Mampre, David

OBJECTIVE The extent of resection has been shown to improve outcomes in patients with meningiomas. However, resection can be complicated by constraining local anatomy, leading to subtotal resections. An understanding of the natural history of residual tumors is necessary to better guide postsurgical management and minimize recurrence. This study seeks to identify predictors of recurrence and high growth rate following subtotal resection of intracranial meningiomas. METHODS Adult patients who underwent primary surgical resection of a WHO grade I meningioma at a tertiary care institution from 2007–2017 were retrospectively reviewed. Volumetric tumor measurements were made on patients with subtotal resections. Stepwise multivariate proportional hazards regression analyses were performed to identify factors associated with time to recurrence, as well as stepwise multivariate regression analyses to assess for factors associated with high postoperative growth rate. RESULTS Of the 141 patients (18%) who underwent radiographic subtotal resection of an intracranial meningioma during the reviewed period, 74 (52%) suffered a recurrence, in which the median (interquartile range, IQR) time to recurrence was 14 (IQR 6–34) months. Among those tumors subtotally resected, the median pre- and postoperative tumor volumes were 17.19 cm 3 (IQR 7.47–38.43 cm 3 ) and 2.31 cm 3 (IQR 0.98–5.16 cm 3 ), which corresponded to a percentage resection of 82% (IQR 68%–93%). Postoperatively, the median growth rate was 0.09 cm 3 /year (IQR 0–1.39 cm 3 /year). Factors associated with recurrence in multivariate analysis included preoperative tumor volume (hazard ratio [HR] 1.008,95% confidence interval [CI] 1.002–1.013, p = 0.008), falcine location (HR 2.215, 95% CI 1.179–4.161, p = 0.021), tentorial location (HR 2.410, 95% CI 1.203–4.829, p = 0.024), and African American race (HR 1.811, 95% CI 1.042–3.146, p = 0.044). Residual volume (RV) was associated with high absolute annual growth rate (odds ratio [OR] 1.175, 95% CI 1.078–1.280, p < 0.0001), with the maximum RV benefit at < 5 cm 3 (OR 4.056, 95% CI 1.675–9.822, p = 0.002). CONCLUSIONS By identifying predictors of recurrence and growth rate, this study helps identify potential patients with a high chance of recurrence following subtotal resection, which are those with large preoperative tumor volume, falcine location, tentorial location, and African American race. Higher RVs were associated with tumors with higher postoperative growth rates. Recurrences typically occurred 14 months after surgery.

Abstract INTRODUCTION The management of glioblastoma (GBM) has changed over time and varies based on geographic location. Despite its universally fatal prognoses, it is unclear if GBM outcomes have changed over time, if they vary by geographic location, and differ based on type of intervention. As a result, we conducted a systematic review of the literature to identify the average survival differences of GBM patients across time, between different continents, and among various treatments. METHODS The systematic review of PubMed included glioblastoma, GBM, and survival. Inclusion criteria consisted of full-text titles with human subjects, GBM/Grade IV astrocytoma, age >18 years old, and with available survival data. RESULTS 9,162 articles were screened for survival data, 1728 were eligible, 405 complied with the inclusion criteria. Of the 405 studies, 179 (44.2%) were conducted in Europe, 151 (37.3%) in the Americas, 61 (15.1%) in Asia, 9 (2.2%) in Oceania, and 1 (0.2%) in Africa. Leading countries are the United States (33.1%), Germany (12.3%), and Italy (11.1%). Asia had the highest median survival (14.9 months), followed by Europe (13.2 months), and the United States (12.9 months) (P=0.003). Regarding treatment, survival was significantly higher after the introduction of the Stupp protocol (P< 0.001). Post-Stupp Studies had longer survival estimates (15.3 months, range: 3.8–29.6) than Pre-Stupp Studies (12.2 months, range: 2.3–28). In the included clinical trials (182), radiation (43.4%), temozolomide (25.3%), or other chemotherapies (24.2%) were the most common interventions. Clinical trial median survival estimates were significantly higher than all other studies (P< 0.017). Bevacizumab (19.3 months) and Temozolomide (15.9 months) had the longest recorded median survival estimates; while radiation (14 months), other chemotherapies, and carmustine (13.2 months) had the shortest (P=0.009). CONCLUSION This epidemiological study describes the current global state of GBM. Important differences regarding survival and treatment of patients with GBM were found.

Abstract Patients with primary cancers often develop delayed brain metastases. One of the most common cancer types and sources of brain metastasis is lung cancer. For metastasis from lung cancer the 3-year survival is &lt; 5%. Cancer cells in circulation are responsible for metastatic spread. The mechanical microenvironment plays an important role in cancer cells behavior. When cancer cells reach the bloodstream they are exposed to hemodynamic shear stress. It has been shown that most of the circulating tumor cells die once they reach the bloodstream, but the biology of the survival cells is poorly understood. We designed a microfluidics system that simulated the mechanical stress in the human circulating system such as turbulence, change in pressure (0.4-15dyn/cm2) and flow rate (1.06–106.1mm/s). Lung adenocarcinoma cells (A549) were put into circulation and collected after 72 hours. It was found that, 1.4±0.3% of the cells survived, and viability was evaluated by LDH and calcein. CD133, SOX2, and NANOG were downregulated and EMT genes were upregulated in the circulating cancer cells (CCCs) compared with cells in static-suspension or 2D. After re-seeding in 2D, CCCs overexpressed CD133. Female athymic nude rats (6-8weeks,n=16) received intracardiac injections of CCCs or 2D cells (GFP-LUC lentivirus traduced). Bioluminescence imaging was performed every week; the survival in of the CCCs group was lower than the 2D group. One-way ANOVA test was used to analyze survival and gene expression. Survival data was plotted on a Kaplan-Meier curve and compared using the Mantel-Cox logrank test, p=&lt; 0.05. We have isolated a cellular subpopulation of lung adenocarcinoma with high resistance to hemodynamic shear stress that shows a higher metastatic capacity and genetic plasticity compared with cells growing in suspension or 2D. Targeting these cells would potentially allow us to develop personalized treatments to help to stop metastatic spread and improve actual therapeutical strategies.