Multi-modal Characterisation of Hepatocellular Carcinoma (HCC) Treated with Targeted Radionuclide Therapy (TRT): Prospective Interventional Multicentre National Cohort

Hepatocellular carcinoma (HCC) is the most common primary malignant liver tumors, considered the sixth most common cancer and the third major cause of cancer-related death. Its worldwide incidence is expected to increase in the future. Additionally, it shows marked intertumor and intratumor heterogeneity at the microscopic and molecular levels, and there are currently no reliable imaging markers for predicting response to TARE.

TARE is a highly advanced treatment that consists in intra-arterial injection of radioactive microspheres. TARE is already approved for liver metastases and HCC in most countries. So, TARE for HCC, is part of the therapeutic Armamentarium exerting antitumor effects based on radio-biological (DNA damage) and immunological mechanisms. TARE using most currently 90Yttrium-labeled microspheres has proven its non-inferiority with better tolerance and better tumor response in comparison with systemic treatments in patients with HCC.

While highly promising, patient stratification and early identification of responders are currently insufficient due to the lack of pertinent imaging biomarkers, either non-invasive or invasive. Furthermore, prior therapy-induced DNA damages may lead to tumor resistance, therefore reducing TARE efficacy. Hence, the absence of a personalized treatment strategy is an unmet need for patients with HCC. This may result in survival disadvantage for non-responders, who could benefit otherwise from early treatment change, with expected more favorable outcomes.

Simultaneous PET-MRI: OPERANDI proposes a completely innovative and holistic approach via PET-MRI guided therapy. The research hypothesis is that simultaneous PET-MRI imaging provides more robust non-invasive predictive biomarkers than classical approach and better correlation between quantification internal of radiation therapy dosimetry and clinical outcomes than PET-CT. This requires technological development of PET-MRI, with most methodological challenges being attenuation correction, reducing the impact of organ motion due to respiration and cardiac motion, and minimizing truncation and susceptibility artifacts.

A PET/MRI scan is a two-in-one test that combines images from a positron emission tomography (PET) scan and a magnetic resonance imaging (MRI) scan. This new hybrid technology harnesses the strengths of PET and MRI to produce some of the most highly detailed images currently available. MRI scans use a strong (1.5 to 3T for clinical use) magnetic field to produce detailed morphologic images and some sequences provide functioning information (such as diffusion-weighted, dynamic contrast-enhanced, MR elastography sequence). PET scans use tracers according to the clinical indications to highlight metabolism changes. In HCC, the most common radiotracers are fluorodeoxyglucose (FDG) or Choline, which detect metabolically active malignant lesions.