How reliable is secondary risk stratification with stimulated thyroglobulin in patients with differentiated thyroid carcinoma?

 

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Summary

Objective: Primary risk factors in patients with differentiated thyroid carcinoma (DTC) are well established. In our institution, secondary risk stratification has been performed with stimulated Thyroglobulin (sTg; TSH > 30 mIU/l) within six months after primary therapy since 2001. In this study, we evaluated the predictive value of sTg for long-term disease- free survival (DFS). Patients, methods: Data of 202 consecutive patients with DTC were analyzed retrospectively. Median follow-up time was 6.4 years (12 months to 16.2 years). Patients were staged according to Union International Contre le Cancer (UICC) criteria. Primary risk stratification was carried out according to European Thyroid Association criteria. Initially, 134 patients (66%) were classified as low-risk and 68 patients (34%) as high-risk. The influence of established risk factors and sTg on DFS was analyzed at three different time points, up to 36 months after initial therapy. Results: In total, 169 (84%) of all patients remained in complete remission after surgery followed by radioiodine-therapy. Six patients (3%) developed tumour recurrence after initial complete remission. Primary risk factors for persistent disease were male sex, follicular or oncocytic tumour, primary tumour > 4 cm in diameter, initial lymph node involvement, initial metastatic disease and microscopic or macroscopic residual tumor. sTg ≤ 0.3 ng/ml measured within six months after initial therapy was a highly significant predictor (p ≤ 0.001) for lasting DFS, 99% of patients with sTg ≤ 0.3 ng/ml were in complete remission 36 months after initial therapy. Conclusions: A stimulated Tg ≤ 0.3 ng/ml within six months after initial therapy is a reliable predictor for long-term disease- free survival independent of primary risk stratification.

Zusammenfassung

Ziel: Die primären Risikofaktoren bei Patienten mit differenziertem Schilddrüsenkarzinom (DTC) sind im klinischen Alltag gut etabliert. Seit 2001 wurde in unserer Abteilung innerhalb von sechs Monaten nach primärer Therapie eine sekundäre Risikostratifizierung durch die Bestimmung des stimulierten Thyreo globulins (sTg; TSH > 30 mIU/l) durchgeführt. Das Ziel dieser Studie war es, den prädiktiven Wert des sTg für das langfristige krankheitsfreie Überleben (DFS) zu bestimmen. Patienten, Methoden: Die Daten von 202 konsekutiven Patienten mit DTC wurden retrospektiv analysiert. Der mediane Nachsorgezeitraum betrug 6,4 Jahre (12 Monate bis 16,2 Jahre). Das initiale Staging wurde gemäß den Leitlinien der Union International Contre le Cancer (UICC) und die primäre Risikostratifizierung nach den Leitlinien der European Thyroid Association (ETA) durchgeführt. Initial wurden 134 Patienten (66%) als low-risk und 68 Patienten (34%) als high-risk eingestuft. Der Einfluss etablierter Risikofaktoren und des sTg auf das DFS wurden zu drei verschiedenen Zeitpunkten bis 36 Monate nach initialer Therapie untersucht. Ergebnisse: 169 Patienten (84%) blieben nach chirurgischer Therapie und Radioiodablation in kompletter Remission. Sechs Patienten (3%) entwickelten nach initial kompletter Remission Rezidive. Primäre Risikofaktoren für die Rezidiventwicklung waren männliches Geschlecht, follikulärer oder onko zytärer Tumor, Primärtumor > 4 cm im Durchmesser, initialer Lymphknotenbefall, initiale Metastasen sowie ein mikroskopischer oder makroskopischer Resttumor. Ein sTg ≤ 0,3 ng/ml innerhalb von sechs Monaten nach initialer Therapie war ein hochsignifikanter Prädiktor (p < 0,001) für dauerhaftes DFS. 99% der Patienten mit einem sTg ≤ 0,3 ng/ml waren auch 36 Monate nach initialer Therapie noch in kompletter Remission, während 71% der Patienten, deren sTg sechs Monate nach initialer Therapie ≥ 50 ng/ml betrug, auch 36 Monate nach Therapie nicht in Remission waren. Schlussfolgerung: Ein sTg ≤ 0,3 ng/ml innerhalb von sechs Monaten nach initialer Therapie ist – unabhängig von der primären Risikostratifizierung – ein verlässlicher Prädiktor für langfristiges krankheitsfreie Überleben.

• References

• 1 Brassard M, Borget I, Edet-Sanson A. et al. Longterm follow-up of patients with papillary and follicular thyroid cancer: a prospective study on 715 patients. J Clin Endocrinol Metab 2011; 96: 1352-1359.
  CrossrefPubMedGoogle Scholar
• 2 Castagna MG, Maino F, Cipril C. et al. Delayed risk stratification, to include the response to initial treatment (surgery and radioiodine ablation), has better outcome predictivity in differentiated thyroid cancer patients. Eur J Endocrinol 2011; 165: 441-446.
  CrossrefPubMedGoogle Scholar
• 3 Cobum MC, Wanebo HJ. Age correlates with increased frequency of high risk factors in elderly patients with thyroid cancer. Am J Surg 1995; 170: 471-475.
  CrossrefPubMedGoogle Scholar
• 4 Cooper DS, Doherty GM, Haugen BR. et al. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 2009; 19: 1167-1214.
  CrossrefPubMedGoogle Scholar
• 5 Cooper DS, Doherty GM, Haugen BR. et al. Management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 2006; 16: 109-142.
  CrossrefPubMedGoogle Scholar
• 6 De Meer SG, Vriens MR, Zelissen PM. et al. The role of routine diagnostic radioiodine whole-body scintigraphy in patients with high-risk differentiated thyroid cancer. J Nucl Med 2011; 51: 56-59.
  Google Scholar
• 7 Duntas L, Grab-Duntas BM. Risk and prognostic factors for differentiated thyroid cancer. Hell J Nucl Med 2006; 9: 156-162.
  PubMedGoogle Scholar
• 8 Gilliland FD, Hunt WC, Morris DM. et al. Prognostic factors for thyroid carcinoma: a population- based study of 15,698 cases from the surveillance, epidemiology and end results (SEER) program 1973-1991. Cancer 1997; 79: 564-573.
  CrossrefPubMedGoogle Scholar
• 9 Grünwald F, Menzel C, Fimmers R. et al. Prognostic value of thyroglobulin after thyroidectomy before ablative radioiodine therapy in thyroid cancer. J Nucl Med 1996; 37: 1962-1964.
  PubMedGoogle Scholar
• 10 Hundahl SA, Fleming ID, Fremgen AM. et al. A national cancer data base report on 53,856 cases of thyroid carcinoma treated in the US, 1985–1995. Cancer 1998; 15: 2638-2648.
  Google Scholar
• 11 Kloos RT, Mazzaferri EL. A single recombinant human thyrotropin-stimulated serum thyroglobulin measurement predicts differentiated thyroid carcinoma metastases three to five years later. J Clin Endocrinol Metab 2005; 90: 5047-5057.
  CrossrefPubMedGoogle Scholar
• 12 Klubo-Gwiezdzinska J, Burman KD, Nostrand DV. et al. Does an undetectable rhTSH-stimulated Tg level 12 months after initial treatment of thyroid cancer indicate remission?. Clin Endocrinol 2011; 74: 111-117.
  CrossrefPubMedGoogle Scholar
• 13 Luster M, Clarke SE, Dietlein M. et al. Guidelines for radioiodine therapy of differentiated thyroid cancer. Eur J Nucl Med Mol Imaging 2008; 35: 1941-1959.
  CrossrefPubMedGoogle Scholar
• 14 Mazzaferri EL. A randomized trial of remnant ablation – In search of an impossible dream?. J Clin Endocrinol Metab 2004; 89: 3662-3664.
  CrossrefPubMedGoogle Scholar
• 15 Pacini F, Molinaro M, Castagna MG. et al. Recombinant human thyrotropin-stimulated serum thyroglobulin combined with neck ultrasonography has the highest sensitivity in monitoring differentiated thyroid carcinoma. J Clin Endocrinol Metab 2003; 88: 3668-3673.
  CrossrefPubMedGoogle Scholar
• 16 Pacini F, Schlumberger M, Dralle H. et al. European consensus for the management of patients with differentiated thyroid carcinoma of the follicular epithelium. Eur J Endocrinol 2006; 154: 787-803.
  CrossrefPubMedGoogle Scholar
• 17 Ruegemer JJ, Hay ID, Bergstrahl EJ. et al. Distant metastases in differentiated thyroid carcinoma: a multivariate analysis of prognostic variables. J Clin Endocrinol Metab 1988; 67: 501-508.
  CrossrefPubMedGoogle Scholar
• 18 Sahlmann CO, Brost B, Lehmann K. et al. Das lokoregionäre Rezidiv des differenzierten Schilddrü-senkarzinoms – Stellenwert diagnostischer Verfahren. Nuklearmedizin 2004; 43: P78.
  Google Scholar
• 19 Sahlmann CO, Schreivogel I, Angerstein C. et al. Clinical evaluation of a new thyroglobulin immunoradiometric assay in the follow-up of differentiated thyroid carcinoma. Nuklearmedizin 2003; 42: 71-77.
  Article in Thieme ConnectPubMedGoogle Scholar
• 20 Showalter TN, Siegel BA, Moley JF. et al. Prognostic factors in patients with well-differentiated thyroid cancer presenting with pulmonary metastasis. Cancer Biother Radiopharm 2008; 23: 655-659.
  CrossrefPubMedGoogle Scholar
• 21 Simpson WJ, McKinney SE, Carruthers JS. et al. Papillary and follicular thyroid cancer. Prognostic factors in 1578 patients. Am J Med 1987; 83: 479-488.
  CrossrefPubMedGoogle Scholar
• 22 Tubiana M, Schlumberger M, Rougier P. et al. Long-Term results and prognostic factors in patients with differentiated thyroid carcinoma. Cancer 1985; 55: 794-804.
  CrossrefPubMedGoogle Scholar
• 23 Tuttle RM, Leboeuf R, Shaha AR. Medical management of thyroid cancer: a risk adapted approach. J Surg Oncol 2008; 97: 712-716.
  CrossrefPubMedGoogle Scholar
• 24 Tuttle RM, Tala H, Shah J. et al. Estimating risk of recurrence in differentiated thyroid cancer after total thyroidectomy and radioactive iodine remnant ablation: using response to therapy variables to modify the initial risk estimates predicted by the new American Thyroid Association staging system. Thyroid 2010; 20: 1341-1349.
  CrossrefPubMedGoogle Scholar
• 25 Verburg FA, de Keizer B, de Klerk JM. et al. Value of diagnostic radioiodine scintigraphy and thyroglobulin measurements after rhTSH injection. Nuklearmedizin 2009; 48: 26-29.
  Article in Thieme ConnectPubMedGoogle Scholar
• 26 Verburg FA, Stokkel MP, Düren C. et al. No survival difference after successful ¹³¹I ablation between patients with initially low-risk and high-risk differentiated thyroid cancer. Eur J Nucl Med Mol Imaging 2010; 37: 276-283.
  CrossrefPubMedGoogle Scholar
• 27 Verburg FA, Verkooijen RB, Stokkel MP. et al. The success of ¹³¹I ablation in thyroid cancer patients is significantly reduced after a diagnostic activity of 40 MBq ¹³¹I. Nuklearmedizin 2009; 48: 138-142.
  Article in Thieme ConnectPubMedGoogle Scholar
• 28 Wittekind C, Greene FL, Henson DE. et al. TNM Supplement. A commentary on uniform use.. 3^rd ed. New York: Wiley-Liss; 2003