Wei SM, Zhu Y, Wei JX, Zhang CN, Shi JY, Lai HC. Accuracy of dynamic navigation in implant surgery: A systematic review and meta-analysis. Clin Oral Implants Res. 2021 Apr;32(4):383-393. doi: 10.1111/clr.13719.
Shanghai Jiao Tong University School of Medicine (grant no. DLY201822); Shanghai Clinical Research Center for Oral Diseases (grant no. 19,411,950,100); Clinical Research Plan of SHDC (grant no. 16CR3033A).
Systematic review with meta-analysis.

Dynamic navigation may be used for most implant surgery scenarios due to its satisfactory accuracy.

Previous studies revealed that the epithelial component is associated with the modulation of the ovarian tumor microenvironment (TME). However, the identification of key transcriptional signatures of laser capture microdissected human ovarian cancer epithelia remains lacking.
We identified the differentially expressed transcriptional signatures of human ovarian cancer epithelia by meta-analysis of GSE14407, GSE2765, GSE38666, GSE40595, and GSE54388. Then we investigated the enrichment of KEGG pathways that are associated with epithelia-derived transcriptomes. Finally, we investigated the correlation of key epithelia-hub genes with the survival prognosis and immune infiltrations. Finally, we investigated the genetic alterations of key prognostic hub genes and their diagnostic efficacy in ovarian cancer epithelia.
We identified 1339 differentially expressed genes (DEGs) in ovarian cancer epithelia including 541upregulated and 798 downregulated genes. We identified 21 (such as E2F4, FOXM1, TFDP1, E2F1, and SIN3A) and 11 (such as JUN, DDX4, FOSL1, NOC2L, and HMGA1) master transcriptional regulators (MTRs) that are interacted with upregulated and the downregulated genes in ovarian tumor epithelium, respectively. The STRING-based analysis identified hub genes (such as CDK1, CCNB1, AURKA, CDC20, and CCNA2) in ovarian cancer epithelia. The significant clusters of identified hub genes are associated with the enrichment of KEGG pathways including cell cycle, DNA replication, cytokine-cytokine receptor interaction, pathways in cancer, and focal adhesion. The upregulation of SCNN1A and CDCA3 and the downregulation of SOX6 are correlated with a shorter survival prognosis in ovarian cancer (OV). The expression level of SOX6 is negatively correlated with immune score and positively correlated with tumor purity in OV. Moreover, SOX6 is negatively correlated with the infiltration of TILs, CD8+ T cells, CD4+ Regulatory T cells, cytolytic activity, T cell activation, pDC, neutrophils, and macrophages in OV. Also, SOX6 is negatively correlated with various immune markers including CD8A, PRF1, GZMA, GZMB, NKG7, CCL3, and CCL4, indicating the immune regulatory efficiency of SOX6 in the TME of OV. Furthermore, SCNN1A, CDCA3, and SOX6 genes are genetically altered in OV and the expression levels of SCNN1A and SOX6 genes showed diagnostic efficacy in ovarian cancer epithelia.
The identified ovarian cancer epithelial-derived key transcriptional signatures are significantly correlated with survival prognosis and immune infiltrations, and may provide new insight into the diagnosis and treatment of epithelial ovarian cancer.

Meta-analysis identifying epithelial-derived transcriptomes predicts poor clinical outcome and immune infiltrations in ovarian cancer.

Graft-versus-host disease (GVHD) is a leading cause of death in patients after hematopoietic stem-cell transplantation (HSCT). Previous studies have shown different efficacy of GVHD prophylaxis therapies.
We reviewed 46 randomized controlled trials (including 8050 participants) systematically from Jun 20, 2004 to Aug 20, 2019. These investigations compared the following drugs or their combination at therapeutic dose range for GVHD after HSCT. The main results were based on the proportion of patients who respond to these therapies.
Cyclosporine + methotrexate + Anti-T cell globulin (ATG), tacrolimus + methotrexate + ATG, tacrolimus + bortezomib + sirolimus and cyclosporine + marrow mesenchymal stem cells (MMSCs) were significantly more efficacious than corticosteroids alone (OR: 12.15, 6.71, 6.25, 3.73). corticosteroids alone were less efficacious than all the other GVHD prophylaxis therapies tested.
Cyclosporine + methotrexate + ATG may be the best choice when starting treatment for GVHD.

Comparative efficacy of 20 graft-versus-host disease prophylaxis therapies for patients after hematopoietic stem-cell transplantation: A multiple-treatments network meta-analysis.

Nutritional status is a significant issue in an aging society; however, the impact of the nutritional status of older individuals using long-term care services on the caregiving burden remains unclear. This systematic review and meta-analysis aimed to investigate the impact of nutritional issues on adverse outcomes in older individuals using long-term care services.
We used data from the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, Web of Science, CINAHL, and Ichu-shi Web databases. Original articles published in English or Japanese between January 2000 and July 2022 were included. The inclusion criteria were interventional and observational studies on individuals using long-term care services with aged ≥65 years and a focus on body weight or weight loss. Data on adverse outcomes related to caregiving burden, including the number of people requiring care, mortality, complications, activities of daily living (ADL), and quality of life, were collected.
The literature search yielded 7873 studies, of which 35 were ultimately included. Seven observational studies investigated mortality outcomes, and seven examined ADL outcomes. The meta-analysis revealed significantly higher mortality rates in individuals classified as underweight (BMI <18.5 kg/m
Our findings indicate that underweight and weight loss are significantly associated with increased mortality in older individuals using long-term care services. Therefore, appropriate weight management is recommended for this population. However, further research is necessary owing to the high heterogeneity observed in this study.

Relationship between nutritional status and clinical outcomes among older individuals using long-term care services: A systematic review and meta-analysis.

Gallbladder cancer is the most common malignancy of the biliary tract. Given the lack of therapeutic alternatives for advanced stage patients studies have suggested that palliative chemotherapy could benefit these patients.
We searched in Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis, and generated a summary of findings table using the GRADE approach.
We identified two systematic reviews including two studies overall, of which one was a randomized trial. We concluded that palliative chemotherapy may increase survival in advanced gallbladder cancer patients. However, palliative chemotherapy probably increases adverse effects. In addition, it is essential to carry out a new systematic review, since methodological errors were identified in the analysis and there is new evidence that has not been included in the previous reviews.
El cáncer de vesícula es el cáncer más frecuente de la vía biliar. Debido a la escasez de alternativas terapéuticas para pacientes con etapas avanzadas de la enfermedad, se ha planteado que quimioterapia paliativa puede ser beneficiosa para estos pacientes.
Realizamos una búsqueda en Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante el cribado de múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, analizamos los datos de los estudios primarios, realizamos un metanálisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE.
Identificamos dos revisiones sistemáticas que en conjunto incluyeron dos estudios primarios, de los cuales, uno corresponde a un ensayo aleatorizado. Concluimos que la quimioterapia paliativa podría aumentar la sobrevida en cáncer de vesícula biliar avanzado. Sin embargo, probablemente aumenta los efectos adversos. Además, es imprescindible realizar una nueva revisión sistemática, ya que se identificaron errores metodológicos importantes en el análisis realizado y existe nueva evidencia que no ha sido incluida en revisiones previas.

Palliative chemotherapy for advanced gallbladder cancer.

Different interventions have been proposed to improve influenza vaccine coverage. The use of reminders, through letters, phone calls, pamphlets or technological applications, among others, has stood out among the different alternatives to increase adherence to vaccination. However, its effectiveness is not clear. In this summary, the first of a series of evaluation of reminders will address the use of a reminder sent by mail.
We searched in Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the identified reviews, analyzed the data from the primary studies, performed a meta-analysis and prepared a summary table of the results using the GRADE method.
We identified eight systematic reviews that included 35 primary studies, of which 32 correspond to randomized trials. We concluded that a reminder sent by mail, probably increase adherence to influenza vaccination in all age groups (adult population, over 60 an under 18).
Distintas intervenciones han sido propuestas para reforzar el uso de la vacuna contra la influenza. El uso de recordatorios, ya sea a través de cartas, llamadas telefónicas, panfletos o aplicaciones tecnológicas, entre otras, ha destacado dentro de aquellas orientadas a incrementar la adherencia al tratamiento. Sin embargo, su efectividad no está clara. En este resumen, el primero de una serie de evaluación de recordatorios, se abordará el uso de un recordatorio enviado por correo.
Realizamos una búsqueda en Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante el cribado de múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, analizamos los datos de los estudios primarios, realizamos un meta-análisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE.
Identificamos ocho revisiones sistemáticas que en conjunto incluyeron 35 estudios primarios, de los cuales, 32 corresponden a ensayos aleatorizados. Concluimos que un recordatorio enviado por correo probablemente aumenta la adherencia a vacunación contra influenza en todos los grupos etarios (población adulta, mayores de 60 años y menores de 18 años).

Reminder sent by mail to increase adherence to influenza vaccination.

This living systematic review aims to provide a timely, rigorous, and continuously updated summary of the evidence available on the role of angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB) in the treatment of patients with COVID-19.
We conducted searches in PubMed/Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), grey literature and in a centralized repository in L·OVE (Living OVerview of Evidence), which retrieves articles from multiple sources such as PubMed/MEDLINE, Cochrane Central Register of Controlled Trials, Embase, among other pre-print and protocols repositories. In response to the COVID-19 emergency, L·OVE (Living OVerview of Evidence) was adapted to expand the range of evidence and customized to group all COVID-19 evidence in one place on a daily search basis. The search covered a period of time up to July 31, 2020.
We adapted an already published standard protocol for multiple parallel living systematic reviews to this question's specificities. We included randomized trials evaluating the effect of either suspension or indication of angiotensin-converting-enzyme inhibitors or angiotensin II receptor blockers as monotherapy, or in combination versus placebo or no treatment in patients with COVID-19. We searched for randomized trials evaluating the effect of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers versus placebo or no treatment in patients with COVID-19. Two reviewers independently screened each study for eligibility, extracted data, and assessed the risk of bias. We pooled the results using meta-analysis and applied the GRADE system to assess the certainty of the evidence for each outcome. We will resubmit results every time the conclusions change or whenever there are substantial updates.
We screened 772 records, but none was considered for eligibility. We identified 55 ongoing studies, including 41 randomized trials evaluating angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers for patients with COVID-19.
We did not find a randomized clinical trial meeting our inclusion criteria, and hence there is no evidence for supporting the role of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in the treatment of patients with COVID-19. A substantial number of ongoing studies would provide valuable evidence to inform researchers and decision-makers in the near future.
CRD42020182495.
10.31219/osf.io/vp9nj.
Esta revisión sistemática viva tiene como objetivo proporcionar un resumen oportuno, riguroso y continuamente actualizado de la evidencia disponible sobre el rol de los inhibidores de la enzima convertidora de angiotensina (iECA) y los bloqueadores del receptor de angiotensina II (ARA-II) en el tratamiento de pacientes con COVID-19.
Realizamos búsquedas en PubMed/Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), literatura gris y en el repositorio centralizado L·OVE (Living OVerview of Evidence) que recupera artículos de múltiples fuentes como PubMed/MEDLINE, Cochrane Central Register of Controlled Trials, Embase, entre otros repositorios de preprints y protocolos. En respuesta a la emergencia de COVID-19, L·OVE (Living OVerview of Evidence) se adaptó para ampliar el rango de información que cubre y se personalizó para agrupar toda la evidencia en torno a COVID-19 en un solo lugar, en una base de búsqueda diaria. La búsqueda cubrió el período hasta el 31 de julio de 2020.
Adaptamos un protocolo común ya publicado para múltiples revisiones sistemáticas vivas paralelas a las especificidades de esta pregunta. Se incluyeron ensayos aleatorizados que evaluaban el efecto de la suspensión o la indicación de inhibidores de la enzima convertidora de angiotensina o bloqueadores de los receptores de angiotensina II, como monoterapia o en combinación, versus placebo o ningún tratamiento, en pacientes con COVID-19. Se buscaron ensayos aleatorizados que evaluaran el efecto de los inhibidores de la enzima convertidora de angiotensina/bloqueadores del receptor de angiotensina II versus placebo o ningún tratamiento en pacientes con COVID-19. Dos revisores examinaron de forma independiente la elegibilidad de cada estudio, extrajeron los datos y evaluaron el riesgo de sesgo. Los resultados se agruparon mediante un metanálisis y se aplicó GRADE para evaluar la certeza de la evidencia para cada resultado. Cada vez que cambien las conclusiones o hayan actualizaciones sustanciales, volveremos a enviar un reporte.
Analizamos 772 artículos, pero ninguno cumplió con los criterios de inclusión. Identificamos 55 estudios en curso, incluidos 41 ensayos aleatorizados que evaluaban inhibidores de la enzima convertidora de angiotensina/bloqueadores del receptor de angiotensina II para pacientes con COVID-19.
No encontramos ningún ensayo clínico aleatorizado que cumpliera con nuestros criterios de inclusión y, por lo tanto, no hay pruebas que respalden el papel de los inhibidores de la enzima convertidora de angiotensina y los bloqueadores de los receptores de angiotensina II en el tratamiento de pacientes con COVID-19. Identificamos un número considerable de estudios en curso que podría proporcionar evidencia valiosa para informar a los investigadores y a los responsables de la toma de decisiones en un futuro próximo.

Angiotensin-converting-enzyme inhibitors and angiotensin II receptor blockers for COVID-19: A living systematic review of randomized clinical trials.

Glioblastoma (GBM) is a highly malignant brain tumour that almost inevitably progresses or recurs after first line standard of care. There is no consensus regarding the best treatment/s to offer people upon disease progression or recurrence. For the purposes of this review, progression and recurrence are considered as one entity.
To evaluate the effectiveness of further treatment/s for first and subsequent progression or recurrence of glioblastoma (GBM) among people who have received the standard of care (Stupp protocol) for primary treatment of the disease; and to prepare a brief economic commentary on the available evidence.
We searched MEDLINE and Embase electronic databases from 2005 to December 2019 and the Cochrane Central Register of Controlled Trials (CENTRAL, in the Cochrane Library; Issue 12, 2019). Economic searches included the National Health Service Economic Evaluation Database (NHS EED) up to 2015 (database closure) and MEDLINE and Embase from 2015 to December 2019.
Randomised controlled trials (RCTs) and comparative non-randomised studies (NRSs) evaluating effectiveness of treatments for progressive/recurrent GBM. Eligible studies included people with progressive or recurrent GBM who had received first line radiotherapy with concomitant and adjuvant temozolomide (TMZ).
Two review authors independently selected studies and extracted data to a pre-designed data extraction form. We conducted network meta-analyses (NMA) and ranked treatments according to effectiveness for each outcome using the random-effects model and Stata software (version 15). We rated the certainty of evidence using the GRADE approach.
We included 42 studies: these comprised 34 randomised controlled trials (RCTs) and 8 non-randomised studies (NRSs) involving 5236 participants. We judged most RCTs to be at a low risk of bias and NRSs at high risk of bias. Interventions included chemotherapy, re-operation, re-irradiation and novel therapies either used alone or in combination. For first recurrence, we included 11 interventions in the network meta-analysis (NMA) for overall survival (OS), and eight in the NMA for progression-free survival (PFS). Lomustine (LOM; also known as CCNU) was the most common comparator and was used as the reference treatment. No studies in the NMA evaluated surgery, re-irradiation, PCV (procarbazine, lomustine, vincristine), TMZ re-challenge or best supportive care. We could not perform NMA for second or later recurrence due to insufficient data. Quality-of-life data were sparse. First recurrence (NMA findings) Median OS across included studies in the NMA ranged from 5.5 to 12.6 months and median progression-free survival (PFS) ranged from 1.5 months to 4.2 months. We found no high-certainty evidence that any treatments tested were better than lomustine. These treatments included the following. Bevacizumab plus lomustine: Evidence suggested probably little or no difference in OS between bevacizumab (BEV) combined with lomustine (LOM) and LOM monotherapy (hazard ratio (HR) 0.91, 0.75 to 1.10; moderate-certainty evidence), although BEV + LOM may improve PFS (HR 0.57, 95% confidence interval (CI) 0.44 to 0.74; low-certainty evidence). Bevacizumab monotherapy: Low-certainty evidence suggested there may be little or no difference in OS (HR 1.22, 95% CI 0.84 to 1.76) and PFS (HR 0.90, 95% CI 0.58 to 1.38; low-certainty evidence) between BEV and LOM monotherapies; more evidence on BEV is needed. Regorafenib (REG): REG may improve OS compared with LOM (HR 0.50, 95% CI 0.33 to 0.76; low-certainty evidence). Evidence on PFS was very low certainty and more evidence on REG is needed. Temozolomide (TMZ) plus Depatux-M (ABT414): For OS, low-certainty evidence suggested that TMZ plus ABT414 may be more effective than LOM (HR 0.66, 95% CI 0.47 to 0.92) and may be more effective than BEV (HR 0.54, 95% CI 0.33 to 0.89; low-certainty evidence). This may be due to the TMZ component only and more evidence is needed. Fotemustine (FOM): FOM and LOM may have similar effects on OS (HR 0.89, 95% CI 0.51 to 1.57, low-certainty evidence). Bevacizumab and irinotecan (IRI): Evidence on BEV + irinotecan (IRI) versus LOM for both OS and PFS is very uncertain and there is probably little or no difference between BEV + IRI versus BEV monotherapy (OS: HR 0.95, 95% CI 0.70 to 1.30; moderate-certainty evidence). When treatments were ranked for OS, FOM ranked first, BEV + LOM second, LOM third, BEV + IRI fourth, and BEV fifth. Ranking does not take into account the certainty of the evidence, which also suggests there may be little or no difference between FOM and LOM. Other treatments Three studies evaluated re-operation versus no re-operation, with or without re-irradiation and chemotherapy, and these suggested possible survival advantages with re-operation within the context of being able to select suitable candidates for re-operation. A cannabinoid treatment in the early stages of evaluation, in combination with TMZ, merits further evaluation. Second or later recurrence Limited evidence from three heterogeneous studies suggested that radiotherapy with or without BEV may have a beneficial effect on survival but more evidence is needed. Evidence was insufficient to draw conclusions about the best radiotherapy dosage. Other evidence suggested that there may be little difference in survival with tumour-treating fields compared with physician's best choice of treatment. We found no reliable evidence on best supportive care. Severe adverse events (SAEs) The BEV+LOM combination was associated with significantly greater risk of SAEs than LOM monotherapy (RR 2.51, 95% CI 1.72 to 3.66, high-certainty evidence), and ranked joint worst with cediranib + LOM (RR 2.51, 95% CI 1.29 to 4.90; high-certainty evidence). LOM ranked best and REG ranked second best. Adding novel treatments to BEV was generally associated with a higher risk of severe adverse events compared with BEV alone.
For treatment of first recurrence of GBM, among people previously treated with surgery and standard chemoradiotherapy, the combination treatments evaluated did not improve overall survival compared with LOM monotherapy and were often associated with a higher risk of severe adverse events. Limited evidence suggested that re-operation with or without re-irradiation and chemotherapy may be suitable for selected candidates. Evidence on second recurrence is sparse. Re-irradiation with or without bevacizumab may be of value in selected individuals, but more evidence is needed.
El glioblastoma (GBM) es un tumor cerebral altamente maligno que casi inevitablemente progresa o recidiva después de un tratamiento de primera línea. No hay consenso sobre el mejor o los mejores tratamientos que se pueden ofrecer a las personas que presentan progresión o recidiva de la enfermedad. A los efectos de la presente revisión, la progresión y la recidiva se consideran como una sola entidad.
Evaluar la efectividad de los tratamientos adicionales para la primera y subsiguiente progresión o recidiva del glioblastoma (GBM) entre las personas que han recibido atención estándar (protocolo Stupp) para el tratamiento primario de la enfermedad, así como preparar un breve comentario económico sobre la evidencia disponible. MÉTODOS DE BÚSQUEDA: Se realizaron búsquedas en las bases de datos electrónicas de MEDLINE y Embase desde 2005 hasta diciembre de 2019 y en el Registro Cochrane central de ensayos controlados (Cochrane Central Register of Controlled Trials) (CENTRAL, en la Cochrane Library; Número 12, 2019). Las búsquedas económicas incluyeron la National Health Service Economic Evaluation Database (NHS EED) hasta 2015 (cierre de la base de datos) y MEDLINE y Embase desde 2015 hasta diciembre de 2019. CRITERIOS DE SELECCIÓN: Ensayos controlados aleatorizados (ECA) y estudios comparativos no aleatorizados (no ECA) que evaluaron la efectividad de los tratamientos para el GBM progresivo/recidivante. Los estudios elegibles incluyeron personas con GBM progresivo o recidivante que habían recibido radioterapia de primera línea con temozolomida (TMZ) concomitante y adyuvante. OBTENCIÓN Y ANÁLISIS DE LOS DATOS: Dos autores de la revisión de forma independiente seleccionaron los estudios y extrajeron los datos en un formulario de extracción de datos prediseñado. Se realizaron metanálisis en red (MAR) y los tratamientos se clasificaron según la efectividad de cada desenlace, mediante el modelo de efectos aleatorios y el software Stata (versión 15). La certeza de la evidencia se evaluó mediante los criterios GRADE.
Se incluyeron 42 estudios, que comprendieron 34 ensayos controlados aleatorizados (ECA) y ocho estudios no aleatorizados (no ECA), con 5236 participantes. Se consideró que la mayoría de los ECA tuvieron bajo riesgo de sesgo y que los no ECA tuvieron alto riesgo de sesgo. Las intervenciones incluyeron quimioterapia, reoperación, reirradiación y tratamientos nuevos, ya sea utilizadas solos o en combinación. Para la primera recidiva se incluyeron 11 intervenciones en el metanálisis en red (MAR) para la supervivencia general (SG), y ocho para la supervivencia sin progresión (SSP). La lomustina (LOM; también conocida como CCNU) fue el comparador más frecuente y se utilizó como tratamiento de referencia. Ningún estudio en el MAR evaluó la cirugía, la reirradiación, la PCV (procarbazina, lomustina, vincristina), la reexposición a TMZ o el mejor tratamiento de apoyo. No fue posible realizar un MAR para una segunda o posterior recidiva debido a que los datos no fueron suficientes. Los datos de calidad de vida fueron escasos. Primera recidiva (hallazgos del MAR) La mediana de la SG en los estudios incluidos en el MAR varió entre 5,5 y 12,6 meses y la mediana de la supervivencia sin progresión (SSP) varió entre 1,5 y 4,2 meses. No se encontró evidencia de certeza alta de que los tratamientos probados fueran mejores que la lomustina. Estos tratamientos incluyeron los siguientes. Bevacizumab más lomustina: La evidencia indicó probablemente poca o ninguna diferencia en la SG entre el bevacizumab (BEV) combinado con lomustina (LOM) y la monoterapia con LOM (cociente de riesgos instantáneo [CRI] 0,91; 0,75 a 1,10; evidencia de certeza moderada), aunque BEV + LOM puede mejorar la SSP (CRI 0,57; intervalo de confianza [IC] del 95%: 0,44 a 0,74; evidencia de certeza baja). Monoterapia con bevacizumab: La evidencia de certeza baja indicó que puede haber poca o ninguna diferencia en la SG (CRI 1,22; IC del 95%: 0,84 a 1,76) y la SSP (CRI 0,90; IC del 95%: 0,58 a 1,38; evidencia de certeza baja) entre las monoterapias con BEV y LOM; se necesita más evidencia sobre el BEV. Regorafenib (REG): El REG puede mejorar la SG en comparación con la LOM (CRI 0,50; IC del 95%: 0,33 a 0,76; evidencia de certeza baja). La evidencia sobre la SSP fue de certeza muy baja y se necesita más evidencia sobre el REG. Temozolomida (TMZ) más Depatux‐M (ABT414): En cuanto a la SG, evidencia de certeza baja indicó que TMZ más ABT414 puede ser más efectiva que LOM (CRI 0,66; IC del 95%: 0,47 a 0,92) y puede ser más efectiva que BEV (CRI 0,54; IC del 95%: 0,33 a 0,89; evidencia de certeza baja). Lo anterior se puede deber solamente al componente de TMZ, y se necesita más evidencia. Fotemustina (FOM): FOM y LOM pueden tener efectos similares sobre la SG (CRI 0,89; IC del 95%: 0,51 a 1,57, evidencia de certeza baja). Bevacizumab e irinotecan (IRI): La evidencia sobre BEV + irinotecan (IRI) versus LOM para la SG y la SSP no está clara y probablemente hay poca o ninguna diferencia entre BEV + IRI versus la monoterapia con BEV (SG: CRI 0,95; IC del 95%: 0,70 a 1,30; evidencia de certeza moderada). Cuando los tratamientos se clasificaron según la SG, FOM se clasificó primero, BEV + LOM segundo, LOM tercero, BEV + IRI cuarto, y BEV quinto. La clasificación no tiene en cuenta la certeza de la evidencia, lo que también indica que puede haber poca o ninguna diferencia entre FOM y LOM. Otros tratamientos Tres estudios evaluaron la reoperación versus ninguna reoperación, con o sin reirradiación y quimioterapia, e indicaron posibles ventajas en la supervivencia con la reoperación, en el contexto de poder seleccionar candidatos adecuados para esta intervención. Un tratamiento con cannabinoides en las primeras etapas de evaluación, en combinación con TMZ, merece evaluación adicional. Segunda o posterior recidiva La evidencia limitada de tres estudios heterogéneos indicó que la radioterapia con o sin BEV puede tener un efecto beneficioso sobre la supervivencia, pero se necesita más evidencia. La evidencia no fue suficiente para establecer conclusiones sobre la mejor dosis de radioterapia. Otra evidencia indicó que puede haber poca diferencia en la supervivencia con los campos de tratamiento del tumor en comparación con la mejor opción de tratamiento del médico. No se encontró evidencia fiable sobre el mejor tratamiento de apoyo. Eventos adversos graves (EAG) La combinación BEV + LOM se asoció con un riesgo significativamente mayor de EAG que la monoterapia con LOM (RR 2,51; IC del 95%: 1,72 a 3,66; evidencia de certeza alta), y se clasificó peor junto con cediranib + LOM (RR 2,51; IC del 95%: 1,29 a 4,90; evidencia de certeza alta). LOM se clasificó como el mejor y REG como el segundo mejor. Agregar nuevos tratamientos al BEV se asoció generalmente con un mayor riesgo de eventos adversos graves, en comparación con BEV solo.
Para el tratamiento de la primera recidiva del GBM en personas tratadas previamente con cirugía y quimiorradioterapia estándar, los tratamientos combinados evaluados no mejoraron la supervivencia general en comparación con la monoterapia con LOM, y a menudo se asociaron con un mayor riesgo de eventos adversos graves. Hay evidencia limitada que indica que la reoperación con o sin reirradiación y quimioterapia puede ser adecuada para candidatos seleccionados. La evidencia sobre la segunda recidiva es escasa. La reirradiación con o sin bevacizumab puede ser de valor en determinados individuos, pero se necesita más evidencia.

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