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Cited by 92Hearing, Cochlea, Tinnitus, GeneticsChemotherapy-induced organ toxicity mitigationHearing Loss and Rehabilitation

Prevalence and risk factors for cisplatin-induced hearing loss in children, adolescents, and young adults: a multi-institutional North American cohort study

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Moke, Diana J, Luo, Chunqiao, Millstein, Joshua, Knight, Kristin R, Rassekh, Shahrad R, Brooks, Beth, Ross, Colin J D, Wright, Michael +5 more·2021·The Lancet Child & Adolescent Health
DOI 10.1016/s2352-4642(21)00020-1PMC PMC9059427
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Abstract

Background Cisplatin is used to treat a wide range of childhood cancers and cisplatin-induced hearing loss (CIHL) is a common and debilitating toxicity. We aimed to address persistent knowledge gaps in CIHL by establishing benchmarks for the prevalence of and risk factors for CIHL.Methods In this multi-institutional cohort study, children (age 0-14 years), adolescents, and young adults (age 15-39 years) diagnosed with a cisplatin-treated tumour from paediatric cancer centres, who had available cisplatin dosing information, and primary audiology data for central review from consortia located in Canada and the USA were eligible for inclusion. Audiology was centrally reviewed and CIHL graded using the consensus International Society of Pediatric Oncology (SIOP) Boston Ototoxicity Scale. We assessed the prevalence of moderate or severe CIHL (SIOP grade ≥2) at latest follow-up and end of therapy, in each demographic, diagnosis, and treatment group and their relative contributions to risk for CIHL. Secondary endpoints explored associations of cisplatin dose reductions and CIHL with survival. We also examined whether cisplatin dose reductions and CIHL were associated with survival outcomes.Findings We included 1481 patients who received cisplatin. Of the 1414 (95·5%) participants who had audiometry at latest follow-up (mean 3·9 years [SD 4·2] since diagnosis), 620 (43·8%) patients developed moderate or severe CIHL. The highest prevalence of CIHL was seen in the youngest patients (aged <5 years; 360 [59·4%] of 606 patients) and those with a CNS tumour (221 [50·9%] of 434 patients), hepatoblastoma (110 [65·9%] of 167 patients), or neuroblastoma (154 [62·1%] of 248 patients). After accounting for cumulative cisplatin dose, higher fractionated doses were associated with risk for CIHL (for each 10mg/m 2 increase per day, adjusted odds ratio [aOR] 1·15 [95% CI 1·07-1·25]; for each 50 mg/m 2 increase per cycle aOR 2·16 [1·37-3·51]). Vincristine exposure was newly identified as a risk factor for CIHL (aOR 3·55 [2·19-5·84]). Dose reductions and moderate or severe CIHL were not significantly associated with survival differences.Interpretation Using this large, multicentre cohort, benchmarks were established for the prevalence of CIHL in patients treated with cisplatin. Variations in cisplatin dosing confer additive risk for developing CIHL and warrant investigation as a potential approach to decrease the burden of therapy.Funding US National Institutes of Health and National Institute on Deafness and Other Communication Disorders, US National Institutes of Health and National Cancer institute, St Baldrick's Foundation, Genome Canada, Genome British Columbia, Canadian Institutes of Health Research, the Canada Foundation for Innovation, University of British Columbia, British Columbia Children's Hospital Research Institute, British Columbia Provincial Health Services Authority, Health Canada, and C17 Research Network.

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  • Inner ear damage and permanent hearing loss is a possible incapacitating late chemotherapy effect of cisplatin use, with moderate to severe hearing loss occurring in <30% of patients with osteosarcoma.

    “Inner ear damage and permanent hearing loss is a possible incapacitating late chemotherapy effect of cisplatin use, with moderate to severe hearing loss occurring in <30% of patients with osteosarcoma 168 .”

    From Osteosarcoma (2022) · cites this paper as [168]

  • In addition to cumulative cisplatin dose, peak drug exposure, young age at treatment, co-administration of other ototoxic drugs and others are well-defined risk factors for more severe auditory damage.

    “In addition to the cumulative cisplatin dose, peak drug exposure, young age at treatment, co-administration of other ototoxic drugs and others are well-defined risk factors for more severe auditory damage 167,168,169 .”

    From Osteosarcoma (2022) · cites this paper as [168]

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Authors
Moke, D. J., Luo, C., Millstein, J., Knight, K. R., Rassekh, S. R., Brooks, B., Ross, C. J. D., Wright, M., Mena, V., Rushing, T., Esbenshade, A. J., Carleton, B. C., & Orgel, E.
Affiliations
  • University of Southern California (US)
  • Oregon Health & Science University (US)
  • University of British Columbia (CA)
  • University of Tennessee Health Science Center (US)
  • Children's Hospital Los Angeles (US)
  • Vanderbilt-Ingram Cancer Center (US)
Corresponding author
Orgel, Etan
ORCID
Venue
The Lancet Child & Adolescent Health
Publisher
Elsevier BV
Published
2021-04
Volume
5
Issue
4
Pages
274-283
ISSN
2352-4642 (ISSN-L)
DOI
10.1016/s2352-4642(21)00020-1
PMC
PMC9059427
OpenAlex
W3127930177
Cited by
92
References
30
Citations by year
2026: 14 · 2025: 19 · 2024: 22 · 2023: 15 · 2022: 13 · 2021: 9
FWCI
8.23
Type
journal article
Language
en
Open access
Licence
Locations
  • The Lancet Child & Adolescent Health (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • Canadian Institutes of Health Research
  • National Cancer Institute (P30CA014089)
  • Canada Foundation for Innovation
  • National Institute on Deafness and Other Communication Disorders (1K23DC014291)
  • Genome British Columbia
  • St. Baldrick&apos;s Foundation
  • Michael Smith Foundation for Health Research
  • University of British Columbia
  • BC Children’s Hospital Foundation
  • Health Canada
  • BC Cancer Agency
  • Genome Canada
Topics
  • Life Sciences › Neuroscience › Sensory Systems › Hearing, Cochlea, Tinnitus, Genetics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Chemotherapy-induced organ toxicity mitigation
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Hearing Loss and Rehabilitation
Keywords
cisplatin-induced hearing loss, cisplatin ototoxicity, chemotherapy-induced hearing loss, risk factors, prevalence, cumulative cisplatin dose, dose fractionation, vincristine, neuroblastoma, hepatoblastoma, central nervous system tumors, childhood cancer, adolescents and young adults, survival outcomes, dose reduction, audiometry
MeSH terms
Ototoxicity, Adolescent, Adult, Antineoplastic Agents, Bone Neoplasms, Canada, Child, Child, Preschool, Cisplatin, Dose-Response Relationship, Drug, Female, Hearing Loss, Sensorineural, Humans, Infant, Infant, Newborn, Liver Neoplasms, Male, Neoplasms, Neoplasms, Germ Cell and Embryonal, Neuroblastoma, Risk Factors, Osteosarcoma, Severity of Illness Index, United States, Vincristine, Prevalence, Odds Ratio, Central Nervous System Neoplasms, Age Distribution, Hepatoblastoma, Young Adult

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