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BACKGROUND: High-grade gliomas (HGG) are the most aggressive primary brain tumors with poor prognoses despite conventional treatments. Immunotherapy has emerged as a promising avenue due to its potential to elicit a targeted immune response against tumor cells. OBJECTIVE: This meta-analysis aimed to evaluate the efficacy and safety of various immunotherapeutic strategies, including immune checkpoint inhibitors (ICI), virotherapy, and dendritic cell vaccines (DCV) in treating HGG. METHODS: Following the PRISMA framework, we searched PubMed, Cochrane, and Embase for studies reporting outcomes of HGG patients treated with immunotherapy. Key metrics included overall survival, progression-free survival, and treatment-related adverse events. RESULTS: We reviewed 47 studies, analyzing data from 3674 HGG patients treated with immunotherapy. The mean overall survival for patients treated with ICI was 11.05 months, with virotherapy at 11.79 months and notably longer for DCV at 24.11 months. The mean progression-free survival (PFS) for ICIs was 3.65 months. Virotherapy demonstrated a PFS favoring the control group, indicating minimal impact, while DCV showed substantial PFS improvement with a median of 0.43 times lower hazard compared to controls (95% CI: 29-64%). Adverse events were primarily Grade 1 or 2 for ICI, included a Grade 5 event for virotherapy, and were predominantly Grade 1 or 2 for DCV, indicating a favorable safety profile. CONCLUSION: Immunotherapy holds potential as an effective treatment for HGG, especially DCV. However, results vary significantly with the type of therapy and individual patient profiles. Further randomized controlled trials are necessary to establish robust clinical guidelines and optimize treatment protocols.
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OBJECTIVE: This study investigated the relationship between PDZK1 expression and Dynamic Contrast-Enhanced MRI (DCE-MRI) perfusion parameters in High-Grade Glioma (HGG). METHODS: Preoperative DCE-MRI scanning was performed on 80 patients with HGG to obtain DCE perfusion transfer coefficient (Ktrans), vascular plasma volume fraction (vp), extracellular volume fraction (ve), and reverse transfer constant (kep). PDZK1 in HGG patients was detected, and its correlation with DCE-MRI perfusion parameters was assessed by the Pearson method. An analysis of Cox regression was performed to determine the risk factors affecting survival, while Kaplan-Meier and log-rank tests to evaluate PDZK1's prognostic significance, and ROC curve analysis to assess its diagnostic value. RESULTS: PDZK1 was upregulated in HGG patients and predicted poor overall survival and progression-free survival. Moreover, PDZK1 expression distinguished grade III from grade IV HGG. PDZK1 expression was positively correlated with Ktrans 90, and ve_90, and negatively correlated with kep_max, and kep_90. CONCLUSION: PDZK1 is upregulated in HGG, predicts poor survival, and differentiates tumor grading in HGG patients. PDZK1 expression is correlated with DCE-MRI perfusion parameters.
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Neoplasias Encefálicas , Medios de Contraste , Glioma , Imagen por Resonancia Magnética , Clasificación del Tumor , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/irrigación sanguínea , Glioma/diagnóstico por imagen , Glioma/patología , Glioma/irrigación sanguínea , Estimación de Kaplan-Meier , Imagen por Resonancia Magnética/métodos , Pronóstico , Curva ROCRESUMEN
PURPOSE: Glioblastoma is a malignant and aggressive brain tumour that, although there have been improvements in the first line treatment, there is still no consensus regarding the best standard of care (SOC) upon its inevitable recurrence. There are novel adjuvant therapies that aim to improve local disease control. Nowadays, the association of intraoperative photodynamic therapy (PDT) immediately after a 5-aminolevulinic acid (5-ALA) fluorescence-guided resection (FGR) in malignant gliomas surgery has emerged as a potential and feasible strategy to increase the extent of safe resection and destroy residual tumour in the surgical cavity borders, respectively. OBJECTIVES: To assess the survival rates and safety of the association of intraoperative PDT with 5-ALA FGR, in comparison with a 5-ALA FGR alone, in patients with recurrent glioblastoma. METHODS: This article describes a matched-pair cohort study with two groups of patients submitted to 5-ALA FGR for recurrent glioblastoma. Group 1 was a prospective series of 11 consecutive cases submitted to 5-ALA FGR plus intraoperative PDT; group 2 was a historical series of 11 consecutive cases submitted to 5-ALA FGR alone. Age, sex, Karnofsky performance scale (KPS), 5-ALA post-resection status, T1-contrast-enhanced extent of resection (EOR), previous and post pathology, IDH (Isocitrate dehydrogenase), Ki67, previous and post treatment, brain magnetic resonance imaging (MRI) controls and surgical complications were documented. RESULTS: The Mantel-Cox test showed a significant difference between the survival rates (p = 0.008) of both groups. 4 postoperative complications occurred (36.6%) in each group. As of the last follow-up (January 2024), 7/11 patients in group 1, and 0/11 patients in group 2 were still alive. 6- and 12-months post-treatment, a survival proportion of 71,59% and 57,27% is expected in group 1, versus 45,45% and 9,09% in group 2, respectively. 6 months post-treatment, a progression free survival (PFS) of 61,36% and 18,18% is expected in group 1 and group 2, respectively. CONCLUSION: The association of PDT immediately after 5-ALA FGR for recurrent malignant glioma seems to be associated with better survival without additional or severe morbidity. Despite the need for larger, randomized series, the proposed treatment is a feasible and safe addition to the reoperation.
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Ácido Aminolevulínico , Neoplasias Encefálicas , Glioblastoma , Recurrencia Local de Neoplasia , Fotoquimioterapia , Cirugía Asistida por Computador , Humanos , Glioblastoma/cirugía , Glioblastoma/tratamiento farmacológico , Glioblastoma/diagnóstico por imagen , Ácido Aminolevulínico/uso terapéutico , Masculino , Neoplasias Encefálicas/cirugía , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/diagnóstico por imagen , Femenino , Persona de Mediana Edad , Fotoquimioterapia/métodos , Recurrencia Local de Neoplasia/cirugía , Anciano , Estudios de Cohortes , Cirugía Asistida por Computador/métodos , Fármacos Fotosensibilizantes/uso terapéutico , Adulto , Estudios Prospectivos , Procedimientos Neuroquirúrgicos/métodosRESUMEN
BACKGROUND AND OBJECTIVES: High-grade gliomas (HGGs) are aggressive tumors of the central nervous system that cause significant morbidity and mortality. Despite advances in surgery and radiation therapy (RT), HGG still has a high incidence of recurrence and treatment failure. Intraoperative radiotherapy (IORT) has emerged as a promising therapeutic approach to achieve local tumor control while sparing normal brain tissue from radiation-induced damage. METHODS: A systematic review and meta-analysis were conducted following PRISMA guidelines to evaluate the use of IORT for HGG. Eligible studies were included based on specific criteria, and data were independently extracted. Outcomes of interest included complications, IORT failure, survival rates at 12 and 24 months, and mortality. RESULTS: Sixteen studies comprising 436 patients were included. The overall complication rate after IORT was 17%, with significant heterogeneity observed. The IORT failure rate was 77%, while the survival rates at 12 and 24 months were 74% and 24%, respectively. The mortality rate was 62%. CONCLUSION: This meta-analysis suggests that IORT may be a promising adjuvant treatment for selected patients with HGG. Despite the high rate of complications and treatment failures, the survival outcomes were comparable or even superior to conventional methods. However, the limitations of the study, such as the lack of a control group and small sample sizes, warrant further investigation through prospective randomized controlled trials to better understand the specific patient populations that may benefit most from IORT. However, the limitations of the study, such as the lack of a control group and small sample sizes, warrant further investigation. Notably, the ongoing RP3 trial (NCT02685605) is currently underway, with the aim of providing a more comprehensive understanding of IORT. Moreover, future research should focus on managing complications associated with IORT to improve its safety and efficacy in treating HGG.
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Neoplasias Encefálicas , Glioma , Humanos , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/cirugía , Neoplasias Encefálicas/tratamiento farmacológico , Estudios Prospectivos , Glioma/radioterapia , Glioma/cirugía , Recurrencia Local de Neoplasia , Radioterapia/efectos adversosRESUMEN
Abstract Objective This study investigated the relationship between PDZK1 expression and Dynamic Contrast-Enhanced MRI (DCE-MRI) perfusion parameters in High-Grade Glioma (HGG). Methods Preoperative DCE-MRI scanning was performed on 80 patients with HGG to obtain DCE perfusion transfer coefficient (Ktrans), vascular plasma volume fraction (vp), extracellular volume fraction (ve), and reverse transfer constant (kep). PDZK1 in HGG patients was detected, and its correlation with DCE-MRI perfusion parameters was assessed by the Pearson method. An analysis of Cox regression was performed to determine the risk factors affecting survival, while Kaplan-Meier and log-rank tests to evaluate PDZK1′s prognostic significance, and ROC curve analysis to assess its diagnostic value. Results PDZK1 was upregulated in HGG patients and predicted poor overall survival and progression-free survival. Moreover, PDZK1 expression distinguished grade III from grade IV HGG. PDZK1 expression was positively correlated with Ktrans 90, and ve_90, and negatively correlated with kep_max, and kep_90. Conclusion PDZK1 is upregulated in HGG, predicts poor survival, and differentiates tumor grading in HGG patients. PDZK1 expression is correlated with DCE-MRI perfusion parameters.
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INTRODUCTION: High-grade gliomas cause cognitive impairment in those who suffer from them. However, there is a lack of precise data describing the cognitive deficit that occurs in this population, which would allow to better focus neuropsychological evaluations and make better clinical decisions in favor of the patient's recovery and quality of life. For this purpose, a systematic review of the literature was carried out to search for studies on neurocognitive alterations in patients with malignant brain tumors. MATERIALS AND METHODS: The systematic review was conducted under the criteria of the PRISMA guideline for reporting systematic review and meta-analysis reports, with a search of the PubMed database (MEDLINE). Descriptive and analytical observational studies between 2015 and 2020 were considered. RESULTS: 506 articles were identified, of which 16 met the inclusion criteria and were selected in the qualitative synthesis and described in the manuscript. CONCLUSIONS: High-grade gliomas cause significant alterations in cognitive domains such as language, attention, memory, empathy and executive functions. However, more studies focused on describing the neuropsychological alterations in this population are needed in order to make better clinical treatment and rehabilitation decisions.
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Neoplasias Encefálicas , Disfunción Cognitiva , Glioma , Adulto , Neoplasias Encefálicas/patología , Cognición , Disfunción Cognitiva/etiología , Glioma/patología , Humanos , Estudios Observacionales como Asunto , Calidad de VidaRESUMEN
Gliomas are the most frequent solid tumors in children. Among these, high-grade gliomas are less common in children than in adults, though they are similar in their aggressive clinical behavior. In adults, glioblastoma is the most lethal tumor of the central nervous system. Insulin-like growth factor 1 receptor (IGF1R) plays an important role in cancer biology, and its nuclear localization has been described as an adverse prognostic factor in different tumors. Previously, we have demonstrated that, in pediatric gliomas, IGF1R nuclear localization is significantly associated with high-grade tumors, worst clinical outcome, and increased risk of death. Herein we explore the role of IGF1R intracellular localization by comparing two glioblastoma cell lines that differ only in their IGF1R capacity to translocate to the nucleus. In vitro, IGF1R nuclear localization enhances glioblastoma cell motility and metabolism without affecting their proliferation. In vivo, IGF1R has the capacity to translocate to the nucleus and allows not only a higher proliferation rate and the earlier development of tumors but also renders the cells sensitive to OSI906 therapy. With this work, we provide evidence supporting the implications of the presence of IGF1R in the nucleus of glioma cells and a potential therapeutic opportunity for patients harboring gliomas with IGF1R nuclear localization.
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Glioblastoma , Glioma , Adulto , Carcinogénesis/metabolismo , Núcleo Celular/metabolismo , Niño , Glioblastoma/metabolismo , Glioma/metabolismo , Humanos , Receptores de Somatomedina/metabolismoRESUMEN
Pediatric high-grade glioma (pHGG) is one of the most aggressive brain tumors. Treatment includes surgery, radiotherapy, chemotherapy, or combination therapy in children older than 3−5 years of age. These devastating tumors are influenced by the hypoxic microenvironment that coordinatively increases the expression of carbonic anhydrases (CA9 and CA12) that are involved in pH regulation, metabolism, cell invasion, and resistance to therapy. The synthetic sulphonamide Indisulam is a potent inhibitor of CAs. The aim of this study was to evaluate the effects of Indisulam on CA9 and CA12 enzymes in pHGG cell lines. Our results indicated that, under hypoxia, the gene and protein expression of CA9 and CA12 are increased in pHGG cells. The functional effects of Indisulam on cell proliferation, clonogenic capacity, and apoptosis were measured in vitro. CA9 and CA12 gene and protein expression were analyzed by RT-PCR and western blot. The treatment with Indisulam significantly reduced cell proliferation (dose-time-dependent) and clonogenic capacity (p < 0.05) and potentiated the effect of apoptosis (p < 0.01). Indisulam promoted an imbalance in the anti-apoptotic BCL2 and pro-apoptotic BAX protein expression. Our results demonstrate that Indisulam contributes to apoptosis via imbalance of apoptotic proteins (BAX/BCL2) and suggests a potential to overcome chemotherapy resistance caused by the regulation these proteins.
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ABSTRACT Introduction: Some gene mutations in high grade glioma patients have many implications in prognosis and treatment response. Objectives: To describe the characteristics and associations of IDH, TP53 gene mutations and MGMT methylation status with some characteristics and treatment response in patients with high grade glioma. Methods: A descriptive, prospective, uncontrolled study was conducted, in 52 patients with high-grade glioma. Research variables include age, sex, Karnofsky score, the rate of IDH, P53 mutation, MGMT methylation; the relationship between genes mutation with some characteristics and response to treatment according to the RECIST classification. Results: For IDH gene mutation, grade III patients (23.1%) have a higher positive rate than grade IV (11.5 %); for P53 gene mutation, grade III patients (55.6 %) have a higher positive rate than grade IV (44.1 %); the rate of MGMT promoter methylation occurred in the study group of patients with the rate of 42.3 %. There is a relationship between IDH gene mutation with pathological results and malignancy in studied patients. Patients with the mutant expression of the IDH gene, p53, MGMT methylation status had better RECIST responses than patients without these expressions. Conclusion: High-grade glioma mainly occurs in men, over 40 years old. The presence of mutations in IDH, P53 genes, and MGMT methylation status was a beneficial factor for treatment response as assessed by RECIST.
RESUMEN Introducción: Algunas mutaciones genéticas en pacientes con glioma de alto grado tienen implicaciones en el pronóstico y respuesta al tratamiento. Objetivos: Describir las características y asociaciones de IDH, mutaciones del gen TP53 y estado de metilación de MGMT con algunas características y respuesta al tratamiento en pacientes con glioma de alto grado. Métodos: Se realizó un estudio descriptivo, prospectivo no controlado, en 52 pacientes con glioma de alto grado. Las variables investigadas fueron: edad, sexo, puntuación de Karnofsky, tasa de IDH, mutación P53, estado de metilación de MGMT, relación entre la mutación de genes con algunas características y la respuesta al tratamiento según la clasificación RECIST. Resultados: Mutación del gen IDH: los pacientes grado III (23,1 %) tienen una tasa positiva más alta que los grado IV (11,5 %). Mutación del gen P53: los grado III (55,6 %) tienen una tasa positiva más alta que los grado IV (44,1 %). La tasa de metilación del promotor de MGMT se produjo con una tasa del 42,3 %. Existe relación entre la mutación del gen IDH con los resultados patológicos y la malignidad. Los pacientes con la expresión mutante del gen IDH, p53, estado de metilación de MGMT tuvieron mejores respuestas RECIST. Conclusión: El glioma de alto grado se presenta principalmente en hombres, mayores de 40 años. La presencia de mutaciones en los genes IDH, P53 y el estado de metilación de MGMT fue un factor beneficioso para la respuesta al tratamiento según lo evaluado por RECIST.
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ABSTRACT Background: Cancer patients in general and glioblastoma patients, in particular, have an increased risk of developing complications from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and reaching a balance between the risk of exposure to infection and the clinical benefit of their treatment is ideal. The aggressive behavior of this group of tumors justifies the need for a multidisciplinary team to assist in clinical decisions during the current pandemic. Brazil is now ranked #2 in the number of cases and deaths from COVID-19 pandemic, and existing disparities in the treatment of neuro-oncology patients in Brazil will challenge the clinical and surgical decisions of this population, possibly affecting global survival. Objective: To search the literature about the management of glioblastomas during COVID-19 pandemic to guide surgical and clinical decisions in this population of patients in Brazil. Methods: We performed a systematic search on the PubMed electronic database targeting consensus statements concerning glioblastoma approaches during COVID-19 pandemic up to July 18, 2020. Results: When approaching glioblastoma during the COVID-19 pandemic, important parameters that help in the decision-making process are age, performance status, tumor molecular profile, and patient consent. Younger patients should follow the standard protocol after maximal safe resection, mainly those with MGMT methylated tumors. Aged and underperforming patients should be carefully evaluated, and probably a monotherapy scheme is to be considered. Centers are advised to engage in telemedicine and to elaborate means to reduce local infection. Conclusion: Approaching glioblastoma during the COVID-19 pandemic will be challenging worldwide, but particularly in Brazil, where a significant inequality of healthcare exists.
RESUMO Introdução: Pacientes com câncer, em geral, e particularmente pacientes com glioblastoma estão sob elevado risco de desenvolver síndrome respiratória aguda grave devido à infecção pelo SARS-CoV-2, e alcançar um equilíbrio entre risco de exposição à infecção e benefício clínico do tratamento seria o ideal. O comportamento agressivo desse grupo de tumores justifica a necessidade de equipe multidisciplinar para auxiliar nas decisões clínicas durante a pandemia vigente. O Brasil ocupa hoje o segundo lugar em número de casos e óbitos pela COVID-19, e as atuais disparidades no tratamento de pacientes neuro-oncológicos desafiarão as decisões clínicas e cirúrgicas dessa população, possivelmente afetando a sobrevida global. Objetivo: Guiar decisões clínicas e cirúrgicas relacionadas ao manejo de glioblastoma durante a pandemia pelo COVID-19 no Brasil por meio de pesquisa em literatura. Métodos: Busca sistemática no banco de dados eletrônico da PubMed por estudos ou consensos quanto à abordagem de glioblastoma durante a pandemia por COVID-19 até 18/07/2020. Resultado: Ao abordar o glioblastoma durante a pandemia pela COVID-19, parâmetros importantes que auxiliam no processo de tomada de decisão são idade, desempenho, perfil molecular tumoral e consentimento do paciente. Pacientes jovens devem seguir protocolo padrão após máxima ressecção cirúrgica, principalmente aqueles com metilação do promotor MGMT. Idosos e pacientes debilitados devem ser cuidadosamente avaliados, e monoterapia deve ser provavelmente considerada. Centros de saúde são orientados a utilizar-se da telemedicina e de meios para reduzir infecção local. Conclusão: A abordagem do glioblastoma durante a pandemia por COVID-19 será mundialmente desafiadora, mas particularmente no Brasil, onde ainda existe significativa inequidade no cuidado com a saúde.
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Humanos , Anciano , Glioblastoma/etiología , Glioblastoma/epidemiología , COVID-19 , Brasil/epidemiología , Pandemias , SARS-CoV-2RESUMEN
PURPOSE: To investigate the magnetic resonance imaging (MRI) images of brain glioma before postoperative radiotherapy, and to provide reference for the delineation of postoperative radiotherapy target area. METHODS: Retrospective analysis was performed on 106 cases of brain glioma confirmed by surgery and pathology in our hospital, including 70 cases of high-grade glioma (HGG) and 36 cases of low-grade glioma (LGG). The MRI images of the lesions within 1 month before and after surgery were analyzed, the apparent diffusion coefficient (ADC) values in the near and far tumor areas were measured, respectively, and the corresponding rADC values were calculated. RESULTS: The incidence of residual tumors of postoperative HGG and LGG was 0, 15.7% (0/36, 11/70), respectively. The incidence of postoperative reactive enhancement was 11.0% and 52.9% (4/36 and 37/70), respectively. About 30.6% and 81.4% (11/36 and 57/70) of patients with adjacent meningeal enhancement were found in the operative area. CONCLUSIONS: The MRI images of HGG and LGG before postoperative radiotherapy had certain characteristics, providing a favorable guidance for the delineation of the target area of radiotherapy and the formulation of treatment plan.
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Neoplasias Encefálicas/diagnóstico por imagen , Glioma/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Adolescente , Adulto , Anciano , Edema Encefálico/diagnóstico por imagen , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/cirugía , Niño , Imagen de Difusión Tensora , Femenino , Glioma/patología , Glioma/radioterapia , Glioma/cirugía , Humanos , Masculino , Meninges/diagnóstico por imagen , Persona de Mediana Edad , Clasificación del Tumor , Recurrencia Local de Neoplasia/diagnóstico por imagen , Neoplasia Residual/diagnóstico por imagen , Cuidados Posoperatorios , Complicaciones Posoperatorias/diagnóstico por imagen , Estudios Retrospectivos , Adulto JovenRESUMEN
PURPOSE: To describe a case series of children with thalamic tumors treated at our institution in a 5-year period. METHOD: A retrospective and observational study was performed. The records of 15 patients between 2013 and 2018 were analyzed. RESULTS: From 2013 to 2018, 15 patients were treated at our institution. The male to female index was 1.5, and the median age was 8.9 (IQR 4.75-13). Seven (46%) tumors were left-sided, seven (46%) were right-sided, and one (6%) was bilateral. All patients were symptomatic at the time of treatment. Motor deficit was the most common form of presentation (73%). Gross-total resection was performed in two (13.3%) patients, subtotal resection was performed in two other patients (13.3%), and for the rest of the patients (73.3%), the chosen surgical approach was a stereotactic-guided biopsy. The average of procedures was 3.4, mostly related to the treatment for hydrocephalus. Twelve patients (80%) received treatment for hydrocephalus. Nine patients (75%) were treated with ventriculoperitoneal shunts, and four patients (33%) underwent endoscopic third ventriculostomy. High-grade tumors predominated. Grade IV tumors were diagnosed in six patients (40%), followed by grade III in four patients (26.6%), grade II in three (20%) patients, and grade I in two (13.3%) patients. Chemotherapy was given in 93% of the cases, being temozolomide, the most used drug. CONCLUSION: The clinical and surgical approaches for thalamic tumors in children have changed over time. At our institution, the lesser invasive surgical procedures are now being used more frequently.
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Neoplasias Encefálicas , Hidrocefalia , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/cirugía , Niño , Femenino , Humanos , Hidrocefalia/etiología , Hidrocefalia/cirugía , Masculino , Estudios Observacionales como Asunto , Estudios Retrospectivos , Resultado del Tratamiento , Derivación Ventriculoperitoneal , VentriculostomíaRESUMEN
PURPOSE: To investigate the dosimetric impact between the anisotropic analytical algorithm (AAA) and the Acuros XB (AXB) algorithm in volumetric-modulated arc therapy (VMAT) plans for high-grade glioma (HGG). METHODS: We used a heterogeneous phantom to quantify the agreement between the measured and calculated doses from the AAA and from the AXB. We then analyzed 14 patients with HGG treated by VMAT, using the AAA. We newly created AXB plans for each corresponding AAA plan under the following conditions: (1) re-calculation for the same number of monitor units with an identical beam and leaf setup, and (2) re-optimization under the same conditions of dose constraints. The dose coverage for the planning target volume (PTV) was evaluated by dividing the coverage into the skull, air, and soft-tissue regions. RESULTS: Compared to the results obtained with the AAA, the AXB results were in good agreement with the measured profiles. The dose differences in the PTV between the AAA and re-calculated AXB plans were large in the skull region contained in the target. The dose difference in the PTV in both types of plan was significantly correlated with the volume of the skull contained in the target (r = 0.71, p = 0.0042). A re-optimized AXB plan's dose difference was lower vs. the re-calculated AXB plan's. CONCLUSIONS: We observed dose differences between the AAA and AXB plans, in particular in the cases in which the skull region of the target was large. Considering the phantom measurement results, the AXB algorithm should be used in VMAT plans for HGG.
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Algoritmos , Glioma/patología , Glioma/radioterapia , Radiometría , Planificación de la Radioterapia Asistida por Computador/métodos , Radioterapia de Intensidad Modulada , Anisotropía , Humanos , Clasificación del Tumor , Fantasmas de ImagenRESUMEN
Angiogenesis, induced by the vascular endothelial growth factor A through its ligation to the vascular endothelial growth receptor 2, has been described as a crucial point in high-grade glioma development. The aim of this study was to evaluate the influence of VEGFA-2578C/A, -2489C/T, -1154G/A, -634G/C, and -460C/T, and KDR-604T/C, -271G/A, +1192G/A, and +1719A/T single-nucleotide polymorphisms on risk and clinicopathological aspects of high-grade glioma. This case-control study enrolled 205 high-grade glioma patients and 205 controls. Individuals with VEGFA-2578 CC or CA, VEGFA-1154 GG, VEGFA-634 GC or CC, and VEGFA-460 CT or TT genotypes were under 2.56, 1.53, 1.54, and 1.84 increased risks of high-grade glioma, compared to others, respectively. And 1.61, 2.66, 2.52, 2.53, and 2.02 increased risks of high-grade glioma were seen in individuals with VEGFA-2578 CC plus VEGFA-1154 GG, VEGFA-2578 CC or CA plus VEGFA-634 GC or CC, VEGFA-2578 CC or CA plus VEGFA-460 CT or TT, VEGFA-1154 GG or GA plus VEGFA-634 GC or CC, and VEGFA 634 GC or CC plus VEGFA-460 CT or TT combined genotypes, respectively, when compared to others. The "CAGT" haplotype of KDR single-nucleotide polymorphisms was more common in patients with grade IV than in those with grade III tumors, and individuals carrying this haplotype were at 1.76 increased risk of developing grade IV tumors than others. We present, for the first time, preliminary evidence that VEGFA-2578C/A and VEGFA-1154G/A single-nucleotide polymorphisms increases high-grade glioma risk, and "CAGT" haplotype of the KDR gene alters high-grade glioma aggressiveness and risk of grade IV tumors in Brazil.
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Glioma/genética , Haplotipos , Polimorfismo de Nucleótido Simple , Factor A de Crecimiento Endotelial Vascular/genética , Receptor 2 de Factores de Crecimiento Endotelial Vascular/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Factores de Riesgo , Adulto JovenRESUMEN
We describe two patients with a confirmed diagnosis of high-grade gliomas (grades III/IV), both presenting with O6-methylguanine-DNA methyltransferase (MGMT) methylated and isocitrate dehydrogenase (IDH-1) mutated who, after subtotal resection, were submitted to chemoradiation and followed by PCV, a multiple drug regimen (procarbazine, lomustine, and vincristine) associated with cannabidiol (CBD). Both patients presented with satisfactory clinical and imaging responses at periodic evaluations. Immediately after chemoradiation therapy, one of the patients presented with an exacerbated and precocious pseudoprogression (PSD) assessed by magnetic resonance imaging (MRI), which was resolved in a short period. The other patient presented with a marked remission of altered areas compared with the post-operative scans as assessed by MRI. Such aspects are not commonly observed in patients only treated with conventional modalities. This observation might highlight the potential effect of CBD to increase PSD or improve chemoradiation responses that impact survival. Further investigation with more patients and critical molecular analyses should be performed.
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PURPOSE: The treatment of recurrent high-grade gliomas (HGG) is controversial. There are different therapeutic schedules but without a clear orientation about which of them should be used in each clinical situation. In addition, when patients suffer a second recurrence or they have poor performance status, they are excluded from clinical trials, although second recurrences and poor performance status are indeed more and more real and common situations in the clinical setting. In this study, we assessed the efficacy and safety of fotemustine (FTM) in HGG [fundamentally, glioblastomas (GB)], independent of time of recurrence or performance status. METHODS/PATIENTS: Retrospective study in HGG patients treated with FTM in second or further line according to standard, the Addeo or any other scheme, starting treatment prior to 30 November 2012. Included patients reflect the regular situation in which the drug is used in terms of comorbidities and analytic situation (hematologic, renal and hepatic functions). Response assessment was performed by MRI and according to the clinical protocols of each center (every 8-12 weeks). Clinical situation and supportive care drugs were evaluated in each medical consultation. Clinical end-points analyzed, among others, were: PFS-6, PFS, OS, response rates, toxicity, quality of life and neurocognitive impact. RESULTS: In terms of activity, an overall response rate of 8 % was observed: partial response 6 % (7 patients) and complete response 2 % (2 patients). The median time to achieve the greater response with FTM was 73 days (4-841 days). Patients treated according to the Addeo schedule had a shorter time to greater response in comparison with other schedules (85.9 vs 114 days), although without statistical significance. There were no significant differences in progression-free survival (PFS) when comparing different FTM schedules or using FTM in first or second recurrence. Median PFS: 3 months. PFS-6: 30.3 %. Overall survival (OS): although without significant differences, a tendency to better survival when using the Addeo schedule versus other schedules was observed (at 6 months, 44.6 vs 34.5 %; at 12 months, 25 vs 23.6 %; at 18 months, 11.5 vs 7.9 %), as well as if earlier use (second vs third line) concerning OS-12 (33.7 vs 18.2 %). Median OS: 5.2 months. Grades 3-4 toxicity was 28 % (31 patients), being neutropenia (4 %) and thrombocytopenia (17 %) the most frequent adverse reactions. From quality of life and neuro-cognitive function perspectives, 11 patients (10 %) and 16 (14 %) improved the Karnofsky Index and neurological impairment, respectively, after FTM treatment. CONCLUSION: This study has shown that FTM is safe and has a comparable activity with other available therapeutic options of use in the treatment of recurrent HGG.
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Antineoplásicos/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Glioma/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Compuestos de Nitrosourea/uso terapéutico , Compuestos Organofosforados/uso terapéutico , Adulto , Anciano , Neoplasias Encefálicas/mortalidad , Femenino , Glioma/mortalidad , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
Nimotuzumab, a humanized antibody targeting epidermal growth factor receptor, has potent anti-proliferative, anti-angiogenic, and pro-apoptotic effects in vitro and in vivo. It also reduces the number of radio-resistant CD133(+) glioma stem cells. The antibody has been extensively evaluated in patients with advanced head and neck, glioma, lung, esophageal, pancreatic, and gastric cancer. In this single institution experience, 35 patients with anaplastic astrocytoma (AA) or glioblastoma multiforme (GBM) were treated with irradiation and 200 mg doses of nimotuzumab. The first 6 doses were administered weekly, together with radiotherapy, and then treatment continued every 21 days until 1 year. The median number of doses was 12, and the median cumulative dose was thus 2400 mg of nimotuzumab. The most frequent treatment-related toxicities were increase in liver function tests, fever, nausea, anorexia, asthenia, dizziness, and tremors. These adverse reactions were classified as mild and moderate. The median survival time was 12.4 mo or 27.0 mo for patients with GBM or AA patients, respectively, who received curative-intent radiotherapy in combination with the antibody. The survival time of a matched population treated at the same hospital with irradiation alone was decreased (median 8.0 and 12.2 mo for GBM and AA patients, respectively) compared with that of the patients who received nimotuzumab and curative-intent radiotherapy. We have thus confirmed that nimotuzumab is a very well-tolerated drug, lacking cumulative toxicity after maintenance doses. This study, in a poor prognosis population, validates the previous data of survival gain after combining nimotuzumab and radiotherapy, in newly diagnosed high-grade glioma patients.
Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos/uso terapéutico , Astrocitoma/tratamiento farmacológico , Neoplasias Encefálicas/tratamiento farmacológico , Adulto , Anciano , Astrocitoma/patología , Astrocitoma/radioterapia , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/radioterapia , Terapia Combinada , Supervivencia sin Enfermedad , Femenino , Glioblastoma/tratamiento farmacológico , Glioblastoma/patología , Glioblastoma/radioterapia , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Adulto JovenRESUMEN
Brain tumors are a major cause of cancer-related mortality in children. Overexpression of epidermal growth factor receptor (EGFR) is detected in pediatric brain tumors and receptor density appears to increase with tumor grading. Nimotuzumab is an IgG1 antibody that targets EGFR. Twenty-three children with high-grade glioma (HGG) were enrolled in an expanded access program in which nimotuzumab was administered alone or with radio-chemotherapy. The mean number of doses was 39. Nimotuzumab was well-tolerated and treatment with the antibody yielded a survival benefit: median survival time was 32.66 mo and the 2-y survival rate was 54.2%. This study demonstrated the feasibility of prolonged administration of nimotuzumab and showed preliminary evidence of clinical benefit in HGG patients with poor prognosis.
Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Astrocitoma/terapia , Neoplasias Encefálicas/terapia , Glioma/terapia , Adolescente , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales Humanizados/administración & dosificación , Astrocitoma/mortalidad , Astrocitoma/patología , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/patología , Niño , Preescolar , Terapia Combinada , Quimioterapia , Receptores ErbB/inmunología , Femenino , Glioma/mortalidad , Glioma/patología , Humanos , Masculino , Clasificación del Tumor , Radioterapia , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
High-grade gliomas are highly vascularized tumors. Neo-angiogenesis plays a key role in tumor growth and resistance to therapy. A cerebrospinal fluid (CSF) sample could be a useful way to obtain pro-angiogenic predictive or prognostic markers at different stages of the disease. As a first step we looked for pro-angiogenic activity in the CSF of patients with high-grade gliomas. We performed the chicken embryo chorio-allantoic membrane (CAM) assay to study the angiogenic potential of the cerebrospinal fluid (CSF), obtained either by lumbar puncture (LP) or craniotomy from six patients with high-grade brain tumors (three glioblastoma (WHO grade IV), one anaplastic oligodendroglioma (WHO grade III), two anaplastic ganglioglioma (WHO grade III)), and four healthy controls. Significantly increased neo-angiogenesis was observed on the surface of the growing CAM in the 6 patients with high-grade gliomas compared to controls (3.69 ± 1.23 versus 2.16 ± 0.97 capillaries per area (mean ± SD), p<0.005). There was no statistical difference related to the hystological grade of the tumor (WHO grade III or IV), previous treatment (radio-chemotherapy plus temozolomide, temozolomide alone or no treatment), or the site of CSF sample (surgery or lumbar puncture). Our results suggest a pro-angiogenic potential in the CSF of patients with high-grade gliomas.