Radiotherapy Versus no Intervention in Adult Patients With Hepatocellular Carcinoma Not Eligible for Transarterial Chemoembolization or Ablation Prior to Liver Transplant (RADBRI)

Liver transplantation (LT) represents the best treatment for patients with selected, early stage hepatocellular carcinoma (HCC). Due to the gap between the number of patients on the waiting list and the available donors, patients with HCC wait \~1 year to be transplanted. While waiting, 25-30% of patients need to come off the transplant list due to tumor progression beyond transplant criteria (extrahepatic disease, vascular invasion or increase in tumor burden beyond enlistment criteria). To try to avoid this progression, patients are treated while waiting with "bridging therapies", mainly transarterial chemoembolization (TACE) and ablation. Around 30% of patients are not eligible for these treatments (.e.g. due to poor liver function). Stereotactic body radiotherapy (SBRT) has been shown to be an effective treatment for advanced HCC in primarily small, single institutional studies and its safety has been reported in cirrhotics. SBRT could be used in patients not eligible to TACE or ablation as a bridge to LT reducing the risk of progression in the waiting list. This study will evaluate if patients with liver cirrhosis and HCC benefit from receiving SBRT while awaiting LT. Patients will be randomized to a treatment arm where they will receive SBRT as a bridge therapy or to a no intervention arm. Outcomes prior and post to transplant will be performed to evaluate the differences between both arms: proportion of patients that do not drop-out of the list (are transplanted), liver decompensation while waiting, perioperative measures in those that are transplanted, time to transplant or drop-out, overall survival, disease-free survival in those that are transplanted in a population of about 330 patients across all sites.

Sex

All

Minimum age

18 Years

Maximum age

75 Years

Inclusion Criteria:

* 18-75 years old
* Patient has been included in the waiting list to receive a Liver Transplant (LT)
* Radiological confirmation of Hepatocellular carcinoma (HCC) according to American Association for the Study of Liver Diseases (AASLD) guidelines
* Tumor burden at randomization within a total tumor volume (TTV) ≤115 cm3 and serum alpha-fetoprotein (AFP) ≤400 ng/mL
* Patient not eligible to bridging therapy with Transarterial Chemoembolization (TACE) and/or ablation.
* Child-Pugh score ≤B9
* Calculated Model of End Stage Liver disease (MELD) score ≤20
* Eligible to Stereotactic body radiotherapy (SBRT): \>40% of liver parenchyma can be spared from radiation and all tumors can be targeted
* No previous treatment of the tumor
* Absence of extra-hepatic disease or vascular invasion on imaging
* Able and willing to provide consent

Exclusion Criteria:

* Patient with HCC not candidate to receive a LT
* Patient is eligible to TACE or ablation as a bridge to LT
* Patient is not eligible to SBRT
* Previous bridging therapies