Precision Oncology Program (POP), an observational study using real-world data and imaging mass cytometry to explore decision support for the Molecular Tumor Board: study protocol

Introduction: Precision oncology aims to provide individualised treatment recommendations based on patient-specific characteristics. In this rapidly evolving field with increasing numbers of biomarkers and potential therapeutic targets, there is a growing unmet need for evidence guiding these individualised treatment recommendations. The Precision Oncology Program (POP) harnesses real-world data (RWD) and imaging mass cytometry (IMC) to evaluate the feasibility and utility of integrating different data modalities to inform personalised treatment recommendations. This program uses patient-matched clinicogenomic data and spatial single-cell proteomics analysis to support profiling-driven decision-making for patients with cancer at the Molecular Tumor Board. Methods and analysis: The collaborative POP project recruits patients across all tumour entities and stages at the Comprehensive Cancer Center Zurich (CCCZ). For patients in the POP, a clinically and molecularly matched cohort is identified within the nationwide (US-based) de-identified Flatiron Health-Foundation Medicine clinicogenomic database (CGDB). It assesses whether clinical, genomic and outcome data of the CGDB cohort can inform treatment recommendations. In addition, multiplexed imaging mass cytometry (IMC) is performed in formalin-fixed paraffin-embedded tissue to assess the potential impact of spatial proteomics on personalised treatment decisions. RWD and IMC information is reviewed in the Molecular Tumor Board to assess the potential impact of this information on therapy decisions. However, since this is an observational study, these additional recommendations remain nonprescriptive and will not be forwarded to the treating physician. Ethics and dissemination: The study is registered at ClinicalTrials.gov (NCT06680726) and approved by the Canton of Zurich Ethics Committee (Project ID: 2022-02289). Project-specific informed consent is obtained from all participants. Deceased patients may also be included. In this case, a signed general consent form must be available. Data privacy is ensured by unique patient numbers for pseudo-anonymised data. Study findings will be disseminated through international peer-reviewed journals, conferences, and direct communication with participants and relevant organisations. Trial registration number: NCT06680726.