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High grade gliomas are associated with poor prognosis and high mortality. Conventional treatments and management of high grade gliomas have shown little improvement in 5-year overall survival. This phase I trial evaluated the safety, immunogenicity, and potential synergy of surgical resection with Gliadel Wafer implantation, followed by autologous tumor lysate-pulsed dendritic cell (DC) vaccine in patients with malignant glioma. Primary end points of this study were safety and surrogate markers of immunogenicity, overall survival, and progression free survival. Following surgical resection, Gliadel Wafers were placed along the resection cavity. Patients subsequently received intradermal injections of autologous tumor lysate-pulsed DC vaccines 3 times at 2 week intervals. Treatment response was evaluated clinically and through MRI at regular intervals. Twenty-eight patients received Gliadel Wafers and DC vaccination: 11 newly diagnosed (8 glioblastoma [GBM], 2 anaplastic astrocytoma [AA], and 1 anaplastic oligodendroglioma [AO]) and 17 recurrent (15 GBMs, 1 AA, and 1 AO) high grade gliomas. Immunogenicity data was collected for 20 of the 28 patients. Five of 20 patients showed elevated IFN-γ responses following vaccination. Median progression-free survival and overall survival for all GBM patients in the trial from the start of vaccination were 3.6 months and 16.9 months respectively. Comparisons between vaccine responders and non-vaccine responders were not statistically significant. Adjuvant autologous dendritic cells pulsed with tumor-lysate following resection and Gliadel Wafer placement is safe, elicits modest immunogenicity and shows similar clinical outcomes in patients who had DC vaccination in previous studies.

Glioblastoma (GBM) is the most prevalent and aggressive primary brain tumor in adults for which recurrence is inevitable and surgical resection is often recommended. We investigated the relationship between multiple tumor resections and overall survival (OS) in adult glioblastoma patients who received adjuvant radiotherapy and temozolomide following initial surgery. We retrospectively reviewed the records of all newly diagnosed adult GBM patients with tumor recurrence at our institution from March 2003 to October 2012. Kaplan-Meier survival estimates and multivariate analysis using Cox's proportional hazards model were utilized to evaluate the impact of multiple resections on OS. A total of 202 GBM patients were analyzed; 83 (41.1%), 94 (46.5%), and 25 (12.4%) patients underwent one, two, and three or more total resections, respectively. Patients who underwent multiple resections were significantly younger (p

Purpose To compare reoperations, health care utilization, and costs in lumbar spinal stenosis (LSS) patients undergoing interspinous process (ISP) device placement in an inpatient versus outpatient setting. Methods The MarketScan database (2007–2009) was queried for adults with LSS undergoing ISP device placement as a primary procedure. Reoperations, health care utilization, and costs in patients with at least 18 months of follow-up were analyzed. Chi-square and Student t tests were used to assess the differences in characteristics and outcomes between patients treated in the inpatient and outpatient setting. Results A total of 411 patients who underwent ISP device placement were identified; the mean age was 72 years, 51% were female, and most patients were insured by Medicare (73.7%). The average postoperative follow-up was 24.9 months. A subset of 182 patients (44.3%) had inpatient procedures; 229 (55.7%) underwent outpatient ISP device placements. The overall reoperation rate was 20.4%. ISP reoperation rates between inpatient and outpatient cohorts were comparable (23.1% versus 18.3%; p = 0.24). Inpatients accrued significantly higher index procedural costs compared with outpatients ($17,432 versus $8854; p = 0.0001), however, the outpatient cohort utilized more postoperative outpatient services (143 versus 112; p = 0.09) and higher outpatient service costs ($25,376 versus $15,481; p = 0.01). Consequently, cumulative overall cost was similar among the two cohorts ($51,059 versus $51,778; p = 0.94). Conclusions Long-term reoperation rates following ISP device placement are comparable in the inpatient and outpatient setting. Upfront cost savings may be achieved with outpatient ISP device placement, but this benefit is lost by 18 months following initial surgery.

BACKGROUND: Research on readmissions has focused mainly on the economic and resource burden it places on hospitals. OBJECTIVE: To evaluate the effect of 30-day readmission on overall survival among newly diagnosed glioblastoma multiforme (GBM) patients. METHODS: A nationwide cohort of GBM patients diagnosed between 1991 and 2007 was studied using the Surveillance, Epidemiology and End Results Medicare database. Multivariate models were used to determine factors associated with readmission and overall survival. Odds ratio, hazard ratio, 95% confidence interval, and P values were reported. Complete case and multiple imputation analyses were performed. RESULTS: Among the 2774 newly diagnosed GBM patients undergoing surgery at 442 hospitals nationwide, 437 (15.8%) were readmitted within 30 days of the index hospitalization. Although 63% of readmitted patients returned to the index hospital where surgery was performed, a significant portion (37%) were readmitted to nonindex hospitals. The median overall survival for readmitted patients (6.0 months) was significantly shorter than for nonreadmitted (7.6 months; P < .001). In a confounder-adjusted imputed model, 30-day readmission increased the hazard of mortality by 30% (hazard ratio, 1.3; P < .001). Neurological symptoms (30.2%), thromboembolic complications (19.7%), and infections (17.6%) were the leading reasons for readmission. CONCLUSION: Prior studies that have reported only the readmissions back to index hospitals are likely underestimating the true 30-day readmission rate. GBM patients who were readmitted within 30 days had significantly shorter survival than nonreadmitted patients. Future studies that attempt to decrease readmissions and evaluate the impact of reducing readmissions on patient outcomes are needed.

Background Approximately 3 to 16% of glioblastoma multiforme (GBM) patients are considered long-term survivors (LTS: 3+ years). Objective Given the improved survival conferred by IDH1 mutations and the fact that these mutations are detected in 12% of newly diagnosed GBM cases, could long-term survivorship be explained by IDH1 mutation status? Our aim was to describe GBM LTS with IDH1 mutations and explore its association with overall survival (OS). Methods Records of 453 newly diagnosed adult GBM patients treated at a single institution from 2004 to 2010 were reviewed retrospectively for patients who survived at least 36 months postsurgery. Descriptive statistics for clinical characteristics, treatments received, and tumor biomarkers were reported. Estimates for progression-free survival (PFS) and OS were provided. Results Forty (8.8%) LTS GBM patients were identified, with a median age of 50 years and a median preoperative Karnofsky Performance Score (KPS) of 80. Most patients underwent near-total/gross-total resection (72.5%), postoperative radiation (97.5%), and adjuvant temozolomide (95%). PFS rates at 12, 36, 48, and 72 months were 67.5%, 40%, 32.7%, and 26.2%, respectively. Median OS has not yet been reached; however, the survival rate at 48 months was 62.1%. Among 35 patients with available tumor samples, only 8 (22.9%) had IDH1 mutations. No significant difference in median PFS was found between IDH1 mutation and wild-type patients (46.6 versus 26.3 months; p =0.45). Conclusions Less than a quarter of our patients' long-term survivorship was associated with favorable IDH1 status. Therefore, IDH1 status does not explain most of the long-term survivorship in the temozolomide era.

Gangliogliomas (GG) are rare tumors of the nervous system. Patient characteristics and clinical outcomes of low and high-grade GG have been difficult to elucidate in the adult population. This study aims to further elaborate on GG treatment and overall survival utilizing a larger cohort than previously published. The USA National Cancer Database was utilized to evaluate adult (age 18years and older) patients diagnosed with GG between 2004 and 2006. Descriptive statistics and Kaplan-Meier overall survival estimates were provided. A total of 198 adult GG patients were diagnosed between 2004 and 2006. Of these, 181 (91.4%) were low-grade and 17 (8.6%) high-grade GG. Overall, the median age was 36years; approximately 50% of patients were female, and 86.5% Caucasian. Most patients (59%) had near/gross total resection. Radiation and chemotherapy were prescribed in 18 (9.1%) and 11 (5.7%) patients, respectively. Radiation (64.7% versus 3.9%, p

Background and Purpose Expeditious treatment is critical in patients with aneurysmal subarachnoid hemorrhage (aSAH) due to the risk of rebleeding. This study aimed to define predictors of treatment delay among aSAH patients. Methods A retrospective study of the Nationwide Inpatient Sample database identified patients diagnosed with SAH between 2002 and 2007. Patient's characteristics such as age, gender, race, insurance, SAH severity, treatment (coil versus clip), and other factors were studied. The Cochrane-Armitage test was used to assess delayed care trends by procedure, time of treatment, and hospital volume. Multivariate logistic regression evaluated factors associated with treatment delays. Results A total of 38,827 patients were admitted between 2002 and 2007; 69.0% were women and 61% were white. The overall median age was 52 years. More patients underwent treatment with surgical clipping than with endovascular coiling (60.4% versus 39.6%, respectively). Overall, 74% of hospital admissions occurred on weekdays; the remaining 26% occurred on weekends. Multivariate analysis revealed that older age (odds ratio [OR]: 1.1; p = 0.0004) and surgical clipping versus endovascular coiling (OR: 1.3; p = 0.02) were independent predictors of delayed treatment (i.e., >2 days from admission). Nonwhite patients experienced greater treatment delays on weekdays compared with white patients (OR: 1.4; p = 0.01). Furthermore, patients treated in low-volume hospitals were significantly more likely to experience delays than those treated in higher volume hospitals (OR: 2.0; p = 0.007). Conclusions Risk factors associated with treatment delay in aSAH patients include older age, nonwhite race, surgical clipping, and admission to low surgical volume hospitals.

Background Controversy exists regarding the prognostic significance of cystic features in newly diagnosed glioblastoma multiforme (GBM) and the pathological origin of cystic GBMs. Objective To determine whether cystic GBMs develop from low-grade gliomas by evaluating IDH1 status and to evaluate the differences in overall survival between patients with cystic and noncystic tumors. Methods We retrospectively reviewed the records of 351 consecutive newly diagnosed adult GBM patients treated at our institution from October 1997 to November 2011; patients with >50% cystic tumor composition were further identified. IDH1 mutation was determined by immunohistochemical staining. Patient characteristics and treatment were reported for cystic and noncystic tumors separately. Overall survival was reported for cystic and noncystic cohorts by using the Kaplan-Meier estimates. Results Of 351 patients, 27 (7.7%) had cystic tumors and 324 (92.3%) had noncystic tumors. Tumor samples for patients with cystic GBMs were immunohistochemically analyzed for IDH1 mutations. Two (7.4%) of the 27 tumor samples were documented as having IDH1 mutations. Characteristics such as age, sex, perioperative Karnofsky Performance Status, tumor size, extent of resection, postsurgery radiation, and temozolomide therapy were comparable in the and noncystic cohorts. Patients in the cystic cohort had a median overall survival of 15.0 months compared with 18.2 months for the noncystic cohort (log-rank P = .77). Conclusion The low frequency of IDH1 mutation status in our cystic cohort strongly suggests that most newly diagnosed cystic GBMs do not arise from malignant transformation of previously undiagnosed low-grade gliomas. Furthermore, there is no difference in overall survival between patients newly diagnosed with cystic and noncystic GBMs.

Postoperative radiotherapy (RT) is utilized routinely in the management of anaplastic World Health Organization Grade III gliomas (AG), including anaplastic astrocytoma (AA) and anaplastic oligodendroglioma (AO). However, the optimal role of RT in elderly AG patients remains controversial. We evaluated the effectiveness of RT in elderly AG patients using a national cancer registry. The USA Surveillance, Epidemiology, and End Results database (1990–2008) was used to query patients over 70 years of age with AA or AO. Independent predictors of overall survival were determined using a multivariate Cox proportional hazards model. Among 390 elderly patients with AG, 333 (85%) had AA and 57 (15%) had AO. Approximately two-thirds of AA patients (64%) and AO patients (65%) received RT. Most AO patients (58%) and many AA patients (41%) underwent surgical resection; the remainder had biopsy. The median overall survival for all patients who underwent RT was 6 months (95% confidence interval [CI], 5–7 months) versus 2 months (95% CI 1–6) in patients who did not have RT. Patients who had gross total resection (GTR) plus RT had a median overall survival of 11 months (95% CI 7–14). Multivariate analysis for all patients showed that undergoing RT was significantly associated with improved survival (hazard ratio [HR] 0.52, p < .0001). AA tumor type (HR 1.37, p = .03) was associated with worse survival than AO tumor type; female sex (HR 0.59, p < .0001) and being married (HR 0.66, p = .002) significantly improved survival. Patients that underwent GTR had a significant reduction in the hazards of mortality compared to biopsy (HR 0.72, p = .04). Elderly AG patients undergoing RT had better overall survival compared to patients who did not receive RT. Treatment strategies involving maximal safe resection plus RT should be considered in the optimal management of AG in elderly patients.

BACKGROUND The prognosis of patients with anaplastic glioma tumors is relatively favorable compared with patients with glioblastoma multiforme. OBJECTIVE To estimate survival differences between anaplastic astrocytoma (AA) and anaplastic oligodendroglioma (AO) patients and factors associated with survival prognosis. METHODS A nationwide cohort of grade III glioma patients diagnosed between 1990 and 2008 was studied using the Surveillance, Epidemiology, and End Results registry. Multivariate Cox proportional hazard models evaluated the role of patient and clinical characteristics on overall survival. RESULTS A total of 1766 patients with AA and 570 patients with AO were studied. The median overall survival was 15 and 42 months among AA and AO patients, respectively. Age increments of 10 years implicated a 50% increase in mortality hazards among AA (hazard ratio [HR], 1.49; P < .001) and AO (HR, 1.51; P < .001) patients. Among AA patients, radiation (HR, 0.62; P < .001), surgery (vs biopsy; HR, 0.73; P < .001), female sex (HR, 0.87; P = .02), and married status (HR, 0.87; P = .02) were associated with a reduction in the hazard of mortality. Longer survival if diagnosed in 2000 relative to 1990 was observed (HR, 0.84; P = .004) in AA patients. Although surgery did not significantly improve survival among AO patients, gross total resection increased the median survival from 40 to 61 months (P = .001) in this cohort. CONCLUSION First-course radiation, younger age, female sex, treatment in recent years, and surgery were associated with improved survival in AA patients. In contrast, age was the most prominent predictor of survival in AO patients. Surgery alone did not seem to benefit AO patients, and gross total resection improved survival by 21 months.

Currently no studies directly compare effectiveness between interspinous devices (IDs) and laminectomy in lumbar spinal stenosis (LSS) patients.To compare reoperations, complications, and costs between LSS patients undergoing ID placement versus laminectomy.Retrospective comparative study.The MarketScan database (2007-2009) was queried for adults with LSS undergoing ID placement as a primary inpatient procedure.Reoperation rates, complication rates, and costs.Each ID patient was matched with a laminectomy patient using propensity score matching. Reoperations, complications, and costs were analyzed in patients with at least 18 months postoperative follow-up. The authors did not receive funding from any external sources for this study.Among 498 inpatients that underwent ID placement between 2007 and 2009; the average age was 73 years. The cumulative reoperation rates after ID at 12 and 18 months were 21% and 23%, respectively. The average inpatient hospitalization lasted 1.6 days with an associated cost of $17,432. Two propensity-matched cohorts of 174 patients that had undergone ID versus laminectomy were analyzed. Longer length of stay was observed in the laminectomy cohort (2.5 days vs. 1.6 days, p.0001), whereas ID patients accrued higher costs at index hospitalization ($17,674 vs. $12,670, p=.0001). Index hospitalization (7.5% vs. 3.5%, p=.099) and 90-day (9.2% vs. 3.5%, p=.028) complications were higher in the laminectomy cohort compared with the ID cohort. The ID patients had significantly higher reoperation rates than laminectomy patients at 12 months follow-up (12.6% vs. 5.8%, p=.026) and incurred higher cumulative costs than laminectomy patients at 12 months follow-up ($39,173 vs. $34,324, p=.289).Twelve-month reoperation rates and index hospitalization costs were significantly higher among patients who underwent ID compared with laminectomy for LSS.

Background Historically, whole brain radiation therapy (WBRT) has been the main treatment for brain metastases. Stereotactic radiosurgery (SRS) delivers high-dose focused radiation and is being increasingly utilized to treat brain metastases. The benefit of adding SRS to WBRT is unclear. This is an updated version of the original Cochrane Review published in Issue 9, 2012. Objectives To assess the efficacy of WBRT plus SRS versus WBRT alone in the treatment of adults with brain metastases. Search methods For the original review, in 2009 we searched the following electronic databases: CENTRAL, MEDLINE, Embase, and CancerLit in order to identify trials for inclusion in this review. For the first update the searches were updated in May 2012. For this update, in May 2017 we searched CENTRAL, MEDLINE, and Embase in order to identify trials for inclusion in the review. Selection criteria We restricted the review to randomized controlled trials (RCTs) that compared use of WBRT plus SRS versus WBRT alone for upfront treatment of adults with newly diagnosed metastases (single or multiple) in the brain resulting from any primary, extracranial cancer. Data collection and analysis We used the generic inverse variance method, random-effects model in Review Manager 5 for the meta-analysis. Main results We identified three studies and one abstract for inclusion but we could only include two studies, with a total of 358 participants in a meta-analysis. This found no difference in overall survival (OS) between the WBRT plus SRS and WBRT alone groups (hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.65 to 1.02; 2 studies, 358 participants; moderate-quality evidence). For participants with one brain metastasis median survival was significantly longer in the WBRT plus SRS group (6.5 months) versus WBRT group (4.9 months; P = 0.04). Participants in the WBRT plus SRS group had decreased local failure compared to participants who received WBRT alone (HR 0.27, 95% CI 0.14 to 0.52; 2 studies, 129 participants; moderate-quality evidence). Furthermore, we observed an improvement in performance status scores and decrease in steroid use in the WBRT plus SRS group (risk ratio (RR) 0.64 CI 0.42 to 0.97; 1 study, 118 participants; low-quality evidence). Unchanged or improved Karnofsky Performance Scale (KPS) at six months was seen in 43% of participants in the combined therapy group versus only 28% in the WBRT-alone group (RR 0.78 CI 0.61 to 1.00; P value = 0.05; 1 study, 118 participants; low-quality evidence). Overall, risk of bias in the included studies was unclear. Authors' conclusions Since the last version of this review we have identified one new study that met the inclusion criteria. However, due to a lack of data from this study we were not able to include it in a meta-analysis. Given the unclear risk of bias in the included studies, the results of this analysis have to be interpreted with caution. In our analysis of all included participants, SRS plus WBRT did not show a survival benefit over WBRT alone. However, performance status and local control were significantly better in the SRS plus WBRT group. Furthermore, significantly longer OS was reported in the combined treatment group for recursive partitioning analysis (RPA) Class I patients as well as patients with single metastasis. Most of our outcomes of interest were graded as moderate-quality evidence according to the GRADE criteria and the risk of bias in the majority of included studies was mostly unclear.