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IntroductionMeningiomas comprise 33% of all CNS tumors. The World Health Organization (WHO) describes meningiomas as benign (BM), atypical (AM), and malignant/anaplastic (MM). High-grade meningiomas such as AMs and MMs are more aggressive, recur more frequently, and portend a worse prognosis than BMs. Currently, the standard treatment for high-grade meningiomas, especially AMs, is ill-defined. In particular, the benefit to survival outcomes of adjuvant radiotherapy post-surgical resection remains unclear. In this study, we investigated the effect of adjuvant radiotherapy (ART) post-surgery on survival outcomes compared to surgery alone for high-grade meningiomas.MethodsPRISMA guidelines were a foundation for our literature review. We screened the PubMed database for studies reporting overall survival (OS), progression free survival (PFS), and tumor recurrence for intracranial, primary AM and MMs treated with surgery+ART or surgery alone. Fixed and random effect models compared tumor control rate for AM aforementioned groups.ResultsMean 5-year PFS was 76.9% for AM (surgery+ART) and 55.9% for AM (surgery alone) patients. Mean 5-year OS was 81.3% and 74% for AM (surgery+ART) and AM (surgery alone) groups, respectively. Overall, the mean 5-year PFS for aggregated high-grade meningiomas AM+MM (surgery+ART) was 67.6%. Fixed effect models revealed tumor control rate as 76% for AM (surgery+ART) and 69% for AM (surgery alone) groups. ART induced toxicity incidence ranged from 12.0% to 35.5% for AM and MM patients.ConclusionsOur analysis suggests that (surgery+ART) may increase PFS, OS, and tumor control rates in high-grade meningiomas. However, further studies involving surgery+ ART should be conducted to fully evaluate the ideal radiosurgical candidate, modality, and dosage.

Abstract BACKGROUND Vestibular schwannomas (VS) are benign tumors derived from Schwann cells ensheathing the vestibulocochlear nerve. The retrosigmoid (RS) surgical approach is useful to resect tumors of multiple sizes while affording the possibility of preserving postoperative hearing. OBJECTIVE To conduct a systematic review of published literature investigating hearing preservation rates in patients who underwent the RS approach for VS treatment. METHODS The PubMed, Scopus, and Embase databases were surveyed for studies that reported preoperative and postoperative hearing grades on VS patients who underwent RS treatment. Hearing preservation rates were calculated, and additional patient demographic data were extracted. Tumor size data were stratified to compare hearing preservation rates after surgery for intracanalicular, small (0-20 mm), and large (>20 mm) tumors. RESULTS Of 383 deduplicated articles, 26 studies (6.8%) met eligibility criteria for a total of 2034 patients with serviceable preoperative hearing, for whom postoperative hearing status was evaluated. Aggregate hearing preservation was 31% and 35% under a fixed and random effects model, respectively. A mixed effects model was used to determine hearing preservation rates depending on tumor size, which were determined to be 57%, 37%, and 12% for intracanalicular, small, and large tumors, respectively. Significant cross-study heterogeneity was found (I2 = 93%, τ2 = .964, P < .01; Q = 287.80, P = < .001), with rates of hearing preservation ranging from 0% to 100%. CONCLUSION Tumor size may have an effect on hearing preservation rates, but multiple factors should be considered. Discussion of a patient's expectations for hearing preservation is critical when deciding on VS treatment plans.

Analysis of extracellular vesicles (EVs) derived from plasma or cerebrospinal fluid (CSF) has emerged as a promising biomarker platform for therapeutic monitoring in glioblastoma patients. However, the contents of the various subpopulations of EVs in these clinical specimens remain poorly defined. Here we characterize the relative abundance of miRNA species in EVs derived from the serum and cerebrospinal fluid of glioblastoma patients. EVs were isolated from glioblastoma cell lines as well as the plasma and CSF of glioblastoma patients. The microvesicle subpopulation was isolated by pelleting at 10,000× g for 30 min after cellular debris was cleared by a 2000× g (20 min) spin. The exosome subpopulation was isolated by pelleting the microvesicle supernatant at 120,000× g (120 min). qRT-PCR was performed to examine the distribution of miR-21, miR-103, miR-24, and miR-125. Global miRNA profiling was performed in select glioblastoma CSF samples. In plasma and cell line derived EVs, the relative abundance of miRNAs in exosome and microvesicles were highly variable. In some specimens, the majority of the miRNA species were found in exosomes while in other, they were found in microvesicles. In contrast, CSF exosomes were enriched for miRNAs relative to CSF microvesicles. In CSF, there is an average of one molecule of miRNA per 150–25,000 EVs. Most EVs derived from clinical biofluids are devoid of miRNA content. The relative distribution of miRNA species in plasma exosomes or microvesicles is unpredictable. In contrast, CSF exosomes are the major EV compartment that harbor miRNAs.

Background High-grade gliomas (HGG) comprise the most common primary adult brain cancers and universally recur. Combination of re-irradiation therapy (reRT) and bevacizumab (BVZ) therapy for recurrent HGG is common, but its reported efficacy is mixed. Objective To assess clinical outcomes after reRT ± BVZ in recurrent HGG patients receiving stereotactic radiosurgery (SRS), hypofractionated radiosurgery (HFSRT), or fully fractionated radiotherapy (FFRT). Methods We performed a systematic review of PubMed, Web of Science, Scopus, Embase, and Cochrane databases, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We identified studies reporting outcomes for patients with recurrent HGG treated via reRT ± BVZ. Cohorts were stratified by BVZ treatment status and re-irradiation modality (SRS, HFSRT, and FFRT). Outcome variables were overall survival (OS), progression-free survival (PFS), and radiation necrosis (RN). Results Data on 1399 patients was analyzed, with 954 patients receiving reRT alone and 445 patients receiving reRT + BVZ. All patients initially underwent standard-of-care therapy for their primary HGG. In a multivariate analysis that adjusted for median patient age, WHO grade, RT dosing, reRT fractionation regimen, time between primary and re-irradiation, and re-irradiation target volume, BVZ therapy was associated with significantly improved OS (2.51, 95% CI [0.11, 4.92] months, P = .041) but no significant improvement in PFS (1.40, 95% CI [− 0.36, 3.18] months, P = .099). Patients receiving BVZ also had significantly lower rates of RN (2.2% vs 6.5%, P < .001). Conclusions Combination of reRT + BVZ may improve OS and reduce RN rates in recurrent HGG, but further controlled studies are needed to confirm these effects.

Purpose/objective(s) To communicate our institutional experience with single isocenter radiosurgery treatments for multiple brain metastases, including challenges with determining planning target volume (PTV) margins and resulting consequences, image-guidance translational and rotational tolerances, intra-fraction patient motion, and prescription considerations with larger PTV margins. Materials/methods Eight patient treatments with 51 targets were planned with various margins using Elements Multiple Brain Mets SRS treatment planning software (Brainlab, Munich, Germany). Forty-eight plans with 0 mm, 1 mm and 2 mm margins were created, including plans with variable margins, where targets more than 6 cm away from the isocenter were planned with larger margins. The dosimetric impact of the margins were analyzed with V5Gy, V8Gy, V10Gy, V12Gy values. Additionally, 12 patient motion data were analyzed to determine both the impact of the repositioning threshold and the distributions of the patient translational and rotational movements. Results The V5Gy, V8Gy, V10Gy, V12Gy volumes approximately doubled when margins change from 0 to 1 mm and tripled when change from 0 to 2 mm. With variable margins, the aggregated results are similar to results from plans using the lower of two margins, since only 12.2% of the targets were more than 6 cm away from the isocenter. With 0.5 mm re-positioning threshold, 57.4% of the time the patients are repositioned. Reducing the threshold to 0.25 mm results in 91.7% repositioning rate, due to limitations of the fusion algorithm and actual patient motion. The 90th percentile of translational movements in all directions is 0.7 mm, while the 90th percentile of rotational movements in all directions is 0.6 degrees. Median translations and rotations are 0.2 mm and 0.2 degrees, respectively. Conclusions Based on the data presented, we have switched our modus operandi from 2 to 1 mm PTV margins, with an eventual goal of using 0.5 and 1.0 mm variable margins when an automated margin assignment method becomes available. The 0.5 mm and 0.5 degrees repositioning thresholds are clinically appropriate with small residual patient movements.

Purpose Stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (fSRT) are noninvasive therapies for vestibular schwannomas providing excellent tumor control. However, delayed hearing loss after radiation therapy remains an issue. One potential target to for improving hearing rates is limiting radiation exposure to the cochlea. Methods We retrospectively reviewed 100 patients undergoing either SRS with 12 Gy (n = 43) or fSRT with 50 Gy over 28 fractions (n = 57) for vestibular schwannoma. Univariate and multivariate analysis were carried out to identify predictors of hearing loss as measured by the Gardner Robertson scale after radiation therapy. Results Deterioration of hearing occurred in 30% of patients with SRS and 26% with fSRT. The overall long term (> 2 year) progression rates were 20% for SRS and 16% for fSRT. Patients with a decrease in their Gardner Robertson hearing score and those that loss serviceable hearing had significantly higher average minimal doses to the cochlea in both SRS and fSRT cohorts. ROC analysis showed that a cut off of 5 Gy and 35 Gy, for SRS and fSRT respectively, predicted hearing loss with high sensitivity/specificity. Conclusion Our data suggests the minimal dose of radiation that the cochlear volume is exposed to is a predictor of delayed hearing loss after either SRS or fSRT. A threshold of 5 Gy/35 Gy may lead to improved hearing preservation after radiotherapy. Further prospective multi center studies can further elucidate this mechanism.

Dendritic cell (DC) vaccines have recently emerged as an innovative therapeutic option for glioblastoma patients. To identify novel surrogates of anti-tumor immune responsiveness, we studied the dynamic expression of activation and inhibitory markers on peripheral blood lymphocyte (PBL) subsets in glioblastoma patients treated with DC vaccination at UCLA. Pre-treatment and post-treatment PBL from 24 patients enrolled in two Phase I clinical trials of dendritic cell immunotherapy were stained and analyzed using flow cytometry. A univariate Cox proportional hazards model was utilized to investigate the association between continuous immune monitoring variables and survival. Finally, the immune monitoring variables were dichotomized and a recursive partitioning survival tree was built to obtain cut-off values predictive of survival. The change in regulatory T cell (CD3(+)CD4(+)CD25(+)CD127(low)) frequency in PBL was significantly associated with survival (p = 0.0228; hazard ratio = 3.623) after DC vaccination. Furthermore, the dynamic expression of the negative co-stimulatory molecule, CTLA-4, was also significantly associated with survival on CD3(+)CD4(+) T cells (p = 0.0191; hazard ratio = 2.840) and CD3(+)CD8(+) T cells (p = 0.0273; hazard ratio = 2.690), while that of activation markers (CD25, CD69) was not. Finally, a recursive partitioning tree algorithm was utilized to dichotomize the post/pre fold change immune monitoring variables. The resultant cut-off values from these immune monitoring variables could effectively segregate these patients into groups with significantly different overall survival curves. Our results suggest that monitoring the change in regulatory T cell frequencies and dynamic expression of the negative co-stimulatory molecules on peripheral blood T cells, before and after DC vaccination, may predict survival. The cut-off point generated from these data can be utilized in future prospective immunotherapy trials to further evaluate its predictive validity.

Investigating life expectancy and mortality is crucial for the development of evidence-based health strategies for companion animals. However, relevant studies are lacking in South Korea, possibly because of challenges in collecting mortality data. In this regard, preliminary analyses were conducted to obtain life tables for companion animals in South Korea. The electronic records of six veterinary hospitals in Seoul, South Korea were examined. The data collected included breed, sex, spay/neuter status, date of birth, and date of death for all dogs and cats with a verifiable date of death since November 1, 2004 until December 31, 2022. After data preprocessing, descriptive statistical analysis was performed to summarize the demographics, and life tables and survival curves were created for dogs and cats. Cox proportional hazards regression was used to analyze the effects of demographic factors on survival. The mean age of dogs at death was 3427.49 days. Spayed or neutered dogs had a significantly higher life expectancy than intact dogs. Mixed-breed dogs had a higher life expectancy than purebred dogs. For cats, the mean age at death was 1965.49 days, with spayed or neutered cats living significantly longer than intact cats. Purebred cats had a higher median survival than Mixed-breed cats. Spaying or neutering and breed significantly affected survival probabilities in both species. Our study provides insights into the longevity of companion animals in South Korea, and reveals that neutering and breed significantly influence life expectancy.

Craniopharyngiomas are locally aggressive tumors which typically are focused in the sellar and suprasellar region near a number of critical neural and vascular structures mediating endocrinologic, behavioral, and visual functions. The present study aims to summarize and compare the published literature regarding morbidity resulting from treatment of craniopharyngioma. We performed a comprehensive search of the published English language literature to identify studies publishing outcome data of patients undergoing surgery for craniopharyngioma. Comparisons of the rates of endocrine, vascular, neurological, and visual complications were performed using Pearson’s chi-squared test, and covariates of interest were fitted into a multivariate logistic regression model. In our data set, 540 patients underwent surgical resection of their tumor. 138 patients received biopsy alone followed by some form of radiotherapy. Mean overall follow-up for all patients in these studies was 54 ± 1.8 months. The overall rate of new endocrinopathy for all patients undergoing surgical resection of their mass was 37% (95% CI = 33–41). Patients receiving GTR had over 2.5 times the rate of developing at least one endocrinopathy compared to patients receiving STR alone or STR + XRT (52 vs. 19 vs. 20%, χ 2 P  < 0.00001). On multivariate analysis, GTR conferred a significant increase in the risk of endocrinopathy compared to STR + XRT (OR = 3.45, 95% CI = 2.05–5.81, P  < 0.00001), after controlling for study size and the presence of significant hypothalamic involvement. There was a statistical trend towards worse visual outcomes in patients receiving XRT after STR compared to GTR or STR alone (GTR = 3.5% vs. STR 2.1% vs. STR + XRT 6.4%, P  = 0.11). Given the difficulty in obtaining class 1 data regarding the treatment of this tumor, this study can serve as an estimate of expected outcomes for these patients, and guide decision making until these data are available.

Patients with glioblastoma (GBM) need bold new approaches to their treatment, yet progress has been hindered by a relative inability to dynamically track treatment response, mechanisms of resistance, evolution of targetable mutations, and changes in mutational burden. We are writing on behalf of a multidisciplinary group of academic neuro-oncology professionals who met at the collaborative Christopher Davidson Forum at Washington University in St Louis in the fall of 2019. We propose a dramatic but necessary change to the routine management of patients with GBM to advance the field: to routinely biopsy recurrent GBM at the time of presumed recurrence. Data derived from these samples will identify true recurrence vs treatment effect, avoid treatments with little chance of success, enable clinical trial access, and aid in the scientific advancement of our understanding of GBM.