Abstract
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.
Highlights
Frontiers in OncologyEpithelial and endothelial cell loss, due to radiationinduced cell death leads to loss of barrier function and vessel integrity thereby reducing micro-vessel density and oxygen perfusion [1, 13]
Reviewed by: Zhongxing Liao, University of Texas MD Anderson Cancer Center, United States Yevgeniy Vinogradskiy, University of Colorado Denver, Specialty section: This article was submitted to Radiation Oncology, a section of the journal
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 radiation-induced lung injury (RILI), and enable a more durable therapeutic tumor response
Summary
Epithelial and endothelial cell loss, due to radiationinduced cell death leads to loss of barrier function and vessel integrity thereby reducing micro-vessel density and oxygen perfusion [1, 13] These effects of ROS are counteracted by direct activation of the hypoxia-inducible factors (HIF) 1α and 2α by ROS in cells, resulting in the activation of cytokines and growth factors including VEGF that promote endothelial cell proliferation. The increased activity of TIMPs and decreased matrix metalloproteinase (MMP) activity (MMP2-MMP9) leads to excessive ECM deposition [36], and excess collagen These changes lead to pulmonary fibrosis resulting in fibrotic areas susceptible to physical trauma (i.e., rupture) and gradual ischemia, which further leads to loss of respiratory capacity, tissue atrophy, and necrosis [37, 38]
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