PP1102 - Clinical Complexities of Defining Ototoxicity Profiles of Pediatric Cancer Treatments

Abstract:
Audiologic monitoring for ototoxicity of pediatric cancer treatments is often considered in the clinic due to treatments with platinum-based chemotherapy (cisplatin; carboplatin) and/or radiation therapy (traditional/photon; current/proton). However, convergence on the best audiologic approaches to characterize the ototoxicity profile of specific treatments as well as approaches for the earliest detection of ototoxicity are needed in the clinical practice despite the clinical complexities. As treatment advances have increased survival rates for childhood cancer, side effects like permanent hearing loss (or ototoxicity) remain impactful to quality of life and highlight the need for the earliest detection and intervention.

Summary:
Rationale
In the United States, central nervous system tumors are one of the most common types of childhood cancer. Treatment options can include surgical resection, cranial radiation therapy, chemotherapy, or a combination. Many of these treatments are established to be ototoxic, resulting in hearing loss and tinnitus adverse events, with national ototoxicity monitoring guidance recommending baseline and regular audiologic monitoring. Ototoxicity monitoring is important for informing treatment decisions, earliest intervention for hearing loss, and supporting hearing loss prevention during and beyond cancer treatment. However, evidence is lacking as to the frequency of monitoring to promote earliest detection and the ototoxic profile for specific treatments.

Ototoxicity typically presents as a permanent bilateral progressive high-frequency sensorineural hearing loss; however, measurable changes and initial onset may differ depending on the specific treatment plan due to differing underlying physiologic changes contributing to the observed ototoxicity. Advances in audiologic techniques utilizing otoacoustic emissions and extended high frequency assessment enhance the earliest detection of audiologic changes as well as help decipher the complex ototoxic profile. This investigation aimed to characterize the enhanced audiological profile and timeline of ototoxicity with a specific focus on cranial radiation treatment.

Design
This study analyzed retrospective data for individuals (n=352 < 18 years at initial treatment) undergoing brain cancer treatments between 2000-2013 at the Mayo Clinic. Sixty-seven individuals were seen for at least two audiologic evaluations and divided into three groups based on treatment type: radiation-only, chemotherapy-only, and chemoradiation. Seven (3 males; mean age=9 years, SD=8) individuals received radiation-only following surgical resection.

Detailed chart reviews to extract radiation treatment specifics and audiologic outcomes were compiled with examined variables including chemotherapy treatment, symptoms, audiometric thresholds (0.25 to 20 kHz), otoacoustic emissions, and tympanometry. Ototoxic changes were assessed relative to baseline for Significant Threshold Shift (STS) and adverse event grading scales in addition to other characterizations of ototoxicity.

Results
Results highlight the primary aim of this investigation to characterize the enhanced audiological profile and timeline of ototoxicity of cranial radiation treatment (n=7) in a cohort of individuals with pediatric brain cancer. Of the seven individuals with radiation-only, three developed significant ototoxic changes. Audiologic changes (n=3) with initial STS observed 4-84 months from baseline. Two individuals had gradable changes in hearing ranging from Grade 1 to 4 at final evaluation (initial onset 5-82 months). Detailed summary of diagnosis, proportion and characterization of audiologic profiles of patients with ototoxicity, and clinical complexities of ototoxicity monitoring will also be presented.

Conclusions
Advances in radiation treatments, increased survivability rates with specific cancer types, and improved audiologic approaches enabled further characterization of adverse effects and highlight the need for further evidence. Results highlight the importance of ototoxic monitoring in pediatric cancer treatments to facilitate the earliest detection of hearing loss. Outcomes define a framework for future exploration with newer, uniformed treatment approaches to assess the ototoxicity profile and enhanced clinical monitoring approaches. Moreover, emerging targeted therapies that account for clinico-radiological risk stratification and molecular subgrouping may further enhance survivability and warrant characterization of ototoxicity to support quality of life.