ArticleThe oncologist2022
Targeted Next-Generation Sequencing Reveals Exceptionally High Rates of Molecular Driver Mutations in Never-Smokers With Lung Adenocarcinoma.
Article in The oncologist, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 2 of them syntheses that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
24 citing papers in PubMed, 2 syntheses or guidelines pooled it, 31 citations in OpenAlex.
- Vitiligo-like Lesions as a Predictor of Response to Immunotherapy in Non-Small Cell Lung Cancer: Comprehensive Review and Case Series from a University Center.Current oncology (Toronto, Ont.) · 2024Pooled it
- A systematic review of genetic ancestry as a risk factor for incidence of non-small cell lung cancer in the US.Frontiers in genetics · 2023Pooled it
- Clinical and molecular characterization of a large Brazilian lung cancer cohort: a real-world observational study.Lancet regional health. Americas · 2026Article
- Review
- Article
- Successful Treatment of HER2 V659E Mutation-Positive Lung Adenocarcinoma With Trastuzumab Deruxtecan: A Case Report.Thoracic cancer · 2025Article
- Next-Generation Sequencing Analysis on Image-Guided Biopsy Samples in Early-Stage Lung Cancer: Feasibility Study and Comparison With Surgical Samples.JTO clinical and research reports · 2025Article
- Evolving trends in lung cancer risk factors in the ten most populous countries: an analysis of data from the 2019 Global Burden of Disease Study.EClinicalMedicine · 2025Article
- Topography of mutational signatures in non-small cell lung cancer: emerging concepts, clinical applications, and limitations.The oncologist · 2024Review
- Molecular profile of driver genes in lung adenocarcinomas of Brazilian patients who have never smoked: implications for targeted therapies.The oncologist · 2024Article
- [Advances in Diagnosis and Targeted Therapy of G719X/L861Q/S768I Mutant Non-small Cell Lung Cancer].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2024Review
- The Genetic Analysis and Clinical Therapy in Lung Cancer: Current Advances and Future Directions.Cancers · 2024Review
- Real-World Clinical Performance of a DNA-Based Comprehensive Genomic Profiling Assay for Detecting Targetable Fusions in Nonsquamous NSCLC.The oncologist · 2024Article
- Article
- Article
- Review
- Lung cancer associated with combustion particles and fine particulate matter (PMBiochemical pharmacology · 2023Review
- New insights into the biology and development of lung cancer in never smokers-implications for early detection and treatment.Journal of translational medicine · 2023Review
- A Functional Genomics Review of Non-Small-Cell Lung Cancer in Never Smokers.International journal of molecular sciences · 2023Review
- A narrative review of methods for the identification ofTranslational lung cancer research · 2023Review
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionHistorically, high rates of actionable driver mutations have been reported in never-smokers with lung adenocarcinoma (ADC). In the era of modern, comprehensive cancer mutation sequencing, this relationship necessitates a more detailed analysis.
methodsAll Mount Sinai patients between January 1, 2015, and June 1, 2020, with a diagnosis of ADC of any stage with known smoking status who received genomic testing were included. Most patients were analyzed using the Sema4 hotspot panel or the Oncomine Comprehensive Assay version 3 next-generation sequencing (NGS) panel conducted at Sema4. Patients were considered fully genotyped if they were comprehensively analyzed for alterations in EGFR, KRAS, MET, ALK, RET, ROS1, BRAF, NTRK1-3, and ERBB2, otherwise they were considered partially genotyped.
resultsTwo hundred and thirty-six never-smokers and 671 smokers met the above criteria. Of the never-smokers, 201 (85%) had a driver mutation with 167 (71%) considered actionable (ie, those with US Food and Drug Administration-approved agents). Among smokers, 439 (65%) had an identified driver mutation with 258 (38%) actionable (P < .0001). When comprehensively sequenced, 95% (70/74) of never-smokers had a driver mutation with 78% (58/74) actionable; whereas, for smokers, 75% (135/180) had a driver with only 47% (74/180) actionable (P < .0001). Within mutations groups, EGFR G719X and KRAS G12Cs were more common to smokers. For stage IV patients harboring EGFR-mutant tumors treated with EGFR-directed therapies, never-smokers had significantly improved OS compared to smokers (hazard ratio = 2.71; P = .025). In multivariable analysis, Asian ancestry and female sex remained significant predictors of (1) OS in stage IV patients and (2) likelihood of harboring a receptor of fusion-based driver.
conclusionComprehensive NGS revealed driver alterations in 95% of never-smokers, with the majority having an associated therapy available. All efforts should be exhausted to identify or rule out the presence of an actionable driver mutation in all metastatic lung ADC.
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