Low dose anti-inflammatory radiotherapy for the treatment of pneumonia by covid-19: A proposal for a multi-centric prospective trial

M Algara, M Arenas, J Marin, I Vallverdu, P Fernandez-Letón, J Villar, G Fabrer, C Rubio, A Montero, M Algara, M Arenas, J Marin, I Vallverdu, P Fernandez-Letón, J Villar, G Fabrer, C Rubio, A Montero

Abstract

Background: COVID-19 is a highly contagious viral infection with high morbidity that is draining health resources. The biggest complication is pneumonia, which has a serious inflammatory component, with no standardized treatment. Low-dose radiation therapy (LD-RT) is non-invasive and has anti-inflammatory effects that can interfere with the inflammatory cascade, thus reducing the severity of associated cytokine release and might be useful in the treatment of respiratory complications caused by COVID-19.

Study design and methods: This multicentric prospective clinical trial seeks to evaluate the efficacy of bilateral lung LD-RT therapy as a treatment for interstitial pneumonia in patients with COVID-19 for improving respiratory function.This prospective study will have 2 phases: I) an exploratory phase enrolling 10 patients, which will assess the feasibility and efficacy of low-dose lung irradiation, evaluated according to an increase in the PaO2/FiO2 ratio of at least 20% at 48-72 h with respect to the pre-irradiation value. If a minimum efficiency of 30% of the patients is not achieved, the study will not be continued. II) Non-randomized comparative phase in two groups: a control group, which will only receive pharmacological treatment, and an experimental arm with pharmacological treatment and LD-RT. It will include 96 patients, the allocation will be 1: 2, that is, 32 in the control arm and 64 in the experimental arm. The primary end-point will be the efficacy of LD-RT in patients with COVID-19 pneumonia according to an improvement in PaO2/FiO2. Secondary objectives will include the safety of bilateral lung LD-RT, an improvement in the radiology image, overall mortality rates at 15 and 30 days after irradiation and characterizing anti-inflammatory mechanisms of LD-RT by measuring the level of expression of adhesion molecules, anti-inflammatory cytokines and oxidative stress mediators.Trial registration: ClinicalTrial.gov NCT-04380818 https://ichgcp.net/clinical-trials-registry/NCT04380818?term=RADIOTHERAPY&cond=COVID&draw=2&rank=4.

Keywords: COVID; Pneumonia; Radiotherapy.

Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

© 2020 Published by Elsevier B.V. on behalf of European Society for Radiotherapy and Oncology.

Figures

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Fig. 1
Study flowchart.

References

    1. Ge H., Wang X., Yuan X. The epidemiology and clinical information about COVID-19 [published online ahead of print, 2020 Apr 14] Eur J ClinMicrobiol Infect Dis. 2020:1–9. doi: 10.1007/s10096-020-03874-z.
    1. Conti P., Ronconi G., Caraffa A. Induction of pro-inflammatory cytokines (IL-1 and IL-6) and lung inflammation by Coronavirus-19 (COVI-19 or SARS-CoV- 2): anti-inflammatory strategies. J Biol Regul Homeost Agents. 2020 Mar;34(2) doi: 10.23812/CONTI-E. pii: 1.
    1. Siddiqi Hasan K., Mehra Mandeep R. COVID-19 illness in native and immunosuppressed states: a clinical–therapeutic staging proposal. J. Heart Lung Transp. 2020;39(5):405–407. doi: 10.1016/j.healun.2020.03.012.
    1. Russell B, Moss C, George G, et al. Associations between immune-suppressive and stimulating drugs and novel COVID-19—a systematic review of current evidence. Ecancermedicalscience 14: 1022. .
    1. Zhang Wen, Zhao Yan, Zhang Fengchun, Wang Qian, Li Taisheng, Liu Zhengyin, Wang Jinglan, Qin Yan, Zhang Xuan, Yan Xiaowei, Zeng Xiaofeng, Zhang Shuyang. The use of anti-inflammatory drugs in the treatment of people with severe coronavirus disease 2019 (COVID-19): The Perspectives of clinical immunologists from China. Clin Immunol. 2020;214:108393. doi: 10.1016/j.clim.2020.108393.
    1. Rödel F, Frey B, Manda K, et al. Immunomodulatory properties and molecular effects in inflammatory diseases of low-dose x-irradiation. Front Oncol 2012. 2: 120. Published 2012 Sep 25. doi:10.3389/fonc.2012.00120.
    1. Arenas M., Sabater S., Hernández V. Anti-inflammatory effects of low-dose radiotherapy. Strahlenther Onkol. 2012;188(11):975–981.
    1. Arenas M, Gil F, Gironella M, et al. Time course of anti-inflammatory effect of low-dose radiotherapy: correlation with Epub 2007 Nov 26.
    1. Torres L, Antelo G, Árquez, M, Arenas M. Low-Dose radiation therapy for benign pathologies. Rep Pract Oncol Radiother. 2020. Mar–Apr; 25(2):250–4. doi: 10.1016/j.rpor.2020.02.004. Epub 2020 Feb 22.
    1. Lödermann B., Wunderlich R., Frey S. Low dose ionising radiation leads to a NF-κB dependent decreased secretion of active IL-1β by activated macrophages with a discontinuous dose-dependency. Int J Radiat Biol. 2012;88(10):727–734.
    1. Kirkby C., Mackenzie M. Is low dose radiation therapy a potential treatment for COVID-19 pneumonia? Radiother Oncol. 2020 doi: 10.1016/j.radonc.2020.04.004.
    1. Dhawan G., Kapoor R., Dhawan R. Low dose radiation therapy as a potential life saving treatment for COVID-19-induced acute respiratory distress syndrome (ARDS) Radiother Oncol. 2020 doi: 10.1016/j.radonc.2020.05.002.
    1. Lara Pedro C., Burgos Javier, Macias David. Low dose lung radiotherapy for COVID-19 pneumonia. The rationale for a cost-effective anti-inflammatory treatment. Clin Trans Radiat Oncol. 2020;23:27–29. doi: 10.1016/j.ctro.2020.04.006.
    1. Calabrese EJ, Dhawan G. How radiotherapy was historically used to treat pneumonia: could it be useful today? Yale J Biol Med. 2013;86(4):555–70. Published 2013 Dec 13.
    1. Calabrese E., Dhawan G., Kapoor R., Kozumbo W. Radiotherapy treatment of human inflammatory diseases and conditions: Optimal dose. Hum Exp Toxicol. 2019;38(8):888–898. doi: 10.1177/0960327119846925].
    1. Jansen J.T.M., Broerse J.J., Zoetelief J. Estimation of the carcinogenic risk of radiotherapy of benign diseases from shoulder to heel. Radiother Oncol. 2005;76(3):270–277.
    1. Trott R., Kamprad F. Estimation of cancer risks from radiotherapy of benign diseases. Strahlenther Onkol. 2006;182(8):431–436.
    1. Mazonakis M., Damilakis J. Cancer risk after radiotherapy for benign diseases. PhysicaMedica: Eur J Med Phys. 2017;42:285–291.
    1. Trott K.R., McKeown S.R., Hatfield P. Radiotherapy for benign disease; assessing the risk of radiation-induced cancer following exposure to intermediate dose radiation. Br J Radiol. 2015;88:20150405.

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