<span class="elsevierStyleSup">18</span>F-FDG PET/CT in staging and delineation of radiotherapy volume for head and neck 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">Head and neck cancer &#40;HNC&#41; refers to a heterogeneous group formed by paranasal sinuses&#44; oral cavity&#44; nasopharynx&#44; oropharynx&#44; hypopharynx and larynx tumors&#46; In these tumors&#44; radiotherapy &#40;RT&#41; has long played an important role providing its main advantage&#58; organ-preservation&#46; From the 1990s&#44; intensity-modulated radiation therapy &#40;IMRT&#41; has revolutionized RT treatment&#46; This technique&#44; which achieves better dose conformity to the treatment volume while sparing organs at risk&#44; has been shown to be useful in HNC treatment planning&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">However&#44; this modern RT requires precise volume delineation&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">2</span></a> Traditionally&#44; head and neck &#40;HN&#41; CT has been the gold standard image technique for staging and RT treatment planning&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">3</span></a> HN-MRI provides complementary information on soft tissue involvement and nodal disease&#44; particularly for the oral cavity&#44; salivary glands and nasopharynx&#44; but due to logistic problems when image co-registration is performed&#44; it is not widely used in RT planning&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">4</span></a> Visual evaluation of positron emission tomography &#40;PET&#41; with fluorine-18 fluorodeoxyglucose &#40;<span class="elsevierStyleSup">18</span>F-FDG&#41; is superior to CT in identifying the tumor extension and nodal disease<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">5&#8211;8</span></a> in patients with HNC&#46; In addition&#44; unsuspected distant disease and synchronous tumors can also be identified&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">9</span></a> Several authors and guidelines&#44; including the International Atomic Energy Agency &#40;IAEA&#41; or the National Comprehensive Cancer Network &#40;NCCN&#41;&#44; have already investigated the role of <span class="elsevierStyleSup">18</span>F-FDG PET integrated with CT &#40;<span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT&#41; in staging and delineation of the primary head and neck tumor and lymph node metastases in HNC&#46;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">1&#44;10&#8211;13</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">The aim of this study is to explore the potential impact of <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT in HNC through our clinical daily practice&#46; We investigated its effect on the initial staging and we analyzed if a variation in staging&#44; alters the therapeutic strategy and therefore RT treatment planning&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Methods and materials</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Study design</span><p id="par0020" class="elsevierStylePara elsevierViewall">In this cohort study&#44; consecutive patients with untreated primary HNC were enrolled between June 2009 and January 2014&#46; Initially&#44; all patients were staged according to the AJCC staging classification<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">14</span></a> by performing a physical examination&#44; fiber-endoscopy if needed&#44; HN-CT and chest radiography&#46; All patients underwent a whole-body <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT for staging and also for delineation RT volumes&#46; Staging based on <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT information was compared with the classical staging based on HN-CT to detect differences&#46; The impact on patient management was determined by comparing the therapeutic management before and after <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT was performed&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Age variable is presented as mean and range&#46; Categorical variables are presented as absolute and relative frequencies&#46; Risk stratification tables<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">15&#44;16</span></a> were used to evaluate the benefit of using <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT information versus HN-CT&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">No formal ethics committee approval was required for this analysis of a routine clinical service&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">CT and <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT image acquisition and interpretation</span><p id="par0035" class="elsevierStylePara elsevierViewall">HN-CT was performed at the Radiology Service by using a <span class="elsevierStyleItalic">Phillips&#174; Brilliance Ict</span> scan&#46; Neck CT images were obtained from the base of the skull to the carina&#44; under quiet breathing&#44; with a 3<span class="elsevierStyleHsp" style=""></span>mm reconstruction&#46; Intravenous contrast was injected unless reported allergy or contraindication&#46; An experienced radiologist interpreted the images&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT scan was done at the Department of Nuclear Medicine by using our standard procedure&#46; Patients were instructed to fast for at least 6<span class="elsevierStyleHsp" style=""></span>hours before 18F-FDG PET&#47;CT&#46; Blood glucose level before the injection of 18F-FDG &#40;5 MBq&#47;Kg&#59; 250-450 MBq&#41; was measured to confirm it was lower than 200<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&#46; Images were taken 60<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleHsp" style=""></span>min after injection&#44; using a hybrid PET-CT SIEMENS&#174; Biograph True Point&#46; Acquisition time was 3<span class="elsevierStyleHsp" style=""></span>min&#47;bed or 4<span class="elsevierStyleHsp" style=""></span>min if patient body mass index &#8805;30&#46; Images were reconstructed with a slice thickness of 5<span class="elsevierStyleHsp" style=""></span>mm&#46; Immediately before CT was acquired&#44; intravenous contrast was administered if no contraindications were present&#46; CT data were used for attenuation correction and anatomic localization&#46; Since 2012 onwards&#44; a selective <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT of HN region with intravenous contrast and with a 3<span class="elsevierStyleHsp" style=""></span>mm reconstruction was also acquired and the CT scan performed at the Radiology Department was canceled&#46; As a result&#44; 28 patients benefited from performing both studies at the same time&#46; PET imaging was evaluated by an experienced nuclear medicine physician by visual assessment &#40;SUVmax-<span class="elsevierStyleSup">18</span>F-FDG uptake in the area of interest&#41;&#46; <span class="elsevierStyleSup">18</span>F-FDG uptake was considered pathological if it was greater than background tissue or blood pool activity at primary tumor site or lymph node and did not correlate with physiological activity&#46; For subcentimeter lymph nodes&#44; other pathological features such us shape and central necrosis were taken into consideration&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Radiotherapy treatment planning</span><p id="par0045" class="elsevierStylePara elsevierViewall">All <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT scans were performed under RT treatment conditions&#46; The scans were performed in conjunction by radiotherapy and nuclear medicine technologists&#44; using a thermoplastic mask for immobilization&#46; <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT images were imported to the Oncentra Planning System&#174; &#40;Oncentra Master Plan 4&#46;1&#46;2&#46;10&#41;&#46; Metabolic images were merged with the CT scan were delineation and RT treatment volumes were planned&#46; Gross tumor volume &#40;GTV&#41; was contoured at 40&#37; of SUVmax &#40;standardized uptake value&#41;&#46;</p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Results</span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Patients characteristics</span><p id="par0050" class="elsevierStylePara elsevierViewall">A total of 100 patients from our Tumor Registry with untreated primary HNC were included in this study&#46; This group comprised 90 men and 10 women with a mean age of 60 years &#40;range&#58; 36&#8211;80&#41;&#46; Staging&#44; primary tumor localization and histopathology are summarized in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46; Treatment intent was discussed at the Head and Neck Multidisciplinary Team &#40;HN-MDT&#41;&#46; Ten of the 100 patients did not receive RT treatment &#40;advanced disease&#44; operable tumor or patient&#39;s preference&#41;&#46; In 90 cases&#44; RT was administered &#40;Conventional 3D RT&#58; 86 patients&#59; Intensity modulated RT&#58; 4 patients&#41; with a mean RT dose of 6703 cGy &#40;range for palliative treatment&#58; 1600&#8211;3700 cGy&#59; range for radical treatment&#58; 6600&#8211;7000 cGy&#41;&#46; Concurrent systemic treatment &#40;Cisplatine 100<span class="elsevierStyleHsp" style=""></span>mg&#47;m<span class="elsevierStyleSup">2</span> or 40<span class="elsevierStyleHsp" style=""></span>mg&#47;m<span class="elsevierStyleSup">2</span>&#44; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>23&#59; Cetuximab 250<span class="elsevierStyleHsp" style=""></span>mg&#47;m<span class="elsevierStyleSup">2</span>&#44; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>45&#41; was administered in 68 and induction chemotherapy &#40;Docetaxel 75<span class="elsevierStyleHsp" style=""></span>mg&#47;m<span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>Cisplatine 75<span class="elsevierStyleHsp" style=""></span>mg&#47;m<span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>5-Fluorouracil 750<span class="elsevierStyleHsp" style=""></span>mg&#47;m<span class="elsevierStyleSup">2</span>&#41; in 33 patients respectively&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Staging modifications</span><p id="par0055" class="elsevierStylePara elsevierViewall">Every change is detailed in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> which represents the proportion of patients whose staging based on CT information was modified by <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT&#46; The main diagonal of the three tables shows those individuals in whom both classifications were coincident&#46; Patients above the diagonal are overstaged and under the main diagonal are understaged&#46; Staging changes are as follow&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">-</span><p id="par0060" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0010"><span class="elsevierStyleItalic">Table 2</span></a><span class="elsevierStyleItalic">a&#58;</span><span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT modified primary tumor extension &#40;cT&#41; revealed a modification in 28 cases&#58; in 14 cases tumor staging increased and in 14 cases it decreased&#46; In all categories reclassification by <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT was higher than 10&#37;&#46; A point to highlight is the cTx stage in CT&#44; which is defined as a primary tumor that cannot be evaluated&#46; Two patients with an undetected tumor were finally staged as cT4 tumor&#44; resulting both in IVA stage&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">-</span><p id="par0065" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0010"><span class="elsevierStyleItalic">Table 2</span></a><span class="elsevierStyleItalic">b&#58;</span> When analyzing nodal disease information &#40;cN&#41;&#44; we found that <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT resulted in a stage migration in 47 patients&#46; Sixteen were down-staged and 31 patients up-staged due to <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT information&#46; Reclassification by <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT was also higher than 10&#37; in all categories&#46; Main changes are as follow&#58; 19 node negative patients were found to present metabolically active disease and 2 patients with suspicious nodal disease in CT were not metabolically active&#46; Eight were diagnosed with bilateral nodal disease &#40;cN2c&#41; but <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT image showed unilateral disease only and 5 staged as N positive &#40;N1&#44; N2A or N2B&#41; turned into N2C &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Image 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">-</span><p id="par0070" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0010"><span class="elsevierStyleItalic">Table 2</span></a><span class="elsevierStyleItalic">c&#58;</span> According to AJCC 7th staging&#44; <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT determined a change in cTNM in 27 of 100 cases&#58; 19 cases were up-staged and 8 down-staged&#46; Reclassification by <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT into IVA category was 5&#46;9&#37; and 0&#37; in IVC&#46; All other category reclassification was above 10&#37;&#46;</p></li></ul></p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Therapeutic management modifications</span><p id="par0075" class="elsevierStylePara elsevierViewall">Treatment intention changed from radical to palliative in 6 patients due to distant metastases detected by <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT&#58; 4 patients suffered from bone metastases&#44; 1 had bone and liver metastases and 1 lung involvement&#46; <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT detected synchronous tumors in 8 patients which implied a modification in the therapeutic strategy&#58; radical treatment intent was maintained in 7 of these patients but one of them received palliative treatment&#46; <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> details clinical findings and therapeutic management&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0080" class="elsevierStylePara elsevierViewall">Tumor metabolic image obtained by the use of <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT was taken into consideration when delineating the gross tumor volume &#40;T-GTV&#41; in all patients&#46; It also helped us to determine nodal-GTV &#40;N-GTV&#41; as well as to select the appropriate nodal levels included in the radiotherapy beam&#46; As no biopsy was undertook in case of disparity between CT and <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT results&#44; individualized decision was taken&#46; No lymph node without metabolic activity was excluded from nodal volume in case of malignant suspicious disease in CT&#46; If bilateral disease was found&#44; nodal volume was enlarged&#46;</p></span></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Discussion</span><p id="par0085" class="elsevierStylePara elsevierViewall">Head and neck cancer &#40;HNC&#41; represents about 4&#37; of all cancers occurring in Europe&#46; Etiologic factors such as tobacco and alcohol are common to other pathologies&#46; In consequence&#44; patients with HNC are in risk of developing second primary tumors of the head and neck area&#44; esophagus or lung&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT provides biological and anatomic tumor information that is more accurate than either PET or CT alone&#46;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">6&#44;10&#44;17</span></a><span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT is a useful tool in HNC due to its well-recognized advantages for diagnosis&#44; staging&#44; evaluation of treatment response and restaging&#46;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">1&#44;11</span></a> However&#44; the use of <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT in RT treatment planning is more controversial&#46; Tumor size accuracy and nodal metastases detection are essential in planning RT&#46; Several investigators have already reported more accurate staging with metabolic information compared with the use of CT alone&#46;<a class="elsevierStyleCrossRefs" href="#bib0215"><span class="elsevierStyleSup">13&#44;15</span></a> Also&#44; it is reported that inter-observer variability in target volume delineation is reduced by using <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">18&#44;19</span></a> and facilitates adaptive RT in HNC&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">20</span></a> This is paramount in HNC where complex anatomic structures are so close&#46; Although there is no consensus on the role of <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT delineation in HNC as compared to other pathologies such as in lung cancer&#44; current data supports changing treatment volumes and dose prescription based on <span class="elsevierStyleSup">18</span>F-FDG-PET&#47;CT information&#46;<a class="elsevierStyleCrossRefs" href="#bib0200"><span class="elsevierStyleSup">10&#44;18&#44;19</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">Our study analyzes how <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT affects HNC staging and studies changes in the therapeutic approach compared to CT image alone&#46; All <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT scans were performed in the RT planning position&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">When studying tumor extension &#40;cT&#41;&#44; <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT provides metabolic information that&#44; correlated with anatomy&#44; offers additional differentiation of tumor from healthy tissue&#46; In this sense&#44; better defining tumoral extent could affect the therapeutic index and could also affect quality of life by reducing acute and chronic toxicity&#46; High sensitivity &#40;93&#8211;100&#37;&#41; and specificity &#40;94&#8211;98&#37;&#41; of <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT for primary lesions <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT has been reported<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">20&#44;21</span></a> as well as its role in a more accurate GTV definition&#46;<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">3&#44;19</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">In the literature&#44; smaller GTV is mainly reported when contouring with <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT&#46; In 2009&#44; a change determined by <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT in tumor stage was observed in 6 of 38 HNC patients &#40;15&#46;75&#37;&#41; by Guido et al&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">22</span></a> The primary tumor GTV based on <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT &#40;PET-GTV&#41; was smaller in 35 patients &#40;92&#37;&#41; compared to the CT image &#40;CT-GTV&#41;&#44; although this difference was not statistically significant&#46; Kajitani et al&#46; did not found changes between PET-GTV and CT-GTV in 43 of 53 cases when they compared the location of the primary tumor&#46; However&#44; the CT-GTV sensitivity was lower than PET-GTV &#40;81&#37; versus 96&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">21</span></a> Delouya also compared primary tumor PET-GTV with CT-GTV&#44; finding that PET-GTV was smaller &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">3</span></a> Most recently&#44; Leclerc et al&#46; have demonstrated the use of <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT in obtaining smaller treatment volumes rather than with CT in their study of 41 patients &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;0001&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">23</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">In our study group&#44; we observed a big percentage of patients reclassified due to <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT&#46; Tumor staging was modified in 27 patients &#40;19&#37; up-staged&#59; 8&#37; down-staged&#41;&#46; Tumor-GTV delineation was based on <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT images&#46; In our experience&#44; it allows easier delineation&#44; especially in tumors difficult to visualize on CT alone&#44; tumors with submucosal affectation or in patients with dental devices&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">In relation to nodal disease &#40;cN&#41;&#44; <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT has low sensitivity in lymph nodes smaller than 1<span class="elsevierStyleHsp" style=""></span>cm diameter which can result in false-negative cases<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">8</span></a> or may over-stage patients&#44; identifying benign inflammatory disease as malignant&#46; In spite of this critical point&#44; the superiority of <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT against anatomical techniques has been described in large studies&#46;<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">7&#44;8&#44;17</span></a> Shu-Hang Ng and colleges studied 135 patients with no nodal disease on physical examination and performed three different imaging tests &#40;<span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT&#44; MRI and CT&#41;&#46; Their results showed that <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT was the most sensitive diagnosis tool&#46; In this line&#44; Jin Taek Park also demonstrated superiority of <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT in detecting contralateral neck metastases compared to CT or MRI scan&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">24</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">Nodal tumor disease is one the most important prognostic factors in HNC&#46;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">6&#44;25</span></a> Therefore&#44; accurate detection is essential in delineating RT treatment volumes&#46; <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT has been considered an important tool to determine which lymph nodes should be included in the treatment boost volume and which should be excluded&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">26</span></a> Simple visual interpretation of the PET image is the most commonly applied technique but it is operator-dependent&#59; other alternatives such as automatic delineation are being studied&#46;<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">4&#44;27&#44;28</span></a> A standardized method for signal segmentation may be established to avoid false-positive readings of the <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT signal caused by peritumoral inflammation around the nodal disease&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">In our study&#44; nodal disease staging has globally changed in 46 patients of the 100 included&#46; Therefore&#44; our treatment volumes were modified to include PET-diagnosis nodal disease and adapt radiotherapy dose&#46; Also&#44; cervical levels irradiated prophylactically were better selected according to <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT information&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Since <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT is a whole-body technique&#44; it has the ability of detecting more distant metastases than conventional studies such as CT or MRI&#46; Kolarova described in 2012&#44; 5&#46;7&#37; of new distant metastases in his study group of 53 patients<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">5</span></a> and Abramyuk reported a 13&#46;7&#37; cM stage modification&#44; mainly due to the new disease diagnosis&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">29</span></a> In our study&#44; new metastases were detected in 6 patients by using <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT and treatment intention changed into palliative&#46; In this line&#44; a synchronous tumor was diagnosed in 8 patients&#44; implying also a modification in the global disease approach&#46; Only one of these had to receive palliative treatment&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">In summary&#44; <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT clearly affects our therapeutic strategy&#46; Studies such as that by Koschy et al&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">30</span></a> have reported 14&#37; of clinical changes and 25&#37; of RT intention changes&#46; Abramyuk and colleges described 27&#37; and 14&#37;&#44; respectively&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">29</span></a> In our group of 100 patients&#44; global disagreement in cTNM staging between CT and <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT was found in 27&#37; of patients and <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT determined a palliative treatment in 7&#37; &#40;6 new metastases diagnosed and 1 synchronous tumor&#41;&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">Although <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT is not part of the routine staging for HNC in many centers&#44; we believe it is useful&#46; Our investigation&#44; which includes one of the largest study samples&#44; suggests that <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT information is more accurate than CT study alone in pre-RT staging of HNC&#46; In our institution the use of <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT in HNC started in 2009 and due to its preliminary benefits&#44; the HN-MDT included it in the protocol for staging and RT planning for all advanced tumors and high risk early disease&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">Our study&#44; however&#44; must be interpreted with caution&#46; It analyzes information retrospectively&#44; which always limits the access to data&#44; includes a variety of head and neck cancer subtypes and we are yet to determine whether it affects survival and&#47;or long-term toxicity&#46; Pathological uptake by <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT at lymph nodes was not histologically confirmed and RT planning was performed at 40&#37; of SUVmax&#46; It is one of the most accepted values for planning&#44; but other methods not yet approved could be superior&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">Modern RT techniques require precise disease identification and delineation of treatment volumes&#46; <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT improves staging in HNC and therefore helps physicians to select the best treatment according to patient&#39;s characteristics&#46; Although planning with <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT in HNC is still being investigated&#44; the most recent studies suggest a greater accuracy in delineating tumor-GTV and nodal-GTV&#46; The modification of both implies adapting the radiotherapy prescribed dose which can be related with a change in the disease outcome and toxicity in HNC&#46; Reference guidelines such as NCCN&#44; IAEA or the Spanish Society of Radiation Oncology consider <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT potentially appropriate and recommend it for RT planning&#46; We believe that the implementation of this tool in locally advanced HNC has advantages&#44; but further studies are required to establish stronger conclusions about clinical outcomes such as disease free-survival&#44; relapse rate&#44; toxicity and mortality&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Conflicts of interest</span><p id="par0155" class="elsevierStylePara elsevierViewall">All authors have no conflicts of interest&#46;</p></span></span>"
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              "titulo" => "CT and F-FDG PET&#47;CT image acquisition and interpretation"
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              "titulo" => "Radiotherapy treatment planning"
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              "titulo" => "Therapeutic management modifications"
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    "fechaRecibido" => "2018-02-26"
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            0 => "<span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT"
            1 => "Head and neck cancer"
            2 => "Staging"
            3 => "Radiotherapy planning"
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            0 => "<span class="elsevierStyleSup">18</span>F-FDG PET&#47;TC"
            1 => "C&#225;ncer cabeza y cuello"
            2 => "Estadificaci&#243;n"
            3 => "Planificaci&#243;n radioterapia"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Purpose</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">The aim is to investigate the use of <span class="elsevierStyleSup">18</span>F-FDG &#40;fluorine-18 fluorodeoxyglucose&#41; PET&#47;CT in head and neck cancer &#40;HNC&#41; staging and its effect on the therapeutic strategy and radiotherapy &#40;RT&#41; planning&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods and materials</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">One hundred patients with HNC were included&#46; Primary tumor sites&#58; 18&#37; oral cavity&#44; 20&#37; oropharynx&#44; 12&#37; hypopharynx&#44; 11&#37; nasopharynx&#44; 37&#37; larynx&#44; 2&#37; paranasal sinuses&#46; Patients were staged according to the American Joint Committee of Cancer 7th edition&#46; Stage&#58; 5&#37; stage I&#44; 7&#37; stage II&#44; 14&#37; stage III&#44; 61&#37; stage IVA&#44; 7&#37; stage IVB and 6&#37; stage IVC&#46; A contrast-enhanced CT and a <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT acquired under RT position were performed&#46; Both exams were compared to analyze patients&#8217; staging reclassification&#46; Changes in therapeutic strategy were analyzed&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT detected 6 distant metastases and treatment intention changed to palliative&#46; Eight synchronous tumors were detected&#59; one received palliative treatment&#46; <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT reclassified cTNM staging in 27patients&#46; Tumor extension changed in 28 &#40;14&#37; up-staged&#59; 14&#37; down-staged&#41;&#44; implying a change in GTV &#40;Gross Tumor Volume&#41; delineation&#46; Nodal detection was reclassified in 47 patients&#58; 8 patients down-staged &#40;N2C to N2A&#47;N2B&#47;N1&#41; and 2 were false positive&#46; Nineteen patients were false negatives and 5 staged as N<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>&#40;N1&#47;N2A&#47;N2B&#41; turned out into N2C&#46; These staging modifications imply adapting the nodal volume to be irradiated&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT reclassification was higher than 10&#37; in almost all categories studied &#40;cTNM&#44; tumor extension and nodal disease&#41; and detects more metastases and synchronous tumors than conventional studies&#44; which has an impact on the therapeutic patient management and RT planning&#46;</p></span>"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivos</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Investigar el uso de la <span class="elsevierStyleSup">18</span>F-FDG&#40;fl&#250;or-18 fluorodesoxiglucosa&#41; PET&#47;TC en la estadificaci&#243;n del c&#225;ncer de cabeza y cuello &#40;CCC&#41; y su repercusi&#243;n en la decisi&#243;n terap&#233;utica y planificaci&#243;n de tratamiento radioter&#225;pico&#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 incluyen 100 pacientes con CCC y la siguiente localizaci&#243;n tumoral&#58; 18&#37; cavidad oral&#44; 20&#37; orofaringe&#44; 12&#37; hipofaringe&#44; 11&#37; nasofaringe&#44; 37&#37; laringe&#44; 2&#37; senos paranasales&#46; La estadificaci&#243;n tumoral seg&#250;n la AJCC &#40;<span class="elsevierStyleItalic">American Joint Committee of Cancer&#44; 7th</span>&#41; es&#58; 5&#37;-I&#44; 7&#37;-II&#44; 14&#37;-III&#44; 61&#37;-IVA&#44; 7&#37;-IVB&#44; 6&#37;-IVC&#46; Se les realiza una TC y una <span class="elsevierStyleSup">18</span>F-FDG PET&#47;TC en condiciones de simulaci&#243;n para comparar la reclasificaci&#243;n del estadiaje&#46; Adem&#225;s&#44; se analizan los cambios de actitud terap&#233;utica&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">La <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT detecta 6 pacientes metast&#225;sicos que requieren tratamiento paliativo y 8 tumores sincr&#243;nicos&#44; siendo uno paliativo&#46; Se produce una reclasificaci&#243;n del estadiaje en 27 pacientes&#46; La extensi&#243;n tumoral var&#237;a en 28 &#40;14&#37; sobre-estadificaci&#243;n&#44; 14&#37; infra-estadificaci&#243;n&#41;&#44; implicando una variaci&#243;n en el contorneo del GTV &#40;<span class="elsevierStyleItalic">Gross Tumor Volume</span>&#41;&#46; La estadificaci&#243;n ganglionar cambia en 47&#58; 8 pacientes son infra-estadificados &#40;N2C cambia a N2A&#47;N2B&#47;N1&#41; y 2 son falsos positivos&#46; Diecinueve pacientes son falsos negativos y 5 con afectaci&#243;n ganglionar unilateral &#40;N1&#47;N2A&#47;N2B&#41; muestran actividad metab&#243;lica bilateral&#46; Estos cambios de estadificaci&#243;n implican una adaptaci&#243;n del volumen ganglionar a irradiar&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">La <span class="elsevierStyleSup">18</span>F-FDG PET&#47;TC produce una reclasificaci&#243;n superior al 10&#37; en casi todas las categor&#237;as estudiadas &#40;cTNM&#44; extensi&#243;n tumoral&#44; enfermedad ganglionar&#41; y detecta m&#225;s estad&#237;os metast&#225;sicos y tumores sincr&#243;nicos que los estudios convencionales&#44; lo que genera un impacto en el manejo del paciente y contorneo de los vol&#250;menes de radioterapia&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Pedraza S&#44; Ruiz-Alonso A&#44; Hern&#225;ndez-Mart&#237;nez AC&#44; Cabello E&#44; Lora D&#44; P&#233;rez-Regadera JF&#46; <span class="elsevierStyleSup">18</span>F-FDG PET&#47;TC para la estadificaci&#243;n y delineaci&#243;n del volumen de radioterapia en el c&#225;ncer de cabeza y cuello&#46; Rev Esp Med Nucl Imagen Mol&#46; 2019&#59;38&#58;154&#8211;159&#46;</p>"
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            "apendice" => "<p id="par0165" class="elsevierStylePara elsevierViewall">The following are the supplementary data to this article&#58;<elsevierMultimedia ident="upi0005"></elsevierMultimedia></p>"
            "etiqueta" => "Appendix A"
            "titulo" => "Supplementary data"
            "identificador" => "sec0065"
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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">CT scan &#40;A&#41; from a patient with a cT3N0 hypofarynx carcinoma&#46; PET-CT show subcentimeter lymph nodes in left retropharynx level &#40;SUVmax<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>13&#46;99&#41; and left IIA level &#40;SUVmax<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>11&#46;19&#41;&#46; Final stage&#58; cT3N2bM0&#44; IVA&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Characteristics&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Patients &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>100&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Stage</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>I&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">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="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">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="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>III&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>IVA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">61&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>IVB&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">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="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>IVC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Tumor localization</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Oral cavity&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Oropharynx&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Hypopharynx&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Nasopharynx&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Larynx&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">37&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Para-nasal sinuses&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Histopathology</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Squamous cell carcinoma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">87&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Lymphoepithelioma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Adenoid cystic carcinoma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">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="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Undifferentiated carcinoma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2021867.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Patient clinical characteristics&#46;</p>"
        ]
      ]
      2 => array:8 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at2"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:1 [
          "tablatextoimagen" => array:3 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " colspan="2" align="center" valign="top" scope="col">&#40;A&#41; cT changes</th><th class="td" title="table-head  " colspan="5" align="center" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleSup">18</span>F-FDG-PET&#47;CT</th><th class="td" title="table-head  " align="left" valign="top" scope="col">Total&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col">Reclassified<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>28&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">T1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">T2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">T3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">T4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Tx&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " rowspan="5" align="left" valign="top">CT</td><td class="td" title="table-entry  " align="left" valign="top">T1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1 &#40;12&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">T2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">9 &#40;36&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">T3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">11 &#40;45&#46;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">T4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">34&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">39&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5 &#40;12&#46;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Tx&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2 &#40;66&#46;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2021871.png"
              ]
            ]
            1 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " colspan="2" align="center" valign="top" scope="col">&#40;B&#41; cN changes</th><th class="td" title="table-head  " colspan="5" align="center" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleSup">18</span>F-FDG-PET&#47;CT</th><th class="td" title="table-head  " align="left" valign="top" scope="col">Total&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col">Reclassified<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>47&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">N0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">N1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">N2A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">N2B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">N2C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " rowspan="5" align="left" valign="top">CT</td><td class="td" title="table-entry  " align="left" valign="top">N0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">19 &#40;54&#46;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">N1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6 &#40;60&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">N2A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6 &#40;37&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">N2B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8 &#40;33&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">N2C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8 &#40;53&#46;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2021868.png"
              ]
            ]
            2 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " colspan="2" align="center" valign="top" scope="col">&#40;C&#41; cTNM changes</th><th class="td" title="table-head  " colspan="6" align="center" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleSup">18</span>F-FDG-PET&#47;CT</th><th class="td" title="table-head  " align="left" valign="top" scope="col">Total&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col">Reclassified<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>27&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">I&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">III&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">IVA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">IVB&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">IVC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " rowspan="7" align="left" valign="top">CT</td><td class="td" title="table-entry  " align="left" valign="top">I&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1 &#40;10&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6 &#40;60&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">III&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">12 &#40;50&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">IVA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">48&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">51&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3 &#40;5&#46;9&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">IVB&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3 &#40;37&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">IVC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0 &#40;0&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Tx&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2 &#40;100&#37;&#41;&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
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Case&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Synchronous tumors&#47;staging &#91;AJCC&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Therapeutic management&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Squamous larynx carcinoma &#40;cT2N0M0&#44; II&#41;<br>Squamous oropharynx carcinoma &#40;cT2N0M0&#44; II&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Chemoradiotherapy in both locations&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">2&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Chemoradiotherapy in HNC<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>Lung surgery&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Squamous larynx carcinoma &#40;cT4N3M0&#44; IVB&#41;<br>Non-small cell lung cancer &#40;cT2N1M0&#44; IIA&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Palliative chemotherapy in both locations&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Squamous larynx carcinoma &#40;cT2N2M0&#44; IVA&#41;<br>Esophagus carcinoma &#40;cT4N0M0&#44; IIIA&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Chemoradiotherapy in both locations&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Squamous hypopharynx carcinoma &#40;cT3N2M0&#44; IVA&#41;<br>Esophagus carcinoma &#40;cT1N0M0&#44; IA&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Chemoradiotherapy in both locations&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Squamous oropharynx carcinoma &#40;cT4aN0M0&#44; IVA&#41;<br>Low risk prostate cancer of NCCN&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Chemoradiotherapy in HNC<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>prostate follow-up&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Squamous hypopharynx carcinoma &#40;cT2N0M0&#44; II&#41;<br>In situ carcinoma of colon &#40;cTisN0M0&#44; 0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Chemoradiotherapy in HNC<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>colon surgery&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Squamous larynx carcinoma &#40;cT1N0M0&#44; I&#41;<br>Hepatocarcinoma grade A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Radical radiotherapy in HNC<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>Liver radiofrequency&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "identificador" => "bibs0015"
          "bibliografiaReferencia" => array:30 [
            0 => array:3 [
              "identificador" => "bib0155"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Head and Neck Cancer &#40;version 2&#46;2018&#41;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "National Comprehensive Cancer Network"
                          ]
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                    0 => array:1 [
                      "Libro" => array:1 [
                        "fecha" => "2018"
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            1 => array:3 [
              "identificador" => "bib0160"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "&#91;The ICRU Report 83&#58; prescribing&#44; recording and reporting photon-beam intensity-modulated radiation therapy &#40;IMRT&#41;&#93;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "N&#46; Hodapp"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Strahlenther Onkol Organ Dtsch Rontgengesellschaft Al"
                        "fecha" => "2012"
                        "volumen" => "188"
                        "paginaInicial" => "97"
                        "paginaFinal" => "99"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0165"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "<span class="elsevierStyleSup">18</span>F-FDG-PET imaging in radiotherapy tumor volume delineation in treatment of head and neck cancer"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "G&#46; Delouya"
                            1 => "L&#46; Igidbashian"
                            2 => "A&#46; Houle"
                            3 => "M&#46; B&#233;lair"
                            4 => "L&#46; Boucher"
                            5 => "C&#46; Cohade"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Radiother Oncol J Eur Soc Ther Radiol Oncol"
                        "fecha" => "2011"
                        "volumen" => "101"
                        "paginaInicial" => "362"
                        "paginaFinal" => "368"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0170"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Functional imaging in radiation therapy planning for head and neck cancer"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "L&#46;A&#46; P&#233;rez Romasanta"
                            1 => "M&#46;J&#46; Garc&#237;a Velloso"
                            2 => "A&#46; L&#243;pez Medina"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Rep Pract Oncol Radiother"
                        "fecha" => "2013"
                        "volumen" => "18"
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