Single patient classifier assay, microsatellite instability, and epstein-barr virus status predict clinical outcomes in stage II/III gastric cancer

Results from CLASSIC trial

Chul Kyu Roh, Yoon Young Choi, Seohee Choi, Won Jun Seo, Minah Cho, Eunji Jang, Taeil Son, Hyoung Il Kim, Hyeseon Kim, WooJin Hyung, yongmin Huh, Sung Hoon Noh, Jae Ho Cheong

Research output: Contribution to journalArticle

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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 quasi-monomorphic 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.

Original languageEnglish
Pages (from-to)132-139
Number of pages8
JournalYonsei medical journal
Volume60
Issue number2
DOIs
Publication statusPublished - 2019 Feb 1

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Microsatellite Instability
Human Herpesvirus 4
Stomach Neoplasms
Adjuvant Chemotherapy
oxaliplatin
Microsatellite Repeats
Drug Therapy
Survival
Neoplasm Staging
Disease-Free Survival
In Situ Hybridization
Neoplasms

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Roh, Chul Kyu ; Choi, Yoon Young ; Choi, Seohee ; Seo, Won Jun ; Cho, Minah ; Jang, Eunji ; Son, Taeil ; Kim, Hyoung Il ; Kim, Hyeseon ; Hyung, WooJin ; Huh, yongmin ; Noh, Sung Hoon ; Cheong, Jae Ho. / Single patient classifier assay, microsatellite instability, and epstein-barr virus status predict clinical outcomes in stage II/III gastric cancer : Results from CLASSIC trial. In: Yonsei medical journal. 2019 ; Vol. 60, No. 2. pp. 132-139.
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title = "Single patient classifier assay, microsatellite instability, and epstein-barr virus status predict clinical outcomes in stage II/III gastric cancer: Results from CLASSIC trial",
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 quasi-monomorphic 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.",
author = "Roh, {Chul Kyu} and Choi, {Yoon Young} and Seohee Choi and Seo, {Won Jun} and Minah Cho and Eunji Jang and Taeil Son and Kim, {Hyoung Il} and Hyeseon Kim and WooJin Hyung and yongmin Huh and Noh, {Sung Hoon} and Cheong, {Jae Ho}",
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Single patient classifier assay, microsatellite instability, and epstein-barr virus status predict clinical outcomes in stage II/III gastric cancer : Results from CLASSIC trial. / Roh, Chul Kyu; Choi, Yoon Young; Choi, Seohee; Seo, Won Jun; Cho, Minah; Jang, Eunji; Son, Taeil; Kim, Hyoung Il; Kim, Hyeseon; Hyung, WooJin; Huh, yongmin; Noh, Sung Hoon; Cheong, Jae Ho.

In: Yonsei medical journal, Vol. 60, No. 2, 01.02.2019, p. 132-139.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Single patient classifier assay, microsatellite instability, and epstein-barr virus status predict clinical outcomes in stage II/III gastric cancer

T2 - Results from CLASSIC trial

AU - Roh, Chul Kyu

AU - Choi, Yoon Young

AU - Choi, Seohee

AU - Seo, Won Jun

AU - Cho, Minah

AU - Jang, Eunji

AU - Son, Taeil

AU - Kim, Hyoung Il

AU - Kim, Hyeseon

AU - Hyung, WooJin

AU - Huh, yongmin

AU - Noh, Sung Hoon

AU - Cheong, Jae Ho

PY - 2019/2/1

Y1 - 2019/2/1

N2 - 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 quasi-monomorphic 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.

AB - 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 quasi-monomorphic 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.

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U2 - 10.3349/ymj.2019.60.2.132

DO - 10.3349/ymj.2019.60.2.132

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EP - 139

JO - Yonsei Medical Journal

JF - Yonsei Medical Journal

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