Background: Radiotherapy (RT) combined with immune checkpoint inhibitors (ICIs) has shown therapeutic benefits, and the potential for enhanced immune activation has raised concerns about increased immune-related adverse events (irAEs). The immunological implications of mediastinal RT combined with ICI therapy remain unclear. Methods: We conducted an exploratory retrospective review of 58 patients with esophageal oresophagogastric junction cancer who received ICIs between 2021 and 2024. Patients were categorized into RT (+) and RT (-) groups based on whether they underwent mediastinal RT. The incidence and severity of irAEs were compared using chi-square testing. Subgroup analyses included treatment sequence (RT before vs. after ICI), interval between RT and ICI (<90 vs. ≥90 days), and ICI regimen (nivolumab [N], pembrolizumab [P], or nivolumab plus ipilimumab [NI]). Results: irAEs occurred in 28.6% of RT (+) and 39.1% of RT (-) (p= 0.42). Severe irAEs were uncommon in both groups. Treatment sequence and RT-ICI interval did not significantly influence irAE incidence. irAEs were more frequent in the NI group (85.7%) than in N (22.9%) or P (31.2%) (p= 0.01). Mediastinal RT itself did not increase irAE risk. Conclusions: Although RT combined with ICIs has been hypothesized to elevate irAEs through enhanced immune activation, mediastinal RT did not increase irAEs in this cohort. However, given the exploratory and small patient cohort, these findings suggest, with caution, that mediastinal irradiation may attenuate systemic immune activation through lymphocyte depletion, potentially balancing ICI-induced immune responses.
背景：放疗（RT）联合免疫检查点抑制剂（ICIs）已显示出治疗获益，但其潜在的免疫激活增强效应引发了人们对免疫相关不良事件（irAEs）增加的担忧。纵隔放疗联合ICI治疗的免疫学影响尚不明确。方法：我们对2021年至2024年间接受ICI治疗的58例食管或食管胃结合部癌患者进行了探索性回顾性分析。根据是否接受纵隔放疗，将患者分为RT（+）组和RT（-）组。采用卡方检验比较irAEs的发生率和严重程度。亚组分析包括治疗顺序（放疗在ICI之前或之后）、放疗与ICI的间隔时间（<90天 vs. ≥90天）以及ICI方案（纳武利尤单抗[N]、帕博利珠单抗[P]或纳武利尤单抗联合伊匹木单抗[NI]）。结果：RT（+）组irAEs发生率为28.6%，RT（-）组为39.1%（p=0.42）。两组中严重irAEs均不常见。治疗顺序和放疗-ICI间隔时间对irAE发生率无显著影响。NI组irAEs发生率（85.7%）高于N组（22.9%）或P组（31.2%）（p=0.01）。纵隔放疗本身并未增加irAE风险。结论：尽管有假说认为放疗联合ICIs可能通过增强免疫激活而增加irAEs，但本队列中纵隔放疗并未增加irAEs。然而，鉴于本研究为探索性研究且患者队列较小，这些结果谨慎提示，纵隔放疗可能通过淋巴细胞耗竭减弱全身免疫激活，从而可能平衡ICI诱导的免疫反应。
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