Should mesenteric tumor deposits be included in staging of well-differentiated small intestine neuroendocrine tumors?

4104 Background: Oxaliplatin-based regimens have shown promising antitumor activity in digestive neuroendocrine tumors (NETs), however the available data are limited. Our aim was to assess the tumor response and survival in a large series of patients treated with oxaliplatin and 5-fluorouracil (FOLFOX) for advanced digestive NETs.Oxaliplatin-based regimens have shown promising antitumor activity in digestive neuroendocrine tumors (NETs), however the available data are limited. Our aim was to assess the tumor response and survival in a large series of patients treated with oxaliplatin and 5-fluorouracil (FOLFOX) for advanced digestive NETs. Methods: All patients with advanced well-differentiated digestive NETs treated with at least 3 cycles of FOLFOX between 2004 and 2018 in 12 centers of the French GTE, were retrospectively included. Best response according to the RECIST 1.1 criteria, progression-free survival (PFS) and overall survival (OS) were evaluated. The prognostic factors for PFS were investigated by multivariate analysis using a Cox proportional hazard model including variables with a p value ⩽ 0.20 in univariate analysis. Results: One hundred and forty-nine patients were included. Primary tumor location was pancreas (n = 88), small intestine (n = 37), stomach (n = 7), rectum (n = 4) and unknown without lung tumor at CT scan (n = 13). Partial response rate was of 31% for pancreatic NETs, 13% for small intestine NETs, 14% for gastric NETs, 25% for rectal NETs and 38% for unknown primary NETs. Median PFS were, respectively, 9, 9, 14, 4 and 6 months, and median OS were 30, 28, 31, 25 and 15 months. Significant poor prognostic factors for PFS after FOLFOX in digestive NETs were: progressive disease (HR = 2.5, p = 0.018), hepatic involvement > 50% (HR = 1.8, p = 0.009), prior targeted therapy (HR = 1.5, p = 0.048) and rectal primary tumor (HR = 4.2, p = 0.01). Among pancreatic NETs, the 9 insulinomas had a 22 months PFS versus 9 months for the others (p = 0.025), and serum glucose normalization was obtained in 8 out of 9 cases. Conclusions: FOLFOX has a promising clinical activity for gastroenteropancreatic NETs, especially in insulinomas.

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Faculty Opinions recommendation of Mesenteric tumor deposits in midgut small intestinal neuroendocrine tumors are a stronger indicator than lymph node metastasis for liver metastasis and poor prognosis.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.726786900.793528248 ◽

2017 ◽

Author(s):

Noam Harpaz ◽

Alexandros Polydorides

Keyword(s):

Lymph Node ◽

Liver Metastasis ◽

Lymph Node Metastasis ◽

Neuroendocrine Tumors ◽

Poor Prognosis ◽

Mesenteric Tumor ◽

Node Metastasis ◽

Small Intestinal

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Prospective study of dynamic whole-body 68Ga-DOTATOC-PET/CT acquisition in patients with well-differentiated neuroendocrine tumors

Scientific Reports ◽

10.1038/s41598-021-83965-9 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Philippe Thuillier ◽

David Bourhis ◽

Jean Philippe Metges ◽

Romain Le Pennec ◽

Karim Amrane ◽

...

Keyword(s):

Neuroendocrine Tumors ◽

Linear Relation ◽

Whole Body ◽

Pet Ct ◽

Non Linear ◽

Well Differentiated ◽

Analog Systems ◽

Pet System ◽

Dynamic Acquisition ◽

Linear Regressions

AbstractTo present the feasibility of a dynamic whole-body (DWB) 68Ga-DOTATOC-PET/CT acquisition in patients with well-differentiated neuroendocrine tumors (WD-NETs). Sixty-one patients who underwent a DWB 68Ga-DOTATOC-PET/CT for a histologically proven/highly suspected WD-NET were prospectively included. The acquisition consisted in single-bed dynamic acquisition centered on the heart, followed by the DWB and static acquisitions. For liver, spleen and tumor (1–5/patient), Ki values (in ml/min/100 ml) were calculated according to Patlak's analysis and tumor-to-liver (TLR-Ki) and tumor-to-spleen ratios (TSR-Ki) were recorded. Ki-based parameters were compared to static parameters (SUVmax/SUVmean, TLR/TSRmean, according to liver/spleen SUVmean), in the whole-cohort and according to the PET system (analog/digital). A correlation analysis between SUVmean/Ki was performed using linear and non-linear regressions. Ki-liver was not influenced by the PET system used, unlike SUVmax/SUVmean. The regression analysis showed a non-linear relation between Ki/SUVmean (R2 = 0.55,0.68 and 0.71 for liver, spleen and tumor uptake, respectively) and a linear relation between TLRmean/TLR-Ki (R2 = 0.75). These results were not affected by the PET system, on the contrary of the relation between TSRmean/TSR-Ki (R2 = 0.94 and 0.73 using linear and non-linear regressions in digital and analog systems, respectively). Our study is the first showing the feasibility of a DWB 68Ga-DOTATOC-PET/CT acquisition in WD-NETs.

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FAS and Subsequent Therapies in Pancreatic Neuroendocrine Tumors

Neuroendocrinology ◽

10.1159/000514339 ◽

2021 ◽

Author(s):

Jane E. Rogers ◽

Michael Lam ◽

Daniel M. Halperin ◽

Cecile G. Dagohoy ◽

James C. Yao ◽

...

Keyword(s):

Neuroendocrine Tumors ◽

Cox Regression ◽

Progression Free Survival ◽

Pancreatic Neuroendocrine Tumors ◽

Free Survival ◽

Prior Therapy ◽

Well Differentiated ◽

Grade 3 ◽

Line Of Therapy

We evaluated outcomes of treatment with 5-fluorouracil (5-FU), doxorubicin, and streptozocin (FAS) in well-differentiated pancreatic neuroendocrine tumors (PanNETs) and its impact on subsequent therapy (everolimus or temozolomide). Advanced PanNET patients treated at our center from 1992 to 2013 were retrospectively reviewed. Patients received bolus 5-FU (400 mg/m2), streptozocin (400 mg/m2) (both IV, days 1-5) and doxorubicin (40 mg/m2 IV, day 1) every 28 days. Overall response rate (ORR) was assessed using RECIST version 1.1. Of 243 eligible patients, 220 were evaluable for ORR, progression-free survival (PFS), and toxicity. Most (90%) had metastatic, nonfunctional PanNETs; 14% had prior therapy. ORR to FAS was 41% (95% confidence interval [CI]: 36-48%). Median follow-up was 61 months. Median PFS was 20 (95% CI: 15-23) months; median overall survival (OS) was 63 (95% CI: 60-71) months. Cox regression analyses suggested improvement with first-line vs subsequent lines of FAS therapy. Main adverse events ≥ grade 3 were neutropenia (10%) and nausea/vomiting (5.5%). Dose reductions were required in 32% of patients. Post-FAS everolimus (n=108; 68% second line) had a median PFS of 10 (95% CI: 8-14) months. Post-FAS temozolomide (n=60; 53% > fourth line) had an ORR of 13% and median PFS of 5.2 (95% CI: 4-12) months. In this largest reported cohort of PanNETs treated with chemotherapy, FAS demonstrated activity without significant safety concerns. FAS did not appear to affect subsequent PFS with everolimus; this sequence is being evaluated prospectively. Responses were noted with subsequent temozolomide-based regimens although PFS was possibly limited by line of therapy.

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Molecular Pathology of Well-Differentiated Pulmonary and Thymic Neuroendocrine Tumors: What Do Pathologists Need to Know?

Endocrine Pathology ◽

10.1007/s12022-021-09668-z ◽

2021 ◽

Vol 32 (1) ◽

pp. 154-168 ◽

Cited By ~ 1

Author(s):

Marco Volante ◽

Ozgur Mete ◽

Giuseppe Pelosi ◽

Anja C. Roden ◽

Ernst Jan M. Speel ◽

...

Keyword(s):

Neuroendocrine Tumors ◽

Young Patients ◽

Carcinoid Tumors ◽

Neuroendocrine Neoplasms ◽

Grey Zone ◽

Cell Hyperplasia ◽

Ki 67 ◽

Familial Form ◽

Well Differentiated ◽

Neuroendocrine Carcinomas

AbstractThoracic (pulmonary and thymic) neuroendocrine tumors are well-differentiated epithelial neuroendocrine neoplasms that are classified into typical and atypical carcinoid tumors based on mitotic index cut offs and presence or absence of necrosis. This classification scheme is of great prognostic value but designed for surgical specimens, only. Deep molecular characterization of thoracic neuroendocrine tumors highlighted their difference with neuroendocrine carcinomas. Neuroendocrine tumors of the lung are characterized by a low mutational burden, and a high prevalence of mutations in chromatin remodeling and histone modification-related genes, whereas mutations in genes frequently altered in neuroendocrine carcinomas are rare. Molecular profiling divided thymic neuroendocrine tumors into three clusters with distinct clinical outcomes and characterized by a different average of copy number instability. Moreover, integrated histopathological, molecular and clinical evidence supports the existence of a grey zone category between neuroendocrine tumors (carcinoid tumors) and neuroendocrine carcinomas. Indeed, cases with well differentiated morphology but mitotic/Ki-67 indexes close to neuroendocrine carcinomas have been increasingly recognized. These are characterized by specific molecular profiles and have an aggressive clinical behavior. Finally, thoracic neuroendocrine tumors may arise in the background of genetic susceptibility, being MEN1 syndrome the well-defined familial form. However, pathologists should be aware of rarer germline variants that are associated with the concurrence of neuroendocrine tumors of the lung or their precursors (such as DIPNECH) with other neoplasms, including but not limited to breast carcinomas. Therefore, genetic counseling for all young patients with thoracic neuroendocrine neoplasia and/or any patient with pathological evidence of neuroendocrine cell hyperplasia-to-neoplasia progression sequence or multifocal disease should be considered.

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