A Study to Examine the Clinical Value of Comprehensive Genomic Profiling Performed by Belgian NGS Laboratories: a Belgian Precision Study of the BSMO in Collaboration With the Cancer Centre

The project, called "BALLETT" (Belgian Approach of Local Laboratory Extensive Tumor Testing), has a double goal: (1) show the relevance of broad molecular profiling to improve oncological patients care, (2) demonstrate that broad molecular testing can be performed in a decentralized setting by local diagnostics laboratories in a fully standardized and uniform way while complying with the highest quality standards.

This 2-year study involves the consortium of 9 cooperating Belgian NGS laboratories and will enroll 936 metastatic or locally advanced cancer patients coming from 13 different Belgian hospitals and cancer centers. Upon inclusion, all cancer patients will be offered 'comprehensive genomic profiling' (CGP) using Illumina's TSO500 NGS panel. This targeted NGS panel of 523 genes allows for the detection of single nucleotide variants, small indels, copy number variations and fusions, as well as for the determination of the 'tumor mutational burden' (TMB) and the 'microsatellite-instability' status (MSI). Both the wet lab execution of the CGP as well as the biological and clinical classification of the variants will be performed in a fully standardized way among the 9 participating Belgian local NGS laboratories.

The CGP results will be interpreted and discussed in the weekly meeting of the BALLETT national molecular tumor board (MTB), composed of oncologists, pathologists, molecular biologists, geneticists and bioinformaticians. The MTB will provide recommendations for targeted or immunotherapy based on the CGP results. Clinical Decision Support platforms OncoKDM (OncoDNA) and Clinical Genomics Workspace (PierianDx), both expert software that turns NGS data into actionable clinical information, will be used. The resulting therapy recommendation may consist of an approved therapy, a clinical trial, a medical need program or off-label use of cancer drugs. Treating physicians will receive the MTB recommendations and decide on the actual management of their patients. Reasons for not following the MTB recommendation will be registered.

The objectives of the project are:

1. To evaluate the clinical value of CGP in "real-world" practice in giving patients with advanced/metastatic solid tumours broader access to precision medicine

2. To describe the landscape of genomic alterations and quantify the actionable variants detected by comprehensive panel testing

3. To evaluate the number of actionable variants that would have been missed if the NGS analysis was limited to the reimbursed NGS panel (ComPerMed panel).

4. To assess the technical success of CGP

5. To standardize CGP data analysis, clinical interpretation, therapy recommendation and reporting among participating laboratories to the highest extent possible

6. To describe and to quantify the uptake of treatments and the inclusion in clinical trials recommended by the molecular tumour board guided by the CGP

7. To assess clinical benefit by calculating PFS ratio for individual patients (PFS on CGP-selected therapy/PFS on prior therapy) (null hypothesis: ≤ 15% of patient population has PFS ratio of ≥ 1.3)

8. To work in a multi-stakeholder approach to attract more innovative treatments and clinical trials in Belgium

9. To establish a Belgian genomic tumor database under the authority of the governmental 'Sciensano' thereby increasing public health knowledge in Belgium