Evaluation of risk factors causing ototoxicity in childhood head and neck cancers

Objective: Approximately 12% of childhood cancers are located in the head and neck region. Overall survival rate is reported 80% on average depending on age, stage, location, histology and molecular genetic characteristics of tumors. Considering the long life expectancy in these patients, early diagnosis of treatment-related side effects becomes even more important. Ototoxicity is a severe side effects of platinum based chemotherapy drugs. The aim of this study is to evaluate risk factors contrubuting to development of ototoxicity in children who received platinum based chemotherapy due to malignancies located in the head and neck region Material and Method: Eighty four children who received platinum based chemoterapy in the pediatric oncology department of Dokuz Eylul University School of Medicine were included in this study. Audiological evaluation of all children were done before and after each chemoterapy session by pure tone audiometry, distorsiton product otoacoustic emissions and auditory brainstem response test. Ototoxicity was evaluated using Brock, Muenster anc Chang classifications. Risk factors such as cranial irradiation, cumulative doses of cisplatin, age, gender, co-treatment with aminoglycosides, duration of treatment and type of chemoterapeutic agents were a analysed. By using Chi-square test, all of the risk factors were matched with the three ototoxicity classifications. Risk factors which were found to be significant for ototoxicity by univariate analyses were reevaluated using logistic regression modelling. Then the patients who had moderate and severe ototoxicity (grade 3 and grade 4) were determined and same analyses were repeated. Results: Of 84 patients, ototoxicity was observed in 25 patients according to Brock, in 29 patients according to Muenster and in 27 patients according to Chang classifications. In univariate analyses to be aged between 5 and 12, cranial irradiation and to be treated with both cisplatin and carboplatin were found to be related with ototoxicity according to both 3 classsifications( p<0,05). Logistic regression modelling analyses with these 3 risk factors showed that, to be aged between 5 and 12 and to be treated with both cisplatin and carboplatin significiantly increased the risk of ototoxicity development (p<0.05). Univariate analyses for the development of moderate to severe ototoxicity showed that cranial irraditon and to be aged between 5 and 12 are significant risk factors according to Muenster and Chang classifications. The fact that the treatment was taken as a single dose also appeared to be a risk factor for univariate analyses conducted according to Brock classification Conclusion: Our findings suggest that to be aged between 5 and 12, cranial irradiation and to be treated with both cisplatin and carboplatin were important risk factors for the development of ototoxicity in pediatric patients with head and neck malignancies. Althought there are some differences according to analyses conducted on different classification systems age, cranial irradiation and treatment timing seems to be important risk factors for the development of moderate to severe ototoxicity.