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Focus on endocrine neoplasia July 9, 2010 Rome

Focus on endocrine neoplasia July 9, 2010 Rome. Differentiated thyroid carcinoma: Treatment and follow-up. Furio Pacini Dipartimento di Medicina Interna e Scienze Endocrino-Metaboliche Università di Siena. Thyroid cancer incidence and mortality in USA (1973-2002) and Italy (1988-2002).

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Focus on endocrine neoplasia July 9, 2010 Rome

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  1. Focus on endocrine neoplasiaJuly 9, 2010Rome Differentiated thyroid carcinoma: Treatment and follow-up Furio Pacini Dipartimento di Medicina Interna e Scienze Endocrino-Metaboliche Università di Siena

  2. Thyroid cancer incidence and mortality in USA (1973-2002) and Italy (1988-2002) APC: USA 3.8% Italy 4.0% Italy USA Italian Network of Cancer Registries, 2006

  3. Thyroid cancer incidence in USA (1973-2002) and Italy (1988-2002) Italy USA Italian Network of Cancer Registries, 2006

  4. Trend incidence of papillary thyroid cancer by size in USA (1988-2002)

  5. CRITICAL STEPS IN THE MANAGEMENT OF DTC Surgery 131I therapy Short term follow up Long term follow up

  6. ATA and ETA Differentiated thyroid cancer guidelines: Surgery for cytology diagnostic of malignancy • Preoperative ultrasound for the contralateral lobe and cervical lymph nodes (central and bilateral) is recommended for all patients undergoing thyroidectomy for suspicious cytology • Near total or total thyroidectomy should be the initial procedure in any malignancy discovered before surgery. • Thyroid lobectomy alone may be sufficient treatment for small, isolated, intrathyroidal papillary carcinomas in the absence of cervical nodal metastases, that have been diagnosed at final histology when the surgical procedure had been performed for other indications.

  7. POST-SURGICAL RADIOIODINE ABLATION • Rationale: • Ablation: eradication of normal thyroid remnants • Treatment: irradiation of persistent disease • Total body scan a few days later • Diagnostic scan useless • The combination of serum Tg, post-therapy WBS and neck ultrasound is a strong predictor of the future outcome.

  8. Metanalysis of radioiodine effectiveness(Sawka et al, J Clin Endocrinol Metab, 2004)

  9. Does post-surgical 131-I decrease DTC recurrence and mortality rates? European Consensus (Pacini et al. EJE 153:1-10, 2005) • Very low-risk patients: Benefit unifocal T1 <1 cm N0 M0 no evidence • Low-risk patients: T1 >1 cm N0 M0 may decrease recurrence T2 N0 M0 but evidence not definitive • High-risk patients: any T3 and T4 evidence of decreased any T N1 recurrence and mortality M1 rate

  10. 100 mCi; hypo vs rhTSH rhTSH; 50 vs 100 mCi

  11. FOLLOW-UP: 3 months after ablation • On l-T4 therapy: Measurements of • Serum Tg and anti-Tg antibodies • Thyroid hormones and TSH: to assess the appropriate dose of l-T4

  12. FOLLOW-UP: 8-12 MONTHS AFTER ABLATION • Clinical examination: poorly sensitive • Neck ultrasonography • Serum Tg determination following TSH stimulation • (131I-total body scan)

  13. Follow-up of differentiated thyroid carcinoma after surgery and radioiodine ablation Options 1.After thyroid hormone withdrawal or after rhTSH ?? 2. based on stimulated serum Tg measurement alone or in combination with 131-I WBS ??

  14. SERUM Tg DETERMINATION • Serum Tg is a marker of disease (Van Herle, 1975), not a disease • Measurement: • Immunometric assay (IMA) • Standardization: CRM-457 • Functional sensitivity < 1ng/mL. Supersensitive methods (<0.1ng/mL): improved sensitivity but decreased specificity. • Search for interferences: • Measurement of anti-Tg antibodies.

  15. DETECTABLE Tg LEVEL AFTER THYROID ABLATION. Eustatia-Rutten, Clin Endocrinol, 61: 61, 2004 The sensitivity of serum Tg determination is improved by 15-20% following TSH stimulation.

  16. SIGNIFICANCE OF DETECTABLE Tg/TSH AT 1 YEAR

  17. J Clin Endocrinol Metab. 2002, 87:1499-501

  18. Metanalysis of the rate of false negative stimulated Tg and WBS

  19. DETECTION OF NECK RECURRENCES Combination of neck US and Tg/TSH determination.

  20. USE OF rhTSH. • The benefits in terms of QOL of rhTSH over withdrawal are obvious. • Is the sensitivity of serum Tg similar following rhTSH and withdrawal?

  21. rhTSH Testing: Metastatic Cancer Detection Rate rhTSH whole-body scan and Tg rhTSH Tg Tg on thyroid hormone therapy 100 100 100 90 100 97 80 88 80 70 77 60 67 Percent 50 57 40 30 20 10 0 5 10 2 Serum Thyroglobulin (ng/mL) Haugen BR, Pacini F, Reiners C, et al: J Clin Endocrinol Metab. 1999;84:3877

  22. 100 10 1 Peak rhTSH Tg Hypo Tg Correlation between peak rhTSH-Tg and hypo-Tg (31 patients, Department of Endocrinology, Pisa) p= 0.001 Tg ng/ml

  23. CONCLUSION: ELEVATED SERUM Tg LEVELS. • Some months after initial treatment, detectable serum Tg (<5-10ng/mL) may be produced by: • irradiated cells that will disappear in 2/3 of cases (Baudin, Pacini, Torlontano, Toubeau), and serum Tg will decrease • neoplastic cells that will progress, and serum Tg will increase. • A control TSH-stimulated Tg obtained some months (or years) later will differentiate these two groups of patients. • The most relevant parameter is the trend of Tg level, rather than its level.

  24. LOW RISK PATIENTS: UNDETECTABLE STIMULATED SERUM Tg AT 8-12 MONTHS • False negative results are rare (excellent NPV) • LT4 dose can be decreased to achieve a low-normal serum TSH level (0.5-2.5 µU/mL) • Patients are followed up on a yearly basis on replacement L-T4 treatment. • In the absence of abnormalities, no other testing is warranted.

  25. ETA and ATA guidelines: l-T4 therapy suppressive vs replacement ETA ATA Persistent disease TSH <0.1 mU/L Evidence of remission low risk replacement high risk suppressive duration 3-5 years

  26. CONCLUSIONS • Follow up based on neck US and Tg/TSH is all we need for nearly 80% of the patients (the low risk) • Other diagnostic and treatment modalities in selected cases at risk of recurrence or metastases.

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