Skip to main content
Top
Published in: Annals of Surgical Oncology 4/2014

01-04-2014 | Gastrointestinal Oncology

Prognostic Significance of Targetable Angiogenic and Growth Factors in Patients Undergoing Resection for Gastric and Gastroesophageal Junction Cancers

Authors: Do Joong Park, MD, PhD, Changhwan Yoon, PhD, Nicholas Thomas, Geoffrey Y. Ku, MD, Yelena Y. Janjigian, MD, David P. Kelsen, MD, David H. Ilson, MD, PhD, Karyn A. Goodman, MD, Laura H. Tang, MD, Vivian E. Strong, MD, Daniel G. Coit, MD, Sam S. Yoon, MD

Published in: Annals of Surgical Oncology | Issue 4/2014

Login to get access

Abstract

Background

Circulating factors in patients with gastric/gastroesophageal junction (GEJ) cancers may promote tumor progression and metastasis and may be targeted for therapy.

Methods

Serum levels of ligands—vascular endothelial growth factor A (VEGF-A), fibroblast growth factor 2 (FGF2), epidermal growth factor (EGF), hepatocyte growth factor (HGF)—from four targetable pathways were measured before surgery, and levels were correlated to clinicopathologic characteristics and overall survival (OS).

Results

In 147 patients who underwent potentially curative resection for gastric/GEJ adenocarcinoma, VEGF-A levels were higher in patients with R1 versus R0 resection (p = 0.037). High EGF levels were associated with poorly differentiated tumors (p = 0.02). Elevated FGF2 levels were found in Lauren diffuse-type tumors (p = 0.017) and tumors with seven or more metastatic nodes (N3) (p < 0.042). Patients with advanced-staged tumors had higher HGF levels (p = 0.012). At a median follow-up of 35 months, 46 patients (31 %) had died. Increased VEGF and HGF levels were correlated with decreased OS (p = 0.009 and 0.005). An adjusted total value (ATV) of all factors was better than any single factor in stratifying patients into good and poor prognosis groups (5-year OS 84.1 vs. 53.9 %, p = 0.005). By multivariate analysis, serum VEGF-A and ATV were significant independent prognostic factors (along with T and N category) for OS (p = 0.028 and 0.013, respectively).

Conclusions

In patients undergoing resection for gastric and GEJ cancer, high levels of angiogenic and growth factors are associated with unfavorable tumor characteristics and poorer overall survival. Thus levels of these factors can help delineate tumor biology and stratify prognosis.
Appendix
Available only for authorised users
Literature
1.
go back to reference Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.PubMedCrossRef Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.PubMedCrossRef
2.
go back to reference Deng N, Goh LK, Wang H, et al. A comprehensive survey of genomic alterations in gastric cancer reveals systematic patterns of molecular exclusivity and co-occurrence among distinct therapeutic targets. Gut. 2012;61:673–84.PubMedCentralPubMedCrossRef Deng N, Goh LK, Wang H, et al. A comprehensive survey of genomic alterations in gastric cancer reveals systematic patterns of molecular exclusivity and co-occurrence among distinct therapeutic targets. Gut. 2012;61:673–84.PubMedCentralPubMedCrossRef
3.
4.
go back to reference De VF, Giuliani F, Silvestris N, et al. Current status of targeted therapies in advanced gastric cancer. Expert Opin Ther Targets. 2012;16(Suppl 2):S29–34. De VF, Giuliani F, Silvestris N, et al. Current status of targeted therapies in advanced gastric cancer. Expert Opin Ther Targets. 2012;16(Suppl 2):S29–34.
5.
go back to reference Pietrantonio F, De BF, Da P, et al. A review on biomarkers for prediction of treatment outcome in gastric cancer. Anticancer Res. 2013;33:1257–66.PubMed Pietrantonio F, De BF, Da P, et al. A review on biomarkers for prediction of treatment outcome in gastric cancer. Anticancer Res. 2013;33:1257–66.PubMed
6.
go back to reference AJCC cancer staging manual. 7th edn. New York: Springer; 2010. AJCC cancer staging manual. 7th edn. New York: Springer; 2010.
7.
go back to reference Wang J, Dang P, Raut CP, 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;255:478–85.PubMedCrossRef Wang J, Dang P, Raut CP, 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;255:478–85.PubMedCrossRef
8.
go back to reference Kattan MW, Karpeh MS, Mazumdar M, Brennan MF. Postoperative nomogram for disease-specific survival after an R0 resection for gastric carcinoma. J Clin Oncol. 2003;21:3647–50.PubMedCrossRef Kattan MW, Karpeh MS, Mazumdar M, Brennan MF. Postoperative nomogram for disease-specific survival after an R0 resection for gastric carcinoma. J Clin Oncol. 2003;21:3647–50.PubMedCrossRef
9.
go back to reference Oakman C, Santarpia L, Di LA. Breast cancer assessment tools and optimizing adjuvant therapy. Nat Rev Clin Oncol. 2010;7:725–32.PubMedCrossRef Oakman C, Santarpia L, Di LA. Breast cancer assessment tools and optimizing adjuvant therapy. Nat Rev Clin Oncol. 2010;7:725–32.PubMedCrossRef
10.
go back to reference Li M, Liu F, Sun P, et al. Correlations between serum levels of vascular endothelial growth factor and endostatin with clinical pathological characteristics of patients with gastrointestinal cancers. Hepatogastroenterology. 2012;59:1865–8.PubMedCrossRef Li M, Liu F, Sun P, et al. Correlations between serum levels of vascular endothelial growth factor and endostatin with clinical pathological characteristics of patients with gastrointestinal cancers. Hepatogastroenterology. 2012;59:1865–8.PubMedCrossRef
11.
go back to reference Katoh M, Katoh M. FGF signaling network in the gastrointestinal tract (review). Int J Oncol. 2006;29:163–8.PubMed Katoh M, Katoh M. FGF signaling network in the gastrointestinal tract (review). Int J Oncol. 2006;29:163–8.PubMed
13.
go back to reference Bang YJ, Van CE, Feyereislova 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.PubMedCrossRef Bang YJ, Van CE, Feyereislova 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.PubMedCrossRef
14.
go back to reference Ohtsu A, Shah MA, Van CE, 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.PubMedCrossRef Ohtsu A, Shah MA, Van CE, 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.PubMedCrossRef
15.
go back to reference Van CE, de HS, Kang YK, et al. Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a biomarker evaluation from the AVAGAST randomized phase III trial. J Clin Oncol. 2012;30:2119–27.CrossRef Van CE, de HS, Kang YK, et al. Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a biomarker evaluation from the AVAGAST randomized phase III trial. J Clin Oncol. 2012;30:2119–27.CrossRef
16.
go back to reference Lordick F, Kang YK, Chung HC, et al. Capecitabine and cisplatin with or without cetuximab for patients with previously untreated advanced gastric cancer (EXPAND): a randomised, open-label phase 3 trial. Lancet Oncol. 2013;14:490–9.PubMedCrossRef Lordick F, Kang YK, Chung HC, et al. Capecitabine and cisplatin with or without cetuximab for patients with previously untreated advanced gastric cancer (EXPAND): a randomised, open-label phase 3 trial. Lancet Oncol. 2013;14:490–9.PubMedCrossRef
17.
go back to reference Waddell T, Chau I, Cunningham D, et al. Epirubicin, oxaliplatin, and capecitabine with or without panitumumab for patients with previously untreated advanced oesophagogastric cancer (REAL3): a randomised, open-label phase 3 trial. Lancet Oncol. 2013;14:481–9.PubMedCentralPubMedCrossRef Waddell T, Chau I, Cunningham D, et al. Epirubicin, oxaliplatin, and capecitabine with or without panitumumab for patients with previously untreated advanced oesophagogastric cancer (REAL3): a randomised, open-label phase 3 trial. Lancet Oncol. 2013;14:481–9.PubMedCentralPubMedCrossRef
Metadata
Title
Prognostic Significance of Targetable Angiogenic and Growth Factors in Patients Undergoing Resection for Gastric and Gastroesophageal Junction Cancers
Authors
Do Joong Park, MD, PhD
Changhwan Yoon, PhD
Nicholas Thomas
Geoffrey Y. Ku, MD
Yelena Y. Janjigian, MD
David P. Kelsen, MD
David H. Ilson, MD, PhD
Karyn A. Goodman, MD
Laura H. Tang, MD
Vivian E. Strong, MD
Daniel G. Coit, MD
Sam S. Yoon, MD
Publication date
01-04-2014
Publisher
Springer US
Published in
Annals of Surgical Oncology / Issue 4/2014
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-013-3429-0

Other articles of this Issue 4/2014

Annals of Surgical Oncology 4/2014 Go to the issue