Head and neck cancers (HNCs) are the seventh most prevalent cancer worldwide, accounting for approximately 890,000 new cases and 450,000 deaths in 2022.1 HNCs comprise a heterogeneous group of tumors, the majority of which are of epithelial origin, with squamous cell carcinomas (SCCs) accounting for more than 90% of cases. Various therapeutic options are available for HNCs, among which radiotherapy (RT) and chemoradiotherapy serve as cornerstone treatments, either as definitive or adjuvant approaches, depending on the primary tumor site and disease stage.2,3 These therapeutic approaches have demonstrated significant improvements in local recurrence-free survival, progression-free survival, and overall survival.2 Nevertheless, both acute and late radiation-related toxicities, are common and negatively impact quality of life (QoL).4 Current efforts, both clinical and technological advances, are aimed to reduce radiation-related toxicities while preserving treatment efficacy, as maintaining good QoL is a key priority for patients with cancer.

Accurate tumor delineation is crucial in RT, as it directly influences both treatment efficacy and toxicity outcomes. Precise identification of tumor boundaries enables adequate dose delivery to malignant tissues while sparing adjacent healthy tissues, hereby contributing to higher tumor control and cure rates by ensuring adequate dose delivery to tumor, while minimizing damage to normal structures. Advances in imaging and contouring/segmentation technologies continue to enhance the accuracy and consistency of tumor delineation, resulting in safer and more effective RT planning.

This review aims to summarize and critically appraise current evidence regarding the role of fibroblast activation protein inhibitors (FAPI) positron emission tomography (PET) in RT planning and assessment in HNCs, with a particular focus on its performance compared to the current gold standard using F-18 fluorodeoxyglucose (FDG) PET and its potential clinical impact.