A Comprehensive Genomic Profiling Study Comparing Primary Tumor, Metastatic Tumor Tissue, and Liquid Biopsy in Patients with Intrahepatic CCA

2020 Year in Review: Cholangiocarcinoma — December 18, 2020

Results of a comprehensive genomic profiling study indicate differences in genomic alterations detected from primary tumor, metastatic tumor tissue, and liquid biopsy in patients with intrahepatic CCA; IDH1 and FGFR2 genomic alterations are detectable in liquid biopsy, with potential practice-changing implications in clinical practice.

Genomic alterations that are characteristic of intrahepatic CCA are well known. Jeffrey S. Ross, MD, Medical Director, Foundation Medicine, Cambridge, MA, led a study that examined whether genomic alterations from a primary tumor would differ from metastatic tumor tissue and liquid biopsy in patients with intrahepatic CCA1; study results were presented at this year’s annual meeting of the American Society of Clinical Oncology (ASCO).

In patients with advanced-stage intrahepatic CCA, comprehensive genomic profiling was performed on 1268 tissue samples using primary tumor in 1048 cases, metastatic tumor in 220 cases, and 364 liquid biopsy cases (solid tissue, 318-327 genes; liquid biopsy, 72 genes).1

Tumor mutational burden was determined on the sequenced DNA. PD-L1 expression in tumor cells was measured by immunohistochemistry. The frequencies of untargetable genomic alterations were similar overall. Less frequent in metastatic tumors than in primary tumors were IDH1 and FGFR2 genomic alterations that are known to be enriched in intrahepatic CCA.

IDH1 and FGFR2 genomic alterations were identified with liquid biopsy. Genomic alterations uncovered in primary tumors versus metastatic tumors in advanced intrahepatic CCA were significantly different; the metastatic tumor cohort had primarily more KRAS and fewer IDH1 and FGFR2 genomic alterations.

These results suggest that the metastatic tumor group may contain patients without intrahepatic CCA whose metastatic lesions were derived from other primary sites and who were incorrectly diagnosed with intrahepatic CCA. Liquid biopsy detected more IDH1 genomic alterations than metastatic tumor biopsy, as well as other potentially targetable alterations.

Source: Ross JS, et al. J Clin Oncol. 2020;38(15_suppl). Abstract 4579.

Reference

  1. Ross JS, Sokol E, Pavlick D, et al. Primary tumor (p-bx) versus metastatic tumor (m-bx) tissue versus liquid biopsy (lb) in intrahepatic cholangiocarcinoma (IHCC): a comparative comprehensive genomic profiling (CGP) study. J Clin Oncol. 2020;38(15_suppl):Abstract 4579.

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