Ex Vivo Activity of Cytotoxic Drugs and Targeted Agents in Small Intestinal Neuroendocrine Tumors Abstract #2018

Introduction: Small Intestinal Neuroendocrine Tumours (SI-NETs) are considered to be generally resistant to systemic treatment. To date predictive markers for drug activity are lacking.
Aim(s): To profile SI-NETs with respect to sensitivity ex vivo to standard chemotherapeutics and targeted agents.
Materials and methods: Tumour samples from 27 patients with SI-NETs were analyzed ex vivo using a short-term total cell kill assay. Samples of renal cancer, colorectal cancer (CRC), ovarian cancer, and chronic lymphocytic leukemia (CLL) were included for comparison. For the SI-NET subset, drug sensitivity was analyzed in relation to clinicopathological variables.
Conference: 15th Annual ENETS conference (2018)
Category: Medical treatment - Chemotherapy Somatostatin analogues, Interferon
Presenting Author: Kosmas Daskalakis

To read results and conclusion, please login ...

Further abstracts you may be interested in

#18 Long-acting release octreotide induce complete response in type 1 gastric carcinoid tumors
Introduction: Gastric endocrine tumors (GET) are increasingly recognized due to expanding indications of upper gastrointestinal endoscopy. Often silent and benign, GET may also be aggressive when sporadic and may sometimes mimic the course of gastric adenocarcinoma. Current incidence of GETs is estimated at around 8% of digestive endocrine tumors. Yearly age-adjusted incidence is around 0.2 per population of 100,000. Gastric carcinoids (ECLomas) develop from gastric enterochromaffin-like cells (ECL cells) in response to chronically elevated gastrin. Type 1 tumors (ECLomas in the course of atrophic gastritis) may occur in conditions of achlorhydria secondary to auto-immune atrophic fundic gastritis. It occurs mostly in women and they are non-functioning tumors, typically found during upper GI endoscopy performed for dyspepsia. ECLomas present frequently as multiple polyps, usually < 1 cm in diameter in the gastric fundus. Type 1 tumors are almost exclusively benign lesions with little risk of deep invasion of the gastric parietal wall. The neoplastic ECL cells become progressively dedifferentiated with an increasing number of Ki-67 immunoreactive (IR) cell nuclei. In addition, there is a substantial decrease in argynophil and IR NE cells that can be visualized by conventional methods. ECLomas secondary to hypergastrinemia should be closely followed for signs of clinical and histopathological tumor progression. Such ECLomas deserve early, active, radical surgical treatment.
Traditionally, gastric carcinoid type 1 (GCA1s) are endoscopically or surgically removed, depending on the number, appearance and size of the tumors. Antrectomy, with surgical excision of the majority of the G cells, is thought to facilitate regression of these tumors by removing the source of excessive gastrin secretion; however, the long-term benefits of antrectomy still remain uncertain. Although proton pump inhibitors are effective in reducing hypergastrinemia-induced gastric acid hypersecretion in GCA2, they do not affect ECL-cell hyperplasia, and therefore their role in GCA1 is limited. Moreover, in selected cases, significant reduction of hypergastrinemia does not prevent development of ECL carcinoid, suggesting that, in addition to hypergastrinemia, other pathogenic or genetic factors may be involved. Treatment with somatostatin analogues (SSA) might impede ECL-cell hyperplasia by suppressing gastrin secretion and/or by a direct anti-proliferative effect on ECL cells. Treatment with SSAs in GCA1 leads to a substantial tumor load reduction, with a concomitant decrease of serum gastrin levels. Published data indicate an important anti-proliferative effect of SSA on ECL cells, providing clinical benefit and obviating, at least temporarily, the need for invasive therapies for GCA1. Morphometric studies demonstrated that, while antrectomy specifically decreased the volume of ECL cells versus the total volume of endocrine cells, octreotide reduces the overall endocrine cell volume. Although the number of treated patients is small, it has been suggested that SSA may exert important anti-proliferative effects either directly, by inhibiting ECL-cells proliferation, or indirectly through suppression of gastrin hypersecretion.
Conference: 7th Annual ENETS Conference (2010)
Category: Clinical
Presenting Author: MD Ricardo Caponero
#20 Paraneoplastic antigen Ma2 (PNMA2) auto-antibodies as biomarkers for early small intestine neuroendocrine tumors detection
Introduction: Small intestine neuroendocrine tumors (NETs) comprise well-differentiated NET (benign carcinoid), well-differentiated neuroendocrine carcinoma (malignant carcinoid) and poorly differentiated neuroendocrine carcinoma (NEC). The majority of NET patients have developed liver metastases at the time of diagnosis and surgery is then seldom curative. Novel predictive, diagnostic and prognostic markers are thus needed to improve our capabilities to diagnose and cure these tumors. We have previously identified six novel marker genes for neuroendocrine tumor cells by using Affymetrix microarrays and advanced bioinformatics. One of this markers, the paraneoplastic antigen Ma2 (PNMA2), which is normally expressed only in nervous tissue, can in the process of carcinogenesis be detected in tumors located outside the nervous system. The finding that Ma2 is expressed in small intestine neuroendocrine primary tumors and their metastases made it interesting to screen whether antibodies against Ma2 are present in the serum of NET patients.
Conference: 7th Annual ENETS Conference (2010)
Category: Basic
Presenting Author: PhD Valeria Giandomenico
Authors: Cui T, Elgue G, Li S C, Hurtig M, ...
#26 Molecular imaging of gastroenteropancreatic neuroendocrine tumours with Ga-68 DOTANOC PET/CT and correlation with an immunhistochemical quantification of somatostatin receptors using novel monoclonal and polyclonal antibodies
Introduction: Receptor PET/CT with somatostatin analogues marked with Gallium-68 (SMS-R-PET/CT) is currently the golden standard in diagnosing gastroenteropancreatic neuroendocrine tumors (GEP-NET), which are known for an overexpression of somatostatin receptors (SSTRs).
Conference: 7th Annual ENETS Conference (2010)
Category: Clinical
Presenting Author: Dr Daniel Kaemmerer
#47 Plasma CCN2/connective tissue growth factor is associated with right ventricular dysfunction in Patients with Neuroendocrine Tumors
Introduction: Carcinoid heart disease (CHD) is a known complication of neuroendocrine tumors (NETs), particularly of those arising from the small intestine, appendix and proximal colon (previously known as mid-gut carcinoids). CHD is characterized by right heart fibrotic lesions and has traditionally been defined by the degree of valvular involvement, most commonly in the form of tricuspid regurgitation. Right ventricular (RV) dysfunction due to mural involvement may also be a manifestation. Connective tissue growth factor (CCN2) is upregulated in many fibrotic disorders. Increased tumor expression of CCN2 has been shown in patients with small intestinal NETs associated with peritoneal fibrosis. At present, its role in carcinoid heart disease is unknown.
Conference: 7th Annual ENETS Conference (2010)
Category: Clinical
Presenting Author: Dr. Deidi S Bergestuen
#55 Metronomic combination therapy including temozolamide, bevacizumab and somatostatin analogue for the treatment of malignant gastroenteropancreatic neuroendocrine tumors
Introduction: Malignant gastroenteropancreatic neuroendocrine tumors (GEPNETS), mainly carcinoids, are not considered to be particularly chemotherapy-sensitive to conventional chemotherapeutic schemes. Long-standing evidence suggests these tumors to be highly vascularised and responsive to antiangiogenic strategies. Newest reports demonstrate benefit by the use of temozolamide, an oral alkylating agent similar to intravenous dacarbazine. The DNA repair enzyme O6-alkylguanine–DNA alkyltransferase (AGAT) confers cancer cell resistance to O6-alkylating agents such as temozolamide through its ability to remove methyl/alkyl groups from the O6-position of guanine, thus correcting drug-induced DNA damage.
Conference: 7th Annual ENETS Conference (2010)
Category: Clinical
Presenting Author: DR Anna Koumarianou