Hearing loss after exposure to vincristine and platinum-based chemotherapy among childhood cancer survivors

Abstract

Background: The role of vincristine as a contributing risk factor for hearing loss among childhood cancer survivors (CCS) treated with platinum-based chemotherapy has not been fully elucidated. We examined the association of vincristine with hearing loss in a national cohort of CCS. Methods: We included CCS registered in the Swiss Childhood Cancer Registry diagnosed at age ≤ 18 years and treated with platinum-based chemotherapy between 1990 and 2014. Audiogram and treatment data were extracted from medical records for all participants in our retrospective cohort study. We identified CCS exposed to vincristine and calculated the total cumulative dose. We defined clinically relevant hearing loss as grade ≥ 2 using the International Society of Pediatric Oncology (SIOP) Boston Ototoxicity Scale at latest follow-up. Results: Our study population included 270 CCS (43% female; median age at cancer diagnosis 6.8 years; interquartile range [IQR]: 2.1–11.7 years) with median age at audiogram 13.5 years (IQR: 9.3–17.0 years). Vincristine exposure was associated with an increased risk of hearing loss in the multivariable logistic regression analysis (odds ratio [OR] 4.8; 95% confidence interval [CI]: 1.8–12.9). We found no evidence of dose-response relationship (OR 1.0; 95% CI: 0.97–1.04) or effect modification from vincristine from other ototoxic treatments, such as type of platinum agent, cranial radiotherapy, and hematopoietic stem cell transplantation. Conclusion: Vincristine is associated with a higher risk of hearing loss in CCS treated with platinum-based chemotherapy. We suggest future studies investigate the underlying mechanism and causality among CCS without exposure to other ototoxic cancer treatments.

Keywords

• Vinca alkaloids
• Vincristine
• Hearing loss
• Ototoxicity
• Platinum compounds
• Cranial radiotherapy