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| Item Type: | Article |
|---|---|
| Title: | Feasibility analysis of using patient-derived tumour organoids for treatment decision guidance in locally advanced head and neck squamous cell carcinoma |
| Creators Name: | Fischer, A.S., Pestana, A., Sachse, V., Doll, C., Hofmann, E., Heiland, M., Obermueller, T., Heidemann, J., Dommerich, S., Schoppe, D., Schallenberg, S., Piwonski, I., Blanc, E. and Tinhofer, I. |
| Abstract: | BACKGROUND: Current treatment for head and neck squamous cell carcinoma (HNSCC) involves surgery, radiotherapy, and chemotherapy. Despite aggressive multimodal approaches, tumour recurrence occurs in 40–60 % of cases, leading to poor survival outcomes. HNSCC lacks common genetic drivers for tailored therapies, and reliable biomarkers for treatment selection are scarce. We investigated the procedural requirements for incorporating drug- and radiosensitivity screens in patient-derived organoids (PDOs) within a clinical trial framework. PATIENTS AND METHODS: Fresh tumour samples (N = 198) from 186 HNSCC patients were included. Success rates of organoid establishment were correlated with clinical and procedural parameters. Timelines for establishment of PDO cultures were determined, and their long-term growth potential assessed by serial passaging. Additionally, we conducted whole exome sequencing on matched tumour-organoid pairs. Three PDO models were employed to establish radiosensitivity assays. RESULTS: In total, PDO models displaying histomorphological features and genomic alterations of parental tumours were successfully established for 35 % of patient tumours. Success rates rose to 77 % for samples with a tumour cell content of 30 % or higher. Advanced patient age, prior radiotherapy, and delays in tissue processing were identified as negative predictors for engraftment. The estimated time interval needed for screens was compatible with PDO-guided selection of curative-intent radiotherapy regimens. CONCLUSIONS: Our findings suggest that with high-quality samples and efficient tissue processing, PDO screens can be successfully performed in 77 % of HNSCC patients. Given the procedural challenges involved, future clinical trials aiming to the utility of PDOs for guiding treatment decisions should consider implementing centralised PDO screening. |
| Keywords: | Patient-Derived Organoids, Functional Precision Oncology, Radiosensitivity Screens |
| Source: | European Journal of Cancer |
| ISSN: | 0959-8049 |
| Publisher: | Elsevier |
| Volume: | 213 |
| Page Range: | 115100 |
| Number of Pages: | 1 |
| Date: | December 2024 |
| Official Publication: | https://doi.org/10.1016/j.ejca.2024.115100 |
| PubMed: | View item in PubMed |
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