Prise en charge thérapeutique des tumeurs neuroendocrines peu différenciées pulmonaires et des carcinomes neuroendocrines digestifs

Pellat, Anna; Wislez, Marie; Svrcek, Magali; Hammel, Pascal; Afchain, Pauline; André, Thierry

doi:10.1016/j.bulcan.2016.06.006

Cited by 7 publications

(6 citation statements)

References 75 publications

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“…Before 2017, all G−3 neuroendocrine lesions were considered as one entity named neuroendocrine carcinomas (NEC) and were equally evaluated in clinical studies [7]. Therefore, therapeutic data regarding NET G−3 specifically is still scarce.…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, therapeutic data regarding NET G−3 specifically is still scarce. Digestive NEC are poorly differentiated tumors with a high Ki−67 index, with poor prognosis [7]. The main treatment in NEC is chemotherapy, with platinum-based regimen as standard first line [7,8].…”

Section: Introductionmentioning

confidence: 99%

“…Digestive NEC are poorly differentiated tumors with a high Ki−67 index, with poor prognosis [7]. The main treatment in NEC is chemotherapy, with platinum-based regimen as standard first line [7,8]. It is well documented that well-differentiated NEN have a better prognosis, even for G−3 lesions [1,2,9].…”

Section: Introductionmentioning

confidence: 99%

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Well Differentiated Grade 3 Neuroendocrine Tumors of the Digestive Tract: A Narrative Review

Pellat

Coriat

2020

JCM

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The 2017 World Health Organization (WHO) classification of neuroendocrine neoplasms (NEN) of the digestive tract introduced a new category of tumors named well-differentiated grade 3 neuroendocrine tumors (NET G−3). These lesions show a number of mitosis, or a Ki−67 index higher than 20% with a well-differentiated morphology, therefore separating them from neuroendocrine carcinomas (NEC) which are poorly differentiated. It has become clear that NET G−3 show differences not only in morphology but also in genotype, clinical presentation, and treatment response. The incidence of digestive NET G−3 represents about one third of NEN G−3 with main tumor sites being the pancreas, the stomach and the colon. Treatment for NET G−3 is not yet standardized because of lack of data. In a non-metastatic setting, international guidelines recommend surgical resection, regardless of tumor grading. For metastatic lesion, chemotherapy is the main treatment with similar regimen as NET G−2. Sunitinib has also shown some positive results in a small sample of patients but this needs confirmation. Peptide receptor radionuclide therapy (PRRT) and immunotherapy could be future available treatments after ongoing studies. The goal of this review was to sum up the latest data on the epidemiology and management of digestive NET G−3.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Well Differentiated Grade 3 Neuroendocrine Tumors of the Digestive Tract: A Narrative Review

Pellat

Coriat

2020

JCM

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“…So far, by lack of specific studies, the management of NET-G3 and NEC are similar. The majority of therapeutic guidelines derive from studies in small cell lung cancer [12, 13]. Patients at an advanced stage are offered systemic chemotherapy combining platinum salts with etoposide (VP16).…”

Section: Introductionmentioning

confidence: 99%

Clinical and Biomarker Evaluations of Sunitinib in Patients with Grade 3 Digestive Neuroendocrine Neoplasms

et al. 2018

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Background/Aims: Angiogenesis is extensively developed in well-differentiated pancreatic neuroendocrine tumours (PanNET) where sunitinib was shown to prolong progression-free survival, leading to nationwide approval. However, clinical experience in patients with grade 3 gastroenteropancreatic neuroendocrine neoplasms (GEPNEN-G3) remains limited. This prospective phase II trial evaluated potential predictive biomarkers of sunitinib activity in patients with advanced GEPNEN-G3. Methods: Sunitinib was given at a dose of 37.5 mg/day as a continuous daily dosing until progression or unacceptable toxicity. Evaluation of activity was based on RECIST1.1. Safety was evaluated according to NCI-CTCAE v4. Pharmacokinetics of sunitinib and its main active metabolite SU12662 were evaluated. All tumour samples were reviewed histologically for tumour differentiation. PDGFRβ, carbonic anhydrase 9, Ki-67, VEGFR2, and p-AKT were quantified using immunohistochemistry and their expression correlated with response by RECIST1.1. Results: Thirty-one patients were included and 26 had available histological tissue. Six and 20 patients presented well-differentiated tumours (NET-G3) and neuroendocrine carcinoma (NEC), respectively. Eighteen patients responded to sunitinib (4 experienced partial responses and 14 tumour stabilization). A high p-AKT expression correlated with lower response to sunitinib (OR 0.94, 95% CI 0.89–0.99, p = 0.04). Safety and PK exposure to sunitinib and SU12662 in these patients were consistent with that reported in PanNET. Conclusion: Sunitinib showed evidence of activity in patients with GEPNEN-G3 with expected toxicity profile. In the NET-G3 and NEC groups, 4/6 and 11/20 patients were responders, respectively. High p-AKT expression predicted a lower response to sunitinib. Our study allowed the identification of a potential biomarker of resistance/sensitivity to sunitinib in aggressive GEPNEN-G3.

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“…Prior to this, all G-3 neuroendocrine samples, or high-grade NEN, were considered as NEC and uniformly evaluated and treated in studies [ 11 ]. Data on NEC is detailed in another paper of this special issue.…”

Section: Introductionmentioning

confidence: 99%

Digestive Well-Differentiated Grade 3 Neuroendocrine Tumors: Current Management and Future Directions

Pellat

Palmieri

Soyer

et al. 2021

Cancers

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Digestive well-differentiated grade 3 neuroendocrine tumors (NET G-3) have been clearly defined since the 2017 World Health Organization classification. They are still a rare category lacking specific data and standardized management. Their distinction from other types of neuroendocrine neoplasms (NEN) not only lies in morphology but also in genotype, aggressiveness, functional imaging uptake, and treatment response. Most of the available data comes from pancreatic series, which is the most frequent tumor site for this entity. In the non-metastatic setting, surgical resection is recommended, irrespective of grade and tumor site. For metastatic NET G-3, chemotherapy is the main first-line treatment with temozolomide-based regimen showing more efficacy than platinum-based regimen, especially when Ki-67 index <55%. Targeted therapies, such as sunitinib and everolimus, have also shown some positive therapeutic efficacy in small samples of patients. Functional imaging plays a key role for detection but also treatment selection. In the second or further-line setting, peptide receptor radionuclide therapy has shown promising response rates in high-grade NEN. Finally, immunotherapy is currently investigated as a new therapeutic approach with trials still ongoing. More data will come with future work now focusing on this specific subgroup. The aim of this review is to summarize the current data on digestive NET G-3 and explore future directions for their management.

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Prise en charge thérapeutique des tumeurs neuroendocrines peu différenciées pulmonaires et des carcinomes neuroendocrines digestifs

Cited by 7 publications

References 75 publications

Well Differentiated Grade 3 Neuroendocrine Tumors of the Digestive Tract: A Narrative Review

Well Differentiated Grade 3 Neuroendocrine Tumors of the Digestive Tract: A Narrative Review

Clinical and Biomarker Evaluations of Sunitinib in Patients with Grade 3 Digestive Neuroendocrine Neoplasms

Digestive Well-Differentiated Grade 3 Neuroendocrine Tumors: Current Management and Future Directions

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