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  • Author: Marie-Louise F. Van Velthuysen x
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Anela Blažević, Wouter T Zandee, Gaston J H Franssen, Johannes Hofland, Marie-Louise F van Velthuysen, Leo J Hofland, Richard A Feelders, and Wouter W de Herder

Mesenteric fibrosis (MF) surrounding a mesenteric mass is a hallmark feature of small intestinal neuroendocrine tumours (SI-NETs). Since this can induce intestinal obstruction, oedema and ischaemia, prophylactic resection of the primary tumour and mesenteric mass is often recommended. This study assessed the predictors for mesenteric metastasis and fibrosis and the effect of MF and palliative surgery on survival. A retrospective analysis of 559 patients with pathologically proven SI-NET and available CT-imaging data was performed. Clinical characteristics, presence of mesenteric mass and fibrosis on CT imaging and the effect of palliative abdominal surgery on overall survival were assessed. We found that MF was present in 41.4%. Older age, 5-HIAA excretion ≥67 μmol/24 h, serum CgA ≥121.5 μg/L and a mesenteric mass ≥27.5 mm were independent predictors of MF. In patients ≤52 years, mesenteric mass was less often found in women than in men (39% vs 64%, P = 0.002). Corrected for age, tumour grade, CgA and liver metastasis, MF was not a prognostic factor for overall survival. In patients undergoing palliative surgery, metastasectomy of mesenteric mass or prophylactic surgery did not result in survival benefit. In conclusion, we confirmed known predictors of MF and mesenteric mass and suggest a role for sex hormones as women ≤52 years have less often a mesenteric mass. Furthermore, the presence of MF has no effect on survival in a multivariate analysis, and we found no benefit of metastasectomy of mesenteric mass or prophylactic surgery on overall survival.

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Louis de Mestier, Angela Lamarca, Jorge Hernando, Wouter Zandee, Teresa Alonso-Gordoa, Marine Perrier, Annemieke M E Walenkamp, Bipasha Chakrabarty, Stefania Landolfi, Marie-Louise F. Van Velthuysen, Gursah Kats-Ugurlu, Alejandra Carminoa, Maxime Ronot, Prakash Manoharan, Alejandro Garcia-Alvarez, Tessa Brabander, María Isabel García Gómez-Muriel, Guillaume Cadiot, Anne Couvelard, Jaume Capdevilla, Marianne E Pavel, and Jerome Cros

There is no standardized treatment for grade 3 neuroendocrine tumors (G3 NETs). We aimed to describe the treatments received in patients with advanced G3 NETs and compare their efficacy. Patients with advanced digestive G3 NETs treated between 2010 and 2018 in seven expert centers were retrospectively studied. Pathological samples were centrally reviewed, and radiological data were locally reviewed. We analyzed RECIST-defined objective response (OR), tumor growth rate (TGR) and progression-free survival (PFS) obtained with first- (L1) or second-line (L2) treatments. We included 74 patients with advanced G3 NETs, mostly from duodenal or pancreatic origin (71.6%), with median Ki-67 of 30%. The 126 treatments (L1=74; L2=52) included alkylating-based (n=32), etoposide-platinum (n=22) or adenocarcinoma-like chemotherapy (n=20), somatostatin analogs (n=21), targeted therapies (n=22) and liver-directed therapies (n=7). Alkylating-based chemotherapy achieved the highest OR rate (37.9%) compared to other treatments (multivariable OR 4.22, 95% CI [1.5-12.2]; p=0.008). Adenocarcinoma-like and alkylating-based chemotherapies showed the highest reductions in 3-month TGR (p<0.001 and p=0.008, respectively). The longest median PFS were obtained with adenocarcinoma-like chemotherapy (16.5 months [9.0-24.0]) and targeted therapies (12.0 months [8.2-15.8]), while the shortest PFS were observed with somatostatin analogues (6.2 months [3.8-8.5]) and etoposide-platinum chemotherapy (7.2 months [5.2-9.1]). Etoposide-platinum CT achieved shorter PFS than adenocarcinoma-like (multivariable HR 3.69 [1.61-8.44], p=0.002) and alkylating-based chemotherapies (multivariable HR 1.95 [1.01-3.78], p=0.049). Overall, adenocarcinoma-like and alkylating-based chemotherapies may be the most effective treatments for patients with advanced G3 NETs regarding OR and PFS. Etoposide-platinum chemotherapy has poor efficacy in this setting.