Controversies in the Management of Differentiated Thyroid Carcinoma

Dimyati AchmadDepartment of Surgery, Faculty of Medicine Padjadjaran University/

Hasan Sadikin Hospital, Bandung Indonesia

Introduction

• Thyroid carcinoma is the most frequent malignancy of the endocrine system

• The incidence has increased sharply in three decades

• Almost 90% of thyroid carcinoma are well-differentiated thyroid carcinoma

Differentiated Thyroid Carcinoma (DTC)

• Is categorized into:– Papillary thyroid carcinoma (85%)– Folliculare thyroid carcinoma (10%)– Hurtle cell carcinoma (3%)

• Slow growing tumor• Good prognosis

LOW RISK HIGH RISK

AMES

Age Males < 41 y, female < 51 y Males > 40 y, female > 50 y

Metastases No distant metastases Distant metastases

Extent Intrathyroidal papillary or follicular with minor capsule invasion

Extrathyroidal papillary or follicular with major invasion

Size < 5 cm > 5 cm

Definition A: Any low-risk age group without metastasesB: High-risk age without metastases and with low-risk extent and size

A: Any patient with metastasesB: High-risk age with either high-risk extent and size

Debated Issue Includes :

• The extent of primary surgical resection and / or need for the extent of regional lymph node dissection

• The role of post operative radio iodine remnant ablation

• The role of B-RAF mutation in management of papillary thyroid carcinoma

Until today, the managementof DTC are still in controversy

The Extent of Primary Surgical Resection

Based on high risk and low risk criteria from prognostic scoring system, the controversial issue especially, in the management of low risk case.

Some group of surgeons performed only thyroid lobectomy, whether performed total thyroidectomy.

The Guidelines of American Thyroid Association 2009:

• Thyroid cancer > 1 cm → recommended to perform total / near total thyroidectomy.

• Thyroid cancer < 1 cm, is a low risk, unifocal intrathyroidal papillary carcinoma and in the absence of prior head and neck irradiation → recommended to perform only thyroid lobectomy.

Neck Dissection

Central – compartment (level VI) neck dissection

should included in total thyroidectomy, especially:

• Patients with clinically present central or

lateral neck lymph node enlargement.

• Advanced primary tumors.

Lateral neck compartement (level II-V) lymph node dissection:

Should be perfomed for patients with lateral cervical lymph node enlargement which is prove have metastatic by histopathological examination.

The Role of Post OperativeRadio Iodine Remnant Ablation

The goals of the treatment are

to destroy any residual thyroid tissue

to prevent locoregional recurrence

and to facilitate surveillance

with whole-body iodine scans

and/or adjusment thyroglobulin value.

Major Factors Impacting Decision Makingin Radioiodine Remnant Ablation

Expected benefit

Factors Description

Decreasedrisk ofdeath

Decreasedrisk of

reccurence

May facilitate initial staging and follow up

RAI ablation usually

recommended

Strengthof

evidence

T1 1 cm or less, intrathyroidal or microscopic multifocal No No Yes No E

1-2 cm, intrathyroidal No Conflicting dataa Yes Selective usea I

T2 > 2-4 cm intrathyroidal No Conflicting dataa Yes Selective usea C

T3 > 4 cm

< 45 years old No Conflicting dataa Yes Yes B

> 45 years old Yes Yes Yes Yes B

Any size, any age, minimal extrathyroidal extension No Inadequate dataa Yes Selective usea I

T4 Any size with gross extrathyroidal extension Yes Yes Yes Yes B

Nx,N0 No metastatic nodes document No No Yes No I

N1 < 45 years old No Conflicting dataa Yes Selective usea C

> 45 years old Conflicting data Conflicting dataa Yes Selective usea C

M1 Distant metastasis present Yes Yes Yes Yes A

• Gross extrathyroidal extension and distant metastasis present → radioiodine ablation is usually recommended

• In low risk case no recommended for radioiodine ablation

The Role of B-RAF Mutationin the Management of

Papillary Thyroid Carcinoma

HGF

Met

Mutant B-RAF Protein

MEK

ERK

C-METECM

ERKB-RAF

Mutation

C-JUNC-FOS

HYPOXIA

HIF-1α

HIF-1α-1β

VEGFVE6F-C

VEGFVEGF-C

Proliferation ↑Extrathyroidal Invasion

Lymph nodemetastases

RET

RAS

RAF

• The recent explosion of knowledge regarding the molecular and cellular pathogenesis of cancer has led to the development of range of targeted therapies

• Efficacy has already been demonstrated for several agents including Sorafenib as tyrosine kinase inhibitor

HGF

Met

Mutant B-RAF Protein

MEK

ERK

C-METECM

ERKB-RAF

Mutation

C-JUNC-FOS

HYPOXIA

HIF-1α

HIF-1α-1β

VEGFVE6F-C

VEGFVEGF-C

Proliferation Extrathyroidal Invasion

SORAFENIB

X

Some of the researchers are recommended to undergo sorafenib utilization

But, there is no guideline of management papillary thyroid carcinoma, describe the role of tyrosine kinase inhibitor

The management of differentiated thyroid carcinoma remains controversial

The choice for management of differentiated thyroid carcinoma:Total thyroidectomy, radioiodine ablation and thyroxine suppresion therapy.

Conclusion

• Lateral neck compartement lymph node dissection should be perfomed for patients with lateral cervical lymph node enlargement which is prove have metastatic by histopathological examination.

• In papillary thyroid carcinoma with B-RAF mutation are recommended to undergo Sorafenib utilization as Tyrosine Kinase Inhibitor (TKI).

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