Low-dose whole-lung radiation for COVID-19 pneumonia: Planned day 7 interim analysis of a registered clinical trial.


Journal

Cancer
ISSN: 1097-0142
Titre abrégé: Cancer
Pays: United States
ID NLM: 0374236

Informations de publication

Date de publication:
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

5109-5113

Subventions

Organisme : NCI NIH HHS
ID : P30 CA138292
Pays : United States

Commentaires et corrections

Type : CommentIn

Informations de copyright

© 2020 American Cancer Society.

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Auteurs

Clayton B Hess (CB)

Department of Radiation Oncology, Emory University, Atlanta, Georgia.
Winship Cancer Institute, Emory University, Atlanta, Georgia.

Zachary S Buchwald (ZS)

Department of Radiation Oncology, Emory University, Atlanta, Georgia.
Winship Cancer Institute, Emory University, Atlanta, Georgia.

William Stokes (W)

Department of Radiation Oncology, Emory University, Atlanta, Georgia.
Winship Cancer Institute, Emory University, Atlanta, Georgia.

Tahseen H Nasti (TH)

Department of Microbiology and Immunology, Emory University, Atlanta, Georgia.

Jeffrey M Switchenko (JM)

Winship Cancer Institute, Emory University, Atlanta, Georgia.
Department of Biostatistics and Bioinformatics, Emory University, Atlanta, Georgia.

Brent D Weinberg (BD)

Department of Diagnostic Radiology, Emory University, Atlanta, Georgia.

James P Steinberg (JP)

Department of Infectious Disease, Emory University, Atlanta, Georgia.

Karen D Godette (KD)

Department of Radiation Oncology, Emory University, Atlanta, Georgia.
Winship Cancer Institute, Emory University, Atlanta, Georgia.

David Murphy (D)

Department of Pulmonary Critical Care, Emory University, Atlanta, Georgia.

Rafi Ahmed (R)

Winship Cancer Institute, Emory University, Atlanta, Georgia.
Department of Microbiology and Immunology, Emory University, Atlanta, Georgia.

Walter J Curran (WJ)

Department of Radiation Oncology, Emory University, Atlanta, Georgia.
Winship Cancer Institute, Emory University, Atlanta, Georgia.

Mohammad K Khan (MK)

Department of Radiation Oncology, Emory University, Atlanta, Georgia.
Winship Cancer Institute, Emory University, Atlanta, Georgia.

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