The outstanding response rates and survival outcomes suggest that PRRT is highly effective in advanced G1/2 pNET when compared to data of other treatment modalities. Independent predictors of survival are the tumour proliferation index, the patient's performance status, tumour burden and baseline plasma NSE level.

Serious nephrotoxicity after PRRT with (177)Lu-octreotate is rare (1.3%). However, slight renal impairment (GFR loss >2 ml/min/m(2) per year) can frequently (43%) be detected by (99m)Tc-DTPA clearance assessments. Cumulative administered activity of (177)Lu-octreotate is not a major determinant of renal impairment in our study.

PRRT is well tolerated and very effective in advanced well-differentiated small intestinal (midgut) NET. A high disease control rate and long PFS can be achieved with this modality after failure of standard biotherapy with somatostatin analogues. Tumour functionality and high plasma CgA appear to be independent predictors of unfavourable patient outcome.

PRRT with (177)Lu-octreotate in the re-treatment setting is safe and effective in patients with metastatic GEP-NET.

Previous radiation therapy of the liver is a contraindication for performing 90 Y microsphere radioembolization, and its safety after internal radiation exposure through peptide receptor radionuclide therapy (PRRT) has not yet been investigated. Methods: We retrospectively assessed a consecutive cohort of 23 neuroendocrine tumor (NET) patients with liver-dominant metastatic disease undergoing radioembolization with 90 Y microspheres as a salvage therapy after failed PRRT. Toxicity was recorded throughout follow-up and reported according to Common Terminology Criteria for Adverse Events (version 3). Radiologic (response evaluation criteria in solid tumors), biochemical, and symptomatic responses were investigated at 3 mo after treatment, and survival analyses were performed with the Kaplan-Meier method (log-rank test, P , 0.05). Results: The median follow-up period after radioembolization was 38 mo (95% confidence interval, 18-58 mo). The mean previous cumulative activity of 177 Lu-DOTA-octreotate was 31.8 GBq. The mean cumulative treatment activity of 90 Y microspheres was 3.4 6 2.1 GBq, administered to the whole liver in a single session (n 5 8 patients), in a sequential lobar fashion (n 5 10 patients), or to only 1 liver lobe (n 5 5 patients). Only transient, mostly minor liver toxicity (no grade 4) was recorded. One patient (4.3%) developed a gastroduodenal ulcer (grade 2). The overall response rates for radiologic, biochemical, and symptomatic responses were 30.4%, 53.8%, and 80%, respectively. The median overall survival was 29 mo (95% confidence interval, 4-54 mo) from the first radioembolization session and 54 mo (95% confidence interval, 47-61 mo) from the first PRRT cycle. A tumor proliferation index Ki-67 greater than 5% predicted shorter survival (P 5 0.007). Conclusion: Radioembolization is a safe and effective salvage treatment option in advanced NET patients with liverdominant tumor burden who failed or reprogressed after PRRT. The lack of relevant liver toxicity despite high applied 90 Y activities and considerable previous cumulative activities of 177 Lu-octreotate is noteworthy and disputes internal radiation exposure by PRRT as a toxicity risk factor in subsequent radioembolization.