Immunomodulatory Low-Dose Whole-Lung Radiation for Patients with Coronavirus Disease 2019-Related Pneumonia

Hess, Clayton B.; Nasti, Tahseen H.; Dhere, Vishal R.; Kleber, T.; Switchenko, Jeffrey M.; Buchwald, Zachary S.; Stokes, William; Weinberg, Brent D.; Rouphael, Nadine; Steinberg, James P.; Godette, Karen D.; Murphy, David J.; Ahmed, Rafi; Curran, Walter J.; Khan, Mohammad K.

doi:10.1016/j.ijrobp.2020.12.011

Cited by 51 publications

(60 citation statements)

References 28 publications

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“…Obtained evidence of diagnostic imaging and hematological tests showed that LDRT can be effective in treating COVID-19 patients. Preliminary results of the investigation carried out by Khan et al showed that performing LDRT to treat COVID-19 is feasible with high potential for treating COVID-19 patients, and the results of phase 2 of their investigation proved this claim (Hess et al 2021 ).…”

Section: Results Of Clinical Trialsmentioning

confidence: 99%

Effectiveness of low-dose radiation therapy to improve mortality of COVID-19

Ghaznavi

2021

J Cancer Res Clin Oncol

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Introduction Performing low-dose radiation therapy (LDRT) is a new approach to treat pneumonia resulting from COVID-19 disease. This paper aims to evaluate the effectiveness of LDRT in treating COVID-19 patients. Methods Medline was searched for “low-dose” and “radiation therapy” and “COVID-19” and “pneumonia” and “inflammation”, to retrieve papers that published on low-dose radiation therapy to improve mortality of COVID-19 patients. Only clinical investigations that included original and case report papers were selected for this paper. Results The completed clinical trials that have performed LDRT to treat COVID-19 showed that the effectiveness of LDRT in treating COVID-19 was up to 90%. Conclusion The vast majority of primary and secondary outcomes of clinical trial investigations regarding LDRT in treating COVID-19 found that LDRT can be considered a feasible treatment to improve mortality of COVID-19 patients.

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Section: Results Of Clinical Trialsmentioning

confidence: 99%

Effectiveness of low-dose radiation therapy to improve mortality of COVID-19

Ghaznavi

2021

J Cancer Res Clin Oncol

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“…Conversely, radiation has well known immunomodulatory properties and can be notably cytotoxic to immune cells even in low doses yielding anti-in ammatory effects [24][25][26] . The immunosuppressive effect of radiation has been recently explored for the treatment of COVID-19-related pneumonia with mixed results 27 . Thus, it is fair to ask whether radiation might suppress the dysregulated and hyperactive mucosal immune response in the rectum leading to improved symptomatology, which is intriguingly what was observed by a Gestaut et al 16 .…”

Section: Discussionmentioning

confidence: 99%

Stereotactic Body Radiation Therapy For The Treatment of Localized Prostate Cancer In Men With Underlying Inflammatory Bowel Disease

Lischalk

Blacksburg

Mendez

et al. 2021

Preprint

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BackgroundHistorically, IBD has been thought to increase the underlying risk of radiation related toxicity in the treatment of prostate cancer. In the modern era, contemporary radiation planning and delivery may mitigate radiation related toxicity in this theoretically high-risk cohort. This is the first manuscript to report clinical outcomes for men diagnosed with prostate cancer and underlying IBD curatively treated with stereotactic body radiation therapy (SBRT). MethodsA large institutional database of patients (n = 4,245) treated with SBRT for adenocarcinoma of the prostate was interrogated to identify patients who were diagnosed with underlying IBD prior to treatment. All patients were treated with SBRT over five treatment fractions using a robotic radiosurgical platform and fiducial tracking. Baseline IBD characteristics including IBD subtype, pre-SBRT IBD medications, and EPIC bowel questionnaires were reviewed for the IBD cohort. Acute and late toxicity was evaluated using the CTCAE version 5.0. ResultsA total of 31 patients were identified who had underlying IBD prior to SBRT for the curative treatment of prostate cancer. The majority (n = 18) were diagnosed with ulcerative colitis and the majority were being treated local steroid suppositories for IBD. No biochemical relapses were observed in the IBD cohort with early follow up. High-grade acute and late toxicities were rare (n = 1, grade 3 proctitis) with a median time to any GI toxicity of 22 months. Hemorrhoidal flare was the most common low-grade toxicity observed (n = 3). ConclusionTo date, this is one of the largest groups of patients with IBD treated safely and effectively with radiation for prostate cancer and the only review of patients treated with SBRT. Caution is warranted when delivering therapeutic radiation to patients with IBD, however modern radiation techniques appear to have mitigated the risk of GI side effects.

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“…Encouraging preliminary results have been reported in several clinical pilot studies [6][7][8][9][10][11][12]. Hess and co-workers recently shown [7] that LDRT of whole lung with 1.5 Gy was effective in reducing intubation time for COVID-19 patients receiving dexamethasone and/or remdesevir. In an earlier trial of predominantly elderly COVID-19 pneumonia patients, the same LDRT treatment protocol [6] produced quicker recoveries to the use room air (vs. ventilatory support), and significant or trending improvements in delirium, radiographs, and (other) biomarkers, without significant acute toxicity observed.…”

Section: Introductionmentioning

confidence: 93%

“…Based on the historically successful clinical use of LDRT, approximately 10 clinical trials are currently underway worldwide to test the safety and effectiveness of LDRT against COVID-19 [5]. Encouraging preliminary results have been reported in several clinical pilot studies [6][7][8][9][10][11][12]. Hess and co-workers recently shown [7] that LDRT of whole lung with 1.5 Gy was effective in reducing intubation time for COVID-19 patients receiving dexamethasone and/or remdesevir.…”

Section: Introductionmentioning

confidence: 99%

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

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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.

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Immunomodulatory Low-Dose Whole-Lung Radiation for Patients with Coronavirus Disease 2019-Related Pneumonia

Cited by 51 publications

References 28 publications

Effectiveness of low-dose radiation therapy to improve mortality of COVID-19

Effectiveness of low-dose radiation therapy to improve mortality of COVID-19

Stereotactic Body Radiation Therapy For The Treatment of Localized Prostate Cancer In Men With Underlying Inflammatory Bowel Disease

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

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