Stereotactic radiosurgery in the management of non-small cell lung cancer brain metastases: a prospective study using the NeuroPoint Alliance Stereotactic Radiosurgery Registry.

OBJECTIVE: The literature on non-small cell lung cancer (NSCLC) brain metastases (BMs) managed using stereotactic radiosurgery (SRS) relies mainly on single-institution studies or randomized controlled trials (RCTs). There is a literature gap on clinical and radiological outcomes of SRS for NSCLC metastases in real-world practice. The objective of this study was to benchmark mortality and progression outcomes in patients undergoing SRS for NSCLC BMs and identify risk factors for these outcomes using a national quality registry. METHODS: The SRS Registry of the NeuroPoint Alliance was used for this study. This registry included patients from 16 enrolling sites who underwent SRS from 2017 to 2022. Data are prospectively collected without a prespecified research purpose. The main outcomes of this analysis were overall survival (OS), out-of-field recurrence, local progression, and intracranial progression. All time-to-event investigations included Kaplan-Meier analyses and multivariable Cox regressions. RESULTS: Two hundred sixty-four patients were identified, with a mean age of 66.7 years and a female proportion of 48.5%. Most patients (84.5%) had a Karnofsky Performance Status (KPS) score of 80-100, and the mean baseline EQ-5D score was 0.539 quality-adjusted life years. A single lesion was present in 53.4% of the patients, and 29.1% of patients had 3 or more lesions. The median OS was 28.1 months, and independent predictors of mortality included no control of primary tumor (hazard ratio [HR] 2.1), KPS of 80 (HR 2.4) or lower (HR 2.4), coronary artery disease (HR 2.8), and 5 or more lesions present at the time of SRS treatment (HR 2.3). The median out-of-field progression-free survival (PFS) was 24.8 months, and the median local PFS was unreached. Intralesional hemorrhage was an independent risk factor of local progression, with an HR of 6.0. The median intracranial PFS was 14.0 months and was predicted by the number of lesions at the time of SRS (3-4 lesions, HR 2.2; 5-14 lesions, HR 2.5). CONCLUSIONS: In this real-world prospective study, the authors used a national quality registry and found favorable OS in patients with NSCLC BMs undergoing SRS compared with results from previously published RCTs. The intracranial PFS was mainly driven by the emergence of new lesions rather than local progression. A greater number of lesions at baseline was associated with out-of-field progression, while intralesional hemorrhage at baseline was associated with local progression.

Association of Autologous Tumor Lysate-Loaded Dendritic Cell Vaccination With Extension of Survival Among Patients With Newly Diagnosed and Recurrent Glioblastoma: A Phase 3 Prospective Externally Controlled Cohort Trial.

Importance: Glioblastoma is the most lethal primary brain cancer. Clinical outcomes for glioblastoma remain poor, and new treatments are needed. Objective: To investigate whether adding autologous tumor lysate-loaded dendritic cell vaccine (DCVax-L) to standard of care (SOC) extends survival among patients with glioblastoma. Design, Setting, and Participants: 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. Interventions: 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. Main Outcomes and Measures: 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. Results: 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). Conclusions and Relevance: 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. Trial Registration: ClinicalTrials.gov Identifier: NCT00045968.

Lumbar cistern Candida intradural abscess following epidural anesthesia.

Background: This report describes a case of an immunocompetent patient with an intradural abscess from Candida dubliniensis. The majority of fungal spine infections, although rare in general, are due to Aspergillus or C. albicans through systemic fungemia. To date, there have only been two reports of spondylodiscitis from C. dubliniensis. Case Description: A 37-year-old immunocompetent female patient presented to the neurosurgical service for worsening headaches with nausea, vomiting, vision changes, and weight loss. MRI studies showed diffuse leptomeningeal enhancement of the distal spinal cord, conus medullaris, and nerve roots of the cauda equina extending beyond the neural foramina bilaterally. She had persistent symptoms and no clear diagnosis on lumbar puncture or systemic testing therefore L5-S1 laminectomy for an intradural tissue biopsy was performed. During surgery, cultures were taken and grew colonies of C. dubliniensis. Conclusion: This organism has been reported rarely in the literature as being an infectious agent, thus diagnosing remains a challenge but should be considered in patients with a suggestive history.

Factors associated with progression and mortality among patients undergoing stereotactic radiosurgery for intracranial metastasis: results from a national real-world registry.

OBJECTIVE: Stereotactic radiosurgery (SRS) has been increasingly employed in recent years to treat intracranial metastatic lesions. However, there is still a need for optimization of treatment paradigms to provide better local control and prevent progressive intracranial disease. In the current study, the authors utilized a national collaborative registry to investigate the outcomes of patients with intracranial metastatic disease who underwent SRS and to determine factors associated with lesion treatment response, overall progression, and mortality. METHODS: The NeuroPoint Alliance SRS registry was queried for all patients with intracranial metastatic lesions undergoing single- or multifraction SRS at participating institutions between 2016 and 2020. The main outcomes of interest included lesion response (lesion-level analysis), progression using Response Assessment for Neuro-Oncology criteria, and mortality (patient-level analysis). Kaplan-Meier analysis was used to report time to progression and overall survival, and multivariable Cox proportional hazards analysis was used to investigate factors associated with lesion response, progression, and mortality. RESULTS: A total of 501 patients (1447 intracranial metastatic lesions) who underwent SRS and had available follow-up were included in the current analyses. The most common primary tumor was lung cancer (49.5%, n = 248), followed by breast (15.4%, n = 77) and melanoma (12.2%, n = 61). Most patients had a single lesion (44.9%, n = 225), 29.3% (n = 147) had 2 or 3 lesions, and 25.7% (n = 129) had > 3 lesions. The mean sum of baseline measurements of the lesions according to Response Evaluation Criteria in Solid Tumors (RECIST) was 35.54 mm (SD 25.94). At follow-up, 671 lesions (46.4%) had a complete response, 631 (43.6%) had a partial response (≥ 30% decrease in longest diameter) or were stable (< 30% decrease but < 20% increase), and 145 (10%) showed progression (> 20% increase in longest diameter). On multivariable Cox proportional hazards analysis, melanoma-associated lesions (HR 0.48, 95% CI 0.34-0.67; p < 0.001) and larger lesion size (HR 0.94, 95% CI 0.93-0.96; p < 0.001) showed lower odds of lesion regression, while a higher biologically effective dose was associated with higher odds (HR 1.001, 95% CI 1.0001-1.00023; p < 0.001). A total of 237 patients (47.3%) had overall progression (local failure or intracranial progressive disease), with a median time to progression of 10.03 months after the index SRS. Factors found to be associated with increased hazards of progression included male sex (HR 1.48, 95% CI 1.108-1.99; p = 0.008), while administration of immunotherapy (before or after SRS) was found to be associated with lower hazards of overall progression (HR 0.62, 95% CI 0.460-0.85; p = 0.003). A total of 121 patients (23.95%) died during the follow-up period, with a median survival of 19.4 months from the time of initial SRS. A higher recursive partitioning analysis score (HR 21.3485, 95% CI 1.53202-3.6285; p < 0.001) was found to be associated with higher hazards of mortality, while single-fraction treatment compared with hypofractionated treatment (HR 0.082, 95% CI 0.011-0.61; p = 0.015), administration of immunotherapy (HR 0.385, 95% CI 0.233-0.64; p < 0.001), and presence of single compared with > 3 lesions (HR 0.427, 95% CI 0.187-0.98; p = 0.044) were found to be associated with lower risk of mortality. CONCLUSIONS: The comparability of results between this study and those of previously published clinical trials affirms the value of multicenter databases with real-world data collected without predetermined research purpose.

Musculoskeletal and Sports Medicine Curriculum Guidelines for Pediatric Residents.

ABSTRACT: Musculoskeletal (MSK) and sports-related conditions are relatively common in the pediatric population. Pediatric residencies should provide residents with the knowledge and skills to assess and manage both acute and chronic MSK and sports injuries and complaints. Residents should develop the competencies and attitudes to safeguard and promote a healthy and active lifestyle for youth. Programs can use a variety of educational tools, both in the clinic and on the field, to provide a well-rounded MSK curriculum throughout the residency years. This article provides a review of general pediatric sports medicine curriculum guidelines and suggested implementation strategies.

Time to treatment initiation and outcomes in high-grade glioma patients in rehabilitation: a retrospective cohort study.

Aims: To investigate wait time (WT) for chemoradiation and survival in post-op high-grade glioma (HGG) patients admitted to inpatient rehabilitation compared with those discharged home. Materials & methods: A total of 291 HGG patients (14.4% grade III and 84.9% grade IV) were included in this retrospective cohort study. Patients were grouped by disposition following surgery. Results: Median length of stay was longer in acute inpatient rehabilitation facility (AIRF) patients (10d) compared with patients discharged home (3d). AIRF admission was associated with higher odds of excessive treatment delay. Median survival for AIRF patients less than for patients discharged home (42.9 vs 72.71 weeks). WT was not associated with survival even after adjusting for prognostic factors. Conclusion: HGG patients discharged to rehabilitation facilities have longer length of stay, longer WT and shorter survival compared with patients discharged home.

Clinical Efficacy of Tumor Treating Fields for Newly Diagnosed Glioblastoma.

BACKGROUND/AIM: Whether adding tumor treating fields (TTF) to the Stupp protocol increases survival for glioblastoma (GBM) patients in routine clinical care remains unknown. PATIENTS AND METHODS: We retrospectively identified adult patients with newly diagnosed GBM (n=104) treated with the Stupp protocol or TTF at our Institution. RESULTS: Thirty-six percent (37/104) of patients received TTF in conjunction with the Stupp protocol and these patients had increased 6-month (p=0.006) and 1-year (p=0.170), but not 2-year survival rates compared to the 67-patients who received Stupp alone. The improvement of survival rate at 6-month was further confirmed by a modified Poisson model (p=0.010). However, we did not observe any improvement in overall survival (OS) with a Cox model. CONCLUSION: While adding TTF to the Stupp protocol appeared to benefit patients with newly diagnosed GBM, this effect was mild and may be largely due to selection bias.

The correlation of fractional anisotropy parameters with Ki-67 index, and the clinical implication in grading of non-enhancing gliomas and neuronal-glial tumors.

PURPOSE: To investigate the correlation between the FA parameters and Ki-67 labeling index, and their diagnostic performance in grading supratentorial non-enhancing gliomas and neuronal-glial tumors (GNGT). METHODS: This institutional review board-approved, Health Insurance Portability and Accountability (HIPAA) compliant retrospective study enrolled 35 patients, including 19 with low grade GNGT and 16 with high grade GNGT. The mean FA, maximal FA and mean maximal FA values derived from diffusion tensor imaging were measured. The correlation between the FA parameters and the Ki-67 labeling index was assessed by Spearman rank test. The receiver operating characteristic curve analysis and multivariate logistic regression analysis were performed to detect the optimal imaging parameters in grading GNGT. RESULTS: The three FA parameters of low grade GNGT were significantly lower than the high grade GNGT (p < 0.001). The mean FA, maximal FA and mean maximal FA had significant positive correlation with Ki-67 labeling index (p = 0.001, p < 0.001, p < 0.001 respectively). The maximal FA showed a higher sensitivity and specificity in grading of non-enhancing GNGT with specificity of 78.9%, sensitivity of 100.0%, respectively. CONCLUSIONS: The FA parameters correlated with Ki-67 labeling index, and were useful surrogates in preoperative grading supratentorial non-enhancing GNGT.

Risk factors associated with early adverse outcomes following craniotomy for malignant glioma in older adults.

INTRODUCTION: Craniotomy for tumor resection improves survival in adults aged ≥65 years with malignant glioma. However, the decision to attempt resection must be weighed against the near-term risks of surgery. This study examined risk factors associated with unfavorable 30-day outcomes following craniotomy for malignant glioma resection in older adult patients. MATERIALS AND METHODS: The American College of Surgeons National Surgical Quality Improvement Program database from 2012 to 2016 was queried for patients aged 65-89 years undergoing craniotomy for primary, supratentorial, malignant, intra-axial tumor resection. 30-day outcomes included mortality, life-threatening complication, unplanned readmission, reoperation, and change in living disposition. Independent risk factors were identified through multiple logistic regression. RESULTS: In total, 1016 cases met eligibility criteria. Death occurred in 35 cases (3.4%). 58 patients (5.7%) suffered at least one life-threatening complication. Risk factors for morbidity and mortality included frontal lobe tumor, corticosteroid use, dependent functional status, and underweight body mass index (BMI). Among 816 patients admitted from home, 33.9% experienced a change in living disposition, which was associated with advanced age, female sex, frontal lobe tumor, underweight BMI, and diabetes mellitus (among others). Readmission (11.8%) was most frequently attributed to altered mental status, seizure, or venous thromboembolism. Reoperation was rare (4.5%). DISCUSSION: Death and life-threatening morbidity were rare early outcomes for older adult patients undergoing malignant glioma resection. However, one in three patients admitted from home experienced a change in living disposition. Factors related to baseline state of health, tumor location, and corticosteroid regimen should be considered when anticipating the immediate postoperative course.

Translational Brain Mapping at the University of Rochester Medical Center: Preserving the Mind Through Personalized Brain Mapping.

The Translational Brain Mapping Program at the University of Rochester is an interdisciplinary effort that integrates cognitive science, neurophysiology, neuroanesthesia, and neurosurgery. Patients who have tumors or epileptogenic tissue in eloquent brain areas are studied preoperatively with functional and structural MRI, and intraoperatively with direct electrical stimulation mapping. Post-operative neural and cognitive outcome measures fuel basic science studies about the factors that mediate good versus poor outcome after surgery, and how brain mapping can be further optimized to ensure the best outcome for future patients. In this article, we describe the interdisciplinary workflow that allows our team to meet the synergistic goals of optimizing patient outcome and advancing scientific understanding of the human brain.

The Impact of Timing of Concurrent Chemoradiation in Patients With High-Grade Glioma in the Era of the Stupp Protocol.

Background: The purpose of this study is to provide a critical review of current evidence for the impact of time to initiation of chemoradiation on overall survival in patients with newly diagnosed high-grade gliomas treated with radiation and concurrent temozolomide chemotherapy. Methods: A literature search was conducted using PubMed/MEDLINE and EMBASE databases. Studies were included if they provided separate analysis for patients treated with current standard of care: radiation and concurrent temozolomide. Bias assessment was performed for each included study using the Newcastle-Ottawa Assessment Scale, with Karnofsky Performance Status (KPS) and extent of resection used for comparability. Results: The initial search yielded 575 citations. Based on the inclusion/exclusion criteria, a total of 10 retrospective cohort studies were included in this review for a total of 30,298 patients. Of these, one study described an indirect relationship between time to initiation of treatment and overall survival. One study found decreased survival only with patients with significantly longer time to treatment. Four studies found no significant effect of time to treatment on overall survival. The four remaining studies found that patients with moderate time to initiation had the best overall survival. Conclusion: This review provides evidence that moderate time to initiation of chemoradiotherapy in patients with high-grade gliomas does not lead to a significant decrease in overall survival, though the effect of significant delays in treatment initiation remains unclear.

Healthcare Costs for High-grade Glioma.

BACKGROUND/AIM: Data on verified healthcare costs for high-grade gliomas (HGGs) are limited. This study aimed to determine the healthcare costs for HGGs. MATERIALS AND METHODS: A total of 88 primary HGGs patients diagnosed and treated at our Institution between 2011 and 2017 who had insurance plans administered with Excellus BCBS were retrospectively identified. Patient clinical information was linked with all verified insurance payment data. RESULTS: Median insurance payments for clinical management of HGGs were $184,159.83. The leading cost was therapeutic radiation oncology. Patients under commercial insurance had a longer survival time, and higher healthcare expenditures in total and in each phase of clinical care. Healthcare costs were higher during therapy initiation and at disease recurrence and lower during the interim. A generalized linear model showed that patients with commercial insurance, better Karnofsky Performance Status, and longer survival time had higher healthcare expenditures. CONCLUSION: Healthcare payments for HGGs patients were substantial and such high healthcare expenditures were positively associated with patient survival and commercial insurance.

Risk Factors for Prolonged Symptoms of Mild Traumatic Brain Injury: A Pediatric Sports Concussion Clinic Cohort.

OBJECTIVE: To examine predictors of prolonged symptom duration from mild traumatic brain injury (mTBI) in a pediatric sports medicine specialty clinic cohort as these predictors may be distinct in this population. DESIGN: Retrospective chart review. SETTING: Outpatient specialty clinic. PATIENTS: Charts of 549 patients (age range: 10-18 years) with concussions were reviewed in an outpatient clinic that predominantly managed sports-related injuries (77.3%). Patients (n = 431) included in the final analysis met the criteria for mTBI and were symptomatic at their first visit. ASSESSMENT OF RISK FACTORS: Patient history, injury, and recovery variables were evaluated. MAIN OUTCOME MEASURES: Predictors of prolonged time to reach self-reported symptom recovery were evaluated using Cox proportional hazards. RESULTS: Median time to symptom recovery of the 431 patients who presented to clinic with symptoms was 40 days (full clinic sample median = 34 days). Analyses identified 3 unique predictors of symptom recovery: loss of consciousness (LOC) [hazard ratio (HR) = 0.56, P < 0.0001], female sex (HR = 0.57, P < 0.0001), and concussion symptom score at first clinic visit (HR = 0.76, P < 0.0001). CONCLUSIONS: Prolonged duration of mTBI symptoms in patients who present to a pediatric sports-based concussion clinic is related to initial symptom severity, female sex, and LOC.

Domain-Specific Diaschisis: Lesions to Parietal Action Areas Modulate Neural Responses to Tools in the Ventral Stream.

Neural responses to small manipulable objects ("tools") in high-level visual areas in ventral temporal cortex (VTC) provide an opportunity to test how anatomically remote regions modulate ventral stream processing in a domain-specific manner. Prior patient studies indicate that grasp-relevant information can be computed about objects by dorsal stream structures independently of processing in VTC. Prior functional neuroimaging studies indicate privileged functional connectivity between regions of VTC exhibiting tool preferences and regions of parietal cortex supporting object-directed action. Here we test whether lesions to parietal cortex modulate tool preferences within ventral and lateral temporal cortex. We found that lesions to the left anterior intraparietal sulcus, a region that supports hand-shaping during object grasping and manipulation, modulate tool preferences in left VTC and in the left posterior middle temporal gyrus. Control analyses demonstrated that neural responses to "place" stimuli in left VTC were unaffected by lesions to parietal cortex, indicating domain-specific consequences for ventral stream neural responses in the setting of parietal lesions. These findings provide causal evidence that neural specificity for "tools" in ventral and lateral temporal lobe areas may arise, in part, from online inputs to VTC from parietal areas that receive inputs via the dorsal visual pathway.

Risk Factors and Associated Complications of Symptomatic Venous Thromboembolism in Patients with Craniotomy for Meningioma.

OBJECTIVE: Patients undergoing surgical resection of meningioma are at increased risk for developing venous thromboembolism (VTE). The aim of this study was to assess occurrence of VTE in patients who underwent surgical resection of meningioma to determine risk factors and associated complications of VTE. METHODS: The American College of Surgeons National Surgical Quality Improvement Project database from 2012 to 2015 was reviewed for patients who had undergone meningioma resection according to primary Current Procedural Terminology codes and International Classification of Diseases, Ninth Revision. RESULTS: The study included 5036 patients with meningioma. Rate of VTE was 3.38%, with pulmonary embolism rate of 1.47% and deep venous thrombosis rate of 2.42%. During the first 30 days after surgery, patients with VTE had a mortality rate of 5.88% compared with 1.15% for patients without VTE. Multivariate binary logistic regression analysis determined 5 risk factors for VTE,: age ≥60 years, American Society of Anesthesiologists classification III, operative time ≥310 minutes, ventilator dependence, and preoperative transfusions. Univariate analysis revealed a number of complications significantly associated with VTE occurrence, including unplanned intubation, ventilator use for >48 hours, stroke, sepsis, septic shock, pneumonia, urinary tract infection, and transfusions. CONCLUSIONS: Risk factors of VTE and associated complications were identified. Understanding these risk factors provides physicians with further insight in managing this subgroup of patients in a personalized fashion in the perioperative period to minimize the incidence and morbidity of VTE.

Sport-Related Concussion in Children and Adolescents.

Sport-related concussion is an important topic in nearly all sports and at all levels of sport for children and adolescents. Concussion knowledge and approaches to management have progressed since the American Academy of Pediatrics published its first clinical report on the subject in 2010. Concussion's definition, signs, and symptoms must be understood to diagnose it and rule out more severe intracranial injury. Pediatric health care providers should have a good understanding of diagnostic evaluation and initial management strategies. Effective management can aid recovery and potentially reduce the risk of long-term symptoms and complications. Because concussion symptoms often interfere with school, social life, family relationships, and athletics, a concussion may affect the emotional well-being of the injured athlete. Because every concussion has its own unique spectrum and severity of symptoms, individualized management is appropriate. The reduction, not necessarily elimination, of physical and cognitive activity is the mainstay of treatment. A full return to activity and/or sport is accomplished by using a stepwise program while evaluating for a return of symptoms. An understanding of prolonged symptoms and complications will help the pediatric health care provider know when to refer to a specialist. Additional research is needed in nearly all aspects of concussion in the young athlete. This report provides education on the current state of sport-related concussion knowledge, diagnosis, and management in children and adolescents.

Correction to: First results on survival from a large Phase 3 clinical trial of an autologous dendritic cell vaccine in newly diagnosed glioblastoma.

Following publication of the original article [1], the authors reported an error in the spelling of one of the author names. In this Correction the incorrect and correct author names are indicated and the author name has been updated in the original publication. The authors also reported an error in the Methods section of the original article. In this Correction the incorrect and correct versions of the affected sentence are indicated. The original article has not been updated with regards to the error in the Methods section.

First results on survival from a large Phase 3 clinical trial of an autologous dendritic cell vaccine in newly diagnosed glioblastoma.

BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.