Filippatos Konstantinos, Koukourakis Ioannis M, Anevlavis Stavros, Giaktzidis Axiotis, Koukourakis Michael I
Department of Radiotherapy-Oncology, Medical School, Democritus University of Thrace, 68100 Alexandroupolis, Greece.
Radiation Oncology Unit, 1st Department of Radiology, "Aretaieion" University Hospital, Medical School, National and Kapodistrian University of Athens (NKUOA), 11528 Athens, Greece.
Cancers (Basel). 2023 Oct 20;15(20):5083. doi: 10.3390/cancers15205083.
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.
8Gy的大分割放疗（超短程大分割放疗，ultra-hypoRT）可促进抗肿瘤免疫反应，这已在与免疫检查点抑制剂（ICI）联合试验中得到临床证实。在本研究中，我们推测超短程大分割放疗联合ICI可能会提高根治性放化疗后局部区域复发的非小细胞肺癌（NSCLC）患者的肿瘤清除率。2019年至2021年期间，11例患者接受了1次或2次8Gy的再程放疗，同时接受抗PD1免疫治疗（纳武单抗或帕博利珠单抗）。放疗相关毒性可忽略不计，而免疫相关不良事件导致36%的患者中断免疫治疗。总缓解率为81.8%。63.5%的患者肿瘤缩小80%至100%。在中位随访22个月时，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%。结果与PD-L1状态无关。本报告提供了令人鼓舞的证据，即采用8Gy分割给予相对低的生物学剂量放疗是可行的，并且可以安全地与抗PD-1免疫治疗联合使用。尽管患者数量较少，但显著的肿瘤消退以及持久的局部区域控制和总无进展间期为在这组预后较差NSCLC患者中开展超短程大分割放疗免疫放疗试验提供了依据。
