Concordance between liquid versus tissue biopsies.

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Presentation transcript:

Concordance between liquid versus tissue biopsies. Concordance between liquid versus tissue biopsies. A, Heat map demonstrating validation of mutations/amplifications detected in plasma by ddPCR, in tissue samples obtained at clinically relevant time points. For NGS variants detected with confidence are reported with a star (posterior probability < 0.05, see Methods). Samples with insufficient coverage (< 20,000×) were excluded and are shown in gray. B, Comparisons between limit of detectability of clinically validated assays (i.e., COBAS) and ultra-deep sequencing used in the study showing that most of the KRAS subclonal mutations causing cetuximab resistance (solid symbols) were below the detection threshold of standard clinical assays. C, Example of a patient with RAS pathway ITH between resected primary and synchronous liver metastases. D, Example of a patient with primary progression and detection of ERBB2 amplification in plasma, further validated with IHC and chromogenic in situ hybridization (CISH) in the tissue obtained both at baseline and PD. Of note, in this case of non–CEA-secreting tumor, baseline biopsy of a supraclavicular lymph node and subsequently of a progressing peritoneal biopsy were conducted and both demonstrated concordance in detection of a (likely clonal) HER2 amplification. E, A case of a patient with no baseline mutation/amplification and initial clinical benefit with PR to cetuximab but later emergence of MET amplification at 2 months (preceding CEA changes) and subsequent increase in fractional abundance (FA) at the time of progression. FISH analysis of the tissue at four different time points confirmed the emergence of foci of MET at PR and PD. F, NGS of tissue biopsies [archival (n = 2), baseline (n = 2), PR (n = 2), 3 months] and disease progression (n = 1) revealed the emergence of an NRASG12C mutation and decay in other mutant clones suggestive of a selection bottleneck (cartoon). Khurum H. Khan et al. Cancer Discov 2018;8:1270-1285 ©2018 by American Association for Cancer Research