Hearing Loss After Radiation and Chemotherapy for CNS and Head-and-Neck Tumors in Children

Abstract

PURPOSE Hearing loss (HL) is a serious secondary effect of treatment for CNS and head-and-neck tumors in children. The goal of this study was to evaluate incidence and risk factors for HL in patients with multiple ototoxic exposures. PATIENTS AND METHODS We evaluated 340 ears from 171 patients with CNS or head-and-neck tumors treated with radiation, with or without chemotherapy, who had longitudinal audiologic evaluation. International Society of Pediatric Oncology-Boston grades were assigned to 2,420 hearing assessments. Multivariable weighted ordinal logistic regression was fitted to evaluate the effect of clinicopathologic features on HL. RESULTS Mean cochlea dose (odds ratio [OR] 1.04 per Gy, P < .001), time since radiotherapy (RT; OR 1.21 per year, P < .001), cisplatin dose (OR 1.48 per 100 mg/m2, P < .001), and carboplatin dose (OR 1.41 per 1,000 mg/m2, P = .002) were associated with increasing International Society of Pediatric Oncology-Boston grade of HL. There was no synergistic effect of RT and cisplatin (interaction term, P = .53) or RT and carboplatin (interaction term, P = .85). Cumulative incidence of high-frequency HL (> 4 kHz) was 50% or greater at 5 years after RT if mean cochlea dose was > 30 Gy, while incidence of HL across all frequencies continued to increase beyond 5 years after RT. CONCLUSION Children treated with radiation and chemotherapy experience a high incidence of HL over time, with associations found between more severe HL and cisplatin or carboplatin dose as well as mean cochlea dose. Mean cochlea dose of ≤ 30 Gy is proposed as a goal to reduce the risk of HL; a lower threshold (20-25 Gy) may be considered in patients receiving platinum chemotherapy to reduce cumulative HL burden.

Patterns of Hearing Loss in Irradiated Survivors of Head and Neck Rhabdomyosarcoma

“…In our series, HL (≥Muenster 2b) was especially observed when the maximum dose to the cochlea exceeded 19 Gy. This observation is confirmed by previous studies [ 23 , 40 , 43 , 44 ]. Recently, Keilty et al (2021) [ 43 ] showed in patients with a brain tumour that the cumulative incidence of high-frequency HL (>4 kHz) was 50% or higher at 5 years after radiotherapy if the mean cochlear dose was >30 Gy.…”

“…This observation is confirmed by previous studies [ 23 , 40 , 43 , 44 ]. Recently, Keilty et al (2021) [ 43 ] showed in patients with a brain tumour that the cumulative incidence of high-frequency HL (>4 kHz) was 50% or higher at 5 years after radiotherapy if the mean cochlear dose was >30 Gy. Additionally, Hua et al (2008) [ 23 ] observed that the incidence of HL increased when the mean cochlear dose was greater than 40–45 Gy.…”

The Burden of Surviving Childhood Medulloblastoma: A Population-Based, Matched Cohort Study in Ontario, Canada

“…Previously, it has been shown that cisplatin-induced ototoxicity impairs cognitive outcome, which may also underlie this observation, and collectively, our results suggest that efforts to limit or omit cisplatin-related ototoxicity are required. 32,34-36…”

Photon versus proton whole ventricular radiotherapy for non‐germinomatous germ cell tumors: A report from the Children's Oncology Group

“…Proton therapy was generally unable to spare the cochlea due to the selection of beam arrangements that traversed the cochleae to treat the ventricular CTV. Higher cochlear RT dose is known to be associated with hearing decline, 23 though the contribution of chemotherapy (including carboplatin, which was used to treat patients enrolled in ACNS1123 stratum 1) also has an important effect 24 . Even when modest reductions of cochlear dose are attained, such as in children treated with proton therapy for medulloblastoma, improvements in hearing function may be difficult to detect due to other ototoxic risk factors 25 .…”