Large fractions of radiotherapy of 8 Gy (ultra-hypofractionated RT, ultra-hypoRT) promote anti-tumor immune responses that have been clinically substantiated in combination trials with immune checkpoint inhibitors (ICIs). In the current study, we postulated that ultra-hypoRT in combination with ICIs may enhance tumor clearance in NSCLC patients with locoregional relapse after radical chemo-RT. Between 2019 and 2021, eleven patients received re-irradiation with one or two fractions of 8 Gy concurrently with anti-PD1 immunotherapy (nivolumab or pembrolizumab). RT-related toxicities were negligible, while immune-related adverse events enforced immunotherapy interruption in 36% of patients. The overall response rate was 81.8%. Tumor reduction between 80 and 100% was noted in 63.5% of patients. Within a median follow-up of 22 months, the locoregional relapse-free rate was 54.5%, while the projected 2-year disease-specific overall survival was 62%. The results were independent of PD-L1 status. The current report provides encouraging evidence that a relatively low biological dose of RT delivered with 8 Gy fractions is feasible and can be safely combined with anti-PD-1 immunotherapy. Despite the low number of patients, the significant tumor regression achieved and the long-lasting locoregional control and overall progression-free intervals provide a basis to pursue immuno-RT trials with U-hypoRT schemes in this group of NSCLC patients of poor prognosis.
8 Gy大分割放疗（超低分割放疗，ultra-hypoRT）可促进抗肿瘤免疫反应，这一效应在与免疫检查点抑制剂联合应用的临床试验中已得到证实。本研究假设，对于根治性放化疗后出现局部区域复发的非小细胞肺癌患者，超低分割放疗联合免疫检查点抑制剂可能增强肿瘤清除效果。2019年至2021年间，11例患者接受了单次或两次8 Gy的再程放疗，同时联合抗PD-1免疫治疗（纳武利尤单抗或帕博利珠单抗）。放疗相关毒性可忽略不计，但36%的患者因免疫相关不良事件需中断免疫治疗。总体缓解率达81.8%，63.5%的患者肿瘤缩小80%至100%。中位随访22个月内，局部区域无复发生存率为54.5%，预计2年疾病特异性总生存率为62%。该结果与PD-L1表达状态无关。本报告提供了令人鼓舞的证据：以8 Gy分割实施的相对低生物剂量放疗具有可行性，且可安全联合抗PD-1免疫治疗。尽管病例数有限，但显著的肿瘤消退效果、持久的局部区域控制及总体无进展生存期为在这类预后不良的非小细胞肺癌患者中开展超低分割放疗联合免疫治疗的临床试验奠定了基础。
肿瘤(癌症)患者之家