Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 41
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
2.
Cancer ; 2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32129893

RESUMO

BACKGROUND: Imaging of glioblastoma patients after maximal safe resection and chemoradiation commonly demonstrates new enhancements that raise concerns about tumor progression. However, in 30% to 50% of patients, these enhancements primarily represent the effects of treatment, or pseudo-progression (PsP). We hypothesize that quantitative machine learning analysis of clinically acquired multiparametric magnetic resonance imaging (mpMRI) can identify subvisual imaging characteristics to provide robust, noninvasive imaging signatures that can distinguish true progression (TP) from PsP. METHODS: We evaluated independent discovery (n = 40) and replication (n = 23) cohorts of glioblastoma patients who underwent second resection due to progressive radiographic changes suspicious for recurrence. Deep learning and conventional feature extraction methods were used to extract quantitative characteristics from the mpMRI scans. Multivariate analysis of these features revealed radiophenotypic signatures distinguishing among TP, PsP, and mixed response that compared with similar categories blindly defined by board-certified neuropathologists. Additionally, interinstitutional validation was performed on 20 new patients. RESULTS: Patients who demonstrate TP on neuropathology are significantly different (P < .0001) from those with PsP, showing imaging features reflecting higher angiogenesis, higher cellularity, and lower water concentration. The accuracy of the proposed signature in leave-one-out cross-validation was 87% for predicting PsP (area under the curve [AUC], 0.92) and 84% for predicting TP (AUC, 0.83), whereas in the discovery/replication cohort, the accuracy was 87% for predicting PsP (AUC, 0.84) and 78% for TP (AUC, 0.80). The accuracy in the interinstitutional cohort was 75% (AUC, 0.80). CONCLUSION: Quantitative mpMRI analysis via machine learning reveals distinctive noninvasive signatures of TP versus PsP after treatment of glioblastoma. Integration of the proposed method into clinical studies can be performed using the freely available Cancer Imaging Phenomics Toolkit.

3.
JCO Clin Cancer Inform ; 4: 234-244, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32191542

RESUMO

PURPOSE: To construct a multi-institutional radiomic model that supports upfront prediction of progression-free survival (PFS) and recurrence pattern (RP) in patients diagnosed with glioblastoma multiforme (GBM) at the time of initial diagnosis. PATIENTS AND METHODS: We retrospectively identified data for patients with newly diagnosed GBM from two institutions (institution 1, n = 65; institution 2, n = 15) who underwent gross total resection followed by standard adjuvant chemoradiation therapy, with pathologically confirmed recurrence, sufficient follow-up magnetic resonance imaging (MRI) scans to reliably determine PFS, and available presurgical multiparametric MRI (MP-MRI). The advanced software suite Cancer Imaging Phenomics Toolkit (CaPTk) was leveraged to analyze standard clinical brain MP-MRI scans. A rich set of imaging features was extracted from the MP-MRI scans acquired before the initial resection and was integrated into two distinct imaging signatures for predicting mean shorter or longer PFS and near or distant RP. The predictive signatures for PFS and RP were evaluated on the basis of different classification schemes: single-institutional analysis, multi-institutional analysis with random partitioning of the data into discovery and replication cohorts, and multi-institutional assessment with data from institution 1 as the discovery cohort and data from institution 2 as the replication cohort. RESULTS: These predictors achieved cross-validated classification performance (ie, area under the receiver operating characteristic curve) of 0.88 (single-institution analysis) and 0.82 to 0.83 (multi-institution analysis) for prediction of PFS and 0.88 (single-institution analysis) and 0.56 to 0.71 (multi-institution analysis) for prediction of RP. CONCLUSION: Imaging signatures of presurgical MP-MRI scans reveal relatively high predictability of time and location of GBM recurrence, subject to the patients receiving standard first-line chemoradiation therapy. Through its graphical user interface, CaPTk offers easy accessibility to advanced computational algorithms for deriving imaging signatures predictive of clinical outcome and could similarly be used for a variety of radiomic and radiogenomic analyses.

4.
Clin Cancer Res ; 26(2): 397-407, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31666247

RESUMO

PURPOSE: The clinical utility of plasma cell-free DNA (cfDNA) has not been assessed prospectively in patients with glioblastoma (GBM). We aimed to determine the prognostic impact of plasma cfDNA in GBM, as well as its role as a surrogate of tumor burden and substrate for next-generation sequencing (NGS). EXPERIMENTAL DESIGN: We conducted a prospective cohort study of 42 patients with newly diagnosed GBM. Plasma cfDNA was quantified at baseline prior to initial tumor resection and longitudinally during chemoradiotherapy. Plasma cfDNA was assessed for its association with progression-free survival (PFS) and overall survival (OS), correlated with radiographic tumor burden, and subjected to a targeted NGS panel. RESULTS: Prior to initial surgery, GBM patients had higher plasma cfDNA concentration than age-matched healthy controls (mean 13.4 vs. 6.7 ng/mL, P < 0.001). Plasma cfDNA concentration was correlated with radiographic tumor burden on patients' first post-radiation magnetic resonance imaging scan (ρ = 0.77, P = 0.003) and tended to rise prior to or concurrently with radiographic tumor progression. Preoperative plasma cfDNA concentration above the mean (>13.4 ng/mL) was associated with inferior PFS (median 4.9 vs. 9.5 months, P = 0.038). Detection of ≥1 somatic mutation in plasma cfDNA occurred in 55% of patients and was associated with nonstatistically significant decreases in PFS (median 6.0 vs. 8.7 months, P = 0.093) and OS (median 5.5 vs. 9.2 months, P = 0.053). CONCLUSIONS: Plasma cfDNA may be an effective prognostic tool and surrogate of tumor burden in newly diagnosed GBM. Detection of somatic alterations in plasma is feasible when samples are obtained prior to initial surgical resection.

5.
Cell ; 180(1): 188-204.e22, 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31883794

RESUMO

Glioblastomas exhibit vast inter- and intra-tumoral heterogeneity, complicating the development of effective therapeutic strategies. Current in vitro models are limited in preserving the cellular and mutational diversity of parental tumors and require a prolonged generation time. Here, we report methods for generating and biobanking patient-derived glioblastoma organoids (GBOs) that recapitulate the histological features, cellular diversity, gene expression, and mutational profiles of their corresponding parental tumors. GBOs can be generated quickly with high reliability and exhibit rapid, aggressive infiltration when transplanted into adult rodent brains. We further demonstrate the utility of GBOs to test personalized therapies by correlating GBO mutational profiles with responses to specific drugs and by modeling chimeric antigen receptor T cell immunotherapy. Our studies show that GBOs maintain many key features of glioblastomas and can be rapidly deployed to investigate patient-specific treatment strategies. Additionally, our live biobank establishes a rich resource for basic and translational glioblastoma research.

6.
Diagn Cytopathol ; 48(4): 342-349, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31883319

RESUMO

BACKGROUND: Pituicytoma is a rare tumor of the sella and suprasellar region. It is common for these tumors to be misdiagnosed radiographically as pituitary adenomas, meningiomas, and craniopharyngiomas. Histologically, pituicytomas are also known to show variable morphology. These factors often complicate intraoperative consultation, especially when tissue is limited. METHODS: A database search (January 1990-June 2019) identified 13 surgically resected pituicytomas that were sent for intraoperative consultation. The intraoperative cytology was reviewed by two pathologists, and both squash preparations/smears and touch preparations were included. RESULTS: The cytological features of pituicytomas were variable. The cytoplasm ranged from fibrillary to fine and wispy. The nuclei were round to ovoid with occasional tumors showing spindled morphology. Small nucleoli were seen in all tumors, and chromatin was fine to vesicular. While squash preparations were cellular and revealed cohesive groups of tumor cells, touch preparations were often paucicellular with the exception of one tumor. The cytological features of pituicytomas are compared to those of other tumors with similar radiographic appearances. CONCLUSIONS: Our findings illustrate the range of cytological features of these rare tumors and highlight the difficulty in making a definitive intraoperative diagnosis. Pituicytomas should be considered in the differential of a sellar/suprasellar lesion with glial and meningioma-like cytological features.

7.
Neurooncol Adv ; 1(1): vdz030, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31807732

RESUMO

Background: Amplification of the epidermal growth factor receptor (EGFR) gene is commonly found in glioblastoma (GBM). About 57% GBM overexpresses EGFR and are associated with tumor progression, poor prognosis, and shorter life expectancy. Molecular profiling of solid tumors usually takes several weeks and may be biased by intrinsic tumor heterogeneity. Methods: The unique sequence created by the fusion of exon 1 and exon 8 in EGFRvIII was used to guide the design of primers and a Minor Groove Binder (MGB) probe. Extracted total RNA was reverse transcribed and pre-amplified by PCR, followed by detection of the EGFRvIII mutation by dPCR. Results: The lowest limit of quantification of our EGFRvIII assay was 0.003%. The EGFRvIII variant was identified in patient-derived glioma neurosphere cell lines, xenograft mouse model, and patient-derived tumor specimens. The overall workflow can be accomplished within 24 hours. In certain samples, EGFRvIII was detected when next-generation sequencing was unable to identify the variant. This finding highlights the ability of the dPCR assay to identify EGFRvIII mutations in heterogeneous solid tumors such as GBM in a rapid fashion by profiling samples from spatially distinct areas of tumors from the same patient. Conclusions: In this study, we developed a highly sensitive digital PCR (dPCR) platform and leveraged our assay to detect the variant III alteration of EGFR (EGFRvIII) and amplified EGFR in patient-derived glioma neurosphere cell lines, orthotopic xenograft GBM mouse models, and patient-derived tumor specimens in less than 24 hours from minute quantities of starting material.

8.
CNS Oncol ; 8(3): CNS43, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31769726

RESUMO

Glioblastoma (GBM) is the most common primary malignant brain tumor in adults and carries a dismal prognosis. The EGFR gene is among the most commonly deranged genes in GBM and thus an important therapeutic target. We report the case of a young female with heavily pretreated EGFR-mutated GBM, for whom we initiated osimertinib, an oral, third-generation tyrosine kinase inhibitor that irreversibly inhibits EGFR and has significant brain penetration. We then review some of the main challenges in targeting EGFR, including lack of central nervous system penetration with most tyrosine kinase inhibitors, molecular heterogeneity of GBM and the need for enhanced specificity for the EGFR mutations relevant in GBM.

9.
J Neurooncol ; 145(2): 321-328, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31542863

RESUMO

PURPOSE: Young adults with isocitrate-dehydrogenase wild-type (IDH-WT) glioblastoma (GBM) represent a rare, understudied population compared to pediatric high-grade glioma, IDH-mutant GBM, or IDH-WT GBM in older patients. We aimed to explore the prognostic impact of epidermal growth factor receptor copy number gain (EGFR CN gain), one of the most common genetic alterations in IDH-WT glioma, in young adults with IDH-WT GBM. METHODS: We performed a retrospective cohort study of patients 18-45 years old with newly diagnosed, IDH-WT GBM whose tumors underwent next-generation sequencing at our institution between 2014 and 2018. The impact of EGFR CN gain on time to tumor progression (TTP) and overall survival (OS) was assessed. A validation cohort of patients 18-45 years old with IDH-WT GBM was analyzed from The Cancer Genome Atlas (TCGA). RESULTS: Ten of 28 patients (36%) from our institution had EGFR CN gain, which was associated with shorter TTP (median 6.5 vs. 11.9 months; p = 0.06) and OS (median 16.3 vs. 23.5 months; p = 0.047). The negative prognostic impact of EGFR CN gain on OS persisted in a multivariate model (HR 6.40, 95% CI 1.3-31.0, p = 0.02). In the TCGA cohort (N = 43), EGFR CN gain was associated with shorter TTP and worse OS, although these did not reach statistical significance (TTP, median 11.5 vs. 14.4 months, p = 0.18; OS, median 23.6 vs. 27.8 months; p = 0.18). CONCLUSIONS: EGFR CN gain may be associated with inferior outcomes in young adults with newly diagnosed, IDH-WT GBM, suggesting a potential role for targeting EGFR in this population.

10.
Sci Rep ; 9(1): 8747, 2019 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-31217496

RESUMO

Glioblastoma (GBM) is the most common primary malignant brain tumor in adults and carries a dismal prognosis. Significant challenges in the care of patients with GBM include marked vascular heterogeneity and arteriovenous (AV) shunting, which results in tumor hypoxia and inadequate delivery of systemic treatments to reach tumor cells. In this study, we investigated the utility of different MR perfusion techniques to detect and quantify arteriovenous (AV) shunting and tumor hypoxia in patients with GBM. Macrovascular shunting was present in 33% of subjects, with the degree of shunting ranging from (37-60%) using arterial spin labeling perfusion. Among the dynamic susceptibility contrast-enhanced perfusion curve features, there were a strong negative correlation between hypoxia score, DSC perfusion curve recovery slope (r = -0.72, P = 0.018) and angle (r = -0.73, P = 0.015). The results of this study support the possibility of using arterial spin labeling and pattern analysis of dynamic susceptibility contrast-enhanced MR Imaging for evaluation of arteriovenous shunting and tumor hypoxia in glioblastoma.

11.
Acad Pathol ; 6: 2374289519848353, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31206012

RESUMO

Molecular profiling of glioblastoma has revealed complex cytogenetic, epigenetic, and molecular abnormalities that are necessary for diagnosis, prognosis, and treatment. Our neuro-oncology group has developed a data-driven, institutional consensus guideline for efficient and optimal workup of glioblastomas based on our routine performance of molecular testing. We describe our institution's testing algorithm, assay development, and genetic findings in glioblastoma, to illustrate current practices and challenges in neuropathology related to molecular and genetic testing. We have found that coordination of test requisition, tissue handling, and incorporation of results into the final pathologic diagnosis by the neuropathologist improve patient care. Here, we present analysis of O6-methylguanine-DNA-methyltransferase promoter methylation and next-generation sequencing results of 189 patients, obtained utilizing our internal processes led by the neuropathology team. Our institutional pathway for neuropathologist-driven molecular testing has streamlined the management of glioblastoma samples for efficient return of results for incorporation of genomic data into the pathological diagnosis and optimal patient care.

12.
Mod Pathol ; 32(10): 1434-1446, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31175328

RESUMO

Malignant peripheral nerve sheath tumors contain loss of histone H3K27 trimethylation (H3K27me3) due to driver mutations affecting the polycomb repressive complex 2 (PRC2). Consequently, loss of H3K27me3 staining has served as a diagnostic marker for this tumor type. However, recent reports demonstrate H3K27me3 loss in numerous other tumors, including some in the differential diagnosis of malignant peripheral nerve sheath tumor. Since these tumors lose H3K27me3 through mechanisms distinct from PRC2 loss, we set out to determine whether loss of dimethylation of H3K27, which is also catalyzed by PRC2, might be a more specific marker of PRC2 loss and malignant peripheral nerve sheath tumor. Using mass spectrometry, we identify a near complete loss of H3K27me2 in malignant peripheral nerve sheath tumors and cell lines. Immunohistochemical analysis of 72 malignant peripheral nerve sheath tumors, seven K27M-mutant gliomas, 43 ependymomas, and 10 Merkel cell carcinomas demonstrates that while H3K27me3 loss is common across these tumor types, H3K27me2 loss is limited to malignant peripheral nerve sheath tumors and is highly concordant with H3K27me3 loss (33/34 cases). Thus, increased specificity does not come at the cost of greatly reduced sensitivity. To further compare H3K27me2 and H3K27me3 immunohistochemistry, we investigated 42 melanomas and 54 synovial sarcomas, histologic mimics of malignant peripheral nerve sheath tumor with varying degrees of H3K27me3 loss in prior reports. While global H3K27me3 loss was not seen in these tumors, weak and limited H3K27me3 staining was common. By contrast, H3K27me2 staining was more clearly retained in all cases, making it a superior binary classifier. This was confirmed by digital image analysis of stained slides. Our findings indicate that H3K27me2 loss is highly specific for PRC2 loss and that PRC2 loss is a rarer phenomenon than H3K27me3 loss. Consequently, H3K27me2 loss is a superior diagnostic marker for malignant peripheral nerve sheath tumor.

13.
Acta Neuropathol Commun ; 7(1): 69, 2019 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-31046843

RESUMO

Pituicytoma is a rare, poorly characterized tumor of the sellar region that is thought to be derived from neurohypophyseal pituicytes. Resection of pituicytomas is often associated with significant morbidity including diabetes insipidus and panhypopituitarism. Most of the literature on this tumor exists as small case series or case reports. Here we describe a cohort of fourteen pituicytoma resections from eleven patients. The average follow-up on these cases is 3.7 years with some patients having over 10 years of follow-up data available in the electronic medical record. Pituicytomas were frequently misdiagnosed on pre-operative imaging, and surgical resection was associated with persistent endocrine abnormalities. Histologically, the tumors showed a range of morphologies from epithelioid to spindled. All tumors were positive for TTF-1 with variable immunostaining for other markers including GFAP, EMA, S100, SSTR2A, and synaptophysin. Within this cohort are two patients with atypical pituicytomas which showed increased cellularity, pleomorphism, mitoses and elevated Ki-67 proliferation indexes when compared to non-atypical pituicytomas. Next generation sequencing performed on three tumors revealed alterations in genes involved in the MAPK pathway. Additionally, immunohistochemical staining for phosphorylated-ERK was positive in the majority of tumors. Increased awareness of the neoplastic entity and identification of targetable mutations have the potential to decrease the morbidity associated with resection of pituicytomas.

14.
Neuroradiol J ; 32(4): 250-258, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31050313

RESUMO

Elevated levels of choline are generally emphasized as marker of increased cellularity and cell membrane turnover in gliomas. In this study, we investigated the incidence rate of lack of choline/creatine and choline/water elevation in a population of grade I-III gliomas. A cohort of 41 patients with histopathologically confirmed gliomas underwent multi-voxel proton magnetic resonance spectroscopy on a 3 T magnetic resonance system prior to treatment. Peak areas for choline and myoinositol were measured from all voxels that exhibited hyperintensity on fluid-attenuated inversion recovery images and were normalized to creatine and unsuppressed water from each voxel. The average metabolite/creatine and metabolite/water ratios from these voxels were then computed. Similarly, average metabolite ratios were computed from normal brain parenchyma. Gliomas were considered for lack of choline elevation when choline/creatine and choline/water ratios from neoplastic regions were less than those from normal brain parenchyma regions. Six of 41 (14.6%) grade I-III gliomas showed lack of elevation for choline/creatine and choline/water ratios compared to normal brain parenchyma. Four of these six gliomas also demonstrated elevated levels of myoinositol/creatine ratio. All other gliomas (n = 35) had elevated choline levels from neoplastic regions relative to normal parenchyma. The sensitivity of choline/creatine or choline/water in determining a grade I-III glioma was 85.4%. These findings suggest that a lack of choline/creatine or choline/water elevation may be seen in some gliomas and low choline levels should not prevent us from considering the possibility of a grade I-III glioma.


Assuntos
Neoplasias Encefálicas/metabolismo , Colina/metabolismo , Glioma/metabolismo , Adulto , Idoso , Neoplasias Encefálicas/patologia , Feminino , Glioma/patologia , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Espectroscopia de Prótons por Ressonância Magnética/métodos , Estudos Retrospectivos , Adulto Jovem
15.
World Neurosurg ; 126: e1211-e1218, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30885869

RESUMO

BACKGROUND: Stereotactic needle biopsy provides a minimally invasive option for the diagnosis of intracranial lesions but is limited by inconclusive diagnoses on frozen pathology. For rapid pathology, 5-aminovelunic acid and sodium fluorescein have previously demonstrated potential as diagnostic adjuvants. Stereotactic biopsy with near-infrared (NIR) fluorophores has not been reported. We identified 5 representative cases using NIR fluorescent dye indocyanine green (ICG) administered in a high dose, delayed manner. METHODS: Five patients underwent second window indocyanine green (SWIG)-guided stereotactic biopsy for diagnosis of suspected glioma or tumor recurrence. Up to 5 mg/kg ICG was administered approximately 24 hours prior to surgery. Biopsies were conducted in the standard fashion, targeting regions of suspected tumor using intraoperative frameless navigation. Samples were examined intraoperatively under standard visible light and for fluorescence using conventional NIR imaging platforms. Findings were correlated with frozen and final tumor pathology for all cases. RESULTS: A total of 10 biopsy specimens were obtained. Three did not fluoresce and did not demonstrate tumor on preliminary or final pathology, including a non-gadolinium-enhancing sample taken proximal to the final target. The remaining 7 fluoresced, of which 6 contained tumor and 1 contained necrosis. Fluorescence was also noted in a patient with radiation treatment effect. Overall fluorescence characteristics were highly concordant with preliminary and final diagnoses. CONCLUSIONS: SWIG provides rapid intraoperative confirmation of pathologic brain tissue by permeating neoplastic or inflammatory brain tissue via a mechanism similar to that of gadolinium enhancement. SWIG-guided stereotactic biopsy can improve surgical efficiency by enhancing confidence in acquisition of target tissue.


Assuntos
Neoplasias Encefálicas/diagnóstico , Corantes Fluorescentes , Glioma/diagnóstico , Verde de Indocianina , Imagem Molecular/métodos , Idoso , Biópsia por Agulha/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico , Técnicas Estereotáxicas
16.
J Magn Reson Imaging ; 49(1): 184-194, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-29676844

RESUMO

BACKGROUND: Accurate differentiation of brain infections from necrotic glioblastomas (GBMs) may not always be possible on morphologic MRI or on diffusion tensor imaging (DTI) and dynamic susceptibility contrast perfusion-weighted imaging (DSC-PWI) if these techniques are used independently. PURPOSE: To investigate the combined analysis of DTI and DSC-PWI in distinguishing brain injections from necrotic GBMs. STUDY TYPE: Retrospective. POPULATION: Fourteen patients with brain infections and 21 patients with necrotic GBMs. FIELD STRENGTH/SEQUENCE: 3T MRI, DTI, and DSC-PWI. ASSESSMENT: Parametric maps of mean diffusivity (MD), fractional anisotropy (FA), coefficient of linear (CL), and planar anisotropy (CP) and leakage corrected cerebral blood volume (CBV) were computed and coregistered with postcontrast T1 -weighted and FLAIR images. All lesions were segmented into the central core and enhancing region. For each region, median values of MD, FA, CL, CP, relative CBV (rCBV), and top 90th percentile of rCBV (rCBVmax ) were measured. STATISTICAL TESTS: All parameters from both regions were compared between brain infections and necrotic GBMs using Mann-Whitney tests. Logistic regression analyses were performed to obtain the best model in distinguishing these two conditions. RESULTS: From the central core, significantly lower MD (0.90 × 10-3 ± 0.44 × 10-3 mm2 /s vs. 1.66 × 10-3 ± 0.62 × 10-3 mm2 /s, P = 0.001), significantly higher FA (0.15 ± 0.06 vs. 0.09 ± 0.03, P < 0.001), and CP (0.07 ± 0.03 vs. 0.04 ± 0.02, P = 0.009) were observed in brain infections compared to those in necrotic GBMs. Additionally, from the contrast-enhancing region, significantly lower rCBV (1.91 ± 0.95 vs. 2.76 ± 1.24, P = 0.031) and rCBVmax (3.46 ± 1.41 vs. 5.89 ± 2.06, P = 0.001) were observed from infective lesions compared to necrotic GBMs. FA from the central core and rCBVmax from enhancing region provided the best classification model in distinguishing brain infections from necrotic GBMs, with a sensitivity of 91% and a specificity of 93%. DATA CONCLUSION: Combined analysis of DTI and DSC-PWI may provide better performance in differentiating brain infections from necrotic GBMs. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:184-194.

17.
Oper Neurosurg (Hagerstown) ; 16(1): 59-70, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-29635300

RESUMO

BACKGROUND: Surgical resection is the primary treatment for nonfunctional (NF) pituitary adenomas, but gross-total resection is difficult to achieve in all cases. NF adenomas overexpress folate receptor alpha (FRα). OBJECTIVE: To test the hypothesis that we could target FRα for highly sensitive and specific intraoperative detection of NF adenomas using near-infrared (NIR) imaging. METHODS: Fourteen patients with NF pituitary adenoma were infused with the folate analog NIR dye OTL38 preoperatively. NIR fluorescence signal-to-background ratio (SBR) was recorded for each tumor during resection of the adenomas. Extent of surgery was not modified based on the presence or absence of fluorescence. Immunohistochemistry was performed to assess FRα expression in all specimens. Magnetic resonance imaging (MRI) was performed postoperatively to assess residual neoplasm. RESULTS: Nine adenomas overexpressed FRα and fluoresced with a NIR SBR of 3.2 ± 0.52, whereas the 5 non-FRα-overexpressing adenomas fluoresced with an SBR of 1.5 ± 0.21. Linear regression demonstrated a significant correlation between intraoperative SBR and the FRα expression (P-value < .001). Analysis of 14 margin samples revealed that the surgeon's impression of the tissue had 83% sensitivity, 100% specificity, 100% positive predictive value, and 89% negative predictive value, while NIR fluorescence had 100% for all values. NIR fluorescence accurately predicted postoperative MRI results in 78% of FRα-overexpressing patients. CONCLUSION: Preoperative injection of folate-tagged NIR dye provides strong signal and visualization of NF pituitary adenomas. It is 100% sensitive and specific for detecting margin neoplasm and can predict postoperative MRI findings. Our results suggest that NIR fluorescence may be superior to white-light visualization alone and may improve resection rates in NF pituitary adenomas.

18.
Neurosurgery ; 85(3): 359-368, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-30113687

RESUMO

BACKGROUND: Meningiomas are well-encapsulated benign brain tumors and surgical resection is often curative. Nevertheless, this is not always possible due to the difficulty of identifying residual disease intraoperatively. We hypothesized that meningiomas overexpress folate receptor alpha (FRα), allowing intraoperative molecular imaging by targeting FRα with a near-infrared (NIR) dye. OBJECTIVE: To determine FRα expression in both human and canine meningioma cohorts to prepare for future clinical studies. Present a case study of a meningioma resection with intraoperative NIR fluorescence imaging. METHODS: Tissue samples of 27 human meningioma specimens and 7 canine meningioma specimens were immunohistochemically stained for FRα along with normal dura, skeletal muscle, and kidney tissue. We then enrolled a patient with a pituitary adenoma and tuberculum sella meningioma in a clinical trial in which the patient received an infusion of folate-linked, NIR fluorescent dye prior to surgery. RESULTS: In the cohort of human meningiomas, 9 WHO grade I, 12 grade II, and 6 grade III tumors were identified. Eighty-nine percent of WHO grade I, 67% of grade II, and 50% of grade III tumors overexpressed FRα. In the 7 canine meningioma samples, 100% stained positively for FRα. Both human and canine normal dura from autopsy samples demonstrated no evidence of FRα overexpression. In the case study, the meningioma demonstrated a high NIR signal-to-background-ratio of 4.0 and demonstrated strong FRα immunohistochemistry staining. CONCLUSION: This study directly demonstrates FRα overexpression in both human and canine meningiomas. We also demonstrate superb intraoperative imaging of a meningioma using a FRα-targeting dye.

19.
J Neurooncol ; 141(2): 421-429, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30446903

RESUMO

PURPOSE: The prognostic impact of the histopathologic features of recurrent glioblastoma surgical specimens is unknown. We sought to determine whether key histopathologic characteristics in glioblastoma tumors resected after chemoradiotherapy are associated with overall survival (OS). METHODS: The following characteristics were quantified in recurrent glioblastoma specimens at our institution: extent of viable tumor (accounting for % of specimen comprised of tumor and tumor cellularity), mitoses per 10 high-power fields (0, 1-10, > 10), Ki-67 proliferative index (0-100%), hyalinization (0-6; none to extensive), rarefaction (0-6), hemosiderin (0-6), and % of specimen comprised of geographic necrosis (0-100%; converted to 0-6 scale). Variables associated with OS in univariate analysis, as well as age, eastern cooperative oncology group performance status (ECOG PS), extent of repeat resection, time from initial diagnosis to repeat surgery, and O6-methylguanine-DNA methyltransferase promoter methylation, were included in a multivariable Cox proportional hazards model. RESULTS: 37 specimens were assessed. In a multivariate model, high Ki-67 proliferative index was the only histopathologic characteristic associated with worse OS following repeat surgery for glioblastoma (hazard ratio (HR) 1.3, 95% CI 1.1-1.5, p = 0.003). Shorter time interval from initial diagnosis to repeat surgery (HR 1.11, 95% CI 1.02-1.21, p = 0.016) and ECOG PS ≥ 2 (HR 4.19, 95% CI 1.72-10.21, p = 0.002) were also independently associated with inferior OS. CONCLUSION: In patients with glioblastoma undergoing repeat resection following chemoradiotherapy, high Ki-67 index in the recurrent specimen, short time to recurrence, and poor PS are independently associated with worse OS. Histopathologic quantification of viable tumor versus therapy-related changes has limited prognostic influence.


Assuntos
Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/cirurgia , Glioblastoma/patologia , Glioblastoma/cirurgia , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/radioterapia , Metilação de DNA , Progressão da Doença , Feminino , Glioblastoma/tratamento farmacológico , Glioblastoma/radioterapia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/radioterapia , Estudos Retrospectivos , Resultado do Tratamento
20.
Br J Cancer ; 120(1): 54-56, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30478409

RESUMO

EGFRvIII targeted chimeric antigen receptor T (CAR-T) cell therapy has recently been reported for treating glioblastomas (GBMs); however, physiology-based MRI parameters have not been evaluated in this setting. Ten patients underwent multiparametric MRI at baseline, 1, 2 and 3 months after CAR-T therapy. Logistic regression model derived progression probabilities (PP) using imaging parameters were used to assess treatment response. Four lesions from "early surgery" group demonstrated high PP at baseline suggestive of progression, which was confirmed histologically. Out of eight lesions from remaining six patients, three lesions with low PP at baseline remained stable. Two lesions with high PP at baseline were associated with large decreases in PP reflecting treatment response, whereas other two lesions with high PP at baseline continued to demonstrate progression. One patient didn't have baseline data but demonstrated progression on follow-up. Our findings indicate that multiparametric MRI may be helpful in monitoring CAR-T related early therapeutic changes in GBM patients.


Assuntos
Receptores ErbB/imunologia , Glioblastoma/terapia , Imunoterapia Adotiva , Recidiva Local de Neoplasia/terapia , Linhagem Celular Tumoral , Receptores ErbB/antagonistas & inibidores , Feminino , Glioblastoma/diagnóstico por imagem , Glioblastoma/imunologia , Glioblastoma/patologia , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/imunologia , Recidiva Local de Neoplasia/patologia , Receptores de Antígenos Quiméricos/imunologia , Receptores de Antígenos Quiméricos/uso terapêutico
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA