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As the world shut down in reaction to the COVID-19 pandemic in April 2020, many radiation oncologists began collaborating to revive a decades-old use of ionizing radiation therapy on a clinical trial to try to help with COVID-19 pneumonia. Using low dose radiation therapy (LDRT) for a non-malignant disease based upon historical data has been highly controversial, but this debate has helped revive questions about the role of radiation therapy in medicine in ways that deserve deeper consideration. The aim of this paper is to provide some historical and scientific perspective on perceptions of radiation therapy and its risks, including questioning the linear no threshold (LNT) hypothesis and the emergence of data on radiation hormesis. The hope is that this review may stimulate debate on whether to expand the use of low dose radiotherapy (LDRT) beyond its current use primarily for neoplastic disease. Areas of interest include the potential use of LDRT for neurodegenerative, neuroinflammatory, autoimmune disease and for acute injury.

Hand osteoarthritis (HOA) is one of the most common causes of pain and functional disability in western countries and there is still no definitive cure. Low-dose radiation therapy (LDRT) has anti-inflammatory properties that have shown to be effective in the symptomatic relief of various degenerative musculoskeletal disorders. We designed a clinical protocol using LDRT for symptomatic HOA and present results and tolerance in the first 100 patients included. Between April 2015 and March 2021, 100 patients with a median age of 60 were treated. Fifty-seven patients suffering from proximal/distal interphalangeal joint pain, 40 patients with thumb arthritis, 2 patients with radiocarpal joint affection and 1 patient with metacarpophalangeal joint pain were enrolled. LDRT comprised of 6 fractions of 0.5–1 Gy on every other day up to a total dose of 3–6 Gy. Clinical response was evaluated according to the visual analog scale (VAS) for pain level and the von Pannewitz score (VPS) for joint functionality. Any patients not achieving subjective adequate pain relief after 8 weeks of treatment were offered a second identical LDRT course. With a median follow-up of 10.5 months (range 7.55–12.45), 94% reported an improvement in the pain, with a significant reduction in the VAS level after 3, 6 and 12 months (p

Coronavirus variants are gaining strongholds throughout the globe. Despite early signals that SARS-CoV-2 coronavirus case numbers are easing up in the United States and during the middle of a (not so easy) vaccination roll out, the country has passed a grim landmark of 600,000 deaths. We contend that these numbers would have been much lower if the medical community undertook serious investigations into the potential of low doses of radiation (LDRT) as a mainstream treatment modality for COVID-19 pneumonia. LDRT has been posited to manifest anti-infectious and anti-inflammatory properties at doses of 0.3-1.0 Gy via the activation of the Nrf-2 pathway. Although some researchers are conducting well-designed clinical trials on the potential of LDRT, the deep-rooted, blind, and flawed acceptance of the Linear No-Threshold (LNT) model for ionizing radiation has led to sidelining of this promising therapy and thus unimaginable numbers of deaths in the United States.

Background:The Coronavirus disease 2019 (COVID-19) is spreading rapidly throughout the world. Lung is the primary organ which the COVID-19 virus affects and leads to pneumonia, an acute respiratory distress syndrome. COVID-19 infects the lower respiratory system, and the lung’s response to this infection is recruiting macrophages and monocytes leading to inflammation, this response causes widespread damage to the lung’s airways.Aim:The purpose of this study is to review studies of using low-dose radiation as a treatment for the inflammation of the tissue and pneumonia resulting from COVID-19. These studies were compared with the risk of developing lung cancer during performed dose for the treatment of COVID-19 in radiation therapy.Materials and methods:Our study focused on in vitro, in vivo and clinical reports of using low-dose radiation for the treatment of inflammation, pneumonia and COVID-19. The risk of lung cancer resulting from suggested dose in these studies was also evaluated.Conclusion:From the review of articles, we have found that low-dose radiation can lead to improvement in inflammation in different line cells and animals; in addition, it has been effective in treating inflammation and pneumonia caused by COVID-19 in human up to 80%. Since suggested doses do not remarkably increase the lung cancer risk, low-dose radiation can be an adjuvant treatment for COVID-19 patients.

COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a pandemic disease and is the major cause of deaths worldwide. The clinical complexities (inflammation, cytokine storm, and multi-organ dysfunction) associated with COVID-19 poses constraints to effective management of critically ill COVID-19 patients. Low dose radiation therapy (LDRT) has been evaluated as a potential therapeutic modality for COVID-19 pneumonia. However, due to heterogeneity in disease manifestation and inter-individual variations, effective planning for LDRT is limited for this large-scale event. 2-deoxy-D-glucose (2-DG) has emerged as a polypharmacological agent for COVID-19 treatment due to its effects on the glycolytic pathway, anti-inflammatory action, and interaction with viral proteins. We suggest that 2-DG will be a potential adjuvant to enhance the efficacy of LDRT in the treatment of COVID-19 pneumonia. Withal, azido analog of 2-DG, 2-azido-2-DG can produce rapid catastrophic oxidative stress and quell the cytokine storm in critically ill COVID-19 patients.

Highlights • The clinical spectrum of COVID-19 ranges from an asymptomatic form to mild respiratory symptoms such as dry cough, fever, and moderate dyspnea, to more severe presentations, such as neurologic manifestations (e.g.- cerebrovascular accident consequential to cytokine-induced changes in blood clotting; direct encephalitic effects), viral pneumonia, acute respiratory distress syndrome (ARDS) and sequential organ failure (SOF) as result of cytokine storm. • The entry of pathogenic COVID-19 virus in humans leads to activation of inflammatory cells. Activated inflammatory cells enter the pulmonary circulation and induce a ubiquity of cytokines (i.e.- “cytokine storm”) that lead to rapid, wide-spread damage of the pulmonary epithelium and alveolar cells, as well as other vital organs. • Low-dose Radiotherapy (RT) induces a highly integrated, complex, and systemic response that involves polarization of macrophages to an M-2 anti-inflammatory phenotype. • Recommend administering a single dose of 0.3 - 0.5 Gy to patients experiencing pneumonia, ARDS (Cytokine storm), to attempt rapid amelioration of the systemic inflammatory cascade., The new coronavirus COVID-19 disease caused by SARS-CoV-2 was declared as 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.

This letter addresses our concerns regarding a paper by Salomaa et al. entitled ‘Low dose radiation therapy for COVID-19 pneumonia: is there any supportive evidence?’ published in International Jou...

The use of low-dose radiation therapy (LDRT) in patients with pneumonia from 1905 to 1943 provided positive results in 83.08 % of cases. Interest in LDRT is supported by researchers of radiation hormesis in the 21st century. Attention is drawn to the dynamics of coronavirus infection in the regions of Ukraine and the Kirovograd region with a minimum incidence. It is known that 95 % of uranium ore deposits in Ukraine are concentrated in the Kirovograd region. The positive experience of LDRT in Iran, India, USA, Spain for the treatment of patients with COVID-19 is described. LDRT (

Cancer is the second leading cause of mortality worldwide accounting for almost 10 million deaths in 2020. Current standard of care treatment varies depending on the type and stage of disease, but commonly includes surgery, chemotherapy, and/or radiation therapy. There is evidence that whole- and half-body exposure to low dose ionizing radiation can also be an effective therapeutic due to its stimulation of anti-cancer immunity. One of the limiting factors for past clinical trials using low dose radiation therapy has been adverse hematological events. However, similar hematological changes are also frequently reported following standard of care treatments in oncology. This review summarizes the effects of various cancer therapies on hematologic toxicity through the evaluation of complete blood count reports. The reviewed literature elucidates hematological trends in patients undergoing chemotherapy, and both high and low dose radiation therapy. In general, high dose radiation and chemotherapy can result in widespread changes in blood counts, with the most severe effects related to leukopenia. Overall, compared to standard of care treatments, low dose radiation results in similar, yet more mild hematological changes. Taken together, hematological toxicities should not be a limiting factor in the applicability of low dose radiation as a cancer therapeutic.

Purpose Radiotherapy represents an effective treatment option in Graves’ ophthalmopathy (GO), leading to palliation of clinical symptoms. However, there are only a limited number of trials comparing the effectiveness of low- vs. high-dose radiotherapy. Methods We analyzed 127 patients treated with radiotherapy for stage 3/4 GO (NOSPECS classification). Patients were treated with single doses of 2.0 Gy (cumulative dose 20 Gy) until 2007, afterwards a single dose of 0.8 Gy (cumulative dose 4.8 Gy) was applied. With a median follow-up-time of 9.0 years, the treatment efficacy (overall improvement, sense of eye pressure, lid edema, ocular motility, exophthalmos, subjective vision, and diplopia) and adverse effects were analyzed by a standardized survey. Results Overall, 63.8% described improvement of symptoms after radiotherapy. No significant differences in overall treatment response and improvement of main outcome measures between low- or high-dose radiotherapy treatments are detectable, while low-dose radiotherapy leads significantly more often to retreatment (13.1% vs. 1.7%, p = 0.016). The main independent predictor of treatment response is the presence of lid edema (odds ratio, OR, 3.53; p = 0.006). Conclusion At long-term follow-up, the majority of patients reported palliation of symptoms with limited adverse effects, suggesting clinical effectiveness of radiotherapy for amelioration of GO symptoms independent of low- or high-dose radiotherapy.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative pathogen of the coronavirus disease 2019 (COVID-19), has caused more than 179 million infections and 3.8 million deaths worldwide. Global health authorities working on the COVID-19 outbreak continue to explore methods to reduce the rate of its transmission to healthy individuals. Treatment protocols thus far have focused on social distancing and masking, treatment with antivirals early in infection, and steroids to reduce the inflammatory response. An alternative approach is therapy with low dose radiation (LDR), which has several advantages compared to the current drugs and medicines. To date more than 10 case reports and pilot clinical trial preliminary outcome are available from different countries. These reports cover a wide range of patient conditions and LDR treatment strategies. Although one report showed the failure to observe the improvement of COVID-19 patients after LDR therapy, the majority showed some clinical improvement, and demonstrated the safety of LDR for COVID-19 patients, particularly with 0.5 Gy. This review aims to summarize the potential rationales and mechanisms of LDR therapy for COVID-19 patients, and its current clinical status and potential use.

Treatment options are rather limited for gastrointestinal cancer patients whose disease has disseminated into the intra-abdominal cavity. Here, we designed pre-clinical studies to evaluate the potential application of chemopotentiation by Low Dose Fractionated Radiation Therapy (LDFRT) for disseminated gastric cancer and evaluate the role of a likely biomarker, Dual Oxidase 2 (DUOX2). Nude mice were injected orthotopically with human gastric cancer cells expressing endogenous or reduced levels of DUOX2 and randomly assigned to four treatment groups: 1, vehicle alone, 2, modified regimen of docetaxel, cisplatin and 5′-fluorouracil (mDCF) for three consecutive days, 3, Low Dose- Whole Abdomen Radiation Therapy (LD-WART) (5 fractions of 0.15 Gy in three days), 4, mDCF and LD-WART. The combined regimen increased the odds of preventing cancer dissemination (mDCF + LD-WART OR = 4.16, 80% CI = 1.0, 17.29) in the DUOX2 positive tumors, while tumors expressing lower DUOX2 levels were more responsive to mDCF alone with no added benefit from LD-WART. The molecular mechanisms underlying DUOX2 effects in response to the combined regimen include NF-κB upregulation. These data are particularly important since our study indicates that about 33% of human stomach adenocarcinoma do not express DUOX2. DUOX2 thus seems a likely biomarker for potential clinical application of chemopotentiation by LD-WART.

Using low-dose radiation therapy (LDRT) to treat inflammation, pneumonia, and coronavirus disease 2019 (COVID-19) has been investigated. Results have revealed that LDRT can improve inflammation in different line cells, animals, and humans. It was demonstrated that LDRT with a single dose (0.3-1 Gy) to the lungs could treat pneumonia resulting from COVID-19 by avoiding normal tissue toxicities. These suggested values of doses are obtained from the historical use of ionizing radiation for pneumonia [1]. A clinical study recently treated five patients with COVID-19 in the age range of 64-96 years; the lungs of these patients were exposed to 1.5 Gy of radiation in one fraction. Results showed that their respiratory conditions were quickly improved in four patients in the first 24 hours of exposure. The results of blood tests and imaging also confirmed the positive effect of LDRT on COVID-19 treatment [2]. Short course results of another study carried out on five patients with COVID-19 aged over 60 years, who underwent national COVID-19 therapy protocols, showed that using 0.5 Gy of radiation in one fraction led to the improvement of four patients in the first few days after exposure. Apart from that, they were discharged from the hospital with an average of 6 days, and no radiation toxicity was observed in them [3]. Another clinical investigation has used LDRT on nine patients to treat COVID-19. In this study, patients received 1 Gy to total lungs, and the SatO2/FiO2 index of these patients was evaluated. Results showed that this index significantly improved 72 hours and one week after LDRT, and inflammation of the lungs decreased one week after radiation therapy. Compared to patients who did not receive LDRT, the median days of hospitalization of patients who received LDRT was reduced by approximately one-fifth. Among these patients, seven were discharged, and two patients died [4]. The incidence of cancers such as lung, esophagus, and breast is one of the controversial subjects surrounding the use of LDRT in COVID-19 treatment. According to the Biological Effects of Ionization Radiation VII (BEIR VII) model, the risk of lung cancer was estimated for patients with COVID-19 whose lungs were irradiated to 0.5 Gy. The incidence of lung cancer can increase by 0.84% and 2.3% for males and females aged above 60 years, respectively. On the other hand, for young patients aged 25 years, the incidence of lung cancer was estimated at 1.1% and 3% for males and females, respectively [5]. According to this model, with an increase in the dose received by the lungs, the risk of lung cancer increases linearly; therefore, the incidence of lung cancer for patients whose whole lung receives a dose of 1.5 Gy will be three times for those who have received a dose of 0.5 Gy [6]. Based on these results, exposure of the lungs to the dose in the range 0.5-1.5 Gy can increase the risk of lung cancer up to 9% and 7% for female patients and 3.3% and 2.5% for male patients aged 25 and 65, respectively. Of course, it should be noted that smoking should be considered in estimating the risk of lung cancer in addition to the radiation factor. Besides the lungs, the heart and esophagus may also be exposed to radiation, increasing the risk of esophageal cancer and heart disease. Nevertheless, blood factors, smoking, and a history of heart disease can be influential in the incidence of heart disease in addition to radiation [7,8]. Results of these clinical trials have shown that the recommended dose (0.5-1.5 Gy) can increase lung cancer up to 9%. As one of the possible effects of ionizing radiation is carcinogenicity, no threshold has been defined for its occurrence, but another issue in radiobiology is the risk-benefit of ionizing radiation. As no radiation toxicities were reported in the said clinical studies, it seems that LDRT is safe; however, more clinical studies are needed to prove this claim. We should not hastily recommend the use of LDRT as an adjuvant treatment for COVID-19. To make a definite comment and evaluate the feasibility and efficacy of LDRT to treat COVID-19, we need more clinical studies with many patients.

The treatment of chronic inflammatory and degenerative diseases by low dose radiation therapy (LDRT) is promising especially for patients who were refractory for classical therapies. LDRT aims to reduce pain of patients and to increase their mobility. Although LDRT has been applied since the late 19th century, the immunological mechanisms remain elusive. Within the prospective IMMO-LDRT01 trial (NCT02653079) the effects of LDRT on the peripheral blood immune status, as well as on pain and life quality of patients have been analyzed. Blood is taken before and after every serial irradiation with a single dose per fraction of 0.5Gy, as well as during follow-up appointments in order to determine a detailed longitudinal immune status by multicolor flow cytometry. Here, we report the results of an interim analysis of 125 patients, representing half the number of patients to be recruited. LDRT significantly improved patients’ pain levels and induced distinct systemic immune modulations. While the total number of leukocytes remained unchanged in the peripheral blood, LDRT induced a slight reduction of eosinophils, basophils and plasmacytoid dendritic cells and an increase of B cells. Furthermore, activated immune cells were decreased following LDRT. Especially cells of the monocytic lineage correlated to LDRT-induced improvements of clinical symptoms, qualifying these immune cells as predictive biomarkers for the therapeutic success. We conclude that LDRT improves pain of the patients by inducing systemic immune modulations and that immune biomarkers could be defined for prediction by improved patient stratification in the future.

Mycosis fungoides (MF) represents the most common type of cutaneous T-cell lymphoma. MF is characterized by pruritic patches, plaques, and tumors that wax and wane, often with delayed diagnosis. Although the mortality rate of MF is lower than other types of non-Hodgkin lymphoma, it has a significant impact on quality of life. This case describes refractory facial MF tumors that responded to low-dose radiation therapy (RT).

The covid-19 pandemic has been affecting many countries across the world and lost precious lives. Most patients suffer from respiratory disease which progresses to the severe acute respiratory syndrome, termed as SARS-CoV-2 pneumonia. A systemic inflammatory response occurs in SARS-CoV-2 pneumonia severely ill patients, The inflammation process if uncontrolled has a detrimental effect, and the release of cytokines play an important role leading to lung fibrosis. Radiation therapy used in low doses has an anti-inflammatory and immunomodulatory effect. Its low cost, wider availability, and decreased risk of acute side effects can reduce the burden on the health care system.

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.

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.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.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 (p0.01), analyses of secondary endpoints revealed no significant differences between the groups.Whole-lung LDRT failed to improve clinical outcomes in critically ill patients requiring mechanical ventilation for COVID-19 pneumonia.

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 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 intensive care unit clinicians, who treated patients according to the current standard of care. Patients were followed for the primary endpoint of ventilator-free days at day 15 postintervention. 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 ventilator-free days 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% confidence interval, 40.7%-99.5%) in both arms (P = .69). Apart from a more pronounced reduction in lymphocyte counts after LDRT (P < .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.

International audience; Ionizing radiation interacts with the immune system in many ways with a multiplicity that mirrors thecomplexity of the immune system itself: namely the need to maintain a delicate balance between differentcompartments, cells and soluble factors that work collectively to protect, maintain, and restore tissue function inthe face of severe challenges including radiation damage. The cytotoxic effects of high dose radiation are lessrelevant after low dose exposure, where subtle quantitative and functional effects predominate that may gounnoticed until late after exposure or after a second challenge reveals or exacerbates the effects. For example,low doses may permanently alter immune fitness and therefore accelerate immune senescence and pave the wayfor a wide spectrum of possible pathophysiological events, including early-onset of age-related degenerativedisorders and cancer. By contrast, the so called low dose radiation therapy displays beneficial, anti-inflammatoryand pain relieving properties in chronic inflammatory and degenerative diseases. In this review, epidemiological,clinical and experimental data regarding the effects of low-dose radiation on the homeostasis and functionalintegrity of immune cells will be discussed, as will be the role of immune-mediated mechanisms in the systemicmanifestation of localized exposures such as inflammatory reactions. The central conclusion is that ionizingradiation fundamentally and durably reshapes the immune system. Further, the importance of discovery ofimmunological pathways for modifying radiation resilience amongst other research directions in this field isimplied.

Purpose To evaluate the efficacy and safety of lung low-dose radiation therapy (LD-RT) for pneumonia in patients with coronavirus disease 2019 (COVID-19). Materials and methods Inclusion criteria comprised patients with COVID-19-related moderate–severe pneumonia warranting hospitalization with supplemental O2 and not candidates for admission to the intensive care unit because of comorbidities or general status. All patients received single lung dose of 0.5 Gy. Respiratory and systemic inflammatory parameters were evaluated before irradiation, at 24 h and 1 week after LD-RT. Primary endpoint was increased in the ratio of arterial oxygen partial pressure (PaO2) or the pulse oximetry saturation (SpO2) to fractional inspired oxygen (FiO2) ratio of at least 20% at 24 h with respect to the preirradiation value. Results Between June and November 2020, 36 patients with COVID-19 pneumonia and a mean age of 84 years were enrolled. Seventeen were women and 19 were men and all of them had comorbidities. All patients had bilateral pulmonary infiltrates on chest X‑ray. All patients received dexamethasone treatment. Mean SpO2 pretreatment value was 94.28% and the SpO2/FiO2 ratio varied from 255 mm Hg to 283 mm Hg at 24 h and to 381 mm Hg at 1 week, respectively. In those who survived (23/36, 64%), a significant improvement was observed in the percentage of lung involvement in the CT scan at 1 week after LD-RT. No adverse effects related to radiation treatment have been reported. Conclusions LD-RT appears to be a feasible and safe option in a population with COVID-19 bilateral interstitial pneumonia in the presence of significant comorbidities.

Background and purpose The objective of this work is to evaluate the risk of carcinogenesis of low dose ionizing radiation therapy (LDRT), for treatment of immune-related pneumonia following COVID-19 infection, through the estimation of effective dose and the lifetime attributable risk of cancer (LAR). Material and methods LDRT treatment was planned in male and female computational phantoms. Equivalent doses in organs were estimated using both treatment planning system calculations and a peripheral dose model (based on ionization chamber measurements). Skin dose was estimated using radiochromic films. Later, effective dose and LAR were calculated following radiation protection procedures. Results Equivalent doses to organs per unit of prescription dose range from 10 mSv/cGy to 0.0051 mSv/cGy. Effective doses range from 204 mSv to 426 mSv, for prescription doses ranging from 50 cGy to 100 cGy. Total LAR for a prescription dose of 50 cGy ranges from 1.7 to 0.29% for male and from 4.9 to 0.54% for female, for ages ranging from 20 to 80 years old. Conclusions The organs that mainly contribute to risk are lung and breast. Risk for out-of-field organs is low, less than 0.06 cases per 10000. Female LAR is on average 2.2 times that of a male of the same age. Effective doses are of the same order of magnitude as the higher-dose interventional radiology techniques. For a 60 year-old male, LAR is 8 times that from a cardiac CT, when prescription dose is 50 cGy.

The coronavirus disease-2019 (COVID-19) pandemic caused by SARS-CoV-2 has exacted an enormous toll on healthcare systems worldwide. The cytokine storm that follows pulmonary infection is causally linked to respiratory compromise and mortality in the majority of patients. The sparsity of viable treatment options for this viral infection and the sequelae of pulmonary complications have fueled the quest for new therapeutic considerations. One such option, the long-forgotten idea of using low-dose radiation therapy, has recently found renewed interest in many academic centers. We outline the scientific and logistical rationale for consideration of this option and the mechanistic underpinnings of any potential therapeutic value, particularly as viewed from an immunological perspective. We also discuss the preliminary and/or published results of prospective trials examining low-dose radiation therapy for COVID-19.

Purpose Recently, several studies have reported that low-dose radiation therapy (RT) suppresses the release of proinflammatory cytokines in inflammatory-degenerative disorders, including Alzheimer disease (AD). AD is the most common cause of dementia, and neuroinflammation is one of the major contributing factors in AD pathogenesis. Therefore, low-dose RT may be used clinically for treating AD. However, the appropriate doses, effects, and underlying mechanisms of RT in AD have not been determined. In this study, we aimed to determine the appropriate RT dose and schedule for AD treatment and to investigate the therapeutic effects and mechanisms of low-dose RT in AD. Methods and Materials We first determined the proper dose and schedule for RT in late-stage AD using 8- to 9-month-old 5x Familial AD (5xFAD) mice, a well-known animal model of AD, by comparing the effects of a low total dose with low dose per fraction (LD-LDRT, 5 × 0.6 Gy) with those of a low moderate total dose with conventional dose per fraction (LMD-CDRT, 5 × 2 Gy). Results LD-LDRT and LMD-CDRT were found to reduce the levels of the proinflammatory cytokines CD54, IL-3, CXCL9/10, and CCL2/4 in the hippocampus of 5xFAD mice. Furthermore, increased microgliosis assessed using Iba-1 and CD68 dual immunostaining was significantly reduced by LD-LDRT and LMD-CDRT in the hippocampus of 5xFAD mice. Moreover, LD-LDRT and LMD-CDRT decreased the amyloid plaque burden in the hippocampus of 5xFAD mice and attenuated their cognitive impairment; these effects persisted for 4 to 5 weeks. Conclusions The present study showed that LD-LDRT alleviates cognitive impairments and prevents the accumulation of amyloid plaques by regulating neuroinflammation in the late stage of AD in 5xFAD mice, with an efficacy equivalent to that of LMD-CDRT. Furthermore, the findings suggest that compared with LMD-CDRT, LD-LDRT may facilitate accessible and convenient treatment in clinical trials.

Covid-19 is a morbid respiratory disease that has caused desperate times on a global scale due to the lack of any effective medical treatment. Some in the radiation community are actively proposing low-dose radiation therapy (LDRT) for managing the viral pneumonia associated with Covid-19. This commentary provides a rationale for exercising caution against such a decision as the efficacy of LDRT for viral diseases is unknown, while its long-term adverse risks are well known.

Currently, there are 14 ongoing clinical studies on low dose radiotherapy (LDRT) for COVID-19 pneumonia. An underlying assumption is that irradiation of about 1 Gy is effective at ameliorating viral pneumonia. Its rationale, however, relies on early human case series or animal studies mostly obtained in the pre-antibiotic era, where rigorous statistical analyses were not performed. It therefore remains unclear whether those early data support such assumptions. With standard statistical survival models, and based on a systematic literature review, we re-analyzed 14 radiobiological animal datasets in which animals received mostly fractionated doses of radiation before or after bacterial/viral inoculation, and assessing various health endpoints (mortality, pneumonia morbidity). In most datasets absorbed doses did not exceed 7 Gy. Various different model systems and types of challenging infection are considered. For 7 studies that evaluated post-inoculation radiation exposure (more relevant to LDRT for COVID-19 pneumonia) the results are heterogeneous, with 2 studies showing a significant increase (p, 2 tables, 7 figures, 15 Appendix Tables, 36 references, 49 double spaced pages

The limited impact of treatments for COVID-19 has stimulated several phase 1 clinical trials of whole-lung low-dose radiation therapy (LDRT; 0.3-1.5 Gy) that are now progressing to phase 2 randomized trials worldwide. This novel but unconventional use of radiation to treat COVID-19 prompted the National Cancer Institute, National Council on Radiation Protection and Measurements and National Institute of Allergy and Infectious Diseases to convene a workshop involving a diverse group of experts in radiation oncology, radiobiology, virology, immunology, radiation protection and public health policy. The workshop was held to discuss the mechanistic underpinnings, rationale, and preclinical and emerging clinical studies, and to develop a general framework for use in clinical studies. Without refuting or endorsing LDRT as a treatment for COVID-19, the purpose of the workshop and this review is to provide guidance to clinicians and researchers who plan to conduct preclinical and clinical studies, given the limited available evidence on its safety and efficacy.

Strahlentherapie und Onkologie 196(8), 679 - 682 (2020). doi:10.1007/s00066-020-01635-7, Published by Springer Medizin, Heidelberg

Physicians and scientists around the world are aggressively attempting to develop effective treatment strategies. The treatment goal is to reduce the fatality rate in 15% to 20% of individuals infected with SARS-CoV-2 who develop severe inflammatory conditions that can lead to pneumonia, and acute respiratory distress syndrome. These conditions are major causes of death in these patients. Convalescent plasma (CP) col-lected from patients recovered from the novel corona virus disease (COVID-19) has been considered as an effective treatment method for COVID-19. Moreover, low-dose radiation therapy (LDRT) for COVID-19 pneumonia was historically used to treat pneumonia during the first half of the 20th century. The concept of LDRT for CO-VID-19 pneumonia was first introduced in March 2020. Later scientists from Cana-da, Spain, United States, Germany and France also confirmed the potential efficacy of LDRT for treatment of COVID-19 pneumonia. The rationale behind introducing LDRT as an effective treatment method for pneumonia in COVID-19 patients is not only due to its anti-inflammatory effect, but also in optimization of the activity of the immune system. Moreover, LDRT, unlike other treatment methods such as antiviral drugs, does not have the key disadvantage of exerting a significant selective pressure on the SARS-CoV-2 virus and hence does not lead to evolution of the virus through mutations. Given these considerations, we believe that a hybrid treatment including both CP and LDRT can trigger synergistic responses that will help healthcare providers in mitigating today’s COVID-19 pandemic.

The novel coronavirus, SARS-CoV-2, that causes the COVID-19 disease currently has healthcare systems around the world dealing with unprecedented numbers of critically ill patients. One of the primary concerns associated with this illness is acute respiratory distress syndrome (ARDS) and the pneumonia that accompanies it. Historical literature dating back to the 1940s and earlier contains many reports of successful treatment of pneumonias with ionizing radiation. Although these were not randomized controlled trials, they do suggest a potential avenue for further investigation. Technical details in these reports however were limited. In this work we review the literature and identify details including nominal kilovoltage ranges, filtration, and focus-skin distances (FSDs). Using a freely available and benchmarked code, we generated spectra and used these as sources for Monte Carlo simulations using the EGSnrc software package. The approximate sources were projected through a radiologically anthropomorphic phantom to provide detailed dose distributions within a targeted lung volume (approximate right middle lobe). After accounting for the reported exposure levels, mean lung doses fell in a relatively narrow range: 30-80 cGy. Variation in patient dimensions and other details are expected to result in an uncertainty on the order of ± 20%. This result is consistent with the dose range expected to induce anti-inflammatory effects.

The discovery of X-rays in 1895 had a dramatic impact on many aspects of society. One was the hope that it would be possible to treat some of the numerous infections and inflammatory conditions for...

Purpose Hypofractionated radiation therapy (HFRT) can induce antitumor T cell responses, particularly in combination with immune checkpoint inhibitors (ICI), but abscopal effects are often precluded by insufficient T cell infiltration of distant, nonirradiated tumors. Additional noncytotoxic, low-dose radiation therapy (LDRT) of distant tumors may enhance the abscopal response, but clinical evidence and preclinical studies for this scenario are lacking. Methods and Materials We investigated whether triple treatment consisting of HFRT, ICI, and LDRT could achieve better systemic antitumor response in bilateral mouse tumor models and in patients with stage IV non-small cell lung cancer. Results Our analyses of bilateral mouse tumor models show that HFRT treatment of the primary tumor combined with LDRT treatment of the abscopal tumor and anti-PD1 therapy enhances the abscopal response compared with HFRT/anti-PD1, HFRT/LDRT, or LDRT/anti-PD1 double treatments; complete cure was observed in more than half of the mice treated with triple therapy. The enhanced abscopal effect was associated with increased infiltration of CD8+ effector T cells and upregulated expression of T cell–attracting chemokines. Of 9 patients with metastatic non-small cell lung cancer who were treated with this triple therapy, 3 and 2 patients showed partial responses and stable disease, respectively. Among 9 relatively large (175.7 ± 42.3 cm3) LDRT lesions, 6 lesions decreased by 28% in size, on average. Conclusions Our study demonstrates preclinically that LDRT of established metastases significantly enhances the abscopal response to HFRT plus ICI. It also shows that additional LDRT was well tolerated by patients and that this treatment profile is effective and worth further study.

Very low-dose radiotherapy (4 Gy; VLDRT) is an effective treatment for indolent lymphomas and offers the advantage of a shorter course and improved side effect profile compared to full dose RT regi...