Influence of low-dose radiation on abscopal responses in patients receiving high-dose radiation and immunotherapy
Influence of low-dose radiation on abscopal responses in patients receiving high-dose radiation and immunotherapy
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DOI：
10.1186/s40425-019-0718-6
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发表时间：
2019-09-04
影响因子：
10.9
通讯作者：
Welsh, James W.
中科院分区：
文献类型：
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作者：
Menon, Hari;Chen, Dawei;Welsh, James W.
背景：临床前证据表明，低剂量放射治疗可以克服肿瘤间质的抑制效应，改善肿瘤对免疫治疗的反应，如果与另一肿瘤的高剂量放射治疗相结合的话。这项研究的目的是在临床环境中评估肿瘤对这种组合的反应。方法对3项正在进行的免疫放射试验进行后处理分析。在155例患者中，26例接受了低剂量辐射(总计1-20Gy射线)，无论是高剂量辐射的散射，还是第二个等中心与低剂量辐射的有意治疗，都进行了疗效评估。将低剂量照射的病灶与未接受辐射的病灶(总共1Gy1)进行比较。RECIST标准定义为完全反应和部分反应的反应率被用来比较病变类型。结果26例患者共83个病灶作为对照(低剂量组38个，非剂量组45个)。低剂量组平均剂量为7.3Gy1.1~19.4Gy.平均起效时间为56d。38个低剂量病灶中有22个(58%)符合PR/CR标准，而45个非剂量病灶中有8个(18%)符合PR/CR标准(P=0.0001)。低剂量组病灶最大直径的中位数变化为-38.5%，而非剂量组为8%(P<；0.0001)。在同一患者内至少有一个非剂量病变作为对照的低剂量病变(分别为33个和45个)中，12个(36%)低剂量病变在其非剂量病变中无相应反应；相反，2个(4%)无剂量病变在其低剂量病变中无相应反应(P=0.0004)。结论小剂量照射可提高大剂量照射加免疫治疗的转移性疾病的全身有效率。
Background Preclinical evidence suggests that low-dose radiation may overcome the inhibitory effects of the tumor stroma and improve a tumor's response to immunotherapy, when combined with high-dose radiation to another tumor. The aim of this study was to evaluate tumor responses to this combination in a clinical setting. Methods A post-hoc analysis of 3 ongoing immunoradiation trials was performed. Twenty-six (of 155) patients received low-dose radiation (1-20 Gy total), either as scatter from high-dose radiation or from intentional treatment of a second isocenter with low-dose radiation, were evaluated for response. The low-dose lesions were compared to lesions that received no radiation (< 1 Gy total). Response rates, both defined as complete and partial responses as defined by RECIST criteria were used to compare lesion types. Results The 26 patients had a total of 83 lesions for comparison (38 receiving low-dose, 45 receiving no-dose). The average dose given to low-dose lesions was 7.3 Gy (1.1-19.4 Gy), and the average time to response was 56 days. Twenty-two out of 38 (58%) low-dose lesions met the PR/CR criteria for RECIST compared with 8 out of 45 (18%) no-dose lesions (P = 0.0001). The median change for longest diameter size for low-dose lesions was - 38.5% compared to 8% in no-dose lesions (P < 0.0001). Among the low-dose lesions that had at least one no-dose lesion within the same patient as a control (33 and 45 lesions respectively), 12 low-dose lesions (36%) responded without a corresponding response in their no-dose lesions; Conversely, two (4%) of the no-dose lesions responded without a corresponding response in their low-dose lesion (P = 0.0004). Conclusions Low-dose radiation may increase systemic response rates of metastatic disease treated with high-dose radiation and immunotherapy.