Imaging in the Follow-Up of Differentiated Thyroid Cancer: Current Evidence and Future Perspectives for a Risk-Adapted Approach

175:5

L Lamartina and others Imaging in the follow-up 175:5 R185–R202 Review of DTCs

ENDOCRINE TUMOURS Imaging in the follow-up of differentiated thyroid cancer: current evidence and future perspectives for a risk-adapted approach

1 2 1 1 Livia Lamartina , Désirée Deandreis , Cosimo Durante and Sebastiano Filetti Correspondence should be addressed 1Department of Internal Medicine and Medical Specialties, University of Rome Sapienza, Rome, Italy, to S Filetti 2Department of Nuclear Medicine and Endocrine Oncology, Gustave Roussy and University Paris Saclay, Email Villejuif, France [email protected]

Abstract

The clinical and epidemiological profiles of differentiated thyroid cancers (DTCs) have changed in the last three decades. Today’s DTCs are more likely to be small, localized, asymptomatic papillary forms. Current practice is, though, moving toward more conservative approaches (e.g. lobectomy instead of total thyroidectomy, selective use of radioiodine). This evolution has been paralleled and partly driven by rapid technological advances in the field of diagnostic imaging. The challenge of contemporary DTCs follow-up is to tailor a risk-of-recurrence-based management, taking into account the dynamic nature of these risks, which evolve over time, spontaneously and in response to treatments. This review provides a closer look at the evolving evidence-based views on the use and utility of imaging technology in the post-treatment staging and the short- and long-term surveillance of patients with DTCs. The studies considered range from cervical US with Doppler flow analysis to an expanding palette of increasingly sophisticated second-line studies (cross-sectional, functional, combined-modality approaches), which can be used to detect disease that has spread beyond the neck and, in some cases, shed light on its probable outcome. European Journal European of Endocrinology

European Journal of Endocrinology (2016) 175, R185–R202

Introduction

The clinical and epidemiological profiles of differentiated DTCs are more likely to be small, localized, asymptomatic thyroid cancers (DTCs) have evolved remarkably over the papillary forms, many with subcentimeter diameters (3). past 30 years. In the 1980s and 1990s, patients usually These changes have been paralleled and in large part presented with palpable primaries, often accompanied driven by advances in diagnostic imaging technology. by locoregional or even distant metastases (1, 2). Today’s Since the late 1980s, clinicians’ toolboxes for examining

Invited Author’s profile Sebastiano Filetti, MD, is a full professor of Internal Medicine and Dean of the Faculty of Medicine and Dentistry at Sapienza – University of Rome, Rome, Italy. Prof. Filetti’s current clinical interests include endocrine and thyroid cancer, diabetes, and endocrine/metabolic diseases. In particular, his clinical and research interests are focused on the management of thyroid nodule and advanced thyroid cancer. Thyroid tumorigenesis and the implications of the genetic and epigenetic abnormalities in thyroid cancer are also Prof. Filetti’s research interests.

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the interior of the human body have expanded rapidly increased use of diagnostic imaging does not inevitably to include gray-scale ultrasonography (US), Doppler flow translate into increased overall survival. Greater analysis, computed tomography (CT), magnetic resonance consideration is being given to the potential risks of imaging (MRI), and positron emission tomography (PET). imaging-related radiation exposure (11) and the impact Widespread clinical use of these new techniques for of excessive surveillance on patients’ quality of life (13). assessing structures in the head and neck (e.g. carotid Signs of change are already in the air. Although the arteries) has been responsible for the incidental discovery major goal of post-treatment surveillance of patients with of many of the tiny, silent thyroid cancers being diagnosed DTC is still the timely detection and effective management and treated today (4, 5, 6). of persistent or recurrent cancer, increasing emphasis is The evolving profile of DTCs has been mirrored by being placed on the need to reliably identify patients who changes in our approaches to their treatment and fol- are disease-free and therefore eligible for less-intensive low-up. The standard of care before the 2000s involved surveillance. Recommendations by national and interna- total thyroidectomy (often with neck dissection), liberal tional bodies are increasingly based on assessments of the use of radioiodine remnant ablation (RRA), and life-long individual patient’s risk of recurrence (rather than death) surveillance based chiefly on whole-body radioiodine (Table 1). Emphasis is also being placed on the dynamic scintigraphy (WBS) and serum thyroglobulin (Tg) assays. nature of these risks, which evolve over time, spontane- Support is now growing for more conservative strategies ously and in response to treatment (14). in selected cases: lobectomy, omission of RRA, even active This review will provide a closer look at the evolving surveillance alone, which is now an option for some pap- evidence-based views on the use and utility of imaging illary microcarcinomas (7, 8, 9). These changes, too, have technologies in the post-treatment staging and the been facilitated by the availability of new imaging tools short- and long-term surveillance of patients with DTCs. and techniques. The frequent use in the past of aggressive The modalities considered range from whole-body treatments (e.g. total thyroidectomy followed by RRA) radioiodine scintigraphy and cervical US with Doppler was dictated in part by the need to eradicate not only the flow analysis – the ‘work horses’ in both settings – to an neoplastic thyroid tissue but normal thyroid remnants as expanding palette of increasingly sophisticated cross- well, since their uptake of iodine and production of thyro- sectional, functional, combined-modality imaging globulin diminished the diagnostic performance of WBS approaches, which can be used to detect disease that has and Tg assays during postoperative surveillance. These spread beyond the neck and, in some cases, shed light on constraints were attenuated by increasing reliance on US its probable outcome. European Journal European of Endocrinology surveillance, freeing clinicians to consider more individu- alized treatments for DTCs. Cervical ultrasonography Despite the relatively indolent nature of most thyroid cancers and the increasing prevalence of low-risk tumors, Cervical US includes gray-scale studies performed with the early 2000s witnessed striking increases in the use of high-resolution linear transducers (frequencies of 10 to imaging technology for assessing DTCs. A recent analysis 15–17 MHz) (15) and assessment of lesion vascularity of over 23 000 cases of DTC diagnosed in the U.S. con- with color or power Doppler. First used in the late firmed that, although the tumors identified between 2001 1980s to distinguish cystic from solid thyroid nodules and 2009 were more likely to be small (<1 cm) and localized than in previous years, patients were more rather than less likely to undergo I-131 scintigraphy and cervi- Table 1 American Thyroid Association criteria for assessing cal US (odds ratios, 1.44 (95% confidence interval (CI), risk of recurrence in patients with DTC.

1.35–1.54) and 2.15 (95% CI: 2.02–2.28) respectively) Risk Features (10). PET studies increased more than 30-fold between Low Intrathyroid tumor 1996–2004 and 2005–2009, even in patients with local- ≤5 lymph node micrometastases (<0.2 cm) ized disease (11). Intermediate Aggressive histology, minor extrathyroid extension, vascular invasion Efforts are needed to curb this ‘diagnostic hyperactivity’ >5 involved lymph nodes (0.2–3 cm) and bring post-treatment management strategies more High Gross extrathyroid extension, incomplete in line with the current challenges of thyroid cancer (9, tumor resection 12). Aside from the increasing demands for cost-efficient Lymph node metastases >3 cm Distant metastases healthcare policies, there is a growing awareness that the

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Downloaded from Bioscientifica.com at 10/07/2021 10:13:36AM via free access European Journal of Endocrinology confirmed bycytological analysisofUS-guidedFNA benign andmalignantlesions increaseswhentheyare relatively commonintheabsence ofmalignancy. from ‘indeterminate’findings, whichareatypicalbutalso widely,vary and‘suspicious’ lesionsarethusdistinguished shown in purpose bytheEuropeanThyroidAssociation(ETA) are cancer intheneck.Thoseconsideredmostusefulforthis as markersofpersistentandrecurrentfocithyroid Numerous USfindingshave beenanalyzedovertheyears findings Normal, suspicious,andindeterminate greater lengthbelow. is itsrelativelylowspecificity, whichwillbediscussedat nation results( conducting, interpreting,anddocumentingtheexami USandtostandardizemethodsfor expertise incervical made todefineminimumcriteriaforoperatorsclaiming specialists caringforthesepatients).Effortshavethusbeen nicians, radiologists,endocrinologists,andotherclinical examining thyroid cancer patients (e.g. radiology tech lem aggravatedbythediverseprofilesofoperators availability, andnoknownadverseeffects( number ofpracticaladvantages,includinglowcost,wide findings inWBSandserumTgassays( of anti-Tgantibodies,whichcancausefalse-negative by theradioiodine-avidityoflesionsorpresence patients. Inaddition,itsdiagnosticyieldisunaffected amount of persistent/recurrentdisease is found in DTC lymphnodes,wherethevast the thyroidbedorcervical resolution UScanpinpointlesionsassmall2–3 areas)( orparapharyngeal (e.g. retro- structures also unsuitableforexploringdeepcervical recurrence, including the upper mediastinum. It is and itprovidesnoinformationonextracervical of choiceforover40 (ATA) ( for thispurposebytheAmericanThyroidAssociation ( approach fordetectinglocoregionalDTCinvolvement serum thyroglobulinassayswasthemostsensitive sonographic examinationoftheneckcombinedwith early 2000s, a growing body of evidence indicated that ( 16 15 Review , ), ultrasound’s popularityincreasedsteadily. Bythe The lowspecificityofUS findings fordistinguishing Its mainshortcomingisoperatordependency, aprob US is inferior to WBSin terms of specificity,Cervical 17 20 , 18 ), replacingWBS,whichhadbeentheprocedure Figs 1 , 19 ). In2006,itwasofficiallyrecommended 12 and ). Asecondimportant limitation ofUS 2 years. . Theirsensitivitiesandspecificities L Lamartinaandothers 12 19 ). However, high- ), anditoffersa 21 ). mm in - - -

and/or assayoftheneedlewashoutfluidforTg( lateral compartmentinvolvement( level VIlymphnodemetastases,andupto40%have microcarcinomaspatients withpapillary (<1 prophylactic neckdissectionsindicatethatupto90%of ( hypoparathyroidism, andtrachealoresophagealdamage resection, permanent complications,includingnerve disease. Italsocarriesanincreasedriskofserious,often pathologically confirmedmetastasesfailstoeradicatethe More importantly, in at least 30% of cases, reoperation for stress, morbidity, andcostsassociatedwithbiopsy( recommendations reflect a growing awareness of the management willchangeifpositiveresultsemerge.These on lesionsizeand/orgrowthandthelikelihoodthat by morecautioususeofbiopsy( transcripts ( based assayofthyroid-specificgene(Tg,TSHreceptor) 24 is associatedwithparticularly highinteroperator Margin irregularity( characteristics, shapes, and calcification statuses. indeed bedistinguishedon thebasisoftheirmargin concluded thatbenignand malignantlesionscould abnormalities againstpathologyfindings.Lee small studiesthatassessedthediagnosticvalueofUS the bed( and jugularchainLNsthathaveslidmediallytooccupy benign reactivelymphnodes,parathyroidadenomas( represent autoimmunethyroiditis,suturegranulomas, undeniably difficult( malignant lesionsinthisareaonthebasisofUSalone is ( surgery area should be postponed until at least 3 months after presence ofscartissue).Postoperativeexplorationthis encounters withthesurgeon’s scalpel,owingtothe damaged byresidualtumorgrowth(butalsorepeat the proximityofvitalstructuresthatcanbecompressed/ Thyroid bedlesions are aparticularconcern owing to Thyroid bed patient’s ownpreferences. only aftercarefulconsiderationofcosts,benefits,andthe is clinicallyinsignificant.FNAshouldthusbeundertaken diseasedetectedduringfollow-up portion ofthecervical reported forthesepatients,suggestingthatasubstantial figures farexceedtheclinicallocoregionalrecurrencerates of DTCs Imaging inthefollow-up 27 ); the washout fluid can also be subjected to PCR- , Discordant findingshaveemergedfromthefew 28 ). Finally, analysisofsurgical pathology data on 33 12 ). , 25 32 ). Currenttrends,however, arecharacterized ). Even then, distinguishing benign and Fig. 2 Fig. 1 Downloaded fromBioscientifica.com at10/07/202110:13:36AM ). Hypoechogenicityalonemay E) –afeaturewhosedetection 9 ). Decisionsarebased 175 29 www.eje-online.org , :5 30 , 31 cm) have t al. et ). These 22 R187 ( , 12 26 34 23 via freeaccess ), ). ) , Review L Lamartina and others Imaging in the follow-up 175:5 R188 of DTCs

E F European Journal European of Endocrinology

Figure 1 Classification of post-treatment sonographic findings in the thyroid bed. Panels A and B.Normal findings: (A) The thyroid bed after total thyroidectomy: the hyperechoic bilateral paratracheal areas are consistent with the postoperative proliferation of fibrofatty connective tissue (arrows); (B) normal left tracheal thyroid gland remnant (arrows): ovoid area, hyperechoic vs anterior muscle tissue. Panels C and D. Indeterminate findings: left tracheal thyroid bed nodule (arrows): small, ovoid, hypoecoic nodule, without signs of vascularization, and other US suspicious features. Panels E, F and G. Suspicious findings: (E) A hypoechoic nodule in the left tracheal thyroid bed (arrows) appears taller-than-wide with irregular margins; (F) suspicious left tracheal thyroid bed nodule (arrows) with hypoechoic areas and punctate hyperechogenicity representing microcalcifications; (G) left tracheal thyroid bed nodule (arrow): longitudinal scan of a cystic area, with posterior acoustic enhancement. E, esophagus; LC, left carotid artery; RC, right carotid artery; T, trachea; US, ultrasound.

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Downloaded from Bioscientifica.com at 10/07/2021 10:13:36AM via free access European Journal of Endocrinology RC, rightcarotidartery;RJ, jugularvein;US,ultrasound. round rightcervicallymphnode (arrows)displayingperipheralvascularization.LC,leftcarotid artery;LJ,leftjugularvein; posterior shadowing;(E)suspicious leftcervicallymphnode(arrows)withcysticareas posterior acousticenhancement;(F) and F. C. lymph node(arrows)hasahyperechoichilum,anelongated shape, shortaxis≤5 Classification ofpost-treatmentsonographicfindingscervical lymphnodes.PanelsAandB. Figure 2 Review Indeterminate findings Suspicious findings : (D)Rightcervicallymphnode (arrows):thyroid-tissue-likeappearanceandmicrocalcifications with : Rightcervicallymphnode(arrows) withlossofhilum,roundshape,andshortaxis L Lamartinaandothers I D C AB F of DTCs Imaging inthefollow-up mm, andexclusivelyhilarvascularization.Panel E Downloaded fromBioscientifica.com at10/07/202110:13:36AM Normal findings 175 ≥ www.eje-online.org : Thisrightcervical 5 :5 mm. PanelsD,E

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Downloaded from Bioscientifica.com at 10/07/2021 10:13:36AM via free access European Journal of Endocrinology single-photon emissioncomputed tomography;Tg,thyroglobulin;US,ultrasound. emission tomography;CT, computed tomography;DxWBS,diagnosticwhole-bodyscan;MRI, magneticresonanceimaging;SPECT, (prognostic role)and/orthose with radioiodine-refractorydisease(predictiverole). avid lesions.(c) precise anatomicallocalization ofradioiodineuptake,(ii)exclusionnonspecific and (iii)identificationofnoniodine- Nodules andDifferentiated ThyroidCancer(Haugen2015).(b)InpatientswithuptakeonDxWBS,SPECT–CTallows (i)more of persistent/recurrentdiseaseasreportedinthe2015American ThyroidAssociationGuidelinesfortheManagementof Risk-stratified useofdiagnosticimagingmodalitiesintheinitial post-therapeuticstagingofdifferentiated thyroid cancer. (a)Risk Figure 3 calcifications) (100%),andperipheralvascularization tuate hyperechogenicity(representingcolloidormicro most specificfindingsarecysticchanges(100%),punc (100%), butitsspecificitywasdismallylow(29%).The is themostsensitivepredictoroflymphnodemalignancy gical histology findings indicatethat anonvisualized hilus normal insize( inflammation. Furthermore,manymetastaticnodesare of reactivephenomenarelatedtochronicoralcavity in thesubmandibularregion(levelII),possiblybecause with the location, with larger nodes found ranges vary information on the likelihood of malignancy. Normal axis ratiosof<0.5( Normal nodesaretypicallyoval,withshorttolong III, IV, andVInodesthaninthoseoflevelII( Metastatic involvementismorecommonlyfoundinlevel Cervical lymphnodes graphic examinationsoftheneck( andserialsono safely managedwithcautiousobservation year), suggestingthatsmallthyroidbednodulescanbe that doesoccuristypicallyquite slow (roughly1 thy ordetectable/increasingTgproduction.Thegrowth 2 larly whentheyexhibitnosuspiciousfeatures( (<11 or moredisplayactivegrowth( cally suspiciousthyroidbedlesionsthat measure 10mm not bereliablydifferentiatedwithoutbiopsy( calcification, orvascularityandconcludedthattheycould lesions intermsofsize,shape,echogenicity, margins, no significantdifferencesbetweenthesetwoclassesof those classifiedas‘non-recurrences’.Infact,theyfound confirmed recurrencesreportedbyShin This feature, however, was found in only 10% of the and specific(100%)predictorofthyroidbedrecurrence. variability ( ) and are not accompanied by cervical lymphadenopa ) andarenotaccompaniedbycervical Review Studies correlatingpreoperativesonographicandsur The ETA currentlyrecommendsFNAforsonographi mm), growthisactuallyrare(<10%ofcases),particu 35 18 ) –emergedasthemostsensitive(79%) 40 FDG/PET helpsidentifypatients athighestriskforrapiddiseaseprogressionanddisease-specific mortality ). i. 2 Fig. A) ( 15 L Lamartinaandothers ). Sizeprovideslimited 12 37 ). Forsmallernodules ). et al. 36 and6%of Figs 1 ). 38 , mm/ and 39 ). ------Post-treatment stagingandsurveillance over time,withnotreatmentatall( pression ofvitalstructures,and14%disappearedentirely 3 abnormal nodeslesionsgrew patientsfollowedwithserialUS,only20%ofthe 166 ral courseofUS-detectedlymphnodeabnormalitiesin increase insize.Inaretrospectivestudyonthenatu and especially indeterminate findings do not generally and/or displayactivegrowth( lymph nodes that exceed 8–10 nodes lackingahilus( thorough Doppler-basedassessmentofvascularityinall pinpointing worrisomelymphnodesmightbeginwitha ( (82%), whichalsodisplayrelativelyhighsensitivity(86%) nate findings( basal Tg and TgAb assays, and negative or only indetermi treated withtotalthyroidectomyandRRA,negative Yang and excellentinintermediate-riskpatientsaswell.Peiling low-riskpatientswithmicroPTCs( ally 100%invery outcomes ( scan arestronglyassociatedwithexcellentlong-term second-line studies)( an indicationforadditionalimagingwork-up(USand/or production over time ( available, andcanbeanalyzedtoidentifyincreasesinTg recurrent diseaseonlylater, whenserialmeasurementsare provide reliableinformationonthepresenceofpersistent/ single serumTgassayisoflimiteduse.Inthesecases,assays normal thyroidtissue(evensmallremnants),theresultofa thyroidectomy withoutRRA( patients treated with lobectomy or with total/near total ofthegrowingsubpopulationDTC early surveillance Ultrasound playsanespeciallyimportantroleinthe of DTCs Imaging inthefollow-up 38 years after surgery; moreover,years aftersurgery; nonecausedpainorcom ). Inlightofthesefindings,aproductive The ATA FNAforsonographicallysuspicious reserves Normal findingsintheinitialpost-treatmentneck et al. reviewed 90 cases of ATA intermediate-risk PTC 14 ). Thenegativepredictivepowerisvirtu Figs 1 18 FDG/PET, and Fig. 3 15 44 Downloaded fromBioscientifica.com at10/07/202110:13:36AM 18 2 ). , ) ( ) onthefirstpost-treatmentUS. F-fluorodeoxyglucose positron 45 9 , 12 , 46 12 , 9 42 , ). Nodeswithsuspicious ≥ ). mm (smallest diameter) 47 3 , mm duringthefirst 43 41 ). Substantial rises are ). Substantial rises are 175 ). In the presence of ). Inthepresenceof ). www.eje-online.org :5 strategy for R191 48 via freeaccess ) - - - - Review L Lamartina and others Imaging in the follow-up 175:5 R192 of DTCs

The rate of structural disease recurrence during follow-up of whom are classified as intermediate-risk according to (median 10 years) was 8% (4/49) in the subgroup whose ATA criteria) and only when warranted by pTNM staging, initial US findings were negative (as opposed to 12% serum Tg levels, and responses to therapy (12). For low- (5/41) in the group with indeterminate scan results) (49). and very low-risk patients with normal findings at 6 In many facilities, neck sonography is still done rou- months, ‘regular’ scans are considered unnecessary. tinely, once or even twice a year, even when the risk of When doubts on the presence of distant metastases recurrence is low (12, 50). A recent retrospective analy- arise, additional imaging is required (Fig. 3). The follow- sis of over 1000 cases of PTC treated between 2000 and ing section provides a concise profile of the methods most 2010 at Memorial Sloan Kettering Cancer Center found commonly used. that during the first 3 years of surveillance, the number of US examinations per patient ranged from 1.3 in Cross-sectional imaging low-risk patients to 1.9 and 1.8 in intermediate- and high-risk groups – already appreciably lower than rates The cross-sectional imaging studies include CT and MRI reported in other retrospective studies (51). Nonethe- scans. Both allow high-precision anatomic localization less, the number of scans needed to detect 1 recurrence and measurement of disease foci and are especially event in the low-risk cohort (154.0) was 6–7 times higher useful for assessing the tumor burden in patients with than those of the intermediate and high-risk groups (23.9 extensive local disease or distant metastases. To identify and 13.0 respectively), indicating that there is substantial the nature of the mass, however, the results have to be room for improving the cost-effectiveness of US surveil- interpreted within the clinical context of the individual lance of low-risk patients (50). patient. When doubts arise or discordant findings emerge Similar conclusions were reached in the study cited (e.g. a lesion compatible with metastatic lung disease above by Peiling Yang et al. (49). The 90 intermediate-risk in a low-risk patient with undetectable serum Tg and patients they retrospectively reviewed were followed with negative Tg antibody assays), cytological or histological routine cervical US and Tg assays at 6–12 month intervals, confirmation is needed. When foci of metastatic disease and structural recurrence emerged in only 9 (10%). All are found, options include local or systemic therapy the lesions were sonographically detected. However, in and simple surveillance alone. Lesions that represent no 5/9 cases, the disease was also heralded by other findings immediate threat to the patient should be treated only if (rising Tg levels in most cases) and would thus have been the tumor burden is substantial or when there is obvious identified even if US had not been used so frequently. progression. The latter can be documented using the European Journal European of Endocrinology These authors also underscored the high probability of Response Evaluation Criteria in Solid Tumors, RECIST false-positive findings associated with frequent US exam- 1.1 system) (52). inations in populations of this sort. In 51 (57%) of the Evidence supporting the utility of cross-sectional cohort patients, the routine scans yielded new or persis- imaging modalities comes largely from experience with tently atypical findings, which led to a host of additional other solid tumors; data on their specific use in thyroid diagnostic procedures (first- and second-line imaging cancer are lacking. According to the ATA, cross-sectional procedures, FNA), none of which disclosed any clinically imaging of the neck and chest should be considered in significant structural disease. On the basis of these find- the following cases: (i) patients with extensive recurrent ings, these authors suggest that in intermediate-risk DTC nodal disease; (ii) patients with negative findings on cer- patients whose initial post-treatment assessment reveals vical US and WBS and a high serum Tg level (generally no structural or biochemical evidence of disease, sono- exceeding 10 ng/mL), or rising Tg or Tg antibodies values; graphic surveillance can be discontinued if the second and (iii) in cases where reliable assessment of potential assessment is also negative (49). aerodigestive tract invasion is needed (9). Rarer sites of These conclusions are supported by recent findings thyroid cancer metastases should be explored when a confirming the strong associated between normal find- clinical suspicion arises or in high-risk patients with high ings at the initial assessment and excellent long-term out- serum thyroglobulin levels (10 ng/mL) and no evidence of comes (14). They are also consistent with the ETA’s current lung/mediastinal metastases (Fig. 3). guidelines regarding the first 5 years of follow-up, when The optimal timing for cross-sectional imaging stud- over three-quarters of recurrences are identified 3( ). Dur- ies in patients with DTC is not well defined: recom- ing this period, yearly US scans are recommended only mendations range from 3 to 12 months after treatment, for patients meeting the ETA’s high-risk criteria (some depending on the tumor burden, location of the disease,

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Downloaded from Bioscientifica.com at 10/07/2021 10:13:36AM via free access European Journal of Endocrinology metastases incancer patients, anditsperformance is only ity of80%,and96%accuracy inthedetectionofbone body MRIhasdisplayed100% sensitivity, 80%specific spinal canal)withadetection limitof2 exploring themarrowand paraosseousstructures(e.g. hips ( with highbloodflow:thevertebrae,ribs,and (and metastasesfromothercancersaswell)arethose The bones most frequently targeted by these lesions ing thyroidcancermetastasestothebone,brain,orliver. artifacts. possibility offalse-negativefindingsrelatedtomovement are relatedtothedurationofexaminationand is poorlyvisualized on ultrasound. Its main shortcomings out nodalinvolvementinthemediastinum( in DTC patients ( (95%) forthedetectionofmetastaticlymphadenopathy is relatively low (51%), MRI offers excellent sensitivity invasion is suspected ( is particularly useful when esophageal and/or tracheal exposure. Itoffersexcellentsoft-tissue contrast, which Unlike CT, MRI isassociatedwithabsolutelynoradiation Magnetic resonance imaging lance ofDTCpatients. use andfrequencyofCTinthepost-treatmentsurveil patient’s diseasewhendecisionsarebeingmadeonthe risk shouldbeweighedagainsttheaggressivenessof has beenlinkedtoanincreasedriskofcancer( tracheal space,itisusedasacomplementtoneckUS( areas ofvascularinvasion;forassessmenttheretro- toidentifypossible are alsorecommendedbeforesurgery exploration ofthemediastinum.Contrast-enhancedscans ( can beexploredwithhigh-resolutionCTwithoutcontrast terms ofavailability, cost,andexaminationtimes.Thelungs other second-linestudies,it offers distinct advantages in allow preciselocalizationofdiseasefoci,andcomparedwith The anatomic resolution of a CT scan is sufficiently high to Computed tomography treatment introduction( line assessment performed no more than 4 disease evaluatedoveraperiodof≤12 cer clinicaltrialshaveenrolledpatientswithprogressive histology, andTgtrend( 9 ), but contrast-enhancement with iodine is best for ), butcontrast-enhancementwithiodineisbestfor Review MRI istheimagingmodalityofchoiceforidentify The radiation exposure associated with CT imaging 58 ). Its high soft-tissue contrast is very useful for ). Its high soft-tissue contrast is very 56 ). It is particularly useful for ruling 54 52 9 , ). Anyway, manythyroidcan ). 55 ). Although its specificity L Lamartinaandothers months andbase mm ( weeks before 59 57 ). Whole- 53 ), which ). This 9 ). - - - - - are missedonCT( lesions, roughly 20% of the lesions identified with MRI used withCT( produce significantlystrongerenhancementthanthose partial volumeeffects.Paramagneticcontrastagentsalso higher soft-tissuecontrast,noboneartifacts,andfewer for thedetectionofbrainmetastasesbecauseitprovides 23 patients( of accuracy of thisapproach has proved to besimilarthat accuracy of MRI for bone metastasis detection, and the signal suppression(DWIBS)significantlyincreasesthe 91% respectively( lesion (sensitivity, slightly inferior in patients harboring more than one lesions, however, arerelativelyuncommon inDTC useful for earlydetection of distant metastases. These thyroid remnantablationassessment ( most sensitivetoolforthyroid remnantdetectionand the diseaseinpatientswithotherdistantmetastases in theliver. Theyusuallydeveloplateinthecourseof exceeds itssensitivity(27–55%) ( approximately 84–90%, its specificity (91–100%) far Although theaccuracyofadiagnosticWBS is Diagnostic whole-bodyradioiodinescintigraphy emission computedtomography, SPECT). images (classicradioiodinescintigraphyvssingle-photon can beusedtoobtainplanarorthree-dimensional expression ofiodide-metabolizinggenes( as cells canalsobeinfluencedbysomaticmutations,such NIS might displaydecreased( inthyroidcancercellsalthoughthey generally preserved by thesodiumiodinesymporter(NIS).Thiscapacityis to takeupiodinefromthecirculation, whichismediated Radioiodine imagingexploitsthecapacityofthyroidcells Radioiodine imaging Functional imaging metastases frommostendocrinetumors( but MRIisconsideredpreferabletoCTforexploringliver identification oflivermetastases.DataarelackinginDTC, ( of DTCs Imaging inthefollow-up 62 18 BRAF ). Evidence-basedguidelinesrecommendCTorMRI expression. Iodine metabolism in thyroid cancer Approximately, 0.5% of DTC metastases are located In patientswithsolidtumors,MRIissuperiortoCT F- fluorodeoxyglucose PET(94%)inasmallcohortof V600E,whichisassociatedwithdownregulated 60 ). 61 59 61 ). Inthepresenceofmultiplebrain specificity, andaccuracy:94,76, ). Theadditionofbackgroundbody ). Downloaded fromBioscientifica.com at10/07/202110:13:36AM 65 , 66 ) orevenabsent( 70 , 175 71 www.eje-online.org , 74 :5 69 72 63 , ). Radioiodine , 75 , 73 64 ). Itisalso ). Itisthe ). 67 R193 , 68 via freeaccess ) Review L Lamartina and others Imaging in the follow-up 175:5 R194 of DTCs

patients: they are found in only ~3% of DTC patients at involves administration of a radioactive tracer (albeit at diagnosis and in 10% or less during follow-up (3, 76, 77). low doses). The radiation risk also involves persons who are The ATA thus recommends routine diagnostic WBS during in contact with the patients, so radioprotection measures follow-up only when the risk of persistent/recurrent must be adopted for the 10–15 days following the scan. disease and extracervical metastases is intermediate or Disease is anatomically located based on the RAI uptake high (Fig. 3) (9). Even in these cases, there is no need to observed on the planar whole-body image and, if neces- repeat the DxWBS if the RxWBS yields negative findings, sary, images of specific body regions, such as the neck. The especially if Tg production is undetectable and the Tg precision of this approach is nonetheless limited. Because antibody assay is negative (17, 78, 79, 80, 81). In contrast, RAI can be concentrated by both normal and neoplastic DxWBS can be useful for monitoring (and for planning thyroid tissue, RAI scintigraphy cannot be used to iden- additional imaging work-up) of distant and/or local foci tify foci of persistent/recurrent disease in the thyroid bed. of radioiodine uptake revealed on post-therapeutic WBSs, False-positive results can also be caused by the physiologic and it is also an option for assessing the presence of distant or pathologic accumulation of radioiodine in nonthyroi- metastases when positive Tg antibody levels render serum dal tissues and body fluids Table 2( ) (90). The sensitivity Tg levels unreliable markers of disease (9). of WBS can be reduced in the presence of large amounts DxWBS can also be helpful in calculating therapeu- of normal thyroid tissue: these remnants can sequester tic doses of radioiodine (82). It is important to recall, almost all of the administered 131I activity, thereby reduc- however, that a diagnostic dose of 131I (the isotope most ing visualization of smaller metastatic lesions (9). When widely used for diagnostic scans in DTC patients) can a large remnant is visualized on post-therapeutic WBS, a reportedly reduce the uptake of radioiodine subsequently diagnostic WBS can be evaluated to reassess the presence administered for therapeutic purposes, particularly when of local or distant metastases (9). WBS is also of no value the two administrations are separated by more than in the patients whose tumors have lost the ability to con- 3 days and fewer than 7 days – a phenomenon known as centrate RAI (91), a phenomenon encountered in up to the ‘stunning effect’ (83). However, in a recent study of two-thirds of patients with distant metastases (the subpop- two consecutive cohorts of DTC patients undergoing RRA, ulation most likely to benefit from WBS) 92( ). ablation rates and detection rates of disease recurrence were similar in the patients whose ablations were or were not preceded by a diagnostic scan (84). Stunning is not Single-photon emission computed tomography/ caused by diagnostic scans performed with 123I (85, 86, computed tomography European Journal European of Endocrinology 87). This pure gamma emitter is ideal for use with mod- In single-photon emission computed tomography (SPECT), ern gamma cameras and provides higher image resolution the two-dimensional tomographic images acquired with 131 than I. Its use is limited, however, by its high cost and the SPECT gamma camera are elaborated to provide a three- low availability (due to its short half-life). dimensional representation of the region being examined. WBS has a number of practical drawbacks. The detec- SPECT–CT involves the co-registration and fusion of SPECT tion limit depends on several factors, including the activity images and those acquired with a conventional CT scan. administered, the timing of image acquisition following This dual-modality approach improves the localization RAI administration, the type of equipment used (crystal Table 2 False-positive radioiodine uptake. thickness), and the patient’s renal function status (88). A successful scan also requires a lengthy period of patient Physiologic uptake preparation (3–4 weeks) to maximize tracer uptake. This Choroid plexus involves a low iodine diet and elevation of TSH levels by Lachrymal sac and tears Nasopharynx and nasal secretions withdrawal of thyroid hormone replacement therapy. The Salivary glands and saliva, oral cavity, esophagus latter is often associated with unpleasant symptoms of Breast and breast milk hypothyroidism. Administration of recombinant human Liver, gallbladder, and biliary tract TSH (rhTSH) is an effective alternative that is more expen- Kidneys, urinary tract, and urine Stomach sive but decidedly better tolerated. In addition, patients Large bowel and feces who have recently undergone computed tomography Pathologic uptake scanning with iodinated contrast medium must wait Inflammation 4–8 weeks before they have a radioiodine WBS (89). Radia- Benign tumors Malignant tumors tion exposure is also a consideration. The examination

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Downloaded from Bioscientifica.com at 10/07/2021 10:13:36AM via free access European Journal of Endocrinology PET/CT was appreciably higher than PET alone (93–94% PET/CT wasappreciablyhigher thanPETalone(93–94% ( patients withdetectableTgand noevidenceofRAIuptake PET/CT forthedetectionof persistent/recurrentDTCin the diagnosticperformances of anatomic localizationoflesions.Two meta-analysesanalyzed data furnishedbythisapproachsubstantiallyimprovesthe session. Thecombinationoffunctionalandmorphologic integrated scannerstoacquirePETandCTimagesinasingle PET/CT isamorerecentlydevelopedtechniquethatuses response to treatment and estimating the risk of death).The prognostic tool in cancer patients (e.g. for evaluating the this techniqueisthebasisforPET’s useasadiagnosticand Themetabolicinformation providedby phosphorylation. is farlessefficientforenergyproductionthanoxidative owing to their reliance on anaerobicglycolysis,which cells’ demandforglucose,however, ismarkedlyincreased is takenupbybenignaswellneoplasticcells.Thelatter tracer usedinclinicalsettingsis and moreoftenforalltypesofcancers.Themostcommon Positron emissiontomographyisbeingemployedmore tomography 18 remnants onthebasisofSPECT–CTresults( 40% ofthelesionswerereclassifiedasnormalthyroid lymphnodemetastasis, findings suggestiveofcervical ulated Tglevelswere Results ofthistypewereparticularlycommonwhenstim whose RxWBSshoweduptakeonlyinthethyroidbed. and/or distantmetastases)inabout9%ofthepatients RRA revealedadditionaldiseasefoci(necklymphnodes ( over thatfurnishedbyWBSalonein35–68%ofpatients ( likely toproducefalse-positiveandindeterminateresults that arenotRAI-avid.Forthisreason,SPECT–CTisless precise localizationoffociRAIuptakeaswelllesions images elaboratedbythescannersoftwareallowmore measures. Ontheotherhand,SPECT–CTfusion preparation and the need for postscan radioprotection it hasthesamedrawbacksasRAIWBSintermsofpatient tic ortherapeuticactivitiesofradioiodine.Consequently, patients withDTC,SPECT–CTisperformeddiagnos decisions on the use of SPECT–CT. In the follow-up of 100%) andthesensitivityis50%( scintigraphy. ThespecificityofSPECT–CTishigh(upto and facilitatesmeasurementoflesionsseenonSPECT 99 94 94 F-fluorodeoxyglucose positron emission Review , , , Costs andavailabilityaremajorconsiderationsin 96 95 100 , ), and it reportedly provides a gain in information 97 ). In both cases, the patient-based sensitivity of ). Inbothcases,thepatient-based sensitivityof ). Inarecentstudy, SPECT–CTperformedafter ≥ 1.8 ng/mL. InpatientswithRxWBS 18 FDG, a glucose analog that FDG, aglucoseanalogthat L Lamartinaandothers 93 18 FDG PETand ). 98 ). 18 FDG FDG - -

treatment tosearch andtreatdiseaselocalization.However, pected recurrencearesometimes referredforempiricalRAI Patients withdetectablethyroglobulin productionandsus differentiated thyroidcancer harboringthismutation( and thismayexplainthe V600E mutationcanalsocausethismetabolicpattern, increased expressionofglucosetransporter1.The related with loss or downregulation of ( metabolic progressionduringthefirstyearaftertreatment at highdoses,andmostoftheselesionsexhibitsigns of toradioactiveiodine therapy,frequently refractory even strategies (generally involving the surgical plan) in about 18 Disease relapse andstaging jointchanges)( reactive lymphnodes,inflammatory be increasedmerelybythepresenceofinflammation(e.g. innonthyroidtumors( that observed increased uptakebythyroid-derivedneoplastictissuefrom is usedtostageDTC,caremustbetakendifferentiate inflammation alsoincreasesFDGuptake.When were similar(81–84%)( The specificitiesof false negativeduetothepresenceofmicroscopicdisease. case oflowerthyroglobulinlevels, findings onradioiodineimagingduringfollow-up( or stimulatedserumTg(generally>10 18 vs 83–84%for primaries ( ses presentedmoreaggressivehistologicalfeaturesthanthe tumorwasalsoanalyzed,the primary differentiated cancers.In16(37%)ofthe43patientswhose carcinomas. However, almostone-fourth(23%)werewell- cers, 20% were tall-cell variants, and 9% were Hürthle cell revealed thatalmosthalfwerepoorlydifferentiatedcan of distantmetastasesfrom70 more aggressiveDTCforms.Histopathologicalanalysis of thescan. burden, diseaselocalization,andTSHlevelsatthetime ogy, disease,overalltumor thepresenceofRAI-refractory tumorhistol by severalotherfactors,includingprimary verified intraoperativelyorpreoperativelyviaFNA. lymph nodes must always be metastatic nature of cervical isplannedonthebasisofFDGuptake,true if surgery positivity relatedtoinflammationispossible.Therefore, 30% ofthecases( of DTCs Imaging inthefollow-up 105 FDG PET/CT for high-risk DTC patients with elevated basal FDG PET/CTforhigh-riskDTCpatientswithelevatedbasal FDG PET findings lead to changes in patient management 18 ). FDG PET positivity in thyroid cancer is influenced FDG PETpositivityinthyroidcancerisinfluenced 18 FDG uptake in RAI-refractory thyroidcancer iscor FDG uptakeinRAI-refractory 104 18 FDG avidity is most commonly seen in the FDG avidityismostcommonlyseeninthe ). Distantmetastasesthattakeup 18 FDG PET).TheATA stronglyrecommends 101 18 FDG PET alone and PET/CT methods FDG PETaloneandPET/CTmethods , 102 99 Downloaded fromBioscientifica.com at10/07/202110:13:36AM , 18 100 , 103 FDG uptake observed inwell- FDG uptakeobserved ). This is due to the fact that ). Thisisduetothefactthat 18 ). Asnoted,however, false FDG-avid thyroid tumors FDG-avid thyroidtumors 18 Fig. 4 FDG PET/CT can be FDG PET/CTcanbe 175 ng/mL) and negative ng/mL) andnegative 18 NIS FDG-avid metasta www.eje-online.org :5 ). Uptake can also ). Uptakecanalso expression and expression and 18 18 FDG PET FDG PET FDG are FDG are Fig. 4 R195 9 BRAF ). In ). In 69 via freeaccess ). ). ). - - - - -

Review L Lamartina and others Imaging in the follow-up 175:5 R196 of DTCs

F C

A D E G

Figure 4 18FDG PET findings in the follow-up of differentiated thyroid cancer.18 FDG PET/CT in a patient with tall-cell variant thyroid cancer (panel A) showed a retroclavicular left metastatic lymph node (panel B, axial view) and high and focal uptake also in the left clavicle (panel C, axial view) suspicious of bone metastases. MRI confirmed to be arthrosis (panel D). FDG PET in a patient with recurrent papillary thyroid cancer (panel E). High FDG uptake was detected in a superior mediastinal lymph node (panel F, axial view) and in mesenteric lymph node (panel G, axial view) suspicious for recurrence. Biopsy confirmed thyroid cancer recurrence in the mediastinal lymph node, but it was in favor of a B cells lymphoma in the mesenteric lymph node.

in roughly one-third of these patients, the post-treatment detected in this cohort, 41% were detected only by 18FDG whole-body RAI scan is negative and 18FDG PET is more PET/CT and 31% were seen only on the post-therapeutic European Journal European of Endocrinology sensitive to detect recurrence, suggesting that it might be WBS, indicating the two techniques play complementary useful to perform 18FDG PET before giving empiric radioac- roles (108). Additional studies are nonetheless necessary to tive iodine treatment in these patients (106). validate the utility of this approach in routine practice. In addition to its recommended role in the follow-up The serum thyroglobulin level is an indirect index of of patients with aggressive histology and RAI-refractory the tumor burden. Current guidelines recommend 18FDG disease, FDG PET is also potentially useful in the primary PET/CT when Tg levels exceed 10 ng/mL (9), and this staging of high-risk patients (Table 1). Lee et al. retrospec- threshold has been used in several studies. However, FDG tively analyzed 258 patients who underwent RRA and PET positivity is also associated with lower thyroglobulin 18FDG PET/CT during the same period of time. Compared levels (101, 109). For this reason, lower thresholds have with the post-treatment WBS, 18FDG PET/CT revealed addi- been proposed. Giovanella et al., for example, suggested a tional positive findings in 25% of the patients with high- level of 4.6 ng/mL, which was associated with a sensitivity or intermediate-risk thyroid cancers (pT3-T4N1 and tumor of 96% (110). Based on a subsequent analysis of 102 cases, size >2 cm) but only 3–6% of those with lower-risk tumors the same investigators also demonstrated that 18FDG-PET (T3-T4 N0 or T1-T2 N1 and size <2 cm), and the gain in positivity is predicted by a serum thyroglobulin doubling information led to a change in management in 17% of the time of less than 1 year, regardless of the Tg level itself (111). cases (107). Nascimento et al. retrospectively evaluated 38 Ultrasonography is still the best tool for detection patients with aggressive thyroid cancer histotypes and no of cervical lymph node metastases, but 18FDG PET can evidence of disease after surgery. 18FDG PET/CT performed be useful for identifying recurrence in areas that are dif- after the first RRA revealed persistent disease in 15 (39%) ficult or impossible to explore sonographically, such as of these patients; only 12 of these cases were identified the upper mediastinum or the retropharyngeal region with the post-therapeutic RAI WBS (108). Of the 86 lesions (101, 112). As for distant metastases, 18FDG PET can often

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Downloaded from Bioscientifica.com at 10/07/2021 10:13:36AM via free access European Journal of Endocrinology sensitivity ofthisapproach exceedsthatofdiagnostic PET can also be performed with iodine-124 ( Other radiopharmaceuticals age over45 and/or nonresponse to nonsurvival is alsocorrelatedwithotherclinicalfactorsthatpredict that alsotookupradioactiveiodine( therapy inlesionsthatdisplayed et al. which isconsistentwithpreviousfindings( of >5)andnumber also associated with the was unrelatedtothelesions’RAIavidity. Mortalitywas Furthermore, inthePET-positive subgroup,overallsurvival lesions butonly60%forthosewhowere at 2 rates the only independent predictor of overall survival: distant metastasesfromthyroidcancer, therapy in this population. In a study of 80 patients with andresponseto tool forpredictingoverallsurvival ( diseaseisamajordeterminantofmortality RAI-refractory ratesrangefrom25to42%,andthepresenceof survival In DTCpatientswithdistantmetastases,reported10-year Prognostic value treatment totakeadvantageoftheTSHstimulation. tion during follow-up, it can be done at the time of RAI sons, must beinterpretedwithcaution( cal lymph nodes. As noted above, positive associated withfalse-positivefindings,especiallyincervi performed aftertheadministrationofrhTSHhasalsobeen done duringLT4 treatment( was performedunderTSHstimulationthanwhenit ings andabettertumor/backgroundratiowhen and per-lesionanalysesbothrevealedmorepositivefind tive controlledclinicaltrials(168patients),per-patient issue. However, inarecentmeta-analysisofsevenprospec stimulation. Conflictingresultshavebeenreportedonthis often that issocommoninthyroidcancer. Theselesionsare tifying lungmetastasis,especiallythemicronodular form scans. However, CTisstillthemethodofchoiceforiden detect smallbonelesionsthataremissedonCTorMRI 92 Review ). The sensitivity of years were 100% in patients with foundnosignificantresponsetoradioactiveiodine 18 18 18 FDG uptakeiscurrentlyconsideredanimportant FDG PETcannotbeperformedunderTSHstimula FDG-negative duetoapartialvolumeeffect( years andthepresenceofnecrosis( 18 FDG PET can be influenced by TSH FDG PET can beinfluenced by TSH 18 18 FDG-avid lesions(>10)( FDG uptake level (SUV Max 114 18 L Lamartinaandothers 102 ). However, FDG uptake,eventhose 131 ). If,forpracticalrea 105 I treatment, such as 18 FDG uptakewas ). 18 18 18 FDG-positive. FDG-negative 18 FDG findings FDG findings FDG uptake 116 18 115 18 124 FDG PET FDG PET FDG PET FDG PET ). Wang I). The , 116 113 115 ). ). ), ------

these lesionsmakestheirevaluationdifficult( metastases fromthyroidcancer, butthelyticnatureof 18 and therapeuticWBSdonewith has recently been evaluated in thyroid cancer. Vrachimis growing useofSPECT–CTforpost-therapeutic owing tothelimitedavailabilityoftracerand 124 predict responsestoRAItreatment( safest and most effective predict theabsorbedlesiondose,improveselectionof togetherwithbloodclearancestudiescan 3D dosimetry uptake quantificationover time. (4.2 lungnodules( with miliary been associatedwithfalse-negativefindingsinpatients higher resolution( it providestomographicimages,but can beusefulforroutineuse inseveralpatientsubsets). includes anuclearmedicine department,WBS/SPECT–CT in thefirst-linearmamentarium (e.g.ina facilitythat and dependingonlocalresources, theymayhavea place highly specializedcentersmaybeusefulinmanypatients, ity havetobeconsidered.Studiesavailableonlyinafew center, depending onlocalresources. Costandavailabil somewhat fromcenterto tools forthisprocessmayvary Thechoice offirst-line ing andsubsequentsurveillance. follow-up assessments,includingpost-treatmentstag the ATA forrational useofimagingstudiesduringDTC is selectingthepropertool(s)fortaskathand. patients withDTC.Asinothersettings,thekeytosuccess of fundamental rolesinpost-treatmentsurveillance The diagnosticimagingstudiesreviewedaboveplay Conclusions issue requiresfurtherstudy. nodes, especially those smaller than 10 was superiortoCTforidentifyingpathologicallymph lymph nodesmetastases.TheauthorsreportedthatMRI inhigh-riskthyroidcancerpatientswith and dosimetry 124 PET/MRIhasalsobeenusedforlesiondetection PET/MRI (85%vs97%forFDGPET/CT)( recurrence detectionrateswereactuallylowerwithFDG found thatthenew method offerednodiagnostic gains: patients withdetectablethyroglobulinproductionand et al. of DTCs Imaging inthefollow-up F-Fluoride PEThasbeenproposedforevaluatingbone I PET is used almost exclusively in research settings The performanceofanewhybridPET/MRImachine Figure 3 days) allowstheacquisitionofsequentialimagesfor comparedFDGPET/MRIwithPET/CTinDTC summarizes thecurrentrecommendationsof 117 , 118 Downloaded fromBioscientifica.com at10/07/202110:13:36AM 131 , 119 I activity to administer, and 120 ). Nonetheless,ithasalso 124 ). Thehalf-lifeof 131 121 I PET-guided lesional 175 I notonlybecause 124 mm ( , www.eje-online.org :5 I PETalsooffers 122 125 ). Nowadays, 124 123 ), but this 131 ). Iodine ). R197 I scan. 124 via freeaccess I - -

Review L Lamartina and others Imaging in the follow-up 175:5 R198 of DTCs

However, they are likely to be problematic for repeated Journal of Clinical Endocrinology and Metabolism 2001 86 1447–1463. use on patients being followed in facilities not located in (doi:10.1210/jcem.86.4.7407) 3 Durante C, Montesano T, Torlontano M, Attard M, Monzani F, metropolitan areas. Likewise, safety and tolerability are Tumino S, Costante G, Meringolo D, Bruno R, Trulli F et al. Papillary always valid concerns, but they play particularly impor- thyroid cancer: time course of recurrences during postsurgery tant roles in ensuring patients’ continuing participation surveillance. Journal of Clinical Endocrinology and Metabolism 2013 98 636–642. (doi:10.1210/jc.2012-3401) in routine surveillance activities. 4 Davies L, Ouellette M, Hunter M & Welch HG. The increasing In the end, however, the final choice will be deter- incidence of small thyroid cancers: where are the cases coming from? mined largely by the likelihood and probable location of Laryngoscope 2010 120 2446–2451. (doi:10.1002/lary.v120:12) 5 Sosa JA, Hanna JW, Robinson KA & Lanman RB. Increases in persistent/recurrent disease and the sensitivity of the test thyroid nodule fine-needle aspirations, operations, and diagnoses for detecting this type of disease. In this context, the fact of thyroid cancer in the United States. Surgery 2013 154 1420–1426. that over 85% of all thyroid cancers are PTCs (126, 127) (doi:10.1016/j.surg.2013.07.006) 6 Davies L, Morris LG, Haymart M, Chen AY, Goldenberg D, Morris J, is highly pertinent since these tumors spread via the lym- Ogilvie JB, Terris DJ, Netterville J, Wong RJ et al. American phatics. One out of four PTC patients will develop cervical Association of Clinical Endocrinologists and American College of lymph node metastases (http://seer.cancer.gov/stat-facts/ Endocrinology disease state clinical review: the increasing incidence of thyroid cancer. Endocrine Practice 2015 21 686–696. (doi:10.4158/ html/thyro.html; last accessed 17 January 2016), whereas EP14466.DSCR) distant metastases are rare in PTC, particularly in the 7 Ito Y, Miyauchi A, Inoue H, Fukushima M, Kihara M, Higashiyama T, absence of cervical lymphadenopathy. Given its high sen- Tomoda C, Takamura Y, Kobayashi K & Miya A. An observational trial for papillary thyroid microcarcinoma in Japanese patients. World sitivity for thyroid bed and cervical lymph node lesions, its Journal of Surgery 2010 34 28–35. (doi:10.1007/s00268-009-0303-0) excellent safety and tolerability profiles, wide availability, 8 Sugitani I, Toda K, Yamada K, Yamamoto N, Ikenaga M & Fujimoto Y. and low cost, neck US is thus an ideal first-line imaging tool Three distinctly different kinds of papillary thyroid microcarcinoma should be recognized: our treatment strategies and outcomes. World for use in almost all DTC patients and in almost all settings. Journal of Surgery 2010 34 1222–1231. (doi:10.1007/s00268-009-0359-x) Second-line imaging studies are used more selectively 9 Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, and in cases where there is at least some reason to suspect Nikiforov YE, Pacini F, Randolph GW, Sawka AM, Schlumberger M et al. 2015 American Thyroid Association Management Guidelines for Adult metastasis (elevated or increasing levels of serum Tg, rising Patients with Thyroid Nodules and Differentiated Thyroid Cancer: Tg antibody titers, atypical first-line imaging findings). The American Thyroid Association Guidelines Task Force on Thyroid The importance of specificity increases at the second-line Nodules and Differentiated Thyroid Cancer. Thyroid 2016 26 1–133. (doi:10.1089/thy.2015.0020) level, and the higher risk status also justifies the use of 10 Wiebel JL, Banerjee M, Muenz DG, Worden FP & Haymart MR. methods that are most costly, less accessible, and/or more Trends in imaging after diagnosis of thyroid cancer. Cancer 2015 121 likely to be associated with some adverse effects. 1387–1394. (doi:10.1002/cncr.29210) 11 Lang K, Huang H, Lee DW, Federico V & Menzin J. National trends in European Journal European of Endocrinology advanced outpatient diagnostic imaging utilization: an analysis of the medical expenditure panel survey, 2000–2009. BMC Medical Imaging Declaration of interest 2013 13 40. (doi:10.1186/1471-2342-13-40) The authors declare that there is no conflict of interest that could be 12 Leenhardt L, Erdogan MF, Hegedus L, Mandel SJ, Paschke R, perceived as prejudicing the impartiality of the research reported. Rago T & Russ G. European thyroid association guidelines for cervical ultrasound scan and ultrasound-guided techniques in the postoperative management of patients with thyroid cancer. European Funding Thyroid Journal 2013 2 147–159. (doi:10.1159/000354537) This work was supported by Umberto Di Mario Foundation ONLUS and 13 DeKay ML & Asch DA. Is the defensive use of diagnostic tests good for Banca d’Italia. patients, or bad? Medical Decision Making 1998 18 19–28. (doi:10.1177/ 0272989X9801800105) 14 Momesso DP & Tuttle RM. Update on differentiated thyroid cancer staging. Endocrinology and Metabolism Clinics of North America 2014 43 Acknowledgements 401–421. (doi:10.1016/j.ecl.2014.02.010) Livia Lamartina is a fellow of PhD Program in ‘Biomedical Technologies 15 Fish SA, Langer JE & Mandel SJ. Sonographic imaging of thyroid in Clinical Medicine’ at the University of Rome Sapienza. The authors are nodules and cervical lymph nodes. Endocrinology and Metabolism grateful to Marian Everett Kent for her help in editing the manuscript. Clinics of North America 2008 37 401–417. (doi:10.1016/j. ecl.2007.12.003) 16 Pacini F, Molinaro E, Castagna MG, Agate L, Elisei R, Ceccarelli C, Lippi F, Taddei D, Grasso L & Pinchera A. Recombinant human References thyrotropin-stimulated serum thyroglobulin combined with 1 Mazzaferri EL & Jhiang SM. Long-term impact of initial surgical neck ultrasonography has the highest sensitivity in monitoring and medical therapy on papillary and follicular thyroid cancer. differentiated thyroid carcinoma. Journal of Clinical Endocrinology and American Journal of Medicine 1994 97 418–428. (doi:10.1016/0002- Metabolism 2003 88 3668–3673. (doi:10.1210/jc.2002-021925) 9343(94)90321-2) 17 Torlontano M, Crocetti U, D’Aloiso L, Bonfitto N, Di Giorgio A, 2 Mazzaferri EL & Kloos RT. Clinical review 128: current approaches Modoni S, Valle G, Frusciante V, Bisceglia M, Filetti S et al. Serum to primary therapy for papillary and follicular thyroid cancer. thyroglobulin and 131I whole body scan after recombinant

www.eje-online.org

Downloaded from Bioscientifica.com at 10/07/2021 10:13:36AM via free access European Journal of Endocrinology 31 30 29 28 27 26 25 24 23 22 21 20 19 18 Review Ito Y, Tomoda C, Uruno T, Takamura Y, Miya A,Kobayashi K, Ito Y, Tomoda C, Uruno T, Takamura Y, Miya A,Kobayashi K, Moreno MA, Edeiken-Monroe BS,Siegel ER,Sherman SI& Onkendi EO, McKenzie TJ,Richards ML,Farley DR,Thompson GB, Lang BH, Lee GC,Ng CP, Wong KP, Wan KY &Lo CY. Evaluating Leboulleux S, Borget I,Labro S,Bidault S,Vielh P, Hartl D,Dauchy S, Arturi F, Russo D,Giuffrida D,Ippolito A,Perrotti N,Vigneri R Jo K, Kim MH,Lim Y, Jung SL,Bae JS,Jung CK,Kang MI,Cha BY Jeon MJ, Kim WG,Jang EK,Choi YM,Lee YM,Sung TY, Yoon JH, Grani G &Fumarola A.Thyroglobulininlymphnodefine-needle Aygun N. Imagingofrecurrentthyroidcancer. Cooper DS, Doherty GM,Haugen BR,Kloos RT, Lee SL,Mandel SJ, thyroidcancerpatients Durante C &Filetti S.Managementofpapillary Torlontano M, Attard M,Crocetti U,Tumino S, Bruno R,Costante G, metastasis to the central compartment from papillary microcarcinomametastasis tothecentralcompartment frompapillary Matsuzuka F, Kuma K&Miyauchi A.Clinical significanceof 917–920. thyroid carcinoma.with papillary inpatients compartment asindicatorsofworse relapse-freesurvival anatomopathologically detectablenodemetastasesinthelateral Matsuzuka F, Kuma K&Miyauchi A.Ultrasonographicallyand Thyroid findings predictexcellentlong-termregionalcontrolandsurvival. ultrasound detectsonlymacroscopicsurgicaldisease,butnegative thyroidcancer,Clayman GL. Inpapillary preoperativecentralneck (doi:10.1007/s00268-013-2379-9) thyroidcancer.papillary Kasperbauer JL, Hay ID&Grant CS.Reoperativeexperiencewith 2202-7) World ofSurgery Journal thyroidcarcinoma.compartment forpersistent/recurrentpapillary inthecentral the morbidityandefficacyofreoperativesurgery 2013 pain relatedtothyroidnodulefine-needleaspirationcytology. Chougnet CN, Girard E,Azoulay S jcem.82.5.4062) Endocrinology andMetabolism thyroid cancermetastasesinsmalllymphnodes. & Filetti S.Earlydiagnosisbygeneticanalysisofdifferentiated 489–497. thyroglobulin antibody. thyroglobulin inthyroidcancerpatientswithserumanti- & Lim DJ.Loweredcutoffoflymphnodefine-needleaspiration 410–416. values accordingtoserumthyroglobulinlevel. thyroidcarcinoma:in patientswithpapillary twodifferentcutoff lymphnodemetastasis aspirates forpreoperativediagnosisofcervical Chung KW, Hong SJ,Baek JH 2014 diagnostic accuracy. aspiration washout:asystematicreviewandmeta-analysisof America of North 16 with thyroidnodulesanddifferentiatedcancer. Association GuidelinesTaskforce. Managementguidelinesforpatients Mazzaferri EL, McIver B,Sherman SI&Tuttle RM. AmericanThyroid Metabolism follow-up bynecksonography. in absenceofpostoperativeradioiodineremnantablation:tailoring and Metabolism in detectinglymphnodemetastases. thyroidcancer:roleofneckultrasonography patients withpapillary D’Azzò G, Meringolo D,Ferretti E,Sacco R 148 differentiated thyroidcancer. human TSHstimulationinthefollow-upoflow-riskpatientswith 109–142. 19–24. 23 99 2012 1113–1118. 1970–1982. (doi:10.1530/EJE-15-0344) (doi:10.1089/thy.2014.0544) (doi:10.1007/s00268-005-7789-x) 2011 (doi:10.1530/eje.0.1480019) (doi:10.1089/thy.2006.16.109) 22 2004 2008 347–355. 96 3059–3061. Journal ofClinicalEndocrinologyandMetabolism Journal (doi:10.1089/thy.2012.0461) (doi:10.1210/jc.2014-1098) 89 41 2013 3402–3407. European Journal ofEndocrinology European Journal 1095–1106. World ofSurgery Journal (doi:10.1089/thy.2011.0121) 1997 37 European Journal ofEndocrinology European Journal et al. Journal of Clinical Endocrinology and ofClinicalEndocrinologyand Journal 2853–2859. (doi:10.1210/jc.2011-1379) World ofSurgery Journal Thyroglobulinlevelinfine-needle 82 et al. (doi:10.1210/jc.2003-031521) Journal ofClinicalEndocrinology Journal 1638–1641. L Lamartinaandothers Frequencyandintensityof et al. (doi:10.1007/s00268-013- Otolaryngologic Clinics Otolaryngologic Thyroid Follow-upoflowrisk 2014 Journal ofClinical Journal (doi:10.1210/ 38 2015 Thyroid 2015 645–652. 2005 25 2003 173 Thyroid

2006 29

38 37 36 35 34 33 32 46 45 44 43 42 41 40 39 of DTCs Imaging inthefollow-up Leboulleux S, Girard E,Rose M,Travagli JP, Sabbah N,Caillou B, Rondeau G, Fish S,Hann LE,Fagin JA&Tuttle RM. Shin JH, Han BK,Ko EY&Kang SS.Sonographicfindingsinthe Wienke JR, Chong WK,Fielding JR,Zou KH&Mittelstaedt CA. Lee JH, Lee HK,Lee DH,Choi CG,Gong G,Shong YK&Kim SJ. Frates MC. Ultrasoundinrecurrentthyroiddisease. Lepoutre-Lussey C, Maddah D,Golmard JL,Russ G,Tissier F, Rosario PW, Mourão GF, Siman TL&Calsolari MR.Serum thyroglobulin Angell TE, Spencer CA,Rubino BD, Nicoloff JT &LoPresti JS.Insearch Durante C, Montesano T, Attard M,Torlontano M, Monzani F, Matsuzu K, Sugino K,Masudo K,Nagahama M,Kitagawa W, Lee J, Park JH,Lee CR,Chung WY&Park CS.Long-termoutcomes Robenshtok E, Fish S,Bach A,Domínguez JM,Shaha A&Tuttle RM. Loevner LA. Thyroidandparathyroidglands:imaging,treatment Kuna SK, Bracic I,Tesic V, Kuna K,Herceg GH &Dodig D. Metabolism differentiated thyroidcancer. lymphnodesinpatientsfollowedupfor of malignancyforcervical Hartl DM, Lassau N,Baudin E&Schlumberger M.Ultrasoundcriteria 845–853. after totalthyroidectomyfordifferentiatedthyroidcancerseldom Ultrasonographically detectedsmallthyroidbednodulesidentified 1359–1366. and nonrecurrentlesions. surgical bedafterthyroidectomy:comparisonofrecurrenttumors Medicine reliability andoverlapwithmalignancy. Sonographic featuresofbenignthyroidnodules:interobserver clinimag.2006.11.001) aspiration biopsy. correlation withtheresultsofultrasonography-guidedfine-needle thyroid bedinpostoperativepatientsforcarcinoma: Ultrasonographic findingsofanewlydetectednoduleonthe America Clinics ofNorth Endocrinology patients withinitiallymphnodeinvolvement. neck ultrasoundandriskstratificationindifferentiatedthyroidcancer Trésallet C, Menegaux F, Aurengo A&Leenhardt L.Post-operative s00268-005-0113-y) of thethyroid. measured with a second-generation assay in patients undergoing total measured withasecond-generationassay inpatientsundergoingtotal Thyroid thyroid carcinoma patientsnotreceivingradioactiveiodine ablation. of anunstimulatedthyroglobulinbaseline valueinlow-riskpapillary jc.2012-1123) Endocrinology andMetabolism a roleforserumthyroglobulinmeasurement? not undergopostoperativeradioiodineremnantablation:isthere thyroid cancerpatientswhodo ofpapillary Long-term surveillance Costante G, Meringolo D,Ferdeghini M,Tumino S, Lamartina L s00268-013-2224-1) of 1,088cases. thyroidcancer:long-termfollow-up study lobectomy forpapillary Shibuya H, Ohkuwa K,Uruno T, Suzuki A,Magoshi S matching. thyroid microcarcinoma: comparativeanalysisafterpropensityscore of totalthyroidectomyversusthyroidlobectomyforpapillary 97 selected patients. thyroidcancerusuallyremainstableoveryearsinproperly papillary lymphnodesdetectedafterthyroidectomyfor Suspicious cervical beyond. Preface. 2006 lymphadenopathy inthyroidcancer. Ultrasonographic differentiationofbenignfrommalignantneck show clinicallysignificantstructuralprogression. 2706–2713. 25 2014 1531–1537. 2003 (doi:10.1089/thy.2011.0011) Thyroid 2007 2014 24 22 World ofSurgery Journal World ofSurgery Journal (doi:10.1210/jc.2012-1553) 1127–1133. Neuroimaging Clinics of North America Neuroimaging ClinicsofNorth 92 1027–1031. Journal ofClinicalEndocrinologyandMetabolism Journal 2013 Clinical Imaging 170 3590–3594. 2008 837–846. 23 Journal ofUltrasoundinMedicine Journal 1408–1415. Downloaded fromBioscientifica.com at10/07/202110:13:36AM 2012 (doi:10.1089/thy.2013.0691) 41 Journal ofClinicalEndocrinologyand Journal 1107–1116. (doi:10.1210/jc.2007-0444) (doi:10.1530/EJE-13-0888) 2007 97 Journal ofUltrasoundinMedicine Journal 2748–2753. 2014 2006 (doi:10.1089/thy.2012.0463) 31 Journal ofUltrasoundin Journal 109–113. 38 175 30 Journal ofClinical Journal 68–79. 91–99. European Journal of European Journal www.eje-online.org :5 Thyroid (doi:10.1210/ Otolaryngologic Otolaryngologic 2008 (doi:10.1016/j. et al. (doi:10.1007/ (doi:10.1007/ 2011 2007 Thyroid 18 xiii–xiv. R199 21 26 2012 et al.

via freeaccess

Review L Lamartina and others Imaging in the follow-up 175:5 R200 of DTCs

thyroidectomy without radioiodine remnant ablation: a prospective 61 Schellinger PD, Meinck HM & Thron A. Diagnostic accuracy of MRI study. Thyroid 2015 25 769–775. (doi:10.1089/thy.2014.0496) compared to CCT in patients with brain metastases. Journal of Neuro- 47 Momesso DP, Vaisman F, Yang SP, Bulzico DA, Corbo R, Vaisman M Oncology 1999 44 275–281. (doi:10.1023/A:1006308808769) & Tuttle RM. Dynamic risk stratification in differentiated thyroid 62 Salvatori M, Perotti G, Rufini V, Maussier ML, Summaria V, Fadda G & cancer patients treated without radioactive iodine . Journal of Clinical Troncone L. Solitary liver metastasis from Hürthle cell thyroid cancer: Endocrinology and Metabolism 2016. (doi:10.1210/jc.2015-4290) a case report and review of the literature. Journal of Endocrinological 48 Durante C, Attard M, Torlontano M, Ronga G, Monzani F, Investigation 2004 27 52–56. Costante G, Ferdeghini M, Tumino S, Meringolo D, Bruno R et al. 63 Giraudet AL, Vanel D, Leboulleux S, Aupérin A, Dromain C, Chami Identification and optimal postsurgical follow-up of patients with L, Ny Tovo N, Lumbroso J, Lassau N, Bonniaud G et al. Imaging very low-risk papillary thyroid microcarcinomas. Journal of Clinical medullary thyroid carcinoma with persistent elevated calcitonin levels. Endocrinology and Metabolism 2010 95 4882–4888. (doi:10.1210/ Journal of Clinical Endocrinology and Metabolism 2007 92 4185–4190. jc.2010-0762) (doi:10.1210/jc.2007-1211) 49 Peiling Yang S, Bach AM, Tuttle RM & Fish SA. Frequent screening 64 Dromain C, de Baere T, Lumbroso J, Caillet H, Laplanche A, Boige V, with serial neck ultrasound is more likely to identify false-positive Ducreux M, Duvillard P, Elias D, Schlumberger M et al. Detection of abnormalities than clinically significant disease in the surveillance of liver metastases from endocrine tumors: a prospective comparison intermediate risk papillary thyroid cancer patients without suspicious of somatostatin receptor scintigraphy, computed tomography, and findings on follow-up ultrasound evaluation.Journal of Clinical magnetic resonance imaging. Journal of Clinical Oncology 2005 1 70–78. Endocrinology and Metabolism 2015 100 1561–1567. (doi:10.1210/ 65 Arturi F, Russo D, Schlumberger M, du Villard JA, Caillou B, Vigneri jc.2014-3651) P, Wicker R, Chiefari E, Suarez HG & Filetti S. Iodide symporter gene 50 Wang LY, Roman BR, Palmer FL, Tuttle RM, Shaha AR, Shah JP, expression in human thyroid tumors. Journal of Clinical Endocrinology Patel SG & Ganly I. Effectiveness of routine ultrasonographic and Metabolism 1998 83 2493–2496. (doi:10.1210/jcem.83.7.4974) surveillance of patients with low-risk papillary carcinoma 66 Arturi F, Russo D, Giuffrida D, Schlumberger M & Filetti S. Sodium- of the thyroid. Surgery 2016 159 1390–1395. (doi:10.1016/j. iodide symporter (NIS) gene expression in lymph-node metastases of surg.2015.11.018) papillary thyroid carcinomas. European Journal of Endocrinology 2000 51 Pitoia F, Abelleira E, Tala H, Bueno F, Urciuoli C & Cross G. 143 623–627. (doi:10.1530/eje.0.1430623) Biochemical persistence in thyroid cancer: is there anything to worry 67 Schlumberger M, Lacroix L, Russo D, Filetti S & Bidart JM. Defects in about? Endocrine 2014 46 532–537. (doi:10.1007/s12020-013-0097-6) iodide metabolism in thyroid cancer and implications for the follow-up 52 Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, and treatment of patients. Nature Clinical Practice Endocrinology and Dancey J, Arbuck S, Gwyther S, Mooney M et al. New response Metabolism 2007 3 260–269. (doi:10.1038/ncpendmet0449) evaluation criteria in solid tumours: revised RECIST guideline (version 68 Trapasso F, Iuliano R, Chiefari E, Arturi F, Stella A, Filetti S, Fusco A 1.1). European Journal of Cancer 2009 45 228–247. (doi:10.1016/j. & Russo D. Iodide symporter gene expression in normal and ejca.2008.10.026) transformed rat thyroid cells. European Journal of Endocrinology 1999 53 Einstein AJ, Henzlova MJ & Rajagopalan S. Estimating risk of 140 447–451. (doi:10.1530/eje.0.1400447) cancer associated with radiation exposure from 64-slice computed 69 Durante C, Puxeddu E, Ferretti E, Morisi R, Moretti S, Bruno R, Barbi F, tomography coronary angiography. JAMA 2007 18 317–323. Avenia N, Scipioni A, Verrienti A et al. BRAF mutations in papillary (doi:10.1001/jama.298.3.317) thyroid carcinomas inhibit genes involved in iodine metabolism. 54 Wang JC, Takashima S, Takayama F, Kawakami S, Saito A, Journal of Clinical Endocrinology and Metabolism 2007 92 2840–2843. Matsushita T, Matsuba H & Kobayashi S. Tracheal invasion by thyroid (doi:10.1210/jc.2006-2707) carcinoma: prediction using MR imaging. AJR. American Journal of 70 Lubin E, Mechlis-Frish S, Zatz S, Shimoni A, Segal K, Avraham A, European Journal European of Endocrinology Roentgenology 2001 177 929–936. (doi:10.2214/ajr.177.4.1770929) Levy R & Feinmesser R. Serum thyroglobulin and iodine-131 whole- 55 Wang J, Takashima S, Matsushita T, Takayama F, Kobayashi T & body scan in the diagnosis and assessment of treatment for metastatic Kadoya M. Esophageal invasion by thyroid carcinomas: prediction differentiated thyroid carcinoma. Journal of Nuclear Medicine 1994 35 using magnetic resonance imaging. Journal of Computer Assisted 257–262. Tomography 2003 27 18–25. (doi:10.1097/00004728-200301000-00004) 71 Franceschi M, Kusić Z, Franceschi D, Lukinac L & Roncević S. 56 Gross ND, Weissman JL, Talbot JM, Andersen PE, Wax MK & Thyroglobulin determination, neck ultrasonography and iodine-131 Cohen JI. MRI detection of cervical metastasis from differentiated whole-body scintigraphy in differentiated thyroid carcinoma. Journal thyroid carcinoma. Laryngoscope 2001 111 1905–1909. of Nuclear Medicine 1996 37 446–451. 57 Toubert ME, Cyna-Gorse F, Zagdanski AM, Noel-Wekstein S, 72 Filesi M, Signore A, Ventroni G, Melacrinis FF & Ronga G. Role Cattan P, Billotey C, Sarfati E & Rain JD. Cervicomediastinal of initial iodine-131 whole-body scan and serum thyroglobulin magnetic resonance imaging in persistent or recurrent papillary in differentiated thyroid carcinoma metastases. Journal of Nuclear thyroid carcinoma: clinical use and limits. Thyroid 1999 9 591–597. Medicine 1998 39 1542–1546. (doi:10.1089/thy.1999.9.591) 73 Mazzaferri EL & Kloos RT. Is diagnostic iodine-131 scanning with 58 Muresan MM, Olivier P, Leclère J, Sirveaux F, Brunaud L, Klein M, recombinant human TSH useful in the follow-up of differentiated Zarnegar R & Weryha G. Bone metastases from differentiated thyroid thyroid cancer after thyroid ablation? Journal of Clinical Endocrinology carcinoma. Endocrine-Related Cancer 2008 15 37–49. (doi:10.1677/ and Metabolism 2002 87 1490–1498. (doi:10.1210/jcem.87.4.8338) ERC-07-0229) 74 Pacini F, Ladenson PW, Schlumberger M, Driedger A, Luster M, 59 Schmidt GP, Schoenberg SO, Schmid R, Stahl R, Tiling R, Becker CR, Kloos RT, Sherman S, Haugen B, Corone C, Molinaro E et al. Reiser MF & Baur-Melnyk A. Screening for bone metastases: whole- Radioiodine ablation of thyroid remnants after preparation with body MRI using a 32-channel system versus dual-modality PET-CT. recombinant human thyrotropin in differentiated thyroid carcinoma: European Radiology 2007 17 939–949. (doi:10.1007/s00330-006-0361-8) results of an international, randomized, controlled study. Journal of 60 Sakurai Y, Kawai H, Iwano S, Ito S, Ogawa H & Naganawa S. Clinical Endocrinology and Metabolism 2006 91 926–932. (doi:10.1210/ Supplemental value of diffusion-weighted whole-body imaging jc.2005-1651) with background body signal suppression (DWIBS) technique to 75 Rosario PW, Xavier AC & Calsolari MR. Value of postoperative whole-body magnetic resonance imaging in detection of bone thyroglobulin and ultrasonography for the indication of ablation and metastases from thyroid cancer. Journal of Medical Imaging and Radiation 131I activity in patients with thyroid cancer and low risk of recurrence. Oncology 2013 57 297–305. (doi:10.1111/jmiro.2013.57.issue-3) Thyroid 2011 21 49–53. (doi:10.1089/thy.2010.0145)

www.eje-online.org

Downloaded from Bioscientifica.com at 10/07/2021 10:13:36AM via free access European Journal of Endocrinology 89 88 87 86 85 84 83 82 81 80 79 78 77 76 Review Hay ID, Thompson GB,Grant CS,Bergstralh EJ,Dvorak CE, Hänscheid H, Lassmann M,Buck AK,Reiners C&Verburg FA. The Chen MK, Yasrebi M, Samii J,Staib LH,Doddamane I&Cheng DW. Mavi A,Houseni M,Chamroonrat W,Urhan M, Dadparvar S, Mandel SJ, Shankar LK,Benard F, Yamamoto A &Alavi A.Superiorityof Yap BK &Murby B.Noadverseaffectinclinicaloutcomeusinglow Yin Y, Mao Q,Chen S,Li N,Li X&Li Y. Aclinicaltrialofoptimal Van Nostrand D,Aiken M,Atkins F, Moreau S,Garcia C, Acio E, Jeon EJ &Jung ED.Diagnosticwhole-bodyscanmaynotbenecessary Rosario PW, FurtadoMde S,MineiroFilho AF, Lacerda RX& de Meer SG,Vriens MR, Zelissen PM,BorelRinkes IH&deKeizer B. Pacini F, Capezzone M,Elisei R,Ceccarelli C,Taddei D &Pinchera A. Goffredo P, Sosa JA&Roman SA.Differentiatedthyroidcancer Elisei R, Molinaro E,Agate L,Bottici V, Masserini L,Ceccarelli C, 002-6612-1) World ofSurgery Journal and long-termoutcomein2444consecutively treatedpatients. during sixdecades(1940–1999):temporal trendsininitialtherapy thyroidcarcinomaPapillary managedatthe MayoClinic Gorman CA, Maurer MS,McIver B, Mullan BP, Oberg AL 59 differentiated thyroidcarcinoma. limit ofdetectioninscintigraphicimagingwithI-131patients thy.2011.0203) for thyroidcancer. The utilityofI-123pretherapyscaninI-131radioiodinetherapy (doi:10.1007/s00259-006-0341-x) ofNuclearMedicineandMolecularImaging Journal treatment scanningandserumthyroglobulinmeasurement. differentiated thyroidcarcinoma: acomparisonwithiodine-131post- Alavi A &Mandel SJ.Iodine-123asadiagnosticimagingagentin 2001 in patientswithdifferentiatedthyroidcancer. iodine-123 comparedwithiodine-131scanningforthyroidremnants Metabolism refuting thyroid-stunningeffect. preablation diagnostic(131)iactivityindifferentiatedthyroidcancer: MD.0000000000001308) thyroid carcinoma. pretherapy RAIscanningisperformedonpatientswithdifferentiated betweenablationanddiagnosticactivitywhena time interval cancer. iodine 131ablationinpatientswithwell-differentiatedthyroid Burman K &Wartofsky L. Theutilityofradioiodinescans priorto Metabolism low-dose (30mCi)radioactiveiodideablation. for intermediate-riskpatientswithdifferentiatedthyroidcancerafter (doi:10.1089/thy.2012.0026) intermediate andhighriskforrecurrence. after initialtherapyinpatientswithdifferentiatedthyroidcancerat Calsolari MR. Value ofdiagnosticradioiodinewhole-bodyscanning Medicine patients withhigh-riskdifferentiatedthyroidcancer. The roleofroutinediagnosticradioiodinewhole-bodyscintigraphyin 2002 after initialtreatment. cancer patientswhohaveundetectablestimulatedserumTglevels Diagnostic 131-iodinewhole-bodyscanmaybeavoidedinthyroid s00268-013-2006-9) decades. presenting withdistantmetastases:apopulationanalysisovertwo Metabolism institution toanswerthisquestion. over thelast35years?Studyon4187patientsfromasingleItalian pathological featuresofdifferentiatedthyroidcarcinoma reallychanged Lippi F, Grasso L,Basolo F, Bevilacqua G 2353–2368. 26 87 Thyroid 6–9. 1499–1501. 2011 World ofSurgery Journal 2010 2014 2014 (doi:10.1097/00003072-200101000-00002) 52 2009 (doi:10.1088/0031-9155/59/10/2353) 95 99 29 56–59. 1516–1527. Thyroid Medicine 2433–2440. 33–39. 19 (doi:10.1210/jcem.87.4.8274) Journal ofClinicalEndocrinologyand Metabolism Journal 849–855. 2002 (doi:10.2967/jnumed.110.080697) 2012 (doi:10.3803/EnM.2014.29.1.33) 2015 26 (doi:10.1210/jc.2009-1536) 2013 22 (doi:10.1210/jc.2014-1405) 879–885. Journal ofClinicalEndocrinologyand Journal Physics inMedicineandBiology (doi:10.1089/thy.2008.0419) 94 Journal of Clinical Endocrinology and ofClinicalEndocrinologyand Journal 304–309. e1308. 37 L Lamartinaandothers et al 1599–1605. Thyroid . Are the clinical and . Aretheclinicaland (doi:10.1007/s00268- (doi:10.1097/ Clinical NuclearMedicine (doi:10.1089/ Endocrinology and 2007 2012 Journal ofNuclear Journal (doi:10.1007/ 34 22 1012–1017. 1165–1169. 1165–1169. et al.

European

2014

102 101 100

of DTCs Imaging inthefollow-up 95 94 93 91 90 99 98 97 96 92 Aide N, Heutte N,Rame JP, Rousseau E,Loiseau C,Henry-Amar M Tharp K, Israel O,Hausmann J,Bettman L,Martin WH, Barwick T, Murray I, Megadmi H,Drake WM,Plowman PN, Xing M, Haugen BR&Schlumberger M.Progressinmolecular- Oh JR &Ahn BC.False-positiveuptakeonradioiodinewhole-body Dong MJ, Liu ZF, Zhao K,Ruan LX,Wang GL, Yang SY, Sun F& Jeong SY, Lee SW, Kim HW, Song BI,Ahn BC&Lee J.Clinical Spanu A, Solinas ME,Chessa F, Sanna D,Nuvoli S&Madeddu G. Schmidt D, Szikszai A,Linke R,Bautz W&Kuwert T. Impactof Durante C, Haddy N,Baudin E,Leboulleux S,Hartl D,Travagli JP, Caetano R,BastosCR,deOliveira I,daSilvaRM,FortesCP, PepeVL, Leboulleux S, Schroeder PR,Busaidy NL, Auperin A,Corone C, Giammarile F, Hafdi Z,Bournaud C,Janier M,Houzard C, 1565-2) and MolecularImaging patients withthyroidcarcinoma. CT imagesobtainedwithanintegratedsysteminthefollow-upof Daitzchman M, Sandler MP&Delbeke D.Impactof131I-SPECT/ of Endocrinology value overwholebodyplanarimagingandSPECT. Iodine-123 inpatientswithdifferentiatedthyroidcancer:additional computed tomography(SPECT)/computedusing Akker SA, Chew SL,Grossman AB&Avril N. Singlephotonemission 2892–2899. based managementofdifferentiatedthyroidcancer. Imaging thyroid cancer. scintigraphy: physiologicandpathologicvariantsunrelatedto emission tomography/computedtomography imagingtolocalize stimulation before2-[18F]-Fluoro-2-deoxy-D-glucose positron Assessment oftheincrementalvalue ofrecombinantthyrotropin Jacene HA, Ewertz ME,Bournaud C, Wahl RL, Sherman SI 149 detectable radioiodineuptake. of suspectedmetastaticthyroidcarcinoma inpatientswithno positron emissiontomographyusefulinthediagnosticmanagement fluoro-2-deoxy-d-glucose (FDG)scintigraphywithnon-dedicated Desuzinges C, Itti R,Sassolas G&Borson-Chazot F. Is[18F]-2- hed.23881) results: ameta-analysis. thyroid cancerrecurrencewithnegative131Iwhole-bodyscan positron emissiontomography-CTinthedetectionofdifferentiated Reis LG&BragaJU.Accuracyofpositronemissiontomographyand (doi:10.1097/MNM.0b013e32832dcfa7) analysis. carcinoma withradioiodine-negative whole-bodyscan:ameta- Luo XG. Value of18F-FDG-PET/PET-CT indifferentiatedthyroid 445–451. with differentiatedthyroidcancer. applications ofSPECT/CTafterfirstI-131ablationinpatients 2009 incremental valueversusplanarimaging. 131I SPECT/CTinthefollow-upofdifferentiatedthyroidcarcinoma: 50 carcinoma atthefirstradioablation. 131I SPECT/spiralCTonnodalstagingofdifferentiatedthyroid jc.2008-2313) Endocrinology andMetabolism postablation (131)I scintigraphy for thyroid cancer. tomography/computed tomographyoftheneckandthoraxin & Bardet S.Clinicalrelevanceofsingle-photonemissioncomputed therapy. and follicularthyroidcarcinoma: benefitsandlimitsofradioiodine outcome of444patientswithdistantmetastasesfrompapillary Caillou B, Ricard M,Lumbroso JD,DeVathaire F 1058–1069. 18–23. 293–300. 50 2012 184–190. Journal ofClinicalEndocrinologyand Metabolism Journal Nuclear MedicineCommunications (doi:10.1111/cen.12460) (doi:10.2967/jnumed.108.052746) (doi:10.1210/jc.2005-2838) 2 (doi:10.1530/eje.0.1490293) 362–385. 2010 American Journal ofNuclearMedicine andMolecular American Journal (doi:10.2967/jnumed.108.056572) 2004 162 Head &Neck 1131–1139. Downloaded fromBioscientifica.com at10/07/202110:13:36AM 31 2009 1435–1442. European Journal ofEndocrinology European Journal European Journal ofNuclearMedicine European Journal 94 Clinical Endocrinology 2016 Journal ofNuclearMedicine Journal 2075–2084. (doi:10.1530/EJE-09-1023) 2009 Journal ofNuclearMedicine Journal 38 175 (doi:10.1007/s00259-004- 316–327. www.eje-online.org :5 30 et al (doi:10.1210/ 639–650. European Journal European Journal Journal of Clinical Journal Lancet . Long-term 2006 (doi:10.1002/ 2014 et al. 2013 R201 91 81 2009

2003

23 via freeaccess

Review L Lamartina and others Imaging in the follow-up 175:5 R202 of DTCs

residual differentiated thyroid cancer. Journal of Clinical Endocrinology Do histological, immunohistochemical, and metabolic (radioiodine and Metabolism 2009 94 1310–1316. (doi:10.1210/jc.2008-1747) and fluorodeoxyglucose uptakes) patterns of metastatic thyroid 103 Wiebel JL, Esfandiari NH, Papaleontiou M, Worden FP & cancer correlate with patient outcome? Endocrine-Related Cancer 2011 Haymart MR. Evaluating positron emission tomography use 13 159–169. (doi:10.1677/ERC-10-0233) in differentiated thyroid cancer. Thyroid 2015 25 1026–1032. 116 Robbins RJ, Wan Q, Grewal RK, Reibke R, Gonen M, Strauss HW, (doi:10.1089/thy.2015.0062) Tuttle RM, Drucker W & Larson SM. Real-time prognosis for metastatic 104 Rivera M, Ghossein RA, Schoder H, Gomez D, Larson SM & Tuttle RM. thyroid carcinoma based on 2-[18F]fluoro-2-deoxy-D-glucose-positron Histopathologic characterization of radioactive iodine-refractory emission tomography scanning. Journal of Clinical Endocrinology and fluorodeoxyglucose-positron emission tomography-positive thyroid Metabolism 2006 91 498–505. (doi:10.1210/jc.2005-1534) carcinoma. Cancer 2008 113 48–56. (doi:10.1002/cncr.235150) 117 Freudenberg LS, Antoch G, Jentzen W, Pink R, Knust J, Görges R, 105 Wang W, Larson SM, Tuttle RM, Kalaigian H, Kolbert K, Müller SP, Bockisch A, Debatin JF & Brandau W. Value of (124)I-PET/ Sonenberg M & Robbins RJ. Resistance of [18f]-fluorodeoxyglucose- CT in staging of patients with differentiated thyroid cancer. European avid metastatic thyroid cancer lesions to treatment with Radiology 2004 14 2092–2098. (doi:10.1007/s00330-004-2350-0) high-dose radioactive iodine. Thyroid 2001 11 1169–1175. 118 Phan HT, Jager PL, Paans AM, Plukker JT, Sturkenboom MG, (doi:10.1089/10507250152741028) Sluiter WJ, Wolffenbuttel BH, Dierckx RA & Links TP. The diagnostic 106 Leboulleux S, El Bez I, Borget I, Elleuch M, Déandreis D, Al value of 124I-PET in patients with differentiated thyroid cancer. Ghuzlan A, Chougnet C, Bidault F, Mirghani H, Lumbroso J European Journal of Nuclear Medicine and Molecular Imaging 2008 35 et al. Postradioiodine treatment whole-body scan in the era 958–965. (doi:10.1007/s00259-007-0660-6) of 18-fluorodeoxyglucose positron emission tomography for 119 Van Nostrand D, Moreau S, Bandaru VV, Atkins F, Chennupati S, differentiated thyroid carcinoma with elevated serum thyroglobulin Mete M, Burman K & Wartofsky L. (124)I positron emission tomography levels. Thyroid 2012 22 832–838. (doi:10.1089/thy.2012.0081) versus ( )I planar imaging in the identification of residual thyroid tissue 107 Lee JW, Lee SM, Lee DH & Kim YJ. Clinical utility of 18F-FDG PET/ and/or metastasis in patients who have well-differentiated thyroid CT concurrent with 131I therapy in intermediate-to-high-risk cancer. Thyroid 2010 20 879–83. (doi:10.1089/thy.2009.0430) patients with differentiated thyroid cancer: dual-center experience 120 Freudenberg LS, Jentzen W, Müller SP & Bockisch A. Disseminated with 286 patients. Journal of Nuclear Medicine 2013 54 1230–1236. iodine-avid lung metastases in differentiated thyroid cancer: a (doi:10.2967/jnumed.112.117119) challenge to 124I PET. European Journal of Nuclear Medicine and 108 Nascimento C, Borget I, Al Ghuzlan A, Deandreis D, Hartl D, Molecular Imaging 2008 35 502–508. (doi:10.1007/s00259-007-0601-4) Lumbroso J, Berdelou A, Lepoutre-Lussey C, Mirghani H, Baudin E 121 Sgouros G, Kolbert KS, Sheikh A, Pentlow KS, Mun EF, Barth A, et al. Postoperative fluorine-18-fluorodeoxyglucose positron emission Robbins RJ & Larson SM. Patient-specific dosimetry for 131I thyroid tomography/computed tomography: an important imaging modality cancer therapy using 124I PET and 3-dimensional-internal dosimetry in patients with aggressive histology of differentiated thyroid cancer. (3D-ID) software. Journal of Nuclear Medicine 2004 45 1366–1372. Thyroid 2015 25 437–444. (doi:10.1089/thy.2014.0320) 122 Jentzen W, Hoppenbrouwers J, van Leeuwen P, van der Velden D, 109 Schlüter B, Bohuslavizki KH, Beyer W, Plotkin M, Buchert R & van de Kolk R, Poeppel TD, Nagarajah J, Brandau W, Bockisch A Clausen M. Impact of FDG PET on patients with differentiated & Rosenbaum-Krumme S. Assessment of lesion response in the thyroid cancer who present with elevated thyroglobulin and initial radioiodine treatment of differentiated thyroid cancer using negative 131I scan. Journal of Nuclear Medicine 2001 42 71–76. 124I PET imaging. Journal of Nuclear Medicine 2014 55 1759–1765. 110 Giovanella L, Ceriani L, De Palma D, Suriano S, Castellani M & (doi:10.2967/jnumed.114.144089) Verburg FA. Relationship between serum thyroglobulin and 18FDG- 123 Schirrmeister H, Buck A, Guhlmann A & Reske SN. Anatomical PET/CT in 131I-negative differentiated thyroid carcinomas. Head & distribution and sclerotic activity of bone metastases from thyroid European Journal European of Endocrinology Neck 2012 34 626–631. cancer assessed with F-18 sodium fluoride positron emission 111 Giovanella L, Trimboli P, Verburg FA, Treglia G, Piccardo A, tomography. Thyroid 2001 11 677–683. (doi:10.1089/105072501750 Foppiani L & Ceriani L. Thyroglobulin levels and thyroglobulin 362754) doubling time independently predict a positive 18F-FDG PET/ 124 Vrachimis A, Burg MC, Wenning C, Allkemper T, Weckesser M, CT scan in patients with biochemical recurrence of differentiated Schäfers M & Stegger L. [18F]FDG PET/CT outperforms [18F]FDG thyroid carcinoma. European Journal of Nuclear Medicine and Molecular PET/MRI in differentiated thyroid cancer. European Journal of Nuclear Imaging 2013 40 874–880. (doi:10.1007/s00259-013-2370-6) Medicine and Molecular Imaging 2016 43 212–220. (doi:10.1007/ 112 Grant CS, Thompson GB, Farley DR, Richards ML, Mullan BP & s00259-015-3195-2) Hay ID. The value of positron emission tomography in the surgical 125 Nagarajah J, Jentzen W, Hartung V, Rosenbaum-Krumme S, management of recurrent papillary thyroid carcinoma. World Journal Mikat C, Heusner TA, Antoch G, Bockisch A & Stahl A. Diagnosis of Surgery 2008 32 708–715. (doi:10.1007/s00268-007-9361-3) and dosimetry in differentiated thyroid carcinoma using 124I PET: 113 Zoller M, Kohlfuerst S, Igerc I, Kresnik E, Gallowitsch HJ, Gomez I comparison of PET/MRI vs PET/CT of the neck. European Journal & Lind P. Combined PET/CT in the follow-up of differentiated of Nuclear Medicine and Molecular Imaging 2011 38 1862–1868. thyroid carcinoma: what is the impact of each modality. European (doi:10.1007/s00259-011-1866-1) Journal of Nuclear Medicine and Molecular Imaging 2007 34 487–495. 126 Brito JP, Al Nofal A, Montori VM, Hay ID & Morris JC. The impact (doi:10.1007/s00259-006-0276-2) of subclinical disease and mechanism of detection on the rise in 114 Ma C, Xie J, Lou Y, Gao Y, Zuo S & Wang X. The role of TSH for thyroid cancer incidence: a population-based study in Olmsted 18F-FDG-PET in the diagnosis of recurrence and metastases of County, Minnesota during 1935 through 2012. Thyroid 2015 25 differentiated thyroid carcinoma with elevated thyroglobulin and 999–1007. (doi:10.1089/thy.2014.0594) negative scan: a meta-analysis. European Journal of Endocrinology 2010 127 Bahl M, Sosa JA, Nelson RC, Esclamado RM, Choudhury KR & 163 177–183. (doi:10.1530/EJE-10-0256) Hoang JK. Trends in incidentally identified thyroid cancers over a 115 Deandreis D, Al Ghuzlan A, Leboulleux S, Lacroix L, Garsi JP, decade: a retrospective analysis of 2,090 surgical patients. World Journal Talbot M, Lumbroso J, Baudin E, Caillou B, Bidart JM et al. of Surgery 2014 38 1312–1317. (doi:10.1007/s00268-013-2407-9)

Received 31 January 2016 Revised version received 8 April 2016 Accepted 31 May 2016

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