Background: 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.
Methods: 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.
Results: 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% vs. 51.7%, P=0.13; 88.2% vs. 82.8%, P>0.99; respectively). Similarly, the median progression-free survival and median overall survival were not significantly different (9.9 vs. 10.1 months, P=0.87; 16.0 vs. 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.
Conclusions: The ABCP regimen may be a promising treatment option for non-squamous NSCLC patients with MPE.
{"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":"13 9","pages":"2106-2115"},"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}
Pub Date : 2024-09-30Epub Date: 2024-09-20DOI: 10.21037/tlcr-24-379
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
<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>Patients with stage I invasive cancer had significantly higher density (P=0.01) and percentage (P=0.02) of CD8<sup>+</sup> 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 (<i>EGFR</i>) gene exhibited decreased NK cell infiltration, increased M2 macrophage infiltration, and decreased aggregation of CD4<sup>+</sup> T cells near tumor cells compared to <i>EGFR</i> wild-type patients. As NSCLC progressed from stage I to III, CD8<sup>+</sup> T cell density and proportion increased, while PD-L1<sup>+</sup> tumor cells were in closer proximity to PD-1<sup>+</sup>CD8<sup>+</sup> T cells, potentially inhibiting CD8<sup>+</sup> 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<sup>+</sup> tumor cells more densely clustered around PD-1<sup>+</sup>CD8<sup>+</sup> T cells. Notably, neoadjuvant immuno-chemotherapy induced the development of TLS.</p><p><strong>Conclusions: </strong>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.
{"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":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>Patients with stage I invasive cancer had significantly higher density (P=0.01) and percentage (P=0.02) of CD8<sup>+</sup> 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 (<i>EGFR</i>) gene exhibited decreased NK cell infiltration, increased M2 macrophage infiltration, and decreased aggregation of CD4<sup>+</sup> T cells near tumor cells compared to <i>EGFR</i> wild-type patients. As NSCLC progressed from stage I to III, CD8<sup>+</sup> T cell density and proportion increased, while PD-L1<sup>+</sup> tumor cells were in closer proximity to PD-1<sup>+</sup>CD8<sup>+</sup> T cells, potentially inhibiting CD8<sup>+</sup> 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<sup>+</sup> tumor cells more densely clustered around PD-1<sup>+</sup>CD8<sup>+</sup> T cells. Notably, neoadjuvant immuno-chemotherapy induced the development of TLS.</p><p><strong>Conclusions: </strong>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":"13 9","pages":"2395-2410"},"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}
Pub Date : 2024-09-30Epub Date: 2024-09-12DOI: 10.21037/tlcr-24-391
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
<p><strong>Background: </strong>Lung cancer is a globally prevailing malignancy, and the predominant histological subtype is lung adenocarcinoma (LUAD). IL-1 receptor-associated kinase 3 (<i>IRAK3</i>) has been identified in connection with innate immune and inflammatory response. The aim of this study is to investigate the impact of <i>IRAK3</i> on prognosis and immunotherapy efficacy in LUAD, which remains incompletely elucidated.</p><p><strong>Methods: </strong>Our study delved into multiple online databases to find out expression, methylation and prognostic potentials of <i>IRAK3</i> 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 <i>IRAK3</i> and immune infiltration based on The Cancer Genome Atlas (TCGA) data were analyzed by corresponding algorithms. The contribution of <i>IRAK3</i> 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 <i>IRAK3</i> expression across diverse immune cells. Moreover, we employed genomics of drug sensitivity in cancer (GDSC) databases to examine how <i>IRKA3</i> expression correlates with different drug responses.</p><p><strong>Results: </strong>Compared with normal tissues, various tumor tissues had lower <i>IRAK3</i> 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 <i>IRAK3</i> provoked immune infiltration. Macrophages/monocytes, CD4<sup>+</sup> T cells, CD8<sup>+</sup> T cells and neutrophils correlated significantly with <i>IRAK3</i> expression. With TIDE algorithm, <i>IRAK3</i> was verified to be related to poor immune checkpoint blockade (ICB) response. <i>IRAK3</i> 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 <i>IRAK3</i> 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 <i>IRAK3</i> expression was predicted to be related with better responses to chemotherapeutic and molecular targeted drugs.</p><p><strong>Conclusions: </strong>Our findings indicated that <i>
{"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":"<p><strong>Background: </strong>Lung cancer is a globally prevailing malignancy, and the predominant histological subtype is lung adenocarcinoma (LUAD). IL-1 receptor-associated kinase 3 (<i>IRAK3</i>) has been identified in connection with innate immune and inflammatory response. The aim of this study is to investigate the impact of <i>IRAK3</i> on prognosis and immunotherapy efficacy in LUAD, which remains incompletely elucidated.</p><p><strong>Methods: </strong>Our study delved into multiple online databases to find out expression, methylation and prognostic potentials of <i>IRAK3</i> 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 <i>IRAK3</i> and immune infiltration based on The Cancer Genome Atlas (TCGA) data were analyzed by corresponding algorithms. The contribution of <i>IRAK3</i> 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 <i>IRAK3</i> expression across diverse immune cells. Moreover, we employed genomics of drug sensitivity in cancer (GDSC) databases to examine how <i>IRKA3</i> expression correlates with different drug responses.</p><p><strong>Results: </strong>Compared with normal tissues, various tumor tissues had lower <i>IRAK3</i> 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 <i>IRAK3</i> provoked immune infiltration. Macrophages/monocytes, CD4<sup>+</sup> T cells, CD8<sup>+</sup> T cells and neutrophils correlated significantly with <i>IRAK3</i> expression. With TIDE algorithm, <i>IRAK3</i> was verified to be related to poor immune checkpoint blockade (ICB) response. <i>IRAK3</i> 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 <i>IRAK3</i> 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 <i>IRAK3</i> expression was predicted to be related with better responses to chemotherapeutic and molecular targeted drugs.</p><p><strong>Conclusions: </strong>Our findings indicated that <i>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"13 9","pages":"2139-2161"},"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}
Pub Date : 2024-09-30Epub Date: 2024-09-20DOI: 10.21037/tlcr-24-264
Erick Suazo-Zepeda, Willemijn J Maas, Petra C Vinke, T Jeroen N Hiltermann, Mieke J Aarts, Geertruida Hendrika de Bock, Marjolein A Heuvelmans
Background: Lung cancer is the leading cause of cancer mortality globally, with a 5-year survival rate of 10-20%. In recent years, immune checkpoint inhibitors (ICIs) have significantly improved overall survival (OS) in patients with lung cancer. The approval of nivolumab in 2015 marked a milestone in non-small cell lung cancer (NSCLC) treatment, leading to ongoing trials and approvals of new ICI drugs that have reshaped treatment strategies and clinical outcomes for patients with lung cancer. This study aims to describe ICIs prescription trends for NSCLC in the Netherlands and their association with survival. We compared our results with data from randomized controlled trials (RCTs).
Methods: We analyzed ICIs prescription trends and their relationship with survival using national-level data from the Netherlands Cancer Registry (NCR) for first-line treatments from 2016-2020. Additionally, we performed a secondary analysis using data from the Oncological Life Study (OncoLifeS) for any-line treatments. Descriptive statistics and annual percentage change (APC) assessed trends in patient and treatment characteristics. OS analyses were performed.
Results: In the Netherlands (2016-2020), the proportion of first-line ICI-treated NSCLC patients significantly increased from 1.1% to 54.9% (APC =14.5%, P=0.002), replacing chemotherapy monotherapy. Stage III ICI-treated patients' proportion increased (APC =3.5%, P=0.034), while the proportion of ICI-treated patients with ≥50% programmed death-ligand 1 (PD-L1) expression decreased (APC =-13.82%, P=0.04). Two-year OS was 25.9%. Median OS remained stable, increasing from 2016 to 2018 (16.6 to 19.4 months) and declining slightly in 2019 and 2020 (17.3 and 16.6 months, respectively). In the secondary analysis, median OS varied by treatment line, being 18.8, 9.4 and 7.5 months for first-, second- and third-line treated patients respectively.
Conclusions: Using real-world data, we determined that ICI-based therapies replaced chemotherapy-only schemes as first-line treatment for NSCLC. Our survival data are comparable with data from RCTs on first-line ICI-treated NSCLC. Median OS of ICI treated patients has remained stable, with small decreases in recent years possibly attributed to the proportional decrease of individuals with high PD-L1 expressions in treatment regimens. Further-line treatments are associated with lower survival.
{"title":"Trends in the prescription of immune checkpoint inhibitors for non-small cell lung cancer in the Netherlands from 2016 to 2020, a national cancer registry analysis.","authors":"Erick Suazo-Zepeda, Willemijn J Maas, Petra C Vinke, T Jeroen N Hiltermann, Mieke J Aarts, Geertruida Hendrika de Bock, Marjolein A Heuvelmans","doi":"10.21037/tlcr-24-264","DOIUrl":"10.21037/tlcr-24-264","url":null,"abstract":"<p><strong>Background: </strong>Lung cancer is the leading cause of cancer mortality globally, with a 5-year survival rate of 10-20%. In recent years, immune checkpoint inhibitors (ICIs) have significantly improved overall survival (OS) in patients with lung cancer. The approval of nivolumab in 2015 marked a milestone in non-small cell lung cancer (NSCLC) treatment, leading to ongoing trials and approvals of new ICI drugs that have reshaped treatment strategies and clinical outcomes for patients with lung cancer. This study aims to describe ICIs prescription trends for NSCLC in the Netherlands and their association with survival. We compared our results with data from randomized controlled trials (RCTs).</p><p><strong>Methods: </strong>We analyzed ICIs prescription trends and their relationship with survival using national-level data from the Netherlands Cancer Registry (NCR) for first-line treatments from 2016-2020. Additionally, we performed a secondary analysis using data from the Oncological Life Study (OncoLifeS) for any-line treatments. Descriptive statistics and annual percentage change (APC) assessed trends in patient and treatment characteristics. OS analyses were performed.</p><p><strong>Results: </strong>In the Netherlands (2016-2020), the proportion of first-line ICI-treated NSCLC patients significantly increased from 1.1% to 54.9% (APC =14.5%, P=0.002), replacing chemotherapy monotherapy. Stage III ICI-treated patients' proportion increased (APC =3.5%, P=0.034), while the proportion of ICI-treated patients with ≥50% programmed death-ligand 1 (PD-L1) expression decreased (APC =-13.82%, P=0.04). Two-year OS was 25.9%. Median OS remained stable, increasing from 2016 to 2018 (16.6 to 19.4 months) and declining slightly in 2019 and 2020 (17.3 and 16.6 months, respectively). In the secondary analysis, median OS varied by treatment line, being 18.8, 9.4 and 7.5 months for first-, second- and third-line treated patients respectively.</p><p><strong>Conclusions: </strong>Using real-world data, we determined that ICI-based therapies replaced chemotherapy-only schemes as first-line treatment for NSCLC. Our survival data are comparable with data from RCTs on first-line ICI-treated NSCLC. Median OS of ICI treated patients has remained stable, with small decreases in recent years possibly attributed to the proportional decrease of individuals with high PD-L1 expressions in treatment regimens. Further-line treatments are associated with lower survival.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"13 9","pages":"2202-2211"},"PeriodicalIF":4.0,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11484730/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475701","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: Immune-associated genes play vital roles in the tumorigenesis, progression and immunotherapy responses of malignant tumors. This study aimed to comprehensively evaluate the role and mechanism of novel immune-associated gene integrin β4 (ITGB4) in the progression and immune microenvironment of lung adenocarcinoma (LUAD).
Methods: There were 770 immune-associated genes curated from NanoString PanCancer Immune Profiling Panel. Differentially expressed immune-related genes were initially screened using transcriptome data from 57 paired LUAD samples in The Cancer Genome Atlas (TCGA) and 15 paired LUAD samples in GSE31210, and were further validated in 19 paired LUAD samples from our institution. Log-rank test was adopted to identify LUAD prognosis associated genes. Among the identified differentially expressed genes, ITGB4 was ultimately chosen for further analysis. Subsequently, the functionality and mechanisms of ITGB4 were investigated in two LUAD cell lines, A549 and PC9, which exhibited relatively high expression levels of ITGB4. Following this, the impact of ITGB4 on the proliferation and metastasis of LUAD in vivo was evaluated using nude mice. Additionally, its effect on T cell infiltration was studied using immunocompetent C57BL/6J mice.
Results: ITGB4 was found to be significantly up-regulated in LUAD and associated with an unfavorable prognosis. Functionally, ITGB4 could promote LUAD cell proliferation, migration and invasion. Consistently, in vivo experiments demonstrated that ITGB4 knockdown suppressed LUAD tumor growth and metastasis. Additionally, ITGB4 could suppress CD4+ and CD8+ T-cell infiltrations in LUAD cells. Mechanistically, ITGB4 could activate the NF-κB signaling pathway by interacting with IκBα. Furthermore, TFAP2A could directly bind to the ITGB4 promoter and transcriptionally activate ITGB4 in LUAD cells. In addition, laminin-5, a ligand of ITGB4, was found to promote LUAD progression by activating the ITGB4 signaling.
Conclusions: ITGB4 was transcriptionally activated by TFAP2A, and could promote LUAD progression and inhibit CD4+/CD8+ T-cell infiltrations by activating the NF-κB signaling pathway. ITGB4 may serve as a potential immunotherapeutic target of LUAD.
{"title":"<i>TFAP2A</i>-activated <i>ITGB4</i> promotes lung adenocarcinoma progression and inhibits CD4<sup>+</sup>/CD8<sup>+</sup> T-cell infiltrations by targeting <i>NF-κB</i> signaling pathway.","authors":"Cheng Pan, Zhibo Wang, Qi Wang, Hongshun Wang, Xiaheng Deng, Liang Chen, Zhihua Li","doi":"10.21037/tlcr-24-50","DOIUrl":"10.21037/tlcr-24-50","url":null,"abstract":"<p><strong>Background: </strong>Immune-associated genes play vital roles in the tumorigenesis, progression and immunotherapy responses of malignant tumors. This study aimed to comprehensively evaluate the role and mechanism of novel immune-associated gene integrin β4 (<i>ITGB4</i>) in the progression and immune microenvironment of lung adenocarcinoma (LUAD).</p><p><strong>Methods: </strong>There were 770 immune-associated genes curated from NanoString PanCancer Immune Profiling Panel. Differentially expressed immune-related genes were initially screened using transcriptome data from 57 paired LUAD samples in The Cancer Genome Atlas (TCGA) and 15 paired LUAD samples in GSE31210, and were further validated in 19 paired LUAD samples from our institution. Log-rank test was adopted to identify LUAD prognosis associated genes. Among the identified differentially expressed genes, <i>ITGB4</i> was ultimately chosen for further analysis. Subsequently, the functionality and mechanisms of <i>ITGB4</i> were investigated in two LUAD cell lines, A549 and PC9, which exhibited relatively high expression levels of <i>ITGB4</i>. Following this, the impact of <i>ITGB4</i> on the proliferation and metastasis of LUAD <i>in vivo</i> was evaluated using nude mice. Additionally, its effect on T cell infiltration was studied using immunocompetent C57BL/6J mice.</p><p><strong>Results: </strong><i>ITGB4</i> was found to be significantly up-regulated in LUAD and associated with an unfavorable prognosis. Functionally, <i>ITGB4</i> could promote LUAD cell proliferation, migration and invasion. Consistently, <i>in vivo</i> experiments demonstrated that <i>ITGB4</i> knockdown suppressed LUAD tumor growth and metastasis. Additionally, <i>ITGB4</i> could suppress CD4<sup>+</sup> and CD8<sup>+</sup> T-cell infiltrations in LUAD cells. Mechanistically, <i>ITGB4</i> could activate the <i>NF-κB</i> signaling pathway by interacting with <i>IκBα</i>. Furthermore, <i>TFAP2A</i> could directly bind to the <i>ITGB4</i> promoter and transcriptionally activate <i>ITGB4</i> in LUAD cells. In addition, <i>laminin-5</i>, a ligand of <i>ITGB4</i>, was found to promote LUAD progression by activating the <i>ITGB4</i> signaling.</p><p><strong>Conclusions: </strong><i>ITGB4</i> was transcriptionally activated by <i>TFAP2A</i>, and could promote LUAD progression and inhibit CD4<sup>+</sup>/CD8<sup>+</sup> T-cell infiltrations by activating the <i>NF-κB</i> signaling pathway. <i>ITGB4</i> may serve as a potential immunotherapeutic target of LUAD.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"13 9","pages":"2116-2138"},"PeriodicalIF":4.0,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11484716/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475651","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 : 2024-09-30Epub Date: 2024-09-27DOI: 10.21037/tlcr-24-252
Ying Ji, Qing Zhao, Yi Liu, Bin Qiu, Guangyu Bai, Siyuan Ai, Wei Feng, Ligong Yuan, Xin Wang, Lulu Rong, Hua Fu, Huihui Xie, Linlin Qi, Ye Tao, Longyu Jin, Jing Zhou, Bin Hu, Shugeng Gao
Background: The prognostic predictors of the synchronous multiple primary lung cancer (SMPLC) still remain unclear, and there is a lack of studies on the prognosis of SMPLC patients excluding those with multifocal ground-glass/lepidic (GG/L) nodules. The aim of this study is to develop an effective model for predicting survival of SMPLC patients.
Methods: In this multicenter cohort study, a total of 831 SMPLC patients presenting for lung cancer resection from January 2004 to January 2018 at five institutions were included for developing and validating a nomogram model. Specifically, 499 patients from the Cancer Hospital, Chinese Academy of Medical Sciences, and Beijing Chao-Yang Hospital, Capital Medical University were served as the training cohort. A total of 332 patients from The Third Xiangya Hospital of Central South University, the First Affiliated Hospital of University of Science and Technology of China, and Beijing Liangxiang Hospital were served as the external validation cohort. The nomogram model was compared with the Tumor Node Metastasis (TNM) system for the overall survival. The C-index, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were used to evaluate the model performance. A user-friendly website for SMPLC survival probability calculation was also provided for a better understanding of prognosis of patients with resected SMPLC.
Results: A total of seven independent risk factors were selected by conducting a multivariate analysis on the training set. Further, a nomogram model was developed with these factors. Both the internal and external validations exhibited good discrimination (C-index: internal, 0.827; external, 0.784). The NRI and IDI of this model were 0.33 and 0.21, respectively. The survival rates for 1-year, 3-year, and 5-year were consistent with the actual observed values. A set of cutoff values were determined by grouping the patients into three different groups. For each group, we should expect a significant distinction between survival curves.
Conclusions: The novel nomogram model enables accurate survival risk stratification of patients with resected SMPLC and may assist in decision-making that is conducive to patients with SMPLC at high risk.
{"title":"Establishment of a survival predictive model for patients with two synchronous multiple primary lung cancers: a multicenter cohort analysis.","authors":"Ying Ji, Qing Zhao, Yi Liu, Bin Qiu, Guangyu Bai, Siyuan Ai, Wei Feng, Ligong Yuan, Xin Wang, Lulu Rong, Hua Fu, Huihui Xie, Linlin Qi, Ye Tao, Longyu Jin, Jing Zhou, Bin Hu, Shugeng Gao","doi":"10.21037/tlcr-24-252","DOIUrl":"10.21037/tlcr-24-252","url":null,"abstract":"<p><strong>Background: </strong>The prognostic predictors of the synchronous multiple primary lung cancer (SMPLC) still remain unclear, and there is a lack of studies on the prognosis of SMPLC patients excluding those with multifocal ground-glass/lepidic (GG/L) nodules. The aim of this study is to develop an effective model for predicting survival of SMPLC patients.</p><p><strong>Methods: </strong>In this multicenter cohort study, a total of 831 SMPLC patients presenting for lung cancer resection from January 2004 to January 2018 at five institutions were included for developing and validating a nomogram model. Specifically, 499 patients from the Cancer Hospital, Chinese Academy of Medical Sciences, and Beijing Chao-Yang Hospital, Capital Medical University were served as the training cohort. A total of 332 patients from The Third Xiangya Hospital of Central South University, the First Affiliated Hospital of University of Science and Technology of China, and Beijing Liangxiang Hospital were served as the external validation cohort. The nomogram model was compared with the Tumor Node Metastasis (TNM) system for the overall survival. The C-index, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were used to evaluate the model performance. A user-friendly website for SMPLC survival probability calculation was also provided for a better understanding of prognosis of patients with resected SMPLC.</p><p><strong>Results: </strong>A total of seven independent risk factors were selected by conducting a multivariate analysis on the training set. Further, a nomogram model was developed with these factors. Both the internal and external validations exhibited good discrimination (C-index: internal, 0.827; external, 0.784). The NRI and IDI of this model were 0.33 and 0.21, respectively. The survival rates for 1-year, 3-year, and 5-year were consistent with the actual observed values. A set of cutoff values were determined by grouping the patients into three different groups. For each group, we should expect a significant distinction between survival curves.</p><p><strong>Conclusions: </strong>The novel nomogram model enables accurate survival risk stratification of patients with resected SMPLC and may assist in decision-making that is conducive to patients with SMPLC at high risk.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"13 9","pages":"2254-2268"},"PeriodicalIF":4.0,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11484729/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475670","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 : 2024-09-30Epub Date: 2024-09-04DOI: 10.21037/tlcr-24-506
Weiran Liu, Chen Chen, Qiang Zhang, Jiping Xie, Xinyi Wu, Zhenfa Zhang, Lin Shao, Haiwei Du, Songan Chen, Hirokazu Iso, Kakeru Hisakane, Dongsheng Yue, Bin Zhang
Background: The benefit of adjuvant therapy remains controversial in completely resected (R0) stage IB non-small cell lung cancer (NCLSC) patients. In this study, we aimed to explore potential prognostic factors in stage IB NSCLC patients.
Methods: This study included 215 patients with R0 stage IB lung adenocarcinoma (LUAD) (tumor size: 3-4 cm). DNA sequencing was performed with surgical samples of 126 patients using a panel of 9 driver genes. The molecular risk stratification was assessed by a 14-gene quantitative polymerase chain reaction assay.
Results: Among the 215 patients, 67.9% had micropapillary/solid (MIP/SOL)-predominant tumors. Epidermal growth factor receptor (EGFR) mutations were detected in 75 of 126 patients (59.5%). MIP/SOL tumors harbored less common EGFR mutations than the other histologic patterns (50.6% vs. 79.5%, P=0.003). Molecular risk stratification was successfully assessed in 99 patients, of whom 37.4%, 26.3%, and 36.4% were high, intermediate, and low risk, respectively. The MIP/SOL pattern was associated with shorter disease-free survival (DFS) [hazard ratio (HR) =2.16, 95% confidence interval: 1.28-3.67; P=0.01]. The molecular high-risk patients had shorter DFS than the low- (HR =2.93, P=0.01) and intermediate-risk patients (HR =2.35, P=0.06). The prognostic value of molecular risk stratification was also significant in the MIP/SOL subset (median DFS high-risk: 45 months, low and intermediate risk: not reached; P=0.03).
Conclusions: Our study showed that both the MIP/SOL pattern and molecular high-risk category were adverse prognostic factors in stage IB NSCLC patients. Our results suggest that combining histologic classification and molecular risk stratification may help to identify the subset of patients with poor prognosis.
{"title":"Histopathologic pattern and molecular risk stratification are associated with prognosis in patients with stage IB lung adenocarcinoma.","authors":"Weiran Liu, Chen Chen, Qiang Zhang, Jiping Xie, Xinyi Wu, Zhenfa Zhang, Lin Shao, Haiwei Du, Songan Chen, Hirokazu Iso, Kakeru Hisakane, Dongsheng Yue, Bin Zhang","doi":"10.21037/tlcr-24-506","DOIUrl":"10.21037/tlcr-24-506","url":null,"abstract":"<p><strong>Background: </strong>The benefit of adjuvant therapy remains controversial in completely resected (R0) stage IB non-small cell lung cancer (NCLSC) patients. In this study, we aimed to explore potential prognostic factors in stage IB NSCLC patients.</p><p><strong>Methods: </strong>This study included 215 patients with R0 stage IB lung adenocarcinoma (LUAD) (tumor size: 3-4 cm). DNA sequencing was performed with surgical samples of 126 patients using a panel of 9 driver genes. The molecular risk stratification was assessed by a 14-gene quantitative polymerase chain reaction assay.</p><p><strong>Results: </strong>Among the 215 patients, 67.9% had micropapillary/solid (MIP/SOL)-predominant tumors. Epidermal growth factor receptor (<i>EGFR</i>) mutations were detected in 75 of 126 patients (59.5%). MIP/SOL tumors harbored less common <i>EGFR</i> mutations than the other histologic patterns (50.6% <i>vs.</i> 79.5%, P=0.003). Molecular risk stratification was successfully assessed in 99 patients, of whom 37.4%, 26.3%, and 36.4% were high, intermediate, and low risk, respectively. The MIP/SOL pattern was associated with shorter disease-free survival (DFS) [hazard ratio (HR) =2.16, 95% confidence interval: 1.28-3.67; P=0.01]. The molecular high-risk patients had shorter DFS than the low- (HR =2.93, P=0.01) and intermediate-risk patients (HR =2.35, P=0.06). The prognostic value of molecular risk stratification was also significant in the MIP/SOL subset (median DFS high-risk: 45 months, low and intermediate risk: not reached; P=0.03).</p><p><strong>Conclusions: </strong>Our study showed that both the MIP/SOL pattern and molecular high-risk category were adverse prognostic factors in stage IB NSCLC patients. Our results suggest that combining histologic classification and molecular risk stratification may help to identify the subset of patients with poor prognosis.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"13 9","pages":"2424-2434"},"PeriodicalIF":4.0,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11484734/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475681","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: Use of immune checkpoint inhibitors (ICIs) is associated with new response types, such as hyperprogressive disease (HPD), whose definition is still being discussed. Some authors use dynamic indexes to define HPD. However, since the Checkmate-743 study, ICIs have been a first-line therapy for pleural mesothelioma (PM), thereby making use of dynamic indexes less appropriate. The aim of this study is to describe two cases of HPD and then discuss its definitions and implications.
Case description: Herein, we report two cases of PM HPD on first-line ICI therapy. A 67-year-old man with right unresectable epithelioid PM, without BAP1 or CDKN2A losses, high neutrophil/lymphocyte ratio and rapid-onset pulmonary and mediastinal HPD after two ICI cycles, died of respiratory failure 1 month after starting treatment. A 40-year-old woman with left unresectable epithelioid PM had HPD at first assessment after 4 ICI infusions with jugular thrombosis, liver metastases and more dismal biological parameters. There are multiple different ways to describe HPD, some not applicable to PM. Suspected mechanisms include macrophage reprogramming to M2 cells. There are no known predictive factors of HPD, and future works should focus on identifying them.
Conclusions: HPD is a mode of progression for ICI-treated PM patients. Further investigation is needed to better define and anticipate HPD in these patients.
{"title":"Double immune checkpoint inhibitor therapy for unresectable pleural mesothelioma rarely induces hyperprogressive disease: a case report.","authors":"Gaspard Naulleau, Isabelle Monnet, Gaëlle Rousseau-Bussac, Florent Vinas, Gilles Mangiapan, Laurence Jabot, Amel Boudjemaa, Christos Chouaïd, Jean-Bernard Auliac, Jean-Baptiste Assié","doi":"10.21037/tlcr-24-382","DOIUrl":"10.21037/tlcr-24-382","url":null,"abstract":"<p><strong>Background: </strong>Use of immune checkpoint inhibitors (ICIs) is associated with new response types, such as hyperprogressive disease (HPD), whose definition is still being discussed. Some authors use dynamic indexes to define HPD. However, since the Checkmate-743 study, ICIs have been a first-line therapy for pleural mesothelioma (PM), thereby making use of dynamic indexes less appropriate. The aim of this study is to describe two cases of HPD and then discuss its definitions and implications.</p><p><strong>Case description: </strong>Herein, we report two cases of PM HPD on first-line ICI therapy. A 67-year-old man with right unresectable epithelioid PM, without <i>BAP1</i> or <i>CDKN2A</i> losses, high neutrophil/lymphocyte ratio and rapid-onset pulmonary and mediastinal HPD after two ICI cycles, died of respiratory failure 1 month after starting treatment. A 40-year-old woman with left unresectable epithelioid PM had HPD at first assessment after 4 ICI infusions with jugular thrombosis, liver metastases and more dismal biological parameters. There are multiple different ways to describe HPD, some not applicable to PM. Suspected mechanisms include macrophage reprogramming to M2 cells. There are no known predictive factors of HPD, and future works should focus on identifying them.</p><p><strong>Conclusions: </strong>HPD is a mode of progression for ICI-treated PM patients. Further investigation is needed to better define and anticipate HPD in these patients.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"13 9","pages":"2448-2452"},"PeriodicalIF":4.0,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11484718/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475666","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 : 2024-09-30Epub Date: 2024-09-25DOI: 10.21037/tlcr-24-291
Yuxin Jiang, Tao Liu, Ke Xu, Qinpei Cheng, Wanjun Lu, Jingyuan Xie, Mo Chen, Yu Li, Yanjun Du, Shuo Liang, Yong Song, Jiang Wu, Tangfeng Lv, Ping Zhan
<p><strong>Background: </strong>Frequently recurrent malignant pleural effusion (MPE) significantly hampers the life quality of advanced non-small cell lung cancer (NSCLC) patients. We aimed to explore the effects of progression patterns and local intervention on MPE recurrence and apply fluorodeoxyglucose positron emission tomography/computed tomography (<sup>18</sup>F-FDG PET/CT) to establish a predictive model for MPE recurrence in NSCLC.</p><p><strong>Methods: </strong>We retrospectively recruited two cohorts of patients including treatment-naïve NSCLC diagnosed with MPE at the onset and receiving PET/CT scanning, as well as those with MPE and undergoing first-line epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) treatment. Pleural maximum standardized uptake value (SUV<sub>max</sub>), metabolic tumor burden (MTV), total lesion glycolysis (TLG), and uptake patterns as well as SUV<sub>max</sub> of lymph nodes (LN) were extracted. The primary outcome was MPE recurrence defined as re-accumulation of cytologically proven ipsilateral MPE. Step-wise multivariate Cox regression was used to identify candidate variables. Cox regression analysis and random survival forest were applied to establish models.</p><p><strong>Results: </strong>A total of 148 treatment-naïve patients with EGFR-TKI treatment and MPE were recruited during the median follow-up period of 683 days, with 69 (46.6%) and 35 (23.6%) witnessing MPE recurrence at least once and twice. Intrapleural perfusion therapy at first recurrence was a protective factor for the second MPE recurrence (P=0.006), while intrapleural perfusion therapy at baseline could not benefit the first MPE recurrence (P=0.14). Conversely, prior systemic progression indicative of the change of systemic treatment was a protective factor for time to the first MPE recurrence (P<0.001); instead, the change of systemic treatment at the first MPE recurrence was not associated with second MPE recurrence (P=0.53). In another cohort with treatment-naïve NSCLC patients with MPE and PET/CT scanning, 103 patients regardless of the actionable mutation status were recruited during the median follow-up period of 304 days. Multivariate analysis suggested that the LN SUV<sub>max</sub> >4.50 g/mL [hazard ratio (HR), 2.54; P=0.01], female gender (HR, 0.40; P=0.01), bone metastases (HR, 3.16; P=0.001), and systemic treatment (targeted therapy <i>vs.</i> chemotherapy: HR, 0.32; P=0.002; immunotherapy therapy <i>vs.</i> chemotherapy: HR, 0.99; P=0.97) could collectively indicate MPE recurrence with an optimal 300-day area under the curve (AUC) of 0.83. For patients with actionable mutation, LN SUV<sub>max</sub> >4.50 g/mL (P=0.02) could forecast MPE recurrence independently.</p><p><strong>Conclusions: </strong>In summary, LN rather than pleural metabolic activity or uptake patterns could predict MPE recurrence for patients with or without targeted therapy. We should re-consider the application of intrapleural perfus
{"title":"Lymph nodes rather than pleural metabolic activity in <sup>18</sup>F-FDG PET/CT correlates with malignant pleural effusion recurrence in advanced non-small cell lung cancer.","authors":"Yuxin Jiang, Tao Liu, Ke Xu, Qinpei Cheng, Wanjun Lu, Jingyuan Xie, Mo Chen, Yu Li, Yanjun Du, Shuo Liang, Yong Song, Jiang Wu, Tangfeng Lv, Ping Zhan","doi":"10.21037/tlcr-24-291","DOIUrl":"10.21037/tlcr-24-291","url":null,"abstract":"<p><strong>Background: </strong>Frequently recurrent malignant pleural effusion (MPE) significantly hampers the life quality of advanced non-small cell lung cancer (NSCLC) patients. We aimed to explore the effects of progression patterns and local intervention on MPE recurrence and apply fluorodeoxyglucose positron emission tomography/computed tomography (<sup>18</sup>F-FDG PET/CT) to establish a predictive model for MPE recurrence in NSCLC.</p><p><strong>Methods: </strong>We retrospectively recruited two cohorts of patients including treatment-naïve NSCLC diagnosed with MPE at the onset and receiving PET/CT scanning, as well as those with MPE and undergoing first-line epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) treatment. Pleural maximum standardized uptake value (SUV<sub>max</sub>), metabolic tumor burden (MTV), total lesion glycolysis (TLG), and uptake patterns as well as SUV<sub>max</sub> of lymph nodes (LN) were extracted. The primary outcome was MPE recurrence defined as re-accumulation of cytologically proven ipsilateral MPE. Step-wise multivariate Cox regression was used to identify candidate variables. Cox regression analysis and random survival forest were applied to establish models.</p><p><strong>Results: </strong>A total of 148 treatment-naïve patients with EGFR-TKI treatment and MPE were recruited during the median follow-up period of 683 days, with 69 (46.6%) and 35 (23.6%) witnessing MPE recurrence at least once and twice. Intrapleural perfusion therapy at first recurrence was a protective factor for the second MPE recurrence (P=0.006), while intrapleural perfusion therapy at baseline could not benefit the first MPE recurrence (P=0.14). Conversely, prior systemic progression indicative of the change of systemic treatment was a protective factor for time to the first MPE recurrence (P<0.001); instead, the change of systemic treatment at the first MPE recurrence was not associated with second MPE recurrence (P=0.53). In another cohort with treatment-naïve NSCLC patients with MPE and PET/CT scanning, 103 patients regardless of the actionable mutation status were recruited during the median follow-up period of 304 days. Multivariate analysis suggested that the LN SUV<sub>max</sub> >4.50 g/mL [hazard ratio (HR), 2.54; P=0.01], female gender (HR, 0.40; P=0.01), bone metastases (HR, 3.16; P=0.001), and systemic treatment (targeted therapy <i>vs.</i> chemotherapy: HR, 0.32; P=0.002; immunotherapy therapy <i>vs.</i> chemotherapy: HR, 0.99; P=0.97) could collectively indicate MPE recurrence with an optimal 300-day area under the curve (AUC) of 0.83. For patients with actionable mutation, LN SUV<sub>max</sub> >4.50 g/mL (P=0.02) could forecast MPE recurrence independently.</p><p><strong>Conclusions: </strong>In summary, LN rather than pleural metabolic activity or uptake patterns could predict MPE recurrence for patients with or without targeted therapy. We should re-consider the application of intrapleural perfus","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"13 9","pages":"2236-2253"},"PeriodicalIF":4.0,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11484712/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475684","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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号