Association between Neuroendocrine Tumors Biomarkers and Primary Tumor Site and Disease Type based on Total ⁶⁸Ga-DOTATATE-Avid Tumor Volume Measurements

Abstract

Objective

To determine the association between neuroendocrine tumor (NET) biomarker levels and extent of disease as assessed by ⁶⁸Ga DOTATATE PET/CT imaging.

Design

A retrospective analysis of a prospective database of patients with NETs.

Methods

Fasting plasma chromogranin A (CgA), neuron-specific enolase (NSE), gastrin, glucagon, vasoactive intestinal peptide (VIP) and pancreatic polypeptide (PP), and 24-hour urinary 5-hydroxyindoleacetic acid (5-HIAA) levels were measured. Correlation between biomarkers and total ⁶⁸Ga-DOTATATE-avid tumor volume (TV) was analyzed.

Results

The analysis included 232 patients. In patients with pancreatic NETs (n=112), ⁶⁸Ga-DOTATATE TV correlated with CgA (r=0.6, p=0.001, Spearman). In patients with multiple endocrine neoplasia type 1 (n=39), ⁶⁸Ga-DOTATATE TV correlated with glucagon (r=0.5, p=0.02) and PP levels (r=0.5, p=0.049). In patients with von Hippel-Lindau (n=24), plasma VIP (r=0.5, p=0.02) and PP levels (r=0.7, p<0.001) correlated with ⁶⁸Ga-DOTATATE TV. In patients with small intestine NET (SINET, n=74), ⁶⁸Ga-DOTATATE TV correlated with CgA (r=0.5, p=0.02) and 5-HIAA levels (r=0.7, p<0.001), with 5-HIAA ≥8.1 mg/24h associated with metastatic disease with high positive (81.8%) and negative (85.7%) predictive values (p=0.001). ⁶⁸Ga-DOTATATE TV in patients with NET of unknown primary (n=16) and those with NET of other primary location (n=30) correlated with 5-HIAA levels (r=0.8, p=0.002, and r=0.7, p=0.02, respectively).

Conclusions

Our data supports the use of specific NET biomarkers based on the site of the primary NET and the presence of hereditary syndrome-associated NET. High urinary 5-HIAA levels indicate the presence of metastatic disease in patients with SINET.