PDF herunterladen
Horm Metab Res 2017; 49(11): 860-868
DOI: 10.1055/s-0043-119462
Endocrine Care
© Georg Thieme Verlag KG Stuttgart · New York

Only a Rapid Complete Biochemical Remission After 131I-Therapy is Associated with an Unimpaired Life Expectancy in Differentiated Thyroid Cancer

Frederik A. Verburg
1   Department of Nuclear Medicine, University of Wuerzburg, Wuerzburg, Germany
2   University Hospital Marburg, Department of Nuclear Medicine, Marburg, Germany
,
Uwe Mäder
3   Comprehensive Cancer Center Mainfranken, University of Wuerzburg, Wuerzburg, Germany
,
Inge Grelle
1   Department of Nuclear Medicine, University of Wuerzburg, Wuerzburg, Germany
,
Luca Giovanella
4   Oncology Institute of Southern Switzerland, Department of Nuclear Medicine and Thyroid Centre, Bellinzona, Switzerland
,
Christoph Reiners
1   Department of Nuclear Medicine, University of Wuerzburg, Wuerzburg, Germany
,
Heribert Hänscheid
1   Department of Nuclear Medicine, University of Wuerzburg, Wuerzburg, Germany
› Institutsangaben
Weitere Informationen

Publikationsverlauf

received 12. Dezember 2016

accepted 05. September 2017

Publikationsdatum:
14. November 2017 (online)

Auch verfügbar auf
    Lizenzen und Reprints

Abstract

The objective of the work was to investigate the relationship between thyroglobulin doubling time (TgDT) as a marker of speed of response to 131I-therapy and the differentiated thyroid cancer (DTC) recurrence rate, DTC specific mortality rate, and relative survival rate in a DTC population followed over a long period of time after 131I-therapy. From our database, data of 1354 patients were reviewed. TgDT could be calculated in 174 patients, however, 376 patients did not have sufficient Tg values available for TgDT calculation and 804 patients reached biochemical remission before a sufficient number of Tg measurements for TgDT calculation was acquired. Main outcome measures were recurrence-free, DTC specific, and relative survival rates. In patients<45 years, TgDT in multivariate analysis was identified as the solitary significant determinant of DTC specific and relative survival. In patients≥45 years of age at diagnosis, TgDT is an independent, but not the only determinant of recurrence free, DTC specific, and relative survival. Importantly, in this age group life expectancy is normal in patients reaching rapid biochemical remission (i. e., before TgDT can be calculated); it was reduced in patients with a negative TgDT, which normally is deemed a marker of response to therapy. Only DTC patients with a rapid biochemical remission have a very good prognosis with a normal life expectancy. If no rapid biochemical remission occurs, both biochemically progressive disease and a slower biochemical remission of disease are associated with a reduced prognosis, especially in older DTC patients.

Key words

differentiated thyroid carcinoma - thyroglobulin - thyroglobulin doubling time - prognosis - life expectancy
 

  • References

  • 1 Mazzaferri EL, Jhiang SM. Long-term impact of initial surgical and medical therapy on papillary and follicular thyroid cancer. Am J Med 1994; 97: 418-428
    CrossrefPubMedGoogle Scholar
  • 2 Verburg FA, de Keizer B, Lips CJ, Zelissen PM, de Klerk JM. Prognostic significance of successful ablation with radioiodine of differentiated thyroid cancer patients. Eur J Endocrinol 2005; 152: 33-37
    CrossrefPubMedGoogle Scholar
  • 3 Tuttle RM, Tala H, Shah J, Leboeuf R, Ghossein R, Gonen M, Brokhin M, Omry G, Fagin JA, Shaha A. 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
  • 4 Verburg FA, Stokkel MP, Duren C, Verkooijen RB, Mader U, van Isselt JW, Marlowe RJ, Smit JW, Reiners C, Luster M. No survival difference after successful (131)I 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
  • 5 Thies ED, Tanase K, Maeder U, Luster M, Buck AK, Hanscheid H, Reiners C, Verburg FA. The number of 131I therapy courses needed to achieve complete remission is an indicator of prognosis in patients with differentiated thyroid carcinoma. Eur J Nucl Med Mol Imaging 2014; 41: 2281-2290
    CrossrefPubMedGoogle Scholar
  • 6 Feldt-Rasmussen U. Serum thyroglobulin and thyroglobulin autoantibodies in thyroid diseases. Pathogenic and diagnostic aspects. Allergy 1983; 38: 369-387
    CrossrefPubMedGoogle Scholar
  • 7 Spencer CA, Wang CC. Thyroglobulin measurement. Techniques, clinical benefits, and pitfalls. Endocrinol Metab Clin North Am 1995; 24: 841-863
    PubMedGoogle Scholar
  • 8 Spencer CA, Bergoglio LM, Kazarosyan M, Fatemi S, LoPresti JS. Clinical impact of thyroglobulin (Tg) and Tg autoantibody method differences on the management of patients with differentiated thyroid carcinomas. J Clin Endocrinol Metab 2005; 90: 5566-5575
    CrossrefPubMedGoogle Scholar
  • 9 Cooper DS, Doherty GM, Haugen BR, Kloos RT, Lee SL, Mandel SJ, Mazzaferri EL, McIver B, Pacini F, Schlumberger M, Sherman SI, Steward DL, Tuttle RM. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 2009; 19: 1167-1214
    CrossrefPubMedGoogle Scholar
  • 10 Pacini F, Schlumberger M, Dralle H, Elisei R, Smit JW, Wiersinga W. European consensus for the management of patients with differentiated thyroid carcinoma of the follicular epithelium. Eur J Endocrinol 2006; 154: 787-803
    CrossrefPubMedGoogle Scholar
  • 11 Pacini F, Castagna MG, Brilli L, Pentheroudakis G. Thyroid cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2010; 21 (Suppl. 05) v214-v219
    CrossrefPubMedGoogle Scholar
  • 12 Schlumberger MJ. Papillary and follicular thyroid carcinoma. N Engl J Med 1998; 338: 297-306
    CrossrefPubMedGoogle Scholar
  • 13 Feldt-Rasmussen U, Rasmussen AK. Serum thyroglobulin (Tg) in presence of thyroglobulin autoantibodies (TgAb). Clinical and methodological relevance of the interaction between Tg and TgAb in vitro and in vivo. J Endocrinol Invest 1985; 8: 571-576
    CrossrefPubMedGoogle Scholar
  • 14 Spencer C, Petrovic I, Fatemi S. Current thyroglobulin autoantibody (TgAb) assays often fail to detect interfering TgAb that can result in the reporting of falsely low/undetectable serum Tg IMA values for patients with differentiated thyroid cancer. J Clin Endocrinol Metab 2011; 96: 1283-1291
    CrossrefPubMedGoogle Scholar
  • 15 Verburg FA, Luster M, Cupini C, Chiovato L, Duntas LH, Elisei R, Feldt-Rasmussen U, Smit JW, Rimmele H, Seregni E, Theimer C, Giovanella L. Implications of thyroglobulin antibody positivity in patients with differentiated thyroid cancer: a clinical position statement. Thyroid 2013; 23: 1211-1215
    CrossrefPubMedGoogle Scholar
  • 16 Giovanella L, Keller F, Ceriani L, Tozzoli R. Heterophile antibodies may falsely increase or decrease thyroglobulin measurement in patients with differentiated thyroid carcinoma. Clin Chem Lab Med 2009; 47: 952-954
    PubMedGoogle Scholar
  • 17 Giovanella L, Toffalori E, Tozzoli R, Caputo M, Ceriani L, Verburg FA. Multiplexed immunoassay of thyroglobulin autoantibodies in patients with differentiated thyroid carcinoma. Head Neck 2012; 34: 1369-1371
    CrossrefPubMedGoogle Scholar
  • 18 Verburg FA, Waschle K, Reiners C, Giovanella L, Lentjes EG. Heterophile antibodies rarely influence the measurement of thyroglobulin and thyroglobulin antibodies in differentiated thyroid cancer patients. Horm Metab Res 2010; 42: 736-739
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 19 Verburg FA, Grelle I, Giovanella L, Reiners C. Evaluation of the BRAHMS KRYPTOR Thyroglobulin “Mini-recovery” Test in Thyroid Healthy Subjects. Horm Metab Res 2012; 44: 555-557
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 20 Miyauchi A, Kudo T, Miya A, Kobayashi K, Ito Y, Takamura Y, Higashiyama T, Fukushima M, Kihara M, Inoue H, Tomoda C, Yabuta T, Masuoka H. Prognostic impact of serum thyroglobulin doubling-time under thyrotropin suppression in patients with papillary thyroid carcinoma who underwent total thyroidectomy. Thyroid 2011; 21: 707-716
    CrossrefPubMedGoogle Scholar
  • 21 Rossing RM, Jentzen W, Nagarajah J, Bockisch A, Gorges R. Serum Thyroglobulin Doubling Time in Progressive Thyroid Cancer. Thyroid 2016; 26: 1712-1718
    CrossrefPubMedGoogle Scholar
  • 22 Giovanella L, Trimboli P, Verburg FA, Treglia G, Piccardo A, Foppiani L, Ceriani L. Thyroglobulin levels and thyroglobulin doubling time independently predict a positive (18)F-FDG PET/CT scan in patients with biochemical recurrence of differentiated thyroid carcinoma. Eur J Nucl Med Mol Imaging 2013; 40: 874-880
    CrossrefPubMedGoogle Scholar
  • 23 Kelders A, Kennes LN, Krohn T, Behrendt FF, Mottaghy FM, Verburg FA. Relationship between positive thyroglobulin doubling time and 18F-FDG PET/CT-positive, 131I-negative lesions. Nucl Med Commun 2014; 35: 176-181
    CrossrefPubMedGoogle Scholar
  • 24 Verburg FA, Mader U, Tanase K, Thies ED, Diessl S, Buck AK, Luster M, Reiners C. Life expectancy is reduced in differentiated thyroid cancer patients >= 45 years old with extensive local tumor invasion, lateral lymph node, or distant metastases at diagnosis and normal in all other dtc patients. J Clin Endocrinol Metab 2013; 98: 172-180
    CrossrefPubMedGoogle Scholar
  • 25 Verburg FA, Mader U, Luster M, Reiners C. Primary tumor diameter as a risk factor for advanced disease features of differentiated thyroid carcinoma. Clin Endocrinol (Oxf) 2008; 71: 291-297
    PubMedGoogle Scholar
  • 26 Verburg FA, Mader U, Luster M, Reiners C. Histology does not influence prognosis in differentiated thyroid carcinoma when accounting for age, tumour diameter, invasive growth and metastases. Eur J Endocrinol 2009; 160: 619-624
    CrossrefPubMedGoogle Scholar
  • 27 Verburg FA, Mader U, Kruitwagen CL, Luster M, Reiners C. A comparison of prognostic classification systems for differentiated thyroid carcinoma. Clin Endocrinol (Oxf) 2010; 72: 830-838
    PubMedGoogle Scholar
  • 28 Verburg FA, Mader U, Grelle I, Visser TJ, Peeters RP, Smit JW, Reiners C. The thyroid axis ‘setpoints’ are significantly altered after long-term suppressive lt4 therapy. Horm Metab Res 2014; 46: 794-799
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 29 Verburg FA, Mader U, Reiners C, Hanscheid H. Long-term survival in differentiated thyroid cancer is worse after low-activity initial post-surgical (131)i therapy in both high- and low-risk patients. J Clin Endocrinol Metab 2014; 99: 4487-4496
    CrossrefPubMedGoogle Scholar
  • 30 Sobin LH, Gospodarowicz MK, Wittekind C. TNM classification of malignant tumours. 7th ed. New-York: Wiley-Blackwell; 2009
    Google Scholar
  • 31 Morgenthaler NG, Froehlich J, Rendl J, Willnich M, Alonso C, Bergmann A, Reiners C. Technical evaluation of a new immunoradiometric and a new immunoluminometric assay for thyroglobulin. Clin Chem 2002; 48: 1077-1083
    PubMedGoogle Scholar
  • 32 Rendl J, Grelle I, Reiners C. Methodical properties and clinical efficiency of a novel Tg-assay in the follow-up of differentiated thyroid carcinomas. Nuklearmedizin 1994; 33: A13
    PubMedGoogle Scholar
  • 33 Verburg FA, Hanscheid H, Biko J, Hategan MC, Lassmann M, Kreissl MC, Reiners C, Luster M. Dosimetry-guided high-activity (131)I therapy in patients with advanced differentiated thyroid carcinoma: initial experience. Eur J Nucl Med Mol Imaging 2010; 37: 896-903
    CrossrefPubMedGoogle Scholar
  • 34 Geiss K, Meyer M. A Windows application for computing standardized mortality ratios and standardized incidence ratios in cohort studies based on calculation of exact person-years at risk. Comput Methods Programs Biomed 2013; 111: 735-739
    CrossrefPubMedGoogle Scholar
  • 35 Ederer F, Axtell LM, Cutler SJ. The relative survival rate: a statistical methodology. Natl Cancer Inst Monogr 1961; 6: 101-121
    PubMedGoogle Scholar
  • 36 Pohar M, Stare J. Making relative survival analysis relatively easy. Comput Biol Med 2007; 37: 1741-1749
    CrossrefPubMedGoogle Scholar
  • 37 Haugen BR, Pacini F, Reiners C, Schlumberger M, Ladenson PW, Sherman SI, Cooper DS, Graham KE, Braverman LE, Skarulis MC, Davies TF, DeGroot LJ, Mazzaferri EL, Daniels GH, Ross DS, Luster M, Samuels MH, Becker DV, Maxon III HR, Cavalieri RR, Spencer CA, McEllin K, Weintraub BD, Ridgway EC. A comparison of recombinant human thyrotropin and thyroid hormone withdrawal for the detection of thyroid remnant or cancer. J Clin Endocrinol Metab 1999; 84: 3877-3885
    PubMedGoogle Scholar
  • 38 Pacini F, Molinaro E, Lippi F, Castagna MG, Agate L, Ceccarelli C, Taddei D, Elisei R, Capezzone M, Pinchera A. Prediction of disease status by recombinant human TSH-stimulated serum Tg in the postsurgical follow-up of differentiated thyroid carcinoma. J Clin Endocrinol Metab 2001; 86: 5686-5690
    CrossrefPubMedGoogle Scholar