立体定向放疗联合免疫治疗在晚期胃肠癌中的远隔效应：一项回顾性研究
Abscopal Effect of Radiotherapy Combined with Immunotherapy in Advanced Gastrointestinal Cancer: A Retrospective Study
摘要
目的：评估立体定向放疗（SBRT）联合 PD-1 单抗治疗晚期胃肠癌患者的非照射病灶远隔效应发生率，分析其临床预测因素及联合治疗的安全性与生存获益。方法：回顾性纳入 2020 年 1 月-2025 年 4 月在解放军总医院第八医学中心接受 SBRT 联合 PD-1 单抗治疗的 68 例晚期胃癌或结直肠癌患者。收集患者基线特征、SBRT 参数、免疫治疗方案及临床结局数据。主要终点为非照射病灶远隔效应发生率（定义为非照射病灶达部分缓解 / 完全缓解，PR/CR）；次要终点包括照射病灶局部控制率（LC）、无进展生存期（PFS）、总生存期（OS）及≥3 级不良反应发生率。采用单因素与多因素 Logistic 回归分析远隔效应的独立预测因素，Kaplan-Meier 法行生存分析。结果：68 例患者中，19 例出现远隔效应，发生率为 27.9%（95% CI：17.6%~38.2%）。照射病灶局部控制率为 73.5%（50/68）。单因素分析显示，BED10≥80Gy、一线免疫治疗、肝 / 肺转移、微卫星高度不稳定（MSI-H）与远隔效应显著相关（P<0.05）；多因素 Logistic 回归分析证实，BED10≥80Gy（OR=4.215，95% CI：1.523~11.657，P=0.006）、一线免疫治疗（OR=3.782，95% CI：1.386~10.325，P=0.009）及 MSI-H 状态（OR=5.103，95% CI：1.674~15.552，P=0.004）是远隔效应的独立有利预测因素。全组患者≥3 级不良反应发生率为 17.6%（12/68），主要为放射性肺炎、免疫性肠炎及骨髓抑制，无治疗相关死亡。生存分析显示，远隔效应组中位 PFS（10.2 个月 vs 4.1 个月，HR=0.32，95%CI：0.18~0.58，P<0.001）与中位 OS（18.5 个月 vs 9.3 个月，HR=0.28，95%CI：0.15~0.52，P<0.001）显著优于无远隔效应组。结论：SBRT 联合 PD-1 单抗治疗晚期胃肠癌可诱导可观的远隔效应，且安全性可控。高生物等效剂量（BED10≥80Gy）、一线联合免疫及 MSI-H 状态是预测远隔效应的关键临床因素，可为优化晚期胃肠癌放免联合策略提供真实世界依据。
Abstract
Objective: To evaluate the incidence of abscopal effect in non-irradiated lesions of patients with advanced gastrointestinal cancer treated with stereotactic body radiotherapy (SBRT) combined with PD-1 monoclonal antibodies, analyze its clinical predictors, and assess the safety and survival benefits of the combined therapy. Methods: This retrospective study included 68 patients with advanced gastric cancer or colorectal cancer who received SBRT combined with PD-1 monoclonal antibody therapy at the Eighth Medical Center of Chinese PLA General Hospital from January 2020 to April 2025. Baseline patient characteristics, SBRT parameters, immunotherapy regimens, and clinical outcome data were collected. The primary endpoint was the incidence of abscopal effect in non-irradiated lesions (defined as partial response/complete response [PR/CR] of non-irradiated lesions). Secondary endpoints included local control (LC) of irradiated lesions, progression-free survival (PFS), overall survival (OS), and incidence of grade ≥3 adverse events. Univariate and multivariate logistic regression analyses were used to identify independent predictors of the abscopal effect, and the Kaplan-Meier method was used for survival analysis. Results: Among the 68 patients, 19 developed an abscopal effect, with an incidence rate of 27.9% (95% CI: 17.6%–38.2%). The local control rate of irradiated lesions was 73.5% (50/68). Univariate analysis showed that BED10 ≥80 Gy, first-line immunotherapy, liver/lung metastasis, and microsatellite instability-high (MSI-H) status were significantly associated with the abscopal effect (P < 0.05). Multivariate logistic regression analysis confirmed that BED10 ≥80 Gy (OR = 4.215, 95% CI: 1.523–11.657, P = 0.006), first-line immunotherapy (OR = 3.782, 95% CI: 1.386–10.325, P = 0.009), and MSI-H status (OR = 5.103, 95% CI: 1.674–15.552, P = 0.004) were independent favorable predictors of the abscopal effect. The incidence of grade ≥3 adverse events in the entire cohort was 17.6% (12/68), primarily including radiation pneumonitis, immune-related enteritis, and myelosuppression, with no treatment-related deaths. Survival analysis showed that the abscopal effect group had significantly better median PFS (10.2 months vs. 4.1 months, HR=0.32, 95%CI: 0.18–0.58, P<0.001) and median OS (18.5 months vs. 9.3 months, HR=0.28, 95%CI: 0.15–0.52, P<0.001) compared to the non-abscopal effect group. Conclusion: SBRT combined with PD-1 monoclonal antibody therapy can induce a considerable abscopal effect in advanced gastrointestinal cancer patients with a manageable safety profile. High biologically effective dose (BED10 ≥80 Gy), first-line combined immunotherapy, and MSI-H status are key clinical factors predicting the abscopal effect, providing real-world evidence to optimize the combination strategy of radiotherapy and immunotherapy for advanced gastrointestinal cancer.关键词
晚期胃肠癌/立体定向放疗/PD-1 单抗/远隔效应/预测因素/预后Key words
advanced gastrointestinal cancer/stereotactic body radiotherapy/PD-1 monoclonal antibody/abscopal effect/predictive factors/prognosis引用本文复制引用
张林,侯艳红,吴凯,张静.立体定向放疗联合免疫治疗在晚期胃肠癌中的远隔效应：一项回顾性研究[EB/OL].(2026-06-08)[2026-06-13].https://www.biomedrxiv.org.cn/article/doi/10.12201/bmr.202606.00027.学科分类
肿瘤学/临床医学
