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.     

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.     

Combined modality treatment of newly diagnosed glioblastoma multiforme in a regional neurosurgical centre

The “local experience” of the Stupp protocol was examined in the treatment of patients with newly diagnosed glioblastoma multiforme (GBM) with particular emphasis given to the extent of surgical resection and its effect on survival. Thirty-one patients with newly diagnosed GBM who underwent combined modality treatment according to the Stupp protocol were assessed retrospectively. Variables assessed were the extent of surgery, size and site of the tumour, age and performance status. Primary end points were overall survival (OS) and progression-free survival (PFS). Median OS was 33 months for macroscopic tumour resection (9 patients; 29%), 15 months for debulking (15; 48%) and 9 months for biopsy (7; 22%). Macroscopic tumour resection resulted in significantly improved OS and PFS compared to the two less radical surgical options (p < 0.001). Patients with GBM undergoing maximal resection of the tumour followed by adjuvant radiotherapy and chemotherapy have an improved survival compared to patients undergoing either subtotal resection or biopsy alone. This statistically significant survival benefit was achieved in a regional neurosurgical centre with minimal additional toxicity.     

Outcome and prognostic factors in adult cerebellar glioblastoma

Cerebellar glioblastoma multiforme (GBM) occurs rarely in adults, accounting for 0.4–3.4% of all GBM. Current studies have all involved small patient numbers, limiting the clear identification of prognostic factors. Additionally, while few studies have compared cerebellar GBM to their supratentorial counterparts, there is conflicting data regarding their relative prognosis. To better characterize outcome and identify patient and treatment factors which affect survival, the authors analyzed cases of adult cerebellar GBM from the Surveillance, Epidemiology, and End Results database. A total of 247 adult patients with cerebellar GBM were identified, accounting for 0.67% of all adult GBM. Patients with cerebellar GBM were significantly younger than those with supratentorial tumors (56.6 versus 61.8 years, p < 0.0001), but a larger percentage of patients with supratentorial GBM were Caucasian (91.7% versus 85.0%, p < 0.0001). Overall median survival did not differ between those with cerebellar and supratentorial GBM (7 versus 8 months, p = 0.24), with similar rates of long-term (greater than 2 years) survival (13.4% versus 10.6%, p = 0.21). Multivariate analysis revealed age greater than 40 years (hazard ratio [HR]: 2.20; 95% confidence interval [CI]: 1.47–3.28; p = 0.0001) to be associated with worse patient survival, while the use of radiotherapy (HR: 0.33; 95% CI: 0.24–0.47; p < 0.0001) and surgical resection (HR: 0.66; 95% CI: 0.45–0.96; p = 0.028) were seen to be independent favorable prognostic factors. In conclusion, patients with cerebellar GBM have an overall poor prognosis, with radiotherapy and surgical resection significantly improving survival. As with supratentorial GBM, older age is a poor prognostic factor. The lack of differences between supratentorial and cerebellar GBM with respect to overall survival and prognostic factors suggests these tumors to be biologically similar.     

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.     

Survival analysis of 205 patients with glioblastoma multiforme: Clinical characteristics,treatment and prognosis in China

To study the clinical characteristics, treatment and prognosis of patients with glioblastoma multiforme (GBM) in China, we retrospectively analyzed 205 Chinese patients with histologically proven GBM. A univariate analysis of prognosis factors for survival time was performed and significant factors were tested in a multivariate analysis using the Cox regression method. Median overall survival time was 12.0 months (95% confidence interval [CI] 11.0–13.1 months). Survival rates after diagnosis were 82% at 6 months, 52% at 12 months, 27% at 18 months and 17% at 24 months. Age, preoperative Karnofsky’s performance status score and tumour location were independent preoperative predictors of prognosis and among the treatment methods of GBM, radiotherapy was the strongest predictor of prognosis followed by radical surgery and chemotherapy. The median survival time post diagnosis for Chinese patients is comparable to the 11.0–15.9 month range observed in western patients. The data suggest a lack of ethnic differences in GBM prognosis of Chinese and western patients.     

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.     

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.     

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.     

Clinical outcome with gamma-knife surgery or surgery for brain metastases from colorectal cancer

The aim of this study was to investigate the clinical outcomes after gamma knife surgery (GKS) or surgery as the first treatment for brain metastases in colorectal cancer (CRC). Of the 4350 patients diagnosed with CRC at our institution identified from 1987 to 2009, 27 patients who underwent GKS (GKS group) and 11 who underwent surgery (surgery group) were included. The oncologic outcomes were compared between the two groups. Local control was significantly better in the surgery group than in the GKS group (90% versus [vs.] 71.4%, respectively; p = 0.006). The rate of symptom relief after 3 months was significantly higher in the surgery group than in the GKS group (72.7 vs.18.5%, respectively; p = 0.005). The median survival after GKS was 5.6 months and surgery was 16.2 months. In multivariate analysis, controlled primary tumor (p = 0.038) and solitary metastasis (p = 0.028) were correlated with prolonged overall survival, whereas surgery (p = 0.034) was associated with longer local control. Surgery for brain metastasis from CRC is more advantageous in local control and neurologic symptom palliation than GSK. In multivariate analysis, overall survival was associated with controlled primary tumor and solitary metastasis.     

Gefitinib and erlotinib for non-small cell lung cancer patients who fail to respond to radiotherapy for brain metastases

Survival and treatment options are limited for patients with brain metastases arising from non-small cell lung cancer (NSCLC). We evaluated erlotinib and gefitinib as salvage treatments for NSCLC patients with brain metastases that failed to respond to radiotherapy in a retrospective study. Survival was estimated using Kaplan–Meier analysis and log-rank tests. Multivariable predictors were assessed using the Cox proportional hazards model. Epidermal growth factor receptor (EGFR) mutations were assessed in part using sequencing methods. The 103 NSCLC patients who were treated with gefitinib or erlotinib for salvage treatment for brain metastases between January 2005 and December 2011 had overall objective response rates (ORR) of 11.7%, disease control rates (DCR) of 53.4%, 3.6 months of median progression-free survival (PFS), and 7.5 months of median survival. Intracranial disease had an ORR of 11.7% and a DCR of 70.9%. Extracranial disease had an ORR of 8.7% and a DCR of 66.0%. Nine patients (of 22 tested) were documented with EGFR mutations (five with deletion in exon 19 and four with L858R in exon 21). The median PFS for EGFR mutation patients was 9.0 months, versus 3.1 months for wild-type patients (p = 0.001). The recursive partitioning analysis class was the only factor predictive of PFS using univariate analyses and was associated with survival in the multivariate analysis. Our retrospective data suggest a potential role for gefitinib and erlotinib in advanced NSCLC patients with brain metastases which have failed to respond to radiotherapy. Patients with EGFR mutations benefited most from treatment.     

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.     

Efficacy of bevacizumab therapy in recurrent malignant gliomas in relation to the prior recurrence pattern or tumor location

Although promising preliminary results have been widely observed with bevacizumab for recurrent malignant gliomas, many unanswered questions remain to be resolved to achieve an optimal outcome. No predictive biomarkers of a survival benefit from bevacizumab have been established, and no consensus exists about the response or survival benefit regarding the prior recurrence pattern or tumor location. Here we retrospectively analyzed the clinical benefit from bevacizumab for recurrent malignant gliomas in relation to the prior recurrence pattern or tumor location. Thirty-one consecutive patients with recurrent malignant gliomas who were treated with bevacizumab were investigated. The treatment response and survival benefit from bevacizumab were analyzed in association with age, sex, Karnofsky performance status, prior pathological diagnosis, prior recurrence pattern, primary location of tumor, recurrence status, and expression of angiogenic and hypoxic markers. The group with leptomeningeal dissemination had a significantly shorter median overall survival with bevacizumab (OS_Bev) (6.0 months, 95% confidence interval (CI) 1.4–10.7) compared to those in the local/distant group (11.8 months, 95% CI 6.1–17.4). The median OS_Bev of the infratentorial tumor group and supratentorial tumor group were 9.2 months (95% CI 5.0–13.4) and 10.4 months (95% CI 6.6–14.3), respectively. With multivariate analysis, the prior recurrence pattern was the only independent prognostic factor of OS_Bev. Patients with leptomeningeal dissemination of recurrent malignant glioma experienced minimal benefit from bevacizumab. Therefore, in the context of cost effectiveness, bevacizumab is not recommended for patients with leptomeningeal dissemination.     

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.     

Communicating hydrocephalus associated with surgery or radiosurgery for vestibular schwannoma

The purpose of this cohort study was to determine the incidence of communicating hydrocephalus (HCP) associated with the treatment of vestibular schwannoma (VS). Between January 2002 and December 2007, a total of 291 patients diagnosed with VS underwent either surgical resection or gamma knife radiosurgery (GKS). By analyzing the clinical data and MRI scans, we retrospectively reviewed and compared the incidence of communicating HCP between the two treatment modalities. During their clinical course, 10 of 291 patients developed new communicating HCP (3.4%): nine of 90 patients who were treated using GKS (10%) developed communicating HCP post-procedure, while only one of 146 patients who underwent surgical resection alone (0.68%) developed subsequent communicating HCP (p = 0.002). The median event-free survival from the initial treatment with GKS to the development of communicating HCP was 22 months (range: 7–55 months). Three patients who developed new communicating HCP in the GKS group required surgical intervention, including ventriculoperitoneal shunt or endoscopic third ventriculostomy. There was no significant correlation between sex or tumor size and the incidence of communicating HCP in the GKS group (p > 0.05). We found a relatively high incidence of communicating HCP after treatment in patients with VS, particularly for those patients in the GKS group. Therefore, the risk of communicating HCP should be considered in the follow-up of patients who undergo GKS for treatment of VS.     

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.     

Central nervous system lymphoma in immunocompetent patients: The North Shore-Long Island Jewish Health System experience

Of the 74 immunocompetent patients diagnosed between July 2004 and June 2011 at the North Shore University Hospital and Long Island Jewish Medical Center with primary central nervous system lymphoma, 71 (95.9%) had diffuse large B-cell lymphomas (DLBCL). The median patient age was 68 years (range: 19–87 years) with a slight male preponderance (1.1:1). The overall median survival time was 21 months. For patients older than 70 years, the median survival time was 8 months while for those 70 years or younger, the median survival time was 27 months (p < 0.01). Female patients had a worse prognosis than male patients (p < 0.05, median survival time, 17 months compared to 23 months). We had enough data from 52 of these 71 patients to define the lymphomas as either germinal center B-cell-like (GCB) or activated B-cell-like (ABC) DLBCL. Of these 52 patients, 42 (80.8%) had ABC DLBCL while only 10 (19.2%) had GCB DLBCL. The patients in the GCB subgroup seemed to survive longer than the patients in the ABC subgroup, although the difference did not reach statistical significance. No statistically significant difference in overall survival was seen between patients with BCL-6 positive or negative DLBCL; or between patients with BCL-2 positive or negative DLBCL.     

Cumulative volumetric analysis as a key criterion for the treatment of brain metastases

BackgroundRecent studies have demonstrated diminished cognitive function, worse quality of life, and no overall survival benefit from the addition of adjuvant whole brain radiation therapy (WBRT) to stereotactic radiosurgery (SRS) in the management of brain metastases. This study analyzes the treatment outcome of SRS, specifically CyberKnife Radiosurgery, based on the total tumor volume compared to the absolute number of lesions.MethodsA retrospective analysis of hospital records at Virginia Hospital Center for patients with brain metastases who underwent CyberKnife Radiosurgery between June 2008 and June 2014 was performed. Previous treatment history, metastatic tumor dimensions, and outcomes were recorded. Predictors of neurological defects, local tumor progression, and overall survival were assessed with univariate and multivariate analysis.ResultsWe identified 130 adult patients with a median age of 61.5 years and a median follow-up of 7.1 months. Unfavorable outcomes such as death, tumor progression, or neurological defect showed correlation with cumulative tumor volume greater than the median volume of 7 cc (p < 0.05). Worsening neurological defects showed an association with an increased number of lesions (p < 0.02) and age (p < 0.05). For local tumor progression, patients who have received WBRT were less likely to progress (.74, 95% CI, .48, 1.10), while those who received chemotherapy (1.48 95% CI, .98, 2.26), or surgery (1.56 95%, CI .98, 2.47) without WBRT were more likely to progress.ConclusionsOur data suggest that a cumulative tumor volume greater than 7 cc correlates with worse outcomes following CyberKnife Radiosurgery. In addition, WBRT appears to have a role in improved survival for patients with increased tumor burden. A prospective study is warranted to validate these findings.     

Cholangiocarcinoma with spinal metastasis: Single center survival analysis

The aim of this study was to perform a survival analysis of Cholangiocarcinoma (CCA) with spinal metastases. 55 cases of CCA with spinal metastases were retrospectively reviewed. We recorded age, sex, Kanofsky performance score, Frankel scale, number and region of affected vertebrae, presence of appendicular bone metastases, treatment received, and survival time; then performed a survival analysis. Overall median survival was 4 months (95%CI, 2.89–5.11). Frankel A had the poorest survival (2 months—95%CI, 1.15–2.85) compared to Frankel C and D (P = 0.004 and <0.001, respectively). One-level spinal metastasis had the longest survival (8 months—95%CI, 5.98–10.02) compared to two-level and more than two-level involvement (P = 0.036 and 0.001, respectively). The higher Kanofsky score had the longer survival (11 months—95%CI, 9.61–12.39) compared with the low and moderate score groups (P < 0.001 and 0.012, respectively). Radiation therapy had a survival of 6 months (95%CI, 3.41–8.59), significantly longer than the 3 months for palliative spine surgery and 2 months for palliative treatment alone. CCA resection and palliative spine surgery—when performed together and/or combined with other adjuvant treatment(s)—had a survival time of longer than 9 months. In conclusion, CCA with spinal metastases had a poor median survival. A single level of affected spine, a Frankel scale of C or better, a moderate to high Kanofsky score, and radiation therapy were associated with significantly longer median survival. CCA resection and spinal surgery may play an important role in prolonging survival when used in conjunction with other adjuvant treatment modalities.