update on thyroid cancer

Update on Thyroid Cancer

Prof. Ranil Fernando

Dept of Surgery

Faculty of Medicine

University of Kelaniya

SETS December 2009

Update on Thyroid CancerIntroduction

Thyroid cancer is an uncommon cancer with a good prognosis

Rising incidence in the West ( smaller tumors)- Sri Lanka?

Management of differentiated thyroid cancer based on risk stratification is important

Total thyroidectomy is gaining wider acceptance

There is some debate about the treatment of low grade cancers

Genetics of thyroid cancer is being studied in detail therapeutic and preventive measures will emerge from these studies

Management of Medullary Carcinoma needs further evaluation


Risk stratification

Many groups have developed a systems of assigning patients with

Differentiated Thyroid Carcinoma (DTC)into well- defined risk groups

This has enabled clinicians to develop a rationale treatment policy

with predictable outcome

AGES age grade extent size - Lahey Clinic

AMES age mets extent size - Mayo Clinic

DAMES Diploid age mets extent size - Memorial Sloan-Kettering

MACIS mets age completeness invasion size - Mayo Clinic

Prognostic scoring systems do not include lymph node metastases


M + 3 if metastasis is found

A <= 39 years of age = 3.1. = 40 = age (y) x 0.08

C + 1 if resection is in Complete

I + 1 if invasive growth (pathologists report)

S 0.3 x largest diameter in centimeters

Prognostic score 20 year survival

< 6 99 %

6 - 6 89 %

7 - 8 56 %

> 8 24 %

MACIS Score of > 6 High risk


The Memorial Sloan Kettering hospital in New York Introduced the

concept of an intermediate group - Shaha et al

Low-risk group

• age younger than 45 years

• tumors <4 cm in size

• low-grade histology

• absence of distant metastasis

• absence of extrathyroidal extension

High Risk

• age over 45 years

• follicular histology ( some types)

• extrathyroidal extension

• tumor size exceeding 4 cm

• presence of distant metastases


Papillary thyroid cancer risk groupsLow Intermediate Intermediate Highrisk risk risk risk

<45 <45 >~45 >45

TI/T2 T3/T4 and/or TI/T2 T3/ T4 and/orMO Ml an d/or M0 M 1 and/or

Low grade High grade Low grade High grade

Ashok R. Shaha, Jatin P. Shah, and Thom R. Loree Annals of Surgical Oncology, 1996 3(6):534--53

20-year survival low-risk - 99%intermediate-risk - 83%high-risk group - 43%

Treatment of low grade cancers is controversial


*Hürthle cell or Tall cell variant histology

Low-risk Intermediate-risk High-risk

Criteria

Age: <45 years >45 years <45 years >45 years

Tumour size <4c <4cm >4cm >4cm

Histology: favourable favourable unfavourable* unfavourable*

Extrathyroidal extension: No No Yes Yes

Distant metastases: No No Yes Yes

Nodal metastases: +/- - +/- +

Treatment

Therapy options

Thyroid surgery: Limited? Individualized Total

Thyroxine: Yes Yes YesRadioiodine No +/- Yes

Selective management of differentiated thyroid carcinoma


GeneticsThyroid cell growth requires the combined effects of TSH, working via cAMP, and growth factor signaling (e.g. IGF-I)

These factors work through MAP kinase (MAPK) and phosphatidylinositol-3-kinase (PI3K)

Mutations along these same signaling pathways play prominent roles in the pathogenesis of thyroid neoplasia

MicroRNA (miRNAs) are non-coding single stranded RNAs that control cell growth, differentiation and apoptosis

MiRNAs negatively regulate their target genes and recently have been implicated in tumourigenesis


Oncogene (defective)

Target Cell

microRNA

Altered Differentiation, Growth, Apoptosis

Tumour

+

RET/PTC (an oncogene) -induced tyrosine phosphorylation of PDK1 may be one of the mechanisms by which it acts as an oncogenic tyrosine kinase in thyroid carcinogenesis.

70% of papillary thyroid cancers have mutations of either RET/PTC, RASor B-RAF Mutations


This cancer is derived from the parafollicular C cells

Accounts for about 5 to 10 % of all cancers of the thyroid gland

Hereditary autosomal dominant type genetic defect hasbeen located in chromosome 10 - RET proto oncogene

Screening for RET proto-oncogene is very effective

Siblings can be offered Pre- emptive surgery (codon Based)

MEN2b has the worst prognosis in Medullary carcinomaUnaffected siblings must be offered surgery before the age of 2

Prophylactic Node dissection ( even Bilateral) is indicated inMedullary Cancer

Medullary Carcinoma


Hurtle Cell Tumours

Hurthle cell tumours are diagnosed when morethan 75% of a lesion is composed of Hürthle cells

They are thought to be variants of follicular (& papillary)adenoma & carcinoma -5% - Follicular? /Papillary ?

Differentiation between adenoma and carcinoma is difficult

Hurtle cell cancer is often bilateral and less sensitive for treatment with radioactive isotopes

Higher rate of metastasis and lower survival than differentiated thyroid cancers

The prognosis is not as good as for papillary or follicular thyroid cancer

Hurthle cell(Askanazy cell)

Update on Thyroid CancerSurgery

Surgery remains the main form of therapy for thyroid cancer

In Medullary , Follicular and Intermediate and High grade papillary cancers - Total Thyroidectomy is the treatment of choice

Low grade Papillary ,Micro papillary & Minimally invasive follicular lesions may be dealt with by a lesser procedure

Lymph nodes - Selective Dissection Level VIis a must in all other levels Dissect Palpable nodes

In Medullary there is a place for Prophylactic dissection


If a diagnostic whole body I-131 scan is positive, further imagingto evaluate the possibility of surgical resection

If no surgically resectable disease is identified, thyroid hormone( Suppressive Dose)withdrawal and I-131 treatment is recommended

I-131 treatment is recommended prior to external beam radiation therapy unless the Whole Body iodine scan is negative

Iodine negative & thyroglobulin positive patients may be considered for FDG-PET before treatment to assess surgical options

FDG PET is effective for detecting recurrent or metastatic DTC with high sensitivity and specificity, particularly in patients with negative radioiodine scans and elevated Tg levels

Post Operative Treatment of DTC


Dose of I-131 sodium iodide

Remnant ablation (post-op)

Low Risk 50 mCi

High Risk 100 mCi

Regional Lymph Node metastasis 150 mCi

Distant Metastasis 200 mCi

The above doses can be administered on an outpatient basis.

Written radiation safety guidelines will be given to the patient.

RAI doses > 200 mCi require hospital admission.

University of California, Los Angeles

Guidelines for I-131 Therapy in Differentiated Thyroid Cancer

Post Operative Radioiodine

Diagnostic - small dose

Therapeutic


“Newer” treatments

Stimulation Protocol with Thyrogen - Recombinant TSH

Consider if contraindications to thyroid hormone withdrawal

Thyrogen 0.9 mg IM for 2 days and treat on 3rd day - Costly

Targeted treatment / Genetic Modulators ( Still being studied)

Sorafenib - Tyrosine Kinase inhibitor ( Only in trials)

EGFR inhibitors ( Only in trials)

update on thyroid cancer

Documents

thyroid cancerm

thyroid carcinogenesis

thyroid cancerprof

papillary thyroid cancers

risk group age younger

year survival lowrisk

uncommon cancer

yearstumour size