Abstract: SUN 137

Association Between Neuroendocrine Tumors Biomarkers and Total 68Ga-Dotatate-Avid Tumor Volume in a Large Cohort of Patients with Neuroendocrine Tumors

Presenter: Amit Tirosh


Abstract


Amit Tirosh*1, Georgios Papadakis2, Corina M Millo3, Samira Mercedes Sadowski4, Peter Herscovitch3, Karel Pacak1, Stephen J Marx5, Lily Yang1, Pavel Nockel2, Jasmine Shell2, Patience Green2, Dhaval Patel6, Naris Nilubol7 and Electron Kebebew6 view more

Amit Tirosh*1, Georgios Papadakis2, Corina M Millo3, Samira Mercedes Sadowski4, Peter Herscovitch3, Karel Pacak1, Stephen J Marx5, Lily Yang1, Pavel Nockel2, Jasmine Shell2, Patience Green2, Dhaval Patel6, Naris Nilubol7 and Electron Kebebew6
1National Institutes of Health, Bethesda, MD, 2National Institutes of Health, 3NIH -Clinical Center, Bethesda, MD, 4University Hospitals of Geneva, Geneva, Switzerland, 5National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, 6National Cancer Institute, NIH, Bethesda, MD, 7National Cancer Institute, Bethesda, MD

Objective
Although biomarkers of neuroendocrine tumors (NETs) have been used for diagnosis and surveillance in NET patients, their clinical utility is unclear. Furthermore, no study has assessed the potential correlation between biochemical biomarkers and NETs burden as determined by quantification of abnormal uptake of new generation radiolabeled somatostatin analogues using PET/CT. The aim of this prospective study was to determine which NET markers were associated with total disease burden.

Methods
We performed a retrospective analysis of a prospective database of patients diagnosed with NETs undergoing 68Ga-DOTATATE imaging. Levels of seven tumor biomarkers were measured at enrollment and included 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 (5HIAA). Total 68Ga-DOTATATE-avid tumor volume (TV) was measured. Both TV and biochemical biomarker levels were logarithmically transformed to induce approximate normality.

Results
Of 232 patients, 112 had pancreatic NET [PNET], 74 had small intestine NET [SINET], 16 had NET of unknown primary [NEToUP] and 30 had NET of other primary. Among patients with PNETs, TV positively correlated with 5HIAA (r=0.3, p=0.01), and among those with metastatic PNETs TV had trend towards positive correlation with 5HIAA (r=0.3, p=0.06) and plasma NSE (r=0.5, p=0.07). Patients with SINETs had positive correlation between TV and CGA (r=0.5, p=0.004) and 5HIAA (r=0.7, p<0.001). Similarly, among subjects with metastatic SINET, TV positively correlated with plasma CGA (r=0.5, p=0.007) and urinary 5HIAA levels (r=0.7, p<0.001). Patients with NEToUP had a positive correlation between TV and urinary 5HIAA levels (r=0.8, p=0.01). Subjects with NET of other primary location had positive correlation between TV and 5HIAA (r=0.6, p=0.04) and plasma gastrin levels showed similar trend (r=0.5, p=0.05), mainly accounted by duodenal gastrinomas (n=7, r=0.9, p=0.009).

Conclusions
Our data supports the use of specific NET markers based on the site of the primary NET in patients. 5HIAA and plasma CGA levels should be used to determine the tumor burden for SINET, 5HIAA for patients with NEToUP, and urinary 5HIAA and plasma NSE levels for patients with PNET.

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