Radiation Major Hepatectomy to Selectively Treat Large Unifocal Hepatocellular Carcinoma

An Open-label, Single-arm, Single-center Clinical Trial to Evaluate the Efficacy and Safety of Yttrium-90 Ablative Radioembolization (Radiation Major Hepatectomy) for Unifocal Large Hepatocellular Carcinoma

The RESCUE trial is a prospective, single-arm clinical study to evaluate the efficacy and safety of ablative radioembolization using Yttrium-90. This treatment is being investigated as a potential curative approach, as well as a bridging or downstaging strategy for surgery, in patients with large hepatocellular carcinoma (greater than 8 cm) who maintain good liver function.

Patients presenting with large hepatocellular carcinoma (greater than 8 cm), whether accompanied by satellite nodules or not, but retaining good liver function, will undergo ablative radioembolization utilizing Yttrium-90 resin microspheres. This approach is designed to deliver an ablative dose to both tumors and the surrounding liver (i.e., margin) with curative intent, while preserving over 30% of the non-tumorous liver volume. The efficacy and safety of this treatment will be evaluated over a period of two years and 90 days, respectively.

Inclusion Criteria:

1. Adults aged 18 and over.

2. Patients diagnosed with hepatocellular carcinoma histologically and/or radiologically (LI-RADS 4 or 5).

3. Patients with no more than five lesions in dynamic contrast-enhanced CT or MRI, and the largest tumor diameter exceeding 8 cm.

4. Patients without vascular invasion and bile duct invasion in dynamic contrast-enhanced CT or MRI.

5. Patients with no extrahepatic metastasis in lung CT and contrast-enhanced abdominal CT or MRI.

6. Patients with no prior treatment for liver cancer.

7. Child-Pugh class A.

8. ECOG performance status of 1 or less.

9. Patients with no major organ dysfunction according to blood tests performed within one month of study enrollment.

   1. Leukocytes ≥ 2,500/µL and ≤ 12,000/µL
   2. Absolute neutrophil count ≥ 1,500 /mm^3
   3. Hemoglobin ≥ 8.0 g/dL (transfusion allowed to meet this criterion)
   4. Total bilirubin ≤ 3.0 mg/dL
   5. Platelet ≥ 50,000/µL
   6. INR ≤ 2.0 for patients not taking anticoagulants
   7. AST ≤ 200 IU/L (i.e., ≤ 5X upper normal limit)
   8. ALT ≤ 200 IU/L (i.e., ≤ 5X upper normal limit)
   9. ALP ≤ 575 IU/L (i.e., ≤ 5X upper normal limit)
   10. Creatinine ≤ 2.0 mg/dL

10. Patients with a life expectancy of more than 3 months.

11. Patients who have adequately understood the clinical trial and consented in writing.

12. Non-pregnant women of childbearing potential.

Exclusion Criteria:

1. Patients who are not suitable for ablative radioembolization as indicated by pre-treatment testing with macro-aggregated albumin labeled with technetium-99 (99mTc-MAA) for radioembolization.

   1. Cases where the estimated lung dose exceeds 15 Gy when 150 Gy of absorbed dose is administered to the tumor based on the partition method.
   2. Cases with severe hepatic artery-portal vein shunting that might lead to irradiation of the non-tumorous liver segments.

2. Patients whose volume of non-tumorous liver not included in the treatment area is less than 30% of the total non-tumorous liver volume.

3. Patients scheduled to use immunotherapy irrespective of the response to radioembolization.

4. Patients who have had active cancer within the last two years prior to the clinical trial participation.

5. Patients who have undergone surgery or procedures related to the bile duct.

6. Women who are pregnant or breastfeeding.