Ga-68 DOTANOC PET/CT imaging in detection of primary site in patients with metastatic neuroendocrine tumours of unknown origin and its impact on clinical decision making: experience from a tertiary care centre in India

Background: Neuroendocrine tumours (NETs) are rare, heterogeneous group of tumours which usually originate from small, occult primary sites and are characterized by over-expression of somatostatin receptors (SSTRs). Positron emission tomography/computed tomography (PET/CT) using Ga-68-labeled-somatostatin-analogues have shown superiority over other modalities for imaging of NETs. The objective of the study was to retrospectively evaluate the efficacy of Ga-68 DOTANOC PET/CT imaging in detecting the primary site in patients with metastatic NETs of unknown origin and its impact on clinical decision making in such patients. Methods: Between December 2011 and September 2014, a total of 263 patients underwent Ga-68 DOTANOC PET/CT study in our department for various indications. Out of them, 68 patients (45 males, 23 females; mean age, 54.9 +/- 10.7 years; range, 31-78 years) with histopathologically proven metastatic NETs and unknown primary site (CUP-NET) on conventional imaging, who underwent Ga-68 DOTANOC PET/CT scan as part of their clinical work-up were included for analyses. Histopathology (wherever available) and/or follow-up imaging were taken as reference standard. Quantitative estimation of SSTR expression in the form of maximal standardized uptake value (SUVmax) of detected primary and metastatic sites was calculated. Follow-up data of individual patients was collected through careful survey of hospital medical records and telephonic interviews. Results: Maximum patients presented to our department with hepatic metastasis (50 out of 68 patients) and grade I NETs (>50%). Ga-68 DOTANOC PET/CT scan identified primary sites in 40 out of these 68 patients i.e., in approximately 59% patients. Identified primary sites were: small intestine [19], rectum [8], pancreas [7], stomach [4], lung [1] and one each in rare sites in kidney and prostate. In one patient, 2 primary sites were identified (one each in stomach and duodenum). Mean SUVmax of the detected primary sites was 25.1 +/- 18.0 (median: 16.25; range, 2.1-150). Significant positive correlation was found between SUVmax of detected primary site and SUVmax of the histopathologically proven sites of metastasis (r=0.662; P<0.0001). Based on the findings of the Ga-68 DOTANOC PET/CT scan, 3 out of 40 patients underwent definitive treatment for their primary tumour (1 gastric, 1 ileal and 1 prostatic tumour). One patient was being planned for resection of primary rectal lesion at the time of data-collection. Thirty-six out of 68 patients were started on long-acting somatostatin analogues or chemotherapy or targeted therapy. Two patients underwent multiple cycles of peptide receptor radionuclide therapy (PRRNT) using Y-90 and Lu-177 labeled somatostatin analogues. Conclusions: Our findings indicate that Ga-68 DOTANOC PET/CT is a promising imaging modality in patients with metastatic NETs of unknown origin for detection of the primary site and in guiding their therapeutic management.