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Association Between the Microsatellite Instability Status and the Efficacy of Postoperative Adjuvant Chemoradiotherapy in Patients With Gastric Cancer.

ABSTRACT: Purpose: The effect of microsatellite instability (MSI) on the response to radiotherapy remains unknown. The aim of this study was to investigate the association between the MSI status and the outcomes of gastric cancer (GC) treated by surgical resection with or without postoperative adjuvant chemoradiotherapy. Methods: The records of patients who underwent surgical resection of stage IB-III GC with or without postoperative adjuvant chemoradiotherapy were retrospectively retrieved from the Affiliated Hospital of Jiangsu University (n = 89), The Cancer Genome Atlas (n = 202), and the Asian Cancer Research Group (n = 138). The primary endpoint was overall survival (OS). Results: The MSI status had no significant influence on OS in all cohorts. Compared with surgery alone, adjuvant chemoradiotherapy improved or tended to improve OS of patients with stage III disease, irrespective of the MSI status, in all cohorts. Among patients with stage Ib/II disease, only those with microsatellite stability (MSS) benefited from chemoradiotherapy in terms of OS, whereas those with MSI showed no improvement in OS. A comparison of gene expression profiles between MSI stage Ib/II GC and MSS stage Ib/II GC revealed that MSI correlated with the overexpression of thymidylate synthetase, a marker of fluoropyrimidine resistance. Furthermore, tumor hypoxia scoring for stage Ib/II lesions showed significantly greater hypoxia in MSI tumors than in MSS tumors. Conclusions: The findings of this study suggest that postoperative adjuvant chemoradiotherapy is effective for stage III GC, regardless of the MSI status. However, MSI may predict a poor response to postoperative adjuvant chemoradiotherapy in patients with stage Ib/II GC.

SUBMITTER: Dai D

PROVIDER: S-EPMC6960096 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Association Between the Microsatellite Instability Status and the Efficacy of Postoperative Adjuvant Chemoradiotherapy in Patients With Gastric Cancer.

Dai Dongfang D Zhao Xiaohui X Li Xiaoqin X Shu Yongqian Y Shen Bo B Chen Xiaofeng X Chen Deyu D Wang Deqiang D

Frontiers in oncology 20200108

<b>Purpose:</b> The effect of microsatellite instability (MSI) on the response to radiotherapy remains unknown. The aim of this study was to investigate the association between the MSI status and the outcomes of gastric cancer (GC) treated by surgical resection with or without postoperative adjuvant chemoradiotherapy. <b>Methods:</b> The records of patients who underwent surgical resection of stage IB-III GC with or without postoperative adjuvant chemoradiotherapy were retrospectively retrieved ...[more]

PMID: 31970085

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Project description:ObjectiveTo construct and validate a prediction model based on dual-layer detector spectral CT (DLCT) and clinico-radiologic features to predict the microsatellite instability (MSI) status of gastric cancer (GC) and to explore the relationship between the prediction results and patient prognosis.MethodsA total of 264 GC patients who underwent preoperative DLCT examination were randomly allocated into the training set (n = 187) and validation set (n = 80). Clinico-radiologic features and DLCT parameters were used to build the clinical and DLCT model through multivariate logistic regression analysis. A combined DLCT parameter (CDLCT) was constructed to predict MSI. A combined prediction model was constructed using multivariate logistic regression analysis by integrating the significant clinico-radiologic features and CDLCT. The Kaplan-Meier survival analysis was used to explore the prognostic significant of the prediction results of the combined model.ResultsIn this study, there were 70 (26.52%) MSI-high (MSI-H) GC patients. Tumor location and CT_N staging were independent risk factors for MSI-H. In the validation set, the area under the curve (AUC) of the clinical model and DLCT model for predicting MSI status was 0.721 and 0.837, respectively. The combined model achieved a high prediction efficacy in the validation set, with AUC, sensitivity, and specificity of 0.879, 78.95%, and 75.4%, respectively. Survival analysis demonstrated that the combined model could stratify GC patients according to recurrence-free survival (p = 0.010).ConclusionThe combined model provides an efficient tool for predicting the MSI status of GC noninvasively and tumor recurrence risk stratification after surgery.Critical relevance statementMSI is an important molecular subtype in gastric cancer (GC). But MSI can only be evaluated using biopsy or postoperative tumor tissues. Our study developed a combined model based on DLCT which could effectively predict MSI preoperatively. Our result also showed that the combined model could stratify patients according to recurrence-free survival. It may be valuable for clinicians in choosing appropriate treatment strategies to avoid tumor recurrence and predicting clinical prognosis in GC.Key points• Tumor location and CT_N staging were independent predictors for MSI-H in GC. • Quantitative DLCT parameters showed potential in predicting MSI status in GC. • The combined model integrating clinico-radiologic features and CDLCT could improve the predictive performance. • The prediction results could stratify the risk of tumor recurrence after surgery.

Dataset Information

Association Between the Microsatellite Instability Status and the Efficacy of Postoperative Adjuvant Chemoradiotherapy in Patients With Gastric Cancer.

Publications

Association Between the Microsatellite Instability Status and the Efficacy of Postoperative Adjuvant Chemoradiotherapy in Patients With Gastric Cancer.

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