Real-time Imaging of Holmium Radioembolization: a Feasibility Study

Inclusion criteria

• Patients must have given written informed consent.
• Female or male aged 18 years and over.
• Diagnosis of hepatocellular carcinoma or cholangiocarcinoma in the liver or diagnosis of metastatic malignancy to the liver (primary tumours: colorectal cancer, melanoma, breast cancer or neuro-endocrine tumour) with limited disease outside the liver (i.e. liver-dominant disease) defined as the sum of the diameters of all metastases in the liver be more than 200% of the sum of the diameters of all soft tissue lesions outside the liver.
• Patient is not amenable for standard therapies (other than radioembolisation) or patient refuses standard therapies
• Life expectancy of 12 weeks or longer.
• World Health Organisation (WHO) Performance status 0-1 (see Appendix III).
• One or more measurable lesions of at least 10 mm in the longest diameter by spiral CT according to the Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 criteria.
• Negative pregnancy test for women of childbearing potential.

Exclusion criteria

• Brain metastases or spinal cord compression, unless irradiated at least 4 weeks prior to the date of the experimental treatment and stable without steroid treatment for at least 1 week
• Radiation therapy within the last 4 weeks before the start of study therapy.
• The last dose of prior systemic therapy has been received less than 4 weeks prior the start of study therapy.
• Major surgery within 4 weeks, or incompletely healed surgical incision before starting study therapy.
• Any unresolved toxicity greater than National Cancer Institute (NCI), Common Terminology Criteria for Adverse Events (CTCAE version 4.0, see Appendix II) grade 2 from previous anti-cancer therapy.
• Serum bilirubin > 1.5 x Upper Limit of Normal (ULN).
• Glomerular filtration rate <35 ml/min, determined according to the Modification of Diet in Renal Disease formula.
• Alanine aminotransferase (ALT), aspartate aminotransferase (AST), or alkaline phosphatase (ALP) > 5 x ULN.
• Leukocytes < 4.0 109/l and/or platelet count < 60 109/l.
• Significant cardiac event (e.g. myocardial infarction, superior vena cava (SVC) syndrome, New York Heart Association (NYHA) classification of heart disease ≥2 within 3 months before entry, or presence of cardiac disease that in the opinion of the Investigator increases the risk of ventricular arrhythmia.
• Pregnancy or breast feeding (women of child-bearing potential).
• Patients suffering from diseases with an increased chance of liver toxicity, such as primary biliary cirrhosis or xeroderma pigmentosum.
• Patients suffering from psychic disorders that make a comprehensive judgement impossible, such as psychosis, hallucinations and/or depression.
• Patients ineligible to undergo MR imaging.
• Patients who are claustrophobic.
• Patient who had prior liver resection and/or coil placement inside the liver, expected to cause imaging artefacts on MRI that will limit MR quantification.
• Patients who are declared incompetent.
• Previous enrolment in the present study or previous treatment with radioembolisation.
• Portal vein thrombosis (tumour and/or bland) of the main branch (diagnosed on contrast enhanced transaxial images). Involvement of the right or left portal vein branches and more distal is accepted.
• Evidence of untreated, clinically significant grade 3 portal hypertension (i.e. large varices at oesophago-gastro-duodenoscopy). In these cases, therapy with non-selective beta blocker (propranolol) or rubber band ligation should be instituted according to accepted guidelines. In case of small varices, prophylactic propranolol is advised.
• Untreated active hepatitis.
• Transjugular intrahepatic portosystemic shunt (TIPS).
• Body weight over 150 kg (because of maximum table load).
• Severe allergy for intravenous contrast agents used

• Iomeron®, because of CT evaluation, pre-treatment angiography and treatment angiography.
• Dotarem or Primovist, depending on the agent used at the time of treatment
• Lung shunt >30 Gy, as calculated using scout dose SPECT/CT.
• Uncorrectable extrahepatic deposition of scout dose activity. Activity in the falciform ligament, portal lymph nodes and gallbladder is accepted.