Clinical Predictors of Cisplatin Chemoradiation-Induced Ototoxicity in HPV-Positive Oropharyngeal Squamous Cell Carcinoma: A Case-Control Study

Author:

Lee John JW.1,Alamleh Salahaldin2,Zhan Luna Jia3,Hueniken Katrina3,Mahler Mary B.4,Billfalk-Kelly Astrid5,Davies Joel6,Brown M. Catherine3,Spreafico Anna4,Huang Shao Hui5,Hope Andrew5,Xu Wei37,Goldstein David P.18,Liu Geoffrey347

Affiliation:

1. Department of Otolaryngology—Head and Neck Surgery, University of Toronto, Toronto, ON, Canada

2. Faculty of Medicine, University of Toronto, Toronto, ON, Canada

3. Department of Biostatistics, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada

4. Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada

5. Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada

6. Department of Otolaryngology—Head and Neck Surgery, Sinai Health System, University of Toronto, Toronto, ON, Canada

7. Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada

8. Department of Otolaryngology—Head and Neck Surgery, University Health Network, University of Toronto, Toronto, ON, Canada

Abstract

Background Cisplatin-based chemoradiation is a standard treatment for many patients with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC), an etiologically distinct subset of head and neck cancer. Although associated with good long-term survival, clinical risk factors for ototoxicity have been understudied in this population. This study aimed to evaluate clinical predictors associated with ototoxicity in HPV-positive OPSCC patients treated with cisplatin chemoradiation. Methods This retrospective case-control study included 201 adult patients (>18 years) with histologically confirmed HPV-positive OPSCC who received cisplatin chemoradiation as their primary treatment from 2001 and 2019 at a single tertiary cancer center. Ototoxicity was determined using baseline and follow-up audiometry and the Common Terminology Criteria for Adverse Events v5.0 grading criteria (Grade ≥2). Multivariable logistic regression [adjusted odds ratio (aOR)] identified significant predictors that increased the odds of ototoxicity. Results A total of 201 patients [165 males; median (IQR) age, 57 (11) years] were included in the study. The incidence of ototoxicity in the worst ear was 56.2%, with the greatest hearing loss occurring at high frequencies (4-8 kHz), resulting in a loss of 12.5 dB at 4 to 6 kHz and 20 dB at 6 to 8 kHz. High-dose cisplatin administration compared to weekly administration [aOR 4.93 (95% CI: 1.84-14.99), P = .003], a higher mean cochlear radiation dose [aOR 1.58 (95% CI: 1.12-2.30), P = .01], smoking history [aOR 2.89 (95% CI: 1.51-5.63), P = .001], and a 10 year increase in age [aOR 2.07 (95% CI: 1.25-3.52), P = .006] were each independently associated with increased odds of ototoxicity. Conclusions Clinical predictors of ototoxicity in HPV-positive OPSCC patients treated with cisplatin-based chemoradiation include the use of a high-dose cisplatin regimen, higher cochlear radiation doses, a history of smoking, and older age. With the rising incidence of this malignancy in Western countries and overall improved survivorship, our research motivates future studies into risk stratification and earlier interventions to mitigate and reduce the risk of ototoxicity.

Publisher

SAGE Publications

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