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BMC Cancer
Published in: BMC Cancer 1/2014

Open Access 01-12-2014 | Study protocol

Recurrent differentiated thyroid cancer: towards personalized treatment based on evaluation of tumor characteristics with PET (THYROPET Study): study protocol of a multicenter observational cohort study

Authors: Jakob W Kist, Bart de Keizer, Marcel PM Stokkel, Otto S Hoekstra, Wouter V Vogel, THYROPET study group

Published in: BMC Cancer | Issue 1/2014

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Abstract

Background

After initial treatment of differentiated thyroid carcinoma (DTC) patients are followed with thyroglobulin (Tg) measurements to detect recurrences. In case of elevated levels of Tg and negative neck ultrasonography, patients are treated 'blindly' with Iodine-131 (131I). However, in up to 50% of patients, the post-therapy scan reveals no 131I-targeting of tumor lesions. Such patients derive no benefit from the blind therapy but are exposed to its toxicity. Alternatively, iodine-124 (124I) Positron Emission Tomography/Computed Tomography (PET/CT) has become available to visualize DTC lesions and without toxicity. In addition to this, 18F-fluorodeoxyglucose (18F-FDG) PET/CT detects the recurrent DTC phenotype, which lost the capacity to accumulate iodine. Taken together, the combination of 124I and 18F-FDG PET/CT has potential to stratify patients for treatment with 131I.

Methods/Design

In a multicenter prospective observational cohort study the hypothesis that the combination of 124I and 18F-FDG PET/CT can avoid futile 131I treatments in patients planned for ‘blind’ therapy with 131I, is tested.
One hundred patients planned for 131I undergo both 124I and 18F-FDG PET/CT after rhTSH stimulation. Independent of the outcome of the scans, all patients will subsequently receive, after thyroid hormone withdrawal, the 131I therapy. The post 131I therapeutic scintigraphy is compared with the outcome of the 124I and 18F-FDG PET/CT in order to evaluate the diagnostic value of the combined PET modalities.
This study primary aims to reduce the number of futile 131I therapies. Secondary aims are the nationwide introduction of 124I PET/CT by a quality assurance and quality control (QA/QC) program, to correlate imaging outcome with histopathological features, to compare 124I PET/CT after rhTSH and after withdrawal of thyroid hormone, and to compare 124I and 131I dosimetry.

Discussion

This study aims to evaluate the potential value of the combination of 124I and 18F-FDG PET/CT in the prevention of futile 131I therapies in patients with biochemically suspected recurrence of DTC. To our best knowledge no studies addressed this in a prospective cohort of patients. This is of great clinical importance as a futile 131I is a costly treatment associated with morbidity and therefore should be restricted to those likely to benefit from this treatment.

Trial registration

Clinicaltrials.gov identifier: NCT01641679
Appendix
Available only for authorised users
Literature
1.
Jemal A, Siegel R, Xu J, Ward E: Cancer statistics, 2010. CA Cancer J Clin. 2010, 60: 277-300. 10.3322/caac.20073.CrossRefPubMed
2.
Schvartz C, Bonnetain F, Dabakuyo S, Gauthier M, Cueff A, Fieffé S, Pochart J-M, Cochet I, Crevisy E, Dalac A, Papathanassiou D, Toubeau M: Impact on overall survival of radioactive iodine in low-risk differentiated thyroid cancer patients. J Clin Endocrinol Metab. 2012, 97: 1526-1535. 10.1210/jc.2011-2512.CrossRefPubMed
3.
Welsh L, Powell C, Pratt B, Harrington K, Nutting C, Harmer C, Newbold K: Long-term outcomes following low-dose radioiodide ablation for differentiated thyroid cancer. J Clin Endocrinol Metab. 2013, 98: 1819-1825. 10.1210/jc.2013-1197.CrossRefPubMed
4.
Shaha AR: Recurrent differentiated thyroid cancer. Endocr Pract. 2012, 18: 600-603. 10.4158/EP12047.CO.CrossRefPubMed
5.
Schlumberger M, Challeton C, De Vathaire F, Travagli JP, Gardet P, Lumbroso JD, Francese C, Fontaine F, Ricard M, Parmentier C: Radioactive iodine treatment and external radiotherapy for lung and bone metastases from thyroid carcinoma. J Nucl Med. 1996, 37: 598-605.PubMed
6.
Mazzaferri EL, Kloos RT: Clinical review 128: current approaches to primary therapy for papillary and follicular thyroid cancer. J Clin Endocrinol Metab. 2001, 86: 1447-1463. 10.1210/jcem.86.4.7407.CrossRefPubMed
7.
Husson O, Haak HR, Oranje WA, Mols F, Reemst PHM, van de Poll-Franse LV: Health-related quality of life among thyroid cancer survivors: a systematic review. Clin Endocrinol (Oxf). 2011, 75: 544-554. 10.1111/j.1365-2265.2011.04114.x.CrossRef
8.
9.
Francis Z, Schlumberger M: Serum thyroglobulin determination in thyroid cancer patients. Best Pract Res Clin Endocrinol Metab. 2008, 22: 1039-1046. 10.1016/j.beem.2008.09.015.CrossRefPubMed
10.
Bachelot A, Cailleux AF, Klain M, Baudin E, Ricard M, Bellon N, Caillou B, Travagli JP, Schlumberger M: Relationship between tumor burden and serum thyroglobulin level in patients with papillary and follicular thyroid carcinoma. Thyroid. 2002, 12: 707-711. 10.1089/105072502760258686.CrossRefPubMed
11.
12.
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 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.PubMed
13.
Mazzaferri EL, Robbins RJ, Spencer CA, Braverman LE, Pacini F, Wartofsky L, Haugen BR, Sherman SI, Cooper DS, Braunstein GD, Lee S, Davies TF, Arafah BM, Ladenson PW, Pinchera A: A consensus report of the role of serum thyroglobulin as a monitoring method for low-risk patients with papillary thyroid carcinoma. J Clin Endocrinol Metab. 2003, 88: 1433-1441. 10.1210/jc.2002-021702.CrossRefPubMed
14.
Castro MR, Bergert ER, Goellner JR, Hay ID, Morris JC: Immunohistochemical analysis of sodium iodide symporter expression in metastatic differentiated thyroid cancer: correlation with radioiodine uptake. J Clin Endocrinol Metab. 2001, 86: 5627-5632. 10.1210/jcem.86.11.8048.CrossRefPubMed
15.
Dadachova E, Carrasco N: The Na/I symporter (NIS): imaging and therapeutic applications. Semin Nucl Med. 2004, 34: 23-31. 10.1053/j.semnuclmed.2003.09.004.CrossRefPubMed
16.
Filetti S, Bidart JM, Arturi F, Caillou B, Russo D, Schlumberger M: Sodium/iodide symporter: a key transport system in thyroid cancer cell metabolism. Eur J Endocrinol. 1999, 141: 443-457. 10.1530/eje.0.1410443.CrossRefPubMed
17.
de Meer SG, Vriens MR, Zelissen PM, Borel Rinkes IH, de Keizer B: The role of routine diagnostic radioiodine whole-body scintigraphy in patients with high-risk differentiated thyroid cancer. J Nucl Med. 2011, 52: 56-59. 10.2967/jnumed.110.080697.CrossRefPubMed
18.
Pacini F, Agate L, Elisei R, Capezzone M, Ceccarelli C, Lippi F, Molinaro E, Pinchera A: Outcome of differentiated thyroid cancer with detectable serum Tg and negative diagnostic (131)I whole body scan: comparison of patients treated with high (131)I activities versus untreated patients. J Clin Endocrinol Metab. 2001, 86: 4092-4097. 10.1210/jcem.86.9.7831.CrossRefPubMed
19.
Cailleux AF, Baudin E, Travagli JP, Ricard M, Schlumberger M: Is diagnostic iodine-131 scanning useful after total thyroid ablation for differentiated thyroid cancer?. J Clin Endocrinol Metab. 2000, 85: 175-178. 10.1210/jcem.85.1.6310.CrossRefPubMed
20.
Pacini F, Capezzone M, Elisei R, Ceccarelli C, Taddei D, Pinchera A: Diagnostic 131-iodine whole-body scan may be avoided in thyroid cancer patients who have undetectable stimulated serum Tg levels after initial treatment. J Clin Endocrinol Metab. 2002, 87: 1499-1501. 10.1210/jcem.87.4.8274.CrossRefPubMed
21.
Pacini F, Molinaro E, Castagna MG, Agate L, Elisei R, Ceccarelli C, Lippi F, Taddei D, Grasso L, Pinchera A: 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. 10.1210/jc.2002-021925.CrossRefPubMed
22.
Frasoldati A, Pesenti M, Gallo M, Caroggio A, Salvo D, Valcavi R: Diagnosis of neck recurrences in patients with differentiated thyroid carcinoma. Cancer. 2003, 97: 90-96. 10.1002/cncr.11031.CrossRefPubMed
23.
Torlontano M, Crocetti U, D'Aloiso L, Bonfitto N, Di Giorgio A, Modoni S, Valle G, Frusciante V, Bisceglia M, Filetti S, Schlumberger M, Trischitta V: Serum thyroglobulin and 131I whole body scan after recombinant human TSH stimulation in the follow-up of low-risk patients with differentiated thyroid cancer. Eur J Endocrinol. 2003, 148: 19-24. 10.1530/eje.0.1480019.CrossRefPubMed
24.
Schlumberger M, Mancusi F, Baudin E, Pacini F: 131I therapy for elevated thyroglobulin levels. Thyroid. 1997, 7: 273-276. 10.1089/thy.1997.7.273.CrossRefPubMed
25.
de Keizer B, Koppeschaar HP, Zelissen PM, Lips CJ, van Rijk PP, van Dijk A, de Klerk JM: Efficacy of high therapeutic doses of iodine-131 in patients with differentiated thyroid cancer and detectable serum thyroglobulin. Eur J Nucl Med. 2001, 28: 198-202. 10.1007/s002590000443.CrossRefPubMed
26.
Pacini F, Lippi F, Formica N, Elisei R, Anelli S, Ceccarelli C, Pinchera A: Therapeutic doses of iodine-131 reveal undiagnosed metastases in thyroid cancer patients with detectable serum thyroglobulin levels. J Nucl Med. 1987, 28: 1888-1891.PubMed
27.
Pineda JD, Lee T, Ain K, Reynolds JC, Robbins J: Iodine-131 therapy for thyroid cancer patients with elevated thyroglobulin and negative diagnostic scan. J Clin Endocrinol Metab. 1995, 80: 1488-1492.PubMed
28.
Pachucki J, Burmeister LA: Evaluation and treatment of persistent thyroglobulinemia in patients with well-differentiated thyroid cancer. Eur J Endocrinol. 1997, 137: 254-261. 10.1530/eje.0.1370254.CrossRefPubMed
29.
Ma C, Xie J, Kuang A: Is empiric 131I therapy justified for patients with positive thyroglobulin and negative 131I whole-body scanning results?. J Nucl Med. 2005, 46: 1164-1170.PubMed
30.
van Tol KM, Jager PL, de Vries EGE, Piers DA, Boezen HM, Sluiter WJ, Dullaart RPF, Links TP: Outcome in patients with differentiated thyroid cancer with negative diagnostic whole-body scanning and detectable stimulated thyroglobulin. Eur J Endocrinol. 2003, 148: 589-596. 10.1530/eje.0.1480589.CrossRefPubMed
31.
Sawka AM, Thabane L, Parlea L, Ibrahim-Zada I, Tsang RW, Brierley JD, Straus S, Ezzat S, Goldstein DP: Second primary malignancy risk after radioactive iodine treatment for thyroid cancer: a systematic review and meta-analysis. Thyroid. 2009, 19: 451-457. 10.1089/thy.2008.0392.CrossRefPubMed
32.
Brown AP, Chen J, Hitchcock YJ, Szabo A, Shrieve DC, Tward JD: The Risk of second primary malignancies up to three decades after the treatment of differentiated Thyroid Cancer. J Clin Endocrinol Metab. 2008, 93: 504-515. 10.1210/jc.2007-1154.CrossRefPubMed
33.
Schroeder PR: A comparison of short-term changes in health-related quality of life in thyroid carcinoma patients undergoing diagnostic evaluation with recombinant human thyrotropin compared with thyroid hormone withdrawal. J Clin Endocrinol Metab. 2005, 91: 878-884.CrossRef
34.
Luster M, Felbinger R, Dietlein M, Reiners C: Thyroid hormone withdrawal in patients with differentiated thyroid carcinoma: a one hundred thirty-patient pilot survey on consequences of hypothyroidism and a pharmacoeconomic comparison to recombinant thyrotropin administration. Thyroid. 2005, 15: 1147-1155. 10.1089/thy.2005.15.1147.CrossRefPubMed
35.
Dow KH, Ferrell BR, Anello C: Quality-of-life changes in patients with thyroid cancer after withdrawal of thyroid hormone therapy. Thyroid. 1997, 7: 613-619. 10.1089/thy.1997.7.613.CrossRefPubMed
36.
Bianchi GP, Zaccheroni V, Solaroli E, Vescini F, Cerutti R, Zoli M, Marchesini G: Health-related quality of life in patients with thyroid disorders. Qual Life Res. 2004, 13: 45-54.CrossRefPubMed
37.
Botella-Carretero JI, Galán JM, Caballero C, Sancho J, Escobar-Morreale HF: Quality of life and psychometric functionality in patients with differentiated thyroid carcinoma. Endocr Relat Cancer. 2003, 10: 601-610. 10.1677/erc.0.0100601.CrossRefPubMed
38.
Freudenberg LS, Antoch G, Jentzen W, Pink R, Knust J, Görges R, Müller SP, Bockisch A, Debatin JF, Brandau W: Value of (124)I-PET/CT in staging of patients with differentiated thyroid cancer. Eur Radiol. 2004, 14: 2092-2098. 10.1007/s00330-004-2350-0.CrossRefPubMed
39.
Lubberink M, Abdul Fatah S, Brans B, Hoekstra OS, Teule GJJ: The role of (124)I-PET in diagnosis and treatment of thyroid carcinoma. Q J Nucl Med Mol Imaging. 2008, 52: 30-36.PubMed
40.
Lee J, Nah KY, Kim RM, Oh Y-J, An Y-S, Yoon J-K, An GI, Choi TH, Cheon GJ, Soh E-Y, Chung WY: Effectiveness of [124I]-PET/CT and [18F]-FDG-PET/CT for Localizing Recurrence in Patients with Differentiated Thyroid Carcinoma. J Korean Med Sci. 2012, 27: 1019-10.3346/jkms.2012.27.9.1019.CrossRefPubMedPubMedCentral
41.
Van Nostrand D, Moreau S, Bandaru VV, Atkins F, Chennupati S, Mete M, Burman K, Wartofsky L: (124)I positron emission tomography versus (131)I planar imaging in the identification of residual thyroid tissue and/or metastasis in patients who have well-differentiated thyroid cancer. Thyroid. 2010, 20: 879-883. 10.1089/thy.2009.0430.CrossRefPubMed
42.
Lubberink M, van Schie A, de Jong HWAM, van Dongen GAMS, Teule GJJ: Acquisition settings for PET of 124I administered simultaneously with therapeutic amounts of 131I. J Nucl Med. 2006, 47: 1375-1381.PubMed
43.
Freudenberg LS, Jentzen W, Görges R, Petrich T, Marlowe RJ, Knust J, Bockisch A: 124I-PET dosimetry in advanced differentiated thyroid cancer: therapeutic impact. Nuklearmedizin. 2007, 46: 121-128.PubMed
44.
Rivera M, Ghossein RA, Schoder H, Gomez D, Larson SM, Tuttle RM: Histopathologic characterization of radioactive iodine-refractory fluorodeoxyglucose-positron emission tomography-positive thyroid carcinoma. Cancer. 2008, 113: 48-56. 10.1002/cncr.23515.CrossRefPubMed
45.
Alzahrani AS, Al-Zahrani AS, Abouzied M-EM, Salam SA, Mohamed G, Rifai A, Sugair Al A, Amin T: The role of F-18-fluorodeoxyglucose positron emission tomography in the postoperative evaluation of differentiated thyroid cancer. Eur J Endocrinol. 2008, 158: 683-689. 10.1530/EJE-07-0903.CrossRefPubMed
46.
Mirallié E, Guillan T, Bridji B, Resche I, Rousseau C, Ansquer C, Bodet-Milin C, Curtet C, Carnaille B, Murat A, Charbonnel B, Kraeber-Bodéré F: Therapeutic impact of 18FDG-PET/CT in the management of iodine-negative recurrence of differentiated thyroid carcinoma. Surgery. 2007, 142: 952-958. 10.1016/j.surg.2007.09.015. discussion 952–8CrossRefPubMed
47.
Frilling A, Tecklenborg K, Görges R, Weber F, Clausen M, Broelsch EC: Preoperative diagnostic value of [(18)F] fluorodeoxyglucose positron emission tomography in patients with radioiodine-negative recurrent well-differentiated thyroid carcinoma. Ann Surg. 2001, 234: 804-811. 10.1097/00000658-200112000-00012.CrossRefPubMedPubMedCentral
48.
Brose MS, Nutting CM, Sherman SI, Shong YK, Smit JWA, Reike G, Chung J, Kalmus J, Kappeler C, Schlumberger M: Rationale and design of decision: a double-blind, randomized, placebo-controlled phase III trial evaluating the efficacy and safety of sorafenib in patients with locally advanced or metastatic radioactive iodine (RAI)-refractory, differentiated thyroid cancer. BMC Cancer. 2011, 11: 349-10.1186/1471-2407-11-349.CrossRefPubMedPubMedCentral
49.
Jentzen W, Freudenberg L, Eising EG, Sonnenschein W, Knust J, Bockisch A: Optimized 124I PET Dosimetry protocol for radioiodine therapy of differentiated Thyroid Cancer. J Nucl Med. 2008, 49: 1017-1023. 10.2967/jnumed.107.047159.CrossRefPubMed
50.
Kim M-H, Ko SH, Bae JS, Lee SH, Jung CK, Lim D-J, Baek KH, Kim SH, Lee JM, Kang MI, Cha BY: Non-FDG-avid primary papillary thyroid carcinoma may not differ from FDG-avid papillary thyroid carcinoma. Thyroid. 2013, 23: 1452-1460. 10.1089/thy.2013.0051.CrossRefPubMed
51.
Hooft L, van der Veldt AAM, van Diest PJ, Hoekstra OS, Berkhof J, Teule GJJ, Molthoff CFM: [18F]fluorodeoxyglucose uptake in recurrent thyroid cancer is related to hexokinase i expression in the primary tumor. J Clin Endocrinol Metab. 2005, 90: 328-334. 10.1210/jc.2004-0779.CrossRefPubMed
52.
Freudenberg LS, Antoch G, Frilling A, Jentzen W, Rosenbaum SJ, Kühl H, Bockisch A, Görges R: Combined metabolic and morphologic imaging in thyroid carcinoma patients with elevated serum thyroglobulin and negative cervical ultrasonography: role of 124I-PET/CT and FDG-PET. Eur J Nucl Med Mol Imaging. 2008, 35: 950-957. 10.1007/s00259-007-0634-8.CrossRefPubMed
53.
Boellaard R, O’Doherty MJ, Weber WA, Mottaghy FM, Lonsdale MN, Stroobants SG, Oyen WJG, Kotzerke J, Hoekstra OS, Pruim J, Marsden PK, Tatsch K, Hoekstra CJ, Visser EP, Arends B, Verzijlbergen FJ, Zijlstra JM, Comans EFI, Lammertsma AA, Paans AM, Willemsen AT, Beyer T, Bockisch A, Schaefer-Prokop C, Delbeke D, Baum RP, Chiti A, Krause BJ: FDG PET and PET/CT: EANM procedure guidelines for tumour PET imaging: version 1.0. Eur J Nucl Med Mol Imaging. 2009, 37: 181-200.CrossRefPubMedCentral
54.
Boellaard R, Oyen WJG, Hoekstra CJ, Hoekstra OS, Visser EP, Willemsen AT, Arends B, Verzijlbergen FJ, Zijlstra J, Paans AM, Comans EFI, Pruim J: The Netherlands protocol for standardisation and quantification of FDG whole body PET studies in multi-centre trials. Eur J Nucl Med Mol Imaging. 2008, 35: 2320-2333. 10.1007/s00259-008-0874-2.CrossRefPubMed
Metadata
Title
Recurrent differentiated thyroid cancer: towards personalized treatment based on evaluation of tumor characteristics with PET (THYROPET Study): study protocol of a multicenter observational cohort study
Authors
Jakob W Kist
Bart de Keizer
Marcel PM Stokkel
Otto S Hoekstra
Wouter V Vogel
THYROPET study group
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2014
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-14-405

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