Transpalpebral Transorbital Approach for Pediatric Temporal Epilepsy: 2-Dimensional Operative Video.

The transpalpebral approach provides a minimally invasive corridor to the anterior skull base and temporal lobe. It has been described for anterior circulation aneurysms and skull base tumors as well as more recently for resection of epileptogenic pathology in the adult population. We describe our experience using this approach in a 13-year-old adolescent boy suffering from epilepsy secondary to concomitant left temporal focal cortical dysplasia and pleomorphic xanthoastrocytoma extending throughout the amygdala with excellent results.1-5 To the best of our knowledge, this is the first published case using the transpalpebral approach for this pathology, as well for epilepsy in the pediatric population. The patient consented to the procedure and to the publication of his image.

Thoracic canal morphology on preoperative magnetic resonance imaging in spinal cord stimulation patients.

INTRODUCTION: In high-frequency spinal cord stimulation anatomic placement targeting of the T9-10 disc space is based on "empiric" results that are best replicated with coverage broadly from T8 to T10. This study contains the largest cohort of patients evaluating low thoracic morphology and seeks to address the lack of MRI morphological analysis in literature. METHODS: This study was a retrospective review of a database of 101 consecutive patients undergoing permanent implant of thoracic SCS for chronic pain. Measurements were carried out on preoperative MRI imaging. Anteroposterior (AP) and lateral dimensions of the spinal cord as well as dural sac were measured. In addition, dorsal cerebrospinal fluid thickness and paddle depression distance were also measured. RESULTS: When comparing morphological dimensions by level, dorsal CSF thickness was smaller at T9-10 than T7-8 (p = 0.018). In addition, lateral dural and spinal cord diameters were larger at T10-11 than T9-10, contributing to larger dural surface area at T10-11 (p = 0.028). While trends of dorsal CSF thickness tend to decrease with lower thoracic levels, the ratio of surface area of spinal cord to dural sac appeared to remain relatively constant. CONCLUSIONS: Dorsal CSF thickness is smaller at T9-10 than T7-8 in chronic pain patients in this cohort. More ellipsoid, cord, and spinal canal diameter measurements were noted at lower levels of the thoracic spinal cord, particularly at T10-11. This may correlate with anatomical SCS placement. Future studies should evaluate efficacy of SCS therapy for pain based on these anatomical considerations.

Predictors of recurrence after surgical resection of parafalcine and parasagittal meningiomas.

PURPOSE: Owing to their vicinity near the superior sagittal sinus, parasagittal and parafalcine meningiomas are challenging tumors to surgically resect. In this study, we investigate key factors that portend increased risk of recurrence after surgery. METHODS: This is a retrospective study of patients who underwent resection of parasagittal and parafalcine meningiomas at our institution between 2012 and 2018. Relevant clinical, radiographic, and histopathological variables were selected for analysis as predictors of tumor recurrence. RESULTS: A total of 110 consecutive subjects (mean age: 59.4 ± 15.2 years, 67.3% female) with 74 parasagittal and 36 parafalcine meningiomas (92 WHO grade 1, 18 WHO grade 2/3), are included in the study. A total of 37 patients (33.6%) exhibited recurrence with median follow-up of 42 months (IQR: 10-71). In the overall cohort, parasagittal meningiomas exhibited shorter progression-free survival compared to parafalcine meningiomas (Kaplan-Meier log-rank p = 0.045). On univariate analysis, predictors of recurrence include WHO grade 2/3 vs. grade 1 tumors (p < 0.001), higher Ki-67 indices (p < 0.001), partial (p = 0.04) or complete sinus invasion (p < 0.001), and subtotal resection (p < 0.001). Multivariable Cox regression analysis revealed high-grade meningiomas (HR: 3.62, 95% CI: 1.60-8.22; p = 0.002), complete sinus invasion (HR: 3.00, 95% CI: 1.16-7.79; p = 0.024), and subtotal resection (HR: 3.10, 95% CI: 1.38-6.96; p = 0.006) as independent factors that portend shorter time to recurrence. CONCLUSION: This study identifies several pertinent factors that confer increased risk of recurrence after resection of parasagittal and parafalcine meningiomas, which can be used to devise appropriate surgical strategy to achieve improved patient outcomes.

Radiomic signatures of meningiomas using the Ki-67 proliferation index as a prognostic marker of clinical outcomes.

OBJECTIVE: The clinical behavior of meningiomas is not entirely captured by its designated WHO grade, therefore other factors must be elucidated that portend increased tumor aggressiveness and associated risk of recurrence. In this study, the authors identify multiparametric MRI radiomic signatures of meningiomas using Ki-67 as a prognostic marker of clinical outcomes independent of WHO grade. METHODS: A retrospective analysis was conducted of all resected meningiomas between 2012 and 2018. Preoperative MR images were used for high-throughput radiomic feature extraction and subsequently used to develop a machine learning algorithm to stratify meningiomas based on Ki-67 indices < 5% and ≥ 5%, independent of WHO grade. Progression-free survival (PFS) was assessed based on machine learning prediction of Ki-67 strata and compared with outcomes based on histopathological Ki-67. RESULTS: Three hundred forty-three meningiomas were included: 291 with WHO grade I, 43 with grade II, and 9 with grade III. The overall rate of recurrence was 19.8% (15.1% in grade I, 44.2% in grade II, and 77.8% in grade III) over a median follow-up of 28.5 months. Grade II and III tumors had higher Ki-67 indices than grade I tumors, albeit tumor and peritumoral edema volumes had considerable variation independent of meningioma WHO grade. Forty-six high-performing radiomic features (1 morphological, 7 intensity-based, and 38 textural) were identified and used to build a support vector machine model to stratify tumors based on a Ki-67 cutoff of 5%, with resultant areas under the curve of 0.83 (95% CI 0.78-0.89) and 0.84 (95% CI 0.75-0.94) achieved for the discovery (n = 257) and validation (n = 86) data sets, respectively. Comparison of histopathological Ki-67 versus machine learning-predicted Ki-67 showed excellent performance (overall accuracy > 80%), with classification of grade I meningiomas exhibiting the greatest accuracy. Prediction of Ki-67 by machine learning classifier revealed shorter PFS for meningiomas with Ki-67 indices ≥ 5% compared with tumors with Ki-67 < 5% (p < 0.0001, log-rank test), which corroborates divergent patient outcomes observed using histopathological Ki-67. CONCLUSIONS: The Ki-67 proliferation index may serve as a surrogate marker of increased meningioma aggressiveness independent of WHO grade. Machine learning using radiomic feature analysis may be used for the preoperative prediction of meningioma Ki-67, which provides enhanced analytical insights to help improve diagnostic classification and guide patient-specific treatment strategies.

Improved Functional Outcomes of Stroke Patients Undergoing Mechanical Thrombectomy After Arriving via a Mobile Stroke Unit.

BACKGROUND: Mobile stroke units (MSUs) have been implemented worldwide for stroke care, but outcome data are lacking to show their efficacy specifically in patients undergoing mechanical thrombectomy (MT). Here, we include patients from our stroke network MSU and compare them to patients who arrived conventionally. METHODS: A retrospective review of a stroke database was performed to identify patients who underwent MT after arrival via an MSU from August 2019 to December 2020. Demographic factors, past medical history, stroke characteristics, treatment variables, complications, and functional outcomes were recorded. These were compared to date-matched patients who underwent MT after arrival via conventional means. RESULTS: Seven patients were treated with MT after arriving by an MSU. These patients were compared to 50 date-matched patients who underwent thrombectomy after arrival through conventional means. No statistically significant difference between cohorts was observed in terms of demographic variables, comorbidities, stroke characteristics, or tissue plasminogen activator administration. Patients from the MSU cohort had significantly shorter time from symptom onset to groin puncture time (191.33 minutes ±77.53 vs. 483.51 minutes ±322.66, P = 0.034). Importantly, MSU-transferred patients had significantly better discharge functional status measured by using the modified Rankin Scale (1.86 ± 1.35 vs. 3.57 ± 1.88, P = 0.024). No significant difference in final thrombolysis in cerebral infarction score, complications, length of stay, or mortality was observed. CONCLUSIONS: Our pilot study demonstrates the efficacy of the MSU in decreasing door-to-puncture time and a concordant improvement in the discharge modified Rankin Scale score. Further prospective studies are needed to assess cost-efficacy and optimal protocol for MSUs in stroke care.

Patient-Reported Outcomes for Lumbar Fusion in Patients with Previously Treated Cervical Myelopathy.

BACKGROUND: Patients with a history of surgically treated cervical myelopathy and lumbar pathology requiring fusion present complex challenges, and literature describing patient-reported outcomes in this cohort beyond patients with tandem spinal stenosis is sparse. This has led to unclear guidelines in the literature. We present the first dataset comparing patient-reported outcomes for lumbar fusion in patients with isolated lumbar pathology versus patients with a history of surgically treated cervical myelopathy. METHODS: In this retrospective cohort study of a prospectively collected lumbar fusion database, variables of interest included demographics, comorbidities, type and levels of fusion, Oswestry Disability Index (ODI), and minimal clinically important difference. RESULTS: Of 325 patients identified, 309 met inclusion criteria. Of these, 29 patients had previous cervical surgery to address cervical myelopathy. Median time between cervical and lumbar surgery was 4.0 years (range, 0.3-19.7). There was no statistical difference in preoperative ODI score (24.8 vs. 25.6, P = 0.687), 6-month postoperative ODI score (17.3 vs. 18.7, P = 0.459), change in ODI score (7.5 vs. 6.9, P = 0.673), or minimal clinically important difference for ODI score (62.1% vs. 58.6%, P = 0.710) in patients who had undergone cervical surgery versus patients who had not. CONCLUSIONS: Patients with a history of previously treated cervical myelopathy have a similar rate of clinically relevant improvement after lumbar fusion compared with patients without such history. As such, these patients appear to benefit from lumbar fusion surgery to the same degree as patients without a history of surgically treated cervical myelopathy.

Glioblastoma with deep supratentorial extension is associated with a worse overall survival.

Glioblastoma (GBM) with deep-supratentorial extension (DSE) involving the thalamus, basal ganglia and corpus collosum, poses significant challenges for clinical management. In this study, we present our outcomes in patients who underwent resection of supratentorial GBM with associated involvement of deep brain structures. We conducted a retrospective review of patients who underwent resection of GBM at our institution between 2012 and 2018. A total of 419 patients were included whose pre-operative MRI scans were reviewed. Of these, 143 (34.1%) had GBM with DSE. There were similar rates of IDH-1 mutation (9% versus 7.6%, p = 0.940) and MGMT methylation status (35.7% versus 45.2%, p = 0.397) between the two cohorts. GBM patients without evidence of DSE had higher rates of radiographic gross total resection (GTR) compared to those with DSE: 70.6% versus 53.1%, respectively (p = 0.002). The presence of DSE was not associated with decreased progression-free survival (PFS) compared to patients without DSE (mean 7.24 ± 0.97 versus 8.89 ± 0.76 months, respectively; p = 0.276), but did portend a worse overall survival (OS) (mean 10.55 ± 1.04 versus 15.02 ± 1.05 months, respectively; p = 0.003). There was no difference in PFS or OS amongst DSE and non-DSE patients who underwent GTR, but patients who harbored DSE and underwent subtotal resection had worse OS (mean 8.26 ± 1.93 versus 12.96 ± 1.59 months, p = 0.03). Our study shows that GBM patients with DSE have lower OS compared to those without DSE. This survival difference appears to be primarily related to the limited surgical extent of resection owing to the neurological deficits that may be incurred with involvement of eloquent deep brain structures.

Decompressive Hemicraniectomy in the Modern Era of Mechanical Thrombectomy.

OBJECTIVES: We aim to determine the incidence of decompressive hemicraniectomy (DHC) in the modern era of mechanical thrombectomy techniques and improved revascularization outcomes. METHODS: We performed a retrospective analysis of 512 patients admitted with acute ischemic strokes with anterior circulation large-vessel occlusion that were treated by mechanical thrombectomy from 2010-2019. The primary endpoint was the need for surgical decompression. Secondary endpoints were infarct size, hemorrhagic conversion, and functional outcome at hospital discharge. RESULTS: Of the 512 patients, 18 (3.5%) underwent DHC at a median 2.0 days from stroke onset. The DHC group was significantly younger than the non-DHC group (P < 0.001), had worse reperfusion rates (P = 0.024) and larger infarct size (P < 0.001). Hemorrhagic conversion was more frequent in the DHC group but did not reach statistical significance (P = 0.08). From 2010-2015, 196 patients underwent a mechanical thrombectomy, 13 of whom (6.6%) required a DHC, while 316 patients underwent mechanical thrombectomy from 2016-2019 and only 5 patients required a DHC (1.6%; P = 0.002). Younger age (P < 0.001), urinary tract infection (P < 0.001) and increasing infarct size were significantly associated with needing a DHC. When controlling for other risk factors, higher thrombolysis in cerebral infarction score significantly reduced the need for decompressive hemicraniectomy (P = 0.004). CONCLUSIONS: This is one of the largest single-center experiences demonstrating that improved recanalization decreased the need for DHC without increasing the risk of hemorrhagic conversion.

The Impact of Incorporating Evidence-Based Guidelines for Lumbar Fusion Surgery in Neurosurgical Resident Education.

BACKGROUND: Instrumented fusion procedures are essential in the treatment of degenerative lumbar spine disease to alleviate pain and improve neurological function, but they are being performed with increasing incidence and variability. We implemented a training module for neurosurgery residents that is based on evidence-based criteria for lumbar fusion surgery and measured its effectiveness in residents' decision making regarding whether patients should or should not undergo instrumented fusion. METHODS: The study design was a pretest versus posttest experiment conducted from September 2019 until July 2020 to measure improvement after formalized instruction on evidence-based guidelines. Neurosurgery residents of all training levels at our institution participated. A test was administered at the beginning of each academic year. The highest possible score was 18 points in each pretest and posttest. RESULTS: There was a general trend of test score improvement across all levels of training with a greater degree of change for participants with lower compared with higher pretest scores, indicating a possible ceiling effect. Paired t test demonstrated an overall mean score increase of 2 points (P < 0.0001), equivalent to an 11.11% increase (P < 0.0001). Stratified by training group, mean absolute change in test score was 2 (P = 0.0217), 1.67 (P = 0.0108), and 2.25 (P = 0.0173) points for junior, midlevel, and senior training groups, respectively. CONCLUSIONS: Incorporating a targeted evidence-based learning module for lumbar spine fusion surgery can improve neurosurgery residents' clinical decision making toward a more uniform practice supported by published data.

Extruded disc causes acute cervical epidural hematoma and cord compression: a case report.

INTRODUCTION: Cervical spontaneous epidural hematoma is a serious neurosurgical pathology that often requires prompt surgical intervention. While a variety of causes may contribute, the authors present the first case in the literature of cervical disc extrusion provoking epidural hemorrhage and acute neurological deterioration. CASE PRESENTATION: A 65 year old male presented with six months of worsening signs and symptoms of cervical myelopathy. He had progressive deterioration over the course of two weeks leading to ambulatory dysfunction requiring a cane for assistance. While undergoing his medical workup in the emergency department, the patient became acutely plegic in the right lower extremity prompting emergent surgical decompression and stabilization. DISCUSSION: Based on imaging, pathology, and intraoperative findings, it was concluded that the patient had an extruded disc segment that may have precipitated venous bleeding in the epidural space and findings of acute cervical cord compression. Cervical disc extrusion may lead to venous damage, epidural hematoma, and spinal cord compression. If this unique presentation is recognized and addressed in a timely manner, patient outcomes may still be largely positive as this case demonstrates.

Simultaneous bilateral mechanical thrombectomy in a patient with COVID-19.

Owing to systemic inflammation and widespread vessel endotheliopathy, SARS-CoV-2 has been shown to confer an increased risk of cryptogenic stroke, particularly in patients without any traditional risk factors. In this report, we present a case of a 67-year-old female who presented with acute stroke from bilateral anterior circulation large vessel occlusions, and was incidentally found to be COVID-positive on routine hospital admission screening. The patient had a large area of penumbra bilaterally, and the decision was made to pursue bilateral simultaneous thrombectomy, with two endovascular neurosurgeons working on each side to achieve a faster time to recanalization. Our study highlights the utility and efficacy of simultaneous bilateral thrombectomy, and this treatment paradigm should be considered for use in patients who present with multifocal large vessel occlusions.

Prediction of hematoma expansion in spontaneous intracerebral hemorrhage: Our institutional experience.

BACKGROUND: Spontaneous intracerebral hemorrhage (sICH) is a disease process with high morbidity and mortality. In particular, hematoma expansion (HE) is a feared complication of sICH. With 15-40% of patients experiencing HE, it has become increasingly important to predict which sICH will remain stable and which will expand. OBJECTIVE: With new treatment options being developed, it is becoming increasingly important to be able to predict which hemorrhages are at high versus low risk for expansion. The authors of this study hope to reexamine variables associated with hematoma expansion in hopes of generating newer data on risk factors for expansion. METHODS: A retrospective analysis identified 334 patients who presented with sICH. The primary outcome was HE on follow up head CT. HE was defined as a greater than 33% increase or an absolute increase in 6 mL or more in overall volume between the two sets of CT images. Analysis was performed using unpaired t-test, Chi-square, and Fisher's exact tests, as appropriate. RESULTS: Of the 334 patients, 247 (74.0%) did not experience an expansion of their ICH while 87 (26.0%) did. Multivariable logistic regression was performed demonstrating ICH score of 3 or greater (4.76 (95% CI 2.60-8.72, p < 0.001) , cortical location of the sICH (1.77 (95% CI 1.03-3.04, p = 0.038), and presence of a fluid level (6.46 (95% CI 2.28-18.3, p < 0.001) as significant predictors of HE. CONCLUSIONS: Our study found that fluid-fluid levels on non-contrast CT, an ICH score 3 or greater, and lobar sICH were all more likely to expand.

Comparison of Transradial vs Transfemoral Access in Neurovascular Fellowship Training: Overcoming the Learning Curve.

BACKGROUND: The transradial access (TRA) is rapidly gaining popularity for neuroendovascular procedures as there is strong evidence for its benefits compared to the traditional transfemoral access (TFA). However, the transition to TRA bears some challenges including optimization of the interventional suite set-up and workflow as well as its impact on fellowship training. OBJECTIVE: To compare the learning curves of TFA and TRA for diagnostic cerebral angiograms in neuroendovascular fellowship training. METHODS: We prospectively collected diagnostic angiogram procedural data on the performance of 2 neuroendovascular fellows with no prior endovascular experience who trained at our institution from July 2018 until June 2019. Metrics for operator proficiency were minutes of fluoroscopy time, procedure time, and volume of contrast used. RESULTS: A total of 293 diagnostic angiograms were included in the analysis. Of those, 57.7% were TRA and 42.3% were TFA. The median contrast dose was 60 cc, and the median radiation dose was 14 000 µGy. The overall complication rate was 1.4% consisting of 2 groin hematomas, 1 wrist hematoma, and 1 access-site infection using TFA. The crossover rate to TFA was 2.1%. Proficiency was achieved after 60 femoral and 95 radial cases based on fluoroscopy time, 52 femoral and 77 radial cases based on procedure time, and 53 femoral and 64 radial cases based on contrast volume. CONCLUSION: Our study demonstrates that the use of TRA can be safely incorporated into neuroendovascular training without causing an increase in complications or significantly prolonging procedure time or contrast use.

Onyx Embolization of Carotid-Cavernous Fistulas and Its Impact on Intraocular Pressure and Recurrence: A Case Series.

BACKGROUND: Carotid-cavernous fistulas (CCFs) are acquired pathological shunting lesions between the carotid artery and the cavernous sinus leading to elevated intraocular pressure (IOP). CCFs are commonly treated via endovascular embolization, which theoretically restores physiological pressure differentials. OBJECTIVE: To present our institutional data with CCF treated with embolization and discuss endovascular routes, recurrence rates, and dynamic IOP changes. METHODS: Retrospective analysis of 42 CCF patients who underwent Onyx (Covidien, Irvine, California) embolization and pre- and postoperative IOP measurement at a single institution. RESULTS: CCFs were 19.0% direct (type A) and 81.0% indirect (types B, C, or D). Onyx-18 liquid embolisate was used during all embolizations. Overall rate of total occlusion was 83.3% and was statistically similar between direct and indirect fistulas. Preoperative IOP was elevated in 37.5%, 100.0%, 75.0%, and 50% in type A, B, C, and D fistulas, respectively. Average ΔIOP was -7.3 ± 8.5 mmHg (range: -33 to +8). Follow-up time was 4.64 ± 7.62 mo. Full angiographic occlusion was a predictor of symptom resolution at 1 mo (P = .026) and 6 mo (P = .021). Partial occlusion was associated with persistent symptoms postoperatively at 1 mo (P = .038) and 6 mo follow-up (P = .012). Beyond 6 mo, negative ΔIOP was associated with continued symptom improvement. Recurrence occurred in 9.5% of patients, all of which were indirect CCFs. CONCLUSION: Onyx embolization of CCF is an effective treatment for CCF and often results in the reversal of IOP elevation. Full occlusion predicts favorable clinical outcomes up to 6 mo. Postoperative IOP reduction may indicate favorable long-term clinical outcomes.

A comparison of dual-lumen balloon and simple microcatheters in the embolization of DAVFs and AVMs using onyx.

Endovascular embolization of arteriovenous malformations (AVMs) and dural arteriovenous fistulas (DAVFs) has become the mainstay in treatment for these pathologies. Traditional techniques required the formation of a proximal plug of Onyx around the microcatheter prior to embolization to avoid reflux. Recently, dual-lumen balloon catheters have been introduced as a potential solution to this issue. We sought to compare our institutional experience with dual-lumen balloons to traditional microcatheters in the endovascular embolization of AVMs and DAVFs. A retrospective analysis of consecutive patients treated with Scepter between 2016 and 2020 was obtained. A control cohort treated with Marathon between 2012 and 2020 was also obtained. Variables collected included patient demographics, procedure times, pedicles treated, operative complications, obliteration rate, and retreatment rate. A total of 44 trial (30 DAVFs and 14 AVMs) and 25 control (15 DAVFs and 10 AVMs) subjects were identified. Average Scepter procedure times were 66.0 and 68.0 min for DAVFs and AVMs, respectively. Average Scepter volume of Onyx injected was 2.2 and 1.4 mL for DAVFs and AVMs, respectively. Complete angiographic occlusion Scepter rate was 86.7% and 50.0% for DAVFs and AVMs, respectively. The Scepter retreatment rate was 13.3% and 50.0% for DAVFs and AVMs, respectively. Predictors of angiographic occlusion included the number of pedicles (OR 0.54, 95%CI 0.30-0.97, p = 0.04). Predictors of retreatment included DAVF (OR 0.16, 95%CI 0.04-0.66, p = 0.01) and Marathon (OR 3.34, 95%CI 1.00-11.56, p = 0.05). Our study shows that dual-lumen balloon catheters are a viable option in the embolization of DAVFs and AVMs.

Developing standardized titles to classify the adverse events in 7,418 cranial and spinal neurosurgical procedures.

BACKGROUND: Neurosurgical procedures are life- and function-saving but carry a risk of adverse events (AE) which can cause permanent neurologic deficits. Unfortunately, there is lack of clearly defined AEs associated with given procedures, and their reporting is non-uniform and often arbitrary. However, with an increasing number of neurosurgical procedures performed, there is a need for standardization of AEs for systematic tracking. Such a system would establish a baseline for future quality improvement strategies. OBJECTIVE: To review our institutional AEs and devise standardized titles specific to the spine, tumor, functional, and vascular neurosurgery divisions. METHODS: A review of prospective monthly-reported morbidity and mortality (M&M) conference data within the Department of Neurological Surgery was conducted from January 2017 to December 2019. An AE was defined as any mortality, an "unintended and undesirable diagnostic or therapeutic event", "an event that prolongs the patient's hospital stay", or an outcome with permanent or transient neurologic deficit. RESULTS: A total of 1096 AEs from 7418 total procedures (14.8 %) were identified. Of those, 418 (5.6 %) were in cerebrovascular, 249 (3.4 %) were in neuro-oncology and 429 (5.8 %) were in the spine & functional divisions. The most common AEs across all divisions were infection (17 %), hemorrhage (11 %) and cerebrospinal fluid (CSF) leak (7.8 %). Other AEs were indirectly related to the neurosurgical procedure, such as deep vein thrombosis or pulmonary embolism (2.7 %), or pneumothorax (0.3 %). CONCLUSION: This work illustrates standardized AEs can be implemented universally across the spectrum of neurological surgery. Standardization can help identify recurring AE patterns through better tracking.

Progression-Free but No Overall Survival Benefit for Adult Patients with Bevacizumab Therapy for the Treatment of Newly Diagnosed Glioblastoma: A Systematic Review and Meta-Analysis.

Glioblastoma (GBM) is the most common high-grade primary brain tumor in adults. Standard multi-modality treatment of glioblastoma with surgery, temozolomide chemotherapy, and radiation results in transient tumor control but inevitably gives way to disease progression. The need for additional therapeutic avenues for patients with GBM led to interest in anti-angiogenic therapies, and in particular, bevacizumab. We sought to determine the efficacy of bevacizumab as a treatment for newly diagnosed GBM. We conducted a literature search using the PubMed database and Google Scholar to identify randomized controlled trials (RCTs) since 2014 investigating the safety and efficacy of bevacizumab in the treatment of adult patients (18 years and older) with newly diagnosed GBM. Only Level Ι data that reported progression-free survival (PFS) and overall survival (OS) were included for analysis. Random effects meta-analyses on studies with newly diagnosed glioblastoma were conducted in R to estimate the pooled hazard ratio (HR) for PFS and OS. Six RCTs met requirements for meta-analysis, revealing a pooled estimate of PFS HR suggesting a 33% decreased risk of disease progression (HR 0.67, 95% CI, 0.58-0.78; p < 0.001) with bevacizumab therapy, but no effect on OS (HR = 1, 95% CI, 0.85-1.18; p = 0.97). A pooled estimate of the mean difference in OS months of -0.13 predicts little difference in time of survival between treatment groups (95% CI, -1.87-1.61). The pooled estimate for the mean difference in PFS months was 2.70 (95% CI, 1.89-3.50; p < 0.001). Meta-analysis shows that bevacizumab therapy is associated with a longer PFS in adult patients with newly diagnosed glioblastoma, but had an inconsistent effect on OS in this patient population.

Procarbazine, CCNU and vincristine (PCV) versus temozolomide chemotherapy for patients with low-grade glioma: a systematic review.

Low-grade gliomas (LGG) encompass a heterogeneous group of tumors that are clinically, histologically and molecularly diverse. Treatment decisions for patients with LGG are directed toward improving upon the natural history while limiting treatment-associated toxiceffects. Recent evidence has documented a utility for adjuvant chemotherapy with procarbazine, CCNU (lomustine), and vincristine (PCV) or temozolomide (TMZ). We sought to determine the comparative utility of PCV and TMZ for patients with LGG, particularly in context of molecular subtype. A literature search of PubMed was conducted to identify studies reporting patient response to PCV, TMZ, or a combination of chemotherapy and radiation therapy (RT). Eligibility criteria included patients 16 years of age and older, notation of LGG subtype, and report of progression-free survival (PFS), overall survival (OS), and treatment course. Level I, II, and III data were included. Adjuvant therapy with PCV resulted in prolonged PFS and OS in patients with newly diagnosed high-risk LGG. This benefit was accrued most significantly by patients with tumors harboring 1p/19q codeletion and IDH1 mutation. Adjuvant therapy with temozolomide was associated with lower toxicity than therapy with PCV. In patients with LGG with an unfavorable natural history, such as with intact 1p/19q and wild-type IDH1, RT/TMZ plus adjuvant TMZ may be the best option. Patients with biologically favorable high-risk LGG are likely to derive the most benefit from RT and adjuvant PCV.