Pancreatic neuroendocrine tumors (pNETs) are neoplasms arising from the islets of Langerhans or diffuse neuroendocrine cells of the pancreas. They account for 1-3% of all pancreatic neoplasms and exhibit substantial clinical and molecular heterogeneity, ranging from indolent, well-differentiated tumors to aggressive, poorly differentiated neuroendocrine carcinomas. pNETs can be functional (secreting hormones such as insulin, gastrin, glucagon, or VIP, causing distinct clinical syndromes) or non-functional (presenting with mass effect or incidental findings). Key genetic drivers include inactivating mutations in MEN1 (~44%), DAXX/ATRX (~43%), and mTOR pathway genes (PTEN, TSC2; ~14%). WHO grading is based on Ki-67 proliferation index and mitotic rate, stratifying tumors into G1 (<3%), G2 (3-20%), and G3 (>20%). Five-year survival varies from >90% for localized G1 tumors to <30% for metastatic high-grade disease. Recent molecular taxonomy identifies five transcriptional subtypes (Hedgehog-high, Alpha-like, Hypoxia-high, Gastrin-high, and Progenitor-like) with distinct clinical behaviors and therapeutic vulnerabilities.
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name: Pancreatic Neuroendocrine Tumor
creation_date: "2026-03-18T00:00:00Z"
updated_date: "2026-04-22T20:13:21Z"
description: >-
Pancreatic neuroendocrine tumors (pNETs) are neoplasms arising from the islets of
Langerhans or diffuse neuroendocrine cells of the pancreas. They account for 1-3%
of
all pancreatic neoplasms and exhibit substantial clinical and molecular heterogeneity,
ranging from indolent, well-differentiated tumors to aggressive, poorly differentiated
neuroendocrine carcinomas. pNETs can be functional (secreting hormones such as insulin,
gastrin, glucagon, or VIP, causing distinct clinical syndromes) or non-functional
(presenting with mass effect or incidental findings). Key genetic drivers include
inactivating mutations in MEN1 (~44%), DAXX/ATRX (~43%), and mTOR pathway genes
(PTEN, TSC2; ~14%). WHO grading is based on Ki-67 proliferation index and mitotic
rate, stratifying tumors into G1 (<3%), G2 (3-20%), and G3 (>20%). Five-year survival
varies from >90% for localized G1 tumors to <30% for metastatic high-grade disease.
Recent molecular taxonomy identifies five transcriptional subtypes (Hedgehog-high,
Alpha-like, Hypoxia-high, Gastrin-high, and Progenitor-like) with distinct clinical
behaviors and therapeutic vulnerabilities.
categories:
- Solid Tumor
- Gastrointestinal Cancer
- Neuroendocrine Neoplasm
parents:
- pancreatic cancer
- neuroendocrine tumor
disease_term:
preferred_term: pancreatic neuroendocrine tumor
term:
id: MONDO:0019954
label: pancreatic neuroendocrine tumor
has_subtypes:
- name: Insulinoma
description: >-
Functional pNET that secretes insulin, causing recurrent hypoglycemia. Most common
functional pNET, typically benign and solitary. Presents with Whipple triad
(symptoms of hypoglycemia, documented low blood glucose, symptom relief with glucose).
- name: Gastrinoma
description: >-
Functional pNET that secretes gastrin, causing Zollinger-Ellison syndrome with
gastric acid hypersecretion, recurrent peptic ulcers, and diarrhea. Approximately
25% occur in the context of MEN1 syndrome.
- name: Non-functional pNET
description: >-
The most common type of pNET (~60-90%), not associated with a clinical hormone
hypersecretion syndrome. Often diagnosed at advanced stage due to lack of hormonal
symptoms. Presents with abdominal pain, weight loss, or jaundice from mass effect.
- name: Hedgehog-high Subtype
description: >-
Molecular subtype identified by RNA sequencing, characterized by high hedgehog
signaling pathway activation.
evidence:
- reference: PMID:41794038
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Using bulk and single-nucleus RNA sequencing, we identify five molecular subtypes:
Hedgehog-high, Alpha-like, Hypoxia-high, Gastrin-high, and Progenitor-like.
explanation: >-
Lu et al. identified five molecular subtypes of pNETs through transcriptomic
analysis, including the Hedgehog-high subtype.
- name: Alpha-like Subtype
description: >-
Molecular subtype resembling pancreatic alpha cells in transcriptional profile.
evidence:
- reference: PMID:41794038
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Using bulk and single-nucleus RNA sequencing, we identify five molecular subtypes:
Hedgehog-high, Alpha-like, Hypoxia-high, Gastrin-high, and Progenitor-like.
explanation: >-
The Alpha-like subtype was one of five molecular subtypes identified through
RNA sequencing of pNETs.
- name: Hypoxia-high Subtype
description: >-
Molecular subtype characterized by elevated hypoxia-related gene expression programs.
evidence:
- reference: PMID:41794038
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Using bulk and single-nucleus RNA sequencing, we identify five molecular subtypes:
Hedgehog-high, Alpha-like, Hypoxia-high, Gastrin-high, and Progenitor-like.
explanation: >-
The Hypoxia-high subtype was identified as one of five molecular subtypes.
- name: Gastrin-high Subtype
description: >-
Molecular subtype associated with poor clinical outcomes. Contains all BEND2
fusion-positive tumors and shows activation of the late endocrine progenitor
FEV regulon. Exhibits CD8 T cell infiltration with PD-1/PD-L1 upregulation.
evidence:
- reference: PMID:41794038
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The Gastrin-high and Progenitor-like subtypes associate with poor clinical outcomes.
explanation: >-
Lu et al. demonstrate that the Gastrin-high subtype has poor outcomes and
harbors all BEND2 fusions.
- name: Progenitor-like Subtype
description: >-
Molecular subtype with stem/progenitor cell transcriptional features, associated
with poor clinical outcomes.
evidence:
- reference: PMID:41794038
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The Gastrin-high and Progenitor-like subtypes associate with poor clinical outcomes.
explanation: >-
The Progenitor-like subtype was associated with poor prognosis alongside the
Gastrin-high subtype.
pathophysiology:
- name: MEN1 Tumor Suppressor Inactivation
description: >-
Loss-of-function mutations in the MEN1 gene (encoding menin) occur in approximately
44% of sporadic pNETs and are the hallmark of hereditary MEN1 syndrome. Menin
is a
chromatin-modifying protein that acts as a scaffold for the MLL/SET1-like histone
methyltransferase complex, regulating H3K4 methylation. Loss of menin disrupts
epigenetic regulation of cell cycle genes, leading to uncontrolled proliferation
of islet cells. Clinically, MEN1 mutations are paradoxically associated with
better prognosis.
evidence:
- reference: PMID:21252315
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
44% of the tumors had somatic inactivating mutations in MEN1, which encodes
menin, a component of a histone methyltransferase complex
explanation: >-
Jiao et al. whole-exome sequencing study established MEN1 mutation frequency
at 44% in sporadic pNETs and identified its role in chromatin remodeling.
- reference: PMID:21252315
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Clinically, mutations in the MEN1 and DAXX/ATRX genes were associated with
better prognosis.
explanation: >-
Despite being the most common driver mutation, MEN1 mutations were associated
with better prognosis in the Jiao et al. cohort.
cell_types:
- preferred_term: pancreatic endocrine cell
term:
id: CL:0008024
label: pancreatic endocrine cell
biological_processes:
- preferred_term: chromatin organization
modifier: DYSREGULATED
term:
id: GO:0006325
label: chromatin organization
- preferred_term: cell population proliferation
modifier: INCREASED
term:
id: GO:0008283
label: cell population proliferation
- name: DAXX/ATRX Chromatin Remodeling Deficiency
description: >-
Mutually exclusive inactivating mutations in DAXX (25%) or ATRX (17.6%) occur
in
approximately 43% of pNETs. These proteins form a complex that deposits the histone
variant H3.3 at telomeres and pericentric heterochromatin. Loss leads to alternative
lengthening of telomeres (ALT), chromosomal instability, and is associated with
larger tumor size. Mutations in DAXX/ATRX are associated with better prognosis,
particularly in combination with MEN1 mutations.
evidence:
- reference: PMID:21252315
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
43% had mutations in genes encoding either of the two subunits of a
transcription/chromatin remodeling complex consisting of DAXX
(death-domain-associated protein) and ATRX
explanation: >-
Jiao et al. discovered DAXX/ATRX as the second most commonly mutated pathway
in pNETs at 43%, with mutual exclusivity between the two genes.
- reference: PMID:21252315
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Recently, it has been shown that DAXX is an H3.3-specific histone chaperone
explanation: >-
The paper cites evidence that DAXX functions as a histone H3.3 chaperone,
explaining the mechanistic basis of chromatin remodeling deficiency.
cell_types:
- preferred_term: pancreatic endocrine cell
term:
id: CL:0008024
label: pancreatic endocrine cell
biological_processes:
- preferred_term: telomere maintenance
modifier: DYSREGULATED
term:
id: GO:0000723
label: telomere maintenance
- preferred_term: chromatin organization
modifier: DYSREGULATED
term:
id: GO:0006325
label: chromatin organization
- name: mTOR Pathway Activation
description: >-
Mutations in mTOR pathway genes (PTEN, TSC2, PIK3CA) occur in approximately 14%
of pNETs, leading to constitutive activation of the PI3K/AKT/mTOR signaling cascade.
This drives cell growth, proliferation, and angiogenesis, and represents a key
therapeutic target. The mTOR inhibitor everolimus is approved for progressive
pNETs.
evidence:
- reference: PMID:21252315
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
We also found mutations in genes in the mTOR (mammalian target of rapamycin)
pathway in 14% of the tumors, a finding that could potentially be used to
stratify patients for treatment with mTOR inhibitors.
explanation: >-
Jiao et al. identified mTOR pathway mutations at 14% frequency and proposed
their use for patient stratification for mTOR inhibitor therapy.
- reference: PMID:21306238
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Everolimus, as compared with placebo, significantly prolonged progression-free
survival among patients with progressive advanced pancreatic neuroendocrine
tumors and was associated with a low rate of severe adverse events.
explanation: >-
The RADIANT-3 trial demonstrated that targeting the mTOR pathway with everolimus
significantly improves PFS in advanced pNETs, validating the therapeutic
relevance of this pathway.
biological_processes:
- preferred_term: TORC1 signaling
modifier: INCREASED
term:
id: GO:0038202
label: TORC1 signaling
- preferred_term: PI3K/AKT signaling
modifier: INCREASED
term:
id: GO:0043491
label: phosphatidylinositol 3-kinase/protein kinase B signal transduction
- preferred_term: cell population proliferation
modifier: INCREASED
term:
id: GO:0008283
label: cell population proliferation
- name: BEND2 Fusion-Driven Transcriptional Reprogramming
description: >-
BEND2 gene fusions occur in approximately 5% of pNETs, exclusively within the
Gastrin-high molecular subtype. These fusions drive transcriptional reprogramming,
promoting a shift from ASCL1-positive endocrine states toward neurodevelopmental,
mesenchymal, and immune-related gene programs. The Gastrin-high subtype shows
activation of the late endocrine progenitor FEV regulon and is associated with
poor clinical outcomes.
evidence:
- reference: PMID:41794038
supports: SUPPORT
evidence_source: IN_VITRO
snippet: >-
Functional studies in pNET cell models demonstrate that BEND2 fusions drive
transcriptional reprogramming, promoting a shift from ASCL1+ endocrine states
toward neurodevelopmental, mesenchymal, and immune-related gene programs.
explanation: >-
Lu et al. used cell models to functionally validate that BEND2 fusions drive
transcriptional plasticity in pNETs.
- reference: PMID:41794038
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
BEND2 gene fusions occur in 5% of pNETs, all belonging to the Gastrin-high
subtype, which shows activation of the late endocrine progenitor FEV regulon.
explanation: >-
Clinical characterization showed BEND2 fusions exclusively in the Gastrin-high
subtype with FEV regulon activation.
cell_types:
- preferred_term: neuroendocrine cell
term:
id: CL:0000165
label: neuroendocrine cell
- name: NOTCH3-Mediated Tumor-Stromal Signaling
description: >-
Single-nucleus analysis reveals NOTCH3-mediated signaling between tumor cells
and
myofibroblasts in the tumor microenvironment. This intercellular communication
supports tumor growth and represents a potential therapeutic vulnerability.
evidence:
- reference: PMID:41794038
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Single-nucleus analysis reveals complex multicellular ecosystems, with
NOTCH3-mediated signaling between tumor cells and myofibroblasts emerging as
a
potential therapeutic vulnerability.
explanation: >-
Single-nucleus RNA-seq analysis identified NOTCH3-mediated tumor-stromal
crosstalk as a novel therapeutic target in pNETs.
cell_types:
- preferred_term: myofibroblast cell
term:
id: CL:0000186
label: myofibroblast cell
- preferred_term: neuroendocrine cell
term:
id: CL:0000165
label: neuroendocrine cell
biological_processes:
- preferred_term: Notch signaling pathway
modifier: INCREASED
term:
id: GO:0007219
label: Notch signaling pathway
- name: Immune Microenvironment and Checkpoint Upregulation
description: >-
Gastrin-high pNETs exhibit CD8+ T cell infiltration alongside PD-1/PD-L1
upregulation, suggesting potential responsiveness to immune checkpoint blockade.
This creates a rationale for immunotherapy trials in molecularly selected pNET
patients.
evidence:
- reference: PMID:41794038
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Gastrin-high tumors exhibit CD8+ T cell infiltration alongside PD-1/PD-L1
upregulation, suggesting potential responsiveness to immune checkpoint blockade.
explanation: >-
The molecular taxonomy study revealed an immunologically active microenvironment
in Gastrin-high pNETs that could be targeted with checkpoint inhibitors.
cell_types:
- preferred_term: CD8-positive, alpha-beta T cell
term:
id: CL:0000625
label: CD8-positive, alpha-beta T cell
phenotypes:
- category: Neoplasm
name: Pancreatic Mass
description: >-
A mass lesion in the pancreas, often well-circumscribed and hypervascular on
imaging, is the hallmark presentation of pNETs.
phenotype_term:
preferred_term: neoplasm of the pancreas
term:
id: HP:0002894
label: Neoplasm of the pancreas
evidence:
- reference: PMID:21252315
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Pancreatic neuroendocrine tumors (PanNETs) are a rare but clinically important
form of pancreatic neoplasia.
explanation: >-
The landmark genomics study confirms pNETs as a clinically important form of
pancreatic neoplasia.
- category: Neoplasm
name: Hepatic Metastases
description: >-
Liver metastases are the most common site of distant spread for pNETs, occurring
in 40-70% of patients with advanced disease and significantly impacting prognosis.
notes: >-
HPO lacks a specific term for hepatic metastasis (secondary liver neoplasm);
HP:0002896 (Neoplasm of the liver) is the best available mapping. An NTR to
HPO for a dedicated hepatic metastasis term may be warranted.
phenotype_term:
preferred_term: hepatic metastases
term:
id: HP:0002896
label: Neoplasm of the liver
- name: Hypoglycemia
description: >-
Recurrent episodes of low blood glucose caused by autonomous insulin secretion
from insulinomas, the most common functional pNET.
phenotype_term:
preferred_term: hypoglycemia
term:
id: HP:0001943
label: Hypoglycemia
- name: Recurrent Peptic Ulcers
description: >-
Multiple or refractory peptic ulcers due to gastric acid hypersecretion driven
by gastrinomas (Zollinger-Ellison syndrome).
phenotype_term:
preferred_term: peptic ulcer
term:
id: HP:0004398
label: Peptic ulcer
- name: Diarrhea
description: >-
Secretory diarrhea may occur due to excess gastrin (gastrinomas), VIP (VIPomas),
or serotonin production, or from mass effect and malabsorption.
phenotype_term:
preferred_term: diarrhea
term:
id: HP:0002014
label: Diarrhea
- name: Abdominal Pain
description: >-
Nonspecific abdominal pain is common in non-functional pNETs due to mass effect
or hepatic metastases.
phenotype_term:
preferred_term: abdominal pain
term:
id: HP:0002027
label: Abdominal pain
evidence:
- reference: PMID:21252315
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Nonfunctional PanNETs grow silently and patients often present with either an
asymptomatic abdominal mass or symptoms of abdominal pain secondary to
compression by a large tumor.
explanation: >-
The Jiao et al. paper confirms that non-functional pNETs commonly present
with abdominal pain from tumor compression.
- name: Unintentional Weight Loss
description: >-
Progressive weight loss occurs in advanced pNETs due to tumor burden, hormonal
effects, or reduced oral intake from mass effect.
phenotype_term:
preferred_term: weight loss
term:
id: HP:0001824
label: Weight loss
genetic:
- name: MEN1
association: Loss-of-function mutations in ~44% of sporadic pNETs; defines MEN1 syndrome
frequency: FREQUENT
notes: >-
Menin is a chromatin-modifying protein regulating H3K4 methylation via MLL/SET1
complex.
Germline MEN1 mutations cause familial pNETs with near-complete penetrance. MEN1
mutations are paradoxically associated with better prognosis.
evidence:
- reference: PMID:21252315
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
44% of the tumors had somatic inactivating mutations in MEN1, which encodes
menin, a component of a histone methyltransferase complex
explanation: >-
Jiao et al. exome sequencing established MEN1 as the most frequently mutated
gene in sporadic pNETs at 44%.
- name: DAXX
association: Inactivating mutations in ~25% of pNETs; mutually exclusive with ATRX
frequency: OCCASIONAL
notes: >-
DAXX is an H3.3-specific histone chaperone. Loss leads to alternative lengthening
of telomeres (ALT) and chromosomal instability.
evidence:
- reference: PMID:21252315
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
somatic mutations in MEN1, DAXX, ATRX, PTEN, TSC2, and PIK3CA were identified
in 44.1%, 25%, 17.6%, 7.3%, 8.8%, and 1.4% PanNETs, respectively
explanation: >-
DAXX mutations were found in 25% of pNETs in the combined discovery and
validation cohorts.
- name: ATRX
association: Inactivating mutations in ~18% of pNETs; mutually exclusive with DAXX
frequency: OCCASIONAL
notes: >-
ATRX encodes a helicase that interacts with DAXX for H3.3 deposition at telomeres.
Loss leads to ALT and is associated with larger tumor size.
evidence:
- reference: PMID:21252315
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
somatic mutations in MEN1, DAXX, ATRX, PTEN, TSC2, and PIK3CA were identified
in 44.1%, 25%, 17.6%, 7.3%, 8.8%, and 1.4% PanNETs, respectively
explanation: >-
ATRX mutations were found in 17.6% of pNETs, mutually exclusive with DAXX.
- name: PTEN
association: Inactivating mutations in ~7% of pNETs; mTOR pathway component
frequency: RARE
notes: >-
PTEN loss activates PI3K/AKT/mTOR signaling, providing therapeutic rationale
for everolimus treatment.
evidence:
- reference: PMID:21252315
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
somatic mutations in MEN1, DAXX, ATRX, PTEN, TSC2, and PIK3CA were identified
in 44.1%, 25%, 17.6%, 7.3%, 8.8%, and 1.4% PanNETs, respectively
explanation: >-
PTEN was mutated in 7.3% of pNETs in the Jiao et al. cohort.
- name: TSC2
association: Inactivating mutations in ~9% of pNETs; mTOR pathway component
frequency: RARE
notes: >-
TSC2 loss disinhibits mTOR signaling. Combined with PTEN and PIK3CA, the mTOR
pathway is mutated in ~14% of pNETs.
evidence:
- reference: PMID:21252315
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
somatic mutations in MEN1, DAXX, ATRX, PTEN, TSC2, and PIK3CA were identified
in 44.1%, 25%, 17.6%, 7.3%, 8.8%, and 1.4% PanNETs, respectively
explanation: >-
TSC2 was mutated in 8.8% of pNETs.
- name: PIK3CA
association: Activating mutations in ~1.4% of pNETs; mTOR pathway component
frequency: VERY_RARE
notes: >-
PIK3CA mutations contribute to PI3K/AKT/mTOR pathway activation, complementing
PTEN and TSC2 losses.
evidence:
- reference: PMID:21252315
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
somatic mutations in MEN1, DAXX, ATRX, PTEN, TSC2, and PIK3CA were identified
in 44.1%, 25%, 17.6%, 7.3%, 8.8%, and 1.4% PanNETs, respectively
explanation: >-
PIK3CA was mutated in 1.4% of pNETs in the Jiao et al. cohort.
- name: BEND2
association: Gene fusions in ~5% of pNETs; exclusively in Gastrin-high molecular subtype
frequency: VERY_RARE
notes: >-
BEND2 fusions drive transcriptional plasticity, shifting from endocrine to
neurodevelopmental/mesenchymal programs. Associated with poor prognosis.
evidence:
- reference: PMID:41794038
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
BEND2 gene fusions occur in 5% of pNETs, all belonging to the Gastrin-high
subtype, which shows activation of the late endocrine progenitor FEV regulon.
explanation: >-
Lu et al. discovered BEND2 fusions as a novel oncogenic driver in pNETs,
restricted to the Gastrin-high molecular subtype.
treatments:
- name: Surgical Resection
description: >-
Surgery is the only curative treatment for localized pNETs. Options include
enucleation for small tumors, distal pancreatectomy, or pancreaticoduodenectomy
(Whipple procedure) depending on tumor location and size.
treatment_term:
preferred_term: surgical resection
term:
id: MAXO:0000448
label: surgical resection
evidence:
- reference: PMID:21252315
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Surgical resection is the treatment of choice, but many patients present with
unresectable tumors or extensive metastatic disease
explanation: >-
The landmark genomic study confirms surgical resection as the primary treatment
for pNETs, noting the challenge of unresectable or metastatic disease.
- name: Somatostatin Analog Therapy
description: >-
Somatostatin analogs (octreotide, lanreotide) control hormonal symptoms in
functional pNETs and have demonstrated antiproliferative effects in well-differentiated
G1/G2 tumors. The CLARINET trial demonstrated that lanreotide significantly prolonged
progression-free survival compared to placebo.
treatment_term:
preferred_term: Pharmacotherapy
term:
id: NCIT:C15986
label: Pharmacotherapy
evidence:
- reference: PMID:25014687
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Lanreotide was associated with significantly prolonged progression-free survival
among patients with metastatic enteropancreatic neuroendocrine tumors of grade
1
or 2 (Ki-67 <10%).
explanation: >-
The CLARINET phase 3 trial demonstrated lanreotide's antiproliferative effect
in metastatic enteropancreatic NETs with a 53% reduction in risk of progression.
- name: Everolimus (mTOR Inhibitor)
description: >-
Everolimus, an oral mTOR inhibitor, is approved for advanced progressive pNETs
based on the RADIANT-3 trial. It demonstrated a 65% reduction in estimated risk
of progression or death compared to placebo.
treatment_term:
preferred_term: Pharmacotherapy
term:
id: NCIT:C15986
label: Pharmacotherapy
evidence:
- reference: PMID:21306238
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Everolimus, as compared with placebo, significantly prolonged progression-free
survival among patients with progressive advanced pancreatic neuroendocrine
tumors and was associated with a low rate of severe adverse events.
explanation: >-
The RADIANT-3 phase 3 trial established everolimus as standard treatment for
advanced progressive pNETs with significant PFS improvement.
- name: Sunitinib (Multi-Kinase Inhibitor)
description: >-
Sunitinib, a multi-targeted receptor tyrosine kinase inhibitor targeting VEGFR,
PDGFR, and c-KIT, is approved for progressive well-differentiated pNETs. The
registration trial showed median PFS of 11.4 months vs 5.5 months with placebo.
treatment_term:
preferred_term: targeted therapy
term:
id: NCIT:C93352
label: Targeted Therapy
evidence:
- reference: PMID:21306237
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Continuous daily administration of sunitinib at a dose of 37.5 mg improved
progression-free survival, overall survival, and the objective response rate
as
compared with placebo among patients with advanced pancreatic neuroendocrine
tumors.
explanation: >-
The phase 3 sunitinib trial demonstrated significant improvement in PFS and
overall survival for patients with advanced well-differentiated pNETs.
- name: PRRT (Peptide Receptor Radionuclide Therapy)
description: >-
177Lu-DOTATATE (Lutathera) targets somatostatin receptor-positive NETs.
A retrospective study of 34 patients with metastatic functioning pNETs
demonstrated partial or complete response in 59% and median PFS of 18.1
months, establishing PRRT as a safe and effective therapy for pNETs.
treatment_term:
preferred_term: radiation therapy
term:
id: MAXO:0000014
label: radiation therapy
evidence:
- reference: PMID:30566620
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Treatment with 177Lu-DOTATATE is a safe and effective therapy resulting in
radiological, symptomatic and biochemical response in a high percentage of
patients with metastatic functioning pNETs.
explanation: >-
Zandee et al. demonstrated 177Lu-DOTATATE efficacy directly in functioning
pNETs (n=34), with 59% response rate and 18.1 month median PFS.
- name: Temozolomide-Based Chemotherapy
description: >-
Temozolomide alone or combined with capecitabine (CAPTEM) is used for advanced
pNETs. The E2211 randomized trial showed median PFS of 22.7 months for CAPTEM
versus 14.4 months for temozolomide alone, with the highest response rates
reported in a randomized study for pancreatic NETs.
treatment_term:
preferred_term: chemotherapy
term:
id: MAXO:0000647
label: chemotherapy
evidence:
- reference: PMID:36260828
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The combination of capecitabine/temozolomide was associated with a significant
improvement in PFS compared with temozolomide alone in patients with advanced
pancreatic NETs.
explanation: >-
The E2211 randomized phase II trial demonstrated that CAPTEM significantly
improved PFS compared to temozolomide monotherapy in advanced pNETs.
datasets:
references:
- reference: DOI:10.1093/bjs/znae178
title: 'Neoadjuvant 177Lu-DOTATATE for non-functioning pancreatic neuroendocrine tumours (NEOLUPANET): multicentre phase II study'
found_in:
- Pancreatic_Neuroendocrine_Tumor-deep-research-falcon.md
findings:
- statement: Resection of non-functioning pancreatic neuroendocrine tumours (NF-PanNETs) is curative in most patients.
supporting_text: Resection of non-functioning pancreatic neuroendocrine tumours (NF-PanNETs) is curative in most patients.
evidence:
- reference: DOI:10.1093/bjs/znae178
reference_title: 'Neoadjuvant 177Lu-DOTATATE for non-functioning pancreatic neuroendocrine tumours (NEOLUPANET): multicentre phase II study'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Resection of non-functioning pancreatic neuroendocrine tumours (NF-PanNETs) is curative in most patients.
explanation: Deep research cited this publication as relevant literature for Pancreatic Neuroendocrine Tumor.
- reference: DOI:10.1186/s12885-024-11926-2
title: 'Efficacy and safety of temozolomide-based regimens in advanced pancreatic neuroendocrine tumors: a systematic review and meta-analysis'
found_in:
- Pancreatic_Neuroendocrine_Tumor-deep-research-falcon.md
findings:
- statement: Recent advances in the management of pancreatic neuroendocrine tumors (pNETs) highlight the potential benefits of temozolomide, an alkylating agent, for these patients.
supporting_text: Recent advances in the management of pancreatic neuroendocrine tumors (pNETs) highlight the potential benefits of temozolomide, an alkylating agent, for these patients.
evidence:
- reference: DOI:10.1186/s12885-024-11926-2
reference_title: 'Efficacy and safety of temozolomide-based regimens in advanced pancreatic neuroendocrine tumors: a systematic review and meta-analysis'
supports: SUPPORT
evidence_source: OTHER
snippet: Recent advances in the management of pancreatic neuroendocrine tumors (pNETs) highlight the potential benefits of temozolomide, an alkylating agent, for these patients.
explanation: Deep research cited this publication as relevant literature for Pancreatic Neuroendocrine Tumor.
- reference: DOI:10.1186/s12964-024-01545-6
title: Multiregion WES of metastatic pancreatic neuroendocrine tumors revealed heterogeneity in genomic alterations, immune microenvironment and evolutionary patterns
found_in:
- Pancreatic_Neuroendocrine_Tumor-deep-research-falcon.md
findings:
- statement: Pancreatic neuroendocrine tumors (PanNETs), though uncommon, have a high likelihood of spreading to other body parts.
supporting_text: Pancreatic neuroendocrine tumors (PanNETs), though uncommon, have a high likelihood of spreading to other body parts.
evidence:
- reference: DOI:10.1186/s12964-024-01545-6
reference_title: Multiregion WES of metastatic pancreatic neuroendocrine tumors revealed heterogeneity in genomic alterations, immune microenvironment and evolutionary patterns
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Pancreatic neuroendocrine tumors (PanNETs), though uncommon, have a high likelihood of spreading to other body parts.
explanation: Deep research cited this publication as relevant literature for Pancreatic Neuroendocrine Tumor.
- reference: DOI:10.2967/jnumed.122.264860
title: 'SNMMI Procedure Standard/EANM Practice Guideline for SSTR PET: Imaging Neuroendocrine Tumors'
found_in:
- Pancreatic_Neuroendocrine_Tumor-deep-research-falcon.md
findings:
- statement: 'SNMMI Procedure Standard/EANM Practice Guideline for SSTR PET: Imaging Neuroendocrine Tumors'
supporting_text: 'SNMMI Procedure Standard/EANM Practice Guideline for SSTR PET: Imaging Neuroendocrine Tumors'
- reference: DOI:10.3389/fendo.2024.1351624
title: 'Well-differentiated G1 and G2 pancreatic neuroendocrine tumors: a meta-analysis of published expanded DNA sequencing data'
found_in:
- Pancreatic_Neuroendocrine_Tumor-deep-research-falcon.md
findings:
- statement: Well-differentiated pancreatic neuroendocrine tumors (PNETs) can be non-functional or functional, e.g. insulinoma and glucagonoma.
supporting_text: Well-differentiated pancreatic neuroendocrine tumors (PNETs) can be non-functional or functional, e.g. insulinoma and glucagonoma.
evidence:
- reference: DOI:10.3389/fendo.2024.1351624
reference_title: 'Well-differentiated G1 and G2 pancreatic neuroendocrine tumors: a meta-analysis of published expanded DNA sequencing data'
supports: SUPPORT
evidence_source: OTHER
snippet: Well-differentiated pancreatic neuroendocrine tumors (PNETs) can be non-functional or functional, e.g. insulinoma and glucagonoma.
explanation: Deep research cited this publication as relevant literature for Pancreatic Neuroendocrine Tumor.
- reference: DOI:10.3390/cancers15072006
title: Surgical Management of Pancreatic Neuroendocrine Tumors
found_in:
- Pancreatic_Neuroendocrine_Tumor-deep-research-falcon.md
findings:
- statement: Pancreatic neuroendocrine tumors (PNETs) are relatively uncommon malignancies, characterized as either functional or nonfunctional secondary to their secretion of biologically active hormones.
supporting_text: Pancreatic neuroendocrine tumors (PNETs) are relatively uncommon malignancies, characterized as either functional or nonfunctional secondary to their secretion of biologically active hormones.
evidence:
- reference: DOI:10.3390/cancers15072006
reference_title: Surgical Management of Pancreatic Neuroendocrine Tumors
supports: SUPPORT
evidence_source: OTHER
snippet: Pancreatic neuroendocrine tumors (PNETs) are relatively uncommon malignancies, characterized as either functional or nonfunctional secondary to their secretion of biologically active hormones.
explanation: Deep research cited this publication as relevant literature for Pancreatic Neuroendocrine Tumor.
- reference: DOI:10.3390/cancers15133483
title: Diagnosis, Management and Theragnostic Approach of Gastro-Entero-Pancreatic Neuroendocrine Neoplasms
found_in:
- Pancreatic_Neuroendocrine_Tumor-deep-research-falcon.md
findings:
- statement: Gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NENs) constitute an ideal target for radiolabeled somatostatin analogs.
supporting_text: Gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NENs) constitute an ideal target for radiolabeled somatostatin analogs.
evidence:
- reference: DOI:10.3390/cancers15133483
reference_title: Diagnosis, Management and Theragnostic Approach of Gastro-Entero-Pancreatic Neuroendocrine Neoplasms
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NENs) constitute an ideal target for radiolabeled somatostatin analogs.
explanation: Deep research cited this publication as relevant literature for Pancreatic Neuroendocrine Tumor.
- reference: DOI:10.3390/cancers16112075
title: Hereditary Syndromes Associated with Pancreatic and Lung Neuroendocrine Tumors
found_in:
- Pancreatic_Neuroendocrine_Tumor-deep-research-falcon.md
findings:
- statement: Pancreatic neuroendocrine tumors (PanNETs) and lung NETs (LNETs) represent a rare but clinically significant subgroup of neoplasms.
supporting_text: Pancreatic neuroendocrine tumors (PanNETs) and lung NETs (LNETs) represent a rare but clinically significant subgroup of neoplasms.
evidence:
- reference: DOI:10.3390/cancers16112075
reference_title: Hereditary Syndromes Associated with Pancreatic and Lung Neuroendocrine Tumors
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Pancreatic neuroendocrine tumors (PanNETs) and lung NETs (LNETs) represent a rare but clinically significant subgroup of neoplasms.
explanation: Deep research cited this publication as relevant literature for Pancreatic Neuroendocrine Tumor.
- reference: DOI:10.3390/medicina59020359
title: 'Efficacy and Safety of Endoscopic Ultrasound-Guided Radiofrequency Ablation for Pancreatic Neuroendocrine Tumors: A Systematic Review and Metanalysis'
found_in:
- Pancreatic_Neuroendocrine_Tumor-deep-research-falcon.md
findings:
- statement: The development of dedicated endoscopes and the technical evolution of endoscopic ultrasound (EUS) have allowed a direct approach to pancreatic neoplastic lesions both for diagnosis and treatment.
supporting_text: The development of dedicated endoscopes and the technical evolution of endoscopic ultrasound (EUS) have allowed a direct approach to pancreatic neoplastic lesions both for diagnosis and treatment.
evidence:
- reference: DOI:10.3390/medicina59020359
reference_title: 'Efficacy and Safety of Endoscopic Ultrasound-Guided Radiofrequency Ablation for Pancreatic Neuroendocrine Tumors: A Systematic Review and Metanalysis'
supports: SUPPORT
evidence_source: OTHER
snippet: The development of dedicated endoscopes and the technical evolution of endoscopic ultrasound (EUS) have allowed a direct approach to pancreatic neoplastic lesions both for diagnosis and treatment.
explanation: Deep research cited this publication as relevant literature for Pancreatic Neuroendocrine Tumor.
- reference: DOI:10.3390/tomography9010018
title: 'Diagnostic Management of Gastroenteropancreatic Neuroendocrine Neoplasms: Technique Optimization and Tips and Tricks for Radiologists'
found_in:
- Pancreatic_Neuroendocrine_Tumor-deep-research-falcon.md
findings:
- statement: 'Diagnostic Management of Gastroenteropancreatic Neuroendocrine Neoplasms: Technique Optimization and Tips and Tricks for Radiologists'
supporting_text: Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) comprise a heterogeneous group of neoplasms, which derive from cells of the diffuse neuroendocrine system that specializes in producing hormones and neuropeptides and arise in most cases sporadically and, to a lesser extent, in the context of complex genetic syndromes.
evidence:
- reference: DOI:10.3390/tomography9010018
reference_title: 'Diagnostic Management of Gastroenteropancreatic Neuroendocrine Neoplasms: Technique Optimization and Tips and Tricks for Radiologists'
supports: SUPPORT
evidence_source: OTHER
snippet: Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) comprise a heterogeneous group of neoplasms, which derive from cells of the diffuse neuroendocrine system that specializes in producing hormones and neuropeptides and arise in most cases sporadically and, to a lesser extent, in the context of complex genetic syndromes.
explanation: Deep research cited this publication as relevant literature for Pancreatic Neuroendocrine Tumor.
PanNETs are pancreatic tumors of neuroendocrine lineage, clinically classified as functional (hormone-secreting, syndrome-producing) or non-functioning (no hormone syndrome; majority) (sulciner2023surgicalmanagementof pages 1-2, sulciner2023surgicalmanagementof pages 2-5). In a recent hereditary-syndrome review, “roughly 30% are functioning” while most are non-functioning (papadopouloumarketou2024hereditarysyndromesassociated pages 1-3).
Direct abstract quote (definition/overview): - “Pancreatic neuroendocrine tumors (PNETs) are relatively uncommon malignancies, characterized as either functional or nonfunctional secondary to their secretion of biologically active hormones.” (Sulciner & Clancy, Cancers, 2023-03-30; DOI:10.3390/cancers15072006) (sulciner2023surgicalmanagementof pages 1-2)
Available in retrieved sources/tools during this run - MONDO (subtypes): - Non-functional pancreatic neuroendocrine tumor: MONDO_0004334 (OpenTargets mapping in context) (papadopouloumarketou2024hereditarysyndromesassociated pages 1-3) - Functional pancreatic neuroendocrine tumor: MONDO_0023206 (OpenTargets mapping in context) (papadopouloumarketou2024hereditarysyndromesassociated pages 1-3)
Not recovered from the currently retrieved sources/tools (will require explicit ontology lookups outside this run) - ICD-10 / ICD-11, MeSH ID, Orphanet ORPHA code, and a MONDO ID for the parent concept “pancreatic neuroendocrine tumor” were not directly available in the accessible documents returned by the tools in this session.
The evidence summarized here derives predominantly from aggregated disease-level resources (systematic reviews/meta-analyses and clinical practice guidelines) plus selected primary clinical trials and sequencing studies (andersen2024welldifferentiatedg1and pages 1-2, taherifard2024efficacyandsafety pages 1-3, partelli2024neoadjuvant177ludotatatefor pages 1-2, jiang2024multiregionwesof pages 1-2).
Most PanNETs are sporadic, but a clinically important fraction occurs in monogenic tumor syndromes (papadopouloumarketou2024hereditarysyndromesassociated pages 1-3, andersen2024welldifferentiatedg1and pages 1-2).
Quantitative hereditary burden: - “About 17% of PanNETs … develop in the context of monogenic familial tumor syndromes” (Papadopoulou-Marketou et al., Cancers, 2024-05-31; DOI:10.3390/cancers16112075) (papadopouloumarketou2024hereditarysyndromesassociated pages 1-3).
Authoritative 2024 review synthesis indicates hereditary PanNETs most often occur in: - MEN1 (MEN1 gene; tumor suppressor menin) - VHL (VHL) - TSC (TSC1/TSC2) - NF1 (NF1) - MEN4 (CDKN1B/p27Kip1) (papadopouloumarketou2024hereditarysyndromesassociated pages 1-3, papadopouloumarketou2024hereditarysyndromesassociated pages 14-16)
MEN1-specific quantitative penetrance/risk (from 2024 review): - MEN1 prevalence: 3–10/100,000, with “>95% of mutation carriers develop manifestations by age 50” (papadopouloumarketou2024hereditarysyndromesassociated pages 4-6). - “Lifetime risks” in MEN1: primary hyperparathyroidism 95%, duodenopancreatic NETs 80%, pituitary adenomas 50% (papadopouloumarketou2024hereditarysyndromesassociated pages 4-6). - Pancreatic NETs occur “in up to 80% of MEN1 patients” (papadopouloumarketou2024hereditarysyndromesassociated pages 4-6).
Direct abstract quote (screening recommendation): - “Genetic screening is recommended in childhood, and diagnostic screening starts often in adolescence, even in asymptomatic mutation carriers.” (Papadopoulou-Marketou et al., Cancers, 2024-05-31; DOI:10.3390/cancers16112075) (papadopouloumarketou2024hereditarysyndromesassociated pages 1-3)
No high-quality, PanNET-specific environmental or lifestyle risk-factor evidence was identified in the retrieved 2023–2024 sources used in this run. This is a known evidence gap relative to more common pancreatic cancers.
No PanNET-specific protective factors with quantitative support were identified in the retrieved sources.
No PanNET-specific gene–environment interaction data were identified in the retrieved sources.
The retrieved corpus did not include a dedicated clinical phenotype frequency table for individual functional syndromes (insulinoma, gastrinoma, glucagonoma, VIPoma, somatostatinoma). However, hereditary review context indicates syndrome-specific enrichment (e.g., insulinomas in MEN1/TSC) (papadopouloumarketou2024hereditarysyndromesassociated pages 1-3).
These are ontology mapping suggestions (not extracted from the cited papers): - Nonfunctioning tumor presentation: Abdominal pain (HP:0002027), Weight loss (HP:0001824), Jaundice (HP:0000952) (mass effect), Incidental finding (no single HPO term; often represented via clinical annotation rather than HPO). - Insulinoma syndrome: Hypoglycemia (HP:0001943), Neuroglycopenia (HP:0002187), Confusion (HP:0001289). - Gastrinoma/Zollinger–Ellison: Peptic ulcer (HP:0002592), Diarrhea (HP:0002014). - Glucagonoma syndrome: Necrolytic migratory erythema (HP:0031223), Diabetes mellitus (HP:0000819).
A 2024 systematic review/meta-analysis of expanded DNA sequencing (225 tumors) reported the following recurrent alterations: - MEN1: altered in 42% (95/225) - DAXX: 16% (37/225) - ATRX: 12% (27/225) and DAXX alterations occurred more frequently with MEN1 mutations (p<0.05) (Andersen et al., Frontiers in Endocrinology, 2024-05-30; DOI:10.3389/fendo.2024.1351624) (andersen2024welldifferentiatedg1and pages 1-2).
A 2024 multiregion WES study of treatment-naïve metastatic PanNET (10 patients) sequenced 29 primary samples, 31 lymph node metastases, and 15 liver metastases, reporting that MEN1/DAXX mutations may act as early drivers and that cases with MEN1/DAXX/ATRX mutations had longer median overall survival (median not reached vs 43.63 months; p=0.047) (Jiang et al., Cell Communication and Signaling, 2024-03-15; DOI:10.1186/s12964-024-01545-6) (jiang2024multiregionwesof pages 1-2). The same work reports metastatic lesions (particularly in MEN1/DAXX-mutant cases) showing a more immunosuppressive environment by multiplex IHC (jiang2024multiregionwesof pages 1-2).
Ontology mapping suggestions (not extracted verbatim from papers): - GO biological processes: “mTOR signaling” (GO:0031929), “chromatin organization” (GO:0006325), “DNA repair” (GO:0006281), “cell proliferation” (GO:0008283), “angiogenesis” (GO:0001525). - Cell Ontology (CL) candidates: pancreatic endocrine cell populations including pancreatic alpha cell (CL:0000171), pancreatic beta cell (CL:0000169), and broader neuroendocrine cell (CL:0000160).
No PanNET-specific environmental toxins, infectious etiologies, or strong lifestyle risk/protective factors were supported by the retrieved evidence in this run.
A parsimonious mechanistic chain consistent with recent human sequencing evidence is: 1) Initiating genetic events (sporadic somatic or hereditary germline + second-hit), frequently involving MEN1 and chromatin remodeling genes (MEN1/DAXX/ATRX) (andersen2024welldifferentiatedg1and pages 1-2, papadopouloumarketou2024hereditarysyndromesassociated pages 4-6). 2) Pathway dysregulation (e.g., PI3K/AKT/mTOR alterations in subsets; additional pathway divergence between functional and non-functional tumors) leading to neuroendocrine tumor growth and heterogeneity (andersen2024welldifferentiatedg1and pages 1-2, jiang2024multiregionwesof pages 7-12). 3) Phenotypic divergence into functional hormone-secreting vs nonfunctioning tumors, and across WHO grades (Ki-67-based) that strongly influence prognosis and imaging phenotype (SSTR vs FDG) (sulciner2023surgicalmanagementof pages 1-2, pellegrino2023diagnosticmanagementof pages 5-6). 4) Metastatic progression often to liver/lymph nodes, with genomic and immune microenvironment heterogeneity; metastatic lesions may be more immunosuppressive (jiang2024multiregionwesof pages 1-2).
WHO-grade cutoffs commonly used in current practice: - G1: Ki-67 <3% - G2: Ki-67 3–20% - G3: Ki-67 >20% (sulciner2023surgicalmanagementof pages 1-2).
A radiology review summarizing major guidelines notes that the “correct diagnostic management … includes a combination of morphological and functional evaluations,” with: - ENETS-recommended contrast-enhanced CT for diagnostic workup and staging, - MRI including DWI for liver/pancreas/bone/brain assessment, - US/CEUS for liver metastases detection/characterization and biopsy guidance, - EUS as highly sensitive for pancreatic lesion detection and biopsy (pellegrino2023diagnosticmanagementof pages 1-2, pellegrino2023diagnosticmanagementof pages 11-13).
Quantitative performance examples: - Multiphasic contrast CT sensitivity ≈82%, specificity 96% (sulciner2023surgicalmanagementof pages 2-5). - MRI sensitivity 93%, specificity 88% (sulciner2023surgicalmanagementof pages 2-5). - For small pancreatic NENs: EUS sensitivity 86% and specificity 92%; CT may miss 68.4% of lesions <10 mm (pellegrino2023diagnosticmanagementof pages 11-13).
SSTR PET has largely supplanted 111In-pentetreotide imaging and is used for staging, localization, PRRT selection, and standardized reporting/QC (hope2023snmmiprocedurestandardeanm pages 1-2, hope2023snmmiprocedurestandardeanm pages 2-3). The guideline explicitly notes: - “68Ga-DOTATATE approved by the Food and Drug Administration (FDA) in 2016, 68Ga-DOTATOC approved by the European Medicines Agency in 2016 and the FDA in 2019, and 64Cu-DOTATATE approved by the FDA in 2020.” (Hope et al., J Nucl Med, 2023-02-01; DOI:10.2967/jnumed.122.264860) (hope2023snmmiprocedurestandardeanm pages 1-2)
Administered-activity guidance examples: - 68Ga-DOTATATE: 2 MBq/kg up to 200 MBq - 68Ga-DOTATOC: ~148 MBq - 64Cu-DOTATATE: 148 MBq (hope2023snmmiprocedurestandardeanm pages 3-4).
Surgery remains the primary curative modality for localized PanNETs (sulciner2023surgicalmanagementof pages 1-2). However, practice is evolving toward selective observation for small, low-risk, non-functioning lesions:
Direct abstract quote (active surveillance): - “There is increasing data to suggest small, nonfunctional PNETs (less than 2 cm) are appropriate follow with nonoperative active surveillance.” (Sulciner & Clancy, 2023) (sulciner2023surgicalmanagementof pages 1-2)
Guideline convergence summarized in the surgical review includes: - NANETS: observation for <1 cm (and individualized 1–2 cm) - NCCN: observation ≤2 cm (stronger evidence ≤1 cm) - ENETS: surveillance for ≤2 cm if low-grade, asymptomatic, non-suspicious imaging (sulciner2023surgicalmanagementof pages 10-11).
A multicentre phase II study evaluated neoadjuvant 177Lu-DOTATATE followed by surgery in high-risk, sporadic, well-differentiated non-functioning PanNETs with positive 68Ga-DOTA PET (Partelli et al., Br J Surg, 2024-08-01; DOI:10.1093/bjs/znae178) (partelli2024neoadjuvant177ludotatatefor pages 1-2).
Direct abstract quote (efficacy and safety endpoints): - “A partial radiological response was observed in 18 of 31 patients, and 13 patients had stable disease. Disease progression was not observed.” (partelli2024neoadjuvant177ludotatatefor pages 1-2)
Key outcomes: - Enrolled 31 (March 2020–Feb 2023); 26 completed 4 cycles (partelli2024neoadjuvant177ludotatatefor pages 1-2). - Surgery performed in 29; 24 R0 and 4 R1 resections; 1 unresectable due to vascular involvement (partelli2024neoadjuvant177ludotatatefor pages 1-2). - Postoperative complications: 21/29; severe: 7/29; no postoperative deaths (partelli2024neoadjuvant177ludotatatefor pages 1-2).
ClinicalTrials.gov implementation details (protocol level): - Trial ID NCT04385992, phase II, single arm; 4 cycles 7,400 MBq (200 mCi) every 6–8 weeks with renal-protective amino acid infusion; primary endpoint: 90-day morbidity/mortality after surgery (NCT04385992 chunk 2, NCT04385992 chunk 1).
Supporting visual evidence (trial flow and outcome tables): (partelli2024neoadjuvant177ludotatatefor media 37188ff4, partelli2024neoadjuvant177ludotatatefor media 7fe3253e, partelli2024neoadjuvant177ludotatatefor media 8fe1b3ff)
A 2023 NCI NET clinical trials planning report highlights that PRRT approval has raised sequencing and optimization questions (re-treatment, combinations, dosimetry) (piscopo2023diagnosismanagementand pages 2-4).
A 2024 systematic review/meta-analysis (14 studies; 441 patients) reported pooled outcomes for temozolomide-based regimens: - ORR 41.2% (95% CI 32.4–50.6%) - DCR 85.3% (95% CI 74.9–91.9%) - >50% chromogranin A decline 44.9% - Serious AEs 23.7% (mainly hematologic) (Taherifard et al., BMC Cancer, 2024-02-14; DOI:10.1186/s12885-024-11926-2) (taherifard2024efficacyandsafety pages 1-3).
A 2023 systematic review/meta-analysis of EUS-RFA (19 studies; 183 patients; 196 lesions) reported very high pooled clinical efficacy:
Direct abstract quotes (definitions and results): - Clinical success definition: “the disappearance of clinical symptoms for functional (F-) PanNETs and as complete ablation per nonfunctional (NF)-PanNETs.” (armellini2023efficacyandsafety pages 1-2) - Outcomes: “Pooled estimates for the overall AE rates for the clinical efficacy were 17.8% (95% CI 9.1–26.4%) and 95.1% (95% CI 91.2–98.9%) for F-PanNETs and 24.6% (95% CI 7.4–41.8%) and 93.4% (95% CI 88.4–98.4%) for NF-PanNETs.” (Armellini et al., Medicina, 2023-02-03; DOI:10.3390/medicina59020359) (armellini2023efficacyandsafety pages 1-2)
In metastatic settings, retrospective and registry analyses reported improved 5-year overall survival in selected patients undergoing resection (e.g., 56.6% vs 23.9%; 67.9% vs 22.3%) and prolonged median survival after hepatic metastasectomy (median 160 months in a single-institution series) (sulciner2023surgicalmanagementof pages 12-14).
Ontology mapping suggestions (not extracted verbatim from papers): - Surgical resection (MAXO:0000058) - Active surveillance (MAXO:0000054) - Somatostatin receptor PET imaging (MAXO: imaging procedure; may require local MAXO mapping) - Peptide receptor radionuclide therapy (PRRT) (MAXO:0000146) - Chemotherapy (MAXO:0000059) - Radiofrequency ablation (MAXO:0000500)
No validated primary prevention interventions or population screening programs were identified in the retrieved PanNET-specific evidence. In hereditary syndromes, prevention is implemented as risk-tailored surveillance beginning in childhood/adolescence for mutation carriers (papadopouloumarketou2024hereditarysyndromesassociated pages 1-3, papadopouloumarketou2024hereditarysyndromesassociated pages 4-6).
No comparative natural-disease or cross-species transmission information was identified in the retrieved sources.
A 2024 paper set retrieved in this session includes an immunocompetent mouse model created by combined loss of MEN1, ATRX, and PTEN, intended to model high-grade PanNET biology; however, detailed phenotype recapitulation metrics were not extracted into the current evidence set for citation in this report.
1) Theragnostic standardization: 2023 SNMMI/EANM practice guidance formalizes protocol, reporting, and QA expectations for SSTR PET across approved tracers (68Ga-DOTATATE, 68Ga-DOTATOC, 64Cu-DOTATATE), enabling more reproducible staging and PRRT selection in real-world practice and multicenter trials (hope2023snmmiprocedurestandardeanm pages 1-2, hope2023snmmiprocedurestandardeanm pages 3-4).
2) Neoadjuvant PRRT evidence in PanNET: The 2024 NEOLUPANET phase II trial provides direct prospective evidence that neoadjuvant 177Lu-DOTATATE can produce objective responses and allow high rates of margin-negative resections in selected high-risk resectable NF-PanNETs, with substantial postoperative morbidity typical of pancreatic surgery (partelli2024neoadjuvant177ludotatatefor pages 1-2, partelli2024neoadjuvant177ludotatatefor media 37188ff4, partelli2024neoadjuvant177ludotatatefor media 7fe3253e, partelli2024neoadjuvant177ludotatatefor media 8fe1b3ff).
3) Expanding minimally invasive local therapy: 2023 meta-analytic evidence supports EUS-RFA as a high-efficacy local option for selected low-grade functional and non-functional PanNETs, with nontrivial adverse event rates and the need for careful patient selection and expertise (armellini2023efficacyandsafety pages 1-2).
4) Genomics informing stratification: 2024 meta-analysis quantifies core mutation frequencies in G1/G2 PanNETs (MEN1/DAXX/ATRX) and highlights pathway differences in non-functioning tumors; 2024 multiregion WES extends this to metastatic evolution and microenvironment heterogeneity, supporting a future of more precise prognostic and therapeutic stratification (andersen2024welldifferentiatedg1and pages 1-2, jiang2024multiregionwesof pages 1-2).
The following table consolidates the most actionable identifiers, epidemiology, molecular alterations, diagnostic performance, and treatment outcomes from the retrieved evidence:
| Domain | Finding (with numbers) | Source (first author year) | Publication date | URL/DOI |
|---|---|---|---|---|
| Disease identifiers / synonyms | Pancreatic neuroendocrine tumor; pancreatic neuroendocrine tumour; PanNET; pNET; PNET; pancreatic neuroendocrine neoplasm; classified clinically as functional vs non-functional (sulciner2023surgicalmanagementof pages 1-2, papadopouloumarketou2024hereditarysyndromesassociated pages 1-3) | Sulciner 2023; Papadopoulou-Marketou 2024 | 2023-03; 2024-05 | https://doi.org/10.3390/cancers15072006 ; https://doi.org/10.3390/cancers16112075 |
| MONDO identifiers available in context | Non-functional pancreatic neuroendocrine tumor: MONDO_0004334; functional pancreatic neuroendocrine tumor: MONDO_0023206 (from Open Targets disease mapping in retrieved context) (papadopouloumarketou2024hereditarysyndromesassociated pages 1-3) | Open Targets context | 2024 retrieval context | Open Targets disease-target association context |
| Epidemiology | PanNETs account for ~1-2% of pancreatic cancers / ~2% of pancreatic neoplasms; incidence reported at 0.48 per 100,000/year; ~17% arise in inherited monogenic syndromes; ~30% are functioning and most are non-functioning (sulciner2023surgicalmanagementof pages 1-2, papadopouloumarketou2024hereditarysyndromesassociated pages 1-3) | Sulciner 2023; Papadopoulou-Marketou 2024 | 2023-03; 2024-05 | https://doi.org/10.3390/cancers15072006 ; https://doi.org/10.3390/cancers16112075 |
| WHO grading / prognosis | Grade 1: Ki-67 <3%; Grade 2: Ki-67 3-20%; Grade 3: Ki-67 >20%; median overall survival reported as 12 years for grade 1 vs 10 months for grade 3 (sulciner2023surgicalmanagementof pages 1-2) | Sulciner 2023 | 2023-03 | https://doi.org/10.3390/cancers15072006 |
| Key molecular alterations | Meta-analysis of 225 G1/G2 PanNETs: MEN1 altered in 42% (95/225), DAXX in 16% (37/225), ATRX in 12% (27/225); DAXX alterations more frequent with MEN1 mutations; non-functioning PanNETs showed recurrent alterations in PI3K, Wnt, NOTCH, and RTK-RAS pathways (andersen2024welldifferentiatedg1and pages 1-2) | Andersen 2024 | 2024-05 | https://doi.org/10.3389/fendo.2024.1351624 |
| Metastatic genomics / evolution | Multiregion WES of metastatic PanNETs: 10 treatment-naive patients, 29 primary samples, 31 lymph-node metastases, 15 liver metastases; MEN1/DAXX mutations appeared early; MEN1/DAXX/ATRX-mutant cases had longer median OS (not reached vs 43.63 months, p=0.047) and more immunosuppressive metastatic microenvironment (jiang2024multiregionwesof pages 1-2, jiang2024multiregionwesof pages 4-5) | Jiang 2024 | 2024-03 | https://doi.org/10.1186/s12964-024-01545-6 |
| Imaging: CT | Multiphasic contrast CT sensitivity ~82%, specificity 96% for PanNET detection; ENETS-based imaging review recommends contrast-enhanced CT for diagnosis/staging/surveillance (sulciner2023surgicalmanagementof pages 2-5, pellegrino2023diagnosticmanagementof pages 2-4) | Sulciner 2023; Pellegrino 2023 | 2023-03; 2023-01 | https://doi.org/10.3390/cancers15072006 ; https://doi.org/10.3390/tomography9010018 |
| Imaging: MRI | MRI sensitivity 93%, specificity 88% in Sulciner review; MRI sensitivity for PanNET detection reported as 79% (range 54-100%) and mean sensitivity for liver metastases 91% (range 82-98%) in radiology review; DWI recommended for liver/pancreas evaluation (sulciner2023surgicalmanagementof pages 2-5, pellegrino2023diagnosticmanagementof pages 8-10) | Sulciner 2023; Pellegrino 2023 | 2023-03; 2023-01 | https://doi.org/10.3390/cancers15072006 ; https://doi.org/10.3390/tomography9010018 |
| Imaging: SSTR PET/CT | 68Ga-DOTATATE/DOTANOC PET/CT sensitivity 93%, specificity 91%; detection by grade ~95% for G1, 87.5% for G2, 37.5% for G3; broader SSTR PET review reports 68Ga/64Cu-DOTA-SSA PET/CT sensitivity 86-100% and specificity 79-100% for panNETs overall, but low sensitivity (~25%) for insulinoma (sulciner2023surgicalmanagementof pages 2-5, pellegrino2023diagnosticmanagementof pages 5-6, hope2023snmmiprocedurestandardeanm pages 4-5) | Sulciner 2023; Pellegrino 2023; Hope 2023 | 2023-03; 2023-01; 2023-02 | https://doi.org/10.3390/cancers15072006 ; https://doi.org/10.3390/tomography9010018 ; https://doi.org/10.2967/jnumed.122.264860 |
| Imaging: EUS | EUS mean sensitivity 75-97%; especially useful for lesions <2 cm; intraoperative ultrasound may detect up to 96% of tumors; separate radiology review reports EUS sensitivity 86% and specificity 92% for small PanNETs, and CT misses 68.4% of lesions <10 mm (sulciner2023surgicalmanagementof pages 2-5, pellegrino2023diagnosticmanagementof pages 11-13) | Sulciner 2023; Pellegrino 2023 | 2023-03; 2023-01 | https://doi.org/10.3390/cancers15072006 ; https://doi.org/10.3390/tomography9010018 |
| Surgery / surveillance | Increasing evidence supports active surveillance for small non-functional tumors <2 cm; MEN1-associated PanNETs <2 cm can safely undergo active surveillance (sulciner2023surgicalmanagementof pages 1-2, sulciner2023surgicalmanagementof pages 12-14) | Sulciner 2023 | 2023-03 | https://doi.org/10.3390/cancers15072006 |
| Neoadjuvant PRRT (NEOLUPANET) | Phase II NCT04385992: 31 enrolled; 26 completed 4 cycles of 177Lu-DOTATATE; partial response 18/31, stable disease 13/31, no progression; 29 underwent surgery; 24 R0 and 4 R1 resections; 1 unresectable due to vascular involvement; postoperative complications 21/29, severe complications 7/29, no postoperative deaths (partelli2024neoadjuvant177ludotatatefor pages 1-2, partelli2024neoadjuvant177ludotatatefor pages 2-3, NCT04385992 chunk 2) | Partelli 2024 | 2024-08 | https://doi.org/10.1093/bjs/znae178 |
| Temozolomide-based regimens | Systematic review/meta-analysis (14 studies, 441 patients): pooled ORR 41.2% (95% CI 32.4-50.6%), DCR 85.3% (95% CI 74.9-91.9%), >50% chromogranin A decline 44.9%; non-serious AEs 93.8%, serious AEs 23.7% (mainly hematologic) (taherifard2024efficacyandsafety pages 1-3) | Taherifard 2024 | 2024-02 | https://doi.org/10.1186/s12885-024-11926-2 |
| EUS-guided RFA | Meta-analysis: 19-20 studies, 183 patients, 196 lesions (101 functional, 95 non-functional); pooled clinical efficacy 95.1% (95% CI 91.2-98.9%) for functional PanNETs and 93.4% (95% CI 88.4-98.4%) for non-functional PanNETs; pooled AE rates 17.8% (95% CI 9.1-26.4%) and 24.6% (95% CI 7.4-41.8%), respectively (armellini2023efficacyandsafety pages 1-2, armellini2023efficacyandsafety pages 2-4) | Armellini 2023 | 2023-02 | https://doi.org/10.3390/medicina59020359 |
| Theragnostics / SSTR agents | Approved SSTR PET agents in guideline context: 68Ga-DOTATATE, 68Ga-DOTATOC, 64Cu-DOTATATE; SSTR PET used for initial staging, primary localization, PRRT selection, and post-PRRT assessment; radiology review notes PET spatial resolution superiority over SRS (0.5 cm vs 1.5 cm) (hope2023snmmiprocedurestandardeanm pages 4-5, hope2023snmmiprocedurestandardeanm pages 2-3, hope2023snmmiprocedurestandardeanm pages 3-4, pellegrino2023diagnosticmanagementof pages 5-6) | Hope 2023; Pellegrino 2023 | 2023-02; 2023-01 | https://doi.org/10.2967/jnumed.122.264860 ; https://doi.org/10.3390/tomography9010018 |
Table: This table compiles the most decision-relevant identifiers, epidemiology, molecular features, imaging performance, and treatment outcomes for pancreatic neuroendocrine tumors from the retrieved 2023-2024 evidence. It is useful as a compact reference for populating structured disease knowledge base fields.
References
(sulciner2023surgicalmanagementof pages 1-2): Megan L. Sulciner and Thomas E. Clancy. Surgical management of pancreatic neuroendocrine tumors. Cancers, 15:2006, Mar 2023. URL: https://doi.org/10.3390/cancers15072006, doi:10.3390/cancers15072006. This article has 42 citations.
(papadopouloumarketou2024hereditarysyndromesassociated pages 1-3): Nektaria Papadopoulou-Marketou, Marina Tsoli, Eleftherios Chatzellis, Krystallenia I. Alexandraki, and Gregory Kaltsas. Hereditary syndromes associated with pancreatic and lung neuroendocrine tumors. Cancers, 16:2075, May 2024. URL: https://doi.org/10.3390/cancers16112075, doi:10.3390/cancers16112075. This article has 16 citations.
(hope2023snmmiprocedurestandardeanm pages 1-2): Thomas A. Hope, Martin Allen-Auerbach, Lisa Bodei, Jeremie Calais, Magnus Dahlbom, Lisa K. Dunnwald, Michael M. Graham, Heather A. Jacene, Courtney Lawhn Heath, Erik S. Mittra, Chadwick L. Wright, Wolfgang P. Fendler, Ken Herrmann, David Taïeb, and Andreas Kjaer. Snmmi procedure standard/eanm practice guideline for sstr pet: imaging neuroendocrine tumors. The Journal of Nuclear Medicine, 64:204-210, Feb 2023. URL: https://doi.org/10.2967/jnumed.122.264860, doi:10.2967/jnumed.122.264860. This article has 124 citations.
(sulciner2023surgicalmanagementof pages 2-5): Megan L. Sulciner and Thomas E. Clancy. Surgical management of pancreatic neuroendocrine tumors. Cancers, 15:2006, Mar 2023. URL: https://doi.org/10.3390/cancers15072006, doi:10.3390/cancers15072006. This article has 42 citations.
(andersen2024welldifferentiatedg1and pages 1-2): Kirstine Øster Andersen, Sönke Detlefsen, Klaus Brusgaard, and Henrik Thybo Christesen. Well-differentiated g1 and g2 pancreatic neuroendocrine tumors: a meta-analysis of published expanded dna sequencing data. Frontiers in Endocrinology, May 2024. URL: https://doi.org/10.3389/fendo.2024.1351624, doi:10.3389/fendo.2024.1351624. This article has 10 citations.
(taherifard2024efficacyandsafety pages 1-3): Erfan Taherifard, Muhammad Bakhtiar, Mahnoor Mahnoor, Rabeea Ahmed, Ludimila Cavalcante, Janie Zhang, and Anwaar Saeed. Efficacy and safety of temozolomide-based regimens in advanced pancreatic neuroendocrine tumors: a systematic review and meta-analysis. BMC Cancer, Feb 2024. URL: https://doi.org/10.1186/s12885-024-11926-2, doi:10.1186/s12885-024-11926-2. This article has 10 citations and is from a peer-reviewed journal.
(partelli2024neoadjuvant177ludotatatefor pages 1-2): Stefano Partelli, Luca Landoni, Mirco Bartolomei, Alessandro Zerbi, Chiara Maria Grana, Ugo Boggi, Giovanni Butturini, Riccardo Casadei, Roberto Salvia, and Massimo Falconi. Neoadjuvant 177lu-dotatate for non-functioning pancreatic neuroendocrine tumours (neolupanet): multicentre phase ii study. The British Journal of Surgery, Aug 2024. URL: https://doi.org/10.1093/bjs/znae178, doi:10.1093/bjs/znae178. This article has 35 citations.
(jiang2024multiregionwesof pages 1-2): Yu Jiang, Yi-han Dong, Shi-wei Zhao, Dong-yu Liu, Ji-yang Zhang, Xiao-ya Xu, Hao Chen, Hao Chen, and Jia-bin Jin. Multiregion wes of metastatic pancreatic neuroendocrine tumors revealed heterogeneity in genomic alterations, immune microenvironment and evolutionary patterns. Cell Communication and Signaling : CCS, Mar 2024. URL: https://doi.org/10.1186/s12964-024-01545-6, doi:10.1186/s12964-024-01545-6. This article has 8 citations.
(papadopouloumarketou2024hereditarysyndromesassociated pages 14-16): Nektaria Papadopoulou-Marketou, Marina Tsoli, Eleftherios Chatzellis, Krystallenia I. Alexandraki, and Gregory Kaltsas. Hereditary syndromes associated with pancreatic and lung neuroendocrine tumors. Cancers, 16:2075, May 2024. URL: https://doi.org/10.3390/cancers16112075, doi:10.3390/cancers16112075. This article has 16 citations.
(papadopouloumarketou2024hereditarysyndromesassociated pages 4-6): Nektaria Papadopoulou-Marketou, Marina Tsoli, Eleftherios Chatzellis, Krystallenia I. Alexandraki, and Gregory Kaltsas. Hereditary syndromes associated with pancreatic and lung neuroendocrine tumors. Cancers, 16:2075, May 2024. URL: https://doi.org/10.3390/cancers16112075, doi:10.3390/cancers16112075. This article has 16 citations.
(jiang2024multiregionwesof pages 7-12): Yu Jiang, Yi-han Dong, Shi-wei Zhao, Dong-yu Liu, Ji-yang Zhang, Xiao-ya Xu, Hao Chen, Hao Chen, and Jia-bin Jin. Multiregion wes of metastatic pancreatic neuroendocrine tumors revealed heterogeneity in genomic alterations, immune microenvironment and evolutionary patterns. Cell Communication and Signaling : CCS, Mar 2024. URL: https://doi.org/10.1186/s12964-024-01545-6, doi:10.1186/s12964-024-01545-6. This article has 8 citations.
(pellegrino2023diagnosticmanagementof pages 5-6): Fabio Pellegrino, Vincenza Granata, Roberta Fusco, Francesca Grassi, Salvatore Tafuto, Luca Perrucci, Giulia Tralli, and Mariano Scaglione. Diagnostic management of gastroenteropancreatic neuroendocrine neoplasms: technique optimization and tips and tricks for radiologists. Tomography, 9:217-246, Jan 2023. URL: https://doi.org/10.3390/tomography9010018, doi:10.3390/tomography9010018. This article has 22 citations.
(sulciner2023surgicalmanagementof pages 12-14): Megan L. Sulciner and Thomas E. Clancy. Surgical management of pancreatic neuroendocrine tumors. Cancers, 15:2006, Mar 2023. URL: https://doi.org/10.3390/cancers15072006, doi:10.3390/cancers15072006. This article has 42 citations.
(papadopouloumarketou2024hereditarysyndromesassociated pages 3-4): Nektaria Papadopoulou-Marketou, Marina Tsoli, Eleftherios Chatzellis, Krystallenia I. Alexandraki, and Gregory Kaltsas. Hereditary syndromes associated with pancreatic and lung neuroendocrine tumors. Cancers, 16:2075, May 2024. URL: https://doi.org/10.3390/cancers16112075, doi:10.3390/cancers16112075. This article has 16 citations.
(pellegrino2023diagnosticmanagementof pages 1-2): Fabio Pellegrino, Vincenza Granata, Roberta Fusco, Francesca Grassi, Salvatore Tafuto, Luca Perrucci, Giulia Tralli, and Mariano Scaglione. Diagnostic management of gastroenteropancreatic neuroendocrine neoplasms: technique optimization and tips and tricks for radiologists. Tomography, 9:217-246, Jan 2023. URL: https://doi.org/10.3390/tomography9010018, doi:10.3390/tomography9010018. This article has 22 citations.
(pellegrino2023diagnosticmanagementof pages 11-13): Fabio Pellegrino, Vincenza Granata, Roberta Fusco, Francesca Grassi, Salvatore Tafuto, Luca Perrucci, Giulia Tralli, and Mariano Scaglione. Diagnostic management of gastroenteropancreatic neuroendocrine neoplasms: technique optimization and tips and tricks for radiologists. Tomography, 9:217-246, Jan 2023. URL: https://doi.org/10.3390/tomography9010018, doi:10.3390/tomography9010018. This article has 22 citations.
(hope2023snmmiprocedurestandardeanm pages 2-3): Thomas A. Hope, Martin Allen-Auerbach, Lisa Bodei, Jeremie Calais, Magnus Dahlbom, Lisa K. Dunnwald, Michael M. Graham, Heather A. Jacene, Courtney Lawhn Heath, Erik S. Mittra, Chadwick L. Wright, Wolfgang P. Fendler, Ken Herrmann, David Taïeb, and Andreas Kjaer. Snmmi procedure standard/eanm practice guideline for sstr pet: imaging neuroendocrine tumors. The Journal of Nuclear Medicine, 64:204-210, Feb 2023. URL: https://doi.org/10.2967/jnumed.122.264860, doi:10.2967/jnumed.122.264860. This article has 124 citations.
(hope2023snmmiprocedurestandardeanm pages 3-4): Thomas A. Hope, Martin Allen-Auerbach, Lisa Bodei, Jeremie Calais, Magnus Dahlbom, Lisa K. Dunnwald, Michael M. Graham, Heather A. Jacene, Courtney Lawhn Heath, Erik S. Mittra, Chadwick L. Wright, Wolfgang P. Fendler, Ken Herrmann, David Taïeb, and Andreas Kjaer. Snmmi procedure standard/eanm practice guideline for sstr pet: imaging neuroendocrine tumors. The Journal of Nuclear Medicine, 64:204-210, Feb 2023. URL: https://doi.org/10.2967/jnumed.122.264860, doi:10.2967/jnumed.122.264860. This article has 124 citations.
(hope2023snmmiprocedurestandardeanm pages 5-6): Thomas A. Hope, Martin Allen-Auerbach, Lisa Bodei, Jeremie Calais, Magnus Dahlbom, Lisa K. Dunnwald, Michael M. Graham, Heather A. Jacene, Courtney Lawhn Heath, Erik S. Mittra, Chadwick L. Wright, Wolfgang P. Fendler, Ken Herrmann, David Taïeb, and Andreas Kjaer. Snmmi procedure standard/eanm practice guideline for sstr pet: imaging neuroendocrine tumors. The Journal of Nuclear Medicine, 64:204-210, Feb 2023. URL: https://doi.org/10.2967/jnumed.122.264860, doi:10.2967/jnumed.122.264860. This article has 124 citations.
(sulciner2023surgicalmanagementof pages 10-11): Megan L. Sulciner and Thomas E. Clancy. Surgical management of pancreatic neuroendocrine tumors. Cancers, 15:2006, Mar 2023. URL: https://doi.org/10.3390/cancers15072006, doi:10.3390/cancers15072006. This article has 42 citations.
(NCT04385992 chunk 2): Massimo Falconi. Neoadjuvant PRRT With 177Lu-DOTATATE Followed by Surgery for Resectable PanNET. IRCCS San Raffaele. 2020. ClinicalTrials.gov Identifier: NCT04385992
(NCT04385992 chunk 1): Massimo Falconi. Neoadjuvant PRRT With 177Lu-DOTATATE Followed by Surgery for Resectable PanNET. IRCCS San Raffaele. 2020. ClinicalTrials.gov Identifier: NCT04385992
(partelli2024neoadjuvant177ludotatatefor media 37188ff4): Stefano Partelli, Luca Landoni, Mirco Bartolomei, Alessandro Zerbi, Chiara Maria Grana, Ugo Boggi, Giovanni Butturini, Riccardo Casadei, Roberto Salvia, and Massimo Falconi. Neoadjuvant 177lu-dotatate for non-functioning pancreatic neuroendocrine tumours (neolupanet): multicentre phase ii study. The British Journal of Surgery, Aug 2024. URL: https://doi.org/10.1093/bjs/znae178, doi:10.1093/bjs/znae178. This article has 35 citations.
(partelli2024neoadjuvant177ludotatatefor media 7fe3253e): Stefano Partelli, Luca Landoni, Mirco Bartolomei, Alessandro Zerbi, Chiara Maria Grana, Ugo Boggi, Giovanni Butturini, Riccardo Casadei, Roberto Salvia, and Massimo Falconi. Neoadjuvant 177lu-dotatate for non-functioning pancreatic neuroendocrine tumours (neolupanet): multicentre phase ii study. The British Journal of Surgery, Aug 2024. URL: https://doi.org/10.1093/bjs/znae178, doi:10.1093/bjs/znae178. This article has 35 citations.
(partelli2024neoadjuvant177ludotatatefor media 8fe1b3ff): Stefano Partelli, Luca Landoni, Mirco Bartolomei, Alessandro Zerbi, Chiara Maria Grana, Ugo Boggi, Giovanni Butturini, Riccardo Casadei, Roberto Salvia, and Massimo Falconi. Neoadjuvant 177lu-dotatate for non-functioning pancreatic neuroendocrine tumours (neolupanet): multicentre phase ii study. The British Journal of Surgery, Aug 2024. URL: https://doi.org/10.1093/bjs/znae178, doi:10.1093/bjs/znae178. This article has 35 citations.
(piscopo2023diagnosismanagementand pages 2-4): Leandra Piscopo, Emilia Zampella, Sara Pellegrino, Fabio Volpe, Carmela Nappi, Valeria Gaudieri, Rosa Fonti, Silvana Del Vecchio, Alberto Cuocolo, and Michele Klain. Diagnosis, management and theragnostic approach of gastro-entero-pancreatic neuroendocrine neoplasms. Cancers, 15:3483, Jul 2023. URL: https://doi.org/10.3390/cancers15133483, doi:10.3390/cancers15133483. This article has 14 citations.
(armellini2023efficacyandsafety pages 1-2): Elia Armellini, Antonio Facciorusso, and Stefano Francesco Crinò. Efficacy and safety of endoscopic ultrasound-guided radiofrequency ablation for pancreatic neuroendocrine tumors: a systematic review and metanalysis. Medicina, 59:359, Feb 2023. URL: https://doi.org/10.3390/medicina59020359, doi:10.3390/medicina59020359. This article has 63 citations.
(jiang2024multiregionwesof pages 4-5): Yu Jiang, Yi-han Dong, Shi-wei Zhao, Dong-yu Liu, Ji-yang Zhang, Xiao-ya Xu, Hao Chen, Hao Chen, and Jia-bin Jin. Multiregion wes of metastatic pancreatic neuroendocrine tumors revealed heterogeneity in genomic alterations, immune microenvironment and evolutionary patterns. Cell Communication and Signaling : CCS, Mar 2024. URL: https://doi.org/10.1186/s12964-024-01545-6, doi:10.1186/s12964-024-01545-6. This article has 8 citations.
(pellegrino2023diagnosticmanagementof pages 2-4): Fabio Pellegrino, Vincenza Granata, Roberta Fusco, Francesca Grassi, Salvatore Tafuto, Luca Perrucci, Giulia Tralli, and Mariano Scaglione. Diagnostic management of gastroenteropancreatic neuroendocrine neoplasms: technique optimization and tips and tricks for radiologists. Tomography, 9:217-246, Jan 2023. URL: https://doi.org/10.3390/tomography9010018, doi:10.3390/tomography9010018. This article has 22 citations.
(pellegrino2023diagnosticmanagementof pages 8-10): Fabio Pellegrino, Vincenza Granata, Roberta Fusco, Francesca Grassi, Salvatore Tafuto, Luca Perrucci, Giulia Tralli, and Mariano Scaglione. Diagnostic management of gastroenteropancreatic neuroendocrine neoplasms: technique optimization and tips and tricks for radiologists. Tomography, 9:217-246, Jan 2023. URL: https://doi.org/10.3390/tomography9010018, doi:10.3390/tomography9010018. This article has 22 citations.
(hope2023snmmiprocedurestandardeanm pages 4-5): Thomas A. Hope, Martin Allen-Auerbach, Lisa Bodei, Jeremie Calais, Magnus Dahlbom, Lisa K. Dunnwald, Michael M. Graham, Heather A. Jacene, Courtney Lawhn Heath, Erik S. Mittra, Chadwick L. Wright, Wolfgang P. Fendler, Ken Herrmann, David Taïeb, and Andreas Kjaer. Snmmi procedure standard/eanm practice guideline for sstr pet: imaging neuroendocrine tumors. The Journal of Nuclear Medicine, 64:204-210, Feb 2023. URL: https://doi.org/10.2967/jnumed.122.264860, doi:10.2967/jnumed.122.264860. This article has 124 citations.
(partelli2024neoadjuvant177ludotatatefor pages 2-3): Stefano Partelli, Luca Landoni, Mirco Bartolomei, Alessandro Zerbi, Chiara Maria Grana, Ugo Boggi, Giovanni Butturini, Riccardo Casadei, Roberto Salvia, and Massimo Falconi. Neoadjuvant 177lu-dotatate for non-functioning pancreatic neuroendocrine tumours (neolupanet): multicentre phase ii study. The British Journal of Surgery, Aug 2024. URL: https://doi.org/10.1093/bjs/znae178, doi:10.1093/bjs/znae178. This article has 35 citations.
(armellini2023efficacyandsafety pages 2-4): Elia Armellini, Antonio Facciorusso, and Stefano Francesco Crinò. Efficacy and safety of endoscopic ultrasound-guided radiofrequency ablation for pancreatic neuroendocrine tumors: a systematic review and metanalysis. Medicina, 59:359, Feb 2023. URL: https://doi.org/10.3390/medicina59020359, doi:10.3390/medicina59020359. This article has 63 citations.