Actualización de las Guías de Estudio Molecular para la Selección de Pacientes con Cáncer de Pulmón para Terapias Dirigidas con Inhibidores de Tirosina Quinasa-download

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The article discusses the updated guidelines for molecular testing in lung cancer patients developed by the American College of Pathologists (CAP), the International Association for the Study of Lung Cancer (IASLC), and the Association for Molecular Pathology (AMP). The guidelines recommend testing for EGFR mutations and ALK rearrangements in all advanced-stage lung cancer patients with adenocarcinoma. They also recommend the study of ROS1 for all patients with adenocarcinoma and the inclusion of additional genes in next-generation sequencing panels. The use of immunohistochemistry as an alternative to FISH for ALK and ROS1 testing is also suggested. The update includes new recommendations such as the use of a 5% sensitivity assay for EGFR T790M mutations in patients with secondary resistance to EGFR inhibitors and the use of circulating cell-free DNA when tissue is limited. Molecular testing is important as targeted therapies have shown significant improvements in survival and quality of life. The guidelines will be reviewed regularly and should be considered in the context of each patient's specific circumstances.<br /> <br />The new recommendations classify genes into three categories: those that should be studied in all lung cancer patients (EGFR, ALK, ROS1), those that can be included in expanded gene panels (BRAF, MET, RET, ERBB2, KRAS), and those for research purposes only. ROS1 testing is recommended for all advanced-stage adenocarcinoma patients. The evidence for studying BRAF, RET, ERBB2, MET, and KRAS is considered inadequate, but future evidence may support their inclusion as single gene studies.<br /><br />Immunohistochemistry is recommended as an alternative to FISH for ALK rearrangement testing, and validated IHC assays should be used. A meta-analysis shows that IHC has high sensitivity and specificity for detecting ALK rearrangements. Cases with discordant FISH and IHC results should be further evaluated using validated methods.<br /><br />Next-generation sequencing can be used for the evaluation of gene fusions and mutations beyond EGFR, ALK, and ROS1. Panel-based sequencing is preferred over multiple single gene tests. Laboratories should confirm or resolve discordant results with alternative methods or samples.<br /><br />For patients with limited tissue, circulating cell-free DNA testing can be used to identify EGFR mutations, but negative results should be confirmed with tissue testing. Testing for EGFR T790M mutations should be performed in patients with EGFR-mutant adenocarcinoma who progress on EGFR-targeted therapy. Testing for ALK mutations is not currently recommended in patients who progress on ALK-targeted therapy.<br /><br />Recommendations for using molecular testing in the selection of patients for immunomodulatory therapies are not available yet, but tissues should be preserved for future testing.

Keywords

molecular testing

lung cancer patients

EGFR mutations

ALK rearrangements

adenocarcinoma

ROS1

next-generation sequencing panels

immunohistochemistry

targeted therapies

circulating cell-free DNA