Carmustine wafers implantation in patients with newly diagnosed high grade glioma: is it still an option?

Background: The implantation protocol for Carmustine Wafers (CWs) in high grade glioma (HGG) was developed to offer a bridge between surgical resection and adjuvant treatments, such as radio- and chemotherapy. In the last years, however, a widespread use of CWs has been limited due to uncertainties regarding efficacy, in addition to increased risk of infection and elevated costs of treatment. Objective: The aims of our study were to investigate the epidemiology of patients that underwent surgery for HGG with CW implantation, in addition to the assessment of related complications, long-term overall survival (OS), and associated prognostic factors. Methods: Three different medical databases were screened for conducting a systematic review of the literature, according to the PRISMA statement guidelines, evaluating the role of BCNU wafer implantation in patients with newly diagnosed HGG. The search query was based on a combination of medical subject headings (MeSH): "high grade glioma " [MeSH] AND "Carmustine " [MeSH] and free text terms: "surgery " OR "BCNU wafer " OR "Gliadel " OR "systemic treatment options " OR "overall survival. " Results: The analysis of the meta-data demonstrated that there was a significant advantage in using CWs in newly diagnosed GBM in terms of OS, and a very low heterogeneity among the included studies [mean difference 2.64 (95% CI 0.85, 4.44); p = 0.004; I2149 = 0%]. Conversely, no significant difference between the two treatment groups in terms of PFS wad detected (p = 0.55). The analysis of complications showed a relatively higher rate in Carmustine implanted patients, although this difference was not significant (p = 0.53). Conclusions: This meta-analysis seems to suggest that CWs implantation plays a significant role in improving the OS, when used in patients with newly diagnosed HGG. To minimize the risk of side effects, however, a carful patient selection based mainly on patient age and tumor volume should be desirable

Circulating Exosomal-DNA in Glioma Patients. A Quantitative Study and Histopathological Correlations—A Preliminary Study

Glial neoplasms are a group of diseases with poor prognoses. Not all risk factors are known, and no screening tests are available. Only histology provides certain diagnosis. As already reported, DNA transported by exosomes can be an excellent source of information shared by cells locally or systemically. These vesicles seem to be one of the main mechanisms of tumor remote intercellular signaling used to induce immune deregulation, apoptosis, and both phenotypic and genotypic modifications. In this study, we evaluated the exosomal DNA (exoDNA) concentration in blood samples of patients affected by cerebral glioma and correlated it with histological and radiological characteristics of tumors. From 14 patients with diagnosed primary or recurrent glioma, we obtained MRI imaging data, histological data, and preoperative blood samples that were used to extract circulating exosomal DNA, which we then quantified. Our results demonstrate a relationship between the amount of circulating exosomal DNA and tumor volume, and mitotic activity. In particular, a high concentration of exoDNA was noted in low-grade gliomas. Our results suggest a possible role of exoDNAs in the diagnosis of brain glioma. They could be particularly useful in detecting early recurrent high-grade gliomas and asymptomatic low-grade gliomas

Immune Checkpoint Modulators: An Emerging Antiglioma Armamentarium

Immune checkpoints have come to the forefront of cancer therapies as a powerful and promising strategy to stimulate antitumor T cell activity. Results from recent preclinical and clinical studies demonstrate how checkpoint inhibition can be utilized to prevent tumor immune evasion and both local and systemic immune suppression. This review encompasses the key immune checkpoints that have been found to play a role in tumorigenesis and, more specifically, gliomagenesis. The review will provide an overview of the existing preclinical and clinical data, antitumor efficacy, and clinical applications for each checkpoint with respect to GBM, as well as a summary of combination therapies with chemotherapy and radiation

The semisitting position: analysis of the risks and surgical outcomes in a contemporary series of 425 adult patients undergoing cranial surgery

OBJECTIVE The objective of this study was to analyze the incidence of the primary complications related to positioning or surgery and their impact on neurological outcome in a consecutive series of patients undergoing elective surgery in the semisitting position. METHODS The authors prospectively collected and retrospectively analyzed data from adult patients undergoing elective surgery in the semisitting position for a cranial disease. Patients were managed perioperatively according to a standard institutional protocol, a standardized stepwise positioning, and surgical maneuvers to decrease the risk of venous air embolism (VAE) and other complications. Intraoperative and postoperative complications were recorded. Neurointensive care unit (NICU) length of stay (LOS) and hospital LOS were the intermediate endpoints. Neurological outcome was the primary endpoint as determined by the modified Rankin scale (mRS) score at 6 months after surgery. RESULTS Four hundred twenty-five patients were included in the analysis. VAE occurred in 90 cases (21%) and it made no significant statistical difference in NICU LOS, hospital LOS, and neurological outcome. No complication was directly related to the semisitting position, although 46 patients (11%) experienced at least 1 surgery-related complication and NICU LOS and hospital LOS were significantly prolonged in this group. Neurological outcome was significantly worse for patients with complications (p < 0.0001). CONCLUSIONS Even in the presence of intraoperative VAE, the semisitting position was not related to an increased risk of postoperative deficits and can represent a safe additional option for the benefit of specific surgical and patient needs

Molecular Analysis in a Glioblastoma Cohort&mdash;Results of a Prospective Analysis

The prognostic role of epidermal growth factor receptor variant III (EGFRvIII), a constitutively activated oncogenic receptor, in glioblastoma is controversial. We performed a prospective study enrolling 355 patients operated on for de novo glioblastoma at a large academic center. The molecular profile, including EGFRvIII status, MGMT promoter methylation, and VEGF expression, was assessed. Standard parameters (age, clinical status and extent of surgical resection) were confirmed to hold prognostic value. MGMT promoter methylation portended a slightly improved survival. In the whole series, confirming previous results, EGFRvIII was not associated with worsened prognosis. Interestingly, female sex was associated with a better outcome. Such findings are of interest for the design of future trials