Laser interstitial thermal therapy for new and recurrent meningioma: a prospective and retrospective case series.

OBJECTIVE: Meningiomas are the most common primary brain tumors in adults and a subset are aggressive lesions resistant to standard therapies. Laser interstitial thermal therapy (LITT) has been successfully applied to other brain tumors, and recent work aims to explore the safety and long-term outcome experiences of LITT for both new and recurrent meningiomas. The authors' objective was to report safety and outcomes data of the largest cohort of LITT-treated meningioma patients to date. METHODS: Eight United States-based hospitals enrolled patients with meningioma in the Laser Ablation of Abnormal Neurological Tissue Using Robotic NeuroBlate System (LAANTERN) prospective multicenter registry and/or contributed additional retrospective enrollments for this cohort study. Demographic, procedural, safety, and outcomes data were collected and analyzed using standard statistical methods. RESULTS: Twenty adult patients (12 prospective and 8 retrospective) with LITT-targeted meningiomas were accrued. Patients underwent LITT for new (6 patients) and recurrent (14 patients) tumors (ranging from the 1st to 12th recurrence). The 30-day complication rate was 10%. Twenty percent of patients (4/20) had exhausted all other treatment options. Median length of follow-up was 1.3 years. One-third of new (2/6) and one-half of recurrent (7/14) meningiomas had disease progression during follow-up. One-year estimated local control (LC), progression-free survival, and overall survival rates were 55.3%, 48.4%, and 86.3%, respectively. In the 12 patients who had ≥ 91% ablative coverage, 1-year estimated LC was 61.4%. The complication rate was 10% (2/20), with 1 complication being transient and resolving postoperatively. CONCLUSIONS: This cohort study supports the safety of the procedure for this tumor type. LITT can offer a much-needed treatment option, especially for patients with multiply recurrent meningiomas who have limited remaining alternatives.

Automated neonatal nnU-Net brain MRI extractor trained on a large multi-institutional dataset.

Brain extraction, or skull-stripping, is an essential data preprocessing step for machine learning approaches to brain MRI analysis. Currently, there are limited extraction algorithms for the neonatal brain. We aim to adapt an established deep learning algorithm for the automatic segmentation of neonatal brains from MRI, trained on a large multi-institutional dataset for improved generalizability across image acquisition parameters. Our model, ANUBEX (automated neonatal nnU-Net brain MRI extractor), was designed using nnU-Net and was trained on a subset of participants (N = 433) enrolled in the High-dose Erythropoietin for Asphyxia and Encephalopathy (HEAL) study. We compared the performance of our model to five publicly available models (BET, BSE, CABINET, iBEATv2, ROBEX) across conventional and machine learning methods, tested on two public datasets (NIH and dHCP). We found that our model had a significantly higher Dice score on the aggregate of both data sets and comparable or significantly higher Dice scores on the NIH (low-resolution) and dHCP (high-resolution) datasets independently. ANUBEX performs similarly when trained on sequence-agnostic or motion-degraded MRI, but slightly worse on preterm brains. In conclusion, we created an automatic deep learning-based neonatal brain extraction algorithm that demonstrates accurate performance with both high- and low-resolution MRIs with fast computation time.

Automated segmentation of ablated lesions using deep convolutional neural networks: A basis for response assessment following laser interstitial thermal therapy.

BACKGROUND: Laser interstitial thermal therapy (LITT) of intracranial tumors or radiation necrosis enables tissue diagnosis, cytoreduction, and rapid return to systemic therapies. Ablated tissue remains in situ, resulting in characteristic post-LITT edema associated with transient clinical worsening and complicating post-LITT response assessment. METHODS: All patients receiving LITT at a single center for tumors or radiation necrosis from 2015 to 2023 with ≥9 months of MRI follow-up were included. An nnU-Net segmentation model was trained to automatically segment contrast-enhancing lesion volume (CeLV) of LITT-treated lesions on T1-weighted images. Response assessment was performed using volumetric measurements. RESULTS: Three hundred and eighty four unique MRI exams of 61 LITT-treated lesions and 6 control cases of medically managed radiation necrosis were analyzed. Automated segmentation was accurate in 367/384 (95.6%) images. CeLV increased to a median of 68.3% (IQR 35.1-109.2%) from baseline at 1-3 months from LITT (P = 0.0012) and returned to baseline thereafter. Overall survival (OS) for LITT-treated patients was 39.1 (9.2-93.4) months. Lesion expansion above 40% from volumetric nadir or baseline was considered volumetric progression. Twenty-one of 56 (37.5%) patients experienced progression for a volumetric progression-free survival of 21.4 (6.0-93.4) months. Patients with volumetric progression had worse OS (17.3 vs 62.1 months, P = 0.0015). CONCLUSIONS: Post-LITT CeLV expansion is quantifiable and resolves within 6 months of LITT. Development of response assessment criteria for LITT-treated lesions is feasible and should be considered for clinical trials. Automated lesion segmentation could speed the adoption of volumetric response criteria in clinical practice.

Accuracy of routine external ventricular drain placement following a mixed reality-guided twist-drill craniostomy.

OBJECTIVE: The traditional freehand placement of an external ventricular drain (EVD) relies on empirical craniometric landmarks to guide the craniostomy and subsequent passage of the EVD catheter. The diameter and trajectory of the craniostomy physically limit the possible trajectories that can be achieved during the passage of the catheter. In this study, the authors implemented a mixed reality-guided craniostomy procedure to evaluate the benefit of an optimally drilled craniostomy to the accurate placement of the catheter. METHODS: Optical marker-based tracking using an OptiTrack system was used to register the brain ventricular hologram and drilling guidance for craniostomy using a HoloLens 2 mixed reality headset. A patient-specific 3D-printed skull phantom embedded with intracranial camera sensors was developed to automatically calculate the EVD accuracy for evaluation. User trials consisted of one blind and one mixed reality-assisted craniostomy followed by a routine, unguided EVD catheter placement for each of two different drill bit sizes. RESULTS: A total of 49 participants were included in the study (mean age 23.4 years, 59.2% female). The mean distance from the catheter target improved from 18.6 ± 12.5 mm to 12.7 ± 11.3 mm (p = 0.0008) using mixed reality guidance for trials with a large drill bit and from 19.3 ± 12.7 mm to 10.1 ± 8.4 mm with a small drill bit (p < 0.0001). Accuracy using mixed reality was improved using a smaller diameter drill bit compared with a larger bit (p = 0.039). Overall, the majority of the participants were positive about the helpfulness of mixed reality guidance and the overall mixed reality experience. CONCLUSIONS: Appropriate indications and use cases for the application of mixed reality guidance to neurosurgical procedures remain an area of active inquiry. While prior studies have demonstrated the benefit of mixed reality-guided catheter placement using predrilled craniostomies, the authors demonstrate that real-time quantitative and visual feedback of a mixed reality-guided craniostomy procedure can independently improve procedural accuracy and represents an important tool for trainee education and eventual clinical implementation.

Utility of Routine Preoperative Urinalysis in the Prevention of Surgical Site Infections.

OBJECTIVE: Preoperative assessment is important for neurosurgical risk stratification, but the level of evidence for individual screening tests is low. In preoperative urinalysis (UA), testing may significantly increase costs and lead to inappropriate antibiotic treatment. We prospectively evaluated whether eliminating preoperative UA was noninferior to routine preoperative UA as measured by 30-day readmission for surgical site infection in adult elective neurosurgical procedures. METHODS: A single-institution prospective, pragmatic study of patients receiving elective neurosurgical procedures from 2018 to 2020 was conducted. Patients were allocated based on same-day versus preoperative admission status. Rates of preoperative UA and subsequent wound infection were measured along with detailed demographic, surgical, and laboratory data. RESULTS: The study included 879 patients. The most common types of surgery were cranial (54.7%), spine (17.4%), and stereotactic/functional (19.5%). No preoperative UA was performed in 315 patients, while 564 underwent UA. Of tested patients, 103 (18.3%) met criteria for suspected urinary tract infection, and 69 (12.2%) received subsequent antibiotic treatment. There were 14 patients readmitted within 30 days (7 without UA [2.2%] vs. 7 with UA [1.2%]) for subsequent wound infection with a risk difference of 0.98% (95% confidence interval -0.89% to 2.85%). The upper limit of the confidence interval exceeded the preselected noninferiority margin of 1%. CONCLUSIONS: In this prospective study of preoperative UA for elective neurosurgical procedures using a pragmatic, real-world design, risk of readmission due to surgical site infection was very low across the study cohort, suggesting a limited role of preoperative UA for elective neurosurgical procedures.

Gold Nanostars Obviate Limitations to Laser Interstitial Thermal Therapy (LITT) for the Treatment of Intracranial Tumors.

PURPOSE: Laser interstitial thermal therapy (LITT) is an effective minimally invasive treatment option for intracranial tumors. Our group produced plasmonics-active gold nanostars (GNS) designed to preferentially accumulate within intracranial tumors and amplify the ablative capacity of LITT. EXPERIMENTAL DESIGN: The impact of GNS on LITT coverage capacity was tested in ex vivo models using clinical LITT equipment and agarose gel-based phantoms of control and GNS-infused central "tumors." In vivo accumulation of GNS and amplification of ablation were tested in murine intracranial and extracranial tumor models followed by intravenous GNS injection, PET/CT, two-photon photoluminescence, inductively coupled plasma mass spectrometry (ICP-MS), histopathology, and laser ablation. RESULTS: Monte Carlo simulations demonstrated the potential of GNS to accelerate and specify thermal distributions. In ex vivo cuboid tumor phantoms, the GNS-infused phantom heated 5.5× faster than the control. In a split-cylinder tumor phantom, the GNS-infused border heated 2× faster and the surrounding area was exposed to 30% lower temperatures, with margin conformation observed in a model of irregular GNS distribution. In vivo, GNS preferentially accumulated within intracranial tumors on PET/CT, two-photon photoluminescence, and ICP-MS at 24 and 72 hours and significantly expedited and increased the maximal temperature achieved in laser ablation compared with control. CONCLUSIONS: Our results provide evidence for use of GNS to improve the efficiency and potentially safety of LITT. The in vivo data support selective accumulation within intracranial tumors and amplification of laser ablation, and the GNS-infused phantom experiments demonstrate increased rates of heating, heat contouring to tumor borders, and decreased heating of surrounding regions representing normal structures.

Laser ablation of a sphenoid wing meningioma: A case report and review of the literature.

Background: Meningiomas are the most common primary central nervous system neoplasm in the United States. While the majority of meningiomas are benign, the World Health Organization (WHO) Grade I tumors, a not-insignificant proportion of tumors are in anatomically complex locations or demonstrate more aggressive phenotypes, presenting a challenge for local disease control with surgery and radiation. Laser interstitial thermal therapy (LITT) consists of stereotactic delivery of laser light for tumor ablation and is minimally invasive, requiring implantation of a laser fiber through a cranial burr hole. Herein, we demonstrate the first use of this technology in a progressive atypical sphenoid wing meningioma for a previously resected and irradiated tumor. Case Description: A 47-year-old female was diagnosed with a left-sided atypical meningioma, the WHO 2, of the sphenoid wing following acute worsening of bitemporal headache and dizziness. Given neurovascular involvement, a subtotal resection was performed, followed by stereotactic radiosurgery. Following progression 9 months from resection, the patient elected to proceed with LITT. The patient's postoperative course was uncomplicated and she remains progression free at 24 months following LITT. Conclusion: We present the first use of LITT for a sphenoid wing meningioma documented in the literature, which demonstrated enhanced disease control for a lesion that was refractory to both surgery and radiation. LITT could represent an additional option for local control of progressive meningiomas, even in locations that are challenging to access surgically. More evidence is needed regarding the technical nuances of LITT for lesions of the skull base.

Revisiting flow augmentation bypass for cerebrovascular atherosclerotic vaso-occlusive disease: Single-surgeon series and review of the literature.

OBJECTIVE: Despite advances in the nonsurgical management of cerebrovascular atherosclerotic steno-occlusive disease, approximately 15-20% of patients remain at high risk for recurrent ischemia. The benefit of revascularization with flow augmentation bypass has been demonstrated in studies of Moyamoya vasculopathy. Unfortunately, there are mixed results for the use of flow augmentation in atherosclerotic cerebrovascular disease. We conducted a study to examine the efficacy and long term outcomes of superficial temporal artery to middle cerebral artery (STA-MCA) bypass in patients with recurrent ischemia despite optimal medical management. METHODS: A single-institution retrospective review of patients receiving flow augmentation bypass from 2013-2021 was conducted. Patients with non-Moyamoya vaso-occlusive disease (VOD) who had continued ischemic symptoms or strokes despite best medical management were included. The primary outcome was time to post-operative stroke. Time from cerebrovascular accident to surgery, complications, imaging results, and modified Rankin Scale (mRS) scores were aggregated. RESULTS: Twenty patients met inclusion criteria. The median time from cerebrovascular accident to surgery was 87 (28-105.0) days. Only one patient (5%) had a stroke at 66 days post-op. One (5%) patient had a post-operative scalp infection, while 3 (15%) developed post-operative seizures. All 20 (100%) bypasses remained patent at follow-up. The median mRS score at follow up was significantly improved from presentation from 2.5 (1-3) to 1 (0-2), P = .013. CONCLUSIONS: For patients with high-risk non-Moyamoya VOD who have failed optimal medical therapy, contemporary approaches to flow augmentation with STA-MCA bypass may prevent future ischemic events with a low complication rate.

Erratum to "E.C. Lerner, E.S. Srinivasan, G. Broadwater, et al. Factors Associated With New-Onset Seizures Following Stereotactic Radiosurgery for Newly Diagnosed Brain Metastases. Adv Radiat Oncol. 2022;7:101054."

[This corrects the article DOI: 10.1016/j.adro.2022.101054.].

Risk of Tract Seeding Following Laser Interstitial Thermal Therapy for Brain Tumors.

BACKGROUND: The management of intracranial oncological disease remains a significant challenge despite advances in systemic cancer therapy. Laser interstitial thermal therapy (LITT) represents a novel treatment for local control of brain tumors through photocoagulation with a stereotactically implanted laser fiber. Because the use of laser interstitial thermal therapy continues to increase within neurosurgery, characterization of LITT is necessary to improve outcomes. OBJECTIVE: To quantify the risk of tumor seeding along the laser fiber tract in patients receiving LITT for primary or metastatic brain tumors at a high-volume treatment center. METHODS: We retrospectively reviewed all patients receiving LITT from 2015 to 2021 at our medical center. Patients with biopsy-confirmed tumors were included in this study. Tract seeding was identified as discontinuous, newly enhancing tumor along the LITT tract. RESULTS: Fifty-six patients received LITT for biopsy-confirmed tumors from 2015 to 2021, with tract seeding identified in 3 (5.4%). Twenty-nine (51.8%) patients had gliomas, while the remainder had metastases, of which lung was the most common histology (20 patients, 74%). Tract seeding was associated with ablation proceeding inward from superficial tumor margin closest to the cranial entry point ( P = .03). Patients with tract seeding had a shorter median time to progression of 1.1 (0.1-1.3) months vs 4.2 (2.2-8.6) months ( P = .03). CONCLUSION: Although the risk of tract seeding after LITT is reassuringly low, it is associated with decreased progression-free survival. This risk may be related to surgical technique or experience. Follow-up radiosurgery to the LITT tract has the potential to prevent this complication.

Factors Associated With New-Onset Seizures Following Stereotactic Radiosurgery for Newly Diagnosed Brain Metastases.

Purpose: Stereotactic radiosurgery (SRS) is a highly effective therapy for newly diagnosed brain metastases. Prophylactic antiepileptic drugs are no longer routinely used in current SRS practice, owing to a perceived low overall frequency of new-onset seizures and potential side effects of medications. It is nonetheless desirable to prevent unwanted side effects following SRS. Risk factors for new-onset seizures after SRS have not been well established. As such, we aimed to characterize variables associated with increased seizure risk. Methods and Materials: Patients treated with SRS for newly diagnosed brain metastases between 2013 and 2016 were retrospectively reviewed at a single institution. Data on baseline demographics, radiation parameters, and clinical courses were collected. Results: The cohort consisted of 305 patients treated with SRS without prior seizure history. Median age and baseline Karnofsky Performance Scale score were 64 years (interquartile range, 55-70) and 80 (interquartile range, 80-90), respectively. Twenty-six (8.5%) patients developed new-onset seizures within 3 months of SRS. There was no association between new-onset seizures and median baseline Karnofsky Performance Scale score, prior resection, or prior whole brain radiation therapy. There were significant differences in the combined total irradiated volume (12.5 vs 3.7 cm3, P < .001), maximum single lesion volume (8.8 vs 2.8 cm3, P = .003), lesion diameter (3.2 vs 2.0 cm, P = .003), and number of lesions treated (3 vs 1, P = .018) between patients with and without new-onset seizures, respectively. On multivariate logistic regression, total irradiated volume (odds ratio, 1.09 for every 1-cm1 increase in total volume; confidence interval, 1.02-1.17; P = .016) and pre-SRS neurologic symptoms (odds ratio, 3.08; 95% confidence interval, 1.19-7.99; P = .020) were both significantly correlated with odds of seizures following SRS. Conclusions: Our data suggest that larger total treatment volume and the presence of focal neurologic deficits at presentation are associated with new-onset seizures within 3 months of SRS. High-risk patients undergoing SRS may benefit from counseling or prophylactic antiseizure therapy.

Correlation between social media utilization by academic neurosurgery departments and higher online patient ratings.

OBJECTIVE: Patients increasingly utilize online physician review websites (PRWs) and social media to inform healthcare-related decisions. This provides neurosurgeons with opportunities for increased patient engagement. And despite the growing use of social media among neurosurgeons, the relationship between social media utilization and online reviews remains unknown. The goal of this study was to characterize the relationship between social media utilization and PRW ratings across academic neurosurgery departments. METHODS: Social media accounts (Twitter, Facebook, YouTube, Instagram) of academic neurosurgery departments were identified. Online reviews for individual faculty were obtained from Healthgrades, Vitals, WebMD, and Google. Reviews were aggregated to identify the total number of reviews per department, to generate a composite departmental rating, and to calculate a summed departmental score. US News & World Report (USNWR) and Doximity rankings were recorded for each department. Social media utilization by individual neurosurgeons and associated ratings were investigated within the departments with the highest social media utilization. RESULTS: Seventy-eight percent of academic neurosurgery departments utilized social media. The most prevalent platform was YouTube (49.1%), followed by Twitter (46.5%), Facebook (38.6%), and Instagram (16.7%). Higher patient ratings on PRWs were associated with the utilization of YouTube (p = 0.048) or Twitter (p = 0.02). The number of social media platforms utilized demonstrated a significant, positive correlation with patient ratings (p = 0.006) and summed patient ratings (p = 0.048). Although USNWR (p = 0.02) and Doximity (p = 0.0008) rankings correlated with patient ratings, only the number of social media platforms utilized remained a significant predictor of patient ratings on multivariate analysis (p = 0.0001). Thirty-one percent of academic neurosurgeons from departments with high social media utilization were active on social media. The most prevalent social media platform among individual neurosurgeons was Twitter (27.4%), followed by Instagram (8.4%), Facebook (4.9%), and YouTube (2.2%). Higher summed patient scores were associated with individual neurosurgeon utilization of YouTube (p = 0.04), Facebook (p < 0.0001), and Instagram (p = 0.01). Increased social media utilization among neurosurgeons was correlated with a greater number of patient reviews (p = 0.006) and higher summed patient scores (p = 0.003). On multivariate analysis, only Facebook use remained a significant predictor of the number of patient reviews received (p = 0.002) and summed patient satisfaction scores (p < 0.001). CONCLUSIONS: An increased social media presence is associated with higher ratings on PRWs. As neurosurgeons continue to expand their online presence, they should be aware of the possible impact of social media on online patient reviews.

Targeting Immunometabolism in Glioblastoma.

We have only recently begun to understand how cancer metabolism affects antitumor responses and immunotherapy outcomes. Certain immunometabolic targets have been actively pursued in other tumor types, however, glioblastoma research has been slow to exploit the therapeutic vulnerabilities of immunometabolism. In this review, we highlight the pathways that are most relevant to glioblastoma and focus on how these immunometabolic pathways influence tumor growth and immune suppression. We discuss hypoxia, glycolysis, tryptophan metabolism, arginine metabolism, 2-Hydroxyglutarate (2HG) metabolism, adenosine metabolism, and altered phospholipid metabolism, in order to provide an analysis and overview of the field of glioblastoma immunometabolism.