Comprehensive genomic landscape and precision therapeutic approach in biliary tract cancers

Autor: Razelle Kurzrock, Paul T. Fanta, Bryan M. Clary, Jason K. Sicklick, Adam M. Burgoyne, Ryosuke Okamura, Robert J. Mallory, Shumei Kato
Rok vydání: 2020
Předmět:
Male
Cancer Research
medicine.disease_cause
Gastroenterology
Circulating Tumor DNA
0302 clinical medicine
CDKN2A
Medicine
Precision Medicine
Cancer
circulating tumor DNA
Aged
80 and over
Hazard ratio
High-Throughput Nucleotide Sequencing
DNA
Neoplasm
Middle Aged
Primary tumor
Biliary Tract Neoplasms
Treatment Outcome
Oncology
Biliary tract
030220 oncology & carcinogenesis
biomarker
Biomarker (medicine)
Female
KRAS
cholangiocarcinoma
Biotechnology
Adult
medicine.medical_specialty
Class I Phosphatidylinositol 3-Kinases
molecular profiling
Oncology and Carcinogenesis
Antineoplastic Agents
biliary tract cancers
Article
Proto-Oncogene Proteins p21(ras)
03 medical and health sciences
molecular oncology
biliary tract cancer
Internal medicine
Statistical significance
Genetics
Humans
Oncology & Carcinogenesis
personalized cancer therapy
Liquid biopsy
Cyclin-Dependent Kinase Inhibitor p16
Aged
Cyclin-Dependent Kinase Inhibitor p15
liquid biopsy
business.industry
Human Genome
Sequence Analysis
DNA
medicine.disease
Survival Analysis
Good Health and Well Being
Feasibility Studies
Tumor Suppressor Protein p53
Digestive Diseases
business
Zdroj: Int J Cancer
International journal of cancer, vol 148, iss 3
ISSN: 1097-0215
Popis: 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.
Databáze: OpenAIRE
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