Recommendations for ototoxicity surveillance for childhood, adolescent, and young adult cancer survivors: a report from the International Late Effects of Childhood Cancer Guideline Harmonization Group in collaboration with the PanCare Consortium

Summary

Childhood, adolescent, and young adult (CAYA) cancer survivors treated with platinum-based drugs, head or brain radiotherapy, or both have an increased risk of ototoxicity (hearing loss, tinnitus, or both). To ensure optimal care and reduce consequent problems—such as speech and language, social–emotional development, and learning difficulties—for these CAYA cancer survivors, clinical practice guidelines for monitoring ototoxicity are essential. The implementation of surveillance across clinical settings is hindered by differences in definitions of hearing loss, recommendations for surveillance modalities, and remediation. To address these deficiencies, the International Guideline Harmonization Group organised an international multidisciplinary panel, including 32 experts from ten countries, to evaluate the quality of evidence for ototoxicity following platinum-based chemotherapy and head or brain radiotherapy, and formulate and harmonise ototoxicity surveillance recommendations for CAYA cancer survivors.

Introduction

Advances in the treatment of childhood, adolescent, and young adult (CAYA) cancer over recent decades have greatly improved long-term survival, with 5-year overall survival exceeding 80% in most high-income countries.1, 2, 3 However, improvements in outcomes are often compromised by the presence of long-term adverse effects from treatment. Ototoxicity is an adverse effect that has been reported by approximately 50% of CAYA cancer survivors following treatment with platinum-based compounds, head or brain radiotherapy, or both.4, 5 Treatment-induced ototoxicity typically presents as hearing loss of high-frequency sounds, often accompanied by tinnitus.6, 7, 8, 9 Platinum-based compounds (eg, cisplatin and carboplatin) have been shown to be highly effective for a variety of paediatric malignancies, such as osteosarcoma, neuroblastoma, hepatoblastoma, brain tumours, and malignant germ cell tumours. In addition, head and brain radiotherapy is a crucial part of treatment for several head and neck tumours, most brain tumours, and relapsed leukaemia. Radiotherapy treatment for such tumours might include the temporal bone and brain stem area, typically with relatively high doses (≥30 Gy). Hence, the middle ear, inner ear, and brain stem are often exposed to substantial ionising radiation dose. Older radiotherapy techniques are more likely to cause serious ototoxic sequelae than available therapies, such as intensity-modulated radiotherapy (IMRT), which reduce exposure to crucial aural structures because of their improved conformality in targeting tumours.5, 10 Ototoxicity can occur in both children and adults treated with these modalities, but children are more vulnerable to treatment-induced hearing loss because their auditory pathways and language are still developing,4, 5, 11 which is important because hearing deficits can adversely affect speech and language, social–emotional development, and academic performance in children.12, 13

Recent population-based surveys suggest that, despite recommendations, monitoring of hearing loss in CAYA survivors is insufficient, with only 72% of those considered at risk having hearing tests during follow-up, and only 43% having full audiological monitoring before, during, and after treatment.¹⁴ Therefore, clinical practice guidelines are needed to facilitate timely identification of, and intervention for, ototoxicity among at-risk CAYA patients with cancer and cancer survivors after completion of therapy.

Clinical practice guidelines for CAYA cancer survivors have been developed by representatives from several multinational, national, and institutional paediatric cancer groups.15, 16, 17, 18, 19, 20, 21 Definitions of at-risk populations, surveillance modality and frequency, and recommendations for interventions differ across national clinical practice guidelines for CAYA cancer survivors, hindering the implementation of surveillance across international settings. To establish global consensus, an international effort was organised to harmonise existing surveillance recommendations for CAYA cancer survivors. In this Review, we present a summary of the evidence and recommendations for ototoxicity surveillance in CAYA cancer survivors, proposed by an expert panel within the International Late Effects of Childhood Cancer Guideline Harmonization Group (IGHG) in collaboration with the European Union-funded PanCare Consortium.