Current practice in approaching controversial diagnostic and therapeutic topics in gastroenteropancreatic neuroendocrine neoplasm management : Belgian multidisciplinary expert discussion based on a modified Delphi method

Background and study aims: Neuroendocrine neoplasms (NENs) are relatively rare, with marked clinical and biological heterogeneity. Consequently, many controversial areas remain in diagnosis and optimal treatment stratification for NEN patients. We wanted to describe current clinical practice regarding controversial NEN topics and stimulate critical thinking and mutual learning among a Belgian multidisciplinary expert panel Patients and methods: A 3-round, Delphi method based project, coordinated by a steering committee (SC), was applied to a predefined multidisciplinary NEN expert panel studying the following controversial topics : factors guiding therapeutic decision making, the use of somatostatin analogues (SSA) in adjuvant setting, the interference between non-radioactive and radioactive SSAs, challenging small intestine neuroendocrine tumor (NET) cases, the approach of the carcinoid syndrome, the role of chemotherapy in well differentiated NET, the relevance of NET G3 and neuroendocrine carcinoma subclassification and the role of imaging techniques in NEN management. Results: A high level of consensus exists regarding the necessary diagnostic work-up, use of imaging techniques and interference between non-radioactive and radioactive SSAs. However, the prognostic impact of tumor functionality might be overrated and adequate diarrhea differential diagnostic work-up in these patients is underused. Significant differences are seen between individual experts and centers regarding treatment preferences both on the treatment modality level, as well as the choice of specific drugs (e.g. chemotherapy regimen). Conclusions: A Delphi-like multi-round expert discussion proves useful to boost critical thinking and discussion among experts of different background, as well as to describe current clinical practice and stimulate mutual learning in the absence of high-level scientific guidance

Comparison of 111in-[DTPA]octreotide versus non carrier added 177Lu-[DOTA,Tyr3]-octreotate efficacy in patients with GEP-NET treated intra-arterially for liver metastases

Aim: In patients with progressive, metastatic neuroendocrine tumors (NET), intra-arterial radionuclide infusions with high activities of 111In-[DTPA]-octreotide and more recently with non-carrier added (nca) 177Lu-[DOTA, Tyr3]-octreotate have been performed with encouraging results. However, the affinity profiles (IC50) of these radiopeptides for human sst2 receptors are markedly different (111In-[DTPA]-octreotide, 22 ± 3.6 nM and nca 177Lu-[DOTA,Tyr3]-octreotate, 1.5 ± 4.0 nM). The total administered activity is determined by organ dose limits (kidneys and bone marrow), and our aim therefore was to compare and evaluate the therapeutic efficacy of both radiopeptides in metastatic NETs. Methods: Thirty patients with gastroenteropancreatic (GEP) somatostatinpositive NETs with liver metastases confirmed on biopsy and 111In-pentetreotide scan were included. They were treated with 111In-[DTPA]-octreotide (n = 17) or nca 177Lu-[DOTA,Tyr3]-octreotate (n = 13). Blood samples were collected 2, 4, 8, and 24 hours postadministration to calculate residence time in blood and in red marrow. The maximum percentage uptake in organs and tumors was estimated by region of interest analysis, and tumor dosimetry calculations were performed using OLINDA/EXM/1.0 software. Results: nca177Lu-[DOTA,Tyr3]-octreotate blood radioactivity, expressed as a percentage of the injected dose, was significantly lower than 111In-[DTPA]-octreotide (P < 0.05), as clearly depicted from the time-activity curves; the background-corrected tumor uptake was significantly higher than 111In-[DTPA]-octreotide but without any significant difference in other organs (spleen, kidneys, and liver). Conclusions: Using 177Lu-[DOTA,Tyr3]-octreotate, a 3-fold higher absorbed dose to tumor tissue was achieved compared with 111In-[DTPA] octreotide. Residence time of nca 177Lu-[DOTA,Tyr3]-octreotate results in a significantly higher absorbed dose to bone marrow compared with 111In-[DTPA]-octreotide. However, a drawback of 111In-[DTPA]-octreotide therapy is that the number of administrations would need to be almost doubled to achieve an equal therapeutic outcome as compared with 177Lu-[DOTA, Tyr3]-octreotate. © 2015 Wolters Kluwer Health, Inc. All rights reserved

Current practice in approaching controversial diagnostic and therapeutic topics in gastroenteropancreatic neuroendocrine neoplasm management. Belgian multidisciplinary expert discussion based on a modified Delphi method.

BACKGROUND AND STUDY AIMS: Neuroendocrine neoplasms (NENs) are relatively rare, with marked clinical and biological heterogeneity. Consequently, many controversial areas remain in diagnosis and optimal treatment stratification for NEN patients. We wanted to describe current clinical practice regarding controversial NEN topics and stimulate critical thinking and mutual learning among a Belgian multidisciplinary expert panel. PATIENTS AND METHODS: A 3-round, Delphi method based project, coordinated by a steering committee (SC), was applied to a predefined multidisciplinary NEN expert panel studying the following controversial topics : factors guiding therapeutic decision making, the use of somatostatin analogues (SSA) in adjuvant setting, the interference between non-radioactive and radioactive SSAs, challenging small intestine neuroendocrine tumor (NET) cases, the approach of the carcinoid syndrome, the role of chemotherapy in well differentiated NET, the relevance of NET G3 and neuroendocrine carcinoma subclassification and the role of imaging techniques in NEN management. RESULTS: A high level of consensus exists regarding the necessary diagnostic work-up, use of imaging techniques and interference between non-radioactive and radioactive SSAs. However, the prognostic impact of tumor functionality might be overrated and adequate diarrhea differential diagnostic work-up in these patients is underused. Significant differences are seen between individual experts and centers regarding treatment preferences both on the treatment modality level, as well as the choice of specific drugs (e.g. chemotherapy regimen). CONCLUSIONS: A Delphi-like multi-round expert discussion proves useful to boost critical thinking and discussion among experts of different background, as well as to describe current clinical practice and stimulate mutual learning in the absence of high-level scientific guidance