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Furio Pacini, MD Professor of Endocrinology, Director, Section of Endocrinology and Metabolism University of Siena, Siena, Italy
Martin Schlumberger , MD Professor of Oncology, University of Paris-Sud, Director, Nuclear Medicine and Endocrine Tumors Division, Institut Gustave-Roussy, Villejuif, Paris, France.
Patients with advanced DTC who are refractory to 131I treatment have a life expectancy of 3-6 years and represent a group for whom there is a clear unmet medical need (1). Radioiodine refractory thyroid cancer is not common, with an estimated incidence of four cases per million population year (5% of patients with clinical thyroid cancer, 250 patients per year in France) (2,3) ADDIN REFMGR.CITE Schlumberger2011707[Management of refractory thyroid cancers]Journal707[Management of refractory thyroid cancers]Schlumberger,M.2011/4adverse effectsAngiogenesis Inhibitorsantagonists & inhibitorsCarcinomadrug therapyFrancegeneticsHumansinhibitorsMitogen-Activated Protein KinasesProtein Kinase InhibitorsRandomized Controlled Trials as TopicReceptors,Vascular Endothelial Growth Factortherapeutic useThyroid NeoplasmsNot in File149157Ann.Endocrinol.(Paris).722Ann.Endocrinol.(Paris).1. It occurs more frequently in older patients, in those with large metastases or with poorly differentiated thyroid cancer, and in those with high FDG uptake on PET scan (1, 4).
This review proposes a definition for refractory thyroid cancer, and defines those patients who are candidates for treatment with TKIs.
DEFINITION OF REFRACTORY THYROID CANCER In all patients treated with 131I, treatment efficacy is assessed by functional parameters (serum Tg level during l-thyroxine therapy and following hormone withdrawal or rhTSH injections, and quantitative 131I uptake in metastases on post-therapy WBS) and also by anatomical imaging with CT scan and MRI. Favorable responses are characterized by parallel decreases in tumor volume on anatomical imaging, 131I uptake, and serum Tg levels. In contrast, a decrease in 131I uptake without a decrease in tumor volume denotes the destruction of differentiated cells with high uptake and the persistence of poorly differentiated foci that will progress. These patients should then be considered DTC refractory to 131I treatment, and they fall into six categories: a) Patients with metastatic disease that does not take-up 131I at the time of initial treatment. For these patients there is evidence that treatment with 131I does not provide any benefit. This group includes patients with structurally evident disease with no 131I uptake on a diagnostic whole-body scan (WBS), because in such patients uptake when present on post-therapy scans will not be sufficient to induce benefit (5). b) Patients whose tumors lose the ability to take-up 131I after previous evidence of uptake. This is due to the eradication by 131I treatment of differentiated cells able to take-up 131I but not of poorly differentiated cells that do not take-up 131I. Progression is likely to occur in these poorly differentiated cells c) Patients with 131I uptake retained in some lesions but not in others. This is frequently seen in patients with multiple large metastases as shown by 124I studies on PET scan (6) and by comparing results of imaging modalities (FDG-PET or diagnostic CT scans) with 131I WBS. In such patients, progression is likely to occur in metastases without 131I uptake (in particular when FDG uptake is present) and 131I treatment will not be beneficial (4, 7, 8) d) Patients with metastatic disease that progresses despite significant uptake of 131I. It has been clearly shown that if progression occurs following a course of adequate radioiodine treatment, subsequent 131I treatment will be ineffective (9). e) Less clear is the situation for patients with persistent visible 131I uptake in all residual lesions who are not cured despite several treatment courses but whose disease does not progress according to RECIST criteria. For these patients, the probability of obtaining a cure with further 131I treatment is low (1) and side effects may significantly increase, including the risk of secondary cancers and leukemias (10). It is controversial as to whether these patients (particularly after receiving more than 600 mCi of 131I) should be considered 131I-refractory and whether 131I treatment should be abandoned. The decision to continue 131I treatment in such patients is generally based on their response to previous treatment courses, persistence of a significant level of 131I uptake on the previous post-therapy WBS, low FDG uptake in tumor foci, and absence of side effects.
f) Finally, there is a subgroup of patients with advanced disease for whom thyroidectomy is not feasible. In such patients, 131I treatment is usually not administered because 131I is ineffective when the thyroid gland is still present and 131I uptake status cannot be assessed. These patients could be managed as iodine-refractory patients, or if desired, treated with RAI to destroy the thyroid..
TREATMENT OF REFRACTORY THYROID CANCER-ACTIVE SURVEILLANCE (Table 1)
Once 131I treatment is terminated, L-thyroxine treatment is maintained to suppress TSH secretion and focal treatment of metastases is performed whenever needed. This may include surgery, external radiation beam therapy, and thermo-ablation (radiofrequency or cryo-ablation and cement injection). Also, because bone metastases may induce skeletal related events at short term interval (11), bisphosphonate or denosumab treatment may be effective in patients with bone metastases.
Active surveillance includes a FDG-PET/CT scan or a CT scan of the neck, chest, abdomen and pelvis with contrast, at an interval that is dictated by the pace of prior disease-progression if known, and typically a period of at least one year. Most patients with refractory advanced disease have an aggressive course and a life expectancy of 3-6 years after the discovery of distant metastases. However, metastatic DTC can be asymptomatically stable for long periods of time, in particular in young patients with small lung metastases from a well differentiated papillary or follicular carcinoma and in such patients the benefits of novel therapies may be largely outweighed by drug toxicities.
Table 1--MANAGEMENT OF REFRACTORY DTCL-T4 treatment with serum TSH <0.1mU/lFocal treatments when neededImaging follow-up every 4-6 monthsSTABLE DISEASE- continued active follow-upPROGRESSION: >20% BY RECIST criteria in 6-12 months and significant tumor burdenINCLUSION IN A TRIAL- --Chemotherapy-low efficacy, significant toxicity (eg-doxorubicin=<5% PR, median PFS= 7 months) --Targeted Therapy as first line (ATA, Cooper, Thyroid 2009, 19:1167)
TREATMENT OF REFRACTORY THYROID CANCER--INDICATION FOR SYSTEMIC THERAPY The decision to initiate systemic treatment is based on several parameters, including tumor burden, disease progression, symptoms, or high risk of local complications. a) Progression rate can be evaluated by the doubling time of serum Tg ADDIN REFMGR.CITE ADDIN EN.CITE.DATA (12), b) Progression should always be confirmed before initiating a treatment with TKI by imaging using Response Evaluation Criteria in Solid Tumor (RECIST) (13). RECIST consists in measuring the longest diameter of each target lesion (lesion >1cm in diameter) at each imaging control and in comparing the sum of these diameters: progression is defined by an increase of this sum by 20% or by the appearance of new lesions; partial response is defined by a decrease in this sum by 30% and complete response is the disappearance of all visible lesion.
Patients with multiple lesions >1-2 cm and with progression within less than 12 months are considered for systemic treatment. On the contrary, patients with few and/or small lung lesions <1cm, and those with no evidence of progression are considered for active follow-up (2). c) Some patients with large tumor burden and lacking 131I uptake and for whom there is no data on progression, may be considered for systemic treatment based on uptake of FDG on PET scanning or even on primary tumor histology (7,8), but only when active surveillance is not feasible, or there is a high risk of complications.
CHOICE OF SYSTEMIC THERAPY In the past, cytotoxic chemotherapy was used in these patients, but response rates obtained with doxorubicin, the most frequently used agent ranged from 0% to 20%, all responses being partial and transient, and toxicity was significant. The combination with cisplatinum did not improve the efficacy but increased the toxicity (14). Experience is limited with other cytotoxic agents, but reported results were not better than with doxrubicin, and for this reason the ATA recommendations stated in 2009 that kinase inhibitors should be used as first line treatment in patients with refractory DTC in whom progression has been documented. However, toxicities of kinase inhibitors are significant and include fatigue, diarrhea, hypertension and skin toxicities. They occurred in the majority of patients and led to dose reduction in 1173% of patients and to drug withdrawal in 725%. This is why patients education is mandatory and why these treatments should be managed by experienced teams.
Also, tumor responses were observed in only a fraction of patients and most were partial and transient; improvement of progression free survival has been documented in only one phase 2 trials (15) and in one phase 3 trial (16). There is no evidence that treatment at an early stage may be more efficient than a treatment performed at a later stage when progression has been documented. The duration of treatment is not yet validated and, for this reason, treatment is usually given as long as toxicities remain manageable and there is no evidence of tumor progression. This is the rationale for initiating these treatments only in patients with significant tumour burden and with documented progressive disease.
References
Durante C, Haddy N, Baudin E, Leboulleux S, Hartl D, Travagli JP, Caillou B, Ricard M, Lumbroso JD, De Vathaire F, Schlumberger M. 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; 91:2892-9
Xing MM, Haugen B, Schlumberger M. Progress in molecular-based management of differentiated thyroid cancer. Lancet 2013; 381: 1058698.
Schlumberger M, Brose M, Elisei R, Leboulleux S, Luster M, Pitoia F, Pacini F Definition and Management of Radioactive Iodine-Refractory Differentiated Thyroid Cancer: Recommendations by an International Expert Panel. Lancet Endocrinol 2014
Robbins RJ, Wan Q, Grewal RK, Reibke R, Gonen M, Strauss HW, Tuttle RM, Drucker W, Larson SM. HYPERLINK "http://www.ncbi.nlm.nih.gov/pubmed/16303836"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.
Sabra MM, Grewal RK, Tala H, Larson SM, Tuttle RM. HYPERLINK "http://www.ncbi.nlm.nih.gov/pubmed/22827641"Clinical outcomes following empiric radioiodine therapy in patients with structurally identifiable metastatic follicular cell-derived thyroid carcinoma with negative diagnostic but positive post-therapy 131I whole-body scans. Thyroid 2012; 22: 877-83.
Sgouros G, Kolbert KS, Sheikh A, Pentlow KS, Mun EF, Barth A, Robbins RJ, Larson SM. HYPERLINK "http://www.ncbi.nlm.nih.gov/pubmed/15299063"Patient-specific dosimetry for 131I thyroid cancer therapy using 124I PET and 3-dimensional-internal dosimetry (3D-ID) software. J Nucl Med. 2004; 45:1366-72.
Deandreis D, Al Ghuzlan A, Leboulleux S, Lacroix L, Garsi JP, Talbot M, Lumbroso J, Baudin E, Caillou B, Bidart JM, Schlumberger M. HYPERLINK "http://www.ncbi.nlm.nih.gov/pubmed/21118976"Do histological, immunohistochemical and metabolic (radioiodine and fluorodeoxyglucose uptake) patterns of metastatic thyroid cancer correlate with patient outcome? Endocr Relat Cancer 2011; 18:159-69.
Rivera M, Ghossein RA, Schoder H, Gomez D, Larson SM, Tuttle RM. HYPERLINK "http://www.ncbi.nlm.nih.gov/pubmed/18484584"Histopathologic characterization of radioactive iodine-refractory fluorodeoxyglucose-positron emission tomography-positive thyroid carcinoma. Cancer 2008;113: 48-56.
HYPERLINK "http://www.ncbi.nlm.nih.gov/pubmed?term=Vaisman%20F%5BAuthor%5D&cauthor=true&cauthor_uid=22136267"Vaisman F, HYPERLINK "http://www.ncbi.nlm.nih.gov/pubmed?term=Tala%20H%5BAuthor%5D&cauthor=true&cauthor_uid=22136267"Tala H, HYPERLINK "http://www.ncbi.nlm.nih.gov/pubmed?term=Grewal%20R%5BAuthor%5D&cauthor=true&cauthor_uid=22136267"Grewal R, HYPERLINK "http://www.ncbi.nlm.nih.gov/pubmed?term=Tuttle%20RM%5BAuthor%5D&cauthor=true&cauthor_uid=22136267"Tuttle RM. In differentiated thyroid cancer, an incomplete structural response to therapy is associated with significantly worse clinical outcomes than only an incomplete thyroglobulin response. Thyroid 2011;21:1317-22.
Rubino C, De Vathaire F, Dottorini ME, Hall P, Schvartz C, Couette JE, Dondon MG, Abbas MT, Langlois C, Schlumberger M. Second primary malignancies in thyroid cancer patients. Br J Cancer 2003; 89: 1638-44.
HYPERLINK "http://www.ncbi.nlm.nih.gov/pubmed?term=Farooki%20A%5BAuthor%5D&cauthor=true&cauthor_uid=22564664" Farooki A, HYPERLINK "http://www.ncbi.nlm.nih.gov/pubmed?term=Leung%20V%5BAuthor%5D&cauthor=true&cauthor_uid=22564664" Leung V, HYPERLINK "http://www.ncbi.nlm.nih.gov/pubmed?term=Tala%20H%5BAuthor%5D&cauthor=true&cauthor_uid=22564664" Tala H, HYPERLINK "http://www.ncbi.nlm.nih.gov/pubmed?term=Tuttle%20RM%5BAuthor%5D&cauthor=true&cauthor_uid=22564664" Tuttle RM. Skeletal-related events due to bone metastases from differentiated thyroid cancer. HYPERLINK "http://www.ncbi.nlm.nih.gov/pubmed/22564664" \l "#" \o "The Journal of clinical endocrinology and metabolism." J Clin Endocrinol Metab. 2012; 97: 2433-9.
Miyauchi A, Kudo T, Miya A, Kobayashi K, Ito Y, Takamura Y 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.
Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. HYPERLINK "http://www.ncbi.nlm.nih.gov/pubmed/19097774" New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45:228-47
Sherman SI. Cytotoxic chemotherapy for differentiated thyroid carcinoma. Clin Oncol (R Coll Radiol ) 2010;22: 464-8.
Leboulleux S, Bastholt L, Krause T, de la Fouchardiere C, Tennvall J, Awada A et al. Vandetanib in locally advanced or metastatic differentiated thyroid cancer: a randomised, double-blind, phase 2 trial. Lancet Oncol 2012;13: 897-905.
Brose MS, Nutting CM, Jarzab B, Elisei R, Siena S, Bastholt L, de la Fouchardiere C, Pacini F, Paschke R, Shong YK, Sherman SI, Smit JWA, Chung J, Kappeler C, Pena C, Molnar I, Schlumberger M Sorafenib in locally advanced or metastatic, radioactive iodine refractory, differentiated thyroid cancer: a randomized, double-blind, phase 3 trial. ASCO 2013
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| Institut Gustave Roussy 7 ? N Radioiodine Refractory Thyroid Cancer: Definition and Selection for Treatment N Radioiodine Refractory Thyroid Cancer: Definition and Selection for Treatment Title Titre 8 @ _PID_HLINKS A Z ! 1 2 , h t t p : / / w w w . n c b i . n l m . n i h . g o v / p u b m e d / 1 9 0 9 7 7 7 4 5 / , h t t p : / / w w w . n c b i . n l m . n i h . g o v / p u b m e d / 2 2 5 6 4 6 6 4 # | \ , b h t t p : / / w w w . n c b i . n l m . n i h . g o v / p u b m e d ? t e r m = T u t t l e % 2 0 R M % 5 B A u t h o r % 5 D & c a u t h o r = t r u e & c a u t h o r _ u i d = 2 2 5 6 4 6 6 4 p ) _ h t t p : / / w w w . n c b i . n l m . n i h . g o v / p u b m e d ? t e r m = T a l a % 2 0 H % 5 B A u t h o r % 5 D & c a u t h o r = t r u e & c a u t h o r _ u i d = 2 2 5 6 4 6 6 4 R f & ` h t t p : / / w w w . n c b i . n l m . n i h . g o v / p u b m e d ? t e r m = L e u n g % 2 0 V % 5 B A u t h o r % 5 D & c a u t h o r = t r u e & c a u t h o r _ u i d = 2 2 5 6 4 6 6 4 ) # b h t t p : / / w w w . n c b i . n l m . n i h . g o v / p u b m e d ? t e r m = F a r o o k i % 2 0 A % 5 B A u t h o r % 5 D & c a u t h o r = t r u e & c a u t h o r _ u i d = 2 2 5 6 4 6 6 4 } Z b h t t p : / / w w w . n c b i . n l m . n i h . g o v / p u b m e d ? t e r m = T u t t l e % 2 0 R M % 5 B A u t h o r % 5 D & c a u t h o r = t r u e & c a u t h o r _ u i d = 2 2 1 3 6 2 6 7
r a h t t p : / / w w w . n c b i . n l m . n i h . g o v / p u b m e d ? t e r m = G r e w a l % 2 0 R % 5 B A u t h o r % 5 D & c a u t h o r = t r u e & c a u t h o r _ u i d = 2 2 1 3 6 2 6 7 v _ h t t p : / / w w w . n c b i . n l m . n i h . g o v / p u b m e d ? t e r m = T a l a % 2 0 H % 5 B A u t h o r % 5 D & c a u t h o r = t r u e & c a u t h o r _ u i d = 2 2 1 3 6 2 6 7 ! b h t t p : / / w w w . n c b i . n l m . n i h . g o v / p u b m e d ? t e r m = V a i s m a n % 2 0 F % 5 B A u t h o r % 5 D & c a u t h o r = t r u e & c a u t h o r _ u i d = 2 2 1 3 6 2 6 7 # 9 , h t t p : / / w w w . n c b i . n l m . n i h . g o v / p u b m e d / 1 8 4 8 4 5 8 4 / < , h t t p : / / w w w . n c b i . n l m . n i h . g o v / p u b m e d / 2 1 1 1 8 9 7 6 * < , h t t p : / / w w w . n c b i . n l m . n i h . g o v / p u b m e d / 1 5 2 9 9 0 6 3 9 , h t t p : / / w w w . n c b i . n l m . n i h . g o v / p u b m e d / 2 2 8 2 7 6 4 1 ( 2 , h t t p : / / w w w . n c b i . n l m . n i h . g o v / p u b m e d / 1 6 3 0 3 8 3 6
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