Lung Cancer最新文献

{"title":"PRIMALung (EORTC-1901): PRophylactic cerebral irradiation (PCI) or active brain MAgnetic resonance imaging (MRI) surveillance in small-cell lung cancer (SCLC) patients","authors":"Antonin Levy ,&nbsp;Thierry Berghmans ,&nbsp;Michael Koller ,&nbsp;Beatrice Fournier ,&nbsp;Murielle Mauer ,&nbsp;Nicolaus Andratschke ,&nbsp;Corinne Faivre-Finn","doi":"10.1016/j.lungcan.2024.107993","DOIUrl":"10.1016/j.lungcan.2024.107993","url":null,"abstract":"<div><div>The PRIMALung EORTC-1901 trial investigates brain MRI ± PCI in all-stages of SCLC, aiming for non-inferior survival, improve cognition in the era of immunotherapy.</div><div>@finn_corinne</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"198 ","pages":"Article 107993"},"PeriodicalIF":4.5,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621737","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":"Confronting synchronous multiple primary lung cancers: Navigating the intersection of challenges and opportunities","authors":"Xue He ,&nbsp;Zhihui Yang ,&nbsp;Fang Wu ,&nbsp;Qingchun Liang ,&nbsp;Wenliang Liu ,&nbsp;Fenglei Yu ,&nbsp;Chen Chen","doi":"10.1016/j.lungcan.2024.107994","DOIUrl":"10.1016/j.lungcan.2024.107994","url":null,"abstract":"<div><div>The increased detection of synchronous multiple primary lung cancers (sMPLC) through advanced computed tomography underscores the necessity for innovative therapeutic approaches. sMPLC typically manifests as ground-glass opacities, mixed ground-glass opacities, and/or solid nodules, predominantly in early-stage, non-smoking female patients, with a majority being adenocarcinomas. The high prevalence of EGFR mutations and considerable heterogeneity among lesions pose distinct diagnostic and therapeutic challenges for sMPLC. This study provides a comprehensive review and analysis of recent clinical and radiological studies, genomic profiling, and the efficacy of the “Surgery + X” treatment model for sMPLC. Additionally, the article discusses several intricate and complex sMPLC cases, shedding light on the disease’s complexities and identifying existing gaps and potential breakthroughs in clinical diagnosis, treatment, and research. It underscores the critical role of a multidisciplinary approach and advocates for targeted research on sMPLC, highlighting its potential to impact lung cancer research significantly.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"197 ","pages":"Article 107994"},"PeriodicalIF":4.5,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142503191","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":"Segmentectomy vs. Lobectomy in stage IA non-small cell lung cancer: A systematic review and meta-analysis of perioperative and survival outcomes","authors":"Luca Bertolaccini ,&nbsp;Antonino Carmelo Tralongo ,&nbsp;Marzia Del Re ,&nbsp;Francesco Facchinetti ,&nbsp;Roberto Ferrara ,&nbsp;Tindara Franchina ,&nbsp;Paolo Graziano ,&nbsp;Umberto Malapelle ,&nbsp;Jessica Menis ,&nbsp;Antonio Passaro ,&nbsp;Sara Pilotto ,&nbsp;Sara Ramella ,&nbsp;Giulio Rossi ,&nbsp;Rocco Trisolini ,&nbsp;Michela Cinquini ,&nbsp;Francesco Passiglia ,&nbsp;Silvia Novello","doi":"10.1016/j.lungcan.2024.107990","DOIUrl":"10.1016/j.lungcan.2024.107990","url":null,"abstract":"<div><div>While recent randomized controlled trials (RCT) have suggested superior overall survival (OS) outcomes with segmentectomy over lobectomy, questions remain regarding the comparability of these surgical procedures for treating early-stage non-small cell lung cancer (NSCLC). This systematic review and meta-analysis aimed to synthetize existing evidence and to compare the survival outcomes observed for stage IA NSCLC following segmentectomy or lobectomy.</div><div>40 studies (38 observational, 2 RCTs) encompassing 103,926 patients were analyzed. Primary outcomes included overall survival (OS), disease-free survival (DFS), local recurrences, harvested lymph nodes, postoperative morbidity, and length of hospital stay. Risk of bias was assessed using established tools, and evidence certainty was evaluated using GRADE.</div><div>Non-RCTs showed an OS HR of 1.10 (95 % CI: 0.94–1.30, p = 0.24) with low certainty, contrasting with RCTs’ HR of 0.82 (95 % CI: 0.66–1.02, p = 0.7) with moderate certainty. Local recurrences exhibited OR 1.40 (95 % CI: 0.94–2.08, p = 0.09) in non-RCTs with low certainty, and RR 1.61 (95 % CI: 1.12–2.31, p = 0.01) in RCTs with low certainty. Non-RCTs showed DFS HR 1.13 (95 % CI: 0.95–1.34, p = 0.18) with low certainty, while RCTs yielded HR 1.00 (95 % CI: 0.85–1.18, p = 0.97) with moderate certainty. Lobectomy resulted in more harvested lymph nodes. Postoperative morbidity and length of hospital stay did not differ significantly.</div><div>While definitive evidence for OS, DFS, and postoperative outcomes differences was inconclusive, a potential increase in local recurrences following lobectomy was noted. Further well-designed studies are warranted to enhance evidence and inform clinical practice in stage I lung cancer surgery.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"197 ","pages":"Article 107990"},"PeriodicalIF":4.5,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142503193","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":"Lung cancer survival trends and prognostic factors: A 26-year population-based study in Girona Province, Spain","authors":"Eduard Teixidor-Vilà ,&nbsp;Jan Trallero ,&nbsp;Montse Puigdemont ,&nbsp;Anna Vidal-Vila ,&nbsp;Alejandro Hernandez-Martínez ,&nbsp;Elia Sais ,&nbsp;Josep Sabaté-Ortega ,&nbsp;Sara Verdura ,&nbsp;Javier A. Menendez ,&nbsp;Joaquim Bosch-Barrera ,&nbsp;Arantza Sanvisens ,&nbsp;Rafael Marcos-Gragera","doi":"10.1016/j.lungcan.2024.107995","DOIUrl":"10.1016/j.lungcan.2024.107995","url":null,"abstract":"<div><h3>Background</h3><div>Lung cancer (LC) is Europe’s primary cause of cancer-related mortality largely due to its historically low survival rates. The aim of this study was to analyze 26-year survival trends in the province of Girona, Spain, and to identify key prognostic factors.</div></div><div><h3>Methods</h3><div>Population-based study of LC cases collected between 1994 and 2019, with follow-up until December 31, 2021. Variables included date of diagnosis, sex, age, histology, and tumor stage (the latter since 2010). Diagnosis dates were categorized into three periods (1994–2002, 2003–2011, and 2012–2019). Multivariate flexible parametric models, incorporating age as a non-linear, time-varying covariate, were used to analyze net survival (NS) and trends. Annual absolute change in survival (AAC_S) was calculated using 3-year NS.</div></div><div><h3>Results</h3><div>The analysis of 9,113 LC cases showed a NS improvement between the first and last period (7.1 months (95 %CI: 6.5;7.6) to 8.5 months (95 %CI: 7.9;9.1)). Squamous cell carcinoma (NSC-SCC) showed the greatest improvement with an AAC_S of 0.32 % (95 % CI: 0.21; 0.43), while survival for non-small cell lung cancer not otherwise specified declined (AAC_S of −0.19 % (95 %CI: −0.26; −0.12)). Prognostic analysis of the 3,642 cases (2010–2019) indicated a lower LC death risk for adenocarcinoma and NSC-SCC compared to LC not otherwise specified (HR 0.52 and 0.62, respectively). Increasing tumor stage correlated with higher LC mortality risk (1.8-, 4.0-, and 10.1-fold increase for stage II, III, and IV, respectively, compared to stage I).</div></div><div><h3>Conclusions</h3><div>LC survival has notably improved, particularly for NSC-SCC. Survival is influenced by sex, age, date of diagnosis, tumor histology and especially by stage, underscoring comprehensive data collection’s importance.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"197 ","pages":"Article 107995"},"PeriodicalIF":4.5,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142503192","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":"CD8+ T cells infiltrating into tumors were controlled by immune status of pulmonary lymph nodes and correlated with non-small cell lung cancer (NSCLC) patients’ prognosis treated with chemoimmunotherapy","authors":"Zhexin Bai ,&nbsp;Xu Cheng ,&nbsp;Tianyu Ma ,&nbsp;Gege Li ,&nbsp;Xiaojue Wang ,&nbsp;Ziyu Wang ,&nbsp;Ling Yi ,&nbsp;Zhidong Liu","doi":"10.1016/j.lungcan.2024.107991","DOIUrl":"10.1016/j.lungcan.2024.107991","url":null,"abstract":"<div><h3>Purpose</h3><div>Neoadjuvant chemoimmunotherapy has the potential to reduce tumor burden, improve the pathological complete response (pCR) rate, and significantly prolong patients’ disease-free survival (DFS). However, the treatment’s effectiveness varies among NSCLC patients. The immunological mechanisms contributing to tumor regression still require further exploration and elucidation.</div></div><div><h3>Methods</h3><div>The immune status of patients’ local tumor microenvironment (TME) before and after neoadjuvant chemoimmunotherapy, their paired pulmonary lymph nodes (11th LNs) after therapy, including infiltrating immune cell densities and their correlations, were analyzed using multiplex immunofluorescence.</div></div><div><h3>Results</h3><div>Fifty-six NSCLC patients undergoing neoadjuvant chemoimmunotherapy were enrolled and subsequently underwent surgical resection and pathological evaluation. Among these, 19 patients achieved a pCR, 6 patients exhibited a major pathological response (MPR), and 31 patients did not achieve MPR. There were no significant difference in the densities of CD8+ T cell, Treg and Dendritic cell (DC) in patients’ TME before neoadjuvant therapy (n = 26, P = 0.091, P = 0.753, P = 0.905, respectively), but after treament, these immune cells’ dynamics were significantly different between different response group. CD8+ T cell densities were increased in pCR gourp (P = 0.006), but not in non-pCR group (P = 0.389); the densities of Treg were increased in non-pCR gourp (P = 0.0004), but DC were significantly decreased in non-pCR gourp (P = 0.005). After surgery, the TME were also significantly different: patients achieving pCR typically demonstrated high densities of CD8+ T cell, DC and low densities of Tregs (P = 0.0001, P &lt; 0.0001 and P = 0.0004). The immune status of 11th LNs also exhibited significant differences. DC densities were much higher in pCR patients, whereas Treg in the pCR group were significantly lower than those in the non-pCR group (P = 0.0008 and P = 0.003). Furthermore, the densities of DC in the TME showed a moderate positive correlation with DC in 11th LNs (P = 0.0002), while the densities of Tregs in the TME exhibited a moderate negative correlation with DC densities in 11th LNs (P = 0.03). Patients who had high densities of CD8+ T cell in the resection tissues and DC in the LNs, experienced longer DFS (P = 0.048 and P = 0.024).</div></div><div><h3>Conclusion</h3><div>Immune cells in both pulmonary LNs and the TME collectively influence the remodeling of the NSCLC patient’s TME, thus impacting treatment response and prognosis.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"197 ","pages":"Article 107991"},"PeriodicalIF":4.5,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142503190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of immune checkpoint inhibitors plus platinum-based chemotherapy as 1st line treatment for patients with non-small cell lung cancer harboring HER2 mutations: Results from LC-SCRUM-Asia","authors":"Yuki Kato ,&nbsp;Hibiki Udagawa ,&nbsp;Shingo Matsumoto ,&nbsp;Hiroki Izumi ,&nbsp;Yuichiro Ohe ,&nbsp;Terufumi Kato ,&nbsp;Kazumi Nishino ,&nbsp;Shingo Miyamoto ,&nbsp;Sachiko Kawana ,&nbsp;Kenichi Chikamori ,&nbsp;Masato Shingyoji ,&nbsp;Yuki Sato ,&nbsp;Yuji Takada ,&nbsp;Ryo Toyozawa ,&nbsp;Koichi Azuma ,&nbsp;Yu Tanaka ,&nbsp;Tetsuya Sakai ,&nbsp;Yuji Shibata ,&nbsp;Eri Sugiyama ,&nbsp;Kaname Nosaki ,&nbsp;Koichi Goto","doi":"10.1016/j.lungcan.2024.107992","DOIUrl":"10.1016/j.lungcan.2024.107992","url":null,"abstract":"<div><h3>Introduction</h3><div><em>HER2</em> mutations are reported to occur in 2%–5% of all cases of non-small cell lung cancer (NSCLC). The clinical outcomes in patients with <em>HER2</em>-mutant NSCLC treated with immune checkpoint inhibitors (ICIs) plus platinum-based chemotherapy as 1st line treatment still remain unclear.</div></div><div><h3>Methods</h3><div>Using the large-scale clinico-genomic database of LC-SCRUM-Asia, the clinico-genomic characteristics and therapeutic outcomes of patients with <em>HER2</em>-mutant NSCLC were investigated.</div></div><div><h3>Results</h3><div>Of the 15,251 patients with NSCLC enrolled in the LC-SCRUM-Asia database, tumor <em>HER2</em> mutations were detected in 402 patients (2.6 %). The most common subtype of <em>HER2</em> mutations was exon 20 in-frame insertions (79 %), followed in frequency by mutations in the tyrosine kinase domain other than Exon20ins (10 %) and mutations in extracellular domains (7 %). NSCLCs harboring <em>HER2</em> mutations showed a higher tumor mutation burden (TMB) as compared with NSCLCs harboring <em>EGFR</em> mutations or <em>ALK</em> fusions (median: 4.22 vs. 2.54 and 2.52 mutation per megabase, respectively). Of the 402 patients, 268 patients had received platinum-based chemotherapy with ICIs (Chemo-ICI, n = 95) or without ICI (Chemo-alone, n = 173) as 1st line treatment. The progression-free survival (PFS) was significantly longer in the Chemo-ICI group as compared with the Chemo-alone group (median 8.5 vs. 6.3 months; HR [95 %CI]: 0.66 [0.50–0.88]; <em>P</em> &lt; 0.005). Multivariate analysis identified use of ICIs in addition to platinum-based chemotherapy as an independent favorable prognostic factor for PFS. There was no significant difference in the overall survival between the patients of the Chemo-ICI and Chemo-alone groups (median 31.1 vs. 23.3 months; HR [95 %CI]: 0.80 [0.57–1.12], <em>P</em> = 0.20).</div></div><div><h3>Conclusions</h3><div>Addition of ICIs to platinum-based chemotherapy in 1st line treatment may improve the PFS in patients with <em>HER2</em>-mutant NSCLC. The relatively high TMB might be involved in the prolongation of the PFS in patients with <em>HER2</em>-mutant NSCLC receiving platinum-based chemotherapy with ICIs.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"197 ","pages":"Article 107992"},"PeriodicalIF":4.5,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142446990","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":"Reassessing pembrolizumab dosing in NSCLC for methodological and clinical accuracy","authors":"Da Qiu ,&nbsp;Chao Qiu ,&nbsp;Yongneng Wang ,&nbsp;Dan Shan","doi":"10.1016/j.lungcan.2024.107989","DOIUrl":"10.1016/j.lungcan.2024.107989","url":null,"abstract":"","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"197 ","pages":"Article 107989"},"PeriodicalIF":4.5,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142432439","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":"Afatinib plus bevacizumab combination after osimertinib resistance in advanced EGFR-mutant non-small cell lung cancer: Phase II ABCD-study","authors":"Akito Hata ,&nbsp;Nobuyuki Katakami ,&nbsp;Naoto Takase ,&nbsp;Kayoko Kibata ,&nbsp;Yuta Yamanaka ,&nbsp;Motohiro Tamiya ,&nbsp;Masahide Mori ,&nbsp;Takashi Kijima ,&nbsp;Satoshi Morita ,&nbsp;Kazuko Sakai ,&nbsp;Kazuto Nishio","doi":"10.1016/j.lungcan.2024.107988","DOIUrl":"10.1016/j.lungcan.2024.107988","url":null,"abstract":"<div><h3>Introduction</h3><div>Many clinical studies showed a synergy of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) and vascular endothelial growth factor inhibitors. We hypothesized afatinib plus bevacizumab exerts clinical potency after developing various osimertinib resistant mechanisms.</div></div><div><h3>Methods</h3><div><em>EGFR</em>-mutant non-small cell lung cancer patients were enrolled after osimertinib resistance. Afatinib at 30–40 mg/day and bevacizumab at 15 mg/kg tri-weekly were administered until progression. Plasma/histologic rebiopsied samples after osimertinib failure were analyzed to examine resistant mechanisms: gene alterations/copy-number gain using cancer personalized profiling by deep sequencing.</div></div><div><h3>Results</h3><div>Between January 2018 and October 2020, 28 patients were enrolled. Response and disease control rates were 17.9 % and 78.6 %, respectively. Median duration of response was 9.0 (range, 4.2–22.3) months. Median progression-free and overall survivals were 2.7 and 9.3 months, respectively. Twenty-eight (100 %) plasma and/or 21 (75 %) histologic rebiopsies identified: 17 (61 %) <em>TP53</em>; 15 (54 %) <em>T790M</em>; 9 (32 %) uncommon <em>EGFR</em>; 9 (32 %) <em>MET</em>; 6 (21 %) <em>C797S</em>; 3 (11 %) <em>BRAF</em>; 2 (7 %) <em>HER2</em>; 2 (7 %) <em>KRAS</em>; and 2 (7 %) <em>PI3K</em> mutations. One (17 %) of 6 <em>C797S</em> patients showed complete response. Three (33 %) of 9 uncommon <em>EGFR</em>-mutated patients achieved radiographic response. Neither 15 <em>T790M</em>-positive nor 6 <em>EGFR</em> downstream signaling mutations: <em>BRAF</em>; <em>KRAS</em>; or <em>PI3K</em>-positive patients responded, but 5 (38 %) of 13 <em>T790M</em>-negative patients responded. Adverse events ≥ grade 3 and incidence ≥ 5 % were: hypertension (29 %); proteinuria (7 %); and diarrhea (7 %). There were neither treatment-related death nor interstitial lung disease.</div></div><div><h3>Conclusions</h3><div>Selected population could obtain clinical benefit from afatinib plus bevacizumab, based on rebiopsy results after osimertinib resistance.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"197 ","pages":"Article 107988"},"PeriodicalIF":4.5,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406587","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":"Crispr-mediated genome editing reveals a preponderance of non-oncogene addictions as targetable vulnerabilities in pleural mesothelioma","authors":"Duo Xu ,&nbsp;Shun-Qing Liang ,&nbsp;Min Su ,&nbsp;Haitang Yang ,&nbsp;Rémy Bruggmann ,&nbsp;Simone Oberhaensli ,&nbsp;Zhang Yang ,&nbsp;Yanyun Gao ,&nbsp;Thomas M. Marti ,&nbsp;Wenxiang Wang ,&nbsp;Ralph A. Schmid ,&nbsp;Yongqian Shu ,&nbsp;Patrick Dorn ,&nbsp;Ren-Wang Peng","doi":"10.1016/j.lungcan.2024.107986","DOIUrl":"10.1016/j.lungcan.2024.107986","url":null,"abstract":"<div><div>Pleural mesothelioma (PM) is an aggressive cancer with limited treatment options. In particular, the frequent loss of tumor suppressors, a key oncogenic driver of the disease that is therapeutically intractable, has hampered the development of targeted cancer therapies. Here, we interrogate the PM genome using CRISPR-mediated gene editing to systematically uncover PM cell susceptibilities and provide an evidence-based rationale for targeted cancer drug discovery. This analysis has allowed us to identify with high confidence numerous known and novel gene dependencies that are surprisingly highly enriched for non-oncogenic pathways involved in response to various stress stimuli, in particular DNA damage and transcriptional dysregulation. By integrating genomic analysis with a series of <em>in vitro</em> and <em>in vivo</em> functional studies, we validate and prioritize several non-oncogene addictions conferred by CDK7, CHK1, HDAC3, RAD51, TPX2, and UBA1 as targetable vulnerabilities, revealing previously unappreciated aspects of PM biology. Our findings support the growing consensus that stress-responsive non-oncogenic signaling plays a key role in the initiation and progression of PM and provide a functional blueprint for the development of unprecedented targeted therapies to combat this formidable disease.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"197 ","pages":"Article 107986"},"PeriodicalIF":4.5,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142391654","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":"Stereologic consequences of iatrogenic collapse: The morphology of adenocarcinoma in situ overlaps with invasive patterns. Proposal for a necessary modified classification of pulmonary adenocarcinomas","authors":"Federica Filipello ,&nbsp;Hans Blaauwgeers ,&nbsp;Birgit Lissenberg-Witte ,&nbsp;Andreas Schonau ,&nbsp;Claudio Doglioni ,&nbsp;Gianluigi Arrigoni ,&nbsp;Teodora Radonic ,&nbsp;Idris Bahce ,&nbsp;Arthur Smit ,&nbsp;Chris Dickhoff ,&nbsp;Antonio Nuccio ,&nbsp;Alessandra Bulotta ,&nbsp;Yuko Minami ,&nbsp;Masayuki Noguchi ,&nbsp;Francesca Ambrosi ,&nbsp;Erik Thunnissen","doi":"10.1016/j.lungcan.2024.107987","DOIUrl":"10.1016/j.lungcan.2024.107987","url":null,"abstract":"<div><div>Recognizing non-invasive growth patterns is necessary for correct diagnosis, invasive size determination and pT-stage in resected non-small cell lung carcinoma. Due to iatrogenic collapse after resection, the distinction between adenocarcinoma <em>in-situ</em> (AIS) and invasive adenocarcinoma may be difficult. The aim of this study is to investigate the complex morphology of non-mucinous non-invasive patterns of AIS in resection specimen with iatrogenic collapse, and to relate this to follow-up.</div><div>The effects of iatrogenic collapse on the morphology of collapsed AIS were simulated in a mathematical model. Three dimensional related criteria applied in a modified classification, using also cytokeratin 7 and elastin as additional stains, in two independent retrospective cohorts of primary pulmonary adenocarcinomas ≤3 cm resection specimen with available follow-up information.</div><div>The model demonstrated that infolding of alveolar walls occurs during iatrogenic collapse and lead to a significant increase in tumor cell heights in maximal collapse areas, compared to less collapsed areas. The morphology of infolded AIS overlaps with patterns described as papillary and acinar adenocarcinoma according to the WHO classification, necessitating an adaptation.</div><div>The modified classification incorporates recognition of iatrogenic and biologic collapse, tangential cutting effect true invasion and surrogate markers of invasion i.e. grey zone, covering a multilayering falling short of micropapillary, cribriform and solid alveolar filling growth. The use of elastin and CK7 staining aids in the morphologic recognition of iatrogenic collapsed AIS and the distinction from invasive adenocarcinoma. Out of a total of 70 resection specimens 1 case was originally classified as AIS and 9 were reclassified as iatrogenic collapsed AIS. Patients with collapsed AIS showed a 100 % recurrence-free survival after a mean follow-up time of 69.5 months.</div><div>With the current WHO classification, AIS is overdiagnosed as invasive adenocarcinoma due to infolding. The modified classification facilitates the diagnosis of AIS.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"197 ","pages":"Article 107987"},"PeriodicalIF":4.5,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400695","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}