期刊
INTERNATIONAL JOURNAL OF CANCER
卷 148, 期 3, 页码 702-712出版社
WILEY
DOI: 10.1002/ijc.33230
关键词
biliary tract cancers; biomarker; cholangiocarcinoma; circulating tumor DNA; liquid biopsy; molecular profiling; personalized cancer therapy
类别
资金
- National Cancer Institute [P30 CA023100]
- The Joan and Irwin Jacobs Fund
Biliary tract cancers have poor prognoses even with cytotoxic chemotherapy, highlighting the need for precision treatment approaches using comprehensive genomic profiling. Analysis of circulating-tumor DNA (ctDNA) and tissue-based tumor DNA is feasible in these cancers. Molecularly matched therapeutic regimens based on genomic profiling show significantly longer progression-free survival and higher disease control rates compared to unmatched regimens.
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 inTP53(38%),KRAS(28%), andPIK3CA(14%) for ctDNA vsTP53(44%),CDKN2A/B (33%) andKRAS(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% forTP53, 100% vs 74% forKRASand 100% vs 87% forPIK3CA[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.
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