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 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. cruk.org/cancerstats

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 fine- needle 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 KI ATP KI P Y Y ATP Activated pathway Cancer Activated Pathway Cancer VEGFR inhibition Tumor angiogenesis Tumor growth RET, BRAF….. inhibition

Graphic adapted from Keefe SM, et al. Clin Cancer Res. 2010;16: Motesanib Sorafenib Sunitinib Vandetanib XL-184 Axitinib Motesanib Sorafenib Sunitinib Vandetanib Sorafenib Targeting cell signalling in thyroid cancer RET/PTC HIF1a Inhibition of apoptosis Migration EGFR PI3K VEGFR-2 Endothelial Cell Migration Angiogenesis Ras B-Raf MEK ERK PI3K AKT mTOR S6K Ras Raf MEK ERK AKT mTOR S6K Tumor Cell Growth Survival Proliferation Growth Survival Proliferation Everolimus Sirolimus Everolimus Sirolimus

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