881P - SOTO study: Prospective study to correlate the treatment sensitivity of patient-derived organoids (PDOs) with treatment outcomes in head and neck cancer patients

Background

Apart from HPV status, there is no accurate way of predicting patients’ response to treatment in head and neck squamous cell carcinoma (HNSCC). Moreover, there is no easy way to test radiosensitivity and chemosensitivity of these tumours. Large living biobanks of PDOs have been developed from several tumours and they were shown to preserve the characteristics of the original tumour. This study aims to generate PDOs from HNSCC samples and to collect preliminary data on the ability of PDOs to predict patients’ treatment response.

Methods

This is a prospective observational study to generate PDOs from HNSCC patients’ samples (NCT05400239). The study aims to recruit 3 groups: cohort 1 surgically resectable disease, cohort 2 primary radical radiotherapy +/- concurrent chemotherapy, cohort 3 recurrent or metastatic disease. Samples collected include tumour and relevant normal tissues samples at baseline (+/-recurrence) for generation of PDOs and genetic analysis, blood, and saliva samples (baseline and different time points during treatment) for PBMC isolation/analysis and ctDNA analysis. The successfully generated PDOs are subjected to increasing radiotherapy dose (2Gy,4Gy,8Gy), cisplatin (0.1μM-100μM) and cetuximab (1-1000μg/ml). The recapitulation of PDOs to that of the human samples will be investigated using immunohistochemistry and genetic analysis.

Results

This is an ongoing study and to date, 15 patients with HNSCC have been consented and appropriate samples were collected (Cohort 1: n=9, Cohort 2: n=3, Cohort 3: n=3). 9 patients were treated with surgery, 10 patients received radiotherapy (7 post-op; 3 radical). Following protocol optimisation, 6 samples were successfully generated into PDOs. Response to radiotherapy and chemotherapy varied across the different organoid lines.

Conclusions

We provide the preliminary results from utilising HNSCC PDOs as an ex-vivo pre-clinical model to predict patient’s response to treatment in a personalised cancer treatment approach. Moreover, further translation research will be conducted to investigate the role of ctDNA and peripheral immune system as potential prognostic and predictive biomarkers.

Clinical trial identification

NCT05400239.

Editorial acknowledgement

Legal entity responsible for the study

King's College London.

Funding

Guy’s and St Thomas’ (GSTT) charity via a generous philanthropic donation from Charles Wilson and Rowena Olegario.

Disclosure

C. Regenbrecht: Financial Interests, Institutional, Full or part-time Employment, CEO at CELLphenomics; supplying media and providing advice for PDOs generation: CELLphenomics. L. Wedeken: Financial Interests, Institutional, Full or part-time Employment, Head of Laboratory at CELLphenomics; supplying media and providing advice for PDOs generation: CELLphenomics. A. Kong: Non-Financial Interests, Personal, Advisory Board: MSD; Non-Financial Interests, Institutional, Research Funding: AstraZeneca, PUMA; Non-Financial Interests, Personal, Invited Speaker: Merck, BMS; Non-Financial Interests, Personal, Advisory Role: Avinnity. All other authors have declared no conflicts of interest.