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1.
Nat Cancer ; 3(5): 526-527, 2022 05.
Article in English | MEDLINE | ID: covidwho-1873559
2.
J Appl Clin Med Phys ; 23(3): e13506, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1733832

ABSTRACT

PURPOSE: To evaluate a knowledge-based (KB) planning model for RapidPlan, generated using a five-field intensity-modulated radiotherapy (IMRT) class solution beam strategy and rigorous dosimetric constraints for accelerated partial breast irradiation (APBI). MATERIALS AND METHODS: The RapidPlan model was configured using 64 APBI treatment plans and validated for 120 APBI patients who were not included in the training dataset. KB plan dosimetry was compared to clinical plan dosimetry, the clinical planning constraints, and the constraints used in phase III APBI trials. Dosimetric differences between clinical and KB plans were evaluated using paired two-tailed Wilcoxon signed-rank tests. RESULTS: KB planning was able to produce IMRT-based APBI plans in a single optimization without manual intervention that are comparable or better than the conventionally optimized, clinical plans. Comparing KB plans to clinical plans, differences in PTV, heart, contralateral breast, and ipsilateral lung dose-volume metrics were not clinically significant. The ipsilateral breast volume receiving at least 50% of the prescription dose was statistically and clinically significantly lower in the KB plans. CONCLUSION: KB planning for IMRT-based APBI provides equivalent or better dosimetry compared to conventional inverse planning. This model may be reliably applied in clinical practice and could be used to transfer planning expertise to ensure consistency in APBI plan quality.


Subject(s)
Breast Neoplasms , Radiotherapy, Intensity-Modulated , Breast/radiation effects , Breast Neoplasms/radiotherapy , Female , Humans , Knowledge Bases , Radiometry , Radiotherapy Dosage , Radiotherapy Planning, Computer-Assisted
3.
Cells ; 11(3)2022 01 29.
Article in English | MEDLINE | ID: covidwho-1667055

ABSTRACT

The Coronavirus disease 2019 (COVID-19) pandemic continues to spread worldwide with over 260 million people infected and more than 5 million deaths, numbers that are escalating on a daily basis. Frontline health workers and scientists diligently fight to alleviate life-threatening symptoms and control the spread of the disease. There is an urgent need for better triage of patients, especially in third world countries, in order to decrease the pressure induced on healthcare facilities. In the struggle to treat life-threatening COVID-19 pneumonia, scientists have debated the clinical use of ionizing radiation (IR). The historical literature dating back to the 1940s contains many reports of successful treatment of pneumonia with IR. In this work, we critically review the literature for the use of IR for both diagnostic and treatment purposes. We identify details including the computed tomography (CT) scanning considerations, the radiobiological basis of IR anti-inflammatory effects, the supportive evidence for low dose radiation therapy (LDRT), and the risks of radiation-induced cancer and cardiac disease associated with LDRT. In this paper, we address concerns regarding the effective management of COVID-19 patients and potential avenues that could provide empirical evidence for the fight against the disease.


Subject(s)
COVID-19/radiotherapy , Lung/radiation effects , Pneumonia, Viral/radiotherapy , Radiation, Ionizing , SARS-CoV-2/radiation effects , COVID-19/epidemiology , COVID-19/virology , Humans , Lung/virology , Pandemics/prevention & control , Pneumonia, Viral/diagnosis , Pneumonia, Viral/virology , Prognosis , Radiation Dosage , Radiotherapy Dosage , Risk Factors , SARS-CoV-2/physiology
4.
Radiat Oncol ; 17(1): 10, 2022 Jan 20.
Article in English | MEDLINE | ID: covidwho-1643167

ABSTRACT

BACKGROUND: Low dose radiotherapy (LDRT) of whole lungs with photon beams is a novel method for treating COVID-19 pneumonia. This study aimed to estimate cancer risks induced by lung LDRT for different radiotherapy delivery techniques. METHOD: Four different radiotherapy techniques, including 3D-conformal with anterior and posterior fields (3D-CRT AP-PA), 3D-conformal with 8 coplanar fields (3D-CRT 8 fields), eight fields intensity-modulated radiotherapy (IMRT), and volumetric modulated arc therapy using 2 full arcs (VMAT) were planned on the CT images of 32 COVID-19 patients with the prescribed dose of 1 Gy to the lungs. Organ average and maximum doses, and PTV dose distribution indexes were compared between different techniques. The radiation-induced cancer incidence and cancer-specific mortality, and cardiac heart disease risks were estimated for the assessed techniques. RESULTS: In IMRT and VMAT techniques, heart (mean and max), breast (mean, and max), and stomach (mean) doses and also maximum dose in the body were significantly lower than the 3D-CRT techniques. The calculated conformity indexes were similar in all the techniques. However, the homogeneity indexes were lower (i.e., better) in intensity-modulated techniques (P < 0.03) with no significant differences between IMRT and VMAT plans. Lung cancer incident risks for all the delivery techniques were similar (P > 0.4). Cancer incidence and mortality risks for organs located closer to lungs like breast and stomach were higher in 3D-CRT techniques than IMRT or VMAT techniques (excess solid tumor cancer incidence risks for a 30 years man: 1.94 ± 0.22% Vs. 1.68 ± 0.17%; and women: 6.66 ± 0.81% Vs. 4.60 ± 0.43%: cancer mortality risks for 30 years men: 1.63 ± 0.19% Vs. 1.45 ± 0.15%; and women: 3.63 ± 0.44% Vs. 2.94 ± 0.23%). CONCLUSION: All the radiotherapy techniques had low cancer risks. However, the overall estimated risks induced by IMRT and VMAT radiotherapy techniques were lower than the 3D-CRT techniques and can be used clinically in younger patients or patients having greater concerns about radiation induced cancers.


Subject(s)
COVID-19/radiotherapy , Neoplasms, Radiation-Induced/prevention & control , Radiotherapy Planning, Computer-Assisted , Adult , Aged , Breast/radiation effects , COVID-19/pathology , Female , Heart/radiation effects , Heart Disease Risk Factors , Humans , Iran , Lung/pathology , Lung/radiation effects , Male , Middle Aged , Neoplasms, Radiation-Induced/diagnosis , Neoplasms, Radiation-Induced/etiology , Organs at Risk/radiation effects , Pneumonia, Viral/radiotherapy , Prognosis , Radiotherapy Dosage , Radiotherapy Planning, Computer-Assisted/methods , Radiotherapy, Conformal/methods , Radiotherapy, Intensity-Modulated/methods , Retrospective Studies , Risk Assessment , SARS-CoV-2
5.
Int J Radiat Oncol Biol Phys ; 110(5): 1550-1551, 2021 08 01.
Article in English | MEDLINE | ID: covidwho-1536609
6.
Br J Radiol ; 94(1126): 20210187, 2021 Oct 01.
Article in English | MEDLINE | ID: covidwho-1430508

ABSTRACT

OBJECTIVES: The World Health Organization (WHO) has declared coronavirus disease 2019 (COVID-19) as pandemic in March 2020. Currently there is no specific effective treatment for COVID-19. The major cause of death in COVID-19 is severe pneumonia leading to respiratory failure. Radiation in low doses (<100 cGy) has been known for its anti-inflammatory effect and therefore, low dose radiation therapy (LDRT) to lungs can potentially mitigate the severity of pneumonia and reduce mortality. We conducted a pilot trial to study the feasibility and clinical efficacy of LDRT to lungs in the management of patients with COVID-19. METHODS: From June to Aug 2020, we enrolled 10 patients with COVID-19 having moderate to severe risk disease [National Early Warning Score (NEWS) of ≥5]. Patients were treated as per the standard COVID-19 management guidelines along with LDRT to both lungs with a dose of 70cGy in single fraction. Response assessment was done based on the clinical parameters using the NEWS. RESULTS: All patients completed the prescribed treatment. Nine patients had complete clinical recovery mostly within a period ranging from 3 to 7 days. One patient, who was a known hypertensive, showed clinical deterioration and died 24 days after LDRT. No patients showed the signs of acute radiation toxicity. CONCLUSION: The results of our pilot study suggest that LDRT is feasible in COVID-19 patients having moderate to severe disease. Its clinical efficacy may be tested by conducting randomized controlled trials. ADVANCES IN KNOWLEDGE: LDRT has shown promising results in COVID-19 pneumonia and should be researched further through randomized controlled trials.


Subject(s)
COVID-19/radiotherapy , Pneumonia, Viral/radiotherapy , Adult , Aged , Early Warning Score , Feasibility Studies , Female , Humans , Male , Middle Aged , Pandemics , Pilot Projects , Pneumonia, Viral/virology , Radiotherapy Dosage , SARS-CoV-2
7.
Arch Toxicol ; 95(10): 3425-3432, 2021 10.
Article in English | MEDLINE | ID: covidwho-1321732

ABSTRACT

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.


Subject(s)
COVID-19/radiotherapy , Dose-Response Relationship, Radiation , Humans , NF-E2-Related Factor 2 , Radiotherapy Dosage
8.
Int J Radiat Oncol Biol Phys ; 109(3): 756-763, 2021 03 01.
Article in English | MEDLINE | ID: covidwho-1318870

ABSTRACT

PURPOSE: Fewer attendances for radiation therapy results in increased efficiency and less foot traffic within a radiation therapy department. We investigated outcomes after single-fraction (SF) stereotactic body radiation therapy (SBRT) in patients with oligometastatic disease. METHODS AND MATERIALS: Between February 2010 and June 2019, patients who received SF SBRT to 1 to 5 sites of oligometastatic disease were included in this retrospective study. The primary objective was to describe patterns of first failure after SBRT. Secondary objectives included overall survival (OS), progression-free survival (PFS), high-grade treatment-related toxicity (Common Terminology Criteria for Adverse Events grade ≥3), and freedom from systemic therapy (FFST). RESULTS: In total, 371 patients with 494 extracranial oligometastases received SF SBRT ranging from 16 Gy to 28 Gy. The most common primary malignancies were prostate (n = 107), lung (n = 63), kidney (n = 52), gastrointestinal (n = 51), and breast cancers (n = 42). The median follow-up was 3.1 years. The 1-, 3-, and 5-year OS was 93%, 69%, and 55%, respectively; PFS was 48%, 19%, and 14%, respectively; and FFST was 70%, 43%, and 35%, respectively. Twelve patients (3%) developed grade 3 to 4 treatment-related toxicity, with no grade 5 toxicity. As the first site of failure, the cumulative incidence of local failure (irrespective of other failures) at 1, 3 and 5 years was 4%, 8%, and 8%, respectively; locoregional relapse at the primary was 10%, 18%, and 18%, respectively; and distant failure was 45%, 66%, and 70%, respectively. CONCLUSIONS: SF SBRT is safe and effective, and a significant proportion of patients remain FFST for several years after therapy. This approach could be considered in resource-constrained or bundled-payment environments. Locoregional failure of the primary site is the second most common pattern of failure, suggesting a role for optimization of primary control during metastasis-directed therapy.


Subject(s)
Neoplasm Metastasis/radiotherapy , Radiosurgery/methods , Adult , Aged , Aged, 80 and over , COVID-19/epidemiology , Female , Humans , Male , Middle Aged , Neoplasms/radiotherapy , Neoplasms/surgery , Pandemics , Progression-Free Survival , Radiation Injuries/pathology , Radiosurgery/adverse effects , Radiotherapy Dosage , Retrospective Studies , Salvage Therapy , Treatment Failure , Young Adult
9.
Respir Med ; 186: 106531, 2021 09.
Article in English | MEDLINE | ID: covidwho-1300990

ABSTRACT

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.


Subject(s)
COVID-19/radiotherapy , Radiotherapy/methods , Severe Acute Respiratory Syndrome/radiotherapy , COVID-19/complications , COVID-19/virology , Cytokines/metabolism , Disease Progression , Humans , Inflammation , Inflammation Mediators/metabolism , Macrophages , Pulmonary Fibrosis/etiology , Pulmonary Fibrosis/radiotherapy , Radiotherapy Dosage , SARS-CoV-2 , Severe Acute Respiratory Syndrome/etiology , Severity of Illness Index
10.
Strahlenther Onkol ; 197(11): 1010-1020, 2021 11.
Article in English | MEDLINE | ID: covidwho-1298545

ABSTRACT

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 X­ray. 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.


Subject(s)
COVID-19/radiotherapy , Radiotherapy, Conformal/methods , SARS-CoV-2 , Aged , Aged, 80 and over , Anti-Inflammatory Agents/therapeutic use , C-Reactive Protein/analysis , COVID-19/diagnostic imaging , COVID-19/mortality , COVID-19/therapy , Cause of Death , Combined Modality Therapy , Comorbidity , Dexamethasone/therapeutic use , Female , Ferritins/blood , Fibrin Fibrinogen Degradation Products/analysis , Hospital Mortality , Humans , Interleukin-6/blood , L-Lactate Dehydrogenase/blood , Lung/diagnostic imaging , Lung/radiation effects , Lung Diseases, Interstitial/diagnostic imaging , Lung Diseases, Interstitial/drug therapy , Lung Diseases, Interstitial/radiotherapy , Lung Diseases, Interstitial/therapy , Male , Oxygen/blood , Oxygen/therapeutic use , Oxygen Inhalation Therapy , Partial Pressure , Prospective Studies , Radiotherapy Dosage , Severity of Illness Index , Tomography, X-Ray Computed , Treatment Outcome
11.
J Cancer Res Clin Oncol ; 147(6): 1757-1761, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1287438

ABSTRACT

PURPOSE: Low-dose total skin electron beam therapy (TSEBT) over 3 weeks has proved to be a safe and effective treatment for cutaneous T cell lymphomas (CTCL). In this prospective trial, we examined the feasibility of ultra-hypofractionated low-dose TSEBT regimen in two fractions with 4 Gy combined with systemic therapy to minimize the number of visits to radiation centers. PATIENTS AND METHODS: Six patients with mycosis fungoides (MF) or Sézary syndrome (SS) received TSEBT with a total radiation dose of 8 Gy in two fractions between April 2020 and June 2020. Patient and treatment characteristics, tumor burden, the impact on the quality of life using Skindex-29 questionnaires, and acute toxicities were analyzed. RESULTS: During TSEBT, all patients developed grade 1 toxicities while two patients developed grade 2 toxicities. One patient experienced sepsis. The most common adverse effects were erythema and edema. All grade 2 toxicities regressed after 4 weeks following TSEBT. Based on the reported symptoms measured by Skindex-29, we detected a significant reduction in total Skindex-29 score after 8 weeks of radiation (P = 0.03), particularly in the symptoms (P = 0.01) and emotional domains (P = 0.04). CONCLUSION: Ultra-hypofractionated low-dose TSEBT followed by systemic therapy seems to be a safe and feasible alternative to conventional fractionated TSEBT for patients with MF/SS. The skin tumor burden and the health-related quality of life have been significantly improved within 8 weeks following radiotherapy.


Subject(s)
Dose Fractionation, Radiation , Lymphoma, T-Cell, Cutaneous/radiotherapy , Radiotherapy, Conformal/methods , Skin Neoplasms/radiotherapy , Aged , Feasibility Studies , Female , Humans , Lymphoma, T-Cell, Cutaneous/complications , Male , Middle Aged , Mycosis Fungoides/complications , Mycosis Fungoides/radiotherapy , Quality of Life , Radiation Injuries/diagnosis , Radiation Injuries/etiology , Radiotherapy Dosage , Radiotherapy, Conformal/adverse effects , Sezary Syndrome/complications , Sezary Syndrome/radiotherapy , Skin Neoplasms/complications , Treatment Outcome
12.
Br J Radiol ; 94(1124): 20201265, 2021 Aug 01.
Article in English | MEDLINE | ID: covidwho-1288671

ABSTRACT

Infection, the invasion of pathogenic microorganisms and viruses, causes reactive inflammation mediated by endogenous signals, with influx of leucocytes with distinct properties and capable of mounting a cellular or antibody response. Different forms of inflammation may also occur in response to tumours, in allergy and autoimmune disorders. Pneumonia, respiratory tract infection and septic shock for instance can arise as serious complications of the Covid-19 virus. While radiotherapy has been most widely used to control malignant tumours, it has also been used for treatment of non-malignant diseases, including acute and chronic inflammation in situations where anti-inflammatory drugs may be ineffective or contraindicated. The present review examines the history and prospects for low-dose anti-inflammatory radiation treatments, the present interest largely being motivated by the increased incidence of pulmonary disease associated Covid-19 infections. Evidence in support of the suggested efficacy are covered, together with an appraisal of one of the number of potential convenient sources that could complement external beam arrangements.


Subject(s)
Asthma/radiotherapy , COVID-19/radiotherapy , Pneumonia/radiotherapy , Respiratory Distress Syndrome/radiotherapy , Humans , Radiotherapy Dosage
13.
J Cancer Res Ther ; 17(2): 295-302, 2021.
Article in English | MEDLINE | ID: covidwho-1268380

ABSTRACT

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.


Subject(s)
COVID-19/radiotherapy , Cytokine Release Syndrome/radiotherapy , SARS-CoV-2/immunology , COVID-19/complications , COVID-19/immunology , COVID-19/virology , Clinical Decision-Making , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/virology , Humans , Radiotherapy Dosage , Severity of Illness Index , Treatment Outcome
14.
Int J Radiat Oncol Biol Phys ; 111(1): 233-239, 2021 09 01.
Article in English | MEDLINE | ID: covidwho-1209500

ABSTRACT

PURPOSE: The respiratory disease COVID-19 reached global pandemic status in 2020. Excessive inflammation is believed to result in the most severe symptoms and death from this disease. Because treatment options for patients with severe COVID-19 related pulmonary symptoms remain limited, whole-lung low-dose radiation therapy is being evaluated as an anti-inflammatory modality. However, there is concern about the long-term risks associated with low-dose pulmonary irradiation. To help quantify the benefit-risk balance of low-dose radiation therapy for COVID-19, we estimated radiation-induced lifetime risks of both lung cancer and heart disease (major coronary events) for patients of different sexes, treated at ages 50 to 85, with and without other relevant risk factors (cigarette smoking and baseline heart disease risk). METHODS AND MATERIALS: These estimates were generated by combining state-of-the-art radiation risk models for lung cancer and for heart disease together with background lung cancer and heart disease risks and age/sex-dependent survival probabilities for the U.S. RESULTS: Estimated absolute radiation-induced risks were generally higher for lung cancer compared with major coronary events. The highest estimated lifetime radiation-induced lung cancer risks were approximately 6% for female smokers treated between ages 50 and 60. The highest estimated radiation-induced heart disease risks were approximately 3% for males or females with high heart disease risk factors and treated between ages 50 and 60. CONCLUSIONS: The estimated summed lifetime risk of lung cancer and major coronary events reached up to 9% in patients with high baseline risk factors. Predicted lung cancer and heart disease risks were lowest in older nonsmoking patients and patients with few cardiac risk factors. These long-term risk estimates, along with consideration of possible acute reactions, should be useful in assessing the benefit-risk balance for low-dose radiation therapy to treat severe COVID-19 pulmonary symptoms, and suggest that background risk factors, particularly smoking, should be taken into account in such assessments.


Subject(s)
COVID-19/radiotherapy , Heart Diseases/etiology , Lung Neoplasms/etiology , Lung/radiation effects , Neoplasms, Radiation-Induced/etiology , Radiation Dosage , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Radiotherapy Dosage , Risk Factors
15.
Cancer Radiother ; 25(5): 494-501, 2021 Jul.
Article in French | MEDLINE | ID: covidwho-1202974

ABSTRACT

The world has now been facing the coronavirus disease 2019 (COVID-19) pandemic due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) since over a year. If most of clinical presentations are benign, fragile patients are at greater risk of developing severe or fatal lung disease. Many therapies have been explored with very low impact on mortality. In this context, Kirkby et Mackenzie have published in April 2020 a report reminding the anti-inflammatory properties of low-dose radiotherapy (delivering less than 1Gy) and its use in the treatment of viral and bacterial pneumopathies before antibiotics era. Large in vivo and in vitro data have demonstrated the biological rationale and anti-inflammatory activity of low-dose radiotherapy in many pathologies. Over the past year, three phase I/II clinical trials have been published, as well as one randomized controlled trial, reporting the feasibility and the clinical and biological improvement of a 0.5 to 1Gy treatment dose to the entire lung. 13 other studies, including a randomized phase III trial, are currently ongoing worldwide. These studies may provide data in the effect of low-dose radiotherapy in the treatment of SARS-CoV-2 pneumonia. This article explains biological rationale of low-dose radiotherapy, and reports already published or ongoing studies on low-dose radiotherapy for SARS-CoV-2 pneumonia.


Subject(s)
COVID-19/radiotherapy , COVID-19/physiopathology , Clinical Trials as Topic , Humans , Radiotherapy Dosage
16.
Radiat Res ; 195(5): 474-479, 2021 05 01.
Article in English | MEDLINE | ID: covidwho-1136341

ABSTRACT

In this work, we considered the theoretical role of low-dose radiation therapy (approximately 0.5-1.0 Gy) in the treatment of respiratory distress syndrome associated with COVID-19 infection. Monte Carlo calculations were performed to gauge the ability to deliver low-dose radiation to the thoracic mid-plane using an orthovoltage machine. In addition, the potential harm of a single dose of 0.75 Gy (whole-lung irradiation) was assessed based on the recommendations of the BEIR-VII committee of the U.S. National Research Council. Based on the results of this work, it was determined that an orthovoltage machine (minimum 300 kVp) can be used to deliver 0.75 Gy dose to the lungs while respecting cutaneous tolerance. Using data from the BEIR-VII Committee, it is evident that the apparent benefits of such radiation treatment for patients suffering from severe manifestations of the COVID-19 infectious syndrome outweigh the potential loss of life due to radiation-induced malignancy. Although the vaccination against COVID-19 has become a reality, the spread and mortality in severely ill patients remain unacceptably high. The risk of outbreaks in the future is unknown. We suggest herein that low-dose radiotherapy at the bedside should be rigorously considered as a therapeutic option since it appears to be feasible and safe in the short and long term.


Subject(s)
COVID-19/radiotherapy , Lung/radiation effects , SARS-CoV-2 , COVID-19/complications , Female , Humans , Male , Monte Carlo Method , Neoplasms, Radiation-Induced/mortality , Radiotherapy Dosage
17.
Int J Radiat Oncol Biol Phys ; 110(5): 1283-1294, 2021 08 01.
Article in English | MEDLINE | ID: covidwho-1129036

ABSTRACT

PURPOSE: Severe pneumonia and acute respiratory distress syndrome (ARDS) have been described in patients with severe coronavirus disease 2019 (COVID-19). Recently, early clinical data reported the feasibility of low doses of radiation therapy (RT) in the treatment of ARDS in patients with severe COVID-19. However, the involved mechanisms remained unknown. METHODS AND MATERIALS: Here, we used airways-instilled lipopolysaccharide (LPS) and influenza virus (H1N1) as murine models of pneumonia, and toll-like receptor (TLR)-3 stimulation in human lung macrophages. RESULTS: Low doses of RT (0.5-1 Gray) decreased LPS-induced pneumonia, and increased the percentage of nerve- and airway-associated macrophages producing interleukin (IL) 10. During H1N1 viral infection, we observed decreased lung tissue damage and immune cell infiltration in irradiated animals. Low doses of RT increased IL-10 production by infiltrating immune cells into the lung. Irradiation of TLR-3 ligand-stimulated human lung macrophages ex vivo increased IL-10 secretion and decreased interferon γ production in the culture supernatant. The percentage of human lung macrophages producing IL-6 was also decreased. CONCLUSIONS: Our data highlight a mechanism by which low doses of RT regulate lung inflammation and skew lung macrophages toward an anti-inflammatory profile. These data provide a preclinical mechanistic support to clinical trials evaluating low doses of RT, such as COVID-19-induced ARDS.


Subject(s)
Epithelial Cells/radiation effects , Influenza A Virus, H1N1 Subtype , Interleukin-10/biosynthesis , Macrophages/radiation effects , Pneumonia, Viral/radiotherapy , Respiratory Distress Syndrome/radiotherapy , Animals , Anti-Inflammatory Agents/pharmacology , COVID-19/complications , Dexamethasone/pharmacology , Disease Models, Animal , Epithelial Cells/drug effects , Epithelial Cells/immunology , Epithelial Cells/metabolism , Female , Flow Cytometry , Humans , Influenza A Virus, H1N1 Subtype/radiation effects , Interferon-gamma/biosynthesis , Interleukin-6/biosynthesis , Lipopolysaccharides , Lung/cytology , Lung/pathology , Lung/radiation effects , Macrophages/drug effects , Macrophages/immunology , Macrophages/metabolism , Mice , Mice, Inbred C57BL , Pneumonia, Viral/etiology , Pneumonia, Viral/prevention & control , Poly I-C , Radiotherapy Dosage , Respiratory Distress Syndrome/etiology , Toll-Like Receptor 3 , Viral Load/radiation effects
18.
Int J Radiat Oncol Biol Phys ; 110(5): 1274-1282, 2021 08 01.
Article in English | MEDLINE | ID: covidwho-1116867

ABSTRACT

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.


Subject(s)
COVID-19/radiotherapy , Aged , Aged, 80 and over , COVID-19/diagnostic imaging , COVID-19/drug therapy , COVID-19/mortality , Confidence Intervals , Double-Blind Method , Female , Humans , Intensive Care Units , Kaplan-Meier Estimate , Lung/radiation effects , Lymphocyte Count , Male , Middle Aged , Oxygen Consumption , Patient Positioning , Radiotherapy Dosage , Respiration, Artificial/statistics & numerical data , Time Factors , Treatment Outcome , Ventilator Weaning
19.
Int J Radiat Oncol Biol Phys ; 109(4): 867-879, 2021 03 15.
Article in English | MEDLINE | ID: covidwho-1096007

ABSTRACT

PURPOSE: Phase 1 clinical trials have established low-dose, whole-lung radiation therapy (LD-RT) as safe for patients with coronavirus disease 2019 (COVID-19)-related pneumonia. By focally dampening cytokine hyperactivation, LD-RT may improve disease outcomes through immunomodulation. METHODS AND MATERIALS: Patients with COVID-19-related pneumonia were treated with 1.5 Gy whole-lung LD-RT, followed for 28 days or until hospital discharge, and compared with age- and comorbidity-matched controls meeting identical disease severity criteria. Eligible patients were hospitalized, severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) positive, had radiographic consolidations, and required supplemental oxygen but had not rapidly declined on admission or before drug therapy or LD-RT. Efficacy endpoints were time to clinical recovery, radiographic improvement, and biomarker response. RESULTS: Ten patients received whole-lung LD-RT between April 24 and May 24, 2020 and were compared with 10 control patients blindly matched by age and comorbidity. Six controls received COVID-19 drug therapies. Median time to clinical recovery was 12 days in the control cohort compared with 3 days in the LD-RT cohort (hazard ratio 2.9, P = .05). Median time to hospital discharge (20 vs 12 days, P = .19) and intubation rates (40% vs 10%, P = .12) in the control and LD-RT cohorts were compared. Median time from admission to recovery was 10 versus 13 days (P = .13). Hospital duration average was 19 versus 22.6 days (P = .53). Average hospital days on supplemental oxygen of any duration was 13.1 versus 14.7 days (P = .69). Average days with a documented fever was 1 versus 4.3 days (P = .12). Twenty-eight-day overall survival was 90% for both cohorts. The LD-RT cohort trended toward superior rates of improved radiographs (P = .12) and delirium (P < .01). Statistically significant reductions were observed in numerous hematologic, cardiac, hepatic, and inflammatory markers. CONCLUSIONS: A prospective cohort of predominantly elderly hospitalized patients with COVID-19-related pneumonia were recovered to room air quicker than age- and comorbidity-matched controls, with trending or significant improvements in delirium, radiographs, and biomarkers, and no significant acute toxicity. Low-dose, whole-lung radiation for patients with COVID-19-related pneumonia appears safe and may be an effective immunomodulatory treatment. Larger prospective randomized trials are needed to define the efficacy of LD-RT for COVID-19.


Subject(s)
COVID-19/immunology , COVID-19/radiotherapy , Immunomodulation/radiation effects , Lung/radiation effects , Radiation Dosage , Adult , Aged , Aged, 80 and over , COVID-19/blood , COVID-19/diagnostic imaging , Female , Hospitalization , Humans , Lung/diagnostic imaging , Lung/immunology , Male , Middle Aged , Radiotherapy Dosage , Safety , Tomography, X-Ray Computed , Treatment Outcome
20.
Int J Radiat Oncol Biol Phys ; 109(4): 880-885, 2021 03 15.
Article in English | MEDLINE | ID: covidwho-1083767

ABSTRACT

PURPOSE: Low-dose radiation therapy (LD-RT) has been shown to have an anti-inflammatory effect, and preliminary results suggest it is feasible to treat patients with coronavirus disease 2019 (COVID-19) pneumonia. MATERIALS AND METHODS: We conducted a prospective, single-arm, phase 1/2 clinical trial enrolling patients aged ≥50 years, who were coronavirus disease 2019 (COVID-19) positive, at phase 2 or 3 with lung involvement at imaging study and oxygen requirement. Patients received 100 cGy to total lungs in a single fraction. Primary outcome was radiologic response using severity and extension score on baseline computed tomography (CT), at days 3 and 7 after LD-RT. Secondary outcomes were toxicity using Common Terminology Criteria for Adverse Events v.5.0, duration of hospitalization, blood work evolution, and oxygen requirements using SatO2/FiO2 index (SAFI), at days 3 and 7 after LD-RT. RESULTS: Nine patients were included. Median age was 66 (interquartile range, 57-77). Severity score was stable or decreased in the third CT but was not statistically significant (P = .28); however, there were statistically significant changes in the extension score (P = .03). SAFI index significantly improved 72 hours and 1 week after LD-RT (P = .01). Inflammatory blood parameters decreased 1 week after RT compared with baseline; only lactate dehydrogenase decreased significantly (P = .04). Two patients presented grade 2 lymphopenia after RT and another (with baseline grade 3) worsened to grade 4. Overall, the median number of days of hospitalization was 59 (range, 26-151). After RT the median number of days in the hospital was 13 (range, 4-77). With a median follow-up after RT of 112 days (range, 105-150), 7 patients were discharged and 2 patients died, 1 due to sepsis and the other with severe baseline chronic obstructive pulmonary disease from COVID-19 pneumonia. CONCLUSIONS: Our preliminary results show that LD-RT was a feasible and well-tolerated treatment, with potential clinical improvement. Randomized trials are needed to establish whether LD-RT improves severe pneumonia.


Subject(s)
COVID-19/radiotherapy , Radiation Dosage , Aged , Aged, 80 and over , COVID-19/epidemiology , Female , Humans , Male , Middle Aged , Pandemics , Radiotherapy Dosage , Treatment Outcome
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