18F-FDG PET/CT in locally advanced cervical cancer: A review | Revista Española de Medicina Nuclear e Imagen Molecular (English Edition)

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La RM muestra un voluminoso tumor primario (diámetro máximo de 61,9mm) con probable invasión de la pared posterior de la vejiga urinaria (A). La PET/TC con 18F-FDG muestra captación elevada en el tumor primario (SUVmáx 16,3) que contacta con la pared posterior de la vejiga (B), y afectación ganglionar pélvica (C), y retroperitoneal (D). La imagen hipermetabólica orofaríngea corresponde a mucositis por Candida y la paracardíaca a actividad metabólica en la unión gastroesfágica por esofagitis." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "A.P. Caresia-Aróztegui, R.C. Delgado-Bolton, S. Alvarez-Ruiz, M. del Puig Cózar-Santiago, J. Orcajo-Rincon, M. de Arcocha-Torres, M.J. García-Velloso" "autores" => array:8 [ 0 => array:2 [ "nombre" => "A.P." "apellidos" => "Caresia-Aróztegui" ] 1 => array:2 [ "nombre" => "R.C." "apellidos" => "Delgado-Bolton" ] 2 => array:2 [ "nombre" => "S." "apellidos" => "Alvarez-Ruiz" ] 3 => array:2 [ "nombre" => "M." 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Caresia-Aróztegui, R.C. Delgado-Bolton, S. Alvarez-Ruiz, M. del Puig Cózar-Santiago, J. Orcajo-Rincon, M. de Arcocha-Torres, M.J. García-Velloso" "autores" => array:8 [ 0 => array:4 [ "nombre" => "A.P." "apellidos" => "Caresia-Aróztegui" "email" => array:1 [ 0 => "paulacaresia@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "R.C." "apellidos" => "Delgado-Bolton" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "S." "apellidos" => "Alvarez-Ruiz" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] ] ] 3 => array:3 [ "nombre" => "M." "apellidos" => "del Puig Cózar-Santiago" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "d" "identificador" => "aff0020" ] ] ] 4 => array:3 [ "nombre" => "J." 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"apellidos" => "García-Velloso" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "g" "identificador" => "aff0035" ] ] ] 7 => array:1 [ "colaborador" => "on behalf of the Grupo de Trabajo de Oncología de la Sociedad Española de Medicina Nuclear e Imagen Molecular" ] ] "afiliaciones" => array:7 [ 0 => array:3 [ "entidad" => "Servicio de Medicina Nuclear, UDIAT, Hospital de Sabadell, Corporació Sanitària Parc Taulí, Sabadell, Barcelona, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Departamento de Diagnóstico por Imagen y Medicina Nuclear, Hospital San Pedro-Centro de Investigación Biomédica de La Rioja (CIBIR), Logroño, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Servicio de Medicina Nuclear, Hospital Universitario Miguel Servet, Zaragoza, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Servicio de Medicina Nuclear, ERESA, Hospital General Universitario de Valencia, Valencia, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Servicio de Medicina Nuclear, Hospital General Universitario Gregorio Marañón, Madrid, Spain" "etiqueta" => "e" "identificador" => "aff0025" ] 5 => array:3 [ "entidad" => "Unidad de Radiofarmacia, Hospital Universitario Marqués de Valdecilla, Santander, Spain" "etiqueta" => "f" "identificador" => "aff0030" ] 6 => array:3 [ "entidad" => "Servicio de Medicina Nuclear, Clínica Universidad de Navarra, Pamplona, Spain" "etiqueta" => "g" "identificador" => "aff0035" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "PET/TC con 18F-FDG en cáncer de cérvix localmente avanzado" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1504 "Ancho" => 2833 "Tamanyo" => 292063 ] ] "descripcion" => array:1 [ "en" => "A 54-year-old patient with locally advanced cervical cancer (by physical examination for suspicion of FIGO IIIB). The MR shows a voluminous primary tumor (maximum diameter of 61.9mm) with probable invasion of the posterior wall of the urinary bladder (A). PET/CT with 18F-FDG shows elevated uptake in the primary tumor (SUVmax 16.3) in contact with the posterior wall of the bladder (B), and pelvic (C) and retroperitoneal lymph node involvement (D). The hypermetabolic oropharyngeal image corresponds to mucositis by Candida and the paracardiac metabolic activity at the gastroesophageal junction due to esophagitis." ] ] ] "textoCompleto" => "IntroductionCervical cancer is the second most frequent gynecological cancer in women worldwide and around 85% of the cases are found in developing countries.<a class="elsevierStyleCrossRef" href="#bib0300">1</a> The incidence of cervical cancer in Spain is within the lower range in Europe, having a mean age-adjusted rate (AAR) of 6.3×100,000women/year, with 1948 new cases diagnosed each year.This AAR places cervical cancer in eleventh position among women of all ages but in second position in the group of women from 15 to 44 years of age, which has a rate of 7.7 that is surpassed by only breast cancer with a rate of 32.4.In Spain, death by cervical cancer occurs in 1.9×100,000 women-year; that is, 712 cases per year. This makes cervical cancer the fifteenth cause of death by tumors in women of any age but third among those from 15 to 44 years of age, with an AAR of 1.2 behind breast and lung cancer.<a class="elsevierStyleCrossRef" href="#bib0305">2</a>Squamous carcinoma is the most frequent histological type, representing 85–95% of the cases. Adenocarcinoma is the second most frequent histological type followed by adenosquamous and neuroendocrine carcinoma. Squamous cervical cancer is found among sexually active women and is directly associated with high risk human papillomavirus (HPV) infection. A premalignant precursor squamous intraepitheal lesion (SIL) initially develops, and then a cervical intraepithelial neoplasm (CIN) is established. HPV types 16 and 18 are the cause of 70–75% of cervical cancers.<elsevierMultimedia ident="tb0005"></elsevierMultimedia>Disease extensionSince most patients with cervical cancer are diagnosed in developing countries with limited access to diagnostic imaging techniques, the International Federation of Gynecology and Obstetrics (FIGO) considers that the initial staging of cervical cancer should be based on clinical manifestations, according to a physical examination performed by an experienced gynecologist and under anesthesia, if necessary.<elsevierMultimedia ident="tb0010"></elsevierMultimedia>The last version of the FIGO classification made in 2009 includes a FIGO classification by stages which takes the following into account: tumor size, vaginal or parametrial involvement, extension to the bladder/rectum and distant extension.<a class="elsevierStyleCrossRef" href="#bib0310">3</a> The initial FIGO stage conditions patient treatment and prognosis and does not change with the histopathological results after surgery or with recurrence. However, for years the American Joint Committee of Cancer (AJCC) has recommended reporting the FIGO stage and the histopathological tumor, node, metastasis (pTNM). The last version of the AJCC TNM is from 2017.<a class="elsevierStyleCrossRefs" href="#bib0315">4,5</a><a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows the FIGO classification, and <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> shows survival by stages.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia>Tumors less than 4cm in size are defined as early disease. To the contrary, locally advanced cervical cancer (LACC) involves a tumor of greater than or equal to 4cm in size (FIGO greater than or equal to IIA2). Several studies have compared the initial FIGO stage (clinical manifestations) with the TNM classification after surgery. It is known that in small tumors or early disease the clinical stage agrees with the histopathological results (>85% in stages IA and IB1). However, this concordance becomes progressively lower according to the increase in tumor size, being 35% in IIA and 21% in FIGO IIB tumors.<a class="elsevierStyleCrossRef" href="#bib0325">6</a><elsevierMultimedia ident="tb0015"></elsevierMultimedia>Another aspect to take into account, despite being somewhat controversial, is the histological type, since this may be a predictive factor of survival. Although some studies have not found differences in the survival between patients with adenocarcinoma and squamous carcinoma, most studies report that adenocarcinoma carries a worse prognosis, with 10–20% of differences in the overall survival at 5 years.<a class="elsevierStyleCrossRef" href="#bib0330">7</a>Lymph node involvement is the most significant factor of bad prognosis in cervical cancer, although it is not included in the FIGO classification. <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> shows the factors of bad prognosis.<a class="elsevierStyleCrossRef" href="#bib0305">2</a><elsevierMultimedia ident="tb0020"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia>The dissemination pattern of cervical cancer begins at the squamo-columnar junction, growing spherically from there and invading the cervical stroma and the parametrium, the uterus and the vagina. The disease spreads through three lymphatic pathways: the external iliac route, the hypogastric region toward the internal iliac chain and finally the presacral region toward the uterus-sacrum ligament. These three routes drain to the common iliac region and then to the retroperitoneal paraaortic lymph nodes.<a class="elsevierStyleCrossRef" href="#bib0335">8</a>The AJCC classification recognizes regional adenopathies as those localized in the pelvic region. The 2017 edition of the AJCC classification also includes adenopathies located in the retroperitoneal paraaortic region which were considered as stage M1 in the previous 2010 classification.<a class="elsevierStyleCrossRef" href="#bib0315">4</a>The incidence of paraaortic lymph node tumor involvement is greater according to an increase in FIGO stage. In their meta-analysis, Smits et al.<a class="elsevierStyleCrossRef" href="#bib0340">9</a> showed that involvement of this lymph node territory is presented in 11% of patients in stage Ib2, in 13% in stage IIA, in 16% in stage IIB, in 29% in stage III and in 36% in stage IV. It should be taken into account that paraaortic lymph node involvement influences the treatment and the tendency to recurrence, and therefore, is of prognostic value. The 5-year survival of patients treated without lymph node involvement is 95% and is less than 80% in women with pelvic lymph node involvement. However, if the lymph nodes in the common iliac or paraaortic regions are affected, the 5-year survival is less than 40%.<a class="elsevierStyleCrossRef" href="#bib0325">6</a><elsevierMultimedia ident="tb0025"></elsevierMultimedia>Once the paraaortic region is involved, cervical cancer spreads to the supraclavicular region achieving the stage of distant metastasis (M1). The presence of extraabdominal lymph node disease is infrequent. Only 8–12% of the patients present metastasis beyond the regional lymph nodes at the time of diagnosis. Hematogenous dissemination (M1) is even less frequent, being of approximately 5% and may affect the lungs, the liver, the bones and the peritoneum. Although distant metastasis may be presented in any FIGO stage, it is improbable in cases without pelvic lymph node involvement.<a class="elsevierStyleCrossRefs" href="#bib0315">4,8</a> Nonetheless, it is essential to know the presence of distant metastasis since in these cases the treatment becomes palliative and survival is precarious.<a class="elsevierStyleCrossRef" href="#bib0305">2</a>TreatmentThe treatment of cervical cancer is surgical in patients with a tumor confined within the upper cervix and vagina. In tumors >IA1 with lympovascular invasion or a higher stage, pelvic lymph node dissection is indicated in order to evaluate lymph node infiltration. It is in this latter group of patients that the use of the laparascopic sentinel lymph node technique might be of interest with the aim of advancing toward less aggressive approaches.<a class="elsevierStyleCrossRefs" href="#bib0305">2,10</a>Patients with stages IB2 or IIA can be treated with surgery or with the combination of chemotherapy (CHT) and radiotherapy (RT). In patients with LACC (stage greater than IIA2), treatment involves the combination of CHT and concomitant RT. At present, the standard CHT schedule is cisplatin (CDDP) 40mg/m2 weekly during 6 weeks.<a class="elsevierStyleCrossRef" href="#bib0305">2</a>It is important to highlight the value of the detection of paraaortic lymph node involvement, because when it is present, it is recommended to extend the RT field to the retroperitoneal region. In the case of distant metastasis, the alternatives are palliative CHT and RT.Brachytherapy is indicated in patients who are not candidates for surgery. This technique usually has two approaches: one intrauterine component and another vaginal. Brachytherapy is also used post-hysterectomy in patients with positive or close margins.<a class="elsevierStyleCrossRef" href="#bib0345">10</a>Initial stagingClinical guidelinesAccording to FIGO, the initial staging should be based on the clinical manifestations, by examination and colposcopy (with sedation is necesssary) in order to obtain adequate biopsy tissue. FIGO recommends completing the study with a chest radiography, intravenous pyelography, cystoscopy and proctosigmoidoscopy (on suspicion of rectal or vesical extension). The classification makes it clear that other diagnostic procedures can be used for comparative purposes but not to determine treatment.On the other hand, the guidelines of the principal international societies such as the National Comprehensive Cancer Network (NCCN), the European Society for Medical Oncology (ESMO), the European Society of Gynaecological Oncology (ESGO), the Spanish Society of Medical Oncology (SEOM), and the Spanish Society of Gynecological Oncology (SEGO) accept the performance of lymph node dissection in LACC to determine lymph node status and state that there is insufficient evidence for paraaortic lymph node dissection to be replaced by imaging techniques.<a class="elsevierStyleCrossRefs" href="#bib0305">2,7,10,11</a>According to the ESMO, imaging techniques are not able to detect small sized lymph node metastasis in early disease (T1a, T1b1, T2a1), and surgical staging is more reliable for both the prognosis and to establish the most adequate treatment to be implemented.<a class="elsevierStyleCrossRef" href="#bib0330">7</a> In a study of 555 patients carried out by the Gynecologic Oncology Group (GOG) which retrospectively evaluated the GOG 85, GOG 120 and GOG 165 clinical trials, it was shown that patients undergoing paraaortic lymph node dissection had a better survival than patients who had undergone staging by imaging techniques (lymphography, computerized tomography [CT] or magnetic resonance [MR]).<a class="elsevierStyleCrossRefs" href="#bib0345">10,12</a> However, there is controversy regarding the use of pelvic and paraaortic lymph node dissection. On one hand, the surgical approach seems to be more accurate for diagnosing lymph node involvement, but on the other hand, this approach has a greater morbimortality and delays the initiation of CHT-RT treatment.<a class="elsevierStyleCrossRef" href="#bib0325">6</a>Currently, CT, MR, positron emission tomography (PET)/CT with 18F-fluorodeoxyglucose (FDG) and surgical staging are used in both Europe and the United States for staging and treatment decision making. <a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a> provides a summary of the recommendations regarding the diagnostic techniques recommended by the different scientific societies – FIGO, NCCN, ESMO, ESGO, SEOM, SEGO.<a class="elsevierStyleCrossRefs" href="#bib0305">2,7,10,11,13,14</a> MR presents the greatest spatial resolution in soft tissues and therefore provides the highest diagnostic yield with respect to local disease extension. This imaging technique provides information on tumor size, extension toward the uterine corpus, involvement of the parametrium and neighboring organs as well as pelvic lymph node status. FIGO therefore recognizes the utility of MR and accepts it use for staging of cervical cancer, if available.<elsevierMultimedia ident="tbl0020"></elsevierMultimedia>MR has a very important role in the placement of brachytherapy instruments and also in the evaluation of response.<elsevierMultimedia ident="tb0030"></elsevierMultimedia>In LACC it is important to rule out the presence of lymph node and distant metastases. CT has classically been used for this. However, up to 24% of women with negative CT results present histological lymph node involvement since the threshold for lymph node detection normally used with this technique is 10mm.The first studies on initial staging with PET with 18F-FDG in cervical cancer showed a low diagnostic yield, but the results were improved with multimodality PET/CT, which obtained a better diagnostic yield than with the two techniques of CT and PET separately.PET/CT with 18F-FDGThe value of PET/CT with 18F-FDG in cervical cancer lies in the detection of regional lymph node involvement and distant metastasis.<a class="elsevierStyleCrossRefs" href="#bib0330">7,10,15,16</a> Indeed, the use of PET/CT for the initial staging modifies the therapeutic management in 10–32% of the cases in patients with cervical cancer because it is able to detect paraaortic adenopathies which are not identified by other techniques as well as distant metastasis and other additional findings such as second neoplasms.<a class="elsevierStyleCrossRefs" href="#bib0380">17–20</a><elsevierMultimedia ident="tb0035"></elsevierMultimedia>Study protocolAs defined by the guidelines of action of the European Association of Nuclear Medicine (EANM), the protocol for the acquisition of PET/CT with 18F-FDG in oncology indicates the need for a minimum fasting period of 6h, adequate hydration and glycemia less than 200mg/dl. The standard acquisition includes from the orbital-meatal line to the middle third of the femur in a caudal-cranial direction and recommends the acquisition of images with an empty bladder.<a class="elsevierStyleCrossRef" href="#bib0400">21</a>Since these patients are usually of reproductive age it is important to register the data of the last menstruation since it may be useful to adequately interpret the presence of functional cysts which may be hypermetabolic during ovulation or the usual diffuse endometrial hypermetabolism during menstruation.When PET/CT is aimed at the planning of RT, it is important to perform the acquisition with a flat table using immobilization material, if available, to facilitate the fusion of images with the simulator or to do the planning directly on the PET/CT images.<a class="elsevierStyleCrossRef" href="#bib0405">22</a> Patient position is essential, and it is recommended to tattoo three points on the skin (right, left and ventral side) as a reference to situate the laser of the PET/CT equipment and reproduce the position at the time of treatment.It is recommended to use oral and intravenous iodine contrast. In the case of allergy, it is possible to consider pre-medication for the intravenous iodine contrast. An alternative to the use of oral contrast is to use water as a negative contrast.In patients with gynecological tumors, and especially in cervical cancer, correct hydration is fundamental. It may be interesting to perform a manuever which helps to differentiate the urinary excretion of FDG in the ureters in retroperitoneal or pelvic disease. These manuevers include:<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005">•Administration of a diuretic 1h before the acquisition to force urinary elimination of the radiotracer.</li><li class="elsevierStyleListItem" id="lsti0010">•Administration of an intravenous contrast in a split bolus. In the case of administering 120ml of contrast, 40ml are initially injected, and the remaining 80ml are administered 9min later. Then, 50s after the last injection, the CT acquisition is started. This manuever obtains images with iodine contrast in the excretory phase (urinary tract) and in the portal phase in the remainder of the body.<a class="elsevierStyleCrossRefs" href="#bib0410">23,24</a></li><li class="elsevierStyleListItem" id="lsti0015">•Delayed PET imaging, which is especially important in doubtful findings, movement artifacts or on suspicion of peritoneal disease. It also allows the acquisition of images of the pelvis with the bladder in different stages of repletion in patients who are candidates to treatment with RT.</li></ul>Staging of the primary tumorAlthough it is possible to determine tumor size with PET/CT, this is not an indication in cervical cancer. It has been demonstrated that the grade of metabolic activity of the primary tumor is related to the histological type. Squamous tumors present greater metabolism than adenocarcinomas, and poorly differentiated tumors also present significantly greater metabolic activity than tumors which are well differentiated.<a class="elsevierStyleCrossRef" href="#bib0420">25</a>An elevated standardized uptake value (SUVmax) of the primary tumor is a prognostic factor and implies a worse overall survival (OS), greater tumor aggressiveness and a high probability of lymph node involvement.<a class="elsevierStyleCrossRefs" href="#bib0425">26,27</a> The heterogeneity of the basal intratumoral metabolism of the primary tumor, calculated by segmentation in the PET/CT, is able to predict not only the risk of lymph node involvement at diagnosis but also worse response to treatment, and therefore, a greater risk of recurrence.<a class="elsevierStyleCrossRef" href="#bib0435">28</a>Lymph node stagingIt is vitally important to determine the presence of lymph node involvement in LACC in order to develop the therapeutic management. Paraaortic lymph node dissection is considered as option (although the primary tumor is not resected), but the possibility of amplifying the RT field to the paraaortic region is also accepted in the case of high suspicion of paraaortic lymph node involvement by imaging and the impossibility of histological confirmation (SEGO, NCCN, ESGO, ESMO).<a class="elsevierStyleCrossRefs" href="#bib0330">7,10,11,14</a> This subject remains under debate, since in most countries PET/CT with 18F-FDG is routinely used for lymph node staging while other countries prefer to perform paraaortic lymph node dissection (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).<elsevierMultimedia ident="fig0005"></elsevierMultimedia>There are several meta-analyses on the capacity of detection of tumoral adenopathies in cervical cancer, with a great variability in the results. The differences in the values of the diagnostic yield of PET/CT with 18F-FDG are based on the probability of lymph node involvement and the size of the metastases in the samples analyzed. Therefore, in series with LACC (sensitivity of 83% [62–94] and a specificity of 91% [85–94]), the values markedly improve versus series with early cervical cancer (sensitivity of 53–73% and specificity of 90–97%). The review by Grant et al.<a class="elsevierStyleCrossRef" href="#bib0335">8</a> (<a class="elsevierStyleCrossRef" href="#tbl0025">Table 5</a>) present the results of 5 metaanalyses in list form and shows that compared with CT and MR, PET or PET/CT is the technique with the best accumulated values of sensitivity and specificity in lymph node detection.<a class="elsevierStyleCrossRefs" href="#bib0375">16,29–33</a><elsevierMultimedia ident="tbl0025"></elsevierMultimedia>Liu et al.<a class="elsevierStyleCrossRef" href="#bib0465">34</a> recently published the latest meta-analysis based on 67 studies, comparing the capacity of detecting lymph node involvement by MR (including diffusion sequences), PET and PET/CT and CT. This meta-analysis also included articles of patients with early disease (<a class="elsevierStyleCrossRef" href="#tbl0025">Table 5</a>). The results show that to detect lymph node involvement the use of these techniques makes sense in LACC, and that MR with diffusion (not considered in previous meta-analyses, with a sensitivity of 87% and specificity of 83%) seems to be the most sensitive technique, while PET and PET/CT are more specific. On the other hand, the same meta-analysis showed what was referred to in some previous reports, and that is that the diagnostic yield of PET/CT is greater in the paraaortic region (accumulated sensitivity of 81%, accumulated specificity of 98%) compared to the pelvic region (accumulated sensitivity of 55%, accumulated specificity of 97%).<a class="elsevierStyleCrossRef" href="#bib0465">34</a>All the series with LACC coincide in that PET/CT presents an elevated positive predictive value (PPV) and negative predictive value (NPV) for the detection of paraaortic lymph node involvement.<a class="elsevierStyleCrossRefs" href="#bib0340">9,35</a> False negative results are due to metastases of less than 5mm in size and are lower with PET/CT (6–15%) than with MR (9–35%). In 2013, a randomized clinical study of 237 patients with LACC was published. All the patients had negative PET/CT results and paraaortic lymph node dissection with a mean follow-up of 30 months. In this study the rate of false negative PET/CT results was 12%, being similar to that of other series. The authors highlighted that the number and size of the lymph node metastases were important since the survival of patients with lymph node metastasis <5mm or who presented a single paraaortic adenopathy was similar to that of patients without lymph node involvement. On the other hand, the patients with lymph node metastases >5mm presented a significantly worse prognosis.<a class="elsevierStyleCrossRef" href="#bib0470">35</a> The doubt which arises from these studies is whether the survival is really related to the combination of lymph node dissection and RT or to the biology of the tumor itself. An interesting data provided by the prospective randomized study carried out by Tsai et al.<a class="elsevierStyleCrossRef" href="#bib0475">36</a> with the same objective was that the performance of PET/CT had no impact on the OS but did have an impact on the reduction of the risk of extrapelvic relapse.Grigsby<a class="elsevierStyleCrossRef" href="#bib0480">37</a> demonstrated that PET/CT is better than CT for the detection of lymph node involvement and that the lymph node stage determined by PET with 18F-FDG is the most significant independent pretreatment prognostic factor of progression-free survival (PFS) and OS. Regarding the data of pelvic lymph node involvement, the disease-free survival at 2 years was 84% in patients with negative CT and PET results, 64% with negative CT results and positive PET/CT results and 48% in cases with positive PET and PET/CT results. For the paraaortic lymph node region, the disease-free survival at 2 years was 78% if the CT and PET were negative, 31% if the CT was negative but the PET/CT was positive, and 14% if the results of both studies were positive (p=0.0001). No patient with supraclavicular adenopathies survived at 2 years. These results suggest an opportunity to cure these patients with paraaortic lymph node involvement by PET which is not detected by CT.A study by Kidd et al.<a class="elsevierStyleCrossRef" href="#bib0440">29</a> in 560 patients with FIGO stages IA1 to IVB (treated according to the FIGO stage with exclusive surgery, surgery and post-operative RT or CHT-RT) showed that 47% of the patients present lymph node involvement in the diagnosis by PET/CT similar to the lymph node involvement reported in historical surgical series. All the patients with positive PET results presented pelvic lymph node involvement, 35% in the paraaortic region and 12% in the supraclavicular region. The patients with paraaortic involvement also had pelvic involvement. The patients with positive PET results had a significantly worse prognosis than those with negative PET results (p<0.01). Taking into account the categories of the study (non lymph node involvement, pelvic, paraaortic and supraclavicular involvement), the patients with the most distant metastatic lymph node disease of the primary tumor presented a worse survival. The greater the distance of lymph node involvement the greater the probability of recurrence, with hazard ratio values (index of risk) of the pelvis of 2.4 (confidence interval [CI] 95%: 1.6–3.5), 5.9 for paraaortic lymph nodes (CI 95%: 3.8–9.1) and 30 for supraclavicular lymph nodes (CI 95%: 17–55).It is interesting to note that according to Yen et al.,<a class="elsevierStyleCrossRef" href="#bib0485">38</a> the grade of metabolic activity of the retroperitoneal lymph nodes is relevant in patients with cervical cancer. The results of their study show that paraaortic adenopathies with a SUVmax value ≥3.3g/ml are significantly associated with a worse survival, a greater tendency to recurrence and a higher mortality.<elsevierMultimedia ident="tb0040"></elsevierMultimedia>In view of this problematic, we must wait for the results of the multicenter Lymphadenectomy In Locally Advanced cervical Cancer Study (LILACS) clinical trial which includes patients with stage IB2-IVA disease who are candidates for CHT-RT treatment. The objective of this study is to compare the survival of patients undergoing a PET/CT extension study with patients undergoing paraaortic lymph node dissection.<a class="elsevierStyleCrossRef" href="#bib0490">39</a>Distant stagingThere are few studies aimed principally at the detection of distant metastasis by PET/CT in cervical cancer.PET/CT is better than CT in the detection of metastatic disease, especially in the form of extraabdominal tumoral adenopathies. As mentioned previously, adenopathies in the supraclavicular region are quite a usual localization of distant metastasis in patients with cervical cancer. Both the study by Tran et al.<a class="elsevierStyleCrossRef" href="#bib0495">40</a> including 186 patients diagnosed with cervical cancer and that of Grigsby et al.<a class="elsevierStyleCrossRefs" href="#bib0480">37,41</a> including a series of 101 patients found 8% of patients with metastatic supraclavicular adenopathies in PET/CT, with all being histologically confirmed.The last study published to data on this question is a retrospective review of the data of the multicenter ACRIN6671/GOG0233 clinical trial. The main aim of this study was to detect lymph node involvement with PET/CT in patients with cervical cancer. This randomized double-blind study included 153 patients with LACC (FIGO IB=25, IIA=6, IIB=8, III=1). M1 metastasis was confirmed by biopsy in all the patients in whom this was suspected (21 metastatic patients, 13.7% of the total), and all underwent a control CT at 6 months after surgery. Preoperative PET/CT to detect metastasis of LACC demonstrated a sensitivity of 54.8%, a specificity of 97.7%, a PPV of 79.3% and a NPV of 93.1%.<a class="elsevierStyleCrossRefs" href="#bib0505">42,43</a>In another study, Mittra et al.<a class="elsevierStyleCrossRef" href="#bib0395">20</a> included patients in more advanced stages of the disease (n=30 patients, FIGO Ib2=2, IIA=4, IIB=10, III=12, IVA=2) and reported a higher percentage of detection of metastasis in the PET/CT (50%), with a sensitivity of 96%, specificity of 95%, a PPV of 96%, NPV of 95% and diagnostic efficacy of 95%.Radiotherapy planningAlthough surgery is indicated in small tumors, patients with stage IB2-IVA tumors with extension to the parametrials and pelvic organs or with pelvic and paraaortic lymph node disease are treated with CHT-RT.<a class="elsevierStyleCrossRef" href="#bib0515">44</a> Imaging techniques are necessary in the RT treatment planning for cervical cancer, and it is recommended that radiologists and nuclear medicine physicians work together with the specialists in radiotherapy because a multidisplinary approach optimizes the process of delimitation of the disease to be treated.<a class="elsevierStyleCrossRef" href="#bib0405">22</a> The classical definition of tumor volumes is based on the CT gross tumor volume (GTV), but the concepts of metabolic tumor volume (MTV) or biological tumor volume (BTV) defined in the molecular PET/CT imaging have recently been incorporated.<a class="elsevierStyleCrossRef" href="#bib0520">45</a> In the histological subtypes with an elevated avidity for FDG, PET/CT presents a better diagnostic yield than CT and MR for the detection of metastatic pelvic and retroperitoneal lymph nodes, because it is able to identify infiltrated lymph nodes smaller than 1cm. This thereby provides a more accurate definition of the lymph node tumor volume in the RT planning and modifies the patient treatment plans, widening the field to the infiltrated and metabolically active lymph nodes, with a reduction in toxicity to the normal adjacent tissues.<a class="elsevierStyleCrossRef" href="#bib0525">46</a> The criteria of positivity in the visual interpretation is a focally increased uptake of intensity greater than that of the normal adjacent tissues. It is necessary to know the lymphatic drainage pattern for better interpretation of the findings. PET/CT also has a better yield compared to CT for the detection of distant metastasis, leading to a change in curative treatment with RT to palliative treatment.<a class="elsevierStyleCrossRef" href="#bib0480">37</a>In patients with LACC the combination of RT with CHT prolongs disease-free survival and reduces the mortality. However, 20–40% of the patients treated with conventional RT present locoregional relapse.<a class="elsevierStyleCrossRef" href="#bib0530">47</a> Intensity modulated radiotherapy (IMRT) has achieved better results with less toxicity than conventional RT.<a class="elsevierStyleCrossRef" href="#bib0345">10</a> Esthappan et al.<a class="elsevierStyleCrossRef" href="#bib0535">48</a> used PET/CT with 18F-FDG to guide IMRT, modifying the treatment plan in infiltrated paraaortic lymph nodes in the PET/CT (60Gy) versus the dose of 50Gy in paraaortic and pelvic lymph node chains without disease in the PET/CT and achieving more effective treatment of the disease with a reduction in the toxicity to kidneys and the intestine. Kidd et al.<a class="elsevierStyleCrossRef" href="#bib0540">49</a> performed at study in patients treated with IMRT guided by PET/CT and with conventional RT. The patients treated with IMRT had a better survival and less treatment-related toxicity compared to those receiving treatment with conventional RT.PET/CT with 18F-FDG can define the MTV of not only the cervix but also the lymph nodes detected in the pelvis and paraaortic lymph node chains. There are different algorithms for the definition of the isocontour in hypermetabolic lesions. The simplest is a threshold of 40% with respect to the SUVmax and is applicable in tumors with an elevated avidity for FDG, although visual verification and manual optimization are always necessary taking into account clinical findings and other imaging studies. Treatment with platin-based CHT, IMRT and RT boosts in the primary tumor and the lymph node metastases detected has shown to be effective and has an acceptable toxicity.<a class="elsevierStyleCrossRef" href="#bib0545">50</a> In the study by Lazzari et al.<a class="elsevierStyleCrossRef" href="#bib0380">17</a> PET/CT with 18F-FDG changed the lymph node tumoral stage, and thus, the treatment plan with IMRT in 25% of the patients treated with exclusive RT and in 7.7% of those receiving adjuvant IMRT. Nonetheless, these preliminary results are from studies with small sample sizes and without surgical validation, and therefore, prospective multicenter studies are needed to determine the impact of PET on survival.<elsevierMultimedia ident="tb0045"></elsevierMultimedia>PET/CT with 18F-FDG can also be used in the planning of brachytherapy treatment. Malyapa et al.<a class="elsevierStyleCrossRef" href="#bib0550">51</a> compared three dimensional (3D) brachytherapy based on PET with two dimensional (2D) brachytherapy and demonstrated that 3D brachytherapy improved the dose received by the tumor and reduced radiation to critical organs. Several studies used MR and PET in brachytherapy planning in patients with cervical cancer and concluded that PET/CT with 18F-FDG reduces the variability between observers in the determination of tumor volumes.<a class="elsevierStyleCrossRef" href="#bib0555">52</a>Although still under investigation, in the future new PET/MR equipment which integrate the windows of both techniques may become the technique of choice for the study of extension and RT planning in patients with cervical cancer.<a class="elsevierStyleCrossRef" href="#bib0560">53</a>Evaluation of response and detection of recurrenceAfter treatment, clinical follow-up is fundamental. Controls including physical examination are recommended every 3 months during the first 2 years, every 6 months the following 3 years and then every year thereafter. According to the guidelines of action of the ESMO, NCCN, ESGO and SEGO, the use of imaging studies (MR, CT or PET/CT) should be based on clinical suspicion for symptomatology of recurrence or metastatic disease.<a class="elsevierStyleCrossRefs" href="#bib0330">7,10,11,54</a>According to the NCCN, the most in depth guideline in this context, PET/CT is the technique of choice in patients suspected of having local relapse (sensitivity of 86%, specificity of 87%) as well as in patients suspected of presenting metastasis (sensitivity of 90%, specificity of 99%). The same guidelines emphasize that the recommendation of PET/CT is in patients who have undergone complete radical treatment with FIGO stage Ib2 or greater or who require adjuvant RT or concomitant CHT-RT because of the presence of factors of risk (positive adenopathies, affected parametrium, positive margins or local risk factors) in order to rule out distant metastasis. The guidelines note that PET/CT with intravenous iodine contrast can be used at 3–6 months after finalizing treatment to evaluate response and attempt to detect patients with localized disease recurrence/persistence who could benefit from curative treatment and exenteration. Nonetheless, the best time to carry out an evaluation of response in these patients is still under debate.<a class="elsevierStyleCrossRefs" href="#bib0345">10,54–56</a>Apart from the guidelines, it has been reported that during follow-up PET/CT can detect recurrence in asymptomatic patients who are candidates to additional treatment with intention to cure, with a 3-year survival of 59–86%.<a class="elsevierStyleCrossRefs" href="#bib0565">54,57</a> The conclusions of two cost-effective analyses published on the recurrence of cervical cancer differ. On one hand, the study by Auguste et al.<a class="elsevierStyleCrossRef" href="#bib0585">58</a> in treated patients in different FIGO stages compared two models: one conventional (MR or CT or both during follow-up) and another which adds PET/CT to the conventional study without taking into account patient symptoms. The authors concluded that PET/CT is not cost-effective in this context. On the other hand, the more recent cost-effective analysis published by Phippen et al.<a class="elsevierStyleCrossRef" href="#bib0590">59</a> focused on locally advanced tumors treated with CHT-RT compared conventional follow-up with physical examination and radiological studies only in the case of suspicion of relapse (without PET/CT) with a second model in which PET/CT was added at 3 months after finalizing treatment. They concluded that while the overall cost was higher, the PET/CT strategy to detect the presence of a viable tumor and select patients who might benefit from hysterectomy obtained a lower rate of recurrence and was, therefore, cost-effective.Further studies are likely needed to determine the most accurate time to carry out PET/CT in the evaluation of treatment and cost-effective analyses to demonstrate benefits in symptomatic and asymptomatic patients.Conflict of interestThe authors declare no conflict of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres1135724" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1067760" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1135725" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1067761" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0015" "titulo" => "Disease extension" ] 6 => array:2 [ "identificador" => "sec0040" "titulo" => "Treatment" ] 7 => array:3 [ "identificador" => "sec0045" "titulo" => "Initial staging" "secciones" => array:7 [ 0 => array:2 [ "identificador" => "sec0050" "titulo" => "Clinical guidelines" ] 1 => array:2 [ "identificador" => "sec0060" "titulo" => "PET/CT with F-FDG" ] 2 => array:2 [ "identificador" => "sec0070" "titulo" => "Study protocol" ] 3 => array:2 [ "identificador" => "sec0075" "titulo" => "Staging of the primary tumor" ] 4 => array:2 [ "identificador" => "sec0080" "titulo" => "Lymph node staging" ] 5 => array:2 [ "identificador" => "sec0090" "titulo" => "Distant staging" ] 6 => array:2 [ "identificador" => "sec0095" "titulo" => "Radiotherapy planning" ] ] ] 8 => array:2 [ "identificador" => "sec0105" "titulo" => "Evaluation of response and detection of recurrence" ] 9 => array:2 [ "identificador" => "sec0110" "titulo" => "Conflict of interest" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2018-03-21" "fechaAceptado" => "2018-08-29" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1067760" "palabras" => array:6 [ 0 => "Cervical cancer" 1 => "18F-FDG PET/CT" 2 => "Staging" 3 => "Radiotherapy planning" 4 => "Response" 5 => "Recurrence" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1067761" "palabras" => array:6 [ 0 => "Cáncer de cérvix" 1 => "PET/TC con 18F-FDG" 2 => "Estadificación" 3 => "Planificación de radioterapia" 4 => "Respuesta" 5 => "Recidiva" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "Cervical cancer is the second most common gynecological cancer worldwide. In locally advanced cervical cancer, 18F-FDG PET/CT has become important in the initial staging, particularly in the detection of nodal and distant metastasis, aspects with treatment implications and prognostic value.The aims of this study were to review the role of 18F-FDG PET/CT in uterine cervical cancer, according to the guidelines of the main scientific institutions (FIGO, NCCN, SEGO, SEOM, ESGO, and ESMO) and its diagnostic accuracy compared to conventional radiological techniques, as well as to review the acquisition protocol and its utility in radiotherapy planning, response assessment and detection of recurrence." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "El cáncer de cérvix es el segundo cáncer ginecológico en frecuencia a nivel mundial. En tumores localmente avanzados la PET/TC con 18F-FDG tiene un papel relevante en la detección de enfermedad ganglionar y a distancia, factores en los que se basan el tratamiento y el pronóstico de estas pacientes.El objetivo de este trabajo es revisar las indicaciones actuales de la PET/TC con 18F-FDG en el cáncer de cérvix para cada una de las principales sociedades científicas (FIGO, NCCN, SEGO, SEOM, ESGO, ESMO) y la rentabilidad diagnóstica de la prueba comparada con las técnicas radiológicas convencionales, así como el procedimiento y su utilidad en la planificación de la radioterapia, en la valoración de respuesta y en la detección de recidiva." ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Caresia-Aróztegui AP, Delgado-Bolton RC, Alvarez-Ruiz S, del Puig Cózar-Santiago M, Orcajo-Rincon J, de Arcocha-Torres M, et al. PET/TC con 18F-FDG en cáncer de cérvix localmente avanzado. Rev Esp Med Nucl Imagen Mol. 2019;38:59–68." ] ] "multimedia" => array:15 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1504 "Ancho" => 2833 "Tamanyo" => 292063 ] ] "descripcion" => array:1 [ "en" => "A 54-year-old patient with locally advanced cervical cancer (by physical examination for suspicion of FIGO IIIB). The MR shows a voluminous primary tumor (maximum diameter of 61.9mm) with probable invasion of the posterior wall of the urinary bladder (A). PET/CT with 18F-FDG shows elevated uptake in the primary tumor (SUVmax 16.3) in contact with the posterior wall of the bladder (B), and pelvic (C) and retroperitoneal lymph node involvement (D). The hypermetabolic oropharyngeal image corresponds to mucositis by Candida and the paracardiac metabolic activity at the gastroesophageal junction due to esophagitis." ] ] 1 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array: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="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">TNM \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">FIGO \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Description \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Tx \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">The primary tumor cannot be evaluated. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">T0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">There is no evidence of the primary tumor. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Tis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Carcinoma in situ (pre-invasive carcinoma). \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">T1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">I \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Cervical carcinoma confined to the uterus (extension to the body should not be taken into account). \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">T1a \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Invasive carcinoma only diagnosed by microscopy. Invasion of the stroma with a maximum depth of 5mm and a horizontal extension ≤7mm. Compromise of the vascular, venous or lymphatic component does not affect the classification. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">T1a1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ia1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Stromal invasion ≤3mm in depth and ≤7mm in horizontal extension. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">T1a2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ia2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Stromal invasion >3mm and ≤5mm in depth with a horizontal extension ≤7mm. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">T1b \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">IB \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Clinically visible lesion confined to the neck of the uterus or microscopic lesions greater than T1a/IA2. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">T1b1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">IB1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Clinically visible lesion ≤4cm at greatest diameter. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">T1b2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">IB2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Clinically visible lesion >4cm at greatest diameter. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">T2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">II \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Cervical carcinoma invading beyond the uterus but not compromising the pelvic wall or the lower third of the vagina. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">T2a \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">IIA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Tumor without invasion to the parametrials. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">T2a1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">IIA1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Clinically visible lesion ≤4cm at greatest diameter. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">T2a2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">IIA2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Clinically visible lesion >4cm at greatest diameter. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">T2b \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">IIB \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Tumor with invasion of the parametrials without reaching the pelvic wall. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">T3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">III \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Tumor extending to the pelvic wall and/or compromising the lower third of the vagina and/or causes hydronephrosis or alteration of renal function. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">T3a \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">IIIA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">The tumor compromises the lower third of the vagina, without extension to the pelvic wall. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">T3b \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">IIIB \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">The tumor extends to the pelvic wall and/or causes hydronephrosis or alteration of renal function. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">T4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">IVA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">The tumor invades the mucosa of the bladder or the rectum and/or extends beyond the pelvic (bullous edema is not sufficient to classify a tumor as T4). \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1937621.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Classification of cervical cancer according to FIGO and the equivalent TNM.<a class="elsevierStyleCrossRefs" href="#bib0305">2,3</a>" ] ] 2 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Stage 0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">93% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Stage IA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">93% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Stage IB \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">80% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Stage IIA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">63% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Stage IIB \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">58% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Stage IIIA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">35% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Stage IIIB \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">32% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Stage IVA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">16% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Stage IVB \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">15% \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1937622.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Rate of survival by stages according to the AJCC. Statistics based on information collected by the National Database on cancer from 2000 and 2002. These survival statistics are available for the 2010 classification system.<a class="elsevierStyleCrossRefs" href="#bib0315">4,5</a>" ] ] 3 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at3" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array: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=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Lymph node involvement: most significant prognostic factor \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Tumor size <4cm \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Invasion of lymphovascular space (LVI) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Depth of invasion of cervical stroma \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1937618.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Presurgical factors of bad prognosis in cervical cancer." ] ] 4 => array:8 [ "identificador" => "tbl0020" "etiqueta" => "Table 4" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at4" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array: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=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">FIGO 2009<a class="elsevierStyleCrossRef" href="#bib0360">13</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">-Recommended: chest X-ray, skeletal X-ray, pyelography/cystography/proctoscopy (if invasion suspected). \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">-Accepted: CT or MR if clinically indicated (not essential). \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">NCCN 2017<a class="elsevierStyleCrossRef" href="#bib0345">10</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Stage I \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Without preservation of fertility. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">-Recommended: chest X-ray. In case of pathologic findings a CT without contrast should be performed. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">-Recommended: Pelvic MR with contrast if ≥IB2. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">-Recommended: PET/CT or thoracic-abdominal-pelvic CT. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Preservation of fertility. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">-Recommended: chest X-ray. In case of pathological findings a CT without contrast should be performed. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">-Recommended: pelvic MR with contrast (preferential option). Transvaginal ultrasound if MR is contraindicated. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Stages II–IV \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">-Recommended: PET/CT (preferential option) or thoracic-abdominal-pelvic CT to rule out metastasis. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">-Recommended: pelvic MR with contrast (preferential option). Transvaginal ultrasound if MR contraindicated. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">-On incidental finding of a cervical neoplasm in a hysterectomy, consider PET/CT or thoracic-abdominal-pelvic CT (for distant dissemination) and MR (for eventual residual pelvic disease). \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">-NCCN recommends sentinel lymph node in tumors ≤2cm. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">-Other studies may be optional on suspicion of metastasis. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">-PET/CT alternative to lymph node dissection or if positive in order to rule out M1. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">-In stages IB2 or LACC, PET/CT, MR or CT are recommended for RT planning. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ESMO 2017<a class="elsevierStyleCrossRef" href="#bib0330">7</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Recommended: chest X-ray, pyelography. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Optional (does not alter stage). \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• CT to detect pathological adenopathies. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• MR to determine tumor size, the grade of stromal invasion, parametrial involvement and vaginal/uterine extension. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• RT planning based on surgical stage or PET/CT. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ESGO 2017<a class="elsevierStyleCrossRef" href="#bib0350">11</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Primary tumor: \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• MR recommended to evaluate pelvic extension of the disease and to guide treatment. Transrectal or tansvaginal ultrasonography is optional if performed by experts. Invasion of the bladder or the rectum should be histologically confirmed. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Cytoscopy and rectoscopy can be considered to achieve a biopsy in the case of suspicious lesions in the MR or US. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Evaluation of disease extension: \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• PET/CT or thoracic-abdominal CT recommended to evaluate lymph node or distant involvement in LACC or in patients with early diseae but with suspicion of lymph node involvement by imaging study. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• PET/CT is recommended for RT planning in LACC prior to radical CHT treatment. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">SEOM 2015<a class="elsevierStyleCrossRef" href="#bib0365">14</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Recommendations: \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Chest X-ray, pyelography and cystoscopy and proctoscopy (in the case of invasion of the bladder or rectum) to better define the FIGO. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">The remaining imaging techniques do not modify the stage, are optional in early stages but are recommended in LACC. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Pelvic MR is the preferential imaging technique for treatment planning, especially in patients who wish to preserve fertility. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• PET/CT is used to determine lymph node involvement and distant dissemination. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">SEGO 2013<a class="elsevierStyleCrossRef" href="#bib0305">2</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Optional: PET/CT and MR in initial staging in stages IB2, IIA2, III, and IV as alternative to lymph node dissection or in the case of a positive lymph node dissection to rule out M1. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Optional: sentinel lymph node in study protocols in stage II1. \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1937619.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Diagnostic procedures recocmmended by the different scientific socieites." ] ] 5 => array:8 [ "identificador" => "tbl0025" "etiqueta" => "Table 5" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at5" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "Source: adapted from Grant et al.<a class="elsevierStyleCrossRef" href="#bib0335">8</a> and Liu et al.<a class="elsevierStyleCrossRef" href="#bib0465">34</a>" "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-with-role" title="table-head ; entry_with_role_rowhead " align="left" valign="top" scope="col">Author \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">No. of studies \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">PET or PET/CT</th><th class="td" title="table-head " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">CT</th><th class="td" title="table-head " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">MR</th></tr><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Sensitivity (%) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Specificity (%) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Sensitivity (%) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Specificity (%) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Sensitivity (%) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Specificity (%) \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Chol and cols. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">41 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">82 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">95 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">50 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">92 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">56 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">91 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Bipat and cols. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">57 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">43 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">60 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Havrilesky and cols. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">84 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">95 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">47 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">54 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">96 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Kang and cols. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">34 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">97 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Selman and cols. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">72 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">75 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">98 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">58 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">92 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">56 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">93 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Liu and cols. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">67 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">66 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">97 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">57 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">91 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">54 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">93 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Liu and cols. Locally advanced \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">83 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">91 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">88 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">90 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1937620.png" ] ] ] ] "descripcion" => array:1 [ "en" => "List of metaanalyses of cervical cancer with the diagnostic yield of PET or PET/CT, CT, and MR in the evaluation of lymph node involvement." ] ] 6 => array:5 [ "identificador" => "tb0005" "tipo" => "MULTIMEDIATEXTO" "mostrarFloat" => false "mostrarDisplay" => true "texto" => array:1 [ "textoCompleto" => "Teaching pointSquamous type cervical cancer is a disease found in sexually active women and is directly associated with high risk human papillomavirus (HPV)." ] ] 7 => array:5 [ "identificador" => "tb0010" "tipo" => "MULTIMEDIATEXTO" "mostrarFloat" => false "mostrarDisplay" => true "texto" => array:1 [ "textoCompleto" => "Teaching pointThe International Federation of Gynecology and Obstetric (FIGO) considers that the initial staging of cervical cancer should be based on clinical manifestations, according to a physical examination performed by an experienced gynecologist and under anesthesia, if necessary." ] ] 8 => array:5 [ "identificador" => "tb0015" "tipo" => "MULTIMEDIATEXTO" "mostrarFloat" => false "mostrarDisplay" => true "texto" => array:1 [ "textoCompleto" => "Teaching pointLocally advanced cervical cancer (LACC) is defined as a tumor of greater than 4cm in size or a tumor which invades tissues beyond the uterus (FIGO greater than or equal to IIA2)." ] ] 9 => array:5 [ "identificador" => "tb0020" "tipo" => "MULTIMEDIATEXTO" "mostrarFloat" => false "mostrarDisplay" => true "texto" => array:1 [ "textoCompleto" => "Teaching pointLymph node involvement is the most significant factor of bad prognosis in cervical cancer, although it is not included in the FIGO classification." ] ] 10 => array:5 [ "identificador" => "tb0025" "tipo" => "MULTIMEDIATEXTO" "mostrarFloat" => false "mostrarDisplay" => true "texto" => array:1 [ "textoCompleto" => "Teaching pointThe incidence of paraaortic lymph node tumor involvement is greater according to an increase in FIGO stage (29% in stage III and 36% in stage IV) and influences treatment decisions (if present, the radiotherapy field should be extended to this region) and patient survival." ] ] 11 => array:5 [ "identificador" => "tb0030" "tipo" => "MULTIMEDIATEXTO" "mostrarFloat" => false "mostrarDisplay" => true "texto" => array:1 [ "textoCompleto" => "Teaching pointMR is the technique of choice in local evaluation of disease, providing information related to tumor size, extension to the uterine corpus, involvement of the parametrium and neighboring organs as well as pelvic lymph node status." ] ] 12 => array:5 [ "identificador" => "tb0035" "tipo" => "MULTIMEDIATEXTO" "mostrarFloat" => false "mostrarDisplay" => true "texto" => array:1 [ "textoCompleto" => "Teaching pointThe value of PET/CT with 18F-FDG in cervical cancer lies in the detection of regional lymph node involvement and distant metastasis. 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18F-FDG PET/CT in locally advanced cervical cancer: A review

PET/TC con 18F-FDG en cáncer de cérvix localmente avanzado

A.P. Caresia-Arózteguia,

Corresponding author

paulacaresia@gmail.com

Corresponding author.

, R.C. Delgado-Boltonb, S. Alvarez-Ruizc, M. del Puig Cózar-Santiagod, J. Orcajo-Rincone, M. de Arcocha-Torresf, M.J. García-Vellosog, on behalf of the Grupo de Trabajo de Oncología de la Sociedad Española de Medicina Nuclear e Imagen Molecular

a Servicio de Medicina Nuclear, UDIAT, Hospital de Sabadell, Corporació Sanitària Parc Taulí, Sabadell, Barcelona, Spain

b Departamento de Diagnóstico por Imagen y Medicina Nuclear, Hospital San Pedro-Centro de Investigación Biomédica de La Rioja (CIBIR), Logroño, Spain

c Servicio de Medicina Nuclear, Hospital Universitario Miguel Servet, Zaragoza, Spain

d Servicio de Medicina Nuclear, ERESA, Hospital General Universitario de Valencia, Valencia, Spain

e Servicio de Medicina Nuclear, Hospital General Universitario Gregorio Marañón, Madrid, Spain

f Unidad de Radiofarmacia, Hospital Universitario Marqués de Valdecilla, Santander, Spain

g Servicio de Medicina Nuclear, Clínica Universidad de Navarra, Pamplona, Spain

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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Cervical cancer is the second most frequent gynecological cancer in women worldwide and around 85&#37; of the cases are found in developing countries&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">1</span></a> The incidence of cervical cancer in Spain is within the lower range in Europe&#44; having a mean age-adjusted rate &#40;AAR&#41; of 6&#46;3<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>100&#44;000<span class="elsevierStyleHsp" style=""></span>women&#47;year&#44; with 1948 new cases diagnosed each year&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">This AAR places cervical cancer in eleventh position among women of all ages but in second position in the group of women from 15 to 44 years of age&#44; which has a rate of 7&#46;7 that is surpassed by only breast cancer with a rate of 32&#46;4&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">In Spain&#44; death by cervical cancer occurs in 1&#46;9<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>100&#44;000 women-year&#59; that is&#44; 712 cases per year&#46; This makes cervical cancer the fifteenth cause of death by tumors in women of any age but third among those from 15 to 44 years of age&#44; with an AAR of 1&#46;2 behind breast and lung cancer&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">2</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Squamous carcinoma is the most frequent histological type&#44; representing 85&#8211;95&#37; of the cases&#46; Adenocarcinoma is the second most frequent histological type followed by adenosquamous and neuroendocrine carcinoma&#46; Squamous cervical cancer is found among sexually active women and is directly associated with high risk human papillomavirus &#40;HPV&#41; infection&#46; A premalignant precursor squamous intraepitheal lesion &#40;SIL&#41; initially develops&#44; and then a cervical intraepithelial neoplasm &#40;CIN&#41; is established&#46; HPV types 16 and 18 are the cause of 70&#8211;75&#37; of cervical cancers&#46;<elsevierMultimedia ident="tb0005"></elsevierMultimedia></p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Disease extension</span><p id="par0030" class="elsevierStylePara elsevierViewall">Since most patients with cervical cancer are diagnosed in developing countries with limited access to diagnostic imaging techniques&#44; the International Federation of Gynecology and Obstetrics &#40;FIGO&#41; considers that the initial staging of cervical cancer should be based on clinical manifestations&#44; according to a physical examination performed by an experienced gynecologist and under anesthesia&#44; if necessary&#46;<elsevierMultimedia ident="tb0010"></elsevierMultimedia></p><p id="par0040" class="elsevierStylePara elsevierViewall">The last version of the FIGO classification made in 2009 includes a FIGO classification by stages which takes the following into account&#58; tumor size&#44; vaginal or parametrial involvement&#44; extension to the bladder&#47;rectum and distant extension&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">3</span></a> The initial FIGO stage conditions patient treatment and prognosis and does not change with the histopathological results after surgery or with recurrence&#46; However&#44; for years the American Joint Committee of Cancer &#40;AJCC&#41; has recommended reporting the FIGO stage and the histopathological tumor&#44; node&#44; metastasis &#40;pTNM&#41;&#46; The last version of the AJCC TNM is from 2017&#46;<a class="elsevierStyleCrossRefs" href="#bib0315"><span class="elsevierStyleSup">4&#44;5</span></a><a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows the FIGO classification&#44; and <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> shows survival by stages&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">Tumors less than 4<span class="elsevierStyleHsp" style=""></span>cm in size are defined as early disease&#46; To the contrary&#44; locally advanced cervical cancer &#40;LACC&#41; involves a tumor of greater than or equal to 4<span class="elsevierStyleHsp" style=""></span>cm in size &#40;FIGO greater than or equal to IIA2&#41;&#46; Several studies have compared the initial FIGO stage &#40;clinical manifestations&#41; with the TNM classification after surgery&#46; It is known that in small tumors or early disease the clinical stage agrees with the histopathological results &#40;&#62;85&#37; in stages IA and IB1&#41;&#46; However&#44; this concordance becomes progressively lower according to the increase in tumor size&#44; being 35&#37; in IIA and 21&#37; in FIGO IIB tumors&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">6</span></a><elsevierMultimedia ident="tb0015"></elsevierMultimedia></p><p id="par0055" class="elsevierStylePara elsevierViewall">Another aspect to take into account&#44; despite being somewhat controversial&#44; is the histological type&#44; since this may be a predictive factor of survival&#46; Although some studies have not found differences in the survival between patients with adenocarcinoma and squamous carcinoma&#44; most studies report that adenocarcinoma carries a worse prognosis&#44; with 10&#8211;20&#37; of differences in the overall survival at 5 years&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">7</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">Lymph node involvement is the most significant factor of bad prognosis in cervical cancer&#44; although it is not included in the FIGO classification&#46; <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> shows the factors of bad prognosis&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">2</span></a><elsevierMultimedia ident="tb0020"></elsevierMultimedia></p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">The dissemination pattern of cervical cancer begins at the squamo-columnar junction&#44; growing spherically from there and invading the cervical stroma and the parametrium&#44; the uterus and the vagina&#46; The disease spreads through three lymphatic pathways&#58; the external iliac route&#44; the hypogastric region toward the internal iliac chain and finally the presacral region toward the uterus-sacrum ligament&#46; These three routes drain to the common iliac region and then to the retroperitoneal paraaortic lymph nodes&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">8</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">The AJCC classification recognizes regional adenopathies as those localized in the pelvic region&#46; The 2017 edition of the AJCC classification also includes adenopathies located in the retroperitoneal paraaortic region which were considered as stage M1 in the previous 2010 classification&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">4</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">The incidence of paraaortic lymph node tumor involvement is greater according to an increase in FIGO stage&#46; In their meta-analysis&#44; Smits et al&#46;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">9</span></a> showed that involvement of this lymph node territory is presented in 11&#37; of patients in stage Ib2&#44; in 13&#37; in stage IIA&#44; in 16&#37; in stage IIB&#44; in 29&#37; in stage III and in 36&#37; in stage IV&#46; It should be taken into account that paraaortic lymph node involvement influences the treatment and the tendency to recurrence&#44; and therefore&#44; is of prognostic value&#46; The 5-year survival of patients treated without lymph node involvement is 95&#37; and is less than 80&#37; in women with pelvic lymph node involvement&#46; However&#44; if the lymph nodes in the common iliac or paraaortic regions are affected&#44; the 5-year survival is less than 40&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">6</span></a><elsevierMultimedia ident="tb0025"></elsevierMultimedia></p><p id="par0090" class="elsevierStylePara elsevierViewall">Once the paraaortic region is involved&#44; cervical cancer spreads to the supraclavicular region achieving the stage of distant metastasis &#40;M1&#41;&#46; The presence of extraabdominal lymph node disease is infrequent&#46; Only 8&#8211;12&#37; of the patients present metastasis beyond the regional lymph nodes at the time of diagnosis&#46; Hematogenous dissemination &#40;M1&#41; is even less frequent&#44; being of approximately 5&#37; and may affect the lungs&#44; the liver&#44; the bones and the peritoneum&#46; Although distant metastasis may be presented in any FIGO stage&#44; it is improbable in cases without pelvic lymph node involvement&#46;<a class="elsevierStyleCrossRefs" href="#bib0315"><span class="elsevierStyleSup">4&#44;8</span></a> Nonetheless&#44; it is essential to know the presence of distant metastasis since in these cases the treatment becomes palliative and survival is precarious&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">2</span></a></p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Treatment</span><p id="par0095" class="elsevierStylePara elsevierViewall">The treatment of cervical cancer is surgical in patients with a tumor confined within the upper cervix and vagina&#46; In tumors &#62;IA1 with lympovascular invasion or a higher stage&#44; pelvic lymph node dissection is indicated in order to evaluate lymph node infiltration&#46; It is in this latter group of patients that the use of the laparascopic sentinel lymph node technique might be of interest with the aim of advancing toward less aggressive approaches&#46;<a class="elsevierStyleCrossRefs" href="#bib0305"><span class="elsevierStyleSup">2&#44;10</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">Patients with stages IB2 or IIA can be treated with surgery or with the combination of chemotherapy &#40;CHT&#41; and radiotherapy &#40;RT&#41;&#46; In patients with LACC &#40;stage greater than IIA2&#41;&#44; treatment involves the combination of CHT and concomitant RT&#46; At present&#44; the standard CHT schedule is cisplatin &#40;CDDP&#41; 40<span class="elsevierStyleHsp" style=""></span>mg&#47;m<span class="elsevierStyleSup">2</span> weekly during 6 weeks&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">2</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">It is important to highlight the value of the detection of paraaortic lymph node involvement&#44; because when it is present&#44; it is recommended to extend the RT field to the retroperitoneal region&#46; In the case of distant metastasis&#44; the alternatives are palliative CHT and RT&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Brachytherapy is indicated in patients who are not candidates for surgery&#46; This technique usually has two approaches&#58; one intrauterine component and another vaginal&#46; Brachytherapy is also used post-hysterectomy in patients with positive or close margins&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">10</span></a></p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Initial staging</span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Clinical guidelines</span><p id="par0115" class="elsevierStylePara elsevierViewall">According to FIGO&#44; the initial staging should be based on the clinical manifestations&#44; by examination and colposcopy &#40;with sedation is necesssary&#41; in order to obtain adequate biopsy tissue&#46; FIGO recommends completing the study with a chest radiography&#44; intravenous pyelography&#44; cystoscopy and proctosigmoidoscopy &#40;on suspicion of rectal or vesical extension&#41;&#46; The classification makes it clear that other diagnostic procedures can be used for comparative purposes but not to determine treatment&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">On the other hand&#44; the guidelines of the principal international societies such as the National Comprehensive Cancer Network &#40;NCCN&#41;&#44; the European Society for Medical Oncology &#40;ESMO&#41;&#44; the European Society of Gynaecological Oncology &#40;ESGO&#41;&#44; the Spanish Society of Medical Oncology &#40;SEOM&#41;&#44; and the Spanish Society of Gynecological Oncology &#40;SEGO&#41; accept the performance of lymph node dissection in LACC to determine lymph node status and state that there is insufficient evidence for paraaortic lymph node dissection to be replaced by imaging techniques&#46;<a class="elsevierStyleCrossRefs" href="#bib0305"><span class="elsevierStyleSup">2&#44;7&#44;10&#44;11</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">According to the ESMO&#44; imaging techniques are not able to detect small sized lymph node metastasis in early disease &#40;T1a&#44; T1b1&#44; T2a1&#41;&#44; and surgical staging is more reliable for both the prognosis and to establish the most adequate treatment to be implemented&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">7</span></a> In a study of 555 patients carried out by the Gynecologic Oncology Group &#40;GOG&#41; which retrospectively evaluated the GOG 85&#44; GOG 120 and GOG 165 clinical trials&#44; it was shown that patients undergoing paraaortic lymph node dissection had a better survival than patients who had undergone staging by imaging techniques &#40;lymphography&#44; computerized tomography &#91;CT&#93; or magnetic resonance &#91;MR&#93;&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0345"><span class="elsevierStyleSup">10&#44;12</span></a> However&#44; there is controversy regarding the use of pelvic and paraaortic lymph node dissection&#46; On one hand&#44; the surgical approach seems to be more accurate for diagnosing lymph node involvement&#44; but on the other hand&#44; this approach has a greater morbimortality and delays the initiation of CHT-RT treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">6</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">Currently&#44; CT&#44; MR&#44; positron emission tomography &#40;PET&#41;&#47;CT with <span class="elsevierStyleSup">18</span>F-fluorodeoxyglucose &#40;FDG&#41; and surgical staging are used in both Europe and the United States for staging and treatment decision making&#46; <a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a> provides a summary of the recommendations regarding the diagnostic techniques recommended by the different scientific societies &#8211; FIGO&#44; NCCN&#44; ESMO&#44; ESGO&#44; SEOM&#44; SEGO&#46;<a class="elsevierStyleCrossRefs" href="#bib0305"><span class="elsevierStyleSup">2&#44;7&#44;10&#44;11&#44;13&#44;14</span></a> MR presents the greatest spatial resolution in soft tissues and therefore provides the highest diagnostic yield with respect to local disease extension&#46; This imaging technique provides information on tumor size&#44; extension toward the uterine corpus&#44; involvement of the parametrium and neighboring organs as well as pelvic lymph node status&#46; FIGO therefore recognizes the utility of MR and accepts it use for staging of cervical cancer&#44; if available&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0135" class="elsevierStylePara elsevierViewall">MR has a very important role in the placement of brachytherapy instruments and also in the evaluation of response&#46;<elsevierMultimedia ident="tb0030"></elsevierMultimedia></p><p id="par0145" class="elsevierStylePara elsevierViewall">In LACC it is important to rule out the presence of lymph node and distant metastases&#46; CT has classically been used for this&#46; However&#44; up to 24&#37; of women with negative CT results present histological lymph node involvement since the threshold for lymph node detection normally used with this technique is 10<span class="elsevierStyleHsp" style=""></span>mm&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">The first studies on initial staging with PET with <span class="elsevierStyleSup">18</span>F-FDG in cervical cancer showed a low diagnostic yield&#44; but the results were improved with multimodality PET&#47;CT&#44; which obtained a better diagnostic yield than with the two techniques of CT and PET separately&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">PET&#47;CT with <span class="elsevierStyleSup">18</span>F-FDG</span><p id="par0155" class="elsevierStylePara elsevierViewall">The value of PET&#47;CT with <span class="elsevierStyleSup">18</span>F-FDG in cervical cancer lies in the detection of regional lymph node involvement and distant metastasis&#46;<a class="elsevierStyleCrossRefs" href="#bib0330"><span class="elsevierStyleSup">7&#44;10&#44;15&#44;16</span></a> Indeed&#44; the use of PET&#47;CT for the initial staging modifies the therapeutic management in 10&#8211;32&#37; of the cases in patients with cervical cancer because it is able to detect paraaortic adenopathies which are not identified by other techniques as well as distant metastasis and other additional findings such as second neoplasms&#46;<a class="elsevierStyleCrossRefs" href="#bib0380"><span class="elsevierStyleSup">17&#8211;20</span></a><elsevierMultimedia ident="tb0035"></elsevierMultimedia></p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Study protocol</span><p id="par0165" class="elsevierStylePara elsevierViewall">As defined by the guidelines of action of the European Association of Nuclear Medicine &#40;EANM&#41;&#44; the protocol for the acquisition of PET&#47;CT with <span class="elsevierStyleSup">18</span>F-FDG in oncology indicates the need for a minimum fasting period of 6<span class="elsevierStyleHsp" style=""></span>h&#44; adequate hydration and glycemia less than 200<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&#46; The standard acquisition includes from the orbital-meatal line to the middle third of the femur in a caudal-cranial direction and recommends the acquisition of images with an empty bladder&#46;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">21</span></a></p><p id="par0170" class="elsevierStylePara elsevierViewall">Since these patients are usually of reproductive age it is important to register the data of the last menstruation since it may be useful to adequately interpret the presence of functional cysts which may be hypermetabolic during ovulation or the usual diffuse endometrial hypermetabolism during menstruation&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">When PET&#47;CT is aimed at the planning of RT&#44; it is important to perform the acquisition with a flat table using immobilization material&#44; if available&#44; to facilitate the fusion of images with the simulator or to do the planning directly on the PET&#47;CT images&#46;<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">22</span></a> Patient position is essential&#44; and it is recommended to tattoo three points on the skin &#40;right&#44; left and ventral side&#41; as a reference to situate the laser of the PET&#47;CT equipment and reproduce the position at the time of treatment&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">It is recommended to use oral and intravenous iodine contrast&#46; In the case of allergy&#44; it is possible to consider pre-medication for the intravenous iodine contrast&#46; An alternative to the use of oral contrast is to use water as a negative contrast&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall">In patients with gynecological tumors&#44; and especially in cervical cancer&#44; correct hydration is fundamental&#46; It may be interesting to perform a manuever which helps to differentiate the urinary excretion of FDG in the ureters in retroperitoneal or pelvic disease&#46; These manuevers include&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">&#8226;</span><p id="par0190" class="elsevierStylePara elsevierViewall">Administration of a diuretic 1<span class="elsevierStyleHsp" style=""></span>h before the acquisition to force urinary elimination of the radiotracer&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">&#8226;</span><p id="par0195" class="elsevierStylePara elsevierViewall">Administration of an intravenous contrast in a split bolus&#46; In the case of administering 120<span class="elsevierStyleHsp" style=""></span>ml of contrast&#44; 40<span class="elsevierStyleHsp" style=""></span>ml are initially injected&#44; and the remaining 80<span class="elsevierStyleHsp" style=""></span>ml are administered 9<span class="elsevierStyleHsp" style=""></span>min later&#46; Then&#44; 50<span class="elsevierStyleHsp" style=""></span>s after the last injection&#44; the CT acquisition is started&#46; This manuever obtains images with iodine contrast in the excretory phase &#40;urinary tract&#41; and in the portal phase in the remainder of the body&#46;<a class="elsevierStyleCrossRefs" href="#bib0410"><span class="elsevierStyleSup">23&#44;24</span></a></p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">&#8226;</span><p id="par0200" class="elsevierStylePara elsevierViewall">Delayed PET imaging&#44; which is especially important in doubtful findings&#44; movement artifacts or on suspicion of peritoneal disease&#46; It also allows the acquisition of images of the pelvis with the bladder in different stages of repletion in patients who are candidates to treatment with RT&#46;</p></li></ul></p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Staging of the primary tumor</span><p id="par0205" class="elsevierStylePara elsevierViewall">Although it is possible to determine tumor size with PET&#47;CT&#44; this is not an indication in cervical cancer&#46; It has been demonstrated that the grade of metabolic activity of the primary tumor is related to the histological type&#46; Squamous tumors present greater metabolism than adenocarcinomas&#44; and poorly differentiated tumors also present significantly greater metabolic activity than tumors which are well differentiated&#46;<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">25</span></a></p><p id="par0210" class="elsevierStylePara elsevierViewall">An elevated standardized uptake value &#40;SUVmax&#41; of the primary tumor is a prognostic factor and implies a worse overall survival &#40;OS&#41;&#44; greater tumor aggressiveness and a high probability of lymph node involvement&#46;<a class="elsevierStyleCrossRefs" href="#bib0425"><span class="elsevierStyleSup">26&#44;27</span></a> The heterogeneity of the basal intratumoral metabolism of the primary tumor&#44; calculated by segmentation in the PET&#47;CT&#44; is able to predict not only the risk of lymph node involvement at diagnosis but also worse response to treatment&#44; and therefore&#44; a greater risk of recurrence&#46;<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">28</span></a></p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Lymph node staging</span><p id="par0215" class="elsevierStylePara elsevierViewall">It is vitally important to determine the presence of lymph node involvement in LACC in order to develop the therapeutic management&#46; Paraaortic lymph node dissection is considered as option &#40;although the primary tumor is not resected&#41;&#44; but the possibility of amplifying the RT field to the paraaortic region is also accepted in the case of high suspicion of paraaortic lymph node involvement by imaging and the impossibility of histological confirmation &#40;SEGO&#44; NCCN&#44; ESGO&#44; ESMO&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0330"><span class="elsevierStyleSup">7&#44;10&#44;11&#44;14</span></a> This subject remains under debate&#44; since in most countries PET&#47;CT with <span class="elsevierStyleSup">18</span>F-FDG is routinely used for lymph node staging while other countries prefer to perform paraaortic lymph node dissection &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0220" class="elsevierStylePara elsevierViewall">There are several meta-analyses on the capacity of detection of tumoral adenopathies in cervical cancer&#44; with a great variability in the results&#46; The differences in the values of the diagnostic yield of PET&#47;CT with <span class="elsevierStyleSup">18</span>F-FDG are based on the probability of lymph node involvement and the size of the metastases in the samples analyzed&#46; Therefore&#44; in series with LACC &#40;sensitivity of 83&#37; &#91;62&#8211;94&#93; and a specificity of 91&#37; &#91;85&#8211;94&#93;&#41;&#44; the values markedly improve versus series with early cervical cancer &#40;sensitivity of 53&#8211;73&#37; and specificity of 90&#8211;97&#37;&#41;&#46; The review by Grant et al&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">8</span></a> &#40;<a class="elsevierStyleCrossRef" href="#tbl0025">Table 5</a>&#41; present the results of 5 metaanalyses in list form and shows that compared with CT and MR&#44; PET or PET&#47;CT is the technique with the best accumulated values of sensitivity and specificity in lymph node detection&#46;<a class="elsevierStyleCrossRefs" href="#bib0375"><span class="elsevierStyleSup">16&#44;29&#8211;33</span></a></p><elsevierMultimedia ident="tbl0025"></elsevierMultimedia><p id="par0225" class="elsevierStylePara elsevierViewall">Liu et al&#46;<a class="elsevierStyleCrossRef" href="#bib0465"><span class="elsevierStyleSup">34</span></a> recently published the latest meta-analysis based on 67 studies&#44; comparing the capacity of detecting lymph node involvement by MR &#40;including diffusion sequences&#41;&#44; PET and PET&#47;CT and CT&#46; This meta-analysis also included articles of patients with early disease &#40;<a class="elsevierStyleCrossRef" href="#tbl0025">Table 5</a>&#41;&#46; The results show that to detect lymph node involvement the use of these techniques makes sense in LACC&#44; and that MR with diffusion &#40;not considered in previous meta-analyses&#44; with a sensitivity of 87&#37; and specificity of 83&#37;&#41; seems to be the most sensitive technique&#44; while PET and PET&#47;CT are more specific&#46; On the other hand&#44; the same meta-analysis showed what was referred to in some previous reports&#44; and that is that the diagnostic yield of PET&#47;CT is greater in the paraaortic region &#40;accumulated sensitivity of 81&#37;&#44; accumulated specificity of 98&#37;&#41; compared to the pelvic region &#40;accumulated sensitivity of 55&#37;&#44; accumulated specificity of 97&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0465"><span class="elsevierStyleSup">34</span></a></p><p id="par0230" class="elsevierStylePara elsevierViewall">All the series with LACC coincide in that PET&#47;CT presents an elevated positive predictive value &#40;PPV&#41; and negative predictive value &#40;NPV&#41; for the detection of paraaortic lymph node involvement&#46;<a class="elsevierStyleCrossRefs" href="#bib0340"><span class="elsevierStyleSup">9&#44;35</span></a> False negative results are due to metastases of less than 5<span class="elsevierStyleHsp" style=""></span>mm in size and are lower with PET&#47;CT &#40;6&#8211;15&#37;&#41; than with MR &#40;9&#8211;35&#37;&#41;&#46; In 2013&#44; a randomized clinical study of 237 patients with LACC was published&#46; All the patients had negative PET&#47;CT results and paraaortic lymph node dissection with a mean follow-up of 30 months&#46; In this study the rate of false negative PET&#47;CT results was 12&#37;&#44; being similar to that of other series&#46; The authors highlighted that the number and size of the lymph node metastases were important since the survival of patients with lymph node metastasis &#60;5<span class="elsevierStyleHsp" style=""></span>mm or who presented a single paraaortic adenopathy was similar to that of patients without lymph node involvement&#46; On the other hand&#44; the patients with lymph node metastases &#62;5<span class="elsevierStyleHsp" style=""></span>mm presented a significantly worse prognosis&#46;<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">35</span></a> The doubt which arises from these studies is whether the survival is really related to the combination of lymph node dissection and RT or to the biology of the tumor itself&#46; An interesting data provided by the prospective randomized study carried out by Tsai et al&#46;<a class="elsevierStyleCrossRef" href="#bib0475"><span class="elsevierStyleSup">36</span></a> with the same objective was that the performance of PET&#47;CT had no impact on the OS but did have an impact on the reduction of the risk of extrapelvic relapse&#46;</p><p id="par0235" class="elsevierStylePara elsevierViewall">Grigsby<a class="elsevierStyleCrossRef" href="#bib0480"><span class="elsevierStyleSup">37</span></a> demonstrated that PET&#47;CT is better than CT for the detection of lymph node involvement and that the lymph node stage determined by PET with <span class="elsevierStyleSup">18</span>F-FDG is the most significant independent pretreatment prognostic factor of progression-free survival &#40;PFS&#41; and OS&#46; Regarding the data of pelvic lymph node involvement&#44; the disease-free survival at 2 years was 84&#37; in patients with negative CT and PET results&#44; 64&#37; with negative CT results and positive PET&#47;CT results and 48&#37; in cases with positive PET and PET&#47;CT results&#46; For the paraaortic lymph node region&#44; the disease-free survival at 2 years was 78&#37; if the CT and PET were negative&#44; 31&#37; if the CT was negative but the PET&#47;CT was positive&#44; and 14&#37; if the results of both studies were positive &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;0001&#41;&#46; No patient with supraclavicular adenopathies survived at 2 years&#46; These results suggest an opportunity to cure these patients with paraaortic lymph node involvement by PET which is not detected by CT&#46;</p><p id="par0240" class="elsevierStylePara elsevierViewall">A study by Kidd et al&#46;<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">29</span></a> in 560 patients with FIGO stages IA1 to IVB &#40;treated according to the FIGO stage with exclusive surgery&#44; surgery and post-operative RT or CHT-RT&#41; showed that 47&#37; of the patients present lymph node involvement in the diagnosis by PET&#47;CT similar to the lymph node involvement reported in historical surgical series&#46; All the patients with positive PET results presented pelvic lymph node involvement&#44; 35&#37; in the paraaortic region and 12&#37; in the supraclavicular region&#46; The patients with paraaortic involvement also had pelvic involvement&#46; The patients with positive PET results had a significantly worse prognosis than those with negative PET results &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#41;&#46; Taking into account the categories of the study &#40;non lymph node involvement&#44; pelvic&#44; paraaortic and supraclavicular involvement&#41;&#44; the patients with the most distant metastatic lymph node disease of the primary tumor presented a worse survival&#46; The greater the distance of lymph node involvement the greater the probability of recurrence&#44; with hazard ratio values &#40;index of risk&#41; of the pelvis of 2&#46;4 &#40;confidence interval &#91;CI&#93; 95&#37;&#58; 1&#46;6&#8211;3&#46;5&#41;&#44; 5&#46;9 for paraaortic lymph nodes &#40;CI 95&#37;&#58; 3&#46;8&#8211;9&#46;1&#41; and 30 for supraclavicular lymph nodes &#40;CI 95&#37;&#58; 17&#8211;55&#41;&#46;</p><p id="par0245" class="elsevierStylePara elsevierViewall">It is interesting to note that according to Yen et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0485"><span class="elsevierStyleSup">38</span></a> the grade of metabolic activity of the retroperitoneal lymph nodes is relevant in patients with cervical cancer&#46; The results of their study show that paraaortic adenopathies with a SUVmax value &#8805;3&#46;3<span class="elsevierStyleHsp" style=""></span>g&#47;ml are significantly associated with a worse survival&#44; a greater tendency to recurrence and a higher mortality&#46;<elsevierMultimedia ident="tb0040"></elsevierMultimedia></p><p id="par0255" class="elsevierStylePara elsevierViewall">In view of this problematic&#44; we must wait for the results of the multicenter Lymphadenectomy In Locally Advanced cervical Cancer Study &#40;LILACS&#41; clinical trial which includes patients with stage IB2-IVA disease who are candidates for CHT-RT treatment&#46; The objective of this study is to compare the survival of patients undergoing a PET&#47;CT extension study with patients undergoing paraaortic lymph node dissection&#46;<a class="elsevierStyleCrossRef" href="#bib0490"><span class="elsevierStyleSup">39</span></a></p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Distant staging</span><p id="par0260" class="elsevierStylePara elsevierViewall">There are few studies aimed principally at the detection of distant metastasis by PET&#47;CT in cervical cancer&#46;</p><p id="par0265" class="elsevierStylePara elsevierViewall">PET&#47;CT is better than CT in the detection of metastatic disease&#44; especially in the form of extraabdominal tumoral adenopathies&#46; As mentioned previously&#44; adenopathies in the supraclavicular region are quite a usual localization of distant metastasis in patients with cervical cancer&#46; Both the study by Tran et al&#46;<a class="elsevierStyleCrossRef" href="#bib0495"><span class="elsevierStyleSup">40</span></a> including 186 patients diagnosed with cervical cancer and that of Grigsby et al&#46;<a class="elsevierStyleCrossRefs" href="#bib0480"><span class="elsevierStyleSup">37&#44;41</span></a> including a series of 101 patients found 8&#37; of patients with metastatic supraclavicular adenopathies in PET&#47;CT&#44; with all being histologically confirmed&#46;</p><p id="par0270" class="elsevierStylePara elsevierViewall">The last study published to data on this question is a retrospective review of the data of the multicenter ACRIN6671&#47;GOG0233 clinical trial&#46; The main aim of this study was to detect lymph node involvement with PET&#47;CT in patients with cervical cancer&#46; This randomized double-blind study included 153 patients with LACC &#40;FIGO IB<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>25&#44; IIA<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>6&#44; IIB<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>8&#44; III<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#41;&#46; M1 metastasis was confirmed by biopsy in all the patients in whom this was suspected &#40;21 metastatic patients&#44; 13&#46;7&#37; of the total&#41;&#44; and all underwent a control CT at 6 months after surgery&#46; Preoperative PET&#47;CT to detect metastasis of LACC demonstrated a sensitivity of 54&#46;8&#37;&#44; a specificity of 97&#46;7&#37;&#44; a PPV of 79&#46;3&#37; and a NPV of 93&#46;1&#37;&#46;<a class="elsevierStyleCrossRefs" href="#bib0505"><span class="elsevierStyleSup">42&#44;43</span></a></p><p id="par0275" class="elsevierStylePara elsevierViewall">In another study&#44; Mittra et al&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">20</span></a> included patients in more advanced stages of the disease &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>30 patients&#44; FIGO Ib2<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#44; IIA<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>4&#44; IIB<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>10&#44; III<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>12&#44; IVA<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#41; and reported a higher percentage of detection of metastasis in the PET&#47;CT &#40;50&#37;&#41;&#44; with a sensitivity of 96&#37;&#44; specificity of 95&#37;&#44; a PPV of 96&#37;&#44; NPV of 95&#37; and diagnostic efficacy of 95&#37;&#46;</p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Radiotherapy planning</span><p id="par0280" class="elsevierStylePara elsevierViewall">Although surgery is indicated in small tumors&#44; patients with stage IB2-IVA tumors with extension to the parametrials and pelvic organs or with pelvic and paraaortic lymph node disease are treated with CHT-RT&#46;<a class="elsevierStyleCrossRef" href="#bib0515"><span class="elsevierStyleSup">44</span></a> Imaging techniques are necessary in the RT treatment planning for cervical cancer&#44; and it is recommended that radiologists and nuclear medicine physicians work together with the specialists in radiotherapy because a multidisplinary approach optimizes the process of delimitation of the disease to be treated&#46;<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">22</span></a> The classical definition of tumor volumes is based on the CT gross tumor volume &#40;GTV&#41;&#44; but the concepts of metabolic tumor volume &#40;MTV&#41; or biological tumor volume &#40;BTV&#41; defined in the molecular PET&#47;CT imaging have recently been incorporated&#46;<a class="elsevierStyleCrossRef" href="#bib0520"><span class="elsevierStyleSup">45</span></a> In the histological subtypes with an elevated avidity for FDG&#44; PET&#47;CT presents a better diagnostic yield than CT and MR for the detection of metastatic pelvic and retroperitoneal lymph nodes&#44; because it is able to identify infiltrated lymph nodes smaller than 1<span class="elsevierStyleHsp" style=""></span>cm&#46; This thereby provides a more accurate definition of the lymph node tumor volume in the RT planning and modifies the patient treatment plans&#44; widening the field to the infiltrated and metabolically active lymph nodes&#44; with a reduction in toxicity to the normal adjacent tissues&#46;<a class="elsevierStyleCrossRef" href="#bib0525"><span class="elsevierStyleSup">46</span></a> The criteria of positivity in the visual interpretation is a focally increased uptake of intensity greater than that of the normal adjacent tissues&#46; It is necessary to know the lymphatic drainage pattern for better interpretation of the findings&#46; PET&#47;CT also has a better yield compared to CT for the detection of distant metastasis&#44; leading to a change in curative treatment with RT to palliative treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0480"><span class="elsevierStyleSup">37</span></a></p><p id="par0285" class="elsevierStylePara elsevierViewall">In patients with LACC the combination of RT with CHT prolongs disease-free survival and reduces the mortality&#46; However&#44; 20&#8211;40&#37; of the patients treated with conventional RT present locoregional relapse&#46;<a class="elsevierStyleCrossRef" href="#bib0530"><span class="elsevierStyleSup">47</span></a> Intensity modulated radiotherapy &#40;IMRT&#41; has achieved better results with less toxicity than conventional RT&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">10</span></a> Esthappan et al&#46;<a class="elsevierStyleCrossRef" href="#bib0535"><span class="elsevierStyleSup">48</span></a> used PET&#47;CT with <span class="elsevierStyleSup">18</span>F-FDG to guide IMRT&#44; modifying the treatment plan in infiltrated paraaortic lymph nodes in the PET&#47;CT &#40;60<span class="elsevierStyleHsp" style=""></span>Gy&#41; versus the dose of 50<span class="elsevierStyleHsp" style=""></span>Gy in paraaortic and pelvic lymph node chains without disease in the PET&#47;CT and achieving more effective treatment of the disease with a reduction in the toxicity to kidneys and the intestine&#46; Kidd et al&#46;<a class="elsevierStyleCrossRef" href="#bib0540"><span class="elsevierStyleSup">49</span></a> performed at study in patients treated with IMRT guided by PET&#47;CT and with conventional RT&#46; The patients treated with IMRT had a better survival and less treatment-related toxicity compared to those receiving treatment with conventional RT&#46;</p><p id="par0290" class="elsevierStylePara elsevierViewall">PET&#47;CT with <span class="elsevierStyleSup">18</span>F-FDG can define the MTV of not only the cervix but also the lymph nodes detected in the pelvis and paraaortic lymph node chains&#46; There are different algorithms for the definition of the isocontour in hypermetabolic lesions&#46; The simplest is a threshold of 40&#37; with respect to the SUVmax and is applicable in tumors with an elevated avidity for FDG&#44; although visual verification and manual optimization are always necessary taking into account clinical findings and other imaging studies&#46; Treatment with platin-based CHT&#44; IMRT and RT boosts in the primary tumor and the lymph node metastases detected has shown to be effective and has an acceptable toxicity&#46;<a class="elsevierStyleCrossRef" href="#bib0545"><span class="elsevierStyleSup">50</span></a> In the study by Lazzari et al&#46;<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">17</span></a> PET&#47;CT with <span class="elsevierStyleSup">18</span>F-FDG changed the lymph node tumoral stage&#44; and thus&#44; the treatment plan with IMRT in 25&#37; of the patients treated with exclusive RT and in 7&#46;7&#37; of those receiving adjuvant IMRT&#46; Nonetheless&#44; these preliminary results are from studies with small sample sizes and without surgical validation&#44; and therefore&#44; prospective multicenter studies are needed to determine the impact of PET on survival&#46;<elsevierMultimedia ident="tb0045"></elsevierMultimedia></p><p id="par0300" class="elsevierStylePara elsevierViewall">PET&#47;CT with <span class="elsevierStyleSup">18</span>F-FDG can also be used in the planning of brachytherapy treatment&#46; Malyapa et al&#46;<a class="elsevierStyleCrossRef" href="#bib0550"><span class="elsevierStyleSup">51</span></a> compared three dimensional &#40;3D&#41; brachytherapy based on PET with two dimensional &#40;2D&#41; brachytherapy and demonstrated that 3D brachytherapy improved the dose received by the tumor and reduced radiation to critical organs&#46; Several studies used MR and PET in brachytherapy planning in patients with cervical cancer and concluded that PET&#47;CT with <span class="elsevierStyleSup">18</span>F-FDG reduces the variability between observers in the determination of tumor volumes&#46;<a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">52</span></a></p><p id="par0305" class="elsevierStylePara elsevierViewall">Although still under investigation&#44; in the future new PET&#47;MR equipment which integrate the windows of both techniques may become the technique of choice for the study of extension and RT planning in patients with cervical cancer&#46;<a class="elsevierStyleCrossRef" href="#bib0560"><span class="elsevierStyleSup">53</span></a></p></span></span><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Evaluation of response and detection of recurrence</span><p id="par0310" class="elsevierStylePara elsevierViewall">After treatment&#44; clinical follow-up is fundamental&#46; Controls including physical examination are recommended every 3 months during the first 2 years&#44; every 6 months the following 3 years and then every year thereafter&#46; According to the guidelines of action of the ESMO&#44; NCCN&#44; ESGO and SEGO&#44; the use of imaging studies &#40;MR&#44; CT or PET&#47;CT&#41; should be based on clinical suspicion for symptomatology of recurrence or metastatic disease&#46;<a class="elsevierStyleCrossRefs" href="#bib0330"><span class="elsevierStyleSup">7&#44;10&#44;11&#44;54</span></a></p><p id="par0315" class="elsevierStylePara elsevierViewall">According to the NCCN&#44; the most in depth guideline in this context&#44; PET&#47;CT is the technique of choice in patients suspected of having local relapse &#40;sensitivity of 86&#37;&#44; specificity of 87&#37;&#41; as well as in patients suspected of presenting metastasis &#40;sensitivity of 90&#37;&#44; specificity of 99&#37;&#41;&#46; The same guidelines emphasize that the recommendation of PET&#47;CT is in patients who have undergone complete radical treatment with FIGO stage Ib2 or greater or who require adjuvant RT or concomitant CHT-RT because of the presence of factors of risk &#40;positive adenopathies&#44; affected parametrium&#44; positive margins or local risk factors&#41; in order to rule out distant metastasis&#46; The guidelines note that PET&#47;CT with intravenous iodine contrast can be used at 3&#8211;6 months after finalizing treatment to evaluate response and attempt to detect patients with localized disease recurrence&#47;persistence who could benefit from curative treatment and exenteration&#46; Nonetheless&#44; the best time to carry out an evaluation of response in these patients is still under debate&#46;<a class="elsevierStyleCrossRefs" href="#bib0345"><span class="elsevierStyleSup">10&#44;54&#8211;56</span></a></p><p id="par0320" class="elsevierStylePara elsevierViewall">Apart from the guidelines&#44; it has been reported that during follow-up PET&#47;CT can detect recurrence in asymptomatic patients who are candidates to additional treatment with intention to cure&#44; with a 3-year survival of 59&#8211;86&#37;&#46;<a class="elsevierStyleCrossRefs" href="#bib0565"><span class="elsevierStyleSup">54&#44;57</span></a> The conclusions of two cost-effective analyses published on the recurrence of cervical cancer differ&#46; On one hand&#44; the study by Auguste et al&#46;<a class="elsevierStyleCrossRef" href="#bib0585"><span class="elsevierStyleSup">58</span></a> in treated patients in different FIGO stages compared two models&#58; one conventional &#40;MR or CT or both during follow-up&#41; and another which adds PET&#47;CT to the conventional study without taking into account patient symptoms&#46; The authors concluded that PET&#47;CT is not cost-effective in this context&#46; On the other hand&#44; the more recent cost-effective analysis published by Phippen et al&#46;<a class="elsevierStyleCrossRef" href="#bib0590"><span class="elsevierStyleSup">59</span></a> focused on locally advanced tumors treated with CHT-RT compared conventional follow-up with physical examination and radiological studies only in the case of suspicion of relapse &#40;without PET&#47;CT&#41; with a second model in which PET&#47;CT was added at 3 months after finalizing treatment&#46; They concluded that while the overall cost was higher&#44; the PET&#47;CT strategy to detect the presence of a viable tumor and select patients who might benefit from hysterectomy obtained a lower rate of recurrence and was&#44; therefore&#44; cost-effective&#46;</p><p id="par0325" class="elsevierStylePara elsevierViewall">Further studies are likely needed to determine the most accurate time to carry out PET&#47;CT in the evaluation of treatment and cost-effective analyses to demonstrate benefits in symptomatic and asymptomatic patients&#46;</p></span><span id="sec0110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Conflict of interest</span><p id="par0330" class="elsevierStylePara elsevierViewall">The authors declare no conflict of interest&#46;</p></span></span>"
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        1 => array:2 [
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          "titulo" => "Introduction"
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        5 => array:2 [
          "identificador" => "sec0015"
          "titulo" => "Disease extension"
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        6 => array:2 [
          "identificador" => "sec0040"
          "titulo" => "Treatment"
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        7 => array:3 [
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          "titulo" => "Initial staging"
          "secciones" => array:7 [
            0 => array:2 [
              "identificador" => "sec0050"
              "titulo" => "Clinical guidelines"
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            1 => array:2 [
              "identificador" => "sec0060"
              "titulo" => "PET&#47;CT with F-FDG"
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              "identificador" => "sec0070"
              "titulo" => "Study protocol"
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              "identificador" => "sec0075"
              "titulo" => "Staging of the primary tumor"
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              "identificador" => "sec0080"
              "titulo" => "Lymph node staging"
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              "identificador" => "sec0090"
              "titulo" => "Distant staging"
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              "identificador" => "sec0095"
              "titulo" => "Radiotherapy planning"
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          "titulo" => "References"
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    "fechaRecibido" => "2018-03-21"
    "fechaAceptado" => "2018-08-29"
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          "clase" => "keyword"
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            0 => "Cervical cancer"
            1 => "<span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT"
            2 => "Staging"
            3 => "Radiotherapy planning"
            4 => "Response"
            5 => "Recurrence"
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          "clase" => "keyword"
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          "palabras" => array:6 [
            0 => "C&#225;ncer de c&#233;rvix"
            1 => "PET&#47;TC con <span class="elsevierStyleSup">18</span>F-FDG"
            2 => "Estadificaci&#243;n"
            3 => "Planificaci&#243;n de radioterapia"
            4 => "Respuesta"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Cervical cancer is the second most common gynecological cancer worldwide&#46; In locally advanced cervical cancer&#44; <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT has become important in the initial staging&#44; particularly in the detection of nodal and distant metastasis&#44; aspects with treatment implications and prognostic value&#46;</p><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">The aims of this study were to review the role of <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT in uterine cervical cancer&#44; according to the guidelines of the main scientific institutions &#40;FIGO&#44; NCCN&#44; SEGO&#44; SEOM&#44; ESGO&#44; and ESMO&#41; and its diagnostic accuracy compared to conventional radiological techniques&#44; as well as to review the acquisition protocol and its utility in radiotherapy planning&#44; response assessment and detection of recurrence&#46;</p></span>"
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        "titulo" => "Resumen"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">El c&#225;ncer de c&#233;rvix es el segundo c&#225;ncer ginecol&#243;gico en frecuencia a nivel mundial&#46; En tumores localmente avanzados la PET&#47;TC con <span class="elsevierStyleSup">18</span>F-FDG tiene un papel relevante en la detecci&#243;n de enfermedad ganglionar y a distancia&#44; factores en los que se basan el tratamiento y el pron&#243;stico de estas pacientes&#46;</p><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">El objetivo de este trabajo es revisar las indicaciones actuales de la PET&#47;TC con <span class="elsevierStyleSup">18</span>F-FDG en el c&#225;ncer de c&#233;rvix para cada una de las principales sociedades cient&#237;ficas &#40;FIGO&#44; NCCN&#44; SEGO&#44; SEOM&#44; ESGO&#44; ESMO&#41; y la rentabilidad diagn&#243;stica de la prueba comparada con las t&#233;cnicas radiol&#243;gicas convencionales&#44; as&#237; como el procedimiento y su utilidad en la planificaci&#243;n de la radioterapia&#44; en la valoraci&#243;n de respuesta y en la detecci&#243;n de recidiva&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Caresia-Ar&#243;ztegui AP&#44; Delgado-Bolton RC&#44; Alvarez-Ruiz S&#44; del Puig C&#243;zar-Santiago M&#44; Orcajo-Rincon J&#44; de Arcocha-Torres M&#44; et al&#46; PET&#47;TC con <span class="elsevierStyleSup">18</span>F-FDG en c&#225;ncer de c&#233;rvix localmente avanzado&#46; Rev Esp Med Nucl Imagen Mol&#46; 2019&#59;38&#58;59&#8211;68&#46;</p>"
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          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">A 54-year-old patient with locally advanced cervical cancer &#40;by physical examination for suspicion of FIGO IIIB&#41;&#46; The MR shows a voluminous primary tumor &#40;maximum diameter of 61&#46;9<span class="elsevierStyleHsp" style=""></span>mm&#41; with probable invasion of the posterior wall of the urinary bladder &#40;A&#41;&#46; PET&#47;CT with <span class="elsevierStyleSup">18</span>F-FDG shows elevated uptake in the primary tumor &#40;SUVmax 16&#46;3&#41; in contact with the posterior wall of the bladder &#40;B&#41;&#44; and pelvic &#40;C&#41; and retroperitoneal lymph node involvement &#40;D&#41;&#46; The hypermetabolic oropharyngeal image corresponds to mucositis by <span class="elsevierStyleItalic">Candida</span> and the paracardiac metabolic activity at the gastroesophageal junction due to esophagitis&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">TNM&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">FIGO&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Description&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Tx&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">The primary tumor cannot be evaluated&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">T0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">There is no evidence of the primary tumor&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Tis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Carcinoma <span class="elsevierStyleItalic">in situ</span> &#40;pre-invasive carcinoma&#41;&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">T1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">I&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Cervical carcinoma confined to the uterus &#40;extension to the body should not be taken into account&#41;&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">T1a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Invasive carcinoma only diagnosed by microscopy&#46; Invasion of the stroma with a maximum depth of 5<span class="elsevierStyleHsp" style=""></span>mm and a horizontal extension &#8804;7<span class="elsevierStyleHsp" style=""></span>mm&#46; Compromise of the vascular&#44; venous or lymphatic component does not affect the classification&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">T1a1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Ia1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Stromal invasion &#8804;3<span class="elsevierStyleHsp" style=""></span>mm in depth and &#8804;7<span class="elsevierStyleHsp" style=""></span>mm in horizontal extension&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">T1a2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Ia2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Stromal invasion &#62;3<span class="elsevierStyleHsp" style=""></span>mm and &#8804;5<span class="elsevierStyleHsp" style=""></span>mm in depth with a horizontal extension &#8804;7<span class="elsevierStyleHsp" style=""></span>mm&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">T1b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IB&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Clinically visible lesion confined to the neck of the uterus or microscopic lesions greater than T1a&#47;IA2&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">T1b1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IB1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Clinically visible lesion &#8804;4<span class="elsevierStyleHsp" style=""></span>cm at greatest diameter&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">T1b2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IB2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Clinically visible lesion &#62;4<span class="elsevierStyleHsp" style=""></span>cm at greatest diameter&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">T2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Cervical carcinoma invading beyond the uterus but not compromising the pelvic wall or the lower third of the vagina&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">T2a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IIA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Tumor without invasion to the parametrials&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">T2a1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IIA1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Clinically visible lesion &#8804;4<span class="elsevierStyleHsp" style=""></span>cm at greatest diameter&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">T2a2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IIA2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Clinically visible lesion &#62;4<span class="elsevierStyleHsp" style=""></span>cm at greatest diameter&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">T2b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IIB&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Tumor with invasion of the parametrials without reaching the pelvic wall&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">T3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">III&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Tumor extending to the pelvic wall and&#47;or compromising the lower third of the vagina and&#47;or causes hydronephrosis or alteration of renal function&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">T3a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IIIA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">The tumor compromises the lower third of the vagina&#44; without extension to the pelvic wall&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">T3b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IIIB&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">The tumor extends to the pelvic wall and&#47;or causes hydronephrosis or alteration of renal function&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">T4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IVA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">The tumor invades the mucosa of the bladder or the rectum and&#47;or extends beyond the pelvic &#40;bullous edema is not sufficient to classify a tumor as T4&#41;&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab1937621.png"
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Classification of cervical cancer according to FIGO and the equivalent TNM&#46;<a class="elsevierStyleCrossRefs" href="#bib0305"><span class="elsevierStyleSup">2&#44;3</span></a></p>"
        ]
      ]
      2 => array:8 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at2"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Stage 0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">93&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Stage IA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">93&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Stage IB&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">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="table-entry ; entry_with_role_rowhead " align="left" valign="top">Stage IIA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">63&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Stage IIB&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">58&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Stage IIIA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">35&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Stage IIIB&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">32&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Stage IVA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">16&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Stage IVB&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">15&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab1937622.png"
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Rate of survival by stages according to the AJCC&#46; Statistics based on information collected by the National Database on cancer from 2000 and 2002&#46; These survival statistics are available for the 2010 classification system&#46;<a class="elsevierStyleCrossRefs" href="#bib0315"><span class="elsevierStyleSup">4&#44;5</span></a></p>"
        ]
      ]
      3 => array:8 [
        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at3"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array: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=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Lymph node involvement&#58; most significant prognostic factor&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Tumor size &#60;4<span class="elsevierStyleHsp" style=""></span>cm&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Invasion of lymphovascular space &#40;LVI&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Depth of invasion of cervical stroma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab1937618.png"
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          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Presurgical factors of bad prognosis in cervical cancer&#46;</p>"
        ]
      ]
      4 => array:8 [
        "identificador" => "tbl0020"
        "etiqueta" => "Table 4"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at4"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array: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=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">FIGO 2009<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">13</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Recommended&#58; chest X-ray&#44; skeletal X-ray&#44; pyelography&#47;cystography&#47;proctoscopy &#40;if invasion suspected&#41;&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Accepted&#58; CT or MR if clinically indicated &#40;not essential&#41;&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">NCCN 2017<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">10</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Stage I&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Without preservation of fertility&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Recommended&#58; chest X-ray&#46; In case of pathologic findings a CT without contrast should be performed&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Recommended&#58; Pelvic MR with contrast if &#8805;IB2&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Recommended&#58; PET&#47;CT or thoracic-abdominal-pelvic CT&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Preservation of fertility&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Recommended&#58; chest X-ray&#46; In case of pathological findings a CT without contrast should be performed&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Recommended&#58; pelvic MR with contrast &#40;preferential option&#41;&#46; Transvaginal ultrasound if MR is contraindicated&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Stages II&#8211;IV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Recommended&#58; PET&#47;CT &#40;preferential option&#41; or thoracic-abdominal-pelvic CT to rule out metastasis&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Recommended&#58; pelvic MR with contrast &#40;preferential option&#41;&#46; Transvaginal ultrasound if MR contraindicated&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-On incidental finding of a cervical neoplasm in a hysterectomy&#44; consider PET&#47;CT or thoracic-abdominal-pelvic CT &#40;for distant dissemination&#41; and MR &#40;for eventual residual pelvic disease&#41;&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-NCCN recommends sentinel lymph node in tumors &#8804;2<span class="elsevierStyleHsp" style=""></span>cm&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Other studies may be optional on suspicion of metastasis&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-PET&#47;CT alternative to lymph node dissection or if positive in order to rule out M1&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-In stages IB2 or LACC&#44; PET&#47;CT&#44; MR or CT are recommended for RT planning&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ESMO 2017<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">7</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Recommended&#58; chest X-ray&#44; pyelography&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Optional &#40;does not alter stage&#41;&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>&#8226; CT to detect pathological adenopathies&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>&#8226; MR to determine tumor size&#44; the grade of stromal invasion&#44; parametrial involvement and vaginal&#47;uterine extension&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>&#8226; RT planning based on surgical stage or PET&#47;CT&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ESGO 2017<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">11</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Primary tumor&#58;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>&#8226; MR recommended to evaluate pelvic extension of the disease and to guide treatment&#46; Transrectal or tansvaginal ultrasonography is optional if performed by experts&#46; Invasion of the bladder or the rectum should be histologically confirmed&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>&#8226; Cytoscopy and rectoscopy can be considered to achieve a biopsy in the case of suspicious lesions in the MR or US&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Evaluation of disease extension&#58;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>&#8226; PET&#47;CT or thoracic-abdominal CT recommended to evaluate lymph node or distant involvement in LACC or in patients with early diseae but with suspicion of lymph node involvement by imaging study&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>&#8226; PET&#47;CT is recommended for RT planning in LACC prior to radical CHT treatment&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">SEOM 2015<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">14</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Recommendations&#58;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Chest X-ray&#44; pyelography and cystoscopy and proctoscopy &#40;in the case of invasion of the bladder or rectum&#41; to better define the FIGO&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">The remaining imaging techniques do not modify the stage&#44; are optional in early stages but are recommended in LACC&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>&#8226; Pelvic MR is the preferential imaging technique for treatment planning&#44; especially in patients who wish to preserve fertility&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>&#8226; PET&#47;CT is used to determine lymph node involvement and distant dissemination&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">SEGO 2013<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">2</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Optional&#58; PET&#47;CT and MR in initial staging in stages IB2&#44; IIA2&#44; III&#44; and IV as alternative to lymph node dissection or in the case of a positive lymph node dissection to rule out M1&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Optional&#58; sentinel lymph node in study protocols in stage II1&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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        "descripcion" => array:1 [
          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Diagnostic procedures recocmmended by the different scientific socieites&#46;</p>"
        ]
      ]
      5 => array:8 [
        "identificador" => "tbl0025"
        "etiqueta" => "Table 5"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at5"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Source</span>&#58; adapted from Grant et al&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">8</span></a> and Liu et al&#46;<a class="elsevierStyleCrossRef" href="#bib0465"><span class="elsevierStyleSup">34</span></a></p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td-with-role" title="table-head ; entry_with_role_rowhead " align="left" valign="top" scope="col">Author&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col">No&#46; of studies&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">PET or PET&#47;CT</th><th class="td" title="table-head  " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">CT</th><th class="td" title="table-head  " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">MR</th></tr><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Sensitivity &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Specificity &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Sensitivity &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Specificity &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Sensitivity &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Specificity &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Chol and cols&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">41&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">82&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">95&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">50&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">92&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">56&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">91&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Bipat and cols&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">57&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">43&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">60&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Havrilesky and cols&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">84&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">95&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">47&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">54&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">96&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Kang and cols&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">34&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">97&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Selman and cols&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">72&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">75&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">98&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">58&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">92&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">56&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">93&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Liu and cols&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">67&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">66&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">97&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">57&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">91&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">54&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">93&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Liu and cols&#46;<br>Locally advanced&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">83&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">91&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">88&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">90&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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        "descripcion" => array:1 [
          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">List of metaanalyses of cervical cancer with the diagnostic yield of PET or PET&#47;CT&#44; CT&#44; and MR in the evaluation of lymph node involvement&#46;</p>"
        ]
      ]
      6 => array:5 [
        "identificador" => "tb0005"
        "tipo" => "MULTIMEDIATEXTO"
        "mostrarFloat" => false
        "mostrarDisplay" => true
        "texto" => array:1 [
          "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Teaching point</span><p id="par0025" class="elsevierStylePara elsevierViewall">Squamous type cervical cancer is a disease found in sexually active women and is directly associated with high risk human papillomavirus &#40;HPV&#41;&#46;</p></span></span>"
        ]
      ]
      7 => array:5 [
        "identificador" => "tb0010"
        "tipo" => "MULTIMEDIATEXTO"
        "mostrarFloat" => false
        "mostrarDisplay" => true
        "texto" => array:1 [
          "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Teaching point</span><p id="par0035" class="elsevierStylePara elsevierViewall">The International Federation of Gynecology and Obstetric &#40;FIGO&#41; considers that the initial staging of cervical cancer should be based on clinical manifestations&#44; according to a physical examination performed by an experienced gynecologist and under anesthesia&#44; if necessary&#46;</p></span></span>"
        ]
      ]
      8 => array:5 [
        "identificador" => "tb0015"
        "tipo" => "MULTIMEDIATEXTO"
        "mostrarFloat" => false
        "mostrarDisplay" => true
        "texto" => array:1 [
          "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Teaching point</span><p id="par0050" class="elsevierStylePara elsevierViewall">Locally advanced cervical cancer &#40;LACC&#41; is defined as a tumor of greater than 4<span class="elsevierStyleHsp" style=""></span>cm in size or a tumor which invades tissues beyond the uterus &#40;FIGO greater than or equal to IIA2&#41;&#46;</p></span></span>"
        ]
      ]
      9 => array:5 [
        "identificador" => "tb0020"
        "tipo" => "MULTIMEDIATEXTO"
        "mostrarFloat" => false
        "mostrarDisplay" => true
        "texto" => array:1 [
          "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Teaching point</span><p id="par0065" class="elsevierStylePara elsevierViewall">Lymph node involvement is the most significant factor of bad prognosis in cervical cancer&#44; although it is not included in the FIGO classification&#46;</p></span></span>"
        ]
      ]
      10 => array:5 [
        "identificador" => "tb0025"
        "tipo" => "MULTIMEDIATEXTO"
        "mostrarFloat" => false
        "mostrarDisplay" => true
        "texto" => array:1 [
          "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Teaching point</span><p id="par0085" class="elsevierStylePara elsevierViewall">The incidence of paraaortic lymph node tumor involvement is greater according to an increase in FIGO stage &#40;29&#37; in stage III and 36&#37; in stage IV&#41; and influences treatment decisions &#40;if present&#44; the radiotherapy field should be extended to this region&#41; and patient survival&#46;</p></span></span>"
        ]
      ]
      11 => array:5 [
        "identificador" => "tb0030"
        "tipo" => "MULTIMEDIATEXTO"
        "mostrarFloat" => false
        "mostrarDisplay" => true
        "texto" => array:1 [
          "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Teaching point</span><p id="par0140" class="elsevierStylePara elsevierViewall">MR is the technique of choice in local evaluation of disease&#44; providing information related to tumor size&#44; extension to the uterine corpus&#44; involvement of the parametrium and neighboring organs as well as pelvic lymph node status&#46;</p></span></span>"
        ]
      ]
      12 => array:5 [
        "identificador" => "tb0035"
        "tipo" => "MULTIMEDIATEXTO"
        "mostrarFloat" => false
        "mostrarDisplay" => true
        "texto" => array:1 [
          "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Teaching point</span><p id="par0160" class="elsevierStylePara elsevierViewall">The value of PET&#47;CT with <span class="elsevierStyleSup">18</span>F-FDG in cervical cancer lies in the detection of regional lymph node involvement and distant metastasis&#46; In the initial staging the therapeutic management is modified in 10&#8211;32&#37; of the cases&#46;</p></span></span>"
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        "identificador" => "tb0040"
        "tipo" => "MULTIMEDIATEXTO"
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        "identificador" => "tb0045"
        "tipo" => "MULTIMEDIATEXTO"
        "mostrarFloat" => false
        "mostrarDisplay" => true
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          "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Teaching point</span><p id="par0295" class="elsevierStylePara elsevierViewall">PET&#47;CT with <span class="elsevierStyleSup">18</span>F-FDG contributes to the definition of tumor volume of the cervix and extension of the treatment plan to the lymph nodes detected in the pelvis and paraaortic lymph nodes chains&#46;</p></span></span>"
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    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
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          "identificador" => "bibs0015"
          "bibliografiaReferencia" => array:59 [
            0 => array:3 [
              "identificador" => "bib0300"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "International Agency for Research on Cancer&#46; World Health Organization&#46; Globocan 2012&#58; estimated cancer incidence&#44; mortality and prevalence worldwide&#46; Fact Sheets by Population&#44; 2012&#46; Available at&#58; <a id="intr0010" class="elsevierStyleInterRef" href="http://globocan.iarc.fr/Pages/fact_sheets_population.aspx">http&#58;&#47;&#47;globocan&#46;iarc&#46;fr&#47;Pages&#47;fact&#95;sheets&#95;population&#46;aspx</a> &#91;accessed August 2018&#93;&#46;"
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0305"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "Oncogu&#237;a SEGO&#58; C&#225;ncer de Cuello Uterino 2013&#46; Gu&#237;as de pr&#225;ctica cl&#237;nica en c&#225;ncer ginecol&#243;gico y mamario&#46; Publicaciones SEGO&#44; 2013&#46; Available at&#58; <a id="intr0015" class="elsevierStyleInterRef" href="http://studylib.es/doc/8289846/gu%C3%ADas-de-pr%C3%A1ctica-cl%C3%ADnica-en-c%C3%A1ncer-ginecol%C3%B3gico-y-mamario">http&#58;&#47;&#47;studylib&#46;es&#47;doc&#47;8289846&#47;gu&#37;C3&#37;ADas-de-pr&#37;C3&#37;A1ctica-cl&#37;C3&#37;ADnica-en-c&#37;C3&#37;A1ncer-ginecol&#37;C3&#37;B3gico-y-mamario</a> &#91;accessed August 2018&#93;&#46;"
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0310"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Revised FIGO staging for carcinoma of the vulva&#44; cervix&#44; and endometrium"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "S&#46; Pecorelli"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Int J Gynaecol Obstet"
                        "fecha" => "2009"
                        "volumen" => "105"
                        "paginaInicial" => "103"
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