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1.
Medicine (Baltimore) ; 99(2): e18591, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31914038

RESUMO

This analysis aimed to investigate whether the long-term administration of temozolomide (TMZ) claimed a survival advantage for patients with glioblastoma in China.A total of 75 patients with newly diagnosed glioblastoma at the Department of Radiation Oncology, Shenzhen People's Hospital between August 2008 and August 2016 were retrospectively evaluated during analysis. A propensity-matched analysis was performed to balance the basic characteristics of patients between compared groups. Kaplan-Meier method and Cox proportional hazards model were used to assess progression-free survival (PFS) and overall survival (OS) of patients receiving 6 adjuvant TMZ cycles compared with patients treated with more than 6 cycles.Twenty of 75 patients received more than 6 cycles of TMZ, and the other 55 patients were treated with a median of 6 cycles ranging from 1 to 6. The patients with long-term administration of TMZ had better OS (47.0 months, 95% CI 20.0-73.9 vs 20.6 months, 95% CI 17.9-23.2, P = .014) but not PFS (17.0 months, 95% CI 10.1-24.5 vs 14.2 months, 95% CI 11.8-16.6, P = .133). Balancing the clinical factors with a propensity-matched analysis also showed the significant advantage of prolonged TMZ application in terms of OS but not PFS.Prolonged administration of TMZ beyond 6 cycles did demonstrate survival benefits for patients with initially diagnosed glioblastoma.


Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/mortalidade , Glioblastoma/tratamento farmacológico , Glioblastoma/mortalidade , Temozolomida/uso terapêutico , Adolescente , Adulto , Idoso , Antineoplásicos Alquilantes/administração & dosagem , Neoplasias Encefálicas/terapia , Quimioterapia Adjuvante , Esquema de Medicação , Feminino , Glioblastoma/terapia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Pontuação de Propensão , Estudos Retrospectivos , Temozolomida/administração & dosagem , Adulto Jovem
2.
World Neurosurg ; 133: e640-e645, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31568907

RESUMO

BACKGROUND: Concomitant chemoradiation (CCRT) after surgical resection has been established as standard care for patients with newly diagnosed glioblastoma (GBM). However, the optimal time interval from surgery to starting CCRT (IST) remains controversial. METHODS: The electronic medical records of 160 patients with newly diagnosed GBM treated at our institution between 2009 and 2016 were examined retrospectively. The eligibility criteria were newly diagnosed GBM, pathology confirmed by craniotomy or stereotactic biopsy, and CCRT performed in our institution. Patients who received CCRT within 28 days after surgery were defined as the early group, and those who received CCRT at >28 days after surgery were defined as the delayed group. RESULTS: We included 138 patients who met our eligibility criteria. The median IST was 26 days (range, 10-55 days). In a Kaplan-Meier analysis, overall survival (OS) did not differ between groups (15.5 month for the early group vs. 14.5 months for the delayed group; P = 0.707). In the gross total resection (GTR) subgroup, OS did not differ significantly (20.0 months for the early vs. 21.0 months for the delayed group; P = 0.854). In the non-GTR subgroup, however, the early group had better OS than the delayed group (11.0 months vs. 5.0 months; P = 0.029). CONCLUSIONS: Performing CCRT within versus after 28 days after surgery did not result in a statistically significant difference in OS. However, a subgroup analysis showed that delayed CCRT may be associated with worse OS in the non-GTR group.


Assuntos
Neoplasias Encefálicas/terapia , Quimiorradioterapia/métodos , Glioblastoma/terapia , Procedimentos Neurocirúrgicos/métodos , Adulto , Idoso , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Quimiorradioterapia/mortalidade , Intervalo Livre de Doença , Feminino , Glioblastoma/mortalidade , Glioblastoma/patologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos/mortalidade , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
3.
World Neurosurg ; 133: e583-e591, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31561040

RESUMO

OBJECTIVE: To assess the prognostic profile, clinical outcome, treatment-associated morbidity, and treatment burden of elderly patients with glioblastoma (GBM) undergoing microsurgical tumor resection as part of contemporary treatment algorithms. METHODS: We retrospectively identified patients with GBM ≥65 years of age who were treated by resection at 2 neuro-oncology centers. Survival was assessed by Kaplan-Meier analyses; log-rank tests identified prognostic factors. RESULTS: The study population included 160 patients (mean age, 73.1 ± 5.1 years), and the median contrast-enhancing tumor volume was 31.0 cm3. Biomarker analyses revealed O(6)-methylguanine-DNA methyltransferase-promoter methylation in 62.7% and wild-type isocitrate dehydrogenase in 97.5% of tumors. The median extent of resection (EOR) was 92.3%, surgical complications were noted in 10.0% of patients, and the median postoperative hospitalization period was 8 days. Most patients (60.0%) received adjuvant radio-/chemotherapy. The overall treatment-associated morbidity was 30.6%. The median progression-free and overall survival were 5.4 months (95% confidence interval [CI], 4.6-6.4 months) and 10.0 months (95% CI, 7.9-11.7 months). The strongest predictors for favorable outcome were patient age ≤73.0 years (P = 0.0083), preoperative Karnofsky Performance Status Scale score ≥80% (P = 0.0179), postoperative modified Rankin Scale score ≤1 (P < 0.0001), adjuvant treatment (P < 0.0001), and no treatment-associated morbidity (P = 0.0478). Increased EOR did not correlate with survival (P = 0.5046), but correlated significantly with treatment-associated morbidity (P = 0.0031). CONCLUSIONS: Clinical outcome for elderly patients with GBM remains limited. Nonetheless, the observed treatment-associated morbidity and treatment burden were moderate in the patients, and patient age and performance status remained the strongest predictors for survival. The risks and benefits of tumor resection in the age of biomarker-adjusted treatment concepts require further prospective evaluation.


Assuntos
Neoplasias Encefálicas/cirurgia , Glioblastoma/cirurgia , Procedimentos Neurocirúrgicos , Idoso , Idoso de 80 Anos ou mais , Áustria , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Feminino , Glioblastoma/mortalidade , Glioblastoma/patologia , Humanos , Masculino , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
4.
World Neurosurg ; 133: 366-380.e2, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31473344

RESUMO

BACKGROUND: With the 2016 update of the World Health Organization (WHO) Classification of Tumors of the Central Nervous System incorporating molecular subtyping to histology, WHO grade II diffuse astrocytic and oligodendroglial tumors are subcategorized by distinct molecular markers. There are no reported systematic reviews quantifying differences in progression-free survival (PFS) and overall survival (OS) on the basis of molecular subtypes of WHO grade II diffuse gliomas, against the background of administered treatments. METHODS: Using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and the Cochrane Handbook of Systemic Reviews of Interventions, we conducted a systematic review through MEDLINE, Embase, and CENTRAL (Cochrane Central Register of Controlled Trails). RESULTS: For OS, the first quartile (25%), median (50%), third quartile (75%), and 95% confidence interval, respectively, were identified (in months): astrocytoma-wild-type WHO II (A-wt II): 22.8, 32.2, 40.7, and 21.6-61.2; astrocytoma-mutant WHO II (A-mt II): 69.85, 115.2, 128.4, and 55.4-164.0; oligodendroglioma WHO II (OD-II): 106.3, 163.7, 213.3, and 67.3-235.4 (P value = 0.0002). For PFS, the 25th, 50th, and 75th percentiles, and 95% confidence interval, respectively, are as follows (in months): A-wt II: 6.90, 17.45, 19.57, and 3.00-23.69; A-mt II: 37.20, 43.20, 55.63, and 35.7-60.0; OD-II: 47.42, 59.2, 88.28, and 46.3-91.2 (P value = 0.015). CONCLUSIONS: This seems to be the first systematic review of OS and PFS in patients with WHO grade II low-grade gliomas (LGGs), against treatment modalities, in molecularly stratified subsets introduced by the WHO 2016 classification of central nervous system tumors. Overall, A-wt II was confirmed to have a significantly shorter OS than did A-mt II; no significant difference was found between OS of OD-II with A-wt II and A-mt II. In addition, all 3 molecular subtypes were found to have statistically significant differences between PFS, with OD-II having a statistically better PFS than A-mt II. These data can provide valuable prognostic insight to patients and clinicians. In addition, assessing survival differences enhances understanding of treatment recommendations against molecular markers and may facilitate future clinical trial design.


Assuntos
Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/terapia , Glioma/mortalidade , Glioma/terapia , Neoplasias Encefálicas/patologia , Glioma/patologia , Humanos , Gradação de Tumores , Intervalo Livre de Progressão , Taxa de Sobrevida
5.
Int J Cancer ; 146(3): 803-809, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30980539

RESUMO

Metformin has been linked to improve survival of patients with various cancers. There is little information on survival of glioblastoma patients after use of metformin. We assessed the association between metformin use and survival in a pooled analysis of patient data from 1,731 individuals from the randomized AVAglio, CENTRIC and CORE trials. We performed multivariate Cox analyses for overall survival (OS) and progression-free survival (PFS) comparing patients' use of metformin at baseline and/or during concomitant radiochemotherapy (TMZ/RT). Further exploratory analyses investigated the effect of metformin with a history of diabetes and nonfasting glucose levels in relation to OS or PFS of glioblastoma patients. Metformin alone or in any combination was not significantly associated with OS or PFS (at baseline, hazard ratio [HR] for OS = 0.87; 95% confidence interval [CI] = 0.65-1.16; HR for PFS = 0.84; 95% CI = 0.64-1.10; during TMZ/RT HR for OS = 0.97; 95% CI = 0.68-1.38; HR for PFS = 1.02; 95% CI = 0.74-1.41). We found a statistically nonsignificant association of metformin monotherapy with glioblastoma survival at baseline (HR for OS = 0.68; 95% CI = 0.42-1.10; HR for PFS = 0.57; 95% CI = 0.36-0.91), but not during the TMZ/RT period (HR for OS = 0.90; 95% CI = 0.51-1.56; HR for PFS = 1.05; 95% CI = 0.64-1.73). Diabetes mellitus or increased nonfasting glucose levels were not associated with a difference in OS or PFS in our selected study population. Metformin did not prolong survival of patients with newly diagnosed glioblastoma in our analysis. Additional studies may identify patients with specific tumor characteristics that are associated with potential benefit from treatment with metformin, possibly due to metabolic vulnerabilities.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/mortalidade , Glioblastoma/mortalidade , Metformina/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Alquilantes/uso terapêutico , Neoplasias Encefálicas/terapia , Quimiorradioterapia , Feminino , Glioblastoma/terapia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Ensaios Clínicos Controlados Aleatórios como Assunto , Temozolomida/uso terapêutico , Adulto Jovem
6.
Cancer Radiother ; 23(8): 860-866, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31677901

RESUMO

PURPOSE: Stereotactic radiosurgery and hypofractionated stereotactic radiotherapy are standard treatments for brain metastases when they are small in size (at the most 3cm in diameter) and limited in number, in patients with controlled extracerebral disease and a good performance status. Large inoperable brain metastases usually undergo hypofractionated stereotactic radiotherapy while haemorrhagic brain metastases have often been contraindicated for both stereotactic radiosurgery or hypofractionated stereotactic radiotherapy. The objective of this retrospective study was to assess a six 6Gy-fractions hypofractionated stereotactic radiotherapy scheme in use at our institution for haemorrhagic brain metastases, large brain metastases (size greater than 15cm3) or brain metastases located next to critical structures. MATERIAL AND METHODS: Patients with brain metastases treated with the 6×6Gy scheme since 2012 to 2016 were included. Haemorrhagic brain metastases were defined by usual criteria on CT scan and MRI. Efficacy, acute and late toxicity were evaluated. RESULTS: Sixty-two patients presenting 92 brain metastases were included (32 haemorrhagic brain metastases). Median follow up was 10.1 months. One-year local control rate for haemorrhagic brain metastases, large brain metastases, or brain metastases next to critical structures were 90.7%, 73% and 86.7% respectively. Corresponding overall survival rates were 61.2%, 32% and 37.8%, respectively. Haemorrhagic complications occurred in 5.3% of patients (N=5), including two cases of brain metastases with pretreatment haemorrhagic signal. Tolerance was good with only one grade 3 acute toxicity. CONCLUSION: The 6×6Gy hypofractionated stereotactic radiotherapy scheme seems to yield quite good results in patients with haemorrhagic brain metastases, which must be confirmed in a prospective way.


Assuntos
Neoplasias Encefálicas/radioterapia , Hemorragia Cerebral/radioterapia , Hipofracionamento da Dose de Radiação , Radiocirurgia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/secundário , Hemorragia Cerebral/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Radiocirurgia/efeitos adversos , Radiocirurgia/mortalidade , Estudos Retrospectivos , Fatores de Tempo , Carga Tumoral
7.
Medicine (Baltimore) ; 98(44): e17773, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31689842

RESUMO

OBJECTIVE: To evaluate the prognostic value of pancreatic neuroendocrine tumors (pNETs) with different metastatic patterns. METHODS: Data of pNETs cases were extracted from the Surveillance, Epidemiology, and End Result (SEER) database. They were classified according to the different metastatic patterns. We utilized chi-square test to compare the clinical and metastasis characteristics among different groups. We used Kaplan-Meier analysis and log-rank testing for survival comparisons. Adjusted HRs with 95% CIs was calculated using Cox regression model to estimate prognostic factors. P < .05 was considered statistically significant. RESULTS: Among the 3909 patients, liver is the most metastatic organ, and isolated brain metastasis is the least common. At the same time, many patients have had multiple metastases. We studied the overall survival (OS) and cancer-specific survival (CCS) of the groups. OS: Non-organ metastasis: 5-year OS = 77.1%; Bone metastasis: median survival time (MST) = 56 m, 5-year OS = 42.7%; Liver metastasis: MST = 24 m, 5-year OS = 25.5%; Lung metastasis: MST = 14 m, 5-year OS = 33.7%; multiple metastases: MST = 7m, 5-year OS = 12.0%. CCS: Non-organ metastasis: 5-year OS = 84.2%; Bone metastasis: 5-year OS = 52.5%; Liver metastasis: MST = 27 m, 5-year OS = 28.6%; Lung metastasis: MST = 49 m, 5-year OS = 40.1%; multiple metastases: MST = 8 m, 5-year OS = 14.5%. In addition, the results showed that there were all statistical significances between the surgery and the no surgery group (all, P < .001). Multivariate analysis revealed that brain metastasis, multiple metastases, age over 60 years, unmarried, grade III/IV, regional/distant and no surgery were independently associated with decreased OS and CCS. CONCLUSIONS: pNETs patients without organ metastasis had the best survival outcomes, while multiple had the worst outcomes. There were no significant differences in bone metastasis, liver metastasis and lung metastasis. Surgery was still an option for patients with metastasis.


Assuntos
Neoplasias Ósseas/mortalidade , Neoplasias Encefálicas/mortalidade , Neoplasias Hepáticas/mortalidade , Neoplasias Pulmonares/mortalidade , Tumores Neuroendócrinos/mortalidade , Neoplasias Pancreáticas/mortalidade , Idoso , Neoplasias Ósseas/secundário , Neoplasias Encefálicas/secundário , Distribuição de Qui-Quadrado , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/secundário , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Tumores Neuroendócrinos/secundário , Neoplasias Pancreáticas/patologia , Prognóstico , Programa de SEER , Taxa de Sobrevida
8.
Cancer Immunol Immunother ; 68(12): 1995-2004, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31690954

RESUMO

Glioblastoma is a highly prevalent and aggressive form of primary brain tumor. It represents approximately 56% of all the newly diagnosed gliomas. Macrophages are one of the major constituents of tumor-infiltrating immune cells in the human gliomas. The role of immunosuppressive macrophages is very well documented in correlation with the poor prognosis of patients suffering from breast, prostate, bladder and cervical cancers. The current study highlights the correlation between the tumor-associated macrophage phenotypes and glioma progression. We observed an increase in the pool of M2 macrophages in high-grade gliomas, as confirmed by their CD68 and CD163 double-positive phenotype. In contrast, less M1 macrophages were noticed in high-grade gliomas, as evidenced by the down-regulation in the expression of CCL3 marker. In addition, we observed that higher gene expression ratio of CD163/CCL3 is associated with glioma progression. The Kaplan-Meier survival plots indicate that glioma patients with lower expression of M2c marker (CD163), and higher expression of M1 marker (CCL3) had better survival. Furthermore, we examined the systemic immune response in the peripheral blood and noted a predominance of M2 macrophages, myeloid-derived suppressor cells and PD-1+ CD4 T cells in glioma patients. Thus, the study indicates a high gene expression ratio of CD163/CCL3 in high-grade gliomas as compared to low-grade gliomas and significantly elevated frequency of M2 macrophages and PD-1+ CD4 T cells in the blood of tumor patients. These parameters could be used as an indicator of the early diagnosis and prognosis of the disease.


Assuntos
Neoplasias Encefálicas/imunologia , Linfócitos T CD4-Positivos/patologia , Glioblastoma/imunologia , Macrófagos/imunologia , Células Supressoras Mieloides/imunologia , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Neoplasias Encefálicas/mortalidade , Carcinogênese , Quimiocina CCL3/metabolismo , Citocinas/metabolismo , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Glioblastoma/mortalidade , Humanos , Tolerância Imunológica , Imunidade Humoral , Receptor de Morte Celular Programada 1/metabolismo , Receptores de Superfície Celular/metabolismo , Análise de Sobrevida , Células Th2/imunologia
9.
Eur J Radiol ; 120: 108609, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31606714

RESUMO

OBJECTIVES: To develop a radiomic signature to predict overall survival (OS) for high-grade glioma (HGG), and construct a nomogram by combining selected radiomic, genetic and clinical risk factors to further improve the performance of the risk model. MATERIALS AND METHODS: 147 cases of HGG with MRI images, genetic data, clinical data were studied, wherein 112 patients were used as training cohort, and 35 patients were as independent test cohort. Radiomics features were extracted from tumor area and peritumoral edema area on CE-T1WI and T2FLAIR images. Association between radiomics signature, genetic, clinical risk factors and OS was explored by Kaplan-Meier survival analysis and log rank test. The multivariate Cox regression analysis was trained with radiomic features along with selected genetic and clinical risk factors, which was presented as a nomogram. RESULTS: The radiomic signature constructed by 11 radiomics features stratified patients into low- and high-risk groups, and the C-Index for OS prediction was 0.707 and 0.711 in training and test cohorts, respectively. The multivariable Cox regression analysis identified radiomics signature (hazard ratio (HR): 2.18, P = 0.005), IDH (HR: 0.490, P = 0.007) and age (HR: 1.039, P = 0.005) as independent risk factors. A nomogram combining these independent risk factors further improved the performance for OS estimation (C-index = 0.764 and 0.758 in training and test cohorts, respectively). CONCLUSION: The radiomics signature is a new prognostic biomarker for HGG. A nomogram incorporating radiomics signature, IDH and age improved the performance of OS estimation, which might be a new complement to the treatment guidelines of glioma.


Assuntos
Neoplasias Encefálicas/mortalidade , Glioma/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/genética , Estudos de Coortes , Feminino , Glioma/genética , Humanos , Estimativa de Kaplan-Meier , Aprendizado de Máquina , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Mutação/genética , Nomogramas , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
10.
Anticancer Res ; 39(10): 5797-5801, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570484

RESUMO

Grade IV glioblastoma multiforme is a deadly disease, with a median survival of around 14 to 16 months. Maximal resection followed by adjuvant radiochemotherapy has been the mainstay of treatment since many years, although survival is only extended by a few months. In recent years, an increasing number of data from in vitro and in vivo research with cannabinoids, particularly with the non-intoxicating cannabidiol (CBD), point to their potential role as tumour-inhibiting agents. Herein, a total of nine consecutive patients with brain tumours are described as case series; all patients received CBD in a daily dose of 400 mg concomitantly to the standard therapeutic procedure of maximal resection followed by radiochemotherapy. By the time of the submission of this article, all but one patient are still alive with a mean survival time of 22.3 months (range=7-47 months). This is longer than what would have been expected.


Assuntos
Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/terapia , Canabidiol/uso terapêutico , Glioblastoma/tratamento farmacológico , Glioblastoma/terapia , Adolescente , Adulto , Neoplasias Encefálicas/mortalidade , Quimiorradioterapia Adjuvante/métodos , Pré-Escolar , Terapia Combinada/métodos , Feminino , Glioblastoma/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida
11.
Eur J Radiol ; 120: 108642, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31546124

RESUMO

PURPOSE: On MR imaging, peritumoral T2 hyperintensity surrounding glioblastoma is known to contain tumor cell infiltrates, thus contributing to poor prognosis. This study aimed to determine the incremental prognostic value of radiomics on peritumoral T2 hyperintensity in pretreatment glioblastoma. METHODS: One hundred fourteen pathologically confirmed glioblastoma patients were retrospectively selected from March 2008 to May 2018 (our institution, n = 61; the Cancer Imaging Archive, n = 53). All patients were randomly divided into either training (n = 80) or test set (n = 34). Manually segmented peritumoral T2 hyperintensity yielded 106 radiomic features per patient. A random forest variable selection was used to select the most relevant radiomic features. Four Cox proportional hazards models were fitted with clinical features, clinical features with tumor/peritumoral volumes, radiomics, and all of them combined. Kaplan-Meier survival curves of the models were plotted with log-rank tests. All models were validated on a test set using prediction error curves over survival times. RESULTS: A random forest variable selection yielded five relevant features among the 106 radiomic features (two shape, two gray-level and one first order features). These radiomic features increased survival prediction accuracy when they were added onto clinical and tumor/peritumoral volumetric features (combined model, P = 0.011). On test set, the combined model showed lower mean survival prediction error rate (0.14) than clinical (0.191) or radiomic (0.178) model. CONCLUSIONS: The clinical model with radiomic features demonstrated improved survival predictive performance than the model without radiomic features, thus suggesting incremental prognostic value of peritumoral radiomics as MR imaging biomarker in pretreatment glioblastoma.


Assuntos
Neoplasias Encefálicas/patologia , Glioblastoma/patologia , Biomarcadores Tumorais , Neoplasias Encefálicas/mortalidade , Estudos de Casos e Controles , Feminino , Glioblastoma/mortalidade , Humanos , Estimativa de Kaplan-Meier , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Carga Tumoral
12.
Turk Neurosurg ; 29(5): 778-784, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31529454

RESUMO

AIM: To evaluate the frequency and prognostic significance of microsatellite instability (MSI) in patients with glioblastoma (GBM), an immunohistochemical analysis of mismatch repair (MMR) proteins was performed. MATERIAL AND METHODS: A total of 71 patients with GBM who underwent surgery between 2011 and 2019, were included in the study. MMR protein expression was examined using immunohistochemistical analysis of tumor tissue samples; the association between the MMR status and clinicopathological findings was evaluated. RESULTS: Immunohistochemical analysis revealed expressions of MLH1, MSH2, MSH6, and PMS2 proteins in 67 (94.4%), 65 (91.5%), 67 (94.4%), and 64 (90.1%) patients, respectively. Among the 71 patients, 64 (90.1%) expressing all MMR proteins were considered microsatellite stable (MSS), and 7 (9.9%) patients showing loss of at least one of the MMR proteins were considered to show MSI. Tumor recurrence was noted in 25 (39.1%) patients in the MSS GBM group, and 4 (57.1%) patients in the MSI GBM group (p=0.433). The overall median survival was 30.65 ± 5.1 and 10.71 ± 5.2 months in the MSS GBM and MSI GBM groups, respectively (p=0.059). CONCLUSION: The results of this study showed no significant relationships between MMR protein expression and recurrence rates or overall survival in patients with GBM.


Assuntos
Neoplasias Encefálicas/genética , Glioblastoma/genética , Instabilidade de Microssatélites , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Criança , Pré-Escolar , Reparo de Erro de Pareamento de DNA/genética , Feminino , Glioblastoma/mortalidade , Glioblastoma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Adulto Jovem
13.
Cancer Sci ; 110(11): 3486-3496, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31483918

RESUMO

Bone morphogenetic protein (BMP) signaling plays important roles in glioblastoma multiforme (GBM), a lethal form of brain tumor. BMP reduces GBM tumorigenicity through its differentiation- and apoptosis-inducing effects on glioma-initiating cells (GIC). However, some GIC do not respond to the tumor suppressive effects of BMP. Using a phosphoreceptor tyrosine kinase array, we found that EPHA6 (erythropoietin-producing hepatocellular carcinoma receptor A6) phosphorylation was regulated by BMP-2 signaling in some GIC. Analysis of The Cancer Genome Atlas showed that EPHA6 expression was lower in patients with GBM than in the normal brain, and that high EPHA6 expression was correlated with better prognosis. EPHA6 receptor increased the susceptibility of both sensitive and resistant GIC to BMP-2-induced apoptosis. The cooperative effect on apoptosis induction depended on the kinase activity of BMP type I receptor but was independent of EPHA6 kinase function. Overexpression of the EPHA6 receptor in GIC resulted in the formation of a protein complex of EPHA6 receptor and the BMP type I receptor ALK-2, which was associated with BMP-induced apoptosis in GIC. Intracranial injection of GIC into nude mice showed that gain-of-function of EPHA6 together with BMP-2 pretreatment slowed GBM tumor progression in the mouse brain and promoted mouse survival. In summary, EPHA6 together with BMP-2 signaling led to apoptotic cell death in GIC, and thus is a putative tumor suppressor in GBM.


Assuntos
Receptores de Ativinas Tipo I/metabolismo , Apoptose , Proteína Morfogenética Óssea 2/metabolismo , Neoplasias Encefálicas/metabolismo , Glioblastoma/metabolismo , Receptor EphA6/metabolismo , Animais , Proteína Morfogenética Óssea 2/farmacologia , Receptores de Proteínas Morfogenéticas Ósseas Tipo I/metabolismo , Proteínas Morfogenéticas Ósseas/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Progressão da Doença , Glioblastoma/mortalidade , Glioblastoma/patologia , Glioma/metabolismo , Glioma/patologia , Humanos , Camundongos , Camundongos Nus , Transplante de Neoplasias , Fosforilação , Prognóstico , Proteínas Supressoras de Tumor/metabolismo
14.
World Neurosurg ; 132: e350-e365, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31476477

RESUMO

BACKGROUND: Improved life expectancy and advanced diagnostic tools including computed tomography and magnetic resonance imaging have increased the awareness and diagnosis of intracranial meningiomas in the elderly population. The risk/benefit ratio of surgery in elderly patients with intracranial meningioma has not been clearly defined because of the lack of objective measurement tools. We aimed to understand the risk factors associated with postsurgical outcomes and how these risk factors affected postsurgical outcomes in elderly patients with intracranial meningioma. METHODS: We retrospectively evaluated 1372 patients, who were operated on for intracranial meningioma, using our prospectively collected database. The same senior author operated on all patients at 2 different tertiary clinics. Patients' clinical charts, presurgical postcontrast T1-weighted magnetic resonance images, operative reports, and pathology reports were reviewed. The relevant literature was also reviewed. RESULTS: Higher age, higher American Society of Anesthesiologists class, presence of comorbidities, tumor location, larger initial tumor size, and presence of peritumoral edema were all associated with postsurgical complications in elderly patients with intracranial meningioma. Age ≥50 years was the strongest predictor of postsurgical systemic complications, whereas higher American Society of Anesthesiologists class was the strongest predictor of postsurgical neurologic complications. A literature review showed higher morbidity and mortality of elderly patients with intracranial meningioma. Initial tumor size and postsurgical MIB-1 labeling index were higher in the elderly patients, both of which were predictors of tumor growth. CONCLUSIONS: Even though elderly patients operated on for intracranial meningioma had higher morbidity and mortality compared with younger patients, surgery is still much more beneficial than wait-and-see strategy in elderly patients.


Assuntos
Neoplasias Encefálicas/cirurgia , Neoplasias Meníngeas/cirurgia , Meningioma/cirurgia , Procedimentos Neurocirúrgicos , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/mortalidade , Feminino , Humanos , Masculino , Neoplasias Meníngeas/mortalidade , Meningioma/mortalidade , Procedimentos Neurocirúrgicos/mortalidade , Fatores de Risco , Resultado do Tratamento
15.
Medicine (Baltimore) ; 98(33): e16766, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31415376

RESUMO

Patients with non-small cell lung cancer (NSCLC) and de novo brain metastasis (BM) have poor prognosis. We aim to investigate the characteristic of brain magnetic resonance (MR) imaging and the association with the treatment response of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) for lung cancer with BM.EGFR-mutated NSCLC patients with BM from October 2013 to December 2017 in a tertiary referral center were retrospectively analyzed. Patient's age, sex, cell type, EGFR mutation status, treatment, and characteristics of BM were collected. Survival analysis was performed using Kaplan-Meier method. The efficacy of different EGFR-TKIs were also analyzed.Among the 257 eligible patients, 144 patients with Exon 19 deletion or Exon 21 L858R were included for analysis. The erlotinib group had the best progression free survival (PFS) (median PFS 13 months, P = .04). The overall survival (OS) revealed no significant difference between three EGFR-TKI groups. Brain MR imaging features including tumor necrosis, rim enhancement and specific tumor locations (frontal lobe, putamen or cerebellum) were factors associated with poor prognosis. Patients with poor prognostic imaging features, the high-risk group, who received erlotinib had the best PFS (median PFS 12 months, P < .001). However, the OS revealed no significant difference between 3 EGFR-TKI groups. The low risk group patients had similar PFS and OS treated with three different EGFR-TKIs.In NSCLC patients with common EGFR mutation and de novo BM, those with poor prognostic brain MR characteristics, erlotinib provided better PFS than afatinib or gefitinib.


Assuntos
Neoplasias Encefálicas/terapia , Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/terapia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/secundário , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/secundário , Terapia Combinada , Intervalo Livre de Doença , Receptores ErbB/genética , Cloridrato de Erlotinib/uso terapêutico , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Mutação , Metástase Neoplásica , Valor Preditivo dos Testes , Inibidores de Proteínas Quinases/uso terapêutico , Estudos Retrospectivos , Taiwan
16.
Br J Radiol ; 92(1103): 20190324, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31386559

RESUMO

OBJECTIVE: This study was to investigate the relationship of diffusion features with molecule information, and then predict grade and survival in lower-grade gliomas. METHODS: 65 patients with primary lower-grade gliomas (WHO Grade II & III) who underwent conventional MRI and diffusion tensor imaging were retrospectively studied. The tumor region was automatically segmented into contrast-enhancing tumor, non-enhancing tumor, edematous and necrotic volumes. Diffusion features, including fractional anisotropy (FA), axial diffusivity, radial diffusivity and apparent diffusion coefficient (ADC), were extracted from each volume using histogram analysis. To estimate molecule biomarkers and predict clinical characteristics of grade and survival, support vector machine, generalized linear model, logistic regression and Cox regression were performed on the related features. RESULTS: The diffusion features in non-enhancing tumor volume showed differences between isocitrate dehydrogenase mutant and wild-type gliomas. And the mean accuracy of support vector machine classifiers was 0.79. Ki-67 labeling index was correlated with these features, which were combined to significantly estimate Ki-67 expression level (r = 0.657, p < 0.001). These features also showed differences between Grade II and III gliomas. A combination of them for grade classification resulted in an area under the curve of 0.914 (0.857-0.971). Mean FA and fifth percentile of ADC were independently associated with overall survival, with lower FA and higher ADC showing better survival outcome. CONCLUSION: In lower-grade gliomas, multiparametric and multiregional diffusion features could help predict molecule information, histological grade and survival. ADVANCES IN KNOWLEDGE: The multi parametric diffusion features in non-enhancing tumor were associated with molecule information, grade and survival in lower-grade gliomas.


Assuntos
Astrocitoma/patologia , Neoplasias Encefálicas/patologia , Oligodendroglioma/patologia , Adulto , Idoso , Anisotropia , Astrocitoma/mortalidade , Neoplasias Encefálicas/mortalidade , Imagem de Tensor de Difusão/métodos , Estudos de Viabilidade , Feminino , Humanos , Antígeno Ki-67/metabolismo , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Oligodendroglioma/mortalidade , Estudos Retrospectivos , Carga Tumoral , Adulto Jovem
17.
BMC Cancer ; 19(1): 793, 2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31399067

RESUMO

BACKGROUND: The treatment strategy for brain metastasis (BM) in patients with epidermal growth factor receptor (EGFR) -mutant lung adenocarcinoma (LAC) remains controversial. In the present study, we compared the efficacy of brain radiotherapy (RT) in combination with tyrosine kinase inhibitors (TKIs) and TKIs alone for advanced LAC patients with EGFR mutations and BM. METHODS: We retrospectively studied 78 patients diagnosed with EGFR-mutant LAC who developed BM. These patients were divided into two groups: 49 patients in the combination treatment group who received brain RT in combination with EGFR-TKIs (including 23 patients with asymptomatic BM before RT); 29 patients in the TKI group who received EGFR-TKI targeted therapy alone (including 22 patients with asymptomatic BM before TKI treatment). RESULTS: The median intracranial progression-free survival (iPFS) of the combination treatment group was longer than that of the TKI alone group (21.5 vs. 15 months; P = 0.036). However, there were no significant differences in median progression-free survival (PFS, 12 vs. 13 months; P = 0.242) and median overall survival (mOS, 36 vs. 23 months; P = 0.363) between the two groups. Further analysis of asymptomatic BM showed that both the median iPFS and the mOS of the combination treatment group were significantly longer than for the TKI alone group (iPFS, 21.5 vs. 14.8 months, P = 0.026; mOS, 36 vs. 23 months, P = 0.041). Cox multivariate regression analysis found no independent adverse predictors of iPFS in all patients. CONCLUSIONS: The synchronous combination of brain RT and TKIs was superior to EGFR-TKIs alone for EGFR-mutant LAC patients with BM. The combination treatment group exhibited longer iPFS, while the PFS and OS were not significantly different between the two groups. In addition, the combination treatment could result in better iPFS and OS in those with asymptomatic BM. Therefore, addition of brain RT was useful for intracranial metastatic lesions.


Assuntos
Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/terapia , Mutação , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/mortalidade , Terapia Combinada , Receptores ErbB/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/uso terapêutico , Radioterapia Adjuvante , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
18.
World Neurosurg ; 131: e379-e391, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31369883

RESUMO

BACKGROUND: Pineal region tumors represent challenging surgical lesions with wide ranges of survival reported in different surgical series. In this article, we emphasize the role of complete microsurgical resection (CMR) to obtain a favorable long-term outcome of pineal region tumors. METHODS: We report a retrospective study of pineal region tumors operated on in Helsinki Neurosurgery between 1997 and 2015. Information was obtained from the hospital records, and an evaluation of the Finnish population register was conducted in July 2018 to determine the current status of the patients. RESULTS: A total of 76 pineal region tumors were operated on. The survival was 62% at a mean follow-up of 125 ± 105 months (range, 0-588 months), and the disease-related mortality was limited to 14 patients (18.4%). Up to July 2018, 29 patients had died. Two patients died 1 and 3 months after surgery of delayed thalamic infarctions, 12 patients of disease progression, and 15 had non-disease-related deaths. Only 1 patient was lost in the long-term follow-up. Ten of 14 disease-related deaths occurred during the first 5 years of follow-up: 5 diffuse gliomas, 3 germ cell tumors, 1 grade II-III pineal parenchymal tumor of intermediate differentiation, and 1 meningioma. CMR was linked to better tumor-free survival and long-term survival, with the exception of diffuse gliomas. CONCLUSIONS: CMR, in the setting of a multidisciplinary management of pineal region tumors, correlates with favorable survival and with minimal mortality. Surgically treated grade II-IV gliomas constitute a particular group with high mortality within the first 5 years independently of the microsurgical resection.


Assuntos
Neoplasias Encefálicas/cirurgia , Glioma/cirurgia , Neoplasias Meníngeas/cirurgia , Meningioma/cirurgia , Neoplasias Embrionárias de Células Germinativas/cirurgia , Glândula Pineal/cirurgia , Pinealoma/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Astrocitoma/mortalidade , Astrocitoma/patologia , Astrocitoma/cirurgia , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Quimioterapia Adjuvante , Criança , Pré-Escolar , Feminino , Finlândia , Glioma/mortalidade , Glioma/patologia , Humanos , Lactente , Masculino , Neoplasias Meníngeas/mortalidade , Neoplasias Meníngeas/patologia , Meningioma/mortalidade , Meningioma/patologia , Microcirurgia , Pessoa de Meia-Idade , Neoplasias Embrionárias de Células Germinativas/mortalidade , Neoplasias Embrionárias de Células Germinativas/patologia , Procedimentos Neurocirúrgicos , Glândula Pineal/patologia , Pinealoma/mortalidade , Pinealoma/patologia , Radioterapia Adjuvante , Estudos Retrospectivos , Sobrevida , Carga Tumoral , Adulto Jovem
19.
Artigo em Inglês | MEDLINE | ID: mdl-31370357

RESUMO

Mortality-to-incidence ratios (MIRs) are alternative parameters used to evaluate the prognosis of a disease. In addition, MIRs are associated with the ranking of health care systems and expenditures for certain types of cancer. However, a lack of association between MIRs and pancreatic cancer has been noted. Given the poor prognosis of brain and nervous system cancers, similar to pancreatic cancer, the relation of MIRs and health care disparities is worth investigating. We used the Spearman's rank correlation coefficient (CC) to analyze the correlation between the MIRs in brain and nervous system cancers and inter-country disparities, including expenditures on health and human development index. Interestingly, the MIRs in brain and nervous system cancers are associated with the human development index score (N = 157, CC = -0.394, p < 0.001), current health expenditure (CHE) per capita (N = 157, CC = -0.438, p < 0.001), and CHE as percentage of gross domestic product (N = 157, CC = -0.245, p = 0.002). In conclusion, the MIRs in the brain and nervous system cancer are significantly associated with health expenditures and human development index. However, their role as an indicator of health disparity warrants further investigation.


Assuntos
Saúde Global/economia , Gastos em Saúde/estatística & dados numéricos , Disparidades em Assistência à Saúde/economia , Neoplasias do Sistema Nervoso/economia , Neoplasias do Sistema Nervoso/epidemiologia , Neoplasias Encefálicas/economia , Neoplasias Encefálicas/epidemiologia , Neoplasias Encefálicas/mortalidade , Estudos Transversais , Bases de Dados Factuais , Saúde Global/estatística & dados numéricos , Produto Interno Bruto , Desenvolvimento Humano , Humanos , Incidência , Neoplasias do Sistema Nervoso/mortalidade , Prognóstico
20.
J Clin Neurosci ; 68: 45-50, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31371189

RESUMO

There is limited information on the patterns of care and outcomes of high grade gliomas (HGGs) in young adults, in particular, the impact it has on a person's employment. We retrospectively identified young adult patients (age ≤ 40 years old) with newly diagnosed high grade gliomas treated between January 2013 and June 2018 across four major neuro-oncology centres in Australia. Patient demographics, tumour characteristics and treatment parameters were collected and outcomes determined. A total of 113 patients were identified with a median follow up of 27.0 months (range 1.0-70.2 months). The median age was 31 years, majority were male (65%) and employed (71.6%). IDH mutations were detected in 66 (62%) cases. The median progression-free survival (PFS) was 38.0 months (95% CI 23.3-52.7 months) and median overall survival (OS) was not reached. Patients with IDH wild type anaplastic astrocytoma and glioblastoma had a significantly shorter median PFS (19.3 months vs. NR, p = 0.001) and median OS (43.5 months vs NR, p = 0.007) than those with IDH mutated grade III anaplastic astrocytoma and oligodendroglioma. There was no significant difference in median OS or PFS between patients who underwent gross or subtotal tumour resection. Significantly, after diagnosis only 36 (32%) patients reported being employed. Young patients with IDH wild type astrocytomas and glioblastoma had better outcomes than reported historical controls. Most patients did not continue in employment post diagnosis.


Assuntos
Neoplasias Encefálicas , Emprego/estatística & dados numéricos , Glioma , Adolescente , Adulto , Austrália , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/cirurgia , Feminino , Glioma/mortalidade , Glioma/patologia , Glioma/cirurgia , Humanos , Masculino , Intervalo Livre de Progressão , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
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