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Chest Jul 2019Radiation-induced lung injury (RILI) encompasses any lung toxicity induced by radiation therapy (RT) and manifests acutely as radiation pneumonitis and chronically as... (Review)
Review
Radiation-induced lung injury (RILI) encompasses any lung toxicity induced by radiation therapy (RT) and manifests acutely as radiation pneumonitis and chronically as radiation pulmonary fibrosis. Because most patients with thoracic and breast malignancies are expected to undergo RT in their lifetime, many with curative intent, the population at risk is significant. Furthermore, indications for thoracic RT are expanding given the advent of stereotactic body radiation therapy (SBRT) or stereotactic ablative radiotherapy (SABR) for early-stage lung cancer in nonsurgical candidates as well as oligometastatic pulmonary disease from any solid tumor. Fortunately, the incidence of serious pulmonary complications from RT has decreased secondary to advances in radiation delivery techniques. Understanding the temporal relationship between RT and injury as well as the patient, disease, and radiation factors that help distinguish RILI from other etiologies is necessary to prevent misdiagnosis. Although treatment of acute pneumonitis is dependent on clinical severity and typically responds completely to corticosteroids, accurately diagnosing and identifying patients who may progress to fibrosis is challenging. Current research advances include high-precision radiation techniques, an improved understanding of the molecular basis of RILI, the development of small and large animal models, and the identification of candidate drugs for prevention and treatment.
Topics: Humans; Lung Injury; Neoplasms; Pulmonary Fibrosis; Radiation Injuries; Radiation Pneumonitis
PubMed: 30998908
DOI: 10.1016/j.chest.2019.03.033 -
BMC Pulmonary Medicine Jan 2021Chemo-radiotherapy and systemic therapies have proven satisfactory outcomes as standard treatments for various thoracic malignancies; however, adverse pulmonary effects,... (Review)
Review
Chemo-radiotherapy and systemic therapies have proven satisfactory outcomes as standard treatments for various thoracic malignancies; however, adverse pulmonary effects, like pneumonitis, can be life-threatening. Pneumonitis is caused by direct cytotoxic effect, oxidative stress, and immune-mediated injury. Radiotherapy Induced Lung Injury (RILI) encompasses two phases: an early phase known as Radiation Pneumonitis (RP), characterized by acute lung tissue inflammation as a result of exposure to radiation; and a late phase called Radiation Fibrosis (RF), a clinical syndrome that results from chronic pulmonary tissue damage. Currently, diagnoses are made by exclusion using clinical assessment and radiological findings. Pulmonary function tests have constituted a significant step in evaluating lung function status during radiotherapy and useful predictive tools to avoid complications or limit toxicity. Systemic corticosteroids are widely used to treat pneumonitis complications, but its use must be standardized, and consider in the prophylaxis setting given the fatal outcome of this adverse event. This review aims to discuss the clinicopathological features of pneumonitis and provide practical clinical recommendations for prevention, diagnosis, and management.
Topics: Humans; Lung Injury; Neoplasms; Radiation Injuries; Radiation Pneumonitis; Respiratory Function Tests
PubMed: 33407290
DOI: 10.1186/s12890-020-01376-4 -
Frontiers in Immunology 2021Radiation-induced lung injury (RILI) is a form of radiation damage to normal lung tissue caused by radiotherapy (RT) for thoracic cancers, which is most commonly... (Review)
Review
Radiation-induced lung injury (RILI) is a form of radiation damage to normal lung tissue caused by radiotherapy (RT) for thoracic cancers, which is most commonly comprised of radiation pneumonitis (RP) and radiation pulmonary fibrosis (RPF). Moreover, with the widespread utilization of immunotherapies such as immune checkpoint inhibitors as first- and second-line treatments for various cancers, the incidence of immunotherapy-related lung injury (IRLI), a severe immune-related adverse event (irAE), has rapidly increased. To date, we know relatively little about the underlying mechanisms and signaling pathways of these complications. A better understanding of the signaling pathways may facilitate the prevention of lung injury and exploration of potential therapeutic targets. Therefore, this review provides an overview of the signaling pathways of RILI and IRLI and focuses on their crosstalk in diverse signaling pathways as well as on possible mechanisms of adverse events resulting from combined radiotherapy and immunotherapy. Furthermore, this review proposes potential therapeutic targets and avenues of further research based on signaling pathways. Many new studies on pyroptosis have renewed appreciation for the value and importance of pyroptosis in lung injury. Therefore, the authors posit that pyroptosis may be the common downstream pathway of RILI and IRLI; discussion is also conducted regarding further perspectives on pyroptosis as a crucial signaling pathway in lung injury treatment.
Topics: HMGB1 Protein; Humans; Immune Checkpoint Inhibitors; Lung Injury; NF-E2-Related Factor 2; Pulmonary Fibrosis; Pyroptosis; Radiation Pneumonitis; Signal Transduction; Transforming Growth Factor beta
PubMed: 34925345
DOI: 10.3389/fimmu.2021.774807 -
Radiation Oncology (London, England) Sep 2020Lung, breast, and esophageal cancer represent three common malignancies with high incidence and mortality worldwide. The management of these tumors critically relies on... (Review)
Review
Lung, breast, and esophageal cancer represent three common malignancies with high incidence and mortality worldwide. The management of these tumors critically relies on radiotherapy as a major part of multi-modality care, and treatment-related toxicities, such as radiation-induced pneumonitis and/or lung fibrosis, are important dose limiting factors with direct impact on patient outcomes and quality of life. In this review, we summarize the current understanding of radiation-induced pneumonitis and pulmonary fibrosis, present predictive factors as well as recent diagnostic and therapeutic advances. Novel candidates for molecularly targeted approaches to prevent and/or treat radiation-induced pneumonitis and pulmonary fibrosis are discussed.
Topics: Humans; Pulmonary Fibrosis; Radiation Injuries; Radiation Pneumonitis; Radiotherapy Dosage
PubMed: 32912295
DOI: 10.1186/s13014-020-01654-9 -
Cell Death & Disease May 2021Radiation-induced pulmonary fibrosis (RIPF) is a late toxicity of therapeutic radiation in clinic with poor prognosis and limited therapeutic options. Previous results...
Radiation-induced pulmonary fibrosis (RIPF) is a late toxicity of therapeutic radiation in clinic with poor prognosis and limited therapeutic options. Previous results have shown that senescent cells, such as fibroblast and type II airway epithelial cell, are strongly implicated in pathology of RIPF. However, the role of senescent macrophages in the development RIPF is still unknown. In this study, we report that ionizing radiation (IR) increase cellular senescence with higher expression of senescence-associated β-galactosidase (SA-β-Gal) and senescence-specific genes (p16, p21, Bcl-2, and Bcl-xl) in irradiated bone marrow-derived monocytes/macrophages (BMMs). Besides, there's a significant increase in the expression of pro-fibrogenic factors (TGF-β1 and Arg-1), senescence-associated secretory phenotype (SASP) proinflammatory factors (Il-1α, Il-6, and Tnf-α), SASP chemokines (Ccl2, Cxcl10, and Ccl17), and SASP matrix metalloproteinases (Mmp2, Mmp9 and Mmp12) in BMMs exposed to 10 Gy IR. In addition, the percentages of SA-β-Gal senescent macrophages are significantly increased in the macrophages of murine irradiated lung tissue. Moreover, robustly elevated expression of p16, SASP chemokines (Ccl2, Cxcl10, and Ccl17) and SASP matrix metalloproteinases (Mmp2, Mmp9, and Mmp12) is observed in the macrophages of irradiated lung, which might stimulate a fibrotic phenotype in pulmonary fibroblasts. In summary, irradiation can induce macrophage senescence, and increase the secretion of SASP in senescent macrophages. Our findings provide important evidence that senescent macrophages might be the target for prevention and treatment of RIPF.
Topics: Animals; Cells, Cultured; Cellular Senescence; Chemokines; Cytokines; Lung; Macrophages; Male; Mice; Mice, Inbred C57BL; Pulmonary Fibrosis; Radiation Injuries, Experimental; Radiation Pneumonitis; Radiation, Ionizing
PubMed: 34023858
DOI: 10.1038/s41419-021-03811-8 -
Seminars in Radiation Oncology Apr 2021Radiation-induced lung injury encompasses radiation-induced pneumonitis, inflammation of the lung which may manifest as a dose-limiting acute or subacute toxicity, and... (Review)
Review
Radiation-induced lung injury encompasses radiation-induced pneumonitis, inflammation of the lung which may manifest as a dose-limiting acute or subacute toxicity, and radiation-induced lung fibrosis, a late effect of lung exposure to radiation. This review aims to highlight developments in molecular radiation biology of radiation-induced lung injury and their implications in clinical practice.
Topics: Humans; Lung; Lung Injury; Pulmonary Fibrosis; Radiation Pneumonitis; Radiobiology
PubMed: 33610273
DOI: 10.1016/j.semradonc.2020.11.006 -
Nature Communications Apr 2023Radiation Induced Lung Injury (RILI) is one of the main limiting factors of thorax irradiation, which can induce acute pneumonitis as well as pulmonary fibrosis, the...
Radiation Induced Lung Injury (RILI) is one of the main limiting factors of thorax irradiation, which can induce acute pneumonitis as well as pulmonary fibrosis, the latter being a life-threatening condition. The order of cellular and molecular events in the progression towards fibrosis is key to the physiopathogenesis of the disease, yet their coordination in space and time remains largely unexplored. Here, we present an interactive murine single cell atlas of the lung response to irradiation, generated from C57BL6/J female mice. This tool opens the door for exploration of the spatio-temporal dynamics of the mechanisms that lead to radiation-induced pulmonary fibrosis. It depicts with unprecedented detail cell type-specific radiation-induced responses associated with either lung regeneration or the failure thereof. A better understanding of the mechanisms leading to lung fibrosis will help finding new therapeutic options that could improve patients' quality of life.
Topics: Female; Animals; Mice; Pulmonary Fibrosis; Radiation Pneumonitis; Quality of Life; Lung; Radiation Injuries; Lung Injury; Thorax
PubMed: 37117166
DOI: 10.1038/s41467-023-38134-z -
Journal of General Internal Medicine Oct 2011
Topics: Female; Humans; Middle Aged; Radiation Pneumonitis; Radiography
PubMed: 21538170
DOI: 10.1007/s11606-011-1687-8 -
BMC Medicine Sep 2020The synergistic effect of radiotherapy (RT) in combination with immunotherapy has been shown in several clinical trials and case reports. The overlapping pulmonary... (Review)
Review
BACKGROUND
The synergistic effect of radiotherapy (RT) in combination with immunotherapy has been shown in several clinical trials and case reports. The overlapping pulmonary toxicity induced by thoracic RT and programmed death 1/programmed death ligand-1 (PD-1/PD-L1) blockades is an important issue of clinical investigation in combination treatment. Thus far, the underlying mechanism of this toxicity remains largely unknown.
MAIN TEXT
In this review, we discuss the unique pattern of radiation recall pneumonitis (RRP) induced by PD-1 blockade. The clinical presentation is different from common radiation pneumonitis (RP) or RRP induced by cytotoxic drugs. The immune checkpoint inhibitors may evoke an inflammatory reaction in patients' previously irradiated fields, with infiltrating lymphocytes and potential involvement of related cytokines. All RRP patients have showed durable response to anti-PD-1/PD-L1. RRP is manageable; however, interruption of checkpoint blockades is necessary and immunosuppressive treatment should be started immediately. Further analyses of the predictive factors, including RT dosimetric parameters, tumor-infiltrating lymphocytes (TILs), and PD-L1 expression, are needed given the wide use of immune checkpoint inhibitors and high mortality from lung toxicity with the combination treatment.
CONCLUSION
Immune checkpoint inhibitors may evoke an RRP in the patients' previously irradiated fields. Interactions between immune checkpoint inhibitors and radiotherapy should be studied further.
Topics: Aged; Antineoplastic Agents; Humans; Immune Checkpoint Inhibitors; Immunotherapy; Programmed Cell Death 1 Receptor; Radiation Pneumonitis
PubMed: 32943072
DOI: 10.1186/s12916-020-01718-3 -
In Vivo (Athens, Greece) 2023Adjuvant radiotherapy (RT) for breast cancer can be associated with acute dermatitis (ARD) and pneumonitis (RP). Prevalence and risk factors were characterized.
BACKGROUND/AIM
Adjuvant radiotherapy (RT) for breast cancer can be associated with acute dermatitis (ARD) and pneumonitis (RP). Prevalence and risk factors were characterized.
PATIENTS AND METHODS
This study included 489 breast cancer patients receiving adjuvant RT with conventional fractionation (CF) ± sequential or simultaneous integrated boost, or hypo-fractionation ± sequential boost. RT-regimen and 15 characteristics were investigated for grade ≥2 ARD and RP.
RESULTS
Prevalence of grade ≥2 ARD and RP was 25.3% and 2.5%, respectively. On univariate analyses, ARD was significantly associated with CF and radiation boost (p<0.0001), age ≤60 years (p=0.008), Ki-67 ≥15% (p=0.012), and systemic treatment (p=0.002). On multivariate analysis, RT-regimen (p<0.0001) and age (p=0.009) were associated with ARD. Chronic inflammatory disease was significantly associated with RP on univariate (p=0.007) and multivariate (p=0.016) analyses.
CONCLUSION
Risk factors for grade ≥2 ARD and RP were determined that may help identify patients who require closer monitoring during and after RT.
Topics: Humans; Middle Aged; Female; Breast Neoplasms; Radiation Pneumonitis; Radiodermatitis; Pneumonia; Dose Fractionation, Radiation; Lung Neoplasms
PubMed: 37905621
DOI: 10.21873/invivo.13374