Lung Cancer最新文献

{"title":"MiR-137 mediated high expression of TIGD1 promotes migration, invasion, and suppresses apoptosis of lung adenocarcinoma","authors":"Yiqun Wei ,&nbsp;Runmiao Wu ,&nbsp;Shuanying Yang ,&nbsp;Yanfei Cao ,&nbsp;Jing Li ,&nbsp;Huihui Ma ,&nbsp;Junfang Wu ,&nbsp;Jinjin Duan ,&nbsp;Shumei Yang","doi":"10.1016/j.lungcan.2024.107918","DOIUrl":"10.1016/j.lungcan.2024.107918","url":null,"abstract":"<div><h3>Objectives</h3><p>Tigger transposable element-derived 1 (TIGD1) expression and its underlying functions and regulatory mechanisms in lung adenocarcinoma (LUAD) remain unknown. Therefore, we intended to explore the expression, potential functions, and regulatory mechanisms of TIGD1 in LUAD.</p></div><div><h3>Materials and methods</h3><p>TIGD1 expression in LUAD tissues was determined by immunohistochemistry analysis of a tissue microarray. Functional experiments were conducted to determine how TIGD1 affects LUAD tumorigenesis and metastasis. The molecular mechanisms by which TIGD1 induces LUAD progression were determined.</p></div><div><h3>Results</h3><p>TIGD1 was upregulated in LUAD tissues and was related to lymph node metastases. TIGD1 knockdown suppressed LUAD cell proliferation, migration, and invasion, while promoted cell apoptosis. Furthermore, decreased metastatic nodules were observed in the TIGD1 knockdown mouse metastasis model. Moreover, microarray analysis was performed to determine the potential downstream genes of TIGD1 in LUAD. Hallmark pathway analysis revealed that the downstream genes of TIGD1 were involved in epithelial-mesenchymal transition (EMT). Western blotting confirmed that vimentin and TWIST was downregulated in TIGD1 knockdown cells, while E-cadherin was upregulated. Ingenuity pathway and hallmark pathway analyses revealed that TIGD1 regulated the interleukin-6 signaling pathway and related gene members. Western blotting, quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay indicated that downregulation of TIGD1 decreased interleukin-6 and CXCL1 expression. TIGD1 expression was negatively correlated with immune infiltration in LUAD. The upstream microRNA of TIGD1 was predicted, and subsequent luciferase reporter gene experiments confirmed the interactions between miR-137 and TIGD1. The expression of miR-137 was significantly downregulated in LUAD tissues and miR-137 suppressed the proliferation, migration, and invasion of LUAD cells, partially through negatively regulating the expression of TIGD1.</p></div><div><h3>Conclusion</h3><p>Our findings suggest that TIGD1, which was regulated by miR-137, contributed to LUAD progression by promoting cell proliferation, migration, invasion, and EMT and suppressing cell apoptosis.</p></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"195 ","pages":"Article 107918"},"PeriodicalIF":4.5,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0169500224004525/pdfft?md5=1e665bf0e5a69be50ea5a3d4465969fc&pid=1-s2.0-S0169500224004525-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142020622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exomic and epigenomic analysis of pulmonary blastoma","authors":"Najmeh Alirezaie ,&nbsp;Anne-Laure Chong ,&nbsp;Felix K.F. Kommoss ,&nbsp;Nelly Sabbaghian ,&nbsp;Jose Camacho Valenzuela ,&nbsp;Dylan Pelletier ,&nbsp;Javad Nadaf ,&nbsp;Shailesh B. Kolekar ,&nbsp;Pradeesh Sivapalan ,&nbsp;Mark G. Evans ,&nbsp;Paul S. Thorner ,&nbsp;Pierre-Olivier Fiset ,&nbsp;Andreas von Deimling ,&nbsp;William D. Foulkes","doi":"10.1016/j.lungcan.2024.107916","DOIUrl":"10.1016/j.lungcan.2024.107916","url":null,"abstract":"<div><h3>Objective</h3><p>Pulmonary blastoma is a rare, biphasic, adult-onset lung tumor. In this study, we investigate whether DICER1 pathogenic variants are a feature of pulmonary blastomas through in-depth analysis of the molecular events defining them.</p></div><div><h3>Methods</h3><p>We performed exome-wide sequencing and DNA methylation profiling of 8 pulmonary blastomas from 6 affected persons.</p></div><div><h3>Results</h3><p>We identified biallelic somatic <em>DICER1</em> pathogenic variants in 7 of 8 cases. The remaining case had a solitary missense pathogenic variant in the RNase IIIb domain of DICER1. Six of 8 cases carried a <em>CTNNB1</em> hotspot variant and 4 of 8 had a somatic pathogenic variant in <em>TP53</em>. Methylation analysis showed that the pulmonary blastomas clustered with other <em>DICER1</em>-mutated tumors and not with other more common types of lung cancer.</p></div><div><h3>Conclusion</h3><p>We conclude somatic <em>DICER1</em> pathogenic variants are the major driver of pulmonary blastoma and are likely to act in conjunction with <em>CTNNB1</em> hotspot variants that are often present.</p></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"195 ","pages":"Article 107916"},"PeriodicalIF":4.5,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141913176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms of resistance and correlation between pre-treatment co-alterations and p-prognosis to osimertinib in chemo-naïve advanced non-small cell lung cancer","authors":"Akihiro Tamiya ,&nbsp;Mitsuo Osuga ,&nbsp;Daijiro Harada ,&nbsp;Shun-ichi Isa ,&nbsp;Yoshihiko Taniguchi ,&nbsp;Keiichi Nakamura ,&nbsp;Yasuyuki Mizumori ,&nbsp;Tsutomu Shinohara ,&nbsp;Hidetoshi Yanai ,&nbsp;Katsumi Nakatomi ,&nbsp;Masahide Oki ,&nbsp;Masahide Mori ,&nbsp;Tomohito Kuwako ,&nbsp;Koji Yamazaki ,&nbsp;Atsuhisa Tamura ,&nbsp;Masahiko Ando ,&nbsp;Yasuhiro Koh","doi":"10.1016/j.lungcan.2024.107917","DOIUrl":"10.1016/j.lungcan.2024.107917","url":null,"abstract":"<div><h3>Background</h3><p>Several patients treated with osimertinib experience progressive disease. The aim was to clarify the mechanisms underlying resistance to osimertinib.</p></div><div><h3>Methods</h3><p>ELUCIDATOR: A multi-centre, prospective, observational study involved chemotherapy-naive patients with advanced non-small cell lung cancer receiving osimertinib. Mutations in cancer-associated genes, detected via ultrasensitive next-generation sequencing of circulating tumour deoxyribonucleic acid samples, were collected at baseline and after progressive disease detection. These paired plasma samples were compared.</p></div><div><h3>Results</h3><p>Of 188 patients enrolled (May 2019-January 2021), 178 (119 females [67 %]) median age 74 years, were included. Patients, n = 95 (53 %) had epidermal growth factor receptor exon 19 deletion mutations. Among 115 patients with progressive disease, circulating tumour deoxyribonucleic acid levels of 85 patients were analysed. <em>MET</em> amplification (n = 4), <em>TP53</em> mutations (n = 4), <em>PIK3CA</em> mutations (n = 3), <em>BRINP3</em> mutation (n = 2), <em>BRAF</em> mutation (n = 2), <em>APC</em> mutation (n = 1), <em>RET</em> mutation (n = 1) and epidermal growth factor receptor (EGFR) resistance mutation, and <em>C797S</em> (n = 1) were detected. Patients with baseline <em>TP53</em> mutations, with <em>MET</em> or <em>EGFR</em> amplification had shorter progression-free (PFS) and overall survival. Patients with <em>PIK3CA</em> mutations tended to shorter PFS.</p></div><div><h3>Conclusion</h3><p><em>MET</em> amplification and <em>PIK3CA</em> mutation mechanisms underly resistance to osimertinib in patients. Patients with coexisting mutations or amplifications at baseline had shorter PFS and overall survival.</p></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"195 ","pages":"Article 107917"},"PeriodicalIF":4.5,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0169500224004513/pdfft?md5=e2dc34b44774c91db765513395ec6f32&pid=1-s2.0-S0169500224004513-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141906924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-world treatment sequencing and effectiveness of second- and third-generation ALK tyrosine kinase inhibitors for ALK-positive advanced non-small cell lung cancer","authors":"Jessica R. Bauman ,&nbsp;Geoffrey Liu ,&nbsp;Isabel Preeshagul ,&nbsp;Stephen V. Liu ,&nbsp;Barbara Melosky ,&nbsp;Devin Abrahami ,&nbsp;Benjamin Li ,&nbsp;Despina Thomaidou ,&nbsp;Kirsten Duncan ,&nbsp;Stan Krulewicz ,&nbsp;Martin Rupp ,&nbsp;Jessica J. Lin","doi":"10.1016/j.lungcan.2024.107919","DOIUrl":"10.1016/j.lungcan.2024.107919","url":null,"abstract":"<div><h3>Introduction</h3><p>With multiple targeted therapies approved for anaplastic lymphoma kinase (<em>ALK</em>)-positive metastatic non-small cell lung cancer (NSCLC), it is increasingly important to understand outcomes with various sequences of next-generation ALK tyrosine kinase inhibitors (TKIs). We describe contemporary sequencing patterns and treatment effectiveness of first-line (1L) and second-line (2L) treatments in patients who received second-generation ALK TKIs in the 1L treatment of <em>ALK</em>-positive NSCLC in the United States.</p></div><div><h3>Methods</h3><p>A cohort of adults with <em>ALK</em>-positive advanced NSCLC who initiated treatment with 1L alectinib or brigatinib between June 2017 and April 2021 in the Flatiron Health electronic health record–derived de-identified database were followed through April 2023. Time to treatment discontinuation (TTD) in 1L and 2L, TTD on 1L plus 2L sequential therapy (TTD2), and total time on sequential ALK TKI therapy (including beyond 2L) were evaluated.</p></div><div><h3>Results</h3><p>Patients (N=273) were followed up for a median duration of 28.9 months. Among patients who discontinued 1L therapy, 22% died after 1L discontinuation (median time from discontinuation to death, 4.0 months) without receiving 2L therapy. Median (95% confidence interval [CI]) TTD was 21.9 (15.2–25.8) and 7.3 (5.3–10.2) months in 1L and 2L, respectively. Median (95% CI) TTD2 was 29.4 (25.1–36.1) months and total time on sequential ALK TKI treatment was 28.0 (23.6–32.9) months.</p></div><div><h3>Conclusions</h3><p>In this large real-world study, TTD2 and the total time on sequential ALK TKIs was approximately 2.5 years. The high attrition rate from 1L to 2L and the longest clinical benefit observed with 1L therapy support using the drug with the longest 1L effectiveness up front in patients with <em>ALK</em>-positive advanced NSCLC.</p></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"195 ","pages":"Article 107919"},"PeriodicalIF":4.5,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0169500224004537/pdfft?md5=2afdf40f65a7de10dc42f9698cd2bb4c&pid=1-s2.0-S0169500224004537-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142083470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of pregabalin combined with tramadol/paracetamol on acute pain in patients with CT-guided puncture localization of pulmonary nodules","authors":"Qingfeng Wang ,&nbsp;Hongyan Liu ,&nbsp;Zhibiao Xu ,&nbsp;Li Zhang ,&nbsp;Yuyun Liu ,&nbsp;Han Gao ,&nbsp;Yunru Jiang ,&nbsp;Linlin Zhao","doi":"10.1016/j.lungcan.2024.107888","DOIUrl":"10.1016/j.lungcan.2024.107888","url":null,"abstract":"<div><h3>Objective</h3><p>To investigate the effects of pregabalin combined with tramadol/paracetamol on acute pain in patients with CT-guided puncture localization of pulmonary nodules.</p></div><div><h3>Materials and Methods</h3><p>In this randomized, placebo-controlled and single-center study, 120 patients were allocated randomly to four groups: the control group (Group P), the pregabalin-placebo group (Group BP), the tramadol/paracetamol-placebo group (Group AP), and the pregabalin-tramadol/paracetamol group (Group AB). The primary outcome was the NRS (Numerical Rating Scale) score. Other outcomes included systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), pulse oxygen saturation (SpO₂), the incidence of moderate to severe pain, the analgesia recovery ratio, the incidence of adverse drug reactions and patients’ satisfaction.</p></div><div><h3>Results</h3><p>No significant interaction was detected between the interventions (<em>P</em> = 0.752). The NRS score of the Taking pregabalin group and the Taking tramadol/paracetamol group were significantly lower than those of the Not-taking pregabalin group and the Not-taking tramadol/paracetamol group respectively (<em>P</em> &lt; 0.05). There was significant difference in the NRS scores among the four groups (<em>P</em> &lt; 0.001). The NRS score of Group AB was significantly lower than that of Group P (<em>P</em> &lt; 0.001), Group BP (<em>P</em> &lt; 0.001) and Group AP (<em>P</em> = 0.001). At the same time, the NRS scores of Group BP (<em>P</em> &lt; 0.001) and Group AP (<em>P</em> &lt; 0.001) were significantly lower than those of Group P, but there was no significant difference between Group BP and Group AP (<em>P</em> = 1.000). The SBP, DBP, HR, the incidence of moderate to severe pain and the analgesia recovery ratio of Group AB were significantly lower than those of Group P (<em>P</em> &lt; 0.05), while the SpO₂ and the number of people who were very satisfied were significantly higher than those of Group P (<em>P</em> &lt; 0.05). There was no significant difference in the incidence of adverse drug reactions among the four groups (<em>P</em> = 0.272).</p></div><div><h3>Conclusions</h3><p>The combination or single use of pregabalin and tramadol/paracetamol can effectively relieve the acute pain after localization. Pregabalin combined with tramadol/paracetamol has the best analgesic effect and significantly reduces the hemodynamic fluctuations, with high safety and low incidence of adverse drug reactions, which has a certain clinical popularization and application value.</p></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"194 ","pages":"Article 107888"},"PeriodicalIF":4.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141716885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analyzing diagnostic and treatment wait times for lung cancer Patients: Key insights from a provincial registry study","authors":"Manuel Luis Blanco-Villar ,&nbsp;José Expósito-Hernández ,&nbsp;Eulalia Navarro-Moreno ,&nbsp;José María López Martín ,&nbsp;Adrián Aparicio Mota ,&nbsp;Felipe Couñago","doi":"10.1016/j.lungcan.2024.107867","DOIUrl":"10.1016/j.lungcan.2024.107867","url":null,"abstract":"<div><h3>Background</h3><p>Lung cancer (LC) remains the leading cause of cancer-related mortality globally, necessitating timely diagnosis and treatment to improve patient outcomes. This study aimed to evaluate the timeliness of care for LC patients at a public hospital in Almería, Spain, assess adherence to guidelines, and explore associations between timeliness and survival.</p></div><div><h3>Methods</h3><p>A retrospective cohort study was conducted, reviewing medical records of LC patients diagnosed between 2019 and 2021. Quality indicators, adapted from prevailing guidelines, facilitated the assessment of care timeliness, with a focus on diagnostic and treatment wait times. Cox regression modeling was employed to explore survival associations, adjusting for covariates including age, performance status, stage, histology, and treatment modalities.</p></div><div><h3>Results</h3><p>Of 539 patients included, most (79.84 %) had initial specialist contact within 7 days, and 82.25 % received diagnosis within 30 days. However, delays were observed in treatment initiation, with surgery experiencing the longest median wait time (78 days). Survival analysis showed no significant difference between shorter and longer diagnostic (HR: 0.87, 95 % CI: 0.62–1.24) or treatment intervals (HR: 1.14, 95 % CI: 0.83–1.58). Multivariate analysis identified age, performance status, stage, histology, and treatment as prognostic factors.</p></div><div><h3>Conclusion</h3><p>This study highlights the importance of timely diagnosis and treatment in improving lung cancer outcomes. Despite achieving diagnostic targets, treatment delays were common, particularly for surgical interventions. These findings underscore the need for enhanced coordination and efficient care pathways to minimize delays, ultimately improving survival rates and quality of life for lung cancer patients. Addressing these issues is crucial for optimizing lung cancer care delivery in the future.</p></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"194 ","pages":"Article 107867"},"PeriodicalIF":4.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S016950022400401X/pdfft?md5=a15e9fda74ecb0b7efec9b08d70aed48&pid=1-s2.0-S016950022400401X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141759645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"First-line doublet immunotherapy: Game changer or hype for patients with mesothelioma?","authors":"L.H. Douma,&nbsp;P. Baas,&nbsp;C.J. de Gooijer","doi":"10.1016/j.lungcan.2024.107891","DOIUrl":"10.1016/j.lungcan.2024.107891","url":null,"abstract":"","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"194 ","pages":"Article 107891"},"PeriodicalIF":4.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141633912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment patterns and outcomes in KRASG12C‐positive advanced NSCLC patients previously treated with immune checkpoint inhibitors: A Canada-wide real-world, multi-center, retrospective cohort study","authors":"Samir H. Barghout ,&nbsp;Luna Jia Zhan ,&nbsp;Starvroula Raptis ,&nbsp;Faisal Al-Agha ,&nbsp;Niki Esfahanian ,&nbsp;Aimee Popovacki ,&nbsp;Goulnar Kasymjanova ,&nbsp;Francis Proulx-Rocray ,&nbsp;Sze Wah Samuel Chan ,&nbsp;Matthew Richardson ,&nbsp;M. Catherine Brown ,&nbsp;Devalben Patel ,&nbsp;Michelle Liane Dean ,&nbsp;Vishal Navani ,&nbsp;Erica Moore ,&nbsp;Lane Carvery ,&nbsp;Elizabeth Yan ,&nbsp;Daniel Goldshtein ,&nbsp;Jasmine Cleary-Gosine ,&nbsp;Amanda JW Gibson ,&nbsp;Stephanie Snow","doi":"10.1016/j.lungcan.2024.107898","DOIUrl":"10.1016/j.lungcan.2024.107898","url":null,"abstract":"<div><h3>Objectives</h3><p><em>KRAS</em> mutations, particularly <em>KRAS^G12C</em>, are prevalent in non-small cell lung cancer (NSCLC). Immune checkpoint inhibitors (ICIs) have been a frontline treatment, but recently developed KRAS^G12C-selective inhibitors, such as sotorasib, present new therapeutic options. We conducted a multi-center retrospective cohort study to gain insights into real-world treatment patterns and outcomes in patients with <em>KRAS^G12C</em>-positive advanced NSCLC receiving systemic therapy post-ICI treatment.</p></div><div><h3>Methods</h3><p>From the CAnadian CAncers With Rare Molecular Alterations-Basket Real-world Observational Study (CARMA-BROS), a cohort of 102 patients with <em>KRAS^G12C</em>-positive advanced NSCLC across 9 Canadian centers diagnosed between 2015 and 2021 was analyzed. Clinico-demographic and treatment data were obtained from electronic health records. Survival outcomes were assessed using Kaplan-Meier curves and Cox proportional hazards models.</p></div><div><h3>Results</h3><p>The patients (median age 66 years; 58 % female; 99 % current/former tobacco exposure; 59 % PD-L1 ≥ 50 %), exhibited heterogeneous treatment patterns post-ICI. Most patients received ICIs as a first-line therapy, with varying subsequent lines including chemotherapy and targeted therapy. In patients receiving systemic therapy post-ICI, median overall survival was 12.6 months, and real-world progression-free survival was 4.7 months. KRAS^G12C-selective targeted therapy post-ICI (n = 20) showed longer real-world progression-free survival compared to single-agent chemotherapy (aHR = 0.39, <em>p</em> = 0.012).</p></div><div><h3>Conclusion</h3><p>This study contributes valuable real-world data on <em>KRAS^G12C</em>-positive advanced NSCLC post-ICI treatment. The absence of a standard treatment sequencing post-ICI underscores the need for further investigation and consensus-building in the evolving landscape of KRAS^G12C-targeted therapies.</p></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"194 ","pages":"Article 107898"},"PeriodicalIF":4.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prediction of prognosis in lung cancer using machine learning with inter-institutional generalizability: A multicenter cohort study (WJOG15121L: REAL-WIND)","authors":"Daichi Fujimoto ,&nbsp;Hidetoshi Hayashi ,&nbsp;Kenta Murotani ,&nbsp;Yukihiro Toi ,&nbsp;Toshihide Yokoyama ,&nbsp;Terufumi Kato ,&nbsp;Teppei Yamaguchi ,&nbsp;Kaoru Tanaka ,&nbsp;Satoru Miura ,&nbsp;Motohiro Tamiya ,&nbsp;Motoko Tachihara ,&nbsp;Takehito Shukuya ,&nbsp;Yuko Tsuchiya-Kawano ,&nbsp;Yuki Sato ,&nbsp;Satoshi Ikeda ,&nbsp;Shinya Sakata ,&nbsp;Takeshi Masuda ,&nbsp;Shinnosuke Takemoto ,&nbsp;Kohei Otsubo ,&nbsp;Ryota Shibaki ,&nbsp;Nobuyuki Yamamoto","doi":"10.1016/j.lungcan.2024.107896","DOIUrl":"10.1016/j.lungcan.2024.107896","url":null,"abstract":"<div><h3>Objectives</h3><p>Predicting the prognosis of lung cancer is crucial for providing optimal medical care. However, a method to accurately predict the overall prognosis in patients with stage IV lung cancer, even with the use of machine learning, has not been established. Moreover, the inter-institutional generalizability of such algorithms remains unexplored. This study aimed to establish machine learning-based algorithms with inter-institutional generalizability to predict prognosis.</p></div><div><h3>Materials and Methods</h3><p>This multicenter, retrospective, hospital-based cohort study included consecutive patients with stage IV lung cancer who were randomly categorized into the training and independent test cohorts with a 2:1 ratio, respectively. The primary metric to assess algorithm performance was the area under the receiver operating characteristic curve in the independent test cohort. To assess the inter-institutional generalizability of the algorithms, we investigated their ability to predict patient outcomes in the remaining facility after being trained using data from 15 other facilities.</p></div><div><h3>Results</h3><p>Overall, 6,751 patients (median age, 70 years) were enrolled, and 1,515 (22 %) showed mutated epidermal growth factor receptor expression. The median overall survival was 16.6 (95 % confidence interval, 15.9–17.5) months. Algorithm performance metrics in the test cohort showed that the areas under the curves were 0.90 (95 % confidence interval, 0.88–0.91), 0.85 (0.84–0.87), 0.83 (0.81–0.85), and 0.85 (0.82–0.87) at 180, 360, 720, and 1,080 predicted survival days, respectively. The performance test of 16 algorithms for investigating inter-institutional generalizability showed median areas under the curves of 0.87 (range, 0.84–0.92), 0.84 (0.78–0.88), 0.84 (0.76–0.89), and 0.84 (0.75–0.90) at 180, 360, 720, and 1,080 days, respectively.</p></div><div><h3>Conclusion</h3><p>This study developed machine learning algorithms that could accurately predict the prognosis in patients with stage IV lung cancer with high inter-institutional generalizability. This can enhance the accuracy of prognosis prediction and support informed and shared decision-making in clinical settings.</p></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"194 ","pages":"Article 107896"},"PeriodicalIF":4.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141752092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The next-generation KRAS inhibitors…What comes after sotorasib and adagrasib?","authors":"Yuko Oya ,&nbsp;Kazuyoshi Imaizumi ,&nbsp;Tetsuya Mitsudomi","doi":"10.1016/j.lungcan.2024.107886","DOIUrl":"10.1016/j.lungcan.2024.107886","url":null,"abstract":"<div><p>The Kirsten rat sarcoma viral oncogene homolog (<em>KRAS</em>) is one of the first driver oncogenes identified in human cancer in the early 1980s. However, it has been deemed ’undruggable’ for nearly four decades until the discovery of KRAS G12C covalent inhibitors, which marked a pivotal breakthrough. Currently, sotorasib and adagrasib have been approved by the US FDA to treat patients with non-small cell lung cancer (NSCLC) harboring <em>KRAS</em> G12C mutation. However, their efficacy is somewhat limited compared to that of other targeted therapies owing to intrinsic resistance or early acquisition of resistance. While G12C is the predominant subtype of <em>KRAS</em> mutations in NSCLC, G12D/V is prevalent in colorectal and pancreatic cancers. These facts have spurred active research to develop more potent KRAS G12C inhibitors as well as inhibitors targeting non-G12C <em>KRAS</em> mutations. Novel approaches, such as molecular shielding or targeted protein degradation, are also under development. Combining KRAS inhibitors with inhibitors of the receptor-tyrosine kinase-RAS-mitogen-activated protein kinase (MAPK) pathway is underway to counteract redundant feedback mechanisms. Additionally, immunological approaches utilizing T-cell receptor (TCR)-engineered T cell therapy or vaccines, and Hapimmune antibodies are ongoing. This review delineates the recent advancements in KRAS inhibitor development in the post-sotorasib/adagrasib era, with a focus on NSCLC.</p></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"194 ","pages":"Article 107886"},"PeriodicalIF":4.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141696651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}