Possibilities of low-dose radiation therapy in the treatment of intrapulmonary injuries caused by COVID-19 infection.

This paper examines the relevance of the use of a single irradiation of lungs in treatment of pneumonia caused by a new coronavirus infection. Clinical observations are presented that demonstrate perspectives in the treatment of this disease. Patients with severe pneumonia who were prescribed LD-RT (low-dose radiation therapy) at a dose of 0.5-1.5 Gy showed shorter recovery times and no complications. This method of treatment has shown its effectiveness in a number of studies from different countries, predicting success and economic benefits in its further use and study. A literature search containing information on relevant studies was carried out in PubMed, EMBASE, Web of Science and Google Scholar systems. Attention was focused on full-text articles given their general availability in a pandemic.Copyright © 2021 VIDAR Publishing House. All right reserved.

Application of low dose radiation therapy in the treatment of COVID-19 pneumonia.

With the global pandemic of COVID-19, cytokine storms in critical patients with pneumonia is really a problem and need to be solved immediately.Low dose radiation therapy (LDRT) has been temporarily used to treat pneumonia.In the past decades, researchers were dedicated to clarify the biological mechanism of LDRT.LDRT plays a unique role in the suppression of inflammation, preliminary outcomes have been acquired in critical patients with COVID-19 pneumonia, and radiotherapy community is paying attention to this treatment strategy.This review summarizes the application of LDRT in pneumonia, its biological mechanism, the result of LDRT in COVID-19 pneumonia, the existing problems and prospective in clinic.Copyright © 2021 Chinese Medical Association

Low-Dose Radiotherapy for Patients with Pneumonia Due to COVID-19: A Single-Institution Prospective Study.

PURPOSE: Results of the low-dose radiation therapy (LDRT) in patients with pneumonia due to COVID-19 has been presented. METHODS: Fifteen patients received a single-fraction radiation dose of 1 Gy to the bilateral lungs due to pre-ARDS pneumonia in the course of COVID-19. Follow-up was performed on days 1, 3, 5, 7, 14 after LDRT. RESULTS: Eleven patients (73%) were released up until day 28. Median hospitalization was 20 days; 28-day mortality was 13%. Median O2 saturation improved within 24 h after LDRT in 14/15, with median SpO2 values of 84.5% vs. 87.5% p = 0.016, respectively. At day 14 of hospitalization, 46% did not require oxygen supplementation. Significant decline in CRP and IL-6 was observed within 24 h post LDRT. No organ toxicities were noted. CONCLUSION: LDRT is feasible, well tolerated and may translate to early clinical recovery in patients with severe pneumonia. Further studies are needed to determine optimal candidate, time and dose of LDRT for COVID-19 patients with pneumonia.

Low-dose radiotherapy for COVID-19 pneumonia and cancer: summary of a recent symposium and future perspectives.

The lessons learned from the Coronavirus Disease 2019 (COVID-19) pandemic are numerous. Low dose radiotherapy (LDRT) was used in the pre-antibiotic era as treatment for bacterially/virally associated pneumonia. Motivated in part by these historic clinical and radiobiological data, LDRT for treatment of COVID-19-associated pneumonia was proposed in early 2020. Although there is a large body of epidemiological and experimental data pointing to effects such as cancer at low doses, there is some evidence of beneficial health effects at low doses. It has been hypothesized that low dose radiation could be combined with immune checkpoint therapy to treat cancer. We shall review here some of these old radiobiological and epidemiological data, as well as the newer data on low dose radiation and stimulated immune response and other relevant emerging data. The paper includes a summary of several oral presentations given in a Symposium on "Low dose RT for COVID and other inflammatory diseases" as part of the 67th Annual Meeting of the Radiation Research Society, held virtually 3-6 October 2021.

Systemic Abscopal Effect of Low-dose Radiotherapy (2 Gy ×2) against Palatine Tonsil Follicular Lymphoma.

A 52-year-old man presented with palatine tonsillar swelling caused by follicular lymphoma. His tumor burden was low, but exacerbation of snoring and dysphagia was observed. Considering the first wave of coronavirus disease 2019 (COVID-19) pandemic, he received palliative 4-Gy irradiation to the tonsils in 2 fractions, which induced partial regression of tonsillar swellings and eradication of the circulating lymphoma cells. We suggest that low-dose radiotherapy triggered an abscopal effect of lymphoma, which allowed the patient time to receive COVID-19 vaccination before starting immunosuppressive chemo-immunotherapy.

Impact of X-radiation in the management of COVID-19 disease.

Coronaviruses are a diverse group of viruses that infect both animals and humans. Even though the existence of coronavirus and its infection to humans is not new, the 2019-novel coronavirus (nCoV) caused a major burden to individuals and society i.e., anxiety, fear of infection, extreme competition for hospitalization, and more importantly financial liability. The nCoV infection/disease diagnosis was based on non-specific signs and symptoms, biochemical parameters, detection of the virus using reverse-transcription polymerase chain reaction (RT-PCR), and X-ray-based imaging. This review focuses on the consolidation of potentials of X-ray-based imaging modality [chest-X radiography (CXR) and chest computed tomography (CT)] and low-dose radiation therapy (LDRT) for screening, severity, and management of COVID-19 disease. Reported studies suggest that CXR contributed significantly toward initial rapid screening/diagnosis and CT- imaging to monitor the disease severity. The chest CT has high sensitivity up to 98% and low specificity for diagnosis and severity of COVID-19 disease compared to RT-PCR. Similarly, LDRT compliments drug therapy in the early recovery/Less hospital stays by maintaining the physiological parameters better than the drug therapy alone. All the results undoubtedly demonstrated the evidence that X-ray-based technology continues to evolve and play a significant role in human health care even during the pandemic.

Low-dose radiotherapy to the lungs using an interventional radiology C-arm fluoroscope: Monte Carlo treatment planning and dose measurements in a postmortem subject.

Objective.The goal of this study was to use Monte Carlo (MC) simulations and measurements to investigate the dosimetric suitability of an interventional radiology (IR) c-arm fluoroscope to deliver low-dose radiotherapy to the lungs.Approach.A previously-validated MC model of an IR fluoroscope was used to calculate the dose distributions in a COVID-19-infected patient, 20 non-infected patients of varying sizes, and a postmortem subject. Dose distributions for PA, AP/PA, 3-field and 4-field treatments irradiating 95% of the lungs to a 0.5 Gy dose were calculated. An algorithm was created to calculate skin entrance dose as a function of patient thickness for treatment planning purposes. Treatments were experimentally validated in a postmortem subject by using implanted dosimeters to capture organ doses.Main results.Mean doses to the left/right lungs for the COVID-19 CT data were 1.2/1.3 Gy, 0.8/0.9 Gy, 0.8/0.8 Gy and 0.6/0.6 Gy for the PA, AP/PA, 3-field, and 4-field configurations, respectively. Skin dose toxicity was the highest probability for the PA and lowest for the 4-field configuration. Dose to the heart slightly exceeded the ICRP tolerance; all other organ doses were below published tolerances. The AP/PA configuration provided the best fit for entrance skin dose as a function of patient thickness (R2 = 0.8). The average dose difference between simulation and measurement in the postmortem subject was 5%.Significance.An IR fluoroscope should be capable of delivering low-dose radiotherapy to the lungs with tolerable collateral dose to nearby organs.

Low-dose Lung Radiotherapy for COVID-19-related Pneumonia: Preliminary Results of the Italian Mono-institutional COLOR-19 Trial.

AIM: To evaluate the feasibility and tolerability of low-dose radiotherapy (LDRT) delivered to both lungs in the treatment of SARS-CoV-2-immune-mediated pneumonia in the COLOR-19 study (NCT0437747). PATIENTS AND METHODS: From May 2020 to April 2021 at Brescia University Radiation Oncology Department, three patients with COVID-19-related pneumonia were treated with LDRT according to the COLOR-19 protocol. All patients were treated with a single fraction at the average prescription dose of 0.7 Gy to both lungs. RESULTS: Three patients were enrolled (two males and one female, aged 61-81 years) and underwent LDRT. Despite LDRT being safely performed without significant side-effects, two patients died (one 81-year-old male due to septic shock secondary to Escherichia coli infection and one 79-year-old male, already in poor condition, due to worsening of COVID-19). The remaining female patient (61 years old) underwent LDRT for less severe COVID-19: her clinical condition and chest X-ray improved, and she was discharged home completely asymptomatic 27 days after hospital admission. Blood levels of C-reactive protein and ferritin generally decreased after LDRT. CONCLUSION: Early results of the COLOR-19 study demonstrate the feasibility of LDRT for therapy of COVID-19-related pneumonia; no conclusions on the efficacy have been reached due to poor accrual.

The clinical efficacy of low-dose whole-lung irradiation in moderate-to-severe COVID-19 pneumonia: RTMX-20 trial.

This is a paired prospective comparative cohort study with 58 patients, in order to analyze the clinical LD-WLI in patients with moderate or severe COVID19 pneumonia. The results of this study show that the Radiotherapy could be an option to improve the clinical response for patients with COVID-19.

Whole lung irradiation as a novel treatment for COVID-19: Final results of the prospective randomized trial (WINCOVID trial).

BACKGROUND AND PURPOSE: The ability of low dose radiotherapy (LDRT) to control the unprecedented cytokine release associated with COVID-19 pathogenesis has been an area of widespread research since the COVID pandemic. It has not been studied adequately whether the anti-inflammatory effect of LDRT provides additional benefit when used concurrently with steroids amongst other standard pharmacologic therapy. MATERIAL AND METHODS: 51 RT-PCR positive COVID-19 patients were recruited between November 2020 and July 2021. 34 patients were allotted to receive 0.5 Gy single session LDRT along with standard pharmacologic therapy while 17 patients received standard pharmacologic therapy alone. All had SpO2 <94% on room air, respiratory frequency >24/min and SpO2/FiO2 (SF) ratio between >89 but <357. All patients underwent a baseline CT scan. They were followed up for 28 days during when serial SF ratio, blood biomarkers (CRP, Serum ferritin, IL-6), Absolute lymphocyte count (ALC), repeat CT scan were performed at pre-defined time points. RESULTS: LDRT showed a statistically significant early improvement in oxygenation, an early time to clinical recovery, early hospital discharge and better radiological resolution compared to control group. There was no statistically significant difference between the two groups with respect to ALC or blood biomarkers at any of the measured time points. The 28-day mortality rate did not show statistically significant difference between the two groups. CONCLUSION: LDRT can be considered for selected oxygen-dependent moderate to severe COVID-19 patients for rapid relief of respiratory distress. It can be safely combined with standard pharmacologic treatment in such patients for added clinical benefit.

COVID-19: The Disease, the Immunological Challenges, the Treatment with Pharmaceuticals and Low-Dose Ionizing Radiation.

The year 2020 will be carved in the history books-with the proliferation of COVID-19 over the globe and with frontline health workers and basic scientists worldwide diligently fighting to alleviate life-threatening symptoms and curb the spread of the disease. Behind the shocking prevalence of death are countless families who lost loved ones. To these families and to humanity as a whole, the tallies are not irrelevant digits, but a motivation to develop effective strategies to save lives. However, at the onset of the pandemic, not many therapeutic choices were available besides supportive oxygen, anti-inflammatory dexamethasone, and antiviral remdesivir. Low-dose radiation (LDR), at a much lower dosage than applied in cancer treatment, re-emerged after a 75-year silence in its use in unresolved pneumonia, as a scientific interest with surprising effects in soothing the cytokine storm and other symptoms in severe COVID-19 patients. Here, we review the epidemiology, symptoms, immunological alterations, mutations, pharmaceuticals, and vaccine development of COVID-19, summarizing the history of X-ray irradiation in non-COVID diseases (especially pneumonia) and the currently registered clinical trials that apply LDR in treating COVID-19 patients. We discuss concerns, advantages, and disadvantages of LDR treatment and potential avenues that may provide empirical evidence supporting its potential use in defending against the pandemic.

Whole lung irradiation as a novel treatment for COVID-19: Interim results of an ongoing phase 2 trial in India.

BACKGROUND AND PURPOSE: The main cause of death in COVID-19 pneumonia is acute respiratory distress syndrome which is preceded by massive cytokine release. Low-dose radiation therapy (LDRT) has anti-inflammatory and immunomodulatory effects that can interfere with the inflammatory cascade, reducing the severity of associated cytokine release. MATERIAL & METHODS: 25 patients with RT-PCR proven COVID-19 pneumonia were enrolled between November 2020 and May 2021. All patients had SpO2 < 94 % on room air, respiratory frequency > 24/min and SpO2/FiO2 ratio (SF ratio) of >89 but <357. Patients were treated according to standard COVID-19 management guidelines along with single fraction LDRT of 0.5 Gy to bilateral whole lungs within 10 days of symptom onset and 5 days of hospital admission. RESULTS: LDRT was well tolerated by all patients. There was a statistically significant improvement in oxygenation as given by the SF ratio between pre-RT and day 2 (p < 0.05), day 3 (p < 0.001) and day 7 (p < 0.001) post RT. Demand for supplemental oxygen showed statistically significant reduction between pre-RT and day 2 (p < 0.05), day 3 (p < 0.001), day 7 (p < 0.001) post RT. 88 % patients attained clinical recovery within 10 days post LDRT and median time to hospital discharge from day of LDRT was 6 days. Three patients deteriorated and died. CONCLUSION: As per our initial experience, LDRT appears to be a promising modality of treatment with rapid relief of respiratory distress in selected patients with moderate to severe COVID-19 pneumonia. This translates to early clinical recovery and hospital discharge in the selected patient group.

Low-dose radiotherapy for COVID 19: A radioimmunological perspective.

The world is fighting the onslaught of COVID 19 for the last 10 months, ever since the first case was reported in December 2019 in Wuhan, China. Now, it has spread to over 200 countries. COVID 19-associated respiratory syndrome is causing a lot of mortality and morbidity. There are reports suggesting that the complications and ARDS associated with COVID 19 is an immune response reaction. The cytokine storm associated with severe cases of COVID 19 acts as a cause of death in many sick patients. It has been shown that COVID 19 is associated with a peculiar immune profile: Decrease in CD3, CD4, CD8, natural killer cell and B-cells; Rise in interleukin (IL)-4, IL-6 and tumor necrosis factor (TNF) alpha; Decrease in IL-10; Decrease in interferon-gamma. Low-dose radiotherapy (LDRT) immunosuppressive features resulting from M2 macrophage phenotype activation, increase in IL-10, transforming growth factor beta, a decrease in IL-6, TNF alpha and an increase in CD3, CD4, and CD8 T cell counts may negate the harmful effects of cytokine release syndrome. Literature review shows that radiation was previously used to treat viral pneumonia with a good success rate. This practice was discontinued in view of the availability of effective antibiotics and antivirals. As there are no scientifically proven treatment for severe COVID 19-associated respiratory distress today, it is prudent that we understand the benefits of LDRT at this critical juncture and take rational decisions to treat the same. This article provides an radioimmunological rationale for the treatment of immune crisis mediated complications in severe cases of COVID 19.

Saving time in the radiotherapy procedures for COVID-19 pneumonia treatment. A single-institution experience.

BACKGROUND: The use of low dose radiotherapy (LD-RT) for the treatment of COVID-19 pneumonia is supported by biological rationale for its immunomodulatory effect. Some institutions have started to treat these patients showing encouraging results. To shorten procedure times is crucial for the comfort of symptomatic patients receiving respiratory support and to optimize institutional facilities. PATIENTS AND METHODS: At our institution, LD-RT is offered to hospitalized patients with COVID-19 pneumonia and signs of early cytokine-released syndrome on behalf of a multicenter study. We designed a coordinated process flow starting from the patient transfer to the simulation CT-scan (first-step), to the end of the LD-RT treatment (last step). The times spent on each step of the process flow were evaluated. RESULTS: Mean age of treated patients was 83 (72-91) years-old. The timing parameters of the first 10 consecutive patients were analyzed. Except for the first (dummy run), patients were managed from the first to the last step in a median of 38 min (25-58, SD 10.67). The most time-consuming sub-process was the contouring of the treatment volumes and dosimetry. CONCLUSIONS: LD-RT is not only an encouraging option for COVID-19 pneumonia patients, but a convenient and feasible procedure if performed in a coordinated way by reducing procedure times.

Feasibility of Treatment Planning System in Localizing the COVID-19 Pneumonia Lesions and Evaluation of Volume Indices of Lung Involvement.

BACKGROUND AND PURPOSE: To assess the feasibility of a treatment planning system in localizing, contouring, and targeting lung lesions along with an evaluation of volume indices of lung involvement in patients with COVID-19 pneumonia. METHODS: We evaluated 10 patients with PCR-confirmed COVID-19 pneumonia. The CT images were imported into the ISOgray® treatment planning system to anatomically define and contour the volumes of the pulmonary lesions, the lungs, and other nearby organs. RESULTS: The ratio of lung lesion volume to lung volume in this study was 0.11 ± 0.13 (11.13%). The highest mean biosynthesis ratio of lung lesions was 0.36. The ratio of lesion volume in the left lung of patients with the highest volume of involvement, was 0.44, and the ratio of lesion volume in the right lung of these patients was 0.27 (approximately 1.5 times more in the left lung than the right lung). On average, CTDIvol and DLP for all patients studied in our study were 11.22 ± 2.47 mGy and 354.20 ± 65.11 mGy.cm. CONCLUSION: We reported the feasibility of using a treatment planning system in localizing COVID-19 pulmonary lesions and its validity in the volumetric assessment of infected lung regions.

Low-dose radiotherapy for COVID-19 pneumonia treatment: case report, procedure, and literature review.

BACKGROUND: The COVID-19 pandemic outbreak has set the emergency services in developing countries on major alert, as the installed response capacities are easily overwhelmed by the constantly increasing high demand. The deficit of intensive care unit beds and ventilators in countries like Peru is forcing practitioners to seek preventive or early interventional strategies to prevent saturating these chronically neglected facilities. CASE PRESENTATION: A 64-year-old patient is reported after presenting with COVID-19 pneumonia and rapidly progressing to deteriorated ventilatory function. Compassionate treatment with a single 1­Gy dose to the bilateral whole-lung volume was administered, with gradual daily improvement of ventilatory function and decrease in serum inflammatory markers and oxygen support needs, including intubation. No treatment-related toxicity developed. Procedures of transport, disinfection, and treatment planning and delivery are described. CONCLUSION: Whole-lung low-dose radiotherapy seems to be a promising approach for avoiding or delaying invasive respiratory support. Delivered low doses are far from meeting toxicity ranges. On-going prospective trials will elucidate the effectiveness of this approach.

Is there any supportive evidence for low dose radiotherapy for COVID-19 pneumonia?

Since early April 2020, there has been intense debate over proposed clinical use of ionizing radiation to treat life-threatening pneumonia in Coronavirus Disease 2019 (COVID-19) patients. At least twelve relevant papers appeared by 20 May 2020. The radiation dose proposed for clinical trials are a single dose (0.1-1 Gy) or two doses (a few mGy followed by 0.1-0.25 Gy involving a putative adaptive response, or 1-1.5 Gy in two fractions 2-3 days apart). The scientific rationale for such proposed so-called low dose radiotherapy (LDRT) is twofold (note that only doses below 0.1 Gy are considered as low doses in the field of radiation protection, but here we follow the term as conventionally used in the field of radiation oncology). Firstly, the potentially positive observations in human case series and biological studies in rodent models on viral or bacterial pneumonia that were conducted in the pre-antibiotic era. Secondly, the potential anti-inflammatory properties of LDRT, which have been seen when LDRT is applied locally to subacute degenerative joint diseases, mainly in Germany. However, the human and animal studies cited as supportive evidence have significant limitations, and whether LDRT produces anti-inflammatory effects in the inflamed lung or exacerbates ongoing COVID-19 damage remains unclear. Therefore, we conclude that the available scientific evidence does not justify clinical trials of LDRT for COVID-19 pneumonia, with unknown benefit and known mortality risks from radiogenic cancer and circulatory disease. Despite the significant uncertainties in these proposals, some clinical trials are ongoing and planned. This paper gives an overview of current situations surrounding LDRT for COVID-19 pneumonia.

Low dose radiation therapy as a potential life saving treatment for COVID-19-induced acute respiratory distress syndrome (ARDS).

The new coronavirus COVID-19 disease caused by SARS-CoV-2 was declared a global public health emergency by WHO on Jan 30, 2020. Despite massive efforts from various governmental, health and medical organizations, the disease continues to spread globally with increasing fatality rates. Several experimental drugs have been approved by FDA with unknown efficacy and potential adverse effects. The exponentially spreading pandemic of COVID-19 deserves prime public health attention to evaluate yet unexplored arenas of management. We opine that one of these treatment options is low dose radiation therapy for severe and most critical cases. There is evidence in literature that low dose radiation induces an anti-inflammatory phenotype that can potentially afford therapeutic benefit against COVID-19-related complications that are associated with significant morbidity and mortality. Herein, we review the effects and putative mechanisms of low dose radiation that may be viable, useful and of value in counter-acting the acute inflammatory state induced by critical stage COVID-19.

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

The COVID-19 pandemia is affecting people worldwide. Most of the patients suffered of a respiratory disease that will progress to an acute respiratory distress syndrome (ARDS). SARS-CoV-2 pneumonia severely ill patients, develop a systemic inflammatory response with a Cytokine Release Syndrome (CRS), that is characterized by a sudden increase in several pro-inflammatory cytokines, mainly IL-1, IL-6 and TNF-alfa by activated macrophages (M1 phenotype). Blocking IL-6 with tocilizumab and using respirator equipment seems to be a very important issue in this (SARS-CoV-2) pneumonia, but not all patients are referred to such treatments. Low dose radiotherapy (0,5 Gy), is an evidence-based anti-inflammatory treatment, that could modify the immune landscape in the lung affected of SARS-CoV-2 pneumonia, through macrophages polarization to alternatively activated Macrophages (M2 phenotype). Radiation-induced cancer risk could be assumed due to the very low dose used, the advanced age of the patients and the life-threatening condition of SARS-Cov2 pneumonia. LDRT is a cost-effective non-toxic treatment already available in most general hospitals. This fact allows that it would be used for the large number of patients that will suffer this disease, and that would not receive specific anti-IL-6 treatments in ICUs in low and middle income countries.