Lee David S, Mahal Rajwant S, Tharakan Theresa, Kallogjeri Dorina, Thorstad Wade L, Adkins Douglas R, Oppelt Peter, Ley Jessica, Wick Cameron C, Zevallos Jose
Department of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St Louis, Missouri, USA.
Department of Otolaryngology-Head and Neck Surgery, Division of Adult Audiology, Washington University School of Medicine, St Louis, Missouri, USA.
Otolaryngol Head Neck Surg. 2023 May;168(5):1089-1096. doi: 10.1002/ohn.182. Epub 2023 Jan 19.
To explore whether deintensification of adjuvant therapy reduces ototoxicity among patients with human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC).
Retrospective cohort study.
Single academic center.
The ototoxicity rate among adult patients with HPV-related OPSCC enrolled in the Minimalist Trial (MINT), a prospective phase 2 trial of surgery followed by risk-adjusted deintensified adjuvant therapy (42 Gy radiation given alone or with a single 100 mg/m dose of cisplatin), was compared to that among a historical cohort treated with standard adjuvant therapy (60-66 Gy radiation with up to three 100 mg/m doses of cisplatin). Ototoxicity was defined as Common Terminology Criteria for Adverse Events v5.0 ≥ Grade 2. Mixed model analysis was performed to investigate the association between deintensified adjuvant therapy and treatment-related hearing loss.
A total of 29 patients (58 ears) were analyzed in the MINT cohort, and 27 patients (54 ears) in the historical cohort. The ototoxicity rate was 5% (n = 3/58 ears) in the MINT cohort and 46% (n = 25/54 ears) in the historical cohort (difference, 41%; 95% confidence interval [CI] = 27%-56%). Patients in the MINT cohort demonstrated a 95% decrease in risk of ototoxicity compared to those in the historical cohort (adjusted odds ratio: 0.05, 95% CI = 0.01-0.31). Differences in estimated marginal mean threshold shifts were statistically and clinically significant at frequencies ≥ 3 kHz.
The deintensified adjuvant therapy given in MINT led to less ototoxicity than standard adjuvant therapy among patients with HPV-related OPSCC.
探讨辅助治疗强度降低是否能减少人乳头瘤病毒(HPV)相关口咽鳞状细胞癌(OPSCC)患者的耳毒性。
回顾性队列研究。
单一学术中心。
将参加极简主义试验(MINT)的成年HPV相关OPSCC患者的耳毒性发生率与接受标准辅助治疗(60 - 66 Gy放疗,最多三次100 mg/m顺铂剂量)的历史队列患者的耳毒性发生率进行比较。MINT是一项前瞻性2期试验,手术治疗后采用风险调整的强化辅助治疗(单独给予42 Gy放疗或联合单次100 mg/m顺铂剂量)。耳毒性定义为不良事件通用术语标准第5.0版≥2级。进行混合模型分析以研究强化辅助治疗与治疗相关听力损失之间的关联。
MINT队列共分析了29例患者(共58只耳),历史队列共分析了27例患者(共54只耳)。MINT队列的耳毒性发生率为5%(n = 3/58只耳),历史队列的耳毒性发生率为46%(n = 25/54只耳)(差异为41%;95%置信区间[CI] = 27% - 56%)。与历史队列相比,MINT队列患者耳毒性风险降低了95%(调整后的优势比:0.05,95% CI = 0.01 - 0.31)。在频率≥3 kHz时,估计的边际平均阈值变化差异在统计学和临床上均具有显著意义。
在HPV相关OPSCC患者中,MINT试验中给予的强化辅助治疗比标准辅助治疗导致的耳毒性更小。