, the CRYO-GRATHP method appeared to be a feasible and safe cryobiopsy technique for small PPLs, particularly those located in the upper lobe.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"15 9","pages":"280"},"PeriodicalIF":3.4,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657866/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149184233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Amivantamab plus chemotherapy <i>vs.</i> chemotherapy in participants with <i>EGFR</i>-mutant advanced non-small cell lung cancer after progression on osimertinib: a MARIPOSA-2 analysis of the Asian subgroup.","authors":"Jin-Yuan Shih, Jie Wang, Yongsheng Wang, Jialei Wang, Se-Hoon Lee, Koichi Azuma, Toshiaki Takahashi, Jiunn-Liang Tan, Chien-Chung Lin, Sandip Ganguly, Victor Ho-Fun Lee, Zeynep Hande Turna, Richu Sharma, Yu Jung Kim, Pei-Ling Chu, Sujay Shah, Brooke Diorio, Byoung Chul Cho","doi":"10.21037/tlcr-2026-0202","DOIUrl":"https://doi.org/10.21037/tlcr-2026-0202","url":null,"abstract":"<p><strong>Background: </strong>The Phase 3 MARIPOSA-2 study showed that amivantamab, a bispecific antibody with immune cell-directing activity, plus chemotherapy significantly improved progression-free survival (PFS) compared with chemotherapy alone in participants with common epidermal growth factor receptor <i>(EGFR)</i>-mutated non-small cell lung cancer (NSCLC), whose disease had progressed on osimertinib monotherapy. We conducted a post hoc analysis to assess clinical outcomes in the Asian subgroup of participants from MARIPOSA-2 (NCT04988295).</p><p><strong>Methods: </strong>Participants were randomised 2:2:1 to amivantamab-lazertinib-chemotherapy, chemotherapy alone, or amivantamab-chemotherapy. The primary endpoint was PFS by blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumors v1.1 (RECIST 1.1). Secondary endpoints included objective response rate (ORR), intracranial PFS, and safety. Due to mid-study modifications to the amivantamab-lazertinib-chemotherapy dosing schedule, follow-up of this group is ongoing. We present results for the amivantamab-chemotherapy <i>vs.</i> chemotherapy arms in the Asian subgroup.</p><p><strong>Results: </strong>There were 190 participants in the Asian subgroup, 63 in the amivantamab-chemotherapy group and 127 in the chemotherapy group. At a median follow-up of 9.5 months, median PFS in the amivantamab-chemotherapy arm was 6.8 <i>vs.</i> 4.2 months in the chemotherapy arm [hazard ratio (HR) 0.54, 95% confidence interval (CI): 0.37-0.81; nominal P=0.002]. The ORR was 66% and 32%, respectively (odds ratio 4.0, 95% CI: 2.1-7.7; nominal P<0.001) and median intracranial PFS was 12.5 and 8.5 months (HR 0.58, 95% CI: 0.34-1.00; nominal P=0.049). The safety profile in the Asian subgroup was in line with the overall MARIPOSA-2 population.</p><p><strong>Conclusions: </strong>Amivantamab-chemotherapy demonstrated superior PFS <i>vs.</i> chemotherapy in Asian patients. Amivantamab-chemotherapy provides an effective option for patients whose disease had progressed on third-generation EGFR tyrosine kinase inhibitors.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"15 9","pages":"284"},"PeriodicalIF":3.4,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657905/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149184327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synergistic effects and molecular mechanisms of pirfenidone combined with EGFR-TKIs in non-small cell lung cancer.","authors":"Pan Tang, Chen Huang, Fengmei Zhang, Jiayi Li, Weimin Li, Chenliang Zhang, Zhoufeng Wang","doi":"10.21037/tlcr-2026-0900","DOIUrl":"https://doi.org/10.21037/tlcr-2026-0900","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related mortality globally. While epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), such as osimertinib (OS) and afatinib (AF), have markedly improved clinical outcomes, their efficacy is significantly hindered by the development of acquired resistance. Emerging evidence suggests that p38γ is involved in the progression of NSCLC and the emergence of resistance to EGFR-TKIs. However, whether the p38γ inhibitor pirfenidone (PFD) can enhance the sensitivity of NSCLC to EGFR-TKIs remains unclear. This study aims to evaluate the synergistic antitumor effects of PFD in combination with OS or AF and to elucidate the underlying molecular mechanisms.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;EGFR-mutant NSCLC cell lines (PC9 and HCC827) and their OS-resistant derivatives (HCC827 OR) were utilized to evaluate cell proliferation by Cell Counting Kit-8 (CCK-8) assays and colony formation experiments. Western blotting was performed to analyze the expression of p38γ, proteins within the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling pathway, and autophagy-related markers. Drug interactions were assessed using the SynergyFinder platform. Autophagic flux was investigated via a dual-fluorescent adenovirus (mRFP-GFP-LC3) and further validated using the autophagy inhibitor bafilomycin A1. Additionally, an HCC827 nude mouse xenograft model was employed for &lt;i&gt;in vivo&lt;/i&gt; validation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The combination of PFD with either OS or AF exhibited significant synergistic antitumor effects in both &lt;i&gt;in vitro&lt;/i&gt; and &lt;i&gt;in vivo&lt;/i&gt; NSCLC models, consistently achieving Bliss synergy scores exceeding 14. Notably, this combination successfully restored drug sensitivity in OS-resistant cells and reversed acquired resistance to EGFR-TKIs. Mechanistic investigations revealed that PFD enhanced EGFR-TKI sensitivity via two distinct pathways: firstly, by specifically inhibiting p38γ, a critical mediator of resistance, which leads to the downregulation of the PI3K/AKT/mTOR signaling pathway; and secondly, by promoting the autophagy cascade in a p38γ-independent manner. These synergistic effects were not reversed by ferroptosis or pyroptosis inhibitors and were only partially attributed to apoptosis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;PFD enhances the efficacy of EGFR-TKIs through a dual mechanism: first, by specifically inhibiting the p38γ-mediated PI3K/AKT/mTOR signaling pathway, and second, by activating a p38γ-independent autophagy pathway. The activation of the p38γ-mediated PI3K/AKT/mTOR pathway may represent a key mechanism underlying OS resistance. This study provides the first evidence that PFD can restore drug sensitivity in OS-resistant cells, offering valuable experimental support for its potential clinical application as an EGFR-TKI sensitizer and a therapeutic strategy to overcom","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"15 9","pages":"272"},"PeriodicalIF":3.4,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657879/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149184014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}