Radioiodine treatment of differentiated thyroid cancer related to guidelines and scientific literature | Revista Española de Medicina Nuclear e Imagen Molecular (English Edition)

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Caballero" "autores" => array:5 [ 0 => array:4 [ "nombre" => "M." "apellidos" => "Estorch" "email" => array:1 [ 0 => "mestorch@santpau.cat" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "M." "apellidos" => "Mitjavila" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "M.A." "apellidos" => "Muros" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] ] ] 3 => array:3 [ "nombre" => "E." "apellidos" => "Caballero" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "d" "identificador" => "aff0020" ] ] ] 4 => array:1 [ "colaborador" => "on behalf of the Grupo de Trabajo de Endocrinología de la SEMNIM" ] ] "afiliaciones" => array:4 [ 0 => array:3 [ "entidad" => "Servicio de Medicina Nuclear, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Medicina Nuclear, Hospital Universitario Puerta de Hierro, Majadahonda, Madrid, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Servicio de Medicina Nuclear, Hospital Universitario Virgen de las Nieves, Granada, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Servicio de Medicina Nuclear, Hospital Doctor Peset, Valencia, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Tratamiento del cáncer diferenciado de tiroides con radioyodo a la luz de las guías y de la literatura científica" ] ] "textoCompleto" => "1IntroductionDifferentiated thyroid cancer (DTC) is a papillary or follicular cancer, and the treatment of patients with these tumors is similar despite having numerous biological differences.Surgery is the first treatment to carry out in a patient with DTC. Afterwards, most patients receive hormone and ablative treatment with radioiodine (131I). The follow-up of patients with DTC is performed based on the basal determinations, and when necessary, stimulated, of thyroglobulin (Tg) and antithyroglobulin antibodies (TgAb) is performed as well as imaging techniques according to risk.Although most patients with DTC do not die from the disease, prognostic factors associated with high risk of recurrence and death have been identified, the most important being age at diagnosis, tumor size and the presence of local or distant tumoral invasion.<a class="elsevierStyleCrossRefs" href="#bib0290">1–3</a> Follicular cancer usually appears in older patients and usually has a more aggressive course with a higher mortality than papillary cancer. Female sex is related to a better prognosis.This document of continuing education was prepared considering the 2015 guidelines of the American Thyroid Association (ATA), the British Thyroid Society, the European and American Societies of Nuclear Medicine, the consensus of the European Group an the last edition of the National Comprehensive Cancer Network (NCCN).<a class="elsevierStyleCrossRefs" href="#bib0305">4–9</a> Likewise, we also made an extensive and complete review of the scientific literature related to DTC.At present, the decision how to treat and follow patients with DTC should be made by consensus in a multidisciplinary committee made up of specialists specifically and preferentially devoted to thyroid cancer (endocrinology, general surgery or otorhinolaryngology, nuclear medicine, anatomic pathology, medical oncology, radiodiagnosis and clinical biochemistry) which can provide integrated care with optimization of resources.<a class="elsevierStyleCrossRef" href="#bib0335">10</a>2Treatment and follow-up of differentiated thyroid cancer2.1Surgical treatmentPreoperative ultrasonography with evaluation of the central lymphatic and laterocervical compartments enable programming the most optimal surgical procedure in each patient. The choice of this procedure is currently based on retrospective studies and consensus documents since there are no prospective studies in this respect.<a class="elsevierStyleCrossRefs" href="#bib0305">4,6,8,9</a>The surgical procedure depends, among other factors, on tumor size and the presence or not of local extension or locoregional lymphatic involvement:<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005">•Tumors ≤1cm without local or lymphatic extension: lobectomy.</li><li class="elsevierStyleListItem" id="lsti0010">•Tumors >1cm and ≤4cm without local or lymphatic extension: lobectomy or thyroidectomy. Thyroidectomy is performed when the ultrasonography of the contralateral lobe is not completely normal or when ablative treatment with 131I is carried out. The patient can decide which procedure to undergo.</li><li class="elsevierStyleListItem" id="lsti0015">•Tumors >4cm, local or lymphatic extension or metastasis: total thyroidectomy.</li><li class="elsevierStyleListItem" id="lsti0020">•Tumor of any size with a history of cervical irradiation: total thyroidectomy.</li><li class="elsevierStyleListItem" id="lsti0025">•Multifocal papillary microcarcinoma: total thyroidectomy (especially for 8–9mm lesions).</li></ul>Lobectomy of tumors between 1 and 4cm in size without local or lymphatic extension excludes ablative treatment with 131I, and makes follow-up with Tg much more difficult. Retrospective studies have described the utility of treatment with 131I in DTC of >1cm.<a class="elsevierStyleCrossRef" href="#bib0340">11</a> On the other hand, the experience of the surgeon is fundamental and is considered in the guidelines of the European Society of Nuclear Medicine,<a class="elsevierStyleCrossRef" href="#bib0315">6</a> as is postoperative Tg which helps to identify patients who may benefit from radioiodine.<a class="elsevierStyleCrossRef" href="#bib0345">12</a> It has been shown that compared to thyroidectomy, lobectomy in tumors >1cm is associated with a 15% risk of recurrence and 31% increase in the risk of death.<a class="elsevierStyleCrossRef" href="#bib0350">13</a> In a recent retrospective study in a group of 394 patients with DTC of low or low-intermediate risk (1–4cm), Kluijfhout et al.<a class="elsevierStyleCrossRef" href="#bib0355">14</a> demonstrated that 19.5% would have required completion of thyroidectomy and 25.6% would have required treatment with 131I if they had been treated with lobectomy. However, there are also multiple studies reporting that thyroidectomy has no benefits over lobectomy with regard to survival in tumors ≤4cm.<a class="elsevierStyleCrossRefs" href="#bib0360">15,16</a> The British guidelines recommend that the type of intervention should be decided individually based on each clinical scenario (tumor size, ultrasonography of the doubtful contralateral lobe and/or evidence of suspicious lymph nodes, patient age, among others) and additional factors of risk (history of radiation, etc.), and the decision should always be made by a multidisciplinary committee.<a class="elsevierStyleCrossRef" href="#bib0310">5</a><elsevierMultimedia ident="tb0005"></elsevierMultimedia>2.2Hormone treatmentFollowing surgery most patients receive hormone replacement treatment with levothyroxine (LT4) to maintain an euthyroid status and/or to control tumoral growth.Patients undergoing lobectomy might not be treated with LT4. In this case, 6 weeks after surgery, thyrotropin levels (TSH) are determined to assess the need or not to administer the hormone.Patients treated with total thyroidectomy should start hormone treatment when they are not candidates for ablative treatment with 131I or when this is administered under stimulus with recombinant human TSH (rhTSH). If ablative treatment is administered by withdrawing hormone treatment, the patient cannot initiate hormone treatment after surgery, provided that 131I is given at 4/6 weeks (with TSH >30mU/l). When hormone treatment is administered after surgery, TSH levels should be determined beforehand and after, again at 4–6 weeks, to adjust the dose of LT4 if necessary.2.3Initial stratification of riskThe need or not to administer additional treatment after surgery and especially whether 131I should be administered is decided based on the initial stratification of risk.The determination of TSH and Tg 4–6 weeks after surgery provides an orientation as to the status of the disease. Although the optimal stimulated and non stimulated Tg levels are not clearly defined,<a class="elsevierStyleCrossRef" href="#bib0305">4</a> it has been established that non stimulated levels should be <30ng/ml in the case of lobectomy and <5ng/ml in the case of total thyroidectomy. Levels above these indicate the need for reassessment to complete thyroidectomy and/or administer radioiodine.<a class="elsevierStyleCrossRefs" href="#bib0370">17,18</a>The Tg values can vary according to the method of determination used and also in the presence or not of TgAb.2.3.1Stratification of riskThe stratification of risk is made based on the tumor, node, metastasis (TNM) classification (8th edition<a class="elsevierStyleCrossRef" href="#bib0380">19</a>) of the American Joint Committee on Cancer (AJCC), which can estimate mortality, and the 2015 ATA stratification of risk system,<a class="elsevierStyleCrossRef" href="#bib0305">4</a> which estimates the risk of disease persistence or recurrence (<a class="elsevierStyleCrossRefs" href="#tbl0005">Tables 1 and 2</a>, respectively). Patients are classified into 3 categories of risk (low, intermediate or high) based on their clinical-pathological characteristics.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia>Stratification of risk can decide the initial treatment as well as establish the follow-up strategy to be followed. However, this strategy may have to be changed along the course of the disease, and this will be determined by dynamic stratification of risk.<a class="elsevierStyleCrossRef" href="#bib0385">20</a><elsevierMultimedia ident="tb0010"></elsevierMultimedia>2.4Dynamic stratification of riskDuring follow-up patients are reclassified into one of the following clinical categories, and imaging studies and treatments, if necessary, are adapted to the classification since it has been observed that the risk of recurrence varies based on the response to the different treatments<a class="elsevierStyleCrossRef" href="#bib0385">20</a>:<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0030">•Excellent response: no clinical, biochemical or structural evidence of disease.</li><li class="elsevierStyleListItem" id="lsti0035">•Incomplete biochemical response: detectable Tg or increased TgAb.</li><li class="elsevierStyleListItem" id="lsti0040">•Incomplete structural response: persistence or new locoregional or distant tumor tumoral lesions.</li><li class="elsevierStyleListItem" id="lsti0045">•Indeterminate response: biochemical or structural finidings that can not rule out malignancy or persistence of TgAb with no evidence of structural disease.</li></ul>During the first year, follow-up is made by cervical ultrasonography and determination of plasma TSH and Tg levels under hormone suppression treatment at 6 or 12 months depending on the initial risk. Tg is determined by stimulation with rhTSH in patients with intermediate or high risk with undectable basal Tg (to confirm excellent response) or to identify persistent/recurrent disease. The use of imaging or histological studies, if needed, also depends on the initial risk or whether the patient shows biochemical or incomplete structural response.After the first year, plasma TSH levels are determined annually to adjust the dose or LT4 or to determine that these levels are maintained at <0.1–0.5mU/l in patients with incomplete structural response.Likewise, according to dynamic stratification of risk, imaging studies are performed according to the case: cervical ultrasonography on suspicion of locoregional disease, whole body scan with 131I and/or 18F-FDG PET/CT in cases suspected of having locoregional or distant disease, 18F-FDG PET/CT with contrast in iodine refractory disease or magnetic resonance in patients suspected of presenting brain disease.<elsevierMultimedia ident="tb0015"></elsevierMultimedia>3Treatment with radioiodineThe first treatment with 131I for DTC was administered in 1945. However, at present the management of DTC is still controversial due to the lack of prospective randomized clinical trials, and therefore, the recommendations of the experts are based on retrospective observational data and may be influenced by multiple factors related to the course of the disease according to their interpretation of the literature as well as their clinical perspective and experience.<a class="elsevierStyleCrossRefs" href="#bib0390">21–23</a>Treatment with 131I is based on the fact that tumoral thyroid tissue has the capacity to incorporate iodine from the blood by the sodium/iodine transporter membrane. Compared with normal tissue, the expression of this transporter is reduced in tumoral tissue, and thus, the uptake of 131I may be reduced. Nonetheless, the beta radiation of 131I leads to the formation of free radicals at an intracellular level, DNA lesion, and finally, cell death, which is the objective of the treatment.Treatment with 131I in DTC is administered: to eliminate residual healthy thyroid tissue post-thyroidectomy presenting great avidity for the iodine (ablative treatment); to treat recurrence/persistence of lymph node involvement showing less avidity for the iodine (adjuvant treatment) or to treat macroscopic or metastatic disease.Apart from destroying healthy thyroid tissue post-thyroidectomy, the objective of ablative treatment is to destroy possible microscopic foci, minimize the risk of recurrence in patients with predisposition (i.e. history of cervical irradiation), increase the specificity of Tg as a tumoral marker and increase the specificity of the scan with 131I for the detection of recurrent or metastatic disease. On the other hand, the objective of adjuvant treatment with 131I in recurrence/persistence of lymph node involvement and metastatic disease is to destroy all micro- and macroscopic disease that cannot be treated with surgery, thereby reducing the risk of recurrence and death.<elsevierMultimedia ident="tb0020"></elsevierMultimedia>3.1IndicationsThe administration of 131I after thyroidectomy depends on the clinical–pathological characteristics of each tumor (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>) as well as the initial stratification of risk (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>). The introduction of the 8th edition of the AJCC TNM classification of DTC raised the limit of age of risk from ≥45 to ≥55 years. This has led to reclassification of 23–35% of the patients with DTC to lower stages than previously, with an increase in stages I and II and an increase in the probability of recurrence in stage II patients ≥55 years of age. On the other hand, stage III includes patients with more aggressive cervical disease without distant metastasis, with the vital prognosis in stages III and IV being worse than in the 7th edition of the AJCC TNM classification (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>). At present, the 2015 ATA guidelines are the most widely used and have the greatest following among specialists involved in the treatment of DTC.<a class="elsevierStyleCrossRef" href="#bib0305">4</a> Except in tumors of low risk ≤1cm (T1a) and in those of high risk (T4), the 2015 ATA recommendations on ablative treatment are ambiguous and open to different interpretations in relation to local factors (<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>):<ul class="elsevierStyleList" id="lis0025"><li class="elsevierStyleListItem" id="lsti0055">•Low risk: 131I not routinely administered when the tumor is ≤1cm, even in the presence of affected regional lymph nodes (<5 lymph nodes of <2mm), of multifocal tumor (all foci <1cm) and intrathyroid tumor >1 and ≤4cm. Low doses can be administered (1.1GBq/30mCi) in a selected group of patients. The decision to administer 131I or not can be based on local factors such as the experience of the ultrasonographer, the surgeon or the method of Tg measurement.The decision to not administer 131I in low risk cases is based on retrospective studies, systematic reviews and metaanalyses which have shown no benefits of this treatment with respect to the rate of recurrence or mortality.<a class="elsevierStyleCrossRefs" href="#bib0405">24,25</a> To the contrary, other retrospective studies have shown benefits in terms of overall survival and recurrence-free interval in tumors >1cm<a class="elsevierStyleCrossRef" href="#bib0340">11</a> with the administration of 131I. In a retrospective study including 574 patients, Tran et al.<a class="elsevierStyleCrossRef" href="#bib0415">26</a> recently reported that tumors >2cm are associated with a 5-fold greater risk of recurrence in patients ≥55 years of age. Three prospective randomized, multicenter, clinical trials are currently ongoing (ESTIMABL2, IoN and CLERAD-PROBE). The 5- and 10-year follow-up results of these studies are expected at the beginning of 2022 and 2027, respectively.<a class="elsevierStyleCrossRefs" href="#bib0420">27–29</a> The position of the European Society of Nuclear Medicine (EANM) is to administer 131I in all tumors >1cm.<a class="elsevierStyleCrossRef" href="#bib0315">6</a> Therefore, while awaiting the results of the previously mentioned ongoing trials, the administration or not of 131I remains controversial.<a class="elsevierStyleCrossRef" href="#bib0395">22</a></li><li class="elsevierStyleListItem" id="lsti0060">•Intermediate risk: 131I is administered according to the characteristics of the tumor, presence of significant lymph node metastasis, vascular invasion or aggressive histology, combined with patient age (≥55 years). The decision to treat or not should be made by a multidisciplinary committee. The data in the literature are limited in this group of patients, although they do indicate benefits with respect to overall survival.<a class="elsevierStyleCrossRefs" href="#bib0305">4,30,31</a></li><li class="elsevierStyleListItem" id="lsti0065">•High risk: 131I is routinely administered, having shown benefits in overall survival.<a class="elsevierStyleCrossRefs" href="#bib0440">31,32</a></li></ul><elsevierMultimedia ident="tb0025"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><elsevierMultimedia ident="tbl0020"></elsevierMultimedia>3.2Patient preparationThe 131I uptake depends on adequate cellular stimulation by an elevation of plasma TSH levels as well as stable low iodine levels in blood. The first is achieved by withdrawing hormone treatment or by administering rhTSH. The second can be achieved by instructing the patient to follow a diet low in iodine and to avoid any exogenous source of iodine (special care with iodized salt, amiodarone and radiological contrasts).Suspension of hormone treatment: LT4 is withdrawn 3–4 weeks before the administration of 131I, and plasma TSH levels should be determined to ensure that they are >30mU/l prior to its administration.<a class="elsevierStyleCrossRef" href="#bib0450">33</a> Pre-treatment with LT3 can also be carried out during 1–2 weeks (25μg×3/day) to reduce the symptoms of hypothyroidism.rhTSH: an intramuscular injection of 0.9mg of rhTSH is made on 2 consecutive days, administering the 131I on the third day. The determination of Tg is made 72h after the injection of rhTSH; that is, on the fifth day.3.2.1What stimulation method should be used?Suspension of hormonal treatment is the method of choice for the treatment of local metastatic (recurrence/persistence of lymph node involvement) or metastatic disease. However, it is not advised in elderly patients or in those with comorbidities which may be aggravated in a maintained state of hypothyroidism (i.e. depression, heart failure or severe sleep apnea).rhTSH should be used in ablative treatment with 131I (destruction of normal thyroid tissue) and for the preparation of follow-up scans. It should also be used in the treatment with 131I of residual microscopic disease in patients with low or intermediate risk.Randomized studies and metaanalyses have shown a similar short-term ablative efficacy with the two methods.<a class="elsevierStyleCrossRefs" href="#bib0455">34–38</a> In a multicenter study including 752 patients with low risk DTC randomly treated with low or high doses of 131I (1.1 vs. 3.7GBq/30 vs. 100mCi) and hormone suspension vs. rhTSH, similar rates of ablation were found at 6–10 months with both doses and methods of preparation (rhTSH 89.1% and hormone suspension 88.9%). Later, after a follow-up of 5.4 years, 98% of these patients did not present disease persistence or recurrence; structural disease was identified in 0.6% and biochemical disease in 0.7% and was not associated with either the dose of 131I administered or the method of preparation (ESTIMABL1 trial<a class="elsevierStyleCrossRefs" href="#bib0465">36,37</a>). Mallick et al.<a class="elsevierStyleCrossRef" href="#bib0475">38</a> published the results of the HiLo trial and also reported that in patients with low risk DTC randomly treated with low or high doses of 131I (1.1 vs. 3.7GBq/30 vs. 100mCi) and also prepared with both methods, the ablation was similar with both doses and methods (rhTSH 87% and hormone suspension 87%).Few studies have evaluated the two preparation methods in the long term. One prospective study with a 10-year follow-up described similar results for both methods of preparation in patients treated with 1.1GBq of 131I, and another retrospective study with a 9-year follow-up reported the same, but this latter study also included patients with intermediate and high risk.<a class="elsevierStyleCrossRefs" href="#bib0480">39,40</a> In a retrospective review including 84 patients, Tuttle et al.<a class="elsevierStyleCrossRef" href="#bib0490">41</a> concluded that rhTSH is effective for the treatment of lymph node and pulmonary micrometastases shown by ablative treatment with 131I. On the other hand, in a retrospective study including 175 patients with a follow-up of 5 years, Tala et al.<a class="elsevierStyleCrossRef" href="#bib0495">42</a> described a similar effectiveness with rhTSH and hormone suspension in patients with macroscopic metastasis with iodine uptake.<elsevierMultimedia ident="tb0030"></elsevierMultimedia>4Dose (activity) of radioiodine<ul class="elsevierStyleList" id="lis0040"><li class="elsevierStyleListItem" id="lsti0070">•Ablative treatment: this is administered to patients considered as having low risk who are candidates for ablation.<a class="elsevierStyleCrossRefs" href="#bib0305">4,5</a> The optimal dose of 131I to administer is based on achieving good ablation, which is the objective of the treatment, and on the risk of recurrence/mortality (<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>). Several studies have evaluated the optimal dose.<a class="elsevierStyleCrossRefs" href="#bib0465">36,37,43,44</a> However, to date, the lack of uniformity in relation to the patients, method and even the definition of ablation have impeded establishing the most optimal dose. The proposal of 1.1GBq (30mCi) as the ablative dose of 131I is based on results obtained in studies aimed at evaluating the short term effectiveness of ablative treatment but not at evaluating its effectiveness to avoid recurrence, which requires a longer follow-up. Although 2 retrospective studies<a class="elsevierStyleCrossRefs" href="#bib0510">45,46</a> did not find any differences in regard to recurrence at 5 and 14.7 years of follow-up in patients treated with low vs. high doses of 131I, it is the results of prospective, randomized, multicenter, clinical studies that will indicate the optimal dose of 131I to be administered for ablative purposes.</li><li class="elsevierStyleListItem" id="lsti0075">•Adjuvant treatment: after thyroidectomy, patients with DTC of intermediate risk are treated with 131I with 2 objectives: ablation and treatment of residual microscopic disease post-surgery. A dose of 131I of between 2.8 and 3.7GBq (75–100mCi) has been proposed. Two retrospective studies performed in patients with DTC of intermediate risk treated with a low (1.1GBq/30mCi) vs. a high dose (3.7–5.5GBq/100–15mCi) of 131I found no significant differences in regard to the rate of ablation.<a class="elsevierStyleCrossRefs" href="#bib0520">47,48</a> In another retrospective study comparing doses of 100, 150 and 200mCi of 131I, Sabra et al.<a class="elsevierStyleCrossRef" href="#bib0530">49</a> concluded that the administration of more than 100mCi in N1b patients, especially in younger patients, does not improve initial response to treatment. In a study including 1298 patients with low and high risk DTC divided into two age groups(<45 and ≥45 years), Verburg et al.<a class="elsevierStyleCrossRef" href="#bib0535">50</a> concluded that the high dose was associated with a greater survival in patients ≥45 years of age and that the low dose should be used with caution in this age group. At present, and as mentioned previously, the change in the age limt of risk to ≥55 years represents an increase in patients in stages I and II with a greater probability of recurrence in stage II, since in this stage the patient is no longer of low risk and the low dose should not be considered.</li><li class="elsevierStyleListItem" id="lsti0080">•Treatment of residual macroscopic and local and/or distant metastatic disease: high empiric doses of 131I are administered:<ul class="elsevierStyleList" id="lis0045"><li class="elsevierStyleListItem" id="lsti0085">–5.6GBq (150mCi): cervical and mediastinic lymph nodes.</li><li class="elsevierStyleListItem" id="lsti0090">–5.6–7.5GBq (150–200mCi): pulmonary metastases.</li><li class="elsevierStyleListItem" id="lsti0095">–7.5GBq (200mCi): bone metastasis or other distant metastasis.</li><li class="elsevierStyleListItem" id="lsti0100">–The administration of higher doses requires a dosimetric study.</li><li class="elsevierStyleListItem" id="lsti0105">–The dose should not be greater than 5.6GBq (150mCi) in patients with pulmonary metastases over the age of 70 due to a greater risk of bone marrow toxicity.</li><li class="elsevierStyleListItem" id="lsti0110">–Patients with renal insufficiency or on hemodialysis can be treated by decreasing the dose of 131I with posterior dialysis according to the usual protocol or administer the standard dose of 131I followed by more frequent dialysis.<a class="elsevierStyleCrossRef" href="#bib0540">51</a></li></ul></li></ul>The treatment is repeated when there is evidence of iodine uptake disease in a follow-up scan with 131I. At 6–12 months after treatment, a scan with 131I is made in patients with intermediate-high risk and those with low risk with detectable maintained or increased Tg. The scan should be done with a low dose of 131I (185MBq/5mCi) and preparation with rhTSH or with suspension of hormone treatment which induces hypothyroidism. If the scan shows evidence of significant cervical uptake, a second treatment is given with 3.7–5.6GBq (100–150mCi) of 131I to complete the ablation. If cervical uptake is not significant or there is no evidence of disease by other imaging techniques, treatment is not administered. If there is evidence of disease in other localizations, the corresponding dose of 131I is administered.<elsevierMultimedia ident="tb0035"></elsevierMultimedia><elsevierMultimedia ident="tb0040"></elsevierMultimedia>4.1Persistent, recurrent or distant diseaseDuring the first 2 years the treatment interval with 131I is 4–8 months according to the guidelines of the European and American Societies of Nuclear Medicine<a class="elsevierStyleCrossRefs" href="#bib0320">7,8</a> and 6–12 months according to the 2015 ATA and British guidelines<a class="elsevierStyleCrossRefs" href="#bib0305">4,5</a>:<ul class="elsevierStyleList" id="lis0065"><li class="elsevierStyleListItem" id="lsti0115">•Cervical disease: Cervical tumor recurrence can be detected by clinical examination or an increase in plasma Tg levels, with cervical ultrasonography being the method of choice for localization. Surgical resection in the central and laterocervical compartment is the first treatment when the disease is of low volume. However, on occasions aggressive surgical resection in stable, low volume disease is difficult to justify, especially when its benefits in relation to an increase in the overall survival have not been demonstrated. In these cases surgery is avoided, and the patients are followed to ensure that they continue to be at low risk and a wait and see approach is taken.The extension of recurrence beyond the thyroid bed (larynx, trachea, esophagus or soft tissue) implies the need for wider surgical resection based on CT study with contrast or magnetic resonance.If disease persists following surgery a scan with 131I with rhTSH stimulation is indicated. If this is positive, treatment with 131I in the same conditions is carried out. To the contrary, if disease persists but 131I uptake is not observed, a 18F-FDG PET/CT is performed to localize dedifferentiated disease (not presenting iodine uptake). In this case, positive results with 18F-FDG PET/CT are considered to be an independent indicator of bad prognosis, being correlated with global mortality when disease with no iodine uptake is shown.<a class="elsevierStyleCrossRef" href="#bib0545">52</a></li><li class="elsevierStyleListItem" id="lsti0120">•Distant disease: patients who develop distant disease during follow-up should be treated with the same dose of 131I that would have been given if they had presented metastasis at the onset. However, in these cases the treatment with 131I is less effective.<a class="elsevierStyleCrossRef" href="#bib0550">53</a> The efficacy of treatment with 131I is related to the radiosensitivity of the tumoral tissue, which is greater in young patients with small-sized metastasis and with an elevated uptake of 131I. In general, the therapeutic efficacy is achieved with accumulated activity less than 22.2GBq (600mCi). Recently, 22.2GBq was arbitrarily established as the limit of accumulated activity for treatment with radioiodine.<a class="elsevierStyleCrossRef" href="#bib0305">4</a> However, to date there is no extensive experience with greater activities without the development of significant toxicity. Nonetheless, the decision should be made by a multidisciplinary committee and should always consider that the objective is to achieve benefits.When 131I does not control the disease, the disease is considered to be iodine refractory. The most frequent scenarios of refractoriness to 131I are: evident structural disease which has no avidity for 131I from the onset, loss of avidity by 131I in a structural disease which showed previous uptake of 131I and structural disease which progresses despite 131I uptake. In these scenarios treatment with local therapies (percutaneous injection of ethanol, radiofrequency, embolization or radiotherapy) may be considered, with surgery in single metastasis and the administration of systemic treatments (i.e. kinase inhibitors).</li></ul><elsevierMultimedia ident="tb0045"></elsevierMultimedia>Distant disease is treated with the same dose of 131I that would have been given if metastasis had been presented at the beginning.4.2Elevated thyroglobulin and negative 131I scan (TENIS syndrome)It is not infrequent for a patient to present elevated Tg levels with a negative 131I scan (Thyroglobulin Elevation/Negative Iodine Scintigraphy Syndrome – TENIS syndrome). After ruling out the possible cause for false negative scan results (inadequate TSH stimulation, elevated plasma iodine levels due to excess exogenous iodine or very small disease volume), this situation reflects the loss of the capacity of the tumoral tissue to take up iodine, or in other words, dedifferentiation. The management of these patients is complicated and there are very few data to determine the optimal treatment to follow.<a class="elsevierStyleCrossRef" href="#bib0555">54</a> The management of these patients is based on:<ul class="elsevierStyleList" id="lis0075"><li class="elsevierStyleListItem" id="lsti0125">•Ruling out an excess of exogenous iodine by the 24h measurement of urinary iodine excretion.</li><li class="elsevierStyleListItem" id="lsti0130">•Performing ultrasonography of the neck and a CT of the neck and thorax (without contrast).</li><li class="elsevierStyleListItem" id="lsti0135">•Performing 18F-FDG PET/CT in patients with high risk of non stimulated Tg ≥10ng/ml.</li><li class="elsevierStyleListItem" id="lsti0140">•Treatment with radiotherapy (i.e. single bone metastasis) or systemic therapy (disease in progression without response to 131I).</li><li class="elsevierStyleListItem" id="lsti0145">•Treatment with 131I: 42–72% of patients with a negative 131I scan empirically treated with high doses, present 131I uptake in the post-treatment scan, especially at a cervical and mediastinic level, more frequently identifying distant metastasis when the plasma Tg level is >200ng/ml.<a class="elsevierStyleCrossRef" href="#bib0560">55</a> However, the benefits of this treatment are limited, with 44% of stable disease and 56% of progression after radioiodine treatment.<a class="elsevierStyleCrossRef" href="#bib0565">56</a> Although some studies have shown a reduction in Tg levels after treatment with 131I, this reduction has not been shown to change the prognosis of the disease. However, despite not seeming to achieve clinical benefits beyond localizing the disease, it does enable restaging and reclassifying the disease as biochemical persistence or as iodine refractory.<a class="elsevierStyleCrossRefs" href="#bib0560">55,57</a></li></ul><elsevierMultimedia ident="tb0050"></elsevierMultimedia>5ConclusionThe treatment of DTC with 131I is controversial in some aspects due to the lack of prospective, randomized, clinical studies. In DTC, treatment with 131I is administered with ablative objectives to eliminate healthy residual microscopic thyroid tissue or to treat macroscopic or metastatic disease. Apart from destroying healthy thyroid tissue post-thyroidectomy, the objective of ablative treatment is to destroy possible microscopic foci, minimize the risk of recurrence in patients with predisposition, increase the specificity of Tg as a tumoral marker and increase the specificity of scans with 131I for the detection of recurrent or metastatic disease. On the other hand, the objective of treatment of residual and/or metastatic disease with 131I is to destroy all macroscopic disease that cannot be treated with surgery, thereby reducing the risk of recurrence and mortality. While awaiting the results of ongoing prospective trials, the use of 131I seems to be justified not only in patients with high risk but also in those with intermediate risk and those with low risk associated with other factors.6Conflict of interestThe authors declare no conflict of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres1185617" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1105412" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1185616" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1105413" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Treatment and follow-up of differentiated thyroid cancer" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Surgical treatment" ] 1 => array:2 [ "identificador" => "sec0025" "titulo" => "Hormone treatment" ] 2 => array:3 [ "identificador" => "sec0030" "titulo" => "Initial stratification of risk" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0035" "titulo" => "Stratification of risk" ] ] ] 3 => array:2 [ "identificador" => "sec0045" "titulo" => "Dynamic stratification of risk" ] ] ] 6 => array:3 [ "identificador" => "sec0055" "titulo" => "Treatment with radioiodine" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0065" "titulo" => "Indications" ] 1 => array:3 [ "identificador" => "sec0075" "titulo" => "Patient preparation" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0080" "titulo" => "What stimulation method should be used?" ] ] ] ] ] 7 => array:3 [ "identificador" => "sec0090" "titulo" => "Dose (activity) of radioiodine" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0105" "titulo" => "Persistent, recurrent or distant disease" ] 1 => array:2 [ "identificador" => "sec0115" "titulo" => "Elevated thyroglobulin and negative I scan (TENIS syndrome)" ] ] ] 8 => array:2 [ "identificador" => "sec0125" "titulo" => "Conclusion" ] 9 => array:2 [ "identificador" => "sec0130" "titulo" => "Conflict of interest" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2018-12-12" "fechaAceptado" => "2018-12-20" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1105412" "palabras" => array:5 [ 0 => "Radioiodine treatment" 1 => "131I" 2 => "Differentiated thyroid cancer" 3 => "Initial risk stratification" 4 => "Dynamic risk stratification" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1105413" "palabras" => array:5 [ 0 => "Tratamiento con radioyodo" 1 => "131I" 2 => "Cáncer diferenciado de tiroides" 3 => "Estratificación inicial de riesgo" 4 => "Estratificación dinámica de riesgo" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "In differentiated thyroid cancer (DTC), radioiodine is administered to eliminate residual normal thyroid tissue after thyroidectomy (ablative treatment), to treat residual microscopic disease (adjuvant treatment), and to treat macroscopic or metastatic disease. Currently, treatment of DTC with 131I is still a matter of controversy due to the absence of prospective clinical trials assessing its benefit in terms of overall survival and recurrence-free interval. The current recommendations of the experts are based on observational retrospective data and on their interpretation of the literature. Pending the results of the prospective trials that are currently underway, the use of 131I seems to be justified not only in high-risk patients, but also in intermediate-risk and low-risk patients. The guidelines of The American and British Thyroid Association, European and American Societies of Nuclear Medicine, The European Consensus Group and the latest edition of National Comprehensive Cancer Network (NCCN) were considered in drawing up this continuing education document, we also undertook a review of the related scientific literature." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "En el cáncer diferenciado de tiroides (CDT), el tratamiento con 131I se administra para eliminar tejido tiroideo residual sano postiroidectomía (tratamiento ablativo), para tratar enfermedad residual microscópica (tratamiento adyuvante) y para tratar enfermedad macroscópica o metastásica. A día de hoy, el tratamiento con 131I del CDT es todavía un tema de controversia debido a la ausencia de ensayos clínicos prospectivos que evalúen su beneficio en cuanto a supervivencia global e intervalo libre de recurrencia. Las recomendaciones actuales de los expertos se basan en datos retrospectivos observacionales y en su interpretación de la literatura. A la espera de los resultados de los ensayos prospectivos actualmente en marcha, la utilización del 131I parece estar justificada no solamente en los pacientes de alto riesgo, sino también en los de riesgo intermedio y bajo. Para la realización del presente documento de formación continuada se han considerado las guías de la Sociedad Americana y Británica de Tiroides, de las Sociedades Europea y Americana de Medicina Nuclear, el consenso del Grupo Europeo y la última edición del National Comprehensive Cancer Network (NCCN), así como se ha revisado la literatura científica relacionada." ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Estorch M, Mitjavila M, Muros MA, Caballero E, en nombre del Grupo de Trabajo de Endocrinología de la SEMNIM. Tratamiento del cáncer diferenciado de tiroides con radioyodo a la luz de las guías y de la literatura científica. Rev Esp Med Nucl Imagen Mol. 2019;38:195–203." ] ] "multimedia" => array:14 [ 0 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "AJCC: American Joint Committee on Cancer; TNM: tumor/node/metastasis; UICC: Union for International Cancer Control." "tablatextoimagen" => array:2 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">T: primary tumor</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Tx \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Non localized primary tumor \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">T0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No evidence of primary tumor \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">T1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Tumor ≤2cm<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">T1a \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Tumor ≤1cm<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">T1b \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Tumor >1cm and ≤2cm \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">T2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Tumor >2cm and ≤4cm<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">T3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Tumor >4cm<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> or extension to adjacent muscles \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">T3a \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Tumor >4cm<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> limited to the thyroid glands \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">T3b \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Tumor of any size with extension to adjacent muscles \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">T4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Tumor of any size with extrathyroid extension \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">T4a \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Tumor of any size with recurrent extension to subcutaneous tissue, larynx, trachea, espophagus or nerve \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">T4b \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Tumor of any size with invasion of the prevertebral fascia, carotid or mediastinic vessels \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">N: regional lymph nodes</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Nx \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Non localized lymph nodes \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">N0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No evidence of lymph nodes \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">N0a \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">One or more with benign cytology or histology \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">N0b \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No radiological or clinical evidence \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">N1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Metastatic lymph nodes \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">N1a \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Uni- or bilateral metastasis at level VI or VII \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">N1b \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Uni, bilateral or contralateral metastasis at level I, II, III, IV or V or at a retropharyngeal level \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">M: distant metastasis</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">M0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No metastasis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">M1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Distant metastasis \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2021927.png" ] ] 1 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " colspan="5" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Staging according to age <55 or ≥55 years</th></tr><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Age \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">T \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">N \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">M \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Stage \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><55 years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Any T \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Any N \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">i \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><55 years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Any T \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Any N \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ii \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">≥55 Years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">T1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">N0/Nx \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">I \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">≥55 Years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">T1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">N1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ii \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">≥55 Years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">T2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">N0/Nx \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">I \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">≥55 Years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">T2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">N1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ii \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">≥55 Years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">T3a/T3b \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Any N \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ii \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">≥55 Years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">T4a \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Any N \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Iii \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">≥55 Years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">T4b \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Any N \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Iva \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">≥55 Years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Any T \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Any N \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">IVB \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2021926.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "Greatest diameter. Note: The tumors may be solitary or multifocal. If multifocal, the T is determined by the tumor of greatest size. Source: Amin et al.<a class="elsevierStyleCrossRef" href="#bib0380">19</a>" ] ] ] "descripcion" => array:1 [ "en" => "2017 TNM classification of the American Joint Committee on Cancer and the Union for International Cancer Control for differentiated thyroid cancer." ] ] 1 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "ATA: American Thyroid Association; Tg: thyroglobulin." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Low risk \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Pillary thyroid cancer including all the following characteristics: \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">No local or distant metastasis. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Macroscopic resection of all the tumor. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">No local invasion. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Not presenting aggressive histology (tall, columnar, Hürthle cells, etc.). \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">No vascular invasion. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">No 131I uptake outside the thyroid bed. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">N0 or ≤5 N1 micrometastasis (<0.2cm<a class="elsevierStyleCrossRef" href="#tblfn0010">a</a>) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Follicular thyroid cancer encapsulated papillary variant. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Well differentiated follicular thyroid cancer with invasion of the capsule or minimal vascular invasion (<4 foci). \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Uni or multifocal papillary microcarcinoma, including BRAF V600E mutation. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Intermediate risk \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Thyroid cancer with at least one of the following characteristics: \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Microscopic invasion of perithyroid soft tissue. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Metastatic regional lymph nodes or 131I uptake in the post ablative treatment scan. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Tumor with aggressive histology (tall, columnar, Hürthle cells, etc.) or vascular invasion. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">N1 clinical manifestations or >5N, with all the nodes being <3cm<a class="elsevierStyleCrossRef" href="#tblfn0010">a</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Multifocal papillary microcarcinoma with extrathyroid extension and BRAF V600E mutation. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">High risk \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Thyroid cancer with any of the following characteristics: \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Macroscopic tumoral invasion \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Incomplete resection \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Distant metastasis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Postsurgical plasma Tg levels suggestive of distant metastasis. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Pathological N1 ≥3cm<a class="elsevierStyleCrossRef" href="#tblfn0010">a</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Follicular thyroid cancer iwht extensive vascular invasion (>4 foci). \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2021929.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "a" "nota" => "Greatest diameter. Source: Haugen et al.<a class="elsevierStyleCrossRef" href="#bib0305">4</a>" ] ] ] "descripcion" => array:1 [ "en" => "Stratification of risk of persistence/recurrence of differentiated thyroid cancer according to the ATA 2015." ] ] 2 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at3" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "AJCC: American Joint Committee on Cancer; TNM: tumor/node/metastasis." "tablatextoimagen" => array:2 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " colspan="4" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">7th edition</th><th class="td" title="table-head " colspan="4" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">8th edition</th></tr><tr title="table-row"><th class="td" title="table-head " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black"><45 years</th><th class="td" title="table-head " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Survival at 10 years</th><th class="td" title="table-head " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black"><55 years</th><th class="td" title="table-head " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Survival at 10 years</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">I \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Any T and N \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">97–100% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">I \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Any T and N \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">98–100% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">II \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Any T and N \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">95–99% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">II \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Any T and N \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">85–95% \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2021928.png" ] ] 1 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " colspan="5" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">≥45 years</th><th class="td" title="table-head " colspan="5" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">≥55 years</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">I \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">T1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">N0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">97–100% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">I \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">T1 or 2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">N0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">98–100% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">II \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">T2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">N0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">97–100% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">II \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">T1 or 2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">N1a/b \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">85–95% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">T3a/b any N \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">III \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">T1 or 2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">N1a \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">88–95% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">III \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">T4a \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Any N \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">60–70% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">T3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">N0 or 1a \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">IVA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">T1or 2 or 3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">N1b \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">50–75% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">IVA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">T4b \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Any N \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><50% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">T4a \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Any N \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">IVB \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">T4b \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Any N M0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">IVB any T and N \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">IVC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Any T and N \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2021925.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Comparison between the 7th and 8th edition of the TNM Classification of the AJCC for differentiated thyroid cancer." ] ] 3 => array:8 [ "identificador" => "tbl0020" "etiqueta" => "Table 4" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at4" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "ATA: American Thyroid Association; EET: extrathyroid extension; NTCTCSG: National Thyroid Cancer Treatment Cooperative Study Group; TNM: tumor/node/metastasis; 131I: radioiodine." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">ATA risk (TNM) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Description \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Is there evience that 131I increases survival? \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Is there evidence that 131I increases disease-free survival? \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Is ablation with 131I indicated? \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ATA low risk T1a N0, Nx M0, Mx \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">≤1cm Uni or multifocal \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ATA low risk T1b, T2 N0, Nx M0, Mx \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">>1cm ≤4cm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Conflictive observational data \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Not routine use<a class="elsevierStyleCrossRef" href="#tblfn0015">a</a> Consider in aggressive histology or vascular invasion \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ATA low/intermediate risk T3 N0, Nx M0, Nx \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">>4cm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Conflictive data \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Conflictive observational data \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Consider<a class="elsevierStyleCrossRef" href="#tblfn0015">a</a> According to whether adverse characteristics or patient age \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ATA low/intermediate risk T3 N0, Nx M0, Mx \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Microscopic EET (any T) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Conflictive observational data \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Consider<a class="elsevierStyleCrossRef" href="#tblfn0015">a</a> Small tumors with microscopic EET can avoid 131I \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ATA low/intermediate risk T1–T3 N1a M0, Mx \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Lymph node metastasis in central compartment \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No, except age ≥55 (NTCTCSG stage III) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Conflictive observational data \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Consider<a class="elsevierStyleCrossRef" href="#tblfn0015">a</a> - Yes 131I for risk of persistence/ Recurrence by size, Lymph node metastasis or EET - No 131I if <5 lymph node metstasis In central compartment \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ATA low/intermediate risk T1–T3 N1b M0, Mx \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Laterocervical or mediastinic lymph node metastasis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No, except age ≥55 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Conflictive observational data \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Consider<a class="elsevierStyleCrossRef" href="#tblfn0015">a</a> In general favorable to 131I for risk of persistence/recurrence \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ATA high risk T4 Any N Any M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Any T Macroscopic EET \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ATA high risk M1 Any T Any N \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Distant metastasis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2021924.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0015" "etiqueta" => "a" "nota" => "In addition to the clinical pathological characteristics, the experience of the ultrasonographer, the surgeon, the multidisciplinary committee and the method of thyroglobulin measurement should also be taken into account. Source: Haugen et al.<a class="elsevierStyleCrossRef" href="#bib0305">4</a>" ] ] ] "descripcion" => array:1 [ "en" => "Ablative treatment with 131I according to the ATA 2015." ] ] 4 => array:5 [ "identificador" => "tb0005" "tipo" => "MULTIMEDIATEXTO" "mostrarFloat" => false "mostrarDisplay" => true "texto" => array:1 [ "textoCompleto" => "1Teaching pointIn tumors >1cm and ≤4cm without local or lymphatic extension, the decision as to the surgical technique to perform should be made by a multidisciplinary committee since lobectomy leaves the non resected lobe without a histological study and excludes treatment with 131I and follow-up with Tg." ] ] 5 => array:5 [ "identificador" => "tb0010" "tipo" => "MULTIMEDIATEXTO" "mostrarFloat" => false "mostrarDisplay" => true "texto" => array:1 [ "textoCompleto" => "1Teaching pointThe stratification of risk classifies patients with DTC as having low, intermediate or high risk and can decide the initial treatment to be administered and establish the follow-up strategy." ] ] 6 => array:5 [ "identificador" => "tb0015" "tipo" => "MULTIMEDIATEXTO" "mostrarFloat" => false "mostrarDisplay" => true "texto" => array:1 [ "textoCompleto" => "1Teaching pointDynamic stratification of risk classifies patients with DTC during follow-up as having:<ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0050">•Excellent response.</li><li class="elsevierStyleListItem" id="lsti0150">•Incomplete biochemical response.</li><li class="elsevierStyleListItem" id="lsti0155">•Incomplete structural response.</li><li class="elsevierStyleListItem" id="lsti0160">•Indeterminate response.</li></ul>" ] ] 7 => array:5 [ "identificador" => "tb0020" "tipo" => "MULTIMEDIATEXTO" "mostrarFloat" => false "mostrarDisplay" => true "texto" => array:1 [ "textoCompleto" => "1Teaching pointIn DTC treatment with 131I may be:<ul class="elsevierStyleList" id="lis0020"><li class="elsevierStyleListItem" id="lsti0165">•Ablative: to eliminate healthy residual thyroid tissue post-thyroidectomy.</li><li class="elsevierStyleListItem" id="lsti0170">•Adjuvant: to treat residual microscopic disease.</li><li class="elsevierStyleListItem" id="lsti0175">•To treat macroscopic or metastatic disease.</li></ul>" ] ] 8 => array:5 [ "identificador" => "tb0025" "tipo" => "MULTIMEDIATEXTO" "mostrarFloat" => false "mostrarDisplay" => true "texto" => array:1 [ "textoCompleto" => "1Teaching pointIndications for treatment with 131I:<ul class="elsevierStyleList" id="lis0030"><li class="elsevierStyleListItem" id="lsti0180">•Low risk: 131I is not routinely administered when the tumor is ≤1cm.There is controversy as to whether to treat or not tumors >1 and ≤4cm (while awaiting the results of ongoing prospective, randomized, multicenter studies). The decision to administer or not 131I is based on local factors such as the experience of the ultrasonographer, the surgeon, or the method of Tg measurement. The EANM recommends the administration of 131I in tumors >1cm.</li><li class="elsevierStyleListItem" id="lsti0185">•Intermediate risk: 131I is administered according to the characteristics of the tumor, the presence of significant lymph node metastasis, vascular invasion or aggressive histology, combined with patient age (≥55 years). The decision to treat or not should be made by a multidisciplinary committee.</li><li class="elsevierStyleListItem" id="lsti0190">•High risk: 131I is routinely administered.</li></ul>" ] ] 9 => array:5 [ "identificador" => "tb0030" "tipo" => "MULTIMEDIATEXTO" "mostrarFloat" => false "mostrarDisplay" => true "texto" => array:1 [ "textoCompleto" => "1Teaching pointWhat stimulation method should be used?<ul class="elsevierStyleList" id="lis0035"><li class="elsevierStyleListItem" id="lsti0195">•Suspension of hormonal treatment in local metastatic disease (recurrence/persistence of lymph node involvement) and distant metastasis (not in elderly patients and those with important comorbidity).</li><li class="elsevierStyleListItem" id="lsti0200">•rhTSH in the treatment for ablative purposes and in the treatment of residual microscopic disease with 131I (patients with low or intermediate risk).</li></ul>" ] ] 10 => array:5 [ "identificador" => "tb0035" "tipo" => "MULTIMEDIATEXTO" "mostrarFloat" => false "mostrarDisplay" => true "texto" => array:1 [ "textoCompleto" => "1Teaching pointDose (activity) of 131I:<ul class="elsevierStyleList" id="lis0050"><li class="elsevierStyleListItem" id="lsti0205">•Ablative treatment: 1.1GBq (30mCi) (low risk, candidates for ablation). This dose is based on the results obtained in short-term studies aimed at evaluating its effectiveness with respect to ablation. Although the premise is that the optimal dose of 131I to administer should not only achieve good ablation but also reduce the risk of recurrence/mortality, the results of long-term studies are still needed to evaluate the effectiveness of this dose in relation to the risk of recurrence.</li><li class="elsevierStyleListItem" id="lsti0210">•Adjuvant treatment: 2.8–3.7GBq (75–100mCi) (intermediate risk with residual microscopic disease post-surgery).</li><li class="elsevierStyleListItem" id="lsti0215">•Treatment of residual macroscopic and local and/or distant metastatic disease:<ul class="elsevierStyleList" id="lis0055"><li class="elsevierStyleListItem" id="lsti0220">–150mCi (5.6GBq): infiltrated cervical and mediastinic lymph nodes.</li><li class="elsevierStyleListItem" id="lsti0225">–150–200mCi (5.6–7.5GBq): pulmonary metastasis.</li><li class="elsevierStyleListItem" id="lsti0230">–200mCi (7.5GBq): bone metastasis or other distant metastases.</li></ul></li></ul>" ] ] 11 => array:5 [ "identificador" => "tb0040" "tipo" => "MULTIMEDIATEXTO" "mostrarFloat" => false "mostrarDisplay" => true "texto" => array:1 [ "textoCompleto" => "1Teaching pointIn intermediate-high and low risk DTC with detectable maintained or increased Tg levels, a scan with 131I is made at 6–12 months after treatment and if the following is shown:<ul class="elsevierStyleList" id="lis0060"><li class="elsevierStyleListItem" id="lsti0235">•Significant cervical uptake, 3.7–5.6GBq (100–150mCi) of 131I is administered to complete the ablation.</li><li class="elsevierStyleListItem" id="lsti0240">•Non significant cervical uptake, or no evidence of disease by other imaging techniques, treatment is not administered.</li><li class="elsevierStyleListItem" id="lsti0245">•Disease in other localizations, the corresponding empiric dose of 131I is administered.</li></ul>" ] ] 12 => array:5 [ "identificador" => "tb0045" "tipo" => "MULTIMEDIATEXTO" "mostrarFloat" => false "mostrarDisplay" => true "texto" => array:1 [ "textoCompleto" => "1Teaching pointCervical tumoral recurrence is treated with:<ul class="elsevierStyleList" id="lis0070"><li class="elsevierStyleListItem" id="lsti0250">•Surgical resection whenever possible (evaluate the aggressiveness of the procedure with respect to the expected benefits).</li><li class="elsevierStyleListItem" id="lsti0255">•5.5 GBq (150mCi) of 131I after surgery if disease showing iodine uptake persists.</li><li class="elsevierStyleListItem" id="lsti0260">•If disease not showing iodine uptake persists after surgery, 18F-FDG PET/CT is performed.</li></ul>" ] ] 13 => array:5 [ "identificador" => "tb0050" "tipo" => "MULTIMEDIATEXTO" "mostrarFloat" => false "mostrarDisplay" => true "texto" => array:1 [ "textoCompleto" => "1Teaching pointThe benefits of empiric treatment with 131I in the TENIS syndrome are questionable, since this treatment has not shown to have an impact on the prognosis of the disease. 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Continuing Education

Radioiodine treatment of differentiated thyroid cancer related to guidelines and scientific literature

Tratamiento del cáncer diferenciado de tiroides con radioyodo a la luz de las guías y de la literatura científica

M. Estorcha,

Corresponding author

mestorch@santpau.cat

Corresponding author.

, M. Mitjavilab, M.A. Murosc, E. Caballerod, on behalf of the Grupo de Trabajo de Endocrinología de la SEMNIM

a Servicio de Medicina Nuclear, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

b Servicio de Medicina Nuclear, Hospital Universitario Puerta de Hierro, Majadahonda, Madrid, Spain

c Servicio de Medicina Nuclear, Hospital Universitario Virgen de las Nieves, Granada, Spain

d Servicio de Medicina Nuclear, Hospital Doctor Peset, Valencia, Spain

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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">1</span><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Differentiated thyroid cancer &#40;DTC&#41; is a papillary or follicular cancer&#44; and the treatment of patients with these tumors is similar despite having numerous biological differences&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Surgery is the first treatment to carry out in a patient with DTC&#46; Afterwards&#44; most patients receive hormone and ablative treatment with radioiodine &#40;<span class="elsevierStyleSup">131</span>I&#41;&#46; The follow-up of patients with DTC is performed based on the basal determinations&#44; and when necessary&#44; stimulated&#44; of thyroglobulin &#40;Tg&#41; and antithyroglobulin antibodies &#40;TgAb&#41; is performed as well as imaging techniques according to risk&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Although most patients with DTC do not die from the disease&#44; prognostic factors associated with high risk of recurrence and death have been identified&#44; the most important being age at diagnosis&#44; tumor size and the presence of local or distant tumoral invasion&#46;<a class="elsevierStyleCrossRefs" href="#bib0290"><span class="elsevierStyleSup">1&#8211;3</span></a> Follicular cancer usually appears in older patients and usually has a more aggressive course with a higher mortality than papillary cancer&#46; Female sex is related to a better prognosis&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">This document of continuing education was prepared considering the 2015 guidelines of the American Thyroid Association &#40;ATA&#41;&#44; the British Thyroid Society&#44; the European and American Societies of Nuclear Medicine&#44; the consensus of the European Group an the last edition of the National Comprehensive Cancer Network &#40;NCCN&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0305"><span class="elsevierStyleSup">4&#8211;9</span></a> Likewise&#44; we also made an extensive and complete review of the scientific literature related to DTC&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">At present&#44; the decision how to treat and follow patients with DTC should be made by consensus in a multidisciplinary committee made up of specialists specifically and preferentially devoted to thyroid cancer &#40;endocrinology&#44; general surgery or otorhinolaryngology&#44; nuclear medicine&#44; anatomic pathology&#44; medical oncology&#44; radiodiagnosis and clinical biochemistry&#41; which can provide integrated care with optimization of resources&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">10</span></a></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">2</span><span class="elsevierStyleSectionTitle" id="sect0030">Treatment and follow-up of differentiated thyroid cancer</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">2&#46;1</span><span class="elsevierStyleSectionTitle" id="sect0035">Surgical treatment</span><p id="par0030" class="elsevierStylePara elsevierViewall">Preoperative ultrasonography with evaluation of the central lymphatic and laterocervical compartments enable programming the most optimal surgical procedure in each patient&#46; The choice of this procedure is currently based on retrospective studies and consensus documents since there are no prospective studies in this respect&#46;<a class="elsevierStyleCrossRefs" href="#bib0305"><span class="elsevierStyleSup">4&#44;6&#44;8&#44;9</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">The surgical procedure depends&#44; among other factors&#44; on tumor size and the presence or not of local extension or locoregional lymphatic involvement&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">&#8226;</span><p id="par0040" class="elsevierStylePara elsevierViewall">Tumors &#8804;1<span class="elsevierStyleHsp" style=""></span>cm without local or lymphatic extension&#58; lobectomy&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">&#8226;</span><p id="par0045" class="elsevierStylePara elsevierViewall">Tumors &#62;1<span class="elsevierStyleHsp" style=""></span>cm and &#8804;4<span class="elsevierStyleHsp" style=""></span>cm without local or lymphatic extension&#58; lobectomy or thyroidectomy&#46; Thyroidectomy is performed when the ultrasonography of the contralateral lobe is not completely normal or when ablative treatment with <span class="elsevierStyleSup">131</span>I is carried out&#46; The patient can decide which procedure to undergo&#46;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">&#8226;</span><p id="par0050" class="elsevierStylePara elsevierViewall">Tumors &#62;4<span class="elsevierStyleHsp" style=""></span>cm&#44; local or lymphatic extension or metastasis&#58; total thyroidectomy&#46;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">&#8226;</span><p id="par0055" class="elsevierStylePara elsevierViewall">Tumor of any size with a history of cervical irradiation&#58; total thyroidectomy&#46;</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">&#8226;</span><p id="par0060" class="elsevierStylePara elsevierViewall">Multifocal papillary microcarcinoma&#58; total thyroidectomy &#40;especially for 8&#8211;9<span class="elsevierStyleHsp" style=""></span>mm lesions&#41;&#46;</p></li></ul></p><p id="par0065" class="elsevierStylePara elsevierViewall">Lobectomy of tumors between 1 and 4<span class="elsevierStyleHsp" style=""></span>cm in size without local or lymphatic extension excludes ablative treatment with <span class="elsevierStyleSup">131</span>I&#44; and makes follow-up with Tg much more difficult&#46; Retrospective studies have described the utility of treatment with <span class="elsevierStyleSup">131</span>I in DTC of &#62;1<span class="elsevierStyleHsp" style=""></span>cm&#46;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">11</span></a> On the other hand&#44; the experience of the surgeon is fundamental and is considered in the guidelines of the European Society of Nuclear Medicine&#44;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">6</span></a> as is postoperative Tg which helps to identify patients who may benefit from radioiodine&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">12</span></a> It has been shown that compared to thyroidectomy&#44; lobectomy in tumors &#62;1<span class="elsevierStyleHsp" style=""></span>cm is associated with a 15&#37; risk of recurrence and 31&#37; increase in the risk of death&#46;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">13</span></a> In a recent retrospective study in a group of 394 patients with DTC of low or low-intermediate risk &#40;1&#8211;4<span class="elsevierStyleHsp" style=""></span>cm&#41;&#44; Kluijfhout et al&#46;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">14</span></a> demonstrated that 19&#46;5&#37; would have required completion of thyroidectomy and 25&#46;6&#37; would have required treatment with <span class="elsevierStyleSup">131</span>I if they had been treated with lobectomy&#46; However&#44; there are also multiple studies reporting that thyroidectomy has no benefits over lobectomy with regard to survival in tumors &#8804;4<span class="elsevierStyleHsp" style=""></span>cm&#46;<a class="elsevierStyleCrossRefs" href="#bib0360"><span class="elsevierStyleSup">15&#44;16</span></a> The British guidelines recommend that the type of intervention should be decided individually based on each clinical scenario &#40;tumor size&#44; ultrasonography of the doubtful contralateral lobe and&#47;or evidence of suspicious lymph nodes&#44; patient age&#44; among others&#41; and additional factors of risk &#40;history of radiation&#44; etc&#46;&#41;&#44; and the decision should always be made by a multidisciplinary committee&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">5</span></a><elsevierMultimedia ident="tb0005"></elsevierMultimedia></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">2&#46;2</span><span class="elsevierStyleSectionTitle" id="sect0045">Hormone treatment</span><p id="par0075" class="elsevierStylePara elsevierViewall">Following surgery most patients receive hormone replacement treatment with levothyroxine &#40;LT4&#41; to maintain an euthyroid status and&#47;or to control tumoral growth&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Patients undergoing lobectomy might not be treated with LT4&#46; In this case&#44; 6 weeks after surgery&#44; thyrotropin levels &#40;TSH&#41; are determined to assess the need or not to administer the hormone&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Patients treated with total thyroidectomy should start hormone treatment when they are not candidates for ablative treatment with <span class="elsevierStyleSup">131</span>I or when this is administered under stimulus with recombinant human TSH &#40;rhTSH&#41;&#46; If ablative treatment is administered by withdrawing hormone treatment&#44; the patient cannot initiate hormone treatment after surgery&#44; provided that <span class="elsevierStyleSup">131</span>I is given at 4&#47;6 weeks &#40;with TSH &#62;30<span class="elsevierStyleHsp" style=""></span>mU&#47;l&#41;&#46; When hormone treatment is administered after surgery&#44; TSH levels should be determined beforehand and after&#44; again at 4&#8211;6 weeks&#44; to adjust the dose of LT4 if necessary&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">2&#46;3</span><span class="elsevierStyleSectionTitle" id="sect0050">Initial stratification of risk</span><p id="par0090" class="elsevierStylePara elsevierViewall">The need or not to administer additional treatment after surgery and especially whether <span class="elsevierStyleSup">131</span>I should be administered is decided based on the initial stratification of risk&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">The determination of TSH and Tg 4&#8211;6 weeks after surgery provides an orientation as to the status of the disease&#46; Although the optimal stimulated and non stimulated Tg levels are not clearly defined&#44;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">4</span></a> it has been established that non stimulated levels should be &#60;30<span class="elsevierStyleHsp" style=""></span>ng&#47;ml in the case of lobectomy and &#60;5<span class="elsevierStyleHsp" style=""></span>ng&#47;ml in the case of total thyroidectomy&#46; Levels above these indicate the need for reassessment to complete thyroidectomy and&#47;or administer radioiodine&#46;<a class="elsevierStyleCrossRefs" href="#bib0370"><span class="elsevierStyleSup">17&#44;18</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">The Tg values can vary according to the method of determination used and also in the presence or not of TgAb&#46;</p><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">2&#46;3&#46;1</span><span class="elsevierStyleSectionTitle" id="sect0055">Stratification of risk</span><p id="par0105" class="elsevierStylePara elsevierViewall">The stratification of risk is made based on the tumor&#44; node&#44; metastasis &#40;TNM&#41; classification &#40;8th edition<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">19</span></a>&#41; of the American Joint Committee on Cancer &#40;AJCC&#41;&#44; which can estimate mortality&#44; and the 2015 ATA stratification of risk system&#44;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">4</span></a> which estimates the risk of disease persistence or recurrence &#40;<a class="elsevierStyleCrossRefs" href="#tbl0005">Tables 1 and 2</a>&#44; respectively&#41;&#46; Patients are classified into 3 categories of risk &#40;low&#44; intermediate or high&#41; based on their clinical-pathological characteristics&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0110" class="elsevierStylePara elsevierViewall">Stratification of risk can decide the initial treatment as well as establish the follow-up strategy to be followed&#46; However&#44; this strategy may have to be changed along the course of the disease&#44; and this will be determined by dynamic stratification of risk&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">20</span></a><elsevierMultimedia ident="tb0010"></elsevierMultimedia></p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">2&#46;4</span><span class="elsevierStyleSectionTitle" id="sect0065">Dynamic stratification of risk</span><p id="par0120" class="elsevierStylePara elsevierViewall">During follow-up patients are reclassified into one of the following clinical categories&#44; and imaging studies and treatments&#44; if necessary&#44; are adapted to the classification since it has been observed that the risk of recurrence varies based on the response to the different treatments<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">20</span></a>&#58;<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">&#8226;</span><p id="par0125" class="elsevierStylePara elsevierViewall">Excellent response&#58; no clinical&#44; biochemical or structural evidence of disease&#46;</p></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">&#8226;</span><p id="par0130" class="elsevierStylePara elsevierViewall">Incomplete biochemical response&#58; detectable Tg or increased TgAb&#46;</p></li><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">&#8226;</span><p id="par0135" class="elsevierStylePara elsevierViewall">Incomplete structural response&#58; persistence or new locoregional or distant tumor tumoral lesions&#46;</p></li><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">&#8226;</span><p id="par0140" class="elsevierStylePara elsevierViewall">Indeterminate response&#58; biochemical or structural finidings that can not rule out malignancy or persistence of TgAb with no evidence of structural disease&#46;</p></li></ul></p><p id="par0145" class="elsevierStylePara elsevierViewall">During the first year&#44; follow-up is made by cervical ultrasonography and determination of plasma TSH and Tg levels under hormone suppression treatment at 6 or 12 months depending on the initial risk&#46; Tg is determined by stimulation with rhTSH in patients with intermediate or high risk with undectable basal Tg &#40;to confirm excellent response&#41; or to identify persistent&#47;recurrent disease&#46; The use of imaging or histological studies&#44; if needed&#44; also depends on the initial risk or whether the patient shows biochemical or incomplete structural response&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">After the first year&#44; plasma TSH levels are determined annually to adjust the dose or LT4 or to determine that these levels are maintained at &#60;0&#46;1&#8211;0&#46;5<span class="elsevierStyleHsp" style=""></span>mU&#47;l in patients with incomplete structural response&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">Likewise&#44; according to dynamic stratification of risk&#44; imaging studies are performed according to the case&#58; cervical ultrasonography on suspicion of locoregional disease&#44; whole body scan with <span class="elsevierStyleSup">131</span>I and&#47;or <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT in cases suspected of having locoregional or distant disease&#44; <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT with contrast in iodine refractory disease or magnetic resonance in patients suspected of presenting brain disease&#46;<elsevierMultimedia ident="tb0015"></elsevierMultimedia></p></span></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">3</span><span class="elsevierStyleSectionTitle" id="sect0075">Treatment with radioiodine</span><p id="par0185" class="elsevierStylePara elsevierViewall">The first treatment with <span class="elsevierStyleSup">131</span>I for DTC was administered in 1945&#46; However&#44; at present the management of DTC is still controversial due to the lack of prospective randomized clinical trials&#44; and therefore&#44; the recommendations of the experts are based on retrospective observational data and may be influenced by multiple factors related to the course of the disease according to their interpretation of the literature as well as their clinical perspective and experience&#46;<a class="elsevierStyleCrossRefs" href="#bib0390"><span class="elsevierStyleSup">21&#8211;23</span></a></p><p id="par0190" class="elsevierStylePara elsevierViewall">Treatment with <span class="elsevierStyleSup">131</span>I is based on the fact that tumoral thyroid tissue has the capacity to incorporate iodine from the blood by the sodium&#47;iodine transporter membrane&#46; Compared with normal tissue&#44; the expression of this transporter is reduced in tumoral tissue&#44; and thus&#44; the uptake of <span class="elsevierStyleSup">131</span>I may be reduced&#46; Nonetheless&#44; the beta radiation of <span class="elsevierStyleSup">131</span>I leads to the formation of free radicals at an intracellular level&#44; DNA lesion&#44; and finally&#44; cell death&#44; which is the objective of the treatment&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">Treatment with <span class="elsevierStyleSup">131</span>I in DTC is administered&#58; to eliminate residual healthy thyroid tissue post-thyroidectomy presenting great avidity for the iodine &#40;ablative treatment&#41;&#59; to treat recurrence&#47;persistence of lymph node involvement showing less avidity for the iodine &#40;adjuvant treatment&#41; or to treat macroscopic or metastatic disease&#46;</p><p id="par0200" class="elsevierStylePara elsevierViewall">Apart from destroying healthy thyroid tissue post-thyroidectomy&#44; the objective of ablative treatment is to destroy possible microscopic foci&#44; minimize the risk of recurrence in patients with predisposition &#40;i&#46;e&#46; history of cervical irradiation&#41;&#44; increase the specificity of Tg as a tumoral marker and increase the specificity of the scan with <span class="elsevierStyleSup">131</span>I for the detection of recurrent or metastatic disease&#46; On the other hand&#44; the objective of adjuvant treatment with <span class="elsevierStyleSup">131</span>I in recurrence&#47;persistence of lymph node involvement and metastatic disease is to destroy all micro- and macroscopic disease that cannot be treated with surgery&#44; thereby reducing the risk of recurrence and death&#46;<elsevierMultimedia ident="tb0020"></elsevierMultimedia></p><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">3&#46;1</span><span class="elsevierStyleSectionTitle" id="sect0085">Indications</span><p id="par0225" class="elsevierStylePara elsevierViewall">The administration of <span class="elsevierStyleSup">131</span>I after thyroidectomy depends on the clinical&#8211;pathological characteristics of each tumor &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41; as well as the initial stratification of risk &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46; The introduction of the 8th edition of the AJCC TNM classification of DTC raised the limit of age of risk from &#8805;45 to &#8805;55 years&#46; This has led to reclassification of 23&#8211;35&#37; of the patients with DTC to lower stages than previously&#44; with an increase in stages I and II and an increase in the probability of recurrence in stage II patients &#8805;55 years of age&#46; On the other hand&#44; stage III includes patients with more aggressive cervical disease without distant metastasis&#44; with the vital prognosis in stages III and IV being worse than in the 7th edition of the AJCC TNM classification &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46; At present&#44; the 2015 ATA guidelines are the most widely used and have the greatest following among specialists involved in the treatment of DTC&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">4</span></a> Except in tumors of low risk &#8804;1<span class="elsevierStyleHsp" style=""></span>cm &#40;T1a&#41; and in those of high risk &#40;T4&#41;&#44; the 2015 ATA recommendations on ablative treatment are ambiguous and open to different interpretations in relation to local factors &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41;&#58;<ul class="elsevierStyleList" id="lis0025"><li class="elsevierStyleListItem" id="lsti0055"><span class="elsevierStyleLabel">&#8226;</span><p id="par0230" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Low risk</span>&#58; <span class="elsevierStyleSup">131</span>I not routinely administered when the tumor is &#8804;1<span class="elsevierStyleHsp" style=""></span>cm&#44; even in the presence of affected regional lymph nodes &#40;&#60;5 lymph nodes of &#60;2<span class="elsevierStyleHsp" style=""></span>mm&#41;&#44; of multifocal tumor &#40;all foci &#60;1<span class="elsevierStyleHsp" style=""></span>cm&#41; and intrathyroid tumor &#62;1 and &#8804;4<span class="elsevierStyleHsp" style=""></span>cm&#46; Low doses can be administered &#40;1&#46;1<span class="elsevierStyleHsp" style=""></span>GBq&#47;30<span class="elsevierStyleHsp" style=""></span>mCi&#41; in a selected group of patients&#46; The decision to administer <span class="elsevierStyleSup">131</span>I or not can be based on local factors such as the experience of the ultrasonographer&#44; the surgeon or the method of Tg measurement&#46;</p><p id="par0235" class="elsevierStylePara elsevierViewall">The decision to not administer <span class="elsevierStyleSup">131</span>I in low risk cases is based on retrospective studies&#44; systematic reviews and metaanalyses which have shown no benefits of this treatment with respect to the rate of recurrence or mortality&#46;<a class="elsevierStyleCrossRefs" href="#bib0405"><span class="elsevierStyleSup">24&#44;25</span></a> To the contrary&#44; other retrospective studies have shown benefits in terms of overall survival and recurrence-free interval in tumors &#62;1<span class="elsevierStyleHsp" style=""></span>cm<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">11</span></a> with the administration of <span class="elsevierStyleSup">131</span>I&#46; In a retrospective study including 574 patients&#44; Tran et al&#46;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">26</span></a> recently reported that tumors &#62;2<span class="elsevierStyleHsp" style=""></span>cm are associated with a 5-fold greater risk of recurrence in patients &#8805;55 years of age&#46; Three prospective randomized&#44; multicenter&#44; clinical trials are currently ongoing &#40;ESTIMABL2&#44; IoN and CLERAD-PROBE&#41;&#46; The 5- and 10-year follow-up results of these studies are expected at the beginning of 2022 and 2027&#44; respectively&#46;<a class="elsevierStyleCrossRefs" href="#bib0420"><span class="elsevierStyleSup">27&#8211;29</span></a> The position of the European Society of Nuclear Medicine &#40;EANM&#41; is to administer <span class="elsevierStyleSup">131</span>I in all tumors &#62;1<span class="elsevierStyleHsp" style=""></span>cm&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">6</span></a> Therefore&#44; while awaiting the results of the previously mentioned ongoing trials&#44; the administration or not of <span class="elsevierStyleSup">131</span>I remains controversial&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">22</span></a></p></li><li class="elsevierStyleListItem" id="lsti0060"><span class="elsevierStyleLabel">&#8226;</span><p id="par0240" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Intermediate risk</span>&#58; <span class="elsevierStyleSup">131</span>I is administered according to the characteristics of the tumor&#44; presence of significant lymph node metastasis&#44; vascular invasion or aggressive histology&#44; combined with patient age &#40;&#8805;55 years&#41;&#46; The decision to treat or not should be made by a multidisciplinary committee&#46; The data in the literature are limited in this group of patients&#44; although they do indicate benefits with respect to overall survival&#46;<a class="elsevierStyleCrossRefs" href="#bib0305"><span class="elsevierStyleSup">4&#44;30&#44;31</span></a></p></li><li class="elsevierStyleListItem" id="lsti0065"><span class="elsevierStyleLabel">&#8226;</span><p id="par0245" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">High risk</span>&#58; <span class="elsevierStyleSup">131</span>I is routinely administered&#44; having shown benefits in overall survival&#46;<a class="elsevierStyleCrossRefs" href="#bib0440"><span class="elsevierStyleSup">31&#44;32</span></a></p></li></ul><elsevierMultimedia ident="tb0025"></elsevierMultimedia></p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">3&#46;2</span><span class="elsevierStyleSectionTitle" id="sect0095">Patient preparation</span><p id="par0275" class="elsevierStylePara elsevierViewall">The <span class="elsevierStyleSup">131</span>I uptake depends on adequate cellular stimulation by an elevation of plasma TSH levels as well as stable low iodine levels in blood&#46; The first is achieved by withdrawing hormone treatment or by administering rhTSH&#46; The second can be achieved by instructing the patient to follow a diet low in iodine and to avoid any exogenous source of iodine &#40;special care with iodized salt&#44; amiodarone and radiological contrasts&#41;&#46;</p><p id="par0280" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Suspension of hormone treatment</span>&#58; LT4 is withdrawn 3&#8211;4 weeks before the administration of <span class="elsevierStyleSup">131</span>I&#44; and plasma TSH levels should be determined to ensure that they are &#62;30<span class="elsevierStyleHsp" style=""></span>mU&#47;l prior to its administration&#46;<a class="elsevierStyleCrossRef" href="#bib0450"><span class="elsevierStyleSup">33</span></a> Pre-treatment with LT3 can also be carried out during 1&#8211;2 weeks &#40;25<span class="elsevierStyleHsp" style=""></span>&#956;g<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>3&#47;day&#41; to reduce the symptoms of hypothyroidism&#46;</p><p id="par0285" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">rhTSH</span>&#58; an intramuscular injection of 0&#46;9<span class="elsevierStyleHsp" style=""></span>mg of rhTSH is made on 2 consecutive days&#44; administering the <span class="elsevierStyleSup">131</span>I on the third day&#46; The determination of Tg is made 72<span class="elsevierStyleHsp" style=""></span>h after the injection of rhTSH&#59; that is&#44; on the fifth day&#46;</p><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">3&#46;2&#46;1</span><span class="elsevierStyleSectionTitle" id="sect0100">What stimulation method should be used&#63;</span><p id="par0290" class="elsevierStylePara elsevierViewall">Suspension of hormonal treatment is the method of choice for the treatment of local metastatic &#40;recurrence&#47;persistence of lymph node involvement&#41; or metastatic disease&#46; However&#44; it is not advised in elderly patients or in those with comorbidities which may be aggravated in a maintained state of hypothyroidism &#40;i&#46;e&#46; depression&#44; heart failure or severe sleep apnea&#41;&#46;</p><p id="par0295" class="elsevierStylePara elsevierViewall">rhTSH should be used in ablative treatment with <span class="elsevierStyleSup">131</span>I &#40;destruction of normal thyroid tissue&#41; and for the preparation of follow-up scans&#46; It should also be used in the treatment with <span class="elsevierStyleSup">131</span>I of residual microscopic disease in patients with low or intermediate risk&#46;</p><p id="par0300" class="elsevierStylePara elsevierViewall">Randomized studies and metaanalyses have shown a similar short-term ablative efficacy with the two methods&#46;<a class="elsevierStyleCrossRefs" href="#bib0455"><span class="elsevierStyleSup">34&#8211;38</span></a> In a multicenter study including 752 patients with low risk DTC randomly treated with low or high doses of <span class="elsevierStyleSup">131</span>I &#40;1&#46;1 vs&#46; 3&#46;7<span class="elsevierStyleHsp" style=""></span>GBq&#47;30 vs&#46; 100<span class="elsevierStyleHsp" style=""></span>mCi&#41; and hormone suspension vs&#46; rhTSH&#44; similar rates of ablation were found at 6&#8211;10 months with both doses and methods of preparation &#40;rhTSH 89&#46;1&#37; and hormone suspension 88&#46;9&#37;&#41;&#46; Later&#44; after a follow-up of 5&#46;4 years&#44; 98&#37; of these patients did not present disease persistence or recurrence&#59; structural disease was identified in 0&#46;6&#37; and biochemical disease in 0&#46;7&#37; and was not associated with either the dose of <span class="elsevierStyleSup">131</span>I administered or the method of preparation &#40;ESTIMABL1 trial<a class="elsevierStyleCrossRefs" href="#bib0465"><span class="elsevierStyleSup">36&#44;37</span></a>&#41;&#46; Mallick et al&#46;<a class="elsevierStyleCrossRef" href="#bib0475"><span class="elsevierStyleSup">38</span></a> published the results of the HiLo trial and also reported that in patients with low risk DTC randomly treated with low or high doses of <span class="elsevierStyleSup">131</span>I &#40;1&#46;1 vs&#46; 3&#46;7<span class="elsevierStyleHsp" style=""></span>GBq&#47;30 vs&#46; 100<span class="elsevierStyleHsp" style=""></span>mCi&#41; and also prepared with both methods&#44; the ablation was similar with both doses and methods &#40;rhTSH 87&#37; and hormone suspension 87&#37;&#41;&#46;</p><p id="par0305" class="elsevierStylePara elsevierViewall">Few studies have evaluated the two preparation methods in the long term&#46; One prospective study with a 10-year follow-up described similar results for both methods of preparation in patients treated with 1&#46;1<span class="elsevierStyleHsp" style=""></span>GBq of <span class="elsevierStyleSup">131</span>I&#44; and another retrospective study with a 9-year follow-up reported the same&#44; but this latter study also included patients with intermediate and high risk&#46;<a class="elsevierStyleCrossRefs" href="#bib0480"><span class="elsevierStyleSup">39&#44;40</span></a> In a retrospective review including 84 patients&#44; Tuttle et al&#46;<a class="elsevierStyleCrossRef" href="#bib0490"><span class="elsevierStyleSup">41</span></a> concluded that rhTSH is effective for the treatment of lymph node and pulmonary micrometastases shown by ablative treatment with <span class="elsevierStyleSup">131</span>I&#46; On the other hand&#44; in a retrospective study including 175 patients with a follow-up of 5 years&#44; Tala et al&#46;<a class="elsevierStyleCrossRef" href="#bib0495"><span class="elsevierStyleSup">42</span></a> described a similar effectiveness with rhTSH and hormone suspension in patients with macroscopic metastasis with iodine uptake&#46;<elsevierMultimedia ident="tb0030"></elsevierMultimedia></p></span></span></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">4</span><span class="elsevierStyleSectionTitle" id="sect0110">Dose &#40;activity&#41; of radioiodine</span><p id="par0325" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0040"><li class="elsevierStyleListItem" id="lsti0070"><span class="elsevierStyleLabel">&#8226;</span><p id="par0330" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Ablative treatment</span>&#58; this is administered to patients considered as having low risk who are candidates for ablation&#46;<a class="elsevierStyleCrossRefs" href="#bib0305"><span class="elsevierStyleSup">4&#44;5</span></a> The optimal dose of <span class="elsevierStyleSup">131</span>I to administer is based on achieving good ablation&#44; which is the objective of the treatment&#44; and on the risk of recurrence&#47;mortality &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41;&#46; Several studies have evaluated the optimal dose&#46;<a class="elsevierStyleCrossRefs" href="#bib0465"><span class="elsevierStyleSup">36&#44;37&#44;43&#44;44</span></a> However&#44; to date&#44; the lack of uniformity in relation to the patients&#44; method and even the definition of ablation have impeded establishing the most optimal dose&#46; The proposal of 1&#46;1<span class="elsevierStyleHsp" style=""></span>GBq &#40;30<span class="elsevierStyleHsp" style=""></span>mCi&#41; as the ablative dose of <span class="elsevierStyleSup">131</span>I is based on results obtained in studies aimed at evaluating the short term effectiveness of ablative treatment but not at evaluating its effectiveness to avoid recurrence&#44; which requires a longer follow-up&#46; Although 2 retrospective studies<a class="elsevierStyleCrossRefs" href="#bib0510"><span class="elsevierStyleSup">45&#44;46</span></a> did not find any differences in regard to recurrence at 5 and 14&#46;7 years of follow-up in patients treated with low vs&#46; high doses of <span class="elsevierStyleSup">131</span>I&#44; it is the results of prospective&#44; randomized&#44; multicenter&#44; clinical studies that will indicate the optimal dose of <span class="elsevierStyleSup">131</span>I to be administered for ablative purposes&#46;</p></li><li class="elsevierStyleListItem" id="lsti0075"><span class="elsevierStyleLabel">&#8226;</span><p id="par0335" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Adjuvant treatment</span>&#58; after thyroidectomy&#44; patients with DTC of intermediate risk are treated with <span class="elsevierStyleSup">131</span>I with 2 objectives&#58; ablation and treatment of residual microscopic disease post-surgery&#46; A dose of <span class="elsevierStyleSup">131</span>I of between 2&#46;8 and 3&#46;7<span class="elsevierStyleHsp" style=""></span>GBq &#40;75&#8211;100<span class="elsevierStyleHsp" style=""></span>mCi&#41; has been proposed&#46; Two retrospective studies performed in patients with DTC of intermediate risk treated with a low &#40;1&#46;1<span class="elsevierStyleHsp" style=""></span>GBq&#47;30<span class="elsevierStyleHsp" style=""></span>mCi&#41; vs&#46; a high dose &#40;3&#46;7&#8211;5&#46;5<span class="elsevierStyleHsp" style=""></span>GBq&#47;100&#8211;15<span class="elsevierStyleHsp" style=""></span>mCi&#41; of <span class="elsevierStyleSup">131</span>I found no significant differences in regard to the rate of ablation&#46;<a class="elsevierStyleCrossRefs" href="#bib0520"><span class="elsevierStyleSup">47&#44;48</span></a> In another retrospective study comparing doses of 100&#44; 150 and 200<span class="elsevierStyleHsp" style=""></span>mCi of <span class="elsevierStyleSup">131</span>I&#44; Sabra et al&#46;<a class="elsevierStyleCrossRef" href="#bib0530"><span class="elsevierStyleSup">49</span></a> concluded that the administration of more than 100<span class="elsevierStyleHsp" style=""></span>mCi in N1b patients&#44; especially in younger patients&#44; does not improve initial response to treatment&#46; In a study including 1298 patients with low and high risk DTC divided into two age groups&#40;&#60;45 and &#8805;45 years&#41;&#44; Verburg et al&#46;<a class="elsevierStyleCrossRef" href="#bib0535"><span class="elsevierStyleSup">50</span></a> concluded that the high dose was associated with a greater survival in patients &#8805;45 years of age and that the low dose should be used with caution in this age group&#46; At present&#44; and as mentioned previously&#44; the change in the age limt of risk to &#8805;55 years represents an increase in patients in stages I and II with a greater probability of recurrence in stage II&#44; since in this stage the patient is no longer of low risk and the low dose should not be considered&#46;</p></li><li class="elsevierStyleListItem" id="lsti0080"><span class="elsevierStyleLabel">&#8226;</span><p id="par0340" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Treatment of residual macroscopic and local and&#47;or distant metastatic disease</span>&#58; high empiric doses of <span class="elsevierStyleSup">131</span>I are administered&#58;<ul class="elsevierStyleList" id="lis0045"><li class="elsevierStyleListItem" id="lsti0085"><span class="elsevierStyleLabel">&#8211;</span><p id="par0345" class="elsevierStylePara elsevierViewall">5&#46;6<span class="elsevierStyleHsp" style=""></span>GBq &#40;150<span class="elsevierStyleHsp" style=""></span>mCi&#41;&#58; cervical and mediastinic lymph nodes&#46;</p></li><li class="elsevierStyleListItem" id="lsti0090"><span class="elsevierStyleLabel">&#8211;</span><p id="par0350" class="elsevierStylePara elsevierViewall">5&#46;6&#8211;7&#46;5<span class="elsevierStyleHsp" style=""></span>GBq &#40;150&#8211;200<span class="elsevierStyleHsp" style=""></span>mCi&#41;&#58; pulmonary metastases&#46;</p></li><li class="elsevierStyleListItem" id="lsti0095"><span class="elsevierStyleLabel">&#8211;</span><p id="par0355" class="elsevierStylePara elsevierViewall">7&#46;5<span class="elsevierStyleHsp" style=""></span>GBq &#40;200<span class="elsevierStyleHsp" style=""></span>mCi&#41;&#58; bone metastasis or other distant metastasis&#46;</p></li><li class="elsevierStyleListItem" id="lsti0100"><span class="elsevierStyleLabel">&#8211;</span><p id="par0360" class="elsevierStylePara elsevierViewall">The administration of higher doses requires a dosimetric study&#46;</p></li><li class="elsevierStyleListItem" id="lsti0105"><span class="elsevierStyleLabel">&#8211;</span><p id="par0365" class="elsevierStylePara elsevierViewall">The dose should not be greater than 5&#46;6<span class="elsevierStyleHsp" style=""></span>GBq &#40;150<span class="elsevierStyleHsp" style=""></span>mCi&#41; in patients with pulmonary metastases over the age of 70 due to a greater risk of bone marrow toxicity&#46;</p></li><li class="elsevierStyleListItem" id="lsti0110"><span class="elsevierStyleLabel">&#8211;</span><p id="par0370" class="elsevierStylePara elsevierViewall">Patients with renal insufficiency or on hemodialysis can be treated by decreasing the dose of <span class="elsevierStyleSup">131</span>I with posterior dialysis according to the usual protocol or administer the standard dose of <span class="elsevierStyleSup">131</span>I followed by more frequent dialysis&#46;<a class="elsevierStyleCrossRef" href="#bib0540"><span class="elsevierStyleSup">51</span></a></p></li></ul></p></li></ul></p><p id="par0375" class="elsevierStylePara elsevierViewall">The treatment is repeated when there is evidence of iodine uptake disease in a follow-up scan with <span class="elsevierStyleSup">131</span>I&#46; At 6&#8211;12 months after treatment&#44; a scan with <span class="elsevierStyleSup">131</span>I is made in patients with intermediate-high risk and those with low risk with detectable maintained or increased Tg&#46; The scan should be done with a low dose of <span class="elsevierStyleSup">131</span>I &#40;185<span class="elsevierStyleHsp" style=""></span>MBq&#47;5<span class="elsevierStyleHsp" style=""></span>mCi&#41; and preparation with rhTSH or with suspension of hormone treatment which induces hypothyroidism&#46; If the scan shows evidence of significant cervical uptake&#44; a second treatment is given with 3&#46;7&#8211;5&#46;6<span class="elsevierStyleHsp" style=""></span>GBq &#40;100&#8211;150<span class="elsevierStyleHsp" style=""></span>mCi&#41; of <span class="elsevierStyleSup">131</span>I to complete the ablation&#46; If cervical uptake is not significant or there is no evidence of disease by other imaging techniques&#44; treatment is not administered&#46; If there is evidence of disease in other localizations&#44; the corresponding dose of <span class="elsevierStyleSup">131</span>I is administered&#46;<elsevierMultimedia ident="tb0035"></elsevierMultimedia><elsevierMultimedia ident="tb0040"></elsevierMultimedia></p><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">4&#46;1</span><span class="elsevierStyleSectionTitle" id="sect0125">Persistent&#44; recurrent or distant disease</span><p id="par0435" class="elsevierStylePara elsevierViewall">During the first 2 years the treatment interval with <span class="elsevierStyleSup">131</span>I is 4&#8211;8 months according to the guidelines of the European and American Societies of Nuclear Medicine<a class="elsevierStyleCrossRefs" href="#bib0320"><span class="elsevierStyleSup">7&#44;8</span></a> and 6&#8211;12 months according to the 2015 ATA and British guidelines<a class="elsevierStyleCrossRefs" href="#bib0305"><span class="elsevierStyleSup">4&#44;5</span></a>&#58;<ul class="elsevierStyleList" id="lis0065"><li class="elsevierStyleListItem" id="lsti0115"><span class="elsevierStyleLabel">&#8226;</span><p id="par0440" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Cervical disease</span>&#58; Cervical tumor recurrence can be detected by clinical examination or an increase in plasma Tg levels&#44; with cervical ultrasonography being the method of choice for localization&#46; Surgical resection in the central and laterocervical compartment is the first treatment when the disease is of low volume&#46; However&#44; on occasions aggressive surgical resection in stable&#44; low volume disease is difficult to justify&#44; especially when its benefits in relation to an increase in the overall survival have not been demonstrated&#46; In these cases surgery is avoided&#44; and the patients are followed to ensure that they continue to be at low risk and a wait and see approach is taken&#46;</p><p id="par0445" class="elsevierStylePara elsevierViewall">The extension of recurrence beyond the thyroid bed &#40;larynx&#44; trachea&#44; esophagus or soft tissue&#41; implies the need for wider surgical resection based on CT study with contrast or magnetic resonance&#46;</p><p id="par0450" class="elsevierStylePara elsevierViewall">If disease persists following surgery a scan with <span class="elsevierStyleSup">131</span>I with rhTSH stimulation is indicated&#46; If this is positive&#44; treatment with <span class="elsevierStyleSup">131</span>I in the same conditions is carried out&#46; To the contrary&#44; if disease persists but <span class="elsevierStyleSup">131</span>I uptake is not observed&#44; a <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT is performed to localize dedifferentiated disease &#40;not presenting iodine uptake&#41;&#46; In this case&#44; positive results with <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT are considered to be an independent indicator of bad prognosis&#44; being correlated with global mortality when disease with no iodine uptake is shown&#46;<a class="elsevierStyleCrossRef" href="#bib0545"><span class="elsevierStyleSup">52</span></a></p></li><li class="elsevierStyleListItem" id="lsti0120"><span class="elsevierStyleLabel">&#8226;</span><p id="par0455" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Distant disease</span>&#58; patients who develop distant disease during follow-up should be treated with the same dose of <span class="elsevierStyleSup">131</span>I that would have been given if they had presented metastasis at the onset&#46; However&#44; in these cases the treatment with <span class="elsevierStyleSup">131</span>I is less effective&#46;<a class="elsevierStyleCrossRef" href="#bib0550"><span class="elsevierStyleSup">53</span></a> The efficacy of treatment with <span class="elsevierStyleSup">131</span>I is related to the radiosensitivity of the tumoral tissue&#44; which is greater in young patients with small-sized metastasis and with an elevated uptake of <span class="elsevierStyleSup">131</span>I&#46; In general&#44; the therapeutic efficacy is achieved with accumulated activity less than 22&#46;2<span class="elsevierStyleHsp" style=""></span>GBq &#40;600<span class="elsevierStyleHsp" style=""></span>mCi&#41;&#46; Recently&#44; 22&#46;2<span class="elsevierStyleHsp" style=""></span>GBq was arbitrarily established as the limit of accumulated activity for treatment with radioiodine&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">4</span></a> However&#44; to date there is no extensive experience with greater activities without the development of significant toxicity&#46; Nonetheless&#44; the decision should be made by a multidisciplinary committee and should always consider that the objective is to achieve benefits&#46;</p><p id="par0460" class="elsevierStylePara elsevierViewall">When <span class="elsevierStyleSup">131</span>I does not control the disease&#44; the disease is considered to be iodine refractory&#46; The most frequent scenarios of refractoriness to <span class="elsevierStyleSup">131</span>I are&#58; evident structural disease which has no avidity for <span class="elsevierStyleSup">131</span>I from the onset&#44; loss of avidity by <span class="elsevierStyleSup">131</span>I in a structural disease which showed previous uptake of <span class="elsevierStyleSup">131</span>I and structural disease which progresses despite <span class="elsevierStyleSup">131</span>I uptake&#46; In these scenarios treatment with local therapies &#40;percutaneous injection of ethanol&#44; radiofrequency&#44; embolization or radiotherapy&#41; may be considered&#44; with surgery in single metastasis and the administration of systemic treatments &#40;i&#46;e&#46; kinase inhibitors&#41;&#46;</p></li></ul><elsevierMultimedia ident="tb0045"></elsevierMultimedia></p><p id="par0485" class="elsevierStylePara elsevierViewall">Distant disease is treated with the same dose of <span class="elsevierStyleSup">131</span>I that would have been given if metastasis had been presented at the beginning&#46;</p></span><span id="sec0115" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">4&#46;2</span><span class="elsevierStyleSectionTitle" id="sect0135">Elevated thyroglobulin and negative <span class="elsevierStyleSup">131</span>I scan &#40;TENIS syndrome&#41;</span><p id="par0490" class="elsevierStylePara elsevierViewall">It is not infrequent for a patient to present elevated Tg levels with a negative <span class="elsevierStyleSup">131</span>I scan &#40;Thyroglobulin Elevation&#47;Negative Iodine Scintigraphy Syndrome &#8211; TENIS syndrome&#41;&#46; After ruling out the possible cause for false negative scan results &#40;inadequate TSH stimulation&#44; elevated plasma iodine levels due to excess exogenous iodine or very small disease volume&#41;&#44; this situation reflects the loss of the capacity of the tumoral tissue to take up iodine&#44; or in other words&#44; dedifferentiation&#46; The management of these patients is complicated and there are very few data to determine the optimal treatment to follow&#46;<a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">54</span></a> The management of these patients is based on&#58;<ul class="elsevierStyleList" id="lis0075"><li class="elsevierStyleListItem" id="lsti0125"><span class="elsevierStyleLabel">&#8226;</span><p id="par0495" class="elsevierStylePara elsevierViewall">Ruling out an excess of exogenous iodine by the 24<span class="elsevierStyleHsp" style=""></span>h measurement of urinary iodine excretion&#46;</p></li><li class="elsevierStyleListItem" id="lsti0130"><span class="elsevierStyleLabel">&#8226;</span><p id="par0500" class="elsevierStylePara elsevierViewall">Performing ultrasonography of the neck and a CT of the neck and thorax &#40;without contrast&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0135"><span class="elsevierStyleLabel">&#8226;</span><p id="par0505" class="elsevierStylePara elsevierViewall">Performing <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT in patients with high risk of non stimulated Tg &#8805;10<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#46;</p></li><li class="elsevierStyleListItem" id="lsti0140"><span class="elsevierStyleLabel">&#8226;</span><p id="par0510" class="elsevierStylePara elsevierViewall">Treatment with radiotherapy &#40;i&#46;e&#46; single bone metastasis&#41; or systemic therapy &#40;disease in progression without response to <span class="elsevierStyleSup">131</span>I&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0145"><span class="elsevierStyleLabel">&#8226;</span><p id="par0515" class="elsevierStylePara elsevierViewall">Treatment with <span class="elsevierStyleSup">131</span>I&#58; 42&#8211;72&#37; of patients with a negative <span class="elsevierStyleSup">131</span>I scan empirically treated with high doses&#44; present <span class="elsevierStyleSup">131</span>I uptake in the post-treatment scan&#44; especially at a cervical and mediastinic level&#44; more frequently identifying distant metastasis when the plasma Tg level is &#62;200<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#46;<a class="elsevierStyleCrossRef" href="#bib0560"><span class="elsevierStyleSup">55</span></a> However&#44; the benefits of this treatment are limited&#44; with 44&#37; of stable disease and 56&#37; of progression after radioiodine treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0565"><span class="elsevierStyleSup">56</span></a> Although some studies have shown a reduction in Tg levels after treatment with <span class="elsevierStyleSup">131</span>I&#44; this reduction has not been shown to change the prognosis of the disease&#46; However&#44; despite not seeming to achieve clinical benefits beyond localizing the disease&#44; it does enable restaging and reclassifying the disease as biochemical persistence or as iodine refractory&#46;<a class="elsevierStyleCrossRefs" href="#bib0560"><span class="elsevierStyleSup">55&#44;57</span></a></p></li></ul></p><p id="par0520" class="elsevierStylePara elsevierViewall"><elsevierMultimedia ident="tb0050"></elsevierMultimedia></p></span></span><span id="sec0125" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">5</span><span class="elsevierStyleSectionTitle" id="sect0145">Conclusion</span><p id="par0530" class="elsevierStylePara elsevierViewall">The treatment of DTC with <span class="elsevierStyleSup">131</span>I is controversial in some aspects due to the lack of prospective&#44; randomized&#44; clinical studies&#46; In DTC&#44; treatment with <span class="elsevierStyleSup">131</span>I is administered with ablative objectives to eliminate healthy residual microscopic thyroid tissue or to treat macroscopic or metastatic disease&#46; Apart from destroying healthy thyroid tissue post-thyroidectomy&#44; the objective of ablative treatment is to destroy possible microscopic foci&#44; minimize the risk of recurrence in patients with predisposition&#44; increase the specificity of Tg as a tumoral marker and increase the specificity of scans with <span class="elsevierStyleSup">131</span>I for the detection of recurrent or metastatic disease&#46; On the other hand&#44; the objective of treatment of residual and&#47;or metastatic disease with <span class="elsevierStyleSup">131</span>I is to destroy all macroscopic disease that cannot be treated with surgery&#44; thereby reducing the risk of recurrence and mortality&#46; While awaiting the results of ongoing prospective trials&#44; the use of <span class="elsevierStyleSup">131</span>I seems to be justified not only in patients with high risk but also in those with intermediate risk and those with low risk associated with other factors&#46;</p></span><span id="sec0130" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">6</span><span class="elsevierStyleSectionTitle" id="sect0150">Conflict of interest</span><p id="par0535" class="elsevierStylePara elsevierViewall">The authors declare no conflict of interest&#46;</p></span></span>"
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            0 => "Radioiodine treatment"
            1 => "<span class="elsevierStyleSup">131</span>I"
            2 => "Differentiated thyroid cancer"
            3 => "Initial risk stratification"
            4 => "Dynamic risk stratification"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec1105413"
          "palabras" => array:5 [
            0 => "Tratamiento con radioyodo"
            1 => "<span class="elsevierStyleSup">131</span>I"
            2 => "C&#225;ncer diferenciado de tiroides"
            3 => "Estratificaci&#243;n inicial de riesgo"
            4 => "Estratificaci&#243;n din&#225;mica de riesgo"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">In differentiated thyroid cancer &#40;DTC&#41;&#44; radioiodine is administered to eliminate residual normal thyroid tissue after thyroidectomy &#40;ablative treatment&#41;&#44; to treat residual microscopic disease &#40;adjuvant treatment&#41;&#44; and to treat macroscopic or metastatic disease&#46; Currently&#44; treatment of DTC with <span class="elsevierStyleSup">131</span>I is still a matter of controversy due to the absence of prospective clinical trials assessing its benefit in terms of overall survival and recurrence-free interval&#46; The current recommendations of the experts are based on observational retrospective data and on their interpretation of the literature&#46; Pending the results of the prospective trials that are currently underway&#44; the use of <span class="elsevierStyleSup">131</span>I seems to be justified not only in high-risk patients&#44; but also in intermediate-risk and low-risk patients&#46; The guidelines of The American and British Thyroid Association&#44; European and American Societies of Nuclear Medicine&#44; The European Consensus Group and the latest edition of National Comprehensive Cancer Network &#40;NCCN&#41; were considered in drawing up this continuing education document&#44; we also undertook a review of the related scientific literature&#46;</p></span>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">En el c&#225;ncer diferenciado de tiroides &#40;CDT&#41;&#44; el tratamiento con <span class="elsevierStyleSup">131</span>I se administra para eliminar tejido tiroideo residual sano postiroidectom&#237;a &#40;tratamiento ablativo&#41;&#44; para tratar enfermedad residual microsc&#243;pica &#40;tratamiento adyuvante&#41; y para tratar enfermedad macrosc&#243;pica o metast&#225;sica&#46; A d&#237;a de hoy&#44; el tratamiento con <span class="elsevierStyleSup">131</span>I del CDT es todav&#237;a un tema de controversia debido a la ausencia de ensayos cl&#237;nicos prospectivos que eval&#250;en su beneficio en cuanto a supervivencia global e intervalo libre de recurrencia&#46; Las recomendaciones actuales de los expertos se basan en datos retrospectivos observacionales y en su interpretaci&#243;n de la literatura&#46; A la espera de los resultados de los ensayos prospectivos actualmente en marcha&#44; la utilizaci&#243;n del <span class="elsevierStyleSup">131</span>I parece estar justificada no solamente en los pacientes de alto riesgo&#44; sino tambi&#233;n en los de riesgo intermedio y bajo&#46; Para la realizaci&#243;n del presente documento de formaci&#243;n continuada se han considerado las gu&#237;as de la Sociedad Americana y Brit&#225;nica de Tiroides&#44; de las Sociedades Europea y Americana de Medicina Nuclear&#44; el consenso del Grupo Europeo y la &#250;ltima edici&#243;n del National Comprehensive Cancer Network &#40;NCCN&#41;&#44; as&#237; como se ha revisado la literatura cient&#237;fica relacionada&#46;</p></span>"
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0040">Please cite this article as&#58; Estorch M&#44; Mitjavila M&#44; Muros MA&#44; Caballero E&#44; en nombre del Grupo de Trabajo de Endocrinolog&#237;a de la SEMNIM&#46; Tratamiento del c&#225;ncer diferenciado de tiroides con radioyodo a la luz de las gu&#237;as y de la literatura cient&#237;fica&#46; Rev Esp Med Nucl Imagen Mol&#46; 2019&#59;38&#58;195&#8211;203&#46;</p>"
      ]
    ]
    "multimedia" => array:14 [
      0 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at1"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:3 [
          "leyenda" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">AJCC&#58; American Joint Committee on Cancer&#59; TNM&#58; tumor&#47;node&#47;metastasis&#59; UICC&#58; Union for International Cancer Control&#46;</p>"
          "tablatextoimagen" => array:2 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">T&#58; primary tumor</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Tx&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Non localized primary tumor&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>T0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No evidence of primary tumor&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>T1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Tumor &#8804;2<span class="elsevierStyleHsp" style=""></span>cm<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>T1a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Tumor &#8804;1<span class="elsevierStyleHsp" style=""></span>cm<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>T1b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Tumor &#62;1<span class="elsevierStyleHsp" style=""></span>cm and &#8804;2<span class="elsevierStyleHsp" style=""></span>cm&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>T2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Tumor &#62;2<span class="elsevierStyleHsp" style=""></span>cm and &#8804;4<span class="elsevierStyleHsp" style=""></span>cm<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>T3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Tumor &#62;4<span class="elsevierStyleHsp" style=""></span>cm<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> or extension to adjacent muscles&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>T3a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Tumor &#62;4<span class="elsevierStyleHsp" style=""></span>cm<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> limited to the thyroid glands&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>T3b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Tumor of any size with extension to adjacent muscles&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>T4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Tumor of any size with extrathyroid extension&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>T4a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Tumor of any size with recurrent extension to subcutaneous tissue&#44; larynx&#44; trachea&#44; espophagus or nerve&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>T4b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Tumor of any size with invasion of the prevertebral fascia&#44; carotid or mediastinic vessels&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">N&#58; regional lymph nodes</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Nx&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Non localized lymph nodes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>N0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No evidence of lymph nodes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>N0a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">One or more with benign cytology or histology&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>N0b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No radiological or clinical evidence&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>N1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Metastatic lymph nodes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>N1a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Uni- or bilateral metastasis at level VI or VII&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>N1b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Uni&#44; bilateral or contralateral metastasis at level I&#44; II&#44; III&#44; IV or V or at a retropharyngeal level&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">M&#58; distant metastasis</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>M0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No metastasis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>M1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Distant metastasis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " colspan="5" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Staging according to age &#60;55 or &#8805;55 years</th></tr><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Age&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">T&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">N&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">M&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Stage&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">&#60;55 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Any T&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Any N&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">M0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">i&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">&#60;55 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Any T&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Any N&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">M1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Ii&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">&#8805;55 Years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">T1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">N0&#47;Nx&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">M0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">I&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">&#8805;55 Years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">T1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">N1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">M0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Ii&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">&#8805;55 Years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">T2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">N0&#47;Nx&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">M0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">I&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">&#8805;55 Years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">T2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">N1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">M0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Ii&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">&#8805;55 Years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">T3a&#47;T3b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Any N&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">M0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Ii&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">&#8805;55 Years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">T4a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Any N&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">M0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Iii&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">&#8805;55 Years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">T4b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Any N&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">M0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Iva&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">&#8805;55 Years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Any T&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Any N&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">M1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IVB&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab2021926.png"
              ]
            ]
          ]
          "notaPie" => array:1 [
            0 => array:3 [
              "identificador" => "tblfn0005"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Greatest diameter&#46;</p> <p class="elsevierStyleNotepara" id="npar0010"><span class="elsevierStyleItalic">Note</span>&#58; The tumors may be solitary or multifocal&#46; If multifocal&#44; the T is determined by the tumor of greatest size&#46;</p> <p class="elsevierStyleNotepara" id="npar0015"><span class="elsevierStyleItalic">Source</span>&#58; Amin et al&#46;<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">19</span></a></p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">2017 TNM classification of the American Joint Committee on Cancer and the Union for International Cancer Control for differentiated thyroid cancer&#46;</p>"
        ]
      ]
      1 => array:8 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at2"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:3 [
          "leyenda" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">ATA&#58; American Thyroid Association&#59; Tg&#58; thyroglobulin&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleBold">Low risk</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Pillary thyroid cancer including all the following characteristics&#58;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>No local or distant metastasis&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Macroscopic resection of all the tumor&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>No local invasion&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Not presenting aggressive histology &#40;tall&#44; columnar&#44; H&#252;rthle cells&#44; etc&#46;&#41;&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>No vascular invasion&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>No <span class="elsevierStyleSup">131</span>I uptake outside the thyroid bed&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>N0 or &#8804;5 N1 micrometastasis &#40;&#60;0&#46;2<span class="elsevierStyleHsp" style=""></span>cm<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Follicular thyroid cancer encapsulated papillary variant&#46;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Well differentiated follicular thyroid cancer with invasion of the capsule or minimal vascular invasion &#40;&#60;4 foci&#41;&#46;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Uni or multifocal papillary microcarcinoma&#44; including BRAF V600E mutation&#46;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleBold">Intermediate risk</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Thyroid cancer with at least one of the following characteristics&#58;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Microscopic invasion of perithyroid soft tissue&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Metastatic regional lymph nodes or <span class="elsevierStyleSup">131</span>I uptake in the post ablative treatment scan&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Tumor with aggressive histology &#40;tall&#44; columnar&#44; H&#252;rthle cells&#44; etc&#46;&#41; or vascular invasion&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>N1 clinical manifestations or &#62;5<span class="elsevierStyleHsp" style=""></span>N&#44; with all the nodes being &#60;3<span class="elsevierStyleHsp" style=""></span>cm<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Multifocal papillary microcarcinoma with extrathyroid extension and <span class="elsevierStyleItalic">BRAF V600E</span> mutation&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleBold">High risk</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Thyroid cancer with any of the following characteristics&#58;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Macroscopic tumoral invasion&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Incomplete resection&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Distant metastasis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Postsurgical plasma Tg levels suggestive of distant metastasis&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Pathological N1 &#8805;3<span class="elsevierStyleHsp" style=""></span>cm<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Follicular thyroid cancer iwht extensive vascular invasion &#40;&#62;4 foci&#41;&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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            0 => array:3 [
              "identificador" => "tblfn0010"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0020">Greatest diameter&#46;</p> <p class="elsevierStyleNotepara" id="npar0025"><span class="elsevierStyleItalic">Source</span>&#58; Haugen et al&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">4</span></a></p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Stratification of risk of persistence&#47;recurrence of differentiated thyroid cancer according to the ATA 2015&#46;</p>"
        ]
      ]
      2 => array:8 [
        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at3"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">AJCC&#58; American Joint Committee on Cancer&#59; TNM&#58; tumor&#47;node&#47;metastasis&#46;</p>"
          "tablatextoimagen" => array:2 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " colspan="4" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">7th edition</th><th class="td" title="table-head  " colspan="4" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">8th edition</th></tr><tr title="table-row"><th class="td" title="table-head  " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">&#60;45 years</th><th class="td" title="table-head  " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Survival at 10 years</th><th class="td" title="table-head  " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">&#60;55 years</th><th class="td" title="table-head  " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Survival at 10 years</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">I&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Any T and N&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">M0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">97&#8211;100&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">I&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Any T and N&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">M0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">98&#8211;100&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Any T and N&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">M1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">95&#8211;99&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Any T and N&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">M1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">85&#8211;95&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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            1 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " colspan="5" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">&#8805;45 years</th><th class="td" title="table-head  " colspan="5" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">&#8805;55 years</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">I&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">T1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">N0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">M0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">97&#8211;100&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">I&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">T1 or 2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">N0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">M0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">98&#8211;100&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">T2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">N0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">M0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">97&#8211;100&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">T1 or 2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">N1a&#47;b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">M0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">85&#8211;95&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">T3a&#47;b any N&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">III&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">T1 or 2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">N1a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">M0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">88&#8211;95&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">III&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">T4a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Any N&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">M0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">60&#8211;70&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">T3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">N0 or 1a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">IVA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">T1or 2 or 3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">N1b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">M0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">50&#8211;75&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IVA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">T4b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Any N&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">M0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;50&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">T4a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Any N&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">IVB&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">T4b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Any N M0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IVB any T and N&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">M1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">IVC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Any T and N&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">M1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Comparison between the 7th and 8th edition of the TNM Classification of the AJCC for differentiated thyroid cancer&#46;</p>"
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          "leyenda" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">ATA&#58; American Thyroid Association&#59; EET&#58; extrathyroid extension&#59; NTCTCSG&#58; National Thyroid Cancer Treatment Cooperative Study Group&#59; TNM&#58; tumor&#47;node&#47;metastasis&#59; <span class="elsevierStyleSup">131</span>I&#58; radioiodine&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">ATA risk<br>&#40;TNM&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Description&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Is there evience that <span class="elsevierStyleSup">131</span>I increases survival&#63;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Is there evidence that <span class="elsevierStyleSup">131</span>I increases disease-free survival&#63;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Is ablation with <span class="elsevierStyleSup">131</span>I indicated&#63;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">ATA low risk</span><br><span class="elsevierStyleHsp" style=""></span>T1a<br><span class="elsevierStyleHsp" style=""></span>N0&#44; Nx<br><span class="elsevierStyleHsp" style=""></span>M0&#44; Mx&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8804;1<span class="elsevierStyleHsp" style=""></span>cm<br>Uni or multifocal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">ATA low risk</span><br><span class="elsevierStyleHsp" style=""></span>T1b&#44; T2<br><span class="elsevierStyleHsp" style=""></span>N0&#44; Nx<br><span class="elsevierStyleHsp" style=""></span>M0&#44; Mx&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#62;1<span class="elsevierStyleHsp" style=""></span>cm<br>&#8804;4<span class="elsevierStyleHsp" style=""></span>cm&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Conflictive observational data&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Not routine use<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">a</span></a><br>Consider in aggressive histology or<br>vascular invasion&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">ATA low&#47;intermediate risk</span><br><span class="elsevierStyleHsp" style=""></span>T3<br><span class="elsevierStyleHsp" style=""></span>N0&#44; Nx<br><span class="elsevierStyleHsp" style=""></span>M0&#44; Nx&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#62;4<span class="elsevierStyleHsp" style=""></span>cm&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Conflictive data&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Conflictive observational data&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Consider<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">a</span></a><br>According to whether adverse<br>characteristics or patient age&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">ATA low&#47;intermediate risk</span><br><span class="elsevierStyleHsp" style=""></span>T3<br><span class="elsevierStyleHsp" style=""></span>N0&#44; Nx<br><span class="elsevierStyleHsp" style=""></span>M0&#44; Mx&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Microscopic EET &#40;any T&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Conflictive observational data&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Consider<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">a</span></a><br>Small tumors with microscopic EET<br>can avoid <span class="elsevierStyleSup">131</span>I&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">ATA low&#47;intermediate risk</span><br><span class="elsevierStyleHsp" style=""></span>T1&#8211;T3<br><span class="elsevierStyleHsp" style=""></span>N1a<br><span class="elsevierStyleHsp" style=""></span>M0&#44; Mx&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Lymph node metastasis in central compartment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&#44; except age &#8805;55 &#40;NTCTCSG stage III&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Conflictive observational data&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Consider<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">a</span></a><br>- Yes <span class="elsevierStyleSup">131</span>I for risk of persistence&#47;<br>Recurrence by size&#44;<br>Lymph node metastasis or EET<br>- No <span class="elsevierStyleSup">131</span>I if &#60;5 lymph node metstasis<br>In central compartment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">ATA low&#47;intermediate risk</span><br><span class="elsevierStyleHsp" style=""></span>T1&#8211;T3<br><span class="elsevierStyleHsp" style=""></span>N1b<br><span class="elsevierStyleHsp" style=""></span>M0&#44; Mx&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Laterocervical or mediastinic lymph node metastasis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&#44; except age &#8805;55&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Conflictive observational data&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Consider<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">a</span></a><br>In general favorable to <span class="elsevierStyleSup">131</span>I<br>for risk of persistence&#47;recurrence&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">ATA high risk</span><br><span class="elsevierStyleHsp" style=""></span>T4<br><span class="elsevierStyleHsp" style=""></span>Any N<br><span class="elsevierStyleHsp" style=""></span>Any M&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Any T<br><br>Macroscopic EET&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">ATA high risk</span><br><span class="elsevierStyleHsp" style=""></span>M1<br><span class="elsevierStyleHsp" style=""></span>Any T<br><span class="elsevierStyleHsp" style=""></span>Any N&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Distant metastasis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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              "identificador" => "tblfn0015"
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              "nota" => "<p class="elsevierStyleNotepara" id="npar0030">In addition to the clinical pathological characteristics&#44; the experience of the ultrasonographer&#44; the surgeon&#44; the multidisciplinary committee and the method of thyroglobulin measurement should also be taken into account&#46;</p> <p class="elsevierStyleNotepara" id="npar0035"><span class="elsevierStyleItalic">Source</span>&#58; Haugen et al&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">4</span></a></p>"
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          "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Ablative treatment with <span class="elsevierStyleSup">131</span>I according to the ATA 2015&#46;</p>"
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        "mostrarDisplay" => true
        "texto" => array:1 [
          "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">1</span><span class="elsevierStyleSectionTitle" id="sect0040">Teaching point</span><p id="par0070" class="elsevierStylePara elsevierViewall">In tumors &#62;1<span class="elsevierStyleHsp" style=""></span>cm and &#8804;4<span class="elsevierStyleHsp" style=""></span>cm without local or lymphatic extension&#44; the decision as to the surgical technique to perform should be made by a multidisciplinary committee since lobectomy leaves the non resected lobe without a histological study and excludes treatment with <span class="elsevierStyleSup">131</span>I and follow-up with Tg&#46;</p></span></span>"
        ]
      ]
      5 => array:5 [
        "identificador" => "tb0010"
        "tipo" => "MULTIMEDIATEXTO"
        "mostrarFloat" => false
        "mostrarDisplay" => true
        "texto" => array:1 [
          "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">1</span><span class="elsevierStyleSectionTitle" id="sect0060">Teaching point</span><p id="par0115" class="elsevierStylePara elsevierViewall">The stratification of risk classifies patients with DTC as having low&#44; intermediate or high risk and can decide the initial treatment to be administered and establish the follow-up strategy&#46;</p></span></span>"
        ]
      ]
      6 => array:5 [
        "identificador" => "tb0015"
        "tipo" => "MULTIMEDIATEXTO"
        "mostrarFloat" => false
        "mostrarDisplay" => true
        "texto" => array:1 [
          "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">1</span><span class="elsevierStyleSectionTitle" id="sect0070">Teaching point</span><p id="par0160" class="elsevierStylePara elsevierViewall">Dynamic stratification of risk classifies patients with DTC during follow-up as having&#58;<ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0050"><span class="elsevierStyleLabel">&#8226;</span><p id="par0165" class="elsevierStylePara elsevierViewall">Excellent response&#46;</p></li><li class="elsevierStyleListItem" id="lsti0150"><span class="elsevierStyleLabel">&#8226;</span><p id="par0170" class="elsevierStylePara elsevierViewall">Incomplete biochemical response&#46;</p></li><li class="elsevierStyleListItem" id="lsti0155"><span class="elsevierStyleLabel">&#8226;</span><p id="par0175" class="elsevierStylePara elsevierViewall">Incomplete structural response&#46;</p></li><li class="elsevierStyleListItem" id="lsti0160"><span class="elsevierStyleLabel">&#8226;</span><p id="par0180" class="elsevierStylePara elsevierViewall">Indeterminate response&#46;</p></li></ul></p></span></span>"
        ]
      ]
      7 => array:5 [
        "identificador" => "tb0020"
        "tipo" => "MULTIMEDIATEXTO"
        "mostrarFloat" => false
        "mostrarDisplay" => true
        "texto" => array:1 [
          "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">1</span><span class="elsevierStyleSectionTitle" id="sect0080">Teaching point</span><p id="par0205" class="elsevierStylePara elsevierViewall">In DTC treatment with <span class="elsevierStyleSup">131</span>I may be&#58;<ul class="elsevierStyleList" id="lis0020"><li class="elsevierStyleListItem" id="lsti0165"><span class="elsevierStyleLabel">&#8226;</span><p id="par0210" class="elsevierStylePara elsevierViewall">Ablative&#58; to eliminate healthy residual thyroid tissue post-thyroidectomy&#46;</p></li><li class="elsevierStyleListItem" id="lsti0170"><span class="elsevierStyleLabel">&#8226;</span><p id="par0215" class="elsevierStylePara elsevierViewall">Adjuvant&#58; to treat residual microscopic disease&#46;</p></li><li class="elsevierStyleListItem" id="lsti0175"><span class="elsevierStyleLabel">&#8226;</span><p id="par0220" class="elsevierStylePara elsevierViewall">To treat macroscopic or metastatic disease&#46;</p></li></ul></p></span></span>"
        ]
      ]
      8 => array:5 [
        "identificador" => "tb0025"
        "tipo" => "MULTIMEDIATEXTO"
        "mostrarFloat" => false
        "mostrarDisplay" => true
        "texto" => array:1 [
          "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">1</span><span class="elsevierStyleSectionTitle" id="sect0090">Teaching point</span><p id="par0250" class="elsevierStylePara elsevierViewall">Indications for treatment with <span class="elsevierStyleSup">131</span>I&#58;<ul class="elsevierStyleList" id="lis0030"><li class="elsevierStyleListItem" id="lsti0180"><span class="elsevierStyleLabel">&#8226;</span><p id="par0255" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Low risk</span>&#58; <span class="elsevierStyleSup">131</span>I is not routinely administered when the tumor is &#8804;1<span class="elsevierStyleHsp" style=""></span>cm&#46;</p><p id="par0260" class="elsevierStylePara elsevierViewall">There is controversy as to whether to treat or not tumors &#62;1 and &#8804;4<span class="elsevierStyleHsp" style=""></span>cm &#40;while awaiting the results of ongoing prospective&#44; randomized&#44; multicenter studies&#41;&#46; The decision to administer or not <span class="elsevierStyleSup">131</span>I is based on local factors such as the experience of the ultrasonographer&#44; the surgeon&#44; or the method of Tg measurement&#46; The EANM recommends the administration of <span class="elsevierStyleSup">131</span>I in tumors &#62;1<span class="elsevierStyleHsp" style=""></span>cm&#46;</p></li><li class="elsevierStyleListItem" id="lsti0185"><span class="elsevierStyleLabel">&#8226;</span><p id="par0265" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Intermediate risk</span>&#58; <span class="elsevierStyleSup">131</span>I is administered according to the characteristics of the tumor&#44; the presence of significant lymph node metastasis&#44; vascular invasion or aggressive histology&#44; combined with patient age &#40;&#8805;55 years&#41;&#46; The decision to treat or not should be made by a multidisciplinary committee&#46;</p></li><li class="elsevierStyleListItem" id="lsti0190"><span class="elsevierStyleLabel">&#8226;</span><p id="par0270" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">High risk</span>&#58; <span class="elsevierStyleSup">131</span>I is routinely administered&#46;</p></li></ul></p></span></span>"
        ]
      ]
      9 => array:5 [
        "identificador" => "tb0030"
        "tipo" => "MULTIMEDIATEXTO"
        "mostrarFloat" => false
        "mostrarDisplay" => true
        "texto" => array:1 [
          "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">1</span><span class="elsevierStyleSectionTitle" id="sect0105">Teaching point</span><p id="par0310" class="elsevierStylePara elsevierViewall">What stimulation method should be used&#63;<ul class="elsevierStyleList" id="lis0035"><li class="elsevierStyleListItem" id="lsti0195"><span class="elsevierStyleLabel">&#8226;</span><p id="par0315" class="elsevierStylePara elsevierViewall">Suspension of hormonal treatment in local metastatic disease &#40;recurrence&#47;persistence of lymph node involvement&#41; and distant metastasis &#40;not in elderly patients and those with important comorbidity&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0200"><span class="elsevierStyleLabel">&#8226;</span><p id="par0320" class="elsevierStylePara elsevierViewall">rhTSH in the treatment for ablative purposes and in the treatment of residual microscopic disease with <span class="elsevierStyleSup">131</span>I &#40;patients with low or intermediate risk&#41;&#46;</p></li></ul></p></span></span>"
        ]
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      10 => array:5 [
        "identificador" => "tb0035"
        "tipo" => "MULTIMEDIATEXTO"
        "mostrarFloat" => false
        "mostrarDisplay" => true
        "texto" => array:1 [
          "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">1</span><span class="elsevierStyleSectionTitle" id="sect0115">Teaching point</span><p id="par0380" class="elsevierStylePara elsevierViewall">Dose &#40;activity&#41; of <span class="elsevierStyleSup">131</span>I&#58;<ul class="elsevierStyleList" id="lis0050"><li class="elsevierStyleListItem" id="lsti0205"><span class="elsevierStyleLabel">&#8226;</span><p id="par0385" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Ablative treatment</span>&#58; 1&#46;1<span class="elsevierStyleHsp" style=""></span>GBq &#40;30<span class="elsevierStyleHsp" style=""></span>mCi&#41; &#40;low risk&#44; candidates for ablation&#41;&#46; This dose is based on the results obtained in short-term studies aimed at evaluating its effectiveness with respect to ablation&#46; Although the premise is that the optimal dose of <span class="elsevierStyleSup">131</span>I to administer should not only achieve good ablation but also reduce the risk of recurrence&#47;mortality&#44; the results of long-term studies are still needed to evaluate the effectiveness of this dose in relation to the risk of recurrence&#46;</p></li><li class="elsevierStyleListItem" id="lsti0210"><span class="elsevierStyleLabel">&#8226;</span><p id="par0390" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Adjuvant treatment</span>&#58; 2&#46;8&#8211;3&#46;7<span class="elsevierStyleHsp" style=""></span>GBq &#40;75&#8211;100<span class="elsevierStyleHsp" style=""></span>mCi&#41; &#40;intermediate risk with residual microscopic disease post-surgery&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0215"><span class="elsevierStyleLabel">&#8226;</span><p id="par0395" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Treatment of residual macroscopic and local and&#47;or distant metastatic disease</span>&#58;<ul class="elsevierStyleList" id="lis0055"><li class="elsevierStyleListItem" id="lsti0220"><span class="elsevierStyleLabel">&#8211;</span><p id="par0400" class="elsevierStylePara elsevierViewall">150<span class="elsevierStyleHsp" style=""></span>mCi &#40;5&#46;6<span class="elsevierStyleHsp" style=""></span>GBq&#41;&#58; infiltrated cervical and mediastinic lymph nodes&#46;</p></li><li class="elsevierStyleListItem" id="lsti0225"><span class="elsevierStyleLabel">&#8211;</span><p id="par0405" class="elsevierStylePara elsevierViewall">150&#8211;200<span class="elsevierStyleHsp" style=""></span>mCi &#40;5&#46;6&#8211;7&#46;5<span class="elsevierStyleHsp" style=""></span>GBq&#41;&#58; pulmonary metastasis&#46;</p></li><li class="elsevierStyleListItem" id="lsti0230"><span class="elsevierStyleLabel">&#8211;</span><p id="par0410" class="elsevierStylePara elsevierViewall">200<span class="elsevierStyleHsp" style=""></span>mCi &#40;7&#46;5<span class="elsevierStyleHsp" style=""></span>GBq&#41;&#58; bone metastasis or other distant metastases&#46;</p></li></ul></p></li></ul></p></span></span>"
        ]
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        "identificador" => "tb0040"
        "tipo" => "MULTIMEDIATEXTO"
        "mostrarFloat" => false
        "mostrarDisplay" => true
        "texto" => array:1 [
          "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">1</span><span class="elsevierStyleSectionTitle" id="sect0120">Teaching point</span><p id="par0415" class="elsevierStylePara elsevierViewall">In intermediate-high and low risk DTC with detectable maintained or increased Tg levels&#44; a scan with <span class="elsevierStyleSup">131</span>I is made at 6&#8211;12 months after treatment and if the following is shown&#58;<ul class="elsevierStyleList" id="lis0060"><li class="elsevierStyleListItem" id="lsti0235"><span class="elsevierStyleLabel">&#8226;</span><p id="par0420" class="elsevierStylePara elsevierViewall">Significant cervical uptake&#44; 3&#46;7&#8211;5&#46;6<span class="elsevierStyleHsp" style=""></span>GBq &#40;100&#8211;150<span class="elsevierStyleHsp" style=""></span>mCi&#41; of <span class="elsevierStyleSup">131</span>I is administered to complete the ablation&#46;</p></li><li class="elsevierStyleListItem" id="lsti0240"><span class="elsevierStyleLabel">&#8226;</span><p id="par0425" class="elsevierStylePara elsevierViewall">Non significant cervical uptake&#44; or no evidence of disease by other imaging techniques&#44; treatment is not administered&#46;</p></li><li class="elsevierStyleListItem" id="lsti0245"><span class="elsevierStyleLabel">&#8226;</span><p id="par0430" class="elsevierStylePara elsevierViewall">Disease in other localizations&#44; the corresponding empiric dose of <span class="elsevierStyleSup">131</span>I is administered&#46;</p></li></ul></p></span></span>"
        ]
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      12 => array:5 [
        "identificador" => "tb0045"
        "tipo" => "MULTIMEDIATEXTO"
        "mostrarFloat" => false
        "mostrarDisplay" => true
        "texto" => array:1 [
          "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">1</span><span class="elsevierStyleSectionTitle" id="sect0130">Teaching point</span><p id="par0465" class="elsevierStylePara elsevierViewall">Cervical tumoral recurrence is treated with&#58;<ul class="elsevierStyleList" id="lis0070"><li class="elsevierStyleListItem" id="lsti0250"><span class="elsevierStyleLabel">&#8226;</span><p id="par0470" class="elsevierStylePara elsevierViewall">Surgical resection whenever possible &#40;evaluate the aggressiveness of the procedure with respect to the expected benefits&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0255"><span class="elsevierStyleLabel">&#8226;</span><p id="par0475" class="elsevierStylePara elsevierViewall">5&#46;5 GBq &#40;150<span class="elsevierStyleHsp" style=""></span>mCi&#41; of <span class="elsevierStyleSup">131</span>I after surgery if disease showing iodine uptake persists&#46;</p></li><li class="elsevierStyleListItem" id="lsti0260"><span class="elsevierStyleLabel">&#8226;</span><p id="par0480" class="elsevierStylePara elsevierViewall">If disease not showing iodine uptake persists after surgery&#44; <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT is performed&#46;</p></li></ul></p></span></span>"
        ]
      ]
      13 => array:5 [
        "identificador" => "tb0050"
        "tipo" => "MULTIMEDIATEXTO"
        "mostrarFloat" => false
        "mostrarDisplay" => true
        "texto" => array:1 [
          "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0120" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">1</span><span class="elsevierStyleSectionTitle" id="sect0140">Teaching point</span><p id="par0525" class="elsevierStylePara elsevierViewall">The benefits of empiric treatment with <span class="elsevierStyleSup">131</span>I in the TENIS syndrome are questionable&#44; since this treatment has not shown to have an impact on the prognosis of the disease&#46; However&#44; it does enable reclassification of the patients&#46;</p></span></span>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0015"
          "bibliografiaReferencia" => array:57 [
            0 => array:3 [
              "identificador" => "bib0290"
              "etiqueta" => "1"
              "referencia" => array:1 [
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                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "E&#46;L&#46; Mazzaferri"
                            1 => "S&#46;M&#46; Jhiang"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
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                        "fecha" => "1994"
                        "volumen" => "97"
                        "paginaInicial" => "418"
                        "paginaFinal" => "428"
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                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0295"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
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                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "C&#46;F&#46; Eustatia-Rutten"
                            1 => "E&#46;P&#46; Corssmit"
                            2 => "N&#46;R&#46; Biermasz"
                            3 => "A&#46;M&#46; Pereira"
                            4 => "J&#46;A&#46; Romijn"
                            5 => "J&#46;W&#46; Smit"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "J Clin Endocrinol Metab"
                        "fecha" => "2006"
                        "volumen" => "91"
                        "paginaInicial" => "313"
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                      ]
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                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0300"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Risk-adapted management of thyroid cancer"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "R&#46;M&#46; Tuttle"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Endocr Pract"
                        "fecha" => "2008"
                        "volumen" => "14"
                        "paginaInicial" => "764"
                        "paginaFinal" => "774"
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                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0305"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "2015 American Thyroid Association Management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer&#58; the American Thyroid Association guidelines task force on thyroid nodules and differentiated thyroid cancer"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "B&#46;R&#46; Haugen"
                            1 => "E&#46;K&#46; Alexander"
                            2 => "K&#46;C&#46; Bible"
                            3 => "G&#46;M&#46; Doherty"
                            4 => "S&#46;J&#46; Mandel"
                            5 => "Y&#46;E&#46; Nikiforov"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Thyroid"
                        "fecha" => "2016"
                        "volumen" => "26"
                        "paginaInicial" => "1"
                        "paginaFinal" => "133"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0310"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "British Thyroid Association guidelines for the management of thyroid cancer"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "P&#46; Perros"
                            1 => "S&#46; Colley"
                            2 => "K&#46; Boelaert"
                            3 => "C&#46; Evans"
                            4 => "R&#46;M&#46; Evans"
                            5 => "G&#46;E&#46; Gerrard"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Endocrinol"
                        "fecha" => "2014"
                        "volumen" => "81"
                        "numero" => "Suppl&#46;"
                        "paginaInicial" => "1"
                        "paginaFinal" => "122"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0315"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Guidelines for radioiodine therapy of differentiated thyroid cancer"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Luster"
                            1 => "S&#46;E&#46; Clarke"
                            2 => "M&#46; Dietlein"
                            3 => "M&#46; Lassmann"
                            4 => "P&#46; Lind"
                            5 => "Oyen"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Eur J Nucl Med Mol Imaging"
                        "fecha" => "2008"
                        "volumen" => "35"
                        "paginaInicial" => "1941"
                        "paginaFinal" => "1959"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib0320"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The SNMMI practice guideline for therapy of thyroid disease with <span class="elsevierStyleSup">131</span>I"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "E&#46;B&#46; Silberstein"
                            1 => "A&#46; Alavi"
                            2 => "H&#46;R&#46; Balon"
                            3 => "S&#46;E&#46; Clarke"
                            4 => "C&#46; Divgi"
                            5 => "M&#46;J&#46; Gelfand"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "J Nucl Med"
                        "fecha" => "2012"
                        "volumen" => "53"
                        "paginaInicial" => "1633"
                        "paginaFinal" => "1651"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib0325"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "European Consensus for the management of patients with differentiated thyroid carcinoma of the folicular epithelium"
                      "autores" => array:1 [
                        0 => array:3 [
                          "colaboracion" => "European Thyroid Cancer Taskforce"
                          "etal" => true
                          "autores" => array:6 [
                            0 => "F&#46; Pacini"
                            1 => "M&#46; Schlumberger"
                            2 => "H&#46; Dralle"
                            3 => "R&#46; Elisei"
                            4 => "J&#46;W&#46; Smit"
                            5 => "W&#46; Wiersinga"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Eur J Endocrinol"
                        "fecha" => "2006"
                        "volumen" => "154"
                        "paginaInicial" => "787"
                        "paginaFinal" => "803"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib0330"
              "etiqueta" => "9"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "National Comprehensive Cancer Network &#40;NCCN&#41;&#46; NCCN Clinical practice guidelines in oncology &#40;Version 1&#46;2017&#41;&#46; Available from&#58; <a id="intr0010" class="elsevierStyleInterRef" href="http://www.klinikum.uni-muenchen.de/Schilddruesenzentrum/.../NCCN/thyroid_2017.pdf">http&#58;&#47;&#47;www&#46;klinikum&#46;uni-muenchen&#46;de&#47;Schilddruesenzentrum&#47;&#46;&#46;&#46;&#47;NCCN&#47;thyroid&#95;2017&#46;pdf</a> &#91;accessed 18&#46;07&#46;18&#93;&#46;"
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib0335"
              "etiqueta" => "10"
              "referencia" => array:1 [
                0 => array:2 [
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