Comparative effectiveness of adjuvant treatments for resected gastric cancer: a network meta-analysis
- 358 Downloads
Different adjuvant treatments are available for patients with gastric cancer, but conventional meta-analyses performing direct comparisons between two alternative treatments did not have enough power to compare all the adjuvant treatments. Thus, we did a network meta-analysis summarizing the direct and indirect comparisons to identify the optimum treatment.
We systematically searched for RCTs of adjuvant treatments for gastric cancer comparing two or more of the following treatments: surgery alone, radiotherapy with fluoropyrimidine, S-1-based regimens, and XELOX. The treatments offering available indirect evidence to investigate the comparative effectiveness of adjuvant treatments mentioned above were also included. Then we performed a Bayesian network meta-analysis to summarize the direct and indirect comparisons. We estimated hazard ratios with 95% credible intervals (CrI) for OS and DFS.
11 eligible RCTs (5620 patients) were included in the network meta-analysis. Radiotherapy with fluorouracil (5-FU/RT), S-1-based regimens, and XELOX significantly improved OS as compared with surgery alone [(HR = 0.75 with 95% CrI: 0.63–0.89), (HR = 0.63 with 95% CrI: 0.52–0.76), and (HR = 0.66 with 95% CrI: 0.51–0.85), respectively]. No treatment was clearly superior to others; however, S-1-based regimes and XELOX showed a statistically non-significant trend to better survival as compared with 5-FU/RT.
S-1-based chemotherapy and XELOX are likely to be the most effective adjuvant treatments for patients with resected gastric cancer. 5-FU alone provided little survival benefits as compared with surgery alone. Further clinical trials may be required to investigate S-1-based and XELOX-based adjuvant treatment strategies.
KeywordsGastric cancer Adjuvant Chemotherapy Chemoradiotherapy, network meta-analysis
Bo Zhang, Zhaolun Cai, Yiqiong Yin designed the study. Jian Wang and Xiaonan Yin screened studies and extracted data. Disagreements were resolved by discussion with Yuan Yin. Zhaolun Cai did the statistical analyses and prepared figures. Bo Zhang, Zhixin Chen, Ye Zhou, Yuan Yin, Chaoyong Shen, Zhaolun Cai reviewed the results, interpreted data, and wrote the manuscript. All authors saw and approved the final version of the paper.
There was no sponsor for this study.
Compliance with Ethical Standards
Conflict of interest
The authors declare no conflict of interest.
This article does not contain any studies with human or animal subjects performed by any of the authors.
- 3.Dangelica MI, Gonen M, Brennan MF, Turnbull AD, Bains MS, Karpeh MS. Patterns of initial recurrence in completely resected gastric adenocarcinoma. Ann Surg. 2004;240(5):808–16.Google Scholar
- 5.Diaz-Nieto R, Orti-Rodriguez R, Winslet M. Post-surgical chemotherapy versus surgery alone for resectable gastric cancer. The Cochrane database of systematic reviews. 2013;9:CD008415. https://doi.org/10.1002/14651858.CD008415.pub2 (Epub 2013/09/04)
- 6.Zhou ML, Kang M, Li GC, Guo XM, Zhang Z. Postoperative chemoradiotherapy versus chemotherapy for R0 resected gastric cancer with D2 lymph node dissection: an up-to-date meta-analysis. World J Surg Oncol. 2016;14(1):209. https://doi.org/10.1186/s12957-016-0957-7 (Epub 2016/08/10)CrossRefPubMedPubMedCentralGoogle Scholar
- 7.Noh SH, Park SR, Yang HK, Chung HC, Chung IJ, Kim SW, et al. Adjuvant capecitabine plus oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC]: 5-year follow-up of an open-label, randomised phase 3 trial. Lancet Oncol. 2014;15(12):1389–96. https://doi.org/10.1016/s1470 (Epub 2014/12/03)CrossRefPubMedPubMedCentralGoogle Scholar
- 8.Sasako M, Sakuramoto S, Katai H, Kinoshita T, Furukawa H, Yamaguchi T, et al. Five-year outcomes of a randomized phase III trial comparing adjuvant chemotherapy with S-1 versus surgery alone in stage II or III gastric cancer. J Clin Oncol. 2011;29(33):4387–93. https://doi.org/10.1200/jco.2011.36.5908 (Epub 2011/10/20)CrossRefGoogle Scholar
- 9.Di Costanzo F, Gasperoni S, Manzione L, Bisagni G, Labianca R, Bravi S, et al. Adjuvant chemotherapy in completely resected gastric cancer: a randomized phase III trial conducted by GOIRC. J Natl Cancer Inst. 2008;100(6):388–98. https://doi.org/10.1093/jnci/djn054 (Epub 2008/03/13)CrossRefGoogle Scholar
- 10.Nakajima T, Kinoshita T, Nashimoto A, Sairenji M, Yamaguchi T, Sakamoto J, et al. Randomized controlled trial of adjuvant uracil-tegafur versus surgery alone for serosa-negative, locally advanced gastric cancer. Br J Surg. 2007;94(12):1468–76. https://doi.org/10.1002/bjs.5996 (Epub 2007/10/20)CrossRefGoogle Scholar
- 11.Smalley SR, Benedetti JK, Haller DG, Hundahl SA, Estes NC, Ajani JA, et al. Updated analysis of SWOG-directed intergroup study 0116: a phase III trial of adjuvant radiochemotherapy versus observation after curative gastric cancer resection. J Clin Oncol. 2012;30(19):2327–33. https://doi.org/10.1200/jco.2011.36.7136 (Epub 2012/05/16)CrossRefPubMedPubMedCentralGoogle Scholar
- 12.Park SH, Sohn TS, Lee J, Lim DH, Hong ME, Kim KM, et al. Phase III trial to compare adjuvant chemotherapy with capecitabine and cisplatin versus concurrent chemoradiotherapy in gastric cancer: final report of the adjuvant chemoradiotherapy in stomach tumors trial, including survival and subset analyses. J Clin Oncol. 2015;33(28):3130–6. https://doi.org/10.1200/jco.2014.58.3930 (Epub 2015/01/07)CrossRefPubMedPubMedCentralGoogle Scholar
- 13.Ajani JA, Damico TA, Almhanna K, Bentrem DJ, Chao J, Das P, et al. Gastric Cancer, Version 3.2016; Clinical Practice Guidelines in Oncology. J Natl Comprehensive Cancer Netw. 2016;14(10):1286–312.Google Scholar
- 14.Japanese gastric cancer treatment guidelines 2014 (ver. 4] Gastric Cancer. 2016;20(1):1–19. https://doi.org/10.1007/s10120-016-0622-4.
- 16.Shitara K, Chin K, Yoshikawa T, Katai H, Terashima M, Ito S, et al. Phase II study of adjuvant chemotherapy of S-1 plus oxaliplatin for patients with stage III gastric cancer after D2 gastrectomy. Gastric Cancer. 2017;20(1):175–81. https://doi.org/10.1007/s10120-015-0581-1 (Epub 2015/12/03)CrossRefGoogle Scholar
- 21.Dias S, Sutton AJ, Ades AE, Welton NJ. Evidence synthesis for decision making 2: a generalized linear modeling framework for pairwise and network meta-analysis of randomized controlled trials. Med Decis Making. 2013;33(5):607–17. https://doi.org/10.1177/0272989X12458724. (Epub 2012/10/30)CrossRefPubMedPubMedCentralGoogle Scholar
- 22.Gs HJP. Cochrane handbook for systematic reviews of interventions version 5.1.0 (updated March 2011]. Naunyn-Schmiedebergs Archiv für experimentelle Pathologie Pharmakologie. 2014;5(2):S38.Google Scholar
- 23.Greene FL. AJCC Cancer Staging Manual (6th Edition).Google Scholar
- 25.Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JP, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. J Clin Epidemiol. 2009;62(10]):e1–34. https://doi.org/10.1016/j.jclinepi.2009.06.006 CrossRefGoogle Scholar
- 29.Tsuburaya A, Yoshida K, Kobayashi M, Yoshino S, Takahashi M, Takiguchi N, et al. Sequential paclitaxel followed by tegafur and uracil (UFT] or S-1 versus UFT or S-1 monotherapy as adjuvant chemotherapy for T4a/b gastric cancer (SAMIT]: a phase 3 factorial randomised controlled trial. Lancet Oncol. 2014;15(8):886–93. https://doi.org/10.1016/s1470-2045(14)70025-7 (Epub 2014/06/24)CrossRefGoogle Scholar
- 30.Cascinu S, Labianca R, Barone C, Santoro A, Carnaghi C, Cassano A, et al. Adjuvant treatment of high-risk, radically resected gastric cancer patients with 5-fluorouracil, leucovorin, cisplatin, and epidoxorubicin in a randomized controlled trial. J Natl Cancer Inst. 2007;99(8):601-7. https://doi.org/10.1093/jnci/djk131 (Epub 2007/04/19)CrossRefGoogle Scholar
- 31.Lee JJ, Kim SY, Shin IS, Cho KS, Joo HZ, Yoon C, et al. Randomized phase III trial of cisplatin, epirubicin, leucovorin, 5-fluorouracil (PELF] combination versus 5-fluorouracil alone as adjuvant chemotherapy in curative resected stage III gastric cancer. Cancer Res Treatment. 2004;36(2):140–5. https://doi.org/10.4143/crt.2004.36.2.140 (Epub 2004/04/01)CrossRefGoogle Scholar
- 32.Zhu WG, Xua DF, Pu J, Zong CD, Li T, Tao GZ, et al. A randomized, controlled, multicenter study comparing intensity-modulated radiotherapy plus concurrent chemotherapy with chemotherapy alone in gastric cancer patients with D2 resection. Radiother Oncol J Eur Soc Therapeutic Radiol Oncol. 2012;104(3):361–6. https://doi.org/10.1016/j.radonc.2012.08.024 (Epub 2012/09/19)CrossRefGoogle Scholar
- 33.Nakajima T, Nashimoto A, Kitamura M, Kito T, Iwanaga T, Okabayashi K, et al. Adjuvant mitomycin and fluorouracil followed by oral uracil plus tegafur in serosa-negative gastric cancer: a randomised trial. Lancet (London England). 1999;354(9175):273–7. https://doi.org/10.1016/S0140-6736%2899%2901048-X CrossRefGoogle Scholar
- 34.Kwon HC, Kim MC, Kim KH, Jang JS, Oh SY, Kim SH, et al. Adjuvant chemoradiation versus chemotherapy in completely resected advanced gastric cancer with D2 nodal dissection. Asia Pac J Clin Oncol. 2010;6(4):278–85. https://doi.org/10.1111/j.1743-7563.2010.01331.x (Epub 2010/12/01)CrossRefGoogle Scholar
- 36.Sterne JA, Sutton AJ, Ioannidis JP, Terrin N, Jones DR, Lau J, et al. Recommendations for examining and interpreting funnel plot asymmetry in meta-analyses of randomised controlled trials. BMJ. 2011;343:d4002. https://doi.org/10.1136/bmj.d4002 (Epub 2011/07/26)CrossRefPubMedPubMedCentralGoogle Scholar
- 39.Fujitani K, Tamura S, Kimura Y, Tsuji T, Matsuyama J, Iijima S, et al. Three-year outcomes of a phase II study of adjuvant chemotherapy with S-1 plus docetaxel for stage III gastric cancer after curative D2 gastrectomy. Gastric Cancer. 2014;17(2):348–53. https://doi.org/10.1007/s10120-013-0273-7 (Epub 2013/06/06)CrossRefGoogle Scholar
- 40.Nakamura Y, Yamanaka T, Chin K, Cho H, Katai H, Terashima M, et al. Three-year outcomes of two phase II studies of adjuvant chemotherapy with S-1 plus oxaliplatin or capecitabine plus oxaliplatin in patients with stage III gastric cancer after D2 gastrectomy. American Society of Clinical Oncology; 2018.Google Scholar
- 42.Bamias A, Karina M, Papakostas P, Kostopoulos I, Bobos M, Vourli G, et al. A randomized phase III study of adjuvant platinum/docetaxel chemotherapy with or without radiation therapy in patients with gastric cancer. Cancer Chemother Pharmacol. 2010;65(6):1009–21. https://doi.org/10.1007/s00280-010-1256-6 (Epub 2010/02/05)CrossRefGoogle Scholar