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Review
. 2022 Feb;11(2):307-322.
doi: 10.21037/tlcr-22-108.

Exploration of radiation-induced lung injury, from mechanism to treatment: a narrative review

Affiliations
Review

Exploration of radiation-induced lung injury, from mechanism to treatment: a narrative review

Yujie Yan et al. Transl Lung Cancer Res. 2022 Feb.

Abstract

Background and objective: Radiation-induced lung injury (RILI) is often found in thoracic tumor patients after thoracic radiation therapy, and influences patient quality of life. However, systematic exploration of RILI, including its molecular biological mechanisms and standardized treatment, has not yet been fully elucidated. The main objective of the narrative review was to describe the available evidence concerning RILI, from the biological mechanism to the clinical management. The underlying causes of RILI are multifactorial, including gene-level changes, the influence of signaling pathways, the convergence of various cells, as well as the expression of cytokines and chemokines. Based on the various mechanisms of RILI, several novel treatment strategies have been proposed and gradually applied in clinical practice.

Methods: PubMed was used to collect articles about RILI from 1995 to 2021. The papers included clinical trials, reviews, as well as systematic reviews and meta-analyses. Based on the mechanism, diagnosis, and treatment, we synthesized and analyzed these papers to form a clearly logical and normative suggestion to guide clinical application.

Key content and findings: RILI is a constantly developing and changing process including radiation pneumonitis and radiation lung fibrosis. Different kinds of inflammatory and immune cells such as macrophages, fibroblasts, and T cells play key roles in the development of RILI, and transforming growth factor-β (TGF-β), interleukin-4 (IL-4), IL-13, and interferon-γ (IFN-γ) are also participants in this process. At present, glucocorticoids are mainly therapeutic drugs for the early stage of RILI, and drugs treatment should abide early period, sufficient doses, and the individual principles. Other novel drugs such as Azithromycin also have been tried in clinical application. radiation dose, combination therapy modality, the condition of the tumor, and the age and underlying conditions of patients all effect the occurrence of RILI. Importantly, RILI has a relatively higher incidence in patients who received radiotherapy combined with other treatments, especially immunotherapy.

Conclusions: The occurrence of RILI after radiotherapy will greatly affect the prognosis and quality of life of patients. In clinical practice, early intervention, active treatment, and more effective therapeutic drugs should be found.

Keywords: Radiation-induced lung injury (RILI); mechanism; predisposing factors; treatment.

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Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-22-108/coif). The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
The mechanism of DNA damage and ROS generation. ROS, reactive oxygen species; RNS, reactive nitrogen species; DNA, deoxyribonucleic acid; mRNA, messenger RNA; IKK, IκB kinase; TNFR, tumor necrosis factor receptor; TLR, Toll-like receptor; IL, interleukin; TNF-α, tumor necrosis factor-α; GM-CSF, granulocyte-macrophage colony stimulating factor; MIP-1α, macrophage inflammatory protein-1α; MCP-1, monocyte chemoattractant protein-1; INOS, inducible nitric oxide synthase; COX-2, cyclooxygenase-2; PLA, polylactic acid; VACM-1, vascular cell adhesion molecule-1; ICAM-1, intercellular adhesion molecule 1.
Figure 2
Figure 2
The predisposing factor of RILI. CTLA-4, cytotoxic T-lymphocyte-associated antigen 4; DC, dendritic cell; RILI, radiation-induced lung injury.
Figure 3
Figure 3
Challenges and solutions.

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