Low doses of radiation in the form of chest x-rays has been in the past to treat peoplewith pneumonia. This treatment was thought to reduce inflammation and was found to beeffective without side effects. However, it was an expensive treatment and was eventuallyreplaced with less expensive treatment options like penicillin.The COVID-19 virus has emerged recently, causing high rates of pneumonia in people. Theauthors believe that giving a small dose of radiation to the lungs may reduceinflammation and neutralize the pneumonia caused by COVID-19. For this study, the x-raygiven is called radiation therapy. Radiation therapy uses high-energy X-ray beams from alarge machine to target the lungs and reduce inflammation. Usually, it is given at muchhigher doses to treat cancers.The purpose of this study is to find out if adding a single treatment of low-dose x-raysto the lungs might reduce the amount of inflammation in the lungs from COVID-19infection, which could reduce the need for a ventilator or breathing tube.
The authors propose a two-step randomized Phase II study to determine if single fraction
low dose whole thorax megavoltage radiotherapy (LD-WTRT) can produce meaningful clinical
benefit in COVID-19 patients. In Step 1, patients would be randomized 1:2 to standard of
care without or with LD-WTRT. Patients randomized to LD-WTRT would be further randomized
to either 35 cGy or 100 cGy. After 20 patients have been enrolled on each low-dose
radiotherapy arm, they will be evaluated to determine the selection of the "best
radiotherapy dose-arm" for the remainder of the patients. This will be done by analyzing
clinical benefit, risk profile, and the dynamics of biomarker change, specifically
focusing on IL-6
1. If the rate of Grade 4 toxicity is lower by an absolute rate of 15% when comparing
the 35 cGy and 100 cGy arms, the arm with the lower toxicity rate will be used for
Step 2 of the trial.
2. If the crude clinically meaningful event rate (CMER) which is a composite endpoint,
is lower by an absolute rate of 20% when comparing the 35 cGy and 100 cGy arms, the
lower CMER rate arm will be used for Step 2. CMER is defined as a composite of :
1. Rate of mechanical ventilation (MV)
2. Rate of prolonged hospital stay >10 days (PHS)
3. Crude all-cause mortality rate at the time of analysis
3. If the crude CMER is < 20% difference between the 35 cGy and 100 cGy arms, the
investigators will determine whether there is a trend suggesting less Facility
Resource Utilization Rate (FRUR). If the FRUR is 20% lower in either the 35 cGy or
100 cGy arms, that dose will be used for Step 2. The FRUR is based upon:
1. Days of mechanical ventilation
2. Days of hospitalization.
4. If both crude CMER and FRU rates do not differ by at least 20%, the investigators
will evaluate the area under the curve (AUC) for IL-6 levels drawn within 24 hours
before LD-WTRT and at 48 hours (2d) and 168 hours (7d) after radiation. If one of
the two arms has a 20% lower serum IL-6 AUC one week after radiotherapy, the
investigators will select that arm for Step 2.
5. If none of the parameters in numbers 1-4 above differ in the criteria listed, the
investigators will use the lower dose of 35 cGy for Step 2.
Radiation: Low dose radiation 35 cGy
A dose of 35 cGy of whole thorax irradiation will be delivered at a single timepoint
Radiation: High dose radiation 100 cGy
A dose of 100 cGy of whole thorax irradiation will be delivered at a single timepoint
Inclusion Criteria:
- Laboratory-confirmed diagnosis of SARS-CoV-2 pneumonia
- Currently hospitalized with COVID-19
- Symptomatic fever, cough and/or dyspnea for < 9 days
- Patient or legal/authorized representative can understand and sign the study
informed consent document
- Able to be positioned on a linear-accelerator couch for Radiation Therapy delivery
- And at least one of the following risk factors for significant pulmonary compromise:
1. Fever > 102 degrees Fahrenheit during index admission
2. Respiratory rate of ≥ 26 / minute within 24 hours of screening
3. SpO2 ≤ 95% on room air within 24 hours of screening
4. Any patient requiring 4 L/min oxygen therapy to maintain SpO2 >93% within 24
hours of screening
5. Ratio of partial pressure of arterial oxygen to fraction of inspired air < 320.
- Patients may be enrolled on this trial while concurrently enrolled on other COVID-19
clinical trials.
Exclusion Criteria:
- Currently requiring mechanical ventilation
- Prior thoracic radiotherapy, with the exception of the following:
1. Breast or post-mastectomy chest wall radiation (without regional nodal
irradiation) may be included at the discretion of the site primary
investigator, and
2. Thoracic skin radiation therapy (without regional nodal irradiation) is
allowed.
- Known hereditary syndrome with increased sensitivity to radiotherapy, including
ataxia-telangiectasia, xeroderma pigmentosum, and Nijmegen Breakage Syndrome
- Known prior systemic use of the following drugs: Bleomycin, Carmustine,
Methotrexate, Busulfan, Cyclophosphamide, or Amiodarone
- History of or current diagnosis of pulmonary fibrosis, or an alternative pulmonary
condition responsible for significant lung compromise at the discretion of the site
primary investigator
- History of lung lobectomy or pneumonectomy
- Known history of pulmonary sarcoidosis, Wegener's granulomatosis, systemic lupus
erythematosus, rheumatoid arthritis, systemic sclerosis,
polymyositis/dermatomyositis, Sjögren's syndrome, mixed connective tissue disease,
Churg-Strauss syndrome, Goodpasture's syndrome, or ankylosing spondylitis.
- Symptomatic congestive heart failure within the past 6 months including during
current hospitalization
- History of recent or current malignancy receiving any cytotoxic chemotherapy or
immunotherapy within the past 6 months.
- History of bone marrow transplantation.
- History of any solid organ transplant (renal, cardiac, liver, lung) requiring
immunosuppressive therapy.
- Females who are pregnant or breast feeding.
- Inability to undergo radiotherapy for any other medical or cognitive issues.
Boca Raton Regional Hospital Lynn Cancer Institute
Boca Raton, Florida, United States
Miami Cancer Institute
Miami, Florida, United States
Loyola University Chicago
Maywood, Illinois, United States
Indiana University School of Medicine
Indianapolis, Indiana, United States
Lowell General Hospital Cancer Center
Lowell, Massachusetts, United States
Ohio State University James Cancer Hospital
Columbus, Ohio, United States
Hospital Universitario San Ignacio
Bogotá, Colombia
Arnab Chakravarti, MD, Principal Investigator
James Cancer Hospital, Department of Radiation Oncology