Unravelling Tumour Biology In Ovarian Cancer With Precision Imaging

Introduction

High-grade serous ovarian cancer (HGSOC) is the most common subtype of ovarian cancer. The early rapid onset of chemoresistance poses a major clinical challenge. Recent research highlighted high tumor heterogeneity (TH) and identified key mutational signatures that associate with prognosis and may aid in individualized treatment selection.

Challenges in Current Research

Since HGSOC often presents with multisite disease and distinct populations of malignant cells, multi-region analysis of multimodal data is essential to study HGSOC. Single time point, single site biopsies cannot assess the entire tumor while multiple biopsies at several time points are not feasible in clinical routine.

Non-Invasive Imaging Solutions

Limitations of invasive sampling may be addressed with non-invasive imaging that captures morphologic and functional information about the entire tumor in space and, if repeated, in time. Radiomics has the potential for “whole tumour virtual sampling” using a single or serial non-invasive examinations in place of biopsies.

Current Gaps in Research

To date, no study has evaluated the value of radiomics at macroscopic (in vivo 1.5T/3T MRI) and microscopic (ex vivo 9.4T MRI) scales to better understand the black box of radiomics features (explainable radiomics) or examine whether radiomics habitats are underpinned by tumour biology to provide a better insight into TH of HGSOC.

Project Objectives

Specifically, in this project, I will implement a model to capture imaging-based TH with a multiscale radiomics approach by obtaining the mirror tumor image at:

1. in vivo MRI
2. ex vivo MRI
3. histology

I will evaluate if imaging-based TH reflects underlying tumor histology by testing associations with:

• imaging features
• tumor-stroma proportion
• infiltrative lymphocytes density
• HRD status

Conclusion

Finally, I will unravel HGSOC TH biology through habitat imaging combined with an integrated Multi-O-Mics approach. Successful completion of this proposal will lead to a comprehensive characterization of HGSOC TH which will then be accessible non-invasively through radiomics.