Comprehensive genomic landscape and precision therapeutic approach in biliary tract cancers. Int J Cancer 2021 Feb 01;148(3):702-712
Date
07/24/2020Pubmed ID
32700810Pubmed Central ID
PMC7739197DOI
10.1002/ijc.33230Scopus ID
2-s2.0-85089978472 (requires institutional sign-in at Scopus site) 34 CitationsAbstract
Biliary tract cancers have dismal prognoses even when cytotoxic chemotherapy is administered. There is an unmet need to develop precision treatment approaches using comprehensive genomic profiling. A total of 121 patients with biliary tract cancers were analyzed for circulating-tumor DNA (ctDNA) and/or tissue-based tumor DNA (tissue-DNA) using clinical-grade next-generation sequencing: 71 patients (59%) had ctDNA; 90 (74%), tissue-DNA; and 40 (33%), both. Efficacy of targeted therapeutic approaches was assessed based upon ctDNA and tissue-DNA. At least one characterized alteration was detected in 76% of patients (54/71) for ctDNA [median, 2 (range, 0-9)] and 100% (90/90) for tissue-DNA [median, 4 (range, 1-9)]. Most common alterations occurred in TP53 (38%), KRAS (28%), and PIK3CA (14%) for ctDNA vs TP53 (44%), CDKN2A/B (33%) and KRAS (29%) for tissue-DNA. In 40 patients who had both ctDNA and tissue-DNA sequencing, overall concordance was higher between ctDNA and metastatic site tissue-DNA than between ctDNA and primary tumor DNA (78% vs 65% for TP53, 100% vs 74% for KRAS and 100% vs 87% for PIK3CA [But not statistical significance]). Among 80 patients who received systemic treatment, the molecularly matched therapeutic regimens based on genomic profiling showed a significantly longer progression-free survival (hazard ratio [95%confidence interval], 0.60 [0.37-0.99]. P = .047 [multivariate]) and higher disease control rate (61% vs 35%, P = .04) than unmatched regimens. Evaluation of ctDNA and tissue-DNA is feasible in biliary tract cancers.
Author List
Okamura R, Kurzrock R, Mallory RJ, Fanta PT, Burgoyne AM, Clary BM, Kato S, Sicklick JKAuthor
Razelle Kurzrock MD Center Associate Director, Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdultAged
Aged, 80 and over
Antineoplastic Agents
Biliary Tract Neoplasms
Circulating Tumor DNA
Class I Phosphatidylinositol 3-Kinases
Cyclin-Dependent Kinase Inhibitor p15
Cyclin-Dependent Kinase Inhibitor p16
DNA, Neoplasm
Feasibility Studies
Female
High-Throughput Nucleotide Sequencing
Humans
Male
Middle Aged
Precision Medicine
Proto-Oncogene Proteins p21(ras)
Sequence Analysis, DNA
Survival Analysis
Treatment Outcome
Tumor Suppressor Protein p53
