Management and Prognosis of Localized Duodenal Neuroendocrine Neoplasms

Gay-Chevallier, Servane; Mestier, Louis de; Périnel, Julie; Forestier, Julien; Hervieu, Valérie; Ruszniewski, Philippe; Millot, Ingrid; Valette, Pierre-Jean; Pioche, Mathieu; Lombard‐Bohas, Catherine; Subtil, Fabien; Adham, Mustapha; Walter, Thomas

doi:10.1159/000508102

Cited by 14 publications

(7 citation statements)

References 39 publications

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“… 6 , 7 Genetic alterations may explain their clinical heterogeneity, divergence for treatment response, and prognosis. 8 However, more studies are need to provide further details on genetic characteristics of GI‐NENs. Genetic alterations, identified through next‐generation sequencing (NGS), may provide the unprecedented opportunity to investigate genomic differences in the various histological types of GI‐NENs.…”

Section: Introductionmentioning

confidence: 99%

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Genetic alterations of GI‐NECs involving three main signaling pathways

et al. 2023

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Background Gastrointestinal (GI)‐neuroendocrine neoplasms (NENs) are subclassified in neuroendocrine tumors (NETs), neuroendocrine carcinomas (NECs), and mixed neuroendocrine–non‐neuroendocrine neoplasms (MiNENs). The genetic characteristics of GI‐NEN has been a hot issue in recent years, but more studies are needed to provide further details. This study aims to provide additional data about genomic characteristics of GI‐NENs and the genetic differences between NETs and NECs. Patients and Methods Thirteen samples were selected for next‐generation sequencing (NGS) analysis with a 425‐gene panel. Microsatellite instability (MSI) and tumor mutational burden (TMB) were calculated as well as immunohistochemistry (IHC) was used to test for protein expression. Results Genetic alterations were very common in NECs, but rare in NETs. The average TMB of NETs and NECs was 2.3 and 6.9, respectively. The TMB of NECs was significantly higher compared to NETs. The TP53 mutation rate was significantly higher in NECs than in NETs (100% vs. 20%), other mutations involved MTOR (n = 2, 15.4%), DDR2 (n = 3, 23.1%), ERBB4 (n = 1, 7.7%), BRCA1 (n = 1, 7.7%), BRCA2 (n = 1, 7.7%), ATM (n = 1, 7.7%), and SMAD4 (n = 1, 7.7%). Deep loss of SMAD4 (1/3, 33.3%), SDHB (1/3, 33.3%), RB1 (1/3, 33.3%), and BRCA2 (1/3, 33.3%), high‐level amplification of CRKL (1/3, 33.3%), CCNE1(1/3, 33.3%), and MCL1(1/3, 33.3%) were found in NECs. The integrated analysis found these genetic alterations frequently involve DNA repair and cell cycle, PI3K/AKT/mTOR and TGF‐β/SMAD4 signaling pathways. Conclusion Genetic alterations were very common in NECs and rare in NETs, and frequently involved three main signaling pathways. NEC patients harboring these genetic alterations may benefit from targeted therapy and PD‐1/PD‐L1 immunotherapy.

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Section: Introductionmentioning

confidence: 99%

“…A few noteworthy findings had indicated the possible genomic characteristics of GI‐NENs 6,7 . Genetic alterations may explain their clinical heterogeneity, divergence for treatment response, and prognosis 8 . However, more studies are need to provide further details on genetic characteristics of GI‐NENs.…”

Section: Introductionmentioning

confidence: 99%

Genetic alterations of GI‐NECs involving three main signaling pathways

et al. 2023

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“…Importantly, they are more frequently associated with neurofibromatosis type 1 (NF1) and tend to occur in younger individuals [4]. Although most studies showed a lack of significant prognostic differences between Amp-NENs and non-Amp-Duo-NENs, especially when only well-differentiated neuroendocrine tumors (NETs) were considered [3][4][5][6][7][8][9][10], Amp-NENs were shown to display a more aggressive behavior with a trend towards reduced overall survival in some studies [11][12][13][14][15]. In addition, there are several histologic differences between Amp-NENs and non-Amp-NENs.…”

Section: Introductionmentioning

confidence: 99%

Ampullary Neuroendocrine Neoplasms: Identification of Prognostic Factors in a Multicentric Series of 119 Cases

et al. 2022

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Neuroendocrine neoplasms (NENs) of the major and minor ampulla are rare diseases with clinico-pathologic features distinct from non-ampullary-duodenal NENs. However, they have been often combined and the knowledge on prognostic factors specific to ampullary NENs (Amp-NENs) is limited. The aim of this study was to identify factors associated with metastatic potential and patient prognosis in Amp-NENs. We clinically and histologically investigated an international series of 119 Amp-NENs, comprising 93 ampullary neuroendocrine tumors (Amp-NETs) and 26 neuroendocrine carcinomas (Amp-NECs). Somatostatin-producing tubulo-acinar NET represented the predominant Amp-NET histologic subtype (58 cases, 62%, 12 associated with type 1 neurofibromatosis). Compared to Amp-NETs, Amp-NECs arose in significantly older patients and showed a larger tumor size, a more frequent small vessel invasion, a deeper level of invasion and a higher rate of distant metastasis, and, importantly, a tremendously worse disease-specific patient survival. In Amp-NETs, the WHO grade proved to be a strong predictor of disease-specific survival (hazard ratio: 12.61, p < 0.001 for G2 vs G1), as well as patient age at diagnosis > 60 years, small vessel invasion, pancreatic invasion, and distant metastasis at diagnosis. Although nodal metastatic disease was not associated with survival by itself, patients with > 3 metastatic lymph nodes showed a worse outcome in comparison with the remaining Amp-NET cases with lymphadenectomy. Tumor epicenter in the major ampulla, small vessel invasion, and tumor size > 16 mm were independent predictors of nodal metastases in Amp-NETs. In conclusion, we identified prognostic factors, which may eventually help guide treatment decisions in Amp-NENs.

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“…Patients with tumor diameters of 1–2 cm have a higher likelihood of lymphatic metastasis 1 , 4 and it is challenging for endoscopists to deal with the d-NETs because they have a thinner wall in the duodenum than in other gastrointestinal tracts 10 . Therefore, the rate of surgical resection is currently higher for these patients as our results (214/159).…”

Section: Discussionmentioning

confidence: 99%

“…The incidence of d-NETs has increased significantly in recent years with the popularization of endoscopy. World Health Organization (WHO) classification, lymph node status and tumor size have historically been important prognostic factors 1 – 4 . A recent study 1 reported that the incidence of lymph node metastasis (LNM) increased with d-NETs size (≤ 1 cm: 40.0% vs 1–2 cm: 65.7% vs > 2 cm: 80.0%).…”

Section: Introductionmentioning

confidence: 99%

Survival comparison between endoscopic and surgical resection for non-ampullary duodenal neuroendocrine tumor (1–2 cm)

Xie

Zhang

et al. 2022

Sci Rep

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The treatment plan for non-ampullary duodenal neuroendocrine tumors (d-NETs) with diameters 1–2 cm remains controversial. We therefore aimed to compare the prognostic effects of endoscopic treatment and surgical resection on non-ampullary d-NETs with 1–2 cm diameters. A total of 373 eligible patients were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (PSM) was performed to match patients 1:1 according to clinicopathological characteristics. Disease-specific survival (DSS) and overall survival (OS) were calculated. Before PSM, there was no significant difference in DSS or OS (all P > 0.05), but the T stage, N stage, and TNM stage were significantly different between the two surgical methods (all P < 0.05). After 1:1 PSM, the differences in clinicopathological characteristics were significantly reduced (all P > 0.05). Survival analysis showed that tumor grade was correlated with DSS and that age was correlated with OS (all P < 0.05); however, the surgical method and other clinicopathological characteristics were not correlated with prognosis (all P > 0.05). Subgroup survival analysis of patients with T2N0M0 disease and tumors invading the lamina propria or submucosa showed that the 5-year DSS and OS rates were not significantly different according to the surgical approach (all P > 0.05). The surgical approach has no significant effect on the prognosis of patients with non-ampullary d-NETs with 1–2 cm diameters, especially those with T2N0M0 disease. This suggests that endoscopic treatment may be a preferred option for these patients.

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Management and Prognosis of Localized Duodenal Neuroendocrine Neoplasms

Cited by 14 publications

References 39 publications

Genetic alterations of GI‐NECs involving three main signaling pathways

Genetic alterations of GI‐NECs involving three main signaling pathways

Ampullary Neuroendocrine Neoplasms: Identification of Prognostic Factors in a Multicentric Series of 119 Cases

Survival comparison between endoscopic and surgical resection for non-ampullary duodenal neuroendocrine tumor (1–2 cm)

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