Molecular Testing Guideline for the Selection of Lung Cancer Patients for Treatment With Targeted Tyrosine Kinase Inhibitors-Actualización de las guías de estudio molecular para la selección de pacientes con cáncer de pulmón para terapias dirigidas con inhibidores de tirosina quinasa

Actualización de las guías de estudio molecular para la selección de pacientes con cáncer de pulmón para terapias dirigidas con inhibidores de tirosina quinasa

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The 2018 guidelines for molecular testing in lung cancer recommend the inclusion of specific genes such as EGFR, ALK, and ROS1 in testing for all patients. Other genes like BRAF, MET, RET, ERBB2, and KRAS can be included in expanded panels if enough material is available. The use of immunohistochemistry (IHC) is recommended as a cost-effective alternative to fluorescence in situ hybridization (FISH) for ALK testing. IHC has shown comparable results to FISH and can be used to select patients for ALK-targeted therapy. However, weak staining in IHC can be challenging to interpret, and additional testing methods like FISH, RT-PCR, or next-generation sequencing (NGS) may be needed in some cases.<br /><br />While IHC, RT-PCR, and NGS have shown comparable results to determine ALK fusions, only IHC is currently FDA-approved as a first-line method in the US. NGS is a promising method that can evaluate multiple genomic regions simultaneously, but more data is needed to develop specific recommendations for its use in ALK fusions. Multiplex genetic sequencing panels are preferred over individual gene testing for identifying therapeutic options beyond EGFR, ALK, and ROS1. However, the strength of evidence supporting the routine use of confirmatory tests and orthogonal methods to validate molecular markers is insufficient.<br /><br />In situations where tissue is limited or insufficient for testing, cell-free DNA (cfDNA) assays can be used to identify EGFR mutations. However, negative cfDNA results do not exclude the possibility of a mutation, and a tumor tissue test should be performed if the plasma result is negative. There is currently insufficient evidence to support the use of circulating tumor cells for the diagnosis of primary adenocarcinoma of the lung or the identification of EGFR or other mutations. The role of cfDNA in selecting patients for immunomodulatory therapies is still being explored, and no recommendations can be made at this time. <br /><br />Overall, the updated guidelines aim to provide clinicians and pathologists with a comprehensive framework for the molecular testing of lung cancer patients, but further research and evidence are needed to support the use of certain biomarkers and technologies in clinical practice. Confirmation tests and additional methods may be necessary in some cases, and the role of cfDNA and circulating tumor cells in guiding treatment decisions requires further investigation.

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Meta Tag

Concept Advanced-Stage Lung Cancer

Concept Terapia-Alvo

Concept EGFR

Concept Anaplastic Lymphoma Kinase

Concept ROS1

Concept EGFR T790M

Keywords

molecular testing

lung cancer

specific genes

EGFR

ALK

ROS1

immunohistochemistry

FISH

RT-PCR

cfDNA assays

Advanced-Stage Lung Cancer

Terapia-Alvo

EGFR

Anaplastic Lymphoma Kinase

ROS1

EGFR T790M