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

2

• S

urvival rates for childhood cancer 

• Long term side effects: 

Ototoxicity

3

• Long term side effect: ototoxicity
• Hearing loss

 45%

• f survivors t reat ed wit h cisplat in¹

 Y

• ung age at diagnosis, high dose cisplat in, co-t reat ment furosemide¹

 Irreversible²

• 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

Genetics ototoxicity

4

• 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

PanCareLIFE

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• 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

PanCareLIFE methods

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• 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