Optimizing Hearing Outcomes in Nasopharyngeal Cancer Survivors in the Era of Modern Radiotherapy and Systemic Therapy

Simple Summary Sensorineural hearing loss is a common late complication among nasopharyngeal cancer survivors, primarily due to the close proximity of the auditory apparatus to the treatment volume and the use of cisplatin-based chemotherapy. The incidence of hearing loss in the era of intensity-modulated radiation therapy varies widely, influenced by factors such as patient demographics, auditory assessment methods, and the duration of follow-up. While guidelines have provided recommendations on radiation dose constraints to the cochlea to mitigate hearing loss, significant risks remain. To improve hearing outcomes, strategies such as radiotherapy de-escalation, personalized treatment planning, and the consideration of alternative systemic agents in localized nasopharyngeal cancer are being investigated. This review discusses the context and relevant evidence regarding potential strategies to improve hearing outcomes in this patient population.Abstract Intensity-modulated radiation therapy (IMRT) improves disease control and reduces treatment-related toxicity in patients with localized nasopharyngeal carcinoma (NPC). However, due to the proximity of the auditory apparatus to the treatment volume and the frequent incorporation of cisplatin-based chemotherapy, treatment-related sensorineural hearing loss (SNHL) remains a common debilitating complication among NPC survivors. The reported crude incidence of SNHL following IMRT for NPC varies widely at 1-46% due to differences in auditory assessment methods and thresholds, follow-up durations, chemotherapy usage, and patient compositions. International guidelines and radiation dosimetric studies have recommended constraining the cochlear mean dose to less than 44-50 Gy, but the risk of SNHL remains high despite adherence to these constraints. Potential strategies to improve hearing outcomes in NPC survivors include cautious de-escalation of radiotherapy dose and volume, individualization of cochlear constraints, optimization of radiotherapy planning techniques, and the use of substitutes or alternative schedules for cisplatin-based chemotherapy. The addition of immune checkpoint inhibitors to chemoradiotherapy did not impact ototoxicity. Prospective studies that employ both objective and patient-reported auditory outcomes are warranted to test the long-term benefits of various approaches. This article aims to provide a comprehensive review of the incidence and radiation dose-toxicity relationship of SNHL in NPC survivors and to summarize potential strategies to optimize hearing outcomes in relation to nuances in radiotherapy planning and the selection of systemic therapy.