Low-dose whole-lung radiation for COVID-19 pneumonia: Planned day 7 interim analysis of a registered clinical trial.
Aged
Aged, 80 and over
Betacoronavirus
/ isolation & purification
COVID-19
Clinical Trials as Topic
Coronavirus Infections
/ complications
Dose-Response Relationship, Radiation
Female
Follow-Up Studies
Humans
Male
Middle Aged
Pandemics
Pneumonia, Viral
/ complications
Prognosis
Risk Factors
SARS-CoV-2
Survival Rate
United States
/ epidemiology
coronavirus
coronavirus disease 2019 (COVID-19)
immune modulation
pandemic
radiation
Journal
Cancer
ISSN: 1097-0142
Titre abrégé: Cancer
Pays: United States
ID NLM: 0374236
Informations de publication
Date de publication:
01 12 2020
01 12 2020
Historique:
received:
28
05
2020
revised:
25
06
2020
accepted:
27
06
2020
pubmed:
29
9
2020
medline:
1
12
2020
entrez:
28
9
2020
Statut:
ppublish
Résumé
Individuals of advanced age with comorbidities face a higher risk of death from coronavirus disease 2019 (COVID-19), especially once they are ventilator-dependent. Respiratory decline in patients with COVID-19 is precipitated by a lung-mediated aberrant immune cytokine storm. Low-dose lung radiation was used to treat pneumonia in the pre-antibiotic era. Radiation immunomodulatory effects may improve outcomes for select patients with COVID-19. A single-institution trial evaluating the safety and efficacy of single-fraction, low-dose whole-lung radiation for patients with COVID-19 pneumonia is being performed for the first time. This report describes outcomes of a planned day 7 interim analysis. Eligible patients were hospitalized, had radiographic consolidation, required supplemental oxygen, and were clinically deteriorating. Of 9 patients screened, 5 were treated with whole-lung radiation on April 24 until April 28 2020, and they were followed for a minimum of 7 days. The median age was 90 years (range, 64-94 years), and 4 were nursing home residents with multiple comorbidities. Within 24 hours of radiation, 3 patients (60%) were weaned from supplemental oxygen to ambient air, 4 (80%) exhibited radiographic improvement, and the median Glasgow Coma Scale score improved from 10 to 14. A fourth patient (80% overall recovery) was weaned from oxygen at hour 96. The mean time to clinical recovery was 35 hours. There were no acute toxicities. In a pilot trial of 5 oxygen-dependent elderly patients with COVID-19 pneumonia, low-dose whole-lung radiation led to rapid improvements in clinical status, encephalopathy, and radiographic consolidation without acute toxicity. Low-dose whole-lung radiation appears to be safe, shows early promise of efficacy, and warrants further study. Researchers at Emory University report preliminary safety outcomes for patients treated with low-dose lung irradiation for coronavirus disease 2019 (COVID-19) pneumonia. Five residents of nursing or group homes were hospitalized after testing positive for COVID-19. Each had pneumonia visible on a chest x-ray, required supplemental oxygen, and experienced a clinical decline in mental status or in work of breathing or a prolonged or escalating supplemental oxygen requirement. A single treatment of low-dose (1.5-Gy) radiation to both lungs was delivered over the course of 10 to 15 minutes. There was no acute toxicity attributable to radiation therapy. Within 24 hours, 4 patients had rapidly improved breathing, and they recovered to room air at an average of 1.5 days (range, 3-96 hours). Three were discharged at a mean time of 12 days, and 1 was preparing for discharge. Blood tests and repeat imaging confirm that low-dose whole-lung radiation treatment appears safe for COVID-19 pneumonia. Further trials are warranted.
Sections du résumé
BACKGROUND
Individuals of advanced age with comorbidities face a higher risk of death from coronavirus disease 2019 (COVID-19), especially once they are ventilator-dependent. Respiratory decline in patients with COVID-19 is precipitated by a lung-mediated aberrant immune cytokine storm. Low-dose lung radiation was used to treat pneumonia in the pre-antibiotic era. Radiation immunomodulatory effects may improve outcomes for select patients with COVID-19.
METHODS
A single-institution trial evaluating the safety and efficacy of single-fraction, low-dose whole-lung radiation for patients with COVID-19 pneumonia is being performed for the first time. This report describes outcomes of a planned day 7 interim analysis. Eligible patients were hospitalized, had radiographic consolidation, required supplemental oxygen, and were clinically deteriorating.
RESULTS
Of 9 patients screened, 5 were treated with whole-lung radiation on April 24 until April 28 2020, and they were followed for a minimum of 7 days. The median age was 90 years (range, 64-94 years), and 4 were nursing home residents with multiple comorbidities. Within 24 hours of radiation, 3 patients (60%) were weaned from supplemental oxygen to ambient air, 4 (80%) exhibited radiographic improvement, and the median Glasgow Coma Scale score improved from 10 to 14. A fourth patient (80% overall recovery) was weaned from oxygen at hour 96. The mean time to clinical recovery was 35 hours. There were no acute toxicities.
CONCLUSIONS
In a pilot trial of 5 oxygen-dependent elderly patients with COVID-19 pneumonia, low-dose whole-lung radiation led to rapid improvements in clinical status, encephalopathy, and radiographic consolidation without acute toxicity. Low-dose whole-lung radiation appears to be safe, shows early promise of efficacy, and warrants further study.
LAY SUMMARY
Researchers at Emory University report preliminary safety outcomes for patients treated with low-dose lung irradiation for coronavirus disease 2019 (COVID-19) pneumonia. Five residents of nursing or group homes were hospitalized after testing positive for COVID-19. Each had pneumonia visible on a chest x-ray, required supplemental oxygen, and experienced a clinical decline in mental status or in work of breathing or a prolonged or escalating supplemental oxygen requirement. A single treatment of low-dose (1.5-Gy) radiation to both lungs was delivered over the course of 10 to 15 minutes. There was no acute toxicity attributable to radiation therapy. Within 24 hours, 4 patients had rapidly improved breathing, and they recovered to room air at an average of 1.5 days (range, 3-96 hours). Three were discharged at a mean time of 12 days, and 1 was preparing for discharge. Blood tests and repeat imaging confirm that low-dose whole-lung radiation treatment appears safe for COVID-19 pneumonia. Further trials are warranted.
Identifiants
pubmed: 32986274
doi: 10.1002/cncr.33130
pmc: PMC7748390
mid: NIHMS1652368
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
5109-5113Subventions
Organisme : NCI NIH HHS
ID : P30 CA138292
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2020 American Cancer Society.
Références
Lancet. 1974 Jul 13;2(7872):81-4
pubmed: 4136544
BMC Med Imaging. 2015 Dec 29;15:61
pubmed: 26714630
Lancet. 2020 Feb 15;395(10223):497-506
pubmed: 31986264
Yale J Biol Med. 2013 Dec 13;86(4):555-70
pubmed: 24348219
Radiat Res. 1990 Aug;123(2):224-7
pubmed: 2117766
N Engl J Med. 2020 May 21;382(21):2012-2022
pubmed: 32227758
Lancet. 2020 Mar 28;395(10229):1033-1034
pubmed: 32192578
N Engl J Med. 2020 Nov 5;383(19):1813-1826
pubmed: 32445440