Discipline of Audiology, School of Health Sciences, University of KwaZulu-Natal, Durban, South Africa.
Division of Epidemiology & Biostatistics, Department of Global Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
PLoS One. 2023 Apr 4;18(4):e0283639. doi: 10.1371/journal.pone.0283639. eCollection 2023.
Concurrent chemoradiotherapy using weekly cisplatin remains standard of care for locally advanced cervical cancer in Sub-Saharan Africa. While cisplatin remains a popular cancer chemotherapeutic, it has an irreversible ototoxic effect on patients' auditory system. However, there is a paucity of epidemiological information on its extent and severity during cervical cancer treatment. In a region with a high burden of cervical cancer, this has serious consequences for aural intervention and rehabilitation.
Using a prospective cohort study design, 82 patients with incident cervical cancer, receiving weekly cisplatin chemotherapy (50 mg/m2 body surface) at a tertiary level hospital in KwaZulu-Natal Province of South Africa, underwent audiological assessments at various intervals. We describe the temporal impact of cisplatin exposure on hearing loss, its combined effect with HIV-infection, and estimate ototoxicity incidence in this cohort. The median age was 52 years with Stages IIB (45%) and IIIB (35.4%) cancers being most common. Complaints of reduced hearing sensitivity increased significantly (p<0.0001). Bilateral, asymmetrical sensorineural hearing loss, with greater effect in the extended high-frequency range, was evident. Cisplatin dosage was significantly associated with ototoxicity severity at one- (p = 0.017), three- (p = 0.010), and six-month (p = 0.015) post-treatment follow-up. HIV-seropositivity (53.7%) was significantly associated with NCI-CTCAE Grading Scale at three- (p = 0.022) and six-months (p = 0.023) post-treatment. Multiple Tobit regression revealed a cumulative dose effect bilaterally, after adjustment for age and HIV status, evident from 9000Hz and above in the right ear, while a plateau effect was observed at 250mg/m2 in the left ear. The incidence was ototoxicity was 98% at a cumulative dose of 150mg/m2.
The findings of this epidemiologic study highlight the temporal course and severity of ototoxicity experienced by cervical cancer patients treated with cisplatin, with greater impact in HIV-positive subgroup, thus underscores the need for audiological monitoring and timely interventions in this cohort.
在撒哈拉以南非洲地区，每周顺铂联合放化疗仍然是局部晚期宫颈癌的标准治疗方法。虽然顺铂仍是一种常用的癌症化疗药物，但它会对患者的听觉系统造成不可逆转的耳毒性。然而，关于宫颈癌治疗期间其程度和严重程度的流行病学信息却很少。在宫颈癌负担沉重的地区，这对听觉干预和康复造成了严重后果。
本研究采用前瞻性队列研究设计，纳入了在南非夸祖鲁-纳塔尔省一家三级医院接受每周顺铂化疗（50mg/m2 体表面积）的 82 例新发宫颈癌患者，在不同时间点进行了听力评估。我们描述了顺铂暴露对听力损失的时间影响、它与 HIV 感染的综合影响，并估计了该队列中的耳毒性发生率。中位年龄为 52 岁，最常见的是 IIB 期（45%）和 IIIB 期（35.4%）癌症。听力敏感度降低的抱怨显著增加（p<0.0001）。双侧、不对称感音神经性听力损失，高频扩展范围的影响更大，这一点很明显。顺铂剂量与治疗后 1 个月（p=0.017）、3 个月（p=0.010）和 6 个月（p=0.015）时的耳毒性严重程度显著相关。HIV 血清阳性（53.7%）与治疗后 3 个月（p=0.022）和 6 个月（p=0.023）时的 NCI-CTCAE 分级量表显著相关。多 Tobit 回归显示，在调整年龄和 HIV 状态后，双侧均存在累积剂量效应，在右耳 9000Hz 及以上频率，而在左耳 250mg/m2 时出现平台效应。累积剂量为 150mg/m2 时，耳毒性发生率为 98%。
这项流行病学研究的结果强调了接受顺铂治疗的宫颈癌患者经历的耳毒性的时间过程和严重程度，在 HIV 阳性亚组中影响更大，因此强调了在该队列中进行听力监测和及时干预的必要性。
