Characteristics and Risk Factors of Cisplatin-Induced Ototoxicity in Testicular Cancer Patients Detected by Distorsion Product Otoacoustic Emission

Abstract

Objective: The characteristics and risk factors of the long-term ototoxic effect of cisplatin in testicular cancer patients was studied by measuring distortion product otoacoustic emissions (DPOAEs), which is a highly sensitive, new method for detecting high-frequency hearing loss. Methods: 223 patients with a median follow-up time of 4.27 years (range 0.5–20 years) and a median age of 37 years (range 18–55 years) were assessed by DPOAE. 100 mg/m² cisplatin were administered per cycle, in EP, BEP, VeIP, VIP or VPB regimens. The control group consisted of 40 testicular cancer patients without chemotherapy (median age 35 years, range 16–54 years). A detailed medical history evaluated audiological risk factors and hearing complaints. DPOAE was measured in eight frequencies from 750 to 8,000 Hz. Paired t test and Mann-Whitney test were used for statistical evaluation. Results: Symptomatic ototoxicity was observed in 20% of the patients. In patients receiving ≤300 mg/m² cisplatin, no amplitude changes were detected. Beyond this dose, hearing impairment proved to be dose dependent. Contrary to the literature, not only high frequencies were affected. In patients receiving ≧400 mg/m², our method could detect significant hearing impairment at lower frequencies that are important for speech perception. At 400 mg/m², significant amplitude change was detected at 3,000 Hz (p = 0.01); at 500–600 mg/m², significant amplitude change was detected at 1,500, 2,000 and 3,000 Hz (p = 0.004, 0.0001 and 0.0002, respectively), and at 700 mg/m² significant amplitude change was detected at 3,000 Hz (p = 0.01). We detected the lowest amplitudes in those 44 patients who had symptomatic ototoxicity. The only statistically significant risk factor was the cumulative dose of cisplatin; neither smoking nor noise exposure were independent risk factors. Conclusion: DPOAE is a fast, noninvasive and reliable method in detecting late ototoxicity in testicular cancer patients. Contrary to the literature, not only high frequencies are affected. In patients receiving at least 400 mg/m², using DPOAE we were able to detect significant hearing impairment at lower frequencies that are important for speech perception.

Prevention of Cisplatin‐Induced Hearing Loss by Intratympanic Dexamethasone: A Randomized Controlled Study

“…35 The increase in high frequencies pure tone thresholds was accompanied by significant decrease in the DPOAEs average SNR for 4000 to 8000 Hz in the control group confirming previous observations pointing to the organ of Corti outer hair cells as the primary target for Cisplatin ototoxicity. 31,32 The specific mechanisms involved in the attenuation of CIHL by Dexamethasone are not known yet. However, recent studies suggest the relevance of various cellular processes that might explain this otoprotection.…”

Report on hearing loss in oncology

“…Audiologically, there are monitoring proposals using conventional frequencies (Testa et al 15 , Kushner et al 16 , Marshall et al 17 , Toral-Martinnon et al 18 ), monitoring proposals using transient otoacoustic emissions (Liberman 19 ) or distortion products (Biro et al 20 ; Hyppolito et al 21 ), and monitoring proposals using high frequencies (over 8000 Hz) (Garcia 22 ), which may be first affects by ototoxic drugs. In this case, patients with hearing loss normally do not complain and not always perceive loss of hearing (Liberman 23 ).…”

Emissões otoacústicas produto de distorção em normo ouvintes e em perdas auditivas neurossensoriais leve e moderada com os protocolos 65/55 dB NPS E 70/70 dB NPS

“…Indivíduos expostos a sons intensos ou a agentes ototóxicos podem apresentar mudanças na amplitude das EOA. Estudos relatam que, quando existem alterações de CCE, mesmo que ainda não exista mudança dos limiares tonais, já é possível observar uma redução da amplitude das EOA, demonstrando a sensibilidade deste parâmetro no diagnóstico precoce e/ou acompanhamento nos tratamentos quimioterápicos bem como nas questões de saúde do trabalhador [9][10][11][12] .…”