Mariona Riudavets MD, PhD , David Planchard MD, PhD
{"title":"Erratum to ‘Targeting DLL3: A New Weapon in Lung Neuroendocrine Tumors?’ [JTO Clinical and Research Reports Volume 6 Issue 5 (2025) 100796]","authors":"Mariona Riudavets MD, PhD , David Planchard MD, PhD","doi":"10.1016/j.jtocrr.2025.100840","DOIUrl":"10.1016/j.jtocrr.2025.100840","url":null,"abstract":"","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 7","pages":"Article 100840"},"PeriodicalIF":3.0,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144203729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kassandra R. Bisson MHSc , Andrea Beharry MLT , Normand Blais MD , Michael D. Carter MD, PhD , Parneet K. Cheema MD , Patrice Desmeules MD , John G. Garratt RT , Barbara Melosky MD , Bryan Lo PhD , Stephanie Snow MD , Basile Tessier-Cloutier MD , Edwin Tio MD , Stephen Yip MD, PhD , Jennifer R. Won PhD , Brandon S. Sheffield MD
{"title":"Novel Approach to Proficiency Testing Reveals Significant Variations in Biomarker Practice Leading to Critical Differences in Lung Cancer Management","authors":"Kassandra R. Bisson MHSc , Andrea Beharry MLT , Normand Blais MD , Michael D. Carter MD, PhD , Parneet K. Cheema MD , Patrice Desmeules MD , John G. Garratt RT , Barbara Melosky MD , Bryan Lo PhD , Stephanie Snow MD , Basile Tessier-Cloutier MD , Edwin Tio MD , Stephen Yip MD, PhD , Jennifer R. Won PhD , Brandon S. Sheffield MD","doi":"10.1016/j.jtocrr.2025.100837","DOIUrl":"10.1016/j.jtocrr.2025.100837","url":null,"abstract":"<div><h3>Introduction</h3><div>Timely access to quality biomarker testing in NSCLC is critical to patient outcomes. The Canadian Pathology Quality Assurance provides external quality assurance (EQA) to laboratories in Canada. The Canadian Pathology Quality Assurance has recently developed a novel approach to molecular biomarker EQA testing, assessing accuracy, turnaround time, and interpretation of reports. This study reports the results of the first end-to-end biomarker EQA challenge in NSCLC.</div></div><div><h3>Methods</h3><div>Three challenge specimens were made using NSCLC tissue and paired with clinical vignettes mimicking referred-in cases. Participants were to provide all required molecular testing (immunohistochemistry and gene sequencing) and submit final reports for each case, while being timed. Reports were assessed by molecular pathologists and medical oncologists who recommended a systemic treatment based on vignettes and reports.</div></div><div><h3>Results</h3><div>A total of 13 Canadian laboratories participated. The turnaround time of molecular reporting ranged from five to 57 (median 22.5) calendar days. Two laboratories (15%) reported their results within 2 weeks. Four laboratories (31%) reported the results of their biomarkers after more than 30 days.</div><div>Only three laboratories received optimal status (23%). One laboratory (8%) failed due to a critical genotyping error, three (23%) received a suboptimal status due to inappropriately long turnaround times, and the remaining six (69%) received an adequate status.</div></div><div><h3>Conclusions</h3><div>This report demonstrates the utility of this proficiency testing style compared with standard laboratory self-reporting. The approach has elucidated substantial differences in the quality of NSCLC biomarker results produced by Canadian laboratories. Ongoing efforts to improve turnaround times and clarity of reporting, including regular external measurement, are tools that can improve patient outcomes in NSCLC.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 7","pages":"Article 100837"},"PeriodicalIF":3.0,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144263817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Turtle Study: A Phase 2 Study of Durvalumab Plus Carboplatin and Etoposide in Elderly Patients With Extensive-Stage SCLC (LOGiK 2003)","authors":"Hidenobu Ishii MD, PhD , Koichi Azuma MD, PhD , Yuta Yamanaka MD , Hiroshige Yoshioka MD, PhD , Yukihiro Toi MD , Naoki Shingu MD , Katsuhiko Naoki MD, PhD , Masaki Okamoto MD, PhD , Yuko Tsuchiya-Kawano MD, PhD , Taishi Harada MD , Hiroyuki Inoue MD, PhD , Hiroshi Ishii MD, PhD , Kazunori Tobino MD, PhD , Chiho Nakashima MD, PhD , Yoshifusa Koreeda MD , Yasushi Hisamatsu MD , Shinsuke Tsumura MD , Takashi Inagaki MD , Keiko Mizuno MD, PhD , Takayuki Shimose MMath , Isamu Okamoto MD, PhD","doi":"10.1016/j.jtocrr.2025.100836","DOIUrl":"10.1016/j.jtocrr.2025.100836","url":null,"abstract":"<div><h3>Introduction</h3><div>The combination of immune checkpoint inhibitors with chemotherapy is the standard treatment for extensive-stage (ES) SCLC. However, its safety for elderly patients is not fully validated. We evaluated the safety and efficacy of durvalumab plus carboplatin and etoposide in elderly patients with ES-SCLC.</div></div><div><h3>Methods</h3><div>In this prospective, single-arm, multicenter, phase 2 clinical trial, patients with ES-SCLC aged above or equal to 75 years received chemotherapy with up to four cycles of durvalumab 1500 mg on day 1, carboplatin at a dose equivalent to an area under the curve of 5 on day 1, and etoposide 80 mg/m<sup>2</sup> on days 1 to 3 every 3 weeks as induction therapy. Maintenance therapy with durvalumab 1500 mg was administered every 4 weeks until disease progression or unacceptable toxicity. The primary end point was safety, and key secondary end points were objective response rate, progression-free survival, overall survival, quality of life, and Geriatric Assessment.</div></div><div><h3>Results</h3><div>Between August 2021 and February 2023, 40 patients were enrolled at 17 institutions and 38 were assessable for safety and efficacy. Grade 3 or higher adverse events occurred in 36 patients (94.6%). The most common adverse events were hematologic, including grade 3 or higher neutropenia (76.3%) and febrile neutropenia (15.8%). The objective response rate, median progression-free survival, and median overall survival were 89.5%, 5.4 months, and 16.1 months, respectively. No decrease in quality of life or functional assessment scores was observed after treatment.</div></div><div><h3>Conclusion</h3><div>Durvalumab plus carboplatin and etoposide was tolerable and expected to be effective in elderly patients with ES-SCLC.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 7","pages":"Article 100836"},"PeriodicalIF":3.0,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144230340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Illaa Smesseim MD , Paul Baas MD, PhD , Jacobus A. Burgers MD, PhD
{"title":"Retreatment With Nivolumab and Ipilimumab in Pleural Mesothelioma Following Disease Progression After a Durable Response: Case Series","authors":"Illaa Smesseim MD , Paul Baas MD, PhD , Jacobus A. Burgers MD, PhD","doi":"10.1016/j.jtocrr.2025.100835","DOIUrl":"10.1016/j.jtocrr.2025.100835","url":null,"abstract":"<div><div>The CheckMate 743 trial established nivolumab and ipilimumab as the standard first-line treatment for unresectable pleural mesothelioma. However, optimal management following disease progression after a durable response to dual immunotherapy remains unclear. We report two cases of patients with pleural mesothelioma (epithelioid subtype) initially treated with nivolumab-ipilimumab, achieving prolonged disease control. Both patients experienced disease progression several years after treatment discontinuation and were subsequently retreated with nivolumab-ipilimumab on regulatory approval. In both cases, retreatment resulted in stable disease for at least 12 months. However, immune-related toxicities occurred, with one patient developing recurrent colitis and the other experiencing nephrotic syndrome, ultimately leading to treatment discontinuation. These cases suggest that retreatment with dual immunotherapy may be a viable strategy for selected patients with previous durable responses, although the risk of immune-related toxicity remains significant. Given the lack of prospective data, further research is needed to determine whether rechallenge with nivolumab-ipilimumab offers superior outcomes compared with chemotherapy or best supportive care in this setting. Rechallenging patients with pleural mesothelioma with nivolumab-ipilimumab after a durable response is feasible but associated with immune-related toxicity.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 7","pages":"Article 100835"},"PeriodicalIF":3.0,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144240390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Combination Therapy With MET Tyrosine Kinase Inhibitor and EGFR Tyrosine Kinase Inhibitor in Patients With MET-Overexpressed EGFR-Mutant Lung Adenocarcinoma","authors":"Jia-Jun Wu MD , Zhe-Rong Zheng MD , Tse-Hsien Lo MD , Cheng-Hsiang Chu MD , Kun-Chieh Chen MD, PhD , Gee-Chen Chang MD, PhD","doi":"10.1016/j.jtocrr.2025.100832","DOIUrl":"10.1016/j.jtocrr.2025.100832","url":null,"abstract":"<div><h3>Introduction</h3><div>Dysregulated <em>MET</em> signaling, such as MET overexpression or <em>MET</em> amplification (<em>MET</em>amp), is a important mechanism of resistance to EGFR tyrosine kinase inhibitors (TKIs) in patients with <em>EGFR</em>-mutant lung adenocarcinoma (LUAD). Combination therapy with EGFR TKIs and MET TKIs has revealed efficacy in these patients. This study aimed to analyze the real-world experience of TKI combination in patients with <em>EGFR</em>-mutant MET-overexpressed LUAD.</div></div><div><h3>Methods</h3><div>This retrospective cohort study included patients with advanced <em>EGFR</em>-mutant LUAD who progressed after EGFR TKIs and were treated with combination therapy of EGFR TKIs and MET TKIs (capmatinib or tepotinib). Immunohistochemistry was used to detect MET overexpression.</div></div><div><h3>Results</h3><div>This study included 27 patients, with a median age of 69 years; 40.7% of the patients were male individuals, and 88.9% never smoked. Overall, the treatment response of the TKI combination reported 29.6% (eight of 27) partial response, 55.6% (15 of 27) stable disease, a median progression-free survival of 7.3 months, and an overall survival of 26.9 months. The adverse events were mostly grade 1 to 2, with only one patient experiencing a grade 3 or greater event, which was peripheral edema. The most common adverse events were hypoalbuminemia (44.4%), increased creatinine (44.4%), and peripheral edema (44.4%). Eight patients underwent next-generation sequencing analysis, and two (25.0%) of them had <em>MET</em>amp. Three patients (37.5%) had <em>TP53</em> mutations, which were the most common concurrent alterations. Those with positive <em>MET</em>amp had significantly longer median progression-free survival than those without (25.3 versus 5.8 mo; <em>p</em> = 0.034).</div></div><div><h3>Conclusions</h3><div>The TKI combination reported clinical activities in patients with advanced <em>EGFR</em>-mutant LUAD resistant to EGFR TKIs and mild toxicity in those with MET overexpression.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 6","pages":"Article 100832"},"PeriodicalIF":3.0,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143912809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sabine Raimann MD , Sämi Schär PhD , Stefanie Hayoz PhD , Matthias Guckenberger MD , Tobias Finazzi MD, PhD , Isabelle Opitz MD , Sabine Schmid MD , Michael Mark MD , Alfredo Addeo MD , Laetitia A. Mauti MD, PhD , Daniel C. Betticher MD , Hans-Beat Ris MD , Roger Stupp MD , Alessandra Curioni-Fontecedro MD , Solange Peters MD, PhD , Martin Früh MD , Sacha I. Rothschild MD, PhD , Miklos Pless MD , David König MD
{"title":"Outcomes in Patients With Resectable Stage III NSCLC Who Did Not Have Definitive Surgery After Neoadjuvant Treatment—A Retrospective Analysis of the SAKK Trials 16/96, 16/00, 16/01, 16/08, and 16/14: A Brief Report","authors":"Sabine Raimann MD , Sämi Schär PhD , Stefanie Hayoz PhD , Matthias Guckenberger MD , Tobias Finazzi MD, PhD , Isabelle Opitz MD , Sabine Schmid MD , Michael Mark MD , Alfredo Addeo MD , Laetitia A. Mauti MD, PhD , Daniel C. Betticher MD , Hans-Beat Ris MD , Roger Stupp MD , Alessandra Curioni-Fontecedro MD , Solange Peters MD, PhD , Martin Früh MD , Sacha I. Rothschild MD, PhD , Miklos Pless MD , David König MD","doi":"10.1016/j.jtocrr.2025.100834","DOIUrl":"10.1016/j.jtocrr.2025.100834","url":null,"abstract":"<div><h3>Introduction</h3><div>Neoadjuvant or perioperative treatment, including an immune checkpoint inhibitor (ICI), has emerged as a new standard for patients with resectable stage III NSCLC. Nevertheless, approximately 20% of patients who start neoadjuvant chemo-immunotherapy will not undergo definitive surgery. Little is known about these patients.</div></div><div><h3>Methods</h3><div>We analyzed outcomes of patients without definitive surgery from five Swiss Group for Clinical Cancer Research (SAKK) trials that investigated different neoadjuvant treatment modalities in patients with resectable stage III-N2 NSCLC. Study treatment included neoadjuvant cisplatin-docetaxel chemotherapy (with or without radiotherapy), either combined with peri-operative durvalumab in the SAKK 16/14 trial (n = 68) or without an ICI (non-ICI trials, n = 431).</div></div><div><h3>Results</h3><div>Of the 499 patients, 102 (20%) did not have definitive surgery. Cancellation of surgery occurred in a similar proportion of patients with or without neoadjuvant ICI (19% versus 21%, <em>p</em> = 0.9). Reasons were in non-ICI trials and SAKK 16/14: disease progression (47% and 54%), nonresectability (18% and 8%), medical reasons (17% and 31%), and unknown (18% and 8%), respectively. Of these patients, no patient in SAKK 16/14 and 17 patients (19%) in the non-ICI trials received curative-intended salvage therapy. Three-year overall survival was higher in patients who had definitive surgery compared with those who did not: 78% versus 32% (SAKK 16/14) and 54% versus 10% (non-ICI trials).</div></div><div><h3>Conclusions</h3><div>In our pooled analysis, patients with definitive surgery had higher survival rates than those without definitive surgery. Prognosis in patients without definitive surgery seems to have improved in the era of ICI.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 6","pages":"Article 100834"},"PeriodicalIF":3.0,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143899129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Angelos Vasilopoulos BS , Alexander Pohlman MD , Ayham Odeh MD , K. Robert Shen MD , Julia M. Coughlin MD , Zaid M. Abdelsattar MD, MS, FACS
{"title":"Cost-Effectiveness of Adjuvant Osimertinib With and Without Chemotherapy for Surgically Resected NSCLC","authors":"Angelos Vasilopoulos BS , Alexander Pohlman MD , Ayham Odeh MD , K. Robert Shen MD , Julia M. Coughlin MD , Zaid M. Abdelsattar MD, MS, FACS","doi":"10.1016/j.jtocrr.2025.100833","DOIUrl":"10.1016/j.jtocrr.2025.100833","url":null,"abstract":"<div><h3>Introduction</h3><div>Osimertinib is now approved as adjuvant therapy for stage IB to III NSCLC with <em>EGFR</em> mutations. Nevertheless, this treatment is lengthy and expensive. Its cost-effectiveness profile as monotherapy versus combination with chemotherapy is unknown. In this context, we investigate the cost-effectiveness of adjuvant osimertinib with and without chemotherapy for NSCLC.</div></div><div><h3>Methods</h3><div>A set of Markov models was established to predict the cost-effectiveness of these different regimens. Data were sourced from the ADAURA trial’s publications and protocols. Health outcomes were quantified as quality-adjusted life-years (QALYs). Costs and incremental cost-effectiveness ratios (ICERs) were estimated in U.S. dollars (USD) and USD per QALY, respectively. Deterministic and probabilistic sensitivity analyses were performed. Data from the Surveillance, Epidemiology, and End Results Program were used to predict additional costs to the U.S. health care system.</div></div><div><h3>Results</h3><div>Compared with treatment with chemotherapy alone, treatment with osimertinib plus chemotherapy yielded 5.86 QALYs with incremental costs of $414,607.69 (ICER = $380,347.85 per QALY). Treatment with osimertinib alone yielded 6.63 QALYs with an incremental cost of $402,224.32 (ICER = $213,447.59 per QALY). Osimertinib is only likely to be cost-effective if the willingness-to-pay threshold per QALY is $200,000 or more. The price of osimertinib had the strongest influence on cost-effectiveness. On the basis of Surveillance, Epidemiology, and End Results Program data, these practices may cost the U.S. health care system an additional 8.9 billion USD/year.</div></div><div><h3>Conclusions</h3><div>Adjuvant osimertinib alone is more cost-effective than combination therapy, but only if the willingness-to-pay is high. A reduction in the price of osimertinib would improve its cost-effectiveness profile.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 6","pages":"Article 100833"},"PeriodicalIF":3.0,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143899127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
V. Paul Doria-Rose DVM, PhD , Gerard A. Silvestri MD, MS , Danielle D. Durham PhD , Philip Connor BS , Lenka Goldman MSE , Lindsey Enewold PhD, MPH , Farhood Farjah MD, MPH , Eric A. Miller PhD, MSPH , Michael Simanowith MD , Robert A. Smith PhD , Louise M. Henderson PhD, MSPH , Raymond U. Osarogiagbon M.B.B.S., FASCO , Ella A. Kazerooni MD, MS , Andrew Ward PhD, MPH , Paul Pinsky PhD
{"title":"The United States’ Early Experience With Lung Cancer Screening—Creation of a National Data Linkage: A Brief Report","authors":"V. Paul Doria-Rose DVM, PhD , Gerard A. Silvestri MD, MS , Danielle D. Durham PhD , Philip Connor BS , Lenka Goldman MSE , Lindsey Enewold PhD, MPH , Farhood Farjah MD, MPH , Eric A. Miller PhD, MSPH , Michael Simanowith MD , Robert A. Smith PhD , Louise M. Henderson PhD, MSPH , Raymond U. Osarogiagbon M.B.B.S., FASCO , Ella A. Kazerooni MD, MS , Andrew Ward PhD, MPH , Paul Pinsky PhD","doi":"10.1016/j.jtocrr.2025.100825","DOIUrl":"10.1016/j.jtocrr.2025.100825","url":null,"abstract":"<div><h3>Introduction</h3><div>Lung cancer screening has been recommended by the United States Preventive Services Taskforce since 2013. The Centers for Medicare and Medicaid Services coverage decision in early 2015 required data submission to a Centers for Medicare and Medicaid Services–approved registry for facilities to receive payment for screening. Only the American College of Radiology’s Lung Cancer Screening Registry (LCSR) received approval for this purpose. Some LCSR elements, such as race, ethnicity, downstream diagnostic procedures, and cancer outcomes, were underreported.</div></div><div><h3>Methods</h3><div>To address underreporting, we linked data from the LCSR to Medicare and Surveillance, Epidemiology, and End Results cancer registry data from 2015 to 2021. We created two different cohorts of individuals aged 65 years and older: (1) those who were enrolled in Medicare fee-for-service plans with parts A and B coverage at the time of at least one LCSR-reported screen, and (2) Medicare beneficiaries (regardless of whether fee-for-service or managed care) living within a Surveillance, Epidemiology, and End Results catchment area at the time of at least one LCSR-reported screen. We compared the characteristics of individuals in the linked cohorts with those of all individuals in the LCSR aged 65 years and over.</div></div><div><h3>Results</h3><div>Demographic, smoking history, and screening examination data elements in the linked data were generally similar to those in the overall LCSR.</div></div><div><h3>Conclusions</h3><div>On the basis of these results, the linked populations seem to be generally representative of older individuals in the LCSR. These unique data linkages provide an unprecedented opportunity to better understand the early implementation of lung cancer screening in the United States.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 6","pages":"Article 100825"},"PeriodicalIF":3.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143899128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jia Liao MD , Song Wu MD , Yi Min MD , Yiran Li MD , Yuanhang Nie MD , Quwen Chen MD , Zhiliang Mao MD , Qinglan Zong MS , Ning Gao MS , Ding Zhang PhD , Weiquan Liang MD
{"title":"The Landscape of MET Exon 14 Skipping Mutations in Patients With Lung Cancer Identified by Next-Generation Sequencing","authors":"Jia Liao MD , Song Wu MD , Yi Min MD , Yiran Li MD , Yuanhang Nie MD , Quwen Chen MD , Zhiliang Mao MD , Qinglan Zong MS , Ning Gao MS , Ding Zhang PhD , Weiquan Liang MD","doi":"10.1016/j.jtocrr.2025.100826","DOIUrl":"10.1016/j.jtocrr.2025.100826","url":null,"abstract":"<div><h3>Introduction</h3><div><em>MET</em> exon 14 (<em>MET</em>ex14) skipping mutations are observed in approximately 0.9% to 4% of patients with NSCLC. This study aimed to compare the detection rates of <em>MET</em>ex14 skipping in Chinese patients with lung cancer using DNA-based next-generation sequencing (NGS) with capture-based library construction and synchronous DNA-based and RNA-based NGS with amplicon-based library construction.</div></div><div><h3>Methods</h3><div>A total of 11,330 tissue samples from 11,330 Chinese patients with lung cancer were included in the study to confirm the presence of <em>MET</em>ex14 skipping. Simultaneously, MET immunohistochemistry testing was performed on 30 patients.</div></div><div><h3>Results</h3><div>The highest detection rate of <em>MET</em>ex14 skipping was observed in the synchronous DNA and RNA-based NGS with amplicon-based library construction, reaching 2.20%. A total of 45 different variants leading to <em>MET</em>ex14 skipping were detected at the DNA level. These variants were widely distributed across a 197–base pair DNA sequence. In the overall population, the incidence of <em>MET</em>ex14 skipping was significantly higher in individuals aged 60 years and above (<em>p</em> < 0.0001) and needle biopsy samples (<em>p</em> < 0.0001) and reported no significant association with gender and tumor location. A positive correlation was observed between microsatellite instability–high and <em>MET</em>ex14 skipping (<em>p</em> < 0.0001).</div></div><div><h3>Conclusions</h3><div>The mutations causing <em>MET</em>ex14 skipping exhibit diversity in terms of variant types and are widely distributed across various genomic regions. Synchronous DNA-based and RNA-based NGS is considered the optimal method for detecting <em>MET</em>ex14 skipping. Furthermore, <em>MET</em>ex14 skipping is enriched in specific populations, including individuals aged 60 years and above, with advanced-stage disease and a microsatellite instability-high status.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 7","pages":"Article 100826"},"PeriodicalIF":3.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144271808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}