Yttrium-90 Radioembolization Neoadjuvant Therapy With Immune Marker Profiling and Dosimetry for Potentially Resectable Patients With Colorectal Liver Metastases

Prior treatment

• Patient initially eligible for surgery or thermal ablation of the liver metastases
• Any surgical contraindication
• Prior liver radiotherapy

Other illness

• Progressive extra-hepatic disease
• Active extra-hepatic disease that cannot be treated
• Life-threatening extra-hepatic disease (i.e. dialysis, unresolved diarrhea, serious unresolved infections (HIV, HBV, HCV etc.))
• Significant toxicities due to prior cancer therapy that have not resolved before the initiation of the study; if the investigator determines that the continuing complication will compromise the safe treatment of the patient
• Severe portal hypertension
• Second primary malignancy within the past 5 years, other that adequately treated non-melanoma skin cancer, carcinoma in situ of any organ or second primary colorectal cancer
• Other serious comorbidity or any other condition, that renders patients unsuitable for the study treatment
• History of allergic reaction to any components of the treatment that cannot be medically corrected.

Other

• Life expectancy ≤3 months
• Uncorrectable coagulopathy
• Contraindication for angiography or MRI
• Ascites
• Expected difficulties for safe execution of TARE based on pretreatment Tc99m-MAA imaging, including;
• Flow to extra-hepatic vessels not correctable by reposition of catheter or embolization Uncorrectable estimated dose to the lungs \>30Gy in a single administration or \>50Gy cumulatively
• Uncorrectable estimated dose to the untreated liver of \>70Gy
• Estimated average dose to the viable tumor volume \<200Gy
• Unresectable primary tumor in situ;
• Pregnancy, lactation or refusal to use adequate contraceptive measures

• Histologically confirmed primary adenocarcinoma of the colon or rectum
• Potentially resectable colorectal liver metastases, with limiting factors for resection including:
  • Insufficient future liver remnant.
  • Unfavorable tumor location (e.g. involvement of a major vessel and/or bile duct)/ large size and/ or number of lesions, which limit resection with R0 margins and requires downsizing of the metastases
• No or limited extrahepatic metastatic disease (limited extrahepatic disease should be amenable to eradicate with locoregional therapies as per multidisciplinary discussion of surgeons, radiation oncologists and interventional radiologists)
• Patient should match standard 90Y radioembolization inclusion criteria:
  • Signed informed consent;
  • Age ≥ 18 years;
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1;
  • Life expectancy of ≥ 3 months;
  • Measurable target tumors in the liver according to RECIST 1.1
• Laboratory parameters: eGFR \>45/mL/min/1.73 m2; albumin \> 3.0 g/dl, normal bilirubin (unless Gilbert syndrome); aminotransferase (ALAT/ASAT) \<3.0 ULN