Sensorineural hearing outcomes in HPV-positive oropharyngeal cancer: a secondary analysis of the TROG 12.01 randomized trial (SHOUT).
rct · Level II
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- Record sourced from PubMed, PMID 42034301.
- Also identified by DOI 10.1016/j.radonc.2026.111550.
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Abstract
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. 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<sup>2</sup>, n = 55) or cetuximab (400 mg/m<sup>2</sup> loading, then 250 mg/m<sup>2</sup> 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. 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. 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.