Endoscopic Endonasal Transclival Approaches: Case Series & Outcomes for Different Clival Regions

Objective Transclival endoscopic endonasal approaches to the skull base are novel with few published cases.We report our institution’s experience with this technique and discuss outcomes according to the clival region involved. Design Retrospective case series. Setting Tertiary care academic medical center Participants All patients who underwent endoscopic endonasal transclival approaches for skull base lesions from 2008 to 2012. Main Outcome Measures Pathologies encountered, mean intraoperative time, intraoperative complications, gross total resection, intraoperative cerebrospinal fluid (CSF) leak, postoperative CSF leak, postoperative complications, and postoperative clinical course. Results A total of 49 patients underwent 55 endoscopic endonasal transclival approaches. Pathology included 43 benign and 12 malignant lesions. Mean follow-up was 15.4 months. Mean operative time was 167.9 minutes, with one patient experiencing an intraoperative internal carotid artery injury. Of the 15 cases with intraoperative cerebrospinal fluid (CSF) leaks, 1 developed postoperative CSF leak (6.7%). There were six other postoperative complications: four systemic complications, one case of meningitis, and one retropharyngeal abscess. Gross total resection was achieved for all malignancies approached with curative intent. Conclusions This study provides evidence that endoscopic endonasal transclival approaches are a safe and effective strategy for the surgical management of a variety of benign and malignant lesions

Electrically Evoked Auditory Event-Related Responses in Patients with Auditory Brainstem Implants: Morphological Characteristics, Test–Retest Reliability, Effects of Stimulation Level, and Association with Auditory Detection

This study aimed to 1) characterize morphological characteristics of the electrically-evoked cortical auditory event-related potentials (eERP) and explore the potential association between onset eERP morphology and auditory vs non-auditory stimulation; 2) assess test-retest reliability of onset eERPs; 3) investigate effects of stimulation level on onset eERPs; and 4) explore the feasibility of using the onset eERP to estimate the lowest stimulation level that can be detected for individual stimulating electrodes in patients with auditory brainstem implants (ABIs)

The Value of the History and Physical for Patients with Newly Diagnosed Brain Metastases Considering Radiosurgery

Background: For patients with brain metastases, systemic disease burden has historically been accepted as a major determinant of overall survival (OS). However, less research has focused on specific history and physical findings made by clinicians and how such findings pertain to patient outcomes at a given time point. The aim of this study is to determine how the initial clinical assessment of patients with brain metastases, as part of the history and physical at the time of consultation, correlates with patient prognosis.Methods: We evaluated a prospective, multi-institutional database of 1523 brain metastases in 507 patients who were treated with radiosurgery (Gamma Knife or CyberKnife) from 2001-2014. Relevant history of present illness (HPI) and past medical history (PMH) variables included comorbidities, Eastern Cooperative Oncology Group (ECOG) performance status, and seizure history. Physical exam findings included a sensory exam, motor exam, and cognitive function. Univariate and multivariate Cox regression analyses were used to identify predictors of OS.Results: 294 patients were included in the final analysis with a median OS of 10.8 months (95% C.I., 7.8-13.7 months). On univariate analysis, significant HPI predictors of OS included age, primary diagnosis, performance status, extracranial metastases, systemic disease status, and history of surgery. Significant predictors of OS from the PMH included cardiac, vascular, and infectious comorbidities. On a physical exam, findings consistent with cognitive deficits were predictive of worse OS. However, motor deficits or changes in vision were not predictive of worse OS. In the multivariate Cox regression analysis, predictors of worse OS were primary diagnosis (p=0.002), ECOG performance status (OR 1.73, p<0.001), and presence of extracranial metastases (OR 1.22, p=0.009).Conclusion: Neurologic deficits and systemic comorbidities noted at presentation are not associated with worse overall prognosis for patients with brain metastases undergoing radiosurgery. When encountering new patients with brain metastases, the most informative patient-related characteristics that determine prognosis remain performance status, primary diagnosis, and extent of extracranial disease

Correlation of MR Perfusion Imaging and Vessel Tortuosity Parameters in Assessment of Intracranial Neoplasms

Advances in noninvasive imaging techniques such as magnetic resonance perfusion imaging have been found useful in grading cerebral neoplasms and have potential for significant clinical benefit. The purpose of this study was to determine the correlation between tumor vessel tortuosity as measured from vessels extracted from magnetic resonance angiograms (MRA) and perfusion parameters of cerebral blood flow (CBF) and cerebral blood volume (CBV) in intracranial neoplasms. We hypothesized that tumor blood vessel tortuosity measures and perfusion measures would be correlated, since both are increased by tumor angiogenesis. 18 patients with 19 cerebral neoplasms were evaluated with conventional MR imaging and dynamic contrast-enhanced T2-weighted perfusion MR imaging (PWI). Both benign and malignant lesions were included, as were hyper- and hypovascular tumors. Regions of interest were plotted within the tumor area to locate foci of maximum CBV and CBF. CBV and CBF measurements were also recorded in contralateral normal appearing white matter to calculate relative CBV (rCBV) and relative CBF (rCBF). Vessel tortuosity analyses were conducted upon vessels segmented from MRA images of the same patients using two tortuosity descriptors (SOAM and ICM), which have previously been demonstrated to have efficacy in separating benign from malignant disease. Linear regression analyses were conducted to determine if correlations exist between CBV or CBF and the two tortuosity measurements. For the overall set of tumors, no significant correlations were found between flow or volume measures and the tortuosity measures. However, when the 7 glioblastoma multiforme tumors were examined as a subgroup, the following significant correlations were found: rCBV and SOAM (R2=0.799), rCBV and ICM (R2=0.214). Our results demonstrate that MR perfusion imaging data do not correlate significantly with vessel tortuosity parameters as determined from the larger vessels seen by MRA. However, for subgroups of a particular tumor type such as GBM, there may be significant correlations. It appears that perfusion and tortuosity data may provide independently useful data in the assessment of cerebral neoplasms

The Electrically Evoked Cortical Auditory Event-Related Potential in Children With Auditory Brainstem Implants

This study explored the feasibility of measuring electrically-evoked cortical auditory event-related potentials (eERPs) in children with auditory brainstem implants (ABIs)

Genomic analysis identifies unique signatures predictive of brain, lung, and liver relapse

The ability to predict metastatic potential could be of great clinical importance, however, it is uncertain if predicting metastasis to specific vital organs is feasible. As a first step in evaluating metastatic predictions, we analyzed multiple primary tumors and metastasis pairs and determined that >90% of 298 gene expression signatures were found to be similarly expressed between matched pairs of tumors and metastases; therefore, primary tumors may be a good predictor of metastatic propensity. Next, using a dataset of >1,000 human breast tumor gene expression microarrays we determined that HER2-enriched subtype tumors aggressively spread to the liver, while basal-like and claudin-low subtypes colonize the brain and lung. Correspondingly, brain and lung metastasis signatures, along with embryonic stem cell, tumor initiating cell, and hypoxia signatures, were also strongly expressed in the basal-like and claudin-low tumors. Interestingly, low “Differentiation Scores,” or high expression of the aforementioned signatures, further predicted for brain and lung metastases. In total, these data identify that depending upon the organ of relapse, a combination of gene expression signatures most accurately predicts metastatic behavior

Stereotactic radiosurgery for single brain metastases from non-small cell lung cancer: progression of extracranial disease correlates with distant intracranial failure

BackgroundLimited data exist regarding management of patients with a single brain lesion with extracranial disease due to non-small cell lung cancer (NSCLC).MethodsEighty-eight consecutive patients with a single brain lesion from NSCLC in the presence of extracranial disease were treated with stereotactic radiosurgery (SRS) alone. Local control (LC), distant intracranial failure (DIF), overall survival (OS), and toxicity were assessed. The logrank test was used to identify prognostic variables.ResultsMedian OS was 10.6 months. One-year DIF was 61%; LC 89%. Treatments were delivered in 1-5 fractions to median BED10 = 60Gy. Five patients developed radionecrosis. Factors associated with shortened OS included poor performance status (PS) (p = 0.0002) and higher Recursive Partitioning Analysis class (p = 0.017). For patients with PS 0, median survival was 22 months. DIF was associated with systemic disease status (progressive vs. stable) (p = 0.0001), as was BED (p = 0.021) on univariate analysis, but only systemic disease (p = 0.0008) on multivariate analysis.ConclusionsThis study identifies a patient population that may have durable intracranial control after treatment with SRS alone. These data support the need for prospective studies to optimize patient selection for up-front SRS and to characterize the impact of DIF on patients’ quality of life

Preservation of neurocognitive function and local control of 1 to 3 brain metastases treated with surgery and carmustine wafers: Neurocognition and Brain Metastases

BACKGROUND: Neurosurgical resection and whole-brain radiation therapy (WBRT) are accepted treatments for single and oligometastatic cancer to the brain. To avoid the decline in neurocognitive function (NCF) linked to WBRT, the authors conducted a prospective, multicenter, phase 2 study to determine whether surgery and carmustine wafers (CW), while deferring WBRT, could preserve NCF and achieve local control (LC). METHODS: NCF and LC were measured in 59 patients who underwent resection and received CW for a single (83%) or dominant (oligometastatic, 2 to 3 lesions) metastasis and received stereotactic radiosurgery (SRS) for tiny nodules not treated with resection plus CW. Preservation of NCF was defined as an improvement or a decline ≤ 1 standard deviation from baseline in 3 domains: memory, executive function, and fine motor skills, evaluated at 2-month intervals. RESULTS: Significant improvements in executive function and memory occurred throughout the 1-year follow-up. Preservation or improvement of NCF occurred in all 3 domains for the majority of patients at each of the 2-month intervals. NCF declined in only 1 patient. The chemowafers were well tolerated, and serious adverse events were reversible. There was local recurrence in 28% of the patients at 1-year follow-up. CONCLUSIONS: Patients with brain metastases had improvements in their cognitive trajectory, especially memory and executive function, after treatment with resection plus CW. The rate of LC (78%) was comparable to historic rates of surgery with WBRT and superior to reports of WBRT alone. For patients who undergo resection for symptomatic or large-volume metastasis or for tissue diagnosis, the addition of CW can be considered as an option

Stereotactic radiosurgery for single brain metastases from non-small cell lung cancer: progression of extracranial disease correlates with distant intracranial failure

BackgroundLimited data exist regarding management of patients with a single brain lesion with extracranial disease due to non-small cell lung cancer (NSCLC).MethodsEighty-eight consecutive patients with a single brain lesion from NSCLC in the presence of extracranial disease were treated with stereotactic radiosurgery (SRS) alone. Local control (LC), distant intracranial failure (DIF), overall survival (OS), and toxicity were assessed. The logrank test was used to identify prognostic variables.ResultsMedian OS was 10.6 months. One-year DIF was 61%; LC 89%. Treatments were delivered in 1-5 fractions to median BED10 = 60Gy. Five patients developed radionecrosis. Factors associated with shortened OS included poor performance status (PS) (p = 0.0002) and higher Recursive Partitioning Analysis class (p = 0.017). For patients with PS 0, median survival was 22 months. DIF was associated with systemic disease status (progressive vs. stable) (p = 0.0001), as was BED (p = 0.021) on univariate analysis, but only systemic disease (p = 0.0008) on multivariate analysis.ConclusionsThis study identifies a patient population that may have durable intracranial control after treatment with SRS alone. These data support the need for prospective studies to optimize patient selection for up-front SRS and to characterize the impact of DIF on patients’ quality of life

Core pathway mutations induce de-differentiation of murine astrocytes into glioblastoma stem cells that are sensitive to radiation but resistant to temozolomide

Glioma stem cells (GSCs) from human glioblastomas (GBMs) are resistant to radiation and chemotherapy and may drive recurrence. Treatment efficacy may depend on GSCs, expression of DNA repair enzymes such as methylguanine methyltransferase (MGMT), or transcriptome subtype