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Download 9 -Thyroid NSSG – Sath Nag - Northern England Clinical Networks
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Northern England Strategic Clinical Network Conference Thyroid Sub-group Update Dr Sath Nag Consultant Endocrinologist Vice Chair, Thyroid NSSG South Tees Hospitals Foundation Trust Thyroid Cancer cruk.org/cancerstats • Most common endocrine malignant tumour, but represents only about 1% of all malignancies • In the UK in 2011 around 2,700 people were diagnosed with thyroid cancer • More common in women than men. Thyroid cancer • Half of all cases in the UK diagnosed in people aged under 50 – under-50s accounting for a higher proportion of female cases (52%) than male cases (40%) • Incidence rates have doubled in males and more than doubled in females since the 1990s cruk.org/cancerstats Thyroid cancer • Global increase in incidence mainly due to papillary carcinomas • Bulk of disease in lower stage tumours due to increased detection of papillary microcarcinomas Mortality • In 2012, around 374 deaths from thyroid cancer – Accounting for <1% of all cancer deaths • Mortality rates stable – reduced by >50% in women in the last 40 years. – Reduced by about 30% in men • UK mortality rate is sixth lowest in Europe for males and ninth lowest for females. cruk.org/cancerstats Incidence • Rising incidence possibly due to: • • • • Genuine increase Better detection Changing iodine status Exposure to radiation Public health and prevention • Nuclear fallout • Therapeutic and diagnostic X-rays in childhood possible causes of thyroid cancer in adults Thyroid cancer Diagnostic update Molecular diagnostics • BRAF mutation present in a large proportion of papillary thyroid cancers • Preoperative BRAF mutation testing of fineneedle aspiration biopsy – Assists with preoperative risk stratification strategy – Potentially predicts extent of initial disease and subsequent clinical outcomes Proteomic signatures • Differentiate thyroid cancer subtypes • Identify prognostic signatures that guide treatment • Help distinguish recurrent/residual disease from disease free state Thyroid Cancer Therapeutic update Kinase Inhibitors ATP KI ATP Y P KI Y Activated pathway Activated Pathway Cancer Cancer RET, BRAF….. inhibition VEGFR inhibition Tumor Tumor growth angiogenesis Targeting cell signalling in thyroid cancer Tumor Cell RET/PTC Motesanib Sorafenib Sunitinib Vandetanib XL-184 Endothelial Cell EGFR VEGFR-2 Vandetanib Ras B-Raf Sorafenib MEK ERK Ras PI3K AKT mTOR S6K Sorafenib Everolimus Sirolimus • Growth • HIF1a • Survival • Inhibition of apoptosis • Proliferation • Migration Raf PI3K MEK AKT ERK mTOR Axitinib Motesanib Sorafenib Sunitinib Vandetanib Everolimus Sirolimus S6K • Growth • Survival • Proliferation • Migration • Angiogenesis Graphic adapted from Keefe SM, et al. Clin Cancer Res. 2010;16:778-83. Achievements Challenges • Increasing incidence of thyroid cancer • Dealing with non-iodine avid refractory recurrent disease • Emerging role of Tyrosine Kinase inhibitors • Restricted access driven by cost despite emerging evidence base in progressive disease
