Treatment of metastatic differentiated thyroid cancer is first based on the use of radioiodine and thyrotropin-suppressive thyroid hormone treatment. The recent availability of molecular-targeted therapies has lead to reconsideration of the treatment strategy in differentiated thyroid cancer patients with distant metastases who are resistant to radioiodine therapy. In those with progressive disease, treatment with kinase inhibitors should be offered preferably in the context of a prospective trial.
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References
1.
SchlumbergerMJ, FilettiS, HayID. 2003. Non toxic goiter and thyroid neoplasia. LarsenRP, KronenbergHM, MelmedS, PolonskyKS. Williams' Textbook of Endocrinology, 10th. WB Saunders Company: Philadelphia, PA, 457–490.
2.
CooperDS, DohertyGM, HaugenBR, KloosRT, LeeSL, MandelSJ, MazzaferriEL, McIverB, PaciniF, SchlumbergerM, ShermanSI, StewardDL, TuttleRM. 2009. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid, 19:1167–1214.
3.
PaciniF, SchlumbergerM, DralleH, EliseiR, SmitJWA, WiersingaW. The European Thyroid Cancer Taskforce. 2006. European consensus for the management of patients with differentiated thyroid cancer of the follicular epithelium. Eur J Endocrinol, 154:787–803.
4.
LeboulleuxS, RubinoC, BaudinE, CaillouB, HartlDM, BidartJM, TravagliJP, SchlumbergerM. 2005. Prognostic factors for persistent or recurrent disease of papillary thyroid carcinoma with neck lymph node metastases and/or tumor extension beyond the thyroid capsule at initial diagnosis. J Clin Endocrinol Metab, 90:5723–5729.
5.
TubianaM, SchlumbergerM, RougierP, LaplancheA, BenhomouE, GardetP, CaillouB, TravagliJP, ParmentierC. 1985. Long-term results and prognostic factors in patients with differentiated thyroid carcinoma. Cancer, 55:794–804.
6.
RouxelA, HejblumG, BernierMO, BoellePY, MenegauxF, MansourG, HoangC, AurengoA, LeenhardtL. 2004. Prognostic factors associated with the survival of patients developing loco-regional recurrences of differentiated thyroid carcinomas. J Clin Endocrinol Metab, 89:5362–5368.
7.
KitamuraY, ShimizuK, NagahamaM, SuginoK, OzakiO, MimuraT, ItoK, ItoK, TanalaS. 1999. Immediate causes of death in thyroid carcinoma: clinicopathological analysis of 161 fatal cases. J Clin Endocrinol Metab, 84:4043–4049.
8.
Eustatia-RuttenCF, CorssmitEP, BiermaszNR, PereiraAM, RomijnJA, SmitJW. 2006. Survival and death causes in differentiated thyroid carcinoma. J Clin Endocrinol Metab, 91:313–319.
9.
DuranteC, HaddyN, BaudinE, LeboulleuxS, HartlD, TravagliJP, CaillouB, RicardM, LumbrosoJD, de VathaireF, SchlumbergerM. 2006. Long term outcome of 444 patients with distant metastases from papillary and follicular thyroid carcinoma: benefits and limits of radioiodine therapy. J Clin Endocrinol Metab, 91:2892–2899.
10.
CasaraD, RubelloD, SaladiniG, MasarottoG, FaveroA, GirelliME, BusnardoB. 1993. Different features of pulmonary metastases in differentiated thyroid cancer: natural history and multivariate statistical analysis of prognostic variables. J Nucl Med, 34:1626–1631.
11.
DinneenSF, ValimakiMJ, BergstralhEJ, GoellnerJR, GormanCA, HayID. 1995. Distant metastases in papillary thyroid carcinoma: 100 cases observed at one institution during 5 decades. J Clin Endocrinol Metab, 80:2041–2045.
12.
BiondiB, FilettiS, SchlumbergerM. 2005. Thyroid-hormone therapy and thyroid cancer: a reassessment. Nat Clin Pract Endocrinol Metab, 1:32–40.
13.
JonklaasJ, SarlisNJ, LitofskyD, AinKB, BigosST, BrierleyJD, CooperDS, HaugenBR, LadensonPW, MagnerJ, RobbinsJ, RossDS, SkarulisM, MaxonHR, ShermanSI. 2006. Outcomes of patients with differentiated thyroid carcinoma following initial therapy. Thyroid, 16:1229–1242.
14.
TravagliJP, CailleuxAF, RicardM, BaudinE, CaillouB, ParmentierC, SchlumbergerM. 1998. Combination of radio-iodine (131I) and probe-guided surgery for persistent or recurrent thyroid carcinoma. J Clin Endocrinol Metab, 83:2675–2680.
15.
BernierMO, LeenhardtL, HoangC, AurengoA, MaryJY, MenegauxF, EnkaouaE, TurpinG, ChirasJ, SaillantG, HejblumG. 2001. Survival and therapeutic modalities in patients with bone metastases of differentiated thyroid carcinomas. J Clin Endocrinol Metab, 86:1568–1573.
16.
ShermanSI. 2009. Advances in chemotherapy of differentiated epithelial and medullary thyroid cancers. J Clin Endocrinol Metab, 94:1493–1499.
17.
TherasseP, ArbuckSG, EisenhauerEA, WandersJ, KaplanRS, RubinsteinL, VerweijJ, van GlabbekeM, van OosteromAT, ChristianMC, GwytherSG. 2000. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst, 92:205–216.
ShimaokaK, SchoenfeldDA, de WysWD, CreechRH, de ContiRA. 1985. Randomized trial of Doxorubicin versus Doxorubicin plus Cisplatin in patients with advanced thyroid carcinoma. Cancer, 56:2155–2160.
20.
WilliamsSD, BirchR, EinhornLH. 1986. Phase II evaluation of Doxorubicin plus Cisplatin in advanced thyroid cancer: a Southeastern Cancer Study Group Trial. Cancer Treat Rep, 70:405–407.
21.
DrozJP, SchlumbergerM, RougierP, GhosnM, GardetP, ParmentierC. 1990. Chemotherapy in metastatic nonanaplastic thyroid cancer: experience at the Institut Gustave-Roussy. Tumori, 76:480–483.
22.
SantiniF, BotticiV, EliseiR, MontanelliL, MazzeoS, BasoloF, PincheraA, PaciniF. 2002. Cytotoxic effects of carboplatinum and epirubicin in the setting of an elevated serum thyrotropin for advanced poorly differentiated thyroid cancer. J Clin Endocrinol Metab, 87:4160–4165.
23.
FaginJA. 2004. How thyroid tumors start and why it matters: kinase mutants as targets for solid cancer pharmacotherapy. J Endocrinol, 183:249–256.
FelsherDW. 2008. Oncogene addiction versus oncogene amnesia: perhaps more than just a bad habit?Cancer Res, 68:3081–3086.
26.
RingelMD, HayreN, SaitoJ, SaunierB, SchuppertF, BurchH, BernetV, BurmanKD, KohnLD, SajiM. 2001. Overexpression and overactivation of Akt in thyroid carcinoma. Cancer Res, 61:6105–6111.
27.
BruniP, BocciaA, BaldassarreG, TrapassoF, SantoroM, ChiappettaG, FuscoA, VigliettoG. 2000. PTEN expression is reduced in a subset of sporadic thyroid carcinomas: evidence that PTEN-growth suppressing activity in thyroid cancer cells mediated by p27kip1. Oncogene, 19:3146–3155.
28.
Ricarte-FilhoJC, RyderM, ChitaleDA, RiveraM, HeguyA, LadanyM, JanakiramenM, SolitD, KnaufJA, TuttleRA, GhosseinRA, FaginJA. 2009. Mutational profile of advanced primary and metastatic radioactive iodine-refractory thyroid cancers reveals distinct pathogenetic roles for BRAF, PIK3CA, and AKT1. Cancer Res, 69:4885–4893.
29.
FaginJA, MatsuoK, KarmakarA, ChenDL, TangSH, KoefflerHP. 1993. High prevalence of mutations of the p53 gene in poorly differentiated human thyroid carcinomas. J Clin Invest, 91:179–184.
30.
García-RostánG, CostaAM, Pereira-CastroI, SalvatoreG, HernandezR, HermsemMJ, HerreroA, FuscoA, Cameselle-TeijeiroJ, SantoroM. 2005. Mutation of the PIK3CA gene in anaplastic thyroid cancer. Cancer Res, 65:10199–10207.
31.
WuG, MamboE, GuoZ, HuS, HuangX, GollinSM, TrinkB, LadensonPW, SidranskyD, XingM. 2005. Uncommon mutation, but common amplifications, of the PIK3CA gene in thyroid tumors. J Clin Endocrinol Metab, 90:4688–4693.
32.
SantarpiaL, El-NaggarAK, CoteGJ, MyersJN, ShermanSI. 2008. Phosphatidylinositol 3-kinase/Akt and RAS/RAF-mitogen-activated protein kinase pathway mutations in anaplastic thyroid cancer. J Clin Endocrinol Metab, 93:278–284.
33.
BunoneG, VigneriP, MarianiL, ButoS, ColliniP, PilottiS, PierottiMA, BongarzoneI. 1999. Expression of angiogenesis stimulators and inhibitors in human thyroid tumors and correlation with pathological features. Am J Pathol, 155:1967–1976.
34.
KleinM, VignaudJM, HennequinV, ToussaintB, BreslerL, PlenatF, LeclereJ, DuprezA, WeryhaG. 2001. Increased expression of the vascular endothelial growth factor is a pejorative prognosis marker in papillary thyroid carcinoma. J Clin Endocrinol Metab, 86:656–658.
35.
de la TorreNG, BuleyI, WassJA, TurnerHE. 2006. Angiogenesis and lymphangiogenesis in thyroid proliferative lesions: relationship to type and tumour behaviour. Endocr Relat Cancer, 13:931–944.
KrauseDS, van EttenRA. 2005. Tyrosine kinase as targets for cancer therapy. N Engl J Med, 353:172–187.
38.
SantoroM, CarlomagnoF. 2006. Drug insight: small molecules inhibitors of protein kinases in the treatment of thyroid cancer. Nat Clin Pract Endocrinol Metab, 2:42–52.
HoftijzerH, HeemstraK, MorreauH, StokkelM, CorssmitE, GelderblomAJ, WeijersK, PereiraA, HuijbertsM, KapiteijnE, RomijnJ, SmitJ. 2009. Beneficial effects of sorafenib on tumor progression, but not on radioiodine uptake, in patients with differentiated thyroid carcinoma. Eur J Endocrinol, 161:923–931.
43.
CohenEE, RosenLS, VokesEE, KiesMS, ForastiereAA, WordenFP, KaneMA, ShermanE, KimS, BycottP, TortoriciM, ShalinskyDR, LiauKF, CohenRB. 2008. Axitinib is an active treatment for all histologic subtypes of advanced thyroid cancer: results from a phase II study. J Clin Oncol, 26:4708–4713.
44.
CohenEE, NeedlesBM, CullenKJ, WongSJ, WadeJL, IvySP, VillaflorVM, SiewertTy, NicholsK, VokesEE. 2008. Phase 2 study of sunitinib in refractory thyroid cancer. J Clin Oncol, 26 Supplabstract 6025.
45.
BibleKC, SmallridgeRC, MaplesWJ, MolinaJR, MenefeeME, SumanVJ, BurtonJK, BieberCC, IvySP, ErlichmanC. 2009. Phase II trial of pazopanib in progressive, metastatic, iodine-insensitive differentiated thyroid cancers. J Clin Oncol, 27 Suppl:15sabstract 3521.
46.
PaciniF, ShermanSI, SchlumbergerM, EliseiR, WirthL, BasholtL, DrozJP, MartinsR, HofmannM, LocatiL, EschenbergM, StepanD. 2007. Exacerbation of postsurgical hypothyroidism during treatment of advanced differentiated (DTC) or medullary (MTC) thyroid carcinoma with AMG 706. Horm Res, 68,Suppl 3:29.
47.
CabanillasME, WaguespackSG, BronsteinY, WilliamsM, FengL, ShermanSI, BusaidyNL. 2009. Treatment (tx) with tyrosine kinase inhibitors (TKIs) for patients (pts) with differentiated thyroid cancer (DTC): the M. D. Anderson Cancer Center (MDACC) experience. J Clin Oncol, 27 Suppl:15sabstract 6060.
48.
ShermanSI. 2009. NCCN practice guidelines for thyroid cancer, version 2009a. www.nccn.org. 2009 June 1.
49.
SchlumbergerM, LacroixL, RussoD, FilettiS, BidartJM. 2007. Defects in iodide metabolism in thyroid cancer and implications for the follow-up and treatment of patients. Nat Clin Pract Endocrinol Metab, 3:260–269.
50.
GruningT, TiepoltC, ZophelK, BredowJ, KroppJ, FrankeWG. 2003. Retinoic acid for redifferentiation of thyroid cancer—does it hold its promise?Eur J Endocrinol, 148:395–402.
51.
LiuYY, StokkelMP, MorreauHA, PereiraAM, RomijnJA, SmitJW. 2008. Radioiodine therapy after pretreatment with bexarotene for metastases of differentiated thyroid carcinoma. Clin Endocrinol (Oxf ), 68:605–609.
52.
SuYB, TuttleRM, FuryM, GhosseinR, SinghB, HermanR, VenkatramanES, StambukH, RobbinsR, PfisteDG. 2006. A phase II study of single agent depsipeptide (DEP) in patients (pts) with radioactive iodine (RAI)-refractory, metastatic, thyroid carcinoma: preliminary toxicity and efficacy experience. J Clin Oncol (ASCO Annu Meet Proc Part I), 24,18S Suppl:5554.
53.
KebebewE, PengM, ReiffE, TreselerP, WoeberKA, ClarkOH, GreenspanFS, LindsayS, DuhQY, MoritaE. 2006. A phase II trial of rosiglitazone in patients with thyroglobulin-positive and radioiodine-negative differentiated thyroid cancer. Surgery, 140:960–966discussion 966–967.
54.
ItoS, KatoK, IkedaM, IwanoS, MakinoN, TadokoroM, AbeS, NakanoS, NishinoM, IshigakiT, NaganawaS. 2007. Comparison of 18F-FDG PET and bone scintigraphy in detection of bone metastases of thyroid cancer. J Nucl Med, 48:889–895.
55.
LeboulleuxS, SchroederPR, SchlumbergerM, LadensonPW. 2007. The role of PET in follow-up of patients treated for differentiated epithelial thyroid cancers. Nat Clin Pract Endocrinol Metab, 3:112–121.
56.
SargentDJ, RubinsteinL, SchwartzL, DanceyJE, GatsonisC, DoddLE, ShankarLK. 2009. Validation of novel imaging methodologies for use as cancer clinical trial end-points. Eur J Cancer, 45:290–299.
57.
HedingerC, WilliamsED, SobinLH. Histological typing of thyroid tumours. International Histological Classification of Tumours. World Health Organization, 1988; 11second. Springer-Verlag: Berlin.
58.
VolanteM, RapaI, PapottiM. 2008. Poorly differentiated thyroid carcinoma: diagnostic features and controversial issues. Endocr Pathol, 19:150–155.
59.
BuyseM, BurzykowskiT, CarrollK, MichielsS, SargentDJ, MillerLL, ElfringGl, PignonJP, PiedboisP. 2007. Progression-free survival is a surrogate for survival in advanced colorectal cancer. J Clin Oncol, 25:5218–5224.
60.
BuyseM, ThirionP, CarlsonRW, BurzykowskiT, MolenberghsG, PiedboisP. 2000. Relation between tumour response to first-line chemotherapy and survival in advanced colorectal cancer: a meta-analysis. Meta-Analysis Group in Cancer. Lancet, 356:373–378.
61.
FlemingTR, RothmannMD, LuHL. 2009. Issues in using progression-free survival when evaluating oncology products. J Clin Oncol, 27:2874–2880.
62.
RatainMJ, SargentDJ. 2009. Optimising the design of phase II oncology trials: the importance of randomisation. Eur J Cancer, 45:275–280.
63.
GningI, TraskPC, MendozaTR, HarleMT, GutierrezKA, KitakaSA, ShermanSI, CleelandCS. 2009. Development and initial validation of the thyroid cancer module of the M. D. Anderson Symptom Inventory. Oncology, 76:59–68.
64.
Pàez-RibesM, AllenE, HudockJ, TakedaT, OkuyamaH, VinalsF, InoueM, BergersG, HanahanD, CasanovasO. 2009. Antiangiogenic therapy elicits malignant progression of tumors to increased local invasion and distant metastasis. Cancer Cell, 15:220–231.
65.
EbosJM, LeeCR, Cruz-MunozW, BjarnasonGA, ChristensenJG, KerbelRS. 2009. Accelerated metastasis after short-term treatment with a potent inhibitor of tumor angiogenesis. Cancer Cell, 15:232–239.
