Department/Division of Radiation Oncology, Emory University, Atlanta, United States; Department/Division of Microbiology and Immunology, Emory University, Atlanta, United States.
Department/Division of Radiation Oncology, Emory University, Atlanta, United States; Winship Cancer Institute, Emory University, Atlanta, United States.
Radiother Oncol. 2021 Dec;165:20-31. doi: 10.1016/j.radonc.2021.10.003. Epub 2021 Oct 13.
Low-dose radiotherapy (LD-RT) has produced anti-inflammatory effects in both animal models and early human trials of COVID-19-related pneumonia. The role of whole-lung LD-RT within existing treatment paradigms merits further study.
A phase II prospective trial studied the addition of LD-RT to standard drug treatments. Hospitalized and oxygen-dependent patients receiving dexamethasone and/or remdesevir were treated with 1.5 Gy whole-lung LD-RT and compared to a blindly-matched contemporaneous control cohort.
Of 40 patients evaluated, 20 received drug therapy combined with whole-lung LD-RT and 20 without LD-RT. Intubation rates were 14% with LD-RT compared to 32% without (p = 0.09). Intubation-free survival was 77% vs. 68% (p = 0.17). Biomarkers of inflammation (C-reactive protein, p = 0.02) and cardiac injury (creatine kinase, p < 0.01) declined following LD-RT compared to controls. Mean time febrile was 1.4 vs 3.3 days, respectively (p = 0.14). Significant differences in clinical recovery (7.5 vs. 7 days, p = 0.37) and radiographic improvement (p = 0.72) were not detected. On subset analysis, CRP decline following LD-RT was predictive of recovery without intubation compared to controls (0% vs. 31%, p = 0.04), freedom from prolonged hospitalizations (21+ days) (0% vs. 31%, p = 0.04), and decline in oxygenation burden (56% reduction, p = 0.06). CRP decline following 1st drug therapy was not similarly predictive of outcome in controls (p = 0.36).
Adding LD-RT to standard drug treatments reduced biomarkers of inflammation and cardiac injury in COVID-19 patients and may have reduced intubation. Durable CRP decline following LD-RT predicted especially favorable recovery, freedom from intubation, reduction in prolonged hospitalization, and reduced oxygenation burden. A confirmatory randomized trial is now ongoing.
NCT04366791.
低剂量放射疗法（LD-RT）在 COVID-19 相关肺炎的动物模型和早期人类试验中均产生了抗炎作用。全肺 LD-RT 在现有治疗模式中的作用值得进一步研究。
一项 II 期前瞻性试验研究了将 LD-RT 添加到标准药物治疗中的效果。接受地塞米松和/或瑞德西韦治疗且需要住院并依赖氧气的患者接受 1.5Gy 的全肺 LD-RT 治疗，并与盲法匹配的同期对照组进行比较。
在评估的 40 名患者中，20 名患者接受了药物治疗联合全肺 LD-RT，20 名患者未接受 LD-RT。接受 LD-RT 的患者插管率为 14%，而未接受 LD-RT 的患者插管率为 32%（p=0.09）。接受 LD-RT 的患者无插管生存时间为 77%，而未接受 LD-RT 的患者为 68%（p=0.17）。与对照组相比，接受 LD-RT 后炎症生物标志物（C 反应蛋白，p=0.02）和心脏损伤标志物（肌酸激酶，p<0.01）下降。发热时间分别为 1.4 天和 3.3 天（p=0.14）。未发现临床恢复（7.5 天 vs. 7 天，p=0.37）和影像学改善（p=0.72）方面的显著差异。亚组分析显示，与对照组相比，接受 LD-RT 后 C 反应蛋白下降可预测无需插管即可恢复（0% vs. 31%，p=0.04）、避免长时间住院（21 天以上）（0% vs. 31%，p=0.04）以及减少氧合负担（减少 56%，p=0.06）。接受首次药物治疗后 C 反应蛋白下降在对照组中同样无法预测结局（p=0.36）。
将 LD-RT 添加到标准药物治疗中可降低 COVID-19 患者的炎症和心脏损伤生物标志物，并且可能减少插管。接受 LD-RT 后 C 反应蛋白持久下降尤其可预测恢复良好、无需插管、减少长时间住院和减少氧合负担。目前正在进行一项确认性随机试验。
NCT04366791。
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