Tian Ruoxi, Wang Siqi, Ji Zhengzheng, Li Jiasong, Zhang Jingjing, Zhang Shasha, Guo Zhanjun
Department of Colorectal Surgery, National Cancer Center, Beijing, China.
Department of Colorectal Surgery, National Clinical Research Center for Cancer, Beijing, China.
Front Oncol. 2025 Jul 25;15:1516643. doi: 10.3389/fonc.2025.1516643. eCollection 2025.
Cancer patients are at a greater risk of experiencing emotional distress (ED) compared to individuals without cancer, with those diagnosed with gastric cancer (GC) exhibiting a higher prevalence of ED than patients with other types of malignancies. A meta-analysis showed that 37% of global GC patients had depressive symptoms. Numerous studies have demonstrated that ED can lead cancer patients to develop immunosuppressive tumor microenvironments (TME), thereby impairing the exertion of antitumor immune effects. Currently, there is a lack of research investigating the correlation between ED and outcomes in GC patients undergoing treatment with immune checkpoint inhibitors (ICIs). We conducted a prospective cohort study to explore the correlation between ED and tumor response as well as prognostic outcomes in patients with advanced gastric cancer(AGC) who received ICIs treatment.
We prospectively enrolled 104 patients with AGC undergoing combination therapy with ICIs, of whom 46 (44.2%) exhibited ED, defined as symptoms of depression (Patient Health Questionnaire-9 score ≥5) and/or anxiety (Generalized Anxiety Disorder 7-item scale score ≥5) at baseline. The Response Evaluation Criteria in Solid Tumors (RECIST v1.1) criteria were employed to evaluate tumor response. We analyzed the correlation between ED and outcomes including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR).
Baseline ED was associated with a higher risk of death (HR: 2.035, 95%CI:1.272-3.254, P=0.003) and higher risk of progression (HR: 3.006, 95%CI: 1.922-4.701, P<0.001), as well as a lower DCR (RR: 0.504, 95%CI: 0.343-0.742,P=0.001), in AGC patients undergoing ICIs therapy. Cox multivariate analysis and propensity score matching (PSM) still indicated a significant correlation between ED status and survival outcomes. The baseline ED was not significantly correlated with cortisol levels with a HR of 2.318 (95% CI: 0.805-6.679, P=0.119). Patients exhibiting baseline depressive symptoms was correlated with reduced OS (HR: 2.231, 95%CI: 1.396 - 3.564, P=0.001) and PFS (HR: 2.488, 95%CI: 1.590 - 3.891, P<0.001) following ICIs therapy. After two cycles of treatment, the new onset of ED was found to have a worse survival prognosis compared to those who had never experienced ED (HR: 2.813, 95%CI: 1.270-6.228, P=0.011).
ED is associated with worse outcomes in AGC patients undergoing treatment with ICIs.
与未患癌症的个体相比，癌症患者经历情绪困扰（ED）的风险更高，其中被诊断为胃癌（GC）的患者比其他类型恶性肿瘤患者的ED患病率更高。一项荟萃分析表明，全球37%的GC患者有抑郁症状。众多研究表明，ED可导致癌症患者形成免疫抑制性肿瘤微环境（TME），从而损害抗肿瘤免疫效应的发挥。目前，缺乏关于接受免疫检查点抑制剂（ICIs）治疗的GC患者中ED与治疗结果之间相关性的研究。我们进行了一项前瞻性队列研究，以探讨接受ICIs治疗的晚期胃癌（AGC）患者中ED与肿瘤反应以及预后结果之间的相关性。
我们前瞻性招募了104例接受ICIs联合治疗的AGC患者，其中46例（44.2%）在基线时表现出ED，定义为抑郁症状（患者健康问卷-9评分≥5）和/或焦虑（广泛性焦虑障碍7项量表评分≥5）。采用实体瘤疗效评价标准（RECIST v1.1）评估肿瘤反应。我们分析了ED与总生存期（OS）、无进展生存期（PFS）、客观缓解率（ORR）和疾病控制率（DCR）等结果之间的相关性。
基线时的ED与AGC患者接受ICIs治疗时更高的死亡风险（HR：2.035，95%CI：1.272 - 3.254，P = 0.003）和更高的进展风险（HR：3.006，95%CI：1.922 - 4.701，P < 0.001）相关，以及更低的DCR（RR：0.504，95%CI：0.343 - 0.742，P = 0.001）。Cox多因素分析和倾向得分匹配（PSM）仍表明ED状态与生存结果之间存在显著相关性。基线时的ED与皮质醇水平无显著相关性，HR为2.318（95%CI：0.805 - 6.679，P = 0.119）。表现出基线抑郁症状的患者与ICIs治疗后的OS降低（HR：2.231，95%CI：1.396 - 3.564，P = 0.001）和PFS降低（HR：2.488，95%CI：1.590 - 3.891，P < 0.001）相关。在两个治疗周期后，发现新出现ED的患者与从未经历过ED的患者相比，生存预后更差（HR：2.813，95%CI：1.270 - 6.228，P = 0.011）。
ED与接受ICIs治疗的AGC患者的较差结果相关。
