Abstract
BackgroundLutetium-177-DOTA-octreotate (177Lu-DOTATATE) significantly increases survival and response rates in patients with grade I and grade II neuroendocrine tumors (NETs). However, survival and response rates are significantly lower in patients with bulky liver metastases. Increasing the tumor-absorbed dose in liver metastases may improve response to 177Lu-DOTATATE. The LUTIA (Lutetium Intra-Arterial) study aims to increase the tumor-absorbed dose in liver metastases by intra-arterial (IA) administration of 177Lu-DOTATATE, compared to conventional intravenous (IV) administration.MethodsA multicenter, within-patient randomized controlled trial (RCT) in 26 patients with progressive, liver-dominant, unresectable grade I or grade II NET will be conducted. Patients with bilobar bulky disease will be randomly allocated to receive IA treatment into either the left or the right hepatic artery. Using this approach, one liver lobe will be treated intra-arterially (first-pass effect), while the contralateral lobe will receive an intravenous treatment as a second-pass effect. The primary endpoint of this study is the difference in tumor-to-non-tumor ratio of 177Lu-DOTATATE uptake between the two liver lobes on post-treatment SPECT/CT (IA versus IV). Secondary endpoints include absorbed dose in both liver lobes, tumor response, dose-response relationship, toxicity, uptake in extrahepatic lesions, and renal uptake.DiscussionThis multicenter, within-patient RCT will investigate whether IA administration of 177Lu-DOTATATE results in a higher activity concentration in liver metastases compared to IV administration.Trial registrationClinicalTrials.gov, NCT03590119. Registered on 17 July 2018.
Highlights
Lutetium-177-DOTA-octreotate (177Lu-DOTATATE) significantly increases survival and response rates in patients with grade I and grade II neuroendocrine tumors (NETs)
In order to control disease progression, to achieve symptomatic relief, and to prolong survival, Peptide receptor radionuclide therapy (PRRT) is increasingly used in the treatment of progressive NETs [5, 6]. 177Lu-DOTATATE is a radiopharmaceutical, consisting of a somatostatin-analog peptide labeled with an isotope with a high-energy beta emission, that binds with high affinity to the somatostatin receptor subtype 2 (SSTR-2), overexpressed in grade I and II NET cells [7, 8]. 177Lu-DOTATATE significantly increases progression-free survival (PFS) and overall survival (OS), with limited toxicity, compared to non-radioactive high-dose somatostatin analogs in patients with advanced stage NET [5, 6, 9,10,11]
Hypothesis The hypothesis is that IA administration of 177LuDOTATATE into the hepatic artery will result in a higher tumor-to-non-tumor (T/N) uptake ratio, compared to IV administration
Summary
Lutetium-177-DOTA-octreotate (177Lu-DOTATATE) significantly increases survival and response rates in patients with grade I and grade II neuroendocrine tumors (NETs). Survival and response rates are significantly lower in patients with bulky liver metastases. Increasing the tumor-absorbed dose in liver metastases may improve response to 177Lu-DOTATATE. Peptide receptor radionuclide therapy (PRRT) with lutetium-177-DOTA-octreotate (177Lu-DOTATATE; Lutathera, Advanced Accelerator Applications, SaintGenis-Pouilly, France) is the standard treatment for inoperable metastasized grade I and grade II gastrointestinal neuroendocrine tumors (NETs) [1]. A post hoc analysis of the NETTER-1 trial showed that the presence of bulky lesions (> 3 cm) was significantly associated with a worse PFS after PRRT [14]
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