Hepatic Arterial Embolization versus Chemoembolization in the Treatment of Liver Metastases from Well-Differentiated Midgut Endocrine Tumors: A Prospective Randomized Study

Abstract

Background: Liver surgery is the best treatment for endocrine liver metastases, but it is often impossible due to diffuse disease. Systemic chemotherapy is poorly effective. Hepatic arterial embolization (HAE) and chemoembolization (HACE) have shown efficacy but have never been compared. Patients and Methods: Patients with progressive unresectable liver metastases from midgut endocrine tumors were randomly assigned to receive HAE or HACE (two procedures at 3-month interval). The primary end point was the 2-year progression-free survival (PFS) rate. Secondary end points were response rates, overall survival, and safety. Results: Twelve patients were assigned to receive HACE and 14 to receive HAE. The patient characteristics were well matched across the treatment arms. The 2-year PFS rates were 38 and 44% in the HACE and HAE arms, respectively (p = 0.90). Age, gender, previous resection of the primary tumor or liver metastases, extent of liver involvement, and concomitant treatment with somatostatin analogues were not associated with changes in PFS, whereas elevated baseline urinary 5-HIAA and serum chromogranin A levels were associated with shorter PFS. The 2-year overall survival rates were 80 and 100% in the HACE and HAE arms, respectively (p = 0.16). The disease control rate on CT scan was 95%. Grade 3 toxicity occurred in 19% of patients, with no treatment-related deaths and no differences in the treatment arms. Conclusion: HACE and HAE are safe and permit tumor control in 95% of patients with progressive liver metastases from midgut endocrine tumors. The 2-year PFS was not higher among patients receiving HACE, not favoring the hypothesis of an additive efficacy of arterial chemotherapy or embolization alone.

ENETS Consensus Guidelines Update for the Management of Distant Metastatic Disease of Intestinal, Pancreatic, Bronchial Neuroendocrine Neoplasms (NEN) and NEN of Unknown Primary Site

“…Locoregional therapies may be considered repetitively during the course of the disease. There is consensus that SIRT is still investigational, and that a comparative trial of SIRT to bland embolization is required, as well as more safety data on long-term tolerability of SIRT to establish this procedure for the management of NEN [14,15,16,17,18]. …”

Systemic chemotherapy with FOLFOX in metastatic grade 1/2 neuroendocrine cancer

“…However, a proportion of G3 NETs are well-differentiated (3). The treatment of G1/G2 NETs has improved, but less so in cases with liver metastases (4–6) compared with disseminated disease, with the demonstration of the efficacy of somatostatin analogs (7,8), targeted therapies (9–11), and, more recently, peptide receptor radionuclide therapy (PRRT) (12–14). After the demonstration of the efficacy of sunitinib and everolimus, these drugs may be considered as the first systemic line of treatment.…”

Comparison of Transarterial Liver-Directed Therapies for Low-Grade Metastatic Neuroendocrine Tumors in a Single Institution

“…Gupta et al analyzed PFS between patients treated with HAE or HACE and found no differences in small intestinal tumors (20.9 vs 23.9 months respectively) or pancreatic islet cell tumors (14.1 vs 18.9 months respectively) 9 . Maire et al found no difference in TTP among 12 patients treated with HAE reporting a median TTP of 24 months and 14 patients treated with HACE reporting a TTP of 19 months 14,18 . Based on these studies, HACE has not been proven to be superior to HAE in increasing time to radiographic progression.…”