局部晚期食管鳞状细胞癌患者新辅助免疫治疗联合化疗后行根治性手术的术后病理学缓解程度及影响因素分析

廖梓伊, 彭杨, 曾蓓蕾, 马影颖, 曾丽, 甘科论, 马代远

  1. 川北医学院附属医院肿瘤内科,四川 南充 637000
  • 收稿日期:2023-11-06 修回日期:2024-04-25 出版日期:2024-07-30 发布日期:2024-08-08
  • 通信作者: 马代远
  • 作者简介:廖梓伊(ORCID: 0009-0000-5379-1350),硕士。
  • 基金资助:
    四川省科技计划项目(2022NSFSC1554)

摘要/Abstract

摘要:

背景与目的:局部晚期食管鳞状细胞癌(locally advanced esophageal squamous cell carcinoma,LAESCC)患者新辅助免疫治疗联合化疗(neoadjuvant immunotherapy combined with chemotherapy,nICT)后行根治性手术治疗具有较好的有效性和安全性,能够提高患者的病理学完全缓解(pathological complete remission,pCR)率、主要病理学缓解(main pathologic response,MPR)率及R0切除率。新辅助治疗后达到pCR/MPR的患者预后明显优于未达到pCR/MPR的患者,因此寻找pCR/MPR的预测因素有助于筛选联合治疗的优势人群。本研究旨在探讨nICT前后的临床资料对LAESCC患者nICT后行根治性手术的不同病理学缓解程度的预测价值并观察其安全性。方法:收集2019年1月—2023年6月于川北医学院附属医院在nICT后行根治性手术的LAESCC患者。收集所有患者的临床资料以及新辅助治疗前后患者的部分血液、炎症和营养学指标,根据新辅助治疗后的不同病理学缓解程度进行分组,通过多组比较方差分析及LSD-t事后检验探索对不同病理学缓解程度具有影响的因素,收集并记录患者新辅助治疗期间的不良反应及最终的手术情况。本研究已获得川北医学院附属医院医学伦理委员会批准(伦理审查编号:2024009)。结果:共收集到62例nICT后行根治性手术的LAESCC患者,新辅助治疗期间只有1例患者出现了4级的骨髓抑制表现,其余患者的不良反应均≤2级;手术的R0切除率为98.39%。本研究与川北医学院附属医院既往LAESCC新辅助化疗后行根治性手术治疗的研究相比,在手术时间、术中出血量、术后住院时间及手术并发症等方面未见明显差异。术后的病理学检查结果显示,pCR率为22.58%(14/62),MPR率为40.32%(25/62)。根据术后不同的肿瘤退缩分级(tumor regression grade,TRG),分为TRG1、TRG2和TRG3~4组,3组患者在新辅助治疗前的血小板分布宽度(platelet distribution width,PDW)及新辅助治疗后术前的中性粒细胞-淋巴细胞比值(neutrophil-to-lymphocyte ratio,NLR)差异有统计学意义(P<0.05)。进一步对3组患者在新辅助治疗前的PDW及新辅助治疗后术前的NLR分别进行组内两两比较,发现TRG2组的PDW及NLR均低于TRG3~4组,差异有统计学意义(P <0.05)。结论:LAESCC患者nICT后行根治性手术可以获得较高的R0切除率、pCR率及MPR率且安全性可靠,新辅助治疗前患者的PDW越低、新辅助治疗后术前患者的NLR越低预示着越好的病理学缓解效果。

关键词: 食管鳞状细胞癌, 新辅助免疫治疗联合化疗, 根治性手术, 病理学缓解程度, 安全性

Abstract:

Background and purpose: Radical surgery after neoadjuvant immunotherapy combined with chemotherapy (nICT) in patients with locally advanced esophageal squamous cell carcinoma (LAESCC) has good efficacy and safety, and it can improve the patients’ pathological complete remission (pCR) rate, main pathologic response (MPR) rate and R0 resection rate. The prognosis of patients with pCR/MPR after nICT is significantly better compared with patients without pCR. The prognosis of patients achieving pCR/MPR after neoadjuvant therapy has been demonstrated to be significantly better than that of patients with non-pCR/MPR. Therefore, finding predictive factors of pCR/MPR is beneficial for us to screen out the advantageous populations for combination therapy. The aim of this study was to investigate the value of clinical data of patients with LAESCC before and after nICT in predicting the degree of remission of different pathologies after radical surgery following neoadjuvant treatment and to observe the safety of the treatment. Methods: Data of patients with locally LAESCC who underwent radical surgery after nICT from January 2019 to June 2023 at the Affiliated Hospital of Chuanbei Medical College were collected. The clinical data of all patients as well as some blood, inflammation and nutritional indexes of patients before and after neoadjuvant therapy were collected, and the patients were grouped according to the different degrees of pathological remission after neoadjuvant therapy. Data were analyzed by multi-group comparative analysis of variance (ANOVA) and LSD-t post-hoc test. We explored the factors that had an influence on the different degrees of pathological remission, and collected and recorded the patients’ adverse reactions during neoadjuvant therapy as well as their eventual surgeries. Results: Data of 62 patients with LAESCC treated with nICT who underwent radical surgery were collected. Only one patient showed grade 4 myelosuppression during neoadjuvant therapy, and the rest of the patients had adverse reactions ≤grade 2. The R0 resection rate of the surgery was 98.39%. The present study was compared with the previous studies of LAESCC treated with neoadjuvant chemotherapy followed by radical surgery performed in Affiliated Hospital of Chuanbei Medical College. Compared with the previous studies conducted in our center, no significant difference was observed in terms of operation time, intraoperative bleeding, postoperative hospitalization time and surgical complications. The postoperative pathologic results showed that the pCR rate was 22.58% (14/62), and the MPR rate was 40.32% (25/62). According to the different tumor regression grade (TRG) after surgery, patients were divided into 3 groups of TRG1, TRG2 and TRG3-4, and differences in the platelet distribution width (PDW) before neoadjuvant therapy and the preoperative neutrophil-to-lymphocyte ratio (NLR) after neoadjuvant therapy were statistically significant among the 3 groups (P<0.05). Further intra-group two-by-two comparisons of PDW before neoadjuvant therapy and NLR before surgery after neoadjuvant therapy were performed for the three groups of patients, respectively, and it was found that the PDW and NLR in the TRG2 group were lower compared with the TRG3-4 group, and the differences were statistically significant (P<0.05). Conclusion: Radical surgery after nICT treatment in patients with LAESCC can have high R0 resection rate, pCR rate, MPR rate and reliable safety, and the lower PDW of patients before neoadjuvant therapy and the lower NLR of patients before surgery after neoadjuvant therapy predict better pathological remission efficacy.

Key words: Esophageal squamous cell carcinoma, Neoadjuvant immunotherapy combined with chemotherapy, Radical surgery, Pathological remission degree, Safety

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