Long-term survival of glioblastoma: A systematic analysis of literature about a case

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Con una flecha blanca sobre fondo negro se indica de realización de la misma, 4 de diciembre del 2008. B) Imagen de corte axial de la RM cerebral en secuencias T1 con contraste, donde se observa un área porencefálica de similares características a la observada en la figura 3. Con una flecha se indica la realización de dicho estudio, 26 de febrero del 2020." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Luis Germán González Bonet, Claudio Piqueras-Sánchez, Esther Roselló-Sastre, Ricardo Broseta-Torres, Ramón de las Peñas" "autores" => array:5 [ 0 => array:2 [ "nombre" => "Luis Germán" "apellidos" => "González Bonet" ] 1 => array:2 [ "nombre" => "Claudio" "apellidos" => "Piqueras-Sánchez" ] 2 => array:2 [ "nombre" => "Esther" "apellidos" => "Roselló-Sastre" ] 3 => array:2 [ "nombre" => "Ricardo" "apellidos" => "Broseta-Torres" ] 4 => array:2 [ "nombre" => "Ramón" "apellidos" => "de las Peñas" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2529849621000496" "doi" => "10.1016/j.neucie.2021.11.001" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2529849621000496?idApp=UINPBA00004B" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1130147321000567?idApp=UINPBA00004B" "url" => "/11301473/0000003300000005/v1_202209010532/S1130147321000567/v1_202209010532/es/main.assets" ] ] "itemSiguiente" => array:17 [ "pii" => "S2529849622000417" "issn" => "25298496" "doi" => "10.1016/j.neucie.2021.01.005" "estado" => "S300" "fechaPublicacion" => "2022-09-01" "aid" => "492" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "crp" "cita" => "Neurocirugia. 2022;33:237-41" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "Case Report" "titulo" => "Primary epidural lumbar Ewing sarcoma presenting as cauda equina syndrome in an adult patient who underwent surgical decompression: A case report" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "237" "paginaFinal" => "241" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Sarcoma de Ewing epidural lumbar primario que se presenta como síndrome de la cola de caballo en un paciente adulto que se sometió a descompresión quirúrgica: informe de caso clínico" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1052 "Ancho" => 3341 "Tamanyo" => 285473 ] ] "descripcion" => array:1 [ "en" => "(A and B) Post first surgery T1WI contrast MRI shows suspected residual tumor in the L3 right pedicle and body with progression. 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Universitario de Castellón, Castellón, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Facultad de Ciencias de la Salud, Universidad Jaume I de Castellón, Castellón, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Servicio de Anatomía Patológica, Hospital General Universitario de Castellón, Castellón, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Ascires/Eresa, Castellón, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Servicio de Oncología Médica, Hospital Provincial de Castellón, Castellón, Spain" "etiqueta" => "e" "identificador" => "aff0025" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Glioblastomas de larga supervivencia: un análisis sistemático de la literatura a propósito de un caso" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 980 "Ancho" => 1305 "Tamanyo" => 328764 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0015" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Current anatomic pathological study from the paraffin block obtained during tumour resection in 1997. (A) Haematoxylin and eosin staining showing endothelial cell hyperplasia and the formation of abnormal vascular structures with multiple lumens simulating renal glomeruli. (B) Arrangement of tumour cells in pseudoepalisade around irregular foci of necrosis. (C) Immunohistochemical staining for IDH1 positive tumour cells. (D) Low power immunohistochemical staining for Ki-67 reflecting a positivity of approximately 5%." ] ] ] "textoCompleto" => "IntroductionGlioblastoma is the most common primary malignant tumour of the central nervous system, representing 75% of all primary malignant brain tumours<a class="elsevierStyleCrossRef" href="#bib0005">1</a>. To be frank, advances in the treatment of glioblastoma have been frustrating. Although it is true that survival has improved since the application of the Stupp<a class="elsevierStyleCrossRef" href="#bib0010">2</a> protocol in 2005, this increase in survival can be classified as poor, with only 16% of cases surviving longer than three years<a class="elsevierStyleCrossRef" href="#bib0015">3</a>. If we compare it with other entities, such as breast cancer, in this type of tumour, survival has improved dramatically in the last 20 years, it being 90.2% in the United States at five years or 82.8% in Spain for women diagnosed in the period 2010–2014<a class="elsevierStyleCrossRef" href="#bib0020">4</a>. This improvement is not only observed in tumours outside the central nervous system, but is also seen in other lesions that exclusively affect the same central nervous system, such as primary brain lymphoma in immunocompetent patients. Classically associated with immunosuppression processes such as HIV, the incidence of this type of lesion in immunocompetent patients has grown dramatically from 0.4 to 1 cases per million in 1980 to 0.5 cases per 100,000 inhabitants<a class="elsevierStyleCrossRef" href="#bib0025">5</a>. Despite all this, the combination of methotrexate, rituximab and autologous transplantation has provided for survivals of 83% at four years, with only one biopsy conducted on the part of neurosurgery<a class="elsevierStyleCrossRef" href="#bib0030">6</a>.Although factors that improve survival have been described for glioblastoma<a class="elsevierStyleCrossRefs" href="#bib0035">7,8</a>, the percentage of patients with long-term survival at 10 years remains unchanged regardless of the Stupp protocol, it being estimated at 0.97% for studies before 1993 and 0.69% in the most current ones<a class="elsevierStyleCrossRef" href="#bib0045">9</a>. However, these figures can vary depending on the studies consulted, with up to 5% and 2.4% for survival at five and 10 years, respectively, in some American series<a class="elsevierStyleCrossRef" href="#bib0050">10</a>.We put forward a systematic review of the literature of those series with the most characteristic long-term survival in relation to a case with a survival of more than 20 years.Material and methodsSearch strategyThe search was carried out using the following databases: PUBMED, Scopus, Cochrane and Scielo. The search strategy used the following keywords and MeSH terms: glioblastoma, glioblastoma multiforme, GBM, long-term survival/survivors, cure, three-year-survival, three-year-survivor. This was combined with the appropriate Boolean operators. A flow chart was constructed with the search strategy (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).<elsevierMultimedia ident="fig0005"></elsevierMultimedia>Inclusion and exclusion criteriaThe inclusion criteria were established: articles in Spanish, English or French; whether they were clinical trials, cohort studies, or cases and follow-up; published after 2005 so that the introduction of the Stupp protocol could be assessed<a class="elsevierStyleCrossRef" href="#bib0010">2</a>, with a cohort of more than 300 patients in whom reviews of the pathological anatomy results could be performed; including WHO grade IV gliomas with a majority representation of classic glioblastoma multiforme, and articles in which the control group was not only representative samples.Exclusion criteria eliminated: articles dealing with grade I, II or III gliomas; those that include the paediatric population; congenital glioblastomas; articles that were systematic reviews, isolated clinical cases or meta-analyses; articles where fewer than five factors were analysed; articles in which the survival value was under three years and, finally, studies where alternative treatments such as immunotherapy, targeted molecular treatments or chemotherapy beyond temozolomide were evaluated.In the specific clinical case, the pathological anatomy is reviewed by making new sections of the paraffin block that was fixed in 4% paraformaldehyde and a diagnostic expansion for the assessment of Ki-67%, IDH, ATRX and P53. Likewise, new haematoxylin and eosin stains are made. Paper records and scanned material regarding the patient’s medical history are accessed. Informed consent is requested from the patient and all personal data that would allow the identity of the patient is kept concealed.ResultsCase reportThe male patient in question with onset in 1997 at the age of 39 with a tonic-clonic seizure and a weakness of the right arm. Magnetic resonance imaging (MRI) revealed a lesion of 3 cm with a peripheral and irregular contrast uptake and probably necrotic cystic interior content. He underwent complete resection surgery on 10/06/1997. The pathological anatomy reported glioblastoma multiforme according to the 1993 WHO classification<a class="elsevierStyleCrossRef" href="#bib0055">11</a>. In fact, the patient presented a tumour recurrence of glioblastoma at five months and underwent surgery again on 13/01/1998 (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). The reports are preserved, but the images are not copied for the elapsed time. The patient received 60 Gy of radiotherapy and three treatment cycles with procarbazine, lomustine and vincristine (PCV) as adjuvant chemotherapy before observing relapse at five months. Two months after this latest intervention, he presented with a deterioration of the general state, as well as weakness in the right hemibody, for which a CT scan was performed that reported a nodular image with peripheral uptake in the tumour bed associated with finger-like oedema. Empirical antibiotic treatment was started due to suspicion of postoperative brain abscess so a trephine with evacuation of the content was carried out without observing a microorganism. After this procedure, the patient was transferred to a brain damage unit. Finally, a further intervention was performed a year later on an irregular uptake area on the tumour bed from which no tumour cells were observed, concluding radionecrosis. After this last intervention, the patient continued with follow-up consultations, the long evolution of the disease being surprising. For this reason in 2020 it was decided to recover the paraffin blocks from the first surgery in 1997 and submit them to a new analysis (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>). A glial lesion is described with areas (approximately 10%) of significant atypia and vascular proliferation, as well as necrosis. Immunohistochemical and molecular study reveals IDH1 mutation, positivity for GFAP+, partial loss of ATRX, P53+, EGFR− and Ki-67 of 5%. Diagnosis with mutated IDH glioblastoma was made according to the 2016 WHO classification<a class="elsevierStyleCrossRef" href="#bib0060">12</a>. The current MRI dated 2020 is shown, as well as the first MRI that we currently have in our PACS dated 2008 where no significant change is observed (<a class="elsevierStyleCrossRef" href="#fig0020">Fig. 4</a>).<elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia>Clinical characteristics of the studiesIn the study by Cantrell JN et al.<a class="elsevierStyleCrossRef" href="#bib0065">13</a> information is extracted from the cancer database of the USA between the period 2004−2009. It is, therefore, a retrospective observational analysis. In total, 48,652 patients were analysed, of which 2249 (4.6%) survived for longer than five years. Among those who survived longer than five years, the average age is 52 years old compared to 64 years in the group under five years old. Mean survival in this long-term evolution group is 88 months compared to seven months in the other group. The Charlson Comorbidity Index was 0 in 85% of the long-term survival patients (72% in the group with survival under five years), 82% received radiotherapy (RT) (68% in the ordinary group) and 46% chemotherapy (CT) (35% in the group with the lowest survival).Reifenberger G et al.<a class="elsevierStyleCrossRef" href="#bib0070">14</a> from the German Glioma Network and subsidised by the German Cancer Aid Association collected the cases from eight centres in Germany retrospectively between 2004 and 2012. They established three groups: short-term survival (<12 months), medium-term survival (12–36 months) and long-term survival (>36 months). Only 28 patients obtained the longest survival. In addition to assessing the sociodemographic and clinical factors, the molecular characteristics among the three survival groups were evaluated, especially IDH1 and 2 mutations, as well as MGMT methylation.Gately L et al.<a class="elsevierStyleCrossRef" href="#bib0075">15</a> performed a retrospective analysis of the databases from two centres in Australia. In total they collected 776 cases of which only 31 (approximately 4%) survived for longer than five years. The study focuses on those who survive for longer than two years with a slightly more superficial analysis of those who survive longer than five years. The mean age of patients with longer than five years' survival is 47 years compared to 65 years in the group with the lowest survival. The percentage of patients who received CT and RT was 97% compared to 40% in the under-two-years group.The study by Marton E et al.<a class="elsevierStyleCrossRef" href="#bib0080">16</a> was a retrospective study of a single centre, this time Italian, but which included 1440 cases between 1998 and 2015, of which 33 cases (2.3%) with a survival of longer than three years and only seven cases (0.5%) longer than 10 years were observed. The mean age of the group with long-term survival of more than ten years was 41 years compared to 65 years in the group with the lowest survival.Scoccianti S et al.<a class="elsevierStyleCrossRef" href="#bib0085">17</a> also analysed a retrospective series of cases, again in Italy, but in a multicentre manner, collecting a total of 1059 patients with glioblastoma multiforme between 2002 and 2007, of which only 3.9% survived longer than five years, that is, 41 cases. Unfortunately, this study offers little descriptive epidemiological data on these long-term surviving patients, although it does do comparative studies with those with low survival.The study by Tian M et al.<a class="elsevierStyleCrossRef" href="#bib0090">18</a> was performed using the Surveillance, Epidemiology, and End Results (SEER) database, which is 17 cancer data registries representing 26% of the US population. The data is collected between 2000 and 2008. In total, 6586 cases were obtained, of which the survivors of more than five years were 483 patients (7.3%), 258 women and 225 men.Finally, we find the study by Zreik J et al.<a class="elsevierStyleCrossRef" href="#bib0095">19</a>, that collect data from the American National Cancer Database between 2004 and 2013. Of the 124,231 cases of glioblastomas scanned, 88,919 had a follow-up of at least three years and 8757 had a survival of longer than three years (9.8%). Many socio-economic, clinical and even molecular variables are analysed such as the year of diagnosis, age, gender, race, the comorbidity scale using the Charlson index, the laterality of the lesion, its location and size, as well as the extension, the adjuvant treatment and even the type of health insurance. Patients who survived three years were younger at diagnosis (mean age 55 compared to 65 for those who survived less than three years), had private insurance, a lower Charlson, and more often received trimodal therapy.Evaluation of associations in patients with long survivalIn the study by Cantrell JN et al.<a class="elsevierStyleCrossRef" href="#bib0065">13</a> the multivariate analysis found differences in favour of greater survival in women, younger patients who were non-white, with greater purchasing power (>$63,000 per month) and a comorbidity index of 0. Interestingly, the location of the lesion was only a factor that implied worse survival if the lesion was established in the trunk. The size of the lesion was not significant for prognosis. The study did find radiotherapy as a therapeutic factor influencing this long-term survival, but not chemotherapy. Unfortunately, the molecular characteristics of the tumour were not analysed in this study.With regard to the German study by Reifenberger G et al.<a class="elsevierStyleCrossRef" href="#bib0070">14</a> significant differences were only found in the group with the longest survival (>36 months) for the youngest and those with a longer disease-free period. When molecular studies were performed, the IDH1 and 2 mutation and MGMT methylation were found to be significant for longer survival.In the study by Gately L et al.<a class="elsevierStyleCrossRef" href="#bib0075">15</a> many variables were found in the multivariate analysis that seem to be involved regarding the long-term survivors, such as age, chemoradiotherapy treatment, the patient's condition, and the degree of resection. However, the study focuses on survivors of more than two years and when the analysis of survivors of more than five years is made and compared with this group of two years, only age is found as a significant variable, the rest being non-significant. This study also did not perform a molecular study of the tumour.The study by Marton E et al.<a class="elsevierStyleCrossRef" href="#bib0080">16</a> did perform molecular and immunohistochemical analyses unlike the Gateli and Cantrell studies. Specifically, they found significant differences in favour of greater survival with age and in patients with a Ki-67 < 10%, no TERTp mutation, MGMTp methylation, and IDH1 and 2 mutation.Scoccianti S et al.<a class="elsevierStyleCrossRef" href="#bib0085">17</a> focused mainly on treatment with radiotherapy and chemotherapy before and after the introduction of the Stupp protocol. In fact, the study was organised by the Italian Association of Radiation Oncology. The variables that were found to be significant after a multivariate analysis for better survival were: age, the pre-RT Karnofsky but not the pre-surgical Karnofsky, the degree of resection but not the symptoms at onset, the use of 3D conformal RT and the use of chemotherapy regardless of whether said use was before or after the introduction of the Stupp protocol in 2005.The study by Tian M et al.<a class="elsevierStyleCrossRef" href="#bib0090">18</a> also performed a multivariate analysis of prognostic factors, but not specifically of five-year survival. The factors that were found to be significant in this multivariate analysis as prognoses of better survival were age, specifically being under 40 years old, being a woman, treatment after 2005, certain tumour locations and lesions less than 5 cm. Molecular data of the types of lesions were again not analysed.Zreik J et al.<a class="elsevierStyleCrossRef" href="#bib0095">19</a> found a lot of statistical significance among all the variables studied. Of all of them, those with the most statistical power after multivariate analysis were age, multimodal therapy, and MGMT methylation (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>DiscussionSince the application of the Stupp protocol in 2005<a class="elsevierStyleCrossRef" href="#bib0010">2</a> the prognosis of glioblastoma patients seemed as if it may have changed, but unfortunately it has not changed much. However, a manner of treating these patients in a systematic way was established that made it possible to compare different series from different countries. Although an improvement in survival has been obtained for this type of tumour<a class="elsevierStyleCrossRef" href="#bib0015">3</a>, if we compare it with the evolution of other types of neoplasms, this improvement could be classified as poor and disappointing<a class="elsevierStyleCrossRefs" href="#bib0020">4,5</a>. Despite this treatment with chemotherapy and radiotherapy, patients with very long survival have not changed significantly before and after the Stupp protocol, it being estimated at only 0.71% at 10 years<a class="elsevierStyleCrossRef" href="#bib0045">9</a>. However, this value may vary depending on the series between 4<a class="elsevierStyleCrossRef" href="#bib0100">20</a> or 0.5% of a very large series of 11,189 cases<a class="elsevierStyleCrossRef" href="#bib0105">21</a>.What is striking when it comes to reviewing the literature is the lack of uniformity in the studies. Single or multicentre studies, with evaluation of very different variables, some being carried out in the same country and obtaining quite varied results of statistical significance among the variables analysed. Many studies are well-conducted reviews with a large number of patients, but due to the fact that they were conducted on patients before 2016, where the classification of tumours of the central nervous system was modified<a class="elsevierStyleCrossRef" href="#bib0060">12</a>, they do not refer to determinations such as the IDH. Even terminologically, long-term survival varies, in some articles the definition of long-term survival being three years<a class="elsevierStyleCrossRefs" href="#bib0080">16,22,23</a>, others five years<a class="elsevierStyleCrossRef" href="#bib0065">13</a> or others 10 years<a class="elsevierStyleCrossRef" href="#bib0045">9</a>. This fact makes it very difficult to carry out a systematic review. Furthermore, it is difficult to find large series, of more than 300 patients, whereby in addition the control group is not a representative sample of those who do not achieve said survival, but the control is the analysis of the rest of the patients.Among the studies found that met our inclusion and exclusion criteria, we discovered a finding common to all of them. Age as a criterion for long-term survival. Another is that the percentage of patients who survive more than five years is close to 5%. From that point, we found a number of differences between the studies. Some found being a woman a prognostic factor for long-term survival<a class="elsevierStyleCrossRefs" href="#bib0065">13,18</a>, others the use of RT, but not the use of CT<a class="elsevierStyleCrossRef" href="#bib0065">13</a>. Regarding the patient’s condition, some evaluated the Charlson index, finding it significant<a class="elsevierStyleCrossRef" href="#bib0065">13</a>, others the Karnofsky, but they only found the pre-RT Karnofsky significant<a class="elsevierStyleCrossRef" href="#bib0085">17</a>. Others did not even find Karnofsky significant<a class="elsevierStyleCrossRef" href="#bib0080">16</a>.Moreover, the improvement in surgical technique is evident reaching increasingly complete resection levels aided by techniques such as the use of 5-ALA, intraoperative MRI as well as STIR sequences and neuronavigation<a class="elsevierStyleCrossRefs" href="#bib0120">24,25</a>. Although such complete resection clearly increases patient survival<a class="elsevierStyleCrossRefs" href="#bib0130">26,27</a>, it is not clear that this resection has to do with the cases of long survival described, this factor only being found to be significant in one of the long-survival studies referred to<a class="elsevierStyleCrossRef" href="#bib0070">14</a>. And in recent reviews it is not clear that the use of these techniques improves the overall survival of patients<a class="elsevierStyleCrossRefs" href="#bib0140">28,29</a>.In our work, taking into account our inclusion and exclusion criteria, several articles are collected that relate a molecular study with long-term survival and do so in relation to a Ki-67 < 10%, a non-mutated TERTp, as well as the presence of MGMT promoter methylation and IDH mutation<a class="elsevierStyleCrossRefs" href="#bib0070">14,16,19</a>. However, there are more and more articles that collect patients with long-term survival at three and five years, although in smaller series than those we wanted to evaluate in this review, with specific molecular characteristics.<a class="elsevierStyleCrossRef" href="#bib0150">30</a>. Specifically for these shorter series, MGMT methylation seems to be, of all these molecular characteristics, the factor that most influences the long-term survivors<a class="elsevierStyleCrossRefs" href="#bib0110">22,23,30,31</a>, although IDH mutation has also been found in some cases to be a statistically significant variable for said survival<a class="elsevierStyleCrossRef" href="#bib0115">23</a>. However, this should not lead to the mistake that patients who survive long-term without methylation have been found<a class="elsevierStyleCrossRefs" href="#bib0070">14,31</a>, although there was almost twice as much probability of being a long-term survivor and having the methylation than not having it. In the same way, it is also rarer, but not impossible, to find a long-term surviving patient who underwent only a biopsy and not a complete resection.<a class="elsevierStyleCrossRef" href="#bib0075">15</a>.There are other smaller series that attempt to relate long-term survival to the anatomical region of the subventricular zone, finding that this zone seems to imply a lower probability of long-term survival<a class="elsevierStyleCrossRefs" href="#bib0160">32,33</a>. This fact is based on the fact that the presence of adult mammalian precursor stem cells has been described in this region<a class="elsevierStyleCrossRef" href="#bib0170">34</a>.On the other hand, isolated cases of long-term survival have been described in association with certain immunisations or states of the patient at a specific time<a class="elsevierStyleCrossRefs" href="#bib0175">35–37</a>. In fact, in the study by Reifenberger G et al.<a class="elsevierStyleCrossRef" href="#bib0070">14</a>, among the long-term survivors, genome and transcriptome sequencing is used to look for relationships between long-term survivors, and similar molecular profiles are found among all IDH-mutated patients with a survival longer than 36 months. However, the profiles of long-term survivors in “wild type” IDH are different and it is concluded that their long-term survival may be due to post-transcriptional changes and/or differences in the anti-tumour immune response of the patients.In all the services there is a documented case of glioblastoma of very long survival. When this happens, it is usually attributed to an error in the initial diagnosis. In our case, the 1997 sample was retrieved and re-evaluated thanks to the fantastic work of the pathological anatomy service at our centre. Following the use of current techniques to broaden its diagnosis, the original sample was confirmed to be a mutated IDH glioblastoma according to the current classification for central nervous system tumours.<a class="elsevierStyleCrossRef" href="#bib0060">12</a> The authors believe that the long-term survival of this specific case is probably due to an immune activation of the patient caused by a larval infectious process at the site of the craniotomy that forced evacuation and the empirical use of antibiotic therapy without being able to concretely isolate a germ.As we have been able to observe, most of the series collected from cases of very long survival belong to national databases (USA <a class="elsevierStyleCrossRefs" href="#bib0065">13,19</a>, Australia<a class="elsevierStyleCrossRef" href="#bib0075">15</a>, Italy<a class="elsevierStyleCrossRefs" href="#bib0080">16,17</a> and Germany<a class="elsevierStyleCrossRef" href="#bib0070">14</a>) that are publicly available. One of the works is even by Chinese authors who collect data from an American database<a class="elsevierStyleCrossRef" href="#bib0090">18</a>. The American National Cancer Database (NCDB), in particular, records the cases from more than 1500 accredited centres, collecting at least 70% of the new cases diagnosed in the United States thanks to the American College of Surgeons Commission on Cancer <a class="elsevierStyleCrossRef" href="#bib0095">19</a>. In Spain, however, there are numerous local databases, some autonomous and others created at the national level, such as the Registro nacional de tumores del sistema nervioso central [National Registry of Central Nervous System Tumours] (RETSINE) developed by the Grupo Español de Investigación en Neurooncología [Spanish Neurooncology Research Group]. Therefore, a change in management is required to try to unify all these databases and all move in the same direction if we want to be at the level of neighbouring countries. The authors of this work believe that, with significant institutional support, with an incentivised data collection or even with the mandatory declaration of glioblastoma cases, we could have collected those cases of unusually long survival that exist in all Spanish services to extract a patient profile that could be resistant to this type of tumour and could be reproduced in some way. Similarly, the individual study of each long-term surviving patient would be very interesting, not just the epidemiological and molecular variables already assessed and discussed in this study. For example, if there were recent vaccinations or immunisations, the patient's epigenetic profile or if the patient had a concomitant infectious process. In addition, tumour samples from these patients could be retrieved to re-evaluate, share, or even be sent to a specific reference centre in charge of collation.With regards to the conservation issue, there are several articles that address the maximum conservation time of pathological anatomy samples <a class="elsevierStyleCrossRef" href="#bib0190">38</a>. In our country this is regulated by law 41/2002<a class="elsevierStyleCrossRef" href="#bib0195">39</a> and the local regulations of each autonomous community. In this way, it is established that after fixation in formaldehyde, paraffin blocks should be stored for at least 10 years, although it is desirable to keep them indefinitely. In that same article<a class="elsevierStyleCrossRef" href="#bib0190">38</a> it is concluded that large hospitals (an average of 650 beds) and private centres tend to keep samples for less time. However, hospitals with an average of 427 public or subsidised beds usually keep samples indefinitely.ConclusionAlthough the long-term survival of glioblastoma patients is rare and has varied little over time, there are increasing numbers of series that collect these cases and are trying to establish some type of situation that characterises them. Unfortunately the studies and results are highly variable. A unified data collection at the national level should be encouraged to allow a more precise analysis of a disease such as glioblastoma.FundingThis work has not received public or private funding.Conflicts of interestThe authors declare that they have no conflicts of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:12 [ 0 => array:3 [ "identificador" => "xres1767521" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Material and method" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1553935" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1767520" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Material y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1553934" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Material and methods" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Search strategy" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Inclusion and exclusion criteria" ] ] ] 6 => array:3 [ "identificador" => "sec0025" "titulo" => "Results" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0030" "titulo" => "Case report" ] 1 => array:2 [ "identificador" => "sec0035" "titulo" => "Clinical characteristics of the studies" ] 2 => array:2 [ "identificador" => "sec0040" "titulo" => "Evaluation of associations in patients with long survival" ] ] ] 7 => array:2 [ "identificador" => "sec0045" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0050" "titulo" => "Conclusion" ] 9 => array:2 [ "identificador" => "sec0055" "titulo" => "Funding" ] 10 => array:2 [ "identificador" => "sec0060" "titulo" => "Conflicts of interest" ] 11 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2021-01-05" "fechaAceptado" => "2021-05-05" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1553935" "palabras" => array:5 [ 0 => "Glioblastoma" 1 => "Long-term survival" 2 => "Very long-term survival" 3 => "Cure" 4 => "Molecular profile" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1553934" "palabras" => array:5 [ 0 => "Glioblastoma" 1 => "Larga supervivencia" 2 => "Muy larga supervivencia" 3 => "Curación" 4 => "Perfil molecular" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "IntroductionIn spite of the changes for the treatment of glioblastoma since 2005, we have not seen differences between long-survival patients of more than 10 years showing a value minor than 1%. Material and methodWe realize a systematic analysis and identify important factors for long survivor patients. We also show an own case with more of 20 years of survival. We make a new pathological study of the old paraffin block of this patient. ResultsThe most important variable associated with long-survival between all multivariant studies is the age. When we try to find genetic and molecular alterations in glioblastoma associated with prolongated survival, the MGMT promoter methylation play the most important role. We find a correct diagnosis in the current analysis of our patient’s sample with very long survival. ConclusionsMultiple variables are found that affect long survival of glioblastoma series but analyzed studies are very heterogeneous and it is very difficult comparation between them. Most articles we review are obtained from databases of different countries with hundreds of patients. It would be very interesting to promote the use of a single database in Spain that allows us to study these long-term glioblastoma survivors." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Material and method" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "IntroducciónA pesar de las modificaciones introducidas en el tratamiento de los glioblastomas a partir del 2005, los pacientes supervivientes de más de 10 años se han mantenido constantes, siendo dicha cifra muy pobre e inferior al 1% en la mayoría de los estudios. Material y métodosSe realiza un análisis sistemático de la literatura identificando los factores que pueden influir en los pacientes de larga supervivencia. Se identifica un caso en nuestro medio de más de 20 años de supervivencia realizándose un análisis actual del bloque de parafina que se conservaba del paciente. ResultadosLa variable que más se asocia a la larga supervivencia en todos los análisis multivariantes es la edad, aunque, cuando se analiza las características genéticas y moleculares de los tumores, parecen existir otras variables como la metilación del promotor MGMT que juegan un papel muy importante. El análisis anatomo-patológico actual de la muestra comprueba la certeza del diagnóstico en nuestro paciente de muy larga supervivencia. ConclusionesMúltiples variables son encontradas que influencian la larga supervivencia en distintas series, si bien los estudios analizados son muy heterogéneos resultando muy difícil la comparación entre ellos. La mayoría de los estudios referenciados pertenecen a bases de datos nacionales de distintos países que engloban a cientos de pacientes. Sería interesante fomentar el uso de una única base de datos en Espa˜na que permita, entre otros, el análisis de estos pacientes de larga supervivencia afectos de glioblastoma." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Material y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: González Bonet LG, Piqueras-Sánchez C, Roselló-Sastre E, Broseta-Torres R, de las Peñas R. Glioblastomas de larga supervivencia: un análisis sistemático de la literatura a propósito de un caso. Neurocirugia. 2021. https://doi.org/10.1016/j.neucir.2021.05.002" ] ] "multimedia" => array:7 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 3834 "Ancho" => 2341 "Tamanyo" => 387078 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Search strategy flowchart." ] ] 1 => array:8 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 990 "Ancho" => 2508 "Tamanyo" => 366340 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "On the left, operative report of the first recurrence of the lesion. A circle shows the preoperative diagnosis that confirms the presence of a recurrence of a glioblastoma. The date of the recurrence of this lesion is indicated with a black arrow. On the right, MRI report confirming the recurrence of the lesion in the left parietal convexity." ] ] 2 => array:8 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 980 "Ancho" => 1305 "Tamanyo" => 328764 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0015" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Current anatomic pathological study from the paraffin block obtained during tumour resection in 1997. (A) Haematoxylin and eosin staining showing endothelial cell hyperplasia and the formation of abnormal vascular structures with multiple lumens simulating renal glomeruli. (B) Arrangement of tumour cells in pseudoepalisade around irregular foci of necrosis. (C) Immunohistochemical staining for IDH1 positive tumour cells. (D) Low power immunohistochemical staining for Ki-67 reflecting a positivity of approximately 5%." ] ] 3 => array:8 [ "identificador" => "fig0020" "etiqueta" => "Fig. 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 893 "Ancho" => 2175 "Tamanyo" => 97760 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0020" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "(A) Axial section image of the brain MRI in T1 sequences with contrast, where a left parietal porencephalic region is observed without significant abnormal uptakes. With a white arrow on a black background it is indicated that it was carried out 4 December 2008. (B) Axial section image of the brain MRI in T1 sequences with contrast, where a porencephalic area with similar characteristics to that observed in <a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a> is observed. An arrow indicates that the performance of said study was 26 February 2020." ] ] 4 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0025" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "ECOG: Eastern Cooperative Oncology Group scale; KPS: Karnofsky Performance Status scale; LTS: long-term survival; STS: short-term survival; VLTS: very long-term survival; CT: chemotherapy; RT: radiotherapy." "tablatextoimagen" => array:1 [ 0 => array:1 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><elsevierMultimedia ident="202209070705054781"></elsevierMultimedia><elsevierMultimedia ident="202209070705054782"></elsevierMultimedia> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] ] "descripcion" => array:1 [ "en" => "Studies meeting inclusion and exclusion criteria for the review." ] ] 5 => array:5 [ "identificador" => "202209070705054781" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => false "mostrarDisplay" => true "figura" => array:1 [ 0 => array:4 [ "imagen" => "fx1.jpeg" "Alto" => 4142 "Ancho" => 3333 "Tamanyo" => 1753597 ] ] ] 6 => array:5 [ "identificador" => "202209070705054782" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => false "mostrarDisplay" => true "figura" => array:1 [ 0 => array:4 [ "imagen" => "fx2.jpeg" "Alto" => 3565 "Ancho" => 3333 "Tamanyo" => 1426900 ] ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:39 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2008-2012" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "Q.T. 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Long-term survival of glioblastoma: A systematic analysis of literature about a case

Glioblastomas de larga supervivencia: un análisis sistemático de la literatura a propósito de un caso

Luis Germán González Boneta,b,

Corresponding author

lbonet@uji.es
luisgermangb@hotmail.com

Corresponding author.

, Claudio Piqueras-Sánchezb, Esther Roselló-Sastreb,c, Ricardo Broseta-Torresd, Ramón de las Peñase

a Servicio de Neurocirugía, Hospital General Universitario de Castellón, Castellón, Spain

b Facultad de Ciencias de la Salud, Universidad Jaume I de Castellón, Castellón, Spain

c Servicio de Anatomía Patológica, Hospital General Universitario de Castellón, Castellón, Spain

d Ascires/Eresa, Castellón, Spain

e Servicio de Oncología Médica, Hospital Provincial de Castellón, Castellón, Spain

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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Current anatomic pathological study from the paraffin block obtained during tumour resection in 1997&#46; &#40;A&#41; Haematoxylin and eosin staining showing endothelial cell hyperplasia and the formation of abnormal vascular structures with multiple lumens simulating renal glomeruli&#46; &#40;B&#41; Arrangement of tumour cells in pseudoepalisade around irregular foci of necrosis&#46; &#40;C&#41; Immunohistochemical staining for IDH1 positive tumour cells&#46; &#40;D&#41; Low power immunohistochemical staining for Ki-67 reflecting a positivity of approximately 5&#37;&#46;</p>"
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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">Glioblastoma is the most common primary malignant tumour of the central nervous system&#44; representing 75&#37; of all primary malignant brain tumours<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a>&#46; To be frank&#44; advances in the treatment of glioblastoma have been frustrating&#46; Although it is true that survival has improved since the application of the Stupp<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> protocol in 2005&#44; this increase in survival can be classified as poor&#44; with only 16&#37; of cases surviving longer than three years<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a>&#46; If we compare it with other entities&#44; such as breast cancer&#44; in this type of tumour&#44; survival has improved dramatically in the last 20 years&#44; it being 90&#46;2&#37; in the United States at five years or 82&#46;8&#37; in Spain for women diagnosed in the period 2010&#8211;2014<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a>&#46; This improvement is not only observed in tumours outside the central nervous system&#44; but is also seen in other lesions that exclusively affect the same central nervous system&#44; such as primary brain lymphoma in immunocompetent patients&#46; Classically associated with immunosuppression processes such as HIV&#44; the incidence of this type of lesion in immunocompetent patients has grown dramatically from 0&#46;4 to 1 cases per million in 1980 to 0&#46;5 cases per 100&#44;000 inhabitants<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a>&#46; Despite all this&#44; the combination of methotrexate&#44; rituximab and autologous transplantation has provided for survivals of 83&#37; at four years&#44; with only one biopsy conducted on the part of neurosurgery<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a>&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Although factors that improve survival have been described for glioblastoma<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7&#44;8</span></a>&#44; the percentage of patients with long-term survival at 10 years remains unchanged regardless of the Stupp protocol&#44; it being estimated at 0&#46;97&#37; for studies before 1993 and 0&#46;69&#37; in the most current ones<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a>&#46; However&#44; these figures can vary depending on the studies consulted&#44; with up to 5&#37; and 2&#46;4&#37; for survival at five and 10 years&#44; respectively&#44; in some American series<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a>&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">We put forward a systematic review of the literature of those series with the most characteristic long-term survival in relation to a case with a survival of more than 20 years&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Material and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Search strategy</span><p id="par0020" class="elsevierStylePara elsevierViewall">The search was carried out using the following databases&#58; PUBMED&#44; Scopus&#44; Cochrane and Scielo&#46; The search strategy used the following keywords and MeSH terms&#58; glioblastoma&#44; glioblastoma multiforme&#44; GBM&#44; long-term survival&#47;survivors&#44; cure&#44; three-year-survival&#44; three-year-survivor&#46; This was combined with the appropriate Boolean operators&#46; A flow chart was constructed with the search strategy &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Inclusion and exclusion criteria</span><p id="par0025" class="elsevierStylePara elsevierViewall">The inclusion criteria were established&#58; articles in Spanish&#44; English or French&#59; whether they were clinical trials&#44; cohort studies&#44; or cases and follow-up&#59; published after 2005 so that the introduction of the Stupp protocol could be assessed<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a>&#44; with a cohort of more than 300 patients in whom reviews of the pathological anatomy results could be performed&#59; including WHO grade IV gliomas with a majority representation of classic glioblastoma multiforme&#44; and articles in which the control group was not only representative samples&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Exclusion criteria eliminated&#58; articles dealing with grade I&#44; II or III gliomas&#59; those that include the paediatric population&#59; congenital glioblastomas&#59; articles that were systematic reviews&#44; isolated clinical cases or meta-analyses&#59; articles where fewer than five factors were analysed&#59; articles in which the survival value was under three years and&#44; finally&#44; studies where alternative treatments such as immunotherapy&#44; targeted molecular treatments or chemotherapy beyond temozolomide were evaluated&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">In the specific clinical case&#44; the pathological anatomy is reviewed by making new sections of the paraffin block that was fixed in 4&#37; paraformaldehyde and a diagnostic expansion for the assessment of Ki-67&#37;&#44; IDH&#44; ATRX and P53&#46; Likewise&#44; new haematoxylin and eosin stains are made&#46; Paper records and scanned material regarding the patient&#8217;s medical history are accessed&#46; Informed consent is requested from the patient and all personal data that would allow the identity of the patient is kept concealed&#46;</p></span></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Results</span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Case report</span><p id="par0040" class="elsevierStylePara elsevierViewall">The male patient in question with onset in 1997 at the age of 39 with a tonic-clonic seizure and a weakness of the right arm&#46; Magnetic resonance imaging &#40;MRI&#41; revealed a lesion of 3&#8239;cm with a peripheral and irregular contrast uptake and probably necrotic cystic interior content&#46; He underwent complete resection surgery on 10&#47;06&#47;1997&#46; The pathological anatomy reported glioblastoma multiforme according to the 1993 WHO classification<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a>&#46; In fact&#44; the patient presented a tumour recurrence of glioblastoma at five months and underwent surgery again on 13&#47;01&#47;1998 &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; The reports are preserved&#44; but the images are not copied for the elapsed time&#46; The patient received 60&#8239;Gy of radiotherapy and three treatment cycles with procarbazine&#44; lomustine and vincristine &#40;PCV&#41; as adjuvant chemotherapy before observing relapse at five months&#46; Two months after this latest intervention&#44; he presented with a deterioration of the general state&#44; as well as weakness in the right hemibody&#44; for which a CT scan was performed that reported a nodular image with peripheral uptake in the tumour bed associated with finger-like oedema&#46; Empirical antibiotic treatment was started due to suspicion of postoperative brain abscess so a trephine with evacuation of the content was carried out without observing a microorganism&#46; After this procedure&#44; the patient was transferred to a brain damage unit&#46; Finally&#44; a further intervention was performed a year later on an irregular uptake area on the tumour bed from which no tumour cells were observed&#44; concluding radionecrosis&#46; After this last intervention&#44; the patient continued with follow-up consultations&#44; the long evolution of the disease being surprising&#46; For this reason in 2020 it was decided to recover the paraffin blocks from the first surgery in 1997 and submit them to a new analysis &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46; A glial lesion is described with areas &#40;approximately 10&#37;&#41; of significant atypia and vascular proliferation&#44; as well as necrosis&#46; Immunohistochemical and molecular study reveals IDH1 mutation&#44; positivity for GFAP<span class="elsevierStyleSup">&#43;</span>&#44; partial loss of ATRX&#44; P53<span class="elsevierStyleSup">&#43;</span>&#44; EGFR<span class="elsevierStyleSup">&#8722;</span> and Ki-67 of 5&#37;&#46; Diagnosis with mutated IDH glioblastoma was made according to the 2016 WHO classification<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a>&#46; The current MRI dated 2020 is shown&#44; as well as the first MRI that we currently have in our PACS dated 2008 where no significant change is observed &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Clinical characteristics of the studies</span><p id="par0045" class="elsevierStylePara elsevierViewall">In the study by Cantrell JN et al&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> information is extracted from the cancer database of the USA between the period 2004&#8722;2009&#46; It is&#44; therefore&#44; a retrospective observational analysis&#46; In total&#44; 48&#44;652 patients were analysed&#44; of which 2249 &#40;4&#46;6&#37;&#41; survived for longer than five years&#46; Among those who survived longer than five years&#44; the average age is 52 years old compared to 64 years in the group under five years old&#46; Mean survival in this long-term evolution group is 88 months compared to seven months in the other group&#46; The Charlson Comorbidity Index was 0 in 85&#37; of the long-term survival patients &#40;72&#37; in the group with survival under five years&#41;&#44; 82&#37; received radiotherapy &#40;RT&#41; &#40;68&#37; in the ordinary group&#41; and 46&#37; chemotherapy &#40;CT&#41; &#40;35&#37; in the group with the lowest survival&#41;&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Reifenberger G et al&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> from the German Glioma Network and subsidised by the German Cancer Aid Association collected the cases from eight centres in Germany retrospectively between 2004 and 2012&#46; They established three groups&#58; short-term survival &#40;&#60;12 months&#41;&#44; medium-term survival &#40;12&#8211;36 months&#41; and long-term survival &#40;&#62;36 months&#41;&#46; Only 28 patients obtained the longest survival&#46; In addition to assessing the sociodemographic and clinical factors&#44; the molecular characteristics among the three survival groups were evaluated&#44; especially IDH1 and 2 mutations&#44; as well as MGMT methylation&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Gately L et al&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> performed a retrospective analysis of the databases from two centres in Australia&#46; In total they collected 776 cases of which only 31 &#40;approximately 4&#37;&#41; survived for longer than five years&#46; The study focuses on those who survive for longer than two years with a slightly more superficial analysis of those who survive longer than five years&#46; The mean age of patients with longer than five years&#39; survival is 47 years compared to 65 years in the group with the lowest survival&#46; The percentage of patients who received CT and RT was 97&#37; compared to 40&#37; in the under-two-years group&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">The study by Marton E et al&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> was a retrospective study of a single centre&#44; this time Italian&#44; but which included 1440 cases between 1998 and 2015&#44; of which 33 cases &#40;2&#46;3&#37;&#41; with a survival of longer than three years and only seven cases &#40;0&#46;5&#37;&#41; longer than 10 years were observed&#46; The mean age of the group with long-term survival of more than ten years was 41&#8239;years compared to 65 years in the group with the lowest survival&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Scoccianti S et al&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> also analysed a retrospective series of cases&#44; again in Italy&#44; but in a multicentre manner&#44; collecting a total of 1059 patients with glioblastoma multiforme between 2002 and 2007&#44; of which only 3&#46;9&#37; survived longer than five years&#44; that is&#44; 41 cases&#46; Unfortunately&#44; this study offers little descriptive epidemiological data on these long-term surviving patients&#44; although it does do comparative studies with those with low survival&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">The study by Tian M et al&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> was performed using the Surveillance&#44; Epidemiology&#44; and End Results &#40;SEER&#41; database&#44; which is 17 cancer data registries representing 26&#37; of the US population&#46; The data is collected between 2000 and 2008&#46; In total&#44; 6586 cases were obtained&#44; of which the survivors of more than five years were 483 patients &#40;7&#46;3&#37;&#41;&#44; 258 women and 225 men&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Finally&#44; we find the study by Zreik J et al&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a>&#44; that collect data from the American National Cancer Database between 2004 and 2013&#46; Of the 124&#44;231 cases of glioblastomas scanned&#44; 88&#44;919 had a follow-up of at least three years and 8757 had a survival of longer than three years &#40;9&#46;8&#37;&#41;&#46; Many socio-economic&#44; clinical and even molecular variables are analysed such as the year of diagnosis&#44; age&#44; gender&#44; race&#44; the comorbidity scale using the Charlson index&#44; the laterality of the lesion&#44; its location and size&#44; as well as the extension&#44; the adjuvant treatment and even the type of health insurance&#46; Patients who survived three years were younger at diagnosis &#40;mean age 55 compared to 65 for those who survived less than three years&#41;&#44; had private insurance&#44; a lower Charlson&#44; and more often received trimodal therapy&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Evaluation of associations in patients with long survival</span><p id="par0080" class="elsevierStylePara elsevierViewall">In the study by Cantrell JN et al&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> the multivariate analysis found differences in favour of greater survival in women&#44; younger patients who were non-white&#44; with greater purchasing power &#40;&#62;&#36;63&#44;000 per month&#41; and a comorbidity index of 0&#46; Interestingly&#44; the location of the lesion was only a factor that implied worse survival if the lesion was established in the trunk&#46; The size of the lesion was not significant for prognosis&#46; The study did find radiotherapy as a therapeutic factor influencing this long-term survival&#44; but not chemotherapy&#46; Unfortunately&#44; the molecular characteristics of the tumour were not analysed in this study&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">With regard to the German study by Reifenberger G et al&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> significant differences were only found in the group with the longest survival &#40;&#62;36 months&#41; for the youngest and those with a longer disease-free period&#46; When molecular studies were performed&#44; the IDH1 and 2 mutation and MGMT methylation were found to be significant for longer survival&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">In the study by Gately L et al&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> many variables were found in the multivariate analysis that seem to be involved regarding the long-term survivors&#44; such as age&#44; chemoradiotherapy treatment&#44; the patient&#39;s condition&#44; and the degree of resection&#46; However&#44; the study focuses on survivors of more than two years and when the analysis of survivors of more than five years is made and compared with this group of two years&#44; only age is found as a significant variable&#44; the rest being non-significant&#46; This study also did not perform a molecular study of the tumour&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">The study by Marton E et al&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> did perform molecular and immunohistochemical analyses unlike the Gateli and Cantrell studies&#46; Specifically&#44; they found significant differences in favour of greater survival with age and in patients with a Ki-67&#8239;&#60;&#8239;10&#37;&#44; no TERTp mutation&#44; MGMTp methylation&#44; and IDH1 and 2 mutation&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Scoccianti S et al&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> focused mainly on treatment with radiotherapy and chemotherapy before and after the introduction of the Stupp protocol&#46; In fact&#44; the study was organised by the Italian Association of Radiation Oncology&#46; The variables that were found to be significant after a multivariate analysis for better survival were&#58; age&#44; the pre-RT Karnofsky but not the pre-surgical Karnofsky&#44; the degree of resection but not the symptoms at onset&#44; the use of 3D conformal RT and the use of chemotherapy regardless of whether said use was before or after the introduction of the Stupp protocol in 2005&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">The study by Tian M et al&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> also performed a multivariate analysis of prognostic factors&#44; but not specifically of five-year survival&#46; The factors that were found to be significant in this multivariate analysis as prognoses of better survival were age&#44; specifically being under 40 years old&#44; being a woman&#44; treatment after 2005&#44; certain tumour locations and lesions less than 5&#8239;cm&#46; Molecular data of the types of lesions were again not analysed&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Zreik J et al&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> found a lot of statistical significance among all the variables studied&#46; Of all of them&#44; those with the most statistical power after multivariate analysis were age&#44; multimodal therapy&#44; and MGMT methylation &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Discussion</span><p id="par0115" class="elsevierStylePara elsevierViewall">Since the application of the Stupp protocol in 2005<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> the prognosis of glioblastoma patients seemed as if it may have changed&#44; but unfortunately it has not changed much&#46; However&#44; a manner of treating these patients in a systematic way was established that made it possible to compare different series from different countries&#46; Although an improvement in survival has been obtained for this type of tumour<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a>&#44; if we compare it with the evolution of other types of neoplasms&#44; this improvement could be classified as poor and disappointing<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;5</span></a>&#46; Despite this treatment with chemotherapy and radiotherapy&#44; patients with very long survival have not changed significantly before and after the Stupp protocol&#44; it being estimated at only 0&#46;71&#37; at 10 years<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a>&#46; However&#44; this value may vary depending on the series between 4<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> or 0&#46;5&#37; of a very large series of 11&#44;189 cases<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a>&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">What is striking when it comes to reviewing the literature is the lack of uniformity in the studies&#46; Single or multicentre studies&#44; with evaluation of very different variables&#44; some being carried out in the same country and obtaining quite varied results of statistical significance among the variables analysed&#46; Many studies are well-conducted reviews with a large number of patients&#44; but due to the fact that they were conducted on patients before 2016&#44; where the classification of tumours of the central nervous system was modified<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a>&#44; they do not refer to determinations such as the IDH&#46; Even terminologically&#44; long-term survival varies&#44; in some articles the definition of long-term survival being three years<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">16&#44;22&#44;23</span></a>&#44; others five years<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> or others 10 years<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a>&#46; This fact makes it very difficult to carry out a systematic review&#46; Furthermore&#44; it is difficult to find large series&#44; of more than 300 patients&#44; whereby in addition the control group is not a representative sample of those who do not achieve said survival&#44; but the control is the analysis of the rest of the patients&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">Among the studies found that met our inclusion and exclusion criteria&#44; we discovered a finding common to all of them&#46; Age as a criterion for long-term survival&#46; Another is that the percentage of patients who survive more than five years is close to 5&#37;&#46; From that point&#44; we found a number of differences between the studies&#46; Some found being a woman a prognostic factor for long-term survival<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13&#44;18</span></a>&#44; others the use of RT&#44; but not the use of CT<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a>&#46; Regarding the patient&#8217;s condition&#44; some evaluated the Charlson index&#44; finding it significant<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a>&#44; others the Karnofsky&#44; but they only found the pre-RT Karnofsky significant<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a>&#46; Others did not even find Karnofsky significant<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a>&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Moreover&#44; the improvement in surgical technique is evident reaching increasingly complete resection levels aided by techniques such as the use of 5-ALA&#44; intraoperative MRI as well as STIR sequences and neuronavigation<a class="elsevierStyleCrossRefs" href="#bib0120"><span class="elsevierStyleSup">24&#44;25</span></a>&#46; Although such complete resection clearly increases patient survival<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">26&#44;27</span></a>&#44; it is not clear that this resection has to do with the cases of long survival described&#44; this factor only being found to be significant in one of the long-survival studies referred to<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a>&#46; And in recent reviews it is not clear that the use of these techniques improves the overall survival of patients<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">28&#44;29</span></a>&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">In our work&#44; taking into account our inclusion and exclusion criteria&#44; several articles are collected that relate a molecular study with long-term survival and do so in relation to a Ki-67&#8239;&#60;&#8239;10&#37;&#44; a non-mutated TERTp&#44; as well as the presence of MGMT promoter methylation and IDH mutation<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">14&#44;16&#44;19</span></a>&#46; However&#44; there are more and more articles that collect patients with long-term survival at three and five years&#44; although in smaller series than those we wanted to evaluate in this review&#44; with specific molecular characteristics&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a>&#46; Specifically for these shorter series&#44; MGMT methylation seems to be&#44; of all these molecular characteristics&#44; the factor that most influences the long-term survivors<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">22&#44;23&#44;30&#44;31</span></a>&#44; although IDH mutation has also been found in some cases to be a statistically significant variable for said survival<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a>&#46; However&#44; this should not lead to the mistake that patients who survive long-term without methylation have been found<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">14&#44;31</span></a>&#44; although there was almost twice as much probability of being a long-term survivor and having the methylation than not having it&#46; In the same way&#44; it is also rarer&#44; but not impossible&#44; to find a long-term surviving patient who underwent only a biopsy and not a complete resection&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a>&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">There are other smaller series that attempt to relate long-term survival to the anatomical region of the subventricular zone&#44; finding that this zone seems to imply a lower probability of long-term survival<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">32&#44;33</span></a>&#46; This fact is based on the fact that the presence of adult mammalian precursor stem cells has been described in this region<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a>&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">On the other hand&#44; isolated cases of long-term survival have been described in association with certain immunisations or states of the patient at a specific time<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">35&#8211;37</span></a>&#46; In fact&#44; in the study by Reifenberger G et al&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a>&#44; among the long-term survivors&#44; genome and transcriptome sequencing is used to look for relationships between long-term survivors&#44; and similar molecular profiles are found among all IDH-mutated patients with a survival longer than 36 months&#46; However&#44; the profiles of long-term survivors in &#8220;wild type&#8221; IDH are different and it is concluded that their long-term survival may be due to post-transcriptional changes and&#47;or differences in the anti-tumour immune response of the patients&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">In all the services there is a documented case of glioblastoma of very long survival&#46; When this happens&#44; it is usually attributed to an error in the initial diagnosis&#46; In our case&#44; the 1997 sample was retrieved and re-evaluated thanks to the fantastic work of the pathological anatomy service at our centre&#46; Following the use of current techniques to broaden its diagnosis&#44; the original sample was confirmed to be a mutated IDH glioblastoma according to the current classification for central nervous system tumours&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> The authors believe that the long-term survival of this specific case is probably due to an immune activation of the patient caused by a larval infectious process at the site of the craniotomy that forced evacuation and the empirical use of antibiotic therapy without being able to concretely isolate a germ&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">As we have been able to observe&#44; most of the series collected from cases of very long survival belong to national databases &#40;USA <a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13&#44;19</span></a>&#44; Australia<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a>&#44; Italy<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">16&#44;17</span></a> and Germany<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a>&#41; that are publicly available&#46; One of the works is even by Chinese authors who collect data from an American database<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a>&#46; The American National Cancer Database &#40;NCDB&#41;&#44; in particular&#44; records the cases from more than 1500 accredited centres&#44; collecting at least 70&#37; of the new cases diagnosed in the United States thanks to the American College of Surgeons Commission on Cancer <a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a>&#46; In Spain&#44; however&#44; there are numerous local databases&#44; some autonomous and others created at the national level&#44; such as the Registro nacional de tumores del sistema nervioso central &#91;National Registry of Central Nervous System Tumours&#93; &#40;RETSINE&#41; developed by the Grupo Espa&#241;ol de Investigaci&#243;n en Neurooncolog&#237;a &#91;Spanish Neurooncology Research Group&#93;&#46; Therefore&#44; a change in management is required to try to unify all these databases and all move in the same direction if we want to be at the level of neighbouring countries&#46; The authors of this work believe that&#44; with significant institutional support&#44; with an incentivised data collection or even with the mandatory declaration of glioblastoma cases&#44; we could have collected those cases of unusually long survival that exist in all Spanish services to extract a patient profile that could be resistant to this type of tumour and could be reproduced in some way&#46; Similarly&#44; the individual study of each long-term surviving patient would be very interesting&#44; not just the epidemiological and molecular variables already assessed and discussed in this study&#46; For example&#44; if there were recent vaccinations or immunisations&#44; the patient&#39;s epigenetic profile or if the patient had a concomitant infectious process&#46; In addition&#44; tumour samples from these patients could be retrieved to re-evaluate&#44; share&#44; or even be sent to a specific reference centre in charge of collation&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">With regards to the conservation issue&#44; there are several articles that address the maximum conservation time of pathological anatomy samples <a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a>&#46; In our country this is regulated by law 41&#47;2002<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">39</span></a> and the local regulations of each autonomous community&#46; In this way&#44; it is established that after fixation in formaldehyde&#44; paraffin blocks should be stored for at least 10 years&#44; although it is desirable to keep them indefinitely&#46; In that same article<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a> it is concluded that large hospitals &#40;an average of 650 beds&#41; and private centres tend to keep samples for less time&#46; However&#44; hospitals with an average of 427 public or subsidised beds usually keep samples indefinitely&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Conclusion</span><p id="par0165" class="elsevierStylePara elsevierViewall">Although the long-term survival of glioblastoma patients is rare and has varied little over time&#44; there are increasing numbers of series that collect these cases and are trying to establish some type of situation that characterises them&#46; Unfortunately the studies and results are highly variable&#46; A unified data collection at the national level should be encouraged to allow a more precise analysis of a disease such as glioblastoma&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Funding</span><p id="par0170" class="elsevierStylePara elsevierViewall">This work has not received public or private funding&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Conflicts of interest</span><p id="par0175" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">In spite of the changes for the treatment of glioblastoma since 2005&#44; we have not seen differences between long-survival patients of more than 10 years showing a value minor than 1&#37;&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Material and method</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">We realize a systematic analysis and identify important factors for long survivor patients&#46; We also show an own case with more of 20 years of survival&#46; We make a new pathological study of the old paraffin block of this patient&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">The most important variable associated with long-survival between all multivariant studies is the age&#46; When we try to find genetic and molecular alterations in glioblastoma associated with prolongated survival&#44; the MGMT promoter methylation play the most important role&#46; We find a correct diagnosis in the current analysis of our patient&#8217;s sample with very long survival&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Multiple variables are found that affect long survival of glioblastoma series but analyzed studies are very heterogeneous and it is very difficult comparation between them&#46; Most articles we review are obtained from databases of different countries with hundreds of patients&#46; It would be very interesting to promote the use of a single database in Spain that allows us to study these long-term glioblastoma survivors&#46;</p></span>"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducci&#243;n</span><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">A pesar de las modificaciones introducidas en el tratamiento de los glioblastomas a partir del 2005&#44; los pacientes supervivientes de m&#225;s de 10 a&#241;os se han mantenido constantes&#44; siendo dicha cifra muy pobre e inferior al 1&#37; en la mayor&#237;a de los estudios&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Material y m&#233;todos</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Se realiza un an&#225;lisis sistem&#225;tico de la literatura identificando los factores que pueden influir en los pacientes de larga supervivencia&#46; Se identifica un caso en nuestro medio de m&#225;s de 20 a&#241;os de supervivencia realiz&#225;ndose un an&#225;lisis actual del bloque de parafina que se conservaba del paciente&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">La variable que m&#225;s se asocia a la larga supervivencia en todos los an&#225;lisis multivariantes es la edad&#44; aunque&#44; cuando se analiza las caracter&#237;sticas gen&#233;ticas y moleculares de los tumores&#44; parecen existir otras variables como la metilaci&#243;n del promotor MGMT que juegan un papel muy importante&#46; El an&#225;lisis anatomo-patol&#243;gico actual de la muestra comprueba la certeza del diagn&#243;stico en nuestro paciente de muy larga supervivencia&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">M&#250;ltiples variables son encontradas que influencian la larga supervivencia en distintas series&#44; si bien los estudios analizados son muy heterog&#233;neos resultando muy dif&#237;cil la comparaci&#243;n entre ellos&#46; La mayor&#237;a de los estudios referenciados pertenecen a bases de datos nacionales de distintos pa&#237;ses que engloban a cientos de pacientes&#46; Ser&#237;a interesante fomentar el uso de una &#250;nica base de datos en Espa&#732;na que permita&#44; entre otros&#44; el an&#225;lisis de estos pacientes de larga supervivencia afectos de glioblastoma&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Gonz&#225;lez Bonet LG&#44; Piqueras-S&#225;nchez C&#44; Rosell&#243;-Sastre E&#44; Broseta-Torres R&#44; de las Pe&#241;as R&#46; Glioblastomas de larga supervivencia&#58; un an&#225;lisis sistem&#225;tico de la literatura a prop&#243;sito de un caso&#46; Neurocirugia&#46; 2021&#46; <span class="elsevierStyleInterRef" id="intr0005" href="https://doi.org/10.1016/j.neucir.2021.05.002">https&#58;&#47;&#47;doi&#46;org&#47;10&#46;1016&#47;j&#46;neucir&#46;2021&#46;05&#46;002</span></p>"
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          "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">On the left&#44; operative report of the first recurrence of the lesion&#46; A circle shows the preoperative diagnosis that confirms the presence of a recurrence of a glioblastoma&#46; The date of the recurrence of this lesion is indicated with a black arrow&#46; On the right&#44; MRI report confirming the recurrence of the lesion in the left parietal convexity&#46;</p>"
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Article information

ISSN: 25298496
Original language: English

DOI:10.1016/j.neucie.2021.11.001

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