RESUMO
PURPOSE: Endoscopic transsphenoidal surgery (ETSS) is a well-established treatment for patients with nonfunctioning pituitary adenomas (NFPAs). Data on the rates of pituitary dysfunction and recovery in a large cohort of NFPA patients undergoing ETSS and the predictors of endocrine function before and after ETSS are scarce. This study is purposed to analyze the comprehensive changes in hormonal function and identify factors that predict recovery or worsening of hormonal axes following ETSS for NFPA. METHODS: A retrospective review of 601 consecutive patients who underwent ETSS between 2010 and 2018 at one institution was performed. Recovery or development of new hypopituitarism was analyzed in 209 NFPA patients who underwent ETSS. RESULTS: Patients with preoperative endocrine deficits (59.8%) in one or more pituitary axes had larger tumor volumes (P = 0.001) than those without preoperative deficits. Recovery of preoperative pituitary deficit occurred in all four axes, with overall mean recovery of 29.7%. The cortisol axis showed the highest recovery whereas the thyroid axis showed the lowest, with 1-year cumulative recovery rates of 44.3% and 6.1%, respectively. Postoperative hypopituitarism occurred overall in 17.2%, most frequently in the thyroid axis (24.3%, 27/111) and least frequently in the cortisol axis (9.7%, 16/165). Axis-specific predictors of post-operative recovery and deficiency were identified. CONCLUSIONS: Dynamic alterations in pituitary hormones were observed in a proportion of patients following ETSS in NFPA patients. Postoperative endocrine vulnerability, recovery, and factors that predicted recovery or loss of endocrine function depended on the hormonal system, necessitating an axis-specific surveillance strategy postoperatively.
Assuntos
Adenoma/cirurgia , Insuficiência Adrenal/metabolismo , Hipogonadismo/metabolismo , Hipopituitarismo/metabolismo , Hipotireoidismo/metabolismo , Neoplasias Hipofisárias/cirurgia , Recuperação de Função Fisiológica , Adenoma/complicações , Adenoma/metabolismo , Insuficiência Adrenal/etiologia , Hormônio Adrenocorticotrópico/metabolismo , Idoso , Estradiol/metabolismo , Feminino , Hormônio Foliculoestimulante/metabolismo , Hormônio do Crescimento Humano/deficiência , Hormônio do Crescimento Humano/metabolismo , Humanos , Hidrocortisona/metabolismo , Hiperprolactinemia/etiologia , Hiperprolactinemia/metabolismo , Hipogonadismo/etiologia , Hipopituitarismo/etiologia , Sistema Hipotálamo-Hipofisário , Hipotireoidismo/etiologia , Fator de Crescimento Insulin-Like I/metabolismo , Hormônio Luteinizante/metabolismo , Masculino , Pessoa de Meia-Idade , Neuroendoscopia , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/metabolismo , Testes de Função Adreno-Hipofisária , Sistema Hipófise-Suprarrenal , Prolactina/metabolismo , Osso Esfenoide , Testosterona/metabolismo , Tireotropina/metabolismo , Tiroxina/metabolismo , Resultado do TratamentoRESUMO
The Gamma Knife Center of St. Louis has established itself as a key facility offering stereotactic radiosurgery (SRS) for a variety of neuro-oncologic disorders. Since the Gamma Knife unit was first brought to Washington University in 1997, we have treated 5,696 patients. In this review, we discuss the effective role of Gamma Knife SRS in the treatment strategies for patients with neuro-oncologic disorders including brain metastases, meningiomas, pituitary adenomas, and acoustic neuromas. While there is active ongoing research evaluating the most effective treatment for patients with these disorders, it is clear that best management practices may be tailored for individual patients utilizing SRS either alone or in conjunction alternative treatment strategies including open neurosurgical procedures, laser thermos-ablative surgery, and even new medical oncological treatment strategies.
Assuntos
Neoplasias Encefálicas/cirurgia , Meningioma/cirurgia , Neuroma Acústico/cirurgia , Neurocirurgia/métodos , Neoplasias Hipofisárias/cirurgia , Radiocirurgia/métodos , Neoplasias Encefálicas/secundário , Humanos , Neurocirurgia/tendências , Radiocirurgia/tendências , Resultado do TratamentoRESUMO
Accumulating evidence suggests cancer cells exhibit a dependency on metabolic pathways regulated by nicotinamide adenine dinucleotide (NAD+). Nevertheless, how the regulation of this metabolic cofactor interfaces with signal transduction networks remains poorly understood in glioblastoma. Here, we report nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting step in NAD+ synthesis, is highly expressed in glioblastoma tumors and patient-derived glioblastoma stem-like cells (GSCs). High NAMPT expression in tumors correlates with decreased patient survival. Pharmacological and genetic inhibition of NAMPT decreased NAD+ levels and GSC self-renewal capacity, and NAMPT knockdown inhibited the in vivo tumorigenicity of GSCs. Regulatory network analysis of RNA sequencing data using GSCs treated with NAMPT inhibitor identified transcription factor E2F2 as the center of a transcriptional hub in the NAD+-dependent network. Accordingly, we demonstrate E2F2 is required for GSC self-renewal. Downstream, E2F2 drives the transcription of members of the inhibitor of differentiation (ID) helix-loop-helix gene family. Finally, we find NAMPT mediates GSC radiation resistance. The identification of a NAMPT-E2F2-ID axis establishes a link between NAD+ metabolism and a self-renewal transcriptional program in glioblastoma, with therapeutic implications for this formidable cancer.
Assuntos
Neoplasias Encefálicas/metabolismo , Citocinas/genética , Glioblastoma/metabolismo , NAD/biossíntese , Nicotinamida Fosforribosiltransferase/genética , Tolerância a Radiação , Transcrição Gênica , Animais , Antineoplásicos/farmacologia , Encéfalo/patologia , Neoplasias Encefálicas/radioterapia , Linhagem Celular Tumoral , Núcleo Celular/metabolismo , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Glioblastoma/radioterapia , Humanos , Camundongos , Mutação , Transplante de Neoplasias , Interferência de RNA , Transdução de Sinais/efeitos dos fármacos , Células-Tronco/citologiaRESUMO
PURPOSE: Characterize the intra-fraction motion management (IFMM) system found on the Gamma Knife Icon (GKI), including spatial accuracy, latency, temporal performance, and overall effect on delivered dose. METHODS: A phantom was constructed, consisting of a three-axis translation mount, a remote motorized flipper, and a thermoplastic sphere surrounding a radiation detector. An infrared marker was placed on the translation mount secured to the flipper. The spatial accuracy of the IFMM was measured via the translation mount in all Cartesian planes. The detector was centered at the radiation focal point. A remote signal was used to move the marker out of the IFMM tolerance and pause the beam. A two-channel electrometer was used to record the signals from the detector and the flipper when motion was signaled. These signals determined the latency and temporal performance of the GKI. RESULTS: The spatial accuracy of the IFMM was found to be <0.1 mm. The measured latency was <200 ms. The dose difference with five interruptions was <0.5%. CONCLUSION: This work provides a quantitative characterization of the GKI IFMM system as required by the Nuclear Regulatory Commission. This provides a methodology for GKI users to satisfy these requirements using common laboratory equipment in lieu of a commercial solution.
Assuntos
Movimento , Neoplasias/cirurgia , Imagens de Fantasmas , Radiocirurgia/instrumentação , Planejamento da Radioterapia Assistida por Computador/métodos , Desenho de Equipamento , Humanos , Radiometria/métodos , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/métodosRESUMO
Anti-vascular endothelial growth factor (anti-VEGF) antibodies are a promising new treatment for late time-to-onset radiation-induced necrosis (RN). We sought to evaluate and validate the response to anti-VEGF antibody in a mouse model of RN. Mice were irradiated with the Leksell Gamma Knife Perfexion™ and then treated with anti-VEGF antibody, beginning at post-irradiation (PIR) week 8. RN progression was monitored via anatomic and diffusion MRI from weeks 4-12 PIR. Standard histology, using haematoxylin and eosin (H&E), and immunohistochemistry staining were used to validate the response to treatment. After treatment, both post-contrast T1-weighted and T2-weighted image-derived lesion volumes decreased (P < 0.001), while the lesion volumes for the control group increased. The abnormally high apparent diffusion coefficient (ADC) for RN also returned to the ADC range for normal brain following treatment (P < 0.001). However, typical RN pathology was still present histologically. Large areas of focal calcification were observed in ~50% of treated mouse brains. Additionally, VEGF and hypoxia-inducible factor 1-alpha (HIF-1α) were continually upregulated in both the anti-VEGF and control groups. Despite improvements observed radiographically following anti-VEGF treatment, lesions were not completely resolved histologically. The subsequent calcification and the continued upregulation of VEGF and HIF-1α merit further preclinical/clinical investigation.
Assuntos
Anticorpos Monoclonais/farmacologia , Lesões Experimentais por Radiação/tratamento farmacológico , Protetores contra Radiação/farmacologia , Radiocirurgia , Fator A de Crescimento do Endotélio Vascular/imunologia , Animais , Encéfalo/diagnóstico por imagem , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Encéfalo/efeitos da radiação , Lesões Encefálicas/diagnóstico por imagem , Lesões Encefálicas/tratamento farmacológico , Lesões Encefálicas/etiologia , Lesões Encefálicas/patologia , Calcinose/diagnóstico por imagem , Calcinose/tratamento farmacológico , Calcinose/etiologia , Calcinose/patologia , Progressão da Doença , Feminino , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Imuno-Histoquímica , Imageamento por Ressonância Magnética , Camundongos Endogâmicos BALB C , Necrose/diagnóstico por imagem , Necrose/tratamento farmacológico , Necrose/etiologia , Necrose/patologia , Lesões Experimentais por Radiação/diagnóstico por imagem , Lesões Experimentais por Radiação/patologia , Distribuição Aleatória , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidoresRESUMO
During the 6 month period following chemoradiotherapy, gliomas frequently develop new areas of contrast enhancement, which are due to treatment effect rather than tumor progression. We sought to characterize this phenomenon in oligodendrogliomas (OG) and mixed oligoastrocytomas (MOA). We reviewed the imaging findings from 143 patients with a WHO grade II or III OG or MOA for evidence of pseudoprogression (PsP) or early tumor progression. We characterized these cases for 1p/19q codeletions by FISH, IDH1 R132H mutation by immunohistochemistry, and TP53, ATRX, and EGFR mutations by next generation sequencing. We then reviewed the pathologic specimens of the patient cases in which a re-resection was performed. We found that OG and MOA that are 1p/19q intact developed PsP at a higher rate than tumors that are 1p/19q codeleted (27 vs. 8 %). Moreover, IDH1 wild-type (WT) tumors developed PsP at a higher rate than IDH1 R132H cases (27 vs. 11 %). Patients with ATRX or TP53 mutations developed PsP at an intermediate rate of 21 %. Ten patients in our cohort underwent a re-resection for early contrast enhancement; these tumors were predominantly 1p/19q intact (90 %) and had a low rate of IDH1 R132H mutation (50 %). 8 of 10 tumors demonstrated primarily treatment effects, while the remaining 2 of 10 demonstrated recurrent/residual tumor of the same grade. Early contrast enhancement that develops during the first 6 months after chemoradiotherapy is typically due to PsP and occurs primarily in OG and MOA that are 1p/19q intact and IDH WT.
Assuntos
Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Glioma/genética , Glioma/patologia , Mutação/genética , Proteínas de Neoplasias/genética , Deleção Cromossômica , Cromossomos Humanos Par 1/genética , Receptores ErbB/genética , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Isocitrato Desidrogenase/genética , Masculino , Recidiva Local de Neoplasia/genética , Prognóstico , Proteína Supressora de Tumor p53/genética , Proteína Nuclear Ligada ao X/genéticaRESUMO
Gliosarcoma (GS) is a rare subtype of glioblastoma (GBM) characterized by both glial and mesenchymal components. Unlike GBM, there are no specific prognostic markers, and optimized treatments for patients with GS do not exist. Recent reports describe BRAFV600E mutation in malignant peripheral nerve sheath tumors, and aberrant Wnt signaling and CTNNB1 (ß-catenin gene) mutations have been described in GBM. We sought to determine whether GS tumors harbor BRAFV600E mutations or aberrant Wnt signaling, as indicated by nuclear localization of ß-catenin, by immunohistochemical detection. Forty-eight (48) cases of primary and secondary adult GS (including recurrent ones) were evaluated by immunohistochemical techniques for the presence of nuclear ß-catenin and the BRAFV600E mutation. A small subset (6/46, 13%) showed nuclear localization of ß-catenin. None of the cases harbored BRAFV600E mutations (0/48). These results are the first to describe the presence of Wnt signaling pathway abnormalities, manifested by nuclear ß-catenin, in a subset, as well as the lack of BRAFV600E mutation in GS. We propose a potential role for Wnt pathway alterations in the pathogenesis of a subset of GS.
Assuntos
Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Núcleo Celular/metabolismo , Gliossarcoma/genética , Gliossarcoma/metabolismo , Proteínas Proto-Oncogênicas B-raf/genética , beta Catenina/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Encéfalo/metabolismo , Encéfalo/patologia , Neoplasias Encefálicas/patologia , Feminino , Gliossarcoma/patologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Mutação , Via de Sinalização WntRESUMO
BACKGROUND AND PURPOSE: Cerebral arterial vasospasm (CVS) is a common complication of aneurysmal subarachnoid hemorrhage strongly associated with neurological deterioration and delayed cerebral ischemia (DCI). The utility of screening for CVS as a surrogate for early detection of DCI, especially in patients without clinical signs of DCI, remains uncertain. METHODS: We performed a retrospective analysis of 116 aneurysmal subarachnoid hemorrhage patients who underwent screening digital subtraction angiography to determine the association of significant CVS and subsequent development of DCI. Patients were stratified into 3 groups: (1) no symptoms of DCI before screening, (2) ≥1 episodes of suspected DCI symptoms before screening, and (3) unable to detect symptoms because of poor examination. RESULTS: Patients asymptomatic before screening had significantly lower rates of CVS (18%) compared with those with transient symptoms of DCI (60%; P<0.0001). None of the 79 asymptomatic patients developed DCI after screening, regardless of digital subtraction angiography findings, compared with 56% of those with symptoms (P<0.0001). Presence of CVS was significantly associated with DCI in those with transient symptoms and in those whose examinations did not permit clear assessment (odds ratio 16.0, 95% confidence interval 2.2-118.3, P=0.003). CONCLUSIONS: Patients asymptomatic before screening have low rates of CVS and seem to be at negligible risk of developing DCI. Routine screening of asymptomatic patients seems to have little utility. Screening may still be considered in patients with possible symptoms of DCI or those with examinations too poor to clinically detect symptoms because finding CVS may be useful for risk stratification and guiding management.
Assuntos
Angiografia Digital , Programas de Rastreamento , Vasoespasmo Intracraniano/diagnóstico por imagem , Vasoespasmo Intracraniano/epidemiologia , Angiografia Digital/métodos , Estudos de Coortes , Bases de Dados Factuais , Feminino , Humanos , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco , Hemorragia Subaracnóidea/diagnóstico por imagem , Hemorragia Subaracnóidea/epidemiologiaRESUMO
PURPOSE: The clinical benefit of combined intraoperative magnetic resonance imaging (iMRI) and endoscopy for transsphenoidal pituitary adenoma resection has not been completely characterized. This study assessed the impact of microscopy, endoscopy, and/or iMRI on progression-free survival, extent of resection status (gross-, near-, and sub-total resection), and operative complications. METHODS: Retrospective analyses were performed on 446 transsphenoidal pituitary adenoma surgeries at a single institution between 1998 and 2012. Multivariate analyses were used to control for baseline characteristics, differences during extent of resection status, and progression-free survival analysis. RESULTS: Additional surgery was performed after iMRI in 56/156 cases (35.9%), which led to increased extent of resection status in 15/156 cases (9.6%). Multivariate ordinal logistic regression revealed no increase in extent of resection status following iMRI or endoscopy alone; however, combining these modalities increased extent of resection status (odds ratio 2.05, 95% CI 1.21-3.46) compared to conventional transsphenoidal microsurgery. Multivariate Cox regression revealed that reduced extent of resection status shortened progression-free survival for near- versus gross-total resection [hazard ratio (HR) 2.87, 95% CI 1.24-6.65] and sub- versus near-total resection (HR 2.10; 95% CI 1.00-4.40). Complication comparisons between microscopy, endoscopy, and iMRI revealed increased perioperative deaths for endoscopy versus microscopy (4/209 and 0/237, respectively), but this difference was non-significant considering multiple post hoc comparisons (Fisher exact, p = 0.24). CONCLUSIONS: Combined use of endoscopy and iMRI increased pituitary adenoma extent of resection status compared to conventional transsphenoidal microsurgery, and increased extent of resection status was associated with longer progression-free survival. Treatment modality combination did not significantly impact complication rate.
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Endoscopia/métodos , Imageamento por Ressonância Magnética/métodos , Neoplasias Hipofisárias/mortalidade , Neoplasias Hipofisárias/cirurgia , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Retrospectivos , Adulto JovemRESUMO
Novel functional and metabolic MRI imaging provides the ability to analyze tumor tissue properties including tumor vasculature, vascular permeability, tumor cellularity, hypoxia, and tumor proliferation. Stereotactic radiosurgery involves the delivery of a very precise, focal dose of radiation to a target. Recent advances in MR imaging have the potential to improve accuracy for target volume delineation and to potentially improve outcome. Novel MR imaging techniques may also be used in subsequent post-treatment follow-up to distinguish between tumor recurrences versus non-neoplastic treatment-related changes. In this paper, we address multiparametric MR imaging and cerebral angiography as tools to reduce toxicity.
Assuntos
Neoplasias/cirurgia , Radiocirurgia/métodos , Cirurgia Assistida por Computador/métodos , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/cirurgia , Humanos , Imageamento por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética/tendências , Radiocirurgia/tendências , Cirurgia Assistida por Computador/tendênciasRESUMO
BACKGROUND AND PURPOSE: Spontaneous idiopathic subarachnoid hemorrhage (SAH) with a perimesencephalic bleeding pattern is usually associated with a benign course, whereas a diffuse bleeding pattern has been associated with a higher risk of vasospasm and disability. We evaluated whether volume of bleeding explains this disparity. METHODS: Pattern and amount of bleeding (by Hijdra and intraventricular hemorrhage scores) were assessed in 89 patients with nonaneurysmal SAH. Outcomes included angiographic vasospasm, delayed cerebral ischemia, and functional outcome at 1 year. RESULTS: Diffuse bleeding was associated with significantly higher Hijdra and intraventricular hemorrhage scores than perimesencephalic SAH, P≤0.003. Angiographic vasospasm was more likely in diffuse versus perimesencephalic SAH (45% versus 27%; odds ratio, 2.9; P=0.08), but adjustment for greater blood burden only partially attenuated this trend (adjusted odds ratio, 2.2; 95% confidence interval, 0.69-7.2; P=0.18); delayed cerebral ischemia was only seen in those with diffuse bleeding. Patients with diffuse bleeding were less likely to be discharged home (68% versus 90%; P=0.01) and tended to have more residual disability (modified Rankin scale, 3-6; 20% versus 6%; P=0.18). CONCLUSIONS: Nonaneurysmal SAH can still result in vasospasm and residual disability, especially in those with diffuse bleeding. This disparity is only partially accounted for by greater cisternal or intraventricular blood, suggesting that the mechanism and distribution of bleeding may be as important as the amount of hemorrhage in patients with idiopathic SAH.
Assuntos
Hemorragia Subaracnóidea/patologia , Vasoespasmo Intracraniano/patologia , Adulto , Idoso , Angiografia Digital , Volume Sanguíneo/fisiologia , Isquemia Encefálica/etiologia , Isquemia Encefálica/patologia , Angiografia Cerebral , Estudos de Coortes , Intervalos de Confiança , Avaliação da Deficiência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Valor Preditivo dos Testes , Estudos Prospectivos , Punção Espinal , Hemorragia Subaracnóidea/complicações , Tomografia Computadorizada por Raios X , Vasoespasmo Intracraniano/etiologiaRESUMO
PURPOSE: Distinguishing recurrent brain tumor from treatment effects, including late time-to-onset radiation necrosis (RN), presents an on-going challenge in post-treatment imaging of neuro-oncology patients. Experiments were performed in a novel mouse model that recapitulates the relevant clinical histologic features of recurrent glioblastoma growing in a RN environment, the mixed tumor/RN model. The goal of this work was to apply single-voxel deuterium (2H) magnetic resonance spectroscopy (MRS), in concert with administration of deuterated glucose, to determine if the metabolic signature of aerobic glycolysis (Warburg effect: glucose â lactate in the presence of O2), a distinguishing characteristic of proliferating tumor, provides a quantitative readout of the tumor fraction (percent) in a mixed tumor/RN lesion. PROCEDURES: 2H MRS employed the SPin-ECho full-Intensity Acquired Localized (SPECIAL) MRS pulse sequence and outer volume suppression at 11.74 T. For each subject, a single 2H MRS voxel was placed over the mixed lesion as defined by contrast enhanced (CE) 1H T1-weighted MRI. Following intravenous administration of [6,6-2H2]glucose (Glc), 2H MRS monitored the glycolytic conversion to [3,3-2H2]lactate (Lac) and glutamate + glutamine (Glu + Gln = Glx). RESULTS: Based on previous work, the tumor fraction of the mixed lesion was quantified as the ratio of tumor volume, defined by 1H magnetization transfer experiments, vs. the total mixed-lesion volume. Metabolite 2H MR spectral-amplitude values were converted to metabolite concentrations using the natural-abundance semi-heavy water (1HO2H) resonance as an internal concentration standard. The 2H MR-determined [Lac] / [Glx] ratio was strongly linearly correlated with tumor fraction in the mixed lesion (n = 9), Pearson's r = 0.87, and 77% of the variation in the [Lac] / [Glx] ratio was due to tumor percent r2 = 0.77. CONCLUSIONS: This preclinical study supports the proposal that 2H MR could occupy a well-defined secondary role when standard-of-care 1H imaging is non-diagnostic regarding tumor presence and/or response to therapy.
Assuntos
Glioblastoma , Animais , Camundongos , Humanos , Deutério , Glioblastoma/diagnóstico por imagem , Espectroscopia de Ressonância Magnética , Modelos Animais de Doenças , Ácido Láctico/metabolismo , Necrose , Glucose , Imageamento por Ressonância MagnéticaRESUMO
BACKGROUND: This study tested the hypothesis that time of day of treatment with stereotactic radiosurgery (SRS) has an effect on local control (LC) and overall survival (OS) in a large cohort of patients with non-small cell lung cancer (NSCLC) brain metastases. METHODS: At Washington University in St. Louis, 437 patients with NSCLC were treated with SRS for NSCLC brain metastases. Receiver operating characteristics analysis was used to identify an optimal cut-point for OS relative to time of day. Kaplan-Meier log-rank statistics, and Cox regression univariate and multivariate analysis were employed to isolate any independent effect of treatment time on OS and LC. Matched-pair analysis was performed to isolate any independent effect of time on OS and LC of day while controlling for confounding variables. RESULTS: Receiver operating characteristics analysis identified a cut-point of 11:41 AM as providing the highest predictive value for OS. On univariate analysis, late SRS was associated with decreased OS, as was age, Karnofsky performance status, risk-stratification schemes, extracranial disease status, and overall burden of brain metastases. On univariate analysis for LC, late SRS was associated with decreased LC, as was burden of brain metastases. On multivariate analysis, only Graded Prognostic Assessment remained predictive of OS, and total number of targets and total tumor volume remained predictive of LC. Matched-pair analysis demonstrated no significant effect of time of day on LC or OS. CONCLUSIONS: Although earlier treatment appears to be associated with improved LC and OS, treatment time fails to remain significant when accounting for confounding variables.
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Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/cirurgia , Carcinoma Pulmonar de Células não Pequenas/secundário , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Ritmo Circadiano , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Fenômenos Cronobiológicos , Estudos de Coortes , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Radiocirurgia/métodos , Análise de Sobrevida , Resultado do TratamentoRESUMO
Oligodendrogliomas are rare central nervous system (CNS) tumors in children. The purpose of this study was to identify prognostic factors for progression free survival (PFS) and overall survival (OS) in pediatric patients with oligodendrogliomas. We retrospectively analyzed clinical data on 37 pediatric patients with oligodendroglial tumors treated at Washington University. Kaplan-Meier method was used to calculate survival rates. Log-rank was used to detect the difference between survival curves. The median age was 11.1 years (range 10 months-18 years), and median follow-up was 4.5 years (range 2 months-30.5 years). The 5-year PFS and OS were 66.4 and 93.4%, respectively. Mixed histology was associated with worse OS compared to patients with pure oligodendroglioma, 5-year OS 77.6 versus 100% (P < 0.01). Patients who underwent gross total resection (GTR) experienced an improved 5-year PFS of 100% compared to 28.8% (P = 0.03) in patients treated with subtotal resection (STR) or biopsy alone. Age >3 years at diagnosis correlated with improved 5-year PFS, 33.3 versus 69.8% (P = 0.01). Neither post-operative chemotherapy nor radiation therapy correlated with improved outcome. GTR and age >3 years at diagnosis remained significant for improved PFS on multivariate analysis. There were no factors correlated with improved overall survival on multivariate analysis. Pediatric oligodendroglial tumors are associated with excellent OS; however, a third of patients developed progressive disease. Our data demonstrate that patients with less than GTR and <3 years at diagnosis are at increased risk for progression and may benefit from more aggressive therapy.
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Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Oligodendroglioma/mortalidade , Oligodendroglioma/patologia , Adolescente , Neoplasias Encefálicas/terapia , Quimioterapia Adjuvante , Criança , Pré-Escolar , Progressão da Doença , Intervalo Livre de Doença , Feminino , Humanos , Lactente , Estimativa de Kaplan-Meier , Masculino , Procedimentos Neurocirúrgicos , Oligodendroglioma/terapia , Prognóstico , Radioterapia Adjuvante , Estudos Retrospectivos , Fatores de Risco , Resultado do TratamentoRESUMO
BACKGROUND: Choroid plexus papillomas are benign tumors of the choroid plexus. Although typically focal, they can metastasize. Rarely, patients may present with numerous cystic lesions throughout the craniospinal axis. OBSERVATIONS: The authors present three cases of pathologically confirmed fourth ventricular World Health Organization (WHO) grade 1 choroid plexus papillomas presenting with numerous cystic lesions throughout the craniospinal axis. Two cases were treated with only resection of the fourth ventricular mass; one was treated with a partial cyst fenestration. During follow-up, there was only mild interval growth of the cystic lesions over time, and all patients remained asymptomatic from their cystic lesions. The authors summarize five additional cases of cystic dissemination in the published literature and discuss hypotheses for the pathophysiology of this rare presentation. LESSONS: Choroid plexus papillomas may present with numerous, widely disseminated cystic lesions within the craniospinal axis. Thus, the authors recommend preoperative and routine imaging of the entire neuroaxis in patients with choroid plexus tumors, regardless of WHO grade. Although the role of adjuvant therapy and cyst fenestration in the treatment of these lesions remains unclear, watchful waiting may be indicated, especially in asymptomatic patients, because the lesions often demonstrate slow, if any, growth over time.
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OBJECTIVE: Colloid cysts of the third ventricle are histologically benign lesions that can cause obstructive hydrocephalus and death. Historically, colloid cysts have been removed by open microsurgical approaches. More recently, minimally invasive endoscopic and port-based techniques have offered decreased complications and length of stay, with improved patient satisfaction. METHODS: A single-center retrospective analysis of patients with colloid cysts who underwent surgery at a large tertiary care hospital was performed. The cohort was assessed based on the surgical approach, comparing endoscopic resection to open microsurgical resection. The primary endpoint was rate of perioperative complications. Univariate analysis was used to assess several procedure-related variables and the cost of treatment. Multivariate analysis was used to assess predictors of perioperative complications. Total inpatient cost for each case was extracted from the health system financial database. RESULTS: The study included 78 patients with colloid cysts who underwent resection either via an endoscopic approach (n = 33) or through a craniotomy (n = 45) with an interhemispheric-transcallosal or transcortical-transventricular approach. Nearly all patients were symptomatic, and half had obstructive hydrocephalus. Endoscopic resection was associated with reduced operative time (3.2 vs 4.9 hours, p < 0.001); lower complication rate (6.1% vs 33.1%, p = 0.009); reduced length of stay (4.1 vs 8.9 days, p < 0.001); and improved discharge to home (100% vs 75.6%, p = 0.008) compared to microsurgical resection. Coagulated residual cyst wall remnants were more common after endoscopic resection (63.6% vs 19.0%, p < 0.001) although this was not associated with a significantly increased rate of reoperation for recurrence. The mean follow-up was longer in the microsurgical resection group (3.1 vs 4.9 years, p = 0.016). The total inpatient cost of endoscopic resection was, on average, one-half (47%) that of microsurgical resection. When complications were encountered, the total inpatient cost of microsurgical resection was 4 times greater than that of endoscopic resection where no major complications were observed. The increased cost-effectiveness of endoscopic resection remained during reoperation. CONCLUSIONS: Endoscopic resection of colloid cysts of the third ventricle offers a significant reduction in perioperative complications when compared to microsurgical resection. Endoscopic resection optimizes nearly all procedure-related variables compared to microsurgical resection, and reduces total inpatient cost by > 50%. However, endoscopic resection is associated with a significantly increased likelihood of residual coagulated cyst wall remnants that could increase the rate of reoperation for recurrence. Taken together, endoscopic resection represents a safe and effective minimally invasive approach for removal of colloid cysts.
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Pituitary tumor apoplexy (PTA) classically comprises sudden-onset headache, loss of vision, ophthalmoparesis, and decreased consciousness. It typically results from hemorrhage and/or infarction within a pituitary adenoma. Presentation is heterologous, and optimal management is debated. The time course of recovery of cranial nerve deficits (CNDs) and headaches is not well established. In this study, a retrospective series of consecutive patients with PTA managed at a single academic institution over a 22-year period is presented. Headaches at the time of surgery were more severe in the early and subacute surgical cohort and improved significantly within 72 h postoperatively (p < 0.01). At one year, 90% of CNDs affecting cranial nerves (CNs) 3, 4, and 6 had recovered, with no differences between early (<4 d), subacute (4−14 d), and delayed (>14 d) time-to-surgery cohorts. Remarkably, half recovered within three days. In total, 56% of CN2 deficits recovered, with the early surgery cohort including more severe deficits and recovering at a lower rate (p = 0.01). No correlation of time-to-surgery and rapidity of recovery of CNDs was observed (p = 0.65, 0.72). Surgery for PTA is associated with rapid recovery of CNDs in the early, subacute, and delayed time frames, and with rapid headache improvement in the early and subacute time frames in 50% or more of patients.
Assuntos
Apoplexia Hipofisária , Neoplasias Hipofisárias , Acidente Vascular Cerebral , Nervos Cranianos/patologia , Cefaleia/complicações , Cefaleia/cirurgia , Humanos , Apoplexia Hipofisária/complicações , Apoplexia Hipofisária/patologia , Apoplexia Hipofisária/cirurgia , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/diagnóstico por imagem , Neoplasias Hipofisárias/cirurgia , Estudos Retrospectivos , Acidente Vascular Cerebral/complicaçõesRESUMO
Purpose: Distinguishing radiation necrosis (RN) from recurrent tumor remains a vexing clinical problem with important health-care consequences for neuro-oncology patients. Here, mouse models of pure tumor, pure RN, and admixed RN/tumor are employed to evaluate hydrogen (1H) and deuterium (2H) magnetic resonance methods for distinguishing RN vs. tumor. Furthermore, proof-of-principle, range-finding deuterium (2H) metabolic magnetic resonance is employed to assess glycolytic signatures distinguishing RN vs. tumor. Materials and Methods: A pipeline of common quantitative 1H MRI contrasts, including an improved magnetization transfer ratio (MTR) sequence, and 2H magnetic resonance spectroscopy (MRS) following administration of 2H-labeled glucose, was applied to C57BL/6 mouse models of the following: (i) late time-to-onset RN, occurring 4-5 weeks post focal 50-Gy (50% isodose) Gamma Knife irradiation to the left cerebral hemisphere, (ii) glioblastoma, growing ~18-24 days post implantation of 50,000 mouse GL261 tumor cells into the left cerebral hemisphere, and (iii) mixed model, with GL261 tumor growing within a region of radiation necrosis (1H MRI only). Control C57BL/6 mice were also examined by 2H metabolic magnetic resonance. Results: Differences in quantitative 1H MRI parametric values of R1, R2, ADC, and MTR comparing pure tumor vs. pure RN were all highly statistically significant. Differences in these parameter values and DCEAUC for tumor vs. RN in the mixed model (tumor growing in an RN background) are also all significant, demonstrating that these contrasts-in particular, MTR-can effectively distinguish tumor vs. RN. Additionally, quantitative 2H MRS showed a highly statistically significant dominance of aerobic glycolysis (glucose â lactate; fermentation, Warburg effect) in the tumor vs. oxidative respiration (glucose â TCA cycle) in the RN and control brain. Conclusions: These findings, employing a pipeline of quantitative 1H MRI contrasts and 2H MRS following administration of 2H-labeled glucose, suggest a pathway for substantially improving the discrimination of tumor vs. RN in the clinic.
RESUMO
OBJECTIVE: To identify factors, including the use of intraoperative magnetic resonance imaging (iMRI), impacting overall survival (OS) and progression-free survival (PFS) after resections of newly diagnosed intracranial grade II ependymomas performed across 4 different institutions. METHODS: Analyses of a multicenter mixed retrospective/prospective database assessed the impact of patient, treatment, and tumor characteristics on OS and PFS. iMRI workflow and logistics were also outlined. RESULTS: Forty-three patients were identified (mean age 25.4 years, mean follow-up 52.8 months). The mean OS was 52.8 ± 44.7 months. Univariate analyses failed to identify prognostic factors associated with OS, likely due to relatively shorter follow-up time for this less aggressive glioma subtype. The mean PFS was 43.7 ± 39.8 months. Multivariate analyses demonstrated that gross-total resection was associated with prolonged PFS compared to both subtotal resection (STR) (P = 0.005) and near-total resection (P = 0.01). Infratentorial location was associated with improved PFS compared to supratentorial location (P = 0.04). Log-rank analyses of Kaplan-Meier survival curves showed that increasing extent of resection (EOR) led to improved OS specifically for supratentorial tumors (P = 0.02) and improved PFS for all tumors (P < 0.001). Thirty cases (69.8%) utilized iMRI, of which 12 (27.9%) involved additional resection after iMRI. Of these, 8/12 (66.7%) resulted in gross-total resection, while 2/12 (16.7%) were near-total resection and 2/12 (16.7%) were subtotal resection. iMRI was not an independent prognosticator of PFS (P = 0.72). CONCLUSIONS: Greater EOR and infratentorial location were associated with increased PFS for grade II ependymomas. Greater EOR was associated with longer OS only for supratentorial tumors. A longer follow-up is needed to establish prognostic factors for this cohort, including use of iMRI.
Assuntos
Neoplasias Encefálicas , Ependimoma , Neoplasias Supratentoriais , Humanos , Adulto , Estudos Retrospectivos , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Ependimoma/diagnóstico por imagem , Ependimoma/cirurgia , Neoplasias Supratentoriais/diagnóstico por imagem , Neoplasias Supratentoriais/cirurgia , Intervalo Livre de Doença , Imageamento por Ressonância Magnética/métodosRESUMO
Glioblastomas display variable phenotypes that include increased drug-resistance associated with enhanced migratory and anti-apoptotic characteristics. These shared characteristics contribute to failure of clinical treatment regimens. Identification of novel compounds that promote cell death and impair cellular motility is a logical strategy to develop more effective clinical protocols. We recently described the ability of the small molecule, KCC009, a tissue transglutaminase (TG2) inhibitor, to sensitize glioblastoma cells to chemotherapy. In the current study, we synthesized a series of related compounds that show variable ability to promote cell death and impair motility in glioblastomas, irrespective of their ability to inhibit TG2. Each compound has a 3-bromo-4,5-dihydroisoxazole component that presumably reacts with nucleophilic cysteine thiol residues in the active sites of proteins that have an affinity to the small molecule. Our studies focused on the effects of the compound, ERW1227B. Treatment of glioblastoma cells with ERW1227B was associated with both down-regulation of the PI-3 kinase/Akt pathway, which enhanced cell death; as well as disruption of focal adhesive complexes and intracellular actin fibers, which impaired cellular mobility. Bioassays as well as time-lapse photography of glioblastoma cells treated with ERW1227B showed cell death and rapid loss of cellular motility. Mice studies with in vivo glioblastoma models demonstrated the ability of ERW1227B to sensitize tumor cells to cell death after treatment with either chemotherapy or radiation. The above findings identify ERW1227B as a potential novel therapeutic agent in the treatment of glioblastomas.