Genetic polymorphisms contributing to hearing loss in children treated with platinum agents : a systematic review and meta-analysis protocol

Article Article scientifique Article Genetic polymorphisms contributing to hearing loss in children treated with platinum agents : a systematic review and meta-analysis protocol eng 2025-09-16 2025-09 author Chavaz Lara Marie 0000-0002-8253-465X CANSEARCH Research Platform for Paediatric Oncology and Haematology, Department of Paediatrics, Gynecology and Obstetrics, University of Geneva Faculty of Medicine, Geneva, GE, Switzerland lara.chavaz@unige.ch.,Division of Paediatric Oncology and Haematology, University Hospitals of Geneva Department of Women-Children-Teenagers, Geneva, GE, Switzerland. 849945 Département de Pédiatrie, Gynécologie et Obstétrique (PETRI) author Ćavar Pavić Jakica Division of Paediatric Oncology and Haematology, Department of Paediatrics, Inselspital University Hospital Bern Children's Clinic, Bern, BE, Switzerland.,Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, BE, Switzerland. author Dupanloup Isabelle CANSEARCH Research Platform for Paediatric Oncology and Haematology, Department of Paediatrics, Gynecology and Obstetrics, University of Geneva Faculty of Medicine, Geneva, GE, Switzerland. 27649 Isabelle Dupanloup De Ceuninck author Fresneau Brice Department of Children and Adolescent Oncology, Gustave Roussy Institute, Villejuif, Île-de-France, France.,U1018 CESP, Radiation Epidemiology team, Paris-Saclay University,Gustave Roussy Cancer Campus, INSERM, Villejuif, Île-de-France, France. 446793 author Cao Van Hélène Division of Paediatric Otolaryngology Unit, Department of Otorhinolaryngology, Head and Neck Surgery, Geneva University Hospitals, Geneva, GE, Switzerland.,Audiology Laboratory, Department of Otorhinolaryngology, Head and Neck Surgery, Geneva University Hospitals, Geneva, GE, Switzerland. 804268 author Waespe Nicolas 0000-0002-2271-8959 CANSEARCH Research Platform for Paediatric Oncology and Haematology, Department of Paediatrics, Gynecology and Obstetrics, University of Geneva Faculty of Medicine, Geneva, GE, Switzerland.,Division of Paediatric Oncology and Haematology, Department of Paediatrics, Inselspital University Hospital Bern Children's Clinic, Bern, BE, Switzerland.,Childhood Cancer Research Group, Institute of Social and Preventive Medicine & Department of Biomedical Research, University of Bern, Bern, GE, Switzerland. 911635 Département de Pédiatrie, Gynécologie et Obstétrique (PETRI) author Gloor Yvonne Sylvia 0000-0002-8790-0479 CANSEARCH Research Platform for Paediatric Oncology and Haematology, Department of Paediatrics, Gynecology and Obstetrics, University of Geneva Faculty of Medicine, Geneva, GE, Switzerland. 135176 Département de Pédiatrie, Gynécologie et Obstétrique (PETRI) author Ansari Djaberi Marc Georges CANSEARCH Research Platform for Paediatric Oncology and Haematology, Department of Paediatrics, Gynecology and Obstetrics, University of Geneva Faculty of Medicine, Geneva, GE, Switzerland.,Division of Paediatric Oncology and Haematology, University Hospitals of Geneva Department of Women-Children-Teenagers, Geneva, GE, Switzerland. 61572 Département de Pédiatrie, Gynécologie et Obstétrique (PETRI) e103735 10.1136/bmjopen-2025-103735 40962343 2044-6055 PMC12443194 https://bmjopen.bmj.com/lookup/doi/10.1136/bmjopen-2025-103735 Introduction: The improved survival rates of children with cancer have heightened concerns about treatment-related chronic health conditions, including platinum-induced hearing loss (PIHL). Cisplatin and carboplatin, widely used in paediatric cancer therapies, frequently cause irreversible sensorineural hearing loss. PIHL affects 1.7-90.1% of patients exposed to these drugs, yet known risk factors-including age, cisplatin dosage, cranial radiation and co-treatment with ototoxic drugs-fail to fully explain interindividual variability. Genetic factors likely play a role in susceptibility to PIHL. Since genetic susceptibility in children may differ from adults, and given the critical window of auditory development, a focused investigation of paediatric genetic factors using quantitative methods is warranted to detect small to moderate effects and understand the polygenic nature of PIHL. Methods and analysis: In this study, we will systematically review and conduct a meta-analysis of genetic polymorphisms associated with PIHL in individuals diagnosed before the age of 21 years. Following Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, the review will include randomised controlled trials, cohort, case-control and cross-sectional studies that analyse the genetic influence on PIHL in paediatric populations treated with cisplatin and carboplatin. A comprehensive search of PubMed, EMBASE and Cochrane databases will be conducted, supplemented by backward citation searching. Data will be extracted on study design, treatment details, hearing loss assessment methods, genetic findings and covariates. We will use forest plots to present the results, and both Mantel-Haenszel fixed-effects model and random-effects model will be used for meta-analysis. Heterogeneity will be assessed with the I² index. The study will address potential heterogeneity, individual study quality, proportion of missing data and meta-analysis bias. The quality of the evidence of the meta-analysis will be assessed using the Grading quality of evidence and strength of Recommendations (GRADE) approach. Discussion: This systematic review will enhance our understanding of the genetic contribution to PIHL in children and serve as a basis for further research for improvement of personalised treatment strategies for paediatric cancer care. Prospero registration number: CRD42024532664. Ethics and dissemination: All the included patient's data are already published with an ethics approval for each study, respectively. No original data will be collected. Antineoplastic Agents / adverse effects Carboplatin / adverse effects Child Cisplatin / adverse effects Genetic Predisposition to Disease Hearing Loss / chemically induced Hearing Loss / genetics Humans Meta-Analysis as Topic Neoplasms / drug therapy Polymorphism, Genetic Research Design Systematic Reviews as Topic Dewey 616.8 Dewey 618 58 Département de pédiatrie, gynécologie et obstétrique 223 61 Département des neurosciences cliniques 226 false 564 Oncologie et hématologie pédiatriques 907 BMJ open 15 9 8e31ad55-d172-47bd-a813-b4a6ef805468 Article (Published version) Public e103735.full.pdf 340771 application/pdf CC BY-4.0 18f798fab6154fb3cae544d24bb495d12d2e598d31c6d0aa230a968166a6c79e openAccess Faculté de médecine / Section de médecine clinique / Département de pédiatrie, gynécologie et obstétrique Faculté de médecine / Section de médecine clinique / Département des neurosciences cliniques

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Genetic polymorphisms contributing to hearing loss in children treated with platinum agents : a systematic review and meta-analysis protocol	BMJ open			2025	20	59

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