Relationship Between 18FDG PET/MRI Patterns and ctDNA to Predict HCC Recurrence After Liver Transplantation

Titre officiel

Relationship Between 18F-Fluorodeoxyglucose Positron Emission Tomography Magnetic Resonance Imaging Patterns and Circulating Tumour DNA to Predict Hepatocellular Carcinoma Recurrence After Liver Transplantation (PET MRI in HCC)


La transplantation hépatique est le traitement standard pour les patients atteints d’un carcinome hépatocellulaire (CHC) au stade précoce. À l’heure actuelle, d’importantes décisions thérapeutiques, comme la sélection des candidats à la greffe, sont prises en fonction des caractéristiques tumorales statiques brutes, comme la taille des lésions et leur nombre, qui ne reflètent pas d’autres aspects de la biologie tumorale. À ce jour, la biopsie percutanée préalable à la transplantation est la meilleure stratégie pour évaluer la différenciation tumorale et, par conséquent, le comportement biologique de la tumeur. Des études antérieures ont démontré que la tomographie par émission de positrons au 18F-fluorodéoxygluose (TEP-18F-FDG) associée à l’imagerie par résonance magnétique (IRM) pourrait servir à évaluer la différenciation tumorale dans les cas de CHC et à prédire la survie après la transplantation hépatique. Les chercheurs évalueront la précision de la TEP-18F-FDG/IRM comme outil permettant de prédire la récurrence du CHC après une transplantation hépatique. Pour comprendre le rôle de la TEP-18F-FDG/IRM dans la prédiction du comportement biologique du CHC et dans les cas de récidive, les chercheurs tenteront de déterminer si les résultats de la TEP-18F-FDG/IRM peuvent prédire une mauvaise différenciation tumorale du CHC et si ces résultats sont liés à la présence d’ADN tumoral circulant dans le plasma; ils tâcheront aussi de préciser le rôle de la TEP-18F-FDG/IRM comme moyen de prédire une récidive du CHC après la résection. Ces résultats pourraient avoir une incidence sur les critères de sélection pour la transplantation hépatique.

Description de l'essai

Primary Outcome:

  • 18F-FDG PET/MRI results can identify aggressive HCC behaviour and recurrence post transplant
Secondary Outcome:
  • 18F-FDG PET/MRI can predict HCC's poor tumoural differentiation
  • 18F-FDG PET/MRI are related to presence of circulating tumour DNA in plasma
Hepatocellular Carcinoma (HCC) is the third leading cause of death by cancer worldwide, being responsible for nearly 700,000 deaths in 2012. Liver transplantation (LT) provides the best results as a curative treatment for patients with early-stage HCC. Other curative treatment strategies for early stages HCC include resection and ablation. However, the recurrence rates are higher than LT. Due to organ shortage, better criteria for recipient selection are necessary. The first widely accepted criteria for graft allocation in HCC patients is the so-called Milan Criteria (MC): single HCC nodule ≤ 5 cm or 3 nodules all ≤ 3 cm, achieving a 4-y survival of 85%. Recently, MC is seen as too restrictive, its inclusion preventing patients who might have better survival following LT when compared to other therapies. Reluctant to have sizing-only criteria, the University of Toronto, since 2004, has applied the so-called Extended Toronto Criteria (ETC) to LT, which offers transplant to patients with any size and any number of tumours provide they do not have systemic cancer-related symptoms, extrahepatic disease, vascular invasion or poorly differentiated tumours. A recent prospective study conducted at University Health Network (UHN) has shown 5-years survival rates of 68% when ECT are applied. Recent studies have demonstrated the need to use, besides the lesion size, variables which can predict the biological behaviour of the tumour. Currently, important treatment decisions, like the selection of patients for transplantation, are made on crude, static tumour characteristics such as the size and number of lesions, but do not reflect other aspects of tumour biology. To date, pre-transplantation percutaneous biopsy is the best strategy to assess tumour differentiation and, consequently, tumour biological behaviour. However, HCC is a very complex disease. Microscopic and molecular analyses have demonstrated a highly heterogeneous degree of cell differentiation. Patients with more than one tumour may have two or three degrees of cell differentiation between the tumours. Even within a single HCC nodule, more than one clonal mutations can be present. To date, there is not a precise method to determinate the degree of differentiation of each patient's disease and percutaneous core biopsy, an invasive method, is the best estimative the investigators can reach. Since it is impossible to precisely determine the degree of differentiation of HCC with one single tissue sample, the use of imaging becomes necessary. Magnetic resonance imaging (MRI) and enhanced computed tomography (CT) are extensively validated as staging methods for HCC. The use of 18F-Fluorodeoxyglucose (18F-FDG) Positron Emission Tomography/Magnetic Resonance Imaging (PET/MRI) is still underevaluated in the field of HCC. However, previous studies have demonstrated that 18F-FDG PET/CT may have role in assessing the HCC tumoural differentiation and predict survival after LT. There is no investigation on use of 18F-FDG PET/MRI as a tool to predict biological behaviour in HCC. Recently, the Pugh Lab has developed a circulating tumour DNA (ctDNA) sequencing assay that combines a hybrid-capture method with a novel bioinformatics algorithm to enable full-length sequence analysis of all exons in genes of interest or any other arbitrary genomic region, rather than mutation hotspots13. With the availability of these technologies in our group, the investigators next sought to determine whether these methods were applicable to HCC patients, gathering two innovative tools in transplant patients' care.

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