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Published in: BMC Cancer 1/2018

Open Access 01-12-2018 | Research article

Venous invasion as a risk factor for recurrence after gastrectomy followed by chemotherapy for stage III gastric cancer

Authors: Keiji Nishibeppu, Shuhei Komatsu, Daisuke Ichikawa, Taisuke Imamura, Toshiyuki Kosuga, Kazuma Okamoto, Hirotaka Konishi, Atsushi Shiozaki, Hitoshi Fujiwara, Eigo Otsuji

Published in: BMC Cancer | Issue 1/2018

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Abstract

Background

Although adjuvant chemotherapy with S-1 after curative gastrectomy has been performed as a standard treatment for Stage II and III gastric cancer (GC) in Japan, patients with Stage III GC still have a high incidence of recurrence and a poor prognostic outcome. The aim of this study was to investigate risk factors for recurrence in patients with Stage III GC despite of curative gastrectomy followed by adjuvant chemotherapy, suggesting an indicator for more intensive management.

Methods

A total of 97 patients with pathological Stage III GC underwent adjuvant chemotherapy after curative gastrectomy between 2001 and 2014, were enrolled in this study. We retrospectively analyzed their hospital records from our hospital.

Results

The 5-year relapse-free survival (RFS) rates of patients with pStage III GC were 42.0%. Univariate and multivariate analyses for RFS revealed that venous invasion (v+) was an independent factor predicting a shorter RFS (v + vs. v-, 36.5% vs. 47.4%, P = 0.034, HR 1.82, 95% CI: 1.01–3.37). Venous invasion also predicted a shorter overall survival (OS) (v + vs. v-, 33.7% vs. 50.4%, P = 0.027). Regarding the patterns of recurrence, hematogenous recurrence was significantly occurred in patients with v + GC than those without (P = 0.022).

Conclusions

Stage III GC with venous invasion is a high-risk subgroup for hematogenous recurrence after curative surgery followed by adjuvant chemotherapy. More intensive and effective adjuvant chemo and/or molecular targeted therapy for Stage III GC patients with venous invasion should be considered to improve their outcomes.
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Literature
1.
2.
go back to reference Gunderson LL. Gastric cancer—patterns of relapse after surgical resection. Semin Radiat Oncol. 2002;12:150–61.CrossRefPubMed Gunderson LL. Gastric cancer—patterns of relapse after surgical resection. Semin Radiat Oncol. 2002;12:150–61.CrossRefPubMed
4.
go back to reference Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127:2893–917.CrossRefPubMed Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127:2893–917.CrossRefPubMed
5.
go back to reference Paoletti X, Oba K, Burzykowski T, Michiels S, Ohashi Y, Pignon JP, et al. Benefit of adjuvant chemotherapy for resectable gastric cancer: a meta-analysis. JAMA. 2010;303:1729–37.CrossRefPubMed Paoletti X, Oba K, Burzykowski T, Michiels S, Ohashi Y, Pignon JP, et al. Benefit of adjuvant chemotherapy for resectable gastric cancer: a meta-analysis. JAMA. 2010;303:1729–37.CrossRefPubMed
6.
go back to reference Iwatsuki M, Mimori K, Fukagawa T, Ishii H, Yokobori T, Sasako M, et al. The clinical significance of vimentin-expressing gastric cancer cells in bone marrow. Ann Surg Oncol. 2010;17:2526–33.CrossRefPubMed Iwatsuki M, Mimori K, Fukagawa T, Ishii H, Yokobori T, Sasako M, et al. The clinical significance of vimentin-expressing gastric cancer cells in bone marrow. Ann Surg Oncol. 2010;17:2526–33.CrossRefPubMed
7.
go back to reference Kurashige J, Kamohara H, Watanabe M, Hiyoshi Y, Iwatsuki M, Tanaka Y, et al. MicroRNA-200b regulates cell proliferation, invasion, and migration by directly targeting ZEB2 in gastric carcinoma. Ann Surg Oncol. 2012;19:656–64.CrossRef Kurashige J, Kamohara H, Watanabe M, Hiyoshi Y, Iwatsuki M, Tanaka Y, et al. MicroRNA-200b regulates cell proliferation, invasion, and migration by directly targeting ZEB2 in gastric carcinoma. Ann Surg Oncol. 2012;19:656–64.CrossRef
8.
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
9.
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;345:725–30.CrossRefPubMed 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;345:725–30.CrossRefPubMed
10.
go back to reference 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;30:2327–33.CrossRefPubMedPubMedCentral 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;30:2327–33.CrossRefPubMedPubMedCentral
11.
go back to reference Sakuramoto S, Sasako M, Yamaguchi T, Kinoshita T, Fujii M, Nashimoto A, et al. Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine. N Engl J Med. 2007;357:1810–20.CrossRefPubMed Sakuramoto S, Sasako M, Yamaguchi T, Kinoshita T, Fujii M, Nashimoto A, et al. Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine. N Engl J Med. 2007;357:1810–20.CrossRefPubMed
12.
go back to reference 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;29:4387–93.CrossRefPubMed 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;29:4387–93.CrossRefPubMed
13.
go back to reference Imamura T, Komatsu S, Ichikawa D, Kubota T, Okamoto K, Konishi H, et al. Poor prognostic subgroup in T3N0 stage IIA gastric cancer, suggesting an indication for adjuvant chemotherapy. J Surg Oncol. 2015;111:221–5.CrossRefPubMed Imamura T, Komatsu S, Ichikawa D, Kubota T, Okamoto K, Konishi H, et al. Poor prognostic subgroup in T3N0 stage IIA gastric cancer, suggesting an indication for adjuvant chemotherapy. J Surg Oncol. 2015;111:221–5.CrossRefPubMed
14.
go back to reference Bang Y-J, Kim Y-W, Yang H-K, Chung HC, Park Y-K, Lee KH, et al. Adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): a phase 3 open-label, randomised controlled trial. Lancet. 2012;379:315–21.CrossRefPubMed Bang Y-J, Kim Y-W, Yang H-K, Chung HC, Park Y-K, Lee KH, et al. Adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): a phase 3 open-label, randomised controlled trial. Lancet. 2012;379:315–21.CrossRefPubMed
15.
go back to reference 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;20:175–81.CrossRefPubMed 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;20:175–81.CrossRefPubMed
16.
go back to reference Fuse N, Bando H, Chin K, Ito S, Yoshikawa T, Tsuburaya A, et al. Adjuvant capecitabine plus oxaliplatin after D2 gastrectomy in Japanese patients with gastric cancer: a phase II study. Gastric Cancer. 2017;20:332–40.CrossRefPubMed Fuse N, Bando H, Chin K, Ito S, Yoshikawa T, Tsuburaya A, et al. Adjuvant capecitabine plus oxaliplatin after D2 gastrectomy in Japanese patients with gastric cancer: a phase II study. Gastric Cancer. 2017;20:332–40.CrossRefPubMed
17.
go back to reference Komatsu S, Ichikawa D, Miyamae M, Kosuga T, Okamoto K, Arita T, et al. Positive lymph node ratio as an indicator of prognosis and local tumor clearance in N3 gastric cancer. J Gastrointest Surg. 2016;20:1565–71.CrossRefPubMed Komatsu S, Ichikawa D, Miyamae M, Kosuga T, Okamoto K, Arita T, et al. Positive lymph node ratio as an indicator of prognosis and local tumor clearance in N3 gastric cancer. J Gastrointest Surg. 2016;20:1565–71.CrossRefPubMed
18.
go back to reference Maehara Y, Kabashima A, Koga T, Tokunaga E, Takeuchi H, Kakeji Y, et al. Vascular invasion and potential for tumor angiogenesis and metastasis in gastric carcinoma. Surgery. 2000;128:408–16.CrossRefPubMed Maehara Y, Kabashima A, Koga T, Tokunaga E, Takeuchi H, Kakeji Y, et al. Vascular invasion and potential for tumor angiogenesis and metastasis in gastric carcinoma. Surgery. 2000;128:408–16.CrossRefPubMed
19.
go back to reference Nakanishi Y, Ohara M, Domen H, Shichinohe T, Hirano S, Ishizaka M. Differences in risk factors between patterns of recurrence in patients after curative resection for advanced gastric carcinoma. World J Surg Oncol. 2013;11:98.CrossRefPubMedPubMedCentral Nakanishi Y, Ohara M, Domen H, Shichinohe T, Hirano S, Ishizaka M. Differences in risk factors between patterns of recurrence in patients after curative resection for advanced gastric carcinoma. World J Surg Oncol. 2013;11:98.CrossRefPubMedPubMedCentral
20.
go back to reference Takahari D, Hamaguchi T, Yoshimura K, Katai H, Ito S, Fuse N, et al. Survival analysis of adjuvant chemotherapy with S-1 plus cisplatin for stage III gastric cancer. Gastric Cancer. 2014;17:383–6.CrossRefPubMed Takahari D, Hamaguchi T, Yoshimura K, Katai H, Ito S, Fuse N, et al. Survival analysis of adjuvant chemotherapy with S-1 plus cisplatin for stage III gastric cancer. Gastric Cancer. 2014;17:383–6.CrossRefPubMed
21.
go back to reference 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;17:348–53.CrossRefPubMed 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;17:348–53.CrossRefPubMed
22.
go back to reference Noh SH, Park SR, Yang H-K, Chung HC, Chung I-J, Kim S-W, 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;15:1389–96.CrossRefPubMed Noh SH, Park SR, Yang H-K, Chung HC, Chung I-J, Kim S-W, 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;15:1389–96.CrossRefPubMed
23.
go back to reference Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010;376:687–97.CrossRefPubMed Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010;376:687–97.CrossRefPubMed
24.
go back to reference Ohtsu A, Shah MA, Van Cutsem E, Rha SY, Sawaki A, Park SR, et al. Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a randomized, double-blind, placebo-controlled phase III study. J Clin Oncol. 2011;29:3968–76.CrossRefPubMed Ohtsu A, Shah MA, Van Cutsem E, Rha SY, Sawaki A, Park SR, et al. Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a randomized, double-blind, placebo-controlled phase III study. J Clin Oncol. 2011;29:3968–76.CrossRefPubMed
25.
go back to reference Wilke H, Muro K, Van Cutsem E, Oh S-C, Bodoky G, Shimada Y, et al. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol. 2014;15:1224–35.CrossRefPubMed Wilke H, Muro K, Van Cutsem E, Oh S-C, Bodoky G, Shimada Y, et al. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol. 2014;15:1224–35.CrossRefPubMed
Metadata
Title
Venous invasion as a risk factor for recurrence after gastrectomy followed by chemotherapy for stage III gastric cancer
Authors
Keiji Nishibeppu
Shuhei Komatsu
Daisuke Ichikawa
Taisuke Imamura
Toshiyuki Kosuga
Kazuma Okamoto
Hirotaka Konishi
Atsushi Shiozaki
Hitoshi Fujiwara
Eigo Otsuji
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2018
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-018-4052-z

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