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Poster display session

3779 - Predictive biomarkers for adjuvant therapy in gastric adenocarcinoma

Date

11 Sep 2017

Session

Poster display session

Topics

Cytotoxic Therapy;  Translational Research;  Gastric Cancer

Presenters

Eirini Pectasides

Citation

Annals of Oncology (2017) 28 (suppl_5): v22-v42. 10.1093/annonc/mdx363

Authors

E. Pectasides1, V. Kotoula2, M. Bobos2, I.D. Chatzidakis2, S. Chrisafi2, G. Fountzilas2

Author affiliations

  • 1 Division Of Hematology/oncology, Beth Israel Deaconess Medical Center, 02215 - Boston/US
  • 2 Data Office, Hellenic Cooperative Oncology Group (HeCOG), 11524 - Athens/GR
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Resources

Abstract 3779

Background

Gastric cancer is a common and lethal malignancy, killing over 700,000 people worldwide. Recurrence rates are high even in early stage disease, with 5-year overall survival being < 50% for stage II disease and above. Current guidelines for adjuvant therapy include 5-fluorouracil (5-FU) chemotherapy in combination with radiation. The aim of our study is to develop immunohistochemical biomarkers to predict response to adjuvant chemoradiation in patients with resected gastric cancer.

Methods

A tissue microarray composed of 100 specimens from primary resected gastric cancer cases was constructed. All patients received 5-FU based chemotherapy, and 92% of patients received radiation. Tumors underwent immunohistochemical staining for 11 proteins (HER2, EGFR, p-AKT, PTEN, MTOR, VEGFA, IGF1R, MLH1, MSH2, MSH6, PMS2), and H-scores were calculated. Primary endpoints were progression-free survival (PFS) and overall survival (OS). Survival analysis was performed by Kaplan-Meier method with log-rank test for assessing statistical significance. Multivariate analysis was performed with Cox regression.

Results

Mean follow-up time for the cohort was 39.4 months. Ninety-one of 100 cases had sufficient tissue for biomarker analysis. Interestingly, low expression of MSH2 and MSH6 was significantly associated with shorter PFS, while there was a trend towards worse OS for patients with low MSH2 expression. In multivariate analysis, adjusting for well-characterized prognostic variables, both MSH2 and MSH6 retained their predictive significance. In addition, nuclear expression of the tumor suppressor PTEN was associated with longer OS. No other biomarkers were significantly associated with PFS or OS.

Conclusions

These results indicate that low expression of MSH2 and MSH6 predicts for poorer outcomes in patients with resected gastric adenocarcinoma, independent of other predictive markers.

Clinical trial identification

Legal entity responsible for the study

Hellenic Cooperative Oncology Group

Funding

None

Disclosure

G. Fountzilas: Honoraria: AstraZeneca, Consulting or advisory role: Pfizer, Sanofi, Roche Stock ownership (an immediate family member): ARIAD. All other authors have declared no conflicts of interest.

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