NRG/RTOG 0837: Randomized, Phase II, Double-Blind, Placebo-Controlled Trial of Chemoradiation With or Without Cediranib in Newly Diagnosed Glioblastoma

BACKGROUND: A randomized, phase II, placebo-controlled, and blinded clinical trial (NCT01062425) was conducted to determine the efficacy of cediranib, an oral pan-vascular endothelial growth factor receptor tyrosine kinase inhibitor, versus placebo in combination with radiation and temozolomide in newly diagnosed glioblastoma. METHODS: Patients with newly diagnosed glioblastoma were randomly assigned 2:1 to receive (1) cediranib (20 mg) in combination with radiation and temozolomide; (2) placebo in combination with radiation and temozolomide. The primary endpoint was 6-month progression-free survival (PFS) based on blinded, independent radiographic assessment of postcontrast T1-weighted and noncontrast T2-weighted MRI brain scans and was tested using a 1-sided RESULTS: One hundred and fifty-eight patients were randomized, out of which 9 were ineligible and 12 were not evaluable for the primary endpoint, leaving 137 eligible and evaluable. 6-month PFS was 46.6% in the cediranib arm versus 24.5% in the placebo arm ( CONCLUSIONS: This study met its primary endpoint of prolongation of 6-month PFS with cediranib in combination with radiation and temozolomide versus placebo in combination with radiation and temozolomide. There was no difference in overall survival between the 2 arms

5-ALA Fluorescence-Guided Surgery and Photodynamic Therapy of Gliomas: A New Frontier

Learning Objectives Importance of translational research Review how maximal resection of high-grade gliomas can impact patient survival Review unmet need for glioma resection Review how fluorescence-guided surgery can provide benefit to glioma patients Propose a new therapeutic intraoperative use for 5-ALA after fluorescence-guided surgery is complete

The Supraorbital Keyhole Craniotomy through an Eyebrow Incision: Its Origins and Evolution

In the modern era of neurosurgery, the use of the operative microscope, rigid rod-lens endoscope, and neuronavigation has helped to overcome some of the previous limitations of surgery due to poor lighting and anatomic localization available to the surgeon. Over the last thirty years, the supraorbital craniotomy and subfrontal approach through an eyebrow incision have been developed and refined to play a legitimate role in the armamentarium of the modern skull base neurosurgeon. With careful patient selection, the supraorbital “keyhole” approach offers a less invasive but still efficacious approach to a number of lesions along the subfrontal corridor. Well over 1000 cases have been reported in the literature utilizing this approach establishing its safety and efficacy. This paper discusses the nuances of this approach, including the benefits and limitations of its use described through our technique, review of the literature, and case illustration

Meningioma With Tyrosine-Rich Crystalloids: A Case Report and Review of the Literature.

We report a case of fibrous meningioma with tyrosine-rich crystalloid in the frontal lobe of a middle-aged woman. The patient presented with a history of several years of worsening headaches and blurry vision, which progressed to include syncopal episodes and right-sided weakness. Imaging demonstrated a dural-based extra-axial mass arising from the right orbital roof and extending superiorly along the right frontal convexity causing right-to-left midline shift. The patient underwent a craniotomy and operative resection. Tumor architecture and cytology was similar to that of a Schwannian neoplasm, with spindled cells arranged in a fascicular architecture and displaying focal nuclear palisading. Immunohistochemical stains confirmed a diagnosis of fibrous meningioma. Light microscopy demonstrated extracellular deposits of eosinophilic crystalline material parallel to the spindled tumor cells, reminiscent of tyrosine-rich crystals described in salivary gland neoplasms. This is the third meningioma featuring tyrosine-rich crystalloid reported in the literature; we also summarize the previous 2 reports

Neuroendoscopic Resection of Intraventricular Tumors and Cysts through a Working Channel with a Variable Aspiration Tissue Resector: A Feasibility and Safety Study

Pure neuroendoscopic resection of intraventricular lesions through a burr hole is limited by the instrumentation that can be used with a working channel endoscope. We describe a safety and feasibility study of a variable aspiration tissue resector, for the resection of a variety of intraventricular lesions. Our initial experience using the variable aspiration tissue resector involved 16 patients with a variety of intraventricular tumors or cysts. Nine patients (56%) presented with obstructive hydrocephalus. Patient ages ranged from 20 to 88 years (mean 44.2). All patients were operated on through a frontal burr hole, using a working channel endoscope. A total of 4 tumors were resected in a gross total fashion and the remaining intraventricular lesions were subtotally resected. Fifteen of 16 patients had relief of their preoperative symptoms. The 9 patients who presented with obstructive hydrocephalus had restoration of cerebrospinal fluid flow though one required a ventriculoperitoneal shunt. Three patients required repeat endoscopic resections. Use of a variable aspiration tissue resector provides the ability to resect a variety of intraventricular lesions in a safe, controlled manner through a working channel endoscope. Larger intraventricular tumors continue to pose a challenge for complete removal of intraventricular lesions

Quantitative Tumor Segmentation for Evaluation of Extent of Glioblastoma Resection to Facilitate Multisite Clinical Trials

AbstractStandard-of-care therapy for glioblastomas, the most common and aggressive primary adult brain neoplasm, is maximal safe resection, followed by radiation and chemotherapy. Because maximizing resection may be beneficial for these patients, improving tumor extent of resection (EOR) with methods such as intraoperative 5-aminolevulinic acid fluorescence-guided surgery (FGS) is currently under evaluation. However, it is difficult to reproducibly judge EOR in these studies due to the lack of reliable tumor segmentation methods, especially for postoperative magnetic resonance imaging (MRI) scans. Therefore, a reliable, easily distributable segmentation method is needed to permit valid comparison, especially across multiple sites. We report a segmentation method that combines versatile region-of-interest blob generation with automated clustering methods. We applied this to glioblastoma cases undergoing FGS and matched controls to illustrate the method's reliability and accuracy. Agreement and interrater variability between segmentations were assessed using the concordance correlation coefficient, and spatial accuracy was determined using the Dice similarity index and mean Euclidean distance. Fuzzy C-means clustering with three classes was the best performing method, generating volumes with high agreement with manual contouring and high interrater agreement preoperatively and postoperatively. The proposed segmentation method allows tumor volume measurements of contrast-enhanced T1-weighted images in the unbiased, reproducible fashion necessary for quantifying EOR in multicenter trials