Full Text:   <102>

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Suppl. Mater.: 

CLC number: R735.8

On-line Access: 2020-07-07

Received: 2019-12-08

Revision Accepted: 2020-03-20

Crosschecked: 2020-06-05

Cited: 0

Clicked: 150

Citations:  Bibtex RefMan EndNote GB/T7714

 ORCID:

Ai-lin Li

https://orcid.org/0000-0002-5526-8392

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Journal of Zhejiang University SCIENCE B 2020 Vol.21 No.7 P.549-559

10.1631/jzus.B1900691


Role of adjuvant (chemo)radiotherapy for resected extrahepatic cholangiocarcinoma: a meta-analysis


Author(s):  Xin-qi Shi, Jing-yu Zhang, Hua Tian, Ling-na Tang, Ai-lin Li

Affiliation(s):  Department of Radiation Oncology, the First Hospital of China Medical University, Shenyang 110001, China

Corresponding email(s):   liailin0312@163.com

Key Words:  Adjuvant (chemo)radiotherapy, Extrahepatic cholangiocarcinoma, Meta-analysis, Disease-free survival, Overall survival


Xin-qi Shi, Jing-yu Zhang, Hua Tian, Ling-na Tang, Ai-lin Li. Role of adjuvant (chemo)radiotherapy for resected extrahepatic cholangiocarcinoma: a meta-analysis[J]. Journal of Zhejiang University Science B, 2020, 21(7): 549-559.

@article{title="Role of adjuvant (chemo)radiotherapy for resected extrahepatic cholangiocarcinoma: a meta-analysis",
author="Xin-qi Shi, Jing-yu Zhang, Hua Tian, Ling-na Tang, Ai-lin Li",
journal="Journal of Zhejiang University Science B",
volume="21",
number="7",
pages="549-559",
year="2020",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B1900691"
}

%0 Journal Article
%T Role of adjuvant (chemo)radiotherapy for resected extrahepatic cholangiocarcinoma: a meta-analysis
%A Xin-qi Shi
%A Jing-yu Zhang
%A Hua Tian
%A Ling-na Tang
%A Ai-lin Li
%J Journal of Zhejiang University SCIENCE B
%V 21
%N 7
%P 549-559
%@ 1673-1581
%D 2020
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1900691

TY - JOUR
T1 - Role of adjuvant (chemo)radiotherapy for resected extrahepatic cholangiocarcinoma: a meta-analysis
A1 - Xin-qi Shi
A1 - Jing-yu Zhang
A1 - Hua Tian
A1 - Ling-na Tang
A1 - Ai-lin Li
J0 - Journal of Zhejiang University Science B
VL - 21
IS - 7
SP - 549
EP - 559
%@ 1673-1581
Y1 - 2020
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1900691


Abstract: 
Background: adjuvant (chemo)radiotherapy (A(C)RT) may be an important supplement to surgery for extrahepatic cholangiocarcinoma (EHCC). However, whether all patients would achieve benefits from A(C)RT and which adjuvant regimen, adjuvant radiotherapy (ART) or adjuvant chemoradiotherapy (ACRT), would be preferred, are still undetermined. The low incidence of EHCC makes it difficult to carry out randomized controlled trials (RCTs); therefore, almost all clinical studies on radiotherapy are retrospective. We have conducted a meta-analysis of these retrospective studies. Methods: We conducted a meta-analysis of current retrospective studies using PubMed, Embase, and ClinicalTrials databases. All studies published in English that were related to A(C)RT and which analyzed overall survival (OS), disease-free survival (DFS), or locoregional recurrence-free survival (LRFS) were included. Estimated hazard ratios (HRs) were calculated for OS, DFS, and LRFS. Results: Data from eight studies including 685 patients were included. Our analysis showed that A(C)RT significantly improved OS (HR 0.69, 95% confidence interval (CI) 0.48–0.97, P=0.03), DFS (HR 0.60, 95% CI 0.47–0.76, P<0.0001), and LRFS (HR 0.27, 95% CI 0.17–0.41, P<0.00001) of EHCC overall. In subgroups, patients with microscopically positive resection margin (R1) could achieve a benefit from A(C)RT (HR 0.44, 95% CI 0.27–0.72, P=0.001). No statistically OS difference was observed in negative resection margin (R0) subgroup (HR 0.98, 95% CI 0.30–3.19, P=0.98).Significant OS benefit was found in patients who received concurrent ACRT (HR 0.40, 95% CI 0.26–0.62, P<0.0001), while the result of ART without chemotherapy showed no significant benefit (HR 1.14, 95% CI 0.29–4.50, P=0.85). In the distal cholangiocarcinoma subgroup, no significant difference was seen when ACRT and ART were included (HR 0.61, 95% CI 0.14–2.72, P=0.52), but a significant difference was seen when analyzing the concurrent ACRT only (HR 0.29, 95% CI 0.13–0.64, P=0.002). Conclusions: A(C)RT may improve OS, DFS, and LRFS in EHCC patients, especially in those with R1 resection margins. ACRT may be superior to ART especially in distal patients.

辅助放(化)疗在肝外胆管细胞癌中的作用:荟萃分析

目的:分析术后辅助放(化)疗在肝外胆管细胞癌中的作用,找到具体哪些临床亚组能从辅助放(化)疗中获益.
创新点:本研究报告了辅助放(化)疗可以改善肝外胆管细胞癌患者尤其是显微镜下切缘阳性患者的总生存期、无病生存期和无转移生存期,为这一无定论的临床问题提供循证证据.
方法:我们检索了截至2019年10月,收录在PubMed、Embase和ClinicalTrials三个数据库中关于术后辅助放(化)疗在肝外胆管细胞癌中的作用的文献.经过筛选,最终有8篇文献符合纳入标准,并采用RevMan软件进行数据分析.
结论:辅助放(化)疗可以改善肝外胆管细胞癌患者的总生存期、无病生存期和无转移生存期,尤其是在显微镜下阳性切缘的患者中. 辅助同步放化疗可能优于单纯辅助放疗,尤其是在远端胆管癌患者中.

关键词:辅助放(化)疗;肝外胆管细胞癌;荟萃分析;无病生存期;总生存期

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

Reference

[1]Begg CB, Mazumdar M, 1994. Operating characteristics of a rank correlation test for publication bias. Biometrics, 50(4):1088-1101.

[2]Ben-Josef E, Guthrie KA, El-Khoueiry AB, et al., 2015. SWOG S0809: a phase II intergroup trial of adjuvant capecitabine and gemcitabine followed by radiotherapy and concurrent capecitabine in extrahepatic cholangiocarcinoma and gallbladder carcinoma. J Clin Oncol, 33(24):2617-2622.

[3]Bonet Beltrán M, Allal AS, Gich I, et al., 2012. Is adjuvant radiotherapy needed after curative resection of extrahepatic biliary tract cancers? A systematic review with a meta-analysis of observational studies. Cancer Treat Rev, 38(2):111-119.

[4]Bridgewater JA, Goodman KA, Kalyan A, et al., 2016. Biliary tract cancer: epidemiology, radiotherapy, and molecular profiling. Am Soc Clin Oncol Educ Book, 35:e194-e203.

[5]Chaiteerakij R, Harmsen WS, Marrero CR, et al., 2014. A new clinically based staging system for perihilar cholangiocarcinoma. Am J Gastroenterol, 109(12):1881-1890.

[6]Chua TC, Mittal A, Arena J, et al., 2017. Resection margin influences survival after pancreatoduodenectomy for distal cholangiocarcinoma. Am J Surg, 213(6):1072-1076.

[7]DerSimonian R, Laird N, 1986. Meta-analysis in clinical trials. Control Clin Trials, 7(3):177-188.

[8]Doherty B, Nambudiri VE, Palmer WC, 2017. Update on the diagnosis and treatment of cholangiocarcinoma. Curr Gastroenterol Rep, 19:2.

[9]Egger M, Smith GD, Schneider M, et al., 1997. Bias in meta-analysis detected by a simple, graphical test. BMJ, 315(7109):629-634.

[10]Gwak HK, Kim WC, Kim HJ, et al., 2010. Extrahepatic bile duct cancers: surgery alone versus surgery plus postoperative radiation therapy. Int J Radiat Oncol Biol Phys, 78(1):194-198.

[11]Higgins JPT, Thompson SG, 2002. Quantifying heterogeneity in a meta-analysis. Stat Med, 21(11):1539-1558.

[12]Hoehn RS, Wima K, Ertel AE, et al., 2015. Adjuvant chemotherapy and radiation therapy is associated with improved survival for patients with extrahepatic cholangiocarcinoma. Ann Surg Oncol, 22(S3):1133-1139.

[13]Hughes MA, Frassica DA, Yeo CJ, et al., 2007. Adjuvant concurrent chemoradiation for adenocarcinoma of the distal common bile duct. Int J Radiat Oncol Biol Phys, 68(1):178-182.

[14]Im JH, Seong J, Lee IJ, et al., 2016. Surgery alone versus surgery followed by chemotherapy and radiotherapy in resected extrahepatic bile duct cancer: treatment outcome analysis of 336 patients. Cancer Res Treat, 48(2):583-595.

[15]Ishihara S, Horiguchi A, Miyakawa S, et al., 2016. Biliary tract cancer registry in Japan from 2008 to 2013. J Hepato-Biliary-Pan Sci, 23(3):149-157.

[16]Itoh H, Nishijima K, Kurosaka Y, et al., 2005. Magnitude of combination therapy of radical resection and external beam radiotherapy for patients with carcinomas of the extrahepatic bile duct and gallbladder. Dig Dis Sci, 50(12):2231-2242.

[17]Jarnagin WR, Ruo L, Little SA, et al., 2003. Patterns of initial disease recurrence after resection of gallbladder carcinoma and hilar cholangiocarcinoma: implications for adjuvant therapeutic strategies. Cancer, 98(8):1689-1700.

[18]Khan SA, Davidson BR, Goldin RD, et al., 2012. Guidelines for the diagnosis and treatment of cholangiocarcinoma: an update. Gut, 61(12):1657-1669.

[19]Kim MY, Kim JH, Kim Y, et al., 2016. Postoperative radiotherapy appeared to improve the disease free survival rate of patients with extrahepatic bile duct cancer at high risk of loco-regional recurrence. Radiat Oncol J, 34(4):297-304.

[20]Kim YJ, Kim K, Min SK, et al., 2017. Role of adjuvant radiotherapy for localized extrahepatic bile duct cancer. Br J Radiol, 90(1071):20160807.

[21]Kim YS, Hwang IG, Park SE, et al., 2016. Role of adjuvant therapy after R0 resection for patients with distal cholangiocarcinoma. Cancer Chemother Pharmacol, 77(5):979-985.

[22]Kim YS, Oh SY, Go SI, et al., 2017. The role of adjuvant therapy after R0 resection for patients with intrahepatic and perihilar cholangiocarcinomas. Cancer Chemother Pharmacol, 79(1):99-106.

[23]Lau J, Ioannidis JPA, Schmid CH, 1997. Quantitative synthesis in systematic reviews. Ann Int Med, 127(9):820-826.

[24]Lee J, Kang SH, Noh OK, et al., 2018. Adjuvant concurrent chemoradiation therapy in patients with microscopic residual tumor after curative resection for extrahepatic cholangiocarcinoma. Clin Transl Oncol, 20(8):1011-1017.

[25]Matsuda T, Fujita H, Harada N, et al., 2013. Impact of adjuvant radiation therapy for microscopic residual tumor after resection of extrahepatic bile duct cancer. Am J Clin Oncol, 36(5):461-465.

[26]Nakeeb A, Pitt HA, Sohn TA, et al., 1996. Cholangiocarcinoma: a spectrum of intrahepatic, perihilar, and distal tumors. Ann Surg, 224(4):463-475.

[27]NCCN, 2019. NCCN Clinical Practice Guidelines in Oncology-Hepatobiliary Cancers (2019 Version 1). https://www. nccn.org/professionals/physician_gls/pdf/hepatobiliary.pdf [Accessed on Nov. 8, 2019].

[28]Primrose JN, Fox RP, Palmer DH, et al., 2019. Capecitabine compared with observation in resected biliary tract cancer (BILCAP):a randomised, controlled, multicentre, phase 3 study. Lancet Oncol, 20(5):663-673.

[29]Sahai P, Kumar S, 2017. External radiotherapy and brachytherapy in the management of extrahepatic and intrahepatic cholangiocarcinoma: available evidence. Br J Radiol, 90(1076):20170061.

[30]Shinohara ET, Mitra N, Guo MY, et al., 2009. Radiotherapy is associated with improved survival in adjuvant and palliative treatment of extrahepatic cholangiocarcinomas. Int J Radiat Oncol Biol Phys, 74(4):1191-1198.

[31]Tierney JF, Stewart LA, Ghersi D, et al., 2007. Practical methods for incorporating summary time-to-event data into meta-analysis. Trials, 8:16.

[32]Vern-Gross TZ, Shivnani AT, Chen K, et al., 2011. Survival outcomes in resected extrahepatic cholangiocarcinoma: effect of adjuvant radiotherapy in a surveillance, epidemiology, and end results analysis. Int J Radiat Oncol Biol Phys, 81(1):189-198.

[33]Wang ML, Ke ZY, Yin S, et al., 2019. The effect of adjuvant chemotherapy in resectable cholangiocarcinoma: a meta-analysis and systematic review. Hepatobiliary Pancreat Dis Int, 18(2):110-116.

[34]Wells GA, Shea B, O'Connell D, et al., 2019. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomized studies in meta-analyses. http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp [Accessed on Oct. 1, 2019].

[35]Yoon JE, Lee SY, Kwak HD, et al., 2019. Oncologic outcomes of postoperative chemoradiotherapy versus chemotherapy alone in stage II and III upper rectal cancer. Ann Coloproctol, 35(3):137-143.

[36]Yu JI, Lim DH, Lee J, et al., 2019. Clinical outcomes and the role of adjuvant concurrent chemoradiation therapy in D2-resected LN-positive young patients (≤45 years) with gastric cancer. Anticancer Res, 39(10):5811-5820.

[37]https://doi.org/10.21873/anticanres.13785

[38]List of electronic supplementary materials

[39]Table S1 Characteristics of the included studies

[40]Table S2 Newcastle-Ottawa Scale (NOS) for quality assessment of non-randomized studies in the meta-analysis (cohort studies)

[41]Table S3 Toxicities (CTCAE Version 3.0) reported in the selected studies

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