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Radioactive Iodine Refractory Patients : Definition and Treatment of Radioactive Iodine Refractory Thyroid Cancer Patients Chul woo Ahn Director of Endocrinology.

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Presentation on theme: "Radioactive Iodine Refractory Patients : Definition and Treatment of Radioactive Iodine Refractory Thyroid Cancer Patients Chul woo Ahn Director of Endocrinology."— Presentation transcript:

1 Radioactive Iodine Refractory Patients : Definition and Treatment of Radioactive Iodine Refractory Thyroid Cancer Patients Chul woo Ahn Director of Endocrinology department Gangnam Severance Hospital Yonsei University College of Medicine, Seoul, Korea

2 Table of Contents I.Incidence of Thyroid cancer II.Definition of RAI refractory Thyroid cancer III.Treatment of RAI refractory Thyroid cancer IV.Summary and Conclusions

3 7 major countries: 64,570 estimated new cases in 2008 –US: 37,340 –EU (5 key countries): 18,100 –Japan : 9130 Fastest increase in US SEER incidence among all cancer types –6.2% annual rate of increase in –May reflect early disease detection Second fastest increase in US SEER death rate among all cancer types –0.5% annual rate of increase in SEER = Surveillance, Epidemiology and End Results Program. 1. National Cancer Institute Web site. Thyroid Cancer.

4 Thyroid cancer increased dramatically in KOREA !!! Estimated Thyroid Cancer Incidence in Annual Incidence % RAI-refractory

5 131 I-Refractory Thyroid Cancer 20%-25% of metastatic thyroid cancer loses the ability to uptake iodine and therefore becomes 131 I refractory 1 Loss of iodine uptake inversely correlates with survival –Expected survival is years 1 No effective systemic therapy currently available –Conventional cytotoxic agents show minimal efficacy –Doxorubicin: 5% PR, 47% SD, median PFS 7 months 2 Novel, effective systemic therapy is needed 1. Schlumberger et al. Nat Clin Pract Endocrinol Metab. 2007:3: Matuszczyk et al. Horm Metab Res. 2008;40:

6 Definition of RAI refractory thyroid cancer Patients who have at least one lesion without radioiodine uptake or that has progressed within a year following radioiodine treatment. The median survival of these patients after the discovery of distant metastases ranges from 3 to 6 years. Slow tumor growth is common, and a long survival rate is observed in young patients who are not candidates for therapy trials. However, the majority of metastases will progress, and these patients will then be candidates for other treatment modalities.

7 Treatment of persistent/recurrent DTC General information of DTC (Differentiated Thyroid Cancer) 85% DTC: limited dis % DTC: persistant/recurrent dis. 25% of persistant/recurrent DTC: distant metastasis (lung. Bone) 10yr OS of DTC with distant metastasis: 25-45% 1/3 of DTC with distant metastasis: RAI  CR Additional surgery, local therapy RAI uptake (+) : RAI treatment (  ) : RAI-Refractory Disease 25-50% of metastatic DTC lose ability to take up Iodine. Iodine Uptake inversely correlates with survival. Limited treatment options Cytotoxic chemotherapy Doxorubicin: Only FDA approved agent for the treatment of thyroid cancer

8 Failure of traditional systemic chemotherapy  Doxorubicin vs Cisplatin 17% vs 26% (12% CR)  Bleomycin, Doxorubicin, + Cisplatin 42% response, median survival 11 months  Etoposide 0% response (failure to recruit) 

9 Selection of metastatic thyroid cancer patients for therapy Candidates for radioiodine treatment Younger age Well-differentiated papillary and follicular thyroid tumor High radioiodine uptake in the metastases Small metastases Location in lungs Apparently stable or slowly progressive disease Low uptake of FDG Candidates for other treatment modalities Older age Poorly differentiated thyroid tumor No or low radioiodine uptake Large metastases, Rapidly progressive disease High uptake of FDG Refractory to radioiodine: should be considered for therapeutic trials

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11 Treatment of RAI-refractory thyroid cancer Standard treatment of thyroid cancer –Surgery –Radioactive iodine (I 131, RAI) –Inoperable, iodine-refractory advanced/metastatic thyroid cancer No effective treatment Doxorubicin as single agent (RR of 30% and up to 45% in some) Local treatment by hyperfractionated radiation Cytotoxic agents and combination Targeted therapy (molecular based)

12 Pathways and targets in thyroid cancer MEK BRAF Erk RAS mTor AKT PI3K Nucleus Transcription VEGF, FGF, IGF Proliferation Differentiation Survival

13 Drugs & Targets -Multi-targeted TKIs-

14 Summary : Targeting therapy for thyroid cancer Unresectable/metastatic/persistent/recurrent, non responsive to RAI thyroid cancer –Novel TKIs : impressive result but many question… Clinical trial enroll Side effect More detailed understanding of the genetics and biology of thyroid cancer Search of other molecular targeted therapy

15 Conclusion The ultimate goal of thyroid cancer treatment is to extend the duration of life without unduly harming the quality of patients’ life. Presently, no novel treatment has yet demonstrated improved survival for thyroid cancer patients. Low rate of partial response, the absence of CR, and emergence of resistance in monotherapy trials identify the need to develop either more effect agents. For advanced thyroid cancer treatment Multi-displinary approach : Endocrine oncologist, surgeon, nuclear medicine specialist, radiotherapist…


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