Real-World Study on Implementation of Genomic Tests for Advanced Lung Adenocarcinoma in Brazil

• Published in: JCO global oncology 2024-11, Vol.10 (10), p.e2400354
• Main Authors: Dienstmann, Rodrigo, da Silva, Leonard M, Orpinelli Ramos do Rego, Fernanda, Muniz Rodrigues, Amanda, Koyama, Fernanda Christtanini, Galindo, Layla Testa, de Bustamante Fernandes, Carolina, de Souza, Bruno Batista, Paes, Rafael Duarte, Montella, Tatiane, de Marchi, Pedro, Jeha Araújo, Breno, Ferrari, Bruno Lemos, Mathias, Clarissa, Pereira, Emilio, Zalis, Mariano Gustavo, Leslin, Chesley, Ferreira, Carlos Gil
• Format: Article
• Language: English
• Subjects: Adenocarcinoma of Lung - diagnosis; Adenocarcinoma of Lung - genetics; Adenocarcinoma of Lung - pathology; Adult; Aged; Aged, 80 and over; Anaplastic Lymphoma Kinase - genetics; B7-H1 Antigen - genetics; Biomarkers, Tumor - genetics; Brazil; ErbB Receptors - genetics; Female; Genomics - methods; High-Throughput Nucleotide Sequencing; Humans; Lung Neoplasms - diagnosis; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Male; Middle Aged; Mutation; Precision Medicine - methods
• ISSN: 2687-8941; 2687-8941
• DOI: 10.1200/GO-24-00354

Tissue inadequacy and operational challenges may limit lung cancer comprehensive biomarker testing. Here, we describe the initial implementation of a tailored tissue molecular journey at Oncoclínicas Precision Medicine Laboratory in Brazil, which includes fast-track (FT) non-next-generation sequencing (NGS) assays combined with a broad NGS panel. From 2021 to 2023, all nonsquamous lung cancer samples eligible for the patient support program "Lung Mapping Consortium" at Oncoclínicas & Co were evaluated using the FT panel (immunohistochemistry for PD-L1 and anaplastic lymphoma kinase [ALK], polymerase chain reaction for and , and fluorescence in situ hybridization for ) plus a broad DNA and RNA sequencing panel of 180 genes (custom ARCHER panel). From 1,272 samples received by the laboratory, 3% had no tissue for any molecular testing, 20% was not eligible for broad NGS panel as per pathologist assessment (tumor purity and quantity), additional 12% did not reach presequencing analytical thresholds (nucleic acid quantity and/or quality), and 3% had postsequencing failure. Most frequent alterations were mutations (28.4%, 9.7%), mutations (23.6%, exon20 insertions 2.9%), fusions (6.4%), exon 14 skipping (4.4%), mutations (3.4%), fusions (3.1%), and (1.9%). In 35% of the samples, FT non-NGS tests were the only molecular diagnostics: mutations (14%), fusions (4.4%), fusions (1.8%), and (0.7%). Overall, high PD-L1 expression (≥50%) was found in 12.3%. This study provides data on the molecular epidemiology of lung adenocarcinoma in Brazil, confirming high prevalence of mutations, fusions, and exon 14 skipping alteration. Biomarker detection is largely affected by biospecimen collection and processing, with one third of the patients eligible for non-NGS testing only, which presents reduced coverage and sensitivity for actionable drivers.