Comparison of the Impact of 68Ga-DOTATATE and 18F-FDG PET/CT on Clinical Management in Patients with Neuroendocrine Tumors.

This study aimed to assess the clinical impact of 68Ga-DOTATATE and 18F-FDG with respect to the management plan and to evaluate the prognostic value of both tracers. METHODS: A total of 104 patients (55 male and 49 female; median age, 58 y; range, 20-90 y) with histologically proven neuroendocrine tumors (NETs) underwent both 68Ga-DOTATATE and 18F-FDG PET/CT. Twenty-eight patients (26.9%) had poorly differentiated tumors, and 76 (73.1%) had well-differentiated tumors. PET/CT results and SUVs were compared with prognostic factors such as histologic grade (G1, G2, or G3, for low-grade [well differentiated], intermediate-grade [moderately differentiated], and high-grade [poorly differentiated], respectively), chromogranin A, and proliferation index (Ki-67). RESULTS: The 68Ga-DOTATATE and 18F-FDG PET/CT findings were discordant in 65 patients (62.5%) and concordant in 39 patients (37.5%). The results changed the therapeutic plan in 84 patients (80.8%). In 22 patients (21.1%), decision making was based on the 18F-FDG findings; in 32 (30.8%), on the findings with both radiotracers; and in 50 (48.1%), on the 68Ga-DOTATATE findings. The most frequent management decision based on 18F-FDG was initiation of chemotherapy (10 patients, 47.6%). The most common treatment decision due to 68Ga-DOTATATE was initiation of peptide receptor radionuclide therapy (14 patients, 27.4%). In 11 (39.2%) of 28 patients with poorly differentiated NETs, the management decision was based on only the 18F-FDG results. For 68Ga-DOTATATE, SUVmax was higher for G1 tumors and lower for G3 tumors (P = 0.012). However, no significant differences in 18F-FDG-derived SUVs were observed between different grades (P = 0.38). The Mann-Whitney test showed significant differences in 68Ga-DOTATATE SUVmax between tumors with a Ki-67 of less than 5% and tumors with a Ki-67 of more than 5% (P = 0.004), without significance differences in 18F-FDG SUVmax Log-rank analysis showed statistically significant differences in survival for patients with bone metastasis versus soft-tissue or no metastasis for both 18F-FDG (P = 0.037) and 68Ga-DOTATATE (P = 0.047). Overall survival declined rapidly with increasing grade (P = 0.001), at an estimated 91 mo for G1, 59 mo for G2, and 48 mo for G3. CONCLUSION: 18F-FDG PET/CT had no clinical impact on G1 NETs and a moderate impact on G2 NETs. However, in poorly differentiated NETs, 18F-FDG PET/CT plays a significant clinical role in combination with 68Ga-DOTATATE. 68Ga DOTATATE SUVmax relates to grade and Ki-67 and can be used prognostically.

Predictive factors of antiproliferative activity of octreotide LAR as first-line therapy for advanced neuroendocrine tumours.

BACKGROUND: The antiproliferative activity of octreotide LAR in neuroendocrine tumours (NETs) has been demonstrated by small retrospective studies and confirmed by a prospective phase III trial (PROMID). However, there are limited data about the duration and predictors of response. The aim of our retrospective study was to determine the time to radiological progression (TTRP) of disease and the factors that were associated with better response. METHODS: A total of 254 treatment naïve patients with advanced NETs and positive somatostatin receptor scintigraphy were included. Mean follow-up period was 42 months. RESULTS: The location of primary was in the small bowel in 204, pancreas in 22, lungs in 14, rectum in 7 and unknown in 7 patients. Most tumours were well-differentiated, G1 (58%) and G2 (23%). The majority of patients commenced octreotide LAR due to functional symptoms (57%), radiological progression (10%) or in the presence of asymptomatic and stable disease on the basis of data from the PROMID trial (18.5%). Partial response occurred in 5%. For all patients, the median TTRP was 37 months (95% confidence interval, CI: 32-52 months). There was a statistically significant shorter TTRP in patients with pancreatic tumours, liver metastases and intermediate grade tumours. Extremely raised (>10 times the upper limit of normal) baseline chromogranin A levels were associated with an unfavourable outcome. In contrast, male sex, carcinoid heart disease and initiation of treatment in the presence of stable disease were predictive of a better response. Age, extra-hepatic metastases, presence of mesenteric desmoplasia, previous resection and functional status of the primary tumour did not affect response. CONCLUSIONS: The duration of the antiproliferative effect of octreotide LAR seems to be longer than previously reported. This study has identified several predictors of response in a large cohort of patients with NETs on somatostatin analogue therapy.

Case report of multimodality treatment for metastatic parathyroid hormone-related peptide-secreting pancreatic neuroendocrine tumour.

AIMS AND BACKGROUND: Hypercalcaemia due to metastatic parathyroid hormone-related peptide-secreting pancreatic neuroendocrine tumour is challenging to manage and requires a multimodality approach. METHODS: We present a case of a woman undergoing liver transplantation for metastatic parathyroid hormone-related peptide-secreting pancreatic neuroendocrine tumour. RESULTS: A young woman with a history of parathyroid hormone-related peptide-secreting pancreatic neuroendocrine tumour (Ki-67 5%) removed in 1998 developed bilobar liver metastases in 2004 and underwent repeated transarterial embolisations of liver tumour and therapy with somatostatin analogue. In view of symptomatic hypercalcaemia refractory to medical therapy, she underwent liver transplantation in 2006. In 2012, follow-up imaging showed a 3-cm hypervascular lesion in the posterior wall of the stomach, which was confirmed on endoscopic ultrasound and on gallium-68-octreotate positron emission tomography scan. A gastric wall resection was performed in February 2013, and biopsies showed a neuroendocrine tumour of intermediate grade (Ki-67 15%). In June 2013, a restaging imaging showed a 2.4 cm lesion in the left breast, which was reported as a primary breast cancer on biopsies, and a 14-mm tissue lesion anterior to the gastric antrum. The patient underwent surgical excision of the breast cancer followed by hormone treatment and radiotherapy. She had surgical removal of the gastric recurrence with adjuvant chemotherapy postoperatively. CONCLUSIONS: Hypercalcaemia related to parathyroid hormone-related peptide-secreting neuroendocrine tumour can be life-threatening, and liver transplantation may be a viable option in case of liver only diffuse neuroendocrine metastases refractory to other therapies. The risk of tumour recurrence remains a significant clinical problem after liver transplantation, and only a few patients might be considered tumour-free 5 years after liver transplantation.