[Analysis of efficacy and prognostic factors of neoadjuvant chemoradiotherapy in locally advanced mid-low rectal cancer patients with RAS gene mutation].

Objective: To analyze the efficacy of neoadjuvant chemoradiotherapy and the factors influencing survival in patients with locally advanced mid-low rectal cancer harboring rat sarcoma virus (RAS) gene mutation. Methods: A retrospective analysis of clinical data from patients with locally advanced mid-low rectal cancer who received neoadjuvant long-course chemoradiotherapy at the Affiliated Hospital of Zunyi Medical University between June 2018 and June 2020 was conducted. Patients were divided into a mutation group (patients with RAS gene mutation) and a wild-type group (patients without RAS gene mutation) based on RAS gene mutation status. Follow-up was carried out until December 31, 2025. The efficacy of neoadjuvant chemoradiotherapy in patients with locally advanced mid-low rectal cancer harboring RAS gene mutation was analyzed, including general information, perioperative indicators, clinical pathological characteristics, pathological remission, overall complete remission, neoadjuvant rectal (NAR) score, recurrence-free survival (RFS) rate, and overall survival (OS) rate.

A multivariate logistic regression model was used to analyze the influencing factors of overall complete remission and NAR score.

A multivariate Cox regression model was used to analyze the influencing factors of patient survival. Results: A total of 146 patients were enrolled, including 62 in the mutation group [39 males and 23 females, aged (61±8) years] and 84 in the wild-type group [62 males and 22 females, aged (62±8) years]. The RAS mutation rate was 42.5% (62/146), with KRAS mutations accounting for 98.4% (61/62). There was no statistically significant difference in baseline demographic characteristics of general information and perioperative indicators between the wild-type group and the mutation group (all P>0.05). The proportion of patients with ypT3 staging [61.0% (36/59) vs 29.9% (23/77), P=0.014] and NAR scores [M (Q1, Q3), 15 (8, 30) vs 8 (8, 15) points, P=0.042] were higher in the mutation group than those in the wild-type group.

Multivariate logistic regression analysis showed that RAS mutation was an influencing factor with high NAR scores (OR=2.33, 95%CI: 1.00-5.41, P=0.049), but it is not a factor influencing overall complete remission (OR=0.71, 95%CI: 0.28-1.77, P=0.463). The follow-up duration was 65 (49, 83) months. The 5-year RFS rate was lower in the mutation group than that in the wild-type group (65.5% vs 82.6%, P=0.010), while there was no statistically significant difference in 5-year OS rate between the two groups (93.0% vs 98.4%, P=0.344).

Cox regression analysis indicated that RAS mutation was a risk factor for 5-year RFS rate (HR=2.47, 95%CI: 1.21-5.05, P=0.013). Conclusions: Patients with locally advanced mid-low rectal cancer harboring RAS gene mutation had a higher proportion of ypT3 staging and higher NAR scores, as well as lower 5-year RFS rate. RAS gene mutation is a risk factor for high NAR scores and low 5-year RFS rate in patients with locally advanced mid-low rectal cancer after neoadjuvant chemoradiotherapy. 目的： 分析伴大鼠肉瘤病毒（RAS）基因突变的局部进展期中低位直肠癌患者新辅助放化疗的疗效及生存的影响因素。 方法： 回顾性分析2018年6月至2020年6月遵义医科大学附属医院局部进展期中低位直肠癌并行新辅助长疗程放化疗患者的临床资料，根据RAS基因突变情况，将患者分为突变组（RAS基因突变的患者）和野生组（RAS基因未突变的患者）。随访至2025年12月31日，分析伴RAS基因突变的局部进展期中低位直肠癌患者行新辅助放化疗后的疗效，包括一般资料、围手术期指标、临床病理特征、病理缓解情况、整体完全缓解、新辅助直肠（NAR）评分、无复发生存率、总生存率等；采用多因素logistic回归模型分析整体完全缓解和NAR评分的影响因素；通过多因素Cox回归模型分析患者生存的影响因素。 结果： 共纳入146例患者，突变组62例，男39例，女23例，年龄（61±8）岁；野生组84例，男62例，女22例，年龄（62±8）岁。RAS基因突变率为42.5%（62/146），其中KRAS基因突变占98.4%（61/62），野生组与突变组患者的一般资料及围手术期指标基线特征差异均无统计学意义（均P>0.05）。突变组ypT3分期的患者比例［61.0%（36/59）比29.9%（23/77），P=0.014］、NAR评分［M（Q1，Q3），15（8，30）比8（8，15）分，P=0.042］均高于野生组。多因素logistic回归模型分析显示，RAS基因突变为NAR评分高的影响因素（OR=2.33，95%CI：1.00~5.41，P=0.049），但不是整体完全缓解的影响因素（OR=0.71，95%CI：0.28~1.77，P=0.463）。随访时间为65（49，83）个月，突变组5年无复发生存率低于野生组（65.5%比82.6%，P=0.010），两组5年生存率差异无统计学意义（93.0%比98.4%，P=0.344）。Cox回归模型分析显示，RAS基因突变是患者5年无复发生存率的危险因素（HR=2.47，95%CI：1.21~5.05，P=0.013）。 结论： 伴RAS基因突变的局部进展期中低位直肠癌患者ypT3分期的患者比例及NAR评分较高，5年无复发生存率较低；RAS基因突变是局部进展期中低位直肠癌患者新辅助放化疗治疗后NAR评分高及5年无复发生存率低的影响因素。.