Translational lung cancer research最新文献

{"title":"Association between fruit intake and non-small cell lung cancer: a Mendelian randomization study.","authors":"Chongde Pan, Ying Du, Yu Jiang, Yuechun Lin, Yulin Zhao, Huiwen Yu, Hengrui Liang, Wanzhe Liao, Xin Xu, Ying Huang","doi":"10.21037/tlcr-24-276","DOIUrl":"10.21037/tlcr-24-276","url":null,"abstract":"<p><strong>Background: </strong>Several studies have explored the potential relationship between fruit consumption and non-small cell lung cancer (NSCLC). However, the impact of dried fruit on NSCLC risk remains unclear. Additionally, the presence of confounding variables in these observational investigations could not be avoided. Therefore, the aim of this article was to explore the potential relationship between fruits intake and NSCLC.</p><p><strong>Methods: </strong>We extracted fruit intake data from the UK Biobank and utilized a genome-wide association study (GWAS) encompassing 218,792 individuals for NSCLC data. We employed a two-sample Mendelian randomization (MR) analysis to investigate the potential causal associations between fruit intake and the risk of NSCLC. The major method of analysis was the inverse variance weighted (IVW). Furthermore, we conducted sensitivity analyses to corroborate the robustness of our findings.</p><p><strong>Results: </strong>The result of our study showed convincing evidence suggesting that dried fruit intake is effective in reducing the risk of NSCLC. Specifically, the odds ratios (ORs) for NSCLC exhibited a noteworthy reduction at 0.32 [95% confidence interval (CI): 0.15, 0.67; P=0.003] with respect to dried fruit intake.</p><p><strong>Conclusions: </strong>Our study underscores a significant correlation between dried fruit consumption and reduced NSCLC risk. In contrast, the association with fresh fruit intake did not reach statistical significance. To substantiate and validate these findings, further prospective randomized controlled trials (RCTs) are warranted in the future.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11484710/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475663","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 of first-line immune checkpoint inhibitors in pulmonary sarcomatoid carcinoma.","authors":"Gary Birsen, Valérie Gounant, Nicolas Girard, Jacques Cadranel, Isabelle Monnet, Christine Raynaud-Donzel, Elizabeth Fabre, Etienne Giroux Leprieur, Karen Leroy, Diane Damotte, Marco Alifano, Jennifer Arrondeau, Isabelle Cremer, Jeanne Chapron, Marie Wislez","doi":"10.21037/tlcr-24-263","DOIUrl":"10.21037/tlcr-24-263","url":null,"abstract":"<p><strong>Background: </strong>Pulmonary sarcomatoid carcinomas (PSC) are notorious for their poor prognosis and resistance to chemotherapy. The literature suggests that immunotherapy might be effective against this aggressive tumor. This study aims to evaluate the efficacy of immunotherapy, either alone or combined with chemotherapy, as first-line treatment for PSC patients.</p><p><strong>Methods: </strong>In a retrospective, multicentric, real-world study conducted between July 2017 and April 2021, patients with stage III (ineligible for surgery or radio-chemotherapy) or stage IV PSC were enrolled. These patients received their first-line treatment with immunotherapy and were categorized into two groups based on their treatment modality: the immuno-chemotherapy (IO CT) group or the immunotherapy-alone (IO) group.</p><p><strong>Results: </strong>This study analyzed a population of 34 patients from eight different hospital centers. In this cohort, the objective response rate (ORR) was 56%, median duration of response was 20.5 months, median progression-free survival (PFS) was 5.11 months, and median overall survival (OS) 13.9 months. Demographic characteristics remained consistent among the treatment groups except for the age (54.0- and 71.0-year-old in the IO CT and IO group, respectively, P=0.02). The IO CT group demonstrated an ORR of 64.0%, a median PFS at 8.72 months, and a median OS of 16.08 months, while the IO group displayed respective values of 52.0%, 3.45 months, and 13.11 months.</p><p><strong>Conclusions: </strong>This study showed the potential efficacy of immunotherapy as a first-line treatment for PSC. While acknowledging the retrospective nature of the study, our findings suggest a trend favoring the combination of IO CT over IO alone in these patients.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11484717/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475668","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":"Serum tumor markers and outcomes in lung cancer patients with brain metastases: a retrospective longitudinal cohort study.","authors":"Yingtong Liu, Shuang Dai, Zheran Liu, Ling He, Lili Zhu, Zijian Qin, Haohan Fan, Fang Fang, Yuping Xie, Xingchen Peng","doi":"10.21037/tlcr-24-404","DOIUrl":"10.21037/tlcr-24-404","url":null,"abstract":"<p><strong>Background: </strong>Serum tumor markers (STMs) are recommended for cancer diagnosis and surveillance. However, their role in lung cancer with brain metastases (BM) is not yet clear. We aim to analyze the roles of baseline levels of STMs or ongoing STM surveillance on survival.</p><p><strong>Methods: </strong>This retrospective longitudinal cohort study included 1,169 lung cancer patients with BM. The STM data during disease course were collected. Distinct trajectory groups were identified using the latent class growth mixed model (LCGMM). The roles of STMs on survival were further analyzed using Kaplan-Meier analysis and Cox proportional hazard models.</p><p><strong>Results: </strong>Serum levels of cytokeratin-19 fragment (CYFRA21-1) (P<0.001), carcinoembryonic antigen (CEA) (P=0.005) and neuron-specific enolase (NSE) (P<0.001) at baseline exhibited significant correlation with overall survival (OS) of patients with BM, serving as independent prognostic factors. Further analysis indicated that baseline CYFRA21-1, CEA, NSE as well as status of key driver genes were independent prognostic factors in non-small cell lung cancer (NSCLC) patients with BM, while for small cell lung cancer (SCLC) patients with BM, baseline NSE and receiving chemotherapy show independent correlations with survival. Furthermore, we delineated the dynamic trajectories of STMs based on changes in disease course. More specifically, compared to those showing a baseline-high trend in CEA levels, the survival of patients with either persistently-rising or consistently normal levels seemed to be more promising. For CYFRA21-1, both early-rising and later-rising trends were observed, indicating a prognosis inferior to that of individuals with normal-level trajectory. Likewise, for NSE, patients with persistently-rising or persistently-descending trends showed no significantly survival difference. However, in comparison with the status of driver genes, receiving radiotherapy and targeted therapy, the dynamic changes in STM levels lacked independent prognostic significance. Further analysis indicated that among BM patients lacking key driver genes, NSE trajectory (P<0.05), CYFRA21-1 trajectory (P<0.05) and receiving chemotherapy (P<0.001) were independent prognostic factors.</p><p><strong>Conclusions: </strong>Baseline levels of serum CYFRA21-1, CEA and NSE, as well as status of key driver genes are recommended for evaluating BM patients' outcome. Dynamic changes of STMs during disease course were not significantly associated with the final outcome of BM patients.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11484733/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475687","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":"Ten-year survival outcomes of video-assisted thoracic surgery <i>vs.</i> open major lung resection for stage I-III non-small cell lung cancer: a large cohort study in China.","authors":"Yiming Li, Jiandong Mei, Zhenyu Yang, Chenglin Guo, Chengwu Liu, Hu Liao, Lin Ma, Feng Lin, Yidan Lin, Yong Yuan, Yunke Zhu, Yuyang Xu, Zheng Liu, Kaidi Li, Yang Hu, Yun Wang, Nan Chen, Zhu Wu, Chuan Li, Liang Xia, Jian Zhou, Xiaolong Zhang, Cheng Shen, Qiang Pu, Lunxu Liu","doi":"10.21037/tlcr-24-150","DOIUrl":"10.21037/tlcr-24-150","url":null,"abstract":"<p><strong>Background: </strong>Despite the widespread adoption of video-assisted thoracoscopic surgery (VATS) for major lung resection, the 10-year long-term survival outcomes of non-small cell lung cancer (NSCLC) treated with VATS compared with open major lung resection is lacking. The purpose of this study was to analyze the short- and long-term outcomes of VATS <i>vs.</i> open major lung resection for NSCLC.</p><p><strong>Methods: </strong>The perioperative outcomes and long-term survival of p-stage I-III NSCLC patients who underwent major lung resection via VATS <i>vs.</i> open major lung resection in the Western China Lung Cancer Database (WCLCD) between May 2006 and June 2018 were studied using propensity score matching (PSM).</p><p><strong>Results: </strong>Of the 10,167 patients who underwent surgery for lung malignancies, 6,405 patients with stage I-III NSCLC were included in the study, including 4,224 in the VATS group and 2,181 in the open group. PSM resulted in 1,487 patients in both the VATS and open groups. The patients were matched by patient demographics, Charlson comorbidity index (CCI), tumor histology and TNM stage. Compared with open surgery, major lung resection via VATS resulted in less blood loss (median: 50 <i>vs.</i> 100 mL, P<0.001) and a shorter postoperative hospital stay (7.6±6.0 <i>vs.</i> 8.6±4.9 days, P<0.001) but higher total hospital costs (52.5±21.2 <i>vs.</i> 45.0±16.4 kRMB, P<0.001). The matched cohort showed that patients who underwent major lung resection via VATS had better overall survival (OS) and recurrence-free survival (RFS) than did patients who underwent major lung resection via open surgery (5-year survival: 64.9% <i>vs.</i> 57.7%, P<0.001; 5-year RFS: 50.3% <i>vs.</i> 45.3%, P=0.003). Patients who underwent VATS had a better 10-year OS rate (47.8% <i>vs.</i> 42.6%). According to the subgroup analysis, patients with stage II NSCLC who underwent major lung resection via VATS had better OS and RFS (OS: P<0.001; RFS: P=0.004), while there were no significant differences in OS or RFS between stage I and III NSCLC patients.</p><p><strong>Conclusions: </strong>Major lung resection via the VATS should be the preferred surgical option for stage I-III NSCLC patients due to its superior long-term survival outcome and advantages of less blood loss and shorter postoperative hospital stays.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11484723/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475699","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":"Tremelimumab and durvalumab with chemotherapy in first-line treatment for metastatic non-small cell lung cancer: a US-based cost-effectiveness analysis.","authors":"Ziying Zhao, Xiaohui Zeng, Zhen Zhou, Qiao Liu","doi":"10.21037/tlcr-24-244","DOIUrl":"10.21037/tlcr-24-244","url":null,"abstract":"<p><strong>Background: </strong>While the tremelimumab plus durvalumab combined with chemotherapy (T + D + CT) has shown promise in treating epidermal growth factor receptor/anaplastic lymphoma kinase (EGFR/ALK) wild-type metastatic non-small cell lung cancer (mNSCLC), particularly in patients with low or no programmed cell death ligand 1 (PD-L1) expression, the economic implications of its high cost remain poorly understood. This study fills a critical gap in knowledge by evaluating the cost-effectiveness of T + D + CT from a US health care perspective, offering valuable insights for clinical and policy decision-making.</p><p><strong>Methods: </strong>A 10-year Markov model was crafted to track the disease progression, survival, and treatment-related toxicities of a patient cohort with EGFR/ALK wild-type mNSCLC. Transition probabilities were derived from the POSEIDON trial, while health state utilities were obtained from the literature. Cost data, including drug acquisition and administration, subsequent anticancer therapies, and adverse event management were estimated using the Centers for Medicare and Medicaid Services and the Healthcare Cost and Utilization Project databases, with additional costs sourced from current literature. All cost and effectiveness measures were discounted at an annual rate of 3%. The model's robustness was assessed through deterministic sensitivity analysis (DSA), probabilistic sensitivity analysis (PSA), and scenario analysis.</p><p><strong>Results: </strong>T + D + CT compared to chemotherapy alone yielded incremental cost-effectiveness ratios (ICERs) of $370,208 to $691,960 per quality-adjusted life-year (QALY) gained, exceeding the standard willingness-to-pay (WTP) threshold of $100,000 to $150,000 per QALY. Against durvalumab plus chemotherapy, T + D + CT was only cost-effective in all subgroups. DSA results for patients with PD-L1 expression <1% showed that the ICER for first-line T + D + CT remained above the WTP threshold range, even with substantial changes to model inputs. PSA revealed a higher likelihood of T + D + CT being cost-effective as WTP thresholds increased. Scenario analysis confirmed the study's primary findings, with the exception of a scenario where durvalumab was offered at no cost.</p><p><strong>Conclusions: </strong>The findings suggests that T + D + CT may not be a cost-effectiveness first-line treatment for EGFR/ALK wild-type mNSCLC in the US, given its high ICERs and limited cost-effectiveness in the majority of PD-L1 expression subgroups.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11484735/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475700","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":"Diagnostic efficacy of cryobiopsy for peripheral pulmonary lesions with ground-glass opacity: a propensity score-matched analysis.","authors":"Hideaki Furuse, Yuji Matsumoto, Toshiyuki Nakai, Midori Tanaka, Kanako Nishimatsu, Keigo Uchimura, Tatsuya Imabayashi, Takaaki Tsuchida","doi":"10.21037/tlcr-24-304","DOIUrl":"10.21037/tlcr-24-304","url":null,"abstract":"<p><strong>Background: </strong>Peripheral pulmonary lesions (PPLs) with ground-glass opacity (GGO) are generally difficult to diagnose via bronchoscopy. Cryobiopsy, a recently introduced technique, provides quantitatively and qualitatively superior tissues compared with conventional biopsy methods and can improve diagnostic outcomes. However, its diagnostic accuracy has not been specifically investigated. Therefore, this study aimed to determine whether the combined use of cryobiopsy improves the diagnostic yield for PPLs with GGO.</p><p><strong>Methods: </strong>Consecutive patients who underwent bronchoscopy combined with radial endobronchial ultrasound and virtual bronchoscopic navigation for PPLs with GGO were retrospectively reviewed between June 2014 and May 2020. Cryobiopsy was introduced at our institution in June 2017. Patients who underwent only conventional biopsy (forceps and/or needle aspiration) between June 2014 and May 2017 were classified as the conventional group, whereas those who underwent cryobiopsy with or without conventional biopsy between June 2017 and May 2020 were categorized as the \"cryo\" group. The diagnostic performance of the two groups was compared using propensity score-matched analysis.</p><p><strong>Results: </strong>Overall, 553 cases were identified, including 250 and 303 in the cryo and conventional groups, respectively. Propensity scoring was implemented to match lesion characteristics and intraprocedural findings, leading to the selection of 232 pairs of cases for each matched (m) group. The diagnostic yield in the m-cryo group was significantly higher than that in the m-conventional group [88.8% <i>vs.</i> 63.8%, odds ratio: 4.50 (95% confidence interval: 2.76-7.33), P<0.001]. Although the incidence of grade 2 and 3 bleeding in the m-cryo group was higher than that in the m-conventional group (40.5% <i>vs.</i> 8.6% and 2.6% <i>vs.</i> 0.4%, respectively; P<0.001), grade 4 bleeding was not reported.</p><p><strong>Conclusions: </strong>The combined use of cryobiopsy provides improved diagnostic yield for PPLs with GGO compared with conventional biopsy methods.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11484722/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475665","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":"Establishing a predictive model for tumor mutation burden status based on ¹⁸F-FDG PET/CT and clinical features of non-small cell lung cancer patients.","authors":"Zheng Chen, Xueping Chen, Linjun Ju, Yue Li, Wenbo Li, Hua Pang","doi":"10.21037/tlcr-24-416","DOIUrl":"10.21037/tlcr-24-416","url":null,"abstract":"<p><strong>Background: </strong>Tumor mutation burden (TMB) has emerged as a promising biomarker for immune checkpoint inhibitors (ICI) response, but its detection through whole exome sequencing (WES) is costly and invasive. This study aims to establish a predictive model for TMB using baseline metabolic parameters (MPs) of ¹⁸F-fluorodeoxyglucose (FDG) uptake on positron emission tomography/computed tomography (PET/CT) and clinical features in non-small cell lung cancer (NSCLC) patients, potentially offering a non-invasive and cost-effective method to predict TMB status.</p><p><strong>Methods: </strong>A total of 223 NSCLC patients with baseline ¹⁸F-FDG PET/CT scans and TMB detection results were retrospectively enrolled from January 2019 to September 2023, and were divided into two groups: TMB-high (≥4 mutations/Mb, 96 patients) and TMB-low (<4 mutations/Mb, 127 patients). Twelve clinical features and five PET parameters were assessed. Univariate analysis was conducted in all patients to reveal the preliminary associations between variables and TMB status. All patients were randomly divided into a training set (n=135) and a validation set (n=88). Feature selection was performed using lasso regression and logistic regression analyses. A predictive model and nomogram were established with the features selected above. Decision curve analysis (DCA) was performed to assess the clinical utility of the developed model.</p><p><strong>Results: </strong>Two clinical features and two PET parameters were identified through lasso regression and logistic regression analysis including pathology type, cancer antigen 125 (CA125) level, maximum standardized uptake value (SUV_max), and metabolic tumor volume (MTV). The predictive model exhibited an area under the curve (AUC) of 0.822 [95% confidence interval (CI), 0.751-0.894], and internal validation yielded an AUC of 0.822 (95% CI, 0.731-0.912). The model was well-calibrated. The developed nomogram, incorporating the four selected variables, showed promising potential in evaluating TMB status in NSCLC patients.</p><p><strong>Conclusions: </strong>In this study, a predictive model combining ¹⁸F-FDG PET/CT and clinical features of NSCLC patients effectively distinguished between TMB-high and TMB-low status. The nomogram generated from this model holds significant promise for predicting TMB status, offering valuable insights for clinical decision-making.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11484715/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475669","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":"Tumor immune microenvironment analysis of non-small cell lung cancer development through multiplex immunofluorescence.","authors":"Jiaping Zhao, Yu Lu, Zhaofeng Wang, Haiying Wang, Ding Zhang, Jinping Cai, Bei Zhang, Junling Zhang, Mengli Huang, Andreas Pircher, Krishna H Patel, Honggang Ke, Yong Song","doi":"10.21037/tlcr-24-379","DOIUrl":"10.21037/tlcr-24-379","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Emerging evidence has underscored the crucial role of infiltrating immune cells in the tumor immune microenvironment (TIME) of non-small cell lung cancer (NSCLC) development and progression. With the implementation of screening programs, the incidence of early-stage NSCLC is rising. However, the high risk of recurrence and poor survival rates associated with this disease necessitate a deeper understanding of the TIME and its relationship with driver alterations. The aim of this study was to provide an in-depth analysis of immune changes in early-stage NSCLC, highlighting the significant transitions in immune response during disease progression.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Tumor tissues were collected from 105 patients with precancerous lesions or stage I-III NSCLC. Next-generation sequencing (NGS) was used to detect cancer driver alterations. Multiplex immunofluorescence (mIF) was performed to evaluate immune cell density, percentage, and spatial proximity to cancer cells in the TIME. Next Among these patients, 64 had NGS results, including three with adenocarcinoma in situ (AIS), 10 with minimally invasive adenocarcinoma (MIA), and 51 with stage I invasive cancers. Additionally, three patients underwent neoadjuvant immuno-chemotherapy and tumor tissue specimens before and after treatment were obtained.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Patients with stage I invasive cancer had significantly higher density (P=0.01) and percentage (P=0.02) of CD8&lt;sup&gt;+&lt;/sup&gt; T cells and higher percentages of M1 macrophages (P=0.04) and immature natural killer (NK) cells (P=0.041) in the tumor parenchyma compared to those with AIS/MIA. Patients with mutated epidermal growth factor receptor (&lt;i&gt;EGFR&lt;/i&gt;) gene exhibited decreased NK cell infiltration, increased M2 macrophage infiltration, and decreased aggregation of CD4&lt;sup&gt;+&lt;/sup&gt; T cells near tumor cells compared to &lt;i&gt;EGFR&lt;/i&gt; wild-type patients. As NSCLC progressed from stage I to III, CD8&lt;sup&gt;+&lt;/sup&gt; T cell density and proportion increased, while PD-L1&lt;sup&gt;+&lt;/sup&gt; tumor cells were in closer proximity to PD-1&lt;sup&gt;+&lt;/sup&gt;CD8&lt;sup&gt;+&lt;/sup&gt; T cells, potentially inhibiting CD8&lt;sup&gt;+&lt;/sup&gt; T cell function. Furthermore, M1 macrophages decreased in density and proportion, and the number of NK cells, macrophages, and B cells around tumor cells decreased. Additionally, patients with tertiary lymphoid structures (TLSs) had significantly higher proportion of M1 macrophages and lymphocytes near tumor cells, whereas those without TLS had PD-L1&lt;sup&gt;+&lt;/sup&gt; tumor cells more densely clustered around PD-1&lt;sup&gt;+&lt;/sup&gt;CD8&lt;sup&gt;+&lt;/sup&gt; T cells. Notably, neoadjuvant immuno-chemotherapy induced the development of TLS.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;This study offers an in-depth analysis of immune changes in NSCLC, demonstrating that the transition from AIS/MIA to invasive stage I NSCLC leads to immune activation, while the advancement from stage I to stage III cancer results in immune suppression. ","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11484713/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475703","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":"Utility of atezolizumab plus bevacizumab, carboplatin, and paclitaxel combination for the treatment of advanced non-squamous non-small cell lung cancer patients with malignant pleural effusion.","authors":"Kakeru Hisakane, Kenichiro Atsumi, Masahiro Seike, Takashi Hirose","doi":"10.21037/tlcr-24-347","DOIUrl":"10.21037/tlcr-24-347","url":null,"abstract":"<p><strong>Background: </strong>Malignant pleural effusion (MPE) remains a negative prognostic factor in non-small cell lung cancer (NSCLC), even after the emergence of immune checkpoint inhibitors. Vascular endothelial growth factor (VEGF) plays a pivotal role in the pathogenesis of MPE. Bevacizumab, a humanized monoclonal antibody against VEGF, is a key agent for patients who develop MPE. However, it is unclear whether MPE is a poor prognostic factor in patients with advanced non-squamous NSCLC receiving treatment with the atezolizumab plus bevacizumab, carboplatin, and paclitaxel (ABCP) regimen. Moreover, the effect of ABCP on MPE control is unknown. This study aimed to elucidate the efficacy and safety of ABCP for non-squamous NSCLC patients with MPE.</p><p><strong>Methods: </strong>We retrospectively analyzed consecutive patients with advanced non-squamous NSCLC who received treatment with ABCP (January 2019-September 2023). Patients were divided into two groups (non-MPE and MPE), and treatment outcomes were compared. In the MPE group, treatment efficacy for MPE control and toxicity were evaluated.</p><p><strong>Results: </strong>Of the 46 patients enrolled, 17 and 29 were included in the non-MPE and MPE groups, respectively. The objective response and disease control rates were not significantly different between the non-MPE and MPE groups (76.5% <i>vs.</i> 51.7%, P=0.13; 88.2% <i>vs.</i> 82.8%, P>0.99; respectively). Similarly, the median progression-free survival and median overall survival were not significantly different (9.9 <i>vs.</i> 10.1 months, P=0.87; 16.0 <i>vs.</i> 19.9 months, P=0.87, respectively). In the MPE group, 25 patients (86.2%) achieved MPE control lasting >8 weeks from the initiation of treatment with ABCP; the median progression-free survival without an unequivocal increase in MPE was 15.0 months. The incidence rates of grade ≥3 non-immune- and immune-related adverse events were 83% and 17%, respectively. There was no treatment-related death.</p><p><strong>Conclusions: </strong>The ABCP regimen may be a promising treatment option for non-squamous NSCLC patients with MPE.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11484719/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475704","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":"IL-1 receptor-associated kinase 3 (IRAK3) in lung adenocarcinoma predicts prognosis and immunotherapy resistance: involvement of multiple inflammation-related pathways.","authors":"Yang Zhou, Wei Rao, Zhao Li, Wei Guo, Fei Shao, Zhen Zhang, Hao Zhang, Tiejun Liu, Zitong Li, Fengwei Tan, Qi Xue, Shugeng Gao, Jie He","doi":"10.21037/tlcr-24-391","DOIUrl":"10.21037/tlcr-24-391","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Lung cancer is a globally prevailing malignancy, and the predominant histological subtype is lung adenocarcinoma (LUAD). IL-1 receptor-associated kinase 3 (&lt;i&gt;IRAK3&lt;/i&gt;) has been identified in connection with innate immune and inflammatory response. The aim of this study is to investigate the impact of &lt;i&gt;IRAK3&lt;/i&gt; on prognosis and immunotherapy efficacy in LUAD, which remains incompletely elucidated.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Our study delved into multiple online databases to find out expression, methylation and prognostic potentials of &lt;i&gt;IRAK3&lt;/i&gt; in LUAD and other malignancies. We employed tissue microarrays to assess IRAK3 protein levels in our LUAD cohort [National Cancer Center (NCC), China] and explore prognostic values. The correlations between &lt;i&gt;IRAK3&lt;/i&gt; and immune infiltration based on The Cancer Genome Atlas (TCGA) data were analyzed by corresponding algorithms. The contribution of &lt;i&gt;IRAK3&lt;/i&gt; to immunotherapy response was explored through the Tumor Immune Dysfunction and Exclusion (TIDE) algorithm. Both LinkedOmics database and gene set enrichment analysis (GSEA) were applied to investigate how IRAK3 influences the tumor immune microenvironment and regulates immunotherapy response. We applied single-cell RNA sequencing datasets for the investigation of &lt;i&gt;IRAK3&lt;/i&gt; expression across diverse immune cells. Moreover, we employed genomics of drug sensitivity in cancer (GDSC) databases to examine how &lt;i&gt;IRKA3&lt;/i&gt; expression correlates with different drug responses.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Compared with normal tissues, various tumor tissues had lower &lt;i&gt;IRAK3&lt;/i&gt; expression which could be regulated by its high methylation level. Reduced IRAK3 protein level was observed to correlate with advanced tumor stages and unfavorable prognosis among patients with LUAD, especially individuals with lymph node metastasis. Gene set enrichment analysis (GSEA) and tumor infiltration analysis proved that &lt;i&gt;IRAK3&lt;/i&gt; provoked immune infiltration. Macrophages/monocytes, CD4&lt;sup&gt;+&lt;/sup&gt; T cells, CD8&lt;sup&gt;+&lt;/sup&gt; T cells and neutrophils correlated significantly with &lt;i&gt;IRAK3&lt;/i&gt; expression. With TIDE algorithm, &lt;i&gt;IRAK3&lt;/i&gt; was verified to be related to poor immune checkpoint blockade (ICB) response. &lt;i&gt;IRAK3&lt;/i&gt; demonstrated positive associations with T-cell dysfunction score and immune checkpoint markers. Conversely, it exhibited negative correlations with microsatellite instability (MSI) and tumor mutation burden (TMB). High &lt;i&gt;IRAK3&lt;/i&gt; expression exacerbated cytotoxic T lymphocyte (CTL) dysfunction and predicted immunotherapy resistance by involvement of multiple inflammation-related pathways including IL-6/JAK/STAT3 signaling, inflammatory response and interferon-gamma (IFN-γ) response pathways. Additionally, elevated &lt;i&gt;IRAK3&lt;/i&gt; expression was predicted to be related with better responses to chemotherapeutic and molecular targeted drugs.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Our findings indicated that &lt;i&gt;","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11484737/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475682","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}