Debra A. Goldman and Katherine S. Panageas
Matthew Z. Sun, Taemin Oh, Michael E. Ivan, Aaron J. Clark, Michael Safaee, Eli T. Sayegh, Gurvinder Kaur, Andrew T. Parsa and Orin Bloch
There are few and conflicting reports on the effects of delayed initiation of chemoradiotherapy on the survival of patients with glioblastoma. The standard of care for newly diagnosed glioblastoma is concurrent radiotherapy and temozolomide chemotherapy after maximal safe resection; however, the optimal timing of such therapy is poorly defined. Given the lack of consensus in the literature, the authors performed a retrospective analysis of The Cancer Genome Atlas (TCGA) database to investigate the effect of time from surgery to initiation of therapy on survival in newly diagnosed glioblastoma.
Patients with primary glioblastoma diagnosed since 2005 and treated according to the standard of care were identified from TCGA database. Kaplan-Meier and multivariate Cox regression analyses were used to compare overall survival (OS) and progression-free survival (PFS) between groups stratified by postoperative delay to initiation of radiation treatment.
There were 218 patients with newly diagnosed glioblastoma with known time to initiation of radiotherapy identified in the database. The median duration until therapy was 27 days. Delay to radiotherapy longer than the median was not associated with worse PFS (HR = 0.918, p = 0.680) or OS (HR = 1.135, p = 0.595) in multivariate analysis when controlling for age, sex, KPS score, and adjuvant chemotherapy. Patients in the highest and lowest quartiles for delay to therapy (≤ 20 days vs ≥ 36 days) did not statistically differ in PFS (p = 0.667) or OS (p = 0.124). The small subset of patients with particularly long delays (> 42 days) demonstrated worse OS (HR = 1.835, p = 0.019), but not PFS (p = 0.74).
Modest delay in initiation of postoperative chemotherapy and radiation does not appear to be associated with worse PFS or OS in patients with newly diagnosed glioblastoma, while significant delay longer than 6 weeks may be associated with worse OS.
Eli T. Sayegh, Shayan Fakurnejad, Taemin Oh, Orin Bloch and Andrew T. Parsa
Patients who undergo craniotomy for brain tumor resection are prone to experiencing seizures, which can have debilitating medical, neurological, and psychosocial effects. A controversial issue in neurosurgery is the common practice of administering perioperative anticonvulsant prophylaxis to these patients despite a paucity of supporting data in the literature. The foreseeable benefits of this strategy must be balanced against potential adverse effects and interactions with critical medications such as chemotherapeutic agents and corticosteroids. Multiple disparate metaanalyses have been published on this topic but have not been applied into clinical practice, and, instead, personal preference frequently determines practice patterns in this area of management. Therefore, to select the current best available evidence to guide clinical decision making, the literature was evaluated to identify meta-analyses that investigated the efficacy and/or safety of anticonvulsant prophylaxis in this patient population. Six meta-analyses published between 1996 and 2011 were included in the present study. The Quality of Reporting of Meta-analyses and Oxman-Guyatt methodological quality assessment tools were used to score these meta-analyses, and the Jadad decision algorithm was applied to determine the highest-quality meta-analysis. According to this analysis, 2 metaanalyses were deemed to be the current best available evidence, both of which conclude that prophylactic treatment does not improve seizure control in these patients. Therefore, this management strategy should not be routinely used.
John D. Rolston, Seunggu J. Han, Orin Bloch and Andrew T. Parsa
Venous thromboembolisms (VTEs) occur frequently in surgical patients and can manifest as pulmonary emboli (PEs) or deep venous thromboses (DVTs). While many medical therapies have been shown to prevent VTEs, neurosurgeons are concerned about the use of anticoagulants in the postoperative setting. To better understand the prevalence of and the patient-level risk factors for VTE, the authors analyzed data from the National Surgical Quality Improvement Program (NSQIP).
Retrospective data on 1,777,035 patients for the years from 2006 to 2011 were acquired from the American College of Surgeons NSQIP database. Neurosurgical cases were extracted by querying the data for which the surgical specialty was listed as “neurological surgery.” Univariate statistics were calculated using the chi-square test, with 95% confidence intervals used for the resultant risk ratios. Multivariate models were constructed using binary logistic regression with a maximum number of 20 iterations.
Venous thromboembolisms were found in 1.7% of neurosurgical patients, with DVTs roughly twice as common as PEs (1.3% vs 0.6%, respectively). Significant independent predictors included ventilator dependence, immobility (that is, quadriparesis, hemiparesis, or paraparesis), chronic steroid use, and sepsis. The risk of VTE was significantly higher in patients who had undergone cranial procedures (3.4%) than in those who had undergone spinal procedures (1.1%).
Venous thromboembolism is a common complication in neurosurgical patients, and the frequency has not changed appreciably over the past several years. Many factors were identified as independently predictive of VTEs in this population: ventilator dependence, immobility, and malignancy. Less anticipated predictors included chronic steroid use and sepsis. Venous thromboembolisms appear significantly more likely to occur in patients undergoing cranial procedures than in those undergoing spinal procedures. A better appreciation of the prevalence of and the risk factors for VTEs in neurosurgical patients will allow targeting of interventions and a better understanding of which patients are most at risk.
Orin Bloch and Geoffrey T. Manley
✓Despite decades of research into the pathogenesis of cerebral edema, nonsurgical therapy for brain swelling has advanced very little after more than half a century. Recent advancements in our understanding of molecular water transport have generated interest in new targets for edema therapy. Aquaporin-4 (AQP4) is the primary cellular water channel in the brain, localized to astrocytic foot processes along the blood–brain barrier and brain–cerebrospinal fluid interface. Multiple studies of transgenic mice with a complete deficiency or altered expression of AQP4 suggest a prominent role for AQP4 in cerebral water transport. In models of cellular (cytotoxic) edema, AQP4 deletion or alteration has been shown to be protective, reducing edema burden and improving overall survival. In contrast, AQP4 deletion in extra-cellular (vasogenic) edema results in decreased edema clearance and greater progression of disease. The data strongly support the conclusion that AQP4 plays a pivotal role in cerebral water transport and is an essential mediator in the formation and resorption of edema fluid from the brain parenchyma. These findings also suggest that drug therapy targeting AQP4 function and expression may dramatically alter our ability to treat cerebral edema.