Magnetic resonance-guided laser interstitial thermal therapy for brain tumors in geriatric patients.

OBJECTIVE: There is a paucity of studies assessing the use of MR-guided laser interstitial thermal therapy (LITT), specifically in the elderly population. The aim of this study was to evaluate the safety of LITT for brain tumors in geriatric patients. METHODS: Geriatric patients (≥ 65 years of age) treated with LITT for intracranial tumors at a single institution between January 2011 and November 2019 were retrospectively identified. The authors grouped patients into two distinct age cohorts: 65-74 years (group 1) and 75 years or older (group 2). Baseline characteristics, operative parameters, postoperative course, and morbidity were recorded for each patient. RESULTS: Fifty-five geriatric patients underwent 64 distinct LITT procedures for brain tumors. The majority of lesions (40 [62.5%]) treated were recurrent brain metastases or radiation necrosis. The median modified frailty index was 0.1 (low frailty; range 0-0.4) for patients in group 1 and 0.2 (intermediate frailty; range 0-0.4) for patients in group 2 (p > 0.05). The median hospital length of stay (LOS) was 1 day (IQR 1-2 days); there was no significant difference in LOS between the age groups. The hospital stay was significantly longer in patients who presented with a neurological symptom and in those who experienced a postoperative complication. The majority of patients (43 [68.3%] of 63 cases) were fit for discharge to their preoperative accommodation following LITT. The rate of discharge to home was not significantly different between the age groups. Those discharged to rehabilitation facilities were more likely to have presented with a neurological symptom. Nine patients (14.1% of cases) were found to have acute neurological complications following LITT, with nearly all patients showing complete or partial recovery at follow-up. The 30-day postoperative mortality rate was 1.6% (1 case). The complication and 30-day postoperative mortality rates were not significantly different between the two age groups. CONCLUSIONS: LITT can be considered a minimally invasive and safe neurosurgical procedure for the treatment of intracranial tumors in geriatric patients. Careful preoperative preparation and postoperative care is essential as LITT is not without risk. Appropriate patient selection for cranial surgery is essential, because neurosurgeons are treating an increasing number of elderly patients, but advanced age alone should not exclude patients from LITT without considering frailty and comorbidities.

Liquid biopsies for the diagnosis and surveillance of primary pediatric central nervous system tumors: a review for practicing neurosurgeons.

OBJECTIVE: Primary brain tumors are the most common cause of cancer-related deaths in children and pose difficult questions for the treating physician regarding issues such as the risk/benefit of performing a biopsy, the accuracy of monitoring methods, and the availability of prognostic indicators. It has been recently shown that tumor-specific DNA and proteins can be successfully isolated in liquid biopsies, and it may be possible to exploit this potential as a particularly useful tool for the clinician in addressing these issues. METHODS: A review of the current literature was conducted by searching PubMed and Scopus. MeSH terms for the search included "liquid biopsy," "brain," "tumor," and "pediatrics" in all fields. Articles were reviewed to identify the type of brain tumor involved, the method of tumor DNA/protein analysis, and the potential clinical utility. All articles involving primary studies of pediatric brain tumors were included, but reviews were excluded. RESULTS: The successful isolation of circulating tumor DNA (ctDNA), extracellular vesicles, and tumor-specific proteins from liquid biopsies has been consistently demonstrated. This most commonly occurs through CSF analysis, but it has also been successfully demonstrated using plasma and urine samples. Tumor-related gene mutations and alterations in protein expression are identifiable and, in some cases, have been correlated to specific neoplasms. The quantity of ctDNA isolated also appears to have a direct relationship with tumor progression and response to treatment. CONCLUSIONS: The use of liquid biopsies for the diagnosis and monitoring of primary pediatric brain tumors is a foreseeable possibility, as the requisite developmental steps have largely been demonstrated. Increasingly advanced molecular methods are being developed to improve the identification of tumor subtypes and tumor grades, and they may offer a method for monitoring treatment response. These minimally invasive markers will likely be used in the clinical treatment of pediatric brain tumors in the future.

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%.

Impact of frailty on surgery for glioblastoma: a critical evaluation of patient outcomes and caregivers' perceptions in a developing country.

OBJECTIVE: The authors aimed to evaluate the impact of age and frailty on the surgical outcomes of patients with glioblastoma (GBM) and to assess caregivers' perceptions regarding postdischarge care and challenges faced in the developing country of India. METHODS: This was a retrospective study of patients with histopathologically proven GBM from 2009 to 2018. Data regarding the clinical and radiological characteristics as well as surgical outcomes were collected from the institute's electronic database. Taking Indian demographics into account, the authors used the cutoff age of 60 years to define patients as elderly. Frailty was estimated using the 11-point modified frailty index (mFI-11). Patients were divided into three groups: robust, with an mFI score of 0; moderately frail, with an mFI score of 1 or 2; and severely frail, with an mFI score ≥ 3. A questionnaire-based survey was done to assess caregivers' perceptions about postdischarge care. RESULTS: Of the 276 patients, there were 93 (33.7%) elderly patients and 183 (66.3%) young or middle-aged patients. The proportion of severely frail patients was significantly more in the elderly group (38.7%) than in the young or middle-aged group (28.4%) (p < 0.001). The authors performed univariate and multivariate analysis of associations of different short-term outcomes with age, sex, frailty, and Charlson Comorbidity Index. On the multivariate analysis, only frailty was found to be a significant predictor for in-hospital mortality, postoperative complications, and length of hospital and ICU stay (p < 0.001). On Cox regression analysis, the severely frail group was found to have a significantly lower overall survival rate compared with the moderately frail (p = 0.001) and robust groups (p < 0.001). With the increase in frailty, there was a concomitant increase in the requirement for readmissions (p = 0.003), postdischarge specialist care (p = 0.001), and help from extrafamilial sources (p < 0.001). Greater dissatisfaction with psychosocial and financial support among the caregivers of severely frail patients was seen as they found themselves ill-equipped to provide postdischarge care at home (p < 0.001). CONCLUSIONS: Frailty is a better predictor of poorer surgical outcomes than chronological age in terms of duration of hospital and ICU stay, postoperative complications, and in-hospital mortality. It also adds to the psychosocial and financial burdens of the caregivers, making postdischarge care challenging.

Liquid biopsy for pediatric diffuse midline glioma: a review of circulating tumor DNA and cerebrospinal fluid tumor DNA.

Diffuse midline glioma (DMG) is a highly malignant childhood tumor with an exceedingly poor prognosis and limited treatment options. The majority of these tumors harbor somatic mutations in genes encoding histone variants. These recurrent mutations correlate with treatment response and are forming the basis for molecularly guided clinical trials. The ability to detect these mutations, either in circulating tumor DNA (ctDNA) or cerebrospinal fluid tumor DNA (CSF-tDNA), may enable noninvasive molecular profiling and earlier prediction of treatment response. Here, the authors review ctDNA and CSF-tDNA detection methods, detail recent studies that have explored detection of ctDNA and CSF-tDNA in patients with DMG, and discuss the implications of liquid biopsies for patients with DMG.

Blood-brain barrier disruption with low-intensity pulsed ultrasound for the treatment of pediatric brain tumors: a review and perspectives.

Pediatric brain tumors are the most common solid tumor and the first cause of cancer death in childhood, adolescence, and young adulthood. Current treatments are far from optimal in most of these tumors and the prognosis remains dismal for many of them. One of the main causes of the failure of current medical treatments is in part due to the existence of the blood-brain barrier (BBB), which limits drug delivery to tumors. Opening of the BBB with low-intensity pulsed ultrasound (LIPU) has emerged during the last 2 decades as a promising technique for enhancing drug delivery to the brain. In preclinical models, enhanced delivery of a wide range of therapeutic agents, from low-molecular-weight drugs, to antibodies and immune cells, has been observed as well as tumor control and increased survival. This technique has recently entered clinical trials with extracranial and intracranial devices. The safety and feasibility of this technique has furthermore been shown in patients treated monthly for recurrent glioblastoma receiving carboplatin chemotherapy. In this review, the characteristics of the BBB in the most common pediatric brain tumors are reviewed. Then, principles and mechanisms of BBB disruption with ultrasound (US) are summarized and described at the histological and biological levels. Lastly, preclinical studies that have used US-induced BBB opening in tumor models, recent clinical trials, and the potential use of this technology in pediatrics are provided.

Incorporating genomic signatures into surgical and medical decision-making for elderly glioblastoma patients.

Glioblastoma (GBM) is the most common type of malignant primary brain tumor in adults. It is a uniformly fatal disease (median overall survival 16 months) even with aggressive resection and an adjuvant temozolomide-based chemoradiation regimen. Age remains an independent risk factor for a poor prognosis. Several factors contribute to the dismal outcomes in the elderly population with GBM, including poor baseline health status, differences in underlying genomic alterations, and variability in the surgical and medical management of this subpopulation. The latter arises from a lack of adequate representation of elderly patients in clinical trials, resulting in limited data on the response of this subpopulation to standard treatment. Results from retrospective and some prospective studies have indicated that resection of only contrast-enhancing lesions and administration of hypofractionated radiotherapy in combination with temozolomide are effective strategies for optimizing survival while maintaining baseline quality of life in elderly GBM patients; however, survival remains dismal relative to that in a younger cohort. Here, the authors present historical context for the current strategies used for the multimodal management (surgical and medical) of elderly patients with GBM. Furthermore, they provide insights into elderly GBM patient-specific genomic signatures such as isocitrate dehydrogenase 1/2 (IDH1/2) wildtype status, telomerase reverse transcriptase promoter (TERTp) mutations, and somatic copy number alterations including CDK4/MDM2 coamplification, which are becoming better understood and could be utilized in a clinical trial design and patient stratification to guide the development of more effective adjuvant therapies specifically for elderly GBM patients.

Glioblastoma multiforme as a secondary malignancy following stereotactic radiosurgery of a meningioma: case report.

The documentation and exact incidence of stereotactic radiosurgery (SRS)-induced neoplasia is not well understood, with most literature restricted to single case reports and single-center retrospective reviews. The authors present a rare case of radiosurgery-induced glioblastoma multiforme (GBM) following radiosurgical treatment of a meningioma. A 74-year-old patient with a sporadic meningioma underwent radiosurgery following surgical removal of a WHO grade II meningioma. Eighteen months later she presented with seizures, and MRI revealed an intraaxial tumor, which was resected and proven to be a glioblastoma. As far as the authors are aware, this case represents the third case of GBM following SRS for a meningioma. This report serves to increase the awareness of this possible complication following SRS. The possibility of this rare complication should be explained to patients when obtaining their consent for radiosurgery.

The role of contrast-enhanced ultrasound in neurosurgical disease.

Contrast-enhanced ultrasound (CEUS) is a relatively new imaging modality in the realm of neurosurgical disease. CEUS permits the examination of blood flow through arteries, veins, and capillaries via intravascular contrast agents and allows vascular architectural mapping with extreme sensitivity and specificity. While it has established utility in other organ systems such as the liver and kidneys, CEUS has not been studied extensively in the brain. This report presents a review of the literature on the neurosurgical applications of CEUS and provides an outline of the imaging modality's role in the diagnosis, evaluation, and treatment of neurosurgical disease.

Tectal gliomas: assessment of malignant progression, clinical management, and quality of life in a supposedly benign neoplasm.

OBJECTIVE Tectal gliomas constitute a rare and inhomogeneous group of lesions with an uncertain clinical course. Because these supposedly benign tumors are frequently followed up by observation over many years, the authors undertook this analysis of their own case series in an effort to demonstrate that the clinical course is highly variable and that there is a potential for a progressive biology. METHODS Clinical data analysis of 23 cases of tectal glioma (involving 9 children and 14 adults) was performed retrospectively. Radiographic data were analyzed longitudinally and MR images were evaluated for tumor volume, contrast enhancement, and growth progression. Quality of life was assessed using the EORTC BN20 and C30 questionnaires during follow-up in a subgroup of patients. RESULTS The patients' mean age at diagnosis was 29.2 years. The main presenting symptom at diagnosis was hydrocephalus (80%). Six patients were treated by primary tumor resection (26.1%), 3 patients underwent biopsy followed by resection (13.1%), and 3 patients underwent biopsy only (13.1%). For additional treatment of hydrocephalus, 14 patients (60.9%) received shunts and/or endoscopic third ventriculostomy. Radiographic tumor progression was observed in 47.9% of the 23 cases. The mean time between diagnosis and growth progression was 51.5 months, and the mean time to contrast enhancement was 69.7 months. Histopathological analysis was obtained in 12 cases (52.2%), resulting in 5 cases of high-grade glioma (3 cases of glioblastoma multiforme [GBM], grade IV, and 2 of anaplastic astrocytoma, grade III), 5 cases of pilocytic astrocytoma, 1 diffuse astrocytoma, and 1 ganglioglioma. Malignant progression was observed in 2 cases, with 1 case progressing from a diffuse astrocytoma (grade II) to a GBM (grade IV) within a period of 13 years. Quality-of-life measurements demonstrated distinct functional deficits compared to a healthy sample as well as glioma control cohorts. CONCLUSIONS Analysis of this case series shows that a major subpopulation of tectal gliomas show progression and malignant transformation in children as well as in adolescents. These tumors therefore cannot be considered inert lesions and require histological confirmation and close follow-up. Quality-of-life questionnaires show that tectal glioma patients might benefit from special psychological support in emotional, social, and cognitive functionality.

Returning to work after multimodal treatment in glioblastoma patients.

OBJECTIVE Although multimodal treatment for glioblastoma (GBM) has resulted in longer survival, uncertainties exist regarding health-related quality of life and functional performance. Employment represents a useful functional end point and an indicator of social reintegration. The authors evaluated the rate of patients resuming their employment and the factors related to work capacity. METHODS The authors performed a retrospective study of working-age patients treated with surgery and radiochemotherapy between 2012 and 2015. Data were collected before and after surgery and at 6, 12, 18, and 24 months. Employment was categorized according to the French Socio-Professional Groups and analyzed regarding demographic and clinical data, performance status, socio-professional category, radiological features, type, and quality of resection. RESULTS A total of 125 patients, mean age 48.2 years, were identified. The mean follow-up was 20.7 months with a median survival of 22.9 months. Overall, 21 patients (18.3%) went back to work, most on a part-time basis (61.9%). Of the patients who were alive at 6, 12, 18, and 24 months after diagnosis, 8.7%, 13.8%, 15.3%, and 28.2%, respectively, were working. Patients going back to work were younger (p = 0.03), had fewer comorbidities (p = 0.02), and had a different distribution of socio-professional groups, with more patients belonging to higher occupation categories (p = 0.02). Treatment-related symptoms (36.2%) represented one of the main factors that prevented the resumption of work. Employment was strongly associated with performance status (p = 0.002) as well as gross-total removal (p = 0.04). No statistically significant difference was found regarding radiological or molecular features and the occurrence of complications after surgery. CONCLUSIONS GBM diagnosis and treatment has a significant socio-professional impact with only a minority of patients resuming work, mostly on a part-time basis.

Dynamic assessment of venous anatomy and function in neurosurgery with real-time intraoperative multimodal ultrasound: technical note.

The relevance of the cerebral venous system is often underestimated during neurosurgical procedures. Damage to this draining system can have catastrophic implications for the patient. Surgical decision-making and planning must consider each component of the venous compartment, from the medullary draining vein to the dural sinuses and extracranial veins. Intraoperative ultrasound (ioUS) permits the real-time study of venous compartments using different modalities, thus allowing complete characterization of their anatomical and functional features. The B-mode (brightness mode) offers a high-resolution anatomical representation of veins and their relationships with lesions. Doppler modalities (color, power, spectral) allow the study of blood flow and identification of vessels to distinguish their functional characteristics. Contrast-enhanced US allows one to perform real-time angiosonography showing both the functional and the anatomical aspects of vessels. In this technical report, the authors demonstrate the different applications of multimodal ioUS in neurosurgery for identifying the anatomical and functional characteristics of the venous compartment. They discuss the general principles and technical nuances of ioUS and analyze their potential implications for the study of various venous districts during neurosurgical procedures.

Use of ICG videoangiography and FLOW 800 analysis to identify the patient-specific venous circulation and predict the effect of venous sacrifice: a retrospective study of 172 patients.

OBJECTIVE The best management of veins encountered during the neurosurgical approach is still a matter of debate. Even if venous sacrifice were to lead to devastating consequences, under certain circumstances, it might prove to be desirable, enlarging the surgical field or increasing the extent of resection in tumor surgery. In this study, the authors present a large series of patients with vascular or oncological entities, in which they used indocyanine green videoangiography (ICG-VA) with FLOW 800 analysis to study the patient-specific venous flow characteristics and the management workflow in cases in which a venous sacrifice was necessary. METHODS Between May 2011 and December 2017, 1972 patients were admitted to the authors' division for tumor and/or neurovascular surgery. They retrospectively reviewed all cases in which ICG-VA and FLOW 800 were used intraoperatively with a specific target in the venous angiographic phase or for the management of venous sacrifice, and whose surgical videos and FLOW 800 analysis were available. RESULTS A total of 296 ICG-VA and FLOW 800 studies were performed intraoperatively. In all cases, the venous structures were clearly identifiable and were described according to the flow direction and speed. The authors therefore defined different patterns of presentation: arterialized veins, thrombosed veins, fast-draining veins with anterograde flow, slow-draining veins with anterograde flow, and slow-draining veins with retrograde flow. In 16 cases we also performed a temporary clipping test to predict the effect of the venous sacrifice by the identification of potential collateral circulation. CONCLUSIONS ICG-VA and FLOW 800 analysis can provide complete and real-time intraoperative information regarding patient-specific venous drainage pattern and can guide the decision-making process regarding venous sacrifice, with a possible impact on reduction of surgical complications.

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.

The role of indocyanine green videoangiography with FLOW 800 analysis for the surgical management of central nervous system tumors: an update.

OBJECTIVE Indocyanine green videoangiography (ICG-VA) is an intraoperative technique used to highlight vessels in neurovascular surgery. Its application in the study of the vascular pathophysiology in CNS tumors and its role in their surgical management are still rather limited. A recent innovation of ICG-VA (i.e., the FLOW 800 algorithm integrated in the surgical microscope) allows a semiquantitative evaluation of cerebral blood flow. The aim of this study was to evaluate for the first time the systematic application of ICG-VA and FLOW 800 analysis during surgical removal of CNS tumors. METHODS Between May 2011 and December 2017, all cases in which ICG-VA and FLOW 800 analysis were used at least one time before, during, or after the tumor resection, and in which surgical videos were available, were retrospectively reviewed. Results of the histological analysis were analyzed together with the intraoperative ICG-VA with FLOW 800 in order to investigate the tumor-related videoangiographic features. RESULTS Seventy-one patients who underwent surgery for cerebral and spinal tumors were intraoperatively analyzed using ICG-VA with FLOW 800, either before or after tumor resection, for a total of 93 videoangiographic studies. The histological diagnosis was meningioma in 25 cases, glioma in 14, metastasis in 7, pineal region tumor in 5, hemangioblastoma in 4, chordoma in 3, and other histological types in 13 cases. The authors identified 4 possible applications of ICG-VA and FLOW 800 in CNS tumor surgery: extradural surveys allowed exploration of sinus patency and the course of veins before dural opening; preresection surveys helped in identifying pathological vascularization (arteriovenous fistulas and neo-angiogenesis) and regional venous outflow, and in performing temporary venous clipping tests, when necessary; postresection surveys were conducted to evaluate arterial and venous patency and parenchymal perfusion after tumor removal; and a premyelotomy survey was conducted in intramedullary tumors to highlight the posterior median sulcus. CONCLUSIONS The authors found ICG-VA with FLOW 800 to be a useful method to monitor blood flow in the exposed vessels and parenchyma during microsurgical removal of CNS tumors in selected cases. In particular, a preresection survey provides useful information about pathophysiological changes of brain vasculature related to the tumor and aids in the individuation of helpful landmarks for the surgical approach, and the postresection survey helps to prevent potential complications associated with the resection (such as local hypoperfusion or venous infarction).

Magnetic resonance-guided interstitial high-intensity focused ultrasound for brain tumor ablation.

Currently, treatment of brain tumors is limited to resection, chemotherapy, and radiotherapy. Thermal ablation has been recently explored. High-intensity focused ultrasound (HIFU) is being explored as an alternative. Specifically, the authors propose delivering HIFU internally to the tumor with an MRI-guided robotic assistant (MRgRA). The advantage of the authors' interstitial device over external MRI-guided HIFU (MRgHIFU) is that it allows for conformal, precise ablation and concurrent tissue sampling. The authors describe their workflow for MRgRA HIFU delivery.

Machine learning applications for the differentiation of primary central nervous system lymphoma from glioblastoma on imaging: a systematic review and meta-analysis.

OBJECTIVEGlioblastoma (GBM) and primary central nervous system lymphoma (PCNSL) are common intracranial pathologies encountered by neurosurgeons. They often may have similar radiological findings, making diagnosis difficult without surgical biopsy; however, management is quite different between these two entities. Recently, predictive analytics, including machine learning (ML), have garnered attention for their potential to aid in the diagnostic assessment of a variety of pathologies. Several ML algorithms have recently been designed to differentiate GBM from PCNSL radiologically with a high sensitivity and specificity. The objective of this systematic review and meta-analysis was to evaluate the implementation of ML algorithms in differentiating GBM and PCNSL.METHODSThe authors performed a systematic review of the literature using PubMed in accordance with PRISMA guidelines to select and evaluate studies that included themes of ML and brain tumors. These studies were further narrowed down to focus on works published between January 2008 and May 2018 addressing the use of ML in training models to distinguish between GBM and PCNSL on radiological imaging. Outcomes assessed were test characteristics such as accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC).RESULTSEight studies were identified addressing use of ML in training classifiers to distinguish between GBM and PCNSL on radiological imaging. ML performed well with the lowest reported AUC being 0.878. In studies in which ML was directly compared with radiologists, ML performed better than or as well as the radiologists. However, when ML was applied to an external data set, it performed more poorly.CONCLUSIONSFew studies have applied ML to solve the problem of differentiating GBM from PCNSL using imaging alone. Of the currently published studies, ML algorithms have demonstrated promising results and certainly have the potential to aid radiologists with difficult cases, which could expedite the neurosurgical decision-making process. It is likely that ML algorithms will help to optimize neurosurgical patient outcomes as well as the cost-effectiveness of neurosurgical care if the problem of overfitting can be overcome.

Chimeric antigen receptor T-cell immunotherapy for glioblastoma: practical insights for neurosurgeons.

The prognosis for glioblastoma (GBM) remains exceedingly poor despite state-of-the-art multimodal therapy. Immunotherapy, particularly with cytotoxic T cells, represents a promising alternative. Perhaps the most prominent T-cell technology is the chimeric antigen receptor (CAR), which in 2017 received accelerated approval from the Food and Drug Administration for the treatment of hematological malignancies. Several CARs for GBM have been recently tested in clinical trials with exciting results. The authors review these clinical data and discuss areas of ongoing research.

High-intensity focused ultrasound: past, present, and future in neurosurgery.

Since Lynn and colleagues first described the use of focused ultrasound (FUS) waves for intracranial ablation in 1942, many strides have been made toward the treatment of several brain pathologies using this novel technology. In the modern era of minimal invasiveness, high-intensity focused ultrasound (HIFU) promises therapeutic utility for multiple neurosurgical applications, including treatment of tumors, stroke, epilepsy, and functional disorders. Although the use of HIFU as a potential therapeutic modality in the brain has been under study for several decades, relatively few neuroscientists, neurologists, or even neurosurgeons are familiar with it. In this extensive review, the authors intend to shed light on the current use of HIFU in different neurosurgical avenues and its mechanism of action, as well as provide an update on the outcome of various trials and advances expected from various preclinical studies in the near future. Although the initial technical challenges have been overcome and the technology has been improved, only very few clinical trials have thus far been carried out. The number of clinical trials related to neurological disorders is expected to increase in the coming years, as this novel therapeutic device appears to have a substantial expansive potential. There is great opportunity to expand the use of HIFU across various medical and surgical disciplines for the treatment of different pathologies. As this technology gains recognition, it will open the door for further research opportunities and innovation.

Safety of stereotactic laser ablations performed as treatment for glioblastomas in a conventional magnetic resonance imaging suite.

OBJECTIVE Stereotactic laser ablation (SLA) is typically performed in the setting of intraoperative MRI or in a staged manner in which probe insertion is performed in the operating room and thermal ablation takes place in an MRI suite. METHODS The authors describe their experience, in which SLA for glioblastoma (GBM) treatment was performed entirely within a conventional MRI suite using the SmartFrame stereotactic device. RESULTS All 10 patients with GBM (2 with isocitrate dehydrogenase 1 mutation [mIDH1] and 8 with wild-type IDH1 [wtIDH1]) were followed for > 6 months. One of these patients underwent 2 independent SLAs approximately 12 months apart. Biopsies were performed prior to SLA for all patients. There were no perioperative morbidities, wound infections, or unplanned 30-day readmissions. The average time for a 3-trajectory SLA (n = 3) was 436 ± 102 minutes; for a 2-trajectory SLA (n = 4) was 321 ± 85 minutes; and for a single-trajectory SLA (n = 4) was 254 ± 28 minutes. No tumor recurrence occurred within the blue isotherm line ablation zone, although 2 patients experienced recurrence immediately adjacent to the blue isotherm ablation line. Overall survival for the patient cohort averaged 356 days, with the 2 patients who had mIDH1 GBMs exhibiting the longest survival (811 and 654 days). CONCLUSIONS Multitrajectory SLA for treatment of GBM can be safely performed using the SmartFrame stereotactic device in a conventional MRI suite.