A Low Dose Whole Lung Radiotherapy for Covid-19 Pneumonia: What have we Learned? Opinion of the International Geriatric Radiotherapy Group.
Main Article Content
Abstract
Background: Coronavirus disease 19 carry a high mortality rate among older patients and minorities such as ethnic Africans and Latinos through the induction of a cytokines storm. Many pharmacologic interventions were proposed to improve the mortality rate from normal organ damage such as pneumonia. Low dose whole lung radiotherapy has been used in the past to treat pneumonia and may improve survival through modulation of the inflammatory cytokines. However, there is a lot of controversy about the efficacy and safety of this treatment modality. Thus, a review of the clinical studies using irradiation for COVID-19 pneumonia is needed to answer those questions
Methods: A literature search of PubMed and Google Scholar was conducted. Reported studies were analyzed to assess safety, efficacy, and inflammatory biomarkers response following low dose whole lung radiotherapy
Results: Patients who required artificial ventilation for COVID-19 did not benefit from low dose whole lung radiotherapy, most likely due to severe lung damage. The inflammatory response may be attenuated after irradiation but it is unclear whether it is independent of the steroid effect.
Conclusion: Randomized studies are required to assess the effect low dose whole lung radiotherapy for COVID-19 pneumonia and its anti-inflammatory property. Such studies are needed for emerging countries with limited resources as radiotherapy may be cost-effective to reduce hospital admission and intensive care unit monitoring.
Keywords:
COVID-19, low dose radiotherapy, pneumonia, cytokines
Article Details
How to Cite
KARLSSON, Ulf et al.
A Low Dose Whole Lung Radiotherapy for Covid-19 Pneumonia: What have we Learned? Opinion of the International Geriatric Radiotherapy Group..
Medical Research Archives, [S.l.], v. 10, n. 9, sep. 2022.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/3085>. Date accessed: 25 apr. 2024.
doi: https://doi.org/10.18103/mra.v10i9.3085.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
1. Grasselli, G, Zangrillo, A, Zanella, A, et al. Baseline and characteristics and outcome of 1591 patients infected with SARS-COVI-2 admitted to ICUs of the Lombardo región, Italy. JAMA 2020; 323: 1574-1581.
2. Mahendra M, Nuchin A, Kumar R, Shreedhar S, Mahesh PA. Predictors of mortality in patients with severe COVID-19 pneumonia-a retrospective study. Adv Resp Med 2021;89:135-144.
3. Tenforde MW, Self WH, Adams K, et al. Association between mRNA vaccination and COVID-19 hospitalization and disease severity. JAMA 2021;326:2043-2054.
4. Lee JE, Hwang M, Kim W, et al, Imaging and clinical features of COVID-19 breakthrough infections: a multicenter study. Radiology 2022; epublication.
5. Owen Schaefer G, Leland RJ, Emanuel EJ. Making vaccines available to other countries before offering domestic booster vaccination. JAMA 2021;326:903-904.
6. Murthy S, Leligdowicg A, Adhikhan NKJ. Intensive care unit capacity in low income countries: a systemic review. PLoS One 2015;10:1-12
7. Beigel JH, Tomashek KM, Dodd LE, et al. Remdesivir for the treatment of COVID-19-preliminary report. N Engl J Med 2020;383:1813-1826
8. Horby P, Lim WS, Emberson JR, et al. Desamethasone in hospitalized patients with COVID-19-Preliminary report. N Engl J Med 2021;384:693-704.
9. Lara PC, Nguyen NP, Macias-Verde D, et al. Pneumonia in the geriatric population: an old effective treatment for a new disease? Recommendation of the International Geriatric Radiotherapy Group. Aging and Disease 2020;11:489-493.
10. Calabrese EJ, Dhawan G. How radiotherapy was historically used to treat pneumonia. Could it be used today? Yale J Biol Med 2013;86:555-570.
11. Arenas M, Sabater S, Hernandez V, et al. Anti-inflammatory effects of low dose radiotherapy. Strahlenther Onkol 2012;188::975-981.
12. Banaei A, Hashemi B, Bakhshandeh M. Estimating cancer risks due to whole lungs radiotherapy with different techniques for treating COVID-19 pneumonia. Radiat Oncol 2022:17:10.
13. Hanna CR, Robb KA, Blyth KG, Jones RJ, Chalmers AJ. Clinicians attitude to using low-dose radiation therapy to treat COVID-19 lung disease. Int J Radiat Oncol Biol Phys 2020;109:886-890.
14. Popescu T, Karlsson U, Vinh-Hung V, et al. Challenges facing radiation oncologists in the management of older cancer patients: Consensus of the International Geriatric Radiotherapy Group. Cancers 2019; 11, 271.
15. Lara PC, Burgos J, Macias D. Low-dose lung radiotherapy for COVID-19 pneumonia. The rationale for a cost-effective agent. Clin Translat Radiat Oncol 2020;23:27-29.
16. Hu H, Pan H, Li R, et al. Increased circulating cytokines have a role in COVID-19 severity and death with a more pronounced effect in males. A systemic review and meta-analysis. Frontiers in Pharmacology 2022, 13.
17. Calabrese EJ, Dhawan G, KapooR R. Radiotherapy treatment of human inflammatory disease and conditions: optimal dose. Hum Exp Toxicol 2019;38:888-898.
18. Arenas M, Gil F, Gironella M, et al. Anti-inflammatory effect of low dose radiotherapy in an experimental model of systemic inflammation in mice. Int J Radiat Oncol Biol Phys 2006;66:560-567.
19. Arenas M, Gil F, Gironella M, et al. Time course of anti-inflammatory effect of low-dose radiotherapy: correlation with TGF β1 expression. Radiother Oncol 2008; 86: 399-406.
20. William Osler. The principles and practice of medicine, 3rd Ed 1898;108-137.
21. Powell EG. Roentgen therapy for lobar pneumonia. JAMA 1938;110:19-22.
22. Oppenheimer A. Roentgen therapy of virus pneumonia. Am J Roentgenol&Rad Ther 1939;49:635-638
23. Oppemheimer A. Roentgen therapy for interstitial pneumonia. J Ped 1943;23:534-538.
24. Scott WR. X-ray therapy in the treatment of acute pneumonia. Am J Roentgenol&Rad Ther 1939;33:331-349.
25. Sanmamed N, Alcantara P, Cerezo E, et al. Low-dose radiation therapy in the management of coronavirus disease 2019 (COVID-19) pneumonia (OWRAD-Cov19): preliminary report. Int J Radiat Oncol Biol Phys 2021;109:880-885.
26. Ghahramani-Asl, Porouhan P, Mehrpouyan M, et al. Feasibility of planning treatment system in localizing the COVID-19 pneumonia lesions and evaluation of volume indices of lung involvement. Dose Response: An Inter J 2020;1-8.
27. Kapoor R, Welsh JS, Dhawan V, et al. Low-dose radiation therapy (LDRT) for COVID-19 and its deadlier variants. Arch Toxicol 2021;95:3425-3432.
28. Papachristofilou A, Finazzi T, Blum A, et al. Low-dose radiation therapy for severe COVID-19 pneumonia: A randomized double-blind study. Int J Radiat Oncol Phys 2021;110: 1274-1282.
29. Talbot CJ, Veldwijk MR, Azria D, et al. Muli-center technical evaluation of the radiation-induced lymphocyte apoptosis assay as a predictive test for radiotherapy toxicity. Clin Translat Radiat Oncol 2019;18:1-8.
30. Ortiz CS, Hernandez D, Trujillo C, et al. The clinical efficacy of low-dose whole-lung irradiation in moderate-to-severe COVID-19 pneumonia: RTMX-20 trial. Radiother Oncol 2022;166:133-136.
31. Darzikolae NM, Kolahdouzan K, Abtahi H, et al. Low-dose whole lung irradiation in severe COVID-19 pneumonia: a controlled clinical trial. J Med Radiat Sci 2021;68:396-406.
32. Auld SC, Caridi-Scheible M, Blum JM, et al. ICU and ventilator mortality among critically ill adults with Corona virus disease 19. Crit Care Med 2021;e publication.
33. de Roquetaillade C, Bredin S, Lascarrou J, et al. Timing and cause of death in severe COVID-19 patients. Crit Care 2021;25:224
34. Elsoukkary SS, Mostika M, Dillard A, et al. Autopsy findings in 32 patients with COVID-19: A single institution experience. Pathol Biol 2021;88:56-68.
35. Fitzek A, Schadler J, Dietz E, et al. Prospective postmortem evaluation of 735 consecutive SARS-CoV-2 associated death cases. Scient Rep 2021;11:19342.
36. Ganesan G, Ponniah S, Sundaram V, et al. Whole lung irradiation as a novel treatment for COVID-19: Final results of the prospective randomized trial (WINCOVID trial. Radiother Oncol 2022:167:133-142.
37. Hess CP, Eng TY, Nasti TH, et al. Whole-lung low-dose radiation therapy (LD-RT) for non-intubated oxygen-dependent patients with COVID-19-related pneumonia receiving dexamethasone and/or remdesivir. Radiat Oncol 2021;165:20-31.
38. Arenas M, Algara M, De Febrer G, et al. 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. Strahlenther Onkol 2021;197:1010-1020.
39. Sharma DN, Guleria R, Wig N, et al. Low-dose radiation therapy for COVID-19 pneumonia: a pilot study. Br J Radiol 2021;94:20210187.
40. Ameri A, Ameri P, Rahnama N, et al. Low-dose whole-lung irradiation for COVID-19 pneumonia: Final results of a pilot study. Int J Radiat Oncol Biol Phys 2020:100:859-866.
41. Moreno-Olmedo E, Gironzini VS, Perez M, et al. COVID-19 pneumonia treates with ultra-low doses of radiotherapy (ULTRA-COVID study): a single institution report of two cases. Strahlenther Onkol 2021;197:429-437.
42. Del Castillo R, Martinez D, Sarria GJ, et al. Low-dose radiotherapy for COVID-19 pneumonia treatment: case report, procedure, and literature review. Strahlenther Onkol 2020;196:1086-1093.
43. Hugo TC, Nguyen HV, Sophie Y, et al. Achieving affordable critical care in low-income and middle-income countries. BMJ Global Health 2019;4:e001675.
44. Dondorp AM, Papali AC, Schu;tz MJ. Recommendations for the management of COVID-19 in low and middle income countries. Am J Trop Med Hyg 2021;104(Suppl):1-2.
45. Dasta JF, McLaughlin TP, Mody SM, Piech CT. Daily cost of an intensive care unit day: the contribution of mechanical ventilation. Crit Care Med 2005;33:1266-1271.
46. Ramachandan R, Ross JS, Miller JE. Access to COVID-19 vaccines in high, middle, and low-income countries hosting clinical trials. JAMA Network open 2021;4:e2134233.
47. Nguyen NP, Vinh-Hung V, Baumert M, et al. Older cancer patients during the COVID-19 epidemic: Practice proposal of the International Geriatric Radiotherapy Group. Cancers 2020;12:1287
2. Mahendra M, Nuchin A, Kumar R, Shreedhar S, Mahesh PA. Predictors of mortality in patients with severe COVID-19 pneumonia-a retrospective study. Adv Resp Med 2021;89:135-144.
3. Tenforde MW, Self WH, Adams K, et al. Association between mRNA vaccination and COVID-19 hospitalization and disease severity. JAMA 2021;326:2043-2054.
4. Lee JE, Hwang M, Kim W, et al, Imaging and clinical features of COVID-19 breakthrough infections: a multicenter study. Radiology 2022; epublication.
5. Owen Schaefer G, Leland RJ, Emanuel EJ. Making vaccines available to other countries before offering domestic booster vaccination. JAMA 2021;326:903-904.
6. Murthy S, Leligdowicg A, Adhikhan NKJ. Intensive care unit capacity in low income countries: a systemic review. PLoS One 2015;10:1-12
7. Beigel JH, Tomashek KM, Dodd LE, et al. Remdesivir for the treatment of COVID-19-preliminary report. N Engl J Med 2020;383:1813-1826
8. Horby P, Lim WS, Emberson JR, et al. Desamethasone in hospitalized patients with COVID-19-Preliminary report. N Engl J Med 2021;384:693-704.
9. Lara PC, Nguyen NP, Macias-Verde D, et al. Pneumonia in the geriatric population: an old effective treatment for a new disease? Recommendation of the International Geriatric Radiotherapy Group. Aging and Disease 2020;11:489-493.
10. Calabrese EJ, Dhawan G. How radiotherapy was historically used to treat pneumonia. Could it be used today? Yale J Biol Med 2013;86:555-570.
11. Arenas M, Sabater S, Hernandez V, et al. Anti-inflammatory effects of low dose radiotherapy. Strahlenther Onkol 2012;188::975-981.
12. Banaei A, Hashemi B, Bakhshandeh M. Estimating cancer risks due to whole lungs radiotherapy with different techniques for treating COVID-19 pneumonia. Radiat Oncol 2022:17:10.
13. Hanna CR, Robb KA, Blyth KG, Jones RJ, Chalmers AJ. Clinicians attitude to using low-dose radiation therapy to treat COVID-19 lung disease. Int J Radiat Oncol Biol Phys 2020;109:886-890.
14. Popescu T, Karlsson U, Vinh-Hung V, et al. Challenges facing radiation oncologists in the management of older cancer patients: Consensus of the International Geriatric Radiotherapy Group. Cancers 2019; 11, 271.
15. Lara PC, Burgos J, Macias D. Low-dose lung radiotherapy for COVID-19 pneumonia. The rationale for a cost-effective agent. Clin Translat Radiat Oncol 2020;23:27-29.
16. Hu H, Pan H, Li R, et al. Increased circulating cytokines have a role in COVID-19 severity and death with a more pronounced effect in males. A systemic review and meta-analysis. Frontiers in Pharmacology 2022, 13.
17. Calabrese EJ, Dhawan G, KapooR R. Radiotherapy treatment of human inflammatory disease and conditions: optimal dose. Hum Exp Toxicol 2019;38:888-898.
18. Arenas M, Gil F, Gironella M, et al. Anti-inflammatory effect of low dose radiotherapy in an experimental model of systemic inflammation in mice. Int J Radiat Oncol Biol Phys 2006;66:560-567.
19. Arenas M, Gil F, Gironella M, et al. Time course of anti-inflammatory effect of low-dose radiotherapy: correlation with TGF β1 expression. Radiother Oncol 2008; 86: 399-406.
20. William Osler. The principles and practice of medicine, 3rd Ed 1898;108-137.
21. Powell EG. Roentgen therapy for lobar pneumonia. JAMA 1938;110:19-22.
22. Oppenheimer A. Roentgen therapy of virus pneumonia. Am J Roentgenol&Rad Ther 1939;49:635-638
23. Oppemheimer A. Roentgen therapy for interstitial pneumonia. J Ped 1943;23:534-538.
24. Scott WR. X-ray therapy in the treatment of acute pneumonia. Am J Roentgenol&Rad Ther 1939;33:331-349.
25. Sanmamed N, Alcantara P, Cerezo E, et al. Low-dose radiation therapy in the management of coronavirus disease 2019 (COVID-19) pneumonia (OWRAD-Cov19): preliminary report. Int J Radiat Oncol Biol Phys 2021;109:880-885.
26. Ghahramani-Asl, Porouhan P, Mehrpouyan M, et al. Feasibility of planning treatment system in localizing the COVID-19 pneumonia lesions and evaluation of volume indices of lung involvement. Dose Response: An Inter J 2020;1-8.
27. Kapoor R, Welsh JS, Dhawan V, et al. Low-dose radiation therapy (LDRT) for COVID-19 and its deadlier variants. Arch Toxicol 2021;95:3425-3432.
28. Papachristofilou A, Finazzi T, Blum A, et al. Low-dose radiation therapy for severe COVID-19 pneumonia: A randomized double-blind study. Int J Radiat Oncol Phys 2021;110: 1274-1282.
29. Talbot CJ, Veldwijk MR, Azria D, et al. Muli-center technical evaluation of the radiation-induced lymphocyte apoptosis assay as a predictive test for radiotherapy toxicity. Clin Translat Radiat Oncol 2019;18:1-8.
30. Ortiz CS, Hernandez D, Trujillo C, et al. The clinical efficacy of low-dose whole-lung irradiation in moderate-to-severe COVID-19 pneumonia: RTMX-20 trial. Radiother Oncol 2022;166:133-136.
31. Darzikolae NM, Kolahdouzan K, Abtahi H, et al. Low-dose whole lung irradiation in severe COVID-19 pneumonia: a controlled clinical trial. J Med Radiat Sci 2021;68:396-406.
32. Auld SC, Caridi-Scheible M, Blum JM, et al. ICU and ventilator mortality among critically ill adults with Corona virus disease 19. Crit Care Med 2021;e publication.
33. de Roquetaillade C, Bredin S, Lascarrou J, et al. Timing and cause of death in severe COVID-19 patients. Crit Care 2021;25:224
34. Elsoukkary SS, Mostika M, Dillard A, et al. Autopsy findings in 32 patients with COVID-19: A single institution experience. Pathol Biol 2021;88:56-68.
35. Fitzek A, Schadler J, Dietz E, et al. Prospective postmortem evaluation of 735 consecutive SARS-CoV-2 associated death cases. Scient Rep 2021;11:19342.
36. Ganesan G, Ponniah S, Sundaram V, et al. Whole lung irradiation as a novel treatment for COVID-19: Final results of the prospective randomized trial (WINCOVID trial. Radiother Oncol 2022:167:133-142.
37. Hess CP, Eng TY, Nasti TH, et al. Whole-lung low-dose radiation therapy (LD-RT) for non-intubated oxygen-dependent patients with COVID-19-related pneumonia receiving dexamethasone and/or remdesivir. Radiat Oncol 2021;165:20-31.
38. Arenas M, Algara M, De Febrer G, et al. 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. Strahlenther Onkol 2021;197:1010-1020.
39. Sharma DN, Guleria R, Wig N, et al. Low-dose radiation therapy for COVID-19 pneumonia: a pilot study. Br J Radiol 2021;94:20210187.
40. Ameri A, Ameri P, Rahnama N, et al. Low-dose whole-lung irradiation for COVID-19 pneumonia: Final results of a pilot study. Int J Radiat Oncol Biol Phys 2020:100:859-866.
41. Moreno-Olmedo E, Gironzini VS, Perez M, et al. COVID-19 pneumonia treates with ultra-low doses of radiotherapy (ULTRA-COVID study): a single institution report of two cases. Strahlenther Onkol 2021;197:429-437.
42. Del Castillo R, Martinez D, Sarria GJ, et al. Low-dose radiotherapy for COVID-19 pneumonia treatment: case report, procedure, and literature review. Strahlenther Onkol 2020;196:1086-1093.
43. Hugo TC, Nguyen HV, Sophie Y, et al. Achieving affordable critical care in low-income and middle-income countries. BMJ Global Health 2019;4:e001675.
44. Dondorp AM, Papali AC, Schu;tz MJ. Recommendations for the management of COVID-19 in low and middle income countries. Am J Trop Med Hyg 2021;104(Suppl):1-2.
45. Dasta JF, McLaughlin TP, Mody SM, Piech CT. Daily cost of an intensive care unit day: the contribution of mechanical ventilation. Crit Care Med 2005;33:1266-1271.
46. Ramachandan R, Ross JS, Miller JE. Access to COVID-19 vaccines in high, middle, and low-income countries hosting clinical trials. JAMA Network open 2021;4:e2134233.
47. Nguyen NP, Vinh-Hung V, Baumert M, et al. Older cancer patients during the COVID-19 epidemic: Practice proposal of the International Geriatric Radiotherapy Group. Cancers 2020;12:1287