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Adrian G. Sacher, MD, Kimberly M. Komatsubara, MD, Geoffrey R

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1 Application of Plasma Genotyping Technologies in Non–Small Cell Lung Cancer: A Practical Review 
Adrian G. Sacher, MD, Kimberly M. Komatsubara, MD, Geoffrey R. Oxnard, MD  Journal of Thoracic Oncology  Volume 12, Issue 9, Pages (September 2017) DOI: /j.jtho Copyright © 2017 International Association for the Study of Lung Cancer Terms and Conditions

2 Figure 1 Interpretation of cell-free DNA (cfDNA) genotyping results at initial diagnosis. (A) An EGFR L858R mutation is detected in the plasma of this patient with widely metastatic disease whose tumor is shedding cfDNA and should be interpreted as a true positive result. The release of tumor DNA into the circulation is potentially associated with factors including high mitotic rate, vascularization, cell necrosis, and burden of metastatic disease. (B) No mutations are detected in the plasma of this patient whose tumor is not shedding cfDNA. In situations where tumors are not shedding cfDNA, plasma genotyping results will be unreliable and may lead to false-negative results, despite highly sensitive assays, and a biopsy for tissue genotyping should be performed. Journal of Thoracic Oncology  , DOI: ( /j.jtho ) Copyright © 2017 International Association for the Study of Lung Cancer Terms and Conditions

3 Figure 2 Interpretation of cell-free DNA (cfDNA) genotyping results at the time of disease resistance. (A) An EGFR T790M mutation, as well as the initial EGFR L858R, mutation are detected in the plasma of this patient whose tumor is shedding cfDNA. This result should be interpreted as a true positive. (B) No driver resistance mutation is detected in this patient, although the original EGFR mutation is still detected, suggesting active tumor shed. A reflex biopsy could be performed in this scenario to look for alternate resistance mechanisms. (C) No mutations are detected in this patient with a T790M mutation whose tumor is not shedding. Notably, the original EGFR L858R mutation is also not detected, suggesting lack of tumor shed. A reflex biopsy should be performed in this scenario. Journal of Thoracic Oncology  , DOI: ( /j.jtho ) Copyright © 2017 International Association for the Study of Lung Cancer Terms and Conditions

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