Microsatellite Status Affects Tumor Response and Survival in Patients Undergoing Neoadjuvant Chemotherapy for Clinical Stage III Gastric Cancer.

Zhenghao Cai,Abraham Fingerhut,Weiwei Rui,Jing Sun,Zhenggang Zhu,Minhua Zheng,Lu Zang,Junjun Ma,Shuchun Li

doi:10.3389/fonc.2020.614785

Zhenghao Cai, Abraham Fingerhut + Show 7 more

Open Access

https://doi.org/10.3389/fonc.2020.614785

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Abstract

BackgroundWe assessed the association between microsatellite instability-high (MSI-H) and tumor response to neoadjuvant chemotherapy (NAC) as well as its prognostic relevance in patients with clinical stage III gastric cancer (cStage III GC).Materials and MethodsThe NAC + surgery and the control cohorts consisted of 177 and 513 cStage III GC patients, respectively. The clinical and pathological features were compared between patients with MSI-H [n=57 (8.3%)] and microsatellite stability or microsatellite instability-low (MSS/MSI-L) [n=633 (91.7%)]. Radiological and histological response to NAC were evaluated based on response evaluation criteria in solid tumors (RECIST) and tumor regression grade (TRG) systems, respectively. The log-rank test and Cox analysis were used to determine the survival associated with MSI status as well as tumor regression between the two groups in both NAC + surgery and the control cohorts.ResultsA statistically significant association was found between MSI-H and poor histological response to NAC (p=0.038). Significant survival priority of responders over poor-responders could only be observed in MSS/MSI-L but not in MSI-H tumors. However, patients with MSI-H had statistically significantly better survival compared to patients with MSS/MSI-L in both the NAC + surgery (hazard ratio=0.125, 95% CI, 0.017–0.897, p=0.037 ) and the control cohort (hazard ratio=0.479, 95% CI, 0.268–0.856, p=0.013).ConclusionMSI-H was associated with poorer regression and better survival after NAC for cStage III GC. TRG evaluation had prognostic significance in MSS/MSI-L but not in MSI-H. Further studies are needed to assess the value of NAC for cStage III GC patients with MSI-H phenotype.

Highlights

Gastric cancer (GC) is the third most common cause of cancerrelated death worldwide [1]
All patients treated by neoadjuvant chemotherapy (NAC) and curative gastrectomy for clinical stage (cStage) III GC or adenocarcinoma of the esophago-gastric junction (AEG) at Ruijin Hospital between February 2016 and June 2018 were eligible for this study
Patients with squamous cell carcinoma, lymphoma, gastrointestinal stromal tumor, neuroendocrine tumor, GC related to other malignancies, AEG type I [according to Siewert et al [15]], those treated with palliative resection or emergency procedures, or patients with incomplete postoperative pathological evaluation records were not included

Summary

Introduction

Gastric cancer (GC) is the third most common cause of cancerrelated death worldwide [1]. While radical gastrectomy with lymphadenectomy remains the cornerstone of curative treatment of GC, prognosis is still poor with a high recurrence rate, especially for patients with locally advanced and/or lymph node (LN) positive cancer, leading to recommendations for routine perioperative or neoadjuvant chemotherapy (NAC) for resectable stage II or III GCs [2,3,4]. Few studies have assessed the impact of MSI phenotype on tumor response to NAC (i.e. histopathological regression of GC after NAC) [13]. We assessed the association between microsatellite instability-high (MSI-H) and tumor response to neoadjuvant chemotherapy (NAC) as well as its prognostic relevance in patients with clinical stage III gastric cancer (cStage III GC)

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