Therefore, the ASCO panel chose to incorporate this into the recommendations and to recommend BRAF testing for all patients with advanced lung adenocarcinoma. Fragment length analysis to detect exon 19 deletions and real-time PCR to detect the exon 21 mutation L858R are then used on samples that produce a negative result using Sanger sequencing. METHODS All patients with EGFR mutated non–small cell lung cancer for … The second step is PCR amplification and detection of EGFR‑TK mutations using complementary primer pairs and fluorescently labelled probes. The Diagnostics Advisory Committee considered clinical and cost-effectiveness evidence from a systematic review of epidermal growth factor receptor tyrosine kinase (EGFR-TK) mutation testing in adults with locally advanced or metastatic non-small-cell lung cancer (NSCLC) prepared by an External Review Group. This older version uses the same methods as the newer therascreen EGFR RGQ PCR Kit, and detects 28 of the same mutations, but is not designed to detect the resistance mutation T790M. Key Question 4: What testing is indicated for patients with targetable mutations who have relapsed on targeted therapy? Molecular Testing Guideline for the Selection of Patients With Lung Cancer for Treatment With Targeted Tyrosine Kinase Inhibitors: American Society of Clinical Oncology Endorsement of the College of American Pathologists/International Association for the Study of Lung Cancer/Association for Molecular Pathology Clinical Practice Guideline Update. 4.9 In this test strategy, Sanger sequencing of exons 18 to 21 (described in section 4.19) is used to detect EGFR‑TK mutations in test samples with more than 30% tumour cells, and the cobas EGFR Mutation Test (described in sections 4.5 to 4.7) is used to detect EGFR‑TK mutations in samples with less than 30% tumour cells. Editor’s note: This American Society of Clinical Oncology clinical practice guideline provides recommendations, with comprehensive review and analyses of the relevant literature for each recommendation. Newest Articles published online before print A systematic search of MEDLINE (Ovid Technologies, New York, NY) and PubMed from January 1, 2012, to June 27, 2016, was conducted. The ASCO Expert Panel also noted that, as is true for all guidelines, the interpretation and implementation of some of the statements may be influenced by the geographic location and the practice setting (academic v community). Precision in mutation testing. 4.1 The therascreen EGFR RGQ PCR Kit (Qiagen) is a CE‑marked real-time polymerase chain reaction (PCR) assay for the targeted detection of 29 mutations in exons 18 to 21 of the epidermal growth factor receptor tyrosine kinase (EGFR‑TK) gene: 4.2 To ensure it complies with the CE marking, the DNA is first isolated from a specimen of formalin-fixed paraffin-embedded tissue using the QIAamp DNA FFPE Tissue Kit. Acti-vating mutations in KRAS gene were shown to be of negative predictive value to TKIs. JCO Precision Oncology, ASCO Educational Book The use of words like “must,” “must not,” “should,” and “should not” indicate that a course of action is recommended or not recommended for either most or many patients, but there is latitude for the treating physician to select other courses of action in individual cases. 4.7 The limits of detection (lowest amount of DNA [nanogram] per reaction well to achieve a 95% or higher 'mutation detected' rate), as reported by the manufacturer for the different mutations, ranged from 0.78 nanograms to 3.13 nanograms of DNA per well. Each of these tests may be used to help determine whether a person's lung cancer will respond to targeted therapy and which … 17. ASCO Meetings If they have an EGFR mutation right now and the patient relapses in 2, 3, or 4 years, you are still going to see that EGFR driver mutation. EGFR mutation testing based on plasma ctDNA in combination with tumor tissue (when required and feasible) is necessary to decide whether TKIs can be used in a patient diagnosed with NSCLC. Recommendation: Physicians should use molecular testing for the appropriate genetic targets on either primary or metastatic lung lesions to guide initial therapy selection. ASCO will continue to follow CAP/IASLC/AMP’s guideline development updates on this topic and will incorporate future versions into our endorsement process as they become available. 3–7 This information does not mandate any particular course of medical care. Following this modification to the CAP/IASLC/AMP recommendations, the ASCO Expert Panel also chose to add BRAF testing to the routine tests listed in recommendations 4 through 7 for other molecular markers as well as to recommendation 9 for multiplexed genetic sequencing panels. Or other incurable lung cancer ( NSCLC ) strongly recommend EGFR mutation testing in (... 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