Characteristics and treatment of patients with G3 gastroenteropancreatic neuroendocrine neoplasms

Abstract

Data on gastroenteropancreatic neuroendocrine neoplasms (NEN) G3 (well-differentiated neuroendocrine tumors (NET G3) and neuroendocrine carcinoma (NEC)) are limited. We retrospectively study patients with NET G3 and NEC from eight European centers. Data examined included clinical and pathological characteristics at diagnosis, therapies and outcomes. Two hundred and four patients were analyzed (37 NET G3 and 167 NEC). Median age was 64 (21-89) years. Tumor origin included pancreas (32%) and colon-rectum (27%). The primary tumor was resected in 82 (40%) patients. Metastatic disease was evident at diagnosis in 88% (liver metastases: 67%). Median Ki-67 index was 70% (30% in NET G3 and 80% in NEC; P!0.001). Median overall survival (OS) for all patients was 23 (95% CI: 18-28) months and significantly higher in NET G3 (99 vs 17 months in NEC; HRZ8.3; P!0.001). Platinum-etoposide first line chemotherapy was administered in 113 (68%) NEC and 12 (32%) NET G3 patients. Disease control rate and progression free survival (PFS) were significantly higher in NEC compared to NET G3 (P!0.05), whereas OS was significantly longer in NET G3 (PZ0.003). Second-and third-line therapies (mainly FOLFIRI and FOLFOX) were given in 79 and 39 of NEC patients; median PFS and OS were 3.0 and 7.6 months respectively after second-line and 2.5 and 6.2 months after third-line chemotherapy. In conclusion, NET G3 and NEC are characterized by significant differences in Ki-67 index and outcomes. While platinum-based chemotherapy is effective in NEC, it seems to have limited value in NET G3.

ENETS Consensus Guidelines Update for the Management of Distant Metastatic Disease of Intestinal, Pancreatic, Bronchial Neuroendocrine Neoplasms (NEN) and NEN of Unknown Primary Site

“…Cisplatin might be replaced by carboplatin, based on the data from the Nordic NEC trial [75]. Although objective remission rates are high (40-67%), the median PFS is limited with 4-6 months [76,77,78]. Second-line systemic therapy options include FOLFOX and FOLFIRI [79,80], while topotecan is not effective in G3 NEC [81].…”

“…Second-line systemic therapy options include FOLFOX and FOLFIRI [79,80], while topotecan is not effective in G3 NEC [81]. Temozolomide-based chemotherapy should be preferably used in pancreatic G3 NET or in gastrointestinal NEC with Ki-67 <55% [67,78]; prospective studies are underway to assess the activity of temozolomide in this setting. Targeted drugs in combination with chemotherapy are under evaluation in clinical trials on G3 NEN.…”

ENETS Consensus Guidelines for High-Grade Gastroenteropancreatic Neuroendocrine Tumors and Neuroendocrine Carcinomas

“…A separation based on the proliferative index (Ki-67 >55%) was shown to have clinical implications regarding response to chemotherapy and prognosis: NEC with Ki-67 >55% responded better to platinum-based chemotherapy and, nevertheless, had a 4 months' shorter median survival than G3 NEN in the lower proliferative range (20-55%) [1]. More recent publications show that morphological differentiation and Ki-67 are able to separate prognostic groups among G3 cases, and therefore a separation of well-differentiated G3 NET from poorly differentiated G3 NEC is emerging [2,3,4]. The exact criteria need to be defined both on the morphological and on the molecular level.…”

Radionuclide imaging and therapy in patients with neuroendocrine tumors

“…2) [14,15]. Недавно выполненные исследования обосновали необходимость разделения груп пы НЭК G3 на подгруппу умеренно диф-ференцированных карцином с высоким индек сом пролиферативной активности и низкодифференцированных крупно-и мелкоклеточного типа [16][17][18]. В первом случае опухоли имеют схожие с НЭК G2 гисто логические характеристики и отлича-ются лучшей выживаемостью (54-99 мес) в сравнении c низкодифференцированными НЭК (11-17 мес) [16][17][18][19][20].…”