Ototoxicity prognostic models in adult and pediatric cancer patients: a rapid review

Abstract

Purpose: A cornerstone of treatment for many cancers is the administration of platinum-based chemotherapies and/or ionizing radiation, which can be ototoxic. An accurate ototoxicity risk assessment would be useful for counseling, treatment planning, and survivorship follow-up in patients with cancer.

Methods: This systematic review evaluated the literature on predictive models for estimating a patient's risk for chemotherapy-related auditory injury to accelerate development of computational approaches for the clinical management of ototoxicity in cancer patients. Of the 1195 articles identified in a PubMed search from 2010 forward, 15 studies met inclusion for the review.

Conclusions: All but 1 study used an abstraction of the audiogram as a modeled outcome; however, specific outcome measures varied. Consistently used predictors were age, baseline hearing, cumulative cisplatin dose, and radiation dose to the cochlea. Just 5 studies were judged to have an overall low risk of bias. Future studies should attempt to minimize bias by following statistical best practices including not selecting multivariate predictors based on univariate analysis, validation in independent cohorts, and clearly reporting the management of missing and censored data. Future modeling efforts should adopt a transdisciplinary approach to define a unified set of clinical, treatment, and/or genetic risk factors. Creating a flexible model that uses a common set of predictors to forecast the full post-treatment audiogram may accelerate work in this area. Such a model could be adapted for use in counseling, treatment planning, and follow-up by audiologists and oncologists and could be incorporated into ototoxicity genetic association studies as well as clinical trials investigating otoprotective agents.

Implications for cancer survivors: Improvements in the ability to model post-treatment hearing loss can help to improve patient quality of life following cancer care. The improvements advocated for in this review should allow for the acceleration of advancements in modeling the auditory impact of these treatments to support treatment planning and patient counseling during and after care.

Keywords: Adverse drug reaction reporting systems; Antineoplastic protocols; Audiology; Audiometry; Drug monitoring; Hearing loss; High frequency; Ototoxicity; Pure-tone.

Fig. 1

PRISMA flow diagram. The figure shows the phases of this systematic review. Of the 1195 articles identified by the PubMed search, 15 studies met inclusion criteria and were included in the final data extraction and risk of bias assessment

Fig. 2

PROBAST Quality Assessment of literature formally reviewed. Results reflect that most included studies are applicable to our goal and that these current models have a high risk of bias overall. Domains in which bias was noted were the inclusion of participants and especially the statistical analysis with fewer problems related to predictors and outcomes