Tumor-Treating Fields for the treatment of glioblastoma: a systematic review and meta-analysis.

BACKGROUND: Tumor-Treating Fields (TTFields) is an emerging treatment modality for glioblastoma (GBM). Studies have shown a good safety profile alongside improved efficacy in newly diagnosed GBM (ndGBM), while a less clear effect was shown for recurrent GBM (rGBM). Despite regulatory support, sectors of the neuro-oncology community have been reluctant to accept it as part of the standard treatment protocol. To establish an objective understanding of TTFields' mechanism of action, safety, efficacy, and economical implications, we conducted a systematic literature review and meta-analysis. METHODS: A systematic search was conducted in PubMed, Scopus, and Cochrane databases. Twenty studies met the pre-defined inclusion criteria, incorporating 1636 patients (542 ndGBM and 1094 rGBM), and 11 558 patients (6403 ndGBM and 5155 rGBM) analyzed for the clinical outcomes and safety endpoints, respectively. RESULTS: This study demonstrated improved clinical efficacy and a good safety profile of TTFields. For ndGBM, pooled median overall survival (OS) and progression-free survival (PFS) were 21.7 (95%CI = 19.6-23.8) and 7.2 (95%CI = 6.1-8.2) months, respectively. For rGBM, pooled median OS and PFS were 10.3 (95%CI = 8.3-12.8) and 5.7 (95%CI = 2.8-10) months, respectively. Compliance of ≥75% was associated with an improved OS and the predominant adverse events were dermatologic, with a pooled prevalence of 38.4% (95%CI = 32.3-44.9). Preclinical studies demonstrated TTFields' diverse molecular mechanism of action, its potential synergistic efficacy, and suggest possible benefits for certain populations. CONCLUSIONS: This study supports the use of TTFields for GBM, alongside the standard-of-care treatment protocol, and provides a practical summary, discussing the current clinical and preclinical aspects of the treatment and their implication on the disease course.

Hemoglobin Levels and Red Blood Cells Distribution Width Highlights Glioblastoma Patients Subgroup With Improved Median Overall Survival.

Glioblastoma multiforme (GBM) is known for its dismal prognosis, though its dependence on patients' readily available RBCs parameters is not fully established. In this work, 170 GBM patients, diagnosed and treated in Soroka University Medical Center (SUMC) over the last 12 years were retrospectively inspected for their survival dependency on pre-operative RBCs parameters. Besides KPS and tumor resection supplemented by oncological treatment, age under 70 (HR = 0.4, 95% CI 0.24-0.65, p = 0.00073), low hemoglobin level (HR = 1.79, 95% CI 1.06-2.99, p = 0.031), and Red Cell Distribution Width (RDW) < 14% (HR = 0.57, 95% CI 0.37-0.88, p = 0.018) were found to be prognostic of patients' overall survival in multivariate analysis, accounting for a false discovery rate of < 5% due to multiple hypothesis testing. According to these results, a stratification tree was made, from which a favorable route highlighted a subgroup of nearly 30% of the cohorts' patients whose median overall survival was 21.1 months (95% CI 16.2-27.2)-higher than the established chemo-radiation standard first-line treatment regimen overall median survival average of about 15 months. The beneficial or detrimental effect of RBCs parameters on GBM prognosis and its possible causes is discussed.

Diagnosing necrotic meningioma: a distinctive imaging pattern in diffusion MRI and MR spectroscopy.

The differential diagnosis of necrotic meningiomas includes brain abscess and malignant neoplasms. We report and discuss hereby the work-up of two patients diagnosed with necrotic meningioma using diffusion-weighted imaging, magnetic resonance spectroscopy, resective surgery, and histopathology. The purpose of the present article is to add to the scant literature on the use of advanced imaging modalities in the routine investigation of brain lesions and their utility in arriving at the final diagnosis.

Dural sinus obstruction following head injury: a diagnostic and clinical study.

OBJECTIVE The aim of this study is to describe the clinical characteristics of patients with skull fracture adjacent to a dural venous sinus (DVS) and evaluate the role of CT venography (CTV) in the diagnosis of the effect of this fracture on the involved DVS. METHODS The study comprised patients with vault or skull base fracture adjacent to a DVS who were admitted to 1 medical center during a 2-year period. The medical records were reviewed for the clinical and radiographic characteristics. All patients had undergone CTV to evaluate potential DVS pathology. The clinical and radiological findings of the patients with DVS pathology were compared with those of the patients with normal DVS. The groups were compared using the chi-square and t-tests for categorical and continuous data, respectively. The potential risk for poor outcome among the patients with DVS pathology was also investigated. RESULTS Of 434 patients with skull fractures, 41 (9.4%) had fractures adjacent to a DVS. DVS pathology was detected in 51% of patients (21 of 41 patients). For 9 (43%) patients, obstruction was extraluminal without thrombosis, and 12 (57%) patients had dural sinus thrombosis (DST). In patients with a positive-CTV scan, the severity of injury according to the Glasgow Coma Scale score at presentation was correlated with the presence of DST (p = 0.007). The sensitivity of noncontrast CT (NCCT) for DVS involvement was 38% among the patients with positive-CTV scans. For patients with DVS pathology, poor outcome was correlated with DST (intraluminal), rather than extraluminal obstruction without thrombosis (p = 0.02), and superior sagittal sinus (SSS) involvement (p = 0.05). CONCLUSIONS NCCT is not sensitive enough to detect DVS obstruction in patients with skull fracture adjacent to a DVS, and CTV should be performed in order to rule it out. A correlation was found between the severity of injury and the presence of DST, rather than extraluminal obstruction. The authors' findings suggest that DST and SSS involvement may be indicators of poor outcome in patients with skull fracture adjacent to DVS.

Free craniotomy versus osteoplastic craniotomy, assessment of flap viability using 99mTC MDP SPECT.

There are currently two accepted neurosurgical methods to perform a bony flap. In an osteoplastic flap, the flap is attached to surrounding muscle. In a free flap, the flap is not attached to adjacent tissues. The former is less common due to its complexity and the extensive time required for the surgery; yet the rate of infection is significantly lower, a clear explanation for which is unknown. The objective of this study was to test the hypothesis that the osteoplastic flap acts as a live implant that resumes its blood flow and metabolic activity; contrasting with the free flap, which does not have sufficient blood flow, and therefore acts as a foreign body. Seven patients who underwent craniotomy with osteoplastic flaps and five with free flaps had planar bone and single photon emission computed tomography (SPECT) scans of the skull at 3-7days postoperative, after injection of the radioisotope, 99m-technetium-methylene diphosphonate (99m-Tc-MDP). We compared radioactive uptake as a measure of metabolic activity between osteoplastic and free flaps. Mean normalized radioactive uptakes in the centers of the flaps, calculated as the ratios of uptakes in the flap centers to uptakes in normal contralateral bone, were [mean: 1.7 (SD: 0.8)] and [0.6 (0.1)] for the osteoplastic and free flap groups respectively and were [2.4 (0.8)] and [1.3 (0.4)] in the borders of the flaps. Our analyses suggest that in craniotomy, the use of an osteoplastic flap, in contrast to free flap, retains bone viability.

Clinical significance of skull base fracture in patients after traumatic brain injury.

About 4% of all head injuries include skull base fractures. Most of these fractures (90%) are secondary to closed head trauma; the remainder are due to penetrating trauma. We reviewed the records from January 2006 through December 2008 of all patients older than 18 years of age who arrived at Soroka Medical Center in Be'er-Sheva, Israel, with skull base fractures following a traumatic brain injury (TBI). We identified 107 patients with a mean age of 42 years at the time of TBI. Glasgow Coma score on arrival predicted the clinical outcome. We observed temporal fractures in 30% of these patients, occipital fractures in 20%, pyramidal fractures in 19%, anterior skull base fractures in 17%, and multiple fractures in 14%. Cerebrospinal fluid (CSF) leak was observed in 16 patients (15%). Of the patients experiencing CSF leaks, otorrhea occurred in 10 (62%) and rhinorrhea occurred in six (37%). Three patients required surgical intervention to repair the leak. Meningitis occurred in four patients with clinically evident CSF leak. Multiple skull base fractures are associated with poor neurological outcome. The low rate of meningitis in this patient sample implies that there is no indication to administer prophylactic antibiotics to patients with skull base fractures.

Supraciliary keyhole craniotomy for anterior frontal lesions in children.

Treatment for anterior frontal space occupying lesions such as epidural hematoma, vascular malformations or brain tumors, have typically involved invasive craniotomies. This method often requires large incisions with wide exposure and may be associated with high morbidity rates. The basis for the "keyhole" method is that a minimally invasive craniotomy is often sufficient for exposing large areas deep in tissue, and may limit exposure and decrease surgically related morbidity while enabling adequate removal and decompression. The supraciliary method includes a cut above the eyebrow and a small craniotomy to uncover the base of the frontal lobe and the orbital roof. We demonstrate our experience with this method. We identified children who were operated via the supraciliary approach between January 2009 and December 2013, and gathered their pre- and post-operative clinical and radiological statistics. Fourteen patients were identified. Pathologies included tumors, abscesses and epidural hematomas. Nine were operated due to epidural hematoma, two due to tumors, two due to brain abscesses, and one for anterior encephalocele. No significant peri-operative or post-operative complications were observed. Long-term follow-up shows that the surgical scars were nearly invisible. The supraciliary approach is a safe, effective and elegant technique for treating lesions in the anterior skull base. The method should be weighed alongside traditional methods on a case-by-case basis.

[Urgent removal of ruptured cerebral arteriovenous malformations in children].

In 60-80% of children with arteriovenous malformation (AVM), the first manifestation is an abrupt rupture resulting in intracranial hemorrhage. Some cases of acute rupture result in compressive hematoma, severe mass effect and comatose patients. Acute surgery on cerebral arteriovenous malformations (AVMs) has seldom been reported or used. The authors present case reports of 3 children (ages: five months, 7 and 9 years) who underwent craniotomy for intraparenchymal hematoma evacuation and AVM removal within a few hours of bleeding. All 3 children arrived with decreased Levels of consciousness and rapid neurological deterioration. The 5 months old boy also suffered hypovolemic shock. The fast neurological worsening and mass effect of the extensive intracerebral hemorrhage prompted early surgical treatment. Due to active bleeding from the AVM, it was already resected in the acute stage using minimal invasive techniques. After one year of follow-up, all 3 children fully recovered with no neurological deficit. Post-operative angiography was performed to confirm that the malformation was totally removed. The management of AVM should include formal angiography, with or without endovascular embolization and late surgery when indicated. In this report, the authors presented 3 children who underwent urgent resection of the lesion with full neurological recovery. The management of AVM is reviewed with comparisons between surgical resection in the acute phase versus the late phase.

Low-dose aspirin prophylaxis and risk of intracranial hemorrhage in patients older than 60 years of age with mild or moderate head injury: a prospective study.

OBJECT: The goal of this paper was to investigate a possible relationship between the consumption of low-dose aspirin (LDA) and traumatic intracranial hemorrhage in an attempt to determine whether older patients receiving prophylactic LDA require special treatment following an incidence of mild-to-moderate head trauma. METHODS: Two hundred thirty-one patients older than 60 years of age, who arrived at the emergency department with a mild or moderate head injury (Glasgow Coma Scale [GCS] Scores 13-15 and 9-12, respectively), were included in the study. One hundred ten patients were receiving prophylactic LDA (100 mg/day) and these formed the aspirin-treated group. One hundred twenty-one patients were receiving no aspirin, and these formed the control group. There was no statistically significant difference between the two groups with respect to age, sex, mechanism of trauma, or GCS score on arrival at the emergency department. Most of the patients sustained the head injury from falls (88.2% of patients in the aspirin-treated group and 85.1% of patients in the control group), and had external signs of head trauma such as bruising or scalp laceration (80.9% of patients in the aspirin-treated group and 86.8% of patients in the control group). All patients underwent similar neurological examinations and computerized tomography (CT) scanning of the head. The CT scans revealed evidence of traumatic intracranial hemorrhage in 27 (24.5%) patients in the aspirin-treated group and in 31 patients (25.6%) in the control group. Surgical intervention was required for five patients in each group (4.5% of patients in the aspirin-treated group and 4.1% of patients in the control group). A surprising number of the patients who arrived with GCS Score 15 were found to have traumatic intracranial hemorrhage, as revealed by CT scanning (11.5% of patients in the aspirin-treated group and 16.5% of patients in the control group). Surgery, however, was not necessary for any of these patients. CONCLUSIONS: There was no statistically significant difference in the frequency or types of traumatic intracranial hemorrhage between patients who had received aspirin prophylaxis and those who had not. The authors conclude that LDA does not increase surgically relevant parenchymal or meningeal bleeding following moderate and minor head injury in patients older than 60 years of age.