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

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.

Preservation of swallowing in resected oral cavity squamous cell carcinoma: examining radiation volume effects (PRESERVE): study protocol for a randomized phase II trial.

BACKGROUND: Patients with resected oral cavity squamous cell carcinoma (OCSCC) are often treated with adjuvant radiation (RT) ± concomitant chemotherapy based on pathological findings. Standard RT volumes include all surgically dissected areas, including the tumour bed and dissected neck. RT has significant acute and long-term toxicities including odynophagia, dysphagia, dermatitis and fibrosis. The goal of this study is to assess the rate of regional failure with omission of radiation to the surgically dissected pathologically node negative (pN0) hemi-neck(s) compared to historical control, and to compare oncologic outcomes, toxicity, and quality of life (QoL) profiles between standard RT volumes and omission of RT to the pN0 neck. METHODS: This is a multicentre phase II study randomizing 90 patients with T1-4 N0-2 OCSCC with at least one pN0 hemi-neck in a 1:2 ratio between standard RT volumes and omission of RT to the pN0 hemi-neck(s). Patients will be stratified based on overall nodal status (nodal involvement vs. no nodal involvement) and use of concurrent chemotherapy. The primary endpoint is regional failure in the pN0 hemi-neck(s); we hypothesize that a 2-year regional recurrence of 20% or less will be achieved. Secondary endpoints include overall and progression-free survival, local recurrence, rate of salvage therapy, toxicity and QoL. DISCUSSION: This study will provide an assessment of omission of RT to the dissected pN0 hemi-neck(s) on oncologic outcomes, QoL and toxicity. Results will inform the design of future definitive phase III trials. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT03997643 . Date of registration: June 25, 2019, Current version: 2.0 on July 11 2020.

Radiologic Extranodal Extension Portends Worse Outcome in cN+ TNM-8 Stage I Human Papillomavirus-Mediated Oropharyngeal Cancer.

PURPOSE: To identify adverse radiologic nodal features in cN+ TNM-8 stage I human papillomavirus-related (HPV+) oropharyngeal cancer (OPC). METHODS AND MATERIALS: All patients with HPV+ cT1-T2cN1 OPC treated with definitive intensity modulated radiation therapy from 2008 to 2015 were included. Radiologically involved lymph node number (LN), radiologic extranodal extension (rENE), retropharyngeal LN (RPLN), and lower neck (level 4 or 5b) LN involvement were assessed on pre-treatment computed tomography/magnetic resonance imaging by a specialized head and neck neuroradiologist. Disease-free survival (DFS), locoregional control, and distant control were compared between those with versus without rENE. Univariable and multivariable analysis with stepwise modal selection were applied to identify prognostic factors for DFS. RESULTS: A total of 45 rENE+ and 234 rENE- were identified. The rENE+ cohort had a higher number of LNs per patient (median: 6 vs 2, P < .001) and was more likely to have necrotic LNs (33 [73%] vs 132 [56%], P = .046). Median follow-up was 4.8 years. Although locoregional control was high in both cohorts (93% vs 97%, P = .34), the rENE+ group had inferior 5-year distant control (78% [59-88] vs 95% [91-97], P < .001) and DFS (58% [43-77] vs 90% [86-94], P < .001). In multivariable analysis, rENE+ (HR [hazard ratio] 4.3 [2.3-8.1], P < .001], T2 (vs T1) category (HR 2.1 [1.0-4.2], P = .039), smoking pack-years (HR 1.02 [1.0-1.03], P = .013), and the addition of systemic agents (HR 0.4 [0.2-0.8], P = .005) were prognostic for DFS. RPLN was prognostic for distant metastasis (HR 3.2, P = .013) but not for DFS after adjusting for rENE. CONCLUSIONS: Data from this contemporaneously treated cT1-T2N1 HPV+ OPC cohort suggest that the presence of rENE is an independent prognostic factor within stage I HPV+ OPC. RPLN is also associated with DM risk but not with DFS.