1. Neuroendocrinal Tumors : A Case of Mistaken Identity. Mohamed Abdulla M.D. Professor of Clinical Oncology, Kasr El-Aini School of Medicine Cairo University. www.oncologyclinic.org mohamed.abdulla@oncologyclinic.org. Alexandria – EGSSO – 24/06/2010

2. ?

3. Objectives: Basic Information. Magnitude of The Problem. Pitfalls in Diagnosis. What is New in Therapeutic Strategies.

4. Origin & Classification:

6. 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.

7. Staging & Survival: SEER Staging & Classification LocalizedRegional Extension to Surroundings Nodal DiseaseBoth Distant Yao et al. JCO. 2008, 26(18)3063-72

8. Staging & Survival: G 1 - 2 Yao et al. JCO. 2008, 26(18)3063-72

9. Staging & Survival: G 3 - 4 Yao et al. JCO. 2008, 26(18)3063-72

10. Neuroendocrinal Tumors: The Hassle

11. Neuroendocrinal Tumors: Yao et al. JCO. 2008, 26(18)3063-72

12. Neuroendocrinal Tumors: Yao et al. JCO. 2008, 26(18)3063-72

13. Neuroendocrinal Tumors: Yao et al. JCO. 2008, 26(18)3063-72

14. Neuroendocrinal Tumors: American Cancer Society. Cancer prevalence: how many people have cancer? Updated October 30, 2008. Accessed May 7, 2009.

15. Neuroendocrinal Tumors: Increased Incidence??Better Understanding??

16. Critical Biomarkers: 1. Plasma Chromogranin (CgA) A Measure of Endocrine Tissues. Non-Specific False Positive Results: Proton Pump Inhibitors. Atrophic Gastritis. Renal Impairment.

17. Critical Biomarkers: 2. Urinary 5-HIAA: Compromised Survival

18. Looking at Neuroendocrine Tumors: Octreoscan. SPECT/CT Hybrid Imaging. MIBG. CT/MRI. Endoscopic Ultrasound. Capsule Endoscopy.

19. Neuroendocrinal Tumors: Management:

20. Neuroendocrinal Tumors: Conventional Medical Treatment: Sterptozotocin. Anthracyclins. Flouroupyremidines. Dacarbazine.

21. Neuroendocrinal Tumors: Somatostatin analogues: sst1sst2sst3sst4sst5 Blocking of Hormone Synthesis Anti-proliferative Effect Symptomatic Relief 60% Tumor Shrinkage 5%

22. ++ PFS (15.6 vs 5.9 months). SD in 67%. Functioning and Non-Functioning Tumors. Neuroendocrinal Tumors: Somatostatin analogues: PROMID Study (2009):

23. Neuroendocrinal Tumors: Molecular Events & Therapeutic Implications: 1. Angiogenesis: vHL GeneOxygenationHypoxia +++ VEGFAngiogenesis PFS 96% 68% Bevacizumab + Octreotid LAR INF + Octreotid LAR

24. Neuroendocrinal Tumors: Molecular Events & Therapeutic Implications: 2. mTOR Inhibitor: Mammalian Target of Rapamycin Cellular Growth Protein Synthesis Autophagy Resistance to Apoptosis ++ Proliferation Altered Metabolism

25. RAD 001 (Everolimus): PR 13% SD 74%. DP 13%. Neuroendocrinal Tumors: Molecular Events & Therapeutic Implications: 2. mTOR Inhibitor:

26. RADIANT – 1 Neuroendocrinal Tumors: Molecular Events & Therapeutic Implications: 2. mTOR Inhibitor: Advanced Chemo-Resistant Neuroendocrinal Tumors RAD001 Octreotid LAR Radiological Response: 77% 84% PFS: 9.7 ms. 16.7 ms. > 50% reduction in > 50% of Patients

27. Quiz?? AdenocarcinomaNET

28. 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.