Childhood cancer related hearing loss and tinnitus

Ototoxicity (hearing loss, tinnitus and/or vertigo) is a serious adverse event of childhood cancer treatment that may have a severe negative impact on quality of life. Up until now, studies have mainly focused on identifying risk factors associated with cisplatin-induced hearing loss in survivors of childhood cancer. As hearing loss often develops early during therapy, it is important to gain more insight into the direct effect of hearing loss in children with cancer. Tinnitus is an equally important adverse event of treatment, but research in children with cancer and survivors remains limited. In this thesis, we further explored clinical and genetic risk factors for hearing loss during childhood cancer treatment, and increased the knowledge on the risk of, and clinical risk factors for tinnitus after therapy. The results show that cumulative incidence of cisplatin-induced hearing loss is higher and develops more rapidly in very young children compared to older children, and that cisplatin dose, vincristine and antibiotic treatment influence the course of hearing loss over time. In addition, we identify a novel genetic variant associated with hearing loss in children treated with cisplatin. It also appears that childhood cancer survivors are three times more likely to suffer from tinnitus compared to siblings, and that cisplatin, cranial irradiation and brain surgery influence this risk. Finally, standardized recommendations for hearing loss monitoring during childhood cancer treatment are described which were developed within a large group of international experts. The results of this thesis contribute to identification of high risk patients, important for stratification towards otoprotective agents.