Sample types applied for molecular diagnosis of therapeutic management of advanced non-small cell lung cancer in the precision medicine

Abstract

Abstract:In this era of precision medicine, molecular biology is becoming increasingly significant for the diagnosis and therapeutic management of non-small cell lung cancer. The specimen as the primary element of the whole testing flow is particularly important for maintaining the accuracy of gene alteration testing. Presently, the main sample types applied in routine diagnosis are tissue and cytology biopsies. Liquid biopsies are considered as the most promising alternatives when tissue and cytology samples are not available. Each sample type possesses its own strengths and weaknesses, pertaining to the disparity of sampling, preparation and preservation procedures, the heterogeneity of inter-or intratumors, the tumor cellularity (percentage and number of tumor cells) of specimens, etc., and none of them can individually be a "one size to fit all". Therefore, in this review, we summarized the strengths and weaknesses of different sample types that are widely used in clinical practice, offered solutions to reduce the negative impact of the samples and proposed an optimized strategy for choice of samples during the entire diagnostic course. We hope to provide valuable information to laboratories for choosing optimal clinical specimens to achieve comprehensive functional genomic landscapes and formulate individually tailored treatment plans for NSCLC patients that are in advanced stages.

Multicenter Evaluation of the Fully Automated PCR-Based Idylla EGFR Mutation Assay on Formalin-Fixed, Paraffin-Embedded Tissue of Human Lung Cancer

“…It is generally accepted that tissue samples obtained from NSCLC patients are mostly small biopsies obtained by endoscopy or by imageguided transthoracic core-needle biopsy. 34 After histologic analysis, which consumes numerous sections, and molecular biology analyses performed with the routine reference method used in the laboratory, usually only a small amount of tissue sample material remains. Also, in this study, in eight discordant cases, the FFPE materials remaining were not sufficient to obtain results from further analysis with additional methods and, thus, unfortunately these samples needed to be excluded from the final concordance data set as inconclusive.…”

Molecular analysis of small tissue samples obtained via transbronchial lung biopsy using radial probe endobronchial ultrasound

“…Fifth, given the retrospective nature of this study, it was not possible to quantitatively analyze the effect of sample volume on the molecular data. Generally, the cellularity of the specimen is important for interpretation of mutation analysis results [44]. Recent guidelines recommend mutation analysis of samples with an at-least 20% malignant cell content [35].…”

Non-Small Cell Lung Cancer in Countries of Central and Southeastern Europe: Diagnostic Procedures and Treatment Reimbursement Surveyed by the Central European Cooperative Oncology Group

“…Lung cancer is the first cause of cancer‐related mortality, with approximately 1.6 million cancer‐related deaths per year worldwide. The diagnosis is usually made when the disease is already advanced, resulting in a low 5‐year combined survival rate of 17% . This number is expected to improve due to the identification of specific oncogenic alterations and development of targeted therapies, particularly in lung adenocarcinoma, as well as by the introduction of promising immune checkpoint inhibitor treatments.…”