treatment Annelot Meij er, PhD st udent PIs: prof. dr. M.M. van den - PowerPoint PPT Presentation

Ototoxicity during and after childhood cancer treatment Annelot Meij er, PhD st udent PI’s: prof. dr. M.M. van den Heuvel-Eibrink, dr. M. van Grot el, dr. A.E. Hoet ink

Introduction childhood cancer urvival rates for childhood cancer  • S Long term side effects:  • 2

Ototoxicity • Long term side effect: ototoxicity - Hearing loss  45% of survivors t reat ed wit h cisplat in¹  Y oung age at diagnosis, high dose cisplat in, co-t reat ment furosemide¹  Irreversible ² - Vert igo (dizziness) - Tinnit us (ear ringing) • Impact on childhood cancer patients and survivors Influence learning + social performances:  QoL - - No approved ot oprot ect ive agent s ¹ Clemens et al., 2016 / ² Clemens et al., 2017 3

Genetics ototoxicity • Clinical characteristics: explain ototoxic response partially - Genet ic suscept ibilit y possible? • Knowledge on molecular mechanisms limited - S everal st udies performed: result s uncert ain  S t udy design, no replicat ion cohort , small sample size  Et hnicit y + non-genet ic risk profile het erogenous  Large cohort + well documented clinical/ treatment data needed 4

PanCareLIFE • Aim: to investigate determinants of long-term health - Ot ot oxicit y, fert ilit y impairment , qualit y of life • Ten European countries collect data - > 12,000 childhood cancer survivors (CCS )! - 8 workpackages (WPs): 5 scient ific • Genetic susceptibility ototoxicity (WP4b) - 598 CCS : <18 years at Dx - Treat ment wit h cisplat in + no CR T - At least 1 audiogram available 5

PanCareLIFE methods • Data collection - Clinical charact erist ics, t reat ment dat a, audiograms • DNA collection - Blood or saliva samples - Novel S NPs ident ified by GWAS - Qualit y cont rol + imput at ions • Genetic susceptibility analysis - Logist ic regression models - Replicat ion cohort Canada 6