Cholangiocarcinoma News

Comparing Primary Tumor, Metastatic Tumor Tissue, and Liquid Biopsy in Intrahepatic Cholangiocarcinoma: Comprehensive Genomic Profiling Study

August 2020, Vol 1, No 1

Genomic alterations that are characteristic of intrahepatic cholangiocarcinoma (CCA) are well known. A study led by Jeffrey S. Ross, MD, Medical Director, Foundation Medicine, Cambridge, MA, examined whether genomic alterations from a primary tumor would differ from metastatic tumor tissue and liquid biopsy in patients with intrahepatic CCA.1 The study results were presented at the 2020 ASCO annual meeting.

Comprehensive genomic profiling was performed on 1268 tissue samples from patients with advanced-stage intrahepatic CCA using primary tumor in 1048 cases, metastatic tumor from 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. IDH1 and FGFR2 genomic alterations that are known to be enriched in intrahepatic CCA were less frequent in metastatic tumors than in primary tumors.

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, principally with the metastatic tumor cohort having 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, and also detected other potentially targetable alterations.

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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