DAXX Mutation Status of Embolization-Treated Neuroendocrine Tumors Predicts Shorter Time to Hepatic Progression

Abstract

PurposeTo identify common gene mutations in patients with neuroendocrine liver metastases (NLM) undergoing transarterial embolization (TAE) and establish relationship between these mutations and response to TAE. Materials and MethodsPatients (n = 51; mean age 61 y; 29 men, 22 women) with NLMs who underwent TAE and had available mutation analysis were identified. Mutation status and clinical variables were recorded and evaluated in relation to hepatic progression-free survival (HPFS) (Cox proportional hazards) and time to hepatic progression (TTHP) (competing risk proportional hazards). Subgroup analysis of patients with pancreatic NLM was performed using Fisher exact test to identify correlation between mutation and event (hepatic progression or death) by 6 months. Changes in mutation status over time and across specimens in a subset of patients were recorded. ResultsTechnical success of TAE was 100%. Common mutations identified were MEN1 (16/51; 31%) and DAXX (13/51; 25%). Median overall survival was 48.7 months. DAXX mutation status (hazard ratio = 6.21; 95% confidence interval [CI], 2.67–14.48; P < .001) and tumor grade (hazard ratio = 3.05; 95% CI, 1.80–5.17; P < .001) were associated with shorter HPFS and TTHP on univariate and multivariate analysis. Median HPFS was 3.6 months (95% CI, 1.7–5.3) for patients with DAXX mutation compared with 8.9 months (95% CI, 6.6–11.4) for patients with DAXX wild-type status. In patients with pancreatic NLMs, DAXX mutation status was associated with hepatic progression or death by 6 months (P = .024). DAXX mutation status was concordant between primary and metastatic sites. ConclusionsDAXX mutation is common in patients with pancreatic NLMs. DAXX mutation status is associated with shorter HPFS and TTHP after TAE.