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| Home > Publications database > Advancing Lung Cancer Staging: Integrating IASLC Recommendations and Bioinformatics to Delineate Tumor Origins. |
| Journal Article | DKFZ-2025-02206 |
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2025
Elsevier
Amsterdam
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Please use a persistent id in citations: doi:10.1016/j.jtho.2025.10.010
Abstract: Accurate distinction between separate primary lung carcinomas (SPLCs) and intrapulmonary metastases (IPMs) is essential for staging and treatment of multifocal non-small cell lung carcinoma (NSCLC). Next-generation sequencing (NGS) enables assessment of clonal relatedness. The proposed IASLC algorithm integrates histological and molecular data, though its clinical utility is yet to be validated.We focused on the molecular component of the algorithm and assessed 240 tumor pairs from 120 patients with formalin-fixed paraffin-embedded (FFPE) tumor samples that underwent small-scale gene panel NGS testing (31-54 genes) within routine clinical care. Most tumors were adenocarcinomas (n=222), 18 tumors other NSCLC subtypes. Inconclusive pairs by molecular classification were subjected to large-scale panel analyses (531 genes). Additionally, we developed a bioinformatic method to complement and refine the IASLC method.In total 22 tumor pairs (18%) remained inconclusive and 16 (13%) were classified ambiguous (probable SPLCs) using the molecular IASLC method. Re-sequencing classified 9 of 22 inconclusive pairs as IPMs. Using a newly developed bioinformatic method for clonality classification incorporating likelihood ratios of mutational prevalence and small-scale sequencing, only 3 pairs remained inconclusive (2%). Tumors classified as SPLCs had a significantly longer overall survival than IPMs.Small-scale panel sequencing of biopsy material allows unambiguous clonality determination in 3 of 4 cases. Large-scale sequencing resolves about half of inconclusive cases. Our bioinformatic method reduces inconclusive pairs to 2% even with small-scale NGS. It is made publicly available as a Shiny App. Clonality is reflected in survival data and therefore pivotal in daily clinical practice.
Keyword(s): (max. n=5) Multiple pulmonary tumors ; IASLC recommendations (2024) ; Next Generation Sequencing (NGS) ; clonality classification
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