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Delve into the complexities of neuroendocrinal tumors, exploring diagnosis pitfalls, treatment strategies, staging, critical biomarkers, management options, and future therapeutic implications.
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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. www.oncologyclinic.org mohamed.abdulla@oncologyclinic.org. Alexandria – EGSSO – 24/06/2010
Objectives: • Basic Information. • Magnitude of The Problem. • Pitfalls in Diagnosis. • What is New in Therapeutic Strategies.
Natural History: Indolent Indolent Aggressive Resistant to ttt • Clinical Manifestations are Vague. • Advanced & Metastatic at Presentation. • Complete Surgical Removal is Questionable. • The Available Therapeutic Options are not Effective. Cure Dismal Outcome
Staging & Survival: 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: Compromised Survival
Looking at Neuroendocrine Tumors: • Octreoscan. • SPECT/CT Hybrid Imaging. • MIBG. • CT/MRI. • Endoscopic Ultrasound. • Capsule Endoscopy.
Neuroendocrinal Tumors:Conventional Medical Treatment: • Sterptozotocin. • Anthracyclins. • Flouroupyremidines. • Dacarbazine.
Neuroendocrinal Tumors:Somatostatin analogues: Symptomatic Relief 60% sst1 sst2 sst3 sst4 sst5 Tumor Shrinkage 5% Anti-proliferative Effect Blocking of Hormone Synthesis
Neuroendocrinal Tumors:Somatostatin analogues:PROMID Study (2009): • ++ PFS (15.6 vs 5.9 months). • SD in 67%. • Functioning and Non-Functioning Tumors.
Neuroendocrinal Tumors:Molecular Events & Therapeutic Implications:1. Angiogenesis: vHL Gene Oxygenation Hypoxia Bevacizumab + Octreotid LAR INF + Octreotid LAR PFS 96% 68% Angiogenesis +++ VEGF
Neuroendocrinal Tumors:Molecular Events & Therapeutic Implications:2. mTOR Inhibitor: Mammalian Target of Rapamycin Altered Metabolism Cellular Growth Resistance to Apoptosis Protein Synthesis ++ Proliferation Autophagy
Neuroendocrinal Tumors:Molecular Events & Therapeutic Implications:2. mTOR Inhibitor: RAD 001 (Everolimus): • PR 13% • SD 74%. • DP 13%.
Neuroendocrinal Tumors:Molecular Events & Therapeutic Implications:2. mTOR Inhibitor: RADIANT – 1 Advanced Chemo-Resistant Neuroendocrinal Tumors RAD001 RAD001 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.