放射線療法誘発性アブスコパル効果：免疫チェックポイント阻害薬抵抗性転移性疾患における大規模多施設リアルワールドコホート研究の結果

Combining radiotherapy with immune checkpoint inhibitors (RT-ICI) triggers systemic antitumor responses, such as abscopal effects (AbE). Predictors of AbE and its impact on survival in real-world settings remain poorly defined. This multicenter, retrospective cohort study assessed the prevalence of AbE in ICI-refractory progressive metastatic patients by evaluating the additive effect of RT on nonirradiated lesions (NIL). We screened 3773 cases to identify patients with stage IV tumors receiving RT during/after ICI. Abscopal benefit (AB) was defined as abscopal response (AR) or control (AC) by measuring NILs according to iRECIST. AB was observed in 61.3% of 142 included patients and associated with improved median overall survival (18 vs. 8 months, p < 0.01) and progression-free survival (7 vs. 3 months, p < 0.01). Logistic regression identified younger age (OR = 0.951, 95% CI: 0.903-0.995, p = 0.039) and longer ICI-RT intervals (OR = 1.077, 95% CI: 1.019-1.171, p = 0.027) as predictors of AB. There was no association between radiation dose or tumor volume and AB. Cox regression identified BMI ≥ 25 kg/m² (HR = 3.348, 95% CI: 1.557-7.202, p = 0.002) and CRP ≥ 5 mg/l (HR = 3.058, 95% CI: 1.211-7.724, p = 0.016) as independent negative prognostic factors for survival in this RT-ICI cohort. Median survival was significantly higher among patients receiving ultrahypofractionated RT, compared to other fractions (21 vs. 11 months; p = 0.024). AbE seems to occur reliably and is prognostically relevant in ICI-refractory patients receiving RT. Patient- and timing-related factors were more predictive than RT details in our cohort. Our findings enhance the understanding of tailored RT-ICI approaches and lay the groundwork for targeted radioimmunotherapy strategies and personalized clinical trial designs.