Controversies in the Management of Differentiated Thyroid Carcinoma

1. Controversies in the Management of Differentiated Thyroid Carcinoma DimyatiAchmad Department of Surgery, Faculty of Medicine Padjadjaran University/ HasanSadikin Hospital, Bandung Indonesia

2. 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

3. Differentiated Thyroid Carcinoma (DTC) • Is categorized into: • Papillary thyroid carcinoma (85%) • Folliculare thyroid carcinoma (10%) • Hurtle cell carcinoma (3%) • Slow growing tumor • Good prognosis

5. Debated Issue Includes : Until today, the management of DTC are still in controversy • 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

6. 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.

7. 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, unifocalintrathyroidal papillary carcinoma and in the absence of prior head and neck irradiation → recommended to performonly thyroid lobectomy.

8. 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.

9. Lateral neckcompartement (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.

10. The Role of Post OperativeRadio Iodine Remnant Ablation

11. 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 adjusmentthyroglobulin value.

12. Major Factors Impacting Decision Makingin Radioiodine Remnant Ablation

13. Grossextrathyroidal extension and distant metastasis present → radioiodine ablation is usually recommended • In low risk caseno recommended for radioiodine ablation

14. The Role of B-RAF Mutationin the Management ofPapillary Thyroid Carcinoma

15. VEGF VEGF-C HGF MutantB-RAFProtein RET Met RAS RAF HYPOXIA MEK ERK HIF-1α ERK B-RAF Mutation HIF-1α-1β C-MET ECM C-JUN C-FOS VEGF VE6F-C Proliferation ↑ Extrathyroidal Invasion Lymph node metastases

16. 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

17. VEGF VEGF-C HGF MutantB-RAFProtein Met X HYPOXIA MEK SORAFENIB ERK HIF-1α ERK B-RAF Mutation HIF-1α-1β C-MET ECM C-JUN C-FOS VEGF VE6F-C Proliferation Extrathyroidal Invasion

18. 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

19. Conclusion • The management of differentiated thyroid carcinoma remains controversial • The choice for management of differentiated thyroid carcinoma: Total thyroidectomy,radioiodine ablation and thyroxine suppresion therapy.

20. Lateral neckcompartement 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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