Treatment and survival of supratentorial and posterior fossa ependymomas in adults

Ependymoma is a rare primary brain or spinal cord tumor that arises from the ependyma, a tissue of the central nervous system. This study analyzed a large cohort of adult supratentorial and posterior fossa ependymoma tumors in order to elucidate factors associated with overall survival. We utilized the USA National Cancer Database to study adult World Health Organization grade II/III supratentorial and posterior fossa ependymoma patients treated between 1998 and 2011. Overall survival was estimated by the Kaplan–Meier method and factors associated with survival were determined using a multivariate Cox proportional hazards model. Among 1318 patients, 1055 (80.0%) had grade II and 263 (20.0%) anaplastic tumors located in the posterior fossa (64.3%) and supratentorial region (35.7%). Overall average age was 44.3 years, 48.0% of patients were female, 86.5% were Caucasian, and 36.8% underwent near/gross total surgical resection. Radiotherapy was given to 662 patients (50.8%) and 75 (5.9%) received chemotherapy. Older age at diagnosis (hazard ratio [HR] 1.51, p < 0.0001), high tumor grade (HR 1.82, p = 0.005), and large tumor size (HR 1.66, p = 0.008) were associated with poor survival. Females compared to males (HR 0.67, p = 0.03) and patients with posterior fossa tumors versus supratentorial (HR 0.64, p = 0.04) had a survival advantage. Our study showed that older patients, with supratentorial tumors, and high histological grade had an increased risk of mortality. A survival benefit was captured in females and patients with posterior fossa tumors. Adjuvant radiotherapy and chemotherapy did not confer a survival benefit among all patients, even after stratification by tumor grade or anatomical location.     

Treatment and survival of patients harboring histological variants of glioblastoma

It is unclear whether the survival difference observed between glioblastoma (GBM), giant cell glioblastoma (gcGBM), and gliosarcoma (GSM) patients is due to differences in tumor histology, patient demographics, and/or treatment regimens. The USA National Cancer Database was utilized to evaluate patients diagnosed with GBM, gcGBM, and GSM between 1998 and 2011. Kaplan–Meier survival estimates and Cox proportional hazards models were utilized to estimate overall survival. A cohort of 69,935 patients was analyzed; 67,509 (96.5%) of these patients had GBM, 592 (0.9%) gcGBM, and 1834 (2.6%) GSM. The median age for GBM and GSM patients was 61 versus 56 years for gcGBM (p < 0.0001). Higher extent of resection (p < 0.0001) and radiation (p = 0.001) were observed in gcGBM patients compared to other histologies. Multivariate analysis showed that gcGBM patients had a 20% reduction in the hazards of mortality (hazard ratio [HR] 0.80, 95% confidence interval [CI] 0.69–0.93) compared to GBM, while GSM patients trended towards higher hazards of mortality (HR 1.04, 95% CI 0.96–1.12) than the GBM cohort. Previous studies have suggested a disparity in the survival of patients with GBM tumors and their histological variants. Using a large cohort of patients treated at hospitals nationwide, this study found a 20% reduction in the hazards of mortality in gcGBM patients compared to GBM. Similarly, gcGBM patients had a 24% reduction in the hazards of mortality compared to the GSM cohort. GSM patients had a 3% increase in the hazards of mortality compared to GBM.     

Outcomes and patterns of care in adult skull base chondrosarcomas from the SEER database

This study aims to demonstrate survival rates and treatment patterns among patients with chondrosarcomas of the skull base using a large population database. Patients with skull base chondrosarcomas between 1973 and 2009 were identified from the USA Surveillance, Epidemiology, and End Results (SEER) database. Kaplan–Meier survival analysis was used to examine the effect of surgery and radiation on overall survival. We identified 226 patients with skull base chondrosarcomas. Median follow-up was 5.4 years. Median overall survival was 22 years, and 10 year survival was 68.2%. Most patients underwent surgery (92.5%). Few received radiation after diagnosis (38.1%). Ten year survival for all patients treated with surgery was significantly increased compared to those without surgery (69.3% versus 53.9%, p = 0.02). There was a significant difference in survival amongst treatment groups (p = 0.02), with median overall survival not yet reached for patients who received surgery and radiation (median follow-up 5.3 years), compared to 22 years for non-irradiated surgical patients. Surgery predicted better overall survival by univariate analysis (hazard ratio [HR] 0.420, p = 0.03). Female sex (HR 0.470, p = 0.011), younger age at diagnosis (HR 1.046, p < 0.0001), and later year of diagnosis (HR 0.949, p = 0.0006) were prognostic of improved survival in a multivariate model. In subgroup analysis of patients with documented tumor size, smaller tumor size (HR 1.054, p = 0.0003) and younger age (HR 1.021, p = 0.0067) predicted improved survival. This population based study further reaffirms the role of surgery as an effective treatment for skull base chondrosarcoma as previously reported in small case series. Adjuvant radiation may also confer survival benefit. Optimal treatment strategy has yet to be defined in the literature.     

Outcomes and patterns of care in adult skull base chordomas from the Surveillance,Epidemiology, and End Results (SEER) database

This study aims to demonstrate survival rates and treatment patterns among patients with chordomas of the skull base using a large population database. Patients with cranial chordomas between 1973 and 2009 were identified from the USA Surveillance, Epidemiology, and End Results (SEER) public use database. Kaplan–Meier analysis was used to examine the effect of surgery and radiation on overall survival. We identified 394 patients with histologically-confirmed cranial chordomas. Median survival was 151 months. Most patients (89.09%) underwent surgery. Less than half (44.92%) received radiation after diagnosis. Patients who underwent surgical resection survived significantly longer than those who did not undergo resection, regardless of other treatments (151 versus 81 months, p < 0.001). Ten year survival was lower among patients receiving radiation (44.8% versus 61.4%, p = 0.66). Surgery predicted better overall survival by univariate analysis (hazard ratio [HR] 0.603, p = 0.0293); younger age at diagnosis (HR 1.028, p < 0.001), and later year of diagnosis (HR 0.971, p = 0.0027) were prognostic of improved survival in a multivariate model. In subgroup analysis of patients with documented tumor size, smaller tumor size (HR 1.021, p = 0.0067), younger age (HR 1.031, p = 0.001), and treatment within a higher volume registry (HR 0.490, p = 0.0129) predicted improved survival. Surgical intervention offers survival benefit for cranial chordomas. Findings of decreased survival in patients receiving radiation may be associated with selection. Studies examining surgical extent of resection data and radiation details are needed to determine the impact of radiotherapy.     

Socio-demographic factors and their impact on the number of resections for patients with recurrent glioblastoma

Glioblastoma multiforme (GBM) is the most aggressive malignant brain tumour. Having a second or subsequent operation at recurrence may be a positive prognostic factor for survival. Recent studies suggest that socio-demographic variables may influence survival, raising the question whether surgical care differs based on these variables. We examined the relationship between selected socio-demographic variables and the number of repeat operations undergone by patients with recurrent GBM. Data from all patients diagnosed with GBM between 2001 and 2011 was obtained from a clinical database maintained across two institutions (one public, one private). The clinical and socio-demographic factors for patients who received one operation were compared to those who had two or more operations, using chi-squared analyses to determine statistical differences between groups. Socioeconomic status was measured using the Index of Relative Socioeconomic Advantage and Disadvantage scores. Of 553 patients, 449 (81%) had one operation and 104 (19%) had ?2 operations. Patients who had ?2 operations were significantly younger (median 55 years versus 64 years, p < 0.001), less likely to have multifocal (p = 0.043) or bilateral (p = 0.037) disease and more likely to have initial macroscopic resection (p = 0.006), than those who had only one operation. Socioeconomic status did not significantly differ between the groups (p = 0.31). Similarly, there was no significant difference between the number of operations in patients from regional versus city residence and public versus private hospital. This is reassuring as it suggests similar surgical management options are available for patients regardless of socio-demographic background.     

Preoperative statin use is not associated with improvement in survival after glioblastoma surgery

Cohort studies have suggested that the use of statins is associated with decreased risk of glioma formation and mortality. Here, a cohort of patients with glioblastoma multiforme (GBM) was analyzed to further investigate associations between preoperative use of statins and recurrence, and progression free and overall survival. Patients who had surgery for GBM (N = 284) were followed up for a median of 18.1 months. Seventy-eight patients were taking statins preoperatively while the rest were not. Cox proportional hazards models adjusted for several covariates of interest were applied before and after propensity score matching. Compared with statin users, those not taking the lipid-lowering drugs had similar progression free survival before (hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.70–1.26; p = 0.68) and after propensity score matching (HR 0.95, 95% CI 0.67–1.35; p = 0.68). Mortality was similar between both groups of patients before (HR 0.94, 95% CI 0.70–1.22; p =  0.73) and after propensity score matching (HR 1.13, 95% CI 0.78–1.64; p = 0.49). Age and dexamethasone use were independent prognostic factors of survival. Contrary to previously published evidence, this study could not find an association between preoperative statin use and longer survival in GBM patients. Due to the small number of patients and retrospective nature of the study, further work is needed to understand the role of perioperative statins in GBM patients.     

Performance status during and after radiotherapy plus concomitant and adjuvant temozolomide in elderly patients with glioblastoma multiforme

For elderly patients with glioblastoma multiforme (GBM), radiotherapy plus concomitant and adjuvant temozolomide has resulted in longer survival. We investigated patient performance status, treatment-related toxicity and overall survival (OS) following treatment. Twenty patients aged 70 years or older with a newly diagnosed GBM were treated with radiotherapy (60 Gy in 16 patients and 40 Gy in four patients) plus concomitant and adjuvant temozolomide. We assessed age, the extent of tumor removal, and initial performance status as possible prognostic factors for OS and good performance status following treatment. The median OS was 11.8 months (95% confidence interval [CI], 8.7–14.8). The median time for patients to reach an Eastern Cooperative Oncology Group (ECOG) performance status grade 2 was 3.0 months (95% CI, 2.4–3.5), and the time to ECOG performance status grade 3 was 5.8 months (95% CI, 1.6–9.9). World Health Organization grade III or grade IV toxicity was observed in four patients (20%), leucopenia and thrombocytopenia was noted in two patients, and major infection occurred in two patients. Univariate analysis showed a significantly longer OS (p = 0.003) and a longer time with good performance status for gross total removal (GTR) (p = 0.003). An initial good performance status was related to a good performance status during and after treatment (p = 0.003). Based on multivariate analysis, GTR was significantly associated with a longer OS (hazard ratio [HR] = 0.236; 95% CI, 0.060–0.922, p = 0.038) and a good performance status (HR = 0.124; 95% CI, 0.022–0.693, p = 0.017). During and after treatment, elderly patients with GBM frequently exhibited an early deterioration of performance status. Therefore, in light of a rapidly fatal illness, elderly patients should be treated to preserve and respect their quality of life.     

Multiple resections and survival of recurrent glioblastoma patients in the temozolomide era

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 < 0.0001) and had higher perioperative Karnofsky Performance Status scores (p < 0.0001) than single resection patients. The median OS in months was 21.1, 25.5, and 29.0 for patients who had one, two, and three or more resections, respectively (Wilcoxon p = 0.03). In a confounder-adjusted multivariate model, patients with multiple resections did not have significantly improved survival (p = 0.55). Older age was strongly associated with poorer OS (hazard ratio 1.34, p < 0.0001). Age at diagnosis was the only predictor of survival for recurrent GBM patients. After adjusting for age at diagnosis, multiple resections were not an independent predictor of OS in our glioblastoma cohort treated in the temozolomide era.     

Early adjuvant radiotherapy in the treatment of atypical meningioma

Atypical meningiomas have a greater propensity to recur than benign meningiomas and the benefits of early adjuvant radiotherapy are unclear. Existing studies report conflicting results. This retrospective cohort study evaluated the role of early adjuvant radiotherapy following surgical resection of atypical meningioma. A triple center case-note review of adults with newly-diagnosed atypical meningiomas between 2001 and 2010 was performed. Pathology diagnosis was made according to the World Health Organization classification in use at the time of surgery. Patients with multiple meningiomas, neurofibromatosis type 2 and radiation-induced meningiomas were excluded. Extent of resection was defined as gross total resection (GTR; Simpson Grade I–III) or subtotal resection (STR; Simpson Grade IV–V). Survival analysis was performed using the Kaplan–Meier method. One hundred thirty-three patients were identified with a median age of 62 years (range 22–86 years) and median follow-up of 57.4 months (range 0.1–152.2 months). Tumors were mostly located in the convexity (50.4%) or falcine/parasagittal regions (27.1%). GTR (achieved in 85%) was associated with longer progression free survival (PFS) (5 year PFS 81.2% versus 40.08%, log-rank = 11.117, p = 0.001) but not overall survival (OS) (5 year OS 76.6% versus 39.7%, log-rank = 3.652, p = 0.056). Following GTR, early adjuvant radiotherapy was administered to 28.3% of patients and did not influence OS (5 year OS 77.0% versus 75.7%, log-rank = 0.075, p = 0.784) or PFS (5 year PFS 82.0% versus 79.3%, log-rank = 0.059, p = 0.808). Although extent of resection emerged as an important prognostic variable, early adjuvant radiotherapy did not influence outcome following GTR of atypical meningiomas. Prospective randomized controlled trials are planned.     

Effectiveness of radiotherapy for elderly patients with anaplastic gliomas

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.     

The use of isoflurane and desflurane as inhalational agents for glioblastoma surgery. A survival analysis

BackgroundSeveral studies have examined the impact of anesthetics on cancer recurrence. Isoflurane but not desflurane has protumoral effects. We hypothesize the use of isoflurane but not desflurane during surgery for primary GBM is an independent predictor of disease progression and mortality.Methods378 adult patients were included in the study. The progression free survival (PFS) and overall survival (OS) rates at 1 and 5 years were compared in patients who had either desflurane or isoflurane alone or in combination with propofol infusion. Multivariate analyses were conducted to test the association between preoperative, intraoperative and postoperative hyperglycemia with PFS and OS.ResultsKaplan–Meier curves demonstrated similar survival in patients who had either desflurane or isoflurane. The use of a propofol infusion during surgery did not affect survival. Univariate analysis demonstrated that age, body mass index and the adjusted Charlson comorbidity score were associated with reduced survival. The multivariate analysis confirmed that age and BMI but not the type volatile anesthetic use were independent prognostic factors for PFS (HR, 95%CI: 1.07, 0.85–1.37, 9 = 0.531) and OS (HR, 95%CI: 1.13, 0.86–1.48, p = 0.531).ConclusionThe use of isoflurane or desflurane during GBM surgery is not associated with reduced PFS or OS.     

Prognosis by tumor location in adults with intracranial ependymomas

Intracranial ependymomas are rare tumors in adults. Thus, factors affecting prognosis are poorly understood. We performed a study to investigate whether tumor location is an important prognostic factor in adults who undergo surgery for intracranial ependymomas. PubMed was searched to identify studies that reported clinical outcomes in adult patients with intracranial ependymoma. Data were extracted for patient and tumor characteristics, extent of resection, progression-free survival (PFS), and overall survival (OS). Tumors were categorized as supratentorial or infratentorial and extraventricular or intraventricular. Presenting clinical features and tumor characteristics were tabulated. Kaplan–Meier and multivariate Cox regression survival analyses were performed to determine PFS and OS by tumor location. Extent of resection was also analyzed by tumor location. A total of 183 patients were included in the meta-analysis. Patients presented at a mean of 8.2 months with a myriad of clinical features. The mean tumor size was 3.38 cm, and 19.3% of tumors were cystic. Supratentorial tumors were most commonly located in the frontal and parietal lobes, and infratentorial tumors in the fourth ventricle. Supratentorial tumors demonstrated significantly poorer PFS (p < 0.001) and OS (p = 0.003) than infratentorial tumors, despite a higher rate of gross total resection (GTR) for the supratentorial tumors (72.6% versus 42.1%). Extraventricular ependymomas displayed significantly poorer PFS than intraventricular ependymomas (p = 0.009). In summary, supratentorial ependymomas have significantly poorer PFS and OS than their infratentorial counterparts, despite being more conducive to GTR, suggesting increased clinical aggressiveness. Extraventricular location is also associated with significantly poorer PFS than intraventricular location.     

Prognostic factors and survival in primary adult high grade brainstem astrocytoma: A population based study from 1973–2008

Adult brainstem astrocytomas are a rare and heterogeneous group of malignancies. Most reports represent low-grade gliomas. This study used the Surveillance, Epidemiology and End Results (SEER) database to analyze the association between survival and demographic factors, tumor histology, and treatment characteristics among adult patients with high-grade brainstem astrocytoma (HGBSA). Adult patients with histologically confirmed diagnoses of primary HGBSA were studied. In univariate and multivariate analysis, we investigated the effect of demographics, tumor histology and treatment modality on survival. Overall median survival in the cohort of 240 adult patients was 7 months, with 1, 2, 5 and 10 year survival rates of 33.2%, 19.7%, 10.1%, and 8.3%, respectively. Age >50 years (hazard ratio [HR] 1.98, 95% confidence interval [CI] 1.45–2.70, p < 0.001) and grade IV versus grade III tumor (HR 1.61, 95% CI 1.15–2.26, p = 0.006) were associated with statistically significant increased mortality in multivariate analyses. Surgical intervention trended toward association with lower mortality (HR 0.68, 95% CI 0.47–1.01, p = 0.055). Our findings suggest that in patients with HGBSA, younger age and lower-grade histology are associated with better prognosis. Surgical intervention trended towards a significant association with better outcome, while radiation treatment was not associated with a statistically significant benefit in survival.     

Phase reversal technique decreases cortical stimulation time during motor mapping

Neurophysiologic mapping of the primary motor cortex (PMC) is commonly used in supratentorial surgery. Electrical cortical stimulation is guided by anatomic landmarks towards the precentral gyrus, with recording of the triggered primary motor responses (TPMR) in the contralateral hemibody. Thus, factors such as distortion of the pericentral anatomy, small surgical fields, brain shifts and miscalibrated neuronavigational systems may lengthen the process and result in unnecessary stimulations, increasing the probability of triggering seizures. We hypothesized that central sulcus localization via the median somatosensory evoked potentials phase reversal technique (MSSEP PRT) accurately guides the surgeon, resulting in prompt identification of the PMC with minimal electrical stimulation. Multivariate Cox regression was used to study the impact of MSSEP PRT on time spent performing electrical cortical stimulation to TPMR. The analysis was adjusted for presence of increased cortical excitability, high motor thresholds, lesions close to PMC and fMRI data, in 100 consecutive standardized motor mapping procedures for brain tumor resection and epilepsy surgery. Phase reversal and change morphology of the recorded somatosensory evoked potentials quadrupled (hazard ratio [HR] 4.13, p < 0.0001) and doubled (HR 2.14, p = 0.02) the rate of obtaining TPMR, respectively. A 1 mA increase in motor threshold decreased the rate by 9% (HR 0.91, p = 0.0002). Afterdischarges triggered before TPMR and lesions in close proximity to PMC decreased the rate of TPMR by 76% (HR 0.23, p < 0.0001) and 48% (HR 0.52, p = 0.04), respectively. Informative PRT decreases stimulation time. Afterdischarges triggered before TPMR, high motor thresholds and lesions close to the PMC increase it.     

Early postoperative emergency department presentation predicts poor long-term outcomes in patients surgically treated for meningioma

Previous authors have identified a number of factors that predict morbidity, mortality, and recurrence in patients undergoing resection of a meningioma. We sought to study a novel potential prognostic indicator: early postoperative visit to the emergency department (ED). We conducted a retrospective cohort study on 239 patients who underwent a meningioma resection at our institution between 2001 and 2013 with over 3 months of follow-up postoperatively. All postoperative entries in the medical record were reviewed to identify any ED visit with a neurologic or wound-related complaint within a 90 day postoperative period. The relationships between ED presentation, tumor grade, and extent of surgical resection with future risk of operative recurrence and mortality were analyzed using Fisher’s exact test. Variables associated with increased risks of mortality or operative recurrence in a univariate analysis were then included in the multivariate logistic regression model. Patients with a postoperative ED visit were found to be significantly more likely to die during the follow-up period (23.0% versus 4.85%, p < 0.0001) or develop an eventual operative recurrence (12.2% versus 3.0%, p = 0.0131). Postoperative ED presentation was found to be associated with a higher risk of mortality and operative recurrence independent of pathological tumor grade (p < 0.0001 and p = 0.0102, respectively). Presentation to the ED is associated with significantly higher rates of future operative recurrence and mortality in patients with recent meningioma resections. This poor prognostic relationship is independent of tumor pathological grade. Increased vigilance and follow-up may be warranted in such patients.     

A meta-analysis of bevacizumab alone and in combination with irinotecan in the treatment of patients with recurrent glioblastoma multiforme

Combining bevacizumab with irinotecan is a new chemotherapy regimen for patients with recurrent glioblastoma multiforme (GBM). Recent phase II trials suggest that this combined chemotherapy is beneficial to patients, but the subsequent adverse events may lead to treatment discontinuation. No comparison has yet demonstrated conclusively that the combined chemotherapy is more beneficial than single-agent chemotherapy. Thus, a meta-analysis was conducted to assess the efficacy and safety of bevacizumab compared to bevacizumab combined with irinotecan for the treatment of recurrent GBM. A total of 480 patients were included in the study, with 183 patients (38.1%) in the bevacizumab group and 297 patients (61.9%) in the bevacizumab plus irinotecan group. The median overall survival was 8.63 months (95% confidence interval [CI], 8.54–8.72 months) and 8.91 months (95% CI, 8.69–9.13 months), respectively. The mean objective response rate (complete response plus partial response rate) was 33.9% (95% CI, 18.1–52.1%) and 45.8% (95% CI, 28.2–66.7%), respectively. The 6-month progression-free survival rates (PFS-6) were 38.8% (95% CI, 18.8–57.0%) and 48.3% (95% CI, 25.4–54.3%), respectively. The rate of discontinuation was 5.5% and 20.0%, respectively. Compared with patients treated with bevacizumab only, those in the bevacizumab plus irinotecan group had higher PFS-6 (p = 0.046), objective response (p = 0.013) and rate of discontinuation (p = 0.000) but there was no statistically significant difference in overall survival between the groups (p = 0.487). Thus, although the combination of bevacizumab and irinotecan may increase the rate of discontinuation, it provided no obvious improvement in overall survival in patients with recurrent GBM. Therefore, the benefits of drug combination are outweighed by the treatment discontinuity and quality of life effects of drug toxicity and should be considered on an individual patient basis only.     

Feasibility and outcomes of intravenous thrombolysis 3–4.5 hours after stroke in Chinese patients

The time window for intravenous (IV) recombinant tissue plasminogen activator (rt-PA) treatment in acute ischemic stroke (AIS) patients has been extended to 4.5 hours. But little is known about the safety and efficacy of IV rt-PA treatment in the 3–4.5 hour time window in Chinese patients with AIS. A total of 119 patients who were treated with standard IV rt-PA therapy within 4.5 hours after symptom onset were included in this study: 85 were treated within 0–3 hours and 34 were treated within 3–4.5 hours. Favorable outcome was defined as a modified Rankin scale (mRS) score of 0–1 at 6 months. The safety of IV rt-PA treatment was assessed by the rate of mortality, symptomatic intracerebral hemorrhage (SICH) and other common complications. There were no significant differences in SICH rates (2.94% versus 2.35%; p = 0.85) at 24–36 hours, mortality (5.88% versus 3.53%; p = 0.56), other complications (14.71% versus 11.76%; p = 0.66), National Institutes of Health Stroke Scale (NIHSS) score improvement at 24 hours (41.18% versus 45.88%; p = 0.64) and favorable mRS at 6 months (52.94% versus 54.12%; p = 0.91) between the two time window groups. Multivariate analysis showed that advanced age, lower admission NIHSS score and shorter time from symptom onset to treatment were associated with a favorable clinical outcome. This finding showed an additional 29% of patients received IV rt-PA because of the treatment window expansion to 4.5 hours. IV rt-PA was feasible and safe for treating AIS patients in the 3–4.5 hour time window in our Chinese population.     

Survival outcomes of giant cell glioblastoma: Institutional experience in the management of 20 patients

Giant cell glioblastoma (GCG) is a rare subtype of glioblastoma (GBM) that is believed to carry an improved prognosis. However, given the rarity of this tumor, best management practices for GCG have yet to be ascertained. Here, we present our experience in managing GCG tumors at the University of California, San Francisco. Patients were retrospectively identified through chart review, and data pertaining to patient demographics, treatment plans, and follow-up were extracted from existing medical records. Overall survival (OS) and progression-free survival (PFS) were the primary and secondary endpoints, respectively. In sum, we identified 22 patients who were managed or followed for GCG. Most patients (78%) initially underwent subtotal resection as primary treatment for their tumor, and most also received post-operative adjuvant therapy (90%), with radiation being the most frequently administered modality (85%). Within this institutional cohort, median OS and PFS were 15.4 months and 5.7 months, respectively. On multivariate survival analysis, age (p = 0.84), sex (p = 0.05), and adjuvant radiation plus temozolomide (p = 0.12) were not associated with prolonged OS. However, adjuvant radiation plus temozolomide was associated with longer PFS (p = 0.01), and patients receiving this therapy demonstrated a median PFS of 32.9 months versus 13.1 months. These findings confirm the comparatively improved prognosis of GCG over GBM. Moreover, they suggest that extent of resection may not significantly delay recurrence or extend survival, and that combination radiation with temozolomide may represent the optimum adjuvant paradigm to delay tumor progression.     

Clinical trial participation and outcome for patients with glioblastoma: Multivariate analysis from a comprehensive dataset

Glioblastoma multiforme (GBM) is the most common malignant brain tumor in adults. Although multiple clinical and tumor-related variables affect survival outcomes, the effect of clinical trial participation has not been explored. The aim of this study was to determine whether clinical trial participation improves outcome for patients with GBM. Data from patients with GBM were accessed from a dataset collected over 12 years (1998–2010) at two institutions. Univariable and multivariate logistic regression analyses were performed to look for relationships between clinical trial participation, other baseline clinical and sociodemographic variables and overall survival (OS). In total, 542 patients were identified and included in the analysis; median age was 62 years. Sixty-one patients (11%) were enrolled in a clinical trial. Clinical trial enrollment was associated with improved median survival (14.5 months compared to 6.3 months, p < 0.001) and this difference remained significant in multivariate analysis (hazard ratio 0.67, p = 0.046). Age, poor performance status and operation type were also independent predictors for OS in multivariate analysis. Disease site, socioeconomic status and co-morbidity did not affect survival outcome. This is the first study in patients with GBM to suggest a survival benefit from clinical trial participation, independent of age and performance status; while also confirming the importance of other previously reported prognostic factors. This should encourage clinicians to offer trial therapies to patients with GBM and encourage patients to participate in available studies.     

Primary lesion location influences postoperative survival in patients with metastatic colorectal spinal lesions

Spinal metastasis from colorectal cancer occurs rarely. However, with increasing incidence of colorectal cancer in the setting of improved therapies, physicians are more likely to encounter such patients. We performed a retrospective review of patients who underwent spine surgery for metastatic colorectal cancer from 2005–2011. Preoperative, operative and postoperative factors; functional outcome as determined by Karnofsky Performance Status (KPS) and modified Rankin scale (mRS); and survival were recorded. Univariate analysis was performed, with patients stratified into two groups based on the position of the primary cancer, either proximal (colon) or distal (rectum) to the rectosigmoid junction. Fourteen patients, with a median age of 52 (interquartile range [IQR] 48–66) years, underwent 21 spine surgeries for metastatic colorectal cancer. Pain was the common presenting symptom (n = 11, 79%), followed by motor weakness (n = 8, 57%). Twenty-seven postoperative complications occurred in 11 (52%) patients. Baseline KPS and mRS remained stable in four (29%), improved in two (14%), worsened in six (43%), and was unknown in two (14%) at last follow-up. Patients with spinal metastasis from a rectal primary (n = 6) had a significantly longer survival compared to those with a colon primary (n = 8), with a median survival of 84 (IQR 56–103) versus 26 (IQR 19–44) months after primary diagnosis (p = 0.002), 19 (IQR 13–27) versus five (IQR 3–9) months after spine metastasis diagnosis (p = 0.010), and six (IQR 4–14) versus three (IQR 2–4) months after surgery (p = 0.030). Patients with spinal metastasis arising from rectal primary lesions display longer survival compared to colon lesions. Consideration of these factors is essential to appropriately assess surgical candidacy.