Visual and semi-quantitative analysis of 6-[18F]FDOPA PET/CT in patients with brain tumors and suspected tumor recurrence versus radionecrosis | Revista Española de Medicina Nuclear e Imagen Molecular (English Edition)

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Un año después de la radioterapia, el paciente experimenta crisis comiciales secundarias a esta lesión. Se realizó una resonancia magnética (RM) cerebral para evaluar la posibilidad de recurrencia tumoral versus radionecrosis que resultó no concluyente. El resultado del PET FDOPA fue negativo (radionecrosis) y ante la persistencia de las crisis comiciales el paciente recibió tratamiento quirúrgico, confirmándose en la pieza resecada la radionecrosis. A) Imágenes del PET 6-[18F]FDOPA que muestran una muy discreta captacion de FDOPA de carácter difuso alrededor de la cavidad quirúrgica. B) Secuencias T1 poscontraste de la RM que muestran captacion de contraste alrededor de los márgenes de la cavidad quirúrgica irradiada de dudosa significación. C) Secuencias de perfusión (PWI) de la RM que no muestran perfusión incrementada. D) Imágenes de fusión PET-RM que no muestran incremento significativo de FDOPA en los márgenes de la cavidad quirúrgica, con unos ratios L/E 0.56 y L/C 1.2. E) Cortes histológicos de la pieza quirúrgica resecada, que muestra cambios secundarios a radionecrosis." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "M. Suárez-Piñera, L. Rodriguez-Bel, M. Alemany, A. Pons-Escoda, M. Pudis, A. Coello, G. Reynes, N. Vidal, M. Cortes-Romera, M. Macia" "autores" => array:10 [ 0 => array:2 [ "nombre" => "M." "apellidos" => "Suárez-Piñera" ] 1 => array:2 [ "nombre" => "L." "apellidos" => "Rodriguez-Bel" ] 2 => array:2 [ "nombre" => "M." "apellidos" => "Alemany" ] 3 => array:2 [ "nombre" => "A." "apellidos" => "Pons-Escoda" ] 4 => array:2 [ "nombre" => "M." "apellidos" => "Pudis" ] 5 => array:2 [ "nombre" => "A." "apellidos" => "Coello" ] 6 => array:2 [ "nombre" => "G." "apellidos" => "Reynes" ] 7 => array:2 [ "nombre" => "N." "apellidos" => "Vidal" ] 8 => array:2 [ "nombre" => "M." "apellidos" => "Cortes-Romera" ] 9 => array:2 [ "nombre" => "M." 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The involvement of the diaphyseal-metaphyseal regions in the proximity of the knees, as shown in these two cases, is a practically pathognomonic image in patients with ECD." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "M. Pudis, A. Palomar-Muñoz, X. Solanich-Moreno, J.J. Robles-Barba, G. Rocamora-Blanch, L. Rodríguez-Bel, J.A. Narváez, M. Cortés-Romera" "autores" => array:8 [ 0 => array:2 [ "nombre" => "M." "apellidos" => "Pudis" ] 1 => array:2 [ "nombre" => "A." "apellidos" => "Palomar-Muñoz" ] 2 => array:2 [ "nombre" => "X." "apellidos" => "Solanich-Moreno" ] 3 => array:2 [ "nombre" => "J.J." "apellidos" => "Robles-Barba" ] 4 => array:2 [ "nombre" => "G." "apellidos" => "Rocamora-Blanch" ] 5 => array:2 [ "nombre" => "L." "apellidos" => "Rodríguez-Bel" ] 6 => array:2 [ "nombre" => "J.A." "apellidos" => "Narváez" ] 7 => array:2 [ "nombre" => "M." 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Suárez-Piñera, L. Rodriguez-Bel, M. Alemany, A. Pons-Escoda, M. Pudis, A. Coello, G. Reynes, N. Vidal, M. Cortes-Romera, M. Macia" "autores" => array:10 [ 0 => array:4 [ "nombre" => "M." "apellidos" => "Suárez-Piñera" "email" => array:1 [ 0 => "marina.suarez.idi@gencat.cat" ] "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "L." "apellidos" => "Rodriguez-Bel" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "M." "apellidos" => "Alemany" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] 1 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] ] ] 3 => array:3 [ "nombre" => "A." 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"apellidos" => "Macia" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] 1 => array:2 [ "etiqueta" => "h" "identificador" => "aff0040" ] ] ] ] "afiliaciones" => array:8 [ 0 => array:3 [ "entidad" => "Unidad PET IDI, Servicio de Medicina Nuclear, Hospital Universitari de Bellvitge, L’Hospitalet de Llobregat, Barcelona, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Neuro-Oncology Functional Unit, Institut d'Investigació Biomèdica de Bellvitge-IDIBELL, L’Hospitalet de Llobregat, Barcelona, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Servicio de Neurología, Hospital Universitari de Bellvitge-ICO L'Hospitalet (IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Servicio de Radiología, Sección de Neuroradiología, Hospital Universitari de Bellvitge, L’Hospitalet de Llobregat, Barcelona, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Servicio de Neurocirugía, Hospital Universitari de Bellvitge, L’Hospitalet de Llobregat, Barcelona, Spain" "etiqueta" => "e" "identificador" => "aff0025" ] 5 => array:3 [ "entidad" => "Servicio de Física Médica, Hospital Universitari de Bellvitge-ICO L'Hospitalet (IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain" "etiqueta" => "f" "identificador" => "aff0030" ] 6 => array:3 [ "entidad" => "Unidad de Neurooncología, Servicio de Anatomía Patológica, Hospital Universitari de Bellvitge, L’Hospitalet de Llobregat, Barcelona, Spain" "etiqueta" => "g" "identificador" => "aff0035" ] 7 => array:3 [ "entidad" => "Servicio de Oncología Radioterápica, Institut Català d'Oncologia (ICO) L'Hospitalet (IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain" "etiqueta" => "h" "identificador" => "aff0040" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Análisis visual y semicuantitativo del 6-[18F]FDOPA PET/TC en pacientes con tumores cerebrales ante la sospecha de recurrencia tumoral versus radionecrosis" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1082 "Ancho" => 1674 "Tamanyo" => 323732 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Images of a patient with a history of stage IV adenocarcinoma of the colon with a single brain metastasis, which was treated with surgery and radiotherapy. Ten months after the end of radiotherapy, due to gait instability and headache, a brain MRI was performed with doubts of tumor recurrence versus radionecrosis. FDOPA PET showed a positive result for tumor recurrence which was later confirmed in the histopathological study of the surgical specimen. A) 6-[18F]FDOPA PET images showing increased FDOPA uptake of moderate intensity and irregular character. A focal area of higher intensity is observed in the medial region intensity in the medial region. (B) Postcontrast T1-weighted MRI sequences revealing contrast uptake around the margins of the irradiated surgical cavity, with uncertain significance. C) MR perfusion (PWI) sequences indicating a discrete increase in perfusion. D) PET-MRI fusion images showing a marked increase in FDOPA, especially D) PET-MRI fusion images showing a marked increase in FDOPA, especially at the medial margin of the cavity, with an L/E ratio of 1.09 and L/C of 2.25. E) Histological section of the resected surgical specimen,where abundant cellularity compatible with colon adenocarcinoma is observed." ] ] ] "textoCompleto" => "IntroductionThe evaluation of response to treatment of brain tumors and, more specifically, the differentiation between tumor recurrence and post-treatment changes (PTC) in patients treated with radiotherapy (RT) continues to be a clinical and neuroimaging challenge. This differentiation has direct implications on the prognosis and management of these patients.Neuroimaging techniques play a fundamental role in the study of central nervous system (CNS) neoplasias. Magnetic resonance (MR) is the technique of choice for both diagnosis and therapeutic planning as well as post-treatment follow-up. Nonetheless, the differentiation between tumor recurrence and post-radiotherapy changes is a critical unresolved clinical necessity because the information provided by MR may be insufficient and non-conclusive.<a class="elsevierStyleCrossRefs" href="#bib0005">1,2</a>After treatment with RT, the brain parenchyma in both intra- and extra-parenchymatous and even head and neck tumors, undergoes inflammatory phenomena secondary to treatments and these are called PTC.<a class="elsevierStyleCrossRefs" href="#bib0015">3–5</a> The physiopathology of these phenomena evolves over a long period of time and they are classified into 3 types according to their evolutive phase: 1. acute phase: these appear within 2 h to 2 weeks after the initiation of RT, being secondary to a disruption of the hematoencephalic barrier (HEB) and causing an increase in intracranial pressure; 2. Subacute phase: from the second week up to 6 months post-RT. These are due to transitory damage to the myelin, triggered by the disruption of the HEB and/or dysfunction of the oligodendrocytes. This phase may present clinical and/or radiological repercussion showing worsening of the radiological findings (pseudo-progression). It should be taken into account that the clinical and radiological changes are not always identified together and, thus, this subacute phase is not always synonymous of pseudo-progression, and 3. Delayed phase: typically from 6 months up to years after RT. These are changes secondary to damage of the vascular endothelium, demyelination and necrosis of the white matter accompanied by loss of oligodendrocytes and neuronal precursors, gliosis and neuroinflammation. This phase may follow with clinical semiology, radioinduced brain tumors and radiological alterations known as radionecrosis (RNC). As in the previous phase, these alterations do not always lead to RNC or vice-versa.<a class="elsevierStyleCrossRefs" href="#bib0030">6,7</a> The incidence of RNC varies, ranging between 5–7% in high-grade primary tumors and between 14–25% in patients with brain M1 and specifically treated with stereotaxic radiosurgery.<a class="elsevierStyleCrossRef" href="#bib0040">8</a> Numerous variables can influence this incidence, such as the type of volume of tissue irradiated, the dose, dose fractionation, type of previous RT treatments or the use of a concomitant systemic treatment as well as the individual predisposition of each patient.<a class="elsevierStyleCrossRef" href="#bib0035">7</a> In addition, this incidence is imprecise due to the usual absence of histopathological confirmation and the lack of strict diagnostic criteria.The clinical and radiological (MR) semiology of RNC is usually undistinguishable from the presence of tumoral viability and, in addition, it assumes that both phenomena frequently coexist. In 2016, the Response Assessment in Neuro-Oncology (RANO) multidisciplinary working group that evaluates the criteria of response to treatment in brain tumors and the European Association of Neuro-oncology (EANO) published the first recommendations that include the use of positron emission tomography (PET) with amino acids as a useful tool for the evaluation of cerebral gliomas in clinical practice.<a class="elsevierStyleCrossRef" href="#bib0045">9</a> In 2018 and 2021 this recommendation was reaffirmed and in the last guidelines published by the European Society of Medical Oncology (ESMO) advanced MR sequences including spectroscopy, perfusion, diffusion and PET with amino acids were recommended with a scientific level of evidence IV for the differential diagnosis of PTC and tumor recurrence in patients with brain tumors.<a class="elsevierStyleCrossRefs" href="#bib0050">10–12</a> PET with amino acids has been proposed as a useful tool together with MR in the evaluation of the brain parenchyma after RT, showing cost-efficient results.<a class="elsevierStyleCrossRef" href="#bib0065">13</a>The physiopathological basis of PET with amino acids is the overexpression of long chain amino acid transporters (LAT) in the membrane of the tumoral cells unlike normal brain tissue as well as their independence from the integrity of the HEB. The first PET radiopharmaceutical with amino acids used in neuro-oncology was methionine labeled with 11C (MET). Due to limitations secondary to the half-life of 11C, other radiopharmaceuticals with amino acids labeled with 18F, L-[2-18F] fluorotyrosine (FET) and 3,4-Dihydroxy-6-[18F]fluoro-l-phenylalanine; fluorodopa (6-[18F]FDOPA)<a class="elsevierStyleCrossRefs" href="#bib0070">14,15</a> were developed. Despite the lesser experience with 6-[18F]FDOPA, the published results overlap those obtained with PET with MET or with FET.<a class="elsevierStyleCrossRefs" href="#bib0075">15–18</a> However, the methodology of the studies that used PET 6-[18F]FDOPA in the differential diagnosis of tumor recurrence versus PTC was not uniform, with variability in the interpretation of images (visual, quantitative), the metrics evaluated (SUVmax, SUVmean), their normalization (ratios, reference zones) and, consequently, the cut-off points. This variability makes it difficult to establish global and standardized criteria for the differential diagnosis between recurrence and PTC.The aim of this study was to present our experience with 6-[18F]FDOPA PET/CT using visual and semiquantitative analysis in patients treated for a brain neoplasia (primary or secondary) with suspicion of tumor recurrence versus RNC.Material and methodsPatientsThis was a retrospective study of 62 patients (29 women, 33 men) with a mean age of 57 years (24−79), in whom a total of 70 lesions were evaluated and previously treated with RT or a combination of surgery + RT or RT + chemosurgery. All the lesions evaluated were suspected of clinical and radiological tumor recurrence versus RNC.The inclusion criteria were patients with clinical and radiological suspicion of recurrence of a primary brain tumor (20 patients) or metastatic brain tumor (42 patients), confirmed histologically (2016 World Health Organization [WHO] classification) and treated. The minimum time after completing the treatment was 9 months. All the patients had undergone previous MR studies with endovenous contrast according to the standard protocol of neuro-oncology studies, with doubtful or non-conclusive results prior to performing (6-[18F]FDOPA) PET. Only lesions suspected of tumor progression by MR and with a lesion diameter greater than or equal to 8 mm were evaluated by 6-[18F]FDOPA PET/CT. Smaller lesions found in MR prior to PET or lesions without diagnostic doubts according to radiological criteria were not assessed in the present study.The 6-[18F]FDOPA PET/CT results correlated with the clinical and radiological follow-up during a minimum of 9–12 months and the final decision was made by the Neuro-oncology Tumor Committee. The following criteria were taken into account: clinical (status and clinical evolution), characteristics of RT treatment (dose, fields and time of treatment), and the findings and evolution of the image obtained with MR. Morphological sequences as well as diffusion and perfusion in the MR were evaluated. The growth or appearance of uptake in T1 post-contrast, the presence of a clear lesion identifiable in T2 sequences, the presence of foci of restriction of diffusion and the presence of foci of an increase in cerebral blood volume in the perfusion sequence (visual and with values of the rate with respect to normal white matter greater than 1.75–2) were the criteria used to label patients with tumor recurrence versus RCN. This was correlated with the histopathological confirmation whenever possible.Acquisition of [18F]FDOPA PET/CTThe 6-[18F]FDOPA PET/CT study was performed in a 4-head (GE Healthcare) Discovery ST PET/CT scanner 20 min after endovenous administration of a dose of 185 MBq of 6-[18F]FDOPA. No patient received premedication with carbidopa. The acquisition of the images was static in 3D mode with correction of attenuation by a CT 120–130 KeV acquisition. Only 1 bed of 20 min duration was acquired. The reconstruction of the images was made by OSEM reconstruction (128 × 128) with 2 iterations, 21 subsets and one post-filtrate 4.1 mm FWHM.Analysis of the imagesThe 6-[18F]FDOPA PET/CT images were fused with the previous MR of the patient. The MR sequence, usually T1 post endovenous contrast, which showed the best identification of the lesions leading to the PET study was chosen for the fusion. The fusion of the images was done using the AW Server 3.2 (GE Healthcare) program. The neuroimaging studies were interpreted visually and semi-quantitatively, with both analyses being carried out by one or two nuclear medicine physicians of the neuroimaging service with experience in 6-[18F]FDOPA PET/CT.The grade of intensity of radiopharmaceutical uptake in the problem region (described in the MR) was evaluated in the visual analysis of the PET images using the cortex as reference and the striate contralateral to the side of the lesion, binary code (positive/negative) and the pattern of uptake. Studies considered visually positive were those with uptake greater than or equal to the striate, and negative was considered with uptake less than the cortex while doubtful studies were those with uptake greater than the cortex and less than the striate. In these cases, semiquantitative analysis helped to determine the positivity and negativity of the study. The pattern of uptake suggestive of positivity was focally increased uptake while a diffuse uptake pattern was indicative of negativity. In cases in which the interpretation was doubtful, the images were independently analysed by two experienced neuro-oncologists and consensus was achieved.In the semiquantitative analysis, the maximum standard uptake value (SUVmax) of the lesion was calculated and two ratios were obtained: SUVmax lesion/SUVmax striate (L/S) and SUVmax lesion/ SUVmax cortex (L/C).The pixel of the tumor of maximum value was obtained by manually drawing a region of interest (ROI) over the whole tumor. Manual ROIs were also drawn on the cortex and contralateral striate.Statistical analysisThe statistical analysis was performed using GraphPad Prism 7.00, version 2.0. The Mann–Whitney test was used to compare the differences between tumor recurrence and RNC. Results with p < 0.05 were considered significant.The diagnostic validity of 6-[18F]FDOPA PET/CT was evaluated by calculating the sensitivity (S), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV) of the lesions studied.The diagnostic performance of the 6-[18F]FDOPA PET/CT to discriminate tumor recurrence versus RNC was evaluated by analysis of the receiver operating characteristic (ROC) curve.ResultsPatientsA total of 70 lesions were studied including 21 lesions of 20 patients with primary brain tumors and 49 lesions of 42 patients with brain M1.Of the 42 patients (49 lesions) treated for brain M1, in 21 the primary lesion was a pulmonary neoplasia (18 adenocarcinomas, 2 squamous carcinomas and 1 small-cell lung cancer), 8 haf primary tumors of the breast, 3 of the colon, 3 melanomas, 2 renal, 2 ovarian, 1 neuroendocrine, 1 lacrimal gland and 1 unknown.Twenty patients (21 lesions) were diagnosed with a primary brain tumor according to the 2016 WHO classification; 5 had glioblastomas (GB), 3 oligodendrogliomas GIII, 3 astrocytomas GIII, 2 oligodendrogliomas GII, 1 astrocytoma GII, 1 anaplastic oligoastrocytoma GIII, 3 diffuse midline gliomas (DMLG),1 ependymoma and 1 had a high-grade germinal tumor (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>The mean time from the completion of RT to performing the 6-[18F]FDOPA PET/CT was 64 months (9–120 months).The mean time from the last MR to performing FDOPA was 5 weeks.Histopathological confirmation was obtained in 15 patients (24.2%). In the remaining patients the diagnosis was obtained after clinical-radiological follow-up.In the 42 patients (49 lesions) with brain metastasis, 24 lesions (49%) were attributed to recurrence and the remaining to RNC by clinical-radiological and/or histopathological criteria. In the case of primary brain tumors,<a class="elsevierStyleCrossRef" href="#bib0080">16</a> lesions (76%) were considered in recurrence and the other 5 were RNC (<a class="elsevierStyleCrossRefs" href="#tbl0010">Tables 2 and 3</a>).<elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia>Analysis of the imagesOf the 70 lesions studied, visual analysis identified 40 as positive, 22 as negative and 8 as doubtful. Semiquantitative analysis of the same lesions showed concordance in 100% of the positives and 86% of the negatives (3 false negatives [FN] of the visual analysis). In the 8 doubtful lesions, semiquantitative evaluation helped classify 3 as positive and 5 as negative.In the case of the M1, the global evaluation (visual and semiquantitative) of the FDOPA, which is used in healthcare practice, identified 23 lesions as true positives (TP), 1 FN, 7 false positive (FP) and 18 true negative (TN) and obtained S, Sp, PPV and NPV values of 96%, 72%, 77% and 95%, respectively (<a class="elsevierStyleCrossRefs" href="#fig0005">Figs. 1 and 2</a>).<elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia>In the case of primary brain tumors the global evaluation of FDOPA identified 15 TP, 1 FN, 1 FP and 4 TN obtaining S, Sp, PPV and NPV values of 94%, 80%, 94% and 80%, respectively (<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>).<elsevierMultimedia ident="tbl0020"></elsevierMultimedia>The semiquantitative analysis showed no significant differences between the primary tumors and M1, although the primary tumors presented slightly higher values.On the other hand, there were significant differences (p < 0.05) between recurrence and RNC in both primary tumors and brain metastasis (<a class="elsevierStyleCrossRef" href="#tbl0025">Table 5</a> and <a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>).<elsevierMultimedia ident="tbl0025"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia>The results of the ROC curve showed a better cut-off point to discriminate RNC by RT. In the case of metastasis, the L/C ratio was 1.44 with an S and Sp of 88 and 79%, respectively, and an area under the curve of 0.839 ± 0.059, (confidence interval: 0.7229−0.955; p < 0.0001) while in the case of primary tumors the L/C ratio was 1.57 with an S and Sp of 100% and 93%, respectively and an area under the curve of 0.975 ± 0.030 (confidence interval: 0.914–1.03, p < 0.0017) (<a class="elsevierStyleCrossRef" href="#fig0020">Fig. 4</a>).<elsevierMultimedia ident="fig0020"></elsevierMultimedia>DiscussionAfter completing treatment with RT, 5–25% of brain tumors present RNC and an elevated and very variable percentage will recur, depending on the type of brain tumor.<a class="elsevierStyleCrossRefs" href="#bib0030">6,7</a> The differential diagnosis between recurrence and RNA is key for correct patient management, avoiding unnecessary procedures and treatments as well as the secondary effects derived from these. However, this differentiation continues to be an unsatisfied critical clinical necessity.The main societies and working groups of nuclear medicine, neuro-oncology and oncology (EANM, SNMMI, EANO, RANO, ESMO)<a class="elsevierStyleCrossRefs" href="#bib0045">9–12</a> have joined efforts and have published guidelines on the follow-up of brain tumors, recommending the use of PET with amino acids on suspicion of recurrence versus RNC. Despite the extensive experience using FDOPA, there is no consensus on the evaluation of these studies, sometimes leading to variable results, that cannot be extrapolated, are discrepant or incongruent.This study evaluated the use of 6-[18F]FDOPA PET/CT in primary brain tumors and M1 performing visual + semiquantitative analysis. Tumor recurrence was present in 76% of the primary tumors studied versus 49% of the M1, and the remaining lesions studied were considered RNC.The visual analysis of 6-[18F]FDOPA PET/CT showed no significant differences to those of the semiquantitative analysis in the lesions considered positive. The visual analysis presented more difficulties in the interpretation of lesions with scarce FDOPA uptake, which were visually interpreted as negative, obtaining 3 FN which were correctly identified by the semiquantitative analysis. Among the non-conclusive lesions, 63% were correctly identified in the joint analysis, with 4 being considered as RNC. As described previously by other authors, visual analysis plays a fundamental role in the initial evaluation of 6-[18F]FDOPA PET/CT studies, although it has limitations in regard to its specificity, which may be solved by semiquantitative analysis.<a class="elsevierStyleCrossRef" href="#bib0090">18</a> In our experience, the best diagnostic performance of FDOPA was obtained with joint visual and semiquantitative analysis.The semiquantitative analysis showed minimum (L/C ratio, p = 0.049) or no significant differences (L/S ratio, p = 0.56) in the values of the ratios of recurrence of primary tumors and M1. These values should be evaluated with caution given the variability in both the primary and M1 tumors included in the study. However, it can be affirmed that, in general, the values of quantification are more elevated in the primary tumors than the M1. This greater index of FDOPA uptake by the primary tumors might, among other factors, be related to the greater aggressiveness of these tumors, demonstrated in the sample with a higher percentage of tumor recurrence than the case of M1.<a class="elsevierStyleCrossRefs" href="#bib0090">18,19</a>The use of 6-[18F]FDOPA PET/CT in both the primary tumors and M1 showed a high NPV, with only one FN in each group, obtaining sensitivity results similar to those of other studies.The specificity of FDOPA in the case of primary tumors was in agreement with that of other publications. There was only 1 FP which was an anaplastic oligodendroglioma with a moderately increased FDOPA uptake with an irregular pattern. The ratios obtained were L/C and L/S of 1.46 and 0.86, respectively, with the L/C value being lower than that obtained in the ROC curve (L/C 1.57).The number of FPs was high in the M1 group (7 FP), obtaining a lower specificity than what has been reported in other studies.<a class="elsevierStyleCrossRefs" href="#bib0100">20–22</a>Three of these FP were in studies performed in the first months of the implementation of the FDOPA PET/CT technique in our center. The reports were not conclusive, although they did not exclude the possibility of tumoral activity. Among the remaining 4 FP, 3 were M1 lesions of primary pulmonary tumors and the other corresponded to a M1 of a primary renal tumor.Two of the patients with FP lesions of pulmonary M1 were in systemic progression and were receiving systemic therapy including immune therapy (anti-PD1/PDL1). To date, there is little knowledge of the possible role of systemic immune therapy in these brain lesions and it is not known whether it might influence the uptake of FDOPA.<a class="elsevierStyleCrossRef" href="#bib0115">23</a>Histological confirmation, which would allow understanding the positivity of the FDOPA images, was only obtained in one case of FP. This case was an M1 of a pulmonary adenocarcinoma with increased uptake with a focal patterns and L/C and L/S ratios of 1.9 and 0.7, respectively. In the histopathological study of the resected piece, the presence of necrosis was observed as well as an infiltrate of macrophages and giant multinucleated cells compatible with a granulomatous foreign body reaction (attributable to previous surgery). It is known that macrophages and other inflammatory cells may present increased FDOPA uptake, being a cause of FP in these studies.In the case of primary tumor the L/C ratio had the greatest diagnostic performance with 1.57 with a S and Sp of 100 and 94%, respectively, being values similar to the L/C 1.61 obtained by Zaragori et al. in a sample of 51 patients with suspicion of tumor recurrence in gliomas. However, these authors found a greater diagnostic performance using the L/S ratio with a cut-off point of 1.0.<a class="elsevierStyleCrossRef" href="#bib0120">24</a>In the case of metastasis, the ROC curve showed a better cut-off point in the L/C 1.44 ratio with an S and Sp of 88 and 79%, respectively, which are slightly lower values compared to those of Cicone et al. in 2015, who published a better L/C ratio with 1.59 with a S and Sp of 90 and 92%, respectively.<a class="elsevierStyleCrossRef" href="#bib0105">21</a> In a later study with a greater number of lesions, the same authors improved the previously obtained results with a cut-off point in the L/C ratio of 1.92, with a S of 96% and a Sp of 100%.<a class="elsevierStyleCrossRef" href="#bib0110">22</a> In this study it should be taken into account that in addition to the learning curve itself, successive studies with FDOPA PET were performed every 6 months, evaluating the metabolic behavior of the lesions over time, allowing observation of their evolution, improving the diagnostic accuracy and obtaining more data for better defining the cut-off point. Chen et al. studied 81 patients with different primary brain tumors and obtained the best results using the L/S ratio with a cut-off point of 1.0 with an S and Sp of 96% and 100%, respectively.<a class="elsevierStyleCrossRef" href="#bib0125">25</a>Similar results were obtained by Domenech et al. in a small sample of 12 patients using the L/S ratio with a cut-off point of 1 with a S of 90% and an Sp of 100%.<a class="elsevierStyleCrossRef" href="#bib0130">26</a> It is clear that the greater the value of the ratio, especially using the ratio with striate (the cerebral region with greater physiological FDOPA uptake), the Sp increases, reducing the S. In our sample, for example, in the M1 a L/C ratio of 1.99 would show a Sp greater than 92% with an S of 23%, and an L/S ratio of 1.04 would show a Sp of 100% with a S of 42%. The European guidelines published in 2019 described that there are no histologically validated values for the semi-quantification of FDOPA in the differential diagnosis of recurrence versus RNC. These guidelines recommend that when using FDOPA the region of reference should be the contralateral striate and the SUVmax value of the lesions should be greater than that of the striate, proposing a SUVmax L/S ratio of 2.1, which as mentioned previously, would offer a high Sp but a very limited S. These are some examples of the disparity of the results found in the literature in relation to the values of semi-quantification and diagnostic validity of FDOPA.<a class="elsevierStyleCrossRef" href="#bib0050">10</a> How are we supposed to interpret these results?At present, the semi-quantification of FDOPA cannot be extrapolated to an inter-center level and should be evaluated taking into account the context of the patient (type of tumor, size, treatment, time since the completion of RT) as well as the methodology used for the performance and interpretation of the 6-[18F]FDOPA PET/CT. Despite the numerous publications and the difference of PET with FET which have some recommended cut-off points, at present, none of the societies involved (EANM, SNMMI, EANO, ESMO) have validated a cut-off point using FDOPA in the differential diagnosis between recurrence and RNC in either primary brain tumors or brain metastasis. While awaiting for the unification of criteria and the publication of FDOPA values recommended for this differential diagnosis, each center must standardize its results, which will not always totally overlap with those of other centers. On the other hand, the cut-off points should be adjusted to the lesion to be evaluated and should be analysed together with the semiology of the MR in an attempt to clarify the aspects of MR which cause doubts and may sometimes require precise criteria that provide a greater Sp and, at other times, greater S.In this study we did not compare 6-[18F]FDOPA PET/C with the perfusion of MR, one of the MR sequences with greater performance in this diagnosis. This was not the objective. We understand that both techniques evaluated different processes involved in the oncogenesis of brain tumors and therefore, the results are not always concordant. One techniques does not exclude the other; both techniques play a relevant role in the evaluation of these patients and provide complementary information, with both being necessary. In our opinion and in our health care practice, the best results are obtained from the team work of both specialties and in the joint analysis of both explorations.<a class="elsevierStyleCrossRef" href="#bib0135">27</a>This study is not free of limitations; FDOPA is a substrate of the DOPA-decarboxylase enzyme, abundant in dopaminergic neurons such as those in the striates, and thus, interfere in tumors localized in the proximity of the striates. On the other hand, FDOPA has affinity for the LAT1 and LAT2 overexpressed in brain tumors and overexpression may also be observed in inflammatory processes and thereby limit the Sp of this radiopharmaceutical.<a class="elsevierStyleCrossRefs" href="#bib0070">14,28–30</a>Lastly, this was a retrospective study and the results of FDOPA of these patients could not always be compared with histopathological confirmation, being a usual limitation in this type of patients.Despite the limitations of this study, we consider that the visual and semiquantitative analysis of 6-[18F]FDOPA PET/CT evaluated together with MR is a necessary tool in the differential diagnosis of tumor recurrence versus RNC. Its use in our country is still limited and efforts must be made to implement it in the algorithms of the neuro-oncology committees for the differential diagnosis of recurrence versus RNC. This would allow also performing follow-up with FDOPA and not only isolated study without the possibility of seeing the metabolic evolution of these lesions, thereby contributinge to achieving a more precise metabolic diagnosis.<a class="elsevierStyleCrossRef" href="#bib0110">22</a>Prospective and multicenter studies are necessary to contribute to the standardization of criteria in the interpretation of 6-[18F]FDOPA PET/CT. This would increase the level of evidence of its use in the differential diagnosis of recurrence versus RNC, and contribute to the diagnosis and management of these patients in uncertain situations.Conflict of interestThe authors have no conflicts of interest to declare." "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:3 [ "identificador" => "xres2072282" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Material and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusion" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1767740" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres2072281" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Material y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusión" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1767739" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Material and methods" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Patients" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Acquisition of [F]FDOPA PET/CT" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Analysis of the images" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Statistical analysis" ] ] ] 6 => array:3 [ "identificador" => "sec0035" "titulo" => "Results" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0040" "titulo" => "Patients" ] 1 => array:2 [ "identificador" => "sec0045" "titulo" => "Analysis of the images" ] ] ] 7 => array:2 [ "identificador" => "sec0050" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0055" "titulo" => "Conflict of interest" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2023-05-02" "fechaAceptado" => "2023-08-12" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1767740" "palabras" => array:4 [ 0 => "FDOPA" 1 => "Radionecrosis" 2 => "Tumores cerebrales" 3 => "Estandarización" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1767739" "palabras" => array:4 [ 0 => "FDOPA" 1 => "Radionecrosis" 2 => "Brain tumour" 3 => "Standardization" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "IntroductionAmino acid PET is a tool recommended by the main neuroimaging societies in the differential diagnosis between radionecrosis (RNC) and umour recurrence (TR) in brain tumours, but its use in our country is still limited. The aim of this work is to present our experience with 6-[18F]FDOPA PET/CT (FDOPA) in brain tumours (primary and M1), comparing these results with other published results. Material and methodsRetrospective study of 62 patients with suspected tumour recurrence (TR): 42 brain metastases (M1) and 20 primary, who underwent FDOPA. Images were analysed visually and semi-quantitatively, obtaining SUVmax and SUVmaxlesion/SUVmaxstriatum (L/S) and SUVmaxlesion/SUVmaxcortex (L/C) ratios. The diagnostic validity of PET was analysed and the best performing cut-off points were calculated. PET results were compared with clinical-radiological follow-up and/or histopathology. ResultsTR was identified in 49% of M1 and 76% of brain primaries. The best performing FDOPA interpretation was visual and semi-quantitative, with a sensitivity and specificity in primaries of 94% and 80% and in M1s of 96% and 72% respectively. The cut-off points with the best diagnostic performance were L/C1.44 in M1 and L/C1.55 in primaries. There are discrepant results with other published results. ConclusionFDOPA PET/CT is a useful tool in the differential diagnosis between recurrence and RNC in brain tumours. It is needed a standardization to contribute to homogenise FDOPA results a inter-centre level." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Material and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusion" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "IntroducciónEl PET con aminoácidos es una herramienta recomendada por las principales sociedades de neuroimagen, en el diagnóstico diferencial entre radionecrosis (RNC) y recurrencial tumoral (RT) en tumores cerebrales, sin embargo su uso en nuestro pais aún es limitado. El objetivo de este trabajo es presentar nuestra experiencia con 6-[18F]FDOPA PET/TC (FDOPA) en tumores cerebrales (primarios y M1), comparando estos resultados con otros publicados. Material y métodosEstudio retrospectivo de 62 pacientes con sospecha de recurrencia tumoral (RT): 42 metástasis cerebrales (M1) y 20 primarios, a los que se les realizó una FDOPA. Las imágenes fueron analizadas visual y semicuantitativamente, obteniendo el SUVmax y los ratios SUVmaxlesión/SUVmaxestriado (L/E) y SUVmaxlesión/SUVmaxcortex (L/C). Se analizó la validez diagnóstica del PET y se calcularon los puntos de corte con mayor rendimiento. Los resultados del PET se compararon con la evolución clínico-radiológica y/o con la histopatología. ResultadosSe identificó RT en el 49% de las M1 y en el 76% de los primarios cerebrales. La interpretación de la FDOPA con mejores resultados fue la conjunta; visual y semicuantitativa, con una sensibilidad y especificidad en los primarios del 94 y 80% y en las M1 del 96 y 72% respectivamente. Los puntos de corte con mejor rendimiento diagnóstico fueron L/C1.44 en M1 y L/C1.55 en primarios. Existen resultados discrepantes con otros publicados. ConclusiónLa FDOPA PET/TC es una herramienta útil en el diagnóstico diferencial entre recurrencia y RNC en tumores cerebrales. Es necesario una estandarización que contribuya a homogeneizar los resultados de la FDOPA a nivel intercentro." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Material y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusión" ] ] ] ] "multimedia" => array:9 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1082 "Ancho" => 1674 "Tamanyo" => 323732 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Images of a patient with a history of stage IV adenocarcinoma of the colon with a single brain metastasis, which was treated with surgery and radiotherapy. Ten months after the end of radiotherapy, due to gait instability and headache, a brain MRI was performed with doubts of tumor recurrence versus radionecrosis. FDOPA PET showed a positive result for tumor recurrence which was later confirmed in the histopathological study of the surgical specimen. A) 6-[18F]FDOPA PET images showing increased FDOPA uptake of moderate intensity and irregular character. A focal area of higher intensity is observed in the medial region intensity in the medial region. (B) Postcontrast T1-weighted MRI sequences revealing contrast uptake around the margins of the irradiated surgical cavity, with uncertain significance. C) MR perfusion (PWI) sequences indicating a discrete increase in perfusion. D) PET-MRI fusion images showing a marked increase in FDOPA, especially D) PET-MRI fusion images showing a marked increase in FDOPA, especially at the medial margin of the cavity, with an L/E ratio of 1.09 and L/C of 2.25. E) Histological section of the resected surgical specimen,where abundant cellularity compatible with colon adenocarcinoma is observed." ] ] 1 => array:8 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1070 "Ancho" => 1674 "Tamanyo" => 183546 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Images of a patient with history of a previosusly treated single brain mestastasis from clear cell carcinoma. One year after radiotherapy, the patien showed focal seizure secondary to this lesion. A brain MRI was performed to assess the possibility of tumor recurrence versus RNC, which was inconclusive. The result of the FDOPA PET was negative ( RNC),and due to the persistence of the seizures the patient received surgical treatment, adn RNC was confirmed in the resected specimen. A) 6-[18F]FDOPA PET images showing a very slight and diffuse increase FDOPA around the cavity. B) Post-contrastost T1-weighted MRI sequences showing contrast enhancement around the margins of the irradiated surgical cavity of doubtful significance. C) MR perfusion (PWI) sequences showing no increased perfusion. D) PET-MRI fusion images that do not show significant increase of FDOPA at the margins of the surgical cavity, with L/E ratios 0.56 and L/C 1.2. E) Histologic sections of the resected surgical specimen,showing changes secondary to radionecrosis." ] ] 2 => array:8 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1925 "Ancho" => 2175 "Tamanyo" => 148836 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0015" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Semiquantitative analysis showed significant differences between tumor recurrence and nonrecurrence (RNC) in both primary brain tumors and metastases. The scatter-plotgure shows in the top row the SUVmax ratios for primary brain tumors, SUVmax lesion/SUVmax cortex ratio (SUVmaxL/C) and SUVmax lesion/SUVmax striatum ratio (SUVmax L/E). The bottom row shows these ratios in the case of metastases. Significant differences are observed in both L/C and L/E ratios in both metastases and primary brain tumors between recurrence and RNC." ] ] 3 => array:8 [ "identificador" => "fig0020" "etiqueta" => "Fig. 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 568 "Ancho" => 1675 "Tamanyo" => 75492 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0020" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "ROC analysis showed higher S and Sp in the analysis of primary brain tumors than in metastases. The best cut-off point in primary tumors was obtained at the L/C ratio 1.57 with an S and Sp of 100 and 93%, respectively. The best cut-off point in metastases was obtained at the L/C ratio 1.44 with an S and Sp of 88 and 79%, respectively." ] ] 4 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0025" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "DMLG, diffuse midline glioma." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\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">n = 62 \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"> \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 " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Age (years) \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">57 (24−79) \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">Women (%) \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">29 (46) \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">Brain metastasis (%) \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">42 (68) \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">Primary neoplasia lung \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">21 \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">Primary neoplasia breast \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 \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">Primary neoplasia colon \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 \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">Primary neoplasia melanoma \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 \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">Primary neoplasia renal \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 \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">Primary neoplasia ovary \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 \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">Primary neuroendocrine \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 \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">Primary lacrimal gland \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 \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">Primary unknown \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 \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">Primary tumor (%) \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">20 (32) \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">Glioblastoma \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 \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">Oligodendrogliomas GIII \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 \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">Astrocitomas GIII \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 \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">Oligodendrogliomas GII \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 \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">Astrocytoma GII \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 \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">Anaplastic oligoastrocytoma \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 \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">DMLG \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 \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">Ependymoma \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 \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">High grade germinal tumor \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 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3431671.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Characteristics of the patients." ] ] 5 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0030" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Brain metastasis (42 patients)</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"> \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">Recurrence \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">Radionecrosis \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">Total \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 " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PET + \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">23 \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">7 \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 \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">PET − \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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">18 \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">19 \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"> \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">24 \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 \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">49 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3431670.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Results obtained in a total of 70 lesions studied. There were 21 lesions in 20 patients, with primary brain tumors and 49 lesions in 42 patients with brain M1. Table 2 shows the results in the brain metastases." ] ] 6 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0035" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Primary brain tumors (20 patients)</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"> \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">Recurrence \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">Radionecrosis \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">Total \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 " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PET + \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 \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 \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 \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">PET − \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 \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 \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 \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"> \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 \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 \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">21 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3431669.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Shows the results in the primary brain tumors." ] ] 7 => array:8 [ "identificador" => "tbl0020" "etiqueta" => "Table 4" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0040" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "FN: false negative, FP: false positive, S: sensitivity, Sp: specificity, PPV: positive predictive value, NPV: negative predictive value." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\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"> \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">n \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">lesions \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">FN \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">FP \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">S \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">Sp \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">PPV \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">NPV \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 " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Primary tumors \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">20 \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">21 \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 \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 \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">94% \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">80% \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">94% \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">80% \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">Metastasis \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">42 \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">49 \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 \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">7 \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">96% \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">72% \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">77% \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">95% \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3431672.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Results of the diagnostic validity of joint visual and semi-quantitative analysis of PET/TC 6-[18F]FDOPA in patients with primary tumors and with brain metastasis and suspicion of tumor recurrence versus radionecrosis." ] ] 8 => array:8 [ "identificador" => "tbl0025" "etiqueta" => "Table 5" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0045" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "L/C: lesion with cortex; L/S: lesion with striate." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\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"> \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 " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Recurrence</th><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">Radionecrosis</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"> \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">L/C ratio \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">L/S ratio \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">L/C ratio \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">L/S ratio \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 " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Primary tumors \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 \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">1.03 \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">1.4 \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">0.6 \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">Metastasis \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">1.7 \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">0.91 \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">1.31 \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">0.79 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3431673.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Medians of the L/C and L/S ratios obtained in the semiquantitative analysis of PET/TC 6-[18F]FDOPA of tumor recurrence and radionecrosis in patients with primary brain tumors and brain metastasis." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:30 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Advanced MRI and PET imaging for assessment of treatment response in patients with gliomas" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "F.G. 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Original Article

Visual and semi-quantitative analysis of 6-[18F]FDOPA PET/CT in patients with brain tumors and suspected tumor recurrence versus radionecrosis

Análisis visual y semicuantitativo del 6-[18F]FDOPA PET/TC en pacientes con tumores cerebrales ante la sospecha de recurrencia tumoral versus radionecrosis

M. Suárez-Piñeraa,b,

Corresponding author

marina.suarez.idi@gencat.cat

Corresponding author.

, L. Rodriguez-Bela, M. Alemanyb,c, A. Pons-Escodab,d, M. Pudisa, A. Coellob,e, G. Reynesf, N. Vidalb,g, M. Cortes-Romeraa, M. Maciab,h

a Unidad PET IDI, Servicio de Medicina Nuclear, Hospital Universitari de Bellvitge, L’Hospitalet de Llobregat, Barcelona, Spain

b Neuro-Oncology Functional Unit, Institut d'Investigació Biomèdica de Bellvitge-IDIBELL, L’Hospitalet de Llobregat, Barcelona, Spain

c Servicio de Neurología, Hospital Universitari de Bellvitge-ICO L'Hospitalet (IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain

d Servicio de Radiología, Sección de Neuroradiología, Hospital Universitari de Bellvitge, L’Hospitalet de Llobregat, Barcelona, Spain

e Servicio de Neurocirugía, Hospital Universitari de Bellvitge, L’Hospitalet de Llobregat, Barcelona, Spain

f Servicio de Física Médica, Hospital Universitari de Bellvitge-ICO L'Hospitalet (IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain

g Unidad de Neurooncología, Servicio de Anatomía Patológica, Hospital Universitari de Bellvitge, L’Hospitalet de Llobregat, Barcelona, Spain

h Servicio de Oncología Radioterápica, Institut Català d'Oncologia (ICO) L'Hospitalet (IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain

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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">The evaluation of response to treatment of brain tumors and&#44; more specifically&#44; the differentiation between tumor recurrence and post-treatment changes &#40;PTC&#41; in patients treated with radiotherapy &#40;RT&#41; continues to be a clinical and neuroimaging challenge&#46; This differentiation has direct implications on the prognosis and management of these patients&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Neuroimaging techniques play a fundamental role in the study of central nervous system &#40;CNS&#41; neoplasias&#46; Magnetic resonance &#40;MR&#41; is the technique of choice for both diagnosis and therapeutic planning as well as post-treatment follow-up&#46; Nonetheless&#44; the differentiation between tumor recurrence and post-radiotherapy changes is a critical unresolved clinical necessity because the information provided by MR may be insufficient and non-conclusive&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;2</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">After treatment with RT&#44; the brain parenchyma in both intra- and extra-parenchymatous and even head and neck tumors&#44; undergoes inflammatory phenomena secondary to treatments and these are called PTC&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#8211;5</span></a> The physiopathology of these phenomena evolves over a long period of time and they are classified into 3 types according to their evolutive phase&#58; 1&#46; acute phase&#58; these appear within 2&#8239;h to 2 weeks after the initiation of RT&#44; being secondary to a disruption of the hematoencephalic barrier &#40;HEB&#41; and causing an increase in intracranial pressure&#59; 2&#46; Subacute phase&#58; from the second week up to 6 months post-RT&#46; These are due to transitory damage to the myelin&#44; triggered by the disruption of the HEB and&#47;or dysfunction of the oligodendrocytes&#46; This phase may present clinical and&#47;or radiological repercussion showing worsening of the radiological findings &#40;pseudo-progression&#41;&#46; It should be taken into account that the clinical and radiological changes are not always identified together and&#44; thus&#44; this subacute phase is not always synonymous of pseudo-progression&#44; and 3&#46; Delayed phase&#58; typically from 6 months up to years after RT&#46; These are changes secondary to damage of the vascular endothelium&#44; demyelination and necrosis of the white matter accompanied by loss of oligodendrocytes and neuronal precursors&#44; gliosis and neuroinflammation&#46; This phase may follow with clinical semiology&#44; radioinduced brain tumors and radiological alterations known as radionecrosis &#40;RNC&#41;&#46; As in the previous phase&#44; these alterations do not always lead to RNC or vice-versa&#46;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6&#44;7</span></a> The incidence of RNC varies&#44; ranging between 5&#8211;7&#37; in high-grade primary tumors and between 14&#8211;25&#37; in patients with brain M1 and specifically treated with stereotaxic radiosurgery&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> Numerous variables can influence this incidence&#44; such as the type of volume of tissue irradiated&#44; the dose&#44; dose fractionation&#44; type of previous RT treatments or the use of a concomitant systemic treatment as well as the individual predisposition of each patient&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> In addition&#44; this incidence is imprecise due to the usual absence of histopathological confirmation and the lack of strict diagnostic criteria&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">The clinical and radiological &#40;MR&#41; semiology of RNC is usually undistinguishable from the presence of tumoral viability and&#44; in addition&#44; it assumes that both phenomena frequently coexist&#46; In 2016&#44; the Response Assessment in Neuro-Oncology &#40;RANO&#41; multidisciplinary working group that evaluates the criteria of response to treatment in brain tumors and the European Association of Neuro-oncology &#40;EANO&#41; published the first recommendations that include the use of positron emission tomography &#40;PET&#41; with amino acids as a useful tool for the evaluation of cerebral gliomas in clinical practice&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> In 2018 and 2021 this recommendation was reaffirmed and in the last guidelines published by the European Society of Medical Oncology &#40;ESMO&#41; advanced MR sequences including spectroscopy&#44; perfusion&#44; diffusion and PET with amino acids were recommended with a scientific level of evidence IV for the differential diagnosis of PTC and tumor recurrence in patients with brain tumors&#46;<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10&#8211;12</span></a> PET with amino acids has been proposed as a useful tool together with MR in the evaluation of the brain parenchyma after RT&#44; showing cost-efficient results&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">The physiopathological basis of PET with amino acids is the overexpression of long chain amino acid transporters &#40;LAT&#41; in the membrane of the tumoral cells unlike normal brain tissue as well as their independence from the integrity of the HEB&#46; The first PET radiopharmaceutical with amino acids used in neuro-oncology was methionine labeled with <span class="elsevierStyleSup">11</span>C &#40;MET&#41;&#46; Due to limitations secondary to the half-life of <span class="elsevierStyleSup">11</span>C&#44; other radiopharmaceuticals with amino acids labeled with <span class="elsevierStyleSup">18</span>F&#44; L-&#91;2-<span class="elsevierStyleSup">18</span>F&#93; fluorotyrosine &#40;FET&#41; and 3&#44;4-Dihydroxy-6-&#91;<span class="elsevierStyleSup">18</span>F&#93;fluoro-<span class="elsevierStyleSmallCaps">l</span>-phenylalanine&#59; fluorodopa &#40;6-&#91;<span class="elsevierStyleSup">18</span>F&#93;FDOPA&#41;<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">14&#44;15</span></a> were developed&#46; Despite the lesser experience with 6-&#91;<span class="elsevierStyleSup">18</span>F&#93;FDOPA&#44; the published results overlap those obtained with PET with MET or with FET&#46;<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">15&#8211;18</span></a> However&#44; the methodology of the studies that used PET 6-&#91;<span class="elsevierStyleSup">18</span>F&#93;FDOPA in the differential diagnosis of tumor recurrence versus PTC was not uniform&#44; with variability in the interpretation of images &#40;visual&#44; quantitative&#41;&#44; the metrics evaluated &#40;SUV<span class="elsevierStyleInf">max</span>&#44; SUV<span class="elsevierStyleInf">mean</span>&#41;&#44; their normalization &#40;ratios&#44; reference zones&#41; and&#44; consequently&#44; the cut-off points&#46; This variability makes it difficult to establish global and standardized criteria for the differential diagnosis between recurrence and PTC&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">The aim of this study was to present our experience with 6-&#91;<span class="elsevierStyleSup">18</span>F&#93;FDOPA PET&#47;CT using visual and semiquantitative analysis in patients treated for a brain neoplasia &#40;primary or secondary&#41; with suspicion of tumor recurrence versus RNC&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Material and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Patients</span><p id="par0035" class="elsevierStylePara elsevierViewall">This was a retrospective study of 62 patients &#40;29 women&#44; 33 men&#41; with a mean age of 57 years &#40;24&#8722;79&#41;&#44; in whom a total of 70 lesions were evaluated and previously treated with RT or a combination of surgery&#8239;&#43;&#8239;RT or RT&#8239;&#43;&#8239;chemosurgery&#46; All the lesions evaluated were suspected of clinical and radiological tumor recurrence versus RNC&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">The inclusion criteria were patients with clinical and radiological suspicion of recurrence of a primary brain tumor &#40;20 patients&#41; or metastatic brain tumor &#40;42 patients&#41;&#44; confirmed histologically &#40;2016 World Health Organization &#91;WHO&#93; classification&#41; and treated&#46; The minimum time after completing the treatment was 9 months&#46; All the patients had undergone previous MR studies with endovenous contrast according to the standard protocol of neuro-oncology studies&#44; with doubtful or non-conclusive results prior to performing &#40;6-&#91;<span class="elsevierStyleSup">18</span>F&#93;FDOPA&#41; PET&#46; Only lesions suspected of tumor progression by MR and with a lesion diameter greater than or equal to 8&#8239;mm were evaluated by 6-&#91;<span class="elsevierStyleSup">18</span>F&#93;FDOPA PET&#47;CT&#46; Smaller lesions found in MR prior to PET or lesions without diagnostic doubts according to radiological criteria were not assessed in the present study&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">The 6-&#91;<span class="elsevierStyleSup">18</span>F&#93;FDOPA PET&#47;CT results correlated with the clinical and radiological follow-up during a minimum of 9&#8211;12 months and the final decision was made by the Neuro-oncology Tumor Committee&#46; The following criteria were taken into account&#58; clinical &#40;status and clinical evolution&#41;&#44; characteristics of RT treatment &#40;dose&#44; fields and time of treatment&#41;&#44; and the findings and evolution of the image obtained with MR&#46; Morphological sequences as well as diffusion and perfusion in the MR were evaluated&#46; The growth or appearance of uptake in T1 post-contrast&#44; the presence of a clear lesion identifiable in T2 sequences&#44; the presence of foci of restriction of diffusion and the presence of foci of an increase in cerebral blood volume in the perfusion sequence &#40;visual and with values of the rate with respect to normal white matter greater than 1&#46;75&#8211;2&#41; were the criteria used to label patients with tumor recurrence versus RCN&#46; This was correlated with the histopathological confirmation whenever possible&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Acquisition of &#91;<span class="elsevierStyleSup">18</span>F&#93;FDOPA PET&#47;CT</span><p id="par0050" class="elsevierStylePara elsevierViewall">The 6-&#91;<span class="elsevierStyleSup">18</span>F&#93;FDOPA PET&#47;CT study was performed in a 4-head &#40;GE Healthcare&#41; Discovery ST PET&#47;CT scanner 20&#8239;min after endovenous administration of a dose of 185&#8239;MBq of 6-&#91;<span class="elsevierStyleSup">18</span>F&#93;FDOPA&#46; No patient received premedication with carbidopa&#46; The acquisition of the images was static in 3D mode with correction of attenuation by a CT 120&#8211;130&#8239;KeV acquisition&#46; Only 1 bed of 20&#8239;min duration was acquired&#46; The reconstruction of the images was made by OSEM reconstruction &#40;128&#8239;&#215;&#8239;128&#41; with 2 iterations&#44; 21 subsets and one post-filtrate 4&#46;1&#8239;mm FWHM&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Analysis of the images</span><p id="par0055" class="elsevierStylePara elsevierViewall">The 6-&#91;<span class="elsevierStyleSup">18</span>F&#93;FDOPA PET&#47;CT images were fused with the previous MR of the patient&#46; The MR sequence&#44; usually T1 post endovenous contrast&#44; which showed the best identification of the lesions leading to the PET study was chosen for the fusion&#46; The fusion of the images was done using the AW Server 3&#46;2 &#40;GE Healthcare&#41; program&#46; The neuroimaging studies were interpreted visually and semi-quantitatively&#44; with both analyses being carried out by one or two nuclear medicine physicians of the neuroimaging service with experience in 6-&#91;<span class="elsevierStyleSup">18</span>F&#93;FDOPA PET&#47;CT&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">The grade of intensity of radiopharmaceutical uptake in the problem region &#40;described in the MR&#41; was evaluated in the visual analysis of the PET images using the cortex as reference and the striate contralateral to the side of the lesion&#44; binary code &#40;positive&#47;negative&#41; and the pattern of uptake&#46; Studies considered visually positive were those with uptake greater than or equal to the striate&#44; and negative was considered with uptake less than the cortex while doubtful studies were those with uptake greater than the cortex and less than the striate&#46; In these cases&#44; semiquantitative analysis helped to determine the positivity and negativity of the study&#46; The pattern of uptake suggestive of positivity was focally increased uptake while a diffuse uptake pattern was indicative of negativity&#46; In cases in which the interpretation was doubtful&#44; the images were independently analysed by two experienced neuro-oncologists and consensus was achieved&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">In the semiquantitative analysis&#44; the maximum standard uptake value &#40;SUV<span class="elsevierStyleInf">max</span>&#41; of the lesion was calculated and two ratios were obtained&#58; SUV<span class="elsevierStyleInf">max</span> lesion&#47;SUV<span class="elsevierStyleInf">max</span> striate &#40;L&#47;S&#41; and SUV<span class="elsevierStyleInf">max</span> lesion&#47; SUV<span class="elsevierStyleInf">max</span> cortex &#40;L&#47;C&#41;&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">The pixel of the tumor of maximum value was obtained by manually drawing a region of interest &#40;ROI&#41; over the whole tumor&#46; Manual ROIs were also drawn on the cortex and contralateral striate&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Statistical analysis</span><p id="par0075" class="elsevierStylePara elsevierViewall">The statistical analysis was performed using GraphPad Prism 7&#46;00&#44; version 2&#46;0&#46; The Mann&#8211;Whitney test was used to compare the differences between tumor recurrence and RNC&#46; Results with p&#8239;&#60;&#8239;0&#46;05 were considered significant&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">The diagnostic validity of 6-&#91;<span class="elsevierStyleSup">18</span>F&#93;FDOPA PET&#47;CT was evaluated by calculating the sensitivity &#40;S&#41;&#44; specificity &#40;Sp&#41;&#44; positive predictive value &#40;PPV&#41; and negative predictive value &#40;NPV&#41; of the lesions studied&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">The diagnostic performance of the 6-&#91;<span class="elsevierStyleSup">18</span>F&#93;FDOPA PET&#47;CT to discriminate tumor recurrence versus RNC was evaluated by analysis of the receiver operating characteristic &#40;ROC&#41; curve&#46;</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Results</span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Patients</span><p id="par0090" class="elsevierStylePara elsevierViewall">A total of 70 lesions were studied including 21 lesions of 20 patients with primary brain tumors and 49 lesions of 42 patients with brain M1&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Of the 42 patients &#40;49 lesions&#41; treated for brain M1&#44; in 21 the primary lesion was a pulmonary neoplasia &#40;18 adenocarcinomas&#44; 2 squamous carcinomas and 1 small-cell lung cancer&#41;&#44; 8 haf primary tumors of the breast&#44; 3 of the colon&#44; 3 melanomas&#44; 2 renal&#44; 2 ovarian&#44; 1 neuroendocrine&#44; 1 lacrimal gland and 1 unknown&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Twenty patients &#40;21 lesions&#41; were diagnosed with a primary brain tumor according to the 2016 WHO classification&#59; 5 had glioblastomas &#40;GB&#41;&#44; 3 oligodendrogliomas GIII&#44; 3 astrocytomas GIII&#44; 2 oligodendrogliomas GII&#44; 1 astrocytoma GII&#44; 1 anaplastic oligoastrocytoma GIII&#44; 3 diffuse midline gliomas &#40;DMLG&#41;&#44;1 ependymoma and 1 had a high-grade germinal tumor &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0105" class="elsevierStylePara elsevierViewall">The mean time from the completion of RT to performing the 6-&#91;<span class="elsevierStyleSup">18</span>F&#93;FDOPA PET&#47;CT was 64 months &#40;9&#8211;120 months&#41;&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">The mean time from the last MR to performing FDOPA was 5 weeks&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Histopathological confirmation was obtained in 15 patients &#40;24&#46;2&#37;&#41;&#46; In the remaining patients the diagnosis was obtained after clinical-radiological follow-up&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">In the 42 patients &#40;49 lesions&#41; with brain metastasis&#44; 24 lesions &#40;49&#37;&#41; were attributed to recurrence and the remaining to RNC by clinical-radiological and&#47;or histopathological criteria&#46; In the case of primary brain tumors&#44;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> lesions &#40;76&#37;&#41; were considered in recurrence and the other 5 were RNC &#40;<a class="elsevierStyleCrossRefs" href="#tbl0010">Tables 2 and 3</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Analysis of the images</span><p id="par0125" class="elsevierStylePara elsevierViewall">Of the 70 lesions studied&#44; visual analysis identified 40 as positive&#44; 22 as negative and 8 as doubtful&#46; Semiquantitative analysis of the same lesions showed concordance in 100&#37; of the positives and 86&#37; of the negatives &#40;3 false negatives &#91;FN&#93; of the visual analysis&#41;&#46; In the 8 doubtful lesions&#44; semiquantitative evaluation helped classify 3 as positive and 5 as negative&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">In the case of the M1&#44; the global evaluation &#40;visual and semiquantitative&#41; of the FDOPA&#44; which is used in healthcare practice&#44; identified 23 lesions as true positives &#40;TP&#41;&#44; 1&#8239;FN&#44; 7 false positive &#40;FP&#41; and 18 true negative &#40;TN&#41; and obtained S&#44; Sp&#44; PPV and NPV values of 96&#37;&#44; 72&#37;&#44; 77&#37; and 95&#37;&#44; respectively &#40;<a class="elsevierStyleCrossRefs" href="#fig0005">Figs&#46; 1 and 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0135" class="elsevierStylePara elsevierViewall">In the case of primary brain tumors the global evaluation of FDOPA identified 15&#8239;TP&#44; 1&#8239;FN&#44; 1&#8239;FP and 4&#8239;TN obtaining S&#44; Sp&#44; PPV and NPV values of 94&#37;&#44; 80&#37;&#44; 94&#37; and 80&#37;&#44; respectively &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0140" class="elsevierStylePara elsevierViewall">The semiquantitative analysis showed no significant differences between the primary tumors and M1&#44; although the primary tumors presented slightly higher values&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">On the other hand&#44; there were significant differences &#40;p&#8239;&#60;&#8239;0&#46;05&#41; between recurrence and RNC in both primary tumors and brain metastasis &#40;<a class="elsevierStyleCrossRef" href="#tbl0025">Table 5</a> and <a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0025"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0150" class="elsevierStylePara elsevierViewall">The results of the ROC curve showed a better cut-off point to discriminate RNC by RT&#46; In the case of metastasis&#44; the L&#47;C ratio was 1&#46;44 with an S and Sp of 88 and 79&#37;&#44; respectively&#44; and an area under the curve of 0&#46;839&#8239;&#177;&#8239;0&#46;059&#44; &#40;confidence interval&#58; 0&#46;7229&#8722;0&#46;955&#59; p&#8239;&#60;&#8239;0&#46;0001&#41; while in the case of primary tumors the L&#47;C ratio was 1&#46;57 with an S and Sp of 100&#37; and 93&#37;&#44; respectively and an area under the curve of 0&#46;975&#8239;&#177;&#8239;0&#46;030 &#40;confidence interval&#58; 0&#46;914&#8211;1&#46;03&#44; p&#8239;&#60;&#8239;0&#46;0017&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>&#41;&#46;</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia></span></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Discussion</span><p id="par0155" class="elsevierStylePara elsevierViewall">After completing treatment with RT&#44; 5&#8211;25&#37; of brain tumors present RNC and an elevated and very variable percentage will recur&#44; depending on the type of brain tumor&#46;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6&#44;7</span></a> The differential diagnosis between recurrence and RNA is key for correct patient management&#44; avoiding unnecessary procedures and treatments as well as the secondary effects derived from these&#46; However&#44; this differentiation continues to be an unsatisfied critical clinical necessity&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">The main societies and working groups of nuclear medicine&#44; neuro-oncology and oncology &#40;EANM&#44; SNMMI&#44; EANO&#44; RANO&#44; ESMO&#41;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9&#8211;12</span></a> have joined efforts and have published guidelines on the follow-up of brain tumors&#44; recommending the use of PET with amino acids on suspicion of recurrence versus RNC&#46; Despite the extensive experience using FDOPA&#44; there is no consensus on the evaluation of these studies&#44; sometimes leading to variable results&#44; that cannot be extrapolated&#44; are discrepant or incongruent&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">This study evaluated the use of 6-&#91;<span class="elsevierStyleSup">18</span>F&#93;FDOPA PET&#47;CT in primary brain tumors and M1 performing visual&#8239;&#43;&#8239;semiquantitative analysis&#46; Tumor recurrence was present in 76&#37; of the primary tumors studied versus 49&#37; of the M1&#44; and the remaining lesions studied were considered RNC&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">The visual analysis of 6-&#91;<span class="elsevierStyleSup">18</span>F&#93;FDOPA PET&#47;CT showed no significant differences to those of the semiquantitative analysis in the lesions considered positive&#46; The visual analysis presented more difficulties in the interpretation of lesions with scarce FDOPA uptake&#44; which were visually interpreted as negative&#44; obtaining 3&#8239;FN which were correctly identified by the semiquantitative analysis&#46; Among the non-conclusive lesions&#44; 63&#37; were correctly identified in the joint analysis&#44; with 4 being considered as RNC&#46; As described previously by other authors&#44; visual analysis plays a fundamental role in the initial evaluation of 6-&#91;<span class="elsevierStyleSup">18</span>F&#93;FDOPA PET&#47;CT studies&#44; although it has limitations in regard to its specificity&#44; which may be solved by semiquantitative analysis&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> In our experience&#44; the best diagnostic performance of FDOPA was obtained with joint visual and semiquantitative analysis&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">The semiquantitative analysis showed minimum &#40;L&#47;C ratio&#44; p&#8239;&#61;&#8239;0&#46;049&#41; or no significant differences &#40;L&#47;S ratio&#44; p&#8239;&#61;&#8239;0&#46;56&#41; in the values of the ratios of recurrence of primary tumors and M1&#46; These values should be evaluated with caution given the variability in both the primary and M1 tumors included in the study&#46; However&#44; it can be affirmed that&#44; in general&#44; the values of quantification are more elevated in the primary tumors than the M1&#46; This greater index of FDOPA uptake by the primary tumors might&#44; among other factors&#44; be related to the greater aggressiveness of these tumors&#44; demonstrated in the sample with a higher percentage of tumor recurrence than the case of M1&#46;<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">18&#44;19</span></a></p><p id="par0180" class="elsevierStylePara elsevierViewall">The use of 6-&#91;<span class="elsevierStyleSup">18</span>F&#93;FDOPA PET&#47;CT in both the primary tumors and M1 showed a high NPV&#44; with only one FN in each group&#44; obtaining sensitivity results similar to those of other studies&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall">The specificity of FDOPA in the case of primary tumors was in agreement with that of other publications&#46; There was only 1&#8239;FP which was an anaplastic oligodendroglioma with a moderately increased FDOPA uptake with an irregular pattern&#46; The ratios obtained were L&#47;C and L&#47;S of 1&#46;46 and 0&#46;86&#44; respectively&#44; with the L&#47;C value being lower than that obtained in the ROC curve &#40;L&#47;C 1&#46;57&#41;&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">The number of FPs was high in the M1 group &#40;7&#8239;FP&#41;&#44; obtaining a lower specificity than what has been reported in other studies&#46;<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">20&#8211;22</span></a></p><p id="par0195" class="elsevierStylePara elsevierViewall">Three of these FP were in studies performed in the first months of the implementation of the FDOPA PET&#47;CT technique in our center&#46; The reports were not conclusive&#44; although they did not exclude the possibility of tumoral activity&#46; Among the remaining 4&#8239;FP&#44; 3 were M1 lesions of primary pulmonary tumors and the other corresponded to a M1 of a primary renal tumor&#46;</p><p id="par0200" class="elsevierStylePara elsevierViewall">Two of the patients with FP lesions of pulmonary M1 were in systemic progression and were receiving systemic therapy including immune therapy &#40;anti-PD1&#47;PDL1&#41;&#46; To date&#44; there is little knowledge of the possible role of systemic immune therapy in these brain lesions and it is not known whether it might influence the uptake of FDOPA&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a></p><p id="par0205" class="elsevierStylePara elsevierViewall">Histological confirmation&#44; which would allow understanding the positivity of the FDOPA images&#44; was only obtained in one case of FP&#46; This case was an M1 of a pulmonary adenocarcinoma with increased uptake with a focal patterns and L&#47;C and L&#47;S ratios of 1&#46;9 and 0&#46;7&#44; respectively&#46; In the histopathological study of the resected piece&#44; the presence of necrosis was observed as well as an infiltrate of macrophages and giant multinucleated cells compatible with a granulomatous foreign body reaction &#40;attributable to previous surgery&#41;&#46; It is known that macrophages and other inflammatory cells may present increased FDOPA uptake&#44; being a cause of FP in these studies&#46;</p><p id="par0210" class="elsevierStylePara elsevierViewall">In the case of primary tumor the L&#47;C ratio had the greatest diagnostic performance with 1&#46;57 with a S and Sp of 100 and 94&#37;&#44; respectively&#44; being values similar to the L&#47;C 1&#46;61 obtained by Zaragori et al&#46; in a sample of 51 patients with suspicion of tumor recurrence in gliomas&#46; However&#44; these authors found a greater diagnostic performance using the L&#47;S ratio with a cut-off point of 1&#46;0&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a></p><p id="par0215" class="elsevierStylePara elsevierViewall">In the case of metastasis&#44; the ROC curve showed a better cut-off point in the L&#47;C 1&#46;44 ratio with an S and Sp of 88 and 79&#37;&#44; respectively&#44; which are slightly lower values compared to those of Cicone et al&#46; in 2015&#44; who published a better L&#47;C ratio with 1&#46;59 with a S and Sp of 90 and 92&#37;&#44; respectively&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> In a later study with a greater number of lesions&#44; the same authors improved the previously obtained results with a cut-off point in the L&#47;C ratio of 1&#46;92&#44; with a S of 96&#37; and a Sp of 100&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> In this study it should be taken into account that in addition to the learning curve itself&#44; successive studies with FDOPA PET were performed every 6 months&#44; evaluating the metabolic behavior of the lesions over time&#44; allowing observation of their evolution&#44; improving the diagnostic accuracy and obtaining more data for better defining the cut-off point&#46; Chen et al&#46; studied 81 patients with different primary brain tumors and obtained the best results using the L&#47;S ratio with a cut-off point of 1&#46;0 with an S and Sp of 96&#37; and 100&#37;&#44; respectively&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a></p><p id="par0220" class="elsevierStylePara elsevierViewall">Similar results were obtained by Domenech et al&#46; in a small sample of 12 patients using the L&#47;S ratio with a cut-off point of 1 with a S of 90&#37; and an Sp of 100&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> It is clear that the greater the value of the ratio&#44; especially using the ratio with striate &#40;the cerebral region with greater physiological FDOPA uptake&#41;&#44; the Sp increases&#44; reducing the S&#46; In our sample&#44; for example&#44; in the M1 a L&#47;C ratio of 1&#46;99 would show a Sp greater than 92&#37; with an S of 23&#37;&#44; and an L&#47;S ratio of 1&#46;04 would show a Sp of 100&#37; with a S of 42&#37;&#46; The European guidelines published in 2019 described that there are no histologically validated values for the semi-quantification of FDOPA in the differential diagnosis of recurrence versus RNC&#46; These guidelines recommend that when using FDOPA the region of reference should be the contralateral striate and the SUV<span class="elsevierStyleInf">max</span> value of the lesions should be greater than that of the striate&#44; proposing a SUV<span class="elsevierStyleInf">max</span> L&#47;S ratio of 2&#46;1&#44; which as mentioned previously&#44; would offer a high Sp but a very limited S&#46; These are some examples of the disparity of the results found in the literature in relation to the values of semi-quantification and diagnostic validity of FDOPA&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> How are we supposed to interpret these results&#63;</p><p id="par0225" class="elsevierStylePara elsevierViewall">At present&#44; the semi-quantification of FDOPA cannot be extrapolated to an inter-center level and should be evaluated taking into account the context of the patient &#40;type of tumor&#44; size&#44; treatment&#44; time since the completion of RT&#41; as well as the methodology used for the performance and interpretation of the 6-&#91;<span class="elsevierStyleSup">18</span>F&#93;FDOPA PET&#47;CT&#46; Despite the numerous publications and the difference of PET with FET which have some recommended cut-off points&#44; at present&#44; none of the societies involved &#40;EANM&#44; SNMMI&#44; EANO&#44; ESMO&#41; have validated a cut-off point using FDOPA in the differential diagnosis between recurrence and RNC in either primary brain tumors or brain metastasis&#46; While awaiting for the unification of criteria and the publication of FDOPA values recommended for this differential diagnosis&#44; each center must standardize its results&#44; which will not always totally overlap with those of other centers&#46; On the other hand&#44; the cut-off points should be adjusted to the lesion to be evaluated and should be analysed together with the semiology of the MR in an attempt to clarify the aspects of MR which cause doubts and may sometimes require precise criteria that provide a greater Sp and&#44; at other times&#44; greater S&#46;</p><p id="par0230" class="elsevierStylePara elsevierViewall">In this study we did not compare 6-&#91;<span class="elsevierStyleSup">18</span>F&#93;FDOPA PET&#47;C with the perfusion of MR&#44; one of the MR sequences with greater performance in this diagnosis&#46; This was not the objective&#46; We understand that both techniques evaluated different processes involved in the oncogenesis of brain tumors and therefore&#44; the results are not always concordant&#46; One techniques does not exclude the other&#59; both techniques play a relevant role in the evaluation of these patients and provide complementary information&#44; with both being necessary&#46; In our opinion and in our health care practice&#44; the best results are obtained from the team work of both specialties and in the joint analysis of both explorations&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a></p><p id="par0235" class="elsevierStylePara elsevierViewall">This study is not free of limitations&#59; FDOPA is a substrate of the DOPA-decarboxylase enzyme&#44; abundant in dopaminergic neurons such as those in the striates&#44; and thus&#44; interfere in tumors localized in the proximity of the striates&#46; On the other hand&#44; FDOPA has affinity for the LAT1 and LAT2 overexpressed in brain tumors and overexpression may also be observed in inflammatory processes and thereby limit the Sp of this radiopharmaceutical&#46;<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">14&#44;28&#8211;30</span></a></p><p id="par0240" class="elsevierStylePara elsevierViewall">Lastly&#44; this was a retrospective study and the results of FDOPA of these patients could not always be compared with histopathological confirmation&#44; being a usual limitation in this type of patients&#46;</p><p id="par0245" class="elsevierStylePara elsevierViewall">Despite the limitations of this study&#44; we consider that the visual and semiquantitative analysis of 6-&#91;<span class="elsevierStyleSup">18</span>F&#93;FDOPA PET&#47;CT evaluated together with MR is a necessary tool in the differential diagnosis of tumor recurrence versus RNC&#46; Its use in our country is still limited and efforts must be made to implement it in the algorithms of the neuro-oncology committees for the differential diagnosis of recurrence versus RNC&#46; This would allow also performing follow-up with FDOPA and not only isolated study without the possibility of seeing the metabolic evolution of these lesions&#44; thereby contributinge to achieving a more precise metabolic diagnosis&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a></p><p id="par0250" class="elsevierStylePara elsevierViewall">Prospective and multicenter studies are necessary to contribute to the standardization of criteria in the interpretation of 6-&#91;<span class="elsevierStyleSup">18</span>F&#93;FDOPA PET&#47;CT&#46; This would increase the level of evidence of its use in the differential diagnosis of recurrence versus RNC&#44; and contribute to the diagnosis and management of these patients in uncertain situations&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Conflict of interest</span><p id="par0255" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare&#46;</p></span></span>"
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              "titulo" => "Analysis of the images"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Amino acid PET is a tool recommended by the main neuroimaging societies in the differential diagnosis between radionecrosis &#40;RNC&#41; and umour recurrence &#40;TR&#41; in brain tumours&#44; but its use in our country is still limited&#46; The aim of this work is to present our experience with 6-&#91;<span class="elsevierStyleSup">18</span>F&#93;FDOPA PET&#47;CT &#40;FDOPA&#41; in brain tumours &#40;primary and M1&#41;&#44; comparing these results with other published results&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Material and methods</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Retrospective study of 62 patients with suspected tumour recurrence &#40;TR&#41;&#58; 42 brain metastases &#40;M1&#41; and 20 primary&#44; who underwent FDOPA&#46; Images were analysed visually and semi-quantitatively&#44; obtaining SUVmax and SUVmaxlesion&#47;SUVmaxstriatum &#40;L&#47;S&#41; and SUVmaxlesion&#47;SUVmaxcortex &#40;L&#47;C&#41; ratios&#46; The diagnostic validity of PET was analysed and the best performing cut-off points were calculated&#46; PET results were compared with clinical-radiological follow-up and&#47;or histopathology&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">TR was identified in 49&#37; of M1 and 76&#37; of brain primaries&#46; The best performing FDOPA interpretation was visual and semi-quantitative&#44; with a sensitivity and specificity in primaries of 94&#37; and 80&#37; and in M1s of 96&#37; and 72&#37; respectively&#46; The cut-off points with the best diagnostic performance were L&#47;C1&#46;44 in M1 and L&#47;C1&#46;55 in primaries&#46; There are discrepant results with other published results&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">FDOPA PET&#47;CT is a useful tool in the differential diagnosis between recurrence and RNC in brain tumours&#46; It is needed a standardization to contribute to homogenise FDOPA results a inter-centre level&#46;</p></span>"
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          1 => array:2 [
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducci&#243;n</span><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">El PET con amino&#225;cidos es una herramienta recomendada por las principales sociedades de neuroimagen&#44; en el diagn&#243;stico diferencial entre radionecrosis &#40;RNC&#41; y recurrencial tumoral &#40;RT&#41; en tumores cerebrales&#44; sin embargo su uso en nuestro pais a&#250;n es limitado&#46; El objetivo de este trabajo es presentar nuestra experiencia con 6-&#91;<span class="elsevierStyleSup">18</span>F&#93;FDOPA PET&#47;TC &#40;FDOPA&#41; en tumores cerebrales &#40;primarios y M1&#41;&#44; comparando estos resultados con otros publicados&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Material y m&#233;todos</span><p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Estudio retrospectivo de 62 pacientes con sospecha de recurrencia tumoral &#40;RT&#41;&#58; 42 met&#225;stasis cerebrales &#40;M1&#41; y 20 primarios&#44; a los que se les realiz&#243; una FDOPA&#46; Las im&#225;genes fueron analizadas visual y semicuantitativamente&#44; obteniendo el SUVmax y los ratios SUV<span class="elsevierStyleInf">max</span>lesi&#243;n&#47;SUV<span class="elsevierStyleInf">max</span>estriado &#40;L&#47;E&#41; y SUV<span class="elsevierStyleInf">max</span>lesi&#243;n&#47;SUV<span class="elsevierStyleInf">max</span>cortex &#40;L&#47;C&#41;&#46; Se analiz&#243; la validez diagn&#243;stica del PET y se calcularon los puntos de corte con mayor rendimiento&#46; Los resultados del PET se compararon con la evoluci&#243;n cl&#237;nico-radiol&#243;gica y&#47;o con la histopatolog&#237;a&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Se identific&#243; RT en el 49&#37; de las M1 y en el 76&#37; de los primarios cerebrales&#46; La interpretaci&#243;n de la FDOPA con mejores resultados fue la conjunta&#59; visual y semicuantitativa&#44; con una sensibilidad y especificidad en los primarios del 94 y 80&#37; y en las M1 del 96 y 72&#37; respectivamente&#46; Los puntos de corte con mejor rendimiento diagn&#243;stico fueron L&#47;C1&#46;44 en M1 y L&#47;C1&#46;55 en primarios&#46; Existen resultados discrepantes con otros publicados&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusi&#243;n</span><p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">La FDOPA PET&#47;TC es una herramienta &#250;til en el diagn&#243;stico diferencial entre recurrencia y RNC en tumores cerebrales&#46; Es necesario una estandarizaci&#243;n que contribuya a homogeneizar los resultados de la FDOPA a nivel intercentro&#46;</p></span>"
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          "en" => "<p id="spar0001" class="elsevierStyleSimplePara elsevierViewall">Images of a patient with a history of stage IV adenocarcinoma of the colon with a single brain metastasis&#44; which was treated with surgery and radiotherapy&#46;</p> <p id="spar0002" class="elsevierStyleSimplePara elsevierViewall">Ten months after the end of radiotherapy&#44; due to gait instability and headache&#44; a brain MRI was performed with doubts of tumor recurrence versus radionecrosis&#46;</p> <p id="spar0003" class="elsevierStyleSimplePara elsevierViewall">FDOPA PET showed a positive result for tumor recurrence which was later confirmed in the histopathological study of the surgical specimen&#46;</p> <p id="spar0004" class="elsevierStyleSimplePara elsevierViewall">A&#41; 6-&#91;<span class="elsevierStyleSup">18</span>F&#93;FDOPA PET images showing increased FDOPA uptake of moderate intensity and irregular character&#46; A focal area of higher intensity is observed in the medial region intensity in the medial region&#46; &#40;B&#41; Postcontrast T1-weighted MRI sequences revealing contrast uptake around the margins of the irradiated surgical cavity&#44; with uncertain significance&#46; C&#41; MR perfusion &#40;PWI&#41; sequences indicating a discrete increase in perfusion&#46; D&#41; PET-MRI fusion images showing a marked increase in FDOPA&#44; especially D&#41; PET-MRI fusion images showing a marked increase in FDOPA&#44; especially at the medial margin of the cavity&#44; with an L&#47;E ratio of 1&#46;09 and L&#47;C of 2&#46;25&#46; E&#41; Histological section of the resected surgical specimen&#44;where abundant cellularity compatible with colon adenocarcinoma is observed&#46;</p>"
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          "en" => "<p id="spar0006" class="elsevierStyleSimplePara elsevierViewall">Images of a patient with history of a previosusly treated single brain mestastasis from clear cell carcinoma&#46; One year after radiotherapy&#44; the patien showed focal seizure secondary to this lesion&#46; A brain MRI was performed to assess the possibility of tumor recurrence versus RNC&#44; which was inconclusive&#46; The result of the FDOPA PET was negative &#40; RNC&#41;&#44;and due to the persistence of the seizures the patient received surgical treatment&#44; adn RNC was confirmed in the resected specimen&#46; A&#41; 6-&#91;<span class="elsevierStyleSup">18</span>F&#93;FDOPA PET images showing a very slight and diffuse increase FDOPA around the cavity&#46; B&#41; Post-contrastost T1-weighted MRI sequences showing contrast enhancement around the margins of the irradiated surgical cavity of doubtful significance&#46; C&#41; MR perfusion &#40;PWI&#41; sequences showing no increased perfusion&#46; D&#41; PET-MRI fusion images that do not show significant increase of FDOPA at the margins of the surgical cavity&#44; with L&#47;E ratios 0&#46;56 and L&#47;C 1&#46;2&#46; E&#41; Histologic sections of the resected surgical specimen&#44;showing changes secondary to radionecrosis&#46;</p>"
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          "en" => "<p id="spar0007" class="elsevierStyleSimplePara elsevierViewall">Semiquantitative analysis showed significant differences between tumor recurrence and nonrecurrence &#40;RNC&#41; in both primary brain tumors and metastases&#46;</p> <p id="spar0008" class="elsevierStyleSimplePara elsevierViewall">The scatter-plotgure shows in the top row the SUVmax ratios for primary brain tumors&#44; SUVmax lesion&#47;SUVmax cortex ratio &#40;SUVmaxL&#47;C&#41; and SUVmax lesion&#47;SUVmax striatum ratio &#40;SUVmax L&#47;E&#41;&#46; The bottom row shows these ratios in the case of metastases&#46; Significant differences are observed in both L&#47;C and L&#47;E ratios in both metastases and primary brain tumors between recurrence and RNC&#46;</p>"
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          "en" => "<p id="spar0009" class="elsevierStyleSimplePara elsevierViewall">ROC analysis showed higher S and Sp in the analysis of primary brain tumors than in metastases&#46; The best cut-off point in primary tumors was obtained at the L&#47;C ratio 1&#46;57 with an S and Sp of 100 and 93&#37;&#44; respectively&#46;</p> <p id="spar0011" class="elsevierStyleSimplePara elsevierViewall">The best cut-off point in metastases was obtained at the L&#47;C ratio 1&#46;44 with an S and Sp of 88 and 79&#37;&#44; respectively&#46;</p>"
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            "detalle" => "Table "
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          "leyenda" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">DMLG&#44; diffuse midline glioma&#46;</p>"
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            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="\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">n&#8239;&#61;&#8239;62&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">&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 " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Age &#40;years&#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">57 &#40;24&#8722;79&#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="\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">Women &#40;&#37;&#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">29 &#40;46&#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="\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">Brain metastasis &#40;&#37;&#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">42 &#40;68&#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="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Primary neoplasia lung&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Primary neoplasia breast&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Primary neoplasia colon&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Primary neoplasia melanoma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Primary neoplasia renal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Primary neoplasia ovary&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Primary neuroendocrine&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></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Primary lacrimal gland&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></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Primary unknown&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></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">Primary tumor &#40;&#37;&#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">20 &#40;32&#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="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Glioblastoma&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-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Oligodendrogliomas GIII&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Astrocitomas GIII&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Oligodendrogliomas GII&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Astrocytoma GII&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></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Anaplastic oligoastrocytoma&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></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>DMLG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Ependymoma&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></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>High grade germinal tumor&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></tr></tbody></table>
                  """
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Characteristics of the patients&#46;</p>"
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        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Brain metastasis &#40;42 patients&#41;</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">&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">Recurrence&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">Radionecrosis&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">Total&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 " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PET &#43;&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">23&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">7&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></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">PET &#8722;&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">18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">19&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">&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">24&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">49&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Results obtained in a total of 70 lesions studied&#46; There were 21 lesions in 20 patients&#44; with primary brain tumors and 49 lesions in 42 patients with brain M1&#46; Table 2 shows the results in the brain metastases&#46;</p>"
        ]
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        "identificador" => "tbl0015"
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Primary brain tumors &#40;20 patients&#41;</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">&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">Recurrence&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">Radionecrosis&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">Total&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 " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PET &#43;&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&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">16&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">PET &#8722;&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">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">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&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&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
                  \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">21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Shows the results in the primary brain tumors&#46;</p>"
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\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">&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">n&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">lesions&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">FN&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">FP&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">S&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">Sp&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">PPV&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">NPV&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 " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Primary tumors&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">20&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">21&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">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">94&#37;&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">80&#37;&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">94&#37;&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">80&#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="\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">Metastasis&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">42&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">49&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">7&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">96&#37;&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">72&#37;&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">77&#37;&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">95&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Results of the diagnostic validity of joint visual and semi-quantitative analysis of PET&#47;TC 6-&#91;<span class="elsevierStyleSup">18</span>F&#93;FDOPA in patients with primary tumors and with brain metastasis and suspicion of tumor recurrence versus radionecrosis&#46;</p>"
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          "leyenda" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">L&#47;C&#58; lesion with cortex&#59; L&#47;S&#58; lesion with striate&#46;</p>"
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            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">&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  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Recurrence</th><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">Radionecrosis</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">&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">L&#47;C ratio&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">L&#47;S ratio&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">L&#47;C ratio&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">L&#47;S ratio&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 " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Primary tumors&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;03&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&#46;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">0&#46;6&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">Metastasis&nbsp;\t\t\t\t\t\t\n
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