Category: Oncology

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Genomic Alterations in Molecularly Defined Oligodendrogliomas

Neurosurgery 96:328–337, 2025

• Study Focus: Genomic alterations in oligodendrogliomas using standardized NGS panels.

• Key Genes: CIC, FUBP1, and TERTp are the most frequently altered genes.

• Patient Cohort: Retrospective analysis of 95 patients with NGS reports.

• Methodology: Kaplan-Meier plots and log-rank tests for survival analysis.

• Findings: CIC alterations linked to reduced PFS at earlier time points.

• Additional Genes: NOTCH1 and PIK3CA show potential prognostic value.

• Clinical Implications: Potential integration of genomic alterations into clinical practice.

• Future Research: Larger studies needed to validate findings.

• Seizures: Most common presenting symptom in patients.

• Treatment: Majority underwent surgery followed by observation.

• Tumor Grade: Predominantly WHO grade 2 at first surgery.

• Mutation Analysis: 435 cancer-related genes analyzed.

• Statistical Tools: MATLAB R2022b used for analysis.

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Clinical Predictors of Overall Survival in Very Elderly Patients With Glioblastoma: A National Cancer Database Multivariable Analysis

Neurosurgery 96:373–385, 2025

• Study Focus: The study analyzes clinical predictors of overall survival in very elderly patients (aged 80 and older) with glioblastoma, using data from the National Cancer Database.

• Patient Demographics: It includes 578 very elderly patients and 2836 elderly patients (aged 65-79), highlighting differences in insurance status and treatment patterns.

• Treatment Patterns: Very elderly patients are less likely to receive gross total resection (GTR), radiotherapy (RT), or chemotherapy (CT) compared to younger elderly counterparts, despite these treatments improving overall survival.

• Survival Outcomes: GTR, RT, and CT are associated with improved survival in very elderly patients, suggesting aggressive treatment may benefit selected patients.

• Statistical Methods: The study employs multivariable regression analysis and Cox proportional-hazards models to assess the effects of age and treatment on survival.

• Key Findings: Aggressive treatment approaches, including GTR, RT, and CT, should be considered for very elderly patients, aligning with patient and family goals.

• Limitations: The study acknowledges limitations in meeting the Cox proportional hazard assumption and suggests further research on quality of life post-treatment.

• Conclusion: The study supports offering standard multimodal treatment protocols for glioblastoma to patients aged 65 and older, enhancing external validity across the U.S.

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Presentation, surgical outcome, and supplementary motor area syndrome risk of posterior superior frontal gyrus tumors

J Neurosurg 142:162–173, 2025

Following resection of posterior superior frontal gyrus (PSFG) tumors, patients can experience supplementary motor area (SMA) syndrome consisting of contralateral hemiapraxia and/or speech apraxia. Given the heterogeneity of PSFG tumors, the authors sought to determine the risk of postoperative deficits and assess predictors of outcomes for all intraparenchymal PSFG tumors undergoing surgery (biopsy or resection), regardless of histology.

METHODS This was a retrospective single-center cohort study of adult PSFG-region tumors undergoing biopsy or resection by a single surgeon.

RESULTS A total of 106 consecutive patients undergoing 123 procedures (21 biopsies, 102 resections) fulfilled inclusion and exclusion criteria. Anaplastic astrocytomas were the most frequent among resected tumors (39% vs 29%), while glioblastomas were most common among biopsies (38% vs 27%) (p < 0.0001). The biopsy cohort was more likely to have tumor involvement outside the PSFG (90% vs 62%) (p = 0.011), most commonly in the motor cortex (67% vs 31%) (p = 0.005). Seizures were the most common presenting symptom in the resection cohort (p = 0.017), while motor deficits were more common in the biopsy cohort (58% vs 29%) (p < 0.001). Immediate postoperative neurological deficits occurred in 71 cases (58%), but only 3 of the deficits were permanent at 6 months of follow-up (2%). Postoperative SMA syndrome occurred in 48 cases (47%) and was significantly associated with involvement of the motor cortex (p = 0.018) or cingulate gyrus (p = 0.023), which were also significant in multivariate analysis as risk factors for SMA syndrome. However, postoperative SMA syndrome was not significantly associated with overall survival (p = 0.51). There were no perioperative deaths, but corpus callosum involvement (p < 0.001), contrast enhancement (p = 0.003), and glioblastoma pathology (p = 0.038) predicted worse overall survival in patients undergoing resection.

CONCLUSIONS Nearly half of all patients undergoing resection of PSFG-region tumors experience a postoperative SMA syndrome. Individuals with corpus callosum and/or motor cortex involvement may be at an increased risk of experiencing SMA syndrome. However, these deficits are usually transient, and the risk of permanent new deficits is very low (3%). Preoperative characteristics including corpus callosum involvement and tumor enhancement—in addition to pathology—might serve as predictors of overall survival within this patient population.

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Long-term survivors in 976 supratentorial glioblastoma, IDH-wildtype patients

J Neurosurg 142:174–186, 2025

Glioblastoma, isocitrate dehydrogenase (IDH)–wildtype is the most aggressive glioma with poor outcomes. The authors explored survival rates and factors associated with long-term survival in patients harboring a glioblastoma, IDH-wildtype.

METHODS In an observational, retrospective, single-center study, the authors examined the medical records of 976 adults newly diagnosed with supratentorial glioblastomas, IDH-wildtype between January 2000 and January 2021. They analyzed clinical-, imaging-, and treatment-related factors associated with 2-year and 5-year survival.

RESULTS The median overall survival was 11.2 months (12.2 months for patients included after 2005 and the introduction of standard combined chemoradiotherapy). The median progression-free survival was 9.4 months (10.0 months for patients included after 2005). Overall, 17.6% of patients reached a 2-year overall survival, while 2.2% of patients reached a 5-year overall survival. Furthermore, 6.6% of patients survived 2 years without progression, while 1.1% of patients survived 5 years without progression. Two factors that were consistently associated with 2-year and 5-year survival were first-line oncological treatment with standard combined chemoradiotherapy and methylated O 6 -methylguanineDNA methyltransferase promoter. Other factors that were significantly associated with 2-year or 5-year survival were age at diagnosis ≤ 60 years, headaches or signs of raised intracranial pressure at diagnosis, cortical contact of contrast enhancement, no contrast enhancement crossing the midline on initial imaging, total or subtotal tumor resection, and a second line of oncological treatment at recurrence. Within 21 cases of 5-year survival, 18 were confirmed to be glioblastomas, IDH-wildtype, and 7 of the 5-year survivors (38.9%) had additional genetic alterations: 3 cases had an FGFR mutation or fusion, 3 cases had a PIK3CA mutation, 1 case had a PTPN11 mutation, and 1 case had a PMS2 mutation in the context of constitutional mismatch repair deficiency syndrome.

CONCLUSIONS Five-year overall survival in patients with glioblastoma, IDH-wildtype is extremely low. Predictors of a longer survival are mostly treatment factors, emphasizing the importance of a complete oncological treatment plan, when achievable. Glioblastoma, IDH-wildtype 5-year survivors could be screened for actionable targets in case of recurrence.

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Noninvasive evaluation of the glymphatic system in diffuse gliomas using diffusion tensor image analysis along the perivascular space

J Neurosurg 142:187–196, 2025

The aim of this study was to noninvasively explore the glymphatic system (GS) in glioma and its association with glioma characteristics and prognosis by using diffusion tensor image analysis along the perivascular space (ALPS).

METHODS In the period from April 2015 to November 2021, all patients with pathologically confirmed unihemispheric glioma who had not undergone surgery, chemotherapy, radiotherapy, or stereotactic biopsy; who did not have severe brain deformation; who had undergone preoperative conventional and advanced whole-brain diffusion-weighted imaging; and whose data were available and uncompromised were included in this study. Age- and sex-matched healthy controls (HCs) who had undergone diffusion-weighted imaging were also included. The ALPS index was calculated based on diffusivity maps, allowing noninvasive analysis of the GS. The contralateral ALPS index was measured in all glioma patients, and the ipsilateral ALPS index was measured in glioma patients without severe deformation of the ipsilateral hemisphere. The ALPS index was compared between glioma patients and HCs according to tumor grade, IDH genotype, tumor and edema volume, and tumor location. The association between the bilateral ALPS index of gliomas and tumor characteristics was further analyzed. Survival analysis was conducted using Kaplan-Meier survival curves with the logrank test and univariable and multivariable Cox regressions.

RESULTS Ninety-one patients with unihemispheric glioma (33 female, mean age 46 ± 13 years) and 59 age- and sex-matched HCs were included in this study. The ipsilateral ALPS index decreased in the glioma group versus the HC group, regardless of tumor grade, IDH genotype, tumor and edema volume, or tumor location (p ≤ 0.048), whereas the contralateral ALPS index decreased in gliomas with a high grade, IDH wildtype, larger edema volume, different tumor volumes and locations (p ≤ 0.009). The ipsilateral versus contralateral ALPS index was lower regardless of tumor grade, IDH genotype, tumor and edema volume, or tumor location (p ≤ 0.044). Univariable linear regression revealed age (β = −0.004, p = 0.026), tumor grade (β = −0.114, p = 0.011), and IDH genotype (β = 0.120, p = 0.008) were associated with the ipsilateral ALPS index in glioma. Age (β = −0.005, p < 0.001), tumor grade (β = −0.144, p < 0.001), IDH genotype (β = 0.154, p < 0.001), tumor volume (β = −0.002, p = 0.001), and peritumoral edema volume (β = −0.002, p < 0.001) were correlated with the contralateral ALPS index in glioma. Multivariable linear regression revealed that tumor grade (β = −0.125, p = 0.005) was independently associated with the ipsilateral ALPS index. Age (β = −0.003, p = 0.022), IDH status (β = 0.132, p = 0.001), and tumor volume (β = −0.002, p < 0.001) were independently associated with the contralateral ALPS index. Kaplan-Meier analysis showed different survival times between low and high contralateral ALPS groups (log-rank = 10.574, p = 0.001). Univariable Cox regression analysis demonstrated that the lower contralateral ALPS index was related to a shorter survival time (HR 0.095, p = 0.005). Multivariable Cox regression analysis revealed IDH status as the only independent factor for survival (HR 0.138, p < 0.001).

CONCLUSIONS GS function was impaired in glioma and correlated with tumor characteristics, and worse contralateral GS function was associated with a shorter survival time.

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Microsurgical anatomy and approaches to thalamic gliomas. Part 2: Maximal safe resection of thalamic gliomas improves outcomes.

J Neurosurg 141:1472–1483, 2024

As presented in Part 1 of this series, thalamic gliomas (TGs) are deep-seated, difficult-to-access tumors surrounded by vital neurovascular structures. Given their high operative morbidity, TGs have historically been considered inoperable lesions. Although maximal safe resection (MSR) has become the treatment standard for lobar and even deep-seated mediobasal temporal and insular gliomas, the eloquent location of TGs has precluded this management strategy, with biopsy and adjuvant treatment being the mainstay. The authors hypothesized that MSR can be achieved with low morbidity and mortality for TGs, thus resulting in improved outcomes.

METHODS A retrospective single-center study was performed on all TG patients from 2006 to 2020. Clinical, imaging, and pathology reports were obtained. Univariate and multivariate analyses were performed to determine prognostic variables. Case examples illustrate various approaches and the rationale for staging resections of more complex TGs.

RESULTS A total of 42 patients (26 males, 16 females), among them 12 pediatric (29%) cases, were included. Their mean age was 36.0 ± 21.4 (median 30, range 3–73) years. The median maximal tumor diameter was 45 (range 19–70) mm. Eighteen patients (43%) had a prior stereotactic needle tumor biopsy, with the ultimate diagnosis changed for 7 patients (39%) following microsurgical resection. The most common surgical approaches were transtemporal (29%), anterior interhemispheric transcallosal (29%), and superior parietal lobule (25%). Overall, the combined subtotal and grosstotal resection rate was 95% (n = 40). Low-grade gliomas (LGGs; grades I and II) comprised one-third of the group, whereas half of the patients had glioblastoma multiforme. There were no operative mortalities. Although temporary postoperative motor deficits were observed in 12 patients (28.6%), all improved during the early postoperative period except 1 (2.4%), who had mild residual hemiparesis. Two patients required CSF diversion for hydrocephalus. The 2-year overall survival rate was 90% for LGG patients and 15% for high-grade glioma (HGG) patients. Multivariate analysis revealed that histological grade, age, and extent of resection were independent prognostic factors associated with survival.

CONCLUSIONS Management of TGs is challenging, with resection avoided by many, if not most, neurosurgeons, especially for HGGs. The results reported here demonstrate improved outcomes with resection, particularly in younger LGG patients. The authors therefore advocate for MSR for a select cohort of TG patients using carefully planned surgical approaches, contemporary intraoperative adjuncts, and meticulous microsurgical techniques.

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The dural attachment length predict prognosis in patients with recurrent meningiomas

Neurosurgical Review (2024) 47:843

To investigate the prognostic factors of recurrent meningioma patients who underwent reoperation, so as to make relevant recommendations for the treatment.

A retrospective analysis was performed on 73 patients with recurrent meningioma. Patients’ clinical data were obtained from their medical records. Progression-free Survival (PFS) was defined as the interval from the date of surgery to the date of tumor recurrence, or to the date of the last imaging review. Overall survival (OS) was defined as the time from the date of surgery to death from any cause, or to the date of the last follow-up.

The multivariate COX regression showed that dural attachment length (HR = 1.238, 95%CI1.011–1.516, P = 0.039) and WHO grade (HR = 2.184, 95%CI1.135–4.203, P = 0.019) were independent risk factors for tumor progression. The factors associated with survival in multivariate regression analysis were preoperative Karnofsky Performance Scale (KPS) (HR = 0.951, 95%CI0.923–0.979, P = 0.001), dural attachment length (HR = 1.520, 95%CI1.124–2.057, P = 0.007) and WHO grade (HR = 4.829, 95%CI1.89112.331, P = 0.001). The dural attachment length (OR = 1.843, 95%CI1.236–2.748, P = 0.003) was the only risk factor associated with postoperative pulmonary infection. No correlation was observed between Simpson’s grade and either PFS or OS.

The dural attachment length is closely related to the prognosis of recurrent meningioma, which should be given importance during the perioperative assessment.

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Microscope-integrated optical coherence tomography for in vivo human brain tumor detection with artificial intelligence

J Neurosurg 141:1343–1351, 2024

It has been shown that optical coherence tomography (OCT) can identify brain tumor tissue and potentially be used for intraoperative margin diagnostics. However, there is limited evidence on its use in human in vivo settings, particularly in terms of its applicability and accuracy of residual brain tumor detection (RTD). For this reason, a microscope-integrated OCT system was examined to determine in vivo feasibility of RTD after resection with automated scan analysis.

METHODS Healthy and diseased brain was 3D scanned at the resection edge in 18 brain tumor patients and investigated for its informative value in regard to intraoperative tissue classification. Biopsies were taken at these locations and labeled by a neuropathologist for further analysis as ground truth. Optical OCT properties were obtained, compared, and used for separation with machine learning. In addition, two artificial intelligence–assisted methods were utilized for scan classification, and all approaches were examined for RTD accuracy and compared to standard techniques.

RESULTS In vivo OCT tissue scanning was feasible and easily integrable into the surgical workflow. Measured backscattered light signal intensity, signal attenuation, and signal homogeneity were significantly distinctive in the comparison of scanned white matter to increasing levels of scanned tumor infiltration (p < 0.001) and achieved high values of accuracy (85%) for the detection of diseased brain in the tumor margin with support vector machine separation. A neuronal network approach achieved 82% accuracy and an autoencoder approach 85% accuracy in the detection of diseased brain in the tumor margin. Differentiating cortical gray matter from tumor tissue was not technically feasible in vivo.

CONCLUSIONS In vivo OCT scanning of the human brain has been shown to contain significant value for intraoperative RTD, supporting what has previously been discussed for ex vivo OCT brain tumor scanning, with the perspective of complementing current intraoperative methods for this purpose, especially when deciding to withdraw from further resection toward the end of the surgery.

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Use of circulating tumor cells and microemboli to predict diagnosis and prognosis in diffuse glioma

J Neurosurg 141:673–683, 2024

Circulating tumor cell (CTC) detection is a promising noninvasive technique that can be used to diagnose cancer, monitor progression, and predict prognosis. In this study, the authors aimed to investigate the clinical utility of CTCs in the management of diffuse glioma.

METHODS Sixty-three patients with newly diagnosed diffuse glioma were included in this multicenter clinical cohort. The authors used a platform based on isolation by size of epithelial tumor cells (ISET) to detect and analyze CTCs and circulating tumor microemboli (CTMs) in the peripheral blood of patients both before and after surgery. Least absolute shrinkage and selector operation (LASSO) and Cox regression analyses were used to verify whether CTCs and CTMs are independent prognostic factors for diffuse glioma.

RESULTS CTC levels were closely related to the degree of malignancy, WHO grade, and pathological subtypes. Receiver operating characteristic curve analysis revealed that a high CTC level was a predictor for glioblastoma. The results also showed that CTMs originate from the parental tumor rather than from the circulation and are an independent prognostic factor for diffuse glioma. The postoperative CTC level is related to the peripheral immune system and patient survival. Cox regression analysis showed that postoperative CTC levels and CTM status are independent prognostic factors for diffuse glioma, and CTC- and CTM-based survival models had high accuracy in internal validation.

CONCLUSIONS The authors revealed a correlation between CTCs and clinical characteristics and demonstrated that CTCs and CTMs are independent predictors for the diagnosis and prognosis of diffuse glioma. Their CTC- and CTMbased survival models can enable clinicians to evaluate patients’ response to surgery as well as their outcomes.

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Berberine as a potential enhancer for 5-ALA–mediated fluorescence in glioblastoma

J Neurosurg 141:653–663, 2024

The prognosis of glioblastoma (GBM) correlates with residual tumor volume after surgery. In fluorescenceguided surgery, 5-aminolevulinic acid (ALA) has been used to maximize resection while avoiding neurological morbidity. However, not all tumor cells, particularly glioma stem cells (GSCs), display 5-ALA–mediated protoporphyrin IX (PpIX) fluorescence (5-ALA fluorescence). The authors searched for repositioned drugs that affect mitochondrial functions and energy metabolism, identifying berberine (BBR) as a potential enhancer of 5-ALA fluorescence. In this study, they investigated whether BBR can enhance 5-ALA fluorescence in GSCs and whether BBR can be applied to clinical practice as a 5-ALA fluorescence enhancer.

METHODS The effects of BBR on 5-ALA fluorescence in glioma and GSCs were evaluated by flow cytometry (fluorescence-activated cell sorting [FACS]) analysis. As 5-ALA is metabolized for heme synthesis, the effects of BBR on mRNA expressions of 7 enzymes in the heme-synthesis pathway were analyzed. Enzymes showing significantly higher expression than control in all cells were identified and protein analysis was performed. To examine clinical availability, the detectability and cytotoxicity of BBR in tumor-transplanted mice were analyzed.

RESULTS Fluorescence microscopy revealed much more intense 5-ALA fluorescence in both GSCs and non-stem cells with 5-ALA and BBR than with 5-ALA alone. FACS showed that BBR greatly enhanced 5-ALA fluorescence compared with 5-ALA alone, and enhancement was much higher for GSCs than for glioma cells. Among the 7 enzymes examined, BBR upregulated mRNA expressions of ALA synthetase 1 (ALAS1) more highly in all cells, and activated ALAS1 through deregulating ALAS1 activity inhibited by the negative feedback of heme. An in vivo study showed that 5-ALA fluorescence with 5-ALA and BBR was significantly stronger than with 5-ALA alone, and the sensitivity and specificity of BBR-enhanced fluorescence were both 100%. In addition, BBR did not show any cytotoxicity for normal brain tissue surrounding the tumor mass.

CONCLUSIONS BBR enhanced 5-ALA–mediated PpIX fluorescence by upregulating and activating ALAS1 through deregulation of negative feedback inhibition by heme. BBR is a clinically used drug with no side effects. BBR is expected to significantly augment fluorescence-guided surgery and photodynamic therapy.

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Longitudinal brain volumetrics in glioma survivors

J Neurosurg 141:634–641, 2024

Radiation therapy (RT) is used selectively for patients with low-grade glioma (LGG) given the concerns for potential cognitive effects in survivors, but prior cognitive outcome studies among LGG survivors have had inconsistent findings. Translational studies that characterize changes in brain anatomy and physiology after treatment of LGG may help to both contextualize cognitive findings and improve the overall understanding of radiation effects in normal brain tissue. This study aimed to investigate the hypothesis that patients with LGG who are treated with RT will experience greater brain volume loss than those who do not receive RT.

METHODS This retrospective longitudinal study included all patients with WHO grade 2 glioma who received posttreatment surveillance MRI at the University of Alabama at Birmingham. Volumetric analysis of contralateral cortical white matter (WM), cortical gray matter (GM), and hippocampus was performed on all posttreatment T1-weighted MRI sequences using the SynthSeg script. The effect of clinical and treatment variables on brain volumes was assessed using two-level hierarchical linear models.

RESULTS The final study cohort consisted of 105 patients with 1974 time points analyzed. The median length of imaging follow-up was 4.6 years (range 0.36–18.9 years), and the median number of time points analyzed per patient was 12 (range 2–40). Resection was performed in 79 (75.2%) patients, RT was administered to 61 (58.1%) patients, and chemotherapy was administered to 66 (62.9%) patients. Age at diagnosis (β = −0.06, p < 0.001) and use of RT (β = −1.12, p = 0.002) were associated with the slope of the contralateral cortical GM volume model (i.e., change in GM over time). Age at diagnosis (β = −0.08, p < 0.001), midline involvement (β = 1.31, p = 0.006), and use of RT (β = −1.45, p = 0.001) were associated with slope of the contralateral cortical WM volume model. Age (β = −0.0027, p = 0.001), tumor resection (β = −0.069, p < 0.001), use of chemotherapy (β = −0.0597, p = 0.003), and use of RT (β = −0.0589, p < 0.001) were associated with the slope of the contralateral hippocampus volume model.

CONCLUSIONS This study demonstrated volume loss in contralateral brain structures among LGG survivors, and patients who received RT experienced greater volume loss than those who did not. The results of this study may help to provide context for cognitive outcome research in LGG survivors and inform the design of future strategies to preserve cognition.

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Impact of Molecular Subgroups on Prognosis and Survival Outcomes in Posterior Fossa Ependymomas: A Retrospective Study of 412 Cases

Neurosurgery 95:651–659, 2024

Posterior fossa ependymomas (PFEs) are rare brain tumors classified as PF-EPN-A (PFA) and PF-EPN-B (PFB) subgroups. The study aimed to evaluate the prognosis and survival outcomes in PFEs, with a focus on the impact of molecular subgroups.

METHODS: A retrospective study was conducted on 412 patients with PFEs. Kaplan–Meier survival analyses were conducted to evaluate the overall survival (OS) and progression-free survival. Cox regression analyses were conducted to assess the prognostic factors. A nomogram was developed to predict the OS rates of PFEs.

RESULTS: The study revealed significant differences between PFA and PFB in patient and tumor characteristics. PFAs were associated with poorer OS (hazard ratios [HR] 3.252, 95% CI 1.777-5.950, P < .001) and progression-free survival (HR 4.144, 95% CI 2.869-5.985, P < .001). World Health Organization grade 3 was associated with poorer OS (HR 2.389, 95% CI 1.236-4.617, P = .010). As for treatment patterns, gross total resection followed by radiotherapy or the combination of radiotherapy and chemotherapy yielded the most favorable OS for PFA (P = .025 for both), whereas gross total resection followed by radiotherapy rather than observation showed improved OS for PFB (P = .046). The nomogram demonstrated a high degree of accuracy and discrimination capacity for the prediction of OS rates for up to 10 years. In addition, 6 cases of PFA (3.51%) with H3K27M mutations were identified.

CONCLUSION: PFAs demonstrate worse prognosis and survival outcomes compared with PFBs. Both PFAs and PFBs necessitate maximal resection followed by intensive adjuvant therapies in long-term effects.

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Efficacy and Safety of Carmustine Wafer Implantation After Ventricular Opening in Glioblastomas, Isocitrate Dehydrogenase-Wildtype, in Adults

Neurosurgery 94:1227–1236, 2024

We assessed the impact of ventricular opening on postoperative complications and survival of carmustine wafer implantation during surgery of newly diagnosed supratentorial glioblastomas, isocitrate dehydrogenase (IDH)-wildtype in adults.

METHODS: We performed an observational, retrospective, single-center cohort study at a tertiary surgical neurooncological center between January 2006 and December 2021.

RESULTS: One hundred ninety-four patients who benefited from a first-line surgical resection with carmustine wafer implantation were included. Seventy patients (36.1%) had a ventricular opening. We showed that ventricular opening (1) did not increase overall postoperative complication rates (P = .201); (2) did not worsen the early postoperative Karnofsky Performance Status score (P = .068); (3) did not increase the time interval from surgery to adjuvant oncological treatment (P = .458); (4) did not affect the completion of the standard radiochemotherapy protocol (P = .164); (5) did not affect progression-free survival (P = .059); and (6) did not affect overall survival (P = .142).

CONCLUSION: In this study, ventricular opening during first-line surgical resection did not affect the survival and postoperative complications after use of carmustine wafer implantation in adult patients with a newly diagnosed supratentorial glioblastoma, IDH-wildtype. This warrants a prospective and multicentric study to clearly assess the impact of the ventricular opening after carmustine wafer implantation in glioblastoma, IDH-wildtype.

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A novel radiological classification of midbrain pilocytic astrocytomas and its implication for surgical management

J Neurosurg 140:1527–1539, 2024

Surgery for midbrain pilocytic astrocytoma (PA) remains a formidable challenge. To facilitate decisionmaking and achieve a better outcome in the management of patients with midbrain PA, the authors have proposed a novel radiological classification of midbrain PAs with long-term follow-up.

METHODS Fifty-seven midbrain PA patients who underwent surgery at Beijing Tiantan Hospital, Capital Medical University, from January 2008 to June 2021, were reviewed. Based on tumor location and the topological anatomical change identified on MRI, midbrain PAs were categorized into four types: crural (12/57, 21.1%), tegmental (25/57, 43.9%), aqueductal (5/57, 8.8%), and tectal (15/57, 26.3%) PAs. The relevant clinical, radiological, and pathological data; surgical procedures and results; and long-term outcomes were collected and analyzed.

RESULTS The 1-, 3-, and 5-year survival rates reached 98%, 96%, and 96%, respectively, with gross-total resection achieved in 66.7% of cases, followed by near-total resection in 17.5% cases. The clinical and radiological features, selection of surgical approaches, and long-term postoperative deficits were distinct among each type. Crural PAs were associated with younger age (median 9 years, IQR 5.0–12.8 years); the largest tumor volume (median 31.9 cm 3 , IQR 17.2–42.6 cm 3 ); the lowest preoperative Karnofsky Performance Scale (KPS) score (median 65, IQR 50–70); the most frequent preoperative motor deficit (91.7%); a mixed solid-cystic component (75%); occupation of the crural cistern; elevation and rotation of the thalamus (medial and/or lateral); displacement of the anterior third ventricle, uncus, and anterior commissure; the most diverse surgical approaches; more frequent use of multimodality image–guided surgery (58.3%); and the most remarkable improvement in KPS score at long-term follow-up. Tegmental PAs were associated with adolescents and young adults (median age 21 years, IQR 8–33 years); tumor volume (median 13.9 cm 3 , IQR 9.5–20.5 cm 3 ); a good preoperative KPS score (median 80, IQR 70–80); a mixed solid-cystic component (72%); occupation of the ambient cistern and cerebellomesencephalic fissure; a close relationship with the dorsal pons, superior cerebellar peduncle, and posterior inferior third ventricle; and a higher probability of permanent postoperative sensory deficits (40%). Aqueductal and tectal PAs were associated with small tumor volume (median 9.14 cm 3 , IQR 5.1–17.4 cm 3 and median 11.84 cm 3 , IQR 5.7–18.3 cm 3 , respectively), a higher percentage of hydrocephalus (80% and 86.7%, respectively), and a straightforward selection of limited surgical approaches.

CONCLUSIONS A novel and comprehensive radiological classification of midbrain PAs was established, which will serve as a valuable tool in patient management and promote uniform communication and comparison across different studies and publications.

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Multidisciplinary surgical considerations for en bloc resection of sacral chordoma

Neurosurg Focus 56(5):E7, 2024

Contemporary management of sacral chordomas requires maximizing the potential for recurrence-free and overall survival while minimizing treatment morbidity. En bloc resection can be performed at various levels of the sacrum, with tumor location and volume ultimately dictating the necessary extent of resection and subsequent tissue reconstruction. Because tumor resection involving the upper sacrum may be quite destabilizing, other pertinent considerations relate to instrumentation and subsequent tissue reconstruction. The primary aim of this study was to survey the surgical approaches used for managing primary sacral chordoma according to location of lumbosacral spine involvement, including a narrative review of the literature and examination of the authors’ institutional case series.

METHODS The authors performed a narrative review of pertinent literature regarding reconstruction and complication avoidance techniques following en bloc resection of primary sacral tumors, supplemented by a contemporary series of 11 cases from their cohort. Relevant surgical anatomy, advances in instrumentation and reconstruction techniques, intraoperative imaging and navigation, soft-tissue reconstruction, and wound complication avoidance are also discussed.

RESULTS The review of the literature identified several surgical approaches used for management of primary sacral chordoma localized to low sacral levels (mid-S2 and below), high sacral levels (involving upper S2 and above), and high sacral levels with lumbar involvement. In the contemporary case series, the majority of cases (8/11) presented as low sacral tumors that did not require instrumentation. A minority required more extensive instrumentation and reconstruction, with 2 tumors involving upper S2 and/or S1 levels and 1 tumor extending into the lower lumbar spine. En bloc resection was successfully achieved in 10 of 11 cases, with a colostomy required in 2 cases due to rectal involvement. All 11 cases underwent musculocutaneous flap wound closure by plastic surgery, with none experiencing wound complications requiring revision.

CONCLUSIONS The modern management of sacral chordoma involves a multidisciplinary team of surgeons and intraoperative technologies to minimize surgical morbidity while optimizing oncological outcomes through en bloc resection. Most cases present with lower sacral tumors not requiring instrumentation, but stabilizing instrumentation and lumbosacral reconstruction are often required in upper sacral and lumbosacral cases. Among efforts to minimize wound-related complications, musculocutaneous flap closure stands out as an evidence-based measure that may mitigate risk.

 

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Beyond fluorescence‑guided resection: 5‑ALA‑based glioblastoma therapies

Acta Neurochirurgica (2024) 166:163

Glioblastoma is the most common primary malignant brain tumor. Despite advances in multimodal concepts over the last decades, prognosis remains poor. Treatment of patients with glioblastoma remains a considerable challenge due to the infiltrative nature of the tumor, rapid growth rates, and tumor heterogeneity.

Standard therapy consists of maximally safe microsurgical resection followed by adjuvant radio- and chemotherapy with temozolomide. In recent years, local therapies have been extensively investigated in experimental as well as translational levels.

External stimuli-responsive therapies such as Photodynamic Therapy (PDT), Sonodynamic Therapy (SDT) and Radiodynamic Therapy (RDT) can induce cell death mechanisms via generation of reactive oxygen species (ROS) after administration of five-aminolevulinic acid (5-ALA), which induces the formation of sensitizing porphyrins within tumor tissue.

Preliminary data from clinical trials are available. The aim of this review is to summarize the status of such therapeutic approaches as an adjunct to current standard therapy in glioblastoma.

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Surgical Outcome of Patients With Supratentorial Meningiomas Aged 80 Years or Older

Neurosurgery 94:399–412, 2024

Demographic changes will lead to an increase in old patients, a population with significant risk of postoperative morbidity and mortality, requiring neurosurgery for meningiomas. This multicenter study aims to report neurofunctional status after resection of patients with supratentorial meningioma aged 80 years or older, to identify factors associated with outcome, and to validate a previously proposed decision support tool.

METHODS: Neurofunctional status was assessed by the Karnofsky Performance Scale (KPS). Patients were categorized in poor (KPS ≤40), intermediate (KPS 50-70), and good (KPS ≥80) preoperative subgroups. Volumetric analyses of tumor and peritumoral brain edema (PTBE) were performed; volumes were scored as small (<10 cm3 ), medium (10-50 cm3 ), and large (>50 cm3 ).

RESULTS: The study population consisted of 262 patients, and the median age at surgery was 83.0 years. The median preoperative KPS was 70; 117 (44.7%) patients were allotted to the good, 113 (43.1%) to the intermediate, and 32 (12.2%) to the poor subgroup. The median tumor and PTBE volumes were 30.2 cm 3 and 27.3 cm3 ; large PTBE volume correlated with poor preoperative KPS status (P = .008). The 90-day and 1-year mortality rates were 9.0% and 13.2%, respectively. Within the first postoperative year, 101 (38.5%) patients improved, 87 (33.2%) were unchanged, and 74 (28.2%) were functionally worse (including deaths). Each year increase of age associated with 44% (23%-70%) increased risk of 90-day and 1-year mortality. In total, 111 (42.4%) patients suffered from surgery-associated complications. Maximum tumor diameter ≥5 cm (odds ratio 1.87 [1.12-3.13]) and large tumor volume (odds ratio 2.35 [1.01-5.50]) associated with increased risk of complications. Among patients with poor preoperative status and large PTBE, most (58.3%) benefited from surgery.

CONCLUSION: Patients with poor preoperative neurofunctional status and large PTBE most often showed postoperative improvements. The decision support tool may be of help in identifying cases that most likely benefit from surgery.

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Preoperative Versus Postoperative Radiosurgery of Brain Metastases: A Meta-Analysis

World Neurosurg. (2024) 182:35-41

OBJECTIVE: While postoperative resection cavity radiosurgery (post-SRS) is an accepted treatment paradigm for brain metastasis (BM) patients who undergo surgical resection, there is emerging interest in preoperative radiosurgery (preSRS) followed by surgical resection as an alternative treatment paradigm. Here, we performed a meta-analysis of the available literature on this matter.

METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a search of all studies evaluating pre-SRS and postSRS was completed. Local recurrence (LR), overall survival (OS), radiation necrosis (RN), and leptomeningeal disease (LMD) were evaluated from the available data. Moderator analysis and pooled effect sizes were performed using a proportional meta-analysis with R using the metafor package. Statistics are presented as mean [95% confidence interval].

RESULTS: We identified 6 pre-SRS and 33 post-SRS studies with comparable tumor volume (4.5-17.6 cm3 ). There were significant differences in the pooled estimates of LR and LMD, favoring pre-SRS over post-SRS. Pooled aggregate for LR was 11.0% [4.9-13.7] and 17.5% [15.1-19.9] for pre- and post-SRS studies (P [ 0.014). Similarly, pooled estimates of LMD favored pre-SRS, 4.4% [2.6-6.2], relative to post-SRS, 12.3% [8.9-15.7] (P [ 0.019). In contrast, no significant differences were found in terms of RN and OS. Pooled estimates for RN were 6.4% [3.1-9.6] and 8.9% [6.3-11.6] for pre- and post-SRS studies (P [ 0.393), respectively. Pooled estimates for OS were 60.2% [55.8-64.6] and 60.5% [56.9-64.0] for pre- and post-SRS studies (P [ 0.974).

CONCLUSIONS: This meta-analysis supports further exploration of pre-SRS as a strategy for the treatment of BM.

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Surgical Management of Craniospinal Axis Solitary Fibrous Tumors

Neurosurgery 94:358–368, 2024

Meningeal solitary fibrous tumors (SFTs) comprise 0.4% of primary central nervous system neoplasms and carry metastatic potential. Disease course and optimal management are largely unknown, and there is currently no literature rigorously describing neurological outcomes in surgically managed SFTs. We present one of the largest craniospinal SFT series, analyze patient outcomes, and extensively review the associated literature.

METHODS: All surgically managed SFTs at our institution between January 2005 and March 2023 were retrospectively reviewed. Patient demographics, tumor and radiographic features, treatment, and clinical outcomes were collected. Neurological function was quantified using Frankel grade and Neurologic Assessment in NeuroOncology scores. Descriptive statistics, multivariate analysis, log-rank test, and Kaplan–Meier survival analysis were performed.

RESULTS: Twenty-one patients satisfied inclusion criteria. Tumor locations included 15 supratentorial, three infratentorial, and three spinal. All patients underwent surgical resection, and 16 (76.2%) underwent radiation. Six (28.6%) patients had tumor recurrence, and three (14.3%) developed metastasis. Younger age and higher postoperative Frankel grade were significantly associated with increased overall survival (OS) (P = .011, P = .002, respectively). All patients symptomatically improved or stabilized after surgery, and Neurologic Assessment in Neuro-Oncology score (P = .001) and functional status significantly improved postoperatively (Karnofsky Performance Status: 65.2 ± 25.2 vs 91.4 ± 13.5, P = .001). Sex, adjuvant radiation, and extent of resection were not significantly associated with OS.

CONCLUSION: SFT of the central nervous system is a rare entity with a variable clinical course. Surgical resection was associated with improved postoperative functional and neurological status. Higher postoperative neurological function was significantly associated with OS. Further studies are warranted to validate a standardized treatment algorithm and investigate the efficacy of adjuvant radiation in SFT.

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Confocal laser endomicroscopy in glial tumors—a histomorphological analysis

Neurosurgical Review (2024) 47:65

The extent of resection and neurological outcome are important prognostic markers for overall survival in glioma patients. Confocal laser endomicroscopy is a tool to examine tissue without the need for fixation or staining. This study aims to analyze gliomas in confocal laser endomicroscopy and identify reliable diagnostic criteria for glial matter and glial tumors.

Material and methods One-hundred-and-five glioma specimens were analyzed using a 670-nm confocal laser endomicroscope and then processed into hematoxylin-eosin-stained frozen sections. All confocal images and frozen sections were evaluated for the following criteria: presence of tumor, cellularity, nuclear pleomorphism, changes of the extracellular glial matrix, microvascular proliferation, necrosis, and mitotic activity. Recurring characteristics were identified. Accuracy, sensitivity, specificity, and positive and negative predictive values were assessed for each feature.

Results All 125 specimens could be processed and successfully analyzed via confocal laser endomicroscopy. We found diagnostic criteria to identify white and grey matter and analyze cellularity, nuclear pleomorphism, changes in the glial matrix, vascularization, and necrosis in glial tumors. An accuracy of > 90.0 % was reached for grey matter, cellularity, and necrosis, > 80.0 % for white matter and nuclear pleomorphism, and > 70.0 % for microvascular proliferation and changes of the glial matrix. Mitotic activity could not be identified. Astroglial tumors showed significantly less nuclear pleomorphism in confocal laser endomicroscopy than oligodendroglial tumors (p < 0.001). Visualization of necrosis aids in the differentiation of low grade gliomas and high grade gliomas (p < 0.002).

Conclusion Autofluorescence-based confocal laser endomicroscopy proved not only useful in differentiation between tumor and brain tissue but also revealed useful clues to further characterize tissue without processing in a lab. Possible applications include the improvement of extent of resection and the safe harvest of representative tissue for histopathological and molecular genetic diagnostics.

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