ArticleClinical cancer research : an official journal of the American Association for Cancer Research2019
Comprehensive Next-Generation Sequencing Unambiguously Distinguishes Separate Primary Lung Carcinomas From Intrapulmonary Metastases: Comparison with Standard Histopathologic Approach.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers, 3 of them syntheses that pooled it.
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Who cites it
64 citing papers in PubMed, 3 syntheses or guidelines pooled it.
- Next-Generation Sequencing vs. Clinical-Pathological Assessment in Diagnosis of Multiple Lung Cancers: A Systematic Review and Meta-Analysis.Thoracic cancer · 2025Pooled it
- Evaluation of surgical outcomes and prognostic factors of second primary lung cancer based on a systematic review and meta-analysis.BMC surgery · 2023Pooled it
- Differential Diagnostic Value of Histology in MPLC and IPM: A Systematic Review and Meta-Analysis.Frontiers in oncology · 2022Pooled it
- Multiple Primary Lung Cancers in Surgical Patients: Revisiting Martini and Melamed 50 Years Later.Cancers · 2026Article
- Utilizing clinical features, genetic mutations, and a 14-gene molecular assay for optimizing the management of multiple primary lung cancer.Translational lung cancer research · 2026Article
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- Comprehensive diagnosis and individualized treatment of multiple primary lung cancer: A case report.Experimental and therapeutic medicine · 2026Article
- Dual primary malignancies in Kashmir: A five-year analysis of temporal patterns, gender-specific presentations and treatment outcomes in a high gastrointestinal cancer risk population.Journal of family medicine and primary care · 2026Review
- Clinicopathological characteristics associated with intrapulmonary metastasis rather than single primary lung cancer at first diagnosis: a study based on the Surveillance, Epidemiology, and End Results database using Bayesian networks and structural equation modeling.Translational lung cancer research · 2026Article
- Article
- Identification ofOncology research · 2026Article
- The Added Value of Genome-Wide Copy Numbers to Objectively Resolve Clonality of Multiple Tumors With Pulmonary Involvement and Ambiguous or Inconclusive Mutational Diagnosis.JTO clinical and research reports · 2025Article
- The impact of spread through air spaces on intrapulmonary metastasis in lung cancer: a retrospective study of multiple primary lung adenocarcinomas with confirmed common origin based on histological classification alone and combined histological-molecular classification.Translational lung cancer research · 2025Article
- Lung metastases.Nature reviews. Disease primers · 2025Review
- Different prognosis of multiple lung cancer identified by 116-gene panel by next-generation sequencing based on an Asian population.Translational lung cancer research · 2025Article
- Performance and considerations in the use of diagnostic mutation panels for clonality testing in non-small-cell lung carcinoma.ESMO open · 2025Article
- Development and validation of machine learning models based on molecular features for estimating the probability of multiple primary lung carcinoma versus intrapulmonary metastasis in patients presenting multiple non-small cell lung cancers.Translational lung cancer research · 2025Article
- Optimizing the NGS-based discrimination of multiple lung cancers from the perspective of evolution.NPJ precision oncology · 2025Article
- Developmental mosaicism underlying EGFR-mutant lung cancer presenting with multiple primary tumors.Nature cancer · 2024Article
- Non-small-cell lung cancer.Nature reviews. Disease primers · 2024Review
4 more citing papers are in PubMed but not listed here.
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Authors and funding
19 authors.
Funding
Abstract
purposeIn patients with >1 non-small cell lung carcinoma (NSCLC), the distinction between separate primary lung carcinomas (SPLCs) and intrapulmonary metastases (IPMs) is a common diagnostic dilemma with critical staging implications. Here, we compared the performance of comprehensive next-generation sequencing (NGS) with standard histopathologic approaches for distinguishing NSCLC clonal relationships in clinical practice. EXPERIMENTAL
designWe queried 4,119 NSCLCs analyzed by 341-468 gene MSK-IMPACT NGS assay for patients with >1 surgically resected tumor profiled by NGS. Tumor relatedness predicted by prospective histopathologic assessment was contrasted with comparative genomic profiling by subsequent NGS.
resultsSixty patients with NGS performed on >1 NSCLCs were identified, yielding 76 tumor pairs. NGS classified tumor pairs into 51 definite SPLCs (median, 14; up to 72 unique somatic mutations per pair), and 25 IPMs (24 definite, one high probability; median, 5; up to 16 shared somatic mutations per pair). Prospective histologic prediction was discordant with NGS in 17 cases (22%), particularly in the prediction of IPMs (44% discordant). Retrospective review highlighted several histologic challenges, including morphologic progression in some IPMs. We subsampled MSK-IMPACT data to model the performance of less comprehensive assays, and identified several clinicopathologic differences between NGS-defined tumor pairs, including increased risk of subsequent recurrence for IPMs.
conclusionsComprehensive NGS allows unambiguous delineation of clonal relationship among NSCLCs. In comparison, standard histopathologic approach is adequate in most cases, but has notable limitations in the recognition of IPMs. Our results support the adoption of broad panel NGS to supplement histology for robust discrimination of NSCLC clonal relationships in clinical practice.
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