European Journal of Endocrinology 10.1530/EJE-16-0960 have sporadic MTC, whereas hereditary MTCisusually have sporadicMTC,whereas hereditary and DJ Gross related deaths (1, it isresponsibleforupto 13.4% ofallthyroidcancer- MTC accountsforonly3–10% ofallthyroidcarcinomas, parafollicular Ccellsofthethyroidgland.Although secreting neuroendocrinetumorderivedfromthe thyroidcarcinomaMedullary (MTC)isararecalcitonin- Introduction should alwaysbeconsidered,irrespectiveofthepresenceextrahepaticmetastasis. improvement andtumorresponseforprolongedperiodsoftimeinthemajoritypatients.Thistherapeuticoption Conclusion: TACE inMTCpatientswithhepaticmetastasesisusuallywelltolerated andinducesbothclinical overall survivalrateof57 progression was38 months(range8–126).Threepatientswerestillaliveattheendoffollow-upperiod(a median TACE. Clinicalimprovementaswelltumorresponse(PR)wereobserved inallpatients.Themediantimetotumor patients. Themediansizeofthelargestliverlesionwas40 liver metastaseswereincluded.Metastaticinvolvementofthewaslessthan50%volumeinall Results: Sevenconsecutivepatients(meanage64.5 Methods: RetrospectivecaseseriesofpatientstreatedatasingletertiaryUniversityMedicalCenterfrom2005to2015. patients. Aim: To exploretheclinicaloutcome, survivalandsafetyprofileof TACE forlivermetastasesinagroupofMTC effectiveness andsafetyofthisprocedureinMTCarelimited. are limitedtocatheter-guided proceduressuchastrans-arterialchemoembolization(TACE). Dataregardingthe carrying anegativeimpactondiseaseprognosis.TheoptionsforselectivetherapyoflivermetastasesinMTCpatients Background: Livermetastasesarerelativelycommoninpatientswithmetastaticmedullarythyroidcarcinoma(MTC), Abstract 2 1 S Grozinsky-Glasberg experience andreview oftheliterature thyroid carcinoma: aspecialistcenter chemoembolization inmetastaticmedullary The role ofhepatictrans-arterial *(S Grozinsky-GlasbergandAIBloomcontributedequallytothiswork) Department ofRadiology, Hadassah-HebrewUniversityMedicalCenter, Jerusalem,Israel Neuroendocrine Tumor Unit,Endocrinology&MetabolismService,DepartmentofMedicine,and DOI: 10.1530/EJE-16-0960 www.eje-online.orgwww.eje-online.org Clinical Study 1 2, 3, 1, 4). The majority of patients (85%) *, AI Bloom ± 44 months). © 2017EuropeanSociety ofEndocrinology © 2017EuropeanSociety ofEndocrinology A IBloomandothers S Grozinsky-Glasberg, 2, *, N Lev-Cohain Printed inGreatBritain ±
10.9 years, 5females)withhistologicallyconfirmedMTC
2 , A Klimov ±
6.9 controversial (2).Distantmetastases(tothe lungs,bones extension andextentofsurgery, thoughthesearestill disease-related factors,such asageatdiagnosis,disease clinical coursevariesaccording tocertainpatient-and and therelatedfamilialMTC(FMTC)syndrome(5).The endocrine neoplasia (MEN) syndromes, MEN2A, MEN2B diagnosed earlierasacomponentofthetype2multiple in MTC Liver chemoembolization Published byBioscientifica Ltd. mm. Thepatientsunderwentintotal20sessionsof 2 , H Besiso 1
Downloaded fromBioscientifica.com at09/25/202101:28:21PM (2017) Endocrinology European Journal of [email protected] Email to SGrozinsky-Glasberg should beaddressed Correspondence 176 176:4 : 4 176, 463–470
463–470 via freeaccess European Journal of Endocrinology or TAE respectively),selectiveinternalradiation therapy regional selectivearterial chemo-/embolization (TACE flushing orabdominalpain), treatmentwitheitherloco- the metastases,with/without symptomssuchasdiarrhea, progressive liver disease occurs (with increase in the size of orradiofrequencyablation (27).When to surgery throughout theparenchymaandareusuallynotamenable advanced MTC,areoftenmultipleanddisseminated patients withmetastaticprogressiveMTC(26). benefit ofradiolabeled minigastrin administration in limiteddata onthepotential receptors, thereisstillvery 90% ofMTCsexpresscholecystokinin(CCK)-B/gastrin adequate SSTRexpression(25).Noteworthy, althoughover analogues may be suggested in selective patients with (PRRT) withdifferenttypesofradiolabeledsomatostatin the utilizationofpeptidereceptorradionuclidetherapy tumor cells may express somatostatin receptors; therefore, 23, although theymaybeindicatedinselectedpatients(22, by low-andshort-durationresponserates(15–20%), cyclophosphamide orvincristine)arecharacterized with doxorubicin,5FUanddacarbazine,streptozotocin, chemotherapeutic regimens (e.g. combination therapy MTC (19, systemic therapyinpatientswithadvancedprogressive or cabozantinibcanbeusedassingleagentfirst-line be consideredassystemictherapy. TheTKIsvandetanib inhibitors (TKIs)targetingbothRETandVEGFRshould metastatic disease,treatmentwithtyrosinekinases with locallyaggressivedisease(17,18). limited roleforexternal-beamradiotherapyinpatients considered ascandidatesforsystemictherapy;thereisa areusually disease whocannotbetreatedbysurgery patients withprogressiveorsymptomaticmetastatic meticulous surgicalresection(14, somatostatin (11,1213). chromogranin, histaminase,neurotensinand hormone (ACTH),B-melanocyte-stimulating hormone, valuable tumormarkers,andrarelyadrenocorticotropic (CLT) and carcinoembryonic antigen (CEA), which are of hormonesorbiogenicamines,mainlycalcitonin at10 years(9,10). 20–40% surviving metastases atdiagnosishaveapoorprognosis,withonly loco-regional disease(6, in patients with MTC, being associated with persistent and liver)arepresentinupto15%atdiseasepresentation www.eje-online.org Clinical Study 24). Severalstudieshavedemonstratedthatthyroid Liver metastasesoccurin~45%ofpatientswith In patientswithsymptomaticandprogressive treatmentforMTCisextensiveand The primary The Ccellsofthethyroidmaysecreteavariety 20, 21). Singleagentorcombinationcytotoxic 7, 8). Patientswithdistant A IBloomandothers S Grozinsky-Glasberg, 15, 16). However, of patients’characteristicswiththosepreviouslyreported. have alsoreviewedtheliteraturetocompareourcohort a groupofconsecutivepatientswithmetastaticMTC.We andsafetyprofileof survival TACE forlivermetastasesin a retrospectiveanalysistoexploretheclinicaloutcome, advanced unresectableMTCarelimited.We conducted trans-arterial loco-regionaltherapyinpatientswith (TACE/TAE orSIRT)needstobeexplored. The possiblerelativebenefitofeitherthesetreatments (SIRT) orsystemictherapyshouldbeconsidered(28, WMA Helsinkiguidelinesforresearch inhumansubjects. well asthelong-termoutcome,weredetermined. chemotherapy, trans-arterialchemoembolization,etc.),as irradiation therapy, somatostatinreceptoranalogues, The applicationoftherapeuticmodalities(e.g.surgery, as well as histopathological findings were all analyzed. the patients,biochemicalandradiologicalassessment, (between 2005and2015).Clinicalcharacteristicsof years been retrospectivelystudiedforaperiodof10 referralcenterinIsraelhave and treatedatatertiary Seven consecutivepatientswithMTCdiagnosed Subjects andmethods diagnosis and also periodically at 3–6 months duringthe diagnosis andalsoperiodically at3–6 months 0–1.46 (Cis-Bio International,Gifsur-Yvette, France;normal commercially available radioimmunoassay ELSA-CT kit the follow-upperiod.Serum CLT was measuredusinga months)during (3–6 and thereafteratregularintervals before treatmentwithTACE afteranovernightfast, assessment. Serum calcitonin (CLT) levels were measured acomplete biochemical All patientsunderwent Biochemical evaluation and theirfamilieswerealsorecorded. other endocrine disorders or malignancies in the patients performing animagingtestwasrecorded.Thepresenceof pain. In the absence of typical symptoms, the reason for including dyspnea,cough,diarrhea, flushing orbone symptoms compatiblewithmetastaticMTCatdiagnosis, MTC, patients’fileswerereviewedforthepresenceof To definesymptomaticorasymptomaticpatientswith Clinical assessment in MTC Liver chemoembolization Data regardingtheeffectivenessandsafetyof This studywasapprovedbytheIRBaccordingto pmol/L). CEAwascollected inallpatients,at
Downloaded fromBioscientifica.com at09/25/202101:28:21PM 176:4 464 29). via freeaccess European Journal of Endocrinology PET-CT, obtained by superior mesenteric artery injectionof obtained bysuperiormesenteric artery access usinga5Frenchcatheter. Aportogramwasfirst Hepatic arterial TACE was performed through a femoral Chemoembolization method the contrastmediawereexcluded(31). chemotherapeutic agentorknownallergicreactions to than 100 serum LDH(morethan425 serum bilirubin(morethan3–5 hepatic insufficiency/failure,portalveininvasion,high of morethan50%liver, withsuspicionofimpending Patients withamassiveordiffusemetastaticinvolvement Contraindications TACEand underwent (30). main source of morbidity and mortality, were included metastases, wheretheintrahepaticcomponentwasa of hyper-vascularprogressiveand/orsymptomaticliver liverfunctioninthepresence Patients withpreserved Indications TACE procedure a functional imaging ( also underwent liver vasculature have been recorded. Some of the patients presence ofcalcifications,aswellthepatency veins. Thenumberofnodules,size,location,edge,the macroscopic vascularinvasionintothehepaticandportal segmental localizationofthetumorandtoevaluate therapy, toassessthesize,extentaswellaccurate ultrasonography oftheliverbeforeinitiation resonance imaging(MRI)oftheliver, aswellaDoppler computerized tomography(CT)and/oramagnetic a high-resolution cross-sectional All patients underwent Radiological assessment the uppernormalrange. reasonable liverfunctiontestsbeforeTACE, uptoX1.5of aftereachtreatment.Allpatientshad to 6-monthinterval andregularlyata3- treatment, andthenafter2–4 weeks and GPT)havealsobeenevaluatedbeforeaftereach (Boehringer, Mannheim,Germany;normal0–3 study period(measuredusingtheEnzymum-testCEAkit Clinical Study Liver enzymes(alkalinephosphatase,GGT, GOT 18 IU/L), aswellknowncontraindicationstothe F-DOPA-PET-CT, orFDG-PET-CT) (Fig. 1). IU/L) andtransaminases(more A IBloomandothers S Grozinsky-Glasberg, mg/dL), highlevelsof 68 Ga-DOTATATE- ng/mL)). cholangitis orfranksepsis(33). the morningofprocedure,topreventliverabscess, Patients alsoreceivedprophylacticantibioticinfusion anorexia) andtoimproveliverfunctionafterTACE (32). (PES) (nausea,vomiting,fever, abdominalpainand day) aimedtoalleviatingthepost-embolizationsyndrome well asoraldexamethasone(atadosageof4 emetics, paincontrolincludingnarcotic analgesics,as Pre- andpost-procedure care included fluid infusion, anti- Peri-procedure medicalprotocol TACE session. later, accordingtothetoleranceoffirst 1–3 months using gel foam powder to complete blood flow stagnation. injection oftheemulsion,embolizationwasperformed sous Bois, France) to obtain a water-in-oil emulsion; after with 7–10 treatment ordoxorubicin50 course of TACE, the cytotoxic agent (mitomycin 30 one liverlobeatatimewasperformed.Foreachsingle tumor liverinvolvementwasover30%,selectiveTACE of selectively embolized prior to treatment. Usually, as itwas if aprominentarterio-portalshuntwasobserved, asamaptoguidetheTACE; wasobtainedtoserve artery trunk anditsbranches,anangiogramofthehepatic contrast mediumtoconfirmthepatencyofportal case ofPD,treatmentwasdiscontinued. which time,anewcycleof TACE wasconsidered; inthe not performedagainuntildisease progressionoccurred,at hormonal deterioration)(34 ). an increaseof25%ormoreintumorsizeandclinical/ (progressive disease,PD)(appearanceofnewlesionsor hormonal measurements)and(4)tumorprogression than 25%increaseintumorsize,clinicalsymptomsand disease (SD)(lessthan50%reductionornogreater levels, withnoappearance of newlesions);(3)stable all measurabletumor, clinical symptoms andhormonal (2) partialresponse(PR)(a50%orgreaterreduction in radiological andhormonalevidenceofthetumor); response (CR)(completeregressionofallclinical, using established WHO criteria, as follows: (1) complete and was defined 6 months and then every at 2–3 months on contrastenhancementCTand/orMRIperformed In allcases,theresponsetotreatmentwasassessedbased Evaluation ofresponse toTACE in MTC Liver chemoembolization The contralateralliverlobewasusuallytreated In thecaseoftumorresponse (CR,PRorSD),TACE was mL ofiodizedoil(Lipiodol;Guerbet,Aulnay
Downloaded fromBioscientifica.com at09/25/202101:28:21PM mg/treatment) wasmixed 176:4 www.eje-online.org mg, 2–3 465 time/ mg/ via freeaccess
European Journal of Endocrinology www.eje-online.org the CLT andCEAlevels. Biological responsewasdefinedasadecreaseof≥25%in in thenumberofstoolsorflushingattacksperday. Familial aggregation Symptomatic Other metastaticsites,bones Previous thyroidectomyandneck Duration ofliverinvolvementbefore Size oflargestliverlesion(range) Caucasians Female Age (years) Characteristics mean ± as liver metastaticMTCincludedinthestudy. Dataarepresented Table 1 with aRETmutationatthe634codon,andwho one patienthadmultipleendocrineneoplasiaMEN2A negative screeningforgermlineRETmutation,whereas (range 52–78). Six patients had sporadic MTC based on patients werefemale,withameanageof64.5 metastatic MTCareshowninTable 1 . Fiveoutoftheseven The clinicalcharacteristicsofthepatientswithliver Results Results wereexpressedasmean Statistical analysis A Pvalueof<0.05wasconsideredsignificant. program (SystatSoftwareInc.,PointRichmond,CA,USA). Student’s variables wereanalyzedbythechi-squaretestand dissection first TACE (months) Clinical Study Clinical responsewasdefinedasadecreaseby≥25% The clinicalcharacteristicsofthepatients(n =7) s . t-test usingtheSigmaStat2.03computerized d . orasn(%) A IBloomandothers S Grozinsky-Glasberg, ± 29.5 s . d . Differencesin m (13–60) ± 18mm 64.5 4/7 (57%) 7 (100%) 7 (100%) 30 1 (14%) 5 (71%) 5 (71%) Values ± 24.5 ± 10.9 years ± 10.9 with 40 the largestliverlesionrangedfrom30to45 (involving bothhepaticlobes),inallpatients.Thesizeof or MRIwaslessthan50%ofthelivervolume,andbilateral tyrosine kinaseinhibitorsbeforeTACE. months.Noneoftheincludedpatientsreceived was 26 between theterminationofchemotherapy and TACE without anyobjectiveresponse;thelengthoftime treated withsystemicchemotherapyadriamycin, diffuse inbothlobes.Onepatient(patient2)hasbeen in mostpatients,thelivermetastasesweremultipleand previously inoneoftheincludedpatients(patient1),as dissection. totalthyroidectomyandnecklymphnodes underwent pheochromocytomas. Alltheincludedpatientspreviously previousbilateraladrenalectomyd/t underwent CLT inallincludedpatients. and CEAhavebeenobserved pain, diarrheaorflushing,andelevationinthelevels of first TACE, intermsofweightsloss,weakness,abdominal involvement. Fivepatientsweresymptomaticbeforethe 63 months (range24–132). betweentheMTCdiagnosisand first interval TACE was first (range4–72),whereas the time TACE was30 months criteria). Themeandurationoflivermetastasesbeforethe progression (PD)atthetimeoffirst TACE (WHO tests (≤1.5uppernormalvalues). cycles during the study period. They were technically patient) wereperformedand weredeliveredduring11 A total of 20 courses of TACE (mean, 2.8; range, 2–5 per Chemoembolization in MTC Liver chemoembolization ± Metastatic involvementoftheliverdeterminedonCT Hepatic singlemetastasectomywasperformed Four outofthesevenpatientshadalsobone All patientshadradiologicalandbiochemical 6.9 mm). Allpatientshadappropriateliverfunction org/10.1530/EJE-16-0960. figure isavailableathttp://dx.doi. metastases. Afullcolourversionofthis reduction inthenumberandsizeofliver demonstrating significantresponsewith patients, beforeand1.5 yearsafterTACE, The F-DOPA PET/CTimagesofoneour Figure 1
Downloaded fromBioscientifica.com at09/25/202101:28:21PM 176:4 mm (median, 466 via freeaccess European Journal of Endocrinology
Table 2 Patients’ characteristics in terms of response to TACE. Clinical Study
Before TACE After TACE
Age Number Liver Calcitonin levels, Tumor Symptoms Calcitonin levels, Tumor TTP Patient (years) Sex of TACE involvement Symptoms mean (0–1.46 pmol/L) status improvement mean (0–1.46 pmol/L) response (months) 1 75 F 5 Bilateral lobes, Weight loss, 8731 PD Yes 2150 PR 126 <50% weakness 2 61 M 2 Bilateral lobes, No 802 PD – 460 PR 24 <50% 3 52 M 2 Bilateral lobes, Weight loss, 3651 PD Yes – PR 49 <50% diarrhea, flushing, abdominal pain 4 78 F 2 Bilateral lobes, Weight loss, flushing 1604 PD Yes 301 PR 8 <50% A IBloomandothers S Grozinsky-Glasberg, 5 74 F 3 Bilateral lobes, Weight loss, 8240 PD Yes 1304 PR 9 <50% weakness, flushing, abdominal pain 6 59 F 3 Bilateral lobes, Abdominal pain, 5193 PD Yes 2264 PR 24 <50% flushing 7 53 F 3 Bilateral lobes, No 4625 PD – 2629 PR 24 <50%
F, female; M, male; PD, progressive disease; PR, partial response; SD, stable disease; TACE, trans-arterial chemoembolization; TTP, time to tumor progression. size from29.5 1), with an averagedecrease in the largest lesion (Fig. inallpatients,usingthedescribed WHOcriteria observed At theendofalltreatments,partialtumorresponsewas Disease statusduringthefollow-upperiod after TACE upto372 787 Plasma CEAlevelsbeforeTACE werealsoincreasedupto significantly decreasedandreached1803 range: 0–1.46 last TACE was38 months(range:8–126). achieved. Theoveralltimeto tumorprogressionsincethe due todiseaseprogression, and diseasestabilizationwas anotherTACEfor aperiodoftwoyears,underwent course experienced apartialresponse afterthefirst TACE cycle of tumormarkers.Onepatient(patientnumber1)who size of liver metastases or tothe decrease in the levels response toTACE wasunrelatedtothenumberand 19.5 reaching levelsof4615 Before thefirst TACE, CLT levelswereelevatedinallpatients Tumor markers pain, tiredness,flushingordiarrhea. and specificallyinsymptomsofweakness,abdominal patients, includingimprovementinthegeneralcondition, inallsymptomatic Clinical responsewasobserved Clinical response Response toTACE and 5 daysafterembolization. Pressolat (nifedipine).Hospitalizationlastedbetween3 to 190/110 (case 1) developed an increase in the blood pressure up that normalized/decreasedwithin7–30 transient, inparallelwiththeelevationofliverenzymes that wereusuallymildtomoderate(grade1–2)and symptoms (nausea,vomiting,abdominalpainandfever) (Table 2) adriamycin/lipiodol emulsion, followed by gelfoam. TACE wasperformed using theinjection of 50 followed bygelfoam,whereasintheothersixpatients, using 15 successful inallcases.Inonepatient,TACE wasperformed in MTC Liver chemoembolization ± After embolization,allpatientsexperiencedPESwith m (mean ± ± 13mm
702 mg ofmitomycin/lipiodolemulsioninjection ng/mL (normalrange:0–3 mmHg that resolved with treatment with pmol/L), whereasatlastfollow-up,CLT levels m (mean ± ± 18mm ± 543ng/mL. s ± .
d Downloaded fromBioscientifica.com at09/25/202101:28:21PM mlL (mean ± 3122pmol/L . , range:7–32 s . d . , range:13–60 ng/mL) and decreased ng/mL) anddecreased 176:4 days. Onepatient www.eje-online.org mm). Thetumor ± pmol/L. 1142pmol/L.
s . d . , normal , normal mm) to mg of 467 via freeaccess European Journal of Endocrinology
www.eje-online.org Table 3 Summary of the literature regarding trans-arterial liver embolization in patients with MTC. Clinical Study
Age at Mean survival since the No. of diagnosis Number of Tumor TTP months, last TACE (months) (mean) Reference patients F/M (%) (years) (mean) Disease-related symptoms TACE (range) Symptomatic response outcome mean (range) (range) (28) 1 M 54 Intractable diarrhea, abdominal 1 Yes PR Stable at UK pain 6 months (37) 1 M 54 Abdominal pain 1 – UK – Died as result of hypertensive crisis (29) 11 5F/6M 53 8/11 (diarrhea, abdominal pain, 6 (1–9) Yes, in all symptomatic 1 UK, 2 MR, 14 (4–48) 26 (1–72) general symptoms) patients 3 PR, 4 SD, 1 PD (27) 12 2F/10M 55 6/12 (5 diarrhea, 18 (1.5; 1–2) Yes, partially (2/5 patients 5 PR, 5 SD, 2 ≥16 UK 1 flushing) with diarrhea) PD Present study 7 5F/2M 64 5/7 (diarrhea, abdominal pain, 20 (2.8; 2–5) Yes, in all symptomatic 7 PR 38 (8–126) 57 (9–126) flushing, general symptoms) patients A IBloomandothers S Grozinsky-Glasberg, Total 32 12F/20M 56 21/32 (67% symptomatic) 46 Yes in most patients 2 UK, 2 MR, 18.5 28 16 PR, 9 SD, 3 PD
F, female; M, male; MR, minimal response; PD, progressive disease; PR, partial response; SD, stable disease; TACE, trans-arterial chemoembolization; TTP, time to tumor progression; UK, unknown. rate of4.77 patients died from progressive disease (an overall survival alive attheendoffollow-upperiod,whereasfour al 3). and withafavorableadverse eventsprofile(Table proliferative remission for prolonged lengths of time, liver metastases,inducing both symptomaticandanti- effective therapeuticoption forMTCpatientswith emphasizing thatTACE appearstobean extremely shorter duration(27). resulted in another partial tumor response, usually of patients could be offered repeated treatment, which often 30-mm in diameter. When disease progression occurred, of theliverinvolvedandwithmetastasessizelessthan results, withbestresponseinpatientslessthan30% of liverinvolvementwasthemainfactorthatinfluenced after asingleTACE cycleexceeding16 months. Theextent 42%, withadurationofpartialresponse and stabilization response occurredin42%,diseasestabilization patients withmetastaticMTC(27),apartialradiological in only6ofthem(55%)(29).Inanotherstudy12 all patients,withbiochemical and radiological responses with metastaticMTC,symptomaticresponsewasnotedin of diarrhea. there havebeennosignsoftumorregrowthorworsening tumors haddisappeared.Aftersixmonthsoffollow-up, arteriogram, tumorstainsindicatingthepresenceoflarge metastases werenolongerenhancing,andonhepatic post-treatment CTscandemonstratedthatthehepatic MTC, withintractablediarrheaandabdominalpain.The to liver metastases in a 54-year-old man with metastatic embolization followedbypercutaneous ethanolinjection first timethesuccessfuluseoftrans-catheterarterial 3).In1999,Isozaki (Table are scarce andlimited to casereportsandsmallseries rare patientswithMTCandprogressivelivermetastases disseminated metastases(22,3536). inefficient andrarelyadministeredinpatientswith hepatic metastases,whereaschemotherapyisusually ablation (RFA) is considered in patients with isolated both hepaticlobes.Surgicalresectionorradiofrequency carcinoma, whichisoftendisseminatedthroughout thyroid The liverisafrequentsiteformetastaticmedullary Discussion in MTC Liver chemoembolization Three out of the seven included patients were still Our presentseriesconfirmthepreviousdata, In a study of liver chemoembolization in 11 patients Data regardingtrans-arterialliverembolizationinthe ± 3.62 years).
Downloaded fromBioscientifica.com at09/25/202101:28:21PM t al.(28)reportedforthe et 176:4 468 via freeaccess European Journal of Endocrinology from retrospectivestudies,such asours. probably havetorelyonpersonal experienceanddata therefore, clinicianswhomanage thesepatientswillmost condition, theprobabilityfor suchtrialsisremote,and However,term survival. duetotheextremerarityofthis efficacy intermsoftimetotumorprogressionandlong- for TACE, fortreatmenttiming and forevaluatingits would beoptimalfordefinitionofthebestcandidates larger numberofMTCpatientswithlivermetastases, the presenceofextrahepaticmetastases. progression occursmainlyintheliver, andirrespectiveof for TACE shouldbethepatientsinwhomdisease factor determining prognosis, the appropriate candidates patients; asthedeteriorationinliverfunctionisamajor always beconsideredearlyinthetreatmentofthese tumor-sites progressionoccurs.However, TACE should kinases inhibitors,bisphosphonates,etc.)whenmultiple therefore, willrequiresystemictherapies(e.g.,tyrosine metastases tolymphnodes,bonesandotherorgans, the MTCpatientswithliverinvolvementwillalsohave with MEN2syndromesshouldberuledout(1).Mostof presence ofpossiblepheochromocytomasinpatients in terms of adequate renal and hepatic function, and the chemoembolization, patientsshouldbecarefullyevaluated therapies, such as tyrosine kinase inhibitors. Before postponing the use of systemic and more complex improving thequalityoflifethesepatientsand majority ofpatientswithMTC-relatedlivermetastases, tumor response for prolonged periods of time in the well tolerated,inducingbothclinicalimprovementand reasonable safetyprofile.Itappearsthat TACE isusually usually responds well to treatment with TACE, within a our dataareimportantastheyhighlightthatthedisease present studyisthesmallnumberofpatientsincluded, is ararecondition;althoughmajorlimitationofthe metastatic MTC. disease-related morbidity and mortality in patients with as liverinvolvementrepresentsamajorreasonfor related symptoms.Theseresultsareindeedimportant, well asnon-specific(weaknessandweightloss)tumor- both specific(diarrhea,flushingandabdominalpain)as symptomatic patients,withsignificantimprovementin years,whereassymptomaticreliefwasreportedinall 3 to tumorprogressionsincethelastTACE reachedabout involvement of up to 50%. Moreover, the median time 30 a beneficialeffectinbothsmallerbutalsolargerthan Noteworthy, inourpatientgroup,wehaveobserved Clinical Study mm lesionsandalso in patients with livermetastatic Prospective multicenterrandomizedstudies,including In summary, thyroidcarcinoma metastaticmedullary A IBloomandothers S Grozinsky-Glasberg, References the public,commercialornot-for-profit sector. This researchdidnotreceiveanyspecificgrantfromfundingagencyin Funding perceived asprejudicingtheimpartialityofresearchreported. The authorsdeclarethatthereisnoconflictofinterestcouldbe Declaration ofinterest
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