Building Evidence for Ablative Internal Radiation Therapy in Localized HCC Beyond the Up-To-7 Criteria

Prior treatment

• Patients who have had active cancer within the last two years prior to the study enrollment

Other illness

• Cases where the operator judges that the occurrence of even mild radiation pneumonitis could be fatal, based on marked emphysema or interstitial lung disease findings on chest CT
• History of severe allergy of intolerance to contrast agents

Lab values

• Patients who are not suitable for ablative radioembolization as indicated by pre-treatment mapping with 99mTc-macroaggregated albumin (MAA):
  • Cases where the estimated lung dose exceeds 30 Gy when 350 Gy of tumor absorbed dose is administered to the tumor based on the multicompartment Medical Internal Radiation Dose (MIRD) model
  • Cases with severe hepatic artery-portal vein shunting that might lead to irradiation of the non-tumorous liver segments
  • Cases where the operator determines that there is substantial adhesion with the surrounding organs such as the bowel, making ablative radioembolization infeasible

Other

• HCC with vascular invasion and/or bile duct invasion on dynamic computed tomography (CT) or magnetic resonance imaging (MRI)
• HCC with extrahepatic spread on chest CT and abdominal CT or MRI
• Multinodular disseminated HCC: largest tumor size \< 6 cm, or number of tumors \> 10
• Contraindication to angiography or selective visceral catheterization

• Adult aged 19 and over
• HCC diagnosed by histology or non-invasive criteria of the American Association for the Study of Liver Disease
• Unresectable HCC beyond the UT7 criteria: the sum of the diameter of the largest tumor (cm) and the number of tumors \> 7
• Localized HCC: all tumors are in the one to five geographically adjacent Couinaud segments
• No current or previous HCC in the untreated liver (i.e., future liver remnant \[FLR\])
• FLR volume \> 30% of total non-tumorous liver volume
• Child-Pugh class A
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
• No major organ dysfunction according to blood test performed within two months of study enrollment:
  • Leukocytes ≥ 2,000/µL and ≤ 15,000/µL
  • Hemoglobin ≥ 8.0 g/dL (transfusion allowed to meet this criterion)
  • Total bilirubin ≤ 2.0 mg/dL
  • Platelet ≥ 40,000/µL
  • International normalized ratio (INR) ≤ 2.0 for patients not taking anticoagulants
  • Aspartate transaminase (AST) ≤ 200 IU/L (i.e., ≤ 5X upper normal limit)
  • Alanine transaminase (ALT) ≤ 200 IU/L (i.e., ≤ 5X upper normal limit)
  • Creatinine ≤ 2.5 mg/dL
• Patients with a life expectancy of more than 3 months
• For women of childbearing age, a negative serum pregnancy test
• Patients who have adequately understood the clinical trial and consented in writing