5-Fluorouracil metabolic pathway genes predict recurrence risk following adjuvant S-1 therapy: Results of an ancillary analysis from a phase III trial of resected biliary tract cancer

被引：0

作者：

Mitsunaga, Shuichi ^{[1
,2
]}

Ikeda, Masafumi ^{[1
]}

Nomura, Shogo ^{[3
]}

Morizane, Chigusa ^{[4
]}

Todaka, Akiko ^{[5
]}

Yamamoto, Naoto ^{[6
]}

Kamata, Ken ^{[7
]}

Yanagibashi, Hiroo ^{[8
]}

Mizuno, Nobumasa ^{[9
]}

Kawamoto, Yasuyuki ^{[10
]}

Gotoh, Kunihito ^{[11
]}

Shirakawa, Hirofumi ^{[12
]}

Okano, Naohiro ^{[13
]}

Nomura, Tatsuya ^{[14
]}

Tanaka, Kazunari ^{[15
]}

Takahashi, Amane ^{[16
]}

Yagi, Shintaro ^{[17
]}

Ohta, Koji ^{[18
]}

Takayama, Yukiko ^{[19
]}

Miwa, Haruo ^{[20
]}

Nagano, Hiroaki ^{[21
]}

Kojima, Yasushi ^{[22
]}

Hisano, Terumasa ^{[23
]}

Tahara, Munenori ^{[24
]}

Sakuma, Yasunaru ^{[25
]}

Arai, Hiroyuki ^{[26
]}

Nakamura, Ikuo ^{[27
]}

Katayama, Hiroshi ^{[3
]}

Konishi, Masaru ^{[28
]}

Ueno, Makoto ^{[29
]}

机构：

[1] Natl Canc Ctr Hosp East, Dept Hepatobiliary & Pancreat Oncol, 6-5-1 Kashiwan, Kashiwa, Chiba 277 8577, Japan

[2] Natl Canc Ctr, Exploratory Oncol Res & Clin Trial Ctr, Div Biomarker Discovery, Kashiwa, Japan

[3] Natl Canc Ctr, JCOG Data Ctr, Operat Off, Tokyo, Japan

[4] Natl Canc Ctr, Dept Hepatobiliary & Pancreat Oncol, Tokyo, Japan

[5] Shizuoka Canc Ctr, Div Gastrointestinal Oncol, Sunto, Shizuoka, Japan

[6] Kanagawa Canc Ctr, Dept Gastrointestinal Surg, Yokohama, Japan

[7] Kindai Univ, Dept Gastroenterol & Hepatol, Fac Med, Osaka, Japan

[8] Chiba Canc Ctr, Dept Hepatobiliary & Pancreat Surg, Chiba, Japan

[9] Aichi Canc Ctr Hosp, Dept Gastroenterol, Nagoya, Aichi, Japan

[10] Hokkaido Univ Hosp, Div Canc Ctr, Sapporo, Hokkaido, Japan

[11] NHO Osaka Natl Hosp, Dept Surg, Osaka, Japan

[12] Tochigi Canc Ctr, Dept Hepatobiliary Pancreat Surg, Utsunomiya, Tochigi, Japan

[13] Kyorin Univ, Fac Med, Dept Med Oncol, Tokyo, Japan

[14] Niigata Canc Ctr Hosp, Dept Digest Surg, Niigata, Japan

[15] Teine Keijinkai Hosp, Ctr Gastroenterol, Sapporo, Japan

[16] Saitama Canc Ctr, Dept Gastroenterol Surg, Saitama, Japan

[17] Kanazawa Univ, Dept Hepatobiliary Pancreat Surg & Transplantat, Kanazawa, Japan

[18] NHO Shikoku Canc Ctr, Dept Digest Surg, Matsuyama, Ehime, Japan

[19] Tokyo Womens Med Univ, Inst Gastroenterol, Dept Internal Med, Tokyo, Japan

[20] Yokohama City Univ, Med Ctr, Gastroenterol Ctr, Yokohama, Japan

[21] Yamaguchi Univ, Dept Gastroenterol Breast & Endocrine Surg, Grad Sch Med, Ube, Japan

[22] Natl Ctr Global Hlth & Med, Dept Gastroenterol, Tokyo, Japan

[23] NHO Kyushu Canc Ctr, Dept Hepatobiliary Pancreatol, Fukuoka, Japan

[24] Sapporo Kosei Gen Hosp, Dept Surg Pathol, Sapporo, Japan

[25] Jichi Med Univ, Dept Surg, Shimotsuke, Japan

[26] St Marianna Univ, Sch Med, Dept Clin Oncol, Kawasaki, Japan

[27] Hyogo Med Univ, Dept Gastroenterol Surg, Nishinomiya, Hyogo, Japan

[28] Natl Canc Ctr Hosp East, Dept Hepatobiliary Pancreat Surg, Kashiwa, Chiba, Japan

[29] Kanagawa Canc Ctr, Div Hepatobiliary & Pancreat Med Oncol, Yokohama, Kanagawa, Japan

来源：

JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES | 2024年

关键词：

5-FU metabolic pathway; adjuvant; biliary tract cancer; DPD; S-1; DIHYDROPYRIMIDINE DEHYDROGENASE; THYMIDYLATE SYNTHASE; EXPRESSION LEVELS; MESSENGER-RNA; THYMIDINE PHOSPHORYLASE; SENSITIVITY; TUMORS; CELLS;

D O I：

10.1002/jhbp.12071

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

background: S- 1, an oral fluoropyrimidine derivative, is standard adjuvant therapy for resected biliary tract cancer (BTC), based on the results of the JCOG1202, a phase III trial evaluating the survival benefit with adjuvant S- 1 following curative resection for BTC compared to surgery alone. This multicenter ancillary study of the JCOG1202 aimed to evaluate the prognostic impact of the 5- fluorouracil (5- FU) metabolic pathway genes including thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD). Methods: The 5- FU metabolic pathway genes were measured in tumor cells from formalin- fixed paraffin- embedded resected specimens from 183 patients (surgery alone: n= 94; adjuvant S- 1: n= 89). We randomly divided them into training (n= 96) and validation sets (n= 87) for evaluating the interaction between gene levels and RFS benefits in the treatment arm. Results: RFS benefits of adjuvant S- 1 were observed in the low DPD (HR = 0.440 and 0.748, respectively in the training and validation sets) and the low TP groups (HR = 0.709 and 0.602, respectively). Clinicopathological characteristics were well balanced between low and high DPD populations. More advanced stage tumors were observed in high TP populations as compared to those in low TP populations (p= .0332). Conclusion: The results suggest the RFS benefit of adjuvant S- 1 in resected BTC patients with low DPD and low TP gene expressions.

引用

页数：11

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