Risk factors of ototoxicity after cisplatin-based chemo-irradiation in patients with locally advanced head-and-neck cancer: a multivariate analysis.
OBJECTIVE
Cisplatin chemo-irradiation is increasingly used in locally advanced squamous cell carcinoma of the head and neck. The objective of this study is to determine risk factors of ototoxicity due to intra-arterial high-dose cisplatin chemoradiation.


METHODS
A prospective analysis of hearing thresholds at low and (ultra) high frequencies obtained before, during, and after treatment in 146 patients. Treatment consisted of intra-arterial infusion of high-dose cisplatin (150 mg/m(2), four courses) with sodium thiosulfate rescue and concurrent radiation therapy (70 Gy). Patient and chemoradiation variables were studied in a multivariate analysis.


RESULTS
After treatment, 23% of the ears were under consideration for hearing aids because of therapy. Twenty-two percent of the patients developed an increase in air-bone gap >10 dB during or after therapy. In the multivariate explanatory analysis, cumulative dose of cisplatin and radiation therapy, and young age displayed a causal relationship with increased sensorineural hearing loss during and after therapy (p < 0.001). In the multivariate prediction analysis, pretreatment hearing level of the concerning ear was identified as an independent predictive factor for hearing capability after therapy (p < 0.0001).


CONCLUSIONS
Both cisplatin and radiation therapy were proven to induce sensorineural hearing loss, in this study with short-term follow-up. Of all patient and treatment variables studied, the patients pretreatment hearing level appeared to be the main predictive factor for hearing capability after high-dose intra-arterial cisplatin chemoradiation.
Zuur
Charlotte L
CL
Department of Otorhinolaryngology, Academical Medical Centre, Amsterdam, The Netherlands. cl.zuur@vumc.nl
Simis
Yvonne J
YJ
Lansdaal
Pauline E
PE
Hart
Augustinus A
AA
Rasch
Coen R
CR
Schornagel
Jan H
JH
Dreschler
Wouter A
WA
Balm
Alfons J
AJ
D000367:Age Factors; D000931:Antidotes / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects*; D003131:Combined Modality Therapy / Q000379:methods; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D006309:Hearing / Q000187:drug effects / Q000528:radiation effects; D006319:Hearing Loss, Sensorineural / Q000139:chemically induced / Q000209:etiology*; D006801:Humans; D007261:Infusions, Intra-Arterial; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011446:Prospective Studies; D011829:Radiation Dosage; D012307:Risk Factors; D013885:Thiosulfates / Q000627:therapeutic use
D000931:Antidotes; D000970:Antineoplastic Agents; D013885:Thiosulfates; C017717:sodium thiosulfate; D002945:Cisplatin