Systematic review of facial deformation following paediatric head and neck radiation therapy: A call for standardised outcome assessment and dose–response evidence

Radiation therapy (RT) is an essential treatment modality for paediatric head and neck (HN) cancer, but irradiation during craniofacial development can cause dentofacial side effects, including facial deformation (FD). This systematic review evaluates the evidence on FD post-RT, including assessment methods, prevalence, and dose-response. A literature search was conducted in PubMed and EMBASE. Studies were included if they reported FD > 2 years post-RT on average across the whole cohort in children treated for HN cancer aged 0-18 years. Studies were assessed using the Cochrane Childhood Cancer Risk of Bias tool. Of 2766 articles identified, 25 met the inclusion criteria, reporting on 1155 children treated between 1965 and 2022 (median cohort size: 24, range: 6 - 192) participants. Median age at treatment/diagnosis was 4.9 years. FD assessment methods were analysed in two categories: objective measures and clinical reporting. Objective measures were further categorised: 1) cephalometric (2D image), 2) external surface (3D), 3) internal anatomy (3D). Clinical reporting included clinician-reported and patient-reported outcomes. Measurement and grading criteria varied considerably. Where it could be calculated, prevalence of FD was between 21% and 97%. In seven of the eight studies which examined dose-response, a range of doses between 24-40 Gy was linked to risk of FD, as was age < 5-7 years at the time of treatment. However, heterogeneity in tumour sites and treatment regimens limited comparability. Additionally, limited data on FD location and severity constrained dose-response study. This review highlights the need for standardised assessment tools and grading criteria that captures both location and severity of FD. Such standardisation would improve clinical reporting and support robust dose-response analysis in future research.