Clinical lung cancer最新文献

{"title":"Correlation Between the Extent of N1 Lymph Node Station Examination and Prognosis in Stage I Non-small Cell Lung Cancer Patients: One Station is Insufficient","authors":"Junhong Liu ,&nbsp;Bingji Cao ,&nbsp;ZhiHua Shi ,&nbsp;Minglei Song ,&nbsp;Junfeng Liu","doi":"10.1016/j.cllc.2024.11.009","DOIUrl":"10.1016/j.cllc.2024.11.009","url":null,"abstract":"<div><h3>Background</h3><div>Examination standards for hilar and intrapulmonary (N1) lymph nodes (LNs) have been debated. The objective of this study was to assess the prognostic significance of the extent of examination for N1 LN stations in patients with pathological stage I non-small cell lung cancer (NSCLC).</div></div><div><h3>Methods</h3><div>A total of 1868 patients were identified and divided into 3 groups on the basis of the number of N1 stations examined: group A (≥3 stations), group B (2 stations) and group C (1 station). Moreover, we investigated the prognostic significance of each individual N1 station examined. The primary outcome was 5-year disease-free survival (DFS).</div></div><div><h3>Results</h3><div>Overall, 1062, 607, and 199 patients were in groups A, B, and C, respectively. The baseline demographic and clinical characteristics were similar among the groups, except for the tumor side. The 5-year DFS rates were comparable between groups A and B (85.1% vs. 82.7%, <em>P</em> = .3), both of which were significantly greater than that of group C (74.4%) (<em>P</em> &lt; .01). Similar results were observed for the corresponding 5-year overall survival rates. The number of N1 stations examined was an independent predictor in multiple analyses. Additionally, the examination of stations 10 and 13 were independent favorable predictors for 5-year DFS.</div></div><div><h3>Conclusion</h3><div>For patients with pathological stage I NSCLC, examination of only 1 N1 station is insufficient. Examinations of a minimum of two N1 stations, including stations 10 and 13, is recommended to obtain the optimal survival benefit.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"26 2","pages":"Pages e108-e117.e3"},"PeriodicalIF":3.3,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intraoperative Molecular Imaging With Pafolacianine: Histologic Characteristics of Identified Nodules","authors":"Inderpal S. Sarkaria ,&nbsp;Timothy G. Biro ,&nbsp;Sunil Singhal ,&nbsp;Rishindra M. Reddy ,&nbsp;Linda W. Martin ,&nbsp;David C. Rice ,&nbsp;Alex S. Lopez ,&nbsp;Gary Stevens ,&nbsp;Tina Barret ,&nbsp;Sudish C. Murthy","doi":"10.1016/j.cllc.2024.11.004","DOIUrl":"10.1016/j.cllc.2024.11.004","url":null,"abstract":"<div><h3>Background</h3><div>With increased early detection efforts, surgery for early-stage lung cancer is expected to rise. Pafolacianine is the first FDA approved targeted optical imaging agent indicated as an adjunct for intraoperative identification of malignant and nonmalignant pulmonary lesions in adult patients with known or suspected cancer in the lung.</div></div><div><h3>Methods</h3><div>This is a retrospective review of the malignant and nonmalignant lesions identified by pafolacianine with intraoperative molecular imaging (IMI) in the multi-center Phase 2 and Phase 3 ELUCIDATE clinical trials. All lesions meeting the intent to treat criteria from the combined studies were included. Histopathology for malignant and nonmalignant lesions and immunohistochemistry (ICH) for folate receptor alpha (FRα) and folate receptor beta (FRβ), which pafolacianine binds to, were assessed.</div></div><div><h3>Results</h3><div>A total of 273 lesions resected from 191 patients were analyzed. The identification of primary and occult malignant lesions with pafolacianine in combination with standard practice was improved (<em>P</em> &lt; .001) when compared to standard practice alone. A range of histologies were demonstrated including adenocarcinoma (primary and metastatic), squamous cell carcinoma, adenoid cystic carcinoma, chordoma, lymphoma, and papillary thyroid cancer. Ninety-two percent (205 of 223) of lesions tested for folate expression were positive for FRα or FRβ expression.</div></div><div><h3>Conclusions</h3><div>While initially intended to identify adenocarcinoma, IMI with pafolacianine targets a broad histological cross-section of malignant and nonmalignant primary and metastatic lesions in the lung. As real-world use expands, additional insight will continue to inform utility of pafolacianine in clinical practice and may broaden clinical applicability.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"26 2","pages":"Pages 104-115"},"PeriodicalIF":3.3,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of Oncogene Driver Mutations with Recurrence and Survival in Stage I Nonsmall Cell Lung Cancer","authors":"Daniel M. Libby ,&nbsp;Laura J. Libby ,&nbsp;Xiaoyue Ma ,&nbsp;Jason Chua ,&nbsp;Tahj Blow ,&nbsp;Peyman Razavi ,&nbsp;Ashish Saxena","doi":"10.1016/j.cllc.2024.10.016","DOIUrl":"10.1016/j.cllc.2024.10.016","url":null,"abstract":"<div><h3>Background</h3><div>Stage I nonsmall cell lung cancer (NSCLC) is primarily treated with surgical resection and has a favorable prognosis with an expected recurrence rate of 30%. New methods to risk stratify patients with stage I NSCLC are needed to help select those that might benefit from more active surveillance or adjuvant therapy.</div></div><div><h3>Methods</h3><div>We analyzed clinical data from 1330 patients (1469 tumors) with NSCLC and correlated it with next-generation sequencing (NGS). To reduce the potential confounding variables of stage and treatment, this analysis only included patients with stage I NSCLC in whom surgical resection was the primary treatment.</div></div><div><h3>Results</h3><div>In 570 patients (600 tumors), 75 (12.5%) developed recurrence. Recurrence occurred in 37.5% of patients with KRAS G12V mutation versus 11.1% of patients without this mutation (<em>P</em> &lt; .001). A lower chance of recurrence was associated with “any EGFR” mutation (6.74% vs. 14.9%, <em>P</em> = .006). A history of coronary artery disease (CAD) increased the chance of recurrence: OR 2.7 (1.57-4.89, <em>P</em> &lt; .001). Shorter survival was predicted by KRAS G12V (<em>P</em> = .009) and “other TP53” mutation (<em>P</em> = .025). KRAS G12V, KRAS G13D, MET E168D, PTEN, and “other TP53” were oncogene mutations associated with reduced survival in stage I NSCLC. CAD, type 2 diabetes (DM2), and “other cancer” were medical comorbidities associated with reduced survival in stage I NSCLC.</div></div><div><h3>Conclusions</h3><div>Oncogene mutations such as KRAS G12V and EGFR may have implications for cancer surveillance strategies and inform future treatment trials of stage I NSCLC.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"26 2","pages":"Pages 116-123"},"PeriodicalIF":3.3,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142823805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Outcomes Following Treatment for Progression in Patients Treated With Durvalumab Consolidation in LA-NSCLC","authors":"Margaret Stalker ,&nbsp;Melina Marmarelis ,&nbsp;Corey Langer ,&nbsp;Roger B. Cohen ,&nbsp;Aditi Singh ,&nbsp;Charu Aggarwal ,&nbsp;Lova Sun","doi":"10.1016/j.cllc.2024.11.002","DOIUrl":"10.1016/j.cllc.2024.11.002","url":null,"abstract":"<div><h3>Introduction</h3><div>PACIFIC established consolidative durvalumab for LA-NSCLC, but only about half of patients completed a year of therapy. Data on treatment patterns and outcomes after durvalumab are limited.</div></div><div><h3>Methods</h3><div>Our analysis included patients from a US nationwide database with LA-NSCLC who received consolidative durvalumab between 2017 and 2023 and had subsequent systemic therapy, classified as PD-L1 monotherapy, PD-L1+chemotherapy, chemotherapy alone, PD-L1+CTLA4, or targeted therapy (TT). Time to next treatment (TTNT) was analyzed from durvalumab start and finish to next line of therapy initiation. Overall survival (OS) from start of postdurvalumab therapy was analyzed using Kaplan Meier methodology.</div></div><div><h3>Results</h3><div>Our cohort included 751 patients, median age 68 (IQR, 61-74), 53% female, 80% White, 91% ECOG 0-1, 90% smoking history, and 53% nonsquamous histology. The most common postdurvalumab treatment was chemotherapy alone in 349 (46%), followed by PD-L1+chemotherapy in 147 (20%), PD-L1 monotherapy in 114 (15%), and TT in 104 (14%).</div><div>Median duration of durvalumab treatment was 5.5 months (IQR 2.3-10.6); only 9% of patients received a full year of durvalumab, and 64% started next treatment within a year of initiation. Patients treated with chemotherapy-containing regimens had shorter TTNT from durvalumab start/end, as well as shorter median OS [10.8 (5.6-18.8) months for chemotherapy and 12.9 (6.0-24.2) months for chemoimmunotherapy, versus 23.8 (8.7-34.5) months for PD-L1 monotherapy and 30.1 (9.5-NR) months for TT (<em>P</em> &lt; .001)].</div></div><div><h3>Conclusion</h3><div>Patients treated with systemic therapy after consolidative durvalumab, particularly those requiring chemotherapy-based treatment, have poor outcomes and are in need of improved treatment strategies.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"26 2","pages":"Pages 124-130.e1"},"PeriodicalIF":3.3,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Medicaid Expansion on the Receipt of Adjuvant Chemotherapy in Patients With Lung Cancer","authors":"Hamza Rshaidat ,&nbsp;Shale J. Mack ,&nbsp;Scott H. Koeneman ,&nbsp;Jonathan Martin ,&nbsp;Gregory L. Whitehorn ,&nbsp;Isheeta Madeka ,&nbsp;Sarah W. Gordon ,&nbsp;T, Olugbenga T. Okusanya","doi":"10.1016/j.cllc.2024.09.007","DOIUrl":"10.1016/j.cllc.2024.09.007","url":null,"abstract":"<div><h3>Objective</h3><div>We aimed to utilize a nationally representative database to study the effect of Medicaid expansion on the receipt of adjuvant chemotherapy in eligible patients.</div></div><div><h3>Materials and Methods</h3><div>Retrospective review of the National Cancer Database (NCDB) was performed between 2006 and 2019. Patients with clinical T1-T3, N1, and M0 were included. Patients with nodal disease or tumors &gt; 4 cm were eligible for adjuvant therapy. Demographic and clinical information were collected. A difference-in-difference analysis was performed to compare changes in the rate of adjuvant chemotherapy.</div></div><div><h3>Results</h3><div>Total 9954 eligible patients were treated in states that expanded Medicaid coverage in January 2014 or later, with 4809 patients treated in the pre-expansion years (2012-2013) and 5145 patients treated in the postexpansion years (2017-2018). Following Medicaid expansion, eligible patients were more likely to receive adjuvant therapy (70.2% vs. 62.3%; <em>P</em> &lt; .001). Compared with the pre-expansion period, patients who received adjuvant therapy were more likely to use Medicaid insurance postexpansion (7.8% vs. 5%, <em>P</em> &lt; .001). Among patients using Medicaid coverage only, a greater percentage started adjuvant therapy within 8 weeks of resection following Medicaid expansion (46.6% vs. 38.3%, <em>P</em> = .048). The observed difference-in-difference in the change in adjuvant therapy rate from the pre-expansion period to the postexpansion period between expansion and nonexpansion states was 1.25% (95% Bootstrap CI −0.36% to −3.18%). There was a modest survival benefit in expansion states postexpansion.</div></div><div><h3>Conclusion</h3><div>Medicaid expansion appears to be associated with increased access to care, as shown by the increased receipt of adjuvant systemic therapy in eligible patients.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"26 2","pages":"Pages 131-139"},"PeriodicalIF":3.3,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of First-Line Nivolumab Plus Ipilimumab in Unresectable Pleural Mesothelioma: A Multicenter Real-World Study (ImmunoMeso LATAM)","authors":"Diego Enrico ,&nbsp;Juan Elias Gomez ,&nbsp;Danilo Aguirre ,&nbsp;Natalia Soledad Tissera ,&nbsp;Florencia Tsou ,&nbsp;Carmen Pupareli ,&nbsp;Delfina Peralta Tanco ,&nbsp;Federico Waisberg ,&nbsp;Andrés Rodríguez ,&nbsp;Manglio Rizzo ,&nbsp;Nicolás Minatta ,&nbsp;Picon Rafael ,&nbsp;Luis Basbus ,&nbsp;Lorena Lupinacci ,&nbsp;Diego Kaen ,&nbsp;Mauro Ramos ,&nbsp;Virginia Bluthgen ,&nbsp;Nicolas Castagneris ,&nbsp;María Pía Coppola ,&nbsp;Alejandra Scocimarro ,&nbsp;Claudio Martín","doi":"10.1016/j.cllc.2024.09.005","DOIUrl":"10.1016/j.cllc.2024.09.005","url":null,"abstract":"<div><h3>Background</h3><div>The phase 3 CheckMate-743 trial demonstrated a prolonged overall survival (OS) benefit with nivolumab plus ipilimumab over chemotherapy as first-line treatment in patients with unresectable pleural mesothelioma (PM). However, given that Latin American (LATAM) patients were notably underrepresented in this trial, we retrospectively assessed the effectiveness and safety of this regimen in this population.</div></div><div><h3>Methods</h3><div>This retrospective study included patients from 15 centers in LATAM with unresectable or metastatic PM treated with first-line nivolumab plus ipilimumab in a real-world data (RWD) scenario. Demographic, clinicopathological characteristics, and safety data were collected from medical charts. Progression-free survival (PFS), and OS were calculated using the Kaplan-Meier method.</div></div><div><h3>Results</h3><div>From June 2017, and January 2024 96 patients were included: epithelioid 78% (n = 75), 81% were ECOG 0-1 (n = 78). With a median follow-up of 24.1 months, median PFS and OS were 8 months (95% CI, 6.6-9.4), and 22 months (95% CI, 18.9-25), respectively. No statistical difference in OS was observed between epithelioid versus nonepithelioid histology (median 23 months vs. 19 months, respectively; <em>P =</em> .29). Treatment efficacy was also consistent among different clinical subgroups. Any and grade 3-4 adverse events were found in 43.1% (n = 28), and 18.5% (n = 12) of patients, respectively. Remarkably, no OS impact was observed in patients who had dose delay or treatment discontinuation due to immune-related adverse events, and those who experienced any adverse event.</div></div><div><h3>Conclusions</h3><div>This multicenter RWD study demonstrated the clinically meaningful benefit of first-line ipilimumab and nivolumab in LATAM patients with unresectable or metastatic PM, and data is consistent with previous trial findings.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"25 8","pages":"Pages 723-731.e2"},"PeriodicalIF":3.3,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FLAIR: A Phase II, Open Label, Randomized Study of Osimertinib Plus Bevacizumab Versus Osimertinib in Recurrent or Metastatic Treatment-Naïve NSCLC Patients Harboring EGFR 21L858R Mutation","authors":"Qing Zhou ,&nbsp;Jie Li ,&nbsp;Shun-Dong Cang ,&nbsp;Jia-Xin Lin ,&nbsp;Hai-Yan Tu ,&nbsp;Yingying Du ,&nbsp;Jian-Wen Qin ,&nbsp;Xiao-Hua Liang ,&nbsp;Yan Yu ,&nbsp;Hai-Tao Lan ,&nbsp;Hua-Qiu Shi ,&nbsp;Dong Hua ,&nbsp;Si-Yang Maggie Liu ,&nbsp;Yi-Long Wu","doi":"10.1016/j.cllc.2024.09.002","DOIUrl":"10.1016/j.cllc.2024.09.002","url":null,"abstract":"<div><h3>Introduction</h3><div>Osimertinib, the 3rd generation EGFR-TKI, has emerged as standard first-line treatment for patients with advanced <em>EGFR</em> mutated nonsmall cell lung cancer (NSCLC). Patients with exon 21 L858R mutation showed lower efficacy with EGFR-TKIs than those with 19Del mutation, even with osimertinib, it remains an unmet medical need to further improve the efficacy in L858R population. We present the rationale and design for FLAIR (NCT04988607), which will investigate the efficacy and safety of osimertinib plus bevacizumab versus osimertinib monotherapy in treatment-naïve recurrent or metastatic NSCLC patients harboring <em>EGFR</em> exon 21 L858R mutation.</div></div><div><h3>Materials and Methods</h3><div>FLAIR is a prospective, multicenter, randomized, open label study, which is initiated by Chinese Thoracic Oncology Group (CTONG2002). Patients age ≥18 years with primary recurrent or metastatic nonsquamous NSCLC who are treatment-naïve with documented <em>EGFR</em> exon 21 L858R mutation is eligible. Patients will be randomized 1:1 to receive osimertinib 80 mg once daily plus bevacizumab 15mg/kg every 3 weeks or osimertinib monotherapy 80 mg once daily until progression or another discontinuation criterion is met. The primary endpoint is investigator-assessed progression free survival (PFS). Secondary endpoints include: overall survival rate at 24 months, time to treatment failure (TTF), overall response rate (ORR), disease control rate (DCR), duration of response (DoR), central nervous system (CNS) PFS, CNS ORR and safety.</div></div><div><h3>Results</h3><div>FLAIR has completed the enrollment, and results are expected in the fourth quarter of 2025 (depending on the actual event rate).</div></div><div><h3>Conclusions</h3><div>This study will offer better perspectives on the efficacy and safety of osimertinib plus bevacizumab combination therapy in treatment-naïve recurrent or metastatic NSCLC patients harboring EGFR exon 21 L858R mutation, providing valuable guidance for clinical practice.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"26 2","pages":"Pages 152-157.e1"},"PeriodicalIF":3.3,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Phase II Study of Neoadjuvant Opnurasib KRAS G12C Inhibitor in Patients With Surgically Resectable Non-Small Cell Lung Cancer (CCTG IND.242A): A Substudy of the IND.242 Platform Master Protocol","authors":"J. Spicer ,&nbsp;N. Blais ,&nbsp;S. Owen ,&nbsp;A.G. Robinson ,&nbsp;Q. Chu ,&nbsp;C. Labbe ,&nbsp;B. Shieh ,&nbsp;P. Brown-Walker ,&nbsp;J. Sederias ,&nbsp;K. Jensen ,&nbsp;A.F. Farago ,&nbsp;M.-S. Tsao ,&nbsp;T.R. Cottrell ,&nbsp;B. Kidane ,&nbsp;S. Laurie ,&nbsp;R. Juergens ,&nbsp;P.A. Bradbury ,&nbsp;W. Tu ,&nbsp;P.-O. Gaudreau","doi":"10.1016/j.cllc.2024.09.003","DOIUrl":"10.1016/j.cllc.2024.09.003","url":null,"abstract":"<div><div>Molecularly targeted agents are increasingly being studied in the treatment of early-stage non-small cell lung cancer (NSCLC) to try and improve cure. However, phase 3 data on neoadjuvant therapy have largely been conducted in a biomarker agnostic manner with inconsistent exclusion of <em>EGFR</em> and <em>ALK</em> alterations. Our objective was to develop IND.242 as a large-scale neoadjuvant platform trial to introduce novel agents into the preoperative window for molecularly-defined NSCLC patient populations. Given that <em>KRAS</em> G12C mutations are common in the overall NSCLC patient population, ranging from 9.4% to 13% of cases across different cohorts, and may be associated to worse prognosis, the initial IND.242A Substudy was designed to test neoadjuvant JDQ443 (opnurasib), a selective KRAS G12C inhibitor. This current trial report describes the multicenter, Canadian Cancer Trials Group (CCTG)-led IND.242 neoadjuvant phase 2 platform master protocol and its first Substudy (IND.242A) of neoadjuvant opnurasib KRAS G12C inhibitor for patients with surgically resectable NSCLC (AJCC 8th edition stage IA2 to IIIA). In IND.242A, a maximum of 27 patients will be accrued in participating Canadian sites. The primary objective is the rate of major pathological response (MPR) following neoadjuvant opnurasib. Secondary objectives include safety and tolerability of the treatment regimen, objective response rate (ORR) by RECIST 1.1 for the neoadjuvant treatment period, pathological complete response (pCR) rate, event-free survival (EFS) at 2 years, and surgical outcomes. Exploratory objectives are to explore patient related outcomes (PROs) and identify potential predictive biomarkers of response and mechanisms of resistance on tissue and peripheral blood samples.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"26 2","pages":"Pages 146-151"},"PeriodicalIF":3.3,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Use of Oncogene Overlap by Tissue-Based Next-Generation Sequencing to Explore the Mutational Landscape and Survival Impact of HER2, KRAS and MET Copy-Number Gain in Nonsmall Cell Lung Cancer","authors":"Alexander S. Watson ,&nbsp;Harris B. Krause ,&nbsp;Andrew Elliott ,&nbsp;Alex Farrell ,&nbsp;Stephen V. Liu ,&nbsp;Patrick C. Ma ,&nbsp;Ari VanderWalde ,&nbsp;George W. Sledge ,&nbsp;David Spetzler ,&nbsp;Erin L. Schenk ,&nbsp;D. Ross Camidge","doi":"10.1016/j.cllc.2024.09.001","DOIUrl":"10.1016/j.cllc.2024.09.001","url":null,"abstract":"<div><h3>Background</h3><div>Gene copy number gain (CNG) is a continuous variable. The relevant cutpoint for <em>HER2, KRAS</em> and <em>MET</em> CNG in non-mall cell lung cancer remains uncertain. As de novo driver oncogenes are largely mutually exclusive, oncogene overlap analysis can be used to explore CNG thresholds.</div></div><div><h3>Patient and Methods</h3><div>We retrospectively analysed NGS of DNA/RNA in 13,702 NSCLC adenocarcinoma samples. Alternate and same-gene driver oncogene co-occurrence with <em>HER2, KRAS</em> and <em>MET</em> CNG was examined. Overall survival (OS) from time of biopsy collection was correlated with CNG and pathogenic mutations in driver oncogenes (Driver+).</div></div><div><h3>Results</h3><div>The frequency of Driver+ tumors decreased with increasing CNG. Setting CNG thresholds by oncogene overlap and dataset size (CNA ≥ 6 for <em>HER2, KRAS</em> and ≥ 4 for <em>MET</em>), tumors considered relevantly amplified (Amp) for <em>MET, HER2</em> and <em>KRAS</em> were significantly less likely to be Driver+ (<em>P</em> &lt; .001). When Driver+ did overlap with Amp status, same-gene alterations (mutation and CNG) were significantly enriched for all 3 genes (<em>HER2, KRAS</em> and <em>MET</em>), while <em>BRAF</em> and <em>EGFR</em> mutations were more common in <em>MET</em>-Amp than in <em>HER2</em>- or <em>KRAS</em>-Amp tumors. A negative OS association with Amp status was independent of Driver+ status for <em>HER2</em> and <em>MET</em>, however not <em>KRAS</em>.</div></div><div><h3>Conclusion</h3><div>Tissue NGS-based <em>HER2, KRAS</em> and <em>MET</em> CNG thresholds set by oncogene overlap identified potentially clinically relevant “Amp” subgroups with altered genetic profiles and decreased survival. Prospective research into targeted therapy benefit in these groups is encouraged.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"25 8","pages":"Pages 712-722.e1"},"PeriodicalIF":3.3,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Smoking and the Risk of Second Primary Lung Cancer Among Breast Cancer Survivors from the Population-Based UK Biobank Study","authors":"Anna Graber-Naidich ,&nbsp;Eunji Choi ,&nbsp;Julie T. Wu ,&nbsp;Timothy J. Ellis-Caleo ,&nbsp;Joel Neal ,&nbsp;Heather A. Wakelee ,&nbsp;Allison W. Kurian ,&nbsp;Summer S. Han","doi":"10.1016/j.cllc.2024.08.017","DOIUrl":"10.1016/j.cllc.2024.08.017","url":null,"abstract":"<div><h3>Objective</h3><div>Long-term breast cancer (BC) survivors are known to develop second malignancies, with second primary lung cancer (SPLC) one common type. Smoking was identified as a main risk factor for SPLC among BC survivors. These findings were limited to the U.S. and focused on smoking status, not incorporating cumulative smoking exposures (eg, pack-years). We examine SPLC incidence and evaluate the associations between SPLC risk and cumulative cigarette smoking exposures and other potential factors among BC survivors in a prospective European cohort.</div></div><div><h3>Methods</h3><div>Of 502,505 participants enrolled in the UK Biobank in 2006 to 2010, we identified 8429 patients diagnosed with BC between 2006 and 2016 and followed for second malignancies through 2016. Smoking information was collected at enrollment, and treatment data were collected using electronic health records. Multivariable cause-specific Cox regression (CSC) evaluated the association between each factor and SPLC risk.</div></div><div><h3>Results</h3><div>Of 8429 BC patients, 40 (0.47%) developed SPLC over 45,376 person-years. The 10-year cumulative SPLC incidence was 0.48% (95% CI = 0.33%-0.62%). The CSC analysis confirmed the association between SPLC and ever-smoking status (adjusted hazard-ratio (aHR) = 3.46 (<em>P</em> &lt; .001). The analysis showed a 24% increment in SPLC risk per 10 smoking pack-years among BC survivors (aHR = 1.24 per-10 pack-years, <em>P</em> = .01). The associations between SPLC and other variables remained statistically insignificant. We applied the USPSTF lung cancer screening eligibility criteria and found that 80% of the 40 BC survivors who developed SPLC would have been ineligible for lung cancer screening.</div></div><div><h3>Conclusion</h3><div>In a large, European cohort, cumulative smoking exposure is significantly associated with SPLC risk among BC survivors.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"25 8","pages":"Pages 705-711.e7"},"PeriodicalIF":3.3,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}