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Oncotarget. 2017 Jul 6;8(46):81394-81404. doi: 10.18632/oncotarget.19037. eCollection 2017 Oct 6.

DCK expression, a potential predictive biomarker in the adjuvant gemcitabine chemotherapy for biliary tract cancer after surgical resection: results from a phase II study.

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Center for Liver Cancer, National Cancer Center, Goyang-Si Gyeonggi-Do, Korea.
College of Veterinary Medicine, Konkuk University, Seoul, Korea.
Department of Pathology, National Cancer Center, Goyang-Si Gyeonggi-Do, Korea.
Biometrics Research Branch, Research Institute, National Cancer Center, Goyang-Si Gyeonggi-Do, Korea.
Molecular Imaging Branch, Research Institute, National Cancer Center, Goyang-Si Gyeonggi-Do, Korea.


The role of adjuvant therapy following resection of biliary tract cancer (BTC) remains unclear. We therefore evaluated the feasibility and toxicity of adjuvant gemcitabine in patients with BTC. This clinical phase II trial was an open-label, single center, single-arm study. Within 8 weeks after gross complete resection of BTC, patients were started on intravenous infusions of gemcitabine 1000 mg/m2 over 30 min on days 1, 8, and 15 of every 28-day cycle. Intratumoral expression of cytidine deaminase (CDA), human equilibrative transporter-1 (hENT1), deoxycytidine kinase (dCK) and ribonucleotide reductase subunit 1 (RRM1) was measured by immunohistochemistry. This study enrolled 72 patients with BTC (26 with gallbladder cancer, 33 with extrahepatic cholangiocarcinoma, and 13 with intrahepatic cholangiocarcinoma). The 2-year recurrence-free survival (RFS) rate was 43% (95% CI, 33-57%). Multivariable analysis showed that DCK expression, vascular invasion, and lymph node metastasis were significantly associated with RFS. Twenty-one (31.8%) were positive for DCK immunoreactivity. The median RFS was 34.95 months for DCK-positive patients, compared with 11.41 months for DCK-negative patients. Although the primary hypothesis of this study, defined as a 2-year RFS of 60%, was not met, intratumoral DCK expression was significantly associated with RFS in patients with resected BTC treated with postoperative gemcitabine chemotherapy. Future randomized controlled trials are warranted.


adjuvant therapy; biliary tract cancer; chemotherapy; gemcitabine

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