Mechanism and Protection of Radiotherapy Induced Sensorineural Hearing Loss for Head and Neck Cancer

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.

Radiation-induced NF-κB activation is involved in cochlear damage in mice via promotion of a local inflammatory response

“…Inevitably these side-effects reduce the quality of life of the cancer survivors. For a long time, the radiation dose received by the cochleae was considered to be responsible for the damage [ 4 ]. In our previous study [ 7 ], we found that the radiation-induced inflammatory response was involved in the damage to the cochleae and subsequent SNHL, but the mechanisms were not completely elucidated.…”

“…For a long time, the radiation dose to the inner ear was considered to be responsible for the damage to the cochlea and SNHL [ 4 ]. However some studies have reported that the inflammatory response induced by radiation can cause apoptosis of hair cells of the inner ear [ 5 ], and a large number of inflammatory cells appear in the inner ear of irradiated experimental animals [ 6 , 7 ].…”

Clinical and genome-wide association analysis of chemoradiation-induced hearing loss in nasopharyngeal carcinoma

“…In addition, radiotherapy to head and neck tumors, such as nasopharyngeal carcinoma (NPC), often inevitably damages the adjacent organs of auditory, which may further increase the risk of hearing loss (HL). Previous studies reported that both platinum and radiation could contribute to DNA damage to auditory cells (Mujica-Mota et al 2014 ), leading to apoptosis and death of hair cells, stria vascularis endothelial cells, and spiral ganglion neurons (Landier 2016 ; Shi et al 2021 ). Platinum-based concurrent chemoradiotherapy has been recommended as the standard treatment modality for advanced NPC (Pfister et al 2020 ), a malignancy particularly prevalent in the east and southeast Asia, especially in Southern China (Chen et al 2019 ).…”

Cochlear Implantation in Radiation-Induced Hearing Loss: A Systematic Review

“…Similarly, a previous study showed that 72.3% of patients with HN cancers treated with radiotherapy developed hearing loss (9). The incidence of radiation-induced SNHL varies and depends on various factors, including radiation dose, patient age, and hearing sensitivity (10). A cumulative body of literature has demonstrated that the high incidence of SNHL positively correlates with the administration of radiotherapy.…”