Restricted accessResearch articleFirst published online 2013-08
18-Fluorodeoxyglucose Positron Emission Tomography in the Early Diagnostic Workup of Differentiated Thyroid Cancer Patients with a Negative Post-Therapeutic Iodine Scan and Detectable Thyroglobulin
Surgery and high-dose radioactive iodine (131I) treatment are the cornerstones in the treatment of differentiated thyroid cancer. Patients without 131I uptake on the post-therapeutic whole body scan (WBS), but with detectable thyroglobulin (Tg) during thyroxine withdrawal (Tg-off), are evaluated with an 18-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) for tumor localization within three months. The yield of 18F-FDG-PET imaging and clinical usefulness of a Tg-off cutoff value to predict a positive scan were assessed.
Methods:
From 2002 to 2011, 52 patients with a negative WBS and concurrent detectable Tg-off were evaluated. Thirty-five PET scans were performed during initial treatment, 17 after recurrent disease. Thirty-two patients were on substitution therapy, 17 were evaluated with endogenous thyrotropin elevation, and 3 after recombinant human thyrotropin stimulation. To determine the Tg-off cutoff value, a receiver operating characteristic curve was used.
Results:
Nine (17%) 18F-FDG-PET scans were true positive, 3 (6%) false positive, 36 (69%) true negative, and 4 (8%) false negative (sensitivity 69%, specificity 92%). In 13%, a true-positive scan resulted in a change in the clinical management. The area under the receiver operating characteristic curve is 0.82 [CI 0.64–0.99] (p<0.01), and the Tg-off cutoff value is 38.00 ng/mL (sensitivity 67%, specificity 95%). Ninety percent of 18F-FDG-PET true-positive patients had a Tg-off >2.00 ng/mL.
Conclusions:
An 18F-FDG-PET within three months after a negative WBS with detectable Tg-off showed additional tumor localization in 17% of the patients, leading to a change in clinical management in 13%. A clinically useful Tg-off cutoff value was not found, but 90% of positive 18F-FDG-PET scans occurred in patients with a Tg-off >2.00 ng/mL.
Get full access to this article
View all access options for this article.
References
1.
MazzaferriEL, KloosRT. 2001. Clinical review 128: current approaches to primary therapy for papillary and follicular thyroid cancer. J Clin Endocrinol Metab, 86:1447–1463.
2.
NixonIJ, GanlyI, PalmerFL, WhitcherMM, PatelSG, TuttleRM, ShahaAR, ShahJP. 2011. Disease-related death in patients who were considered free of macroscopic disease after initial treatment of well-differentiated thyroid carcinoma. Thyroid, 21:501–504.
3.
MazzaferriEL, JhiangSM. 1994. Long-term impact of initial surgical and medical therapy on papillary and follicular thyroid cancer. Am J Med, 97:418–428.
4.
PodnosYD, SmithD, WagmanLD, EllenhornJD. 2005. The implication of lymph node metastasis on survival in patients with well-differentiated thyroid cancer. Am Surg, 71:731–734.
5.
SchlumbergerM, ChalletonC, De VathaireF, TravagliJP, GardetP, LumbrosoJD, FranceseC, FontaineF, RicardM, ParmentierC. 1996. Radioactive iodine treatment and external radiotherapy for lung and bone metastases from thyroid carcinoma. J Nucl Med, 37:598–605.
6.
RobbinsRJ, WanQ, GrewalRK, ReibkeR, GonenM, StraussHW, TuttleRM, DruckerW, LarsonSM. 2006. Real-time prognosis for metastatic thyroid carcinoma based on 2-[18F]fluoro-2-deoxy-D-glucose-positron emission tomography scanning. J Clin Endocrinol Metab, 91:498–505.
7.
van DijkD, PlukkerJT, van der Horst-SchriversAN, JansenL, BrouwersAH, Muller-KoboldA, SluiterWJ, LinksTP. 2011. The value of detectable thyroglobulin in patients with differentiated thyroid cancer after initial 131I therapy. Clin Endocrinol (Oxf), 74:104–110.
8.
ZuijdwijkMD, VogelWV, CorstensFH, OyenWJ. 2008. Utility of fluorodeoxyglucose-PET in patients with differentiated thyroid carcinoma. Nucl Med Commun, 29:636–641.
9.
BertagnaF, BosioG, BiasiottoG, RodellaC, PutaE, GabanelliS, LucchiniS, MerliG, SavelliG, GiubbiniR, RosenbaumJ, AlaviA. 2009. F-18 FDG-PET/CT evaluation of patients with differentiated thyroid cancer with negative I-131 total body scan and high thyroglobulin level. Clin Nucl Med, 34:756–761.
10.
VeraP, Kuhn-LansoyC, Edet-SansonA, HapdeyS, ModzelewskiR, HitzelA, d'AnjouJ, BasuyauJP. 2010. Does recombinant human thyrotropin-stimulated positron emission tomography with [18F]fluoro-2-deoxy-D-glucose improve detection of recurrence of well-differentiated thyroid carcinoma in patients with low serum thyroglobulin?Thyroid, 20:15–23.
11.
LarsonSM, RobbinsR. 2002. Positron emission tomography in thyroid cancer management. Semin Roentgenol, 37:169–174.
12.
van TolKM, JagerPL, PiersDA, PruimJ, de VriesEG, DullaartRP, LinksTP. 2002. Better yield of (18)fluorodeoxyglucose-positron emission tomography in patients with metastatic differentiated thyroid carcinoma during thyrotropin stimulation. Thyroid, 12:381–387.
13.
WangW, MacapinlacH, LarsonSM, YehSD, AkhurstT, FinnRD, RosaiJ, RobbinsRJ. 1999. [18F]-2-fluoro-2-deoxy-D-glucose positron emission tomography localizes residual thyroid cancer in patients with negative diagnostic (131)I whole body scans and elevated serum thyroglobulin levels. J Clin Endocrinol Metab, 84:2291–2302.
14.
LeboulleuxS, SchroederPR, BusaidyNL, AuperinA, CoroneC, JaceneHA, EwertzME, BournaudC, WahlRL, ShermanSI, LadensonPW, SchlumbergerM. 2009. Assessment of the incremental value of recombinant thyrotropin stimulation before 2-[18F]-Fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography imaging to localize residual differentiated thyroid cancer. J Clin Endocrinol Metab, 94:1310–1316.
15.
ZollerM, KohlfuerstS, IgercI, KresnikE, GallowitschHJ, GomezI, LindP. 2007. Combined PET/CT in the follow-up of differentiated thyroid carcinoma: what is the impact of each modality?Eur J Nucl Med Mol Imaging, 34:487–495.
16.
MenzelC, ZaplatnikovK, DiehlM, DobertN, HamschoN, GrunwaldF. 2004. The influence of thyroglobulin on functional imaging in differentiated thyroid cancer. Nucl Med Commun, 25:239–243.
17.
BertagnaF, BiasiottoG, OrlandoE, BosioG, GiubbiniR. 2010. Role of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography in patients affected by differentiated thyroid carcinoma, high thyroglobulin level, and negative 131I scan: review of the literature. Jpn J Radiol, 28:629–636.
18.
SchluterB, BohuslavizkiKH, BeyerW, PlotkinM, BuchertR, ClausenM. 2001. Impact of FDG PET on patients with differentiated thyroid cancer who present with elevated thyroglobulin and negative 131I scan. J Nucl Med, 42:71–76.
19.
FletcherJW, DjulbegovicB, SoaresHP, SiegelBA, LoweVJ, LymanGH, ColemanRE, WahlR, PascholdJC, AvrilN, EinhornLH, SuhWW, SamsonD, DelbekeD, GormanM, ShieldsAF. 2008. Recommendations on the use of 18F-FDG PET in oncology. J Nucl Med, 49:480–508.
20.
SobinLH, WittekindC. International Union Against Cancer (UICC). 1997. TNM Classification of Malignant Tumors. 5th. John Wiley & Sons, Inc.: New York.
21.
LinksTP, HuysmansDA, SmitJW, de HeideLJ, HammingJF, KievitJ, van LeeuwenM, van PelR, de KlerkJM, van der WelY. 2007. Guideline ‘Differentiated thyroid carcinoma’, including diagnosis of thyroid nodules. Ned Tijdschr Geneeskd, 151:1777–1782.
22.
van TolKM, JagerPL, de VriesEG, PiersDA, BoezenHM, SluiterWJ, DullaartRP, LinksTP. 2003. Outcome in patients with differentiated thyroid cancer with negative diagnostic whole-body scanning and detectable stimulated thyroglobulin. Eur J Endocrinol, 148:589–596.
23.
Working Group Thyroid Carcinoma. 2007. ‘Differentiated Thyroid Carcinoma’, version 1.0. http://oncoline.nl/schildkliercarcinoom. 2012 December 20.
24.
ChungJK, SoY, LeeJS, ChoiCW, LimSM, LeeDS, HongSW, YounYK, LeeMC, ChoBY. 1999. Value of FDG PET in papillary thyroid carcinoma with negative 131I whole-body scan. J Nucl Med, 40:986–992.
25.
CooperDS, DohertyGM, HaugenBR, KloosRT, LeeSL, MandelSJ, MazzaferriEL, McIverB, PaciniF, SchlumbergerM, ShermanSI, StewardDL, TuttleRM. American Thyroid Association (ATA) Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid Cancer 2009 Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid, 19:1167–1214.
26.
SchlumbergerM, HitzelA, ToubertME, CoroneC, TroalenF, SchlageterMH, ClaustratF, KoscielnyS, TaiebD, ToubeauM, BonichonF, Borson-ChazotF, LeenhardtL, SchvartzC, DejaxC, Brenot-RossiI, TorlontanoM, TenenbaumF, BardetS, BussiereF, GirardJJ, MorelO, SchneegansO, SchliengerJL, ProstA, SoD, ArchambeaudF, RicardM, BenhamouE. 2007. Comparison of seven serum thyroglobulin assays in the follow-up of papillary and follicular thyroid cancer patients. J Clin Endocrinol Metab, 92:2487–2495.
27.
BaudinE, Do CaoC, CailleuxAF, LeboulleuxS, TravagliJP, SchlumbergerM. 2003. Positive predictive value of serum thyroglobulin levels, measured during the first year of follow-up after thyroid hormone withdrawal, in thyroid cancer patients. J Clin Endocrinol Metab, 88:1107–1111.
28.
EliseiR, SchlumbergerM, DriedgerA, ReinersC, KloosRT, ShermanSI, HaugenB, CoroneC, MolinaroE, GrassoL, LeboulleuxS, RachinskyI, LusterM, LassmannM, BusaidyNL, WahlRL, PaciniF, ChoSY, MagnerJ, PincheraA, LadensonPW. 2009. Follow-up of low-risk differentiated thyroid cancer patients who underwent radioiodine ablation of postsurgical thyroid remnants after either recombinant human thyrotropin or thyroid hormone withdrawal. J Clin Endocrinol Metab, 94:4171–4179.
29.
GrunwaldF, MenzelC, BenderH, PalmedoH, WillkommP, RuhlmannJ, FrancksonT, BiersackHJ. 1997. Comparison of 18FDG-PET with 131iodine and 99mTc-sestamibi scintigraphy in differentiated thyroid cancer. Thyroid, 7:327–335.
30.
NanniC, RubelloD, FantiS, FarsadM, AmbrosiniV, RampinL, BantiE, CarpiA, MuzzioP, FranchiR. 2006. Role of 18F-FDG-PET and PET/CT imaging in thyroid cancer. Biomed Pharmacother, 60:409–413.
31.
PalmedoH, BuceriusJ, JoeA, StrunkH, HortlingN, MeykaS, RoedelR, WolffM, WardelmannE, BiersackHJ, JaegerU. 2006. Integrated PET/CT in differentiated thyroid cancer: diagnostic accuracy and impact on patient management. J Nucl Med, 47:616–624.
