To Örebro University

In Sweden, approximately 400-500 individuals are diagnosed yearly with a neuroendocrine tumor (NET). Primary tumors can arise from all organs in the body, but most commonly from the gastrointestinal (GI) tract (75%) or the lungs (20%). The small intestine (Si) is the most common primary site (35%). The tumor is often diagnosed when metastatic disease has already developed (85% of cases), and spreading is mostly located in the abdominal lymph nodes or liver. Extra-abdominal metastases may also occur. Unlike other tumors, patients with NET and metastatic disease survive for many years. The tumor is diagnosed through a combination of disease-specific biomarkers, radiology and histopathological examination from a biopsy or surgical specimen. 68Ga-DOTATOC-positron emission tomography (PET) and concomitant diagnostic computed tomography (CT) have frequently been used in recent years, due to the high specificity and sensitivity for NET cells.

The aim of this thesis was to evaluate the clinical utility of a commonly used biomarker in patient serum, and to assess the prevalence and importance of metastases to abdominal lymph nodes and extra-abdominal distant metastatic sites with a specific interest in Si-NET and pancreatic NET (pan-NET). Finally, the prognostic impact of disease burden from bone metastases in patients with Si-NET has also been studied.

The first study included one of the most used biomarkers in NET disease and the association between changes in serum 5-HIAA and tumor burden on CT/MRI scan. We also validated the clinical utility of 5-HIAA analysis in patient serum compared to traditional urinary measurement establishing the use of serum analysis at Örebro University Hospital, being less time-consuming and more convenient for patients. In the second study, we assessed the prognostic role of risk factors in patients with locoregional Si-NET, with a specific interest in recurrent disease, and also aimed to define a surgical cut-off for harvested mesenteric lymph nodes to accurately stage these tumors. A minimum of five harvested mesenteric lymph nodes appears to be critical in surgical management. In the third study, we further studied the prevalence of extra-abdominal metastases evident on 68Ga-DOTATOC-PET/CT. The study concluded that metastases to the bones, left supraclavicular lymph nodes, heart, orbit and breast and, in patients with Si-NET, to the pancreas probably occurred more frequently than previously described. Patients with Si-NET harboured extra-abdominal metastases both more frequently and in different locations compared to patients with pan-NET. In the fourth study, we evaluated the prognostic role and clinical symptoms of bone metastases (BM) in patients with Si-NET. In conclusion, the presence of BM, higher extent of BM (>5BM) and synchronous BM at NET diagnosis were independent negative prognostic factors of survival.