Single Patient Classifier Assay, Microsatellite Instability, and Epstein-Barr Virus Status Predict Clinical Outcomes in Stage II/III Gastric Cancer: Results from CLASSIC Trial
10.3349/ymj.2019.60.2.132
- Author:
Chul Kyu ROH
1
;
Yoon Young CHOI
;
Seohee CHOI
;
Won Jun SEO
;
Minah CHO
;
Eunji JANG
;
Taeil SON
;
Hyoung Il KIM
;
Hyeseon KIM
;
Woo Jin HYUNG
;
Yong Min HUH
;
Sung Hoon NOH
;
Jae Ho CHEONG
Author Information
1. Department of Surgery, Yonsei University Health System, Seoul, Korea. JHCHEONG@yuhs.ac
- Publication Type:Randomized Controlled Trial
- Keywords:
Gastric cancer;
microsatellite instability;
single patient classifier;
EBV
- MeSH:
Biomarkers;
Capecitabine;
Chemotherapy, Adjuvant;
Classification;
Disease-Free Survival;
Drug Therapy;
Herpesvirus 4, Human;
Humans;
In Situ Hybridization;
Microsatellite Instability;
Microsatellite Repeats;
Multivariate Analysis;
Prognosis;
RNA;
Stomach Neoplasms
- From:Yonsei Medical Journal
2019;60(2):132-139
- CountryRepublic of Korea
- Language:English
-
Abstract:
PURPOSE: Clinical implications of single patient classifier (SPC) and microsatellite instability (MSI) in stage II/III gastric cancer have been reported. We investigated SPC and the status of MSI and Epstein-Barr virus (EBV) as combinatory biomarkers to predict the prognosis and responsiveness of adjuvant chemotherapy for stage II/III gastric cancer. MATERIALS AND METHODS: Tumor specimens and clinical information were collected from patients enrolled in CLASSIC trial, a randomized controlled study of capecitabine plus oxaliplatin-based adjuvant chemotherapy. The results of nine-gene based SPC assay were classified as prognostication (SPC-prognosis) and prediction of chemotherapy benefit (SPC-prediction). Five quasimonomorphic mononucleotide markers were used to assess tumor MSI status. EBV-encoded small RNA in situ hybridization was performed to define EBV status. RESULTS: There were positive associations among SPC, MSI, and EBV statuses among 586 patients. In multivariate analysis of disease-free survival, SPC-prognosis [hazard ratio (HR): 1.879 (1.101–3.205), 2.399 (1.415–4.067), p=0.003] and MSI status (HR: 0.363, 95% confidence interval: 0.161–0.820, p=0.015) were independent prognostic factors along with age, Lauren classification, TNM stage, and chemotherapy. Patient survival of SPC-prognosis was well stratified regardless of EBV status and in microsatellite stable (MSS) group, but not in MSI-high group. Significant survival benefit from adjuvant chemotherapy was observed by SPC-Prediction in MSS and EBV-negative gastric cancer. CONCLUSION: SPC, MSI, and EBV statuses could be used in combination to predict the prognosis and responsiveness of adjuvant chemotherapy for stage II/III gastric cancer.
