. 2018 Jul 17;19:390. doi: 10.1186/s13063-018-2782-5

Table 1.

RETNET trial inclusion and exclusion criteria

Inclusion criteria	Exclusion criteria
• Participants aged 18 years and older • Biopsy-proven neuroendocrine tumor with tumor burden dominant in the liver • Measurable metastasis to liver with at least one dimension ≥1.0 cm. Known extrahepatic disease should be limited to lymph nodes of < 2 cm and/or any bone metastases. • Liver tumor burden ≤ 70% of the total liver volume by visual estimate • Not a candidate for surgical resection owing to unresectability, anatomy, anesthesia risk, patient preference • Symptoms uncontrolled by somatostatin analogues OR morphologically progressive tumor by RECIST 1.1 criteria in the liver OR baseline tumor burden > 25% of the liver volume • No plans for the patient to receive other concomitant therapy while on this protocol treatment (other than octreotide or bisphosphonate therapy) • Performance status 0–2 on Zubrod performance scale • Serum creatinine ≤ 2.0 mg/dl • Serum bilirubin ≤2.0 mg/dl • Serum albumin ≥3.0 g/dl • Platelet count ≥ 50,000/μl (corrected if needed) • INR ≤ 1.5 (corrected if needed) • All patients must be informed of the investigational nature of this study and must sign a study-specific informed consent form in accordance with institutional and federal guidelines prior to study entry.	• Pregnant or lactating women may not participate, owing to the embryotoxic effects of protocol treatment. • Women/men of reproductive potential may not participate unless they have agreed to use an effective contraceptive method. • Prior hepatic arterial therapy or hepatic radiation therapy. Prior surgical resection or ablation of liver metastases is acceptable. Patients must be at least 1 month beyond prior chemotherapy, PRRT, ablation, or surgery and must have recovered from all therapy-associated toxicities. • Active infection (symptomatic bacterial and fungal infection, newly diagnosed and/or requiring treatment) • Choledochoenteric anastomosis, transpapillary biliary stent, or sphincterotomy of duodenal papilla • Absolute contraindication to intravenous iodinated contrast agent (history of significant previous contrast agent reaction not mitigated by appropriate premedication) • Allergy to doxorubicin • Contraindications to arteriography and selective visceral catheterization: ○ Severe allergy or intolerance to contrast media, narcotics, sedatives, or atropine ○ Bleeding diathesis not correctable by usual forms of therapy ○ Severe peripheral vascular disease precluding catheterization • Contraindications to hepatic artery embolization: ○ Portal vein occlusion without hepatopedal collateral flow demonstrated by angiography or portal hypertension with hepatofugal flow ○ Hepatic encephalopathy

Inclusion criteria

Exclusion criteria

• Participants aged 18 years and older
• Biopsy-proven neuroendocrine tumor with tumor burden dominant in the liver
• Measurable metastasis to liver with at least one dimension ≥1.0 cm. Known extrahepatic disease should be limited to lymph nodes of < 2 cm and/or any bone metastases.
• Liver tumor burden ≤ 70% of the total liver volume by visual estimate
• Not a candidate for surgical resection owing to unresectability, anatomy, anesthesia risk, patient preference
• Symptoms uncontrolled by somatostatin analogues OR morphologically progressive tumor by RECIST 1.1 criteria in the liver OR baseline tumor burden > 25% of the liver volume
• No plans for the patient to receive other concomitant therapy while on this protocol treatment (other than octreotide or bisphosphonate therapy)
• Performance status 0–2 on Zubrod performance scale
• Serum creatinine ≤ 2.0 mg/dl
• Serum bilirubin ≤2.0 mg/dl
• Serum albumin ≥3.0 g/dl
• Platelet count ≥ 50,000/μl (corrected if needed)
• INR ≤ 1.5 (corrected if needed)
• All patients must be informed of the investigational nature of this study and must sign a study-specific informed consent form in accordance with institutional and federal guidelines prior to study entry.

• Pregnant or lactating women may not participate, owing to the embryotoxic effects of protocol treatment.
• Women/men of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.
• Prior hepatic arterial therapy or hepatic radiation therapy. Prior surgical resection or ablation of liver metastases is acceptable. Patients must be at least 1 month beyond prior chemotherapy, PRRT, ablation, or surgery and must have recovered from all therapy-associated toxicities.
• Active infection (symptomatic bacterial and fungal infection, newly diagnosed and/or requiring treatment)
• Choledochoenteric anastomosis, transpapillary biliary stent, or sphincterotomy of duodenal papilla
• Absolute contraindication to intravenous iodinated contrast agent (history of significant previous contrast agent reaction not mitigated by appropriate premedication)
• Allergy to doxorubicin
• Contraindications to arteriography and selective visceral catheterization:
○ Severe allergy or intolerance to contrast media, narcotics, sedatives, or atropine
○ Bleeding diathesis not correctable by usual forms of therapy
○ Severe peripheral vascular disease precluding catheterization
• Contraindications to hepatic artery embolization:
○ Portal vein occlusion without hepatopedal collateral flow demonstrated by angiography or portal hypertension with hepatofugal flow
○ Hepatic encephalopathy

Abbreviations: INR International normalized ratio, PRRT Peptide receptor radionuclide therapy, RECIST Response Evaluation Criteria in Solid Tumors, RETNET Randomized Embolization Trial for NeuroEndocrine Tumor Metastases to the Liver