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 |
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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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