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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 -
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 -
World Journal of Gastroenterology Oct 2020Non-alcoholic fatty liver disease (NAFLD) is among the most frequent etiologies of cirrhosis worldwide, and it is associated with features of metabolic syndrome; the key... (Review)
Review
Non-alcoholic fatty liver disease (NAFLD) is among the most frequent etiologies of cirrhosis worldwide, and it is associated with features of metabolic syndrome; the key factor influencing its prognosis is the progression of liver fibrosis. This review aimed to propose a practical and stepwise approach to the evaluation and management of liver fibrosis in patients with NAFLD, analyzing the currently available literature. In the assessment of NAFLD patients, it is important to identify clinical, genetic, and environmental determinants of fibrosis development and its progression. To properly detect fibrosis, it is important to take into account the available methods and their supporting scientific evidence to guide the approach and the sequential selection of the best available biochemical scores, followed by a complementary imaging study (transient elastography, magnetic resonance elastography or acoustic radiation force impulse) and finally a liver biopsy, when needed. To help with the selection of the most appropriate method a Fagan's nomogram analysis is provided in this review, describing the diagnostic yield of each method and their post-test probability of detecting liver fibrosis. Finally, treatment should always include diet and exercise, as well as controlling the components of the metabolic syndrome, +/- vitamin E, considering the presence of sleep apnea, and when available, allocate those patients with advanced fibrosis or high risk of progression into clinical trials. The final end of this approach should be to establish an opportune diagnosis and treatment of liver fibrosis in patients with NAFLD, aiming to decrease/stop its progression and improve their prognosis.
Topics: Biopsy; Elasticity Imaging Techniques; Humans; Liver; Liver Cirrhosis; Non-alcoholic Fatty Liver Disease; Prognosis
PubMed: 33132645
DOI: 10.3748/wjg.v26.i39.5919 -
Life Sciences Nov 2020Lung injury is characterized by inflammatory processes demonstrated as loss of function of the pulmonary capillary endothelial and alveolar epithelial cells. Autophagy... (Review)
Review
Lung injury is characterized by inflammatory processes demonstrated as loss of function of the pulmonary capillary endothelial and alveolar epithelial cells. Autophagy is an intracellular digestion system that work as an inducible adaptive response to lung injury which is a resultant of exposure to various stress agents like hypoxia, ischemia-reperfusion and xenobiotics which may be manifested as acute lung injury (ALI), acute respiratory distress syndrome (ARDS), chronic lung injury (CLI), bronchopulmonary dysplasia (BPD), chronic obstructive pulmonary disease (COPD), asthma, ventilator-induced lung injury (VILI), ventilator-associated lung injury (VALI), pulmonary fibrosis (PF), cystic fibrosis (CF) and radiation-induced lung injury (RILI). Numerous regulators like LC3B-II, Beclin 1, p62, HIF1/BNIP3 and mTOR play pivotal role in autophagy induction during lung injury possibly for progression/inhibition of the disease state. The present review focuses on the critical autophagic mediators and their potential cross talk with the lung injury pathophysiology thereby bringing to limelight the possible therapeutic interventions.
Topics: Acute Lung Injury; Animals; Autophagy; Autophagy-Related Proteins; Biomarkers; Humans
PubMed: 32828942
DOI: 10.1016/j.lfs.2020.118308 -
Journal of Cellular and Molecular... Sep 2021Radiation-induced lung injury (RILI) mainly contributes to the complications of thoracic radiotherapy. RILI can be divided into radiation pneumonia (RP) and...
Radiation-induced lung injury (RILI) mainly contributes to the complications of thoracic radiotherapy. RILI can be divided into radiation pneumonia (RP) and radiation-induced lung fibrosis (RILF). Once RILF occurs, patients will eventually develop irreversible respiratory failure; thus, a new treatment strategy to prevent RILI is urgently needed. This study explored the therapeutic effect of pirfenidone (PFD), a Food and Drug Administration (FDA)-approved drug for (IPF) treatment, and its mechanism in the treatment of RILF. In vivo, C57BL/6 mice received a 50 Gy dose of X-ray radiation to the whole thorax with or without the administration of PFD. Collagen deposition and fibrosis in the lung were reversed by PFD treatment, which was associated with reduced M2 macrophage infiltration and inhibition of the transforming growth factor-β1 (TGF-β1)/Drosophila mothers against the decapentaplegic 3 (Smad3) signalling pathway. Moreover, PFD treatment decreased the radiation-induced expression of TGF-β1 and phosphorylation of Smad3 in alveolar epithelial cells (AECs) and vascular endothelial cells (VECs). Furthermore, IL-4-induced M2 macrophage polarization and IL-13-induced M2 macrophage polarization were suppressed by PFD treatment in vitro, resulting in reductions in the release of arginase-1 (ARG-1), chitinase 3-like 3 (YM-1) and TGF-β1. Notably, the PFD-induced inhibitory effects on M2 macrophage polarization were associated with downregulation of nuclear factor kappa-B (NF-κB) p50 activity. Additionally, PFD could significantly inhibit ionizing radiation-induced chemokine secretion in MLE-12 cells and consequently impair the migration of RAW264.7 cells. PFD could also eliminate TGF-β1 from M2 macrophages by attenuating the activation of TGF-β1/Smad3. In conclusion, PFD is a potential therapeutic agent to ameliorate fibrosis in RILF by reducing M2 macrophage infiltration and inhibiting the activation of TGF-β1/Smad3.
Topics: Animals; Bone Marrow Cells; Female; Fibrosis; Lung Injury; Macrophage Activation; Mice; Mice, Inbred C57BL; Pyridones; RAW 264.7 Cells; Smad3 Protein; Transforming Growth Factor beta1
PubMed: 34327818
DOI: 10.1111/jcmm.16821 -
Frontiers in Oncology 2022This article is based on recommendations from the 12 WALT Congress, Nice, October 3-6, 2018, and a follow-up review of the existing data and the clinical observations of...
DISCLAIMER
This article is based on recommendations from the 12 WALT Congress, Nice, October 3-6, 2018, and a follow-up review of the existing data and the clinical observations of an international multidisciplinary panel of clinicians and researchers with expertise in the area of supportive care in cancer and/or PBM clinical application and dosimetry. This article is informational in nature. As with all clinical materials, this paper should be used with a clear understanding that continued research and practice could result in new insights and recommendations. The review reflects the collective opinion and, as such, does not necessarily represent the opinion of any individual author. In no event shall the authors be liable for any decision made or action taken in reliance on the proposed protocols.
OBJECTIVE
This position paper reviews the potential prophylactic and therapeutic effects of photobiomodulation (PBM) on side effects of cancer therapy, including chemotherapy (CT), radiation therapy (RT), and hematopoietic stem cell transplantation (HSCT).
BACKGROUND
There is a considerable body of evidence supporting the efficacy of PBM for preventing oral mucositis (OM) in patients undergoing RT for head and neck cancer (HNC), CT, or HSCT. This could enhance patients' quality of life, adherence to the prescribed cancer therapy, and treatment outcomes while reducing the cost of cancer care.
METHODS
A literature review on PBM effectiveness and dosimetry considerations for managing certain complications of cancer therapy were conducted. A systematic review was conducted when numerous randomized controlled trials were available. Results were presented and discussed at an international consensus meeting at the World Association of photobiomoduLation Therapy (WALT) meeting in 2018 that included world expert oncologists, radiation oncologists, oral oncologists, and oral medicine professionals, physicists, engineers, and oncology researchers. The potential mechanism of action of PBM and evidence of PBM efficacy through reported outcomes for individual indications were assessed.
RESULTS
There is a large body of evidence demonstrating the efficacy of PBM for preventing OM in certain cancer patient populations, as recently outlined by the Multinational Association for Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO). Building on these, the WALT group outlines evidence and prescribed PBM treatment parameters for prophylactic and therapeutic use in supportive care for radiodermatitis, dysphagia, xerostomia, dysgeusia, trismus, mucosal and bone necrosis, lymphedema, hand-foot syndrome, alopecia, oral and dermatologic chronic graft-versus-host disease, voice/speech alterations, peripheral neuropathy, and late fibrosis amongst cancer survivors.
CONCLUSIONS
There is robust evidence for using PBM to prevent and treat a broad range of complications in cancer care. Specific clinical practice guidelines or evidence-based expert consensus recommendations are provided. These recommendations are aimed at improving the clinical utilization of PBM therapy in supportive cancer care and promoting research in this field. It is anticipated these guidelines will be revised periodically.
PubMed: 36110957
DOI: 10.3389/fonc.2022.927685 -
Skin fibrosis. Identification and isolation of a dermal lineage with intrinsic fibrogenic potential.Science (New York, N.Y.) Apr 2015Dermal fibroblasts represent a heterogeneous population of cells with diverse features that remain largely undefined. We reveal the presence of at least two fibroblast...
Dermal fibroblasts represent a heterogeneous population of cells with diverse features that remain largely undefined. We reveal the presence of at least two fibroblast lineages in murine dorsal skin. Lineage tracing and transplantation assays demonstrate that a single fibroblast lineage is responsible for the bulk of connective tissue deposition during embryonic development, cutaneous wound healing, radiation fibrosis, and cancer stroma formation. Lineage-specific cell ablation leads to diminished connective tissue deposition in wounds and reduces melanoma growth. Using flow cytometry, we identify CD26/DPP4 as a surface marker that allows isolation of this lineage. Small molecule-based inhibition of CD26/DPP4 enzymatic activity during wound healing results in diminished cutaneous scarring. Identification and isolation of these lineages hold promise for translational medicine aimed at in vivo modulation of fibrogenic behavior.
Topics: Animals; Cell Lineage; Cell Separation; Cicatrix; Disease Models, Animal; Embryonic Development; Embryonic Stem Cells; Fibroblasts; Gene Expression; Homeodomain Proteins; Mice; Mouth; Skin; Translational Research, Biomedical; Wound Healing
PubMed: 25883361
DOI: 10.1126/science.aaa2151 -
Frontiers in Oncology 2019Radiation pneumonitis (RP) and radiation fibrosis (RF) are two dose-limiting toxicities of radiotherapy (RT), especially for lung, and esophageal cancer. It occurs in... (Review)
Review
Radiation pneumonitis (RP) and radiation fibrosis (RF) are two dose-limiting toxicities of radiotherapy (RT), especially for lung, and esophageal cancer. It occurs in 5-20% of patients and limits the maximum dose that can be delivered, reducing tumor control probability (TCP) and may lead to dyspnea, lung fibrosis, and impaired quality of life. Both physical and biological factors determine the normal tissue complication probability (NTCP) by Radiotherapy. A better understanding of the pathophysiological sequence of radiation-induced lung injury (RILI) and the intrinsic, environmental and treatment-related factors may aid in the prevention, and better management of radiation-induced lung damage. In this review, we summarize our current understanding of the pathological and molecular consequences of lung exposure to ionizing radiation, and pharmaceutical interventions that may be beneficial in the prevention or curtailment of RILI, and therefore enable a more durable therapeutic tumor response.
PubMed: 31555602
DOI: 10.3389/fonc.2019.00877