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Reduced Intubation Rates Following Whole-Lung Low-Dose Radiation Therapy (LD-RT) in Patients With COVID-19-Related Pneumonia
PURPOSE/OBJECTIVE(S): Low-dose radiotherapy (LD-RT) is a well-established treatment for multiple human inflammatory conditions. Whole-lung LD-RT may be effective in COVID-19-related pneumonia. MATERIALS/METHODS: Patients hospitalized with COVID-19-related pneumonia receiving supportive care, glucoco...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Published by Elsevier Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8536245/ http://dx.doi.org/10.1016/j.ijrobp.2021.07.365 |
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author | Hess, C.B. Eng, T.Y. Nasti, T. Dhere, V.R. Kleber, T. Switchenko, J. Weinberg, B.D. Rouphael, N. Tian, S. Rudra, S. Taverna, L.S. Perez, A. Ahmed, R. Khan, M.K. |
author_facet | Hess, C.B. Eng, T.Y. Nasti, T. Dhere, V.R. Kleber, T. Switchenko, J. Weinberg, B.D. Rouphael, N. Tian, S. Rudra, S. Taverna, L.S. Perez, A. Ahmed, R. Khan, M.K. |
author_sort | Hess, C.B. |
collection | PubMed |
description | PURPOSE/OBJECTIVE(S): Low-dose radiotherapy (LD-RT) is a well-established treatment for multiple human inflammatory conditions. Whole-lung LD-RT may be effective in COVID-19-related pneumonia. MATERIALS/METHODS: Patients hospitalized with COVID-19-related pneumonia receiving supportive care, glucocorticosteroids, and/or remdesivir were administered LD-RT treatment of 0.5 or 1.5 Gy to the bilateral lungs on a prospective, combined phase I/II, multi-site, single-institution trial. Patients were followed for 28 days or until discharge and compared to controls blindly matched by age, comorbidity, duration of symptoms, and disease severity. Eligible patients were confirmed by SARS-CoV-2 positive PCR, unable to wean from oxygen at enrollment, and had radiographic consolidations. Patients were enrolled into 5 cohorts stratified by treatment variables and severity of illness: LD-RT alone vs. LD-RT with concurrent drug therapies, non-intubated vs. intubated status, and low (1.5 Gy) vs. lower (0.5 Gy) radiation dose. Qualitative aims were to establish safety and explore efficacy. Quantitative endpoints were continuous, categorical, and time-to-event, and included clinical recovery, intubation, radiographic changes, and biomarker responses. Intubation endpoints are reported for all cohorts using the log-rank test and Kaplan-Meier method. RESULTS: Outcomes of 80 patients were available for analysis at study closure. In total, 40 of 70 planned patients (57% trial enrollment) received whole-lung LD-RT between April 24 and December 7, 2020 and were compared to 40 matched controls. Cohorts 1&2: Ten non-intubated patients received 1.5 Gy without concurrent COVID-directed drug therapies (10 of 10 planned, 100% cohort enrollment) and were compared to matched controls. Intubation rates were 40% in controls compared to 10% following LD-RT (P = 0.11). Cohort 3: One intubated patient received 1.5 Gy (1 of 20 planned, 5% cohort enrollment). Cohort 4: Twenty separate non-intubated patients received 1.5 Gy with concurrent dexamethasone/remdesivir (20 of 20 planned, 100% cohort enrollment) and were compared to matched controls. Intubation rates were 32% in controls compared to 14% following LD-RT (P = 0.09). Cohort 5: Nine patients received 0.5 Gy with concurrent drug therapies (9 of 20 planned, 45% cohort enrollment) and were compared to matched controls. Zero controls required intubation compared to 11% following LD-RT (P = 0.32). Among all non-intubated patients and matched controls combined (n = 78), mechanical ventilation was required in 28% of controls compared to 12% following LD-RT (reduced 57%, P = 0.05). The trial was prematurely closed due to observed reproducibility of efficacy. A randomized trial is now ongoing. CONCLUSION: In the first, prospective, phase I/II trial of radiotherapy for COVID-19-related pneumonia, a single treatment of whole-lung LD-RT reduced intubation rates by 57% compared to controls in patients receiving supportive care with or without drug therapies (P = 0.05). |
format | Online Article Text |
id | pubmed-8536245 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Published by Elsevier Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-85362452021-10-25 Reduced Intubation Rates Following Whole-Lung Low-Dose Radiation Therapy (LD-RT) in Patients With COVID-19-Related Pneumonia Hess, C.B. Eng, T.Y. Nasti, T. Dhere, V.R. Kleber, T. Switchenko, J. Weinberg, B.D. Rouphael, N. Tian, S. Rudra, S. Taverna, L.S. Perez, A. Ahmed, R. Khan, M.K. Int J Radiat Oncol Biol Phys 2032 PURPOSE/OBJECTIVE(S): Low-dose radiotherapy (LD-RT) is a well-established treatment for multiple human inflammatory conditions. Whole-lung LD-RT may be effective in COVID-19-related pneumonia. MATERIALS/METHODS: Patients hospitalized with COVID-19-related pneumonia receiving supportive care, glucocorticosteroids, and/or remdesivir were administered LD-RT treatment of 0.5 or 1.5 Gy to the bilateral lungs on a prospective, combined phase I/II, multi-site, single-institution trial. Patients were followed for 28 days or until discharge and compared to controls blindly matched by age, comorbidity, duration of symptoms, and disease severity. Eligible patients were confirmed by SARS-CoV-2 positive PCR, unable to wean from oxygen at enrollment, and had radiographic consolidations. Patients were enrolled into 5 cohorts stratified by treatment variables and severity of illness: LD-RT alone vs. LD-RT with concurrent drug therapies, non-intubated vs. intubated status, and low (1.5 Gy) vs. lower (0.5 Gy) radiation dose. Qualitative aims were to establish safety and explore efficacy. Quantitative endpoints were continuous, categorical, and time-to-event, and included clinical recovery, intubation, radiographic changes, and biomarker responses. Intubation endpoints are reported for all cohorts using the log-rank test and Kaplan-Meier method. RESULTS: Outcomes of 80 patients were available for analysis at study closure. In total, 40 of 70 planned patients (57% trial enrollment) received whole-lung LD-RT between April 24 and December 7, 2020 and were compared to 40 matched controls. Cohorts 1&2: Ten non-intubated patients received 1.5 Gy without concurrent COVID-directed drug therapies (10 of 10 planned, 100% cohort enrollment) and were compared to matched controls. Intubation rates were 40% in controls compared to 10% following LD-RT (P = 0.11). Cohort 3: One intubated patient received 1.5 Gy (1 of 20 planned, 5% cohort enrollment). Cohort 4: Twenty separate non-intubated patients received 1.5 Gy with concurrent dexamethasone/remdesivir (20 of 20 planned, 100% cohort enrollment) and were compared to matched controls. Intubation rates were 32% in controls compared to 14% following LD-RT (P = 0.09). Cohort 5: Nine patients received 0.5 Gy with concurrent drug therapies (9 of 20 planned, 45% cohort enrollment) and were compared to matched controls. Zero controls required intubation compared to 11% following LD-RT (P = 0.32). Among all non-intubated patients and matched controls combined (n = 78), mechanical ventilation was required in 28% of controls compared to 12% following LD-RT (reduced 57%, P = 0.05). The trial was prematurely closed due to observed reproducibility of efficacy. A randomized trial is now ongoing. CONCLUSION: In the first, prospective, phase I/II trial of radiotherapy for COVID-19-related pneumonia, a single treatment of whole-lung LD-RT reduced intubation rates by 57% compared to controls in patients receiving supportive care with or without drug therapies (P = 0.05). Published by Elsevier Inc. 2021-11-01 2021-10-22 /pmc/articles/PMC8536245/ http://dx.doi.org/10.1016/j.ijrobp.2021.07.365 Text en Copyright © 2021 Published by Elsevier Inc. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. |
spellingShingle | 2032 Hess, C.B. Eng, T.Y. Nasti, T. Dhere, V.R. Kleber, T. Switchenko, J. Weinberg, B.D. Rouphael, N. Tian, S. Rudra, S. Taverna, L.S. Perez, A. Ahmed, R. Khan, M.K. Reduced Intubation Rates Following Whole-Lung Low-Dose Radiation Therapy (LD-RT) in Patients With COVID-19-Related Pneumonia |
title | Reduced Intubation Rates Following Whole-Lung Low-Dose Radiation Therapy (LD-RT) in Patients With COVID-19-Related Pneumonia |
title_full | Reduced Intubation Rates Following Whole-Lung Low-Dose Radiation Therapy (LD-RT) in Patients With COVID-19-Related Pneumonia |
title_fullStr | Reduced Intubation Rates Following Whole-Lung Low-Dose Radiation Therapy (LD-RT) in Patients With COVID-19-Related Pneumonia |
title_full_unstemmed | Reduced Intubation Rates Following Whole-Lung Low-Dose Radiation Therapy (LD-RT) in Patients With COVID-19-Related Pneumonia |
title_short | Reduced Intubation Rates Following Whole-Lung Low-Dose Radiation Therapy (LD-RT) in Patients With COVID-19-Related Pneumonia |
title_sort | reduced intubation rates following whole-lung low-dose radiation therapy (ld-rt) in patients with covid-19-related pneumonia |
topic | 2032 |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8536245/ http://dx.doi.org/10.1016/j.ijrobp.2021.07.365 |
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