The Precision Oncology Program (POP) research collaboration aims to help generate information about the individual tumour biology for patients with advanced malignancies, using innovative biotechnologies and patient profile comparison ("matching") against specific databases (Real-world data, RWD) and to inform about potential benefit, or lack of benefit, from a given treatment.

This is an observational clinical project. The aim of this research collaboration is to establish processes to advance precision oncology within the clinical routine. POP generates information about individual tumour for patients with advanced cancers using innovative molecular technologies and patient profile comparison ("matching") against specific public and non-public databases with the aim to support clinical decision-making (therapy prediction).

The POP report will summarize the clinically-relevant findings from the following tests and procedures:

A. Routine genetic testing:

FMI (routine genetic testing) Comprehensive tumour genotyping which includes alterations in cancer-relevant genes and the following parameters: Tumor mutational burden (TMB), Loss of heterozygosity (LoH), Microsatellite Instability (MSI).

B. POP-specific additional testing:

1. Research grade: Imaging Mass Cytometry (IMC) To better capture tumour heterogeneity beyond genetics, and to inform therapy decisions of whether or not a particular treatment may show efficacy, we will perform IMC on existing formalin-fixed paraffin-embedded (FFPE) tissue sections. IMC technology enables quantification of over 40 selected proteins and protein modifications, while simultaneously interrogating phenotype and cell signaling. It allows identification of markers predictive of response (or resistance) of individual cancer patients, and enables the analysis of tumour tissues at single-cell resolution, capturing characteristics of the tumour cells, the tumour microenvironments and the relationship between tumour, stromal and immune compartments. The analysis of the tumour at the protein level and the spatial distribution of the different compartments will significantly increase and broaden the routine genetic analysis to identify potentially druggable alterations.
2. Patient Matching Against Cancer Databases The patient matching will be performed by Roche using the Flatiron Health-Foundation Medicine Clinico-genomic Database (FH-FMI CGDB).

The following scenarios will be explored as part of the project:

(i) a comparison of clinical data (e.g. entity, TNM classification, previous therapies, etc) to extract similar clinical phenotypes and the related treatment history and outcomes (clinical level) (ii) a comparison at the genotype level (genomic level) (iii) a combination of the possibilities above.

The POP report will be shared with the Molecular Tumour Board (MTB) and discussed in the absence of the treating physician. The MTB will consider all available information at its own discretion and in adherence to the available standard guidelines. However, only treatment recommendations based on routine diagnostics will be forwarded to the treating physician. Hypothetical MTB's treatment decisions based on the POP summary report will not be forwarded the treating physician.

NOTE: All additional project specific recommendations remain non-prescriptive and will not be forwarded to the treating physician.

Inclusion Criteria:

• Signed informed consent
• In the case of deceased persons: signed general consent
• All patients with the diagnosis of a solid tumour including adenocarcinoma, squamous cell carcinoma, neuroendocrine carcinoma, sarcoma, etc
• ECOG-performance status 0-2, if applicable
• Willing and able to understand all project related procedures, including transfer of coded (i.e. pseudonymised) or anonymized clinical data to external partners (e.g. Roche), if applicable

Exclusion Criteria:

• Patients with the diagnosis of blood cancer.

All patients with histology based proven diagnosis of cancer; all stages and subtypes can be included. Pre-cancerous lesions, e.g. DCIS, LCIS, CIN, etc. cannot be included.