[Abstract]
Background: 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).
Materials and Methods: 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.
Results: A 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).
Conclusion: 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.
【中文摘要】
目的:探究臨床III期胃癌患者接受新輔助治療(NAC)後的腫瘤退縮及臨床預後與高頻微衛星不穩定 (MSI-H)之間的關係。
方法:NAC組和單純手術組分別有177和513名臨床III期胃癌患者。其中MSI-H佔8.3%(57/690)。分別比較MSI-H與MSS/MSI-L兩組患者的臨床表現、病理特點、腫瘤退縮程度(採用RECIST分級和TRG分級)及生存分析之間的差異。
結果:MSI-H與較差的腫瘤病理學退縮顯著相關(p=0.038)。病理退縮程度僅在MSS/MSI-L組中具有預後價值,而在MSI-H組中沒有。然而,無論在NAC患者中還是在單純手術患者中,MSI-H均表現為顯著的積極預後因素,風險比率(HR)分別為0.125(p=0.037 )和0.479(p=0.013)。
結論:MSI-H與較差的腫瘤退縮與較好的生存預後顯著相關。TRG分級對MSS/MSI-L患者存在預後價值。MSI-H患者行NAC治療是否存在生存獲益還需要進一步研究。