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

Inclusion Criteria:

* Histologically confirmed primary adenocarcinoma of the colon or rectum
* Potentially resectable colorectal liver metastases, with limiting factors for resection including:

  1. Insufficient future liver remnant.
  2. 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:

  1. Signed informed consent;
  2. Age ≥ 18 years;
  3. Eastern Cooperative Oncology Group (ECOG) performance status 0-1;
  4. Life expectancy of ≥ 3 months;
  5. 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

Exclusion Criteria:

* Life expectancy ≤3 months
* Patient initially eligible for surgery or thermal ablation of the liver metastases
* 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.))
* Uncorrectable coagulopathy
* Contraindication for angiography or MRI
* 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
* Any surgical contraindication
* 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
* Prior liver radiotherapy
* 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
* Unresectable primary tumor in situ;
* Other serious comorbidity or any other condition, that renders patients unsuitable for the study treatment
* Pregnancy, lactation or refusal to use adequate contraceptive measures
* History of allergic reaction to any components of the treatment that cannot be medically corrected.