Skip to main content
Top
Published in: Journal of Gastrointestinal Surgery 3/2019

01-03-2019 | Original Article

Prognostic Value of the Number of Lymph Nodes Examined in Patients with Node-Negative Gastric Cancer

Authors: Ze-Long Yang, Ming-Hua Zhu, Quan Shi, Fu-Min Lu, Chun-Xi Wang

Published in: Journal of Gastrointestinal Surgery | Issue 3/2019

Login to get access

Abstract

Background

Our aim was to evaluate the prognostic value of the number of lymph nodes examined (eLNs) in patients with node-negative gastric cancer (GC) and further to adjust the American Joint Committee on Cancer (AJCC) 8th staging system based on the number of eLNs.

Methods

Node-negative GC patients diagnosed during 1988–2015 from the Surveillance, Epidemiology, and End Results (SEER) database were included. On the basis of a primary cohort of 4159 node-negative GC patients, we built the adjusted AJCC 8th staging system, which was then internally validated by a bootstrap method, and externally validated with an independent cohort of 5565 node-negative GC patients.

Results

The median number of eLNs was 10. For the training set, the optimal eLNs thresholds were determined to be 9 for node-negative GC patients. The adjusted AJCC 8th staging system for node-negative GC patients based on the number of eLNs had a significantly higher Harrell’s concordance index than the initial AJCC 8th staging system (C-index, 0.635 versus 0.616; P < 0.001). Thus, the adjusted AJCC 8th staging system had superior prognostic stratification. Similar results were found in the validation set.

Conclusions

For node-negative GC patients in the United States, the adjusted AJCC 8th staging system based on the number of eLNs predicted survival more accurately and discriminatively.
Appendix
Available only for authorised users
Literature
1.
go back to reference Fitzmaurice C, Dicker D, Pain A, Hamavid H, Moradi-Lakeh M, MacIntyre MF, et al. The Global Burden of Cancer 2013. JAMA Oncol 2015;1:505–527.CrossRef Fitzmaurice C, Dicker D, Pain A, Hamavid H, Moradi-Lakeh M, MacIntyre MF, et al. The Global Burden of Cancer 2013. JAMA Oncol 2015;1:505–527.CrossRef
2.
go back to reference Arsoniadis EG, Marmor S, Diep GK, Hui JYC, Jensen EH, Tuttle TM. Survival Rates for Patients with Resected Gastric Adenocarcinoma Finally have Increased in the United States. Ann Surg Oncol 2017;24:3361–3367.CrossRefPubMed Arsoniadis EG, Marmor S, Diep GK, Hui JYC, Jensen EH, Tuttle TM. Survival Rates for Patients with Resected Gastric Adenocarcinoma Finally have Increased in the United States. Ann Surg Oncol 2017;24:3361–3367.CrossRefPubMed
4.
go back to reference Edge SB, Compton CC. The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol 2010;17:1471–1474.CrossRefPubMed Edge SB, Compton CC. The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol 2010;17:1471–1474.CrossRefPubMed
5.
go back to reference Sano T, Coit DG, Kim HH, Roviello F, Kassab P, Wittekind C, et al. Proposal of a new stage grouping of gastric cancer for TNM classification: International Gastric Cancer Association staging project. Gastric Cancer 2017;20:217–225.CrossRefPubMed Sano T, Coit DG, Kim HH, Roviello F, Kassab P, Wittekind C, et al. Proposal of a new stage grouping of gastric cancer for TNM classification: International Gastric Cancer Association staging project. Gastric Cancer 2017;20:217–225.CrossRefPubMed
6.
go back to reference Wang J, Dang P, Raut CP, Pandalai PK, Maduekwe UN, Rattner DW, et al. Comparison of a lymph node ratio-based staging system with the 7th AJCC system for gastric cancer: analysis of 18,043 patients from the SEER database. Ann Surg 2012;255:478–485.CrossRefPubMed Wang J, Dang P, Raut CP, Pandalai PK, Maduekwe UN, Rattner DW, et al. Comparison of a lymph node ratio-based staging system with the 7th AJCC system for gastric cancer: analysis of 18,043 patients from the SEER database. Ann Surg 2012;255:478–485.CrossRefPubMed
7.
go back to reference Aurello P, Petrucciani N, Nigri GR, La Torre M, Magistri P, Tierno S, et al. Log odds of positive lymph nodes (LODDS): what are their role in the prognostic assessment of gastric adenocarcinoma? J Gastrointest Surg 2014;18:1254–1260.CrossRefPubMed Aurello P, Petrucciani N, Nigri GR, La Torre M, Magistri P, Tierno S, et al. Log odds of positive lymph nodes (LODDS): what are their role in the prognostic assessment of gastric adenocarcinoma? J Gastrointest Surg 2014;18:1254–1260.CrossRefPubMed
8.
go back to reference Smith DD, Nelson RA, Schwarz RE. A comparison of five competing lymph node staging schemes in a cohort of resectable gastric cancer patients. Ann Surg Oncol 2014;21:875–882.CrossRefPubMed Smith DD, Nelson RA, Schwarz RE. A comparison of five competing lymph node staging schemes in a cohort of resectable gastric cancer patients. Ann Surg Oncol 2014;21:875–882.CrossRefPubMed
9.
go back to reference Kooby DA, Suriawinata A, Klimstra DS, Brennan MF, Karpeh MS. Biologic predictors of survival in node-negative gastric cancer. Ann Surg 2003;237:828–835; discussion 835–827.PubMedPubMedCentral Kooby DA, Suriawinata A, Klimstra DS, Brennan MF, Karpeh MS. Biologic predictors of survival in node-negative gastric cancer. Ann Surg 2003;237:828–835; discussion 835–827.PubMedPubMedCentral
10.
go back to reference Camp RL, Dolled-Filhart M, Rimm DL. X-tile: a new bio-informatics tool for biomarker assessment and outcome-based cut-point optimization. Clin Cancer Res 2004;10:7252–7259.CrossRefPubMed Camp RL, Dolled-Filhart M, Rimm DL. X-tile: a new bio-informatics tool for biomarker assessment and outcome-based cut-point optimization. Clin Cancer Res 2004;10:7252–7259.CrossRefPubMed
11.
go back to reference Harrell FE, Jr., Lee KL, Mark DB. Multivariable prognostic models: issues in developing models, evaluating assumptions and adequacy, and measuring and reducing errors, Stat Med 1996;15:361–387.CrossRef Harrell FE, Jr., Lee KL, Mark DB. Multivariable prognostic models: issues in developing models, evaluating assumptions and adequacy, and measuring and reducing errors, Stat Med 1996;15:361–387.CrossRef
12.
go back to reference Chaurasia A, Harel O. Using AIC in Multiple Linear Regression framework with Multiply Imputed Data. Health Serv Outcomes Res Methodol 2012;12:219–233.CrossRefPubMedPubMedCentral Chaurasia A, Harel O. Using AIC in Multiple Linear Regression framework with Multiply Imputed Data. Health Serv Outcomes Res Methodol 2012;12:219–233.CrossRefPubMedPubMedCentral
13.
go back to reference Yoon SS, Yang HK. Lymphadenectomy for gastric adenocarcinoma: should west meet east? Oncologist 2009;14:871–882.CrossRefPubMed Yoon SS, Yang HK. Lymphadenectomy for gastric adenocarcinoma: should west meet east? Oncologist 2009;14:871–882.CrossRefPubMed
14.
go back to reference Japanese Gastric Cancer A. Japanese Classification of Gastric Carcinoma - 2nd English Edition. Gastric Cancer 1998;1:10–24.CrossRef Japanese Gastric Cancer A. Japanese Classification of Gastric Carcinoma - 2nd English Edition. Gastric Cancer 1998;1:10–24.CrossRef
15.
go back to reference Ahn HS, Lee HJ, Hahn S, Kim WH, Lee KU, Sano T, et al. Evaluation of the seventh American Joint Committee on Cancer/International Union Against Cancer Classification of gastric adenocarcinoma in comparison with the sixth classification. Cancer 2010;116:5592–5598.CrossRefPubMed Ahn HS, Lee HJ, Hahn S, Kim WH, Lee KU, Sano T, et al. Evaluation of the seventh American Joint Committee on Cancer/International Union Against Cancer Classification of gastric adenocarcinoma in comparison with the sixth classification. Cancer 2010;116:5592–5598.CrossRefPubMed
16.
go back to reference Wong J, Jackson P. Gastric cancer surgery: an American perspective on the current options and standards. Curr Treat Options Oncol 2011;;12:72–84.CrossRefPubMed Wong J, Jackson P. Gastric cancer surgery: an American perspective on the current options and standards. Curr Treat Options Oncol 2011;;12:72–84.CrossRefPubMed
17.
go back to reference Degiuli M, De Manzoni G, Di Leo A, D’Ugo D, Galasso E, Marrelli D, et al. Gastric cancer: Current status of lymph node dissection. World J Gastroenterol 2016;22:2875–2893.CrossRefPubMedPubMedCentral Degiuli M, De Manzoni G, Di Leo A, D’Ugo D, Galasso E, Marrelli D, et al. Gastric cancer: Current status of lymph node dissection. World J Gastroenterol 2016;22:2875–2893.CrossRefPubMedPubMedCentral
18.
go back to reference Zheng WF, Ji TT, Lin Y, Li RZ. The prognostic value of lymph nodes count on survival of patients with node-negative gastric cancer. Oncotarget 2016;7:43680–43688.PubMedPubMedCentral Zheng WF, Ji TT, Lin Y, Li RZ. The prognostic value of lymph nodes count on survival of patients with node-negative gastric cancer. Oncotarget 2016;7:43680–43688.PubMedPubMedCentral
19.
go back to reference Huang CM, Lin JX, Zheng CH, Li P, Xie JW, Lin BJ, et al. Prognostic impact of dissected lymph node count on patients with node-negative gastric cancer. World J Gastroenterol 2009;15:3926–3930.CrossRefPubMedPubMedCentral Huang CM, Lin JX, Zheng CH, Li P, Xie JW, Lin BJ, et al. Prognostic impact of dissected lymph node count on patients with node-negative gastric cancer. World J Gastroenterol 2009;15:3926–3930.CrossRefPubMedPubMedCentral
20.
go back to reference Yonemura Y, Endo Y, Hayashi I, Kawamura T, Yun HY, Bandou E. Proliferative activity of micrometastases in the lymph nodes of patients with gastric cancer. Br J Surg 2007;94:731–736.CrossRefPubMed Yonemura Y, Endo Y, Hayashi I, Kawamura T, Yun HY, Bandou E. Proliferative activity of micrometastases in the lymph nodes of patients with gastric cancer. Br J Surg 2007;94:731–736.CrossRefPubMed
21.
go back to reference Yanagita S, Natsugoe S, Uenosono Y, Kozono T, Ehi K, Arigami T, et al. Sentinel node micrometastases have high proliferative potential in gastric cancer. J Surg Res 2008;145:238–243.CrossRefPubMed Yanagita S, Natsugoe S, Uenosono Y, Kozono T, Ehi K, Arigami T, et al. Sentinel node micrometastases have high proliferative potential in gastric cancer. J Surg Res 2008;145:238–243.CrossRefPubMed
22.
go back to reference George S, Primrose J, Talbot R, Smith J, Mullee M, Bailey D, et al. Will Rogers revisited: prospective observational study of survival of 3592 patients with colorectal cancer according to number of nodes examined by pathologists. Br J Cancer 2006;95:841–847.CrossRefPubMedPubMedCentral George S, Primrose J, Talbot R, Smith J, Mullee M, Bailey D, et al. Will Rogers revisited: prospective observational study of survival of 3592 patients with colorectal cancer according to number of nodes examined by pathologists. Br J Cancer 2006;95:841–847.CrossRefPubMedPubMedCentral
23.
go back to reference Willaert W, Mareel M, Van De Putte D, Van Nieuwenhove Y, Pattyn P, Ceelen W. Lymphatic spread, nodal count and the extent of lymphadenectomy in cancer of the colon. Cancer Treat Rev 2014;40:405–413.CrossRefPubMed Willaert W, Mareel M, Van De Putte D, Van Nieuwenhove Y, Pattyn P, Ceelen W. Lymphatic spread, nodal count and the extent of lymphadenectomy in cancer of the colon. Cancer Treat Rev 2014;40:405–413.CrossRefPubMed
24.
go back to reference Pages F, Galon J, Fridman WH. The essential role of the in situ immune reaction in human colorectal cancer. J Leukoc Biol 2008;84:981–987.CrossRefPubMed Pages F, Galon J, Fridman WH. The essential role of the in situ immune reaction in human colorectal cancer. J Leukoc Biol 2008;84:981–987.CrossRefPubMed
25.
go back to reference Lee JH, Kang JW, Nam BH, Cho GS, Hyung WJ, Kim MC, et al. Correlation between lymph node count and survival and a reappraisal of lymph node ratio as a predictor of survival in gastric cancer: A multi-institutional cohort study. Eur J Surg Oncol 2017;43:432–439.CrossRefPubMed Lee JH, Kang JW, Nam BH, Cho GS, Hyung WJ, Kim MC, et al. Correlation between lymph node count and survival and a reappraisal of lymph node ratio as a predictor of survival in gastric cancer: A multi-institutional cohort study. Eur J Surg Oncol 2017;43:432–439.CrossRefPubMed
26.
go back to reference Marchet A, Mocellin S, Ambrosi A, Morgagni P, Garcea D, Marrelli D, et al. The ratio between metastatic and examined lymph nodes (N ratio) is an independent prognostic factor in gastric cancer regardless of the type of lymphadenectomy: results from an Italian multicentric study in 1853 patients. Ann Surg 2007;245:543–552.CrossRefPubMedPubMedCentral Marchet A, Mocellin S, Ambrosi A, Morgagni P, Garcea D, Marrelli D, et al. The ratio between metastatic and examined lymph nodes (N ratio) is an independent prognostic factor in gastric cancer regardless of the type of lymphadenectomy: results from an Italian multicentric study in 1853 patients. Ann Surg 2007;245:543–552.CrossRefPubMedPubMedCentral
27.
go back to reference Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med 2006;355:11–20.CrossRefPubMed Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med 2006;355:11–20.CrossRefPubMed
28.
go back to reference Macdonald JS, Smalley SR, Benedetti J, Hundahl SA, Estes NC, Stemmermann GN, et al. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med 2001;345:725–730.CrossRef Macdonald JS, Smalley SR, Benedetti J, Hundahl SA, Estes NC, Stemmermann GN, et al. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med 2001;345:725–730.CrossRef
Metadata
Title
Prognostic Value of the Number of Lymph Nodes Examined in Patients with Node-Negative Gastric Cancer
Authors
Ze-Long Yang
Ming-Hua Zhu
Quan Shi
Fu-Min Lu
Chun-Xi Wang
Publication date
01-03-2019
Publisher
Springer US
Published in
Journal of Gastrointestinal Surgery / Issue 3/2019
Print ISSN: 1091-255X
Electronic ISSN: 1873-4626
DOI
https://doi.org/10.1007/s11605-018-3947-y

Other articles of this Issue 3/2019

Journal of Gastrointestinal Surgery 3/2019 Go to the issue