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Neuroendocrinal Tumors: A Case of Mistaken Identity.
Mohamed Abdulla M.D.Professor of Clinical Oncology,Kasr El-Aini School of Medicine
Cairo University.
Alexandria – EGSSO – 24/06/2010
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Objectives:
Basic Information.
Magnitude of The Problem.
Pitfalls in Diagnosis.
What is New in Therapeutic Strategies.
Origin & Classification:
Origin & Classification:
Natural History:
Cure
Indolent
Dismal Outcome
Aggressive Resistant to ttt
Indolent
1. Clinical Manifestations are Vague.
2. Advanced & Metastatic at Presentation.
3. Complete Surgical Removal is Questionable.
4. The Available Therapeutic Options are not Effective.
Staging & Survival:
SEER Staging& Classification
Localized Regional Distant
Extension to Surroundings
Nodal Disease Both
Yao et al. JCO. 2008, 26(18)3063-72
Staging & Survival:
G 1 - 2
Yao et al. JCO. 2008, 26(18)3063-72
Staging & Survival:
G 3 - 4
Yao et al. JCO. 2008, 26(18)3063-72
Neuroendocrinal Tumors:
The Hassle
Neuroendocrinal Tumors:
Yao et al. JCO. 2008, 26(18)3063-72
Neuroendocrinal Tumors:
Yao et al. JCO. 2008, 26(18)3063-72
Neuroendocrinal Tumors:
Yao et al. JCO. 2008, 26(18)3063-72
Neuroendocrinal Tumors:
American Cancer Society. Cancer prevalence: how many people have cancer? Updated October 30, 2008. Accessed May 7, 2009.
Neuroendocrinal Tumors:
Increased Incidence?? Better Understanding??
Critical Biomarkers:1. Plasma Chromogranin (CgA)
A Measure of Endocrine Tissues.Non-Specific
False Positive Results:
• Proton Pump Inhibitors.
• Atrophic Gastritis.
• Renal Impairment.
Critical Biomarkers:2. Urinary 5-HIAA:
Com
promised S
urvival
Looking at Neuroendocrine Tumors:
Octreoscan.SPECT/CT Hybrid Imaging.MIBG.CT/MRI.Endoscopic Ultrasound.Capsule Endoscopy.
Neuroendocrinal Tumors:Management:
Neuroendocrinal Tumors:Conventional Medical Treatment:
Sterptozotocin.Anthracyclins.Flouroupyremidines.Dacarbazine.
Neuroendocrinal Tumors:Somatostatin analogues:
sst1 sst2 sst3 sst4 sst5
Blocking of Hormone Synthesis
Anti-proliferative Effect
Symptomatic Relief60%
Tumor Shrinkage5%
++ PFS (15.6 vs 5.9 months).
SD in 67%.
Functioning and Non-Functioning Tumors.
Neuroendocrinal Tumors:Somatostatin analogues:PROMID Study (2009):
Neuroendocrinal Tumors:Molecular Events & Therapeutic Implications:1. Angiogenesis:
vHL Gene OxygenationHypoxia
+++ VEGFAngiogenesis
PFS 96% 68%
Bevacizumab + Octreotid LAR
INF+ Octreotid LAR
Neuroendocrinal Tumors:Molecular Events & Therapeutic Implications:2. mTOR Inhibitor:
Mammalian Target of Rapamycin
Cellular Growth
ProteinSynthesis
AutophagyResistance to
Apoptosis++
ProliferationAltered
Metabolism
RAD 001 (Everolimus):
PR 13%
SD 74%.
DP 13%.
Neuroendocrinal Tumors:Molecular Events & Therapeutic Implications:2. mTOR Inhibitor:
RADIANT – 1
Neuroendocrinal Tumors:Molecular Events & Therapeutic Implications:2. mTOR Inhibitor:
Advanced Chemo-Resistant Neuroendocrinal Tumors
RAD001RAD001
Octreotid LAR
Radiological Response: 77% 84%
PFS: 9.7 ms. 16.7 ms.
> 50% reduction in > 50% of Patients
Quiz??
Adenocarcinoma NET
Final Take Home Message:
NET not rare.
Surgery is the Cornerstone in Curative Management.
Serum Biomarkers Are Still There to Share.
Tissue Markers Should be more Highlighted.
Molecular Targeted Therapies are The Hope for Tomorrow.
