1. Drug-Eluting Beads on Thyroid Cancer Metastasis: Early Experience of an Oncological Center Dr ANTONIO MANCA MD, PhD Istituto per la Ricerca e la Cura del Cancro Candiolo (Torino) Interventional Radiology Unit Chief: Dr G.C.Anselmetti Radiology Dept - Chief Dr D.Regge

2. Drug-Eluting Beads on Thyroid Cancer Metastasis: VERY Early Experience of an Oncological Center Dr ANTONIO MANCA MD, PhD Istituto per la Ricerca e la Cura del Cancro Candiolo (Torino) Interventional Radiology Unit Chief: Dr G.C.Anselmetti Radiology Dept - Chief Dr D.Regge

3. Drug-Eluting Beads on Thyroid Cancer Metastases Thyroid Cancer is found in one third of autoptic specimen* is found in one third of autoptic specimen* - < 5% of thyroid nodules undergone FNA are T. cancer - < 5% of Thyroid cancer gives distant metastases - 75%-85% papillary cancer with no mets or just N+ - most of distant mets to lungs and bone 0,5 % of patients with Thyroid Cancer have liver metastases (up to 50% of pts w/ medullary thyroid cancer: 5-8% of ThyCa) * Harach et al. "Occult papillary carcinoma of the thyroid. A "normal" finding in Finland. A systematic autopsy study.” Cancer 1985 56 (3): 531–8

4. Drug-Eluting Beads on Thyroid Cancer Metastases Male Patient, 70 y.o. 1998 - Radical Prostatectomy for AdenoCarcinoma 2000 - Local recurrence: RT 70Gy and Casodex (ongoing, PSA t: 0,1-0,3) 2009 - Neck palpable nodule US: Thyroid node (25 mm) on right lobe Biopsy: HURTHLE CELL CARCINOMA March 2009: Total Thyroidectomy (pT2pN0) and I 131

5. July 2009: - CT and PET-CT: multiple liver mets (biopsy: Hurthle cell Ca) - Initial local recurrence and single cervical lymph node met - No indication to I131 therapy unresponsive: - brief disease free survival - no I131 uptake of mets (like most of Hurhle cell Ca) Drug-Eluting Beads on Thyroid Cancer Metastases

6.  Nov 2009: liver PR (31mm vs 40 mm)  Feb 2010: liver PD (50 mm vs 31 mm) Sept 2009: SORAFENIB (400 mg/day) Phase II Trial of Sorafenib in Advanced Thyroid Cancer Gupta-Abramson et al. JCO 2008 Vol 26, No 29: 4714-4719 30 pts - 77% overall clinical benefit (23% PR and 54% SD) Drug-Eluting Beads on Thyroid Cancer Metastases

8. Chemotherapy with Doxorubicin in Progressive Medullary and Thyroid Carcinoma of the Follicular Epitelium Matuszczyk et al. Horm Metab Res 2008; 40: 210-213  SIE-AIMN-AIFM (Italian) Guidelines for Thyroid Cancer Treatment: TACE (and/or RFA) for unresectable liver metastases TACE (and/or RFA) for unresectable liver metastases (treatment of liver mets not mentioned in American guidelines) (treatment of liver mets not mentioned in American guidelines)  Doxorubicin in metastatic thyroid cancer : Bonadonna et al. Cancer Res 1970 Gottlieb Cancer 1972 Haugen et al. Semin Surg Oncolm 1999 Sherman et al. (M.D.Anderson Cancer Center) Clinical Oncology 2010 22 pts. 27 % Hurthle-cell tumors 5% PR, 42% SD, 53% PD Side effects: Hair loss (42%), Nausea (23%), Resp. Infection (13%), Neutropenia (10%) Pneumonia (7%) Drug-Eluting Beads on Thyroid Cancer Metastases

9. Lorenz et al. Surgery 2005 vol. 138 (6) pp. 986-93 Fromigue‘ et al. J Clin Endocrinol Metab 2006 vol. 91 (7) pp. 2496-9 11 Patients: TACE with Lipiodol and Doxorubicin 12 Patients: TACE with Lipiodol and Doxorubicin PR 42%, SD 42% Drug-Eluting Beads on Thyroid Cancer Metastases

10. DEB-TACE Drug-Eluting Beads on Thyroid Cancer Metastases Varela et al. J Hepatol, 2007 C-TACE Lesson learned from HCC…

11. Chemoembolization ( TACE) with 100-300 micron DC Beads loaded with 37,5 mg/mL of DOXORUBICIN First selective TACE with 100mg of Doxorubicin on the main lesion in segment VIII (5 cm) CEUS pre-TACECEUS post-TACE During-TACE Fentanil Midazolam Post-TACE Tramadol Ondasetron Pre-TACE Ondasetron Ranidil Prednisone Drug-Eluting Beads on Thyroid Cancer Metastases

12. March-June 2010: 4 selective TACE sessions (40 -100mg di Doxorubicin per session, 3-4 weeks intervals) No major complications Good compliance for the first three sessions G2 Pain, nausea and vomiting in the last session Drug-Eluting Beads on Thyroid Cancer Metastases

13. Pre-TACE: CT and PET-CT 3 monts Post-TACE: CT and PET-CT Drug-Eluting Beads on Thyroid Cancer Metastases

14. PRE-TACE PET-CT 3 Months POST-TACE PET-CT: Local relapse and bone mets Drug-Eluting Beads on Thyroid Cancer Metastases

15. July 2010 - CT and PET-CT:  Size decrease and good necrosis of bigger lesions (34 mm vs 50 mm) with minor viable tissue percentage (10% in S8)  Complete necrosis of smaller lesions treated but…  Neck local relapse and cervical node metastasis  Bone metastases (detectable only with PET-CT) Drug-Eluting Beads on Thyroid Cancer Metastases The metastatic disease is no longer“Liver dominant” No more DEB-TACE sessions

16. “TAKE HOME MESSAGE” DEB-TACE with DC Bead in this preliminary experience of metastatic Hurthle cell Carcinoma showed: - Safety - Good patient compliance - Local control of liver metastases despite extrahepatic progression Drug-Eluting Beads on Thyroid Cancer Metastases

17. Mild neck discomfort Moderate sciatic pain Pain and discomfort relief after Radiotherapy on Neck and L4-L5 ECOG 0, PS 90% Liver function not impaired

18. Drug-Eluting Beads on Thyroid Cancer Metastases 6 Months 12 Months New lesionsTreated lesions Synergic effect of DEB-TACE + Sorafenib (ongoing) ?

19. “LESSON LEARNED” DEB-TACE with DC Bead in this preliminary experience of metastatic Hurthle cell Carcinoma: - Safe and effective in liver disease control - Should be repeated until disappearance of viable tissue - Uncertain benefit of adjuvant anti-neoangiogenic therapy Drug-Eluting Beads on Thyroid Cancer Metastases … waiting for SPACE trial

20. Aknowledgements Dr. Camillo Aliberti Dr. Gianluca Stoppa (TERUMO Italy) www.chemioembolizzazione.itwww.chemioembolizzazione.it (site under construction) anto.manca@gmail.com

21. Bigger Bead available on the market: 120mm size

22. First Man-Eluting Bead loadable with a medium size IR - Safe - Comfortable