Progress in molecular-based management of differentiated thyroid cancer

The Lancet

Volumn 381, Issue 9871, 2013, Pages 1058-1069

  Xing, Mingzhao ^a   Haugen, Bryan R ^b   Schlumberger, Martin ^c  

^a JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF COLORADO SCHOOL OF MEDICINE   (United States)

^c UNIVERSITÉ PARIS SACLAY   (France)

Author keywords

[No Author keywords available]

Indexed keywords

B RAF KINASE; CABOZANTINIB; FLUORODEOXYGLUCOSE; LENVATINIB; LEVOTHYROXINE; MOLECULAR MARKER; PAZOPANIB; PROTEIN P53; PROTEIN RET; RADIOACTIVE IODINE; RAS PROTEIN;

ARTICLE; CANCER PROGNOSIS; CANCER STAGING; CANCER SURVIVAL; DIARRHEA; DIFFERENTIATED THYROID CANCER; DISEASE COURSE; DRUG EFFICACY; FATIGUE; FINE NEEDLE ASPIRATION BIOPSY; GENE EXPRESSION; GENE MUTATION; GENE REARRANGEMENT; GENETIC ASSOCIATION; HUMAN; HYPERTENSION; MOLECULARLY TARGETED THERAPY; POSITRON EMISSION TOMOGRAPHY; PREDICTIVE VALUE; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; SENSITIVITY AND SPECIFICITY; SKIN TOXICITY; THYROID NODULE; TREATMENT DURATION; TREATMENT RESPONSE;

EID: 84875295216     PISSN: 01406736     EISSN: 1474547X     Source Type: Journal    
DOI: 10.1016/S0140-6736(13)60109-9     Document Type: Review

References (128)

1. Howlader N, Noone AM, Krapcho M, et al. SEER cancer statistics review, 1975-2009 (vintage 2009 populations). Data from November, 2011, posted online April, 2012. http://seer.cancer.gov/csr/1975-2009-pops09/(accessed Jan 15, 2013).
2. Hundahl SA, Fleming ID, Fremgen AM, et al. A National Cancer Data Base report on 53, 856 cases of thyroid carcinoma treated in the US, 1985-1995. Cancer 1998; 83: 2638-48.
3. Leenhardt L, Grosclaude P, Cherie-Challine L. Increased incidence of thyroid carcinoma in France: a true epidemic or thyroid nodule management effects? Report from the French Thyroid Cancer Committee. Thyroid 2004; 14: 1056-60.
4. Sprague BL, Warren AS, Trentham-Dietz A. Thyroid cancer incidence and socioeconomic indicators of health care access. Cancer Causes Control 2008; 19: 585-93.
5. Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA Cancer J Clin 2011; 61: 69-90.
6. Mazzaferri EL. Management of a solitary thyroid nodule. N Engl J Med 1993; 328: 553-59.
7. Guth S, Theune U, Aberle J, et al. Very high prevalence of thyroid nodules detected by high frequency (13 MHz) ultrasound examination. Eur J Clin Invest 2009; 39: 699-706.
8. Cooper DS, Doherty GM, Haugen BR, et al. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 2009; 19: 1167-214.
9. Smallridge RC, Copland JA. Anaplastic thyroid carcinoma: pathogenesis and emerging therapies. Clin Oncol (R Coll Radiol) 2010; 22: 486-97.
10. Brown RL, de Souza JA, Cohen EE. Thyroid cancer: burden of illness and management of disease. J Cancer 2011; 2: 193-99.
11. Mazzaferri EL, Jhiang SM. Long-term impact of initial surgical and medical therapy on papillary and follicular thyroid cancer. Am J Med 1994; 97: 418-28.
12. McLeod DSA, Sawka AM, Cooper DS. Controversies in primary treatment of low-risk papillary thyroid cancer. Lancet 2013; 381: 1046-57.
13. Xing M. Molecular pathogenesis and mechanisms of thyroid cancer. Nat Rev Cancer 2013; 13: 184-99.
14. Wang CC, Friedman L, Kennedy GC, et al. A large multicenter correlation study of thyroid nodule cytopathology and histopathology. Thyroid 2011; 21: 243-51.
15. Baloch ZW, LiVolsi VA, Asa SL, et al. Diagnostic terminology and morphologic criteria for cytologic diagnosis of thyroid lesions: a synopsis of the National Cancer Institute Thyroid Fine-Needle Aspiration State of the Science Conference. Diagn Cytopathol 2008; 36: 425-37.
16. Theoharis C, Roman S, Sosa JA. The molecular diagnosis and management of thyroid neoplasms. Curr Opin Oncol 2012; 24: 35-41.
17. Yang J, Schnadig V, Logrono R, et al. Fine-needle aspiration of thyroid nodules: a study of 4703 patients with histologic and clinical correlations. Cancer 2007; 111: 306-15.
18. Williams MD, Suliburk JW, Staerkel GA, et al. Clinical significance of distinguishing between follicular lesion and follicular neoplasm in thyroid fine-needle aspiration biopsy. Ann Surg Oncol 2009;16: 3146-53.
19. Nikiforov YE, Steward DL, Robinson-Smith TM, et al. Molecular testing for mutations in improving the fine-needle aspiration diagnosis of thyroid nodules. J Clin Endocrinol Metab 2009; 94: 2092-98.
20. Nikiforov YE, Ohori NP, Hodak SP, et al. Impact of mutational testing on the diagnosis and management of patients with cytologically indeterminate thyroid nodules: a prospective analysis of 1056 FNA samples. J Clin Endocrinol Metab 2011; 96: 3390-97.
21. Ferraz C, Eszlinger M, Paschke R. Current state and future perspective of molecular diagnosis of fine-needle aspiration biopsy of thyroid nodules. J Clin Endocrinol Metab 2011; 96: 2016-26.
22. de la Chapelle A, Jazdzewski K. MicroRNAs in thyroid cancer. J Clin Endocrinol Metab 2011; 96: 3326-36.
23. Kouniavsky G, Zeiger MA. The quest for diagnostic molecular markers for thyroid nodules with indeterminate or suspicious cytology. J Surg Oncol 2012; 105: 438-43.
24. Milas M, Shin J, Gupta M, et al. Circulating thyrotropin receptor mRNA as a novel marker of thyroid cancer: clinical applications learned from 1758 samples. Ann Surg 2010; 252: 643-51.
25. Bartolazzi A, Orlandi F, Saggiorato E, et al. Galectin-3-expression analysis in the surgical selection of follicular thyroid nodules with indeterminate fine-needle aspiration cytology: a prospective multicentre study. Lancet Oncol 2008; 9: 543-49.
26. Alexander EK, Kennedy GC, Baloch ZW, et al. Preoperative diagnosis of benign thyroid nodules with indeterminate cytology. N Engl J Med 2012; 367: 705-15.
27. Moses W, Weng J, Sansano I, et al. Molecular testing for somatic mutations improves the accuracy of thyroid fine-needle aspiration biopsy. World J Surg 2010; 34: 2589-94.
28. Faroux MJ, Theobald S, Pluot M, et al. Evaluation of the monoclonal antibody antithyroperoxidase MoAb47 in the diagnostic decision of cold thyroid nodules by fine-needle aspiration. Pathol Res Pract 1997; 193: 705-12.
29. Umbricht CB, Conrad GT, Clark DP, et al. Human telomerase reverse transcriptase gene expression and the surgical management of suspicious thyroid tumors. Clin Cancer Res 2004; 10: 5762-68.
30. Saggiorato E, De Pompa R, Volante M, et al. Characterization of thyroid 'follicular neoplasms' in fine-needle aspiration cytological specimens using a panel of immunohistochemical markers: a proposal for clinical application. Endocr Relat Cancer 2005; 12: 305-17.
31. Franco C, Martinez V, Allamand JP, et al. Molecular markers in thyroid fine-needle aspiration biopsy: a prospective study. Appl Immunohistochem Mol Morphol 2009; 17: 211-15.
32. Samija I, Matesa N, Lukac J, et al. Galectin-3 and CD44v6 as markers for preoperative diagnosis of thyroid cancer by RT-PCR. Diagn Mol Pathol 2011; 20: 233-41.
33. Fadda G, Rossi ED, Raffaelli M, et al. Follicular thyroid neoplasms can be classified as low-and high-risk according to HBME-1 and Galectin-3 expression on liquid-based fine-needle cytology. Eur J Endocrinol 2011; 165: 447-53.
34. Shen R, Liyanarachchi S, Li W, et al. MicroRNA signature in thyroid fine needle aspiration cytology applied to "atypia of undetermined significance" cases. Thyroid 2012; 22: 9-16.
35. Keutgen XM, Filicori F, Crowley MJ, et al. A panel of four miRNAs accurately differentiates malignant from benign indeterminate thyroid lesions on fine needle aspiration. Clin Cancer Res 2012; 18: 2032-38.
36. Agretti P, Ferrarini E, Rago T, et al. MicroRNA expression profile helps to distinguish benign nodules from papillary thyroid carcinomas starting from cells of fine-needle aspiration. Eur J Endocrinol 2012; 167: 393-400.
37. Rossi M, Buratto M, Bruni S, et al. Role of ultrasonographic/clinical profile, cytology, and BRAF V600E mutation evaluation in thyroid nodule screening for malignancy: a prospective study. J Clin Endocrinol Metab 2012; 97: 2354-61.
38. Chudova D, Wilde JI, Wang ET, et al. Molecular classification of thyroid nodules using high-dimensionality genomic data. J Clin Endocrinol Metab 2010; 95: 5296-304.
39. Cantara S, Capezzone M, Marchisotta S, et al. Impact of proto-oncogene mutation detection in cytological specimens from thyroid nodules improves the diagnostic accuracy of cytology. J Clin Endocrinol Metab 2010; 95: 1365-69.
40. Guerra A, Sapio MR, Marotta V, et al. Prevalence of RET/PTC rearrangement in benign and malignant thyroid nodules and its clinical application. Endocr J 2011; 58: 31-38.
41. Li H, Robinson KA, Anton B, et al. Cost-effectiveness of a novel molecular test for cytologically indeterminate thyroid nodules. J Clin Endocrinol Metab 2011; 96: E1719-26.
42. Yip L, Farris C, Kabaker AS, et al. Cost impact of molecular testing for indeterminate thyroid nodule fine-needle aspiration biopsies. J Clin Endocrinol Metab 2012; 97: 1905-12.
43. Fagin JA, Matsuo K, Karmakar A, et al. High prevalence of mutations of the p53 gene in poorly differentiated human thyroid carcinomas. J Clin Invest 1993; 91: 179-84.
44. Donghi R, Longoni A, Pilotti S, et al. Gene p53 mutations are restricted to poorly differentiated and undifferentiated carcinomas of the thyroid gland. J Clin Invest 1993; 91: 1753-60.
45. Murugan AK, Xing M. Anaplastic thyroid cancers harbor novel oncogenic mutations of the ALK gene. Cancer Res 2011;71: 4403-11.
46. Ricarte-Filho JC, Ryder M, Chitale DA, et al. Mutational profile of advanced primary and metastatic radioactive iodine-refractory thyroid cancers reveals distinct pathogenetic roles for BRAF, PIK3CA, and AKT1. Cancer Res 2009; 69: 4885-93.
47. Hou P, Liu D, Shan Y, et al. Genetic alterations and their relationship in the phosphatidylinositol 3-kinase/Akt pathway in thyroid cancer. Clin Cancer Res 2007; 13: 1161-70.
48. Liu Z, Hou P, Ji M, et al. Highly prevalent genetic alterations in receptor tyrosine kinases and phosphatidylinositol 3-kinase/akt and mitogen-activated protein kinase pathways in anaplastic and follicular thyroid cancers. J Clin Endocrinol Metab 2008;93: 3106-16.
49. Fukahori M, Yoshida A, Hayashi H, et al. The association between RAS gene mutations and clinical characteristics in follicular thyroid tumors: new insights from a single center and a large patient cohort. Thyroid 2012; 22: 683-89.
50. Garcia-Rostan G, Zhao H, Camp RL, et al. ras mutations are associated with aggressive tumor phenotypes and poor prognosis in thyroid cancer. J Clin Oncol 2003; 21: 3226-35.
51. Volante M, Rapa I, Gandhi M, et al. RAS mutations are the predominant molecular alteration in poorly differentiated thyroid carcinomas and bear prognostic impact. J Clin Endocrinol Metab 2009; 94: 4735-41.
52. Kim TH, Park YJ, Lim JA, et al. The association of the BRAF(V600E) mutation with prognostic factors and poor clinical outcome in papillary thyroid cancer: a meta-analysis. Cancer 2012; 118: 1764-73.
53. Xing M, Westra WH, Tufano RP, et al. BRAF mutation predicts a poorer clinical prognosis for papillary thyroid cancer. J Clin Endocrinol Metab 2005; 90: 6373-79.
54. Xing M. BRAF mutation in papillary thyroid cancer: pathogenic role, molecular bases, and clinical implications. Endocr Rev 2007; 28: 742-62.
55. Xing M. Prognostic utility of BRAF mutation in papillary thyroid cancer. Mol Cell Endocrinol 2010; 321: 86-93.
56. Nikiforova MN, Nikiforov YE. Molecular diagnostics and predictors in thyroid cancer. Thyroid 2009; 19: 1351-61.
57. Tufano RP, Bishop J, Wu G. Reoperative central compartment dissection for patients with recurrent/persistent papillary thyroid cancer: efficacy, safety, and the association of the BRAF mutation. Laryngoscope 2012; 122: 1634-40.
58. Basolo F, Torregrossa L, Giannini R, et al. Correlation between the BRAF V600E mutation and tumor invasiveness in papillary thyroid carcinomas smaller than 20 millimeters: analysis of 1060 cases. J Clin Endocrinol Metab 2010; 95: 4197-205.
59. V600E mutation is an independent, poor prognostic factor for the outcome of patients with low-risk intrathyroid papillary thyroid carcinoma: single-institution results from a large cohort study. J Clin Endocrinol Metab 2012; 97: 4390-98.
60. Kebebew E, Weng J, Bauer J, et al. The prevalence and prognostic value of BRAF mutation in thyroid cancer. Ann Surg 2007; 246: 466-70.
61. Kim TY, Kim WB, Rhee YS, et al. The BRAF mutation is useful for prediction of clinical recurrence in low-risk patients with conventional papillary thyroid carcinoma. Clin Endocrinol (Oxf) 2006; 65: 364-68.
62. Abubaker J, Jehan Z, Bavi P, et al. Clinicopathological analysis of papillary thyroid cancer with PIK3CA alterations in a Middle Eastern population. J Clin Endocrinol Metab 2008; 93: 611-18.
63. Elisei R, Ugolini C, Viola D, et al. BRAF(V600E) mutation and outcome of patients with papillary thyroid carcinoma: a 15-year median follow-up study. J Clin Endocrinol Metab 2008;93: 3943-49.
64. Riesco-Eizaguirre G, Gutierrez-Martinez P, Garcia-Cabezas MA, et al. The oncogene BRAF V600E is associated with a high risk of recurrence and less differentiated papillary thyroid carcinoma due to the impairment of Na+/I-targeting to the membrane. Endocr Relat Cancer 2006; 13: 257-69.
65. Xing M, Clark D, Guan H, et al. BRAF mutation testing of thyroid fine-needle aspiration biopsy specimens for preoperative risk stratification in papillary thyroid cancer. J Clin Oncol 2009;27: 2977-82.
66. Yip L, Nikiforova MN, Carty SE, et al. Optimizing surgical treatment of papillary thyroid carcinoma associated with BRAF mutation. Surgery 2009; 146: 1215-23.
67. O'Neill CJ, Bullock M, Chou A, et al. BRAF(V600E) mutation is associated with an increased risk of nodal recurrence requiring reoperative surgery in patients with papillary thyroid cancer. Surgery 2010; 148: 1139-45.
68. Prescott JD, Sadow PM, Hodin RA, et al. BRAF(V600E) status adds incremental value to current risk classification systems in predicting papillary thyroid carcinoma recurrence. Surgery 2012; 152: 984-90.
69. Barollo S, Pennelli G, Vianello F, et al. BRAF in primary and recurrent papillary thyroid cancers: the relationship with (131)I and 2-[(18)F]fluoro-2- deoxy-D-glucose uptake ability. Eur J Endocrinol 2010; 163: 659-63.
70. Mian C, Barollo S, Pennelli G, et al. Molecular characteristics in papillary thyroid cancers (PTCs) with no 131I uptake. Clin Endocrinol (Oxf) 2008; 68: 108-16.
71. Liu D, Hu S, Hou P, et al. Suppression of BRAF/MEK/MAP kinase pathway restores expression of iodide-metabolizing genes in thyroid cells expressing the V600E BRAF mutant. Clin Cancer Res 2007; 13: 1341-49.
72. Chakravarty D, Santos E, Ryder M, et al. Small-molecule MAPK inhibitors restore radioiodine incorporation in mouse thyroid cancers with conditional BRAF activation. J Clin Invest 2011; 121: 4700-11.
73. V600E mutation and mortality in patients with papillary thyroid cancer. JAMA (in press).
74. Noguchi S, Yamashita H, Uchino S, Watanabe S. Papillary microcarcinoma. World J Surg 2008; 32: 747-53.
75. Xing M, Tufano RP, Tufaro AP, et al. Detection of BRAF mutation on fine needle aspiration biopsy specimens: a new diagnostic tool for papillary thyroid cancer. J Clin Endocrinol Metab 2004;89: 2867-72.
76. Henderson YC, Shellenberger TD, Williams MD, et al. High rate ofBRAF and RET/PTC dual mutations associated with recurrent papillary thyroid carcinoma. Clin Cancer Res 2009; 15: 485-91.
77. Popadich A, Levin O, Lee JC, et al. A multicenter cohort study of total thyroidectomy and routine central lymph node dissection for cN0 papillary thyroid cancer. Surgery 2011; 150: 1048-57.
78. Joo J Y, Park JY, Yoon YH, et al. Prediction of occult central lymph node metastasis in papillary thyroid carcinoma by preoperative BRAF analysis using fine-needle aspiration biopsy: a prospective study. J Clin Endocrinol Metab 2012; 97: 3996-4003.
79. Lin KL, Wang OC, Zhang XH, et al. The BRAF mutation is predictive of aggressive clinicopathological characteristics in papillary thyroid microcarcinoma. Ann Surg Oncol 2010; 17: 3294-300.
80. Pelizzo MR, Boschin IM, Barollo S, et al. BRAF analysis by fine needle aspiration biopsy of thyroid nodules improves preoperative identification of papillary thyroid carcinoma and represents a prognostic factor. A mono-institutional experience. Clin Chem Lab Med 2011; 49: 325-29.
81. V600E mutation in defining CND. Endocr Relat Cancer 2012; 20: 13-22.
82. Howell GM, Nikiforova MN, Carty SE, et al. BRAF V600E mutation independently predicts central compartment lymph node metastasis in patients with papillary thyroid cancer. Ann Surg Oncol 2013; 20: 47-52.
83. Brown AP, Chen J, Hitchcock YJ, et al. The risk of second primary malignancies up to three decades after the treatment of differentiated thyroid cancer. J Clin Endocrinol Metab 2008; 93: 504-15.
84. Fallahi B, Adabi K, Majidi M, et al. Incidence of second primary malignancies during a long-term surveillance of patients with differentiated thyroid carcinoma in relation to radioiodine treatment. Clin Nucl Med 2011; 36: 277-82.
85. Lang BH, Wong IO, Wong KP, et al. Risk of second primary malignancy in differentiated thyroid carcinoma treated with radioactive iodine therapy. Surgery 2012; 151: 844-50.
86. Rubino C, de Vathaire F, Dottorini ME, et al. Second primary malignancies in thyroid cancer patients. Br J Cancer 2003; 89: 1638-44.
87. Hay ID, Hutchinson ME, Gonzalez-Losada T, et al. Papillary thyroid microcarcinoma: a study of 900 cases observed in a 60-year period. Surgery 2008; 144: 980-87.
88. Sawka AM, Brierley JD, Tsang RW, et al. An updated systematic review and commentary examining the effectiveness of radioactive iodine remnant ablation in well-differentiated thyroid cancer. Endocrinol Metab Clin North Am 2008; 37: 457-80.
89. Sacks W, Fung CH, Chang JT, et al. The effectiveness of radioactive iodine for treatment of low-risk thyroid cancer: a systematic analysis of the peer-reviewed literature from 1966 to April 2008. Thyroid 2010; 20: 1235-45.
90. Jonklaas J, Cooper DS, Ain KB, et al. Radioiodine therapy in patients with stage I differentiated thyroid cancer. Thyroid 2010; 20: 1423-24.
91. Schvartz C, Bonnetain F, Dabakuyo S, et al. Impact on overall survival of radioactive iodine in low-risk differentiated thyroid cancer patients. J Clin Endocrinol Metab 2012; 97: 1526-35.
92. Durante C, Montesano T, Attard M, et al. Long-term surveillance of papillary thyroid cancer patients who do not undergo postoperative radioiodine remnant ablation: is there a role for serum thyroglobulin measurement? J Clin Endocrinol Metab 2012; 97: 2748-53.
93. Mallick U, Harmer C, Yap B, et al. Ablation with low-dose radioiodine and thyrotropin alfa in thyroid cancer. N Engl J Med 2012; 366: 1674-85.
94. Schlumberger M, Catargi B, Borget I, et al. Strategies of radioiodine ablation in patients with low-risk thyroid cancer. N Engl J Med 2012; 366: 1663-73.
95. Schlumberger M. Management of refractory thyroid cancers. Ann Endocrinol (Paris) 2011; 72: 149-57.
96. Durante C, Haddy N, Baudin E, et al. 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 2006; 91: 2892-99.
97. Robbins RJ, Wan Q, Grewal RK, et al. Real-time prognosis for metastatic thyroid carcinoma based on 2-[18F]fluoro-2-deoxy-D-glucose-positron emission tomography scanning. J Clin Endocrinol Metab 2006; 91: 498-505.
98. Miyauchi A, Kudo T, Miya A, et al. Prognostic impact of serum thyroglobulin doubling-time under thyrotropin suppression in patients with papillary thyroid carcinoma who underwent total thyroidectomy. Thyroid 2011; 21: 707-16.
99. Deandreis D, Al GA, Leboulleux S, et al. Do histological, immunohistochemical, and metabolic (radioiodine and fluorodeoxyglucose uptakes) patterns of metastatic thyroid cancer correlate with patient outcome? Endocr Relat Cancer 2011; 18: 159-69.
100. Carr LL, MankoffDA, Goulart BH, et al. Phase II study of daily sunitinib in FDG-PET-positive, iodine-refractory differentiated thyroid cancer and metastatic medullary carcinoma of the thyroid with functional imaging correlation. Clin Cancer Res 2010; 16: 5260-68.
101. Sherman SI. Cytotoxic chemotherapy for differentiated thyroid carcinoma. Clin Oncol (R Coll Radiol) 2010; 22: 464-68.
102. Fagin JA. How thyroid tumors start and why it matters: kinase mutants as targets for solid cancer pharmacotherapy. J Endocrinol 2004; 183: 249-56.
103. Ringel MD, Hayre N, Saito J, et al. Overexpression and overactivation of Akt in thyroid carcinoma. Cancer Res 2001; 61: 6105-11.
104. Xing M. Genetic alterations in the phosphatidylinositol-3 kinase/Akt pathway in thyroid cancer. Thyroid 2010; 20: 697-706.
105. Bunone G, Vigneri P, Mariani L, et al. Expression of angiogenesis stimulators and inhibitors in human thyroid tumors and correlation with clinical pathological features. Am J Pathol 1999; 155: 1967-76.
106. Leboulleux S, Bastholt L, Krause T, et al. Vandetanib in locally advanced or metastatic differentiated thyroid cancer: a randomised, double-blind, phase 2 trial. Lancet Oncol 2012; 13: 897-905.
107. Ahmed M, Barbachano Y, Riddell A, et al. Analysis of the efficacy and toxicity of sorafenib in thyroid cancer: a phase II study in a UK based population. Eur J Endocrinol 2011; 165: 315-22.
108. Gupta-Abramson V, Troxel AB, Nellore A, et al. Phase II trial of sorafenib in advanced thyroid cancer. J Clin Oncol 2008; 26: 4714-19.
109. Kloos RT, Ringel MD, Knopp MV, et al. Phase II trial of sorafenib in metastatic thyroid cancer. J Clin Oncol 2009; 27: 1675-84.
110. Hoftijzer H, Heemstra KA, Morreau H, et al. Beneficial effects of sorafenib on tumor progression, but not on radioiodine uptake, in patients with differentiated thyroid carcinoma. Eur J Endocrinol 2009; 161: 923-31.
111. Sherman SI, Wirth LJ, Droz JP, et al. Motesanib diphosphate in progressive differentiated thyroid cancer. N Engl J Med 2008; 359: 31-42.
112. Cohen EE, Rosen LS, Vokes EE, et al. Axitinib is an active treatment for all histologic subtypes of advanced thyroid cancer: results from a phase II study. J Clin Oncol 2008; 26: 4708-13.
113. Bible KC, Suman VJ, Molina JR, et al. Efficacy of pazopanib in progressive, radioiodine-refractory, metastatic differentiated thyroid cancers: results of a phase 2 consortium study. Lancet Oncol 2010; 11: 962-72.
114. Sherman SI, Jarzab B, Cabanillas ME, et al. A phase II trial of the multi-targeted kinase inhibitor, lenvatinib (E7080), in advanced radioiodine-refractory differentiated thyroid cancer (DTC). J Clin Oncol 2011; 29 (suppl): 5503 (abstr).
115. Cabanillas ME, Brose MS, Ramies DA, et al. Antitumor activity of cabozantinib (XL184) in a cohort of patients with differentiated thyroid cancer (DTC). J Clin Oncol 2012; 30 (suppl): 5547 (abstr).
116. Bayer HealthCare Pharmaceuticals, Onyx Pharmaceuticals. Phase 3 DECISION trial of Nexavar (sorafenib) meets primary endpoint of improving progression-free survival in patients with radioactive iodine refractory differentiated thyroid cancer. 2013. http://finance. yahoo.com/news/phase-3- decision-trial-nexavar-073000142.html (accessed Jan 3, 2013).
117. Hou P, Bojdani E, Xing M. Induction of thyroid gene expression and radioiodine uptake in thyroid cancer cells by targeting major signaling pathways. J Clin Endocrinol Metab 2010; 95: 820-28.
118. Ho AL, Grewal RK, Leboeuf R, et al. Selumetinib-enhanced radioiodine uptake in advanced thyroid cancer. N Engl J Med 2013; 368: 623-32.
119. Tsimberidou AM, Vaklavas C, Wen S, et al. Phase I clinical trials in 56 patients with thyroid cancer: the MD Anderson Cancer Center experience. J Clin Endocrinol Metab 2009; 94: 4423-32.
120. Massicotte M, Brassard M, Claude-Desroches M, et al. Off-label tyrosine kinas inhibitor treatments in patients with metastatic thyroid carcinomas: a study of the TUTHYREF network. 82nd annual meeting of the American Thyroid Association; Québec City; Sept 19-23, 2012. Abstract O21.
121. Sherman EJ, Ho AL, Fury MG, et al. A phase II study of temsirolimus/sorafenib in patients with radioactive iodine (RAI)-refractory thyroid carcinoma. J Clin Oncol 2012; 30 (suppl): 5514 (abstr).
122. Flaherty K T, Puzanov I, Kim KB, et al. Inhibition of mutated, activated BRAF in metastatic melanoma. N Engl J Med 2010; 363: 809-19.
123. Liu D, Hou P, Liu Z, et al. Genetic alterations in the phosphoinositide 3-kinase/Akt signaling pathway confer sensitivity of thyroid cancer cells to therapeutic targeting of Akt and mammalian target of rapamycin. Cancer Res 2009; 69: 7311-19.
124. Liu R, Liu D, Trink E, et al. The Akt-specific inhibitor MK2206 selectively inhibits thyroid cancer cells harboring mutations that can activate the PI3K/Akt pathway. J Clin Endocrinol Metab 2011; 96: E577-85.
125. Bass MB, Sherman SI, Schlumberger MJ, et al. Biomarkers as predictors of response to treatment with motesanib in patients with progressive advanced thyroid cancer. J Clin Endocrinol Metab 2010; 95: 5018-27.
126. Ball DW, Sherman SI, Jarzab B, et al. Lenvatinib treatment of RAI-refractory differentiated thyroid cancer (DTC): cytokine and angiogenic factor (CAF) profiling in combination with tumor genetic analysis to identify markers associated with response. ASCO Annual Meeting; June 1-5, 2012] Chicago, IL. Abstract 5518.
127. Spano JP, Vano Y, Vignot S, et al. GEMOX regimen in the treatment of metastatic differentiated refractory thyroid carcinoma. Med Oncol 2012; 29: 1421-28.
128. Crouzeix G, Michels JJ, Sevin E, et al. Unusual short-term complete response to two regimens of cytotoxic chemotherapy in a patient with poorly differentiated thyroid carcinoma. J Clin Endocrinol Metab 2012; 97: 3046-50.