Detection of Discrepant Driver Mutations in a Patient with Two Synchronous Primary Non–Small Cell Lung Cancers (NSCLCs) with Liquid Biopsy Sotirios Lakis,

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Detection of Discrepant Driver Mutations in a Patient with Two Synchronous Primary Non–Small Cell Lung Cancers (NSCLCs) with Liquid Biopsy Sotirios Lakis, MD, Lukas C. Heukamp, MD, PhD Journal of Thoracic Oncology Volume 12, Issue 11, Pages e186-e188 (November 2017) DOI: 10.1016/j.jtho.2017.07.018 Copyright © 2017 International Association for the Study of Lung Cancer Terms and Conditions

Figure 1 A time line of molecular testing with hybrid capture–based next-generation sequencing. Unique tumor samples are shown in columns A to G. Presumed distinct histogeneses are shown in different background colors. Red font is used for activating mutations, blue for inactivating mutations, and black for functionally uncharacterized/unknown mutations. In the first liquid biopsy (LB) (B) the cluster of mutations containing EGFR overlaps with the middle lobe tumor (A) and disappears from LBs obtained during afatinib treatment (D and E). By contrast, the KRAS cluster, which overlaps with the right upper lobe tumor and the metastases (C, F, and G), remains fully or partially detectable during treatment consistent with the expected primary resistance of this tumor to afatinib. There was one mutation present only in the blood (white cluster). Asterisk indicates level below the limit of detection. Abbreviations: Chemo, chemotherapy; Subcut., subcutaneous; Met., metastasis; MAF, minor allele frequency; BRCA1, BRCA1, DNA repair associated gene; TP53, tumor protein p53 gene; STK11, serine/threonine kinase 11gene; KEAP1, kelch like ECH associated protein 1gene; FGFR2, fibroblast growth factor receptor 2 gene. Journal of Thoracic Oncology 2017 12, e186-e188DOI: (10.1016/j.jtho.2017.07.018) Copyright © 2017 International Association for the Study of Lung Cancer Terms and Conditions

Figure 2 Computed tomography scans of the KRAS-mutated tumor (right upper lobe [top]) and the EGFR-mutated tumor (middle lobe [bottom]) before and after afatinib, illustrating the biologically specific differential treatment response. Journal of Thoracic Oncology 2017 12, e186-e188DOI: (10.1016/j.jtho.2017.07.018) Copyright © 2017 International Association for the Study of Lung Cancer Terms and Conditions