Personal View: Low-dose Lung Radiotherapy for COVID-19 Pneumonia – The Atypical Science and the Unknown Collateral Consequence

BACKGROUND Coronavirus disease 19 (COVID-19) carry a high mortality rate among older patients and minorities such as ethnic Africans and Latinos. The chronic baseline systemic inflammation of older patients and minorities may make them more vulnerable to the cytokines storm generated by the viral infection in addition to preexisting co-morbidity. Even though multiple organs failure result from the cytokine storm, pneumonia and respiratory failure often lead to death. OBJECTIVE Low dose whole lung radiotherapy (LDWLRT) may modulate the inflammatory response and may decrease the need for artificial ventilation, thus improving mortality rate. METHODS A phase I-II prospective trials enrolling 500 patients, 65 years old or older from 25 countries will be conducted to investigate the impact of LDWLRT on mortality rate of COVID-19 patients. The patients who will be selected would have developed pneumonias but did not require artificial ventilation. These patients will be followed for a year after receiving this treatment. Their physical activities will be monitored through the ordinal scale and will be correlated with their cytokines status and oxygen saturation rate to assess the impact of the residual inflammation on their daily life. Mortality rates between different ethnic group will be compared and correlated with their cytokines response to the virus and number of co-morbidities. RESULTS We postulate that LDWLRT may improve survival rates of all patients by preventing the need for artificial ventilation which is associated with a high mortality. The inflammatory response between different ethnic groups before and following radiotherapy will be valuable to serve as baseline for future prospective pandemic studies as it has not been reported before. CONCLUSIONS Once the study is complete, we may be able to demonstrate that LDWLRT may improve survival through its anti-inflammatory property CLINICALTRIAL NCT 04493294

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Low-Dose-Whole-Lung Radiotherapy for Older Patients with Coronavirus Disease (Covid-19) Pneumonia: A Phase I-II Prospective Non-Randomized Protocol by the International Geriatric Radiotherapy Group

Archives of Clinical and Biomedical Research ◽

10.26502/acbr.50170160 ◽

2021 ◽

Vol 05 (02) ◽

Author(s):

Nam P Nguyen ◽

Meritxell Arenas ◽

Te Vuong ◽

Alice Zamagni ◽

Vincent Vinh-Hung ◽

...

Keyword(s):

Phase I ◽

Older Patients ◽

Low Dose ◽

Radiotherapy Group ◽

Lung Radiotherapy ◽

Randomized Protocol

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Low-dose lung radiotherapy for COVID-19 lung disease: a preclinical efficacy study in a bleomycin model of pneumonitis

10.1101/2021.03.03.433704 ◽

2021 ◽

Author(s):

Mark R Jackson ◽

Katrina Stevenson ◽

Sandeep K Chahal ◽

Emer Curley ◽

George E Finney ◽

...

Keyword(s):

Weight Loss ◽

Dendritic Cells ◽

Low Dose ◽

Distress Syndrome ◽

Preliminary Evidence ◽

Lung Imaging ◽

Initial Weight ◽

Initial Weight Loss ◽

Flow Cytometric ◽

Lung Radiotherapy

AbstractPurposeLow-dose whole lung radiotherapy (LDLR) has been proposed as a treatment for patients with acute respiratory distress syndrome associated with SARS-CoV-2 infection and clinical trials are underway. There is an urgent need for preclinical evidence to justify this approach and inform dose, scheduling and mechanisms of action.Materials and methodsFemale C57BL/6 mice were treated with intranasal bleomycin sulphate (7.5 or 11.25 units/kg, day 0), then exposed to whole lung radiation therapy (0.5, 1.0, 1.5 Gy or sham, day 3). Bodyweight was measured daily and lung tissue harvested for histology and flow cytometry on day 10. Computed tomography (CT) lung imaging was performed pre-radiation (day 3) and pre-endpoint (day 10).ResultsBleomycin caused pneumonitis of variable severity which correlated with weight loss. LDLR at 1.0 Gy was associated with a significant increase in the proportion of mice recovering to 98% of initial bodyweight and a proportion of these mice exhibited less severe histopathological lung changes. Mice experiencing moderate initial weight loss were more likely to respond to LDLR than those experiencing severe initial weight loss. Additionally, LDLR (1.0 Gy) significantly reduced bleomycin-induced increases in interstitial macrophages, CD103+ dendritic cells and neutrophil-DC hybrids. Overall,bleomycin-treated mice exhibited significantly higher percentages of non-aerated lung in left than right lungs and LDLR (1.0 Gy) prevented further reductions in aerated lung volume in right but not left lungs. LDLR at 0.5 and 1.5 Gy did not modulate bodyweight or flow cytometric readouts of bleomycin-induced pneumonitis.ConclusionsOur data support the concept that LDLR can ameliorate acute inflammatory lung injury, identify 1.0 Gy as the most effective dose and provide preliminary evidence that it is more effective in the context of moderate than severe pneumonitis. Mechanistically, LDLR at 1.0 Gy significantly suppressed bleomycin-induced accumulation of pulmonary interstitial macrophages, CD103+ dendritic cells and neutrophil-DC hybrids.

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Low dose lung radiotherapy for COVID-19 pneumonia. The rationale for a cost-effective anti-inflammatory treatment

Clinical and Translational Radiation Oncology ◽

10.1016/j.ctro.2020.04.006 ◽

2020 ◽

Vol 23 ◽

pp. 27-29 ◽

Cited By ~ 16

Author(s):

Pedro C. Lara ◽

Javier Burgos ◽

David Macias

Keyword(s):

Low Dose ◽

Cost Effective ◽

Anti Inflammatory ◽

Lung Radiotherapy

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Low-dose, single-fraction, whole-lung radiotherapy for pulmonary hypertension associated with myelofibrosis with myeloid metaplasia

British Journal of Haematology ◽

10.1046/j.1365-2141.2002.03695.x ◽

2002 ◽

Vol 118 (3) ◽

pp. 813-816 ◽

Cited By ~ 65

Author(s):

David P. Steensma ◽

C. Christopher Hook ◽

Scott L. Stafford ◽

Ayalew Tefferi

Keyword(s):

Pulmonary Hypertension ◽

Low Dose ◽

Myeloid Metaplasia ◽

Single Fraction ◽

Myelofibrosis With Myeloid Metaplasia ◽

Lung Radiotherapy

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Ovarian Dysfunction in Fetally Irradiated Beagles

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100080717 ◽

1977 ◽

Vol 35 ◽

pp. 658-659

Author(s):

T. M. Seed ◽

M. H. Sanderson ◽

D. L. Gutzeit ◽

T. E. Fritz ◽

D. V. Tolle ◽

...

Keyword(s):

Gamma Rays ◽

Low Dose ◽

Long Term Effects ◽

Ovarian Dysfunction ◽

Dose Rates ◽

Highly Sensitive ◽

Microscopic Evaluation ◽

Ovarian Pathology ◽

Normal Offspring

The developing mammalian fetus is thought to be highly sensitive to ionizing radiation. However, dose, dose-rate relationships are not well established, especially the long term effects of protracted, low-dose exposure. A previous report (1) has indicated that bred beagle bitches exposed to daily doses of 5 to 35 R 60Co gamma rays throughout gestation can produce viable, seemingly normal offspring. Puppies irradiated in utero are distinguishable from controls only by their smaller size, dental abnormalities, and, in adulthood, by their inability to bear young.We report here our preliminary microscopic evaluation of ovarian pathology in young pups continuously irradiated throughout gestation at daily (22 h/day) dose rates of either 0.4, 1.0, 2.5, or 5.0 R/day of gamma rays from an attenuated 60Co source. Pups from non-irradiated bitches served as controls. Experimental animals were evaluated clinically and hematologically (control + 5.0 R/day pups) at regular intervals.

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