国际肿瘤学杂志

国际肿瘤学杂志 ›› 2025, Vol. 52 ›› Issue (4): 209-216.doi: 10.3760/cma.j.cn371439-20240820-00035

• 论著 • 上一篇    下一篇

放疗联合化疗和免疫治疗对HER2阴性局部晚期或晚期胃癌的临床疗效和安全性

刘前怡1,2, 董洪敏1,2,3(), 王文玲1,2,3, 王刚1,2,3, 陈望花1,2,3   

  1. 1贵州医科大学临床医学院肿瘤学教研室，贵阳 550004
    2贵州医科大学附属肿瘤医院腹部肿瘤科，贵阳 550008
    3贵州医科大学附属医院肿瘤科，贵阳 550001
  • 收稿日期:2024-08-20 修回日期:2025-02-26 出版日期:2025-04-08 发布日期:2025-04-21
  • 通讯作者: 董洪敏，Email：dhm6825@163.com E-mail:dhm6825@163.com

Clinical efficacy and safety of radiotherapy combined with chemotherapy and immunotherapy for HER2-negative locally advanced or advanced gastric cancer

Liu Qianyi1,2, Dong Hongmin1,2,3(), Wang Wenling1,2,3, Wang Gang1,2,3, Chen Wanghua1,2,3   

  1. 1Department of Oncology，Clinical Medical College of Guizhou Medical University，Guiyang 550004，China
    2Department of Abdominal Oncology，Affiliated Cancer Hospital of Guizhou Medical University，Guiyang 550008，China
    3Department of Oncology，Affiliated Hospital of Guizhou Medical University，Guiyang 550001，China
  • Received:2024-08-20 Revised:2025-02-26 Online:2025-04-08 Published:2025-04-21

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摘要：

目的 探讨放疗联合化疗和免疫治疗在人表皮生长因子2（HER2）阴性局部晚期或晚期胃癌中的临床疗效和安全性。方法 选取2021年9月至2024年3月贵州医科大学附属肿瘤医院收治的34例不可手术切除的HER2阴性局部晚期或晚期胃/胃食管结合部（G/GEJ）腺癌患者作为研究对象，接受1周期XELOX方案（卡培他滨+奥沙利铂）或SOX方案（替吉奥+奥沙利铂）联合免疫治疗（信迪利单抗或纳武利尤单抗）后，进行G/GEJ原发灶及转移区域淋巴结放疗，部分患者序贯远处转移灶放疗。主要研究终点为客观缓解率（ORR），次要研究终点为疾病控制率（DCR）、临床症状缓解情况、Karnofsky功能状态（KPS）评分变化、无进展生存期（PFS）、不良反应。采用实体瘤临床疗效评价标准1.1版评估临床疗效，按照美国国立癌症研究所通用不良反应术语标准5.0版、中国临床肿瘤学会免疫检查点抑制剂相关的毒性管理指南进行不良反应评价和分级。中位随访时间7个月（范围：2.3~30个月），以随访过程中出现的最佳疗效定为最终疗效评价。采用Kaplan-Meier法绘制生存曲线。结果 至随访结束，全组患者ORR达58.8%（20/34），DCR达70.6%（24/34）；放疗病灶ORR达73.8%（48/65）、DCR达92.3%（60/65）。单因素分析显示，女性患者的ORR（84.6%，11/13）高于男性患者（42.9%，9/21），远处淋巴结转移患者的ORR（83.3%，15/18）高于远处淋巴结转移合并器官转移或单独器官转移患者（18.2%，2/11），差异均具有统计学意义（P=0.030；P=0.010）。不同年龄（P=0.487）、KPS评分（P=0.198）、原发肿瘤部位（P=0.280）、组织学分化程度（P=0.668）、化疗方案（P=0.728）、免疫治疗方案（P>0.999）患者的ORR差异均无统计学意义。23例上腹疼痛患者缓解22例（95.7%），21例食欲下降患者缓解10例（47.6%），17例上腹饱胀患者缓解15例，14例黑便患者缓解13例，7例进食梗阻患者缓解6例，4例转移部位疼痛患者缓解3例，2例呕血患者均缓解。KPS评分好转率82.4%（28/34），无变化率11.8%（4/34），恶化率5.8%（2/34）。34例患者中位PFS为7.9个月。放疗联合化疗和免疫治疗期间最常见的不良反应为血液系统不良反应，其中中性粒细胞减少占比最高（91.2%，31/34），其次是贫血（50.0%，17/34）；最常见的非血液系统不良反应是疲劳（50.0%，17/34），其次是恶心和呕吐（26.5%，9/34）。6例免疫单药维持治疗患者治疗期间不良反应有贫血、甲状腺功能减退、转氨酶升高、蛋白尿、乏力和疲劳、皮疹，均为1~2级。结论 放疗联合化疗和免疫治疗在HER2阴性局部晚期或晚期胃癌中有较好的近期临床疗效，整体不良反应可耐受；女性、单独淋巴结转移的患者可能是本研究方案的优选人群。

关键词: 胃肿瘤, 化放疗, 免疫疗法, 药物相关性副作用和不良反应, 近期疗效

Abstract:

Objective To explore the clinical efficacy and safety of a multimodal treatment regimen integrating radiotherapy，chemotherapy，and immunotherapy in patients with human epidermal growth factor receptor 2 （HER2）-negative locally advanced or advanced gastric cancer. Methods A total of 34 patients with unresectable，HER2-negative，locally advanced or metastatic gastric/gastroesophageal junction （G/GEJ） adenocarcinoma admitted to the Affiliated Cancer Hospital of Guizhou Medical University from September 2021 to March 2024 were selected as study objects. Participants received one cycle of either XELOX regimen （capecitabine + oxaliplatin） or SOX regimen （S-1 + oxaliplatin） with immunotherapy （sintilimab or nivolumab）. The process was succeeded by radiotherapy targeted at the primary G/GEJ tumor and regional lymph nodes. In selected cases，sequential radiotherapy was also administered for distant metastases. The primary endpoint was Objective response rate （ORR），and secondary endpoints were disease control rate （DCR），clinical symptom response，changes in Karnofsky performance status （KPS） score，progression-free survival （PFS），and adverse reactions. Clinical efficacy was assessed in accordance with Response Evaluation Criteria in Solid Tumors version 1.1. Adverse reactions were assessed and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 and the Chinese Society of Clinical Oncology guidelines for management of immune checkpoint inhibitor-related toxicity. With a median follow-up of 7 months （range：2.3 to 30 months），the final evaluation considered the best response documented throughout follow-up. Survival curves were constructed utilizing Kaplan-Meier analysis. Results By the end of follow-up，an overall ORR of 58.8% （20/34） and DCR of 70.6% （24/34） were observed. The ORR of lesions by radiotherapy reached 73.8% （48/65） and the DCR reached 92.3% （60/65）. Univariate analysis showed that the ORR of female patients （84.6%，11/13） was higher than that of male patients （42.9%，9/21），and the ORR of patients with distant lymph node metastasis alone （83.3%，15/18） was higher than that of patients with distant lymph node metastasis combined with organ metastasis or organ metastasis alone （18.2%，2/11），with statistically significant differences （P=0.030； P=0.010）. There were no statistically significant differences in ORR among patients with different age （P=0.487），KPS score （P=0.198），primary tumor location （P=0.280），histological differentiation （P=0.668），chemotherapy regimen （P=0.728），or immunotherapy regimen （P>0.999）. Twenty-two of 23 （95.7%） patients with upper abdominal pain were relieved，10 of 21 （47.6%） patients with appetite loss were relieved，15 of 17 patients with upper abdominal distension were relieved，13 of 14 patients with melena were relieved，6 of 7 patients with eating obstruction were relieved，3 of 4 patients with metastatic site pain were relieved，and 2 patients with hematemesis were relieved. KPS score enhanced in 82.4% （28/34） of patients，remained stable in 11.8% （4/34），and declined in 5.8% （2/34）. The median PFS of the 34 patients was 7.9 months. The most common adverse reactions during radiotherapy combined with chemotherapy and immunotherapy were hematological adverse reactions，in which neutropenia accounted for the highest proportion （91.2%，31/34），followed by anemia （50.0%，17/34）. Fatigue was the most common non-hematological adverse reaction （50.0%，17/34），followed by nausea and vomiting （26.5%，9/34）. The adverse reactions of 6 patients receiving immune monotherapy maintenance were anemia，hypothyroidism，transaminase elevation，proteinuria，fatigue，and rash，all of which were grade 1-2. Conclusions Radiotherapy combined with chemotherapy and immunotherapy shows good short-term clinical efficacy in patients with HER2-negative locally advanced or advanced gastric cancer，and the overall adverse reactions are tolerable. Female or patients with distant lymph node metastasis alone may be the preferred population for this study protocol.

Key words: Stomach neoplasms, Chemoradiotherapy, Immunotherapy, Drug-related side effects and adverse reactions, Short-term efficacy