Ethnicity in neuro-oncology research: How are we doing and how can we do better?

PURPOSE: This study systematically reviews and meta-analyses the extent of ethnic minority representation in neuro-oncology Phase III and IV clinical trials, explores the effect of ethnicity on outcomes, and identifies predictors for the inclusion of ethnicity data in publications. METHODS: Adhering to PRISMA guidelines, we conducted a comprehensive literature search across multiple databases, on Phase III and IV trials in neuro-oncology that reported on adult and/or paediatric subjects. Through meta-analysis, we synthesized information on overall survival, event-free survival, and the incidence of adverse outcomes across ethnicities. RESULTS: From 448 identified articles, a fraction reported ethnicity data, with an even smaller number providing outcome data stratified by ethnicity. Most study participants were identified as White, underscoring a significant underrepresentation of minorities. Our meta-analysis did not reveal significant outcome differences by ethnicity, which may be attributed to the limited and inadequate reporting of data. Predictors for including ethnicity data were identified, including trials in North America(OR2.39, 95%CI 1.18-5.12, p < 0.02),trials of drugs or biologic agents(OR 5.28, 95%CI 1.43-3.42, p < 0.05),and trials funded by charities(OR 2.28, 95% CI 1.04-5.27, p < 0.05) or pharmaceutical companies(OR 3.98, 95% CI 1.60-10.0, p < 0.005). CONCLUSION: The underrepresentation of minorities in neuro-oncology clinical trials and the inadequately characterized impact of ethnicity on treatment outcomes highlight a critical need for more inclusive recruitment strategies and improved reporting standards. Change is necessary to ensure trials reflect the diversity of the patient population, which is essential for developing tailored strategies and improving outcomes. Future research should prioritize understanding the role of ethnicity in neuro-oncology to facilitate personalized treatment approaches.

Obstructive hydrocephalus due to an enlarged massa intermedia treated with endoscopic third ventriculostomy.

The massa intermedia (MI) or interthalamic adhesion (ITA) is a band of tissue connecting the medial surfaces of the thalami and is present in the majority of healthy individuals. Its enlargement as well as its absence have been associated with some pathological states.We describe the first case report of a 3-year-old child presenting with obstructive hydrocephalus in the context of an enlarged massa intermedia. The patient's symptoms abated following an endoscopic third ventriculostomy.

Prognostic factors and surgical outcomes of spontaneous spinal epidural haematoma: a systematic review and meta-analysis.

Spontaneous spinal epidural haematoma (SSEH) is a rare disease defined as blood accumulation within the vertebral epidural space without a cause identified, which can lead to severe neurological deficits. We aim to provide a comprehensive understanding of the prognostic factors affecting surgical outcomes in true SSEH and propose a critical time frame for operative management. A systematic literature search was performed and registered, using OVID Medline and EMBASE, in line with the PRISMA guidelines. Relevant demographic, clinical, surgical, and outcome data were extracted. The ASIA scale was uniformly used throughout our systematic review. Statistical analysis was performed via logistic regression. Of the 1179 articles examined, we included 181 studies involving 295 adult patients surgically treated for SSEH. SSEH were most commonly found in the cervicothoracic spine, with 2-4 spinal segments most commonly involved. Multivariable logistic regression model showed that the following factors were statistically significant in the post-operative outcome: operation type (P = 0.024), pre-operative neurologic status (P < 0.001), use of warfarin (P = 0.039), and operative interval (P = 0.006). Our retrospective analysis confirms the reversibility of severe neurological deficits after surgical intervention, with a prognosis of post-operative outcomes determined by the use of warfarin, pre-operative ASIA grade, and above all surgical evacuation within 12 h.

Prognostic factors for surgically managed intramedullary spinal cord tumours: a single-centre case series.

PURPOSE: Intramedullary spinal cord tumours (IMSCTs) are comparatively rare neoplasms. We present a single-centre clinical case series of adult patients with surgically managed IMSCTs. METHODS: We performed a retrospective analysis of electronic patient records in the time period spanning July 2010 to July 2021. All adult patients that had undergone surgical management for IMSCTs were eligible for inclusion. Baseline and post-operative clinical and radiological characteristics, along with follow-up data, were assessed. We also performed a literature review with a focus on surgical outcomes for IMSCTs. RESULTS: Sixty-six patients matched our selection criteria, with a median age of 42 years (range 23-85). Thirty-four ependymomas, 17 haemangioblastomas, 12 astrocytomas, 2 lymphomas and 1 teratoma were included. Statistical analysis yielded several significant findings: IMSCTs spanning a greater number of vertebral levels are significantly associated with poor McCormick outcomes (p = 0.03), presence of gait disturbance before surgery is significantly associated with poor outcome for both post-operative McCormick and Nurick scores (p = 0.007), and radicular pain present pre-operatively is significantly associated with a good post-operative McCormick score (p = 0.045). Haemangioblastomas are significantly more likely to have a clear intra-operative dissection plane compared to ependymomas and astrocytomas (p = 0.009). However, astrocytomas have a significantly higher prevalence of good McCormick outcomes compared to ependymomas and haemangioblastomas (p = 0.03). CONCLUSION: Histological diagnosis, cranio-caudal extent of the tumour and the presence or absence of baseline deficits-such as gait impairment and radicular pain-are significant in determining neurological outcomes after surgery for IMSCTs.

Surgical management and outcomes in spinal intradural arachnoid cysts: the experience from two tertiary neurosurgical centres.

PURPOSE: Evaluation of the presentation and outcomes of different surgical treatment approaches for spinal intradural arachnoid cysts (SIAC). METHODS: Cases were identified from electronic records of two major neurosurgical centres in London over the last 10 years (October 2009-October 2019) that have been surgically treated in both institutions. Clinical findings, surgical technique, and recurrence by procedure were statistically analysed. Statistical analysis was performed with STATA 13.1 Software. RESULTS: A total of 42 patients with SIAC were identified for this study with a mean age at the time of surgery of 53.6 years and a male:female ratio of 8:13. There were 31 patients with primary SIACs and 11 with secondary SIACs. The most common presenting symptom was paraesthesia (n = 27). The most common location of the cyst was in the thoracic region (n = 33). Syrinx was present in 26.2% of SIACs (n = 11). Resection was associated with significantly better postoperative pain compared to other surgical techniques (p = 0.01), significantly poorer postoperative urinary function (p = 0.029), and lower rates of sensory recovery in patients who presented preoperatively with sensory deficit (p = 0.041). No significant difference was seen in symptomatic outcomes between patients with primary and secondary SIACs. CONCLUSION: Resection and drainage are both effective methods of managing SIACs. In this observational study, resection was associated with significantly reduced pain postoperatively when compared with drainage, however also with significantly less improvement in postoperative urinary function. Therefore, resection should be the gold standard management option for SIACs, with drainage as an option where resection is unsafe, and drainage should also be considered in patients presenting with urinary dysfunction.

Cost-effectiveness of repeat delayed imaging for spontaneous subarachnoid hemorrhage.

BACKGROUND: In patients with intracranial aneurysm presenting with spontaneous subarachnoid hemorrhage (SAH), 15% of them could be missed by the initial diagnostic imaging. Repeat delayed imaging can help to identify previously undetected aneurysms, however, the cost-effectiveness of this strategy remains uncertain. OBJECTIVE: The aim of this study is to assess the cost-effectiveness of repeat delayed imaging in patients with SAH who had a negative result during their initial imaging. METHODS: A Markov model was developed to estimate the lifetime costs and quality-adjusted life-year (QALY) for patients who received or not received repeat delayed imaging. The analyses were conducted from a healthcare perspective, with costs reported in UK pounds and expressed in 2020 values. Extensive sensitivity analyses were performed to assess the robustness of the results. RESULTS: The base case incremental cost-effectiveness ratio (ICER) of repeat delayed imaging is £9,314 per QALY compared to no-repeat delayed imaging. This ICER is below the National Institute for Health and Care Excellence (NICE) £20,000 per QALY willingness-to-pay threshold. At the NICE willingness-to-pay threshold of £20,000 per QALY, the probability that repeat delayed imaging is most cost-effective is 0.81. The results are sensitive to age, the utility of survived patients with a favorable outcome, the sensitivity of repeat delayed imaging, and the prevalence of aneurysm. CONCLUSIONS: This study showed that, in the UK, it is cost-effective to provide repeat delayed imaging using computed tomographic angiography (CTA) for patients with SAH who had a negative result in their initial imaging.

Prognostic Factors for Surgically Managed Spontaneous Spinal Epidural Hematoma: A Single-Center Case Series of 18 Patients.

BACKGROUND: Spontaneous spinal epidural hematoma (SSEH) is a rare pathology, which carries a significant morbidity. OBJECTIVE: To review our institutional experience of surgically managed patients with SSEH, seeking to better understand clinical prognostic factors related to postoperative outcomes and thereby improve counseling of patients before treatment. METHODS: All patients who underwent surgical management of SSEH between September 2011 and 2021. Baseline and postoperative clinical and radiological characteristics are presented, including the American Spinal Injury Association grade (ASIA). Statistical analyses were performed using Stata 13.1. RESULTS: Eighteen patients were identified in total (11 male patients and 7 female patients) with a median age of 59.5 (range 3-83) years. The most common spinal region affected was cervicothoracic (33.3%). Limb weakness (94.4%) and urinary dysfunction (83.3%) represented the most common presenting symptoms. Preoperatively, the presence of spinal cord edema on imaging was associated with worse preoperative Medical Research Council (MRC) grade ( P = .033), female sex was associated with preserved saddle sensation ( P = .04), and patients receiving antiplatelet medication were associated with a higher risk of preoperative axial back pain ( P = .005). Higher postoperative MRC grade was associated with higher preoperative ASIA ( P = .012) and MRC grade ( P = .005), and preservation of saddle sensation ( P = .018). Postoperative improvements in axial back pain were associated with higher preoperative ASIA grade ( P = .035) and anticoagulation treatment ( P = .029). CONCLUSION: Neurosurgical intervention for SSEH yields positive outcomes and benefits patients. Patients with higher preoperative ASIA, MRC grade, and those presenting with preserved saddle sensation may experience further improved clinical outcomes after intervention.

Fat in the Fossa and the Sphenoid Sinus: A Simple and Effective Solution to CSF Leaks in Transsphenoidal Surgery. Cohort Study and Systematic Review.

Objectives Cerebrospinal fluid (CSF) leak following endoscopic transsphenoidal surgery (TSS) remains a challenge and is associated with high morbidity. We perform a primary repair with f at in the pituitary f ossa and further fat in the s phenoid sinus (FFS). We compare the efficacy of this FFS technique with other repair methods and perform a systematic review. Design, Patients, and Methods This is a retrospective analysis of patients undergoing standard TSS from 2009 to 2020, comparing the incidence of significant postoperative CSF rhinorrhea (requiring intervention) using the FFS technique compared with other intraoperative repair strategies. Systematic review of current repair methods described in the literature was performed following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Results In all, there were 439 patients, with 276 patients undergoing multilayer repair, 68 patients FFS repair, and 95 patients no repair. No significant differences were observed in baseline demographics between the groups. Postoperative CSF leak requiring intervention was significantly lower in the FFS repair group (4.4%) compared with the multilayer (20.3%) and no repair groups (12.6%, p < 0.01). This translated to fewer reoperations (2.9% FFS vs. 13.4% multilayer vs. 8.4% no repair, p < 0.05), fewer lumbar drains (2.9% FFS vs. 15.6% multilayer vs. 5.3% no repair, p < 0.01), and shorter hospital stay (median days: 4 [3-7] FFS vs. 6 (5-10) multilayer vs. 5 (3-7) no repair, p < 0.01). Risk factors for postoperative leak included female gender, perioperative lumbar drain, and intraoperative leak. Conclusion Autologous fat on fat graft for standard endoscopic transsphenoidal approach effectively reduces the risk of significant postoperative CSF leak with reduced reoperation and shorter hospital stay.

MGMT Promoter Methylation: Prognostication beyond Treatment Response.

MGMT promoter methylation is related to the increased sensitivity of tumour tissue to chemotherapy with temozolomide (TMZ) and thus to improved patient survival. However, it is unclear how the extent of MGMT promoter methylation affects outcomes. In our study, a single-centre retrospective study, we explore the impact of MGMT promoter methylation in patients with glioblastoma who were operated upon with 5-ALA. Demographic, clinical and histology data, and survival rates were assessed. A total of 69 patients formed the study group (mean age 53.75 ± 15.51 years old). Positive 5-ALA fluorescence was noted in 79.41%. A higher percentage of MGMT promoter methylation was related to lower preoperative tumour volume (p = 0.003), a lower likelihood of 5-ALA positive fluorescence (p = 0.041) and a larger extent of resection EoR (p = 0.041). A higher MGMT promoter methylation rate was also related to improved progression-free survival (PFS) and overall survival (OS) (p = 0.008 and p = 0.006, respectively), even when adjusted for the extent of resection (p = 0.034 and p = 0.042, respectively). A higher number of adjuvant chemotherapy cycles was also related to longer PFS and OS (p = 0.049 and p = 0.030, respectively). Therefore, this study suggests MGMT promoter methylation should be considered as a continuous variable. It is a prognostic factor that goes beyond sensitivity to chemotherapy treatment, as a higher percentage of methylation is related not only to increased EoR and increased PFS and OS, but also to lower tumour volume at presentation and a lower likelihood of 5-ALA fluorescence intraoperatively.

Systematic Review of Surgical Management of Spinal Intradural Arachnoid Cysts.

OBJECTIVE: Spinal intradural arachnoid cysts (SIACs) are rare pathological lesions that can arise via outpouchings of the arachnoid layer in the spinal canal that can result in neurological deficits. We performed a systematic literature review regarding the current surgical techniques used in the management of SIACs and discussed the prevailing hypotheses surrounding the etiology of SIACs. METHODS: A systematic search of the literature was performed in December 2020 using EMBASE and MEDLINE for reports regarding the surgical management of SIACs. Data were collected regarding the demographics of the patients, classification system used, presence or absence of syrinxes, preoperative imaging modality, surgical approach and extent of resection, and postoperative outcomes and follow-up. RESULTS: Our search yielded 19 reports for inclusion in the present study. The 19 studies included a total of 414 cases, with an overall male/female ratio of 0.93:1. The most common site for the SIACs was the thoracic spinal cord at 77.5%. The symptoms were very similar across the 19 studies. Of the 19 studies, 15 had used resection to manage the SIACs, 10 had used fenestration or marsupialization, and 4 had used cystoarachnoid or cystoperitoneal shunts. CONCLUSIONS: SIACs are rare and debilitating spinal pathological lesions, with the etiology of primary SIACs still not fully elucidated. Multiple surgical approaches have been effective, with the optimal operative strategy largely dependent on the individual patient and cyst factors on a case-by-case basis.

Is Cauda Equina Surgery Safe Out-of-Hours? A Single United Kingdom Institute Experience.

BACKGROUND: Cauda equina syndrome (CES) can have devastating neurological sequelae if surgical treatment is delayed. However, out-of-hours surgery (weekdays from 6:00 pm to 8:00 am and all weekend operations) can potentially result in higher rates of intraoperative complications, resulting in worse outcomes. In the present study, we have described our outcomes for patients with CES during an 8-year period (December 2011 to October 2019) with the aim of assessing the risk of out-of-hours surgery. METHODS: We performed a retrospective analysis of inpatient events and outcomes at 6 months of follow-up. Patient demographics, symptoms, and management data were extracted, and a risk factor analysis was performed using logistic regression. The outcome measures were the incidence of complications and symptom changes at follow-up. Symptom outcome changes between 2 time points were analyzed using repeated measures. RESULTS: A total of 278 patients were included in the present study. Surgery out-of-hours (P = 0.018) and prolonged operations (P = 0.018) were significant risk factors for intraoperative complications. Improved outcomes at 6 months of follow-up were found for lower back pain, sciatica, altered saddle sensation, and urinary sphincter disturbance, with no significant changes for the remaining symptoms. Out-of-hours surgeries did not significantly affect individual symptom outcomes. CONCLUSIONS: Our analysis has suggested that emergency decompressive surgery for patients with CES does not result in worsening of outcomes with out-of-hours surgery compared with in-hours. However, our findings also showed that no clear benefit exists to expediting surgery for those with severe presentations. Thus, decompressive surgery should be undertaken at the earliest possible time to safely do so.

Intraoperative Neurophysiological Monitoring for Intradural Extramedullary Spinal Tumours.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: Intraoperative neurophysiological monitoring (IONM) is widely used in spinal neurosurgery, particularly for intramedullary tumours. However, its validity in intradural extramedullary (IDEM) spinal tumours is less clearly defined, this being the focus of this study. METHODS: We compared outcomes for patients that underwent resection of IDEM tumours with and without IONM between 2010 and 2020. Primary outcomes were postoperative American Spinal Injury Association (ASIA) scores. Other factors assessed were use of intraoperative ultrasound, drain placement, postoperative complications, postoperative Eastern Cooperative Oncology Group (ECOG) score, extent of resection, length of hospital stay, discharge location and recurrence. RESULTS: 163 patients were included, 71 patients in the IONM group and 92 in the non-IONM group. No significant differences were noted in baseline demographics. For preoperative ASIA D patients, 44.0% remained ASIA D and 49.9% improved to ASIA E in the IONM group, compared to 39.7% and 30.2% respectively in the non-IONM group. For preoperative ASIA E patients, 50.3% remained ASIA E and 44.0% deteriorated to ASIA D in the IONM group, compared to 30.2% and 39.7% respectively in the non-IONM group (all other patients deteriorated further). Length of inpatient stay was significantly shorter in the IONM group (P = .043). There were no significant differences in extent of resection, postoperative complications, discharge location or tumour recurrence. CONCLUSIONS: Research focusing on the use of IONM in IDEM tumour surgery remains scarce. Our study supports the use of IONM during surgical excision of IDEM tumours.

5-Aminolevulinic Acid-Guided Resection in Grade III Tumors-A Comparative Cohort Study.

BACKGROUND: The benefits of using 5-aminolevulinic acid (5-ALA) in resection of grade IV tumors have been extensively researched. However, few studies have investigated the use of 5-ALA in grade III gliomas. OBJECTIVE: To discover whether 5-ALA provides significant benefit in assisting resection of grade III gliomas. METHODS: A single-center, retrospective cohort study between January 2013 and January 2019 of adult patients with grade III gliomas. Patients were separated into a 5-ALA-guided surgery group (5-ALA-GS) and non-5-ALA-guided surgery group (non-5-ALA-GS). Primary outcome was overall survival (OS); secondary outcomes were both postoperative and 6-month performance status (PS6m), and extent of resection (EoR). RESULTS: Sixty-nine patients with grade III gliomas were included (39 and 30 patients in the 5-ALA-GS group and non-5-ALA-GS group, respectively). There was no significant difference in tumor characteristics between the groups. No significant difference was observed in OS (P = .072) and EoR (P = .609) between both the groups. In a subgroup of the 5-ALA-GS where gross total resection (GTR) was achieved, there was a better OS (P = .043). Significantly worse outcomes were seen postoperatively (P = .044) and at PS6m (P = .041) in the 5-ALA-GS group, mainly because of the poorer outcome in the subtotal resection subgroup. CONCLUSION: Despite the benefits of 5-ALA in grade IV glioma surgery, these benefits are limited to a smaller group of patients with grade III tumors where there is sufficient fluorescence to allow GTR. In this cohort of patients, 5-ALA use may result in worse neurological outcomes particularly when GTR is not feasible and therefore caution is warranted.

Surgical Management of Spinal Chordoma: A Systematic Review and Single-Center Experience.

OBJECTIVE: Chordoma is a rare neoplasm of the neuraxis derived from remnants of the primitive notochord. The importance of wide margins and use of adjuvant therapy in spinal chordomas are still contentious points in the management of spinal chordomas. We conducted a systematic review of the surgical management of spinal chordomas alongside our 10-year institutional experience. METHODS: A systematic search of the literature was performed in November 2020 using Embase and MEDLINE for articles regarding the surgical management of chordomas arising from the mobile spine and sacrum. We also searched for all adult patients who were surgically managed for spinal chordomas at our institute between 2010 and 2020. In both the systematic review and our institutional case series, data on adequacy of resection, use of adjuvant therapy, complications, recurrence (local or metastatic), and survival outcomes were collected. RESULTS: We identified and analyzed 42 articles, yielding 1531 patients, from which the overall gross total or wide resection rate was 54.9%. Among the 8 cases in our institutional experience (4 sacral, 3 cervical, and 1 lumbar), we achieved gross total resection in 50% of initial operations. The recurrence rate was 25% in our gross total resection group and 50% where initial resection was subtotal. Of patients, 75% had no evidence of recurrence at most recent follow-up. CONCLUSIONS: Albeit difficult at times because of the proximity to neurovascular tissue, achieving a wide resection followed by adjuvant therapy for spinal chordomas is of great importance. Multidisciplinary discussion is valuable to ensure the best outcome for the patient.

Risk Factor Analysis and Surgical Outcomes of Acute Spontaneous Spinal Subdural Hematoma. An Institutional Experience of Four Cases and Literature Review.

OBJECTIVE: Spontaneous spinal subdural hematoma (SSSDH) is exceedingly rare, with significant morbidity in most patients. Acute neurologic deficit in the context of a SSSDH is considered a neurosurgical emergency. We performed a literature review and compared the results with our institutional experience to evaluate the risk factors and neurologic outcomes of SSSDH. METHODS: We retrospectively collected the medical, radiologic, and surgical information of 4 patients with SSSDH who were operated on in our neurosurgical unit. A literature review of surgically managed patients with SSSDH and their neurologic outcomes was performed. Ordered logistic regression statistics were used to study the risk factors influencing the postoperative Domenicucci grade. RESULTS: A total of 112 patients were evaluated, with a female/male ratio of 1.3:1. Mean patient age was 60.25 years. Our analysis of the data showed that the cohort of patients presenting with bladder dysfunction in addition to paraparesis were found to have worse neurologic outcomes postoperatively. Adjusted analysis identified 3 clinical characteristics that influenced surgical outcome: cervical SSSDH (P = 0.029), neurologic deficit (P < 0.001), and anticoagulation medication (P < 0.001). CONCLUSIONS: This review shows that patients aged ≥60 years and on anticoagulation are at an increased risk of sustaining a spontaneous subdural spinal hematoma without history of trauma. To our knowledge, this is also the first study to show a presenting symptom of bladder dysfunction as a significant risk factor for poor surgical outcome in SSSDH. Our study supports surgical evacuation of acute SSSDH in the presence of these risk factors.

5-Aminolevulinic acid-guided resection improves the overall survival of patients with glioblastoma-a comparative cohort study of 343 patients.

BACKGROUND: 5-Aminolevulic acid-guided surgery (5-ALA-GS) improves the extent of resection (EoR) and progression-free survival in patients with glioblastoma multiforme (GBM). METHODS: A single-center retrospective cohort study of adult patients with GBM who had surgical resection between 2013 and 2019, 5-ALA guided versus a non-5-ALA cohort. The primary outcome was the overall survival (OS). Secondary outcomes were EoR, performance status (PS), and new focal neurological deficit. RESULTS: Three hundred and forty-three patients were included: 253 patients in 5-ALA-GS group and 90 patients in the non-5-ALA-GS group. The OS (17.47 vs 10.63 months, P < .0001), postoperative PS (P < .0001), PS at 6 months (P = .002), new focal neurological deficit (23.3% vs 44.9%, P < .0001), and radiological EoR (gross total resection [GTR]-47.4% vs 22.9%, P < .0001) were significantly better in the 5-ALA-GS group compared to non-5-ALA-GS group. In multivariate analysis, use of 5-ALA (P = .003) and MGMT promoter methylation (P = .001) were significantly related with a better OS. In patients with radiological GTR, OS was also significantly better (P < .0001) in the 5-ALA-GS group compared to the non-5-ALA-GS group. CONCLUSIONS: 5-ALA-GS is associated with a significant improvement in the OS, PS after surgery and at 6 months, larger EoR, and fewer new motor deficits in patients with GBM.