ImportanceCisplatin is highly ototoxic but widely used. Evidence is lacking regarding cisplatin-related hearing loss (CRHL) in adult-onset cancer survivors with comprehensive audiologic assessments (eg, Words-in-Noise [WIN] tests, full-spectrum audiometry, and additional otologic measures), as well as the progression of CRHL considering comorbidities, modifiable factors associated with risk, and cumulative cisplatin dose.ObjectiveTo assess CRHL with comprehensive audiologic assessments, including the WIN, evaluate the longitudinal progression of CRHL, and identify factors associated with risk.Design, Setting, and ParticipantsThe Platinum Study is a longitudinal study of cisplatin-treated testicular cancer survivors (TCS) enrolled from 2012 to 2018 with follow-up ongoing. Longitudinal comprehensive audiologic assessments at Indiana University and Memorial Sloan Kettering Cancer Center included 100 participants without audiometrically defined profound hearing loss (HL) at baseline and at least 3.5 years from their first audiologic assessment. Data were analyzed from December 2013 to December 2022.ExposuresFactors associated with risk included cumulative cisplatin dose, hypertension, hypercholesterolemia, diabetes, tobacco use, physical inactivity, body mass index, family history of HL, cognitive dysfunction, psychosocial symptoms, and tinnitus.Main Outcomes and MeasuresMain outcomes were audiometrically measured HL defined as combined-ears high-frequency pure-tone average (4-12 kHz) and speech-recognition in noise performance measured with WIN. Multivariable analyses evaluated factors associated with risk for WIN scores and progression of audiometrically defined HL.ResultsMedian (range) age of 100 participants at evaluation was 48 (25-67) years; median (range) time since chemotherapy: 14 (4-31) years. At follow-up, 78 (78%) TCS had audiometrically defined HL; those self-reporting HL had 2-fold worse hearing than TCS without self-reported HL (48 vs 24 dB HL; P < .001). A total of 54 (54%) patients with self-reported HL showed clinically significant functional impairment on WIN testing. Poorer WIN performance was associated with hypercholesterolemia (β = 0.88; 95% CI, 0.08 to 1.69; P = .03), lower-education (F1 = 5.95; P = .004), and severity of audiometrically defined HL (β̂ = 0.07; 95% CI, 0.06 to 0.09; P < .001). CRHL progression was associated with hypercholesterolemia (β̂ = −4.38; 95% CI, −7.42 to −1.34; P = .01) and increasing age (β̂ = 0.33; 95% CI, 0.15 to 0.50; P < .001). Importantly, relative to age-matched male normative data, audiometrically defined CRHL progression significantly interacted with cumulative cisplatin dose (F1 = 5.98; P = .02); patients given 300 mg/m2 or less experienced significantly less progression, whereas greater temporal progression followed doses greater than 300 mg/m2.Conclusions and RelevanceFollow-up of cisplatin-treated cancer survivors should include strict hypercholesterolemia control and regular audiological assessments. Risk stratification through validated instruments should include querying hearing concerns. CRHL progression relative to age-matched norms is likely associated with cumulative cisplatin dose; investigation over longer follow-up is warranted.

中文翻译：

---

顺铂化疗后的综合听力分析


重要性顺铂具有高度耳毒性，但用途广泛。缺乏关于成人发病癌症幸存者中顺铂相关性听力损失（CRHL）的证据，缺乏全面的听力学评估（例如，噪音中的单词 [WIN] 测试、全谱听力测定和其他耳科措施）以及考虑合并症、与风险相关的可改变因素和累积顺铂剂量来评估 CRHL 的进展。目的通过综合听力学评估（包括 WIN）评估 CRHL，评估 CRHL 的纵向进展，并确定与风险相关的因素。设计、设置和参与者白金该研究是一项针对 2012 年至 2018 年接受顺铂治疗的睾丸癌幸存者 (TCS) 的纵向研究，随访正在进行中。印第安纳大学和纪念斯隆凯特琳癌症中心进行的纵向综合听力学评估包括 100 名参与者，这些参与者在基线时和距首次听力学评估至少 3.5 年没有听力测定定义的深度听力损失 (HL)。数据分析时间为 2013 年 12 月至 2022 年 12 月。暴露与风险相关的因素包括累积顺铂​​剂量、高血压、高胆固醇血症、糖尿病、吸烟、缺乏身体活动、体重指数、HL 家族史、认知功能障碍、心理社会症状和耳鸣。结果和测量主要结果是听力测量的 HL（定义为合耳高频纯音平均值（4-12 kHz））和使用 WIN 测量的噪声中的语音识别性能。多变量分析评估了与 WIN 评分风险和听力测定定义的 HL 进展相关的因素。结果 100 名参加评估的参与者的中位年龄（范围）为 48（25-67）岁；自化疗以来的中位（范围）时间：14（4-31）年。随访时，78 名 (78%) TCS 患有听力测定定义的 HL；那些自我报告 HL 的听力比没有自我报告 HL 的 TCS 差 2 倍（48 与 24 dB HL；P < .001）。共有 54 名 (54%) 自我报告的 HL 患者在 WIN 测试中表现出临床显着的功能障碍。较差的 WIN 表现与高胆固醇血症（β = 0.88；95% CI，0.08 至 1.69；P = .03）、教育程度较低（F1 = 5.95；P = .004）和听力测定定义的 HL 严重程度（β̂ = 0.07）相关。 ；95% CI，0.06 至 0.09； CRHL 进展与高胆固醇血症 (β̂ = −4.38; 95% CI, -7.42 至 -1.34; P = .01) 和年龄增加 (β̂ = 0.33; 95% CI, 0.15 至 0.50; P < .001) 相关。重要的是，相对于年龄匹配的男性正常数据，听力测定定义的 CRHL 进展与累积顺铂剂量显着相互作用（F1 = 5.98；P = .02）；接受 300 mg/m2 或更少剂量的患者的进展显着减少，而剂量大于 300 mg/m2 则出现更大的时间进展。结论和相关性顺铂治疗的癌症幸存者的随访应包括严格的高胆固醇血症控制和定期听力学评估。通过经过验证的工具进行风险分层应包括询问听力问题。相对于年龄匹配标准的 CRHL 进展可能与累积顺铂剂量有关；有必要进行更长时间的随访调查。