Otoprotective Effects of Sodium Thiosulfate by Demographic and Clinical Characteristics: A Report From Children's Oncology Group Study ACCL0431

Timothy J D Ohlsen; Willem H Collier; Jagadeesh Ramdas; Lillian Sung; David R Freyer

doi:10.1002/pbc.31479

Otoprotective Effects of Sodium Thiosulfate by Demographic and Clinical Characteristics: A Report From Children's Oncology Group Study ACCL0431

Pediatr Blood Cancer. 2024 Dec 9:e31479. doi: 10.1002/pbc.31479. Online ahead of print.

Authors

Timothy J D Ohlsen^{1

2}, Willem H Collier³, Jagadeesh Ramdas⁴, Lillian Sung⁵, David R Freyer^{6

7}

Affiliations

¹ Cancer and Blood Disorders Center, Seattle Children's Hospital, University of Washington, Seattle, Washington, USA.
² Ben Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, Seattle, Washington, USA.
³ Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
⁴ Division of Pediatric Hematology/Oncology, Geisinger Medical Center, Danville, Pennsylvania, USA.
⁵ Division of Hematology/Oncology, The Hospital for Sick Children, Toronto, Ontario, Canada.
⁶ Cancer and Blood Disease Institute, Children's Hospital Los Angeles, Los Angeles, California, USA.
⁷ Departments of Pediatrics, Medicine, and Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.

PMID: 39654065
DOI: 10.1002/pbc.31479

Abstract

Background: ACCL0431 was a randomized clinical trial that demonstrated efficacy of sodium thiosulfate (STS) for preventing cisplatin-induced hearing loss (CIHL) among patients 1-18 years old. The purpose of this study was to evaluate possible differential STS otoprotection among patient subgroups.

Procedure: This secondary analysis included ACCL0431 participants treated with cisplatin and randomized to receive STS or not (observation). Hearing status was obtained at 4 weeks and 12 months post cisplatin therapy (SIOP Ototoxicity Scale). Cumulative incidence of CIHL (Grade 1+) was assessed across age, sex, race/ethnicity, cancer diagnosis, and cisplatin infusion duration. Associations between these variables and CIHL were assessed using multivariable logistic regression. Interaction terms were used to evaluate potential heterogeneity in STS effect sizes across subgroups.

Results: Among evaluable participants (n = 121), CIHL incidence was 22.4% with STS and 54.0% with observation. Odds of developing CIHL were greatest among children less than 5 years versus older (randomization-adjusted odds ratio [OR] 2.94, 95% CI: 1.30-7.14) and those with neuroblastoma, hepatoblastoma, or medulloblastoma versus germ cell tumor or osteosarcoma (age- and randomization-adjusted OR 11.26, 95% CI: 3.08-47.35). STS otoprotective effect sizes were also greatest in the same highest risk groups by age (<5 years: OR 0.08, 95% CI: 0.02-0.32; ≥5 years: OR 0.39, 95% CI: 0.15-1.06) and cancer diagnosis (neuroblastoma/hepatoblastoma/medulloblastoma: OR 0.1, 95% CI: 0.02-0.45; germ cell tumor/osteosarcoma: OR 0.32, 95% CI: 0.06-1.25). Significant otoprotection from STS was noted across other subgroups with varied magnitudes of effect.

Conclusions: STS otoprotection appears to differ across clinically meaningful subgroups, particularly age at diagnosis. These results inform clinical decision-making and future research.

Keywords: Children's Oncology Group; otoprotection; pediatric oncology; sensorineural hearing loss; supportive care.

Abstract

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