Abstract

Purpose Radiotherapy-induced sensorineural hearing loss (RISNHL) is a common adverse effect in patients with head and neck cancer. Given that there are few studies on the pathogenesis of RISNHL at present, we summarized the possible pathogenesis of RISNHL and possible protective measures found at present by referring to relevant literatures. Methods We performed a comprehensive literature search in the PubMed database, using keywords “sensorineural hearing loss,” “radiotherapy,” and “cancer,” among others. The literature was examined for the possible mechanism and preventive measures of sensorineural hearing loss induced by radiotherapy. Results We found that the incidence of RISNHL was closely related to the damage directly caused by ionizing radiation and the radiation-induced bystander effect. It also depends on the dose of radiation and the timing of chemotherapy. Studies confirmed that RISNHL is mainly involved in post-RT inflammatory response and changes in reactive oxygen species, mitogen-activated protein kinase, and p53 signaling pathways, leading to specific manners of cell death. We expect to reduce the incidence of hearing loss through advanced radiotherapy techniques, dose limitation of organs at risk, application of cell signaling inhibitors, use of antioxidants, induction of cochlear hair cell regeneration, and cochlear implantation. Conclusion RISNHL is associated with radiation damage to DNA, oxidative stress, and inflammation of cochlear cells, stria vascularis endothelial cells, vascular endothelial cells, spiral ganglion neurons, and other supporting cells. At present, the occurrence mechanism of RISNHL has not been clearly illustrated, and further studies are needed to better understand the underlying mechanism, which is crucial to promote the formulation of better strategies and prevent the occurrence of RISNHL.

Highlights

  • Radiotherapy (RT) is commonly used and sometimes the first choice in treating head and neck tumors, especially nasopharyngeal carcinoma (NPC)

  • Depolarization of outer hair cells (OHC) forms the basis for cochlear sensitivity and frequency resolution, while depolarization of inner hair cells (IHC) releases glutamate from ribbon synapses at their basal poles

  • The possible mechanisms of Radiotherapy-induced sensorineural hearing loss (RISNHL) can be simplified as cells exposed to radiation lead to cell death through direct or indirect deoxyribonucleic acid (DNA) damage, inflammatory cell recruitment, reactive oxygen species (ROS)-mediated oxidative stress response, and activation of multiple signaling pathways

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Summary

Introduction

Radiotherapy (RT) is commonly used and sometimes the first choice in treating head and neck tumors, especially nasopharyngeal carcinoma (NPC). SNHL is a tardive and irreversible complication that can be observed in patients with inner ear exposure to radiation fields. The incidence of SNHL varies widely, because of various reasons such as radiation dose, age, and hearing sensitivity of patients, ranging from 0 to 85% for low-frequency (4 kHz) SNHL. Despite the increased interest in RT-induced ototoxicity in tumors of the head and neck tumors, there is little research on the mechanism and protection of radiotherapy-induced. This article is aimed at describing the progress made to understand the mechanism of RISNHL and the approaches developed so far for its protection or to reduce the associated complications

Cochlear Structure and Function
Mechanism of RISNHL in Head and Neck Cancer
Direct Effects of Radiation Induction
Protection Measures
Promotes GSH synthesis
Conclusions
Conflicts of Interest
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