Rapid establishment of patient-derived organoids from treatment-naive head and neck cancer patients for drug and radiosensitivity screening

e18043 Background: Patient-derived organoids (PDOs) have been shown to be powerful tools for modeling disease and patient-individualized drug sensitivity screening, opening a novel avenue to precision medicine. A major challenge for guidance of clinical decisions is the extended time frame for establishing these models. Here, we report the feasibility of a refined protocol for PDO generation from head neck squamous cell carcinoma (HNSCC) tumors, suitable to guide personalized treatment decisions in the curative setting. Methods: After informed consent, tumor tissue specimens from 145 newly diagnosed HNSCC patients were collected during diagnostic biopsy or curative surgery. Following mechanic / enzymatic dissociation and initial expansion in 2D cultures, tumor cells were seeded in extracellular matrix (Matrigel) to form PDOs. Primary endpoint of the study was the PDO engraftment rate. In additio, the time needed for ex vivo expansion of PDO cultures for personalized drug/radiosensitivity testing was determined. Interference of patient and tumor characteristics with PDO engraftment was analyzed using SPSS version 27. Results: The PDO engraftment rate in the entire cohort was 51% (n = 74 of 145 patients). Neither tumor stage, grading, anatomical sublocalisation, HPV status nor sample type (biopsy vs. surgical specimen) were significantly associated with PDO establishment. Of note, Kaplan-Meier analysis revealed a trend between successful ex vivo engraftment and reduced overall survival (log-rank: p = 0.09), suggesting preferential engraftment of aggressive poor prognosis tumors. Engraftment rate in the subgroup of patients with recommendation for adjuvant chemoradiation was 58%. Time for expansion of PDO cultures for subsequent drug/radiation screening was 18.5 ± 9.6 days (median ± SD). Expansion was completed before start of adjuvant chemoradiation in all but one cases. Conclusions: Our study suggests feasibility of PDO generation for locally advanced aggressive HNSCC within a timeframe suitable for guiding treatment decisions for adjuvant therapy. Planned future directions include clinical validation of drug testing results for individual patients and clinical study cohorts.