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Management of patients with advanced differentiated thyroid cancer

Management of patients with advanced differentiated thyroid cancer. Ashraf Aminorroaya MD Prof. of Internal Medicine and Endocrinology Isfahan Endocrine & Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan, Iran 12 Oct 2012.

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Management of patients with advanced differentiated thyroid cancer

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  1. Management of patients with advanced differentiated thyroid cancer AshrafAminorroaya MD Prof. of Internal Medicine and Endocrinology Isfahan Endocrine & Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan, Iran 12 Oct 2012

  2. Differentiated thyroid cancer(Papillary, follicular and poorly differentiatedthyroid carcinoma) 80%-85%: free of disease after • Surgery • Radioactive iodine and • Thyroid hormone suppression • 15%–20% : recurrence • Locoregionally recurrence (10%-15%) • Distant metastases (<5-10%) Usaidy et al, Journal of Thyroid Research, Volume 2012, Article ID 618985, 12 pages doi:10.1155/2012/618985 M Schlumberger et al, European Journal of Endocrinology (2012) 166 5–11

  3. Locally recurrent differentiated thyroid cancer Mostly in extensive disease: • Large thyroid tumors • Extension beyond the thyroid capsule, and lymph node metastases • An aggressive histologic type M Schlumberger et al, European Journal of Endocrinology (2012) 166 5–11

  4. Locally recurrent differentiated thyroid cancer (cont.) Mostly in: • Lymph nodes (complete remission in most patients) • Thyroid bed (poorer prognosis) Treatment: • Suppressive dose of thyroxine • Surgery • Radioiodine • External radiation therapy (in some patients) M Schlumberger et al, European Journal of Endocrinology (2012) 166 5–11

  5. Distant metastases (<5-10%) • Lungs (50%), bones (25%), lungs and bones (20%), other sites(5%) Treatment of distant metastases includes: • L-T4 treatment at doses that suppress TSH • Local treatment modalities (surgery, radiation therapy, and radiofrequency ablation, etc) • +/-Radioiodine • If iodine resistance, molecular targeted therapies (clinical trials) M Schlumberger et al, European Journal of Endocrinology (2012) 166 5–11

  6. Radioiodine refractory disease Definition: • At least one lesion without radioiodine uptake • Or • that has progressed within a year following radioiodine treatment • Or • with persistent disease after the administration of a cumulative activity of more than 22 GBq (600 mCi) radioiodine M Schlumberger et al, European Journal of Endocrinology (2012) 166 5–11

  7. Distant metastases Metastatic Sites Requiring Special Attention: • CNS Metastases: Surgical resection, radioiodine therapy and/or external beam radiotherapy with steroids,gamma-knife radiosurgery, if indicated) • Bone Metastases: surgery and 131I, EBRT, Intravenous bisphosphonates, if indicated) Usaidy et al, Journal of Thyroid Research, Volume 2012, Article ID 618985, 12 pages doi:10.1155/2012/618985

  8. Advanced radioiodine refractory metastatic DTC • 5% of patients with DTC • 10-year survival rate of 25% compared with 76% in those whose lung metastases have RAI uptake The median survival after the discovery of distant metastases in patients with refractory DTC ranges from 3 to 6 years, but slow tumor growth is common, particularly in young patients with well-differentiated tumors. Journal of Thyroid Research, Volume 2012, Article ID 618985, 12 pages doi:10.1155/2012/618985M Schlumberger et al, European Journal of Endocrinology (2012) 166 5–11

  9. Diagnostic procedures in radioiodine refractory DTC • Neck ultrasonography • contrast-enhanced spiral CT- scan of the neck, chest and abdomen • CT scan or MRI of the brain • MRI of the spine and pelvis • A baseline 18FDG PET scan Schlumberger et al, European Journal of Endocrinology (2012) 166 5–11

  10. Radioiodine refractory recurrent DTC Journal of Thyroid Research, Volume 2012, Article ID 618985, 12 pages doi:10.1155/2012/618985

  11. Treatment of radioiodine refractory DTC • Surgery • Radioiodine? • External Beam Radiotherapy (EBRT) • Radiofrequency ablation, or cryotherapy, cement injection, or embolization of some metastatic sites • Systemic Therapy ? • Molecular targeted therapies (1st line treatment) Journal of Thyroid Research, Volume 2012, Article ID 618985, 12 pages doi:10.1155/2012/618985 Schlumberger et al, European Journal of Endocrinology (2012) 166 5–11

  12. Systemic Therapy • Cytotoxic Chemotherapy: doxorubicin+/-cisplatin Tumor response rate (0%-22%) and partial, only lasting a few months • Molecular targeted therapies: multi-kinase inhibitors (inhibiting Ret and VEGFR, along with other kinases, with the aim of inhibiting the MAPK pathway and angiogenesis): Lenvatinib (E7080), motesanib, sorafenib, sunitinib,andvandetanib Anti-angiogenic agents: axitinib and pazopanib Journal of Thyroid Research, Volume 2012, Article ID 618985, 12 pages doi:10.1155/2012/618985 Schlumberger et al, European Journal of Endocrinology (2012) 166 5–11

  13. Treatment of Advanced or Metastatic DTC (cont.) Journal of Thyroid Research, Volume 2012, Article ID 618985, 12 pages doi:10.1155/2012/618985

  14. Side effects of molecular targeted therapies are significant • Fatigue • Hypertension • Anorexia • Diarrhea • Cytopenias • Skin toxicities Dose reduction or withdrawal of drug may be required TSH levels should be regularly monitored (kinase inhibitors increase the daily L-T4 treatment dose) Schlumberger et al, European Journal of Endocrinology (2012) 166 5–11

  15. Main goal of trials with kinase inhibitors should be • Prolong life • Minimal decrease in quality of life Schlumberger et al, European Journal of Endocrinology (2012) 166 5–11

  16. Journal of Thyroid Research, Volume 2012, Article ID 618985, 12 pages doi:10.1155/2012/618985

  17. Criteria of starting systemic or molecular targeted therapies in radioiodine refractory DTC • No efficacy of the novel treatment at an early stage • Progression rate should be followed by standardized imaging repeated every 6 months • Measurable lesions and documented progression in a given time interval (between 6 and 15 months) should be considered candidates for systemic treatment • Progression rate, that can also be evaluated by the doubling time of serum Tg, should always be confirmed by imaging Schlumberger et al, European Journal of Endocrinology (2012) 166 5–11

  18. Conclusion Advanced thyroid cancer management: • Suppressive dose of L-thyroxine • Local treatment interventions • Radioiodine therapy • In radioiodine refractory cases with progressive disease: • Kinase inhibitors (first-line treatment) • Cytotoxic chemotherapy (poor efficacy)

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