局部进展期直肠癌新辅助免疫治疗免疫相关不良反应的临床管理及分析

安杨; 王晨童; 邱小原; 周皎琳; 林国乐

doi:10.19401/j.cnki.1007-3639.2025.07.005

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局部进展期直肠癌新辅助免疫治疗免疫相关不良反应的临床管理及分析

专题论著 | 更新时间：2025-12-31

- 局部进展期直肠癌新辅助免疫治疗免疫相关不良反应的临床管理及分析
- Clinical management and analysis of immune-related adverse events in neoadjuvant immunotherapy for locally advanced rectal cancer
- 中国癌症杂志 2025年35卷第7期页码：665-671
- 作者机构：
  
  中国医学科学院北京协和医学院北京协和医院基本外科，北京 100730
- 作者简介：
  
  [ "安杨（ORCID: 0000-0001-6225-3028），博士，住院医师。" ]
  [ "林国乐，中国医学科学院北京协和医学院北京协和医院基本外科结直肠专业组主任医师，教授，博士研究生导师。主要研究方向为结直肠外科，尤其是结直肠肿瘤的临床与基础研究。临床上主要从事腹腔镜和开腹结直肠手术、低位直肠癌保肛手术、直肠癌新辅助治疗、经肛门内镜显微手术、痔上直肠黏膜环切钉合术、炎症性肠病的外科治疗、肠梗阻的诊治等研究。中华医学会外科学分会胃肠外科学组委员，中国抗癌协会大肠癌专业委员会常务委员及经肛门内镜显微手术学组副组长，中国医师协会外科医师分会肛肠外科医师委员会委员、结直肠外科医师委员会中青年副主任委员，北京癌症防治学会直肠癌新辅助治疗专业委员会主任委员，中国抗癌协会结直肠肿瘤整合康复专业委员会委员。《中华胃肠外科杂志》、《中国现代手术学杂志》编委，《中华消化外科杂志》《中华结直肠疾病电子杂志》通讯编委，《中华临床医师杂志（电子版）》《中国全科医学》审稿专家。主编著作《肛刚好》，参与编写著作《经肛门内镜微创手术》《经肛微创手术（TAMIS）和经肛全直肠系膜切除术（taTME）》《肛肠外科学》《外科学普通外科分册（规培教材）》《医之心》《协和医生说》等10部。" ]
- 基金信息：
  
  中央高水平医院临床科研专项项目(2022-PUMCH-C-005)
- DOI：10.19401/j.cnki.1007-3639.2025.07.005
  中图分类号： R735.3+7
- 收稿：2025-05-30，
  
  修回：2025-07-18，
  
  纸质出版：2025-07-30
- 稿件说明：
移动端阅览
安杨, 王晨童, 邱小原, 等. 局部进展期直肠癌新辅助免疫治疗免疫相关不良反应的临床管理及分析[J]. 中国癌症杂志, 2025,35(7):665-671.

Yang AN, Chentong WANG, Xiaoyuan QIU, et al. Clinical management and analysis of immune-related adverse events in neoadjuvant immunotherapy for locally advanced rectal cancer[J]. China Oncology, 2025, 35(7): 665-671.
安杨, 王晨童, 邱小原, 等. 局部进展期直肠癌新辅助免疫治疗免疫相关不良反应的临床管理及分析[J]. 中国癌症杂志, 2025,35(7):665-671. DOI： 10.19401/j.cnki.1007-3639.2025.07.005.

Yang AN, Chentong WANG, Xiaoyuan QIU, et al. Clinical management and analysis of immune-related adverse events in neoadjuvant immunotherapy for locally advanced rectal cancer[J]. China Oncology, 2025, 35(7): 665-671. DOI： 10.19401/j.cnki.1007-3639.2025.07.005.

摘要

背景和目的：

目前，新辅助免疫治疗能够显著提升局部进展期直肠癌（locally advanced rectal cancer，LARC）新辅助治疗效果，但免疫相关不良反应（immune-related adverse events，irAEs）的临床管理尚缺乏充分证据。本研究拟探讨直肠癌新辅助免疫治疗中irAEs的发生特征、临床管理策略及转归，为优化irAEs监测与干预提供依据。

方法：

回顾性分析2022年7月—2024年6月于中国医学科学院北京协和医学院北京协和医院接受新辅助免疫治疗并出现irAEs的LARC患者的临床资料。记录irAEs类型、分级、发生时间、治疗措施及转归。所有患者均接受至少6个月的定期随访。本研究经中国医学科学院北京协和医院审批通过（伦理批件号：I-24PJ0024）。采用描述性统计总结irAEs的发生规律与治疗应对措施。

结果：

本研究共纳入30例患者，累计发生41例次irAEs，其中78%（32/41）为1~2级轻度不良反应，22%（9/41）为3~4级严重不良反应，5例（16.7%）因严重不良反应永久停药。内分泌系统不良反应最为常见（36.6%，15/41），以表现为甲状腺功能亢进到减退的动态演变为主，75%需甲状腺激素替代治疗，另有1例迟发性肾上腺皮质功能减退经糖皮质激素（glucocorticoid，GC）治疗后缓解。肝脏毒性（19.5%，8/41）中62.5%为3级损伤，37.5%需GC干预，2例术后辅助化疗期间复发。3例发生重症肌炎并伴发无症状心肌损伤，表现为肌酸激酶显著升高和心肌生物标志物同步变化，均需大剂量GC冲击联合免疫球蛋白或免疫抑制剂治疗，恢复周期2~4个月。9例发生皮肤反应，以局部治疗为主。2例发生胃肠道反应，其中1例为3级腹泻接受GC治疗。总体GC使用率为31.7%（13/41），76.9%用于3级以上irAEs管理。

结论：

LARC新辅助免疫治疗irAEs以轻中度为主，经过对症支持治疗可改善；但仍有部分患者发生3~4级严重不良反应，需多学科综合管理。GC使用集中于3级以上irAEs，其中重症肌炎及心脏受累虽罕见但需强化免疫抑制治疗。少数患者辅助化疗阶段出现irAEs复发，提示早期识别、分级治疗和全治疗周期管理的必要性。

Abstract

Background and Purpose:

Neoadjuvant immunotherapy currently significantly enhances treatment efficacy for

locally advanced rectal cancer (LARC); However

clinical management of immune-related adverse events (irAEs) lacks robust evidence. This study aimed to investigate the characteristics

clinical management strategies

and outcomes of irAEs during neoadjuvant immunotherapy for rectal cancer

providing a basis for optimizing irAEs monitoring and intervention.

Methods:

We retrospectively analyzed clinical data from LARC patients who developed irAEs after receiving neoadjuvant immunotherapy at Peking Union Medical College Hospital

Chinese Academy of Medical Sciences

between July 2022 and June 2024. Types of irAEs

severity

time of onset

management strategies

and outcomes were recorded. All patients underwent regular follow-up for at least 6 months. This study has been approved by Peking Union Medical College Hospital

Chinese Academy of Medical Sciences (ethical approval number: I-24PJ0024). Descriptive statistics were used to summarize irAEs patterns and management approaches.

Results:

A total of 41 irAE episodes occurred among the 30 patients. Mild irAEs (Grade 1-2) accounted for 78.0% (32/41)

while severe irAEs (Grade 3-4) constituted 22.0% (9/41). Five patients (16.7%) permanently discontinued treatment due to severe toxicity. Endocrine toxicities were most frequent (36.6%

15/41)

primarily characterized by progression from hyperthyroidism to hypothyroidism; 75.0% required thyroid hormone replacement therapy. One case of delayed-onset adrenal insufficiency was alleviated with glucocorticoid (GC) therapy. Among hepatotoxicities (19.5%

8/41)

62.5% were Grade 3 injury

and 37.5% required GC intervention; two patients experienced recurrence during adjuvant chemotherapy. Three cases of severe myositis occurred

accompanied by asymptomatic myocardial injury (evidenced by markedly elevated creatine kinase and concurrent changes in cardiac biomarkers)

all requiring high-dose GC pulse therapy combined with intravenous immunoglobulin or immunosuppressants (recovery period: 2-4 months). Ni

ne dermatological reactions were managed with topical therapy. Two gastrointestinal events occurred

including one Grade 3 diarrhea treated with GCs. The overall GC usage rate was 31.7% (13/41)

with 76.9% administered for Grade ≥3 irAEs.

Conclusion:

irAEs during neoadjuvant immunotherapy for LARC are predominantly mild-to-moderate and manageable with supportive care. However

some patients develop severe (Grade 3-4) irAEs requiring multidisciplinary management. GC usage is concentrated in higher-grade irAEs

with severe myositis and cardiac involvement necessitating intensive immunosuppressive therapy despite their rarity. Recurrence of irAEs during adjuvant chemotherapy in a minority of patients underscores the necessity for early recognition

graded intervention

and comprehensive management throughout the entire treatment cycle.

关键词

Keywords

references

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