肌肉减少症对晚期胃癌患者免疫治疗联合化疗疗效及不良反应的影响

Impact of sarcopenia on efficacy and adverse reactions of immunotherapy combined with chemotherapy in patients with advanced gastric cancer

  • 摘要:
    目的 分析肌肉减少症对晚期胃癌患者免疫治疗联合化疗疗效及不良反应的影响。
    方法 选取经病理证实且不能行根治性手术的局部晚期或转移性胃癌患者为研究对象。采用人体成分分析仪测量患者四肢肌肉质量并计算骨骼肌质量指数(SMI), 并依据SMI将患者分为肌肉减少症组和无肌肉减少症组。在营养干预和运动综合治疗的基础上,给予患者免疫治疗联合化疗。评估疗效和不良反应,其中主要观察终点是无进展生存期(PFS), 次要观察终点是客观缓解率(ORR)和治疗相关不良反应。
    结果 纳入52例胃癌患者,其中肌肉减少症组23例,无肌肉减少症组29例。无肌肉减少症组患者中位PFS为9.8个月(95%CI: 8.9~12.4), 肌肉减少症组患者中位PFS为5.4个月(95%CI: 4.9~8.1)。无肌肉减少症组患者中位PFS长于肌肉减少症组患者,差异有统计学意义HR(95%CI)=0.41(0.23~0.73), P=0.003。多因素Cox风险比例回归模型结果显示,合并疾病、治疗周期以及肌肉减少症均是影响胃癌患者PFS的独立预后因素(P<0.05)。无肌肉减少症组ORR为48.28%(14/29), 肌肉减少症组ORR为17.39%(4/23), 差异有统计学意义(χ2=5.276, P<0.05)。2组≥3级治疗相关不良反应以血液学毒性为主。无肌肉减少症组中, ≥3级治疗相关不良反应发生率为27.59%(8/29), <3级治疗相关不良反应(包括未发生不良反应)发生率为72.41%(21/29); 肌肉减少症组中, ≥3级治疗相关不良反应发生率为56.52%(13/23), <3级治疗相关不良反应(包括未发生不良反应)发生率为43.48%(10/23)。无肌肉减少症组≥3级治疗相关不良反应发生率低于肌肉减少症组,差异有统计学意义(P=0.035)。
    结论 合并肌肉减少症的局部晚期或转移性胃癌患者免疫治疗联合化疗的中位PFS更短, ORR更低,且会增加治疗相关不良反应的发生率。因此,应早期干预肌肉减少症,提高晚期胃癌患者的生存质量。

     

    Abstract:
    Objective To analyze the impact of sarcopenia on the efficacy and adverse reactions of immunotherapy combined with chemotherapy in patients with advanced gastric cancer.
    Methods Patients with locally advanced or metastatic gastric cancer confirmed by pathology who were not eligible for radical surgery were selected as study subjects. A body composition analyzer was used to measure the appendicular muscle mass of the patients and calculate the skeletal muscle mass index (SMI). Based on the SMI, the patients were divided into sarcopenia group and non-sarcopenia group. On the basis of nutritional intervention and comprehensive exercise therapy, the patients were administered immunotherapy combined with chemotherapy. The efficacy and adverse reactions were evaluated. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were the objective response rate (ORR) and treatment-related adverse reactions.
    Results A total of 52 gastric cancer patients were included, with 23 in the sarcopenia group and 29 in the non-sarcopenia group. The median PFS in the non-sarcopenia group was 9.8 months (95%CI, 8.9 to 12.4), and was 5.4 months in the sarcopenia group (95%CI, 4.9 to 8.1). The median PFS in the non-sarcopenia group was longer than that in the sarcopenia group, and the difference was statistically significant HR (95%CI)=0.41 (0.23 to 0.73), P=0.003. The results of the multivariate Cox proportional hazards regression model showed that comorbidities, treatment cycles, and sarcopenia were all independent prognostic factors affecting the PFS of gastric cancer patients (P < 0.05). The ORR in the non-sarcopenia group was 48.28%(14/29), and was 17.39%(4/23) in the sarcopenia group (χ2=5.276, P < 0.05). Treatment-related adverse reactions with grading ≥3 in both groups were mainly hematological toxicities. In the non-sarcopenia group, the incidence of grading ≥3 treatment-related adverse reactions was 27.59%(8/29), and the incidence of grading < 3 treatment-related adverse reactions (including those with no adverse reactions) was 72.41%(21/29). In the sarcopenia group, the incidence of grading ≥3 treatment-related adverse reactions was 56.52%(13/23), and the incidence of grading < 3 treatment-related adverse reactions (including those without adverse reactions) was 43.48%(10/23). The incidence of grading ≥3 treatment-related adverse reactions in the non-sarcopenia group was lower than that in the sarcopenia group (P=0.035).
    Conclusion For patients with locally advanced or metastatic gastric cancer complicated with sarcopenia, the median PFS of immunotherapy combined with chemotherapy is shorter, the ORR is lower, and the incidence of treatment-related adverse reactions is increased. Therefore, early intervention for sarcopenia should be implemented to improve the quality of life of patients with advanced gastric cancer.

     

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