Direct (D)-Wave Monitoring Enhancement With Subdural Electrode Placement: A Case Series.

PURPOSE: Direct-wave (D-wave) neuromonitoring is a direct measure of corticospinal tract integrity that detects potential injury during spinal cord surgery. Epidural placement of electrodes used for D-wave measurements can result in high electrical impedances resulting in substantial signal noise that can compromise signal interpretation. Subdural electrode placement may offer a solution. METHODS: Medical records for consecutive patients with epidural and subdural D-wave monitoring were reviewed. Demographic and clinical information including preoperative and postoperative motor strength were recorded. Neuromonitoring charts were reviewed to characterize impedances and signal amplitudes of D-waves recorded epidurally (before durotomy) and subdurally (following durotomy). Nonparametric statistics were used to compare epidural and subdural D-waves. RESULTS: Ten patients (50% women, median age 50.5 years) were analyzed, of which five patients (50%) were functionally independent (modified McCormick grade ≤ II) preoperatively. D-waves were successfully acquired by subdural electrodes in eight cases and by epidural electrodes in three cases. Subdural electrode placement was associated with lower impedance values ( P = 0.011) and a higher baseline D-wave amplitude ( P = 0.007) relative to epidural placement. No association was observed between D-wave obtainability and functional status, and no adverse events relating to subdural electrode placement were encountered. CONCLUSIONS: Subdural electrode placement allows successful D-wave acquisition with accurate monitoring, clearer waveforms, and a more optimal signal-to-noise ratio relative to epidural placement. For spinal surgeries where access to the subdural compartment is technically safe and feasible, surgeons should consider subdural placement when monitoring D-waves to optimize clinical interpretation.

Applications of Functional Magnetic Resonance Imaging to the Study of Functional Connectivity and Activation in Neurological Disease: A Scoping Review of the Literature.

BACKGROUND: Functional magnetic resonance imaging (fMRI) has transformed our understanding of brain's functional architecture, providing critical insights into neurological diseases. This scoping review synthesizes the current landscape of fMRI applications across various neurological domains, elucidating the evolving role of both task-based and resting-state fMRI in different settings. METHODS: We conducted a comprehensive scoping review following the Preferred Reporting Items for Systematic Review and Meta-Analyses Extension for Scoping Reviews guidelines. Extensive searches in Medline/PubMed, Embase, and Web of Science were performed, focusing on studies published between 2003 and 2023 that utilized fMRI to explore functional connectivity and regional activation in adult patients with neurological conditions. Studies were selected based on predefined inclusion and exclusion criteria, with data extracted. RESULTS: We identified 211 studies, covering a broad spectrum of neurological disorders including mental health, movement disorders, epilepsy, neurodegeneration, traumatic brain injury, cerebrovascular accidents, vascular abnormalities, neurorehabilitation, neuro-critical care, and brain tumors. The majority of studies utilized resting-state fMRI, underscoring its prominence in identifying disease-specific connectivity patterns. Results highlight the potential of fMRI to reveal the underlying pathophysiological mechanisms of various neurological conditions, facilitate diagnostic processes, and potentially guide therapeutic interventions. CONCLUSIONS: fMRI serves as a powerful tool for elucidating complex neural dynamics and pathologies associated with neurological diseases. Despite the breadth of applications, further research is required to standardize fMRI protocols, improve interpretative methodologies, and enhance the translation of imaging findings to clinical practice. Advances in fMRI technology and analytics hold promise for improving the precision of neurological assessments and interventions.

The diagnostic accuracy of neuromonitoring for detecting postoperative bowel and bladder dysfunction in spinal oncology surgery: a case series.

PURPOSE: Postoperative bowel and bladder dysfunction (BBD) poses a significant risk following surgery of the sacral spinal segments and sacral nerve roots, particularly in neuro-oncology cases. The need for more reliable neuromonitoring techniques to enhance the safety of spine surgery is evident. METHODS: We conducted a case series comprising 60 procedures involving 56 patients, spanning from September 2022 to January 2024. We assessed the diagnostic accuracy of sacral reflexes (bulbocavernosus and external urethral sphincter reflexes) and compared them with transcranial motor evoked potentials (TCMEP) incorporating anal sphincter (AS) and external urethral sphincter (EUS) recordings, as well as spontaneous electromyography (s-EMG) with AS and EUS recordings. RESULTS: Sacral reflexes demonstrated a specificity of 100% in predicting postoperative BBD, with a sensitivity of 73.33%. While sensitivity slightly decreased to 64.71% at the 1-month follow-up, it remained consistently high overall. TCMEP with AS/EUS recordings did not identify any instances of postoperative BBD, whereas s-EMG with AS/EUS recordings showed a sensitivity of 14.29% and a specificity of 97.14%. CONCLUSION: Sacral reflex monitoring emerges as a robust adjunct to routine neuromonitoring, offering surgeons valuable predictive insights to potentially mitigate the occurrence of postoperative BBD.

Ethical Incorporation of Artificial Intelligence into Neurosurgery: A Generative Pretrained Transformer Chatbot-Based, Human-Modified Approach.

INTRODUCTION: Artificial intelligence (AI) has become increasingly used in neurosurgery. Generative pretrained transformers (GPTs) have been of particular interest. However, ethical concerns regarding the incorporation of AI into the field remain underexplored. We delineate key ethical considerations using a novel GPT-based, human-modified approach, synthesize the most common considerations, and present an ethical framework for the involvement of AI in neurosurgery. METHODS: GPT-4, ChatGPT, Bing Chat/Copilot, You, Perplexity.ai, and Google Bard were queried with the prompt "How can artificial intelligence be ethically incorporated into neurosurgery?". Then, a layered GPT-based thematic analysis was performed. The authors synthesized the results into considerations for the ethical incorporation of AI into neurosurgery. Separate Pareto analyses with 20% threshold and 10% threshold were conducted to determine salient themes. The authors refined these salient themes. RESULTS: Twelve key ethical considerations focusing on stakeholders, clinical implementation, and governance were identified. Refinement of the Pareto analysis of the top 20% most salient themes in the aggregated GPT outputs yielded 10 key considerations. Additionally, from the top 10% most salient themes, 5 considerations were retrieved. An ethical framework for the use of AI in neurosurgery was developed. CONCLUSIONS: It is critical to address the ethical considerations associated with the use of AI in neurosurgery. The framework described in this manuscript may facilitate the integration of AI into neurosurgery, benefitting both patients and neurosurgeons alike. We urge neurosurgeons to use AI only for validated purposes and caution against automatic adoption of its outputs without neurosurgeon interpretation.

Results from a first-in-human phase I safety trial to evaluate the use of a vascularized pericranial/temporoparietal fascial flap to line the resection cavity following resection of newly diagnosed glioblastoma.

PURPOSE: The efficacy of systemic therapies for glioblastoma (GBM) remains limited due to the constraints of systemic toxicity and blood-brain barrier (BBB) permeability. Temporoparietal fascial flaps (TPFFs) and vascularized peri cranial flaps (PCF) are not restricted by the blood-brain barrier (BBB), as they derive their vascular supply from branches of the external carotid artery. Transposition of a vascularized TPFF or PCF along a GBM resection cavity may bring autologous tissue not restricted by the BBB in close vicinity to the tumor bed microenvironment, permit ingrowth of vascular channels fed by the external circulation, and offer a mechanism of bypassing the BBB. In addition, circulating immune cells in the vascularized flap may have better access to tumor-associated antigens (TAA) within the tumor microenvironment. We conducted a first-in-human Phase I trial assessing the safety of lining the resection cavity with autologous TPFF/PCF of newly diagnosed patients with GBM. METHODS: 12 patients underwent safe, maximal surgical resection of newly diagnosed GBMs, followed by lining of the resection cavity with a pedicled, autologous TPFF or PCF. Safety was assessed by monitoring adverse events. Secondary analysis of efficacy was examined as the proportion of patients experiencing progression-free disease (PFS) as indicated by response assessment in neuro-oncology (RANO) criteria and overall survival (OS). The study was powered to determine whether a Phase II study was warranted based on these early results. For this analysis, subjects who were alive and had not progressed as of the date of the last follow-up were considered censored and all living patients who were alive as of the date of last follow-up were considered censored for overall survival. For simplicity, we assumed that a 70% PFS rate at 6 months would be considered an encouraging response and would make an argument for further investigation of the procedure. RESULTS: Median age of included patients was 57 years (range 46-69 years). All patients were Isocitrate dehydrogenase (IDH) wildtype. Average tumor volume was 56.6 cm3 (range 14-145 cm3). Resection was qualified as gross total resection (GTR) of all of the enhancing diseases in all patients. Grade III or above adverse events were encountered in 3 patients. No Grade IV or V serious adverse events occurred in the immediate post-operative period including seizure, infection, stroke, or tumor growing along the flap. Disease progression at the site of the original tumor was identified in only 4 (33%) patients (median 23 months, range 8-25 months), 3 of whom underwent re-operation. Histopathological analyses of those implanted flaps and tumor bed biopsy at repeat surgery demonstrated robust immune infiltrates within the transplanted flap. Importantly, no patient demonstrated evidence of tumor infiltration into the implanted flap. At the time of this manuscript preparation, only 4/12 (33%) of patients have died. Based on the statistical considerations above and including all 12 patients 10/12 (83.3%) had 6-month PFS. The median PFS was 9.10 months, and the OS was 17.6 months. 4/12 (33%) of patients have been alive for more than two years and our longest surviving patient currently is alive at 60 months. CONCLUSIONS: This pilot study suggests that insertion of pedicled autologous TPFF/PCF along a GBM resection cavity is safe and feasible. Based on the encouraging response rate in 6-month PFS and OS, larger phase II studies are warranted to assess and reproduce safety, feasibility, and efficacy. TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION FOR PROSPECTIVELY REGISTERED TRIALS: ClinicalTrials.gov ID NCT03630289, dated: 08/02/2018.

Influence of Preoperative Motor Score and Patient Comorbidities on Transcranial Motor-Evoked Potential Acquisition in Intracranial Surgery: A Retrospective Cohort Study.

BACKGROUND AND OBJECTIVES: Intraoperative neurophysiological monitoring plays a pivotal role in modern neurosurgery, aiding in real-time assessment of eloquent neural structures to mitigate iatrogenic neural injury. This study represents the largest retrospective series to date in monitoring corticospinal tract integrity during intracranial surgery with transcranial motor-evoked potentials (TCMEPs), focusing on the influence of demographic factors, comorbidities, and preoperative motor deficits on the reliability of intraoperative neurophysiological monitoring. While the impact of patient-specific factors affecting TCMEP monitoring in spine surgery is well-documented, similar insights for intracranial surgery are lacking. METHODS: A total of 420 craniotomy patients were retrospectively analyzed from electronic medical records from December 2017 to February 2023, excluding patients without preoperative Medical Research Council scores or medical histories. Using intrinsic hand muscles as a robust data set, 840 hand TCMEPs acquired during intracranial surgery were assessed. Demographic and clinical factors, including preoperative motor scores, were analyzed to identify associations with TCMEP acquisition and amplitude. Nonparametric statistics and multivariate regression analysis were employed. RESULTS: TCMEPs were successfully acquired in 734 (87.7%) patient hands, even in the presence of preoperative motor deficits in 13.9% of total patient hands. Preoperative motor scores did not predict the ability to acquire baseline TCMEPs (P = .6). Notably, older age (P < .001) and hypertension (P = .01) were independent predictors of lower TCMEP acquisition rates. Preoperative motor scores significantly influenced TCMEP amplitudes, with higher scores correlating with higher amplitudes (1771 [SD = 1550] eve vs 882 [SD = 856] µV, P < .0001). Older age (P < .001) and chronic kidney disease (P = .04) were also associated with reduced TCMEP amplitudes. CONCLUSION: Our investigation into TCMEPs during intracranial surgery demonstrated a notably high acquisition rate in hand muscles, irrespective of preoperative motor deficits. Preoperative motor scores reliably correlated with TCMEP amplitudes in a linear fashion while advanced age and renal disease emerged as independent predictors of lower TCMEP amplitudes.

A Quantitative Assessment of ChatGPT as a Neurosurgical Triaging Tool.

BACKGROUND AND OBJECTIVES: ChatGPT is a natural language processing chatbot with increasing applicability to the medical workflow. Although ChatGPT has been shown to be capable of passing the American Board of Neurological Surgery board examination, there has never been an evaluation of the chatbot in triaging and diagnosing novel neurosurgical scenarios without defined answer choices. In this study, we assess ChatGPT's capability to determine the emergent nature of neurosurgical scenarios and make diagnoses based on information one would find in a neurosurgical consult. METHODS: Thirty clinical scenarios were given to 3 attendings, 4 residents, 2 physician assistants, and 2 subinterns. Participants were asked to determine if the scenario constituted an urgent neurosurgical consultation and what the most likely diagnosis was. Attending responses provided a consensus to use as the answer key. Generative pretraining transformer (GPT) 3.5 and GPT 4 were given the same questions, and their responses were compared with the other participants. RESULTS: GPT 4 was 100% accurate in both diagnosis and triage of the scenarios. GPT 3.5 had an accuracy of 92.59%, slightly below that of a PGY1 (96.3%), an 88.24% sensitivity, 100% specificity, 100% positive predictive value, and 83.3% negative predicative value in triaging each situation. When making a diagnosis, GPT 3.5 had an accuracy of 92.59%, which was higher than the subinterns and similar to resident responders. CONCLUSION: GPT 4 is able to diagnose and triage neurosurgical scenarios at the level of a senior neurosurgical resident. There has been a clear improvement between GPT 3.5 and 4. It is likely that the recent updates in internet access and directing the functionality of ChatGPT will further improve its utility in neurosurgical triage.

Connectome-guided initiation of dopamine agonists facilitates cognitive recovery after frontal lobe resection: A case report.

Abulia is a common problem that manifests following various brain conditions, including brain surgeries. Abulia is felt to be related to dysfunction with the brain's dopamine-dependent circuitry. The role of default mode network (DMN) in its pathogenesis is crucial. In this case report, we detail the presentation of abulia in an elderly woman following surgical resection of a right frontal glioblastoma involving the DMN. Connectomic imaging was used pre-operatively and post-operatively, demonstrating disruption of regions integral to the DMN and the central executive network. We observed a significant cognitive improvement following the administration of levodopa and carbidopa. Preoperative assessment of both anatomical and functional networks can help ensure surgical safety and predict postoperative deficits. This evaluation not only enhances preparedness and facilitates early case diagnosis but also expedites the initiation of prompt and potentially targeted treatments. This case highlights the potential efficacy of levodopa and carbidopa in addressing DMN dysfunction and broadly suggests the potential for connectomics-guided post-operative therapies.

Management of Atypical Teratoid/Rhabdoid Tumors in the Pediatric Population: A Systematic Review and Meta-Analysis.

BACKGROUND: Atypical teratoid/rhabdoid tumors are rare and aggressive tumors that mainly affect children <3 years of age. Despite aggressive treatment, the overall survival rate for pediatric atypical teratoid/rhabdoid tumors remains poor. Due to their rarity, little is known regarding prognostic factors, and there is no official standard of treatment. METHODS: A comprehensive database search was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Search terms included "atypical teratoid rhabdoid tumor" and "atypical (teratoid OR rhabdoid) tumor." Variables of interest included, but were not limited to, age, sex, tumor location, treatment modality, extent of resection, and overall survival. RESULTS: The study included 294 articles and 936 patients. The median age of patients was 22 months. There was a significant difference in survival among patients receiving surgery compared with patients receiving nonoperative treatment (50.3 months vs. 28 months; P < 0.005). Extent of resection did not significantly improve survival (P = 0.832 for gross total resection, P = 0.650 for partial resection). Combination therapy with surgical resection, radiotherapy, and chemotherapy demonstrated the largest median overall survival (54.9 months) and significantly improved survival on multivariate analysis (hazard ratio, 0.48; 95% confidence interval, 0.23-0.97; P = 0.042). CONCLUSIONS: The results of this study indicate that while surgery is a crucial treatment modality for pediatric atypical teratoid/rhabdoid tumors, the effect of extent of resection is unclear. Multimodal therapy including surgery, radiotherapy, and chemotherapy is effective in improving overall survival. Future studies should focus on using larger datasets to efficiently account for confounding factors and biases.

Innovations in Spine Surgery: A Narrative Review of Current Integrative Technologies.

Neurosurgical technologies have become increasingly more adaptive, featuring real-time and patient-specific guidance in preoperative, intraoperative, and postoperative settings. This review offers insight into how these integrative innovations compare with conventional approaches in spine surgery, focusing on machine learning (ML), artificial intelligence, augmented reality and virtual reality, and spinal navigation systems. Data on technology applications, diagnostic and procedural accuracy, intraoperative times, radiation exposures, postoperative outcomes, and costs were extracted and compared with conventional methods to assess their advantages and limitations. Preoperatively, augmented reality and virtual reality have applications in surgical training and planning that are more immersive, case specific, and risk-free and have been shown to enhance accuracy and reduce complications. ML algorithms have demonstrated high accuracy in predicting surgical candidacy (up to 92.1%) and tailoring personalized treatments based on patient-specific variables. Intraoperatively, advantages include more accurate pedicle screw insertion (96%-99% with ML), enhanced visualization, reduced radiation exposure (49 µSv with O-arm navigation vs. 556 µSv with fluoroscopy), increased efficiency, and potential for fewer intraoperative complications compared with conventional approaches. Postoperatively, certain ML and artificial intelligence models have outperformed conventional methods in predicting all postoperative complications of >6000 patients as well as predicting variables contributing to in-hospital and 90-day mortality. However, applying these technologies comes with limitations, such as longer operative times (up to 35.6% longer) with navigation, dependency on datasets, costs, accessibility, steep learning curve, and inherent software malfunctions. As these technologies advance, continuing to assess their efficacy and limitations will be crucial to their successful integration within spine surgery.

Whole brain radiation therapy resulting in radionecrosis: a possible link with radiosensitising chemoimmunotherapy.

Radionecrosis describes a rare but serious complication of radiation therapy. In clinical practice, stereotactic radiosurgery (SRS) is increasingly used in combination with systemic therapy, including chemotherapy, immune checkpoint inhibitor and targeted therapy, either concurrently or sequentially. There is a paucity of literature regarding radionecrosis in patients receiving whole brain radiation therapy (WBRT) alone (without additional SRS) in combination with immunotherapy or targeted therapies. It is observed that certain combinations increase the overall radiosensitivity of the tumorous lesions. We present a rare case of symptomatic radionecrosis almost 1 year after WBRT in a patient with non-squamous non-small cell lung cancer on third-line chemoimmunotherapy. We discuss available research regarding factors that may lead to radionecrosis in these patients, including molecular and genetic profiles, specific drug therapy combinations and their timing or increased overall survival.

Health-Related Quality of Life Outcomes in Meningioma Patients Based upon Tumor Location and Treatment Modality: A Systematic Review and Meta-Analysis.

Patients with meningiomas may have reduced health-related quality of life (HRQoL) due to postoperative neurological deficits, cognitive dysfunction, and psychosocial burden. Although advances in surgery and radiotherapy have improved progression-free survival rates, there is limited evidence regarding treatment outcomes on HRQoL. This review examines HRQoL outcomes based on tumor location and treatment modality. A systematic search in PubMed yielded 28 studies with 3167 patients. The mean age was 54.27 years and most patients were female (70.8%). Approximately 78% of meningiomas were located in the skull base (10.8% anterior, 23.3% middle, and 39.7% posterior fossae). Treatment modalities included craniotomy (73.6%), radiotherapy (11.4%), and endoscopic endonasal approach (EEA) (4.0%). The Karnofsky Performance Scale (KPS) was the most commonly utilized HRQoL instrument (27%). Preoperative KPS scores > 80 were associated with increased occurrence of postoperative neurological deficits. A significant difference was found between pre- and post-operative KPS scores for anterior/middle skull base meningiomas (SBMs) in comparison to posterior (SBMs) when treated with craniotomy. Post-craniotomy SF-36 scores were lower for posterior SBMs in comparison to those in the anterior and middle fossae. Risk factors for poor neurological outcomes include a high preoperative KPS score and patients with posterior SBMs may experience a greater burden in HRQoL.

An algorithm for the treatment of concurrent pituitary adenoma and cavernous sinus aneurysm: A systematic review & case report.

BACKGROUND: Rarely, Pituitary adenomas (PA) can co-occur with intrasellar or intracavernous aneurysms. There is currently no clear guidance for the management of this dual pathology. We attempt to provide an algorithm to help guide clinical decision making for treatment of PAs co-occurring with adjacent cerebral aneurysms. METHODS: A comprehensive literature search was conducted following PRISMA guidelines using various databases. Search terms included "(Pituitary Adenoma OR Prolactinoma OR Macroadenoma OR Adenoma) AND (ICA OR Internal Carotid Artery OR paracliniod OR clinoid) Aneurysm AND (Intra-cavernous OR intracavernous OR intrasellar OR Cavernous)." RESULTS: A total of 24 studies with 24 patients were included. Twelve (50%) patients experienced visual symptoms. Ten patients (42%) had an aneurysm embedded within the adenoma. Fourteen patients (58%) had an aneurysm adjacent to the adenoma. Embedded aneurysms were significantly associated with rupture events. CONCLUSION: Vision loss is the most pressing determinant of treatment. In the absence of visual symptoms, the aneurysm should be treated first by coil embolization. If not amenable to coiling, place flow diverting stent followed by six months of anticoagulation and antiplatelet therapy. If visual loss is apparent, the adenoma-aneurysm spatial relationship becomes critical. In cases of an adjacent aneurysm, the adenoma should be removed transsphenoidally with extreme care and aneurysm rupture protocols in place. If the aneurysm is embedded within the adenoma, then a BTO is favored with permanent ICA occlusion followed by transsphenoidal resection if adequate collateral supply is demonstrated. If there is inadequate collateral supply, then an open-approach for amenable aneurysms with transcranial adenoma debulking should be performed.

A Bibliometric Analysis of the Rise of ChatGPT in Medical Research.

The rapid emergence of publicly accessible artificial intelligence platforms such as large language models (LLMs) has led to an equally rapid increase in articles exploring their potential benefits and risks. We performed a bibliometric analysis of ChatGPT literature in medicine and science to better understand publication trends and knowledge gaps. Following title, abstract, and keyword searches of PubMed, Embase, Scopus, and Web of Science databases for ChatGPT articles published in the medical field, articles were screened for inclusion and exclusion criteria. Data were extracted from included articles, with citation counts obtained from PubMed and journal metrics obtained from Clarivate Journal Citation Reports. After screening, 267 articles were included in the study, most of which were editorials or correspondence with an average of 7.5 +/- 18.4 citations per publication. Published articles on ChatGPT were authored largely in the United States, India, and China. The topics discussed included use and accuracy of ChatGPT in research, medical education, and patient counseling. Among non-surgical specialties, radiology published the most ChatGPT-related articles, while plastic surgery published the most articles among surgical specialties. The average citation number among the top 20 most-cited articles was 60.1 +/- 35.3. Among journals with the most ChatGPT-related publications, there were on average 10 +/- 3.7 publications. Our results suggest that managing the inevitable ethical and safety issues that arise with the implementation of LLMs will require further research exploring the capabilities and accuracy of ChatGPT, to generate policies guiding the adoption of artificial intelligence in medicine and science.

First in-human intrathecal delivery of bevacizumab for leptomeningeal spread from recurrent glioblastoma: rationale for a dose escalation trial.

PURPOSE: To outline the dose rationale for the first in-human intrathecal delivery of bevacizumab for LMS of GBM. METHODS: A 19-year-old female patient presented to Lenox Hill Hospital following thalamic GBM recurrence. She subsequently underwent two infusions of intra-arterial BEV (NCT01269853) and experienced a period of relative disease stability until progression in 2022. One month later, MRI disclosed diffuse enhancement representative of LMS of GBM. The patient subsequently underwent five cycles of IT BEV in mid-2022 (IND 162119). Doses of 25 mg, 37.5 mg, 50 mg, 50 mg, and 37.8 mg were delivered at two-week intervals between doses 1-4. The final 37.8 mg dose was given one day following her fourth dose, given that the patient was to be discharged, traveled several hours to our center, and was tolerating therapy well. Dosage was decreased due to the short interval between the final two treatments. Shortly after IT BEV completion, she received a third dose of IA BEV. RESULTS: Our patient did not show any signs of serious adverse effects or dose limiting toxicities following any of the treatments. It is difficult to determine PFS due to the rapid progression associated with LMS of GBM and rapid timeframe of treatment. CONCLUSION: LMS continues to be a devastating progression in many types of cancer, including GBM, and novel ways to deliver therapeutics may offer patients symptomatic and therapeutic benefits.

Hippocampal avoidance in whole brain radiotherapy and prophylactic cranial irradiation: a systematic review and meta-analysis.

PURPOSE: We systematically reviewed the current landscape of hippocampal-avoidance radiotherapy, focusing specifically on rates of hippocampal tumor recurrence and changes in neurocognitive function. METHODS: PubMed was queried for studies involving hippocampal-avoidance radiation therapy and results were screened using PRISMA guidelines. Results were analyzed for median overall survival, progression-free survival, hippocampal relapse rates, and neurocognitive function testing. RESULTS: Of 3709 search results, 19 articles were included and a total of 1611 patients analyzed. Of these studies, 7 were randomized controlled trials, 4 prospective cohort studies, and 8 retrospective cohort studies. All studies evaluated hippocampal-avoidance whole brain radiation treatment (WBRT) and/or prophylactic cranial irradiation (PCI) in patients with brain metastases. Hippocampal relapse rates were low (overall effect size = 0.04; 95% confidence interval [0.03, 0.05]) and there was no significant difference in risk of relapse between the five studies that compared HA-WBRT/HA-PCI and WBRT/PCI groups (risk difference = 0.01; 95% confidence interval [- 0.02, 0.03]; p = 0.63). 11 out of 19 studies included neurocognitive function testing. Significant differences were reported in overall cognitive function and memory and verbal learning 3-24 months post-RT. Differences in executive function were reported by one study, Brown et al., at 4 months. No studies reported differences in verbal fluency, visual learning, concentration, processing speed, and psychomotor speed at any timepoint. CONCLUSION: Current studies in HA-WBRT/HA-PCI showed low hippocampal relapse or metastasis rates. Significant differences in neurocognitive testing were most prominent in overall cognitive function, memory, and verbal learning. Studies were hampered by loss to follow-up.

Brain metastasis screening in the molecular age.

The incidence of brain metastases (BM) amongst cancer patients has been increasing due to improvements in therapeutic options and an increase in overall survival. Molecular characterization of tumors has provided insights into the biology and oncogenic drivers of BM and molecular subtype-based screening. Though there are currently some screening and surveillance guidelines for BM, they remain limited. In this comprehensive review, we review and present epidemiological data on BM, their molecular characterization, and current screening guidelines. The molecular subtypes with the highest BM incidence are epithelial growth factor receptor-mutated non-small cell lung cancer (NSCLC), BRCA1, triple-negative (TN), and HER2+ breast cancers, and BRAF-mutated melanoma. Furthermore, BMs are more likely to present asymptomatically at diagnosis in oncogene-addicted NSCLC and BRAF-mutated melanoma. European screening standards recommend more frequent screening for oncogene-addicted NSCLC patients, and clinical trials are investigating screening for BM in hormone receptor+, HER2+, and TN breast cancers. However, more work is needed to determine optimal screening guidelines for other primary cancer molecular subtypes. With the advent of personalized medicine, molecular characterization of tumors has revolutionized the landscape of cancer treatment and prognostication. Incorporating molecular characterization into BM screening guidelines may allow physicians to better identify patients at high risk for BM development and improve patient outcomes.