Predicting leptomeningeal disease spread after resection of brain metastases using machine learning.

OBJECTIVE: The incidence of leptomeningeal disease (LMD) has increased as treatments for brain metastases (BMs) have improved and patients with metastatic disease are living longer. Sample sizes of individual studies investigating LMD after surgery for BMs and its risk factors have been limited, ranging from 200 to 400 patients at risk for LMD, which only allows the use of conventional biostatistics. Here, the authors used machine learning techniques to enhance LMD prediction in a cohort of surgically treated BMs. METHODS: A conditional survival forest, a Cox proportional hazards model, an extreme gradient boosting (XGBoost) classifier, an extra trees classifier, and logistic regression were trained. A synthetic minority oversampling technique (SMOTE) was used to train the models and handle the inherent class imbalance. Patients were divided into an 80:20 training and test set. Fivefold cross-validation was used on the training set for hyperparameter optimization. Patients eligible for study inclusion were adults who had consecutively undergone neurosurgical BM treatment, had been admitted to Brigham and Women's Hospital from January 2007 through December 2019, and had a minimum of 1 month of follow-up after neurosurgical treatment. RESULTS: A total of 1054 surgically treated BM patients were included in this analysis. LMD occurred in 168 patients (15.9%) at a median of 7.05 months after BM diagnosis. The discrimination of LMD occurrence was optimal using an XGboost algorithm (area under the curve = 0.83), and the time to LMD was prognosticated evenly by the random forest algorithm and the Cox proportional hazards model (C-index = 0.76). The most important feature for both LMD classification and regression was the BM proximity to the CSF space, followed by a cerebellar BM location. Lymph node metastasis of the primary tumor at BM diagnosis and a cerebellar BM location were the strongest risk factors for both LMD occurrence and time to LMD. CONCLUSIONS: The outcomes of LMD patients in the BM population are predictable using SMOTE and machine learning. Lymph node metastasis of the primary tumor at BM diagnosis and a cerebellar BM location were the strongest LMD risk factors.

Risk Factors of Second Local Recurrence in Surgically Treated Recurrent Brain Metastases: An Exploratory Analysis.

BACKGROUND: A first local recurrence is common after resection or radiotherapy for brain metastasis (BM). However, patients with BMs can develop multiple local recurrences over time. Published data on second local recurrences are scarce. This study aimed to report predictors associated with a second local recurrence in patients with BMs who underwent a craniotomy for a first locally recurrent BM. METHODS: Patients were identified from a database at Brigham and Women's Hospital in Boston. Hazard ratios and 95% confidence intervals for predictors of a second local recurrence were computed using a Cox proportional hazards model. RESULTS: Of 170 identified surgically treated first locally recurrent lesions, 74 (43.5%) progressed to second locally recurrent lesions at a median of 7 months after craniotomy. Subtotal resection of the first local BM recurrence was significantly associated with shorter time to second local recurrence (hazard ratio = 2.09; 95% confidence interval, 1.27-3.45). Infratentorial location was associated with a worse second local recurrence prognosis (hazard ratio = 2.22; 95% confidence interval, 1.24-3.96). CONCLUSIONS: A second local recurrence occurred after 43.5% of craniotomies for first recurrent lesions. Subtotal resection and infratentorial location were the strongest risk factors for worse second local recurrence prognosis following resection of first recurrent BM.

The effect of smoking on survival in lung carcinoma patients with brain metastasis: a systematic review and meta-analysis.

The effects of smoking on survival in BM patients have yet to be reviewed and meta-analysed. However, previous studies have shown that smokers had a greater risk of dying from lung cancer compared to non-smokers. This meta-analysis, therefore, aimed to analyse the effects of cigarette smoking on overall survival (OS) and progression-free survival (PFS) in lung cancer BM patients. PubMed, Embase, Web of Science, Cochrane and Google Scholar were searched for comparative studies regarding the effects of smoking on incidence and survival in brain metastases patients up to December 2020. Three independent reviewers extracted overall survival (OS) and progression-free survival data (PFS). Random-effects models were used to pool multivariate-adjusted hazard ratios (HR). Out of 1890 studies, fifteen studies with a total of 2915 patients met our inclusion criteria. Amongst lung carcinoma BM patients, those who were smokers (ever or yes) had a worse overall survival (HR: 1.34, 95% CI 1.13, 1.60, I2: 72.1%, p-heterogeneity < 0.001) than those who were non-smokers (never or no). A subgroup analysis showed the association to remain significant in the ever/never subgroup (HR: 1.34, 95% CI 1.11, 1.63) but not in the yes/no smoking subgroup (HR: 1.30, 95% CI 0.44, 3.88). This difference between the two subgroups was not statistically significant (p = 0.91). Amongst lung carcinoma BM patients, smoking was associated with a worse OS and PFS. Future studies examining BMs should report survival data stratified by uniform smoking status definitions.

Survival Prediction After Neurosurgical Resection of Brain Metastases: A Machine Learning Approach.

BACKGROUND: Current prognostic models for brain metastases (BMs) have been constructed and validated almost entirely with data from patients receiving up-front radiotherapy, leaving uncertainty about surgical patients. OBJECTIVE: To build and validate a model predicting 6-month survival after BM resection using different machine learning algorithms. METHODS: An institutional database of 1062 patients who underwent resection for BM was split into an 80:20 training and testing set. Seven different machine learning algorithms were trained and assessed for performance; an established prognostic model for patients with BM undergoing radiotherapy, the diagnosis-specific graded prognostic assessment, was also evaluated. Model performance was assessed using area under the curve (AUC) and calibration. RESULTS: The logistic regression showed the best performance with an AUC of 0.71 in the hold-out test set, a calibration slope of 0.76, and a calibration intercept of 0.03. The diagnosis-specific graded prognostic assessment had an AUC of 0.66. Patients were stratified into regular-risk, high-risk and very high-risk groups for death at 6 months; these strata strongly predicted both 6-month and longitudinal overall survival ( P < .0005). The model was implemented into a web application that can be accessed through http://brainmets.morethanml.com . CONCLUSION: We developed and internally validated a prediction model that accurately predicts 6-month survival after neurosurgical resection for BM and allows for meaningful risk stratification. Future efforts should focus on external validation of our model.

Practice Variation in Perioperative Steroid Dosing for Brain Tumor Patients: An International Survey.

OBJECTIVE: Steroids are commonly used to treat peritumoral edema and increased intracranial pressure in patients with brain tumors. Despite widespread use of steroids, relatively little evidence is available about their optimal perioperative dosing scheme. This study aimed to increase insight into practice variation of perioperative steroid dosing and tapering schedules used in the neurosurgical community. METHODS: An electronic survey comprising 27 questions regarding steroid dosing, tapering schedules, and adverse events was administered to neurosurgeons between December 6, 2019, and June 1, 2020. The survey was distributed through the European Association of Neurosurgical Societies and social media platforms. Collected data were assessed for quantitative and qualitative analysis. RESULTS: The survey obtained 175 responses from 55 countries across 6 continents, including 30 from low- or middle-income countries; 152 (87%) respondents completed all questions. Of respondents, 130 (80%) indicated prescribing perioperative steroids. Reported doses ranged from 2 to 64 mg/day in schedules ranging from 1 to 4 times daily. The most prescribed steroid was dexamethasone in doses of 16 mg/day (n = 49; 31%), 12 mg/day (n = 31; 20%), and 8 mg/day (n = 18; 12%). No significant association was found between prescribed dose and physician and institutional characteristics. CONCLUSIONS: Steroids are commonly prescribed perioperatively in patients with brain tumors. However, there is great practice variation in dosing and schedules among neurosurgeons. Future investigation in a prospective and preferably randomized manner is needed to identify an optimal dosing scheme and implement international/national guidelines for steroid use.

The low utility of routine cranial imaging after pediatric shunt revision.

OBJECTIVE: Postoperative routine imaging is common after pediatric ventricular shunt revision, but the benefit of scanning in the absence of symptoms is questionable. In this study, the authors aimed to assess how often routine scanning results in a change in clinical management after shunt revision. METHODS: The records of a large, tertiary pediatric hospital were retrospectively reviewed for all consecutive cases of pediatric shunt revision between July 2013 and July 2018. Postoperative imaging was classified as routine (i.e., in the absence of symptoms, complications, or other direct indications) or nonroutine. Reinterventions within 30 days were assessed in these groups. RESULTS: Of 387 included shunt revisions performed in 232 patients, postoperative imaging was performed in 297 (77%), which was routine in 244 (63%) and nonroutine in 53 (14%). Ninety revisions (23%) underwent any shunt-related procedure after postoperative imaging, including shunt reprogramming (n = 35, 9%), shunt tap (n = 10, 3%), and a return to the operating room (OR; n = 58, 15%). Of the 244 cases receiving routine imaging, 241 did not undergo a change in clinical management solely based on routine imaging findings. The remaining 3 cases returned to the OR, accounting for 0.8% (95% CI 0.0%-1.7%) of all cases or 1.2% (95% CI 0.0%-2.6%) of cases that received routine imaging. Furthermore, 27 of 244 patients in this group returned to the OR for other reasons, namely complications (n = 12) or recurrent symptoms (n = 15); all arose after initial routine imaging. CONCLUSIONS: The authors found a low yield to routine imaging after pediatric shunt revision, with only 0.8% of cases undergoing a change in management based on routine imaging findings without corresponding clinical findings. Moreover, routine imaging without abnormal findings was no guarantee of an uneventful postoperative course. Clinical monitoring can be considered as an alternative in asymptomatic, uncomplicated patients.

Leptomeningeal disease in neurosurgical brain metastases patients: A systematic review and meta-analysis.

BACKGROUND: Leptomeningeal disease (LMD) is a complication distinguished by progression of metastatic disease into the leptomeninges and subsequent spread via cerebrospinal fluid (CSF). Although treatments for LMD exist, it is considered fatal with a median survival of 2-4 months. A broader overview of the risk factors that increase the brain metastasis (BM) patient's risk of LMD is needed. This meta-analysis aimed to systematically review and quantitatively assess risk factors for LMD after surgical resection for BM. METHODS: A systematic literature search was performed on 7 May 2021. Pooled effect sizes were calculated using a random-effects model for variables reported by three or more studies. RESULTS: Among 503 studies, thirteen studies met the inclusion criteria with a total surgical sample size of 2105 patients, of which 386 patients developed LMD. The median incidence of LMD across included studies was 16.1%. Eighteen unique risk factors were reported as significantly associated with LMD occurrence, including but not limited to: larger tumor size, infratentorial BM location, proximity of BM to cerebrospinal fluid spaces, ventricle violation during surgery, subtotal or piecemeal resection, and postoperative stereotactic radiosurgery. Pooled results demonstrated that breast cancer as the primary tumor location (HR = 2.73, 95% CI: 2.12-3.52) and multiple BMs (HR = 1.37, 95% CI: 1.18-1.58) were significantly associated with a higher risk of LMD occurrence. CONCLUSION: Breast cancer origin and multiple BMs increase the risk of LMD occurrence after neurosurgery. Several other risk factors which might play a role in LMD development were also identified.

Neurosurgical resection for locally recurrent brain metastasis.

BACKGROUND: In patients with locally recurrent brain metastases (LRBMs), the role of (repeat) craniotomy is controversial. This study aimed to analyze long-term oncological outcomes in this heterogeneous population. METHODS: Craniotomies for LRBM were identified from a tertiary neuro-oncological institution. First, we assessed overall survival (OS) and intracranial control (ICC) stratified by molecular profile, prognostic indices, and multimodality treatment. Second, we compared LRBMs to propensity score-matched patients who underwent craniotomy for newly diagnosed brain metastases (NDBM). RESULTS: Across 180 patients, median survival after LRBM resection was 13.8 months and varied by molecular profile, with >24 months survival in ALK/EGFR+ lung adenocarcinoma and HER2+ breast cancer. Furthermore, 102 patients (56.7%) experienced intracranial recurrence; median time to recurrence was 5.6 months. Compared to NDBMs (n = 898), LRBM patients were younger, more likely to harbor a targetable mutation and less likely to receive adjuvant radiation (P < 0.05). After 1:3 propensity matching stratified by molecular profile, LRBM patients generally experienced shorter OS (hazard ratio 1.67 and 1.36 for patients with or without a mutation, P < 0.05) but similar ICC (hazard ratio 1.11 in both groups, P > 0.20) compared to NDBM patients with similar baseline. Results across specific molecular subgroups suggested comparable effect directions of varying sizes. CONCLUSIONS: In our data, patients with LRBMs undergoing craniotomy comprised a subgroup of brain metastasis patients with relatively favorable clinical characteristics and good survival outcomes. Recurrent status predicted shorter OS but did not impact ICC. Craniotomy could be considered in selected, prognostically favorable patients.

The combined use of steroids and immune checkpoint inhibitors in brain metastasis patients: a systematic review and meta-analysis.

BACKGROUND: Immune checkpoint inhibitors (ICI) have been a breakthrough for selected cancer patients, including those with brain metastases (BMs). Likewise, steroids have been an integral component of symptomatic management of BM patients. However, clinical evidence on the interaction between ICI and steroids in BM patients is conflicting and has not adequately been summarized thus far. Hence, the aim of this study was to perform a systematic literature review and meta-analysis on the association between steroid use and overall survival (OS) in BM patients receiving ICI. METHODS: A systematic literature search was performed. Pooled effect estimates were calculated using random-effects models across included studies. RESULTS: After screening 1145 abstracts, 15 observational studies were included. Fourteen studies reported sufficient data for meta-analysis, comprising 1102 BM patients of which 32.1% received steroids. In the steroid group, median OS ranged from 2.9 to 10.2 months. In the nonsteroid group, median OS ranged from 4.9 to 25.1 months. Pooled results demonstrated significantly worse OS (HR = 1.84, 95% CI 1.22-2.77) and systemic progression-free survival (PFS; HR = 2.00, 95% CI 1.37-2.91) in the steroid group. Stratified analysis showed a consistent effect across the melanoma subgroup; not in the lung cancer subgroup. No significant association was shown between steroid use and intracranial PFS (HR = 1.31, 95% CI 0.42-4.07). CONCLUSIONS: Administration of steroids was associated with significantly worse OS and PFS in BM patients receiving ICI. Further research on dose, timing, and duration of steroids is needed to elucidate the cause of this association and optimize outcomes in BM patients receiving ICI.

Beta-blockers and glioma: a systematic review of preclinical studies and clinical results.

Given the median survival of 15 months after diagnosis, novel treatment strategies are needed for glioblastoma. Beta-blockers have been demonstrated to inhibit angiogenesis and tumor cell proliferation in various cancer types. The aim of this study was to systematically review the evidence on the effect of beta-blockers on glioma growth. A systematic literature search was performed in the PubMed, Embase, Google Scholar, Web of Science, and Cochrane Central to identify all relevant studies. Preclinical studies concerning the pharmacodynamic effects of beta-blockers on glioma growth and proliferation were included, as well as clinical studies that studied the effect of beta-blockers on patient outcomes according to PRISMA guidelines. Among the 980 citations, 10 preclinical studies and 1 clinical study were included after title/abstract and full-text screening. The following potential mechanisms were identified: reduction of glioma cell proliferation (n = 9), decrease of glioma cell migration (n = 2), increase of drug sensitivity (n = 1), induction of glioma cell death (n = 1). Beta-blockers affect glioma proliferation by inducing a brief reduction of cAMP and a temporary cell cycle arrest in vitro. Contrasting results were observed concerning glioma cell migration. The identified clinical study did not find an association between beta-blockers and survival in glioma patients. Although preclinical studies provide scarce evidence for the use of beta-blockers in glioma, they identified potential pathways for targeting glioma. Future studies are needed to clarify the effect of beta-blockers on clinical endpoints including survival outcomes in glioma patients to scrutinize the value of beta-blockers in glioma care.

The ethical and legal status of neurosurgical guidelines: the neurosurgeon's golden fleece or Achilles' heel?

Neurosurgical guidelines are fundamental for evidence-based practice and have considerably increased both in number and content over the last decades. Yet, guidelines in neurosurgery are not without limitations, as they are overwhelmingly based on low-level evidence. Such recommendations have in the past been occasionally overturned by well-designed randomized controlled trials (RCTs), demonstrating the volatility of poorly underpinned evidence. Furthermore, even RCTs in surgery come with several limitations; most notably, interventions are often insufficiently standardized and assume a homogeneous patient population, which is not always applicable to neurosurgery. Lastly, guidelines are often outdated by the time they are published and smaller fields such as neurosurgery may lack a sufficient workforce to provide regular updates. These limitations raise the question of whether it is ethical to use low-level evidence for guideline recommendations, and if so, how strictly guidelines should be adhered to from an ethical and legal perspective. This article aims to offer a critical approach to the ethical and legal status of guidelines in neurosurgery. To this aim, the authors discuss: 1) the current state of neurosurgical guidelines and the evidence they are based on; 2) the degree of implementation of these guidelines; 3) the legal status of guidelines in medical disciplinary cases; and 4) the ethical balance between confident and critical use of guidelines. Ultimately, guidelines are neither laws that should always be followed nor purely academic efforts with little practical use. Every patient is unique, and tailored treatment defined by the surgeon will ensure optimal care; guidelines play an important role in creating a solid base that can be adhered to or deviated from, depending on the situation. From a research perspective, it is inevitable to rely on weaker evidence initially in order to generate more robust evidence later, and clinician-researchers have an ethical duty to contribute to generating and improving neurosurgical guidelines.

Ethical triage during the COVID-19 pandemic: a toolkit for neurosurgical resource allocation.

BACKGROUND: The COVID-19 pandemic confronts healthcare workers, including neurosurgeons, with difficult choices regarding which patients to treat. METHODS: In order to assist ethical triage, this article gives an overview of the main considerations and ethical principles relevant when allocating resources in times of scarcity. RESULTS: We discuss a framework employing four principles: prioritizing the worst off, maximizing benefits, treating patients equally, and promoting instrumental value. We furthermore discuss the role of age and comorbidity in triage and highlight some principles that may seem intuitive but should not form a basis for triage. CONCLUSIONS: This overview is presented on behalf of the European Association of Neurosurgical Societies and can be used as a toolkit for neurosurgeons faced with ethical dilemmas when triaging patients in times of scarcity.

Programmed Death Receptor Ligand One Expression May Independently Predict Survival in Patients With Non-Small Cell Lung Carcinoma Brain Metastases Receiving Immunotherapy.

PURPOSE: Programmed death receptor ligand 1 (PD-L1) expression is known to predict response to PD-1/PD-L1 inhibitors in non-small cell lung cancer (NSCLC). However, the predictive role of this biomarker in brain metastases (BMs) is unknown. The aim of this study was to assess whether PD-L1 expression predicts survival in patients with NSCLC BMs treated with PD-1/PD-L1 inhibitors, after adjusting for established prognostic models. METHODS AND MATERIALS: In this multi-institutional retrospective cohort study, we identified patients with NSCLC-BM treated with PD-1/PD-L1 inhibitors after local BM treatment (radiation therapy or neurosurgery) but before intracranial progression. Cox proportional hazards models were used to assess the predictive value of PD-L1 expression for overall survival (OS) and intracranial progression-free survival (IC-PFS). RESULTS: Forty-eight patients with BM with available PD-L1 expression were identified. PD-L1 expression was positive in 33 patients (69%). Median survival was 26 months. In univariable analysis, PD-L1 predicted favorable OS (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.19-1.02; P = .055). This effect persisted after correcting for lung-graded prognostic assessment and other identified potential confounders (HR, 0.24; 95% CI, 0.10-0.61; P = .002). Moreover, when modeled as a continuous variable, there appeared to be a proportional relationship between percentage of PD-L1 expression and survival (HR, 0.86 per 10% expression; 95% CI, 0.77-0.98; P = .02). In contrast, PD-L1 expression did not predict IC-PFS in uni- or multivariable analysis (adjusted HR, 0.54; 95% CI, 0.26-1.14; P = .11). CONCLUSIONS: In patients with NSCLC-BMs treated with PD-1/PD-L1 checkpoint inhibitors and local treatment, PD-L1 expression may predict OS independent of lung-graded prognostic assessment. IC-PFS did not show association with PD-L1 expression, although the present analysis may lack power to assess this. Larger studies are required to validate these findings.

Central Nervous System-Invading Eccrine Gland Carcinoma: A Clinicopathologic Case Series and Literature Review.

BACKGROUND: Eccrine carcinoma involvement of the central nervous system (CNS) is exceedingly rare. The prognosis and response to treatment of this pathology remain poorly characterized. METHODS: A retrospective case series and literature review were conducted. RESULTS: CNS-invading eccrine carcinoma was diagnosed in 3 patients (2 male and 1 female; age range, 60-79 years), including 2 cases of brain metastases and 1 case of brain-invading skull metastasis with subsequent spinal metastasis. The interval from primary tumor to CNS invasion was 18-51 months. All patients received multimodal therapy following diagnosis of CNS involvement. One patient who harbored a NOTCH1 mutation demonstrated a durable oncologic response after treatment with the immune checkpoint inhibitor pembrolizumab and lived 39 months after CNS invasion. The other 2 patients were discharged to hospice care within 1 month after the diagnosis of eccrine carcinoma brain metastasis. Including this case series, 23 cases of eccrine carcinoma invasion or metastasis to the CNS have been reported, with survival after diagnosis of CNS involvement ranging from a few weeks to 4 years. CONCLUSIONS: We present 3 cases of eccrine carcinoma metastatic to the CNS, including the first reported case to our knowledge of eccrine carcinoma treated with immunotherapy. This case, harboring a NOTCH1 mutation, demonstrated the longest durable oncologic response reported in this rare disease. Genomic and molecular testing may play increasingly important roles in the evaluation of these metastases.

Subtype switching in breast cancer brain metastases: a multicenter analysis.

BACKGROUND: Breast cancer (BC) brain metastases (BM) can have discordant hormonal or human epidermal growth factor receptor 2 (HER2) expression compared with corresponding primary tumors. This study aimed to describe incidence, predictors, and survival outcomes of discordant receptors and associated subtype switching in BM. METHODS: BCBM patients seen at 4 tertiary institutions who had undergone BM resection or biopsy were included. Surgical pathology reports were retrospectively assessed to determine discordance between the primary tumor and the BCBM. In discordant cases, expression in extracranial metastases was also assessed. RESULTS: In BM from 219 patients, prevalence of any discordance was 36.3%; receptor-specific discordance was 16.7% for estrogen, 25.2% for progesterone, and 10.4% for HER2. Because estrogen and progesterone were considered together for hormonal status, 50 (22.8%) patients switched subtype as a result; 20 of these switches were HER2 based. Baseline subtype predicted switching, which occurred in up to 37.5% of primary HR+ patients. Moreover, 14.8% of initially HER2-negative patients gained HER2 in the BM. Most (63.6%) discordant patients with extracranial metastases also had discordance between BM and extracranial subtype. Loss of receptor expression was generally associated with worse survival, which appeared to be driven by estrogen loss (hazard ratio = 1.80, P = 0.03). Patients gaining HER2 status (n = 8) showed a nonsignificant tendency toward improved survival (hazard ratio = 0.64, P = 0.17). CONCLUSIONS: In this multicenter study, we report incidence and predictors of subtype switching, the risk of which varies considerably by baseline subtype. Switches can have clinical implications for prognosis and treatment choice.

Systemic therapy following craniotomy in patients with a solitary breast cancer brain metastasis.

PURPOSE: To describe practice patterns and patient outcomes with respect to the use of postoperative systemic therapy (ST) after resection of a solitary breast cancer brain metastasis (BCBM). METHODS: A multi-institutional retrospective review of consecutive patients undergoing resection of a single BCBM without extracranial metastases was performed to describe subtype-specific postoperative outcomes and assess the impact of types of ST on site of recurrence, progression-free survival (PFS), and overall survival (OS). RESULTS: Forty-four patients were identified. Stratified estimated survival was 15, 24, and 23 months for patients with triple negative, estrogen receptor positive (ER+), and HER2+ BCBMs, respectively. Patients receiving postoperative ST had a longer median PFS (8 versus 4 months, adjusted p-value 0.01) and OS (32 versus 15 months, adjusted p-value 0.21). Nine patients (20%) had extracranial progression, 23 (52%) had intracranial progression, three (8%) had both, and nine (20%) did not experience progression at last follow-up. Multivariate analysis showed that postoperative hormonal therapy was associated with longer OS (HR 0.26; 95% CI 0.08-0.89; p = 0.03) but not PFS (HR 0.35, 95% CI 0.08-1.47, p = 0.15) in ER+ patients. Postoperative HER2-targeted therapy was not associated with longer OS or PFS in HER2+ patients. CONCLUSIONS: Disease progression occurred intracranially more often than extracranially following resection of a solitary BCBM. In ER+ patients, postoperative hormonal therapy was associated with longer OS. Postoperative HER2-targeted therapy did not show survival benefit in HER2+ patients. These results should be validated in larger cohorts.

Routine Blood Tests for Severe Traumatic Brain Injury: Can They Predict Outcomes?

OBJECTIVE: Outcome prediction in severe traumatic brain injury (sTBI) has been studied using clinical and radiographic measurements and by using biomarkers such as glial fibrillary acidic protein, ubiquitin C-terminal hydrolase-L1, and tau. Routine blood tests are regularly performed in patients with sTBI and could be used to predict outcomes. This study aims to investigate whether routine blood tests on admission can be predictive of outcome in patients with sTBI. METHODS: Patients with sTBI were selected from 2 institutional databases based on International Classification of Diseases Ninth and Tenth Revision codes for traumatic brain injury (TBI), ventilatory assistance >24 hours, intracranial pressure monitoring, and Glasgow Coma Score (GCS) score ≤8. Laboratory parameters included blood urea nitrogen, creatinine, glucose, hematocrit, hemoglobin, red blood cells, white blood cells, monocytes, lymphocytes, neutrophils, neutrophil lymphocyte ratio, platelets, international normalized ratio, prothrombin time, sodium, and potassium. Clinical outcome was measured as hospital length of stay, 30-day mortality, and favorable versus unfavorable outcome based on Glasgow Outcome Scale at 3 months. RESULTS: A total of 255 adult patients were selected. Median Injury Severity Score was 14.00 (interquartile range, 9.00-22.00). Of patients, 25.9% died within 30 days and 56.1% had an unfavorable outcome at 3 months. On multivariate analysis, low sodium level was significant for 30-day mortality and high sodium level was significant for unfavorable outcome at 3 months. However, after correction for multiple testing, no routine blood test remained significant. CONCLUSIONS: No routine blood tests measured on admission were significant predictors of outcome in patients with sTBI. Other clinical and radiologic factors may be better suited to predicting outcomes in this patient population.

Long-Term Durability of Open Surgical versus Endovascular Repair of Intracranial Aneurysms: A Systematic Review and Meta-Analysis.

OBJECTIVE: The long-term durability of different modalities of intracranial aneurysm repair remains unclear. The aim of this study was to conduct a meta-analysis comparing long-term rates of intracranial aneurysm recurrence, retreatment, and rebleeding after surgical clipping or endovascular treatment (EVT). METHODS: A systematic review of PubMed and Embase was performed in accordance with the PRISMA guidelines and a meta-analysis was conducted. Cohort studies and randomized controlled trials (RCTs) with a surgical and an endovascular arm of ≥10 patients each and a median follow-up of ≥3 years were included. Pooled-effect estimates for reported outcomes were calculated using the random-effects model; sensitivity analysis was performed using the fixed-effects model. RESULTS: Of 4876 articles, 11 studies including 3 RCTs comprising 4517 patients were analyzed. Coiling was the modality of EVT in all included studies. In the random-effects model, coiling was associated with an increased relative risk of 8.1 for recurrence (95% confidence interval [CI], 3.8-17.2), 4.5 for retreatment (95% CI, 3.4-5.9), and 2.1 for rebleeding (95% CI, 1.3-3.5); the fixed-effects model yielded similar results. Meta-regression by study design, length of follow-up, age, aneurysm size, ruptured versus unruptured aneurysms, or posterior versus anterior location did not yield significant results (all P interactions >0.05). No significant publication bias was identified. CONCLUSIONS: These results indicate better long-term durability of clipping compared with coiling-based EVT. The relatively high incidence of recurrence and retreatment after coiling should be considered when determining treatment strategy.