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000305532 1001_ $$aAllgäuer, M.$$b0
000305532 245__ $$aAdvancing Lung Cancer Staging: Integrating IASLC Recommendations and Bioinformatics to Delineate Tumor Origins.
000305532 260__ $$aAmsterdam$$bElsevier$$c2025
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000305532 520__ $$aAccurate distinction between separate primary lung carcinomas (SPLCs) and intrapulmonary metastases (IPMs) is essential for staging and treatment of multifocal non-small cell lung carcinoma (NSCLC). Next-generation sequencing (NGS) enables assessment of clonal relatedness. The proposed IASLC algorithm integrates histological and molecular data, though its clinical utility is yet to be validated.We focused on the molecular component of the algorithm and assessed 240 tumor pairs from 120 patients with formalin-fixed paraffin-embedded (FFPE) tumor samples that underwent small-scale gene panel NGS testing (31-54 genes) within routine clinical care. Most tumors were adenocarcinomas (n=222), 18 tumors other NSCLC subtypes. Inconclusive pairs by molecular classification were subjected to large-scale panel analyses (531 genes). Additionally, we developed a bioinformatic method to complement and refine the IASLC method.In total 22 tumor pairs (18%) remained inconclusive and 16 (13%) were classified ambiguous (probable SPLCs) using the molecular IASLC method. Re-sequencing classified 9 of 22 inconclusive pairs as IPMs. Using a newly developed bioinformatic method for clonality classification incorporating likelihood ratios of mutational prevalence and small-scale sequencing, only 3 pairs remained inconclusive (2%). Tumors classified as SPLCs had a significantly longer overall survival than IPMs.Small-scale panel sequencing of biopsy material allows unambiguous clonality determination in 3 of 4 cases. Large-scale sequencing resolves about half of inconclusive cases. Our bioinformatic method reduces inconclusive pairs to 2% even with small-scale NGS. It is made publicly available as a Shiny App. Clonality is reflected in survival data and therefore pivotal in daily clinical practice.
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000305532 650_7 $$2Other$$a(max. n=5) Multiple pulmonary tumors
000305532 650_7 $$2Other$$aIASLC recommendations (2024)
000305532 650_7 $$2Other$$aNext Generation Sequencing (NGS)
000305532 650_7 $$2Other$$aclonality classification
000305532 7001_ $$aKluck, K.$$b1
000305532 7001_ $$aChristopoulos, P.$$b2
000305532 7001_ $$aBall, M.$$b3
000305532 7001_ $$aVolckmar, A-L$$b4
000305532 7001_ $$aRadonic, T.$$b5
000305532 7001_ $$aBubendorf, L.$$b6
000305532 7001_ $$aHofman, P.$$b7
000305532 7001_ $$aHeußel, C. P.$$b8
000305532 7001_ $$aWinter, H.$$b9
000305532 7001_ $$aHerth, F.$$b10
000305532 7001_ $$aThomas, M.$$b11
000305532 7001_ $$aYlstra, B.$$b12
000305532 7001_ $$aPeters, S.$$b13
000305532 7001_ $$aSchirmacher, P.$$b14
000305532 7001_ $$0P:(DE-HGF)0$$aKazdal, D.$$b15
000305532 7001_ $$0P:(DE-HGF)0$$aBudczies, J.$$b16
000305532 7001_ $$0P:(DE-HGF)0$$aStenzinger, A.$$b17
000305532 7001_ $$aKirchner, M.$$b18
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