Resection versus biopsy for management of primary central nervous system lymphoma: a meta-analysis.

The role of surgery in the management of primary central nervous system lymphomas (PCNSL) is currently confined to diagnosis. However, over recent years, an increasing number of papers have suggested a possible positive prognostic impact of surgery in selected cases. The present work aims to perform a meta-analysis of the available literature evidence. A meta-analysis with meta-regression on the role of surgical resection compared to biopsy in the management of PCNSL was conducted according to the PRISMA statement, searching MEDLINE via PubMed and Embase. The random effect model was used. The quality of evidence was assessed using the GRADE framework. After screening 1395 records, we included 11 papers in our analysis. Patients who underwent surgical resection harbored superficial and single-lesion tumors. At 1-, 2-, and 5-year follow-up, progression-free survival did not differ between the two groups, while overall survival favored resection, even if in a non-significant fashion. Meta-regression analysis showed that the overall survival rate at 2 years, but not at 1 or 5 years, was significantly influenced by tumor location. There were no differences in terms of age, sex, Karnofsky performance status, adjuvant therapy, or procedure-related complications. Overall, the quality of evidence is low. The results of the present meta-analysis do not change the current standard of care for PCNSL. However, surgery could be non-inferior to biopsy with an acceptable risk profile in selected patients harboring single and superficial lesions. The low quality of evidence prompts future randomized studies.

Applicability and efficacy of ultrasound elastography in neurosurgery: a systematic review of the literature.

INTRODUCTION: Neurosurgery is one of the fields in which intraoperative imaging is paramount. One of these main imaging tools that have been acquiring the interest of the neurosurgical community is Ultrasound elastography (USE), which is an imaging technology sensitive to tissue stiffness. Here we present a systematic review of the use of USE in neurosurgery. EVIDENCE ACQUISITION: A systematic review of the literature has been performed, according to the PRISMA guideline, for the last 30 years on 3 different databases (MEDLINE, Scopus, and Cochrane), to gather all the studies on the use of ultrasound elastography for neurosurgical pathologies, including both clinical and laboratory studies. EVIDENCE SYNTHESIS: A total of 15 articles met the inclusion criteria. USE has widely and safely been used especially for oncological lesions (meningiomas and gliomas) and focal cortical dysplasia. However, there are also encouraging laboratory studies about its application for the management of traumatic brain injury, and ischemic stroke. CONCLUSIONS: This systematic review showed that, despite the lack of strong evidence, USE is a valid intraoperative tool, especially in oncological neurosurgery.

Clinical and NGS predictors of response to regorafenib in recurrent glioblastoma.

Predictive factors for response to regorafenib in recurrent glioblastoma, IDH-wildtype, are scarcely recognized. The objective of this study was to identify molecular predictive factors for response to regorafenib using a clinically available platform. We analyzed a prospective cohort of 30 patients harboring recurrent glioblastoma, IDH-wildtype, and treated with regorafenib. Next-generation sequencing (NGS) analysis was performed on DNA extracted from paraffin-embedded tissues using a clinically available platform. Moreover, MGMT methylation and EGFRvIII expression analyses were performed. Six-month progression-free survival (PFS) was 30% and median overall survival (OS) was 7.5 months, in line with literature data. NGS analysis revealed a mutation in the EGFR pathway in 18% of cases and a mutation in the mitogen-activated protein-kinase (MAPK) pathway in 18% of cases. In the remaining cases, no mutations were detected. Patients carrying MAPK pathway mutation had a poor response to regorafenib treatment, with a significantly shorter PFS and a nonsignificantly shorter OS compared to EGFR-mutated patients (for PFS, 2.5 vs 4.5 months, p = 0.0061; for OS, 7 vs 9 months, p = 0.1076). Multivariate analysis confirmed that MAPK pathway mutations independently predicted a shorter PFS after regorafenib treatment (p = 0.0188). The negative prognostic role of MAPK pathway alteration was reinforced when we combined EGFR-mutated with EGFRvIII-positive cases. Recurrent glioblastoma tumors with an alteration in MAPK pathway could belong to the mesenchymal subtype and respond poorly to regorafenib treatment, while EGFR-altered cases have a better response to regorafenib. We thus provide a molecular selection criterion easy to implement in the clinical practice.

Glioblastoma: from volumetric analysis to molecular predictors.

BACKGROUND: Decades of therapeutic and molecular refinements, the prognosis of patients with glioblastoma (GBM) still remains unfavorable. Integrative clinical studies allow a better understanding of the natural evolution of GBM. To assess independent predictors of overall survival (OS) and progression free survival (PFS) clinical, surgical, molecular and radiological variables were evaluated. A novel preoperative volumetric magnetic resonance imaging (MRI) Index for tumor prognosis in GBM patients was investigated. METHODS: A cohort of 195 cases of patients operated for newly GBM were analyzed. Extent of tumoral resection (EOR), tumor growth pattern, expressed by preoperative volumetric ΔT1-T2 MRI Index, molecular markers such as O6-methylguanine-DNA methyltransferase (MGMT) methylation and isocitrate dehydrogenase 1/2 (IDH1/2) mutation, were analyzed. Analysis of survival was done using Cox-proportional hazard models. RESULTS: The 1-, 2- years estimated OS and PFS rate for the whole population were 61% and 27%, 38% and 17%, respectively. A better survival rate, both in terms of survival and tumor progression, was observed in patient with higher EOR (P=0.000), younger age (P=0.000), MGMT methylation status (P=0.001) and lower preoperative ΔT1-T2 MRI Index (P=0.004). Regarding the tumor growth pattern a cut-off value of 0.75 was found to discriminate patient with different prognosis. Patients with a preoperative ΔT1-T2 MRI Index <0.75 had a 1-year estimated OS of 67%, otherwise patients with a preoperative ΔT1-T2 MRI Index >0.75 had a 1-year estimated OS of 34%. CONCLUSIONS: In this investigation longer survival is associated with younger age, EOR, promoter methylation of MGMT and preoperative tumor volumetric features expressed by ΔT1-T2 MRI Index The preoperative ΔT1-T2 MRI Index could be a promising prognostic factor potentially useful in GBM management. Future investigations based on multiparametric MRI data and next generation sequences analysis, may better clarify this result.

Adjuvant radiotherapy in grossly total resected grade II atypical meningiomas: a protective effect on recurrence?

INTRODUCTION: Management of grade II atypical meningiomas (AM) remains controversial. Conflicting evidence exist on the possible protective effect of adjuvant radiotherapy (ART) on recurrence in grossly resected AMs. The aim of this meta-analysis is to evaluate the role of ART in grossly resected (Simpson grades 1-3) AMs on the recurrence and survival. EVIDENCE ACQUISITION: Literature review was performed by the study investigators who handily queried the MEDLINE database using keywords and MeSH terms in different combinations using the Boolean operators "AND" or "OR," and database-related filters to maximize the chance to identify articles focusing on role of radiotherapy in atypical (WHO grade II) meningiomas. Data were retrieved from comparative studies of AMs undergone surgical resection alone vs. surgery + ART. Only grossly total resected AMs (Simpson grades 1-3) were included. The individual and pooled odds ratio (OR) for the crude recurrence, progression free survival (PFS) at 1, 3 and 5-years, as well as for the overall survival (OS) at 5-years were calculated by using the Mantel-Haenszel model in surgery alone vs. surgery + ART. EVIDENCE SYNTHESIS: Eleven studies were considered eligible. 8 were included for the outcome "crude recurrence;" 6 for PFS at 1-3 years, 7 for PFS at 5-years; 6 for the OS at 5-years. Results suggest that surgery + ART might have a protective role on recurrence in gross-totally resected AMs (OR:1.66). Specifically, surgery + ART slightly improved PFS at 1-year (OR:0.92) and more consistently at 3- and 5-years (OR:0.31 and 0.35 respectively) hence favoring a combined approach. CONCLUSIONS: Current literature on the impact of ART after gross total resection of AM are still heterogeneous and not systematically reported. The present meta-analysis suggests a possible protective role of postoperative RT against long-term recurrence as compared to surgical resection alone.

Application of indocyanine green video angiography in vascular neurosurgery.

Indocyanine green video angiography (ICG-VA) is a non-invasive, easy to use and very useful tool for various neurosurgical procedures. The first application was in neurovascular surgery, because it was born as an intravascular tracer for vessels visualization; this has been really useful in aneurysms, atero-venous malformations (AVMs) and dural fistulas surgery where identification, obliteration or patency of vessels is essential. Introduced in vascular neurosurgery since 2003, ICG-VA applications have broadened over time, both in vascular and in other neurosurgical fields. In 2003 Raabe et al. have been the first to describe the use of ICG-VA for intraoperative assessment of cerebral vascular flow, enabling visualization of vessel patency and aneurysm occlusion during aneurysm surgery. ICG-VA applications in vascular neurosurgery have significantly increased over time including complex aneurysms, bypass, atero-venous malformations (AVM) artero-venous fistulas (AVF), evaluation of cortical perfusion. The procedure can be easily repeated after 5-10 minutes. Adverse reactions are comparable to those of other types of contrast media, with frequencies of 0.05% (hypotension, arrhythmia, or, more rarely, anaphylactic shock) to 0.2% (nausea, pruritus, syncope, or skin eruptions. The aim of the present study was to systematically analyze ICG-VA applications in vascular neurosurgery, highlighting the reported advantages and disadvantages, and discussing future perspectives.

State of the art of fluorescence guided techniques in neurosurgery.

Achieving a safe and extensive neoplasm resection can be considered the main goal of brain tumor surgery. This paper is first aimed at providing an overview of the evolution of those tools serving the purpose. From the dawn of neurosurgery to the present days, major innovations have followed one another. However, those techniques may frequently lack of an instant biological feedback on the true extension and the infiltration of the tumor. Intraoperative fluorescence modalities could indeed fill this gap. Fluorescence guided surgery will be therefore introduced and discussed in this context. Our focus will be on the most common fluorescence techniques used in neurosurgery, namely 5-aminolevulinic acid, sodium fluorescein and in indocyanine green. Mode of action, strengths and weaknesses and level of evidence of each modality will be discussed.

"Dark corridors" in 5-ALA resection of high-grade gliomas: combining fluorescence-guided surgery and contrast-enhanced ultrasonography to better explore the surgical field.

BACKGROUND: Increasing the extent of resection (EOR) is considered a main goal in high grade glioma (HGG) surgery. Significant advancements have been recently made to assist surgery: namely the use of 5-aminolevulinic acid (5ALA) and the application of contrast-enhanced ultrasound (CEUS) embody two of the most recently introduced tools in the neuro-oncology field. A combined approach including the two techniques has been suggested in literature. Our primary aim is to identify in which conditions CEUS final survey has a real impact in a 5-ALA guided context and assess which preoperative tumor characteristics, with specific attention to working corridors can predict strains of the fluorescence guided procedure and hence recommend the use of the combined technique. METHODS: Forty-nine HGG glioma surgeries were performed at our institution with the abovementioned protocol between January 2016 and June 2016. Based on preoperative MRI, we stratified glioma characteristics according to three determinants: localization (deep versus superficial), size (<3.5 versus >3.5 cm) and shape (regular versus irregular). RESULTS: CEUS modified 5-ALA guided resection in 11 cases (22.45%): this appeared to be associated with statistically significance to deep tumor localization (P=0.04) and irregular/multi-lobulated margins (P=0.003). On the other hand, tumor size alone did not appear as a statistically significant determinant. CONCLUSIONS: When dark corridors are presents or when overlying brain parenchyma hinders illumination, drawbacks to the 5-ALA assistance can be expected, hence CEUS final survey has a crucial role of 'refinement'. In those selected cases, an integrated 5ALA+CEUS protocol was shown as advisable in EOR improvement.