Proper time to initiation of adjuvant chemotherapy after radical resection for gastric cancer: a systematic review and Meta-analysis_West China Medical Journal

Authors：

YAN Ruonan , LIU Fang , ZENG Yuanyuan , HE Tao , XIANG Zhongzheng ,  LIU Lei

Oncology Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;

Corresponding?author：

LIU Lei, Email: liuleihx@gmail.com

Keywords：

Gastric cancer; Time to initiation of adjuvant chemotherapy; Meta-analysis

DOI：

10.7507/1002-0179.201810074

Video：

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ObjectiveTo explore the proper time to initiation of adjuvant chemotherapy after radical resection for gastric cancer. MethodsWe searched electronically in PubMed, Embase, China National Knowledge Infrastructure, Wangfang database, and Chongqing VIP database for all relevant studies published before May 1st, 2018. The references included in eligible trials were also searched. All eligible studies were assessed and evaluated by two investigators working independently. The Meta-analysis was conducted using Stata 14 software. ResultsOur literature search included a total of 10 studies. There were 9 studies reporting overall survival (OS), in which 3 studies used a 4-week cutoff for delay from surgery to adjuvant chemotherapy, 4 shared a 6-week cutoff, and 2 studies shared an 8-week cutoff. There were 4 studies reporting disease-free survival (DFS). Initiating adjuvant chemotherapy beyond 4 weeks after surgery was significantly associated with worse OS [hazard ratio (HR)=0.42, 95% confidence interval (CI) (0.27, 0.65), P<0.001]. No significant benefit was found by starting adjuvant chemotherapy within 6 weeks or 8 weeks after surgery [HR=0.91, 95%CI (0.66, 1.26), P=0.577; HR=1.02, 95%CI (0.91, 1.14), P=0.744; respectively]. Four trials reporting DFS did not share a same cutoff delay from surgery to adjuvant chemotherapy, thus it was impossible to conduct a combined Meta-analysis. ConclusionThe initiation of adjuvant chemotherapy within 4 weeks after radical resection for gastric cancer may obtain better OS.

Citation： YAN Ruonan, LIU Fang, ZENG Yuanyuan, HE Tao, XIANG Zhongzheng, LIU Lei. Proper time to initiation of adjuvant chemotherapy after radical resection for gastric cancer: a systematic review and Meta-analysis. West China Medical Journal, 2018, 33(12): 1479-1485. doi: 10.7507/1002-0179.201810074 Copy

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4.	Macdonald JS, Smalley SR, Benedetti J, et al. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med, 2001, 345(10): 725-730.
5.	Smalley SR, Benedetti JK, Haller DG, 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): 2327-2333.
6.	Maeng CH, Han JJ, Baek SK, et al. Optimal interval between surgery and adjuvant chemotherapy of gastric cancer. Ann Oncol, 2015, 26(Suppl 9): 60.
7.	Kang SY, Ahn MS, Song GW, et al. Does the timing of adjuvant chemotherapy for gastric cancer influence patient outcome?. Acta Oncol, 2015, 54(8): 1231-1234.
8.	Qu JL, Qu XJ, Li X, et al. Early initiation of fluorouracil-based adjuvant chemotherapy improves survival in patients with resectable gastric cancer. J BUON, 2015, 20(3): 800-807.
9.	Yamamoto M, Sakaguchi Y, Kinjo N, et al. S-1 adjuvant chemotherapy earlier after surgery clinically correlates with prognostic factors for advanced gastric cancer. Ann Surg Oncol, 2016, 23(2): 546-551.
10.	Wells G, Shea BJ, O’Connell D, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of non-randomized studies in meta-analysis. Appl Eng Agric, 2014, 18(6): 727-734.
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12.	Park HS, Jung M, Kim HS, et al. Proper timing of adjuvant chemotherapy affects survival in patients with stage 2 and 3 gastric cancer. Ann Surg Oncol, 2015, 22(1): 224-231.
13.	Fujitani K, Kurokawa Y, Takeno A, et al. Time to initiation or duration of S-1 adjuvant chemotherapy; which really impacts on survival in stage Ⅱ and Ⅲ gastric cancer?. Gastric Cancer, 2018, 21(3): 446-452.
14.	Kim MJ, Ryu KW, Eom BW, et al. Impact of earlier adjuvant chemotherapy after surgery on prognosis in patients with operable gastric cancer: a propensity score matched analysis. J Clin Oncol, 2016, 34(15): 4057-4057.
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16.	Di Bartolomeo M, Pietrantonio F, Rulli E, et al. Impact on survival of timing and duration of adjuvant chemotherapy in radically resected gastric cancer. Tumori, 2016, 102(4): e15-e19.
17.	Ahmed S, Iqbal N, Yadav S, et al. Time to adjuvant therapy and other variables in localized gastric and gastroesophageal junction (GEJ) cancer (IJGC-D-13-00162). J Gastrointest Canc, 2014, 45(3): 284-290.
18.	Cardoso R, Coburn N, SeevaratnamR, et al. A systematic review of patient surveillance after curative gastrectomy for gastric cancer: a brief review. Gastric Cancer, 2012, 15(Suppl 1): 164-167.
19.	Yoshikawa T, Rino Y, Yukawa N, et al. Neoadjuvant chemotherapy for gastric cancer in Japan: a standing position by comparing with adjuvant chemotherapy. Surg Today, 2014, 44(1): 11-21.
20.	Glimelius B, Hoffman K, Haglund U, et al. Initial or delayed chemotherapy with best supportive care in advanced gastric cancer. Ann Oncol, 1994, 5(2): 189-190.
21.	Pyrh?nen S, Kuitunen T, Nyandoto P, et al. Randomised comparison of fluorouracil, epidoxorubicin and methotrexate (FEMTX) plus supportive care with supportive care alone in patients with non-resectable gastric cancer. Br J Cancer, 1995, 71(3): 587-591.
22.	Folkman J. How is blood vessel growth regulated in normal and neoplastic tissue? G.H.A. Clowes memorial Award lecture. Cancer Res, 1986, 46(2): 467-473.
23.	Folkman J. What is the evidence that tumors are angiogenesis dependent?. J Natl Cancer Inst, 1990, 82(1): 4-6.
24.	Eggermont AM, Steller EP, Sugarbaker PH. Laparotomy enhances intraperitoneal tumor growth and abrogates the antitumor effects of interleukin-2 and lymphokine-activated killer cells. Surgery, 1987, 102(1): 71-78.
25.	Folkman J, Klagsbrun M. Angiogenic factors. Science, 1987, 235(4787): 442-447.
26.	Fidler IJ, Ellis LM. The implications of angiogenesis for the biology and therapy of cancer metastasis. Cell, 1994, 79(2): 185-188.
27.	Goldie JH, Coldman AJ. A mathematic model for relating the drug sensitivity of tumors to their spontaneous mutation rate. Cancer Treat Rep, 1980, 63(11/12): 1727-1733.
28.	Ryu KW, Kim YW, Lee JH, et al. Surgical complications and the risk factors of laparoscopy-assisted distal gastrectomy in early gastric cancer. Ann Surg Oncol, 2008, 15(6): 1625-1631.
29.	An JY, Kim KM, Kim YM, et al. Surgical complications in gastric cancer patients preoperatively treated with chemotherapy: their risk factors and clinical relevance. Ann Surg Oncol, 2012, 19(8): 2452-2458.
30.	James JB, Michael JR, Mackillop WJ, et al. Association between time to initiation of adjuvant chemotherapy and survival in colorectal cancer, a systematic review and meta-analysis. JAMA, 2011, 305(22): 2335-2342.
31.	Des Guetz G, Nicolas P, Perret G, et al. Does delaying adjuvant chemotherapy after curative surgery for colorectal cancer impair survival? A meta-analysis. Eur J Cancer, 2010, 46(6): 1049-1055.

1. Torre LA, Bray F, Siegel RL, et al. Global cancer statistics, 2012. CA Cancer J Clin, 2015, 65(2): 87-108.
2. 戴發祥, 黃華. 進展期胃癌術前分期研究現狀. 中華實用外科雜志, 2016, 36(10): 1115-1117.
3. D’Angelica M, Gonen M, Brennan MF, et al. Patterns of initial recurrence in completely resected gastric adenocarcinoma. Ann Surg, 2004, 240(5): 808-816.
4. Macdonald JS, Smalley SR, Benedetti J, et al. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med, 2001, 345(10): 725-730.
5. Smalley SR, Benedetti JK, Haller DG, 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): 2327-2333.
6. Maeng CH, Han JJ, Baek SK, et al. Optimal interval between surgery and adjuvant chemotherapy of gastric cancer. Ann Oncol, 2015, 26(Suppl 9): 60.
7. Kang SY, Ahn MS, Song GW, et al. Does the timing of adjuvant chemotherapy for gastric cancer influence patient outcome?. Acta Oncol, 2015, 54(8): 1231-1234.
8. Qu JL, Qu XJ, Li X, et al. Early initiation of fluorouracil-based adjuvant chemotherapy improves survival in patients with resectable gastric cancer. J BUON, 2015, 20(3): 800-807.
9. Yamamoto M, Sakaguchi Y, Kinjo N, et al. S-1 adjuvant chemotherapy earlier after surgery clinically correlates with prognostic factors for advanced gastric cancer. Ann Surg Oncol, 2016, 23(2): 546-551.
10. Wells G, Shea BJ, O’Connell D, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of non-randomized studies in meta-analysis. Appl Eng Agric, 2014, 18(6): 727-734.
11. Parmar MK, Torri V, Stewart L. Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints. Stat Med, 1998, 17(24): 2815-2834.
12. Park HS, Jung M, Kim HS, et al. Proper timing of adjuvant chemotherapy affects survival in patients with stage 2 and 3 gastric cancer. Ann Surg Oncol, 2015, 22(1): 224-231.
13. Fujitani K, Kurokawa Y, Takeno A, et al. Time to initiation or duration of S-1 adjuvant chemotherapy; which really impacts on survival in stage Ⅱ and Ⅲ gastric cancer?. Gastric Cancer, 2018, 21(3): 446-452.
14. Kim MJ, Ryu KW, Eom BW, et al. Impact of earlier adjuvant chemotherapy after surgery on prognosis in patients with operable gastric cancer: a propensity score matched analysis. J Clin Oncol, 2016, 34(15): 4057-4057.
15. Greenleaf EK, Kulaylat AN, Hollenbeak CS, et al. Timing of adjuvant chemotherapy and impact on survival for resected gastric cancer. Ann Surg Oncol, 2016, 23(13): 4203-4213.
16. Di Bartolomeo M, Pietrantonio F, Rulli E, et al. Impact on survival of timing and duration of adjuvant chemotherapy in radically resected gastric cancer. Tumori, 2016, 102(4): e15-e19.
17. Ahmed S, Iqbal N, Yadav S, et al. Time to adjuvant therapy and other variables in localized gastric and gastroesophageal junction (GEJ) cancer (IJGC-D-13-00162). J Gastrointest Canc, 2014, 45(3): 284-290.
18. Cardoso R, Coburn N, SeevaratnamR, et al. A systematic review of patient surveillance after curative gastrectomy for gastric cancer: a brief review. Gastric Cancer, 2012, 15(Suppl 1): 164-167.
19. Yoshikawa T, Rino Y, Yukawa N, et al. Neoadjuvant chemotherapy for gastric cancer in Japan: a standing position by comparing with adjuvant chemotherapy. Surg Today, 2014, 44(1): 11-21.
20. Glimelius B, Hoffman K, Haglund U, et al. Initial or delayed chemotherapy with best supportive care in advanced gastric cancer. Ann Oncol, 1994, 5(2): 189-190.
21. Pyrh?nen S, Kuitunen T, Nyandoto P, et al. Randomised comparison of fluorouracil, epidoxorubicin and methotrexate (FEMTX) plus supportive care with supportive care alone in patients with non-resectable gastric cancer. Br J Cancer, 1995, 71(3): 587-591.
22. Folkman J. How is blood vessel growth regulated in normal and neoplastic tissue? G.H.A. Clowes memorial Award lecture. Cancer Res, 1986, 46(2): 467-473.
23. Folkman J. What is the evidence that tumors are angiogenesis dependent?. J Natl Cancer Inst, 1990, 82(1): 4-6.
24. Eggermont AM, Steller EP, Sugarbaker PH. Laparotomy enhances intraperitoneal tumor growth and abrogates the antitumor effects of interleukin-2 and lymphokine-activated killer cells. Surgery, 1987, 102(1): 71-78.
25. Folkman J, Klagsbrun M. Angiogenic factors. Science, 1987, 235(4787): 442-447.
26. Fidler IJ, Ellis LM. The implications of angiogenesis for the biology and therapy of cancer metastasis. Cell, 1994, 79(2): 185-188.
27. Goldie JH, Coldman AJ. A mathematic model for relating the drug sensitivity of tumors to their spontaneous mutation rate. Cancer Treat Rep, 1980, 63(11/12): 1727-1733.
28. Ryu KW, Kim YW, Lee JH, et al. Surgical complications and the risk factors of laparoscopy-assisted distal gastrectomy in early gastric cancer. Ann Surg Oncol, 2008, 15(6): 1625-1631.
29. An JY, Kim KM, Kim YM, et al. Surgical complications in gastric cancer patients preoperatively treated with chemotherapy: their risk factors and clinical relevance. Ann Surg Oncol, 2012, 19(8): 2452-2458.
30. James JB, Michael JR, Mackillop WJ, et al. Association between time to initiation of adjuvant chemotherapy and survival in colorectal cancer, a systematic review and meta-analysis. JAMA, 2011, 305(22): 2335-2342.
31. Des Guetz G, Nicolas P, Perret G, et al. Does delaying adjuvant chemotherapy after curative surgery for colorectal cancer impair survival? A meta-analysis. Eur J Cancer, 2010, 46(6): 1049-1055.

West China Medical Journal

Proper time to initiation of adjuvant chemotherapy after radical resection for gastric cancer: a systematic review and Meta-analysis

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