Advancing precision prognostication in neuro-oncology: Machine learning models for data-driven personalized survival predictions in IDH-wildtype glioblastoma.

Background: Glioblastoma (GBM) remains associated with a dismal prognoses despite standard therapies. While population-level survival statistics are established, generating individualized prognosis remains challenging. We aim to develop machine learning (ML) models that generate personalized survival predictions for GBM patients to enhance prognostication. Methods: Adult patients with histologically confirmed IDH-wildtype GBM from the National Cancer Database (NCDB) were analyzed. ML models were developed with TabPFN, TabNet, XGBoost, LightGBM, and Random Forest algorithms to predict mortality at 6, 12, 18, and 24 months postdiagnosis. SHapley Additive exPlanations (SHAP) were employed to enhance the interpretability of the models. Models were primarily evaluated using the area under the receiver operating characteristic (AUROC) values, and the top-performing models indicated by the highest AUROCs for each outcome were deployed in a web application that was created for individualized predictions. Results: A total of 7537 patients were retrieved from the NCDB. Performance evaluation revealed the top-performing models for each outcome were built using the TabPFN algorithm. The TabPFN models yielded mean AUROCs of 0.836, 0.78, 0.732, and 0.724 in predicting 6, 12, 18, and 24 month mortality, respectively. Conclusions: This study establishes ML models tailored to individual patients to enhance GBM prognostication. Future work should focus on external validation and dynamic updating as new data emerge.

Dose-Painting Linear Accelerator Radiosurgery of Glomus Jugulare With Dosimetric Comparison to Gamma Knife.

Objectives In this study, we outline our rationale for delivering a dose of ≥15 Gy in stereotactic radiosurgery (SRS) of glomus jugulare tumor (GJT) while ensuring the avoidance of complications associated with doses >13 Gy to the facial nerve. To avoid such complications, we initially utilized the Gamma Knife Perfexion (GK) system (Elekta Instrument AB, Stockholm, Sweden) at our institution but encountered challenges related to lengthy treatment times and difficulty in sculpting doses to minimize doses to spare the facial nerve. As a potential solution, we propose the use of HyperArc (Varian Medical Systems, Palo Alto, CA), a newly developed automated delivery platform for linear accelerator (LINAC)-based SRS. HyperArc offers the potential for faster treatment and more complex shaping of the radiotherapy dose with multiple arcs and multi-leaf collimators. Methods We retrospectively reviewed nine cases of patients with GJT treated with HyperArc. Patients' demographic and treatment data were collected. Additionally, simulated GK treatment plans were created and compared with HyperArc plans to assess time savings, PTV coverage, and plan quality. Results One male and eight female patients, with a mean age of 63.9 years, were included. Treatments were delivered on average in 29 minutes, achieving 95-100% of the tumor while limiting the facial nerve to <13 Gy. Treatments replanned using our GK system could achieve only 92-99% tumor coverage while respecting facial nerve constraints, with average treatment times of 180 minutes. Comparable plan quality parameters were attained with both modalities. Conclusions The HyperArc system provides a qualitatively satisfactory and rapid treatment delivery of a highly sculpted radiotherapy dose to maximize tumor coverage and minimize facial nerve complications.

The Learning Curve and Clinical Outcomes With 250 Laser Ablations for Brain Tumors: A Pathway to Experience.

BACKGROUND AND OBJECTIVES: Laser interstitial thermal therapy (LITT) has gained popularity as a minimally invasive technique for treating brain tumors. Despite its proven safety profile, LITT is not yet widely available, and there is a lack of data on the learning curve required to achieve proficiency. This study analyzes a 250-patient cohort of laser-ablated tumors to describe changes in patient selection and clinical outcomes over time and experience, with the aim of providing insight into the learning curve for incorporating LITT into a neuro-oncology program and identifying a cutoff point that distinguishes novice from expert performance. METHODS: We retrospectively reviewed 250 patients with brain tumor who underwent LITT between 2013 and 2022. Demographic and clinical data were analyzed. Kaplan Meier curves were used for survival analysis. Operative time was evaluated using exponential curve-fit regression analysis to identify when consistent improvement began. RESULTS: The patients were divided into quartiles (Q) based on their date of surgery. Mean tumor volume increased over time (Q1 = 5.7 and Q4 = 11.9 cm 3 , P = .004), and newly diagnosed lesions were more frequently ablated ( P = .0001). Mean operative time (Q1 v Q4 = 322.3 v 204.6 min, P < .0001) and neurosurgical readmission rate (Q1 v Q4 = 7.8% v 0%, P = .03) were reduced over time. The exponential curve-fit analysis showed a sustained decay in operative time after case #74. The extent of ablation ( P = .69), the recurrence ( P = .11), and the postoperative complication rate ( P = .78) did not vary over time. CONCLUSION: After treating 74 patients, a downward trend in the operative time is observed. Patient selection is broadened as experience increases.

Widening the Operative Corridor-Evaluating the Transcortical Approach to Giant Falcine Meningiomas.

BACKGROUND: Giant falcine meningiomas are surgically complex as they are deep in location, concealed by normal brain parenchyma, in close proximity to various neurovascular structures, and frequently involve the falx bilaterally. Although classically accessed using a bifrontal craniotomy and interhemispheric approach, little data exist on alternative operative corridors for these challenging tumors. We evaluated perioperative and long-term outcomes in patients undergoing transcortical resection of giant bilateral falcine meningiomas. METHODS: From 2013 to 2022, fourteen patients with giant bilateral falcine meningiomas treated via a transcortical approach at our institution were identified. Perioperative and long-term outcomes were evaluated to determine predictors of adverse events. Corticectomy depth was also analyzed to determine if it correlated with increased postoperative seizure rates. RESULTS: 57.1% of cases were WHO grade 2 meningiomas. Average tumor volume was 77.8 ± 46.5 cm3 and near/gross total resection was achieved in 78.6% of patients. No patient developed a venous infarct or had seizures in the 6 months after surgery. Average corticectomy depth was 0.83 ± 0.71 cm and increasing corticectomy depth did not correlate with higher risk of postoperative seizures (P = 0.44). Increasing extent of tumor resection correlated with lower tumor grade (P = 0.011) and only 1 patient required repeat resection during a median follow-period of 24.9 months. CONCLUSIONS: The transcortical approach is a safe alternative corridor for accessing giant, falcine meningiomas, and postoperative seizures were not found to correlate with increasing corticectomy depth. Further prospective studies are necessary to determine the best approach to these surgically complex lesions.

Ganoderic acids alleviate atherosclerosis by inhibiting macrophage M1 polarization via TLR4/MyD88/NF-κB signaling pathway.

BACKGROUND AND AIMS: Atherosclerosis (AS) is a chronic inflammatory disease characterized by lipid infiltration and plaque formation in blood vessel walls. Ganoderic acids (GA), a class of major bioactive compounds isolated from the Chinese traditional medicine Ganoderma lucidum, have multiple pharmacological activities. This study aimed to determine the anti-atherosclerotic effect of GA and reveal the pharmacological mechanism. METHODS: ApoE-/- mice were fed a high-cholesterol diet and treated with GA for 16 weeks to induce AS and identify the effect of GA. Network pharmacological analysis was performed to predict the anti-atherosclerotic mechanisms. An invitro cell model was used to explore the effect of GA on macrophage polarization and the possible mechanism involved in bone marrow dereived macrophages (BMDMs) and RAW264.7 cells stimulated with lipopolysaccharide or oxidized low-density lipoprotein. RESULTS: It was found that GA at 5 and 25 mg/kg/d significantly inhibited the development of AS and increased plaque stability, as evidenced by decreased plaque in the aorta, reduced necrotic core size and increased collagen/lipid ratio in lesions. GA reduced the proportion of M1 macrophages in plaques, but had no effect on M2 macrophages. In vitro experiments showed that GA (1, 5, 25 µg/mL) significantly decreased the proportion of CD86+ macrophages and the mRNA levels of IL-6, IL-1ß, and MCP-1 in macrophages. Experimental results showed that GA inhibited M1 macrophage polarization by regulating TLR4/MyD88/NF-κB signaling pathway. CONCLUSIONS: This study demonstrated that GA play an important role in plaque stability and macrophage polarization. GA exert the anti-atherosclerotic effect partly by regulating TLR4/MyD88/NF-κB signaling pathways to inhibit M1 polarization of macrophages. Our study provides theoretical basis and experimental data for the pharmacological activity and mechanisms of GA against AS.

The Utility of Transcranial Electrical Stimulation Motor Evoked Potential Monitoring in Predicting Postoperative Supplementary Motor Area Syndrome and Motor Function Recovery.

BACKGROUND: Postoperative hemiparesis following frontal lobe lesion resection is alarming, and predicting motor function recovery is challenging. Supplementary motor area (SMA) syndrome following resection of frontal lobe lesions is often indistinguishable from postoperative motor deficit due to surgical injury of motor tracts. We aimed to describe the use of intraoperative transcranial electrical stimulation (TES) with motor evoked potential monitoring data as a diagnostic tool to distinguish between SMA syndrome and permanent motor deficit (PMD). METHODS: A retrospective analysis of 235 patients undergoing craniotomy and resection with TES-MEP monitoring for a frontal lobe lesion was performed. Patients who developed immediate postoperative motor deficit were included. Motor deficit and TES-MEP findings were categorized by muscle group as left upper extremity, left lower extremity, right upper extremity, or right lower extremity. Statistical analysis was performed to determine the predictive value of stable TES-MEP for SMA syndrome versus PMD. RESULTS: This study included 20 patients comprising 29 cases of immediate postoperative motor deficit by muscle group. Of these, 27 cases resolved and were diagnosed as SMA syndrome, and 2 cases progressed to PMD. TES-MEP stability was significantly associated with diagnosis of SMA syndrome (P = 0.015). TES-MEP showed excellent diagnostic utility with a sensitivity and positive predictive value of 100% and 92.6%, respectively. Negative predictive value was 100%. CONCLUSIONS: Temporary SMA syndrome is difficult to distinguish from PMD immediately postoperatively. TES-MEP may be a useful intraoperative adjunct that may aid in distinguishing SMA syndrome from PMD secondary to surgical injury.

Same-day discharge after craniotomy for brain tumor resection: enhancing patient selection through a prognostic scoring system.

OBJECTIVE: Neurosurgery, among other surgical fields, is amid a shift in patient management with enhanced recovery and same-day discharge (SDD) protocols slowly becoming more popular and feasible. While such protocols reduce the risk of nosocomial complications and improve patient satisfaction, appropriate patient selection remains an area of debate. The authors aimed to better quantify selection criteria through a prospective follow-up study of patients undergoing brain tumor resection with SDD. METHODS: Three arms of analysis were carried out. First, clinical data of SDD patients were prospectively collected between August 2021 and August 2022. In parallel, a retrospective analysis of patients who qualified for SDD but were excluded at surgeon clinical discretion over the same period was performed. Third, a comparative analysis of the pilot and follow-up studies was done from which a clinical scoring system for patient selection was derived. RESULTS: Over the duration of the study, 31 of 334 patients were selected for SDD while 59 qualified for SDD by previously defined criteria but were not selected at the surgeon's discretion. There was no difference in outcomes between the two groups, and there were no postoperative complications among the SDD group within 30 days of surgery. Preoperative clinical characteristics found to be significantly different between the two cohorts (left-sided lesion, extra-axial pathology, prior treatment of brain tumor, and tumor volume ≤ 11.75 cm3) were included in a predictive scoring system for successful SDD. The scoring system was found to significantly predict high or low likelihood for successful SDD when tested on the mixed prospective cohort. CONCLUSIONS: This study provides a straightforward clinical scoring system for appropriate selection of candidates for SDD after craniotomy for brain tumor resection. This clinical tool aims to aid clinicians in appropriate admission course selection and builds on the growing literature surrounding same-day and outpatient cranial neurosurgery.

The anti-hepatocellular carcinoma effects of polysaccharides from Ganoderma lucidum by regulating macrophage polarization via the MAPK/NF-κB signaling pathway.

The response of macrophages to environmental signals demonstrates its heterogeneity and plasticity. After different forms of polarized activation, macrophages reach the M1 or M2 activation state according to their respective environment. Ganoderma lucidum polysaccharide (GLPS) is a major bioactive component of Ganoderma lucidum, a well-known medicinal mushroom. Although the immunomodulatory and anti-tumor effects of GLPS have been proven, GLPS's effect on inhibiting hepatocellular carcinoma (HCC) by regulating macrophage polarization is little known. Our data showed that GLPS notably inhibited the growth of a Hepa1-6 allograft. The expression of M1 marker CD86 was higher in the tumor tissue of the GLPS treatment group than in the control group in vivo. In vitro, the phagocytic activity and NO production of macrophages were increased by GLPS treatment. Moreover, it was discovered that GLPS was able to increase the expression of the M1 phenotype marker CD86, iNOS, and pro-inflammatory cytokines comprising IL-12a, IL-23a, IL-27 and TNF-α, but inhibited macrophage polarization towards the M2 phenotype by decreasing the expression of CD206, Arg-1, and inflammation-related cytokines comprising IL-6 and IL-10. The data suggest that GLPS may regulate macrophage polarization. Mechanistically, GLPS increased the phosphorylation of MEK and ERK. In addition, the phosphorylation of IκBα and P65 was increased by GLPS treatment. These data showed that GLPS can regulate the MAPK/NF-κB signaling pathway responsible for M1 polarization. In a nutshell, our research puts forward a new application of GLPS in anti-HCC treatment by regulating macrophage polarization through activating MAPK/NF-κB signaling.

Radical supramaximal resection for newly diagnosed left-sided eloquent glioblastoma: safety and improved survival over gross-total resection.

OBJECTIVE: Supramaximal resection (SMR) has arisen as a possible surrogate to gross-total resection (GTR) to improve survival in newly diagnosed glioblastoma (nGBM). However, SMR has traditionally been limited to noneloquent regions and its feasibility in eloquent nGBM remains unclear. The authors conducted a retrospective multivariate propensity-matched analysis comparing survival outcomes for patients with left-sided eloquent nGBM undergoing SMR versus GTR. METHODS: A retrospective review was performed of all patients at our institution who underwent SMR or GTR of a left-sided eloquent nGBM during the period from 2011 to 2020. All patients underwent some form of preoperative or intraoperative functional mapping and underwent awake or asleep craniotomy (craniotomy under general anesthesia); however, awake craniotomy was performed in the majority of patients and the focus of the study was SMR achieved via awake craniotomy and functional mapping with lesionectomy and additional peritumoral fluid attenuated inversion recovery (FLAIR) resection. Propensity scores were generated controlling for age, tumor location, and preoperative Karnofsky Performance Status (KPS) score with the nearest-neighbor algorithm. RESULTS: A total of 102 patients (48 SMR, 54 GTR) were included in this study. The median overall survival (OS) and progression-free survival (PFS) for patients receiving SMR were 22.9 and 5.1 months, respectively. Propensity matching resulted in a final cohort of 27 SMR versus 27 GTR patients. SMR conferred improved OS (21.55 vs 15.49 months, p = 0.0098) and PFS (4.51 vs 3.59 months, p = 0.041) compared to GTR. There was no significant difference in postoperative complication rates or KPS score in SMR compared with GTR patients (p = 0.236 and p = 0.736, respectively). In patients receiving SMR, improved OS and PFS showed a dose-dependent relationship with extent of FLAIR resection (EOFR) on log-rank test for trend (p < 0.001). CONCLUSIONS: SMR by means of awake craniotomy with functional mapping for left-sided eloquent nGBM is safe and confers a survival benefit compared to GTR obtained with lesionectomy alone while preserving postoperative neurological integrity. When tolerated, greater EOFR with SMR may be associated with improved survival.

Frameless Robotic-Assisted Biopsy of Pediatric Brainstem Lesions: A Systematic Review and Meta-Analysis of Efficacy and Safety.

BACKGROUND: Pediatric brainstem lesions are diagnoses that require tissue sampling to advance our understanding of them and their management. Frameless, robot-assisted biopsy of these lesions has emerged as a novel, viable biopsy approach. Correspondingly, the aim of this study was to quantitively and qualitatively summarize the contemporary literature regarding the likelihood of achieving tumor diagnosis and experiencing any postoperative complications. METHODS: Searches of 7 electronic databases from inception to September 2022 were conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Articles were screened against prespecified criteria. Outcomes were pooled by random-effects meta-analyses of proportions where possible. RESULTS: A total of 8 cohort studies satisfied all criteria. They described 99 pediatric patients with brainstem lesions in whom frameless, robot-assisted biopsy was involved in their work-up. There were 62 (63%) male and 37 (37%) female patients with a median age of 9 years at time of biopsy. Overall, all patients had sufficient tissue obtained by initial biopsy for evaluation. Pooled estimate of achieving tumor diagnosis was 100% (95% confidence interval [CI] 97%-100%) across all studies with a high degree of certainty. Across all studies, there were no cases of procedure-related mortality. The pooled estimates of transient and permanent complications after biopsy were 10% (95% CI 4%-19%) and 0% (95% CI 0%-2%), respectively, of very low and low degrees of certainty each. CONCLUSIONS: The contemporary metadata demonstrates the frameless, robot-assisted biopsy of pediatric brainstem lesions is both effective and safe when performed in an experienced setting. Further research is needed to augment robot and automated technologies into workup algorithms.

Brusatol Inhibits Proliferation and Metastasis of Colorectal Cancer by Targeting and Reversing the RhoA/ROCK1 Pathway.

Brusatol (BRU) is an important compound extracted from Brucea javanica oil, whose pharmacological effects are able to induce a series of biological effects, including inhibition of tumor cell growth, anti-inflammatory, antiviral, and antitumor. Currently, there are so few studies about the brusatol effects on colorectal cancer that its anticancer mechanism has not been clearly defined. In this study, we made an in-depth investigation into the brusatol effect towards the proliferation and metastasis of colon cancer and the possible mechanism. The inhibitory effect of BRU on the proliferation of colorectal cancer cells was unveiled via CCK-8 method and colony formation assay, while the inhibitory effect of BRU on migration and invasion of colorectal cancer cells was revealed by scratch assay and transwell assay. In addition, Western blot results also revealed that BRU inhibited not only the expressions of RhoA and ROCK1 but also the protein expressions of EMT-related markers e-cadherin, N-cadherin, Vimentin, MMP2, and MMP9 in colon cancer cells. Through the xenotransplantation model, our in vivo experiment further verified the antitumor effect of BRU on colon cancer cells in vitro, and the results were consistent with the protein expression trend. In conclusion, BRU may inhibit the proliferation and metastasis of colorectal cancer by influencing EMT through RhoA/ROCK1 pathway.

Use of virtual magnetic resonance imaging to compensate for brain shift during image-guided surgery: illustrative case.

BACKGROUND: Maximal safe resection is the paramount objective in the surgical management of malignant brain tumors. It is facilitated through use of image-guided neuronavigation. Intraoperative image guidance systems use preoperative magnetic resonance imaging (MRI) as the navigational map. The accuracy of neuronavigation is limited by intraoperative brain shift and can become less accurate over the course of the procedure. Intraoperative MRI can compensate for dynamic brain shift but requires significant space and capital investment, often unavailable at many centers. OBSERVATIONS: The authors described a case in which an image fusion algorithm was used in conjunction with an intraoperative computed tomography (CT) system to compensate for brain shift during resection of a brainstem hemorrhagic melanoma metastasis. Following initial debulking of the hemorrhagic metastasis, intraoperative CT was performed to ascertain extent of resection. An elastic image fusion (EIF) algorithm was used to create virtual MRI relative to both the intraoperative CT scan and preoperative MRI, which facilitated complete resection of the tumor while preserving critical brainstem anatomy. LESSONS: EIF algorithms can be used with multimodal images (preoperative MRI and intraoperative CT) and create an updated virtual MRI data set to compensate for brain shift in neurosurgery and aid in maximum safe resection of malignant brain tumors.

Contemporary outcomes of diffuse leptomeningeal glioneuronal tumor in pediatric patients: A case series and literature review.

BACKGROUND: Diffuse leptomeningeal glioneuronal tumor (DLGNT), also known as oligodendrogliomatosis, is a rare neuro-oncologic condition along the neuraxis that remains poorly understood in children. We sought to describe our institutional experience and quantitively summarize the clinical survival and prognostic features of DLGNT in the pediatric population across the contemporary literature. METHODS: We report four institutional cases of pediatric DLGNT diagnosed between 2000 and 2020 based on retrospective review of our records, and performed a comprehensive literature search for published cases from 2000 onwards to create an integrated cohort for analysis. Kaplan-Meier estimations, Fisher's exact test, and logistic regression were utilized to interrogate the data. RESULTS: Of our four cases, three females aged 2-, 3- and 13-years old at diagnosis survived 6-years, 3-years and 14-months respectively, and one male aged 5-years old at diagnosis was still alive 5 years later. Our overall integrated cohort consisted of 54 pediatric DLGNT patients, with 19 (35%) female and 35 (65%) male patients diagnosed at an average age of 6.4 years (range, 1.3-17 years) by means of surgical biopsy. Chemotherapy was used in 45 cases (83%), and mean follow-up time of 54 months (range, 3-204). Across the entire cohort, overall survival 1 month after diagnosis was 96% (95% CI 86-99%), and by 10 years was 69% (95% CI 49-82%). On multivariate analysis of complete data, chemotherapy treatment (HR=0.23, P = 0.04) was statistically predictive of longer overall survival. CONCLUSIONS: More than 2-out-of-3 pediatric DLGNT patients survive beyond one decade. Chemotherapy is statistically associated with longer survival in DLGNT pediatric patients and should form the core of any treatment regimen in this setting. Early detection by means of judicious imaging and surgical biopsy for tissue diagnosis can lead to earlier treatment and likely superior outcomes.

Systematic Review of Epigenetic Therapies for Treatment of IDH-mutant Glioma.

BACKGROUND: Isocitrate dehydrogenase (IDH) mutations are present in 70% of World Health Organization grade II and III gliomas. IDH mutation induces accumulation of the oncometabolite 2-hydroxyglutarate. Therefore, therapies targeting reversal of epigenetic dysregulation in gliomas have been suggested. However, the utility of epigenetic treatments in gliomas remains unclear. Here, we present the first clinical systematic review of epigenetic therapies in treatment of IDH-mutant gliomas and highlight their safety and efficacy. METHODS: We conducted a systematic search of electronic databases from 2000 to January 2021 following PRISMA guidelines. Articles were screened to include clinical usage of epigenetic therapies in case reports, prospective case series, or clinical trials. Primary and secondary outcomes included safety/tolerability of epigenetic therapies and progression-free survival/overall survival, respectively. RESULTS: A total of 133 patients across 8 clinical studies were included in our analysis. IDH inhibitors appear to have the best safety profile, with an overall grade 3/grade 4 adverse event rate of 9%. Response rates to IDH-mutant inhibitors were highest in nonenhancing gliomas (stable disease achieved in 55% of patients). In contrast, histone deacetylase inhibitors demonstrate a lower safety profile with single-study adverse events as high as 28%. CONCLUSION: IDH inhibitors appear promising given their benign toxicity profile and ease of monitoring. Histone deacetylase inhibitors appear to have a narrow therapeutic index, as lower concentrations do not appear effective, while increased doses can produce severe immunosuppressive effects. Preliminary data suggest that epigenetic therapies are generally well tolerated and may control disease in certain patient groups, such as those with nonenhancing lesions.

Same-day discharge after brain tumor resection: a prospective pilot study.

PURPOSE: Outpatient brain surgery has many advantages for the psychological and physical wellbeing of patients, as well as reduced costs to the health care system. Compared with inpatient admissions, same day discharges reduce patient exposure to nosocomial infection, thromboembolic complications, and medical error. We aim to establish a prospectively collected quality outcomes database to examine the outcomes of patients that undergo brain tumor resection and are discharged home the same day as surgery. METHODS: We have established a prospectively collected quality outcomes database to examine the outcomes of all patients that underwent brain tumor resection by a single neurosurgeon (R.J.K) at our institution from August 2020 to August 2021 and were discharged home the same day as surgery. RESULTS: Over the one-year period this study was conducted, 37 of 334 patients met inclusion criteria for the outpatient protocol. Thirty-two patients were discharged on the same day as surgery. Five patients (14%) were considered eligible for outpatient surgery but were ultimately admitted to the hospital postoperatively and were discharged after an overnight observation. No postoperative complications were noted at two-week postoperative follow-up. CONCLUSION: In select patients undergoing brain tumor surgery, same day discharge should be considered. Establishing a multidisciplinary team of physicians, nurses, radiologists, and physical therapists is critical to achieving this aim. Physicians should have a low threshold to admit a patient with concerning exam findings, complications, or complicated past medical history. Once discharged, open communication with the patient and their family is critical to detect complications that should trigger rehospitalization and intervention.

Intraoperative 5-ALA fluorescence-guided resection of high-grade glioma leads to greater extent of resection with better outcomes: a systematic review.

IMPORTANCE: High-grade gliomas (HGG) are the most aggressive and common malignant brain tumors in adults. They have a dismally fatal prognosis. Even if gross total resection of the enhancing tumor is achieved, inevitably, invading tumor cells that are indistinguishable to the un-aided eye are left behind, which eventually leads to tumor recurrence. 5-aminolevulinic acid (5-ALA) is an increasingly utilized intraoperative fluorescent imaging agent for patients with HGG. It enhances visualization of HGG tissue. Despite early promising randomized clinical trial data suggesting a survival benefit for 5-ALA-guided surgery, the growing body of literature must be analyzed to confirm efficacy on patient outcomes. OBJECTIVE: To perform a systematic review of the literature to evaluate whether there is a beneficial effect upon survival and extent of resection due to the utilization of 5-ALA in HGG surgery. EVIDENCE REVIEW: Literature regarding 5-ALA usage in HGG surgery was reviewed according to the PRISMA guidelines. Two databases, PubMed and SCOPUS, were searched for assorted combinations of the keywords "5-ALA," "high-grade glioma," "5-aminolevulinic acid," and "resection" in July 2020 for case reports and retrospective, prospective, and randomized clinical trials assessing and analyzing 5-ALA intraoperative use in patients with HGG. Entailed studies on PubMed and SCOPUS were found for screening using a snowball search technique upon the initially searched papers. Systematic reviews and meta-analyses were excluded from our PRISMA table. FINDINGS: 3756 previously published studies were screened, 536 of which were further evaluated, and ultimately 45 were included in our systematic review. There were no date restrictions on the screened publications. Our literature search was finalized on July 16, 2020. We found an observed increase in the overall survival (OS) and progression-free survival (PFS) of the 5-ALA group compared to the white light group, as well as an observed increase in the OS and PFS of complete resections compared to incomplete resections. Of the studies that directly compared the use of 5-ALA to white light (13 of the total analyzed 45, or 28.9%), 5-ALA lead to a better PFS and OS in 88.4 and 67.5% of patients, respectively. When the studies that reported postoperative neurologic outcomes of surgeries using 5-ALA vs. white light were analyzed, 42.2% of subjects demonstrated 5-ALA use was associated with less post-op neurological deficits, whereas 34.5% demonstrated no difference between 5-ALA and without. 23.3% of studies showed that intraoperative 5-ALA guided surgeries lead to more post-op neurological deficits. CONCLUSIONS AND RELEVANCE: Utilization of 5-ALA was found to be associated with a greater extent of resection in HGG surgeries, as well as longer OS and PFS. Postop neurologic deficit rates were mixed and inconclusive when comparing 5-ALA groups to white light groups. 5-ALA is a useful surgical adjunct for resection of HGG when patient safety is preserved.

Robotic guidance platform for laser interstitial thermal ablation and stereotactic needle biopsies: a single center experience.

While laser ablation has become an increasingly important tool in the neurosurgical oncologist's armamentarium, deep seated lesions, and those located near critical structures require utmost accuracy during stereotactic laser catheter placement. Robotic devices have evolved significantly over the past two decades becoming an accurate and safe tool for stereotactic neurosurgery. Here, we present our single center experience with the MedTech ROSA ONE Brain robot for robotic guidance in laser interstitial thermal therapy (LITT) and stereotactic biopsies. We retrospectively analyzed the first 70 consecutive patients treated with ROSA device at a single academic medical center. Forty-three patients received needle biopsy immediately followed by LITT with the catheter placed with robotic guidance and 27 received stereotactic needle biopsy alone. All the procedures were performed frameless with skull bone fiducials for registration. We report data regarding intraoperative details, mortality and morbidity, diagnostic yield and lesion characteristics on MRI. Also, we describe the surgical workflow for both procedures. The mean age was 60.3 ± 15 years. The diagnostic yield was positive in 98.5% (n = 69). Sixty-three biopsies (90%) were supratentorial and seven (10%) were infratentorial. Gliomas represented 54.3% of the patients (n = 38). There were two postoperative deaths (2.8%). No permanent morbidity related to surgery were observed. We did not find intraoperative technical problems with the device. There was no need to reposition the needle after the initial placement. Stereotactic robotic guided placement of laser ablation catheters and biopsy needles is safe, accurate, and can be implemented into a neurosurgical workflow.

Augmented reality head-mounted display-based incision planning in cranial neurosurgery: a prospective pilot study.

OBJECTIVE: Monitor and wand-based neuronavigation stations (MWBNSs) for frameless intraoperative neuronavigation are routinely used in cranial neurosurgery. However, they are temporally and spatially cumbersome; the OR must be arranged around the MWBNS, at least one hand must be used to manipulate the MWBNS wand (interrupting a bimanual surgical technique), and the surgical workflow is interrupted as the surgeon stops to "check the navigation" on a remote monitor. Thus, there is need for continuous, real-time, hands-free, neuronavigation solutions. Augmented reality (AR) is poised to streamline these issues. The authors present the first reported prospective pilot study investigating the feasibility of using the OpenSight application with an AR head-mounted display to map out the borders of tumors in patients undergoing elective craniotomy for tumor resection, and to compare the degree of correspondence with MWBNS tracing. METHODS: Eleven consecutive patients undergoing elective craniotomy for brain tumor resection were prospectively identified and underwent circumferential tumor border tracing at the time of incision planning by a surgeon wearing HoloLens AR glasses running the commercially available OpenSight application registered to the patient and preoperative MRI. Then, the same patient underwent circumferential tumor border tracing using the StealthStation S8 MWBNS. Postoperatively, both tumor border tracings were compared by two blinded board-certified neurosurgeons and rated as having an excellent, adequate, or poor correspondence degree based on a subjective sense of the overlap. Objective overlap area measurements were also determined. RESULTS: Eleven patients undergoing craniotomy were included in the study. Five patient procedures were rated as having an excellent correspondence degree, 5 had an adequate correspondence degree, and 1 had poor correspondence. Both raters agreed on the rating in all cases. AR tracing was possible in all cases. CONCLUSIONS: In this small pilot study, the authors found that AR was implementable in the workflow of a neurosurgery OR, and was a feasible method of preoperative tumor border identification for incision planning. Future studies are needed to identify strategies to improve and optimize AR accuracy.