Therapeutic monitoring of gastroenteropancreatic neuroendocrine tumors: the challenges ahead

Background: Gastroenteropancreatic neuroendocrine tumors (NETs), a heterogeneous family of tumors arising in a variety of anatomic sites, are generally well differentiated and often metastatic at diagnosis. Morphologic and functional imaging modalities have vastly improved the understanding and diagnosis of NETs. However, use of conventional imaging techniques and response criteria to assess treatment response is often complicated by the clinical course and cytostatic nature of oncologic treatments for NETs.

Materials and methods: The means of therapeutic monitoring discussed in this review were based on a PubMed search of the medical literature and on the clinical expertise of the authors.

Results: Morphology-based criteria for assessing tumor response in general oncology are presented, along with their limitations for assessing response in gastrointestinal and pancreatic NETs. Functional imaging and preliminary response criteria incorporating functional imaging are presented as possible solutions to monitoring treatment response in NETs.

Conclusions: Morphology-based criteria to assess tumor response have limitations for NETs, which are often slow growing and frequently demonstrate low response rates when based on conventional radiological criteria. Furthermore, many NET treatments do not induce cytotoxic effects despite demonstrated clinical benefit. Novel imaging techniques are available which have the potential to measure changes in tumor physiology and metabolism. These include (68)Ga-labelled somatostatin analogs for PET/CT-based monitoring of NET, molecular imaging with PET tracers that are not based on somatostatin receptor targeting, and functional MRI. These techniques should be explored as options for monitoring treatment in patients with NET.