i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource. Neuroendocrine Tumors are tough to spot, tougher to treat. This infographic, created from Aman Chauhan, MD, Associate Professor of Medical Oncology, Leader of the Neuroendocrine Tumor Program, and Co-Director of the Theranostics Program at the University of Miami, Sylvester Comprehensive Cancer Center, presentation, delivers the latest diagnostic breakthroughs, treatment options, and personalized care strategies to improve patient outcomes. Get the insights you need, now! STATEMENT OF NEED Neuroendocrine tumors (NETs) are a heterogeneous group of rare tumors that originate from epithelial or nervous cells in the neuroendocrine system. They can arise from any organ, most commonly the gastrointestinal tract and lungs. Clinical presentation of NETs is highly variable, and patients can experience a broad spectrum of symptoms that significantly impact well-being and make diagnosis challenging. The last decade has seen progress in therapy for NETs based on improved pathological categorization and molecular understanding, resulting in increasing therapeutic choices. Therefore, it is crucial for clinicians to remain up to date on emerging diagnostic techniques and therapies to improve outcomes for their patients with NETs (Sultana et al, 2023). This actlvity, presented by Aman Chauhan, MD, Associate Professor of Medical Oncology, Leader of the Neuroendocrine Tumor Program, and Co-Director of the Theranostics Program at the University of Miami, Sylvester Comprehensive Cancer Center, will explore strategies for optimizing NET outcomes by closing the gaps in diagnosis and care. TARGET AUDIENCE Medical/radiation/surgical oncologists, pathologists, endocrinologists, gastroenterologists, advanced practice providers, and other healthcare professionals (HCPs) involved in the treatment of patients with neuroendocrine tumors (NETs). LEARNING OBJECTIVES Recognize the diverse clinical presentations of NETs to enhance differential diagnosis skills Identify patients at high risk for recurrence based on disease-related factors and patient characteristics Develop guideline-concordant, personalized treatment plans for patients with NETs, incorporating insights from recent clinical trials of novel therapies Relevant financial relationships exist between the following individuals and ineligible companies: Aman Chauhan, MD, discloses that he has served on an advisory board or panel for Boehringer Ingelheim, Curium, Exelixis, Novartis, Sanofi, and Seneca Therapeutics. The i3 Health planners, reviewers, and managers have nothing to disclose. i3 Health has mitigated all relevant financial relationships. COMMERCIAL SUPPORT This educational activity is supported by a medical education grant from Exelixis, Inc. Aggregate participant data will be shared with commercial supporters of this activity

1. Incidence Prevalence
8.52 NENs per 100,000
(2021)
170,000 US patients
with NETs (2016)
NETs are the solid
tumor with the
4TH HIGHEST
PREVALENCE
4TH HIGHEST
PREVALENCE
after colorectal,
lung and ovarian
Recorded
incidence has
NEARLY
DOUBLED
NEARLY
DOUBLED
in the last 25 years
MEDIAN OVERALL
SURVIVAL
Well-Differentiated
NETs
Poorly-Differentiated
NECs
16.8 YEARS
Spectrum of Neuroendocrine Neoplasms
NENs range from well-differentiated
neuroendocrine tumors to poorly-differentiated
neuroendocrine carcinomas (NECs) and are
graded according to Ki-67 and mitotic index
(grade 1 to grade 3)
Patients with low-to-intermediate–grade
NETs can live for years, whereas high-grade,
poorly-differentiated NETs have a dismal
prognosis
NETs can have dramatically different prognosis
depending on location, functionality, grade,
differentiation, extent of disease, and pace of
growth
WD = well-differentiated; PD = poorly-differentiated
G1 WD NET G2 WD NET G3 WD NET G3 PD NEC
GI
NET
Well-Differentiated NET
NEC
Poorly-Differentiated NET
Typical
Carcinoid
Atypical
Carcinoid
SCLC and
LCNEC
NET
Well-Differentiated NET
NEC
Poorly-Differentiated NET
Lung
SCLC = small cell lung cancer; LCNEC = large cell neuroendocrine carcinoma
Aman Chauhan, MD, Associate Professor of Medical Oncology,
Leader of the Neuroendocrine Tumor Program,
Co-Director of the Theranostics Program, University of Miami,
Sylvester Comprehensive Cancer Center
What Are
NETs?
Neuroendocrine tumors (NETs) are a diverse group
of cancers originating from neuroendocrine tissue
25%
Lungs
14%
No primary site
identified
8%
Pancreas
53%
All
gastrointestinal
(GI)
NETs range from indolent
to aggressive and have
widely ranging treatment
according to location,
grade (G), and stage
Most occur in the
gastrointestinal tract,
lungs, and pancreas, and
14% have no identifiable
primary site
NETs can be functional or
nonfunctional. Functional
NETs produce hormones,
which can cause
symptoms
Neuroendocrine tissues
occur throughout the
body, and NETs can occur
anywhere neuroendocrine
tissues are located
20%-30% of NETs are
functional and
produce hormones,
including:
SEROTONIN
VASOACTIVE INTESTINAL PEPTIDE
GASTRIN
GLUCAGON
INSULIN
Nevertheless, NETs are considered rare cancers with limited treatment options
Extent of Disease​
Low tumor burden/resectable​ High tumor burden/unresectable​
Widely metastatic​ Liver-dominant​
Pathology is key to determining prognosis and treatment
EVALUATION AND PROGNOSIS OF NETS
Characteristics of NETs​
Pace of Growth​
Stable (lower Ki-67, lower mitotic
index)​
Progressive (higher Ki-67, higher
mitotic index)​
Primary Site (Gastrointestinal)​
Foregut​ Midgut Hindgut Pancreas
Grade/Differentiation​
Well-Differentiated NET​ Poorly-Differentiated NEC​
Low-grade (G1)​ Intermediate-grade (G2)​ High-grade (G3)​ High-grade (G3)​
Hormone Status​
Functional​ Non-functional​
Somatostatin Receptor Expression​
High expression​ Low expression​
OPTIMIZING NEUROENDOCRINE
TUMOR OUTCOMES:
Closing the Gaps in Diagnosis and Care
INCIDENCE AND PREVALENCE OF
NEUROENDOCRINE NEOPLASMS (NENs)

2. SYMPTOMS
Abdominal Pain
Nausea
Diarrhea
Indigestion
Weight Loss
Flushing
Persistent Cough
Vomiting
Wheezing
NET patients report having
originally been misdiagnosed
1 in 2
1 in 2
from first symptoms to
correct NET diagnosis
4.3 years
4.3 years
It takes a median of
CORRECT DIAGNOSIS
NETs
NETs
Treatment of NETs
EVALUATION
Imaging
Biochemical
evaluation
Molecular
profiling
Genetic
counseling
Local/
Locoregional
Surgery
Locally
Advanced
Metastatic
Systemic
Therapy
Liver-Directed
Therapy
No role for adjuvant chemotherapy
Immunotherapy
(NECs only)
Chemotherapy
Somatostatin Analogues
Octreotide
Lanreotide
Lu-dotatate
177
Radioligand Therapy
Targeted Therapy
Cabozantinib
Everolimus
Sunitinib
Liver-directed radioembolization
Hepatic arterial embolization
Histotripsy
Liver resection
Thermal ablation
THERAPY
SEQUENCING:
THERAPY
SEQUENCING: Somatostatin
analogues
1
Lu-dotatate
177
(first line for Ki-67 >10%)
2
Cabozantinib, capecitabine/temozolomide
(CAPTEM), everolimus, sunitinib (pNET)
3
1980 1982 1988 2011 2014 2016 2017 2018 2020 2025
SSTR-positive if uptake in
measurable lesions is greater in liver
Ga-dotatate, Ga-dotatoc,
68 68
Cu-dotatate
64
SSTR-PET/CT or SSTR-PET/MRI, or
octreotide SPECT/CT only if SSTR-PET
is not available
Symptoms are
highly variable, from
asymptomatic to
profoundly disabling
Others can cause
mechanical
complications
(bleeding, obstruction)
or hormonal effects
Many NETs are
incidentally
discovered
NETs is a chronic indolent
disease in many
This can be a
not a
Prioritize quality of life
alongside longevity
NETs are
and
Referral to a NET multidisciplinary
program is vital
Accessing a specialized
center is NOT always EASY
Accessing a specialized
center is NOT always EASY
Peptide Receptor
Radionuclide
Therapy (PRRT)
at certain locations
is a significant milestone in NET
treatment, but access can be a
DIAGNOSTIC TOOLS
DIAGNOSTIC TOOLS
Well-Differentiated Poorly-Differentiated
High-grade
(G3)
>20%
>20
High-grade
(G3)
Intermediate-grade
(G2)
Low-grade
(G1)
Grade
Ki-67 Index
Mitotic Index
(mitoses/2 mm )
2
Functional
Imaging
>20%
3%-20%
<3%
>20
2-20
<2
Octreoscan SPECT or SSTR PET-positive
FDG PET-positive
References
Chauhan A, Chan K, Halfdanarson TR, et al (2024). Critical updates in neuroendocrine tumors: version 9 American Joint Committee on Cancer staging system for gastroenteropancreatic neuroendocrine
tumors. CA: A Cancer Journal for Clinicians, 74(4):359-367. DOI:10.3322/caac.21840
Chauhan A, Kohn E & Del Rivero J (2020). Neuroendocrine tumors-less well known, often misunderstood, and rapidly growing in incidence. JAMA Oncol, 6(1):21-22. DOI:10.1001/jamaoncol.2019.4568
Corbett V, Arnold S, Anthony L & Chauhan A (2021). Management of large cell neuroendocrine carcinoma. Front Oncol, 11:653162. DOI:10.3389/fonc.2021.653162
Dasari A, Shen C, Halperin D, et al (2017). Trends in the incidence, prevalence, and survival outcomes in patients with neuroendocrine tumors in the United States. JAMA Oncol, 3(10):1335-1342.
DOI:10.1001/jamaoncol.2017.0589
Dasari A, Wallace K, Halperin DM, et al (2025). Epidemiology of Neuroendocrine Neoplasms in the US. JAMA Netw Open, 8(6):e2515798.
National Comprehensive Cancer Network (2025). Clinical practice guidelines in oncology: Neuroendocrine and Adrenal Tumors. Version 2. 2025. Available at: https://www.nccn.org/guidelines/guidelines-
detail?category=1&id=1448
Oronsky B, Ma PC, Morgensztern D & Carter CA (2017). Nothing but NET: A review of neuroendocrine tumors and carcinomas. Neoplasia, 19(12):991–1002. DOI:10.1016/j.neo.2017.09.002
Perez K, Del Rivero J, Kennedy EB, et al (2025). Symptom management for well-differentiated gastroenteropancreatic neuroendocrine tumors: ASCO Guideline. JCO Oncology Practice, [Online Ahead of Print].
10.1200/OP-25-00133
Singh S, Granberg D, Wolin E, et al (2016). Patient-reported burden of a neuroendocrine tumor (NET) diagnosis: results from the first global survey of patients with NETs. J Glob Oncol, 3(1):34-53.
DOI:10.1200/JGO.2015.002980
Wolin EM, Leyden J, Goldstein G, et al (2017). Patient-reported experience of diagnosis, management, and burden of neuroendocrine tumors. Pancreas, 46(5):639-647. DOI:10.1097/MPA.0000000000000818
This educational activity is supported by a medical education grant from Exelixis, Inc.
GEP-NET = gastroenteropancreatic NET
DIAGNOSIS
DIAGNOSIS PHYSICIAN AWARENESS IS IMPORTANT
PHYSICIAN AWARENESS IS IMPORTANT
If you don’t suspect it, you can’t detect it!
If you don’t suspect it, you can’t detect it!
PATIENT PERSPECTIVES
INCORRECT DIAGNOSIS
Stomach Ulcers
Irritable Bowel Syndrome
Obstructed Bowel
Pneumonia
Gastritis
Asthma
Anxiety or Depression
Menopause
FDG = fluorodeoxyglucose; PET = positron emission tomography; SPECT = single photon emission computed tomography; SSTR = somatostatin receptor; Ga = gallium; Cu = copper
FUNCTIONAL
IMAGING IS KEY
Co-management with a high-volume
multidisciplinary NETs center is highly encouraged
Clinical trials preferred for any line
NEUROENDOCRINE ONCOLOGY
NEUROENDOCRINE ONCOLOGY
ADVANCES IN
ADVANCES IN
Octreotide Lanreotide in
GEP-NET
Telotristat
Ga-Dotatate
PET
68
Streptozocin Everolimus
Sunitinib in
pNET
Everolimus
in Lung/GI NET
Capecitabine/
Temozolomide
Lu-Dotatate
177
Cu-Dotatate PET
64
Cabozanitinib
pNET = pancreatic neuroendocrine tumor
Lu = lutetium
Targeted therapies
(cabozantinib,
everolimus) are effective
but can have side effects
and
are key