RESUMO

OBJECTIVE: High-grade gliomas are aggressive brain tumors with poor prognoses. Understanding the factors that influence their progression is crucial for improving treatment outcomes. This study investigates the prognostic significance of panimmune inflammation in patients diagnosed with high-grade gliomas. MATERIALS-METHODS: Data from 89 high-grade glioma patients were analysed retrospectively. The Panimmune inflammation Value (PIV) of each patient meeting the eligibility criteria was calculated on the basis of platelet, monocyte, neutrophil, and lymphocyte counts obtained from peripheral blood samples taken on the first day of treatment. PIV is calculated using the following formula: PIV = T × M × N ÷ L. A receiver operating characteristic (ROC) analysis was employed to identify the optimal cut-off value for PIV about progression-free survival (PFS) and overall survival (OS) outcomes. The primary and secondary endpoints were the differences in OS and PFS between the PIV groups. The Kaplan‒Meier method was used for survival analyses. RESULTS: The ROC analysis indicated that the optimal PIV threshold was 545.5, which exhibited a significant interaction with PFS and OS outcomes. Patients were subsequently divided into two groups based on their PIV levels: a low PIV (L-PIV) group comprising 45 patients and a high PIV (H-PIV) group comprising 44 patients. A comparative analysis of survival rates indicated that patients with elevated PIV had a shorter median PFS of 4.0 months compared to 8.0 months in the low PIV group (P = 0.797), as well as a reduced median OS of 19.0 months versus not available (NA) in the low PIV group (P = 0.215). CONCLUSION: Our study results did not reveal a statistically significant association between H-PIV measurements and reduced PFS or OS. However, PIV effectively stratified newly diagnosed high-grade glioma patients into two distinct groups with significantly different PFS and OS outcomes.

RESUMO

High-grade gliomas (HGG) are the most common primary brain malignancies and account for more than half of all malignant primary brain tumors. The new 2021 WHO classification divides adult HGG into four subtypes: grade 3 oligodendroglioma (1p/19 codeleted, IDH-mutant); grade 3 IDH-mutant astrocytoma; grade 4 IDH-mutant astrocytoma, and grade 4 IDH wild-type glioblastoma (GB). Radiotherapy (RT) and chemotherapy (CTX) are the current standard of care for patients with newly diagnosed HGG. Several clinically relevant molecular markers that assist in diagnosis and prognosis have recently been identified. The treatment for recurrent high-grade gliomas is not well defined and decision-making is usually based on prior strategies, as well as several clinical and radiological factors. Whereas the prognosis for GB is grim (5-year survival rate of 5-10%) outcomes for the other high-grade gliomas are typically better, depending on the molecular features of the tumor. The presence of neurological deficits and seizures can significantly impact quality of life.

Assuntos

RESUMO

Background/Aim: High-grade gliomas are aggressive brain neoplasms usually refractory to treatment. Recently new treatment approaches have emerged, including immunotherapies. Hence, the aim of the present study was to evaluate the efficacy and safety of immunotherapies in adult patients with high-grade gliomas. Methods: Searches were performed in three databases for relevant studies published until December 2020. Title and abstract screening, full-text review, data extraction, and risk of bias assessment were performed independently by two reviewers. Risk of bias assessment was performed according to the revised Cochrane risk-of-bias tool for randomized trials (RoB 2). Meta-analyses were performed with Review Manager software (version 5.4.1), using risk ratio and 95% confidence intervals as measure of effect, the Mantel-Haenszel method, and random effects models. The quality of evidence assessment was conducted according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Results: Nineteen studies were included in the systematic review, of which 15 reported comparable data for meta-analyses. The outcomes assessed in the meta-analyses were overall survival (OS) and progression-free survival (PFS), with subgroups at 6, 12, and more than 12 months. No statistical differences were observed between immunotherapy and conventional treatment, except for the OS subgroup over 12 months. The certainty on the evidence was moderate. Conclusion: There was no evidence of an additional benefit of immunotherapy compared to standard treatment in the synthesis of results from clinical trials. Further high-quality clinical trials are needed to improve the quality of evidence concerning immunotherapies for the treatment of high-grade gliomas.

RESUMO

BACKGROUND: Anaplastic astrocytoma is a rare disorder in children from 10 to 14 years of age, with an estimated 0.38 new cases per 100,000 people per year worldwide. Panel-based next-generation sequencing opens new possibilities for diagnosis and therapy of rare diseases such as this one. Because it has never been genetically studied in the Ecuadorian population, we chose to genetically characterize an Ecuadorian pediatric patient with anaplastic astrocytoma for the first time. Doing so allows us to provide new insights into anaplastic astrocytoma diagnosis and treatment. CASE PRESENTATION: Our patient was a 13-year-old Mestizo girl with an extensive family history of cancer who was diagnosed with anaplastic astrocytoma. According to ClinVar, SIFT, and PolyPhen, the patient harbored 354 genomic alterations in 100 genes. These variants were mostly implicated in deoxyribonucleic acid (DNA) repair. The top five most altered genes were FANCD2, NF1, FANCA, FANCI, and WRN. Even though TP53 presented only five mutations, the rs11540652 single-nucleotide polymorphism classified as pathogenic was found in the patient and her relatives; interestingly, several reports have related it to Li-Fraumeni syndrome. Furthermore, in silico analysis using the Open Targets Platform revealed two clinical trials for pediatric anaplastic astrocytoma (studying cabozantinib, ribociclib, and everolimus) and 118 drugs that target the patient's variants, but the studies were not designed specifically to treat pediatric anaplastic astrocytoma. CONCLUSIONS: Next-generation sequencing allows genomic characterization of rare diseases; for instance, this study unraveled a pathogenic single-nucleotide polymorphism related to Li-Fraumeni syndrome and identified possible new drugs that specifically target the patient's variants. Molecular tools should be implemented in routine clinical practice for early detection and effective preemptive intervention delivery and treatment.

Assuntos

RESUMO

Introducción: Nimotuzumab es una inmunoglobina de isotipo IgG1, obtenido por tecnología de ADN recombinante. La expectativa de vida de niños con tumores cerebrales recurrentes, refractarios a tratamientos a la cirugía, la radioterapia y la quimioterapia es de un mes aproximadamente. Con este tratamiento la supervivencia alcanza 44,5 meses. Objetivos: Presentar el caso clínico de un paciente con diagnóstico de Astrocitoma anaplásico que recibió tratamiento oncoespecífico concurrente con Nimotuzumab. Presentación de caso: Se realizó la descripción del diagnóstico, tratamiento y evolución de un paciente de 31 años de edad que fue diagnosticado con una neoplasia del sistema nervioso central. (Astrocitoma anaplásico). Recibió la combinación terapéutica de cirugía, radioterapia y anticuerpos monoclonales, lográndose una sobrevida de 39 meses. Conclusiones: La adición del anticuerpo monoclonal al tratamiento estándar de los tumores cerebrales aumentó la sobrevida del paciente, convirtiéndose en una alternativa terapéutica segura, ventajosa y factible como parte del tratamiento convencional en las condiciones asistenciales(AU)

Introduction: Nimotuzumab is an IgG1 isotype immunoglobin, obtained by recombinant DNA technology. Life expectancy is approximately one month in children with recurrent brain tumors, refractory to treatments to surgery, radiotherapy and chemotherapy. Survival reaches 44.5 months when using Nimotuzumab. Objectives: To report the clinical case of a patient diagnosed with anaplastic astrocytoma who received concurrent oncospecific treatment with Nimotuzumab. Case report: This paper describes the diagnosis, treatment and evolution of a 31-year-old male patient with neoplasm of the central nervous system (Anaplastic astrocytoma). He received the therapeutic combination of surgery, radiotherapy and monoclonal antibodies, achieving a survival of 39 months. Conclusions: The adding the monoclonal antibody to the standard treatment of brain tumors increased patient survival, making it a safe, advantageous and feasible therapeutic alternative as part of conventional treatment in healthcare conditions(AU)

Assuntos

RESUMO

RESUMEN Introducción: el astrocitoma anaplásico y el glioblastoma multiforme son las formas más agresivas de glioma maligno. Existen avances en radioterapia, quimioterapia y tratamientos de resección quirúrgica agresiva. Esto último incluye métodos como los de tomografía de coherencia óptica, cirugía guiada por fluorescencia, craneotomía de vigilia, terapia térmica intersticial con láser para la ablación por glioblastoma multiforme, microscopía intraoperatoria confocal y espectrometría de masas intraoperatoria, pero a pesar de todo ello el pronóstico resulta sombrío. Objetivo: determinar el comportamiento de los gliomas de alto grado en el Servicio de Neurocirugía de la provincia Matanzas. Materiales y métodos: estudio observacional, descriptivo, transversal, con los pacientes diagnosticados de gliomas de alto grado, en el Servicio Neurocirugía, de la provincia Matanzas, en el período de 1ero de enero del 2017 a 1ero de enero del 2019, para un total de 40 casos. Resultados: la edad media de las lesiones fue de 52 años, la cefalea fue el síntoma predominante, con el 72,2 %. La sintomatología se presentó con una evolución de menos de un mes. Conclusiones: en el 62 % predominaron los gliomas frontales y la variedad histológica glioblastoma multiforme. La excéresis subtotal se aplicó en la mayor cantidad de cirugías, la calidad de vida al egreso fue superior que al ingreso (AU).

ABSTRACT Introduction. Anaplastic astrocytoma (AA) and Glioblastoma multiforme (GBM) are the most aggressive forms of malignant glioma. Despite advances in radiotherapy, chemotherapy and aggressive surgical resection treatments, such as optical coherence tomography, fluorescence-guided surgery, waking craniotomy, laser interstitial thermal therapy for GBM ablation, intraoperative confocal microscopy and intraoperative mass spectrometry, the prognosis remains bleak. Objective: to determine the behavior of high grade gliomas in the Neurosurgery Service of the province of Matanzas. Materials and methods: cross-sectional, descriptive, observational study with patients diagnosed with high-grade gliomas in the Neurosurgery Service of the province of Matanzas, in the period from January 1, 2017 to January 1, 2019, for a total of 40 cases. Results: the average age of the lesionated patients was 52 years; headache was the predominant symptom, with 72.2 %; the evolution at the presentation of symptoms was less than a month. Conclusions: frontal gliomas predominated in 62 % of the cases, and predominated also glioblastoma multiforme histological variety. Subtotal excision was used in most surgeries. Life quality at discharging was higher than at the moment of admission (AU).

Assuntos

RESUMO

Tumefactive demyelinating lesions are a rare disorder in which inflammatory demyelination manifests as solitary or multiple focal brain lesions (greater than 2 cm in size), which can be mistaken for glioma, lymphoma, metastasis and in some cases even brain abscess. The symptomatology of tumefactive demyelinating lesions depends on the white matter area involved and includes quickly progressing neurological deterioration of motor, sensory and visual function, praxis, language and mood impairment, as well as seizures. Recognising the key imaging features in a patient with a prior history of demyelination may expedite appropriate management. Preoperative diagnosis or at least the consideration of a demyelinating process is important to avoid unnecessary surgery. We report three patients with demyelinating lesions who presented with findings suggestive of demyelination on conventional magnetic resonance imaging studies. However, in all patients the lesions showed high perfusion and in two high permeability, which are findings generally seen with high-grade neoplasias. In rare instances, tumefactive demyelinating lesions may show increased perfusion and high permeability, imaging findings more commonly seen in high-grade gliomas. We suggest that if white matter lesions on conventional magnetic resonance imaging are compatible with tumefactive demyelinating lesions, atypical findings of high perfusion/permeability should not dissuade the radiologist from suggesting the presence of tumefactive demyelinating lesions rather than high-grade gliomas.

Assuntos

RESUMO

Nimotuzumab is a humanized monoclonal antibody that binds specifically to human epidermal growth factor receptor, blocking receptor activation. Evidence of its radiosensitizing capacity has been widely evaluated. This article integrates published research findings regarding the role of nimotuzumab in the treatment of high grade glioma in combination with radiotherapy or radiochemotherapy in adult and pediatric populations. First, the mechanisms of action of nimotuzumab and its current applications in clinical trials containing both radiation and chemoradiation therapies are reviewed. Second, a comprehensive explanation of potential mechanisms driving radiosensitization by nimotuzumab in experimental settings is given. Finally, future directions of epidermal growth factor receptor targeting with nimotuzumab in combination with radiation containing regimens, based on its favorable toxicity profile, are proposed. It is hoped that this review may provide further insight into the rational design of new approaches employing nimotuzumab as a useful alternative for the therapeutic management of high grade glioma.

RESUMO

OBJECTIVE: The relationship between brain tumors and cognitive deficits is well established in the literature. However, studies investigating the cognitive status in low and high-grade gliomas patients are scarce, particularly in patients with average or lower educational level. This study aimed at investigating the cognitive functioning in a sample of patients with low and high-grade gliomas before surgical intervention. METHOD: The low-grade (G1, n=19) and high-grade glioma (G2, n=8) patients underwent a detailed neuropsychological assessment of memory, executive functions, visuo-perceptive and visuo-spatial abilities, intellectual level and language. RESULTS: There was a significant impairment on verbal and visual episodic memory, executive functions including mental flexibility, nominal and categorical verbal fluency and speed of information processing in G2. G1 showed only specific deficits on verbal and visual memory recall, mental flexibility and processing speed. CONCLUSION: These findings demonstrated different levels of impairments in the executive and memory domains in patients with low and high grade gliomas.

OBJETIVO: A associação entre tumores cerebrais e déficits cognitivos é bem estabelecida na literatura. No entanto, estudos sobre a cognição de pacientes com gliomas de baixo e alto grau são escassos, especialmente, em sujeitos com baixa escolaridade. Este estudo investigou o funcionamento cognitivo de uma amostra de pacientes com gliomas de baixo e alto grau antes da intervenção cirúrgica. MÉTODO: Os pacientes com glioma de baixo grau (G1, n=19) e alto grau (G2, n=8) foram avaliados quanto à memória, funções executivas, habilidades visuo-perceptivas e visuo-espaciais, nível intelectual e linguagem. RESULTADOS: Houve prejuízo significativo em G2 na memória episódica verbal e visual, funções executivas incluindo flexibilidade mental, fluência verbal nominal e categórica e velocidade de processamento de informações. G1 demonstrou apenas déficits específicos de evocação verbal e visual, flexibilidade mental e velocidade de processamento. CONCLUSÃO: Estes achados demonstraram níveis diferenciados de comprometimento nos domínios executivos e mnésticos de pacientes com gliomas de baixo e alto grau.

Assuntos