Low-Dose Radiation Therapy in the Management of Coronavirus Disease 2019 (COVID-19) Pneumonia (LOWRAD-Cov19): Preliminary Report

Sanmamed, Noelia; Alçântara, P.; Cerezo, Elena; Gaztañaga, Miren; Cabello, Noemí; Gomez, S; Bustos, Ana; Doval, Anxela; Corona, J.; Rodriguez, Gilhen; Duffort, M.; Ortuño, Francisco Marín; Castro, Javier de; Fuentes, Manuel; Sanz, Álvaro; Lopez, Amanda; Vázquez, Manuel

doi:10.1016/j.ijrobp.2020.11.049

Cited by 55 publications

(65 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Our results are in contrast to the initial experiences reported from small single-arm studies, which observed signs of clinical and radiographic improvement following LDRT for COVID-19 pneumonia ( 13 , 14 , 15 , 16 ). These studies used LDRT doses in the range of 0.5 - 1.5 Gy, and treated non-intubated patients receiving supplemental oxygen via nasal cannula or face mask.…”

Section: Discussioncontrasting

confidence: 99%

“…We acknowledge that our initial hypothesis was optimistic in regards to the magnitude of improvement with whole-lung LDRT. However, we were looking for a clear clinical benefit, which would justify potential risks for patients and staff related to the procedure, and which would reflect the rapid symptom reversal described in historical series of x-ray therapy for pneumonia ( 11 ), and in some early experiences of LDRT use for COVID-19 pneumonia ( 13 , 14 , 15 , 16 ). Our study was not powered to detect small differences in outcomes, which would require a larger sample size.…”

Section: Discussionmentioning

confidence: 99%

“…Due to the limited treatment options for COVID-19 pneumonia, several clinical trials of LDRT have been initiated, using radiation doses in the range of 0.3 – 1.5 Gy ( 12 ). Initial experiences have suggested that LDRT is a feasible and well-tolerated treatment, which appeared to be associated with a reduction of inflammation and possibly bearing signs of clinical improvement in these small single-arm studies ( 13 , 14 , 15 , 16 ). However, due to the lack of prospective controls, the efficacy of LDRT in the treatment of COVID-19 remains unknown.…”

Section: Introductionmentioning

confidence: 98%

See 2 more Smart Citations

Withdrawn: Low dose radiation therapy for severe COVID-19 pneumonia: a randomized double-blind study

Papachristofilou

Finazzi

Blum

et al. 2021

International Journal of Radiation Oncology*Biology*Physics

View full text Add to dashboard Cite

Purpose The morbidity and mortality of patients requiring mechanical ventilation for coronavirus disease 2019 (COVID-19) pneumonia is considerable. We studied the use of whole-lung low dose radiation therapy (LDRT) in this patient cohort. Methods and Materials : Patients admitted to the intensive care unit (ICU) and requiring mechanical ventilation for COVID-19 pneumonia were included in this randomized double-blind study. Patients were randomized to 1 Gy whole-lung LDRT or sham irradiation (sham-RT). Treatment group allocation was concealed from patients and ICU clinicians, who treated patients according to the current standard of care. Patients were followed for the primary endpoint of ventilator-free days (VFDs) at day 15 post-intervention. Secondary endpoints included overall survival, as well as changes in oxygenation and inflammatory markers. Results Twenty-two patients were randomized to either whole-lung LDRT or sham-RT between November and December 2020. Patients were generally elderly and comorbid, with a median age of 75 years in both arms. No difference in 15-day VFDs was observed between groups (p = 1.00), with a median of 0 days (range, 0-9) in the LDRT arm, and 0 days (range, 0-13) in the sham-RT arm. Overall survival at 28 days was identical at 63.6% (95%CI, 40.7-99.5%) in both arms (p = 0.69). Apart from a more pronounced reduction in lymphocyte counts following LDRT (p < 0.01), analyses of secondary endpoints revealed no significant differences between the groups. Conclusions Whole-lung LDRT failed to improve clinical outcomes in critically ill patients requiring mechanical ventilation for COVID-19 pneumonia.

show abstract

Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

See 1 more Smart Citation

Withdrawn: Low dose radiation therapy for severe COVID-19 pneumonia: a randomized double-blind study

Papachristofilou

Finazzi

Blum

et al. 2021

International Journal of Radiation Oncology*Biology*Physics

View full text Add to dashboard Cite

show abstract

“…The findings presented support recent demonstrations of positive clinical responses to LDRT in COVID-19 pneumonia patients [6] , [7] , [8] , [9] , [10] , [11] , [12] . However, animal studies also provide support for the effectiveness of Nrf2 in protecting various tissues from pro-inflammatory challenges.…”

Section: Nrf2 Activation Protects Against Covid-19 Pneumonia Ards and Other Inflammatory Diseasessupporting

confidence: 89%

Nrf2 activation putatively mediates clinical benefits of low-dose radiotherapy in COVID-19 pneumonia and acute respiratory distress syndrome (ARDS): Novel mechanistic considerations

Calabrese

Kozumbo

Kapoor

et al. 2021

Radiotherapy and Oncology

View full text Add to dashboard Cite

Novel mechanistic insights are discussed herein that link a single, nontoxic, low-dose radiotherapy (LDRT) treatment (0.5-1.0 Gy) to (1) beneficial subcellular effects mediated by the activation of nuclear factor erythroid 2-related transcription factor (Nrf2) and to (2) favorable clinical outcomes for COVID-19 pneumonia patients displaying symptoms of acute respiratory distress syndrome (ARDS). We posit that the favorable clinical outcomes following LDRT result from potent Nrf2-mediated antioxidant responses that rebalance the oxidatively skewed redox states of immunological cells, driving them toward anti-inflammatory phenotypes. Activation of Nrf2 by ionizing radiation is highly dose dependent and conforms to the features of a biphasic (hormetic) dose-response. At the cellular and subcellular levels, hormetic doses of < 1.0 Gy induce polarization shifts in the predominant population of lung macrophages, from an M1 pro-inflammatory to an M2 anti-inflammatory phenotype. Together, the Nrf2-mediated antioxidant responses and the subsequent shifts to anti-inflammatory phenotypes have the capacity to suppress cytokine storms, resolve inflammation, promote tissue repair, and prevent COVID-19-related mortality. Given these mechanistic considerations—and the historical clinical success of LDRT early in the 20 th century—we opine that LDRT should be regarded as safe and effective for use at almost any stage of COVID-19 infection. In theory, however, optimal life-saving potential is thought to occur when LDRT is applied prior to the cytokine storms and before the patients are placed on mechanical oxygen ventilators. The administration of LDRT either as an intervention of last resort or too early in the disease progression may be far less effective in saving the lives of ARDS patients.

show abstract

“…Furthermore, our paper is not about vaccine administration, and also, we did not evaluate the efficacy of lung irradiation. In addition to that, up to now, few clinical trials with favorable results without a control arm are available (Ameri et al 2020;Sanmamed et al 2020). Finally, the patients included in these studies have the right to know the risks related to the low dose lung irradiation they are exposed to.…”

Section: Ghadimimentioning

confidence: 99%

Reply to: regarding: ‘the risk of induced cancer and ischemic heart disease following low dose lung irradiation for COVID-19: estimation based on a virtual case’

Arruda

Weber

Bruno

et al. 2021

International Journal of Radiation Biology

View full text Add to dashboard Cite

Low-Dose Radiation Therapy in the Management of Coronavirus Disease 2019 (COVID-19) Pneumonia (LOWRAD-Cov19): Preliminary Report

Cited by 55 publications

References 18 publications

Withdrawn: Low dose radiation therapy for severe COVID-19 pneumonia: a randomized double-blind study

Withdrawn: Low dose radiation therapy for severe COVID-19 pneumonia: a randomized double-blind study

Nrf2 activation putatively mediates clinical benefits of low-dose radiotherapy in COVID-19 pneumonia and acute respiratory distress syndrome (ARDS): Novel mechanistic considerations

Reply to: regarding: ‘the risk of induced cancer and ischemic heart disease following low dose lung irradiation for COVID-19: estimation based on a virtual case’

Contact Info

Product

Resources

About