Role of contrast-enhanced ultrasound to define prognosis and predict response to biotherapy in pancreatic neuroendocrine tumors

J Endocrinol Invest. 2017 Dec;40(12):1373-1380. doi: 10.1007/s40618-017-0723-x. Epub 2017 Jun 30.


Purpose: The incidence of neuroendocrine tumors (NETs) is progressively increasing. Most cases arise from the digestive system, where ileum, rectum and pancreas represent the commonest site of origin. Liver metastases are frequently detected at diagnosis or during the follow-up. Contrast-enhanced ultrasound (CEUS) is used in patients with pancreatic NETs (P-NETs) and liver metastases from P-NET but its role has not been standardized. The aim of this retrospective study was to investigate CEUS in patients with P-NETs and liver metastases from P-NET both as prognostic factor and predictor of response to therapy with somatostatin analogues (SSAs).

Methods: CEUS was performed at the diagnosis of NET and 3, 6 and 12 months after the beginning of SSAs. CEUS pattern was compared with contrast-enhanced computed tomography (CT) pattern.

Results: There was a significant association between CEUS and CT pattern (X 2 = 79.0; p < 0.0001). A significant association was found between CEUS pattern and Ki-67 index (X 2 = 24.6; p < 0.0001). The hypervascular homogeneous CEUS typical pattern was associated with low tumor grading (G1 or G2) (X 2 = 24.0; p < 0.0001). CEUS pattern changed from hypervascular homogeneous in baseline to hypovascular/hypervascular inhomogeneous after SSA therapy, with a significant association between tumor response at CT scan and appearance of hypervascular inhomogeneous pattern at CEUS evaluation (6 months: X 2 = 57.0; p < 0.0001; 12 months: X 2 = 49.8; p < 0.0001).

Conclusions: In patients with P-NET, CEUS pattern correlates with tumor grading, being homogeneous in G1-G2 but not in G3 tumors. After therapy with SSAs, CEUS is predictive of response to SSAs. These findings seem to support a role of CEUS as prognostic and predictive factor of response.

Keywords: CEUS; Neuroendocrine tumors; Prediction of response; Prognosis; Somatostatin analogues.

MeSH terms

  • Adult
  • Aged
  • Biological Therapy*
  • Contrast Media*
  • Female
  • Follow-Up Studies
  • Human Growth Hormone / therapeutic use*
  • Humans
  • Liver Neoplasms / diagnostic imaging
  • Liver Neoplasms / drug therapy
  • Liver Neoplasms / secondary*
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Neuroendocrine Tumors / diagnostic imaging
  • Neuroendocrine Tumors / drug therapy
  • Neuroendocrine Tumors / pathology*
  • Pancreatic Neoplasms / diagnostic imaging
  • Pancreatic Neoplasms / drug therapy
  • Pancreatic Neoplasms / pathology*
  • Prognosis
  • Retrospective Studies
  • Ultrasonography / methods*


  • Contrast Media
  • Human Growth Hormone