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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 9/2018

01-09-2018 | Gastrointestinal Oncology

Preoperative Therapy for Gastric Adenocarcinoma is Protective for Poor Oncologic Outcomes in Patients with Complications After Gastrectomy

Authors: Diego Vicente, MD, Naruhiko Ikoma, MD, Yi-Ju Chiang, MSPH, Keith Fournier, MD, Ching-Wei D. Tzeng, MD, Shumei Song, MD, PhD, Paul Mansfield, MD, Jaffer Ajani, MD, Brian D. Badgwell, MD, MS

Published in: Annals of Surgical Oncology | Issue 9/2018

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Abstract

Background

Postoperative complications (POC) are associated with poor oncologic outcomes in gastric cancer. We sought to evaluate the impact of POC on survival in patients with gastric cancer treated with upfront surgery (UpSurg) versus those treated with preoperative therapy (PreT).

Methods

We analyzed data from a prospectively maintained database of patients who had undergone resection of their gastric cancer at our institution. Patients with T1N0 or M1 lesions, recurrent disease, and mortality within 90 days were excluded. Survival was compared between patients with and without POC in the UpSurg and PreT groups. Cox regression analyses were used to examine factors associated with overall survival (OS) and disease-free survival (DFS).

Results

A total of 421 patients underwent resection of gastric cancer: 30% underwent upfront surgery, and 51% had a POC. Among patients who had POCs, 71% were infectious and 53% were Clavien–Dindo grade III or IV. UpSurg patients with a POC had shorter OS (5-year, 47 vs. 85%; p < 0.001) and DFS (5-year, 46 vs. 76%; p < 0.001) than those without a POC. In contrast, there was no difference in OS (5-year, 57 vs. 63%; p = 0.77) and DFS (5-year, 52 vs. 52%; p = 0.52) between PreT patients with and without POC. Multivariable Cox regression model demonstrated that a POC in UpSurg patients had significant impact on DFS (2.6 [95% confidence interval (CI) 1.48–4.74]), whereas it did not in PreT patients (0.9 [95% CI 0.70–1.33]).

Conclusions

The use of preoperative therapy negated the impact of POCs on OS and DFS in patients undergoing resection for gastric cancer.
Appendix
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Literature
1.
Howlader N NA, Krapcho M, Miller D, Bishop K, Kosary CL, Yu M, Ruhl J, Tatalovich Z, Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds) SEER cancer statistics review, 1975–2014. 2017; https://​seer.​cancer.​gov/​data/​. Accessed 29 Jan 2018.
2.
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):725–30.CrossRefPubMed
3.
Cunningham D, Allum WH, Stenning SP, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006;355(1):11–20.CrossRefPubMed
4.
Noh SH, Park SR, Yang HK, 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.CrossRefPubMed
5.
Ychou M, Boige V, Pignon JP, et al. Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial. J Clin Oncol. 2011;29(13):1715–21.CrossRefPubMed
6.
Sasako M, Sakuramoto S, Katai H, 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.CrossRefPubMed
7.
Sakuramoto S, Sasako M, Yamaguchi T, et al. Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine. N Engl J Med. 2007;357(18):1810–20.CrossRefPubMed
8.
Bang YJ, Kim YW, Yang HK, et al. Adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): a phase 3 open-label, randomised controlled trial. Lancet. 2012;379(9813):315–21.CrossRefPubMed
9.
Lee J, Lim DH, Kim S, et al. Phase III trial comparing capecitabine plus cisplatin versus capecitabine plus cisplatin with concurrent capecitabine radiotherapy in completely resected gastric cancer with D2 lymph node dissection: the ARTIST trial. J Clin Oncol. 2012;30(3):268–73.CrossRefPubMed
10.
Park SH, Sohn TS, Lee J, 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.CrossRefPubMed
11.
Cuschieri A, Fayers P, Fielding J, et al. Postoperative morbidity and mortality after D1 and D2 resections for gastric cancer: preliminary results of the MRC randomised controlled surgical trial. The Surgical Cooperative Group. Lancet. 1996;347(9007):995–9.PubMed
12.
Bonenkamp JJ, Songun I, Hermans J, et al. Randomised comparison of morbidity after D1 and D2 dissection for gastric cancer in 996 Dutch patients. Lancet. 1995;345(8952):745–8.CrossRefPubMed
13.
Strong VE, Devaud N, Allen PJ, Gonen M, Brennan MF, Coit D. Laparoscopic versus open subtotal gastrectomy for adenocarcinoma: a case-control study. Ann Surg Oncol. 2009;16(6):1507–13.CrossRefPubMed
14.
Pucher PH, Aggarwal R, Qurashi M, Darzi A. Meta-analysis of the effect of postoperative in-hospital morbidity on long-term patient survival. Br J Surg. 2014;101(12):1499–508.CrossRefPubMed
15.
Jin LX, Sanford DE, Squires MH, 3rd, et al. Interaction of postoperative morbidity and receipt of adjuvant therapy on long-term survival after resection for gastric adenocarcinoma: results from the U.S. Gastric Cancer Collaborative. Ann Surg Oncol. 2016;23(8):2398–408.CrossRefPubMed
16.
Tsujimoto H, Ichikura T, Ono S, et al. Impact of postoperative infection on long-term survival after potentially curative resection for gastric cancer. Ann Surg Oncol. 2009;16(2):311–8.CrossRefPubMed
17.
Kubota T, Hiki N, Sano T, et al. Prognostic significance of complications after curative surgery for gastric cancer. Ann Surg Oncol. 2014;21(3):891–898.CrossRefPubMed
18.
McSorley ST, Horgan PG, McMillan DC. The impact of the type and severity of postoperative complications on long-term outcomes following surgery for colorectal cancer: a systematic review and meta-analysis. Crit Rev Oncol Hematol. 2016;97:168–77.CrossRefPubMed
19.
Jiang N, Deng JY, Ding XW, et al. Effect of complication grade on survival following curative gastrectomy for carcinoma. World J Gastroenterol. 2014;20(25):8244–52.CrossRefPubMedPubMedCentral
20.
Tokunaga M, Tanizawa Y, Bando E, Kawamura T, Terashima M. Poor survival rate in patients with postoperative intra-abdominal infectious complications following curative gastrectomy for gastric cancer. Ann Surg Oncol. 2013;20(5):1575–83.CrossRefPubMed
21.
Merkow RP, Bentrem DJ, Mulcahy MF, et al. Effect of postoperative complications on adjuvant chemotherapy use for stage III colon cancer. Ann Surg. 2013;258(6):847–53.CrossRefPubMed
22.
Merkow RP, Bilimoria KY, Tomlinson JS, et al. Postoperative complications reduce adjuvant chemotherapy use in resectable pancreatic cancer. Ann Surg. 2014;260(2):372–7.CrossRefPubMed
23.
Mota JM, Leite CA, Souza LE, et al. Post-sepsis state induces tumor-associated macrophage accumulation through CXCR4/CXCL12 and favors tumor progression in mice. Cancer Immunol Res. 2016;4(4):312–22.CrossRefPubMed
24.
Hotchkiss RS, Monneret G, Payen D. Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy. Nat Rev Immunol. 2013;13(12):862–74.CrossRefPubMedPubMedCentral
25.
Cavassani KA, Carson WFt, Moreira AP, et al. The post sepsis-induced expansion and enhanced function of regulatory T cells create an environment to potentiate tumor growth. Blood. 2010;115(22):4403–11.CrossRefPubMedPubMedCentral
26.
27.
Ajani JA, Winter K, Okawara GS, et al. Phase II trial of preoperative chemoradiation in patients with localized gastric adenocarcinoma (RTOG 9904): quality of combined modality therapy and pathologic response. J Clin Oncol. 2006;24(24):3953–8.CrossRefPubMed
28.
Tzeng CW, Tran Cao HS, Lee JE, et al. Treatment sequencing for resectable pancreatic cancer: influence of early metastases and surgical complications on multimodality therapy completion and survival. J Gastrointest Surg. 2014;18(1):16–24 (discussion 24-5).
29.
Bohm S, Montfort A, Pearce OM, et al. Neoadjuvant chemotherapy modulates the immune microenvironment in metastases of tubo-ovarian high-grade serous carcinoma. Clin Cancer Res. 2016;22(12):3025–36.CrossRefPubMed
30.
Biziota E, Mavroeidis L, Hatzimichael E, Pappas P. Metronomic chemotherapy: a potent macerator of cancer by inducing angiogenesis suppression and antitumor immune activation. Cancer Lett. 2017;400:243–51.CrossRefPubMed
31.
Eguchi T, Kodera Y, Nakanishi H, et al. The effect of chemotherapy against micrometastases and isolated tumor cells in lymph nodes: an in vivo study. In vivo (Athens, Greece). 2008;22(6):707–12.
32.
Edge SB BD, Compton CC, Fritz AG, Greene FL, Trotti A AJCC cancer staging manual, 7th edn. New York: Springer; 2010.
33.
Japanese gastric cancer treatment guidelines 2010 (ver. 3). Gastric Cancer. 2011;14(2):113–23.
34.
Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004;240(2):205–13.CrossRefPubMedPubMedCentral
35.
Artinyan A, Orcutt ST, Anaya DA, Richardson P, Chen GJ, Berger DH. Infectious postoperative complications decrease long-term survival in patients undergoing curative surgery for colorectal cancer: a study of 12,075 patients. Ann Surg. 2015;261(3):497–505.CrossRefPubMed
36.
Le AT, Huang B, Hnoosh D, et al. Effect of complications on oncologic outcomes after pancreaticoduodenectomy for pancreatic cancer. J Surg Res. 2017;214:1–8.CrossRefPubMed
37.
Schneider MA, Eshmuminov D, Lehmann K. Major postoperative complications are a risk factor for impaired survival after CRS/HIPEC. Ann Surg Oncol. 2017;24(8):2224–32.CrossRefPubMed
38.
McSorley ST, Watt DG, Horgan PG, McMillan DC. Postoperative systemic inflammatory response, complication severity, and survival following surgery for colorectal cancer. Ann Surg Oncol. 2016;23(9):2832–40.CrossRefPubMedPubMedCentral
39.
Lim SB, Yu CS, Kim CW, Yoon YS, Park IJ, Kim JC. The types of anastomotic leakage that develop following anterior resection for rectal cancer demonstrate distinct characteristics and oncologic outcomes. Int J Colorectal Dis. 2015;30(11):1533–40.CrossRefPubMed
40.
Papenfuss WA, Kukar M, Oxenberg J, et al. Morbidity and mortality associated with gastrectomy for gastric cancer. Ann Surg Oncol. 2014;21(9):3008–14.CrossRefPubMed
41.
Badgwell B, Ajani J, Blum M, et al. Postoperative morbidity and mortality rates are not increased for patients with gastric and gastroesophageal cancer who undergo preoperative chemoradiation therapy. Ann Surg Oncol. 2016;23(1):156–62.CrossRefPubMed
42.
Marrelli D, Pedrazzani C, Neri A, et al. Complications after extended (D2) and superextended (D3) lymphadenectomy for gastric cancer: analysis of potential risk factors. Ann Surg Oncol. 2007;14(1):25–33.CrossRefPubMed
43.
Mita K, Ito H, Hashimoto M, et al. Postoperative complications and survival after gastric cancer surgery in patients older than 80 years of age. J Gastrointest Surg. 2013;17(12):2067–73.CrossRefPubMed
44.
Oh SY, Kwon S, Lee KG, et al. Outcomes of minimally invasive surgery for early gastric cancer are comparable with those for open surgery: analysis of 1,013 minimally invasive surgeries at a single institution. Surg Endosc. 2014;28(3):789–95.CrossRefPubMed
45.
Cools-Lartigue J, Spicer J, McDonald B, et al. Neutrophil extracellular traps sequester circulating tumor cells and promote metastasis. J Clin Investig. 2013.
46.
Ashizawa T, Okada R, Suzuki Y, et al. Clinical significance of interleukin-6 (IL-6) in the spread of gastric cancer: role of IL-6 as a prognostic factor. Gastric Cancer. 2005;8(2):124–31.CrossRefPubMed
47.
48.
Eto K, Hiki N, Kumagai K, et al. Prophylactic effect of neoadjuvant chemotherapy in gastric cancer patients with postoperative complications. Gastric Cancer. 2017.
49.
Matsumoto Y, Tsujimoto H, Ono S, et al. Abdominal infection suppresses the number and activity of intrahepatic natural killer cells and promotes tumor growth in a murine liver metastasis model. Ann Surg Oncol. 2016;23 Suppl 2:S257–65.CrossRefPubMed
50.
Frese-Schaper M, Keil A, Yagita H, et al. Influence of natural killer cells and perforinmediated cytolysis on the development of chemically induced lung cancer in A/J mice. Cancer Immunol Immunother. 2014;63(6):571–80.CrossRefPubMed
51.
Jaime-Ramirez AC, Mundy-Bosse BL, Kondadasula S, et al. IL-12 enhances the antitumor actions of trastuzumab via NK cell IFN-gamma production. J Immunol. 2011;186(6):3401–9.CrossRefPubMedPubMedCentral
52.
Indrova M, Simova J, Bieblova J, Bubenik J, Reinis M. NK1.1 + cells are important for the development of protective immunity against MHC I-deficient, HPV16-associated tumours. Oncol Rep. 2011;25(1):281–8.PubMed
53.
Watt DG, McSorley ST, Park JH, Horgan PG, McMillan DC. A postoperative systemic inflammation score predicts short- and long-term outcomes in patients undergoing surgery for colorectal cancer. Ann Surg Oncol. 2017;24(4):1100–9.CrossRefPubMed
54.
Watt DG, Horgan PG, McMillan DC. Routine clinical markers of the magnitude of the systemic inflammatory response after elective operation: a systematic review. Surgery. 2015;157(2):362–80.CrossRefPubMed
55.
Binkowska AM, Michalak G, Slotwinski R. Current views on the mechanisms of immune responses to trauma and infection. Cent Eur J Immunol. 2015;40(2):206–16.CrossRefPubMedPubMedCentral
56.
Najmeh S, Cools-Lartigue J, Rayes RF, et al. Neutrophil extracellular traps sequester circulating tumor cells via beta1-integrin mediated interactions. Int J Cancer. 2017;140(10):2321–30.CrossRefPubMed
57.
Cata JP, Bauer M, Sokari T, et al. Effects of surgery, general anesthesia, and perioperative epidural analgesia on the immune function of patients with non-small cell lung cancer. J Clin Anesth. 2013;25(4):255–62.CrossRefPubMed
58.
Salvans S, Mayol X, Alonso S, et al. Postoperative peritoneal infection enhances migration and invasion capacities of tumor cells in vitro: an insight into the association between anastomotic leak and recurrence after surgery for colorectal cancer. Ann Surg. 2014;260(5):939–43 (discussion 943-4).
59.
Yamashita S, Sheth RA, Niekamp AS, et al. Comprehensive complication index predicts cancer-specific survival after resection of colorectal metastases independent of RAS mutational status. Ann Surg. 2017;266(6):1045–54.CrossRefPubMed
60.
Tang H, Lu W, Yang Z, et al. Risk factors and long-term outcome for postoperative intra-abdominal infection after hepatectomy for hepatocellular carcinoma. Medicine. 2017;96(17):e6795.CrossRefPubMedPubMedCentral
61.
Margonis GA, Sasaki K, Andreatos N, et al. Prognostic impact of complications after resection of early stage hepatocellular carcinoma. J Surg Oncol. 2017;115(7):791–804.CrossRefPubMed
62.
Richards CH, Leitch EF, Horgan PG, Anderson JH, McKee RF, McMillan DC. The relationship between patient physiology, the systemic inflammatory response and survival in patients undergoing curative resection of colorectal cancer. Br J Cancer. 2010;103(9):1356–61.CrossRefPubMedPubMedCentral
63.
Tu RH, Lin JX, Li P, et al. Prognostic significance of postoperative pneumonia after curative resection for patients with gastric cancer. Cancer Med. 2017;6(12):2757–65.CrossRefPubMedPubMedCentral
64.
Kubota T, Hiki N, Nunobe S, et al. Significance of the inflammation-based Glasgow prognostic score for short- and long-term outcomes after curative resection of gastric cancer. J Gastrointest Surg. 2012;16(11):2037–44.CrossRefPubMed
65.
Ikoma N, Lee JH, Bhutani MS, et al. Preoperative accuracy of gastric cancer staging in patient selection for preoperative therapy: race may affect accuracy of endoscopic ultrasonography. J Gastrointest Oncol. 2017;8(6):1009–17.CrossRefPubMedPubMedCentral
66.
Schuhmacher C, Gretschel S, Lordick F, et al. Neoadjuvant chemotherapy compared with surgery alone for locally advanced cancer of the stomach and cardia: European Organisation for Research and Treatment of Cancer randomized trial 40954. J Clin Oncol. 2010;28(35):5210–8.CrossRefPubMedPubMedCentral
67.
Knight G, Earle CC, Cosby R, et al. Neoadjuvant or adjuvant therapy for resectable gastric cancer: a systematic review and practice guideline for North America. Gastric Cancer. 2013;16(1):28–40.CrossRefPubMed
68.
Li ZY, Shan F, Zhang LH, et al. Complications after radical gastrectomy following FOLFOX7 neoadjuvant chemotherapy for gastric cancer. World J Surg Oncol. 2011;9:110.CrossRefPubMedPubMedCentral
69.
Gallardo-Rincon D, Onate-Ocana LF, Calderillo-Ruiz G. Neoadjuvant chemotherapy with P-ELF (cisplatin, etoposide, leucovorin, 5-fluorouracil) followed by radical resection in patients with initially unresectable gastric adenocarcinoma: a phase II study. Ann Surg Oncol. 2000;7(1):45–50.CrossRefPubMed
70.
Ikoma N, Das P, Blum M, et al. Preoperative chemoradiation therapy does not increase risk of anastomotic leak in patients with gastric cancer. Int J Radiat Oncol Biol Phys. 2017;99(3):660–6.CrossRefPubMed
Metadata
Title
Preoperative Therapy for Gastric Adenocarcinoma is Protective for Poor Oncologic Outcomes in Patients with Complications After Gastrectomy
Authors
Diego Vicente, MD
Naruhiko Ikoma, MD
Yi-Ju Chiang, MSPH
Keith Fournier, MD
Ching-Wei D. Tzeng, MD
Shumei Song, MD, PhD
Paul Mansfield, MD
Jaffer Ajani, MD
Brian D. Badgwell, MD, MS
Publication date
01-09-2018
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology / Issue 9/2018
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-018-6638-8

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