Comprehensive genomic landscape and precision therapeutic approach in biliary tract cancers. Issue 3 (28th August 2020)

• Record Type: Journal Article
• Authors: Okamura, Ryosuke; Kurzrock, Razelle; Mallory, Robert J.; Fanta, Paul T.; Burgoyne, Adam M.; Clary, Bryan M.; Kato, Shumei; Sicklick, Jason K.
• Is Part Of: International journal of cancer. Volume 148:Issue 3(2021)
• Page Start: 702
• Page End: 712
• Publication Date: 2020-08-28
• Subjects: biliary tract cancers -- biomarker -- cholangiocarcinoma -- circulating tumor DNA -- liquid biopsy -- molecular profiling -- personalized cancer therapy; Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.33230
• Languages: English
• ISSNs: 0020-7136

Abstract

Abstract: 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. Abstract : What's new? There is an unmet need for investigating precision therapy approaches in biliary tract cancers using next‐generation sequencing techniques. This study shows that circulating tumour DNA (ctDNA) and tissue DNA tests are complementary, since they often reveal different alterations likely due to tumour heterogeneity. Most biliary tract cancer patients had at least one characterised alteration in ctDNA and in tissue DNA. Among 80 patients who received systemic chemotherapy, molecularly‐matched therapeutic regimens based on genomic profiling were associated with better treatment response and progression‐free survival than unmatched therapies. Evaluation of ctDNA and tissue‐DNA is feasible and potentially beneficial in biliary tract cancers.