Genetic Determinants of Ototoxicity During and After Childhood Cancer Treatment: Protocol for the PanCareLIFE Study (Preprint)

• DOI: 10.2196/preprints.11868
• Publication Date: 2018-08-17T18:15:32Z
• Authors: Eva Clemens; Annelot JM Meijer; Linda Broer; Thorsten Langer; Anne-Lotte LF van...; André G Uitterlinden; Andrica de Vries; Claudia E Kuehni; Maria L Garrè; Tomas Kepak; Jarmila Kruseova; Jeanette F Winther; Leontien C Kremer; Eline van Dulmen-...; Wim JE Tissing; Catherine Rechnitzer; Line Kenborg; Henrik Hasle; Desiree Grabow; Ross Parfitt; Harald Binder; Bruce C Carleton; Julianne Byrne; Peter Kaatsch; Antoinette am Zeh...; Oliver Zolk; Marry M van den H...
• Keywords: Ototoxicity; Carboplatin; Genetic predisposition; Neurocognitive

<sec> <title>BACKGROUND</title> Survival rates after childhood cancer now reach nearly 80% in developed countries. However, treatments that lead to survival and cure can cause serious adverse effects with lifelong negative impacts on survivor quality of life. Hearing impairment is a common effect children treated cisplatin-based chemotherapy or cranial radiotherapy. Ototoxicity extend from high-tone hearing involvement speech frequencies. impede language neurocognitive development. Although treatment-related risk factors for loss following treatment have been identified, the individual variability toxicity similar between patients suggests role genetic susceptibility. Currently, 12 candidate gene approach studies performed identify polymorphisms predisposing platinum-induced ototoxicity being cancer. results were inconsistent most underpowered and/or lacked replication. </sec> <title>OBJECTIVE</title> We describe design PanCareLIFE consortium’s work packages address susceptibility ototoxicity. <title>METHODS</title> As part study within framework PanCare consortium, we addressed treatment-induced during large European cohort by genome-wide association screening. <title>RESULTS</title> This included 1124 survivors cisplatin, carboplatin, radiotherapy cancer, resulting largest clinical assembled this late date. Within defined group 598 cisplatin-treated not confounded The initiative provided, first time, unique opportunity confirm already identified determinants using set up international cisplatin-induced direct novel allelic variants. Results will be validated an independent replication cohort. Patient recruitment started January 2015 final inclusion was October 2017. are currently performing analyses expected end 2019 beginning 2020. <title>CONCLUSIONS</title> Genetic as pan-European project, PanCareLIFE, may contribute future prediction models incorporated trials platinum-based therapies help development prevention strategies. <title>INTERNATIONAL REGISTERED REPOR</title> DERR1-10.2196/11868