High-throughput radiation sensitivity screening of 3D-head and neck squamous cell carcinoma (HNSCC) organoids using...

An automated radiation modulator (ARM) was developed to enable a high-throughput radiation sensitivity test using patient-derived organoids (PDOs) as an in vitro diagnostic device. Treatment strategies for head and neck cancer include surgery and radiotherapy. However, patient responses to radiotherapy vary widely. To overcome limitations in efficiency and scalability, the ARM was developed to provide controlled, reproducible, and high-throughput radiation delivery. Its feasibility was validated by comparing it with conventional radiation methods using two HNSCC cell lines, as well as by applying it to PDO-based radiation sensitivity tests. The ARM successfully classified head and neck cancer PDOs into radiation-sensitive and radiation-resistant groups. OncoSensi, a radiation sensitivity screening method utilizing the ARM, was cross-validated with clinical radiotherapy outcomes, including recurrence status, in 14 patients with head and neck cancer. The multi-parameter OncoSensi model achieved a sensitivity of 80% and a specificity of 75%, demonstrating superior predictive performance compared to the single-parameter model, which yielded a sensitivity of 70% and a specificity of 50%. Statistically significant difference in recurrence-free survival (RFS) was observed between the OncoSensi-sensitive and -resistant groups. Therefore, ARM-based radiation sensitivity screening can serve as a practical tool for implementing precision medicine in radiotherapy for patients with head and neck cancer, ultimately contributing to improved treatment efficacy and patient prognosis.