Liver-Directed Therapy for Neuroendocrine Metastases: From Interventional Radiology to Nuclear Medicine Procedures

Abstract

Neuroendocrine neoplasms (NENs) are rare and heterogeneous epithelial tumors most commonly arising from the gastroenteropancreatic (GEP) system. GEP-NENs account for approximately 60% of all NENs, and the small intestine and pancreas represent two most common sites of primary tumor development. Approximately 80% of metastatic patients have secondary liver lesions, and in approximately 50% of patients, the liver is the only metastatic site. The therapeutic strategy depends on the degree of hepatic metastatic invasion, ranging from liver surgery or percutaneous ablation to palliative treatments to reduce both tumor volume and secretion. In patients with grade 1 and 2 NENs, locoregional nonsurgical treatments of liver metastases mainly include percutaneous ablation and endovascular treatments, targeting few or multiple hepatic metastases, respectively. In the present work, we provide a narrative review of the current knowledge on liver-directed therapy for metastasis treatment, including both interventional radiology procedures and nuclear medicine options in NEN patients, taking into account the patient clinical context and both the strengths and limitations of each modality.

Keywords: interventional radiology; liver metastasis; liver-directed therapy; neuroendocrine; nuclear medicine; radioembolization.

Figure 1

Simplified therapeutic algorithm for the interventional management of liver metastases in patients with G1/G2 NENs without surgical indication.

Figure 2

A 55-year-old woman with grade 1 ileal NEN liver metastases and a previous history of MRI-guided liver metastasis ablation. MRI diffusion-weighted axial image showed a target liver metastasis (arrow) of segment VI (A), effectively treated with percutaneous MRI-guided cryoablation (B, arrow: iceball), which resulted in a complete retraction of the ablation site without any pathologic ¹⁸F-DOPA uptake during follow-up PET/CT (C, arrow). Four years after the first treatment, the patient underwent ¹⁸F-DOPA PET/CT-guided radiofrequency ablation of a 10 mm liver metastasis (D, arrow) of the IV liver segment. Immediate postablation ¹⁸F-DOPA PET-CT showed complete tumor destruction without residual ¹⁸F-DOPA uptake (E, arrow). ¹⁸F-DOPA PET/CT performed 24 months later showed limited parenchymal scarring without pathologic ¹⁸F-DOPA uptake (F, arrow).

Figure 3

A 39-year-old woman with multiple liver metastases from a grade 2 neuroendocrine tumor that previously underwent systemic treatments. (A) Axial contrast-enhanced T1-weighted MRI image showing a single metastasis of 6.5 cm (arrow) of the right liver lobe, which was not responsive to previous therapies. According to a multidisciplinary board recommendation, tumors were treated by microwave ablation performed with a multiantenna approach (B,C), complicated by postablation bleeding and local infection treated by percutaneous embolization and drainage, respectively. Axial (D) and coronal (E) contrast-enhanced T1-weighted MRI images obtained at the 9-month follow-up showing a shrunken residual necrotic area (arrows).

Figure 4

A 66-year-old patient with exclusively hepatic metastasis of a neuroendocrine tumor of unknown origin presented with important abdominal pain and carcinoid syndrome despite cold somatostatin analogues treatment. Preembolization contrast-enhanced arterial CT (A) and digital subtraction angiography (DSA) (B) show bilateral hypervascular liver metastases (arrows). DSA performed after a first TACE session in the right liver (C) shows complete devascularization of right liver lesions and contrast stagnation in the right branch of the hepatic artery (arrow). Postembolization CT performed 2 months after a second TACE session (D) performed on the left liver shows persistent Lipiodol retention in the treated metastasis (arrows).

Figure 5

A 77-year-old woman with a previous history of surgically treated pancreatic grade 1 NEN (Ki67 = 1%) presented during follow-up with exclusive hepatic relapse. Multidisciplinary committee stated for ⁹⁰Y-selective internal radiation therapy (SIRT) treatment. (A) Restaging anterior MIP of ⁶⁸Ga-DOTATOC PET performed during follow-up; (B) arterial-phase contrast-enhanced CT obtained before SIRT; (C) pretreatment scintigraphy (axial SPECT/CT) performed during work-up after injection of macroaggregated albumin labeled with ^99mTechnetium showing intense uptake by metastasis (arrows) and slight uptake by normal liver parenchyma; (D) posttreatment PET/CT (axial slice) confirming the intense uptake by liver metastasis (arrows) perfectly concordant with pretreatment scintigraphy; and (E) 6-month CT (arterial phase, axial slice) after SIRT showing tumoral involvement and treatment efficacy.