Preoperative PRRT Versus Surgical Cytoreduction in Metastatic Pancreatic Neuroendocrine Tumors to the Liver

Inclusion Criteria:

• Metastatic Pancreatic neuroendocrine tumors (PanNET) to the liver

• Well- or moderately differentiated (grade 1 or grade 2, Ki-

• Ability to aim for equal or greater than 90% hepatic cytoreduction surgically

• Proof of SSTR2 expression by uptake of tumor on 68Ga DOTATATE PET CT (Krenning Scoreon all or a majority of lesions

• Age older than 18 years

• No Somatostatin Analogues (SSA) or other systemic therapy for 4 weeks prior tostarting PRRT, if randomized to arm 2.

Exclusion Criteria:

• Patient with G3 or poorly differentiated NET (grade 3, Ki-67 >20%)

• Previous liver-directed therapy with Yttrium-90 (TACE/TAE allowed if performed morethan 12 months prior to enrollment)

• Systemic therapy with Capecitabine and/or Temozolamide within 12 months ofenrollment.

• No tumor uptake on 68Ga DOTATATE PET CT

• Liver tumor burden > 50% (as defined by CT or MRI)

• Signs of early liver failure (T-Bilirubin >3, INR > 1.5, Albumin <3.0 g/dL unlessprothrombin time is within the normal range) or cirrhosis or ascites

• calculated by the Cockroft Gault method, eventually confirmed by measured creatinineclearance

• (or measured glomerular filtration rate (GFR) using plasma clearance methods, notgamma

• camera-based) <50 mL/min (the measured creatinine clearance / GFR is required onlyas - confirmatory exam).

2. Hb concentration <5.0 mmol/L (<8.0 g/dL); WBC <2x109/L (2000/mm3); platelets <75x109/L - (75x103/mm3).

• Known brain metastases, unless these metastases have been treated and stabilized.

• Uncontrolled congestive heart failure (NYHA II, III, IV).

• Uncontrolled diabetes mellitus as defined by a fasting blood glucose >2 ULN.

• Pregnancy or lactation.

• For female patients of childbearing potential (defined as < 2 years after lastmenstruation and not surgically sterile) and male patients, who are not surgicallysterile or with female partners of childbearing potential: absence of effective,non-hormonal means of contraception (intrauterine contraceptive device, barriermethod of contraception in conjunction with spermicidal gel). - Prior external beamradiation therapy to more than 25% of the bone marrow.

• Current spontaneous urinary incontinence making impossible the safe administrationof the radioactive IMP.

• Other known co-existing malignancies except non-melanoma skin cancer and carcinomain situ of the uterine cervix, unless definitively treated and with no evidence ofrecurrence.

• Patients who have not provided a signed informed consent form to accept thistreatment.

• Poor renal function

• Quality Unit language added

• editorial changes