The correlation between tumor markers and Ga-68 DOTA-TATE PET/CT findings in patients with advanced medullary thyroid cancer | Revista Española de Medicina Nuclear e Imagen Molecular (English Edition)

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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Medullary thyroid cancer &#40;MTC&#41; is a rare type of neuroendocrine tumor&#44; accounts for approximately 1&#8211;2&#37; of all thyroid cancer cases&#46; MTC originates from parafollicular&#44; calcitonin-secreting cells&#46; MTC may occur either sporadically or in a hereditary form as a component of type 2 multiple endocrine neoplasia &#40;MEN2&#41; syndromes&#46; The familial or hereditary form accounts for about 25&#37; of all MTC and is inherited as an autosomal dominant mutation and overexpression of the RET &#40;rearranged during transfection&#41; proto-oncogene&#46; The sporadic form accounts for about 75&#37; of all MTC and it mostly occurs in adults aged between 40 and 60 years&#46; Surgery is the only curative treatment modality for MTC in all patients without distant metastases and extra-nodal involvement&#46; In advanced stage diseases&#44; tyrosine kinase inhibitors &#40;TKIs&#41; such as vandetanib and cabozantinib were approved&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Calcitonin &#40;Ctn&#41; and carcinoembryonic antigen &#40;CEA&#41; are used as markers for medullary thyroid cancer&#46; Ctn is a 32-amino acid monomeric peptide that results from cleavage and post-translational processing of procalcitonin&#44; a precursor peptide derived from preprocalcitonin&#46; Serum Ctn levels may be increased in patients with chronic renal failure&#44; and other ailments&#44; such as hyperparathyroidism&#44; autoimmune thyroiditis&#44; small cell and large cell lung cancers&#44; prostate cancer&#44; mastocytosis&#44; and various enteric and pulmonary neuroendocrine tumors&#46; CEA is not a specific biomarker for MTC&#46; Because serum CEA levels do not increase following calcium or pentagastrin stimulation&#44; measurement of this tumor marker is not useful in the early diagnosis of MTC&#46; These tests can establish that the tumor is capable of hypersecreting the hormones and&#44; if so&#44; the values can be compared with postoperative values&#46; Postoperatively&#44; results may provide a prognostic factor or indicate biochemical cure&#46; In advanced stages&#44; doubling times of these markers may be prognostic&#46;<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">2&#8211;8</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">In radiologic evaluation&#44; computed tomography &#40;CT&#41; for lung and mediastinal imaging&#44; three-phase contrast-enhanced multi-detector liver CT and&#47;or contrast-enhanced magnetic resonance imaging &#40;MRI&#41; for liver imaging and bone scintigraphy plus axial MRI for skeletal imaging are used in cases of suspected metastatic disease&#46; Functional imaging techniques are used commonly in oncologic practice such as 2-&#91;fluorine-18&#93; fluoro-2-deoxy-<span class="elsevierStyleSmallCaps">d</span>-glucose &#40;FDG&#41; positron emission tomography &#40;PET&#41;&#47;CT scan but FDG PET&#47;CT is less sensitive in medullary thyroid cancer&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">9</span></a> In recent years&#44; Gallium-68 &#40;Ga-68&#41; DOTA-TATE PET&#47;CT as a new method&#44; has been used to detect metastatic or recurrent disease&#46; In Ga-68 DOTA-TATE PET&#47;CT&#44; some parameters such as whole-body somatostatin receptor-expressing metabolic tumor volume &#40;SSR-E MTV&#41; and total lesion volume &#40;SSR-E TLV&#41; may be used as indicators for functional tumor burden&#46; Total tumor volume is important for both choosing treatment modality such as surgical resection for regional low tumor burden or TKIs for extensive disease and also important for follow-up period&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">We aimed to evaluate the importance of serum Ctn and CEA levels in predicting total tumor volume by analyzing the correlation between tumor markers and tumor volume indicators SSR-E MTV and TLV&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Material and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Study population</span><p id="par0025" class="elsevierStylePara elsevierViewall">This trial was planned as a retrospective single-center study&#46; Medical information was obtained from the archive files of patients who were treated and followed-up between 2017 and 2019 years&#44; for advanced stage medullary thyroid cancer in the medical oncology clinic of &#42;&#42;&#42;&#42;&#42;&#42;&#42;&#42;&#42; Training and Research Hospital&#46; Patients with age under 18&#44; had localized disease and patients who did not perform Ga-68 DOTA-TATE and with no laboratory test results were excluded&#46; Disease staging was performed according to TNM eight edition&#46; Ethics committee approval was received&#46; The patients informed consents were received&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">68Ga-DOTA-TATE imaging protocol</span><p id="par0030" class="elsevierStylePara elsevierViewall">A fully automated Scintomics GRP synthesis module with Scintomics Control Center and GRP-Interface software was used for the radiolabeling of 68Ga-DOTA-TATE&#46; The 68Ge&#47;68Ga generator was purchased from iThemba LABS&#44; South Africa&#46; DOTA-TATE was purchased from Scintomics GRP&#44; Germany via a local distributor&#46; Whole-body PET&#47;CT scans were performed using LSO-based full-ring PET scanner &#40;Siemens Biograph 6&#44; Chicago&#44; IL&#44; USA&#41;&#46; 2<span class="elsevierStyleHsp" style=""></span>MBq&#47;kg 68Ga-DOTA-TATE was injected intravenously&#46; After 1<span class="elsevierStyleHsp" style=""></span>h&#44; whole-body CT scans were obtained from the base of the skull to the upper thigh with slice collimation of 5<span class="elsevierStyleHsp" style=""></span>mm and a slice interval of 3&#46;4<span class="elsevierStyleHsp" style=""></span>mm&#46; The emission data were acquired for 2&#46;5<span class="elsevierStyleHsp" style=""></span>min per bed &#40;6&#8211;7 beds&#41;&#46; Attenuation correction was performed with the digital CT data&#46; Image reconstruction used the ordered subsets expectation-maximization algorithm of 2 iteration and 8 subsets&#46; Image analysis was carried out on the Esoft multimodality computer platform &#40;Siemens Medical Solutions&#44; Erlangen&#44; Germany&#41;&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Imaging analysis</span><p id="par0035" class="elsevierStylePara elsevierViewall">Images were visually interpreted by consensus between two experienced nuclear physicians&#46; The foci of uptake were identified as representing a tumor if the accumulation of 68Ga-DOTA-TATE was increased relative to comparable normal contralateral or surrounding tissues&#46; The SUVmax&#44; SUVmean&#44; and MTV &#40;cm<span class="elsevierStyleSup">3</span>&#41; for each lesion were produced automatically from the VOIs by the workstation&#46; The margin of the target lesion inside the VOI was automatically produced and voxels greater than a threshold of 41&#37; of SUVmax in the VOI were defined to measure MTV and SUVmean&#46; The results were checked by comparison with the fused CT images to determine if the adjustment was needed in the percentage threshold&#46; If the percentage threshold was not appropriate&#44; further adjustment of the percentage threshold was performed until a satisfactory outcome was achieved&#46; The whole-body MTV of each patient was defined as the sum of MTVs of all lesions&#46; The TLV was obtained by multiplying the MTV of each lesion for the corresponding SUVmean determined in the selected volume by is contouring&#46; The whole body TLV of each patient was defined as the sum of TLVs of all lesions&#46; The SUVmax was defined as the one lesion which has the highest SUVmax&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Statistical analysis</span><p id="par0040" class="elsevierStylePara elsevierViewall">For statistical analysis&#44; IBM Statistical Package for the Social Sciences 15&#46;0 for Windows was used&#46; Descriptive statistics were given as number and percent for categoric variables and as mean&#44; standard deviation&#44; minimum and maximum for numerical variables&#46; The relations between numerical variables was evaluated Spearman Correlation Analysis because the parametric test condition is not provided&#46; Statistically alpha significant was accepted as <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#46; Institutional ethics committee approval was received&#46;</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Results</span><p id="par0045" class="elsevierStylePara elsevierViewall">For this purpose&#44; 28 patients with advanced MTC who were treated and followed up in medical oncology clinic of &#42;&#42;&#42;&#42;&#42;&#42;&#42;&#42;&#42; Hospital&#44; were included in the study&#46; Nineteen &#40;67&#46;9&#37;&#41; patients were women and 9 patients &#40;32&#46;1&#37;&#41; were men&#46; The median age of patients was 55&#46;0 &#40;standard deviation &#91;SD&#93;<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>13&#46;1&#41; years&#46; ECOG performance status of all patients were 0&#8211;1&#46; Seven &#40;25&#46;0&#37;&#41; of patients had stage IVa disease and 21 &#40;75&#46;0&#37;&#41; of patients had stage IVc disease&#46; The most common metastases sites were cervical and mediastinal lymphadenopathies&#44; bone&#44; lung&#44; and brain respectively&#46; Patients number with only nodal extra-thyroid involvement was 9 &#40;32&#46;1&#37;&#41; and the number of patients with both nodal and bone involvement was 12 &#40;42&#46;9&#37;&#41;&#46; Ten &#40;35&#46;7&#37;&#41; of patients received TKIs due to inoperability &#40;8 patients vandetanib and 2 patients cabozantinib&#41; and 18 &#40;64&#46;3&#37;&#41; patients only received surgical treatment &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">The median Ctn level was 6671&#46;6<span class="elsevierStyleHsp" style=""></span>pg&#47;mL &#40;min&#8211;max 2&#8211;102&#44;148<span class="elsevierStyleHsp" style=""></span>pg&#47;mL&#41; and median CEA level was 202&#46;8<span class="elsevierStyleHsp" style=""></span>ng&#47;mL &#40;min&#8211;max 1&#46;56&#8211;3271<span class="elsevierStyleHsp" style=""></span>ng&#47;mL&#41;&#46; Median whole-body SSR-E MTV was 37&#46;2<span class="elsevierStyleHsp" style=""></span>cm<span class="elsevierStyleSup">3</span> &#40;min&#8211;max 3&#8211;582&#46;7<span class="elsevierStyleHsp" style=""></span>cm<span class="elsevierStyleSup">3</span>&#41; and median whole-body SSR-E TLV was 198&#46;6 &#40;min&#8211;max 14&#8211;3262&#46;8&#41;&#46; Median SUVmax was 11&#46;1 &#40;min&#8211;max 2&#8211;34&#46;6&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0055" class="elsevierStylePara elsevierViewall">In the correlation analysis&#44; there was a significantly positive correlation between Ctn and whole-body SSR-E MTV &#40;rho<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;503 and <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;008&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> and <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; This correlation was most marked in patients with Ctn &#8805;152<span class="elsevierStyleHsp" style=""></span>pg&#47;mL &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>20&#44; rho<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;714 and <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;004&#41;&#46; There was no statistical significant correlation in patients with Ctn<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>152<span class="elsevierStyleHsp" style=""></span>pg&#47;mL &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>8&#44; rho<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;257 and <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;623&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41;&#46; In subgroup analysis&#44; there was a positive correlation between Ctn and SSR-E MTV in patients with both nodal and bone involvement &#40;rho<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;714 and <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;047&#41; but this correlation was not observed in patients with only nodal extra-thyroid involvement &#40;rho<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;048 and <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;911&#41; &#40;6 of 9 patients with Ctn<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>152<span class="elsevierStyleHsp" style=""></span>pg&#47;mL&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0025">Table 5</a>&#41;&#46; Similarly&#44; positive correlation was observed between Ctn and whole-body SSR-E TLV in all patients &#40;rho<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;436 and <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;023&#41;&#46; This correlation was not shown between Ctn and SUV max &#40;rho<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;323 and <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;164&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> and <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><elsevierMultimedia ident="tbl0025"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">Second correlation analysis was done for CEA&#46; There was a significantly positive correlation between CEA and whole-body SSR-E MTV in all patients &#40;rho<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;584 and <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;007&#41; and in patients with both nodal and bone involvement &#40;rho<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;762 and <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;028&#41; but there was no statistically significant correlation in patients with only nodal extra-thyroid involvement &#40;rho<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;488 <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;010&#41; &#40;<a class="elsevierStyleCrossRefs" href="#tbl0015">Tables 3 and 5</a>&#41;&#46; Also&#44; a positive correlation was observed between CEA and whole-body SSR-E TLV &#40;rho<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;436 <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;023&#41;&#46; But there was no correlation between CEA and SUVmax &#40;rho<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;301 and <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;197&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> and <a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall">We also examined patients who treated with TKIs&#46; After 3 months of treatment beginning&#44; we performed a second Ga-68 DOTA-TATE&#46; Seven patients had stable disease&#44; 2 patients had a partial response and 1 patient had progressive disease according to PET Response Criteria in Solid Tumors &#40;PERCIST&#41;&#46; The Ctn and CEA levels of these patients were consistent with Ga-68 DOTA-TATE PET&#47;CT findings&#46; But there were not sufficient data for statistical analysis &#40;<a class="elsevierStyleCrossRefs" href="#fig0015">Figs&#46; 3 and 4</a>&#41;&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Discussion</span><p id="par0070" class="elsevierStylePara elsevierViewall">We aimed to examine whether CEA and Ctn levels are associated with tumor burden in advanced MTCs patients&#46; Ga-68 DOTA-TATE PET&#47;CT parameters such as whole-body SSR-E MTV and TLV were used to show tumor burden&#46; The correlation of Ctn and CEA levels with Ga-68 DOTA-TATE PET&#47;CT findings were analyzed&#46; A positive correlation was revealed between tumor markers and SSR-E MTV and TLV&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">In a study published in 2007&#44; fifteen patients with rising total Ctn and CEA levels after total thyroidectomy and unknown location of recurrence or metastasis with conventional methods were included&#46; All patients underwent 18F-FDG PET and 18F-DOPA PET and the location of metastasis or recurrence were established in seven patients&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">10</span></a> In another prospective study&#44; Behesti<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">11</span></a> et al&#46; compared FDG PET and DOPA PET&#47;CT in twenty-six patients with MTC and DOPA PET&#47;CT correctly detected 94&#37; &#40;50&#47;53&#41; of malignant lesions&#44; whereas only 62&#37; &#40;33&#47;53&#41; of malignant lesions were detected with FDG PET&#47;CT&#46; DOPA PET-CT showed superior results to FDG PET-CT in the preoperative and follow-up assessment of MTC patients&#46; Rasul<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">12</span></a> et al&#46; evaluated the ability of DOPA PET&#47;CT to stage MTC in thirty-two patients&#46; Of the 32 patients&#44; 28 showed increased DOPA decarboxylase activity in the primary tumor &#40;sensitivity 88&#37;&#41; also the sensitivities of DOPA PET in the detection of central and lateral metastatic neck LN were 53&#37; and 73&#37;&#44; in contrast to 20&#37; and 39&#37;&#44; respectively&#44; for neck ultrasonography&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">In a meta-analysis including nine studies&#44; published in 2017&#44; the detection rate of somatostatin receptor PET or PET&#47;CT in patients with recurrent MTC was calculated as 63&#46;5&#37; but detection rate of somatostatin receptor PET or PET&#47;CT increased in patients with higher serum Ctn levels &#40;83&#37; for Ctn<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>500<span class="elsevierStyleHsp" style=""></span>ng&#47;L&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">13</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">In our trial&#44; we examined 28 patient&#39;s findings of Ga-68 DOTA-TATE&#44; performed for staging or restaging patients with increased Ctn and CEA values at follow-up&#46; Ga-68 DOTA-TATE showed at least one metastatic site in all patients&#46; Most common sites were cervical and mediastinal lymphadenopathies&#44; bone and lung metastases&#46; Eligible patients&#44; especially those with lymphadenopathies&#44; underwent surgery and disease stage was confirmed pathologically&#46; Other patients received TKIs and subsequent clinical follow-up&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">In the literature&#44; there are only a few studies focused on the correlation of tumor markers and findings of nuclear imaging modality&#46; Firstly&#44; a prospective study published in 2017&#44; with eighteen patients with recurrent MTC identified by elevation of Ctn or CEA were included&#46; Each patient underwent an 18F-FDG PET&#47;CT and an 18F-DOPA PET&#47;CT&#46; The aim of this study was to evaluate and compare the usefulness of 18F-DOPA and 18F-FDG PET&#47;CT in the detection of persistent or recurrent MTC&#44; as well as to analyze the correlation between their positivity and Ctn and CEA&#46; Patient based detection rate increased significantly with Ctn levels &#8805;150<span class="elsevierStyleHsp" style=""></span>pg&#47;mL vs&#46; Ctn<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>150<span class="elsevierStyleHsp" style=""></span>pg&#47;mL for 18F-DOPA but there was no given results of correlation analysis between PET positive lesions and tumor markers&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">14</span></a> Secondly&#44; a retrospective cross-sectional study including 13 patients with MTC and high calcitonin&#47;CEA levels that underwent both 68Ga-DOTANOC PET&#47;CT and 18F-FDG PET&#47;CT&#46; The trial aimed to determine the correlation between tumor markers and functional imaging&#46; The number of lesions found in 68Ga-DOTANOC PET&#47;CT was correlated with calcitonin levels but not with CEA&#46; The number of 18F-FDG hypermetabolic focus were correlated with CEA levels but not with Ctn&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">15</span></a> In our trial&#44; we focused on the correlation between total tumor volume and tumor markers&#46; Ga-68 DOTA-TATE PET&#47;CT parameters such whole body SSR-E MTV and TLV were used to show tumor burden&#46; Also&#44; we examined the correlation between SUV max and tumor markers&#46; We found a positive correlation between both Ctn and CEA with whole-body SSR-E MTV and TLV&#46; Also&#44; these correlations were a trend toward to persist in patients who received TKIs but the sample was not sufficient for statistical analysis&#46; There may be some reasons for discrepancies between the results of our trial and the last two studies presented above&#46; Firstly&#44; in both studies&#44; the patient numbers were less than in our trial&#46; Secondly&#44; only the number of PET-positive lesions was examined in both studies&#46; Unlike these studies&#44; we included 28 patients and examined the total tumor burden&#44; not the number of lesions as we thought would not reflect the actual tumor volume&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">The presenting study has a few limitations&#46; Because of MTC is a rare tumor&#44; planning a prospective study is difficult and needed multicenter and a long time&#44; for these reasons retrospective planning of the study is not a limitation&#46; Secondly&#44; the number of patients received TKIs was low for statistical analysis&#46; But this is the first study to describe a positive correlation between whole-body SSR-E MTV and TLV with Ctn and CEA&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Conclusion</span><p id="par0100" class="elsevierStylePara elsevierViewall">Ga-68 DOTA-TATE findings&#44; especially whole body SSR-E MTV and TLV&#44; are correlated with Ctn and CEA&#46; These results could stimulate clinicians to perform Ga-68 PET for treatment decision&#44; especially in patients with high CEA and Ctn levels at the time of diagnosis&#46; Also&#44; these results could help to determine when new imaging is needed in patients receiving systemic therapy&#46; A prospective trial is needed in patients receiving TKIs for MTC&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Conflict of interest</span><p id="par0105" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare&#46;</p></span></span>"
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          "titulo" => "Results"
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    "pdfFichero" => "main.pdf"
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    "fechaRecibido" => "2020-02-21"
    "fechaAceptado" => "2020-03-29"
    "PalabrasClave" => array:2 [
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        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec1363375"
          "palabras" => array:4 [
            0 => "Medullary thyroid cancer"
            1 => "Metabolic tumor volume"
            2 => "Total lesion volume"
            3 => "Calcitonin and carcinoembryonic antigen"
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          "palabras" => array:4 [
            0 => "C&#225;ncer medular de tiroides"
            1 => "Volumen tumoral metab&#243;lico"
            2 => "Volumen total de la lesi&#243;n"
            3 => "Calcitonina y ant&#237;geno carcinoembri&#243;geno"
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      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Medullary thyroid cancer &#40;MTC&#41; is a rare type of neuroendocrine tumor&#46; Calcitonin &#40;Ctn&#41; and carcinoembryonic antigen &#40;CEA&#41; are used as markers for medullary thyroid cancer&#46; The aim of the study was to evaluate the importance of serum calcitonin and carcinoembryonic antigen levels in predicting total tumor volume&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Material and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Ga-68 DOTA-TATE PET&#47;CT findings such as whole-body somatostatin receptor-expressing metabolic tumor volume &#40;SSR-E MTV&#41; and total lesion volume &#40;SSR-E TLV&#41; were calculated and correlation analysis was done for tumor markers and whole-body SSR-E MTV and TLV&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">A total of 28 patients with advanced MTC were included in this retrospective study&#46; In the correlation analysis&#44; there was a statistically significant positive correlation between Ctn and whole-body SSR-E MTV &#40;rho<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;503 and <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;008&#41;&#46; Similarly&#44; significant positive correlation was observed between Ctn and whole-body SSR-E TLV &#40;rho<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;436 and <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;023&#41;&#46; There was a significant positive correlation between CEA and whole-body SSR-E MTV &#40;rho<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;584 and <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;007&#41;&#46; Also&#44; a positive correlation was observed between CEA and whole-body SSR-E TLV &#40;rho<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;436 and <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;023&#41;&#46; These correlations were most marked in patients with Ctn &#8805;152<span class="elsevierStyleHsp" style=""></span>pg&#47;mL and&#47;or both nodal and bone involvement&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">These results could stimulate clinicians to perform Ga-68 PET for treatment decisions&#44; especially in patients with high CEA and Ctn levels at the time of diagnosis&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Background"
          ]
          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Material and methods"
          ]
          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Results"
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          3 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Conclusion"
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      "es" => array:3 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Antecedentes</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">El c&#225;ncer medular de tiroides &#40;CTM&#41; es un tipo raro de tumor neuroendocrino&#46; La calcitonina &#40;Ctn&#41; y el ant&#237;geno carcinoembrionario &#40;CEA&#41; se utilizan como marcadores para el c&#225;ncer medular de tiroides&#46; El objetivo del estudio fue evaluar la importancia de los niveles de calcitonina s&#233;rica y ant&#237;geno carcinoembrionario en la predicci&#243;n del volumen total del tumor&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Material y m&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Se calcularon los hallazgos del Ga-68 DOTA-TATE PET&#47;CT&#44; como el volumen tumoral metab&#243;lico expresado del receptor de somatostatina de cuerpo entero &#40;SSR-E MTV&#41; y el volumen total de la lesi&#243;n &#40;SSR-E TLV&#41; y se hizo un an&#225;lisis de correlaci&#243;n para los marcadores tumorales y el SSR-E MTV y TLV de cuerpo entero&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Un total de 28 pacientes con MTC avanzado fueron incluidos en este estudio retrospectivo&#46; En el an&#225;lisis de correlaci&#243;n&#44; hubo una correlaci&#243;n positiva estad&#237;sticamente significativa entre Ctn y MTV SSR-E de cuerpo entero &#40;rho<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;503 y p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;008&#41;&#46; De manera similar&#44; se observ&#243; una correlaci&#243;n positiva significativa entre el Ctn y el TLV SSR-E de cuerpo entero &#40;rho<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;436 y p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;023&#41;&#46; Se observ&#243; una correlaci&#243;n positiva significativa entre el CEA y el MTV SSR-E de cuerpo entero &#40;rho<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;584 y p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;007&#41;&#46; Tambi&#233;n se observ&#243; una correlaci&#243;n positiva entre el CEA y el TLV SSR-E de cuerpo entero &#40;rho<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;436 p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;023&#41;&#46; Estas correlaciones fueron m&#225;s marcadas en los pacientes con Ctn &#8805;152<span class="elsevierStyleHsp" style=""></span>pg&#47;mL y&#47;o con afectaci&#243;n tanto nodal como &#243;sea&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusi&#243;n</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Estos resultados podr&#237;an estimular a los cl&#237;nicos a realizar una PET de Ga 68 para tomar decisiones de tratamiento&#44; especialmente en pacientes con altos niveles de CEA y Ctn en el momento del diagn&#243;stico&#46;</p></span>"
        "secciones" => array:4 [
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            "identificador" => "abst0025"
            "titulo" => "Antecedentes"
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          1 => array:2 [
            "identificador" => "abst0030"
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          2 => array:2 [
            "identificador" => "abst0035"
            "titulo" => "Resultados"
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            "titulo" => "Conclusi&#243;n"
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    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Arici S&#44; Karyagar SS&#44; Erdemir RU&#44; Cekin R&#44; Atc&#305; MM&#44; G&#252;ven O&#44; et al&#46; La correlaci&#243;n entre los marcadores tumorales y los hallazgos de Ga-68 DOTA-TATE PET&#47;CT en pacientes con c&#225;ncer medular de tiroides avanzado&#46; Rev Esp Med Nucl Imagen Mol&#46; 2021&#59;40&#58;161&#8211;166&#46;</p>"
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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">The relation between calcitonin and 68Ga DOTA-TATE PET&#47;CT findings&#46;</p>"
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          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">68Ga DOTA-TATE PET&#47;CT with whole body PET &#40;A&#41;&#44; axial slice PET &#40;B&#44; D&#44; F&#41; and axial slice CT &#40;C&#44; E&#44; G&#41; images of a 40-year-old MTC patient with serum calcitonin value of 17&#44;919<span class="elsevierStyleHsp" style=""></span>pg&#47;mL and CEA value of 268&#46;78<span class="elsevierStyleHsp" style=""></span>ng&#47;mL&#46; 68Ga DOTA-TATE PET&#47;CT images showed intense somatostatin receptor expressing metastatic multiple lymph nodes at the neck and mediastinum and also metastatic lesion at the right side of the sacral bone&#46;</p>"
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          "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">68Ga DOTA-TATE PET&#47;CT with whole body PET &#40;A&#41;&#44; axial slice PET &#40;B&#41; and axial slice CT &#40;C&#41; images of a 51-year-old MTC patient with serum calcitonin value of 2716<span class="elsevierStyleHsp" style=""></span>pg&#47;mL and CEA value of 46&#46;45<span class="elsevierStyleHsp" style=""></span>ng&#47;mL&#46; 68Ga DOTA-TATE PET&#47;CT images showed intense somatostatin receptor expressing metastatic lymph node at the left inferior jugular chain&#46;</p>"
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          "leyenda" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Abbreviations</span>&#58; ECOG PS&#58; Eastern Cooperative Oncology Group Performance Status&#59; LN&#58; lymph node&#59; Med&#58; median&#59; SD&#58; standard deviation&#59; Min&#58; minimum&#59; Max&#58; maximum&#46;</p>"
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                  \t\t\t\t">13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">46&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Inferior mediastinal LN&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">21&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Bone&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">35&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Lung&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Only LN&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">32&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Both LN and bone&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">42&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Treatment</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Surgery &#40;alone&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">64&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Cabozantinib&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Vandetanib&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">28&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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                  <table border="0" frame="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>CEA &#40;ng&#47;mL&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">202&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>740&#46;6&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#64;&#64;1&#46;56&#8211;3271&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Calcitonin &#40;pg&#47;mL&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">6671&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>22&#44;761&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">2&#8211;102&#44;148&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Ga-68 PET findings</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Whole body SSR-E MTV &#40;cm<span class="elsevierStyleSup">3</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">37&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>129&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">3&#8211;582&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Whole body SSR-E TLV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">198&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>728&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&#8211;3262&#46;8&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>SUVmax&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">11&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>9&#46;7&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#8211;34&#46;6&nbsp;\t\t\t\t\t\t\n
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                0 => """
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Whole body SSR-E MTV &#40;cm<span class="elsevierStyleSup">3</span>&#41;</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="center" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="center" valign="\n
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">rho&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">rho&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">rho&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CEA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">0&#46;584&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">0&#46;436&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleBold">0&#46;023</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">0&#46;301&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">0&#46;197&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Calcitonin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t  " align="char" valign="\n
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          "leyenda" => "<p id="spar0100" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Abbreviation</span>&#58; MTV&#58; metabolic tumor volume&#46;</p><p id="spar4100" class="elsevierStyleSimplePara elsevierViewall">Bold value signifies value is statistically significant&#46;</p>"
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                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Whole body MTV &#40;cm<span class="elsevierStyleSup">3</span>&#41;</th></tr><tr title="table-row"><th class="td" title="\n
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                  \t\t\t\t">Calcitonin<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>152<span class="elsevierStyleHsp" style=""></span>pg&#47;mL&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">0&#46;714&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleBold">0&#46;004</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">20&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Calcitonin<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>152<span class="elsevierStyleHsp" style=""></span>pg&#47;mL&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">0&#46;257&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">0&#46;623&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">8&nbsp;\t\t\t\t\t\t\n
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          "leyenda" => "<p id="spar0110" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Abbreviations</span>&#58; LN&#58; lymph node&#59; CEA&#58; carcinoembryonic antigen&#59; MTV&#58; metabolic tumor volume&#46;</p><p id="spar4120" class="elsevierStyleSimplePara elsevierViewall">Bold value signifies values are statistically significant&#46;</p>"
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                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">&#64;&#64;Only LN involvement</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>CEA&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">0&#46;119&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">0&#46;779&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Calcitonin&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">0&#46;048&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">0&#46;911&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>CEA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">0&#46;762&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">0&#46;028</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="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Calcitonin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">0&#46;714&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleBold">0&#46;047</span>&nbsp;\t\t\t\t\t\t\n
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          "en" => "<p id="spar0105" class="elsevierStyleSimplePara elsevierViewall">Subgroup analysis for correlation between CEA&#47;calcitonin and whole-body MTV&#46;</p>"
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      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0015"
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            0 => array:3 [
              "identificador" => "bib0080"
              "etiqueta" => "1"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "American Thyroid Association Guidelines Task Force on medullary thyroid carcinoma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "S&#46;A&#46; Wells Jr&#46;"
                            1 => "S&#46;L&#46; Asa"
                            2 => "H&#46; Dralle"
                            3 => "R&#46; Elisei"
                            4 => "D&#46;B&#46; Evans"
                            5 => "R&#46;F&#46; Gagel"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1089/thy.2014.0335"
                      "Revista" => array:6 [
                        "tituloSerie" => "Thyroid"
                        "fecha" => "2015"
                        "volumen" => "25"
                        "paginaInicial" => "567"
                        "paginaFinal" => "610"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25810047"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
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                ]
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            1 => array:3 [
              "identificador" => "bib0085"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Medullary thyroid cancer responsiveness to pentagastrin stimulation&#58; an early surrogate parameter of tumor dissemination&#63;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "A&#46; Machens"
                            1 => "S&#46; Hauptmann"
                            2 => "H&#46; Dralle"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "J Clin Endocrinol Metab"
                        "fecha" => "2008"
                        "volumen" => "93"
                        "paginaInicial" => "2234"
                        "paginaFinal" => "2238"
                      ]
                    ]
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                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Reversibility of &#8216;secondary hypercalcitoninemia&#8217; after kidney transplantation"
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