Cai Zhenghao, Rui Weiwei, Li Shuchun, Fingerhut Abraham, Sun Jing, Ma Junjun, Zang Lu, Zhu Zhenggang, Zheng Minhua
Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Shanghai Minimally Invasive Surgery Center, Shanghai, China.
Front Oncol. 2020 Dec 15;10:614785. doi: 10.3389/fonc.2020.614785. eCollection 2020.
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).
The 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.
A statistically significant association was found between MSI-H and poor histological response to NAC (=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, =0.037 ) and the control cohort (hazard ratio=0.479, 95% CI, 0.268-0.856, =0.013).
MSI-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.
我们评估了微卫星高度不稳定（MSI-H）与新辅助化疗（NAC）的肿瘤反应之间的关联及其在临床III期胃癌（cStage III GC）患者中的预后相关性。
NAC+手术组和对照组分别由177例和513例cStage III GC患者组成。比较了MSI-H患者[n=57（8.3%）]与微卫星稳定或微卫星低度不稳定（MSS/MSI-L）患者[n=633（91.7%）]的临床和病理特征。分别根据实体瘤疗效评价标准（RECIST）和肿瘤消退分级（TRG）系统评估对NAC的放射学和组织学反应。采用对数秩检验和Cox分析确定NAC+手术组和对照组中MSI状态与生存以及两组间肿瘤消退的相关性。
发现MSI-H与对NAC的组织学反应差之间存在统计学显著关联（P=0.038）。仅在MSS/MSI-L肿瘤中观察到反应者相对于无反应者有显著的生存优势，而在MSI-H肿瘤中未观察到。然而，在NAC+手术组（风险比=0.125，95%可信区间，0.017-0.897，P=0.037）和对照组（风险比=0.479，95%可信区间，0.268-0.856，P=0.013）中，MSI-H患者的生存均在统计学上显著优于MSS/MSI-L患者。
MSI-H与cStage III GC患者NAC后的较差消退和较好生存相关。TRG评估在MSS/MSI-L中有预后意义，但在MSI-H中无预后意义。需要进一步研究评估NAC对具有MSI-H表型的cStage III GC患者的价值。
