During radiotherapy for NPC, the primary radiation target encompasses the middle ear structures, including the tympanic cavity, Eustachian tube, mastoid sinus and petrous apex (13). The middle ear serves a pivotal role in sound transmission by converting sound waves from the outer ear into mechanical waves for further conduction. Radioactive damage to the middle ear may lead to CHL, and radiation-induced otitis media is considered the predominant clinical manifestation (14). Previous studies demonstrate that radiation-induced injury primarily affects the Eustachian tube and tympanic cavity, where direct radiation damages both mucosa and cartilage of the Eustachian tube (15,16). In addition, radiation damages the innervating muscles, including the tensor veli palatini muscle, resulting in an impaired opening function of the Eustachian tube (17). Radiation injury to the middle ear mucosa, blood vessels and lymphatic endothelium disrupts the local mucociliary clearance system. This process not only increases tissue fluid exudation, but also slows lymphatic drainage, eventually leading to retention and obstruction of secretions. Radiation-induced necrosis of the nasal-pharyngeal or sinus mucosa may result in a bacterial infection (18), which subsequently involves the Eustachian tubes (19). The interplay between the aforementioned pathological processes leads to secretory otitis media, resulting in CHL. Post-radiotherapy, CHL is typically transient, with recovery of Eustachian tube function and improvement in middle ear effusion. As the negative pressure within the middle ear is relieved, hearing loss resolves. The development of atrophic (fibrotic) otitis media and ossicular chain necrosis after radiotherapy is multifactorial, which explains why these complications only arise in partial patients rather than all cases. Based on clinical cohort studies focusing on head and neck radiotherapy, the overall incidence of radiation-related atrophic/fibrotic otitis media is approximately 1 out of 5 to 1 out of 4 patients (20).

SNHL is caused by damage to the cochlea and auditory nerve (21). Following radiotherapy, SNHL is categorized into two types based on its time of onset, namely: i) Early-onset (acute); and ii) late-onset (chronic). Early-onset SNHL may occur within hours to 1 week after exposure to ionizing radiation and, in certain cases, this type of hearing loss may be reversible or partially reversible. Conversely, late-onset SNHL manifests as a chronic, progressive and irreversible process that arises within 6-24 months post-irradiation (22,23). In a number of patients, complete deafness may develop within weeks or months (24). The reported incidence rate of post-radiotherapy SNHL varies between 15 and 30%, with a notably increased occurrence rate observed in patients receiving cisplatin-based chemotherapy compared with those receiving radiotherapy alone (25,26). Additionally, >50% of patients that suffer with SNHL will experience permanent SNHL (27). SNHL develops through complex mechanisms that are not fully understood. Possible contributing factors include blood vessel abnormalities, atrophy of the spiral ligament and basilar membrane, loss of outer hair cells and deterioration of the eighth cranial nerve (28).

MHL is a composite manifestation of both CHL and SNHL, which typically occurs at the same time as damage to the outer or middle ear. MHL impacts the cochlea and auditory nerve, further complicating the intricacy and challenges associated with treating auditory impairment (29).

Hearing loss can impair the communication abilities of patients, leading to limited participation in everyday listening situations. This may affect daily functions and negatively impact the quality of life of the patient (30). A study by Sano et al (31) reveals the limitations of social and daily activity experienced by individuals with hearing loss compared with those without hearing loss, from both a physiological and psychological perspective (31). In addition, a study by Wie et al (32) reports that severe unilateral hearing impairment, such as deafness, notably disrupts speech perception, communication skills and social interactions among patients with hearing loss compared with those without hearing loss (32). In addition, symptoms such as dizziness and tinnitus, which are associated with sudden SNHL (SSHL), may also contribute to anxiety surrounding the potential recurrence or fear of hearing loss in the unaffected ear, further impacting the quality of life of patients (33).

A number of studies substantiate the association between hearing loss and neurocognitive impairments (34,35). Compared with patients without hearing loss, individuals with moderate to severe hearing loss who do not utilize hearing aids exhibit impaired language expression, increased social isolation and accelerated cognitive decline (36). A multi-center, parallel-group, randomized controlled trial conducted in the United States investigated untreated hearing loss among adults aged 70-84 years without severe cognitive impairments. The findings demonstrate that interventions, such as provision of hearing aids and health education, may mitigate the risk of cognitive decline within a 3-year period, promoting stability in the cognitive capacities of older patients (37). A further study examining the association between hearing aid usage and cognitive abilities reveals that patients who wear hearing aids exhibit a notably reduced risk of cognitive decline, compared with those lacking auditory correction during a long-term follow-up period ranging from 2-25 years (38). This long-term protective association has been validated by recent population-based longitudinal cohorts and clinical observational research (38). Large-sample prospective evidence verified that standardized hearing aid intervention effectively cut down dementia and global cognitive deterioration risk in elderly hearing-impaired individuals during multiyear follow-up (39). Additionally, real-world cohort data focusing on middle-aged and elderly subjects further confirmed sustained hearing aid application independently alleviates progressive cognitive impairment and brain function regression in long-term observational trials (40). Moreover, an analysis elucidating the potential association between auditory restoration and changes in short-term cognitive test scores indicates a notable 3% improvement following hearing aid use (24), further corroborating the positive impact of auditory intervention on cognitive function.

Previous studies reveal an association between anxiety and hearing loss, with generalized anxiety being particularly prominent (41,42). Compared with individuals without hearing loss, those with mild hearing impairment may exhibit a markedly increased incidence of anxiety, which may also increase as the degree of hearing loss increases (41). Hearing loss weakens cognitive reserves, exacerbates executive dysfunction and disrupts normal emotional responses and regulatory mechanisms, leading to decreased cognitive performance and increased risk of depression (42).

A 5-year follow-up study demonstrated that patients with existing or deteriorating hearing loss exhibited far more noticeable progression of depressive symptoms than those with intact hearing (43). Meanwhile, aggravated depressive symptoms were accompanied by increased hearing loss at low and mid frequencies, implying a potential correlation between the two conditions (44). A previous study, focusing on the mental health of adolescents, aged 10 to 19 years, also reveals an association between mental health and auditory function (45). The survey conducted among adolescent patients with impaired auditory function reveals that 30% of patients exhibit symptoms of depression, such as persistent low mood, social withdrawal, poor concentration and loss of interest in daily activities, while 21% of patients have symptoms of anxiety, including excessive worry, restlessness and palpitations. Moreover, older adolescents (aged 15 to 19 years) score higher on measures for depressive symptoms than younger adolescents with hearing loss. Among the group with severe to profound auditory impairments, the incidence rates for both depression and anxiety were more pronounced (45). Additionally, results of a previous study reveal that the prevalence rate for depression in deaf or hard-of-hearing populations is ~7%, whereas the lifetime prevalence of depression in this group can be as high as 26% (46). Children who experience ridicule due to their impaired auditory function or other disabilities, such as visual impairments, neurological disorders or developmental delays during upbringing, may face an increased risk of developing depression compared with those who do not endure such ridicule (46).

The HHIA-S is a preliminary diagnostic scale for hearing impairment, which is used worldwide (47). This scale comprises 10 items, including five emotional and five social/contextual aspects (Table I). The scoring criteria are as follows: A response of ‘yes’ receives four points; a response of ‘sometimes’ receives two points; and a response of ‘no’ receives zero points. The total score ranges from 0-40, with higher scores indicating more severe hearing loss. A score of more or equal to eight suggests the presence of an impairment, while scores between eight and 24 indicate mild impairment, and scores >24 indicate severe impairment (47). In China, the HHIA-S was translated in 2014(48), a score >8 on the scale was used as the cut-off to identify participants with hearing loss, those scoring exactly 8 were classified as having normal hearing. When conducting hearing screens for individuals with an average pure tone air conduction threshold (pure tone average; PTA) of >40 dB Hertz, HHIA-S is a user-friendly self-assessment questionnaire that can be administered without the need for specialized personnel or equipment, thereby conserving medical resources (47). However, this method may exhibit certain limitations, as subjective evaluations may introduce inherent biases, and specific types of hearing impairments including conductive hearing loss, retrocochlear hearing impairment, mixed hearing loss, subclinical noise-induced or ototoxic sensorineural hearing loss, asymmetric hearing loss, auditory processing disorder, as well as hearing dysfunction in children and cognitively impaired populations still require integration with objective screening methods to achieve accurate identification and classification (49).

The ETDQ-7 is a valuable tool for evaluating symptoms associated with abnormal Eustachian tube function, encompassing issues such as ear fullness, ear pain, autophony and hearing loss (50). This comprehensive survey comprises seven questions that gauge the severity of these subjective symptoms on a scale ranging from one to seven, where higher scores indicate more pronounced manifestations (Table II). A study by Cao et al (51) utilized the Chinese version of the ETDQ-7 to assess patients with Eustachian tube dysfunction alongside healthy individuals. The results of the aforementioned study demonstrates that the Chinese version of the ETDQ-7 exhibits high levels of reliability (coefficient, 0.879), sensitivity (96.1%) and specificity (85%). Therefore, these results indicate the efficacy of utilizing the Chinese version of the ETDQ-7 in evaluating Eustachian tube dysfunction.

The ETDQ-7 may be used to gather information on the symptoms experienced by patients in an efficient manner, with comprehensible content and convenient completion. However, relying only on the ETDQ-7 scores does not allow for a differentiation between obstructive and patulous Eustachian tube disorders. This limits its utility as a diagnostic tool for obstructive Eustachian tube dysfunction or an objective measurement method for Eustachian tube function (52).

Ototoxicity constitutes a treatment-related adverse event induced by antitumor therapies. The ototoxicity grading criteria assess patients' symptomatic conditions in the week prior to each clinical assessment, incorporating three evaluation dimensions: Symptom frequency, severity and interference with daily functioning. This grading system adopts a 1-5 point rating scale (Table III) (53). A higher score indicates more pronounced symptoms. There are multiple versions of the PRO-CTCAE assessment, which also has extensive dissemination capabilities. Therefore, this serves as a valuable addition to adverse event reporting by healthcare professionals during clinical trials focused on tumors (54).

HHIA-S, ETDQ-7 and PRO-CTCAE complement one another in evaluating hearing impairment from separate perspectives (Table IV): HHIA-S measures psychosocial hearing handicap in daily life, ETDQ-7 assesses eustachian tube-related conductive ear symptoms, and PRO-CTCAE provides standardized toxicity grading of treatment-related hearing loss for clinical trials. Concurrent administration of the three tools achieves full-spectrum auditory outcome assessment integrating middle ear symptoms, functional handicap and treatment adverse events.

Eustachian tube insufflation is a treatment method that aims to loosen adhesions, reduce swelling and reopen the Eustachian tube passage in order to restore healthy ventilation functions through the introduction of air into the tube (Table V) (55-59). This technique eliminates negative pressure in the middle ear, thereby increasing the oxygen partial pressure within the middle ear, facilitates efficient mucus diffusion and accelerates fluid absorption and drainage. Moreover, Eustachian tube insufflation is a useful therapeutic option for secretory otitis media-related hearing loss and can be considered as part of the overall management of otitis media with effusion, alongside other approaches such as watchful waiting, hearing surveillance, periodic reevaluation, and surgical intervention when indicated, particularly tympanostomy tube insertion with or without adenoidectomy depending on the child's age (60). According to published auto-inflation protocols, the patient sits upright while a probe tip is inserted into one nostril and the other nostril is manually compressed. The patient holds a small amount of water in the mouth, airflow is delivered into the nasal cavity, and swallowing is performed after 1-2 sec of airflow to facilitate middle ear inflation. The procedure may be performed twice daily and should be suspended temporarily if an upper respiratory tract infection occurs (61,62).

Inhalation of a high concentration of hydrogen-oxygen mixture (containing 2.0 l/min hydrogen and 1.0 l/min oxygen, equivalent to ~66.7% hydrogen and 33.3% oxygen by flow) may enhance the immune function of patients with low levels of immunity, such as individuals aged ≥65 years or those with chronic lung diseases or malignant tumors. This method aims to increase the quantity and activity of functional helper T lymphocytes, cytotoxic T lymphocytes and natural killer cells (63,64). Inhalation of small doses (typically 1-4%) of hydrogen gas may selectively reduce cytotoxic reactive oxygen species, particularly hydroxyl radicals, by reacting with them rather than by preventing their release. This antioxidant action is novel and effective, and it helps to protect hair cells in the auditory system and improve hearing (65). During this process, patients are administered continuous once-daily treatment for 4-12 weeks, with each session lasting 3-4 h. Patients are required to inhale a mixture of hydrogen-oxygen gas through a nasal cannula, at a rate of 2 liters/min hydrogen gas and 1 liter/min oxygen (~66.7% hydrogen and 33.3% oxygen by flow). The results of a previous study demonstrate that, after 4 weeks of hydrogen inhalation, the Eustachian Tube Dysfunction Questionnaire-7 (ETDQ-7) score, as well as air conduction and bone conduction thresholds, were markedly reduced, indicating alleviation of Eustachian tube dysfunction-related symptoms. Furthermore, in patients receiving radiotherapy or radiochemotherapy, air conduction thresholds were notably reduced. In total, 5 patients (10 ears) underwent hearing examinations 6-9 months after discontinuing hydrogen inhalation. Hearing remained stable or continued to improve in 3 of the 10 ears, although overall hearing thresholds increased during follow-up (Table V) (56).

Acupuncture, a distinct therapeutic modality of Traditional Chinese Medicine, is used for the management of diverse health conditions and symptoms, including improvements in maximum heart rate, pain, swelling, explosive force production and joint mobility. Acupuncture requires the insertion of sterile needles into specific areas of the body to regulate blood flow (66). Acupuncture may increase local blood circulation, optimize metabolism and facilitate blood flow in the ears through modulating inflammatory responses (67). A systematic review demonstrates that a combination of acupuncture with pharmacotherapy leads to improvements in the treatment of SSHL, compared with pharmacotherapy alone (68). Therefore, acupuncture may exhibit potential as an adjunctive treatment option for SSHL (69). To evaluate the role of acupuncture in reducing SSHL risk among patients with NPC, a nested case-control study was conducted. Among 811 patients with initial-onset SSHL, 27 individuals received acupuncture treatment (57). The results of the aforementioned study reveal that patients receiving acupuncture exhibit a reduced likelihood of developing SSHL, compared with the 784 individuals who did not receive such intervention [adjusted odds ratio, 0.39; 95% confidence interval, 0.25-0.60]. Therefore, incorporating acupuncture into routine care for patients with NPC resulted in a 61% decrease in their susceptibility to developing SSHL. Moreover, the observed effect is considered dose-dependent, as an increased frequency of acupuncture treatments corresponded to reduced incidence rates of SSHL (Table V) (57).

A study by Chen et al (58) investigates the efficacy of methylprednisolone in treating radiation-induced hearing loss in patients with NPC undergoing radiotherapy. In the aforementioned study, a total of 25 patients receive a 14-day course of intravenous pulse therapy with methylprednisolone, in combination with radiotherapy. This group is compared with 28 patients who receive radiotherapy alone. Pure tone audiometry, distortion product otoacoustic emission (DPOAE) and auditory brainstem responses were evaluated prior to treatment, and 1 year after the completion of radiotherapy. The results of the aforementioned study reveal that the control group, who received radiotherapy alone, exhibit increased air-bone gap thresholds and decreased DPOAE levels at the 1-year follow-up assessment. By contrast, the treatment group demonstrate reduced pure tone air conduction thresholds and increased DPOAE levels, compared with the control group. Therefore, administration of methylprednisolone during radiotherapy may alleviate early SNHL caused by radiation exposure (Table V) (58).

In a further randomized study, 99 patients were administered either systemic infusion of methylprednisolone alone, or a combined treatment involving intratympanic dexamethasone and systemic methylprednisolone. The results of the aforementioned study indicate that both treatment groups achieve improvements in hearing over a 3-month follow-up period (Table V) (59).