Neuroendocrinal Tumors : A Case of Mistaken Identity. Mohamed Abdulla M.D. Professor of Clinical Oncology, Kasr El-Aini School of Medicine Cairo University.

Neuroendocrinal Tumors: A Case of Mistaken Identity.

Mohamed Abdulla M.D.Professor of Clinical Oncology,Kasr El-Aini School of Medicine

Cairo University.

[email protected].

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.