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Open Access 01-11-2021 | Pneumonia | Original Article

Could pulmonary low-dose radiation therapy be an alternative treatment for patients with COVID-19 pneumonia? Preliminary results of a multicenter SEOR-GICOR nonrandomized prospective trial (IPACOVID trial)

Published in: Strahlentherapie und Onkologie | Issue 11/2021

Abstract

Purpose

To evaluate the efficacy and safety of lung low-dose radiation therapy (LD-RT) for pneumonia in patients with coronavirus disease 2019 (COVID-19).

Materials and methods

Inclusion criteria comprised patients with COVID-19-related moderate–severe pneumonia warranting hospitalization with supplemental O₂ and not candidates for admission to the intensive care unit because of comorbidities or general status. All patients received single lung dose of 0.5 Gy. Respiratory and systemic inflammatory parameters were evaluated before irradiation, at 24 h and 1 week after LD-RT. Primary endpoint was increased in the ratio of arterial oxygen partial pressure (PaO₂) or the pulse oximetry saturation (SpO₂) to fractional inspired oxygen (FiO₂) ratio of at least 20% at 24 h with respect to the preirradiation value.

Results

Between June and November 2020, 36 patients with COVID-19 pneumonia and a mean age of 84 years were enrolled. Seventeen were women and 19 were men and all of them had comorbidities. All patients had bilateral pulmonary infiltrates on chest X‑ray. All patients received dexamethasone treatment. Mean SpO₂ pretreatment value was 94.28% and the SpO₂/FiO₂ ratio varied from 255 mm Hg to 283 mm Hg at 24 h and to 381 mm Hg at 1 week, respectively. In those who survived (23/36, 64%), a significant improvement was observed in the percentage of lung involvement in the CT scan at 1 week after LD-RT. No adverse effects related to radiation treatment have been reported.

Conclusions

LD-RT appears to be a feasible and safe option in a population with COVID-19 bilateral interstitial pneumonia in the presence of significant comorbidities.

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Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ, HLH Across Speciality Collaboration, UK (2020) COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet 395(10229):1033–1034. https://doi.org/10.1016/S0140-6736(20)30628-0CrossRefPubMedPubMedCentral

Calabrese EJ, Dhawan G, Kapoor R (2017) Radiotherapy for pertussis: an historical assessment. Dose Response. https://doi.org/10.1177/1559325817704760CrossRefPubMedPubMedCentral

Calabrese EJ, Dhawan G, Kapoor R (2015) The use of X rays in the treatment of bronchial asthma: a historical assessment. Radiat Res 184(2):180–192. https://doi.org/10.1667/rr14080.1CrossRefPubMed

Calabrese EJ, Dhawan G (2013) How radiotherapy was historically used to treat pneumonia: could it be useful today? Yale J Biol Med 86(4):555–570PubMedPubMedCentral

Arenas M, Sabater S, Hernández V et al (2012) Anti-inflammatory effects of low-dose radiotherapy. Indications, dose, and radiobiological mechanisms involved. Strahlenther Onkol 188(11):975–981. https://doi.org/10.1007/s00066-012-0170-8CrossRefPubMed

Rödel F, Frey B, Manda K et al (2012) Immunomodulatory properties and molecular effects in inflammatory diseases of low-dose x‑irradiation. Front Oncol 2:120. https://doi.org/10.3389/fonc.2012.00120CrossRefPubMedPubMedCentral

Lödermann B, Wunderlich R, Frey S et al (2012) 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 88(10):727–734CrossRefPubMed

Torres Royo L, Antelo Redondo G, ÁrquezPianetta M, Arenas Prat M (2020) Low-Dose radiation therapy for benign pathologies. Rep Pract Oncol Radiother 25(2):250–254. https://doi.org/10.1016/j.rpor.2020.02.004CrossRefPubMedPubMedCentral

Arenas M, Gil F, Gironella M et al (2008) Time course of anti-inflammatory effect of low-dose radiotherapy: correlation with TGF-beta(1) expression. Radiother Oncol 86(3):399–406. https://doi.org/10.1016/j.radonc.2007.10.032CrossRefPubMed

10.

Pandey BN (2020) Low-dose radiation therapy for coronavirus disease-2019 pneumonia: is it time to look beyond apprehensions? Ann Thorac Med 15:199–207CrossRefPubMedPubMedCentral

11.

Algara M, Arenas M, Marin J et al (2020) Low dose anti-inflammatory radiotherapy for the treatment of pneumonia by covid-19: a proposal for a multi-centric prospective trial. Clin Transl Radiat Oncol 24:29–33. https://doi.org/10.1016/j.ctro.2020.06.005CrossRefPubMedPubMedCentral

12.

Jamilloux Y, Henry T, Belot A et al (2020) Should we stimulate or suppress immune responses in COVID-19? Cytokine and anti-cytokine interventions. Autoimmun Rev 19(7):102567. https://doi.org/10.1016/j.autrev.2020.102567CrossRefPubMedPubMedCentral

13.

Siemieniuk RA, Bartoszko JJ, Ge L et al (2020) Drug treatments for covid-19: living systematic review and network meta-analysis. BMJ 370:m2980. https://doi.org/10.1136/bmj.m2980CrossRefPubMed

14.

Conti P, Ronconi G, Caraffa A et al (2020) 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 34(2):327–331. https://doi.org/10.23812/CONTI-ECrossRefPubMed

15.

Siddiqi HK, Mehra MR (2020) COVID-19 illness in native and immunosuppressed states: a clinical-therapeutic staging proposal. J Heart Lung Transplant. https://doi.org/10.1016/j.healun.2020.03.012CrossRefPubMedPubMedCentral

16.

RECOVERY Collaborative Group, Horby P, Lim WS, Emberson JR et al (2020) Dexamethasone in hospitalized patients with Covid-19—preliminary report. N Engl J Med. https://doi.org/10.1056/NEJMoa2021436CrossRef

17.

Beigel JH, Tomashek KM, Dodd LE, ACTT‑1 Study Group Members et al (2020) Remdesivir for the treatment of Covid-19—final report. N Engl J Med. https://doi.org/10.1056/NEJMoa2007764CrossRefPubMedPubMedCentral

18.

Juul S, Nielsen EE, Feinberg J et al (2020) Interventions for treatment of COVID-19: a living systematic review with meta-analyses and trial sequential analyses (the LIVING project). PLoS Med 17(9):e1003293. https://doi.org/10.1371/journal.pmed.1003293CrossRefPubMedPubMedCentral

19.

Sun M, Xu Y, He H et al (2020) A potentially effective treatment for COVID-19: A systematic review and meta-analysis of convalescent plasma therapy in treating severe infectious disease. Int J Infect Dis 98:334–346. https://doi.org/10.1016/j.ijid.2020.06.107CrossRefPubMedPubMedCentral

20.

Dhawan G, Kapoor R, Dhawan R et al (2020) Low dose radiation therapy as a potential life saving treatment for COVID-19-induced acute respiratory distress syndrome (ARDS). Radiother Oncol 147:212–216. https://doi.org/10.1016/j.radonc.2020.05.002CrossRefPubMedPubMedCentral

21.

Lara PC, Burgos J, Macias D (2020) Low dose lung radiotherapy for COVID-19 pneumonia. The rationale for a cost-effective anti-inflammatory treatment. Clin Transl Radiat Oncol 23:27–29. https://doi.org/10.1016/j.ctro.2020.04.006CrossRefPubMedPubMedCentral

22.

Prasanna PG, Woloschak GE, DiCarlo AL et al (2020) Low-dose radiation therapy (LDRT) for COVID-19: benefits or risks? Radiat Res 194(5):452–464. https://doi.org/10.1667/RADE-20-00211.1CrossRefPubMedPubMedCentral

23.

Ameri A, Rahnama N, Bozorgmehr R et al (2020) Low-dose whole-lung irradiation for COVID-19 pneumonia: short course results. Int J Radiat Oncol Biol Phys 108(5):1134–1139. https://doi.org/10.1016/j.ijrobp.2020.07.026CrossRefPubMedPubMedCentral

24.

Hess CB, Buchwald ZS, Stokes W et al (2020) Low-dose whole-lung radiation for COVID-19 pneumonia: planned day 7 interim analysis of a registered clinical trial. Cancer 126:5109–5113. https://doi.org/10.1002/cncr.33130CrossRefPubMed

25.

Hess CB, Nasti TH, Dhere V et al (2021) Immunomodulatory low-dose whole-lung radiation for patients with COVID-19-related pneumonia. Int J Radiat Oncol Biol Phys. https://doi.org/10.1016/j.ijrobp.2020.12.011CrossRefPubMedPubMedCentral

26.

Moreno-Olmedo E, Suárez-Gironzini V, Pérez M, Filigheddu T, Mínguez C, Sanjuan-Sanjuan A, González JA, Rivas D, Gorospe L, Larrea L, López E (2021) COVID-19 pneumonia treated with ultra-low doses of radiotherapy (ULTRA-COVID study): a single institution report of two cases. Strahlenther Onkol 197(5):429–437. https://doi.org/10.1007/s00066-020-01743-4CrossRefPubMedPubMedCentral

27.

Del Castillo R, Martinez D, Sarria GJ et al (2020) Low-dose radiotherapy for COVID-19 pneumonia treatment: case report, procedure, and literature review. Strahlenther Onkol 196(12):1086–1093. https://doi.org/10.1007/s00066-020-01675-zCrossRefPubMedPubMedCentral

28.

Sanmamed N, Alcantara P, Cerezo E et al (2020) Low dose radiotherapy in the management of covid19 pneumonia (LOWRAD-Cov19). Preliminary report. Int J Radiat Oncol Biol Phys. https://doi.org/10.1016/j.ijrobp.2020.11.049CrossRefPubMedPubMedCentral

29.

Papachristofilou A, Finazzi T, Blum A, Zehnder T, Zellweger N, Lustenberger J, Bauer T, Dott C, Avcu Y, Kohler G, Zimmermann F, Pargger H, Siegemund M (2021) Low-dose radiation therapy for severe COVID-19 pneumonia: a randomized double-blind study. Int J Radiat Oncol Biol Phys. https://doi.org/10.1016/j.ijrobp.2021.02.054CrossRefPubMedPubMedCentral

30.

Jansen JT, Broerse JJ, Zoetelief J, Klein C, Seegenschmiedt HM (2005) Estimation of the carcinogenic risk of radiotherapy of benign diseases from shoulder to heel. Radiother Oncol 76(3):270–277. https://doi.org/10.1016/j.radonc.2005.06.034CrossRefPubMed

31.

Mazonakis M, Damilakis J (2017) Cancer risk after radiotherapy for benign diseases. Phys Med 42:285–291CrossRefPubMed

32.

McKeown SR, Hatfield P, Prestwich RJ, Shaffer RE, Taylor RE (2015) Radiotherapy for benign disease; assessing the risk of radiation-induced cancer following exposure to intermediate dose radiation. Br J Radiol 88(1056):20150405. https://doi.org/10.1259/bjr.20150405CrossRefPubMedPubMedCentral

33.

Arruda GV, Weber RRDS, Bruno AC, Pavoni JF (2021) The risk of induced cancer and ischemic heart disease following low dose lung irradiation for COVID-19: estimation based on a virtual case. Int J Radiat Biol 97(2):120–125. https://doi.org/10.1080/09553002.2021CrossRefPubMed

34.

Fan Q, Zhang B, Ma J, Zhang S (2020) Safety profile of the antiviral drug remdesivir: an update. Biomed Pharmacother 130:110532. https://doi.org/10.1016/j.biopha.2020.110532CrossRefPubMedPubMedCentral

35.

Choi SW, Shin JS, Park SJ et al (2020) Antiviral activity and safety of remdesivir against SARS-CoV‑2 infection in human pluripotent stem cell-derived cardiomyocytes. Antiviral Res. https://doi.org/10.1016/j.antiviral.2020.104955CrossRefPubMedPubMedCentral

36.

Khiali S, Khani E, Entezari-Maleki T (2020) A comprehensive review of tocilizumab in COVID-19 acute respiratory distress syndrome. J Clin Pharmacol 60(9):1131–1146. https://doi.org/10.1002/jcph.1693CrossRefPubMed

Title: Could pulmonary low-dose radiation therapy be an alternative treatment for patients with COVID-19 pneumonia? Preliminary results of a multicenter SEOR-GICOR nonrandomized prospective trial (IPACOVID trial)
Publication date: 01-11-2021
Keywords: Pneumonia
COVID-19
Published in: Strahlentherapie und Onkologie / Issue 11/2021
Print ISSN: 0179-7158
Electronic ISSN: 1439-099X
DOI: https://doi.org/10.1007/s00066-021-01803-3

At a glance: The STEP trials

Springer Medicine

Could pulmonary low-dose radiation therapy be an alternative treatment for patients with COVID-19 pneumonia? Preliminary results of a multicenter SEOR-GICOR nonrandomized prospective trial (IPACOVID trial)

Abstract

Purpose

Materials and methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Purpose

Materials and methods

Results

Conclusions

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