Salvage Surgery in the Treatment of Local Recurrences of Nasopharyngeal Carcinomas

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Treatment of NC recurrences is still complex and early detection of recurrence is vital for any salvage therapy to be effective.<a class="elsevierStyleCrossRef" href="#bib0175">5</a> Available therapeutic options include re-irradiation, chemotherapy and surgery. The role of chemotherapy is principally reserved for palliative care for those patients who are not suitable candidates for re-irradiation or surgery.<a class="elsevierStyleCrossRef" href="#bib0180">6</a> Re-irradiation achieves low local control rates<a class="elsevierStyleCrossRef" href="#bib0185">7</a> and complications are frequent and serious.<a class="elsevierStyleCrossRef" href="#bib0190">8</a> As a result, surgery presents a reasonable option when recurrence may be resected. Local control rates are satisfactory and morbidity is lower to high dose re-irradiation.<a class="elsevierStyleCrossRef" href="#bib0195">9</a>Several surgical approaches have been described for this type of tumour,<a class="elsevierStyleCrossRef" href="#bib0200">10</a> but no consensus has been reached regarding which is the best technique for obtaining complete resection of the tumour with the lowest rate of morbidity. The optimum approach will depend on the size and location of the tumour. Standard approaches used have been anterior external (transpalatal, transmaxillary, transmandibular, facial translocation) and lateral (subtemporal-periauricular).<a class="elsevierStyleCrossRefs" href="#bib0195">9,11</a> These approaches result in significant morbidity, as they interfere with a previously irradiated region. An attempt has been made to reduce the morbidity rates associated with open surgery by the progressive use of minimally invasive endoscopic approaches.<a class="elsevierStyleCrossRefs" href="#bib0210">12,13</a>The aim of this study is to present our experience in the surgical treatment of local recurrences of NC, mainly focussing on the type of surgical approach used.MethodThe surgical record of the otorhinolaryngology department of our hospital was reviewed from 1994 until 2014 and data was collected from the medical histories relating to patients with a diagnosis of local recurrence of NC.Data collection was based on the review of medical histories, with recording of data on age, gender, prior treatments, spread and staging of tumour, mean time from treatment of primary tumour to recurrence, surgical approach, complications and follow-up.The study population comprised 20 patients who had undergone surgery. Open surgery was used on the first 12 patients (60%),as has already been described for our group<a class="elsevierStyleCrossRef" href="#bib0220">14</a>: six patients underwent anterior facial translocation surgery and six subtemporal-preauricular surgery.<a class="elsevierStyleCrossRefs" href="#bib0180">6,11</a> Since 2002, due to the standardisation of extended endoscopic endonasal approaches for the treatment of these tumours, the 8 patients (40%) underwent endoscopic endonasal transpterigoid surgery (Castelnuovo type 3 resection).<a class="elsevierStyleCrossRef" href="#bib0225">15</a>Radiologic studies were performed on all patients prior to surgery using computerised tomography CT and magnetic resonance (MR) imaging. Patients also had a chest X-ray, an abdominal scan, a bone scan in the cases of open surgery<a class="elsevierStyleCrossRef" href="#bib0220">14</a> and CT, MR and positron emission tomography (PET) in the cases of endoscopic surgery. Only patients with no presence of distance metastasis were operated on. Statistical data analysis was performed with the SPSS programme for Windows version 11.0.ResultsThe sample comprised 14 male patients and 6 Female patients with a mean age at time of intervention of 54 years (range 42–73). In accordance with the histopathological classification of the World Health Organisation,<a class="elsevierStyleCrossRef" href="#bib0230">16</a> 6 patients presented with stage II tumours and the other 14 with stage III tumours. At initial diagnosis, 7 patients presented with tumours which were classified as T1, 6 as T2, 3 as T3 and 4 asT4, in accordance with the 7th edition of the TNM system of the International Union against Cancer<a class="elsevierStyleCrossRef" href="#bib0235">17</a> (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>For treatment of the primary tumour and cervical nodes all patients received conformal chemotherapy and RT (3D-CRT). The mean dose applied on the nasopharynx was 65.5Gy (range 50–72) and the mean dose received on the cervical nodes was 44Gy (range 32–60).Two months after finalisation of treatment assessment was made of the response through a nasofibroscopic examination and a cervical exploration, together with the performing of CT or MR imaging. This same assessment was performed as follow-up every 3 months for 2 years then every 6 months for 5 years and annually for 10 years after that. In our series, after finalising treatment complete response was obtained in all patients.Local recurrences presented between 7 and 72 months after finalisation of treatment with RT (mean: 33 months). Relapses were diagnosed mainly in advanced stages in the open surgery series and in early stages in the endoscopic series: one patient was staged as rT1, 3 as rT2, 2 as rT3 and 6 as rT4 in the open surgery group whereas in the endoscopic series group 2 patients were staged as rT1, 5 rT2 and one rT3. On diagnosis of local recurrence, none of the patients presented with regional or distance recurrences and all of them had received curative surgery both in the open and endoscopic series.In 3 of the 12 patients who underwent open surgery the surgical margins were microscopically affected by the tumour (one rT4, one rT3 and one rT2). In a fourth patient due to the spread of the tumour to the parasellar region which affected a macroscopically incomplete resection, the administration of adjuvant chemotherapy and stereotaxic RT were required. In the endoscopic series, in all patients (8) free tumour margins were obtained.In the open surgery approach patient series all patients presented with some kind of complication: 5 patients presented with minor complications (trismus, serous otitis, facial paresthesias, haematomas or dehiscences of surgical wound) and 5 suffered from complications classed as moderate which led to permanent sequelae or required further surgery (osteomyelitis, necrosis of the temporal lobe, cerebrospinal fluid fistule. One patient, classified as rT4, as a result of the appearance of an osteomyelitis of the malar bone, developed a fistule between the zygomatic region and the oral cavity which required the addition of a parascapular free flap to close it. Another patient, also classified as rT4, died 18 days following surgery as a result of aspiration pneumonia, after a massive posterior epistaxis during the immediate post operative period. In the endoscopic series 8 patients presented with complications: 7 patients presented a minor complication (serous otitis) whilst one patient (rT1) presented with an osteomyelitis at the base of the skull several months after surgery.Minimum patient follow-up is 3 years. At present 11 patients (55%) are living and disease free; 5 patients underwent open surgery (42%s) and 6, endoscopic surgery (75%s). In the group of patients who underwent open surgery 7 patients died (4 rT4, one rT3 and 2 rT2): in 6 this was a result of the local recurrence of the disease (5) or due to a lymph node recurrence (1) and in one it occurred during the immediate postoperative period (rT4). None of the endoscopically intervened patients had any repeated local relapses. However, 2 patients died, one (rT1) due to radionecrosis and exposure of the skull base and the other due to aspiration pneumonia (rT3), related to palatal incompetence.Overall survival of the patients who underwent open surgery at 3 and 5 years was 53% and 42%, respectively, whereas at 3 and 5 years in the case of those who underwent endoscopic surgery it was 100% and 75% respectively. In the open surgery patient group those cases where tumour free surgical margins were achieved (8) presented with a higher survival rate to those whose margins were affected (4) (P=.0327), all of whom died.DiscussionTherapeutic options for NC relapses include surgery and RT.<a class="elsevierStyleCrossRef" href="#bib0225">15</a> Both achieve acceptable outcomes with regards to local control, especially when recurrences are not very widespread and there is no major intracranial involvement.<a class="elsevierStyleCrossRef" href="#bib0240">18</a>Re-irradiation of local recurrences achieve a survival rate at 5 years which oscillates between 8% and 36%, with a significant correlation between re-irradiation dose and survival. The best local control rates are obtained with accumulated doses of radiation of at least 60Gy.<a class="elsevierStyleCrossRef" href="#bib0195">9</a> The main disadvantage of RT is its low tolerance to the radiation of the nearby structures, resulting in frequent late complications being frequent and varying between 26% and 57% of patients.<a class="elsevierStyleCrossRefs" href="#bib0245">19,20</a> Treatment mortality ranges from 2% to 10% and is mainly due to damage of the central nervous system.<a class="elsevierStyleCrossRef" href="#bib0255">21</a> New radiation techniques such as IMRT, intensity-modulated volumetric arc therapy, tomotherapy and proton-therapy has resulted in high levels of dose in the tumour tissues, preserving adjacent healthy tissues, which increases therapeutic efficacy compared with standard techniques. Several series where IMRT was used have been show to be an excellent local control, with survival figures of >90% after one year and acceptable toxicity levels.<a class="elsevierStyleCrossRefs" href="#bib0160">2,22</a> However, these RT modalities are not always available and in some cases the previous RT doses rule out the use of new irradiation, survival rates after 5 years are yet to be studied.In general, patients with local recurrences are considered not to be candidates for surgery when there is invasion of the cavernous sinus or internal carotid artery or tumours with intracerebral invasion. In the remainder of cases, surgery could be taken into consideration as salvage treatment. Many approaches have been described for the treatment of this type of tumour: transmandibular, Fisch infratemporal fossa approach type C, subtemporal-preauricular, facial translocacion (lateral or anterior), maxillary swing type and transpalatal.<a class="elsevierStyleCrossRefs" href="#bib0265">23,24</a> These open surgery approaches, either in isolation or combined, target the nasopharynx and skull base. However, the rate of complications is high, bearing in mind prior RT. Standardised open surgery approaches have become more limited however and continue to be used for large tumours, particularly when the nasal cavities, the posterior wall of the maxillary sinus, the pterygopalatine fossa or the infratemporal fossa are compromised. The method of choice is facial translocation. Facial translocation with midface degloving and hemicoronal pre-auricular incision has enabled the avoidance of sequelae associated with facial incisions occurring with the standard surgical approach. After RT osteomyellitis is common or the reabsorption of the translocated segment. This is minimised with the use of a temporal flap or performing pediculated maxillary osteotomy to the soft tissue of the cheek.<a class="elsevierStyleCrossRef" href="#bib0275">25</a> The subtemporal pre-auricular approach is used mainly when the tumour has a limited anterior extension but affects the infratemporal fossa, towards the floor of the middle fossa or the parasellar region. This also allows for bilateral access of the cavum. One complication specific to the subtemporal pre-auricular route is trismus, which presented in all patients of our series treated with this approach, although at different stages and was never incapacitating. We should consider that, due to prior RT, the permeability of the deep temporal arteries may be affected, and using the temporal muscle for reconstruction is therefore rejected (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>Disease-free survival after 5 years of the patients in our series who underwent open surgery was 42%, which is within the range described in the literature (20%–44%). Similarly to other series, stage T was an essential factor of prognosis.<a class="elsevierStyleCrossRefs" href="#bib0190">8,12,15,23</a>Endoscopic surgery for the treatment of recurrences of NC was introduced at the beginning of 2000 and after, firstly for the treatment of tumours rT1, rT2 and rT3.<a class="elsevierStyleCrossRef" href="#bib0280">26</a> Endoscopic procedures may now be used in most salvage surgery after local recurrence. Endoscopic approaches enable the targeting of tumours with a more direct exposure and with less handling of the neurovascular structures and the avoidance of osteotomies. Oncological results are similar to those obtained with standard open surgery methods and fragmented resection of tumours does not appear to compromise the oncological outcomes provided that the resection margins are negative. From the patient's viewpoint, the reduction of time in surgery and hospital stay, a lower rate of complications and the absence of facial incision are advantages of endoscopic approaches. With regards to our series: our average time in surgery was 240min, mean hospital stay was 5 days and there were no intraoperative or postoperative complications.The performing of endoscopic nasopharyngectomy is a complex technique due to the proximity of critical neural and vascular structures, and also to the meninges and central nervous system.<a class="elsevierStyleCrossRef" href="#bib0225">15</a> However, endoscopic resection outcomes of these tumours are promising<a class="elsevierStyleCrossRefs" href="#bib0285">27,28</a> and the results of our series are similar to those described by other authors (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>).<a class="elsevierStyleCrossRefs" href="#bib0225">15,16,28</a><elsevierMultimedia ident="tbl0015"></elsevierMultimedia>You et al.<a class="elsevierStyleCrossRef" href="#bib0295">29</a> published a series of 144, in which they compared 72 patients who had undergone endoscopic surgery and 72 patients with IMRT. They concluded that the endoscopic surgery increased overall survival at 5 years (77.1% vs 55.5%; P=.003), increased quality of life (global health status 57.6 vs 29.8; P<.001), reduced post treatment complications (12.5% vs 65.3%; P<.001) and that procedure costs were low (2371.71 vs 11847.80 €; P<.001). Na’ara et al.<a class="elsevierStyleCrossRef" href="#bib0285">27</a> published an analysis with a series of 779 patients (rT1–2: 655 (83%), rT3–4:129 (16.67%), 661 (84.4%) with open surgery approaches and 118 (15.1%) endoscopic approaches. At 5 years, they described an overall survival and a disease-free survival of 58% and 63.4%. In this study, multivariate analysis showed that endoscopic surgery offers better outcomes in T3–rT4 in selected patients and that adjuvant re-irradiation offers an advantage of additional survival over surgery alone. Other authors have achieved a good local control rate with endoscopic surgery in the initial stages of rT1 and rT2 tumours, whilst open surgery is preferred in advanced stages.<a class="elsevierStyleCrossRef" href="#bib0300">30</a> Indication could be cautiously extended to selected rT3 tumours with limited involvement of the skull base. rT4 patients generally present with a repeated local recurrence or die due to metastasis.<a class="elsevierStyleCrossRef" href="#bib0205">11</a> In accordance with these authors, in our endoscopic series, 7 out of the 8 patients were rT1–T2 and only one was rT3, and we therefore agree with the indication for this approach. In extensive recurrences (rT3 and, above all, rT4), in our experience, the performing of facial translocation or a subtemporal pre-auricular<a class="elsevierStyleCrossRef" href="#bib0215">13</a> approach are the ones of choice.ConclusionsAlthough open surgery and endoscopic procedures appear to be equally effective in patients who require surgical salvage, the advantages of the endoscopic skull base approaches include shorter hospital stays, have a lower rate of complications and a better quality of life.Conflict of InterestsThe authors have no conflict of interests to declare relating to this study. We did not receive any financing." "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres1108955" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction and Objectives" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1047840" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1108956" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción y Objetivos" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1047841" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Method" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Conclusions" ] 9 => array:2 [ "identificador" => "sec0030" "titulo" => "Conflict of Interests" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2017-07-26" "fechaAceptado" => "2017-11-21" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1047840" "palabras" => array:4 [ 0 => "Nasopharynx" 1 => "Endoscope" 2 => "Nasopharynx carcinoma" 3 => "Endonasal nasopharyngectomy" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1047841" "palabras" => array:4 [ 0 => "Nasofaringe" 1 => "Endoscopia" 2 => "Carcinoma de nasofaringe" 3 => "Nasofaringectomía endoscópica" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "Introduction and ObjectivesChemoradiotherapy is the treatment of choice for nasopharyngeal carcinoma. Local recurrences are one of the leading causes of death in these patients, and surgical salvage the treatment of choice. Our goal was to evaluate and compare the results of salvage surgery in the treatment of local recurrence of nasopharyngeal carcinomas comparing endoscopic to open approaches. MethodsTwenty patients with local recurrence of nasopharyngeal carcinomas underwent surgery: 12 patients underwent open surgery and 8 endoscopic endonasal transpterygoid nasopharyngectomy. One patient was classified as rT1, three as rT2, two as rT3, and six as rT4 in the group of open approaches; in the endoscopic series, two patients were rT1, five rT2 and one rT3. ResultsIn 3 patients (25%) operated by an open approach (one rT4, one rT3 and one rT2) a complete gross resection was not achieved. Gross total resection was achieved in patients operated by endoscopic surgery. The complication rate in the group operated by an open approach was 92% (five minor complications, five moderate complications, and one serious complication) and in the group that underwent endoscopic surgery all patients had some complication (seven had minor complications and one patient developed a severe complication). Survival at 3 and 5 years was 53% and 42% with the open approach and 100% and 50% with the endoscopic approach, respectively. ConclusionsEndoscopic approaches decrease the morbidity associated with open approaches and allow for favourable oncological control." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction and Objectives" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "Introducción y ObjetivosLa quimiorradioterapia es el tratamiento de elección del carcinoma de nasofaringe. Las recurrencias locales son una de las principales causas de mortalidad en estos pacientes: el rescate quirúrgico o la reirradiación son el tratamiento de elección, según la disponibilidad. El objetivo fue evaluar y comparar los resultados de la cirugía de rescate en el tratamiento de las recidivas locales de los carcinomas nasofaríngeos mediante abordajes abiertos vs. endoscópicos. MétodosVeinte pacientes con recidivas locales de carcinomas nasofaríngeos fueron intervenidos quirúrgicamente: 12 pacientes fueron intervenidos mediante cirugía abierta y 8 mediante un abordaje endoscópico endonasal transpterigoideo. Un paciente fue estadiado como rT1; 3 como rT2; 2 como rT3 y 6 como rT4 en el grupo de abordajes abiertos; en la serie endoscópica, 2 pacientes fueron rT1, 5 fueron rT2 y uno fue rT3. ResultadosEn 3 de los pacientes (25%) intervenidos mediante cirugía abierta (un rT4, un rT3 y un rT2) no se logró una resección macroscópica completa). En el grupo endoscópico la resección fue completa en todos los pacientes. La tasa de complicaciones en el grupo intervenido mediante abordajes abiertos fue del 92% (5 complicaciones leves, 5 complicaciones moderadas y una complicación grave) y en el grupo intervenido mediante endoscopia fue del 100% (7 sufrieron complicaciones leves y un paciente una complicación grave). La supervivencia a los 3 y 5 años fue del 53 y del 42% en el abordaje abierto y del 100 y del 75% en el abordaje endoscópico, respectivamente. ConclusionesLos abordajes endoscópicos disminuyen la morbilidad asociada a los abordajes abiertos y permiten obtener un control oncológico favorable." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción y Objetivos" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Salom MC, López F, Pacheco E, Muñoz G, García-Cabo P, Fernández L, et al. Cirugía de rescate en las recidivas locales del carcinoma de nasofaringe. Acta Otorrinolaringol Esp. 2018;69:339–344." ] ] "multimedia" => array:3 [ 0 => 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="" 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="center" valign="top" scope="col" style="border-bottom: 2px solid black">Open surgery approach (1994–2001) 12 patients \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Endoscopic approach (2002–2014) 8 patients \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " rowspan="2" align="left" valign="top">Gender</td><td class="td" title="table-entry " align="left" valign="top">Males: 9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Males: 5 \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">Females: 3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Females: 3 \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">Age \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">55 years of age (42–71) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">52 years of age (43–73) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="2" align="left" valign="top">Histology (OMS)</td><td class="td" title="table-entry " align="left" valign="top">Stage II: 2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Stage II: 2 \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 III: 10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Stage III: 6 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="4" align="left" valign="top">rT</td><td class="td" title="table-entry " align="left" valign="top">rT1: 1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">rT1: 2 \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">rT2: 3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">rT2: 5 \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">rT3: 2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">rT3: 1 \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">rT4: 6 \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">Surgical time in minutes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">>240 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><240 \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">Intraoperative complications \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="3" align="left" valign="top">Complications</td><td class="td" title="table-entry " align="left" valign="top">Minor 5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Minor 7 \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">Moderate 5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Moderate 0 \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">Severe 2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Severe 1 \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">Hospital stay (days) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">19 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5 \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">Mean follow-up (years) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">>3 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">3 and 5 years survival in % \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">53 and 42 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">100 and 75 \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">Local relapse post treatment in months (mean) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7–72 (33) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7–36 (23) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1897555.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Clinical Characteristics of the Patients." ] ] 1 => 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=""><thead title="thead"><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="center" valign="top" scope="col" style="border-bottom: 2px solid black">Number of cases \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Local control (%) (5 years) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Survival (%) (5 years) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Complications (%) \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">Fee<a class="elsevierStyleCrossRef" href="#bib0195">9</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">37 \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">52 \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></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Vlantis<a class="elsevierStyleCrossRef" href="#bib0270">24</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">79 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">62.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">51.9 \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></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">King<a class="elsevierStyleCrossRef" href="#bib0190">8</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">31 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">53 \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="char" 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">Wei<a class="elsevierStyleCrossRef" href="#bib0175">5</a> \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="char" valign="top">62 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">49 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" 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">Chang<a class="elsevierStyleCrossRef" href="#bib0300">30</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">38 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">60 (3 years) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">73 (3 years) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" 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">Cabanillas<a class="elsevierStyleCrossRef" href="#bib0220">14</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">53 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">42 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">41.6 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1897553.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Open Surgery Series Outcomes." ] ] 2 => 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=""><thead title="thead"><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="center" valign="top" scope="col" style="border-bottom: 2px solid black">Patients \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Staging \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Margins \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Follow-up (months) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Survival \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">Chen<a class="elsevierStyleCrossRef" href="#bib0230">16</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">37 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">rT1N0M0: 17 rT2aN0M0: 4 rT2bN0M0: 14 rT3N0M0: 2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">36 (−) 1 (+) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6–45 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">84% (2 years) \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">Ko<a class="elsevierStyleCrossRef" href="#bib0290">28</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">28 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">rT1N0: 12 rT2aN0: 14 rTaN1: 2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">25 (−) 3 (+) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3–48 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">rT1: 91% (2 years) rT2a: 39% (2 years) \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">Castelnuovo<a class="elsevierStyleCrossRef" href="#bib0225">15</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">rT1: 4 rT2a: 1 rT3: 3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">8 (−) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10–78 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No recurrences \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">Salom \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">rT1: 2 rT2: 5 rT3: 1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">8 (−) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">12–72 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No recurrences \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1897554.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Endoscopic Series Outcomes." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:30 [ 0 => array:3 [ "identificador" => "bib0155" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Overall survival after concurrent cisplatin-radiotherapy compared with radiotherapy alone in locoregionally advanced nasopharyngeal carcinoma" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A.T.C. 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Salvage Surgery in the Treatment of Local Recurrences of Nasopharyngeal Carcinomas

Cirugía de rescate en las recidivas locales del carcinoma de nasofaringe

María Cecilia Salom, Fernando López, Esteban Pacheco, Gabriela Muñoz, Patricia García-Cabo, Laura Fernández, Vanessa Suárez, José Luis Llorente

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llorentependas@telefonica.net

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Unidad de Base de Cráneo, Servicio de Otorrinolaringología, Hospital Universitario Central de Asturias, ISPA, IUOPA, Universidad de Oviedo, CIBERONC, Oviedo (Asturias), Spain

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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Nasopharyngeal carcinoma &#40;NC&#41; is a radiosensitive tumour and radiotherapy &#40;RT&#41; is the first treatment option&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">1</span></a> In initial stages &#40;I and II&#41; the NC is treated with RT while in advanced stages &#40;III and IV&#41; it is treated with concomitant chemoradiotherapy&#46;<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">2&#44;3</span></a> With advances in RT techniques&#44; such as intensity-modulated RT &#40;IMRT&#41; and intensity-modulated volumetric arc therapy and the administration of concomittant chemoradiotherapy&#44; local control rates at five years are between 76&#37; and 91&#37;&#46;<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">3&#44;4</span></a> However&#44; between 20&#37; and 50&#37; of patients develop local recurrences during the 5 years following the appearance of the disease&#44; and this is a major cause of morbidity and mortality&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">5</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">When a local recurrence occurs&#44; salvage treatment must be intensive&#44; as patients who receive salvage treatment have a considerably better overall survival rate than those who do not&#46; Treatment of NC recurrences is still complex and early detection of recurrence is vital for any salvage therapy to be effective&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">5</span></a> Available therapeutic options include re-irradiation&#44; chemotherapy and surgery&#46; The role of chemotherapy is principally reserved for palliative care for those patients who are not suitable candidates for re-irradiation or surgery&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">6</span></a> Re-irradiation achieves low local control rates<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">7</span></a> and complications are frequent and serious&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">8</span></a> As a result&#44; surgery presents a reasonable option when recurrence may be resected&#46; Local control rates are satisfactory and morbidity is lower to high dose re-irradiation&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">9</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Several surgical approaches have been described for this type of tumour&#44;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">10</span></a> but no consensus has been reached regarding which is the best technique for obtaining complete resection of the tumour with the lowest rate of morbidity&#46; The optimum approach will depend on the size and location of the tumour&#46; Standard approaches used have been anterior external &#40;transpalatal&#44; transmaxillary&#44; transmandibular&#44; facial translocation&#41; and lateral &#40;subtemporal-periauricular&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">9&#44;11</span></a> These approaches result in significant morbidity&#44; as they interfere with a previously irradiated region&#46; An attempt has been made to reduce the morbidity rates associated with open surgery by the progressive use of minimally invasive endoscopic approaches&#46;<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">12&#44;13</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">The aim of this study is to present our experience in the surgical treatment of local recurrences of NC&#44; mainly focussing on the type of surgical approach used&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Method</span><p id="par0025" class="elsevierStylePara elsevierViewall">The surgical record of the otorhinolaryngology department of our hospital was reviewed from 1994 until 2014 and data was collected from the medical histories relating to patients with a diagnosis of local recurrence of NC&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Data collection was based on the review of medical histories&#44; with recording of data on age&#44; gender&#44; prior treatments&#44; spread and staging of tumour&#44; mean time from treatment of primary tumour to recurrence&#44; surgical approach&#44; complications and follow-up&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">The study population comprised 20 patients who had undergone surgery&#46; Open surgery was used on the first 12 patients &#40;60&#37;&#41;&#44;as has already been described for our group<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">14</span></a>&#58; six patients underwent anterior facial translocation surgery and six subtemporal-preauricular surgery&#46;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">6&#44;11</span></a> Since 2002&#44; due to the standardisation of extended endoscopic endonasal approaches for the treatment of these tumours&#44; the 8 patients &#40;40&#37;&#41; underwent endoscopic endonasal transpterigoid surgery &#40;Castelnuovo type 3 resection&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">15</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Radiologic studies were performed on all patients prior to surgery using computerised tomography CT and magnetic resonance &#40;MR&#41; imaging&#46; Patients also had a chest X-ray&#44; an abdominal scan&#44; a bone scan in the cases of open surgery<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">14</span></a> and CT&#44; MR and positron emission tomography &#40;PET&#41; in the cases of endoscopic surgery&#46; Only patients with no presence of distance metastasis were operated on&#46; Statistical data analysis was performed with the SPSS programme for Windows version 11&#46;0&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Results</span><p id="par0045" class="elsevierStylePara elsevierViewall">The sample comprised 14 male patients and 6 Female patients with a mean age at time of intervention of 54 years &#40;range 42&#8211;73&#41;&#46; In accordance with the histopathological classification of the World Health Organisation&#44;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">16</span></a> 6 patients presented with stage II tumours and the other 14 with stage III tumours&#46; At initial diagnosis&#44; 7 patients presented with tumours which were classified as T1&#44; 6 as T2&#44; 3 as T3 and 4 asT4&#44; in accordance with the 7th edition of the TNM system of the International Union against Cancer<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">17</span></a> &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">For treatment of the primary tumour and cervical nodes all patients received conformal chemotherapy and RT &#40;3D-CRT&#41;&#46; The mean dose applied on the nasopharynx was 65&#46;5<span class="elsevierStyleHsp" style=""></span>Gy &#40;range 50&#8211;72&#41; and the mean dose received on the cervical nodes was 44<span class="elsevierStyleHsp" style=""></span>Gy &#40;range 32&#8211;60&#41;&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Two months after finalisation of treatment assessment was made of the response through a nasofibroscopic examination and a cervical exploration&#44; together with the performing of CT or MR imaging&#46; This same assessment was performed as follow-up every 3 months for 2 years then every 6 months for 5 years and annually for 10 years after that&#46; In our series&#44; after finalising treatment complete response was obtained in all patients&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Local recurrences presented between 7 and 72 months after finalisation of treatment with RT &#40;mean&#58; 33 months&#41;&#46; Relapses were diagnosed mainly in advanced stages in the open surgery series and in early stages in the endoscopic series&#58; one patient was staged as rT1&#44; 3 as rT2&#44; 2 as rT3 and 6 as rT4 in the open surgery group whereas in the endoscopic series group 2 patients were staged as rT1&#44; 5 rT2 and one rT3&#46; On diagnosis of local recurrence&#44; none of the patients presented with regional or distance recurrences and all of them had received curative surgery both in the open and endoscopic series&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">In 3 of the 12 patients who underwent open surgery the surgical margins were microscopically affected by the tumour &#40;one rT4&#44; one rT3 and one rT2&#41;&#46; In a fourth patient due to the spread of the tumour to the parasellar region which affected a macroscopically incomplete resection&#44; the administration of adjuvant chemotherapy and stereotaxic RT were required&#46; In the endoscopic series&#44; in all patients &#40;8&#41; free tumour margins were obtained&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">In the open surgery approach patient series all patients presented with some kind of complication&#58; 5 patients presented with minor complications &#40;trismus&#44; serous otitis&#44; facial paresthesias&#44; haematomas or dehiscences of surgical wound&#41; and 5 suffered from complications classed as moderate which led to permanent sequelae or required further surgery &#40;osteomyelitis&#44; necrosis of the temporal lobe&#44; cerebrospinal fluid fistule&#46; One patient&#44; classified as rT4&#44; as a result of the appearance of an osteomyelitis of the malar bone&#44; developed a fistule between the zygomatic region and the oral cavity which required the addition of a parascapular free flap to close it&#46; Another patient&#44; also classified as rT4&#44; died 18 days following surgery as a result of aspiration pneumonia&#44; after a massive posterior epistaxis during the immediate post operative period&#46; In the endoscopic series 8 patients presented with complications&#58; 7 patients presented a minor complication &#40;serous otitis&#41; whilst one patient &#40;rT1&#41; presented with an osteomyelitis at the base of the skull several months after surgery&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Minimum patient follow-up is 3 years&#46; At present 11 patients &#40;55&#37;&#41; are living and disease free&#59; 5 patients underwent open surgery &#40;42&#37;s&#41; and 6&#44; endoscopic surgery &#40;75&#37;s&#41;&#46; In the group of patients who underwent open surgery 7 patients died &#40;4 rT4&#44; one rT3 and 2 rT2&#41;&#58; in 6 this was a result of the local recurrence of the disease &#40;5&#41; or due to a lymph node recurrence &#40;1&#41; and in one it occurred during the immediate postoperative period &#40;rT4&#41;&#46; None of the endoscopically intervened patients had any repeated local relapses&#46; However&#44; 2 patients died&#44; one &#40;rT1&#41; due to radionecrosis and exposure of the skull base and the other due to aspiration pneumonia &#40;rT3&#41;&#44; related to palatal incompetence&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Overall survival of the patients who underwent open surgery at 3 and 5 years was 53&#37; and 42&#37;&#44; respectively&#44; whereas at 3 and 5 years in the case of those who underwent endoscopic surgery it was 100&#37; and 75&#37; respectively&#46; In the open surgery patient group those cases where tumour free surgical margins were achieved &#40;8&#41; presented with a higher survival rate to those whose margins were affected &#40;4&#41; &#40;<span class="elsevierStyleItalic">P</span>&#61;&#46;0327&#41;&#44; all of whom died&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Discussion</span><p id="par0085" class="elsevierStylePara elsevierViewall">Therapeutic options for NC relapses include surgery and RT&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">15</span></a> Both achieve acceptable outcomes with regards to local control&#44; especially when recurrences are not very widespread and there is no major intracranial involvement&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">18</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">Re-irradiation of local recurrences achieve a survival rate at 5 years which oscillates between 8&#37; and 36&#37;&#44; with a significant correlation between re-irradiation dose and survival&#46; The best local control rates are obtained with accumulated doses of radiation of at least 60<span class="elsevierStyleHsp" style=""></span>Gy&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">9</span></a> The main disadvantage of RT is its low tolerance to the radiation of the nearby structures&#44; resulting in frequent late complications being frequent and varying between 26&#37; and 57&#37; of patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0245"><span class="elsevierStyleSup">19&#44;20</span></a> Treatment mortality ranges from 2&#37; to 10&#37; and is mainly due to damage of the central nervous system&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">21</span></a> New radiation techniques such as IMRT&#44; intensity-modulated volumetric arc therapy&#44; tomotherapy and proton-therapy has resulted in high levels of dose in the tumour tissues&#44; preserving adjacent healthy tissues&#44; which increases therapeutic efficacy compared with standard techniques&#46; Several series where IMRT was used have been show to be an excellent local control&#44; with survival figures of &#62;90&#37; after one year and acceptable toxicity levels&#46;<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">2&#44;22</span></a> However&#44; these RT modalities are not always available and in some cases the previous RT doses rule out the use of new irradiation&#44; survival rates after 5 years are yet to be studied&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">In general&#44; patients with local recurrences are considered not to be candidates for surgery when there is invasion of the cavernous sinus or internal carotid artery or tumours with intracerebral invasion&#46; In the remainder of cases&#44; surgery could be taken into consideration as salvage treatment&#46; Many approaches have been described for the treatment of this type of tumour&#58; transmandibular&#44; Fisch infratemporal fossa approach type C&#44; subtemporal-preauricular&#44; facial translocacion &#40;lateral or anterior&#41;&#44; maxillary swing type and transpalatal&#46;<a class="elsevierStyleCrossRefs" href="#bib0265"><span class="elsevierStyleSup">23&#44;24</span></a> These open surgery approaches&#44; either in isolation or combined&#44; target the nasopharynx and skull base&#46; However&#44; the rate of complications is high&#44; bearing in mind prior RT&#46; Standardised open surgery approaches have become more limited however and continue to be used for large tumours&#44; particularly when the nasal cavities&#44; the posterior wall of the maxillary sinus&#44; the pterygopalatine fossa or the infratemporal fossa are compromised&#46; The method of choice is facial translocation&#46; Facial translocation with midface degloving and hemicoronal pre-auricular incision has enabled the avoidance of sequelae associated with facial incisions occurring with the standard surgical approach&#46; After RT osteomyellitis is common or the reabsorption of the translocated segment&#46; This is minimised with the use of a temporal flap or performing pediculated maxillary osteotomy to the soft tissue of the cheek&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">25</span></a> The subtemporal pre-auricular approach is used mainly when the tumour has a limited anterior extension but affects the infratemporal fossa&#44; towards the floor of the middle fossa or the parasellar region&#46; This also allows for bilateral access of the cavum&#46; One complication specific to the subtemporal pre-auricular route is trismus&#44; which presented in all patients of our series treated with this approach&#44; although at different stages and was never incapacitating&#46; We should consider that&#44; due to prior RT&#44; the permeability of the deep temporal arteries may be affected&#44; and using the temporal muscle for reconstruction is therefore rejected &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0100" class="elsevierStylePara elsevierViewall">Disease-free survival after 5 years of the patients in our series who underwent open surgery was 42&#37;&#44; which is within the range described in the literature &#40;20&#37;&#8211;44&#37;&#41;&#46; Similarly to other series&#44; stage T was an essential factor of prognosis&#46;<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">8&#44;12&#44;15&#44;23</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">Endoscopic surgery for the treatment of recurrences of NC was introduced at the beginning of 2000 and after&#44; firstly for the treatment of tumours rT1&#44; rT2 and rT3&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">26</span></a> Endoscopic procedures may now be used in most salvage surgery after local recurrence&#46; Endoscopic approaches enable the targeting of tumours with a more direct exposure and with less handling of the neurovascular structures and the avoidance of osteotomies&#46; Oncological results are similar to those obtained with standard open surgery methods and fragmented resection of tumours does not appear to compromise the oncological outcomes provided that the resection margins are negative&#46; From the patient&#39;s viewpoint&#44; the reduction of time in surgery and hospital stay&#44; a lower rate of complications and the absence of facial incision are advantages of endoscopic approaches&#46; With regards to our series&#58; our average time in surgery was 240<span class="elsevierStyleHsp" style=""></span>min&#44; mean hospital stay was 5 days and there were no intraoperative or postoperative complications&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">The performing of endoscopic nasopharyngectomy is a complex technique due to the proximity of critical neural and vascular structures&#44; and also to the meninges and central nervous system&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">15</span></a> However&#44; endoscopic resection outcomes of these tumours are promising<a class="elsevierStyleCrossRefs" href="#bib0285"><span class="elsevierStyleSup">27&#44;28</span></a> and the results of our series are similar to those described by other authors &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">15&#44;16&#44;28</span></a></p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0115" class="elsevierStylePara elsevierViewall">You et al&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">29</span></a> published a series of 144&#44; in which they compared 72 patients who had undergone endoscopic surgery and 72 patients with IMRT&#46; They concluded that the endoscopic surgery increased overall survival at 5 years &#40;77&#46;1&#37; vs 55&#46;5&#37;&#59; <span class="elsevierStyleItalic">P</span>&#61;&#46;003&#41;&#44; increased quality of life &#40;global health status 57&#46;6 vs 29&#46;8&#59; <span class="elsevierStyleItalic">P</span>&#60;&#46;001&#41;&#44; reduced post treatment complications &#40;12&#46;5&#37; vs 65&#46;3&#37;&#59; <span class="elsevierStyleItalic">P</span>&#60;&#46;001&#41; and that procedure costs were low &#40;2371&#46;71 vs 11<span class="elsevierStyleHsp" style=""></span>847&#46;80 &#8364;&#59; <span class="elsevierStyleItalic">P</span>&#60;&#46;001&#41;&#46; Na&#8217;ara et al&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">27</span></a> published an analysis with a series of 779 patients &#40;rT1&#8211;2&#58; 655 &#40;83&#37;&#41;&#44; rT3&#8211;4&#58;129 &#40;16&#46;67&#37;&#41;&#44; 661 &#40;84&#46;4&#37;&#41; with open surgery approaches and 118 &#40;15&#46;1&#37;&#41; endoscopic approaches&#46; At 5 years&#44; they described an overall survival and a disease-free survival of 58&#37; and 63&#46;4&#37;&#46; In this study&#44; multivariate analysis showed that endoscopic surgery offers better outcomes in T3&#8211;rT4 in selected patients and that adjuvant re-irradiation offers an advantage of additional survival over surgery alone&#46; Other authors have achieved a good local control rate with endoscopic surgery in the initial stages of rT1 and rT2 tumours&#44; whilst open surgery is preferred in advanced stages&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">30</span></a> Indication could be cautiously extended to selected rT3 tumours with limited involvement of the skull base&#46; rT4 patients generally present with a repeated local recurrence or die due to metastasis&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">11</span></a> In accordance with these authors&#44; in our endoscopic series&#44; 7 out of the 8 patients were rT1&#8211;T2 and only one was rT3&#44; and we therefore agree with the indication for this approach&#46; In extensive recurrences &#40;rT3 and&#44; above all&#44; rT4&#41;&#44; in our experience&#44; the performing of facial translocation or a subtemporal pre-auricular<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">13</span></a> approach are the ones of choice&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Conclusions</span><p id="par0120" class="elsevierStylePara elsevierViewall">Although open surgery and endoscopic procedures appear to be equally effective in patients who require surgical salvage&#44; the advantages of the endoscopic skull base approaches include shorter hospital stays&#44; have a lower rate of complications and a better quality of life&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Conflict of Interests</span><p id="par0125" class="elsevierStylePara elsevierViewall">The authors have no conflict of interests to declare relating to this study&#46; We did not receive any financing&#46;</p></span></span>"
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          "titulo" => "Resumen"
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              "titulo" => "Introducci&#243;n y Objetivos"
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              "titulo" => "M&#233;todos"
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          "titulo" => "Palabras clave"
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    "fechaRecibido" => "2017-07-26"
    "fechaAceptado" => "2017-11-21"
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        0 => array:4 [
          "clase" => "keyword"
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          "identificador" => "xpalclavsec1047840"
          "palabras" => array:4 [
            0 => "Nasopharynx"
            1 => "Endoscope"
            2 => "Nasopharynx carcinoma"
            3 => "Endonasal nasopharyngectomy"
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        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec1047841"
          "palabras" => array:4 [
            0 => "Nasofaringe"
            1 => "Endoscopia"
            2 => "Carcinoma de nasofaringe"
            3 => "Nasofaringectom&#237;a endosc&#243;pica"
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    "resumen" => array:2 [
      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction and Objectives</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Chemoradiotherapy is the treatment of choice for nasopharyngeal carcinoma&#46; Local recurrences are one of the leading causes of death in these patients&#44; and surgical salvage the treatment of choice&#46; Our goal was to evaluate and compare the results of salvage surgery in the treatment of local recurrence of nasopharyngeal carcinomas comparing endoscopic to open approaches&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Twenty patients with local recurrence of nasopharyngeal carcinomas underwent surgery&#58; 12 patients underwent open surgery and 8 endoscopic endonasal transpterygoid nasopharyngectomy&#46; One patient was classified as rT1&#44; three as rT2&#44; two as rT3&#44; and six as rT4 in the group of open approaches&#59; in the endoscopic series&#44; two patients were rT1&#44; five rT2 and one rT3&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">In 3 patients &#40;25&#37;&#41; operated by an open approach &#40;one rT4&#44; one rT3 and one rT2&#41; a complete gross resection was not achieved&#46; Gross total resection was achieved in patients operated by endoscopic surgery&#46; The complication rate in the group operated by an open approach was 92&#37; &#40;five minor complications&#44; five moderate complications&#44; and one serious complication&#41; and in the group that underwent endoscopic surgery all patients had some complication &#40;seven had minor complications and one patient developed a severe complication&#41;&#46; Survival at 3 and 5 years was 53&#37; and 42&#37; with the open approach and 100&#37; and 50&#37; with the endoscopic approach&#44; respectively&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Endoscopic approaches decrease the morbidity associated with open approaches and allow for favourable oncological control&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Introduction and Objectives"
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          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Methods"
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            "titulo" => "Conclusions"
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        "titulo" => "Resumen"
        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducci&#243;n y Objetivos</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">La quimiorradioterapia es el tratamiento de elecci&#243;n del carcinoma de nasofaringe&#46; Las recurrencias locales son una de las principales causas de mortalidad en estos pacientes&#58; el rescate quir&#250;rgico o la reirradiaci&#243;n son el tratamiento de elecci&#243;n&#44; seg&#250;n la disponibilidad&#46; El objetivo fue evaluar y comparar los resultados de la cirug&#237;a de rescate en el tratamiento de las recidivas locales de los carcinomas nasofar&#237;ngeos mediante abordajes abiertos vs&#46; endosc&#243;picos&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todos</span><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Veinte pacientes con recidivas locales de carcinomas nasofar&#237;ngeos fueron intervenidos quir&#250;rgicamente&#58; 12 pacientes fueron intervenidos mediante cirug&#237;a abierta y 8 mediante un abordaje endosc&#243;pico endonasal transpterigoideo&#46; Un paciente fue estadiado como rT1&#59; 3 como rT2&#59; 2 como rT3 y 6 como rT4 en el grupo de abordajes abiertos&#59; en la serie endosc&#243;pica&#44; 2 pacientes fueron rT1&#44; 5 fueron rT2 y uno fue rT3&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">En 3 de los pacientes &#40;25&#37;&#41; intervenidos mediante cirug&#237;a abierta &#40;un rT4&#44; un rT3 y un rT2&#41; no se logr&#243; una resecci&#243;n macrosc&#243;pica completa&#41;&#46; En el grupo endosc&#243;pico la resecci&#243;n fue completa en todos los pacientes&#46; La tasa de complicaciones en el grupo intervenido mediante abordajes abiertos fue del 92&#37; &#40;5 complicaciones leves&#44; 5 complicaciones moderadas y una complicaci&#243;n grave&#41; y en el grupo intervenido mediante endoscopia fue del 100&#37; &#40;7 sufrieron complicaciones leves y un paciente una complicaci&#243;n grave&#41;&#46; La supervivencia a los 3 y 5 a&#241;os fue del 53 y del 42&#37; en el abordaje abierto y del 100 y del 75&#37; en el abordaje endosc&#243;pico&#44; respectivamente&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Los abordajes endosc&#243;picos disminuyen la morbilidad asociada a los abordajes abiertos y permiten obtener un control oncol&#243;gico favorable&#46;</p></span>"
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            "titulo" => "M&#233;todos"
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            "titulo" => "Resultados"
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            "titulo" => "Conclusiones"
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        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Salom MC&#44; L&#243;pez F&#44; Pacheco E&#44; Mu&#241;oz G&#44; Garc&#237;a-Cabo P&#44; Fern&#225;ndez L&#44; et al&#46; Cirug&#237;a de rescate en las recidivas locales del carcinoma de nasofaringe&#46; Acta Otorrinolaringol Esp&#46; 2018&#59;69&#58;339&#8211;344&#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="" 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="center" valign="top" scope="col" style="border-bottom: 2px solid black">Open surgery approach &#40;1994&#8211;2001&#41; 12 patients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Endoscopic approach &#40;2002&#8211;2014&#41; 8 patients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " rowspan="2" align="left" valign="top">Gender</td><td class="td" title="table-entry  " align="left" valign="top">Males&#58; 9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Males&#58; 5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Females&#58; 3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Females&#58; 3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Age&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">55 years of age &#40;42&#8211;71&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">52 years of age &#40;43&#8211;73&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " rowspan="2" align="left" valign="top">Histology &#40;OMS&#41;</td><td class="td" title="table-entry  " align="left" valign="top">Stage II&#58; 2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Stage II&#58; 2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Stage III&#58; 10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Stage III&#58; 6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " rowspan="4" align="left" valign="top">rT</td><td class="td" title="table-entry  " align="left" valign="top">rT1&#58; 1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">rT1&#58; 2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">rT2&#58; 3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">rT2&#58; 5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">rT3&#58; 2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">rT3&#58; 1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">rT4&#58; 6&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">Surgical time in minutes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#62;240&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#60;240&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">Intraoperative complications&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " rowspan="3" align="left" valign="top">Complications</td><td class="td" title="table-entry  " align="left" valign="top">Minor 5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Minor 7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Moderate 5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Moderate 0&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">Severe 2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Severe 1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hospital stay &#40;days&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Mean follow-up &#40;years&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#62;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">3 and 5 years survival in &#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">53 and 42&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">100 and 75&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">Local relapse post treatment in months &#40;mean&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&#8211;72 &#40;33&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&#8211;36 &#40;23&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Clinical Characteristics of the Patients&#46;</p>"
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                  \t\t\t\t" class=""><thead title="thead"><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="center" valign="top" scope="col" style="border-bottom: 2px solid black">Number of cases&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Local control &#40;&#37;&#41; &#40;5 years&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Survival &#40;&#37;&#41; &#40;5 years&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Complications &#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">Fee<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">9</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \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">52&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></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Vlantis<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">24</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">62&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">51&#46;9&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></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">King<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">8</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">31&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">53&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="char" valign="top">&#8211;&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">Wei<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">5</span></a>&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="char" valign="top">62&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">49&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&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">Chang<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">30</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">38&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">60 &#40;3 years&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">73 &#40;3 years&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&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">Cabanillas<a class="elsevierStyleCrossRef" href="#bib0220"><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="char" valign="top">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">53&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">42&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">41&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Open Surgery Series Outcomes&#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="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Staging&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Follow-up &#40;months&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Survival&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">Chen<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">16</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">37&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">rT1N0M0&#58; 17<br>rT2aN0M0&#58; 4<br>rT2bN0M0&#58; 14<br>rT3N0M0&#58; 2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">36 &#40;&#8722;&#41;<br>1 &#40;&#43;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6&#8211;45&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">84&#37; &#40;2 years&#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">Ko<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">28</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">28&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">rT1N0&#58; 12<br>rT2aN0&#58; 14<br>rTaN1&#58; 2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">25 &#40;&#8722;&#41;<br>3 &#40;&#43;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&#8211;48&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Castelnuovo<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">15</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">rT1&#58; 4<br>rT2a&#58; 1<br>rT3&#58; 3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8 &#40;&#8722;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10&#8211;78&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No recurrences&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">Salom&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">rT1&#58; 2<br>rT2&#58; 5<br>rT3&#58; 1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8 &#40;&#8722;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">12&#8211;72&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No recurrences&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Endoscopic Series Outcomes&#46;</p>"
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      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0015"
          "bibliografiaReferencia" => array:30 [
            0 => array:3 [
              "identificador" => "bib0155"
              "etiqueta" => "1"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Overall survival after concurrent cisplatin-radiotherapy compared with radiotherapy alone in locoregionally advanced nasopharyngeal carcinoma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46;T&#46;C&#46; Chan"
                            1 => "S&#46;F&#46; Leung"
                            2 => "R&#46;K&#46; Ngan"
                            3 => "P&#46;M&#46; Teo"
                            4 => "W&#46;H&#46; Lau"
                            5 => "W&#46;H&#46; Kwan"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/jnci/dji084"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Natl Cancer Inst"
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                        "volumen" => "97"
                        "paginaInicial" => "536"
                        "paginaFinal" => "539"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15812080"
                            "web" => "Medline"
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              ]
            ]
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              "identificador" => "bib0160"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Treatment of nasopharyngeal carcinoma using intensity-modulated radiotherapy&#58; the National Cancer Centre Singapore experience"
                      "autores" => array:1 [
                        0 => array:2 [
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                            0 => "I&#46;W&#46;-K&#46; Tham"
                            1 => "S&#46;W&#46; Hee"
                            2 => "R&#46;M&#46; Yeo"
                            3 => "P&#46;B&#46; Salleh"
                            4 => "J&#46; Lee"
                            5 => "T&#46;W&#46;-K&#46; Tan"
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                  "host" => array:1 [
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            ]
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              "identificador" => "bib0165"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Intensity-modulated radiation therapy in the salvage of locally recurrent nasopharyngeal carcinoma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
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                            1 => "S&#46; Lin"
                            2 => "I&#46;W&#46;K&#46; Tham"
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                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Int J Radiat Oncol"
                        "fecha" => "2012"
                        "volumen" => "83"
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                ]
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              "identificador" => "bib0170"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Update report of nasopharyngeal carcinoma treated with reduced-volume intensity-modulated radiation therapy and hypothesis of the optimal margin"
                      "autores" => array:1 [
                        0 => array:2 [
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                            0 => "S&#46; Lin"
                            1 => "J&#46; Pan"
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                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.radonc.2014.01.011"
                      "Revista" => array:6 [
                        "tituloSerie" => "Radiother Oncol"
                        "fecha" => "2014"
                        "volumen" => "110"
                        "paginaInicial" => "385"
                        "paginaFinal" => "389"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24560755"
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                    ]
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                ]
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Current management strategy of nasopharyngeal carcinoma"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "W&#46;I&#46; Wei"
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                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3342/ceo.2010.3.1.1"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Exp Otorhinolaryngol"
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                        "volumen" => "3"
                        "paginaInicial" => "1"
                        "paginaFinal" => "12"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20379395"
                            "web" => "Medline"
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                ]
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            ]
            5 => array:3 [
              "identificador" => "bib0180"
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                0 => array:2 [
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Article information

ISSN: 21735735
Original language: English

DOI:10.1016/j.otoeng.2017.11.001

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