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Original Article
The efficacy of 18F-FDG PET/CT in monitoring disease progression in malignant pleural mesothelioma
La eficacia de 18F-FDG PET/CT en el seguimiento de la progresión de la enfermedad en el mesotelioma pleural maligno
Yasemin Söylera,
Corresponding author
dryaseminsoyler@gmail.com

Corresponding author.
, Özlem Özmenb, Pınar Akın Kabalaka, Hakan Ertürkc, Feza Uğurmana, Ülkü Yılmaza
a Department of Chest Diseases, Ankara Kecioren Sanatorium Ataturk Chest Diseases and Thoracic Surgery Training and Research Hospital, Ankara, Turkey
b Department of Nuclear Medicine, Ankara Kecioren Sanatorium Ataturk Chest Diseases and Thoracic Surgery Training and Research Hospital, Ankara, Turkey
c Department of Radiology, Ankara Kecioren Sanatorium Ataturk Chest Diseases and Thoracic Surgery Training and Research Hospital, Ankara, Turkey
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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">Malignant pleural mesothelioma &#40;MPM&#41;&#44; which originates from pleural mesothelial cells&#44; is a rare and highly aggressive primary pleural malignancy&#46; The worldwide incidence of MPM is predicted to rise continuously in the next years due to the ongoing exposure to occupational or environmental asbestosis&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#8211;4</span></a> The initial symptoms of MPM including dyspnea&#44; chest pain&#44; weight loss or a combination of these&#44; are generally vague&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> The lack of specific clinical manifestations and the paucity of effective diagnostic tools causes delayed diagnosis and leads to poor prognosis&#46;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6&#44;7</span></a> Furthermore&#44; a previous study has shown recurrence rate of 75&#37; even after multimodality treatment for MPM&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> Its increasing incidence rate and poor prognosis will presumably make MPM one of the most lethal tumours with low survival rate &#40;5-year survival rate of &#8804;5&#37;&#41; in the near future&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;5</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Early diagnosis&#44; accurate staging and appropriate treatment decision is vital to manage patients with MPM&#46; Not only these principles but also follow-up is important in MPM management&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> 3&#8211;4 monthly routine appointments with clinicians or a periodic radiologic assessment at 3&#8211;6 month intervals can be suggested in addition to clinical follow-up&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;9</span></a> The occurrence of signs and symptoms in patients during clinical follow-up should be an indication of disease progression for clinicians&#46; In the event of suspicion of disease progression&#44; CT scan is also considered&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> Considering that MPM is a three-dimensional&#44; heterogeneous&#44; asymmetrical and non-spherical tumour&#44; monitoring with a bi-dimensional method may be insufficient in determining real tumour extension or tumour shrinkage&#46;<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10&#8211;13</span></a> Recent studies have shown that <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT can be an alternative method by showing the real tumour burden&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> With this in mind&#44; the main aim of our study was to evaluate the efficacy of <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT in monitoring disease progression in MPM by comparing it with CT&#46; Furthermore&#44; we analysed the predictive role of <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT and CT in the median overall survival &#40;OS&#41; in MPM patients&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Material and method</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Patients</span><p id="par0015" class="elsevierStylePara elsevierViewall">Patients with histologically proven MPM&#44; who completed the scheduled initial treatment&#44; from March 2009 to February 2020 in a tertiary referral hospital were reviewed retrospectively&#46; The initial treatments were decided by an expert multidisciplinary cancer board of our hospital according to guidelines&#46; A total of 71 patients who had both baseline &#40;before treatment&#41; <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT and CT scans and&#44; had both <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT and CT scans for monitoring disease progression due to clinical suspicion during clinical follow up were enrolled&#46; Patients &#40;1&#41; who did not receive any treatments for MPM due to medical reasons or self-refusal &#40;n&#8239;&#61;&#8239;3&#41;&#44; &#40;2&#41; whose radiologic or metabolic evaluation was considered as unreliable due to history of talc pleurodesis &#40;n&#8239;&#61;&#8239;4&#41;&#44; &#40;3&#41; who had radical surgery procedures &#40;extra pleural pneumonectomy&#41; &#40;n&#8239;&#61;&#8239;6&#41;&#44; &#40;4&#41; whose clinical information could not be reached &#40;n&#8239;&#61;&#8239;2&#41; were excluded&#46; Finally&#44; fifty-six patients were analysed&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Progression status according to CT &#91;as radiologic progression negative &#40;RPN&#41; and radiologic progression positive &#40;RPP&#41;&#93; and according to <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT &#91;as metabolic progression negative &#40;MPN&#41; and metabolic progression positive &#40;MPP&#41;&#93; were evaluated and the discrepancies between two methods were analysed&#46; The flowchart of study population is shown in <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">Electronic medical record systems of our hospital and patients&#8217; files were used to obtain all imaging reports and clinical data&#46; Recorded parameters included demographic data &#40;age&#44; gender&#41;&#44; histologic subtype &#40;epithelioid&#47;non-epithelioid&#41;&#44; disease stage &#40;classified in accordance with the 8th edition of TNM staging system<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a>&#41;&#44; history of talc pleurodesis&#44; history of treatment&#44; radiological and metabolic findings &#91;location of tumour&#44; pleural thickness pattern&#44; diameter of pleural thickness &#40;mm&#41; measured from the thickest region of the pleura&#44; mediastinal lymph-node involvement&#44; restriction on lung volume and tumour maximum standardized uptake value &#40;SUVmax&#41;&#44; &#916; SUVmax&#93;&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Imaging protocols</span><p id="par0030" class="elsevierStylePara elsevierViewall">CT scans were performed in a supine position using 16-detector-row CT scanner AlexionTM &#40;Toshiba&#59; Otawara&#44; Japan&#41; with the following parameters&#58; 120&#8239;kV&#44; 150&#8239;mA&#44; 1&#8239;mm slice thickness&#44; 0&#46;75&#8239;s rotation time&#44; and 1&#46;438 collimation beam pitch or 128-multidetector-row CT scanner &#40;Ingenuity CT&#44; Philips Healthcare&#44; Andover&#44; MA&#44; USA&#41; with the following parameters&#58; 120&#8239;kV&#44; 160&#8239;mA&#44; 1&#44;5&#8239;mm slice thickness&#44; 0&#46;5&#8239;s rotation time&#44; and 64&#8239;&#215;&#8239;0&#46;625 collimation beam pitch&#46; Iodinated contrast material&#44; if used&#44; at an infusion flow rate of 3&#8722;4&#8239;ml&#47;s was administered intravenously using a power injector&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">PET&#47;CT scans were obtained 60&#8239;min after intravenous injection of 370&#8211;555 Mbq &#40;10&#8722;15&#8239;mCi&#41; FDG with Siemens Biograph 6 HI-REZ integrated PET&#47;CT scanner &#40;Siemens Medical Solutions&#44; Knoxville&#44; TN&#44; USA&#41;&#46; FDG injection was administered to patients who confirmed that their blood glucose level was less than 150&#8239;mg&#47;dL after 6&#8239;h of fasting&#46; CareDose &#40;Siemens&#41; CT images were acquired with 130&#8239;kV&#44; automatic&#44; real-time dose modulation amperage&#44; and slice thickness of 5&#8239;mm&#46; Right after the CT scan&#44; PET data were obtained for 3&#8239;min per bed position for a total of 6&#8211;8 bed positions&#46; The CT data were used for attenuation correction&#46; PET images were reconstructed using ordered subsets expectation maximization algorithm with four iterations&#44; eight subsets and a Gaussian post-filtering with a trans-axial spatial resolution of 5&#8239;mm at full width at half maximum&#46; After the reconstruction of the images&#44; SUVmax was obtained for semi quantitative analysis of FDG uptake&#46; SUVmax corrected for body weight was computed by standard methods from the activity in the most intense voxel in the three-dimensional tumour region from the trans-axial whole body images on attenuation-corrected PET&#47;CT images&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Progression status according to CT</span><p id="par0040" class="elsevierStylePara elsevierViewall">A 25&#37; increase in total tumour measurement or the appearance of one or more new lesions &#91;progressive radiologic disease &#40;PRD&#41;&#93; was defined as &#8216;radiologic progression positive &#40;RPP&#41;&#8217;&#46; The disappearance tumour lesions &#91;complete radiologic regression &#40;CRR&#41;&#93; and a 25&#37; decrease in the total tumour measurement &#91;partial radiologic regression &#40;PRR&#41;&#93; and no change in total tumour measurements or the presence of changes in total tumour measurements that did not meet the criteria of progression &#91;stable radiologic disease &#40;SRD&#41;&#93; was defined as &#8216;radiologic progression negative &#40;RPN&#41;&#8217;&#46;<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10&#44;12&#44;15&#44;16</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Progression status according to <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT</span><p id="par0045" class="elsevierStylePara elsevierViewall">A &#8805;25&#37; increase in SUVmax &#40;compared with the previous value&#41; or abnormal <span class="elsevierStyleSup">18</span>F-FDG uptake in another location &#91;progressive metabolic disease &#40;PMD&#41;&#93; was defined as &#8216;metabolic progression positive &#40;MPP&#41;&#8217;&#46; The complete resolution of abnormal <span class="elsevierStyleSup">18</span>F-FDG uptake on PET &#91;complete metabolic regression &#40;CMR&#41;&#93; and a &#8805;25&#37; decrease in SUVmax &#40;compared with the previous value&#41; &#91;partial metabolic regression &#40;PMR&#41;&#93; and no change in <span class="elsevierStyleSup">18</span>F-FDG uptake on PET or the presence of changes in <span class="elsevierStyleSup">18</span>F-FDG uptake on PET that did not meet the criteria of progression &#91;stable metabolic disease &#40;SMD&#41;&#93; was defined as &#8216;metabolic progression negative &#40;MPN&#41;&#8217;&#46;<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">15&#44;17</span></a></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Statistical analysis</span><p id="par0050" class="elsevierStylePara elsevierViewall">Statistical analyses were carried out with SPSS Inc&#46; Released 2009&#46; PASW Statistics for Windows&#44; Version 18&#46;0&#46; Chicago&#58; SPSS Inc&#46; Chi-squared test was used to compare demographic data between RPN and RPP&#44; and MPN and MPP&#46; RPN and RPP were compared in terms of metabolic findings&#46; Student-t test for parametric variables and chi-squared test for non-parametric variables were used&#46; Data showing number&#47;percent &#40;&#37;&#41; of cases according to progression status types were given by using descriptive analyses&#46; The concordance between CT and by <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT in monitoring progression was calculated by Cohen&#39;s K coefficient&#46; The median follow-up duration was calculated with reverse Kaplan&#8211;Meier method&#46; The OS according to radiological or metabolic data were estimated by using the Kaplan&#8211;Meier method&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">IRB approval statement</span><p id="par0055" class="elsevierStylePara elsevierViewall">The study was approved by our hospital&#8217;s Medical Specialty Education Board &#40;Decision no&#58; 701&#44; Date&#58; 19&#46;11&#46;2020&#41; was performed in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines&#46; Written informed consent was waived because of the retrospective nature of the study&#46;</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Results</span><p id="par0060" class="elsevierStylePara elsevierViewall">A total of fifty-six patients &#40;21 females&#44; 35 males&#41; with histologically proven MPM met the inclusion criteria&#46; All patients were grouped as RPN &#40;n&#8239;&#61;&#8239;31&#44; 55&#46;5&#37;&#41; and RPP &#40;n&#8239;&#61;&#8239;25&#44; 44&#46;6&#37;&#41; according to CT and&#44; MPN &#40;n&#8239;&#61;&#8239;26&#44; 46&#46;4&#37;&#41; and MPP &#40;n&#8239;&#61;&#8239;31&#44; 53&#46;5&#37;&#41; according to <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT&#46; Among all patients&#44; the histological subtypes were epithelioid &#40;n&#8239;&#61;&#8239;49&#44; 87&#46;5&#37;&#41; and non-epithelioid &#40;biphasic&#44; sarcomatoid or not otherwise specified&#41; &#40;n&#8239;&#61;&#8239;7&#44; 12&#46;5&#37;&#41;&#46; In accordance with the 8th edition of TNM staging system&#44; 24 &#40;43&#37;&#41; were stage I&#44; 9 &#40;16&#37;&#41; were stage II&#44; 20 &#40;36&#37;&#41; were stage III&#44; and 3 &#40;5&#37;&#41; were stage IV&#46; Forty-five patients &#40;80&#37;&#41; received only chemotherapy while the remaining 11 patients received bimodal treatment &#40;n&#8239;&#61;&#8239;9&#41; &#40;chemotherapy&#8239;&#177;&#8239;pleurectomy&#47;decortication or partial pleurectomy&#41; or trimodal treatment &#40;n&#8239;&#61;&#8239;2&#41; &#40;chemotherapy&#8239;&#43;&#8239;pleurectomy&#47;decortication or partial pleurectomy&#8239;&#43;&#8239;radiotherapy&#41;&#46; The most determined pleural thickness pattern was diffuse pattern &#40;n&#8239;&#61;&#8239;29&#44; 46&#37;&#41; and the diameter of pleural thickness was 15&#46;1&#8239;&#177;&#8239;10&#46;4&#8239;mm&#46; There were no significant differences in terms of general characteristics &#40;age&#44; sex&#44; histologic subtype&#44; diseases stage&#44; history of pleurodesis&#41;&#44; and radiological findings &#40;location of tumour&#44; pleural thickness pattern&#44; diameter of pleural thickness&#41; according to both CT groups and <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT groups &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall">The baseline and follow-up <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT was evaluated&#44; tumour SUVmax and &#916; SUVmax were compared between RPN and RPP&#46; The baseline tumour SUVmax was 7&#46;3&#8239;&#177;&#8239;3&#46;7 in all patients &#40;7&#46;7&#8239;&#177;&#8239;4&#46;1 in RPN vs&#46; 6&#46;9&#8239;&#177;&#8239;3&#46;1 in RPP&#44; p&#8239;&#61;&#8239;0&#46;41&#41;&#46; According to the follow-up <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT&#44; tumour SUVmax was 8&#46;1&#8239;&#177;&#8239;5&#46;8 in all patients &#40;5&#46;1&#8239;&#177;&#8239;3&#46;5 in RPN vs&#46; 11&#46;8&#8239;&#177;&#8239;6&#46;1 in RPP&#44; p&#8239;&#60;&#8239;0&#46;001&#41;&#46; &#916; SUVmax was -2&#46;5&#8239;&#177;&#8239;4&#46;2 in RPN and 4&#46;8&#8239;&#177;&#8239;6&#46; in RPP &#40;p&#8239;&#60;&#8239;0&#46;001&#41;&#46;</p><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">The discrepancies and concordance between CT and <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT in monitoring disease progression</span><p id="par0070" class="elsevierStylePara elsevierViewall">As mentioned above&#44; thirty-one &#40;55&#46;3&#37;&#41; patients were RPN &#91;PRR &#40;n&#8239;&#61;&#8239;26&#44; 46&#46;4&#37;&#41; and SRD &#40;n&#8239;&#61;&#8239;5&#44; 8&#46;9&#37;&#41;&#93; and 25 &#40;44&#46;6&#37;&#41; were RPP according to CT&#44; while twenty-six &#40;46&#46;4&#37;&#41; patients were MPN &#91;PMR &#40;n&#8239;&#61;&#8239;22&#44; 39&#46;2&#37;&#41; and SMD &#40;n&#8239;&#61;&#8239;4&#44; 7&#46;1&#37;&#41;&#93; and 30 &#40;53&#46;5&#37;&#41; were MPP according to <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46; Among all RPN&#44; 26 patients were found to be MPN&#46; In other words&#44; all RPP patients were also found to be MPP&#44; however&#44; among RPN patients&#44; 5 &#40;8&#46;9&#37; of all patients&#41; were evaluated as MPP &#40;or PMD&#41; on <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41; A representative <span class="elsevierStyleSup">18</span>F-FDG-PET&#47;CT and CT images of a patient classified as RPN who was actually MPP is shown in <a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#46; Furthermore&#44; the concordance between CT and <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT in monitoring disease progression was very good &#40;K&#8239;&#61;&#8239;0&#46;423&#59; p&#8239;&#60;&#8239;0&#46;01&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Survival analysis</span><p id="par0075" class="elsevierStylePara elsevierViewall">The median follow-up duration was 79 &#40;range&#59; 8&#46;4&#8211;126&#41; months&#46; At the time of analysis&#44; 36 &#40;64&#37;&#41; patients were dead&#46; The median OS was 26&#8239;&#177;&#8239;2&#46;6 months in all patients&#46; The median OS in RPN was 28&#46;2&#8239;&#177;&#8239;4&#46;6 months&#44; while in RPP was 24&#46;3&#8239;&#177;&#8239;3&#46;1 months &#40;p&#8239;&#61;&#8239;0&#46;56&#41;&#46; The median OS in MPN was 21&#46;9&#8239;&#177;&#8239;2&#46;5 months&#44; while in MPP was 28&#46;1&#8239;&#177;&#8239;3&#46;7 months &#40;p&#8239;&#61;&#8239;0&#46;25&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Discussion</span><p id="par0080" class="elsevierStylePara elsevierViewall">Due to unique patterns of growth and anatomic reasons such as the curved structure of the thoracic wall&#44; initial assessment and follow-up of MPM may pose challenges&#46;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7&#44;11&#44;16</span></a> In this regard&#44; we sought to evaluate the efficacy of <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT in monitoring disease progression in MPM by comparing it with CT&#46; Our results have demonstrated very good concordance in progression status assessment between two methods&#44; even though <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT detected more progression than CT did&#46; On the other hand&#44; the OS has shown no correlation between groups according to both methods&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Beyond the measurement of the morphological data&#44; PET&#47;CT is used as a comprehensive method that evaluate metabolic data and their responses to treatments in oncological patients&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> Until now&#44; tumour SUVmax has been considered as an independent prognostic factor in MPM&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;12&#44;19&#44;20</span></a> Additionally&#44; its increased value was related to advanced stage&#44; histological subtypes with poor prognosis &#40;non-epithelioid histology&#41; and recurrent MPM&#46;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7&#44;15</span></a> In our study&#44; tumour SUVmax&#44; which was similar in both groups before treatment&#44; was found to be higher in radiologic non-responders group after treatment&#44; as expected&#46; In line with this&#44; &#916;SUVmax was also significantly higher in this group&#46; This result thus substantiates the usefulness of SUVmax and &#916;SUVmax in the follow-up and outcome prediction in MPM&#44; which has been proved by previous studies&#46;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12&#44;21</span></a> However&#44; Schaefer et al&#46; has suggested that due to ongoing morphological response in MPM over time&#44; evaluations after treatment should be based on progression in CT not SUVmax&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">Considering MPM is not generally a curable cancer&#44; the follow-up strategies are important to monitor disease progression&#44; preclude redundant aggressive therapy&#44; reduce toxicity from ineffective chemotherapy&#44; and guide decision of an alternative treatment option&#46; Guidelines&#44; however&#44; state that PET&#47;CT is still under investigation for follow-up&#44; and is not validated in MPM&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;9</span></a> They hypothesized that FDG uptake and SUVmax measurements may be affected by several reasons&#46; The presence of an inflammatory response such as previous chemical pleurodesis or parapneumonic effusions&#44; may be causes of false positives&#46; Besides&#44; small volume tumours or early stage epithelioid mesothelioma in which FDG uptake is low&#44; and postoperative settings may lead to misinterpretation&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;9&#44;10</span></a> On the other hand&#44; there have been a number of studies suggesting that <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT may be useful in this regard&#46; In Kitajima et al&#46;&#8217;s study that assessed the clinical utility of PET&#47;CT after surgery in MPM&#44; it has been shown that PET&#47;CT resulted in a change of management in 28&#37; of patients&#44; and detected recurrence in 12&#37; of patients with no recurrence on contrast-enhanced CT&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> The previous studies by Kanemura et al&#46; and Kitajima et al&#46;&#44; and our study reached similar results that demonstrate the discrepancies between PET&#47;CT and CT&#46;<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">15&#44;24</span></a> These may be explained by the better capability of <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT to detect conditions such as local progression&#44; lymph node involvement or distant metastasis&#46; Another possible reason of this discrepancy is limitation of CT including the underestimation of the presence of local tumour invasion into the adjacent chest wall&#44; diaphragm and pericardium or the failure of detection of lymph node metastasis&#46;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7&#44;25&#44;26</span></a> In our study&#44; two methods had very good concordance with each other&#44; even though <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT detected more progression than CT did&#46; However&#44; it should also be noted that there were no other confirmation methods for <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT and CT results&#46; On the other hand&#44; <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT is an expensive&#44; time consuming and less accessible method&#46; Thus&#44; CT&#44; due to being time- and cost-efficient and also easier accessibility&#44; may be used as an initial step by determining whether there is a progression or not&#44; and which patients need to undergo <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> Because there is no need for further evaluation&#44; if CT can detect progression&#46; Nevertheless&#44; <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT may be used in the event of suspicion of disease progression even if it is not detected on CT&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">The median OS is approximately 6&#8211;9 months in untreated MPM patients and varies from 9&#46;4&#8211;29 months despite the advantages in treatment options&#46;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;20&#44;25&#44;27</span></a> Increasing age&#44; male sex&#44; advanced stage&#44; non-epithelioid histology&#44; and poorer performance status are prognostic of worse OS&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> We observed slightly longer median OS with respect to those reported in the literature&#46; However&#44; it cannot be ruled out that our study population characteristics or a reference time point which survival times were measured &#40;it was the date of diagnosis in our study&#41; may have influenced this result&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a> For instance&#44; the mean age and the number of patients with advanced stage is low&#44; and the number of patients with epithelioid histology is high in our study&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">In the estimation of OS between patients with progression and without progression&#44; neither CT nor <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT showed any difference&#46; This is consistent with Asabella et al&#46;&#8217;s results&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> There were also a number of studies in the literature which were incompatible with our results&#46; Schaefer et al&#46; has reported that radiologic evaluation showed higher correlation than metabolic evaluation&#44; while Ceresoli et al&#46; has showed longer OS in metabolic responders&#46;<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">22&#44;28</span></a> Kanemura et al&#46; has demonstrated that metabolic responders&#8217; OS was longer&#44; even though there were no significant difference&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> Interestingly&#44; MPP had longer OS in our study&#44; but this did not reach significant difference&#46; The different results between various studies&#44; including ours&#44; may be explained by the studies&#8217; small sample size&#44; false positive of FDG or biological differences of MPM patients who enrolled into the studies&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">Our study has some limitations&#46; This is a retrospective and single-institution study&#46; However&#44; our hospital is one of the reference institutions for patients with MPM in our country&#46; Our study may be limited by the small sample size and heterogeneous population due to the rarity of MPM&#46; Lastly&#44; it can be thought that there may be a doubt related to FDG uptake in patients with talc pleurodesis&#46; However&#44; <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT data were evaluated carefully by comparing the areas of FDG uptake due to MPM with baseline <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT&#46; Additionally&#44; patients for whom a reliable interpretation could not be made due to talc pleurodesis were not included in the study&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Conclusion</span><p id="par0110" class="elsevierStylePara elsevierViewall">Taken together&#44; our results suggest that both methods are equally acceptable in monitoring disease progression in MPM&#44; even though <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT detected more progression than CT did&#46; It is clear that large-scale&#44; prospective&#44; multi-center studies are required in order to elucidate this topic and also confirm or refute our results&#46; Hopefully&#44; more research into this regard will provide insight into which method is the most accurate for the follow-up of patients with MPM&#46;</p></span><span id="sec1070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Funding</span><p id="par0115" class="elsevierStylePara elsevierViewall">This research did not receive any specific grant&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect8130">Conflict of interest</span><p id="par5115" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Author contributions</span><p id="par0120" class="elsevierStylePara elsevierViewall">All authors have made substantial contributions to all of the following&#58; &#40;1&#41; the conception and design of the study&#44; or acquisition of data&#44; or analysis and interpretation of data&#44; &#40;2&#41; drafting the article or revising it critically for important intellectual content&#44; &#40;3&#41; final approval of the version to be submitted&#46;</p></span></span>"
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            1 => "Follow-up strategies"
            2 => "Malignant pleural mesothelioma &#40;MPM&#41;"
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            0 => "Estrategias de seguimiento"
            1 => "Mesotelioma pleural maligno &#40;MPM&#41;"
            2 => "SUVm&#225;x tumoral"
            3 => "PET&#47;TC con<span class="elsevierStyleSup">18</span>F-FDG"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">In the event of suspicion of malignant pleural mesothelioma &#40;MPM&#41; progression&#44; imaging plays an important role&#46; We aimed to evaluate the efficacy of <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT in monitoring disease progression by comparing it with CT&#44; and estimate median overall survival &#40;OS&#41; according to progression status with CT and <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Materials and Methods</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">This was an observational&#44; retrospective&#44; single-institution study with MPM patients who had both <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT and CT for monitoring disease progression from March 2009 to February 2020&#46; Clinical features&#44; radiological findings&#44; and progression status according to CT &#91;radiologic progression negative &#40;RPN&#41;&#44; radiologic progression positive &#40;RPP&#41;&#93; and <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT &#91;metabolic progression negative &#40;MPN&#41;&#44; metabolic progression positive &#40;MPP&#41;&#93; were recorded&#46; The discrepancies and concordance between two methods were evaluated&#46; The OS was estimated using the Kaplan&#8211;Meier method&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">A total of 56 patients were included&#46; There were thirty-one &#40;55&#46;3&#37;&#41; RPN and 25 &#40;44&#46;7&#37;&#41; RPP&#44; while there were 26 &#40;46&#46;5&#37;&#41; MPN and 30 &#40;53&#46;5&#37;&#41; MPP&#46; All RPP patients were also found to be MPP&#44; however&#44; among RPN&#44; 5 patients &#40;8&#46;9&#37; of all patients&#41; were evaluated as MPP&#46; The concordance between two methods in monitoring disease progression was very good &#40;K&#8239;&#61;&#8239;0&#46;423&#59; p&#8239;&#60;&#8239;0&#46;01&#41;&#46; The OS was 26&#8239;&#177;&#8239;2&#46;6 months in all patients&#46; Kaplan-Meier curves between RPN and RPP&#44; and between MPN and MPP did not show statistically significant differences &#40;p&#8239;&#61;&#8239;0&#46;56 and p&#8239;&#61;&#8239;0&#46;25&#44; respectively&#41;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Both methods are equally acceptable in monitoring disease progression in MPM&#44; even though <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT detected more progression than CT did&#46;</p></span>"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivo</span><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">En caso de sospecha de progresi&#243;n del mesotelioma pleural maligno &#40;MPM&#41;&#44; la imagen juega un papel importante&#46; Nuestro objetivo es evaluar la eficacia de la PET&#47;TC con <span class="elsevierStyleSup">18</span>F-FDG en el seguimiento de la progresi&#243;n de la enfermedad&#44; compar&#225;ndola con la TC&#44; y estimar la mediana de supervivencia global &#40;SG&#41; seg&#250;n el estado de progresi&#243;n con la TC y la PET&#47;TC con <span class="elsevierStyleSup">18</span>F-FDG&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Materiales y m&#233;todos</span><p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Se trata de un estudio observacional&#44; retrospectivo y monoc&#233;ntrico con pacientes con MPM a los que se les realiz&#243; tanto PET&#47;CT con <span class="elsevierStyleSup">18</span>F-FDG como TC para controlar la progresi&#243;n de la enfermedad desde marzo de 2009 hasta febrero de 2020&#46; Se registraron las caracter&#237;sticas cl&#237;nicas&#44; los hallazgos radiol&#243;gicos y el estado de progresi&#243;n seg&#250;n la TC &#91;progresi&#243;n radiol&#243;gica negativa &#40;PRN&#41;&#44; progresi&#243;n radiol&#243;gica positiva &#40;PRP&#41;&#93; y la PET&#47;TC con <span class="elsevierStyleSup">18</span>F-FDG &#91;progresi&#243;n metab&#243;lica negativa &#40;PMN&#41;&#44; progresi&#243;n metab&#243;lica positiva &#40;PMP&#41;&#93;&#46; Se evaluaron las discrepancias y la concordancia entre ambos m&#233;todos&#46; La SG se estim&#243; mediante el m&#233;todo de Kaplan&#8211;Meier&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Se incluyeron un total de 56 pacientes&#46; Hab&#237;a 31 &#40;55&#44;3&#37;&#41; PRN y 25 &#40;44&#46;7&#37;&#41; PRP&#44; mientras que hab&#237;a 26 &#40;46&#46;5&#37;&#41; PMN y 30 &#40;53&#46;5&#37;&#41; PMP&#46; Todos los pacientes con PRP tambi&#233;n resultaron ser PMP&#44; sin embargo&#44; entre los PRN&#44; 5 pacientes &#40;8&#46;9&#37; de todos los pacientes&#41; fueron evaluados como PMP&#46; La concordancia entre los dos m&#233;todos en el seguimiento de la progresi&#243;n de la enfermedad fue muy buena &#40;K&#8239;&#61;&#8239;0&#46;423&#59; p&#8239;&#60;&#8239;0&#46;01&#41;&#46; La SG fue de 26&#8239;&#177;&#8239;2&#46;6 meses en todos los pacientes&#46; Las curvas de Kaplan-Meier entre PRN y PRP&#44; y entre PMN y PMP no mostraron diferencias estad&#237;sticamente significativas &#40;p&#8239;&#61;&#8239;0&#46;56 y p&#8239;&#61;&#8239;0&#46;25&#44; respectivamente&#41;&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Ambos m&#233;todos son igualmente aceptables en el seguimiento de la progresi&#243;n de la enfermedad en el MPM&#44; aunque la PET&#47;TC con <span class="elsevierStyleSup">18</span>F-FDG detect&#243; m&#225;s progresi&#243;n que la TC&#46;</p></span>"
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          "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A representative case of malignant pleural mesothelioma classified as radiologic progression negative according to CT and metabolic progression positive according to <span class="elsevierStyleSup">18</span>F-FDG-PET&#47;CT&#46; CT &#40;A-B-C&#41; and <span class="elsevierStyleSup">18</span>F-FDG-PET&#47;CT &#40;G-H-I&#41; images at baseline &#40;upper row&#41; of a 63-year-old male patient with epithelioid type MPM were shown&#46; In monitoring disease progression due to clinical suspicion of the patient &#40;lower row&#41;&#44; CT &#40;D-E-F&#41; showed a regression in mediastinal lymph nodes&#44; pleural thickening and pleural effusion&#44; <span class="elsevierStyleSup">18</span>F-FDG-PET&#47;CT &#40;J-K-L&#41; showed an intensely increased <span class="elsevierStyleSup">18</span>F-FDG uptake&#46; The patient&#39;s radiological progression was negative but metabolic progression was positive&#46;</p>"
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Talc pleurodesis&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">Treatment&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Chemotherapy&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Bi-modal<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Tri-modal<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">c</span></a>&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">Radiologic findings&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">Location of tumour&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>Left hemithorax&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">12&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;61&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">14&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;41&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
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Right hemithorax&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">11&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">16&nbsp;\t\t\t\t\t\t\n
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                  \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 ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Pleural thickness pattern&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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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
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Nodular&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#46;68&nbsp;\t\t\t\t\t\t\n
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                  \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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;95&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">Mix&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">5&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="left" valign="\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">5&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="left" valign="\n
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                  \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="left" valign="\n
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                  \t\t\t\t">&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">Diameter of pleural thickness &#40;mm&#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">16&#46;4&#8239;&#177;&#8239;11&#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
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&#46;2&#8239;&#177;&#8239;9&#46;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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;44&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">15&#46;6&#8239;&#177;&#8239;11&#46;7&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15&#46;3&#8239;&#177;&#8239;9&#46;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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;93&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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            0 => array:3 [
              "identificador" => "tblfn0005"
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              "nota" => "<p class="elsevierStyleNotepara" id="npar0005">8th edition of TNM staging system&#46;</p>"
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              "identificador" => "tblfn0010"
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          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">General characteristics and radiologic findings of study population&#46;</p>"
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          "leyenda" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">PMD&#44; progressive metabolic disease&#59; PMR&#44; partial metabolic regression&#59; PRD&#44; progressive radiologic disease&#59; PRR&#44; partial radiologic regression&#59; SMD&#44; stable metabolic disease&#59; SRD&#44; stable radiologic disease&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:1 [
              "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="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"></th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"></th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"></th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a>F-FDG PET&#47;CT</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Total</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Metabolic progression negative</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
                  \t\t\t\t" scope="col">Metabolic progression positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr><tr title="table-row"><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
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">PMR&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
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">SMD&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
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">PMD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><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 " rowspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CT</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Radiologic progression negative</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">PRR&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">22&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">&#8211;&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">4&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">26&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  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SRD&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">&#8211;&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">4&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">1&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">5&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  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Radiologic progression positive&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">PRD&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">&#8211;&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">&#8211;&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">25&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">25&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="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Total</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">22&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">4&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">30&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">56&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
            ]
          ]
        ]
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          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">The discrepancies between <a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a>F-FDG PET&#47;CT and CT findings in monitoring disease progression&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
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        0 => array:2 [
          "identificador" => "bibs0005"
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            0 => array:3 [
              "identificador" => "bib0005"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "ERS&#47;ESTS&#47;EACTS&#47;ESTRO guidelines for the management of malignant pleural mesothelioma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
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