Standard therapy for glioblastoma includes surgery, radiotherapy, and temozolomide. This Phase 3 trial evaluates the addition of an autologous tumor lysate-pulsed dendritic cell vaccine (DCVax
-L) to ...standard therapy for newly diagnosed glioblastoma.
After surgery and chemoradiotherapy, patients were randomized (2:1) to receive temozolomide plus DCVax-L (n = 232) or temozolomide and placebo (n = 99). Following recurrence, all patients were allowed to receive DCVax-L, without unblinding. The primary endpoint was progression free survival (PFS); the secondary endpoint was overall survival (OS).
For the intent-to-treat (ITT) population (n = 331), median OS (mOS) was 23.1 months from surgery. Because of the cross-over trial design, nearly 90% of the ITT population received DCVax-L. For patients with methylated MGMT (n = 131), mOS was 34.7 months from surgery, with a 3-year survival of 46.4%. As of this analysis, 223 patients are ≥ 30 months past their surgery date; 67 of these (30.0%) have lived ≥ 30 months and have a Kaplan-Meier (KM)-derived mOS of 46.5 months. 182 patients are ≥ 36 months past surgery; 44 of these (24.2%) have lived ≥ 36 months and have a KM-derived mOS of 88.2 months. A population of extended survivors (n = 100) with mOS of 40.5 months, not explained by known prognostic factors, will be analyzed further. Only 2.1% of ITT patients (n = 7) had a grade 3 or 4 adverse event that was deemed at least possibly related to the vaccine. Overall adverse events with DCVax were comparable to standard therapy alone.
Addition of DCVax-L to standard therapy is feasible and safe in glioblastoma patients, and may extend survival. Trial registration Funded by Northwest Biotherapeutics; Clinicaltrials.gov number: NCT00045968; https://clinicaltrials.gov/ct2/show/NCT00045968?term=NCT00045968&rank=1 ; initially registered 19 September 2002.
Local recurrence following radical resection is one of the most common complications of pediatric craniopharyngioma. Only 28 cases of ectopic recurrence of craniopharyngioma have been reported in the ...literature, and only 13 cases occurred in patients originally treated as children. In this consecutive series of 86 children who underwent radical resection of primary and recurrent craniopharyngiomas, 4 patients (4.7%) experienced ectopic tumor recurrence, accounting for 27% of all recurrences after gross-total resection. The authors report on the successful surgical treatment of these 4 patients and the impact of ectopic craniopharyngioma recurrence on survival.
Glioblastoma is the most lethal primary brain cancer. Clinical outcomes for glioblastoma remain poor, and new treatments are needed.
To investigate whether adding autologous tumor lysate-loaded ...dendritic cell vaccine (DCVax-L) to standard of care (SOC) extends survival among patients with glioblastoma.
This phase 3, prospective, externally controlled nonrandomized trial compared overall survival (OS) in patients with newly diagnosed glioblastoma (nGBM) and recurrent glioblastoma (rGBM) treated with DCVax-L plus SOC vs contemporaneous matched external control patients treated with SOC. This international, multicenter trial was conducted at 94 sites in 4 countries from August 2007 to November 2015. Data analysis was conducted from October 2020 to September 2021.
The active treatment was DCVax-L plus SOC temozolomide. The nGBM external control patients received SOC temozolomide and placebo; the rGBM external controls received approved rGBM therapies.
The primary and secondary end points compared overall survival (OS) in nGBM and rGBM, respectively, with contemporaneous matched external control populations from the control groups of other formal randomized clinical trials.
A total of 331 patients were enrolled in the trial, with 232 randomized to the DCVax-L group and 99 to the placebo group. Median OS (mOS) for the 232 patients with nGBM receiving DCVax-L was 19.3 (95% CI, 17.5-21.3) months from randomization (22.4 months from surgery) vs 16.5 (95% CI, 16.0-17.5) months from randomization in control patients (HR = 0.80; 98% CI, 0.00-0.94; P = .002). Survival at 48 months from randomization was 15.7% vs 9.9%, and at 60 months, it was 13.0% vs 5.7%. For 64 patients with rGBM receiving DCVax-L, mOS was 13.2 (95% CI, 9.7-16.8) months from relapse vs 7.8 (95% CI, 7.2-8.2) months among control patients (HR, 0.58; 98% CI, 0.00-0.76; P < .001). Survival at 24 and 30 months after recurrence was 20.7% vs 9.6% and 11.1% vs 5.1%, respectively. Survival was improved in patients with nGBM with methylated MGMT receiving DCVax-L compared with external control patients (HR, 0.74; 98% CI, 0.55-1.00; P = .03).
In this study, adding DCVax-L to SOC resulted in clinically meaningful and statistically significant extension of survival for patients with both nGBM and rGBM compared with contemporaneous, matched external controls who received SOC alone.
ClinicalTrials.gov Identifier: NCT00045968.
The purpose of this study was to assess the impact of minimal residual calcification without enhancing tumor on the rate of recurrence after gross-total resection (GTR) of craniopharyngioma in ...children.
Data were retrospectively collected in 86 patients younger than 21 years of age in whom 103 craniopharyngioma resections were performed by the senior author between 1986 and 2008. Forty-nine patients (27 boys and 22 girls, with a mean age of 8.6 years) fulfilled the criteria for inclusion in this study by having tumor calcification on the preoperative CT scan, undergoing GTR, and having complete postoperative CT and MR imaging and clinical follow-up.
Thirteen patients (27%) had residual calcification (< or = 2 mm in 12 patients; 3.5 mm in 1 patient) on their postoperative CT scan. At a mean follow-up of 9.4 years (median 10 years), 2 (15%) of 13 patients with and 10 (28%) of 36 patients without residual calcification experienced tumor recurrence. There were no significant differences between these groups in terms of the duration of follow-up, time to recurrence, rate of recurrence, or recurrence-free survival.
The absence or presence of minimal residual calcification does not have an impact on the risk of recurrence after GTR in pediatric craniopharyngiomas. The authors recommend withholding irradiation or other adjuvant therapy in the setting of minimal residual calcification without enhancing tumor. Close follow-up with frequent serial imaging in all patients after GTR is imperative to identify and treat early recurrence.
Electrical stimulation of left temporo-parieto-occipital (TPO) cortex in adult male Wistar rats during their behaviorally active phase (nighttime) transiently increased circulating levels of CD4+ and ...CD8+ T lymphocytes. Comparable stimulation of this cortex on the right decreased circulating levels of these cells. Responses to left or right cortical stimulation were diminished or absent in behaviorally inactive rats (daytime). Since blood glucocorticoid levels were similar before and after left or right stimulation, they did not appear to account for the lateralized changes observed. These lateralized effects were mediated by spinal cord autonomic pathways emerging at Tl-T7 levels. In adult thymectomized rats, CD4+ and CD8+ T cells failed to increase after left sided stimulation. The results suggest that lateralized cerebral cortical functions can acutely and differentially influence blood T cell subset numbers. The results demonstrate a direct neocortical influence on thymic export of mature T cells, mediated by the sympathetic nervous system.
Anteriorly located Type IV thoracic arteriovenous malformations (AVMs) are difficult to treat surgically. Although high-flow fistula subtypes are amenable to treatment using endovascular techniques, ...low-flow fistulas should be treated surgically. There are few reports discussing the diagnosis, behavior, and treatment of these spinal fistulas due to their low incidence. Posterior surgical approaches to Type IV spinal AVMs reported in the literature have been associated with high morbidity rates or aborted procedures. The authors report the successful management of a T-12 Type IV spinal AVM with an emphasis on approach, interoperative angiography, and the use of modern instrumentation. To the authors' knowledge, this is also the first reported case of multiple arterial-side aneurysms in a Type IV AVM of the anterior spinal artery.
Objective: To look for correlations between acridine orange (AO) staining and semen parameters before and after sperm separation procedures and to assess whether the AO test predicts fertilization or ...pregnancy outcomes after standard IVF and intracytoplasmic sperm injection.
Design: Prospective study that simultaneously assesses sperm morphology and nuclear protein maturity on a cell-by-cell basis before and after preparative procedures.
Setting: University teaching hospital.
Patient(s): Men (n = 140) undergoing diagnostic semen analysis.
Main Outcome Measure(s): Acridine orange fluorescence of sperm nuclei, semen parameters, IVF outcome.
Result(s): In unprocessed samples, 90% of sperm with normal heads displayed green fluorescence (mature nuclear protein); significantly lower percentages of green fluorescence were observed in sperm with abnormal heads. The percentage of mature normal sperm in the specimen correlated with motility. Sperm maturity after swim-up or Percoll gradient was significantly improved for sperm with normal or abnormal heads. The percentage of mature normal sperm correlated with motility after either Percoll or swim-up. Neither the percentages of mature nuclei nor mature normal nuclei correlated with fertilization or pregnancy outcome.
Conclusion(s): Nuclear protein maturation correlates with sperm motility and morphology. Because morphologically normal and motile sperm are more mature, separation procedures should generate a population of sperm with the highest fertilization capacity. Acridine orange staining, however, did not predict fertilization efficiency or pregnancy outcome in IVF cycles.
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