Is age an additional factor in the treatment of elderly patients with glioblastoma? A new stratification model: an Italian Multicenter Study.

OBJECTIVE: Approximately half of glioblastoma (GBM) cases develop in geriatric patients, and this trend is destined to increase with the aging of the population. The optimal strategy for management of GBM in elderly patients remains controversial. The aim of this study was to assess the role of surgery in the elderly (≥ 65 years old) based on clinical, molecular, and imaging data routinely available in neurosurgical departments and to assess a prognostic survival score that could be helpful in stratifying the prognosis for elderly GBM patients. METHODS: Clinical, radiological, surgical, and molecular data were retrospectively analyzed in 322 patients with GBM from 9 neurosurgical centers. Univariate and multivariate analyses were performed to identify predictors of survival. A random forest approach (classification and regression tree [CART] analysis) was utilized to create the prognostic survival score. RESULTS: Survival analysis showed that overall survival (OS) was influenced by age as a continuous variable (p = 0.018), MGMT (p = 0.012), extent of resection (EOR; p = 0.002), and preoperative tumor growth pattern (evaluated with the preoperative T1/T2 MRI index; p = 0.002). CART analysis was used to create the prognostic survival score, forming six different survival groups on the basis of tumor volumetric, surgical, and molecular features. Terminal nodes with similar hazard ratios were grouped together to form a final diagram composed of five classes with different OSs (p < 0.0001). EOR was the most robust influencing factor in the algorithm hierarchy, while age appeared at the third node of the CART algorithm. The ability of the prognostic survival score to predict death was determined by a Harrell's c-index of 0.75 (95% CI 0.76-0.81). CONCLUSIONS: The CART algorithm provided a promising, thorough, and new clinical prognostic survival score for elderly surgical patients with GBM. The prognostic survival score can be useful to stratify survival risk in elderly GBM patients with different surgical, radiological, and molecular profiles, thus assisting physicians in daily clinical management. The preliminary model, however, requires validation with future prospective investigations. Practical recommendations for clinicians/surgeons would strengthen the quality of the study; e.g., surgery can be considered as a first therapeutic option in the workflow of elderly patients with GBM, especially when the preoperative estimated EOR is greater than 80%.

Gamma Knife radiosurgery for intracranial benign meningiomas: follow-up outcome in 130 patients.

OBJECTIVEThe authors retrospectively analyzed the follow-up data in 130 patients with intracranial benign meningiomas after Gamma Knife radiosurgery (GKRS), evaluated the tumor progression-free survival (PFS) rate and neurological function preservation rate, and determined the predictors by univariate and multivariate survival analysis.METHODSThis cohort of 130 patients with intracranial benign meningiomas underwent GKRS between May 2012 and May 2015 at the Second Hospital of Tianjin Medical University. The median age was 54.5 years (range 25-81 years), and women outnumbered men at a ratio of 4.65:1. All clinical and radiological data were obtained for analysis. No patient had undergone prior traditional radiotherapy or chemotherapy. The median tumor volume was 3.68 cm3 (range 0.23-45.78 cm3). A median margin dose of 12.0 Gy (range 10.0-16.0 Gy) was delivered to the tumor with a median isodose line of 50% (range 50%-60%).RESULTSDuring a median follow-up of 36.5 months (range 12-80 months), tumor volume regressed in 37 patients (28.5%), was unchanged in 86 patients (66.2%), and increased in 7 patients (5.4%). The actuarial tumor progression-free survival (PFS) rate was 98%, 94%, and 87% at 1, 3, and 5 years, respectively, after GKRS. Tumor recurred in 7 patients at a median follow-up of 32 months (range 12-56 months). Tumor volume ≥ 10 cm3 (p = 0.012, hazard ratio [HR] 8.25, 95% CI 1.60-42.65) and pre-GKRS Karnofsky Performance Scale score < 90 (p = 0.006, HR 9.31, 95% CI 1.88-46.22) were independent unfavorable predictors of PFS rate after GKRS. Of the 130 patients, 101 (77.7%) presented with one or more neurological symptoms or signs before GKRS. Neurological symptoms or signs improved in 40 (30.8%) patients, remained stable in 83 (63.8%), and deteriorated in 7 (5.4%) after GKRS. Two (1.5%) patients developed new cranial nerve (CN) deficit. Tumor volume ≥ 10 cm3 (p = 0.042, HR = 4.73, 95% CI 1.06-21.17) and pre-GKRS CN deficit (p = 0.045, HR = 4.35, 95% CI 0.84-22.48) were independent unfavorable predictors for improvement in neurological symptoms or signs. Six (4.6%) patients developed new or worsening peritumoral edema with a median follow-up of 4.5 months (range 2-7 months).CONCLUSIONSGKRS provided good local tumor control and high neurological function preservation in patients with intracranial benign meningiomas. Patients with tumor volume < 10 cm3, pre-GKRS Karnofsky Performance Scale score ≥ 90, and no pre-GKRS CN deficit (I-VIII) can benefit from stereotactic radiosurgery. It can be considered as the primary or adjuvant management of intracranial benign meningiomas.

An evaluation of outcomes in patients with traumatic brain injury at a referral hospital in Tanzania: evidence from a survival analysis.

OBJECTIVE: The purpose of this study was to determine if patients with traumatic brain injury (TBI) in low- and middle-income countries who receive surgery have better outcomes than patients with TBI who do not receive surgery, and whether this differs with severity of injury. METHODS: The authors generated a series of Kaplan-Meier plots and performed multiple Cox proportional hazard models to assess the relationship between TBI surgery and TBI severity. The TBI severity was categorized using admission Glasgow Coma Scale scores: mild (14, 15), moderate (9-13), or severe (3-8). The authors investigated outcomes from admission to hospital day 14. The outcome considered was the Glasgow Outcome Scale-Extended, categorized as poor outcome (1-4) and good outcome (5-8). The authors used TBI registry data collected from 2013 to 2017 at a regional referral hospital in Tanzania. RESULTS: Of the final 2502 patients, 609 (24%) received surgery and 1893 (76%) did not receive surgery. There were significantly fewer road traffic injuries and more violent causes of injury in those receiving surgery. Those receiving surgery were also more likely to receive care in the ICU, to have a poor outcome, to have a moderate or severe TBI, and to stay in the hospital longer. The hazard ratio for patients with TBI who underwent operation versus those who did not was 0.17 (95% CI 0.06-0.49; p < 0.001) in patients with moderate TBI; 0.2 (95% CI 0.06-0.64; p = 0.01) for those with mild TBI, and 0.47 (95% CI 0.24-0.89; p = 0.02) for those with severe TBI. CONCLUSIONS: Those who received surgery for their TBI had a lower hazard for poor outcome than those who did not. Surgical intervention was associated with the greatest improvement in outcomes for moderate head injuries, followed by mild and severe injuries. The findings suggest a reprioritization of patients with moderate TBI-a drastic change to the traditional practice within low- and middle-income countries in which the most severely injured patients are prioritized for care.

Disparities in health care determine prognosis in newly diagnosed glioblastoma.

OBJECTIVE Glioblastoma (GBM) is an aggressive brain malignancy with a short overall patient survival, yet there remains significant heterogeneity in outcomes. Although access to health care has previously been linked to impact on prognosis in several malignancies, this question remains incompletely answered in GBM. METHODS This study was a retrospective analysis of 354 newly diagnosed patients with GBM who underwent first resection at the authors' institution (2007-2015). RESULTS Of the 354 patients (median age 61 years, and 37.6% were females), 32 (9.0%) had no insurance, whereas 322 (91.0%) had insurance, of whom 131 (40.7%) had Medicare, 45 (14%) had Medicaid, and 146 (45.3%) had private insurance. On average, insured patients survived almost 2-fold longer (p < 0.0001) than those who were uninsured, whereas differences between specific insurance types did not influence survival. The adjusted hazard ratio (HR) for death was higher in uninsured patients (HR 2.27 [95% CI 1.49-3.33], p = 0.0003). Age, mean household income, tumor size at diagnosis, and extent of resection did not differ between insured and uninsured patients, but there was a disparity in primary care physician (PCP) status-none of the uninsured patients had PCPs, whereas 72% of insured patients had PCPs. Postoperative adjuvant treatment rates with temozolomide (TMZ) and radiation therapy (XRT) were significantly less in uninsured (TMZ in 56.3%, XRT in 56.3%) than in insured (TMZ in 75.2%, XRT in 79.2%; p = 0.02 and p = 0.003) patients. Insured patients receiving both agents had better prognosis than uninsured patients receiving the same treatment (9.1 vs 16.34 months; p = 0.025), suggesting that the survival effect in insured patients could only partly be explained by higher treatment rates. Moreover, having a PCP increased survival among the insured cohort (10.7 vs 16.1 months, HR 1.65 [95% CI 1.27-2.15]; p = 0.0001), which could be explained by significant differences in tumor diameter at initial diagnosis between patients with and without PCPs (4.3 vs 4.8 cm, p = 0.003), and a higher rate of clinical trial enrollment, suggesting a critical role of PCPs for a timelier diagnosis of GBM and proactive cancer care management. CONCLUSIONS Access to health care is a strong determinant of prognosis in newly diagnosed patients with GBM. Any type of insurance coverage and having a PCP improved prognosis in this patient cohort. Higher rates of treatment with TMZ plus XRT, clinical trial enrollment, fewer comorbidities, and early diagnosis may explain survival disparities. Lack of health insurance or a PCP are major challenges within the health care system, which, if improved upon, could favorably impact the prognosis of patients with GBM.

Morbidity and mortality associated with hypernatremia in patients with severe traumatic brain injury.

OBJECTIVE Hypernatremia is independently associated with increased mortality in critically ill patients. Few studies have evaluated the impact of hypernatremia on early mortality in patients with severe traumatic brain injury (TBI) treated in a neurocritical care unit. METHODS A retrospective review of patients with severe TBI (admission Glasgow Coma Scale score ≤ 8) treated in a single neurocritical care unit between 1986 and 2012 was performed. Patients with at least 3 serum sodium values were selected for the study. Patients with diabetes insipidus and those with hypernatremia on admission were excluded. The highest serum sodium level during the hospital stay was recorded, and hypernatremia was classified as none (≤ 150 mEq/L), mild (151-155 mEq/L), moderate (156-160 mEq/L), and severe (> 160 mEq/L). Multivariate Cox regression analysis was performed to determine independent predictors of early mortality. RESULTS A total of 588 patients with severe TBI were studied. The median number of serum sodium measurements for patients in this study was 17 (range 3-190). No hypernatremia was seen in 371 patients (63.1%), mild hypernatremia in 77 patients (13.1%), moderate hypernatremia in 50 patients (8.5%), and severe hypernatremia in 90 patients (15.3%). Hypernatremia was detected within the 1st week of admission in 79.3% of patients (n = 172), with the majority of patients (46%) being diagnosed within 72 hours after admission. Acute kidney injury, defined as a rise in creatinine of ≥ 0.3 mg/dl, was observed in 162 patients (27.6%) and was significantly associated with the degree of hypernatremia (p < 0.001). At discharge, 148 patients (25.2%) had died. Hypernatremia was a significant independent predictor of mortality (hazard ratios for mild: 3.4, moderate: 4.4, and severe: 8.4; p < 0.001). Survival analysis showed significantly lower survival rates for patients with greater degrees of hypernatremia (log-rank test, p < 0.001). CONCLUSIONS Hypernatremia after admission in patients with severe TBI was independently associated with greater risk of early mortality. In addition to severe hypernatremia, mild and moderate hypernatremia were significantly associated with increased early mortality in patients with severe TBI.

Bone graft options for spinal fusion following resection of spinal column tumors: systematic review and meta-analysis.

OBJECTIVE With the advent of new adjunctive therapy, the overall survival of patients harboring spinal column tumors has improved. However, there is limited knowledge regarding the optimal bone graft options following resection of spinal column tumors, due to their relative rarity and because fusion outcomes in this cohort are affected by various factors, such as radiation therapy (RT) and chemotherapy. Furthermore, bone graft options are often limited following tumor resection because the use of local bone grafts and bone morphogenetic proteins (BMPs) are usually avoided in light of microscopic infiltration of tumors into local bone and potential carcinogenicity of BMP. The objective of this study was to review and meta-analyze the relevant clinical literature to provide further clinical insight regarding bone graft options. METHODS A web-based MEDLINE search was conducted in accordance with preferred reporting items for systematic review and meta-analysis (PRISMA) guidelines, which yielded 27 articles with 383 patients. Information on baseline characteristics, tumor histology, adjunctive treatments, reconstruction methods, bone graft options, fusion rates, and time to fusion were collected. Pooled fusion rates (PFRs) and I2 values were calculated in meta-analysis. Meta-regression analyses were also performed if each variable appeared to affect fusion outcomes. Furthermore, data on 272 individual patients were available, which were additionally reviewed and statistically analyzed. RESULTS Overall, fusion rates varied widely from 36.0% to 100.0% due to both inter- and intrastudy heterogeneity, with a PFR of 85.7% (I2 = 36.4). The studies in which cages were filled with morselized iliac crest autogenic bone graft (ICABG) and/or other bone graft options were used for anterior fusion showed a significantly higher PFR of 92.8, compared with the other studies (83.3%, p = 0.04). In per-patient analysis, anterior plus posterior fusion resulted in a higher fusion rate than anterior fusion only (98.8% vs 86.4%, p < 0.001). Although unmodifiable, RT (90.3% vs 98.6%, p = 0.03) and lumbosacral tumors (74.6% vs 97.9%, p < 0.001) were associated with lower fusion rates in univariate analysis. The mean time to fusion was 5.4 ± 1.4 months (range 3-9 months), whereas 16 of 272 patients died before the confirmation of solid fusion with a mean survival of 3.1 ± 2.1 months (range 0.5-6 months). The average time to fusion of patients who received RT and chemotherapy were significantly longer than those who did not receive these adjunctive treatments (RT: 6.1 months vs 4.3 months, p < 0.001; chemotherapy: 6.0 months vs 4.3 months, p = 0.02). CONCLUSIONS Due to inter- and intrastudy heterogeneity in patient, disease, fusion criteria, and treatment characteristics, the optimal surgical techniques and factors predictive of fusion remain unclear. Clearly, future prospective, randomized studies will be necessary to better understand the issues surrounding bone graft selection following resection of spinal column tumors.

Application of morphometric analysis to patients with lung cancer metastasis to the spine: a clinical study.

OBJECTIVE Predicting the survival rate for patients with cancer is currently performed using the TNM Classification of Malignant Tumors (TNM). Identifying accurate prognostic markers of survival would allow better treatment stratification between more aggressive treatment strategies or palliation. This is especially relevant for patients with spinal metastases, who all have identical TNM staging and whose surgical decision-making is potentially complex. Analytical morphometrics quantifies patient frailty by measuring lean muscle mass and can predict risk for postoperative morbidity after lumbar spine surgery. This study evaluates whether morphometrics can be predictive of survival in patients with spinal metastases. METHODS Utilizing a retrospective registry of patients with spinal metastases who had undergone stereotactic body radiation therapy, the authors identified patients with primary lung cancer. Morphometric measurements were taken of the psoas muscle using CT of the lumbar spine. Additional morphometrics were taken of the L-4 vertebral body. Patients were stratified into tertiles based on psoas muscle area. The primary outcome measure was overall survival, which was measured from the date of the patient's CT scan to date of death. RESULTS A total of 168 patients were identified, with 54% male and 54% having multiple-level metastases. The median survival for all patients was 185.5 days (95% confidence interval [CI] 146-228 days). Survival was not associated with age, sex, or the number of levels of metastasis. Patients in the smallest tertile for the left psoas area had significantly shorter survival compared with a combination of the other two tertiles: 139 days versus 222 days, respectively, hazard ratio (HR) 1.47, 95% CI 1.06-2.04, p = 0.007. Total psoas tertiles were not predictive of mortality, but patients whose total psoas size was below the median size had significantly shorter survival compared with those greater than the median size: 146 days versus 253.5 days, respectively, HR 1.43, 95% CI 1.05-1.94, p = 0.025. To try to differentiate small body habitus from frailty, the ratio of psoas muscle area to vertebral body area was calculated. Total psoas size became predictive of mortality when normalized to vertebral body ratio, with patients in the lowest tertile having significantly shorter survival (p = 0.017). Left psoas to vertebral body ratio was also predictive of mortality in patients within the lowest tertile (p = 0.021). Right psoas size was not predictive of mortality in any calculations. CONCLUSIONS In patients with lung cancer metastases to the spine, morphometric analysis of psoas muscle and vertebral body size can be used to identify patients who are at risk for shorter survival. This information should be used to select patients who are appropriate candidates for surgery and for the tailoring of oncological treatment regimens.

Perioperative morbidity and mortality after lumbar trauma in the elderly.

OBJECT Traumatic fractures of the thoracolumbar spine are common injuries, accounting for approximately 90% of all spinal trauma. Lumbar spine trauma in the elderly is a growing public health problem with relatively little evidence to guide clinical management. The authors sought to characterize the complications, morbidity, and mortality associated with surgical and nonsurgical management in elderly patients with traumatic fractures of the lumbar spine. METHODS Using the National Sample Program of the National Trauma Data Bank, the authors performed a retrospective analysis of patients ≥ 55 years of age who had traumatic fracture to the lumbar spine. This group was divided into middle-aged (55-69 years) and elderly (≥ 70 years) cohorts. Cohorts were subdivided into nonoperative, vertebroplasty or kyphoplasty, noninstrumented surgery, and instrumented surgery. Univariate and multivariable analyses were used to characterize and identify predictors of medical and surgical complications, mortality, hospital length of stay, ICU length of stay, number of days on ventilator, and hospital discharge in each subgroup. Adjusted odds ratios, mean differences, and associated 95% CIs were reported. Statistical significance was assessed at p < 0.05, and the Bonferroni correction for multiple comparisons was applied for each outcome analysis. RESULTS Between 2003 and 2012, 22,835 people met the inclusion criteria, which represents 94,103 incidents nationally. Analyses revealed a similar medical and surgical complication profile between age groups. The most prevalent medical complications were pneumonia (7.0%), acute respiratory distress syndrome (3.6%), and deep venous thrombosis (3%). Surgical site infections occurred in 6.3% of cases. Instrumented surgery was associated with the highest odds of each complication (p < 0.001). The inpatient mortality rate was 6.8% for all subjects. Multivariable analyses demonstrated that age ≥ 70 years was an independent predictor of mortality (OR 3.16, 95% CI 2.77-3.60), whereas instrumented surgery (multivariable OR 0.38, 95% CI 0.28-0.52) and vertebroplasty or kyphoplasty (OR 0.27, 95% CI 0.17-0.45) were associated with decreased odds of death. In surviving patients, both older age (OR 0.32, 95% CI 0.30-0.34) and instrumented fusion (OR 0.37, 95% CI 0.33-0.41) were associated with decreased odds of discharge to home. CONCLUSIONS The present study confirms that lumbar surgery in the elderly is associated with increased morbidity. In particular, instrumented fusion is associated with periprocedural complications, prolonged hospitalization, and a decreased likelihood of being discharged home. However, fusion surgery is also associated with reduced mortality. Age alone should not be an exclusionary factor in identifying surgical candidates for instrumented lumbar spinal fusion. Future studies are needed to confirm these findings.

Molecular features assisting in diagnosis, surgery, and treatment decision making in low-grade gliomas.

The preferred management of suspected low-grade gliomas (LGGs) has been disputed, and the implications of molecular changes for medical and surgical management of LGGs are important to consider. Current strategies that make use of molecular markers and imaging techniques and therapeutic considerations offer additional options for management of LGGs. Mutations in the isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) genes suggest a role for this abnormal metabolic pathway in the pathogenesis and progression of these primary brain tumors. Use of magnetic resonance spectroscopy can provide preoperative detection of IDH-mutated gliomas and affect surgical planning. In addition, IDH1 and IDH2 mutation status may have an effect on surgical resectability of gliomas. The IDH-mutated tumors exhibit better prognosis throughout every grade of glioma, and mutation may be an early genetic event, preceding lineage-specific secondary and tertiary alterations that transform LGGs into secondary glioblastomas. The O6-methylguanine-DNAmethyltransferase (MGMT) promoter methylation and 1p19q codeletion status can predict sensitivity to chemotherapy and radiation in low- and intermediate-grade gliomas. Thus, these recent advances, which have led to a better understanding of how molecular, genetic, and epigenetic alterations influence the pathogenicity of the different histological grades of gliomas, can lead to better prognostication and may lead to specific targeted surgical interventions and medical therapies.

Liver Transplantation for HCC in HIV-Infected Patients: Long-Term Single-Center Experience.

BACKGROUND: HIV-infected patients now have long life expectation since the introduction of the highly active antiretroviral therapy (HAART). Liver diseases, especially cirrhosis and hepatocellular carcinoma (HCC), currently represent a leading cause of death in this setting of patients. AIM: To address the results of liver transplantation (LT) for HCC in HIV-infected patients. METHODS: All patients with and without HIV infection who underwent LT for HCC (n = 420) between 2001 and 2021 in our center were analyzed with the intent of comparing graft and patient survival. Cox regression analysis was used to determine prognostic survival factors and logistic regression to determine the predictor factors of post-LT recurrence. RESULTS: Among 1010 LT, 32 were HIV-infected recipients. With an average follow-up of 62 ± 51 months, 5-year overall survival in LT recipients with and without HIV-infection was 71.6% and 69.9%, respectively (p = ns), whereas 5-year graft survival in HIV-infected and HIV-non infected was 68.3% and 68.2%, respectively (p = ns). The independent predictive factor of survival in the study group was: HCV infection (HR 1.83, p = 0.024). There were no significant differences in the pathological characteristics of HCC between the two groups. The logistic regression analysis of the study population demonstrated that microvascular invasion (HR 5.18, p< 0.001), HCC diameter (HR 1.16, p = 0.028), and number of HCC nodules (HR 1.26, p = 0.003) were predictors of recurrence post-LT. CONCLUSION: Our study shows that HIV patients undergoing LT for HCC have comparable results in terms of post-LT survival. Excellent results can be achieved for HIV-infected patients with HCC, as long as a strategy of close surveillance and precise treatment of the tumor is adopted while on the waiting list.

Corticotroph hyperplasia and Cushing disease: diagnostic features and surgical management.

OBJECTIVE: This study was done to compare corticotroph hyperplasia and histopathologically proven adenomas in patients with Cushing disease by analyzing diagnostic features, surgical management, and clinical outcomes. METHODS: Patients with suspected pituitary Cushing disease were included in a retrospective cohort study and were excluded if results of pathological analysis of the surgical specimen were nondiagnostic or normal. Cases were reviewed by two experienced neuropathologists. Total lesion removal was used as a dichotomized surgical variable; it was defined as an extracapsular resection (including a rim of normal gland) in patients with an adenoma, and for hyperplasia patients it was defined as removal of the presumed lesion plus a rim of surrounding normal gland. Bivariate and multivariate analyses were performed. Recurrence-free survival was compared between the two groups. RESULTS: The final cohort consisted of 63 patients (15 with hyperplasia and 48 with adenoma). Normal pituitary acinar architecture was highly variable. Corticotroph hyperplasia was diagnosed based on the presence of expanded acini showing retained reticulin architecture and predominant staining for adrenocorticotropic hormone. Crooke's hyaline change was seen in 46.7% of specimens, and its frequency was equal in nonlesional tissue of both groups. The two groups differed only by MRI findings (equivocal/diffuse lesion in 46% of hyperplasia and 17% of adenoma; p = 0.03). Diagnostic uncertainty in the hyperplasia group resulted in additional confirmatory testing by 24-hour urinary free cortisol. Total lesion removal was infrequent in patients with hyperplasia compared to those with adenoma (33% vs 65%; p = 0.03). Initial biochemical remission was similar (67% in hyperplasia and 85% in adenoma; p = 0.11). There was no difference in hypothalamic-pituitary-adrenal axis recovery or disease recurrence. The median follow-up was 1.9 years (IQR 0.7-7.6 years) for the hyperplasia group and 1.2 years (IQR 0.4-2.4 years) for the adenoma group. Lack of a discrete lesion and diagnostic uncertainty were the only significant predictors of hyperplasia (sensitivity 53.3%, specificity 97.7%, positive predictive value 88.9%, negative predictive value 85.7%). An adjusted Cox proportional hazards model showed similar recurrence-free survival in the two groups. CONCLUSIONS: This study suggests an association between biochemically proven Cushing disease and histopathologically proven corticotroph hyperplasia. Imaging and operative findings can be ambiguous, and, compared to typical adenomas with a pseudocapsule, the surgical approach is more nuanced. Nevertheless, if treated appropriately, biochemical outcomes may be similar.

Local control and toxicity outcomes of stereotactic radiosurgery for spinal metastases of gastrointestinal origin.

OBJECTIVE: Colorectal cancer (CRC) and other gastrointestinal (GI) cancers are believed to have greater radioresistance than other histologies. The authors report local control and toxicity outcomes of stereotactic radiosurgery (SRS) to spinal metastases from GI primary cancers. METHODS: A retrospective single-center review was conducted of patients with spinal metastases from GI primary cancers treated with SRS from 2004 to 2017. Patient demographics and lesion characteristics were summarized using medians, interquartile ranges (IQRs), and proportions. Local failure (LF) was estimated using the cumulative incidence function adjusted for the competing risk of death and compared using Gray's test for equality. Multivariable analyses were conducted using Cox proportional hazard models, adjusting for death as a competing risk, on a per-lesion basis. Patients were stratified in the Cox model to account for repeated measures for clustered outcomes. Median survival was calculated using the Kaplan-Meier method. RESULTS: A total of 74 patients with 114 spine lesions were included in our analysis. The median age of the cohort was 62 years (IQR 53-70 years). Histologies included CRC (46%), hepatocellular carcinoma (19%), neuroendocrine carcinoma (13%), pancreatic carcinoma (12%), and other (10%). The 1- and 2-year cumulative incidence rates of LF were 24% (95% confidence interval [CI] 16%-33%) and 32% (95% CI 23%-42%), respectively. Univariable analysis revealed that older age (p = 0.015), right-sided primary CRCs (p = 0.038), and single fraction equivalent dose (SFED; α/ß = 10) < 20 Gy (p = 0.004) were associated with higher rates of LF. The 1-year cumulative incidence rates of LF for SFED < 20 Gy10 versus SFED ≥ 20 Gy10 were 35% and 7%, respectively. After controlling for gross tumor volume and prior radiation therapy to the lesion, SFED < 20 Gy10 remained independently associated with worse LF (hazard ratio 2.92, 95% CI 1.24-6.89, p = 0.014). Toxicities were minimal, with pain flare observed in 6 patients (8%) and 15 vertebral compression fractures (13%). CONCLUSIONS: Spinal metastases from GI primary cancers have high rates of LF with SRS at a lower dose. This study found that SRS dose is a significant predictor of failure and that prescribed SFED ≥ 20 Gy10 (biological equivalent dose ≥ 60 Gy10) is associated with superior local control.

Using a burr hole valve prevents proximal shunt failure in infants and toddlers.

OBJECTIVE: Proximal malfunction is the most common cause of ventriculoperitoneal (VP) shunt failure in young children. In this study, the authors sought to determine factors that affect the migration rate of ventricular catheters in hydrocephalic children who undergo shunt implantation in the first 3 years of life. METHODS: The authors reviewed the medical records and imaging studies of newly diagnosed and treated hydrocephalic children who were younger than 3 years. Patients who received VP shunt insertion through the parieto-occipital route were not included. In total, 78 patients were found who underwent VP shunt insertion between December 2006 and April 2017. Eighteen patients were excluded due to mortality, short follow-up period (< 1 year), and lack of imaging follow-up. The age, sex, etiology of hydrocephalus, initial length of ventricular catheter, valve type (burr hole vs non-burr hole), time to ventricular catheter migration, subsequent revision surgery, and follow-up period were analyzed. The diagnosis of a migrated ventricular catheter was made when serial imaging follow-up showed progressive withdrawal of the catheter tip from the ventricle, with the catheter shorter than 4 mm inside the ventricle, or progressive deviation of the ventricular catheter toward the midline or anterior ventricular wall. RESULTS: Sixty patients were enrolled. The mean age was 5.1 months (range 1-30 months). The mean follow-up period was 50.9 months (range 13-91 months). Eight patients had ventricular catheter migration, and in 7 of these 8 patients a non-burr hole valve was used. In the nonmigration group, a non-burr hole valve was used in only 6 of the 52 patients. Six of the 8 patients with catheter migration needed second surgeries, which included removal of the shunt due to disconnection in 1 patient. The remaining 2 patients with shunt migration were followed for 91 and 46 months, respectively, without clinical and imaging changes. The authors found that patient age at catheter insertion, ventricular catheter length, and the use of a burr hole valve were protective factors against migration. After ventricular catheter length and patient age at catheter insertion were treated as confounding variables and adjusted with multivariable Weibull proportional hazards regression, the use of a burr hole valve shunt remained a protective factor. CONCLUSIONS: The use of burr hole valves is a protective factor against ventricular catheter migration when the shunt is inserted via a frontal route. The authors suggest the use of a burr hole valve along with a frontal entry point in hydrocephalic children younger than 3 years to maintain long-term shunt function.

High rebleeding risk associated with choroidal collateral vessels in hemorrhagic moyamoya disease: analysis of a nonsurgical cohort in the Japan Adult Moyamoya Trial.

OBJECTIVEChoroidal collateral vessels typical of moyamoya disease have received attention as a potential bleeding source. The authors' previous angiographic cross-sectional analysis suggested a possible association between choroidal collaterals and posterior hemorrhage, indicating a high risk for rebleeding. The present longitudinal analysis is intended to determine whether choroidal collaterals are a predictor of rebleeding in hemorrhagic moyamoya disease.METHODSThe Japan Adult Moyamoya Trial group designed an ancillary cohort study using 5-year follow-up data on 37 patients included in the nonsurgical arm of the original randomized controlled trial and compared the rebleeding rate of those with and those without choroidal collaterals, represented by the connection between the anterior or posterior choroidal arteries and the medullary arteries. An expert panel determined whether a choroidal collateral was present in each patient through the measurement of baseline angiography studies. The rebleeding rate comparison was adjusted for age, diagnosis of hypertension, and involvement of the posterior cerebral artery.RESULTSChoroidal collaterals were present in 21 patients (56.8%). The rebleeding rate was 13.1% per year in the collateral-positive group as compared with 1.3% in the negative group (p = 0.008, log-rank test). The adjusted hazard ratio for rebleeding in the collateral-positive group relative to the negative group remained statistically significant (HR 11.10, 95% CI 1.37-89.91). Radiographic assessment of the collateral-positive group revealed good correspondence between the distribution of collaterals and rebleeding sites.CONCLUSIONSResults of this study suggest that choroidal collaterals are a bleeding source with a high risk for hemorrhagic recurrence and a predictor of rebleeding in hemorrhagic moyamoya disease.

Seizure outcomes in children with Rasmussen's encephalitis undergoing resective or hemispheric epilepsy surgery: an individual participant data meta-analysis.

OBJECTIVE: The objective of this study was to perform an individual participant data meta-analysis to identify preoperative factors associated with a good seizure outcome in children with Rasmussen's encephalitis (RE) undergoing resective or hemispheric epilepsy surgery. METHODS: Electronic databases (PubMed, Web of Science, CINAHL) were searched with no language or date restrictions to identify cohort studies of consecutive participants undergoing resective surgery that reported seizure outcomes. The authors recorded all preoperative factors that could plausibly be associated with seizure outcomes and used Cox regression analysis to identify which of these variables were associated with seizure freedom (i.e., Engel class I). RESULTS: Of 720 citations, 19 articles reporting on 187 participants were eligible. Seizure freedom (Engel class I) was observed in 113 participants (60.4%). On univariate analyses, younger age at disease onset (hazard ratio [HR] 0.906, p = 0.001), younger age at surgery (HR 0.928, p < 0.001), shorter time to surgery (HR 0.921, p = 0.001), and hemispherectomy (HR 0.283, p < 0.001) were all associated with longer time to postoperative seizure recurrence. Additionally, multivariable analysis including the aforementioned variables showed that younger age at surgery (HR 0.946, p = 0.043) and hemispherectomy (HR 0.297, p < 0.001) were independently and significantly associated with a greater time to seizure recurrence and longer duration of seizure freedom. CONCLUSIONS: The majority of pediatric patients undergoing resective or hemispheric surgery for RE achieve good seizure outcome. Although small retrospective cohort studies are inherently prone to bias, the best available evidence utilizing individual participant data suggests hemispheric surgery and younger age at surgery are associated with good seizure outcomes following epilepsy surgery. Large, multicenter observational studies with long-term follow-up are required to evaluate the risk factors identified in this review.

The impact of preradiosurgery embolization on intracranial arteriovenous malformations: a matched cohort analysis based on de novo lesion volume.

OBJECTIVE: The benefits and risks of pre-stereotactic radiosurgery (SRS) embolization have been reported in different studies. The goal of this study was to compare the long-term outcome of arteriovenous malformations (AVMs) treated with and without pre-SRS embolization. METHODS: A database including 1159 patients with AVMs who underwent SRS was reviewed. The embolized group was selected by including AVMs with pre-SRS embolization, maximal diameter > 30 mm, and estimated volume > 8 ml. The nonembolized group was defined as AVMs treated by SRS alone with matched de novo nidus volume. Outcomes including incidences of favorable clinical outcome (obliteration without hemorrhage, cyst formation, worsening, or new seizures), obliteration, adverse effects, and angioarchitectural complexity were evaluated. RESULTS: The study cohort comprised 17 patients in the embolized group (median AVM volume 17.0 ml) and 35 patients in the nonembolized group (median AVM volume 13.1 ml). The rates of obliteration (embolized cohort: 33%, 44%, and 56%; nonembolized cohort: 32%, 47%, and 47% at 4, 6, and 10 years, respectively) and favorable outcome were comparable between the 2 groups. However, the embolized group had a significantly higher incidence of repeat SRS (41% vs 23%, p = 0.012) and total procedures (median number of procedures 4 vs 1, p < 0.001), even with a significantly higher margin dose delivered at the first SRS (23 Gy vs 17 Gy, p < 0.001). The median angioarchitectural complexity score was reduced from 7 to 5 after embolization. Collateral flow and neovascularization were more frequently observed in the embolized nonobliterated AVMs. CONCLUSIONS: Both embolization plus SRS and SRS alone were effective therapies for moderately large (8-39 ml) AVMs. Even with a significantly higher prescription dose at the time of initial SRS, the embolized group still required more procedures to reach final obliteration. The presence of collateral flow and neovascularization could be risk factors for a failure to obliterate following treatment.

Insurance type impacts the economic burden and survival of patients with newly diagnosed glioblastoma.

OBJECTIVE: Glioblastoma (GBM) carries a high economic burden for patients and caregivers, much of which is associated with initial surgery. The authors investigated the impact of insurance status on the inpatient hospital costs of surgery for patients with GBM. METHODS: The authors conducted a retrospective review of patients with GBM (2010-2015) undergoing their first resection at the University of California, San Francisco, and corresponding inpatient hospital costs. RESULTS: Of 227 patients with GBM (median age 62 years, 37.9% females), 31 (13.7%) had Medicaid, 94 (41.4%) had Medicare, and 102 (44.9%) had private insurance. Medicaid patients had 30% higher overall hospital costs for surgery compared to non-Medicaid patients ($50,285 vs $38,779, p = 0.01). Medicaid patients had higher intensive care unit (ICU; p < 0.01), operating room (p < 0.03), imaging (p < 0.001), room and board (p < 0001), and pharmacy (p < 0.02) costs versus non-Medicaid patients. Medicaid patients had significantly longer overall and ICU lengths of stay (6.9 and 2.6 days) versus Medicare (4.0 and 1.5 days) and privately insured patients (3.9 and 1.8 days, p < 0.01). Medicaid patients had similar comorbidity rates to Medicare patients (67.8% vs 68.1%), and both groups had higher comorbidity rates than privately insured patients (37.3%, p < 0.0001). Only 67.7% of Medicaid patients had primary care providers (PCPs) versus 91.5% of Medicare and 86.3% of privately insured patients (p = 0.009) at the time of presentation. Tumor diameter at diagnosis was largest for Medicaid (4.7 cm) versus Medicare (4.1 cm) and privately insured patients (4.2 cm, p = 0.03). Preoperative (70 vs 90, p = 0.02) and postoperative (80 vs 90, p = 0.03) Karnofsky Performance Scale (KPS) scores were lowest for Medicaid versus non-Medicaid patients, while in subgroup analysis, postoperative KPS score was lowest for Medicaid patients (80, vs 90 for Medicare and 90 for private insurance; p = 0.03). Medicaid patients had significantly shorter median overall survival (10.7 months vs 12.8 months for Medicare and 15.8 months for private insurance; p = 0.02). Quality-adjusted life year (QALY) scores were 0.66 and 1.05 for Medicaid and non-Medicaid patients, respectively (p = 0.036). The incremental cost per QALY was $29,963 lower for the non-Medicaid cohort. CONCLUSIONS: Patients with GBMs and Medicaid have higher surgical costs, longer lengths of stay, poorer survival, and lower QALY scores. This study indicates that these patients lack PCPs, have more comorbidities, and present later in the disease course with larger tumors; these factors may drive the poorer postoperative function and greater consumption of hospital resources that were identified. Given limited resources and rising healthcare costs, factors such as access to PCPs, equitable adjuvant therapy, and early screening/diagnosis of disease need to be improved in order to improve prognosis and reduce hospital costs for patients with GBM.

Outcome evaluation of patients treated with fractionated Gamma Knife radiosurgery for large (> 3 cm) brain metastases: a dose-escalation study.

OBJECTIVE: Fractionated Gamma Knife radiosurgery (GKS) represents a feasible option for patients with large brain metastases (BM). However, the dose-fractionation scheme balanced between local control and radiation-induced toxicity remains unclear. Therefore, the authors conducted a dose-escalation study using fractionated GKS as the primary treatment for large (> 3 cm) BM. METHODS: The exclusion criteria were more than 3 lesions, evidence of leptomeningeal disease, metastatic melanoma, poor general condition, and previously treated lesions. Patients were randomized to receive 24, 27, or 30 Gy in 3 fractions (8, 9, or 10 Gy per fraction, respectively). The primary endpoint was the development of radiation necrosis assessed by a neuroradiologist blinded to the study. The secondary endpoints included the local progression-free survival (PFS) rate, change in tumor volume, development of distant intracranial progression, and overall survival. RESULTS: Between September 2016 and April 2018, 60 patients were eligible for the study, with 46 patients (15, 17, and 14 patients in the 8-, 9-, and 10-Gy groups, respectively) available for analysis. The median follow-up duration was 9.6 months (range 2.5-25.1 months). The 6-month estimated cumulative incidence of radiation necrosis was 0% in the 8-Gy group, 13% (95% confidence interval [CI] 0%-29%) in the 9-Gy group, and 37% (95% CI 1%-58%) in the 10-Gy group. Being in the 10-Gy group was a significant risk factor for the development of radiation necrosis (p = 0.047; hazard ratio [HR] 7.2, 95% CI 1.1-51.4). The 12-month local PFS rates were 65%, 80%, and 75% in the 8-, 9-, and 10-Gy groups, respectively. Being in the 8-Gy group was a risk factor for local treatment failure (p = 0.037; HR 2.5, 95% CI 1.1-29.6). The mean volume change from baseline was a 47.5% decrease in this cohort. Distant intracranial progression and overall survival did not differ among the 3 groups. CONCLUSIONS: In this dose-escalation study, 27 Gy in 3 fractions appeared to be a relevant regimen of fractionated GKS for large BM because 30 Gy in 3 fractions resulted in unacceptable toxicities and 24 Gy in 3 fractions was associated with local treatment failure.

The impact of statin therapy after surgical or endovascular treatment of cerebral aneurysms.

OBJECTIVE: Cerebral aneurysms represent the most common cause of spontaneous subarachnoid hemorrhage. Statins are lipid-lowering agents that may expert multiple pleiotropic vascular protective effects. The authors hypothesized that statin therapy after coil embolization or surgical clipping of cerebral aneurysms might improve clinical outcomes. METHODS: This was a retrospective cohort study using the National Health Insurance Service-National Sample Cohort Database in Korea. Patients who underwent coil embolization or surgical clipping for cerebral aneurysm between 2002 and 2013 were included. Based on prescription claims, the authors calculated the proportion of days covered (PDC) by statins during follow-up as a marker of statin therapy. The primary outcome was a composite of the development of stroke, myocardial infarction, and all-cause death. Multivariate time-dependent Cox regression analyses were performed. RESULTS: A total of 1381 patients who underwent coil embolization (n = 542) or surgical clipping (n = 839) of cerebral aneurysms were included in this study. During the mean (± SD) follow-up period of 3.83 ± 3.35 years, 335 (24.3%) patients experienced the primary outcome. Adjustments were performed for sex, age (as a continuous variable), treatment modality, aneurysm rupture status (ruptured or unruptured aneurysm), hypertension, diabetes mellitus, household income level, and prior history of ischemic stroke or intracerebral hemorrhage as time-independent variables and statin therapy during follow-up as a time-dependent variable. Consistent statin therapy (PDC > 80%) was significantly associated with a lower risk of the primary outcome (adjusted hazard ratio 0.34, 95% CI 0.14-0.85). CONCLUSIONS: Consistent statin therapy was significantly associated with better prognosis after coil embolization or surgical clipping of cerebral aneurysms.

Venous outflow restriction as a predictor of cavernous sinus dural arteriovenous fistula obliteration after Gamma Knife surgery.

OBJECTIVE: Gamma Knife surgery (GKS) obliterates 65%-87% of cavernous sinus dural arteriovenous fistulas (CSDAVFs). However, the hemodynamic effect on GKS outcomes is relatively unknown. The authors thus used the classification scheme developed by Suh et al. to explore this effect. METHODS: The authors retrospectively (1993-2016) included 123 patients with CSDAVFs who received GKS alone at the institute and classified them as proliferative type (PT; n = 23), restrictive type (RT; n = 61), or late restrictive type (LRT; n = 39) after analyzing their pre-GKS angiography images. Treatment parameters, the presence of numerous arterial feeders, and venous drainage numbers were compared across the CSDAVF types. Patients' follow-up MR images were evaluated for the presence of complete obliteration. A Kaplan-Meier analysis was conducted to determine the correlation between CSDAVF types and outcomes. RESULTS: The 36-month probability of complete obliteration was 74.3% for all patients, with no significant differences across types (p = 0.56). PT had the largest radiation volume (6.5 cm3, p < 0.001), the most isocenters (5, p = 0.015) and venous drainage routes (3, p < 0.001), and the lowest peripheral dose (16.6 Gy, p = 0.011) and isodose level coverage (64.3%, p = 0.006). CSDAVFs presenting with ocular patterns were less likely to be completely obliterated (hazard ratio 0.531, p = 0.009). After adjustment for age, CSDAVFs with more venous drainage routes were less likely to be completely obliterated (hazard ratio 0.784, p = 0.039). CONCLUSIONS: GKS is an equally effective treatment option for all 3 CSDAVF types. Furthermore, the number of venous drainage routes may help in predicting treatment outcomes and making therapeutic decisions.