直肠腺癌75例新辅助放化疗肿瘤退缩分级相关临床病理因素分析

Analysis of clinicopathological factors related to tumor regression grade of neoadjuvant chemoradiotherapy in 75 cases for rectal adenocarcinoma

目的通过评估直肠腺癌患者对新辅助放化疗的反应率,旨在探讨新辅助放化疗后组织学消退的预测因素。方法回顾性分析2015-06-01-2018-05-31郑州大学附属肿瘤医院接受新辅助放化疗,并行手术治疗的75例局部进展期直肠腺癌患者的临床病理资料,KRAS、NRAS和BRAF基因通过等位基因特异性PCR或Sanger测序法检测,并采用多重荧光PCR法检测肿瘤组织基因的微卫星不稳定性。以肿瘤退缩分级(TRG)评价术前放化疗的疗效,并进行单因素和多因素Logistic回归分析。分析临床病理、生物指标与术前放化疗敏感性的关系。结果肿瘤退缩程度:TRG014例(18.7%),TRG120例(26.6%),TRG233例(44.0%),TRG38例(10.7%)。肿瘤退缩良好者(TRG0+1)发生率为45.3%(34/75),肿瘤无明显退缩者(TRG2+3)发生率为54.7%(41/75)。KRAS基因突变率为37.3%(28/75),BRAF突变率为4.0%(3/75),微卫星高度不稳定(MSI-H)检出率为6.7%(5/75)。单因素分析显示,临床T分期(χ^(2)=5.291,P=0.021)、临床N分期(χ^(2)=4.546,P=0.033)、肿瘤周径范围(χ^(2)=6.482,P=0.011)、神经侵犯或脉管癌栓(χ^(2)=5.105,P=0.024)、肿瘤大小(t=2.704,P=0.009)以及KRAS基因型(χ^(2)=5.066,P=0.024)是影响直肠腺癌术前放化疗后TRG分级水平的预测因素。Logistic多因素回归分析结果显示,肿瘤周径范围≤1/2周(OR=4.213,95%CI:1.223~14.515,P=0.023)和神经侵犯或脉管癌栓(OR=4.544,95%CI:1.010~20.444,P=0.049)是直肠腺癌术前放化疗后TRG分级水平的独立预测因子。结论肿瘤周径范围、神经侵犯或脉管癌栓是直肠腺癌患者术前放化疗后TRG分级水平的独立预测因子。

Objective To investigate the predictive factors of histological regression after preoperative chemoradiotherapy(PCRT)by evaluating the response rate of rectal adenocarcinoma patients to PCRT.Methods The clinicopathological date of 75 patients with locally advanced rectal adenocarcinoma who were treated by neoadjuvant chemoradiotherapy and surgery in the Affiliated Cancer Hospital of Zhengzhou University from June 1,2015 to May 31,2018 were retrospectively analyzed.The KRAS/NRAS/BRAFgene mutation was detected by using fluorescence-based allele-specific polymerase chain reaction or Sanger sequencing,and multiplex fluorescence PCR method was used to detect microsatellite instability of tumor tissue genes.Tumor regression grade(TRG)was used to evaluate the effect of peroperative chemoradiotherapy.Single factor and logistic multivariate regression analysis was performed.The relationships between clinicopathological&biological indicators and the sensitivity of PCRT were analyzed.Results Tumor regression grade:TRG0 in 14 cases(18.7%),TRG1 in 20 cases(26.6%),TRG2 in 33 cases(44.0%),TRG3 in 8 cases(10.7%).The incidence of patients with good tumor regression(TRG0+1)was 45.3%(34/75),and with no obvious tumor regression(TRG2+3)was54.7%(41/75).The mutation rates of KRASand BRAFgenes were 37.3%(28/75)and 4.0%(3/75)respectively.The detection rate of microsatellite instability-high(MSI-H)was 6.7%(5/75).According to univariate analysis,clinical T stage(χ^(2)=5.291,P=0.021)&clinical N stage(χ^(2)=4.546,P=0.033),tumor circumferential(χ^(2)=6.482,P=0.011),nerve invasion or vascular tumor thrombus(χ^(2)=5.105,P=0.024),tumor size(t=2.704,P=0.009)and KRASgene type(χ^(2)=5.066,P=0.024)were a predictor of TRG grading level after PCRT for rectal adenocarcinoma.Multivariate logistic regression analysis manifested that tumor circumferential(OR=4.213,95%CI:1.223-14.515,P=0.023)and nerve invasion or vascular tumor thrombus(OR=4.544,95%CI:1.010-20.444,P=0.049)were independent predictors of TRG grade for rectal adenocarcinoma after PCRT.Conclusion Tumor circumferential and nerve invasion or vascular tumor thrombus are independent predictors of TRG grade for rectal adenocarcinoma after PCRT.