Advancing Lung Cancer Staging: Integrating IASLC Recommendations and Bioinformatics to Delineate Tumor Origins

作者：M. Allgäuer, Klaus Kluck, P. Christopoulos, Markus Ball, A-L Volckmar, T. Radonic, L. Bubendorf, Paul Hofman, Claus Peter Heußel, H. Winter, Felix Herth, M. Thomas, Bauke Ylstra, S. Peters, Peter Schirmacher, D. Kazdal, Jan Budczies, A Stenzinger, M. Kirchner · 发表于：Journal of Thoracic Oncology · 年份：2025 · DOI：10.1016/j.jtho.2025.10.010 · 被引用次数：6 · 研究领域：Lung Cancer Treatments and Mutations、Lung Cancer Diagnosis and Treatment、Cancer Genomics and Diagnostics

INTRODUCTION: Accurate distinction between separate primary lung carcinomas (SPLCs) and intrapulmonary metastases (IPMs) is essential for staging and treatment of multifocal NSCLC. Next-generation sequencing (NGS) enables assessment of clonal relatedness. The proposed International Association for the Study of Lung Cancer (IASLC) algorithm integrates histologic and molecular data, though its clinical utility is yet to be validated. METHODS: We focused on the molecular component of the algorithm and assessed 240 tumor pairs from 120 patients with formalin-fixed, paraffin-embedded tumor samples that underwent small-scale gene-panel NGS testing (31-54 genes) within routine clinical care. Most tumors were adenocarcinomas (n = 222), with 18 tumors other NSCLC subtypes. Inconclusive pairs by molecular classification were subjected to large-scale panel analyses (531 genes). In addition, we developed a bioinformatic method to complement and refine the IASLC method. RESULTS: In total, 22 tumor pairs (18%) remained inconclusive and 16 (13%) were classified ambiguous (probable SPLCs) using the molecular IASLC method. Resequencing classified nine 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 three pairs remained inconclusive (2%). Tumors classified as SPLCs had a significantly longer overall survival than IPMs. CONCLUSIONS: Small-scale pa...