19 March 2019 from 16:15 to 17:15

PhD Defence: Clinical and genetic determinants of ototoxicity after childhood cancer

Approximately 550–600 children are diagnosed with cancer every year in the Netherlands. Improvements in treatment protocols brought a large increase in survival for many childhood cancers with a current overall long-term survival of ~80%. With the expansion of the childhood cancer survivor population, side-effects of treatment have become more prevalent and have drawn our attention. One of these side-effects is hearing impairment, induced by platinum treatment. The primary aim of this thesis was to investigate determinants of ototoxicity which occur during and after platinum treatment for childhood cancer. For patients treated with a cumulative cisplatin dose of 300 mg/m2 or more, a 5-fold higher risk of ototoxicity was observed, compared with patients treated with a lower cumulative cisplatin dose. Furthermore, young age at diagnosis, concomitant carboplatin use and furosemide co-treatment increased the risk for hearing impairment in childhood cancer patients treated with platinum agents, but not treated with cranial irradiation. While many factors influence hearing impairment during and after platinum treatment, genetic factors have been suggested to play a role in ototoxicity as well. Meta-analysis of available literature showed that rs1872328 in ACYP2 could possibly be related to platinum ototoxicity in childhood cancer patients and survivors. As platinum-treated or cranial irradiated childhood cancer survivors have an increased risk of developing hearing impairment, clinical practice guidelines are necessary to promote early detection of ototoxicity. The International Late Effects of Childhood Cancer Guideline Harmonization Group has been initiated to harmonize clinical practice guidelines for childhood cancer survivors. We described the overall methods of our worldwide collaborative effort to harmonize the recommendations for surveillance of ototoxicity after treatment for childhood and young adult cancer.

Start date and time
19 March 2019 16:15
End date and time
19 March 2019 17:15
PhD candidate
Eva Clemens
Dissertation
Klinische en genetische determinanten van ototoxiciteit na kinderkanker
PhD supervisor(s)
Prof. M.M. van den Heuvel-Eibrink
Co-supervisor(s)
Prof. M. van GrotelProf. A.C.H. de Vries
Entrance fee
Free