Sensorineural hearing outcomes in HPV-positive oropharyngeal cancer: a secondary analysis of the TROG 12.01 randomized trial (SHOUT)
- Author(s)
- Wishart, LR; O'Shea, J; Rischin, D; Corry, J; Dixon, BJ; O'Leary, S; Wilson, WJ; Zahir, SF; Hanson, D; Smith, J; Porceddu, SV;
- Journal Title
- Radiotherapy and Oncology
- Publication Type
- Research article
- Abstract
- PURPOSE: Cisplatin-associated deterioration in sensorineural hearing thresholds is an important survivorship concern in HPV-positive oropharyngeal squamous cell carcinoma (OPSCC). Weekly low-dose cisplatin may reduce ototoxicity compared with high-dose schedules, but randomized audiometric data are limited. This secondary analysis of TROG 12.01 compared hearing outcomes between weekly cisplatin + radiotherapy (RT) and cetuximab + RT. METHODS: Audiometric data were available for 101 TROG 12.01 trial participants. Patients received 70 Gy in 35 fractions with either weekly cisplatin (40 mg/m(2), n = 55) or cetuximab (400 mg/m(2) loading, then 250 mg/m(2) weekly, n = 46). Pure-tone audiometry (500-8000 Hz) was obtained at baseline and 12-months. Linear mixed-effects models assessed absolute change in air-conduction thresholds. Logistic regression identified predictors of clinically significant deterioration in sensorineural hearing thresholds. To evaluate radiation-specific effects, receiver-operating characteristic (ROC) analyses of cochlea dose were performed in the cetuximab + RT cohort. RESULTS: Across 101 patients, 41% developed clinically significant deterioration in sensorineural hearing thresholds at 12-months: 45.5% with cisplatin + RT and 34.8% with cetuximab + RT. At 8000 Hz, cisplatin + RT was associated with greater deterioration (mean shift 6.83 dB; p = 0.01), remaining significant after multivariable adjustment (estimate 5.58 dB; p = 0.04). In the cetuximab + RT cohort, ROC analysis identified cochlea mean dose > 5.09 Gy (AUC 0.69) and maximum dose > 7.16 Gy (AUC 0.70) as cut-points associated with deterioration in sensorineural hearing thresholds. CONCLUSION: Weekly low-dose cisplatin is associated with clinically significant deterioration in high-frequency hearing. Cochlea RT doses contributed independently to ototoxicity however dose-estimation thresholds require further validation. Findings highlight the value of audiologic monitoring and the relevance of cochlear dose in HPV-positive OPSCC treated with low-dose cisplatin, with implications for future prospective trials.
- Publisher
- Elsevier
- Keywords
- Humans; *Cisplatin/adverse effects/administration & dosage; *Oropharyngeal Neoplasms/virology/therapy; Female; *Hearing Loss, Sensorineural/chemically induced/etiology; Middle Aged; Male; Cetuximab/administration & dosage/adverse effects; *Antineoplastic Agents/adverse effects/administration & dosage; Aged; *Carcinoma, Squamous Cell/virology/therapy; *Papillomavirus Infections/complications; Chemoradiotherapy/adverse effects; Audiometry, Pure-Tone; Auditory Acuity; *Human Papillomavirus Viruses; Audiometry; Cisplatin; Human papillomavirus (HPV); Oropharynx cancer; Ototoxicity
- Department(s)
- Medical Oncology; Radiation Oncology
- Publisher's Version
- https://doi.org/10.1016/j.radonc.2026.111550
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2026-05-21 04:00:20
Last Modified: 2026-07-02 01:34:30