The success of ¹³¹I ablation in thyroid cancer patients is significantly reduced after a diagnostic activity of 40 MBq ¹³¹I

Summary

Objective: Dosimetry studies have shown that activities of ¹³¹I as small as 10-20 MBq may cause a stunning effect. A result of this stunning effect may be a lower success rate of the ablative ¹³¹I therapy for differentiated thyroid carcinoma (DTC). The aim of this study was to determine whether pre-therapeutic uptake measurement with 40 MBq ¹³¹I causes a lower success rate of ablation. Design: retrospective chart review study. Patients, methods: In two hospitals the ablation protocols differed in one respect only: in the one hospital no diagnostic ¹³¹I was applied before ablation (group 1, n = 48), whereas in the other hospital a 24-h uptake-measurement with 40 MBq ¹³¹I was performed (group 2, n = 51). Included were all DTC patients without distant metastases who had undergone ¹³¹I ablation between July 2002 and December 2005, and who had returned for ¹³¹I follow-up. Successful ablation was defined as absence of pathological ¹³¹I uptake on diagnostic whole-body scintigraphy and undetectable thyroglobulin-levels under TSH stimulation. Results: Overall, ablation was successful in 31/48 patients (65%) in group 1 and in 17/51 patients (33%) in group 2 (p=0.002). Multivariate analysis showed that pre-therapeutic uptake measurement using 40 MBq ¹³¹I was an independant determinant for success of ablation (p = 0.002). Conclusions: After applying a diagnostic activity of 40 MBq ¹³¹I before ablation, the success rate of ablation is severely reduced. Consequently, the routine application of ¹³¹I for diagnostic scintigraphy or uptake measurement prior to ¹³¹I ablation is best avoided.

Zusammenfassung

Ziel: Dosimetrische Studien haben gezeigt, dass selbst geringe Aktivitäten wie 10-20 MBq ¹³¹I dazu führen können, dass ein Stunning des Schilddrüsenrestgewebes auftritt. Als Folge könnte die Erfolgsquote der ¹³¹I-Ablation bei differenziertem Schilddrüsenkarzinom (DTC) deutlich erniedrigt sein. Das Ziel dieser Studie war es, festzustellen, ob prätherapeutische Uptake-Messung mit 40 MBq ¹³¹I eine geringere Erfolgsquote der Ablation verursacht. Design: Retrospektive Studie anhand von Krankenakten. Patienten, Methoden: In zwei Krankenhäusern unterschieden sich die Ablationsprotokolle nur in einer Hinsicht: In einem Krankenhaus wurde kein diagnostischer Scan mit ¹³¹I vor Ablation durchgeführt (Gruppe 1, n = 48), im anderen Krankenhaus wurde hingegen ein 24-h-Uptake-Messung mit 40 MBq ¹³¹I gemacht (Gruppe 2, n = 51). In unserer Studie wurden alle Patienten mit DTC ohne Fernmetastasen eingeschlossen, die zwischen Juli 2002 und Dezember 2005 mittels einer ¹³¹I-Ablation behandelt wurden und für ein ¹³¹I-Follow-up erneut aufgenommen wurden. Erfolgreiche Ablation wurde definiert als Abwesenheit von pathologischen ¹³¹I-Speicherungen auf einer diagnostischen Ganz - körperszintigraphie und einer nicht nachweisbaren Thyreoglobulinkonzentration unter TSH-Stimulation. Ergebnisse: Insgesamt war die Ablation erfolgreich in 31/48 Patienten (65%) in Gruppe 1 und in 17/51 Patienten (33%) in Gruppe 2 (p = 0,002). Multivariate Analysen zeigten, dass die prätherapeutische Uptake-Messung mit 40 MBq ¹³¹I ein un - abhängiger Faktor für den Erfolg der Ablation war (p = 0,002). Schlussfolgerungen: Durch der Gabe einer diagnostischen Aktivität von 40 MBq ¹³¹I vor Ablation wird die Erfolgsrate der Ablation stark reduziert. Folglich sollte die routinemäßige diagnostische ¹³¹I-Szinti - graphie oder ¹³¹I-Up take- Messung vor ¹³¹IAblation am besten vermieden werden.

Keywords

Differentiated thyroid cancer - ¹³¹I ablation - stunning

Schlüsselwörter

Differenzieres Schilddrüsenkarzinom - ¹³¹IAblation - Stunning

^* Both authors contributed equally.

• References

• 1 Ali N, Sebastian C, Foley RR. et al. The management of differentiated thyroid cancer using ¹²³I for imaging to assess the need for ¹³¹I therapy. Nucl Med Commun 2006; 27: 165-169.
• 2 Cholewinski SP, Yoo KS, Klieger PS, O'Mara RE. Absence of thyroid stunning after diagnostic whole-body scanning with 185 MBq ¹³¹I. J Nucl Med 2000; 41: 1198-1202.
• 3 Dam HQ, Kim SM, Lin HC, Intenzo CM. ¹³¹I therapeutic efficacy is not influenced by stunning after diagnostic whole-body scanning. Radiology 2004; 232: 527-533.
• 4 De Klerk JM, de Keizer B, Zelissen PM. et al. Fixed dosage of ¹³¹I for remnant ablation in patients with differentiated thyroid carcinoma without pre- ablative diagnostic ¹³¹I scintigraphy. Nucl Med Commun 2000; 21: 529-532.
• 5 Dietlein M, Dressler J, Eschner W. et al. Procedure guidelines for radioiodine therapy of differentiated thyroid cancer (version 3). Nuklearmedizin 2007; 46: 213-219.
• 6 Dietlein M, Dressler J, Eschner W. et al. Deutsche Gesellschaft für Nuklearmedizin, Deutsche Gesellschaft für Medizinische Physik. Procedure guideline for iodine-131 whole-body scintigraphy for differentiated thyroid cancer (version 3). Nuklearmedizin 2007; 46: 206-212.
• 7 Freudenberg LS, Jentzen W, Görges R. et al. 124I-PET dosimetry in advanced differentiated thyroid cancer: therapeutic impact. Nuklearmedizin 2007; 46: 121-128.
• 8 Goslings BM. Proceedings: Effect of a low iodine diet on ¹³¹I therapy in follicular thyroid carcinoma- ta. J Endocrinol 1975; 64: 30P.
• 9 Grosev D, Loncaric S, Huic D, Dodig D. Geometric models in dosimetry of thyroid remnant mass. Nuklearmedizin 2008; 47: 120-126.
• 10 Hilditch TE, Dempsey MF, Bolster AA. et al. Self- stunning in thyroid ablation: evidence from comparative studies of diagnostic ¹³¹I and ¹²³I. Eur J Nucl Med Mol Imaging 2002; 29: 783-788.
• 11 Hu YH, Wang PW, Wang ST. et al. Influence of ¹³¹I diagnostic dose on subsequent ablation in patients with differentiated thyroid carcinoma: discrepancy between the presence of visually apparent stunning and the impairment of successful ablation. Nucl Med Commun 2004; 25: 793-797.
• 12 Jeevanram RK, Shah DH, Sharma SM, Ganatra RD. Influence of initial large dose on subsequent uptake of therapeutic radioiodine in thyroid cancer patients. Int J Rad Appl Instrum B 1986; 13: 277-279.
• 13 Jentzen W, Freudenberg L, Eising E. et al. Optimized 124I PET dosimetry protocol for radioiodine therapy of differentiated thyroid cancer. J Nucl Med 2008; 49: 1017-1023.
• 14 Krohn T, Meyer PT, Ocklenburg C. et al. Stunning in radioiodine theray of benign thyroid disease. Nuklearmedizin 2008; 47: 254.
• 15 Lassmann M, Haenscheid H, Chiesa C. et al. EANM dosimetry committee series on standard operational procedures for pre-therapeutic dosimetry I: blood and bone marrow dosimetry in differentiated thyroid cancer therapy. Eur J Nucl Med Mol Imaging 2008; 35: 1405-1412.
• 16 Lassmann M, Luster M, Hanscheid H, Reiners C. Impact of ¹³¹I diagnostic activities on the biokinetics of thyroid remnants. J Nucl Med 2004; 45: 619-625.
• 17 Lees W, Mansberg R, Roberts J. et al. The clinical effects of thyroid stunning after diagnostic whole- body scanning with 185 MBq ¹³¹I. Eur J Nucl Med Mol Imaging 2002; 29: 1421-1427.
• 18 Leung SF, Law MW, Ho SK. Efficacy of low-dose iod- ine-131 ablation of post-operative thyroid remnants: a study of 69 cases. Br J Radiol 1992; 65: 905-909.
• 19 Lundh C, Norden MM, Nilsson M, Forssell-Aronsson E. Reduced iodide transport (stunning) and DNA synthesis in thyrocytes exposed to low absorbed doses from ¹³¹I in vitro. J Nucl Med 2007; 48: 481-486.
• 20 Luster M, Sherman SI, Skarulis MC. et al. Comparison of radioiodine biokinetics following the administration of recombinant human thyroid stimulating hormone and after thyroid hormone withdrawal in thyroid carcinoma. Eur J Nucl Med Mol Imaging 2003; 30: 1371-1377.
• 21 Mariotti S, Barbesino G, Caturegli P. et al. Assay of thyroglobulin in serum with thyroglobulin auto-antibodies: an unobtainable goal?. J Clin Endocrinol Metab 1995; 80: 468-472.
• 22 McDougall IR. 74 MBq radioiodine ¹³¹I does not prevent uptake of therapeutic doses of ¹³¹I (i.e. it does not cause stunning) in differentiated thyroid cancer. Nucl Med Commun 1997; 18: 505-512.
• 23 Medvedec M. Thyroid stunning in vivo and in vitro. Nucl Med Commun 2005; 26: 731-735.
• 24 Meller B, von Hof K, Genina E. et al. Diagnostic ¹²³I and ¹³¹I activities and radioiodine therapy. Effects on urinary iodine excretion in patients with differentiated thyroid carcinoma. Nuklearmedizin 2005; 44: 243-248.
• 25 Morris LF, Waxman AD, Braunstein GD. The nonimpact of thyroid stunning: remnant ablation rates in ¹³¹I- scanned and nonscanned individuals. J Clin Endocrinol Metab 2001; 86: 3507-3511.
• 26 Muratet JP, Daver A, Minier JF, Larra F. Influence of scanning doses of iodine-131 on subsequent first ablative treatment outcome in patients operated on for differentiated thyroid carcinoma. J Nucl Med 1998; 39: 1546-1550.
• 27 Norden MM, Larsson F, Tedelind S. et al. Down- regulation of the sodium/iodine symporter explains ¹³¹I-induced thyroid stunning. Cancer Res 2007; 67: 7512-7517.
• 28 Pacini F, Ladenson PW, Schlumberger M. et al. Radioiodine ablation of thyroid remnants after preparation with recombinant human thyrotropin in differentiated thyroid carcinoma: results of an international, randomized, controlled study. J Clin Endocrinol Metab 2006; 91: 926-932.
• 29 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.
• 30 Park HM, Perkins OW, Edmondson JW. et al. Influence of diagnostic radioiodines on the uptake of ablative dose of iodine-131. Thyroid 1994; 4: 49-54.
• 31 Phan TT, van Tol KM, Links TP. et al. Diagnostic ¹³¹I scintigraphy in patients with differentiated thyroid cancer: no additional value of higher scan dose. Ann Nucl Med 2004; 18: 641-646.
• 32 Pluijmen MJHM, Eustatia-Rutten C, Goslings BM. et al. Effects of low-iodide diet on postsurgical radioiodide ablation therapy in patients with differentiated thyroid carcinoma. Clin Endocrinol 2003; 58: 428-435.
• 33 Postgard P, Himmelman J, Lindencrona U. et al. Stunning of iodide transport by ¹³¹I irradiation in cultured thyroid epithelial cells. J Nucl Med 2002; 43: 828-834.
• 34 Rahbar K, Hutzenlaub V, Fischer RJ. et al. Risk-profile and outcome of small papillary and follicular thyroid carcinomas (<1 cm). Nuklearmedizin 2008; 47: 188-193.
• 35 Siddiqi A, Foley RR, Britton KE. et al. The role of ¹²³I-diagnostic imaging in the follow-up of patients with differentiated thyroid carcinoma as compared to ¹³¹I-scanning: avoidance of negative therapeutic uptake due to stunning. Clin Endocrinol (Oxf) 2001; 55: 515-521.
• 36 Silberstein EB. Comparison of outcomes after ¹²³I versus ¹³¹I preablation imaging before radioiodine ablation in differentiated thyroid carcinoma. J Nucl Med 2007; 48: 1043-1046.
• 37 Sisson JC, Avram AM, Lawson SA. et al. The so- called stunning of thyroid tissue. J Nucl Med 2006; 47: 1406-1412.
• 38 Sobin LH, Wittekind C. (eds) TNM classification of malignant tumours. Berlin: Springer; 1997
• 39 Spencer CA, Takeuchi M, Kazarosyan M. et al. Serum thyroglobulin autoantibodies: prevalence, influence on serum thyroglobulin measurement, and prognostic significance in patients with differentiated thyroid carcinoma. J Clin Endocrinol Metab 1998; 83: 1121-1127.
• 40 Torlontano M, Crocetti U, D'Aloiso L. et al. 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.
• 41 Verkooijen RB, Stokkel MP, Smit JW, Pauwels EK. Radioiodine-131 in differentiated thyroid cancer: a retrospective analysis of an uptake-related ablation strategy. Eur J Nucl Med Mol Imaging 2004; 31: 499-506.
• 42 Zidan J, Hefer E, Iosilevski G. et al. Efficacy of ¹³¹I ablation therapy using different doses as determined by postoperative thyroid scan uptake in patients with differentiated thyroid cancer. Int J Radiat Oncol Biol Phys 2004; 59: 1330-1336.