Holmium-166 Transarterial Radioembolization in Unresectable, Early Stage Hepatocellular Carcinoma.

Inclusion Criteria:

1. Age ≥ 18 years

2. Multidisciplinary tumor board decision for locoregional treatment

3. Freely given, written informed consent

4. Patients with unresectable HCC with a single nodule ≤ 8 cm or up to three noduleswith a diameter of ≤ 5 cm (each) eligible for selective radioembolization (includingposition changes of infusion catheters)

5. Non-cirrhotic patients or Child-Pugh A cirrhosis

6. ECOG performance status 0-1

7. Using an acceptable method of contraception throughout the study until survivalfollow up (for subjects of childbearing potential)

8. Adequate hematological, renal and liver function.

Adequate hematological function defined as:

• Hemoglobin ≥ 6 mmol/L (9.7 g/dL)

• WBC ≥ 3.0 x 10E9/L

• Absolute neutrophil count ≥ 1.5 x 10E9/L

• Platelet count ≥ 50,000/mm3

Adequate renal function defined as:

• Serum urea and serum creatinine < 1.5 times upper limit of normal (ULN)

• Creatinine clearance ≥ 45 ml/min

Adequate liver function defined as:

• Total bilirubin ≤ 35µmol/L (2.05 mg/dL)

• Albumin ≥ 30 g/L

• AST and ALT ≤ 5X ULN

Exclusion Criteria:

1. Diffuse and/or infiltrative HCC (defined as HCC consisting of multiple tiny livernodules spreading throughout the entire liver or entire lobe, without a dominantnodule)

2. Hypoperfused HCC (defined as a lack of tumor blush (i.e. reduced or no uptake ofcontrast fluid) observed on the intra-procedural CT)

3. No full, selective arterial coverage on intra-procedural CT

4. Life expectancy < 6 months

5. Child-Pugh score ≥7 points

6. Prior liver transplantation

7. Prior locoregional or systemic anti-cancer therapy for HCC and previous malignancies

8. Macrovascular invasion (defined as macrovascular invasion of the hepatic and/orportal vein main branches)

9. Extrahepatic metastases

10. Clinically significant ascites

11. Hepatic encephalopathy

12. Untreated active hepatitis B and/or C

13. Work-up imaging showing:

• Lung shunt > 30 Gy is simulated on 166Ho-scout imaging; or

• Uncorrectable extrahepatic deposition of simulated 166Ho-scout dose activity.Activity in the falciform ligament, portal lymph nodes and gallbladder isaccepted; or

• Anticipated ineffective tumor targeting (< 150 Gy mean tumor simulated absorbeddose) of 166Ho-scout for each lesion; or

• Entire tumor burden not within the perfused liver volume (possible extrahepaticcollateral supply of the tumor); or

• Perfused liver volume > 50% of whole liver tissue

14. Pregnant or breast-feeding

15. Current or history of cancer other than HCC, except adequately treated non-melanomaskin cancer or carcinoma in situ of the cervix

16. In the Investigator's opinion there is a reason that could limit the patient'sability to participate in the study, compliance with follow-up requirements orimpact the scientific integrity of the study

17. Concurrently enrolled in another study, unless it is an observationalnon-interventional study