Northern England Strategic Clinical Network Conference

Thyroid Sub-group Update

Dr Sath NagConsultant EndocrinologistVice 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

KIATP KI

PY Y

ATP

Activated pathway

Cancer

Activated Pathway Cancer

VEGFR inhibition

Tumor

angiogenesisTumor

growth

RET, BRAF….. inhibition

Graphic adapted fromKeefe SM, et al. Clin Cancer Res. 2010;16:778-83.

MotesanibSorafenibSunitinibVandetanibXL-184

Axitinib MotesanibSorafenibSunitinibVandetanib

Vandetanib

Sorafenib 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

EverolimusSirolimus

EverolimusSirolimus

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