经过新辅助化疗放疗的直肠癌患者，完全临床缓解是很具挑战性的。事实上，由于再评估检查的预测价值较差以鉴定病理完全缓解（pCR），因此手术和“观察等待”之间的适应症成为争议点。提高关于突变途径（如 MAPK/ERK）的认识可以帮助评估疾病对预后的实际影响，并选择最佳治疗靶点。该研究旨在评估生物分子参数作为经过化疗放疗后接受根治手术患者的预后因素的意义。回顾性分析包括39名通过对手术标本的以下生物分子标记的额外评估进行新辅助化疗放疗后接受根治手术的直肠腺癌 II-III 期患者：通过测序方法检测 KRAS 和 NRAS 基因的外显子 2、3 和 4 以及 BRAF 基因的外显子 15。绘制 Kaplan-Meier 生存曲线以评估病理反应和 RAS 状态与无进展生存期（PFS）和总生存期（OS）的关联。使用 log-rank 检验评估生存曲线之间的统计差异。数据分析显示15名患者（38.46%）存在 RAS 突变。其中7名患者（18%）实现了 pCR，其中只有2例为 RAS 突变病例。基于病理反应，评估变量的分布在两组中是均匀的。Kaplan-Meier 曲线显示 RAS 突变患者 OS 和 PFS 的预后不良 (p = 0.0022 和 p = 0.000392)，但基于病理反应对于 OS 和 PFS 均无显着差异。 RAS 突变似乎与经过化疗放疗后接受根治手术的直肠癌患者的不良预后和复发风险增加有关。版权所有©2023 International Institute of Anticancer Research (Dr. George J. Delinasios)。

Complete clinical response in rectal cancer after neoadjuvant chemo-radiotherapy is challenging. Indeed, indication to surgery vs. "watch and wait" is a debate due the poor predictive value of restaging exams in order to identify a pathological complete response (pCR). Improving the knowledge on mutational pathways such as MAPK/ERK could be helpful in assessing the real impact of disease on prognosis and in choosing the best therapeutic target. This study aimed to evaluate the significance of biomolecular parameters as prognostic factors in patients undergoing radical surgery after chemo-radiotherapy.A retrospective analysis was performed including 39 patients who had undergone radical surgery after neoadjuvant chemo-radiotherapy for rectal adenocarcinoma stage II-III through additional evaluation of the following biomolecular markers on surgical specimens: exons 2, 3 and 4 of the KRAS and NRAS genes and exon 15 of BRAF by pyrosequencing. Kaplan-Meier survival curves were plotted to evaluate the association of pathologic response and RAS status with progression-free survival (PFS) and overall survival (OS). The log-rank test was used to assess statistical differences among the survival curves.Data analysis showed RAS mutation in 15 patients (38.46%). pCR was achieved in seven patients (18%), including only two RAS mutation cases. The distribution of evaluated variables was homogeneous in the two groups based on pathological response. The Kaplan-Meier curve showed poor outcomes in OS and PFS in patients with RAS mutation (p=0.0022 and p=0.000392, respectively), but no significant differences based on pathological response for both OS and PFS.RAS mutation seems to be related to poor prognosis and increased risk of recurrence in rectal cancer patients undergoing radical surgery after chemo-radiotherapy.Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.