1. Biopsy proven neuroendocrine tumor, which is somatostatin receptor positive as
demonstrated on somatostatin receptor PET.
1. All sites or origin are eligible.
2. Functional and nonfunctional tumors are allowed. 2. Hepatic metastases on imaging
meeting the following criteria:
a. Liver-only or liver-dominant metastases, defined as: i. At least 10% liver parenchyma
replacement by tumor, but less than 70% replacement of the hepatic parenchyma by tumor.
1. For the imaging sub-study: at least one liver lesion must measure greater than 2 cm in
size 2. For the imaging sub-study: treatment must only be performed using a single dose,
and so arterial variant anatomy that would result in a split treatment will not be allowed
ii. And, progression of the liver metastases demonstrated within the past twelve months
defined as either:
1. Appearance of any new liver lesion or
2. 20% increase in size of at least one liver lesion. iii. Presence of low-volume
extrahepatic lesions (including primary tumor) is allowed if they are stable and
b. SUVmax on 68Ga-DOTA-TOC PET of the liver metastases two times greater than the
adjacent liver parenchyma.
3. Not a candidate for surgical debulking.
4. ECOG performance status 0, 1 or 2
5. Age > 18.
6. Ability to understand a written informed consent document, and the willingness to sign
1. Patients not capable of getting PET study due to weight, claustrophobia, or inability
to lie still for the duration of the exam.
a. For patients in the imaging correlate sub-study: contraindication for undergoing
MRI based on UCSF Radiology guidelines.
2. Contraindication to hepatic arteriography (e.g. hepatic artery dissection and/or
thrombosis, uncorrectable coagulopathy, severe allergy to iodinated contrast, severe
vascular disease precluding safe hepatic artery catheterization).
3. Any patient receiving treatment with short-acting octreotide, which cannot be
interrupted for 48 hours before and 24 hours after the administration of 90Y-DOTA-TOC,
or any patient receiving treatment with octreotide LAR or lanreotide, which cannot be
interrupted for at least 4 weeks before the administration of 90Y-DOTA-TOC.
a. Concurrent somatostatin receptor analog (SSA) allowed if progression has been
documented and the SSA dose has been stable for at least two months. Long-acting SSA
cannot be given within four weeks of treatment and short-acting SSA cannot be given
with 48 hours of treatment. SSA therapy can restart one day after treatment.
4. Interferon, everolimus (mTOR-inhibitors), sunitinib or other systemic therapies within
4 weeks prior to enrollment. Bevacizumab within 6 weeks prior to enrollment.
5. Any liver directed treatment (surgery, radioembolization, chemoembolization,
chemotherapy and radiofrequency ablation) within 12 weeks prior to enrollment.
6. Any external beam radiation treatment for hepatic disease. Prior external beam
radiation therapy to more than 25% of the bone marrow.
a. Prior systemic PRRT treatment is allowed, if it was performed at least six months
7. Pregnancy or lactation. Women of childbearing potential and men must agree to use
adequate contraception prior to study entry and for the duration of study
8. Impaired liver function
1. AST (SGOT) / ALT (SGPT) > 3 x ULN.
2. Total bilirubin >1.5 x ULN
3. Serum albumin <3.0 g/dL unless prothrombin time is within the normal range.
4. Thrombosis of the main portal vein
5. Clinical evidence of ascites (trace ascites on imaging acceptable).
9. Impaired bone marrow reserve
1. Hb concentration < 8.0 g/dL;
2. Total WBC <2x109/L (2000/mm3);
3. Platelets <75x109/L (75x103/mm3).
10. Creatinine clearance <50 mL/min calculated by the Cockroft Gault method.
11. Known intracranial metastases.