Background: Studying the relationship between strenuous sports or other exercises (SSOE) and lung cancer risk remains underexplored. Traditional observational studies face challenges like confounders and inverse causation. However, Mendelian randomization (MR) provides a promising approach in epidemiology and genetics, using genetic variants as instrumental variables to investigate causal relationships. By leveraging MR, we have scrutinized the causal link between SSOE and lung cancer development.
Methods: Twelve single-nucleotide polymorphisms (SNPs) associated with SSOE, as identified in previously published genome-wide association studies, were utilized as instrumental variables in our investigation. Summary genetic data at the individual level were obtained from relevant studies and cancer consortia. The study encompassed a total of 11,348 cases and 15,861 controls. The statistical technique of inverse variance-weighting (IVW), commonly employed in meta-analyses and MR studies, was employed to assess the causal relationship between SSOE and lung cancer risk.
Results: The MR risk analysis indicated a causal relationship between SSOE and the incidence of lung cancer, with evidence of a reduced risk for overall lung cancer [odds ratio (OR) =0.129; 95% confidence interval (CI): 0.021-0.779; P=0.03], lung adenocarcinoma (OR =0.161; 95% CI: 0.012-2.102; P=0.16) and squamous cell lung cancer (OR =0.045; 95% CI: 0.003-0.677; P=0.03). The combined OR for lung cancer from SSOE (controlling for waist circumference and smoking status) was 0.054 (95% CI: 0.010-0.302, P<0.001).
Conclusions: Our MR analysis findings indicate a potential correlation between SSOE and a protective effect against lung cancer development. Further investigation is imperative to uncover the precise mechanistic link between them.
{"title":"Association between strenuous sports or other exercises and lung cancer risk: a mendelian randomization study.","authors":"Wushu Chen, Anlin Liu, Yu Jiang, Yuechun Lin, Xingpei Li, Chongde Pan, Yixuan Wang, Huiwen Yu, Yulin Zhao, Junxing Li, Hengrui Liang, Runchen Wang, Wei Wang, Xin Xu, Ying Huang","doi":"10.21037/tlcr-23-810","DOIUrl":"10.21037/tlcr-23-810","url":null,"abstract":"<p><strong>Background: </strong>Studying the relationship between strenuous sports or other exercises (SSOE) and lung cancer risk remains underexplored. Traditional observational studies face challenges like confounders and inverse causation. However, Mendelian randomization (MR) provides a promising approach in epidemiology and genetics, using genetic variants as instrumental variables to investigate causal relationships. By leveraging MR, we have scrutinized the causal link between SSOE and lung cancer development.</p><p><strong>Methods: </strong>Twelve single-nucleotide polymorphisms (SNPs) associated with SSOE, as identified in previously published genome-wide association studies, were utilized as instrumental variables in our investigation. Summary genetic data at the individual level were obtained from relevant studies and cancer consortia. The study encompassed a total of 11,348 cases and 15,861 controls. The statistical technique of inverse variance-weighting (IVW), commonly employed in meta-analyses and MR studies, was employed to assess the causal relationship between SSOE and lung cancer risk.</p><p><strong>Results: </strong>The MR risk analysis indicated a causal relationship between SSOE and the incidence of lung cancer, with evidence of a reduced risk for overall lung cancer [odds ratio (OR) =0.129; 95% confidence interval (CI): 0.021-0.779; P=0.03], lung adenocarcinoma (OR =0.161; 95% CI: 0.012-2.102; P=0.16) and squamous cell lung cancer (OR =0.045; 95% CI: 0.003-0.677; P=0.03). The combined OR for lung cancer from SSOE (controlling for waist circumference and smoking status) was 0.054 (95% CI: 0.010-0.302, P<0.001).</p><p><strong>Conclusions: </strong>Our MR analysis findings indicate a potential correlation between SSOE and a protective effect against lung cancer development. Further investigation is imperative to uncover the precise mechanistic link between them.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11225037/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141555513","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}
Background: Lung adenocarcinoma (LUAD) is one of the most common types of cancer worldwide. Proteasome activator subunit 3 (PSME3) is a subunit of a proteasome activator, and changes in PSME3 can lead to the development of many diseases in organisms. However, the specific mechanism of PSME3 in LUAD has not yet been elucidated. This study initially revealed the mechanism of PSME3 promoting the progression of lung adenocarcinoma, which provided a potential molecular target for clinical treatment.
Methods: PSME3 expression in LUAD cells and tissues was assessed by bioinformatics analysis, immunohistochemistry (IHC), Western blotting (WB), and quantitative real time polymerase chain reaction (qRT-PCR). A series of functional experiments were used to evaluate the effects of PSME3 knockdown and overexpression on LUAD cell proliferation, migration, and apoptosis. The potential mechanism of PSME3 was explored by transcriptome sequencing and WB experiments.
Results: In this study, our initial findings indicated that PSME3 expression was abnormally high in LUAD and was associated with poor patient prognosis. Further, we found that the downregulation of PSME3 significantly inhibited LUAD cell proliferation, an effect that was verified by subcutaneous tumor formation experiments in nude mice. Similarly, the rate of invasion and migration of LUAD cells significantly decreased after the downregulation of PSME3. Using flow cytometry, we found that the knockdown of PSME3 caused cell cycle arrest at the G1/S phase. Through transcriptome sequencing, we found that the transforming growth factor-beta (TGF-β)/SMAD signaling pathway was closely related to LUAD, and we then validated the pathway using WB assays.
Conclusions: We demonstrated that PSME3 was abnormally highly expressed in LUAD and related to poor patient prognosis; therefore, targeting PSME3 in the treatment of LUAD may represent a novel therapeutic approach.
{"title":"PSME3 promotes lung adenocarcinoma development by regulating the TGF-β/SMAD signaling pathway.","authors":"Shuai Wang, Yongmeng Li, Kai Jin, Kenichi Suda, Rongyang Li, Huiying Zhang, Hui Tian","doi":"10.21037/tlcr-24-340","DOIUrl":"10.21037/tlcr-24-340","url":null,"abstract":"<p><strong>Background: </strong>Lung adenocarcinoma (LUAD) is one of the most common types of cancer worldwide. Proteasome activator subunit 3 (PSME3) is a subunit of a proteasome activator, and changes in PSME3 can lead to the development of many diseases in organisms. However, the specific mechanism of PSME3 in LUAD has not yet been elucidated. This study initially revealed the mechanism of PSME3 promoting the progression of lung adenocarcinoma, which provided a potential molecular target for clinical treatment.</p><p><strong>Methods: </strong>PSME3 expression in LUAD cells and tissues was assessed by bioinformatics analysis, immunohistochemistry (IHC), Western blotting (WB), and quantitative real time polymerase chain reaction (qRT-PCR). A series of functional experiments were used to evaluate the effects of PSME3 knockdown and overexpression on LUAD cell proliferation, migration, and apoptosis. The potential mechanism of PSME3 was explored by transcriptome sequencing and WB experiments.</p><p><strong>Results: </strong>In this study, our initial findings indicated that PSME3 expression was abnormally high in LUAD and was associated with poor patient prognosis. Further, we found that the downregulation of PSME3 significantly inhibited LUAD cell proliferation, an effect that was verified by subcutaneous tumor formation experiments in nude mice. Similarly, the rate of invasion and migration of LUAD cells significantly decreased after the downregulation of PSME3. Using flow cytometry, we found that the knockdown of PSME3 caused cell cycle arrest at the G1/S phase. Through transcriptome sequencing, we found that the transforming growth factor-beta (TGF-β)/SMAD signaling pathway was closely related to LUAD, and we then validated the pathway using WB assays.</p><p><strong>Conclusions: </strong>We demonstrated that PSME3 was abnormally highly expressed in LUAD and related to poor patient prognosis; therefore, targeting PSME3 in the treatment of LUAD may represent a novel therapeutic approach.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11225040/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141555520","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}
Background: Chemotherapy and radiotherapy (RT) would induce lymphopenia, leading to a poor prognosis. This study investigated whether chemotherapy increased lymphopenia during RT and explored the impacts of different chemotherapy regimens on the lymphocyte counts of patients receiving RT.
Methods: Clinical parameters and lymphocyte data were collected from 215 patients with locally advanced non-small cell lung cancer (LA-NSCLC). Severe lymphopenia (SRL) was defined as an absolute lymphocyte count (ALC) of ≤0.2×103 cells/μL. Patient overall survival (OS) was analyzed using the Kaplan-Meier method. The predictors of SRL were extracted using univariate and multivariate regression analyses with backward likelihood ratio elimination.
Results: Compared with patients without SRL, patients with SRL with LA-NSCLC showed a poorer prognosis in terms of OS (P=0.003). Of the 215 patients, 130 underwent concurrent chemoradiotherapy (CCRT) and 85 underwent sequential chemoradiotherapy (SCRT). The OS was better in patients without SRL (in the CCRT group, P=0.01 and in the SCRT group, P=0.08). The mean ALCs for CCRT and SCRT did not differ significantly (P=0.27). The minimum ALC of CCRT was significantly lower than that of SCRT (P<0.0001). CCRT was a predictor of SRL (P=0.008). However, multivariate analysis showed that the different chemotherapy regimens were not predictors of SRL (all P>0.1).
Conclusions: In LA-NSCLC, the outcomes of patients with SRL were poorer than those without SRL. RT and chemotherapy were the main factors affecting SRL development, while different chemotherapy regimens were not significantly associated with lymphocyte counts in LA-NSCLC.
{"title":"The impact of different modalities of chemoradiation therapy and chemotherapy regimens on lymphopenia in patients with locally advanced non-small cell lung cancer.","authors":"Yaqi Li, Xingwen Fan, Yulei Pei, Qi Yu, Renquan Lu, Guoliang Jiang, Kailiang Wu","doi":"10.21037/tlcr-24-60","DOIUrl":"10.21037/tlcr-24-60","url":null,"abstract":"<p><strong>Background: </strong>Chemotherapy and radiotherapy (RT) would induce lymphopenia, leading to a poor prognosis. This study investigated whether chemotherapy increased lymphopenia during RT and explored the impacts of different chemotherapy regimens on the lymphocyte counts of patients receiving RT.</p><p><strong>Methods: </strong>Clinical parameters and lymphocyte data were collected from 215 patients with locally advanced non-small cell lung cancer (LA-NSCLC). Severe lymphopenia (SRL) was defined as an absolute lymphocyte count (ALC) of ≤0.2×10<sup>3</sup> cells/μL. Patient overall survival (OS) was analyzed using the Kaplan-Meier method. The predictors of SRL were extracted using univariate and multivariate regression analyses with backward likelihood ratio elimination.</p><p><strong>Results: </strong>Compared with patients without SRL, patients with SRL with LA-NSCLC showed a poorer prognosis in terms of OS (P=0.003). Of the 215 patients, 130 underwent concurrent chemoradiotherapy (CCRT) and 85 underwent sequential chemoradiotherapy (SCRT). The OS was better in patients without SRL (in the CCRT group, P=0.01 and in the SCRT group, P=0.08). The mean ALCs for CCRT and SCRT did not differ significantly (P=0.27). The minimum ALC of CCRT was significantly lower than that of SCRT (P<0.0001). CCRT was a predictor of SRL (P=0.008). However, multivariate analysis showed that the different chemotherapy regimens were not predictors of SRL (all P>0.1).</p><p><strong>Conclusions: </strong>In LA-NSCLC, the outcomes of patients with SRL were poorer than those without SRL. RT and chemotherapy were the main factors affecting SRL development, while different chemotherapy regimens were not significantly associated with lymphocyte counts in LA-NSCLC.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11225056/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141555525","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}
Pub Date : 2024-06-30Epub Date: 2024-06-27DOI: 10.21037/tlcr-24-314
Wenhua Liang, Ran Zhong, Jianxing He
{"title":"Adaptive medicine, a crucial component of optimized decision making: perspectives from lung cancer management.","authors":"Wenhua Liang, Ran Zhong, Jianxing He","doi":"10.21037/tlcr-24-314","DOIUrl":"10.21037/tlcr-24-314","url":null,"abstract":"","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11225041/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141555512","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}
Pub Date : 2024-06-30Epub Date: 2024-06-27DOI: 10.21037/tlcr-24-325
Yiming He, Lin Huang, Jiajun Deng, Yifan Zhong, Tao Chen, Yunlang She, Lei Jiang, Deping Zhao, Dong Xie, Gening Jiang, Stefano Bongiolatti, Mara B Antonoff, René Horsleben Petersen, Chang Chen
Background: Sleeve lobectomy is a challenging procedure with a high risk of postoperative complications. To facilitate surgical decision-making and optimize perioperative treatment, we developed risk stratification models to quantify the probability of postoperative complications after sleeve lobectomy.
Methods: We retrospectively analyzed the clinical features of 691 non-small cell lung cancer (NSCLC) patients who underwent sleeve lobectomy between July 2016 and December 2019. Logistic regression models were trained and validated in the cohort to predict overall complications, major complications, and specific minor complications. The impact of specific complications in prognostic stratification was explored via the Kaplan-Meier method.
Results: Of 691 included patients, 232 (33.5%) developed complications, including 35 (5.1%) and 197 (28.5%) patients with major and minor complications, respectively. The models showed robust discrimination, yielding an area under the receiver operating characteristic (ROC) curve (AUC) of 0.853 [95% confidence interval (CI): 0.705-0.885] for predicting overall postoperative complication risk and 0.751 (95% CI: 0.727-0.762) specifically for major complication risks. Models predicting minor complications also achieved good performance, with AUCs ranging from 0.78 to 0.89. Survival analyses revealed a significant association between postoperative complications and poor prognosis.
Conclusions: Risk stratification models could accurately predict the probability and severity of complications in NSCLC patients following sleeve lobectomy, which may inform clinical decision-making for future patients.
{"title":"Predicting complication risks after sleeve lobectomy for non-small cell lung cancer.","authors":"Yiming He, Lin Huang, Jiajun Deng, Yifan Zhong, Tao Chen, Yunlang She, Lei Jiang, Deping Zhao, Dong Xie, Gening Jiang, Stefano Bongiolatti, Mara B Antonoff, René Horsleben Petersen, Chang Chen","doi":"10.21037/tlcr-24-325","DOIUrl":"10.21037/tlcr-24-325","url":null,"abstract":"<p><strong>Background: </strong>Sleeve lobectomy is a challenging procedure with a high risk of postoperative complications. To facilitate surgical decision-making and optimize perioperative treatment, we developed risk stratification models to quantify the probability of postoperative complications after sleeve lobectomy.</p><p><strong>Methods: </strong>We retrospectively analyzed the clinical features of 691 non-small cell lung cancer (NSCLC) patients who underwent sleeve lobectomy between July 2016 and December 2019. Logistic regression models were trained and validated in the cohort to predict overall complications, major complications, and specific minor complications. The impact of specific complications in prognostic stratification was explored via the Kaplan-Meier method.</p><p><strong>Results: </strong>Of 691 included patients, 232 (33.5%) developed complications, including 35 (5.1%) and 197 (28.5%) patients with major and minor complications, respectively. The models showed robust discrimination, yielding an area under the receiver operating characteristic (ROC) curve (AUC) of 0.853 [95% confidence interval (CI): 0.705-0.885] for predicting overall postoperative complication risk and 0.751 (95% CI: 0.727-0.762) specifically for major complication risks. Models predicting minor complications also achieved good performance, with AUCs ranging from 0.78 to 0.89. Survival analyses revealed a significant association between postoperative complications and poor prognosis.</p><p><strong>Conclusions: </strong>Risk stratification models could accurately predict the probability and severity of complications in NSCLC patients following sleeve lobectomy, which may inform clinical decision-making for future patients.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11225058/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141555446","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}
Pub Date : 2024-06-30Epub Date: 2024-06-25DOI: 10.21037/tlcr-24-185
Danielle Brazel, Misako Nagasaka
{"title":"The APPLE trial in the evolving landscape of ctDNA monitoring.","authors":"Danielle Brazel, Misako Nagasaka","doi":"10.21037/tlcr-24-185","DOIUrl":"10.21037/tlcr-24-185","url":null,"abstract":"","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11225046/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141555523","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}
Background: Immunotherapy functions by leveraging immunoregulation drugs to bolster the immune system's capacity to identify and eliminate cancerous cells. In contrast to radiotherapy and chemotherapy, immunotherapy exhibits diminished side effects, heightened efficacy, and prolonged survival rates. Nevertheless, meticulous exploration into the determinants governing the advantageous effects of immunotherapy among patients who have previously undergone multiple prior therapies has yet to be conducted. Albumin (ALB) as a nutritional indicator has not been thoroughly studied for its prognostic effect on efficacy or survival. This study aims to identify factors that influence treatment outcomes among patients undergoing third-line or later immunological therapies.
Methods: A cohort of 250 lung cancer patients undergoing toripalimab or tislelizumab immunotherapy was the focal point of data collection. The determination of the median value facilitated the establishment of a cut-off point, enabling the categorization of continuous variables. After data collection, a series of statistical analyses of various clinical factors at baseline were performed, including nonparametric tests, logistic regression, and Cox proportional risk modeling. The last follow-up was in May 2022. The primary study endpoint was overall survival (OS).
Results: A total of 250 patients were enrolled in the study, of which 129 patients received first- or second-line immunotherapy and 121 patients received third-line or subsequent immunotherapy. According to Cox multifactor regression analysis, in patients receiving either first- or second-line therapy, the ALB level exhibited negligible prognostic relevance (P>0.05). However, in patients subjected to immunotherapy beyond the second line, the ALB level manifested significant prognostic importance (P=0.039). Notably, patients demonstrating elevated ALB levels achieved a higher disease control rate (DCR) (70.0% vs. 52.5%, P=0.05) and displayed a tendency towards a heightened objective response rate (ORR) (20.0% vs. 16.4%, P=0.61) in comparison to those with lower ALB levels.
Conclusions: Among patients undergoing immunotherapy in the third line or subsequent treatment phases, elevated ALB levels in baseline correlated with DCR and OS. Thus, the pre-immunotherapy ALB level emerges as an autonomous predictor of OS in patients subjected to third- or later line immunotherapy interventions.
背景:免疫疗法通过利用免疫调节药物来增强免疫系统识别和消灭癌细胞的能力。与放疗和化疗相比,免疫疗法副作用小、疗效高、生存期长。然而,对于那些曾接受过多种疗法的患者来说,免疫疗法的优势效果究竟取决于哪些因素,还有待深入研究。白蛋白(ALB)作为一种营养指标,其对疗效或存活率的预后影响尚未得到深入研究。本研究旨在确定影响接受三线或更晚期免疫疗法患者治疗效果的因素:数据收集的重点是250名接受托利帕利单抗或替莱利珠单抗免疫疗法的肺癌患者。中位值的确定有助于确定分界点,从而对连续变量进行分类。数据收集后,对基线时的各种临床因素进行了一系列统计分析,包括非参数检验、逻辑回归和考克斯比例风险模型。最后一次随访是在 2022 年 5 月。研究的主要终点是总生存期(OS):共有250名患者参与研究,其中129名患者接受了一线或二线免疫疗法,121名患者接受了三线或后续免疫疗法。根据Cox多因素回归分析,在接受一线或二线治疗的患者中,ALB水平与预后的相关性微乎其微(P>0.05)。然而,在接受二线以上免疫疗法的患者中,ALB水平对预后有重要影响(P=0.039)。值得注意的是,与ALB水平较低的患者相比,ALB水平升高的患者疾病控制率(DCR)更高(70.0% vs. 52.5%,P=0.05),客观反应率(ORR)也呈上升趋势(20.0% vs. 16.4%,P=0.61):结论:在三线或后续治疗阶段接受免疫治疗的患者中,基线ALB水平升高与DCR和OS相关。因此,免疫治疗前的ALB水平可自主预测接受三线或后续免疫治疗患者的OS。
{"title":"The prognostic role of albumin levels in lung cancer patients receiving third-line or advanced immunotherapy: a retrospective study.","authors":"Yanfei Chen, Tong Liu, Hui Feng, Tiantian Liu, Jing Zhang, Jun Wang, Jihong Lu, Antonio Rossi, Ivy Riano, Pingping Hu, Jiandong Zhang","doi":"10.21037/tlcr-24-378","DOIUrl":"10.21037/tlcr-24-378","url":null,"abstract":"<p><strong>Background: </strong>Immunotherapy functions by leveraging immunoregulation drugs to bolster the immune system's capacity to identify and eliminate cancerous cells. In contrast to radiotherapy and chemotherapy, immunotherapy exhibits diminished side effects, heightened efficacy, and prolonged survival rates. Nevertheless, meticulous exploration into the determinants governing the advantageous effects of immunotherapy among patients who have previously undergone multiple prior therapies has yet to be conducted. Albumin (ALB) as a nutritional indicator has not been thoroughly studied for its prognostic effect on efficacy or survival. This study aims to identify factors that influence treatment outcomes among patients undergoing third-line or later immunological therapies.</p><p><strong>Methods: </strong>A cohort of 250 lung cancer patients undergoing toripalimab or tislelizumab immunotherapy was the focal point of data collection. The determination of the median value facilitated the establishment of a cut-off point, enabling the categorization of continuous variables. After data collection, a series of statistical analyses of various clinical factors at baseline were performed, including nonparametric tests, logistic regression, and Cox proportional risk modeling. The last follow-up was in May 2022. The primary study endpoint was overall survival (OS).</p><p><strong>Results: </strong>A total of 250 patients were enrolled in the study, of which 129 patients received first- or second-line immunotherapy and 121 patients received third-line or subsequent immunotherapy. According to Cox multifactor regression analysis, in patients receiving either first- or second-line therapy, the ALB level exhibited negligible prognostic relevance (P>0.05). However, in patients subjected to immunotherapy beyond the second line, the ALB level manifested significant prognostic importance (P=0.039). Notably, patients demonstrating elevated ALB levels achieved a higher disease control rate (DCR) (70.0% <i>vs.</i> 52.5%, P=0.05) and displayed a tendency towards a heightened objective response rate (ORR) (20.0% <i>vs.</i> 16.4%, P=0.61) in comparison to those with lower ALB levels.</p><p><strong>Conclusions: </strong>Among patients undergoing immunotherapy in the third line or subsequent treatment phases, elevated ALB levels in baseline correlated with DCR and OS. Thus, the pre-immunotherapy ALB level emerges as an autonomous predictor of OS in patients subjected to third- or later line immunotherapy interventions.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11225039/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141555526","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}
Pub Date : 2024-06-30Epub Date: 2024-06-27DOI: 10.21037/tlcr-24-414
Xinchen Zhao, Shengwei Zhang, Xiaoyue Sun, Yao Lin, Luca Capone, Eric C Ko, Benjamin H Kann, Yi Li, Xiaoshan Wang
Background and objective: A significant number of individuals diagnosed with non-small cell lung cancer (NSCLC) have distant metastases, and the concept of oligometastatic NSCLC has shown promise in achieving a cure. Stereotactic body radiation therapy (SBRT) is currently considered a viable treatment option for a limited number of tumor metastases. It has also been demonstrated that third-generation tyrosine kinase inhibitors (TKIs) are effective in extending the survival of patients with epidermal growth factor receptor (EGFR)-mutated NSCLC. Hence, the combination of SBRT with third-generation TKIs holds the potential to enhance treatment efficacy in patients with oligometastatic EGFR-mutated NSCLC. This review aimed to assess the possibility of combining SBRT with TKIs as an optimum treatment option for patients with oligometastatic EGFR-mutated NSCLC.
Methods: We performed a narrative review by searching the PubMed, Web of Science, Elsevier and ClinicalTrials.gov databases for articles published in the English language from January 2009 to February 2024 and by reviewing the bibliographies of key references to identify important literature related to combining SBRT with third-generation TKIs in oligometastatic EGFR-mutated NSCLC.
Key content and findings: This review aimed to assess the viability of combining SBRT and EGFR-TKIs in oligometastatic EGFR-mutated NSCLC. Current clinical trials suggest that the combined therapies have better progression free survival (PFS) when using SBRT as either concurrent with EGFR-TKIs or consolidated with EGFR-TKIs. Furthermore, research with third-generation EGFR-TKIs and SBRT combinations has demonstrated tolerable toxicity levels without significant additional adverse effects as compared to prior therapies. However, further clinical trials are required to establish its effectiveness.
Conclusions: The combined approach of SBRT and TKIs can effectively impede the progression of oligometastatic NSCLC in patients harboring EGFR mutations and, most notably, can prolong progression-free survival rates. However, the feasibility of combining SBRT with third-generation TKIs in clinical trials remains unclear.
{"title":"Narrative review of stereotactic body radiation therapy combined with tyrosine kinase inhibitors for oligometastatic <i>EGFR</i>-mutated non-small cell lung cancer: present and future developments.","authors":"Xinchen Zhao, Shengwei Zhang, Xiaoyue Sun, Yao Lin, Luca Capone, Eric C Ko, Benjamin H Kann, Yi Li, Xiaoshan Wang","doi":"10.21037/tlcr-24-414","DOIUrl":"10.21037/tlcr-24-414","url":null,"abstract":"<p><strong>Background and objective: </strong>A significant number of individuals diagnosed with non-small cell lung cancer (NSCLC) have distant metastases, and the concept of oligometastatic NSCLC has shown promise in achieving a cure. Stereotactic body radiation therapy (SBRT) is currently considered a viable treatment option for a limited number of tumor metastases. It has also been demonstrated that third-generation tyrosine kinase inhibitors (TKIs) are effective in extending the survival of patients with epidermal growth factor receptor (<i>EGFR</i>)-mutated NSCLC. Hence, the combination of SBRT with third-generation TKIs holds the potential to enhance treatment efficacy in patients with oligometastatic <i>EGFR</i>-mutated NSCLC. This review aimed to assess the possibility of combining SBRT with TKIs as an optimum treatment option for patients with oligometastatic <i>EGFR</i>-mutated NSCLC.</p><p><strong>Methods: </strong>We performed a narrative review by searching the PubMed, Web of Science, Elsevier and ClinicalTrials.gov databases for articles published in the English language from January 2009 to February 2024 and by reviewing the bibliographies of key references to identify important literature related to combining SBRT with third-generation TKIs in oligometastatic <i>EGFR</i>-mutated NSCLC.</p><p><strong>Key content and findings: </strong>This review aimed to assess the viability of combining SBRT and EGFR-TKIs in oligometastatic <i>EGFR</i>-mutated NSCLC. Current clinical trials suggest that the combined therapies have better progression free survival (PFS) when using SBRT as either concurrent with EGFR-TKIs or consolidated with EGFR-TKIs. Furthermore, research with third-generation EGFR-TKIs and SBRT combinations has demonstrated tolerable toxicity levels without significant additional adverse effects as compared to prior therapies. However, further clinical trials are required to establish its effectiveness.</p><p><strong>Conclusions: </strong>The combined approach of SBRT and TKIs can effectively impede the progression of oligometastatic NSCLC in patients harboring <i>EGFR</i> mutations and, most notably, can prolong progression-free survival rates. However, the feasibility of combining SBRT with third-generation TKIs in clinical trials remains unclear.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11225050/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141555441","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}
Pub Date : 2024-06-30Epub Date: 2024-06-25DOI: 10.21037/tlcr-24-124
Lan Shen, Jikai Zhao, Ying Yang, Shuya Mu, Yongfeng Yu, Yuchen Han, Shun Lu
Background: Mesenchymal-epithelial transition (MET) represents a potential therapeutic target in various cancers, with amplification of the MET gene identified in a subset of patients with pulmonary adenocarcinomas. However, MET gene amplification is rarely observed in high-grade fetal adenocarcinoma (H-FLAC).
Case description: Here we present a novel case of a patient diagnosed with stage IV H-FLAC harboring MET amplifications and treated with savolitinib. The 69-year-old male patient, who presented with a primary complaint of cough and white sputum, had a history of hypertension for over 10 years and a 45-year smoking history. The patient received savolitinib monotherapy treatment due to brain metastases. Despite the omission of radiotherapy for asymptomatic brain metastases, a notable response to savolitinib therapy was observed, with a partial response (PR) achieved after 4 weeks and a reduction in the brain tumor. At the time of the submission of this report, the patient received over 24 weeks of savolitinib treatment, and was maintained PR. The patient was still undergoing treatment. This highlights the potential clinical benefits of targeted therapy against MET amplification in H-FLAC.
Conclusions: H-FLAC harboring MET amplification and brain metastasis is rare. Treatment with savolitinib monotherapy resulted in a PR, providing preliminary insights to the efficacy of savolitinib for H-FLAC with MET amplification.
背景:间质-上皮转化(MET)是各种癌症的潜在治疗靶点,在肺腺癌患者中发现了MET基因扩增。然而,在高级别胎儿腺癌(H-FLAC)中很少观察到 MET 基因扩增:我们在此介绍一例诊断为携带 MET 扩增的 IV 期 H-FLAC 患者并接受 savolitinib 治疗的新病例。这名 69 岁的男性患者以咳嗽和白痰为主诉,有 10 多年的高血压病史和 45 年的吸烟史。患者因脑转移接受了沙沃利替尼单药治疗。尽管因无症状脑转移而省略了放疗,但观察到患者对萨沃利替尼治疗有明显反应,4周后出现部分反应(PR),脑肿瘤缩小。在提交本报告时,患者接受了超过 24 周的 savolitinib 治疗,并保持 PR。该患者仍在接受治疗。这凸显了针对H-FLAC中MET扩增的靶向治疗的潜在临床益处:携带MET扩增和脑转移的H-FLAC非常罕见。使用萨伐利替尼单药治疗可获得PR,这为萨伐利替尼治疗MET扩增的H-FLAC的疗效提供了初步启示。
{"title":"Prominent response to savolitinib monotherapy in high-grade fetal adenocarcinoma with <i>MET</i> amplification and concurrent brain metastasis: a case report.","authors":"Lan Shen, Jikai Zhao, Ying Yang, Shuya Mu, Yongfeng Yu, Yuchen Han, Shun Lu","doi":"10.21037/tlcr-24-124","DOIUrl":"10.21037/tlcr-24-124","url":null,"abstract":"<p><strong>Background: </strong>Mesenchymal-epithelial transition (<i>MET</i>) represents a potential therapeutic target in various cancers, with amplification of the <i>MET</i> gene identified in a subset of patients with pulmonary adenocarcinomas. However, <i>MET</i> gene amplification is rarely observed in high-grade fetal adenocarcinoma (H-FLAC).</p><p><strong>Case description: </strong>Here we present a novel case of a patient diagnosed with stage IV H-FLAC harboring <i>MET</i> amplifications and treated with savolitinib. The 69-year-old male patient, who presented with a primary complaint of cough and white sputum, had a history of hypertension for over 10 years and a 45-year smoking history. The patient received savolitinib monotherapy treatment due to brain metastases. Despite the omission of radiotherapy for asymptomatic brain metastases, a notable response to savolitinib therapy was observed, with a partial response (PR) achieved after 4 weeks and a reduction in the brain tumor. At the time of the submission of this report, the patient received over 24 weeks of savolitinib treatment, and was maintained PR. The patient was still undergoing treatment. This highlights the potential clinical benefits of targeted therapy against <i>MET</i> amplification in H-FLAC.</p><p><strong>Conclusions: </strong>H-FLAC harboring <i>MET</i> amplification and brain metastasis is rare. Treatment with savolitinib monotherapy resulted in a PR, providing preliminary insights to the efficacy of savolitinib for H-FLAC with <i>MET</i> amplification.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11225042/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141555448","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}
Pub Date : 2024-06-30Epub Date: 2024-06-25DOI: 10.21037/tlcr-24-165
Jiahao Jiang, Mark F Berry, Natalie S Lui, Douglas Z Liou, Winston L Trope, Leah M Backhus, Joseph B Shrager
Background: Epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma (KRAS) are the two most common oncogenic drivers in lung adenocarcinoma, and their roles still need further exploration. Here we aimed to compare the clinical impact of EGFR and KRAS mutations on disease progression in resected unifocal and multifocal lung adenocarcinoma.
Methods: Clinicopathologic and genomic data were collected for patients who underwent resection of lung adenocarcinoma from 2008 to 2022 at Stanford University Hospital. Retrospective review was performed in 241 patients whose tumors harbored EGFR (n=150, 62.2%) or KRAS (n=91, 37.8%) mutations. Clinical outcome was analyzed with special attention to the natural history of secondary nodules in multifocal cases wherein the dominant tumor had been resected.
Results: We confirm that compared with EGFR mutations, patients with KRAS mutations had more smokers, larger tumor size, higher TNM stage, higher positron emission tomography (PET)/computed tomography (CT) standard uptake value max, higher tumor mutation burden, and worse disease-free survival and overall survival on univariate analysis. For patients with multifocal pulmonary nodules, the median follow-up of unresected secondary nodules was 55 months. Secondary nodule progression-free survival (SNPFS) was significantly worse for patients with KRAS mutations than those with EGFR mutations (mean 40.3±6.6 vs. 67.7±6.5 months, P=0.004). Univariate analysis showed tumor size, tumor morphology, pathologic TNM stage, and KRAS mutations were significantly associated with SNPFS, while multivariate analysis showed only KRAS mutations were independently associated with worse SNPFS (hazard ratio 1.752, 95% confidence interval: 1.017-3.018, P=0.043).
Conclusions: Resected lung adenocarcinomas with KRAS mutations have more aggressive clinicopathological features and confer worse prognosis than those with EGFR mutations. Secondary pulmonary nodules in multifocal cases with dominant KRAS-mutant tumors have more rapid progression of the secondary nodules.
背景:表皮生长因子受体(EGFR)和克氏鼠肉瘤(KRAS)是肺腺癌中两种最常见的致癌因子,它们的作用仍需进一步探讨。在此,我们旨在比较EGFR和KRAS突变对切除的单灶和多灶肺腺癌疾病进展的临床影响:收集了2008年至2022年期间在斯坦福大学医院接受肺腺癌切除术的患者的临床病理和基因组数据。对241例肿瘤携带表皮生长因子受体(EGFR)(150例,62.2%)或KRAS(91例,37.8%)突变的患者进行了回顾性分析。对临床结果进行了分析,特别关注了多灶病例中继发性结节的自然病史,其中主要肿瘤已被切除:结果:我们证实,与表皮生长因子受体(EGFR)突变相比,KRAS突变患者吸烟人数更多,肿瘤体积更大,TNM分期更高,正电子发射断层扫描(PET)/计算机断层扫描(CT)标准摄取值最大值更高,肿瘤突变负荷更高,单变量分析显示无病生存率和总生存率更低。对于多灶性肺结节患者,未切除继发性结节的中位随访时间为55个月。KRAS突变患者的继发性结节无进展生存期(SNPFS)明显低于EGFR突变患者(平均40.3±6.6个月 vs. 67.7±6.5个月,P=0.004)。单变量分析显示肿瘤大小、肿瘤形态、病理TNM分期和KRAS突变与SNPFS显著相关,而多变量分析显示只有KRAS突变与较差的SNPFS独立相关(危险比1.752,95%置信区间:1.017-3.018,P=0.043):结论:与表皮生长因子受体(EGFR)突变的肺腺癌相比,切除的KRAS突变的肺腺癌临床病理特征更具侵袭性,预后更差。KRAS突变显性多灶病例的继发性肺结节进展更快。
{"title":"Clinical impact of <i>EGFR</i> and <i>KRAS</i> mutations in surgically treated unifocal and multifocal lung adenocarcinoma.","authors":"Jiahao Jiang, Mark F Berry, Natalie S Lui, Douglas Z Liou, Winston L Trope, Leah M Backhus, Joseph B Shrager","doi":"10.21037/tlcr-24-165","DOIUrl":"10.21037/tlcr-24-165","url":null,"abstract":"<p><strong>Background: </strong>Epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma (KRAS) are the two most common oncogenic drivers in lung adenocarcinoma, and their roles still need further exploration. Here we aimed to compare the clinical impact of <i>EGFR</i> and <i>KRAS</i> mutations on disease progression in resected unifocal and multifocal lung adenocarcinoma.</p><p><strong>Methods: </strong>Clinicopathologic and genomic data were collected for patients who underwent resection of lung adenocarcinoma from 2008 to 2022 at Stanford University Hospital. Retrospective review was performed in 241 patients whose tumors harbored <i>EGFR</i> (n=150, 62.2%) or <i>KRAS</i> (n=91, 37.8%) mutations. Clinical outcome was analyzed with special attention to the natural history of secondary nodules in multifocal cases wherein the dominant tumor had been resected.</p><p><strong>Results: </strong>We confirm that compared with <i>EGFR</i> mutations, patients with <i>KRAS</i> mutations had more smokers, larger tumor size, higher TNM stage, higher positron emission tomography (PET)/computed tomography (CT) standard uptake value max, higher tumor mutation burden, and worse disease-free survival and overall survival on univariate analysis. For patients with multifocal pulmonary nodules, the median follow-up of unresected secondary nodules was 55 months. Secondary nodule progression-free survival (SNPFS) was significantly worse for patients with <i>KRAS</i> mutations than those with <i>EGFR</i> mutations (mean 40.3±6.6 <i>vs.</i> 67.7±6.5 months, P=0.004). Univariate analysis showed tumor size, tumor morphology, pathologic TNM stage, and <i>KRAS</i> mutations were significantly associated with SNPFS, while multivariate analysis showed only <i>KRAS</i> mutations were independently associated with worse SNPFS (hazard ratio 1.752, 95% confidence interval: 1.017-3.018, P=0.043).</p><p><strong>Conclusions: </strong>Resected lung adenocarcinomas with <i>KRAS</i> mutations have more aggressive clinicopathological features and confer worse prognosis than those with <i>EGFR</i> mutations. Secondary pulmonary nodules in multifocal cases with dominant <i>KRAS</i>-mutant tumors have more rapid progression of the secondary nodules.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11225054/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141555515","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}