Category: Oncology

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Stereotactic radiosurgery for Koos grade IV vestibular schwannoma in patients ≥ 65 years old

Acta Neurochirurgica (2023) 165:211–220

Surgery is the preferred treatment for large vestibular schwannomas (VS). Good tumor control and cranial nerve outcomes were described in selected Koos IV VS after single-session stereotactic radiosurgery (SRS), but outcomes in elderly patients have never been specifically studied. The aim of this study is to report clinical and radiological outcomes after single-session SRS for Koos IV VS in patients ≥ 65 years old.

Method This multicenter, retrospective study included patients ≥ 65 years old, treated with primary, single-session SRS for a Koos IV VS, and at least 12 months of follow-up. Patients with life-threatening or incapacitating symptoms were excluded. Tumor control rate, hearing, trigeminal, and facial nerve function were studied at last follow-up.

Results One-hundred and fifty patients (median age of 71.0 (IQR 9.0) years old with a median tumor volume of 8.3 cc (IQR 4.4)) were included. The median prescription dose was 12.0 Gy (IQR 1.4). The local tumor control rate was 96.0% and 86.2% at 5 and 10 years, respectively. Early tumor expansion occurred in 6.7% and was symptomatic in 40% of cases. A serviceable hearing was present in 16.1% prior to SRS and in 7.4% at a last follow-up of 46.5 months (IQR 55.8). The actuarial serviceable hearing preservation rate was 69.3% and 50.9% at 5 and 10 years, respectively. Facial nerve function preservation or improvement rates at 5 and 10 years were 98.7% and 91.0%, respectively. At last follow-up, the trigeminal nerve function was improved in 14.0%, stable in 80.7%, and worsened in 5.3% of the patients. ARE were noted in 12.7%. New hydrocephalus was seen in 8.0% of patients.

Conclusion SRS can be a safe alternative to surgery for selected Koos IV VS in patients ≥ 65 years old. Further follow-up is warranted.

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Natural history of meningiomas: a serial volumetric analysis of 240 tumors

J Neurosurg 137:1639–1649, 2022

The management of asymptomatic intracranial meningiomas is controversial. Through the assessment of growth predictors, the authors aimed to create the basis for practicable clinical pathways for the management of these tumors.

METHODS The authors volumetrically analyzed meningiomas radiologically diagnosed at their institution between 2003 and 2015. The primary endpoint was growth of tumor volume. The authors used significant variables from the multivariable regression model to construct a decision tree based on the exhaustive Chi-Square Automatic Interaction Detection (CHAID) algorithm.

RESULTS Of 240 meningiomas, 159 (66.3%) demonstrated growth during a mean observation period of 46.9 months. On multivariable logistic regression analysis, older age (OR 0.979 [95% CI 0.958–1.000], p = 0.048) and presence of calcification (OR 0.442 [95% CI 0.224–0.872], p = 0.019) had a negative predictive value for tumor growth, while T2-signal iso-/hyperintensity (OR 4.415 [95% CI 2.056–9.479], p < 0.001) had a positive predictive value. A decision tree model yielded three growth risk groups based on T2 signal intensity and presence of calcifications. The median tumor volume doubling time (Td) was 185.7 months in the low-risk, 100.1 months in the intermediate-risk, and 51.7 months in the highrisk group (p < 0.001). Whereas 0% of meningiomas in the low- and intermediate-risk groups had a Td of ≤ 12 months, the percentage was 8.9% in the high-risk group (p = 0.021).

CONCLUSIONS Most meningiomas demonstrated growth during follow-up. The absence of calcifications and iso-/ hyperintensity on T2-weighted imaging offer a practical way of stratifying meningiomas as low, intermediate, or high risk. Small tumors in the low- or intermediate-risk categories can be monitored with longer follow-up intervals.

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Adult diffuse intrinsic pontine glioma: clinical, radiological, pathological, molecular features, and treatments of 96 patients

J Neurosurg 137:1628–1638, 2022

Unlike its pediatric counterpart, adult diffuse intrinsic pontine glioma (DIPG) remains largely unelucidated. In this study, the authors examined the clinical, radiological, pathological, molecular, and clinical aspects of 96 adult DIPGs.

METHODS The National Brain Tumor Registry of China (April 2013–December 2019) was used to collect data on radiologically diagnosed adult DIPG patients. Survival analysis was conducted using Kaplan-Meier curves and univariate and multivariate Cox regression. The chi-square test/Wilcoxon rank-sum test and multivariable logistic regression were used to examine the clinical and radiological characteristics of patients with long-term survival (LTS). Interaction analyses between clinical factors were also conducted.

RESULTS The median age at symptom onset was 33.5 years, and the median duration of symptoms was 4.5 months. The frequencies of H3K27M and IDH1 mutations were 37.2% and 26.5%, respectively. All adult DIPG patients had a median overall survival (OS) of 19.5 months, with 1-, 2-, and 3-year survival rates of 67.0%, 42.8%, and 36.0%, respectively. The median OS of 40 patients who did not undergo treatment was 13.4 months. Patients with H3K27M-mutant tumors had a poorer prognosis than those with IDH-mutant tumors (p < 0.001) and H3K27M(−)/IDH–wild-type tumors (p = 0.002), with a median OS of 11.4 months. The median OSs of patients with H3K27M-mutant tumors who received treatment and those who did not were 13.8 months and 7.5 months, respectively (p = 0.016). Among patients with and without a pathological diagnosis, H3K27M mutation (p < 0.001) and contrast enhancement on MRI (p = 0.003), respectively, imparted a worse prognosis. Treatments were the predictive factor for patients with H3K27M-mutant tumors (p = 0.038), whereas contrast enhancement on MRI was the prognostic factor for the H3K27M(−) group (p = 0.038). In addition, H3K27M mutation and treatment were significant predictors for patients with symptom duration ≤ 4 months (H3K27M, p = 0.020; treatment, p = 0.014) and tumors with no contrast enhancement (H3K27M, p = 0.003; treatment, p = 0.042). Patients with LTS were less likely to have cranial nerve palsy (p = 0.002) and contrast enhancement on MRI at diagnosis (p = 0.022).

CONCLUSIONS It is recommended that all adult DIPG patients undergo genomic testing for H3K27M and IDH mutations. Despite the low prevalence, additional study is needed to better characterize the efficacy of various treatment modalities in adults with DIPG.

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Strategies, considerations, and recent advancements in the development of liquid biopsy for glioblastoma

Neurosurg Focus 53 (6):E14, 2022

Glioblastoma (GBM) is a devasting primary brain tumor with less than a 5% 5-year survival. Treatment response assessment can be challenging because of inflammatory pseudoprogression that mimics true tumor progression clinically and on imaging. Developing additional noninvasive assays is critical. In this article, the authors review various biomarkers that could be used in developing liquid biopsies for GBM, along with strengths, limitations, and future applications. In addition, they present a potential liquid biopsy design based on the use of an extracellular vesicle–based liquid biopsy targeting nonneoplastic extracellular vesicles.

METHODS The authors conducted a current literature review of liquid biopsy in GBM by searching the PubMed, Scopus, and Google Scholar databases. Articles were assessed for type of biomarker, isolation methodology, analytical techniques, and clinical relevance.

RESULTS Recent work has shown that liquid biopsies of plasma, blood, and/or CSF hold promise as noninvasive clinical tools that can be used to diagnose recurrence, assess treatment response, and predict patient outcomes in GBM. Liquid biopsy in GBM has focused primarily on extracellular vesicles, cell-free tumor nucleic acids, and whole-cell isolates as focal biomarkers. GBM tumor signatures have been generated via analysis of tumor gene mutations, unique RNA expression, and metabolic and proteomic alterations. Liquid biopsies capture tumor heterogeneity, identifying alterations in GBM tumors that may be undetectable via surgical biopsy specimens. Finally, biomarker burden can be used to assess treatment response and recurrence in GBM.

CONCLUSIONS Liquid biopsy offers a promising avenue for monitoring treatment response and recurrence in GBM without invasive procedures. Although additional steps must be taken to bring liquid biopsy into the clinic, proof-of-principle studies and isolation methodologies are promising. Ultimately, CSF and/or plasma-based liquid biopsy is likely to be a powerful tool in the neurosurgeon’s arsenal in the near future for the treatment and management of GBM patients.

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Network-level prediction of set-shifting deterioration after lower-grade glioma resection

J Neurosurg 137:1329–1337, 2022

The aim of this study was to predict set-shifting deterioration after resection of low-grade glioma.

METHODS The authors retrospectively analyzed a bicentric series of 102 patients who underwent surgery for low-grade glioma. The difference between the completion times of the Trail Making Test parts B and A (TMT B-A) was evaluated preoperatively and 3–4 months after surgery. High dimensionality of the information related to the surgical cavity topography was reduced to a small set of predictors in four different ways: 1) overlap between surgical cavity and each of the 122 cortical parcels composing Yeo’s 17-network parcellation of the brain; 2) Tractotron: disconnection by the cavity of the major white matter bundles; 3) overlap between the surgical cavity and each of Yeo’s networks; and 4) disconets: signature of structural disconnection by the cavity of each of Yeo’s networks. A random forest algorithm was implemented to predict the postoperative change in the TMT B-A z-score.

RESULTS The last two network-based approaches yielded significant accuracies in left-out subjects (area under the receiver operating characteristic curve [AUC] approximately equal to 0.8, p approximately equal to 0.001) and outperformed the two alternatives. In single tree hierarchical models, the degree of damage to Yeo corticocortical network 12 (CC 12) was a critical node: patients with damage to CC 12 higher than 7.5% (cortical overlap) or 7.2% (disconets) had much higher risk to deteriorate, establishing for the first time a causal link between damage to this network and impaired set-shifting.

CONCLUSIONS The authors’ results give strong support to the idea that network-level approaches are a powerful way to address the lesion-symptom mapping problem, enabling machine learning–powered individual outcome predictions.

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Early Diagnosis and Surgical Intervention Within 3 Weeks From Symptom Onset Are Associated With Prolonged Survival of Patients With Glioblastoma

Neurosurgery 91:741–748, 2022

Glioblastoma (GBM) is a rapidly growing and most life-threatening malignant brain tumor. The significance of early treatment to the clinical outcomes of patients with GBM is unclear.

OBJECTIVE: To determine whether early diagnosis and surgery improve the preoperative and postoperative Karnofsky performance status (KPS) and prognosis of patients with GBM.

METHODS: Data of isocitrate dehydrogenase-wildtype patients with GBM treated at our institution between January 2010 and December 2019 were reviewed. Patients were classified into early or late diagnosis groups with a threshold of 14 days from initial symptoms. In addition, patients were divided into early, intermediate, and late surgery groups with thresholds of 21 and 35 days. Representative symptoms and patient prognoses were examined.

RESULTS: Of 153 patients, 72 and 81 were classified into the early and late diagnosis groups. The median tumor volume was significantly smaller in the former group. The proportion of patients with preoperative KPS scores ≥ 90 was 48.6%and 29.6% in the early and late diagnosis groups (P = .016). The early, intermediate, and late surgery groups included 43, 24, and 86 patients. The median overall survival was significantly longer in the early surgery group than in the late surgery group (28.4 vs 18.7 months, P = .006). Multivariate analysis demonstrated that significant predictors of shorter survival included extent of tumor resection (partial or biopsy), preoperative and postoperative KPS ≤ 60, and O6-methylguanine-DNA-methyltransferase promoter status (unmethylated).

CONCLUSION: Early diagnosis within 2 weeks and surgical interventions within 3 weeks from the symptom onset are associated with prolonged patient survival. Early GBM treatment will benefit patients with GBM.

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Older meningioma patients: a retrospective population‐based study of risk factors for morbidity and mortality after neurosurgery

Acta Neurochirurgica (2022) 164:2987–2997

Meningioma is the most common primary CNS tumour. Most meningiomas are benign, and most patients are 65 years or older. Surgery is usually the primary treatment option. Most prior studies on early surgical outcomes in older patients with meningioma are small, and there is a lack of larger population-based studies to guide clinical decision-making. We aimed to explore the risks for perioperative mortality and morbidity in older patients with meningioma and to investigate changes in surgical incidence over time.

Methods In this retrospective population-based study on patients in Sweden, 65 years or older with surgery 1999–2017 for meningioma, we used data from the Swedish Brain Tumour Registry. We analysed factors contributing to perioperative mor- tality and morbidity and used official demographic data to calculate yearly incidence of surgical procedures for meningioma.

Results Thefinal study cohort included 1676 patients with a 3.1% perioperative mortality and a 37.6% perioperative morbidity. In multivariate analysis, higher age showed a statistically significant association with higher perioperative mortality, whereas larger tumour size and having preoperative symptoms were associated with higher perioperative morbidity. A numerical increased rate of surgical interventions after 2012 was observed, without evidence of worsening short-term surgical outcomes.

Conclusions Higher mortality with increased age and higher morbidity risk in larger and/or symptomatic tumours imply a possible benefit from considering surgery in selected older patients with a growing meningioma before the development of tumour-related symptoms. This study further underlines the need for a standardized method of reporting and classifying complications from neurosurgery.

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The need to consider return to work as a main outcome in patients undergoing surgery for diffuse low‐grade glioma: a systematic review

Acta Neurochirurgica (2022) 164:2789–2809

For a long time, return to work (RTW) has been neglected in patients harboring a diffuse low-grade glioma (LGG). However, a majority of LGG patients worked at time of diagnosis. Moreover, these patients now live longer given current treatment paradigms, especially thanks to early maximal surgery.

Methods We systematically searched available medical databases for studies that reported data on RTW in patients who underwent resection for LGG.

Results A total of 30 studies were selected: 19 considered RTW (especially rate and timing) as an outcome and 11 used scales of health-related quality of life (HRQoL) which included work-related aspects. Series that considered RTW as a main endpoint were composed of 1014 patients, with postoperative RTW rates ranging from 31 to 97.1% (mean 73.1%). Timing to RTW ranged from 15 days to 22 months (mean 6.3 months). Factors related to an increased proportion of RTW were: younger age, better neurologic status, having a white-collar occupation, working pre-operatively, being the sole breadwinner, the use of awake surgery, and greater extent of resection. Female sex, older age, poor neurologic status, pre-operative history of work absences, slow lexical access speed, and postoperative seizures were negatively related to RTW. No studies that used HRQoL scales directly investigated RTW rate or timing.

Conclusions RTW was scarcely analyzed in LGG patients who underwent resection. However, because they are usually young, with no or only mild functional deficits and have a longer life expectancy, postoperative RTW should be assessed more systematically and accurately as a main outcome. As majority (61.5–100%) of LGG patients were working at time of surgery, the responsibility of neurosurgeons is to bring these patients back to their previous activities according to his/her wishes. RTW might also be included as a critical endpoint for future prospective studies and randomized control trials on LGGs.

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Double dose of 5-aminolevulinic acid and its effect on protoporphyrin IX accumulation in low-grade glioma

J Neurosurg 137:943–952, 2022

Administration of 5-aminolevulinic acid (5-ALA) does not regularly elicit fluorescence in low-grade glioma (LGG) at currently established doses and timing of administration. One explanation may be differences in blood-brain barrier (BBB) integrity compared to high-grade glioma. The authors hypothesized that for a BBB semipermeable to 5-ALA there might be a relationship between plasma 5-ALA concentration and its movement into the brain. A higher dose would elicit more 5-ALA conversion into protoporphyrin IX (PPIX). The authors present a case series of patients harboring LGG who received higher doses of 5-ALA.

METHODS Patients undergoing surgery for indeterminate glioma later diagnosed as LGG were included in this study. 5-ALA was administered at a standard dose of 20 mg/kg body weight (bw) 4 hours prior to induction of anesthesia. A subgroup of patients received a higher dose of 40 mg/kg bw. Fluorescence was evaluated visually and PPIX concentration (cPPIX) was determined ex vivo by hyperspectral measurements in freshly extracted tissue. All adverse events were recorded.

RESULTS A total of 23 patients harboring diffuse low-grade astrocytomas (n = 19) and oligodendrogliomas (n = 4) were analyzed. Thirteen patients received 20 mg/kg bw, and 10 patients received 40 mg/kg bw of 5-ALA. In the 20 mg/ kg group, 30.8% (4 of 13) of tumors harbored areas of visible fluorescence, compared to 60% of cases (n = 6 of 10) with 40 mg/kg bw. The threshold to visibility was 1 μg/ml in both groups. Measured over all biopsies, the mean cPPIX was significantly higher in the double-dose group (1.8 vs 0.45 μg/ml; p < 0.001). In non–visibly fluorescent tissue the mean cPPIX was 0.146 μg/ml in the 20 mg/kg and 0.347 μg/ml in the 40 mg/kg group, indicating an increase of 138% (p < 0.001).

CONCLUSIONS These observations demonstrate different regions with different levels of PPIX accumulation in LGG. With higher 5-ALA doses cPPIX increases, leading to more regions surpassing the visibility threshold of 1 μg/ml. These observations can be explained by the fact that the BBB in LGG is semipermeable to 5-ALA. Higher 5-ALA doses result in more PPIX conversion, an observation with implications for future dosing in LGG.

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Circumferential sulcus-guided resection technique for improved outcomes of low-grade gliomas

J Neurosurg 137:1015–1025, 2022

Many neurosurgeons resect nonenhancing low-grade gliomas (LGGs) by using an inside-out piecemeal resection (PMR) technique. At the authors’ institution they have increasingly used a circumferential, perilesional, sulcusguided resection (SGR) technique. This technique has not been well described and there are limited data on its effectiveness. The authors describe the SGR technique and assess the extent to which SGR correlates with extent of resection and neurological outcome.

METHODS The authors identified all patients with newly diagnosed LGGs who underwent resection at their institution over a 22-year period. Demographics, presenting symptoms, intraoperative data, method of resection (SGR or PMR), volumetric imaging data, and postoperative outcomes were obtained. Univariate analyses used ANOVA and Fisher’s exact test. Multivariate analyses were performed using multivariate logistic regression.

RESULTS Newly diagnosed LGGs were resected in 519 patients, 208 (40%) using an SGR technique and 311 (60%) using a PMR technique. The median extent of resection in the SGR group was 84%, compared with 77% in the PMR group (p = 0.019). In multivariate analysis, SGR was independently associated with a higher rate of complete (100%) resection (27% vs 18%) (OR 1.7, 95% CI 1.1–2.6; p = 0.03). SGR was also associated with a statistical trend toward lower rates of postoperative neurological complications (11% vs 16%, p = 0.09). A subset analysis of tumors located specifically in eloquent brain demonstrated SGR to be as safe as PMR.

CONCLUSIONS The authors describe the SGR technique used to resect LGGs and show that SGR is independently associated with statistically significantly higher rates of complete resection, without an increase in neurological complications, than with PMR. SGR technique should be considered when resecting LGGs.

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

Acta Neurochirurgica (2022) 164:2605–2622

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 postoperative 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 postoperative 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 intraoperative 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.

Keywords Intramedullary spinal cord tumours · Spinal ependymomas · Spinal astrocytomas · Spinal oncology · Surgical outcomes

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Survival Prediction After Neurosurgical Resection of Brain Metastases: A Machine Learning Approach

Neurosurgery 91:381–388, 2022

Current prognostic models for brain metastases (BMs) have been constructed and validated almost entirely with data from patients receiving up-front radiotherapy, leaving uncertainty about surgical patients.

OBJECTIVE: To build and validate a model predicting 6-month survival after BM resection using different machine learning algorithms.

METHODS: An institutional database of 1062 patients who underwent resection for BM was split into an 80:20 training and testing set. Seven different machine learning algorithms were trained and assessed for performance; an established prognostic model for patients with BM undergoing radiotherapy, the diagnosis-specific graded prognostic assessment, was also evaluated. Model performance was assessed using area under the curve (AUC) and calibration.

RESULTS: The logistic regression showed the best performance with an AUC of 0.71 in the hold-out test set, a calibration slope of 0.76, and a calibration intercept of 0.03. The diagnosis-specific graded prognostic assessment had an AUC of 0.66. Patients were stratified into regular-risk, high-risk and very high-risk groups for death at 6 months; these strata strongly predicted both 6-month and longitudinal overall survival (P < .0005). The model was implemented into a web application that can be accessed through http:// brainmets.morethanml.com.

CONCLUSION: We developed and internally validated a prediction model that accurately predicts 6-month survival after neurosurgical resection for BM and allows for meaningful risk stratification. Future efforts should focus on external validation of our model.

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The WHO 2021 Classification of Central Nervous System tumours: a practical update on what neurosurgeons need to know—a minireview

Acta Neurochirurgica (2022) 164:2453–2464

The World Health Organization (WHO) Classification of Tumours, also known as WHO Blue Books, represents an international standardised tool in the diagnostic work-up of tumours. This classification system is under continuous revision, and progress in the molecular classification of tumours in the central nervous system (CNS) enforced an update of the WHO 2016 classification, and the fifth edition, WHO CNS5, was published in 2021. The aim of this minireview is to highlight important changes in this new edition relevant for the practicing neurosurgeon.

Methods The sixth volume of the fifth edition of the WHO Blue Books of CNS tumours and related papers formed the basis for this minireview.

Results Major changes encompass standardisation of tumour grading and nomenclature as well as increased incorporation of molecular markers in the classification of CNS tumours.

Conclusion Advances in molecular genetics have resulted in more accurate diagnosis and prognosis of CNS tumours, and this minireview summarises important changes implemented in the last edition of WHO classification of CNS tumours important for the practicing neurosurgeon.

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Perioperative outcomes and survival after surgery for intramedullary spinal cord tumors: a single-institution series of 302 patients

J Neurosurg Spine 37:252–262, 2022

Intramedullary spinal cord tumors (IMSCTs) are rare neoplasms whose treatment is often technically challenging. Given the low volume seen at most centers, perioperative outcomes have been reported infrequently. Here, the authors present the largest single-institution series of IMSCTs, focusing on the clinical presentation, histological makeup, perioperative outcomes, and long-term survival of surgically treated patients.

METHODS A cohort of patients operated on for primary IMSCTs at a comprehensive cancer center between June 2002 and May 2020 was retrospectively identified. Data on patient demographics, tumor histology, neuraxial location, baseline neurological status, functional deficits, and operative characteristics were collected. Perioperative outcomes of interest included length of stay, postoperative complications, readmission, reoperation, and discharge disposition. Data were compared across tumor histologies using the Kruskal-Wallis H test, chi-square test, and Fisher exact test. Pairwise comparisons were conducted using Tukey’s honest significant difference test, chi-square test, and Fisher exact test. Long-term survival was assessed across tumor categories and histological subtype using the log-rank test.

RESULTS Three hundred two patients were included in the study (mean age 34.9 ± 19 years, 77% white, 57% male). The most common tumors were ependymomas (47%), astrocytomas (31%), and hemangioblastomas (11%). Ependymomas and hemangioblastomas disproportionately localized to the cervical cord (54% and 59%, respectively), whereas astrocytomas were distributed almost equally between the cervical cord (36%) and thoracic cord (38%). Clinical presentation, extent of functional dependence, and postoperative 30-day outcomes were largely independent of underlying tumor pathology, although tumors of the thoracic cord had worse American Spinal Injury Association (ASIA) grades than cervical tumors. Rates of gross-total resection were lower for astrocytomas than for ependymomas (54% vs 84%, p < 0.01) and hemangioblastomas (54% vs 100%, p < 0.01). Additionally, 30-day readmission rates were significantly higher for astrocytomas than ependymomas (14% vs 6%, p = 0.02). Overall survival was significantly affected by the underlying pathology, with astrocytomas having poorer associated prognoses (40% at 15 years) than ependymomas (81%) and hemangioblastomas (66%; p < 0.01) and patients with high-grade ependymomas and astrocytomas having poorer longterm survival than those with low-grade lesions (p < 0.01).

CONCLUSIONS The neuraxial location of IMSCTs, extent of resection, and postoperative survival differed significantly across tumor pathologies. However, perioperative outcomes did not vary significantly across tumor cohorts, suggesting that operative details, rather than pathology, may have a stronger influence on the short-term clinical course, whereas pathology appears to have a stronger impact on long-term survival.

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The diagnostic value of contrast enhancement on MRI in diffuse and anaplastic gliomas

Acta Neurochirurgica (2022) 164:2035–2040

We evaluated differentiations in gadolinium contrast enhancement (CE) between low-grade WHO °II and high-grade WHO °III gliomas in conventional MRI, which have been repeatedly questioned.

Methods Ninety-nine patients, who underwent first resection of WHO°II and °III gliomas, were retrospectively retrieved from a prospective database. The quantitative metric volume of Gd-CE in T1-weighted pre-operative MRI was measured using volumetric segmentation.

Results The OR to detect CE in anaplastic gliomas was seven times higher than that in diffuse gliomas (CI95% 2.817.2, p<0.0001). No CE was seen in 50% (8/16) of focal anaplastic and in 28% (10/36) of entirely anaplastic gliomas. CE was present in 21% (10/47) of diffuse gliomas. Anaplasia correlated with a larger CE volume (r=0.49, p<0.0001) and provided additional 4 cm 3 of CE volume compared to entirely diffuse tumors. The OR to have CE was 3.6 times for IDH1 wild-type tumors (CI95% 1.3–10.2, p=0.05) and 4.8 for tumors with ATRX expression (CI95% 1.3–17.2, p=0.05). In all sub-groups, at least a quarter of cases showed no CE at all and there were cases with present CE.

Conclusion CE is associated with higher odds of unfavorable prognostic features like anaplasia, wild-type IDH1 and retained ATRX. There was no CE in one-fourth of anaplastic gliomas and half of gliomas with focal anaplasia.

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Predictors of postoperative seizure outcome in supratentorial meningioma

J Neurosurg 137:515–524, 2022

Meningiomas are the most common primary intracranial tumor. Seizures are common sequelae of meningioma development. Meningioma patients with seizures can be effectively treated with resection, with reports of seizure freedom of 60%–90%. Still, many patients manifest persistent epilepsy. Determining factors associated with worsened seizure outcomes remains critical in improving the quality of life for these patients. The authors sought to identify clinical, radiological, and histological factors associated with worse seizure outcomes in patients with supratentorial meningioma and preoperative seizures.

METHODS The authors retrospectively reviewed the charts of 384 patients who underwent meningioma resection from 2008 to 2020. The charts of patients with a documented history of preoperative seizures were further reviewed for clinical, radiological, operative, perioperative, histological, and postoperative factors associated with seizures. Engel class at last follow-up was retrospectively assigned by the authors and further grouped into favorable (class I) and worse (class II–IV) outcomes. Factors were subsequently compared by group using comparative statistics. Univariable and multivariable regression models were utilized to identify independent predictors of worse seizure outcome.

RESULTS Fifty-nine patients (15.4%) were found to have preoperative seizures, of whom 57 had sufficient postoperative data to determine Engel class outcome. Forty-two patients (74%) had Engel class I outcomes. The median follow-up was 17 months. Distinct margins on preoperative imaging (p = 0.012), Simpson grade I resection (p = 0.004), postresection ischemia (p = 0.019), WHO grade (p = 0.019), and recurrent disease (p = 0.015) were found to be the strongest predictors of Engel class outcome in univariable logistic regression. MIB-1 index (p = 0.001) and residual volume (p = 0.014) at last follow-up were found to be the strongest predictors of Engel class outcome in univariable generalized linear regression. Postresection ischemia (p = 0.012), WHO grade (p = 0.022), recurrent disease (p = 0.038), and MIB-1 index (p = 0.002) were found to be the strongest independent predictors of Engel class outcomes in multivariable analysis.

CONCLUSIONS Postresection ischemia, higher WHO grade, elevated MIB-1 index, and disease recurrence independently predict postresection seizure persistence in patients with supratentorial meningioma. Further understanding of the etiology of these markers may aid in elucidation of this complex disease process and guide management to prevent worse outcomes.

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Circulating Tumor DNA in Adults With Glioma: A Systematic Review and Meta-Analysis of Biomarker Performance

Neurosurgery 91:231–238, 2022

Circulating tumor DNA (ctDNA) has emerged as a promising noninvasive biomarker to capture tumor genetics in patients with brain tumors. Research into its clinical utility, however, has not been standardized because the sensitivity and specificity of ctDNA remain undefined.

OBJECTIVE: To (1) review the primary literature about ctDNA in adults with glioma to compare the sensitivity and specificity of ctDNA in the cerebrospinal fluid vs the plasma and (2) to evaluate the effect of tumor grade on detection of ctDNA.

METHODS: PRISMA-guided systematic review and meta-analysis was performed using published studies that assessed ctDNA in either plasma or cerebrospinal fluid among adult patients with confirmed glioma. Summary receiver operating characteristic curves were generated using the Rücker-Schumacher method, and area under the curve (AUC) was calculated.

RESULTS: Meta-analysis revealed improved biomarker performance for CSF (AUC = 0.947) vs plasma (AUC = 0.741) ctDNA, although this did not reach statistical significance (P = .141). Qualitative analysis revealed greater sensitivities among single-allele PCR and small, targeted next-generation sequencing panels compared with broader panels. It additionally demonstrated higher sensitivity of ctDNA detection in high-grade vs low-grade gliomas, although these analyses were limited by a lack of specificity reporting in many studies.

CONCLUSION: ctDNA seems to be a highly sensitive and specific noninvasive biomarker among adults with gliomas. To maximize its performance, CSF should be studied with targeted genetic analysis platforms, particularly in high-grade gliomas. Further studies on ctDNA are needed to define its clinical utility in diagnosis, prognostication, glioblastoma pseudoprogression, and other scenarios wherein neoadjuvant therapies may be considered.

KEY WORDS: Cell-free DNA, Circulating tumor DNA, CNS tumor, Glioma, Liquid biopsy

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Role of the parietooccipital fissure and its implications in the pathophysiology of posterior medial temporal gliomas

J Neurosurg 137:505–514, 2022

The parietooccipital fissure is an anatomical landmark that divides the temporal, occipital, and parietal lobes. More than 40% of gliomas are located in these three lobes, and the temporal lobe is the most common location. The parietooccipital fissure is located just posterior to the medial temporal lobe, but little is known about the clinical significance of this fissure in gliomas. The authors investigated the anatomical correlations between the parietooccipital fissure and posterior medial temporal gliomas to reveal the radiological features and unique invasion patterns of these gliomas.

METHODS The authors retrospectively reviewed records of all posterior medial temporal glioma patients treated at their institutions and examined the parietooccipital fissure. To clarify how the surrounding structures were invaded in each case, the authors categorized tumor invasion as being toward the parietal lobe, occipital lobe, isthmus of the cingulate gyrus, insula/basal ganglia, or splenium of the corpus callosum. DSI Studio was used to visualize the fiber tractography running through the posterior medial temporal lobe.

RESULTS Twenty-four patients with posterior medial temporal gliomas were identified. All patients presented with a parietooccipital fissure as an uninterrupted straight sulcus and as the posterior border of the tumor. Invasion direction was toward the parietal lobe in 13 patients, the occipital lobe in 4 patients, the isthmus of the cingulate gyrus in 19 patients, the insula/basal ganglia in 3 patients, and the splenium of the corpus callosum in 8 patients. Although the isthmus of the cingulate gyrus and the occipital lobe are located just posterior to the posterior medial temporal lobe, there was a significantly greater preponderance of invasion toward the isthmus of the cingulate gyrus than toward the occipital lobe (p = 0.00030, McNemar test). Based on Schramm’s classification for the medial temporal tumors, 4 patients had type A and 20 patients had type D tumors. The parietooccipital fissure determined the posterior border of the tumors, resulting in a unique and identical radiological feature. Diffusion spectrum imaging (DSI) tractography indicated that the fibers running through the posterior medial temporal lobe toward the occipital lobe had to detour laterally around the bottom of the parietooccipital fissure.

CONCLUSIONS Posterior medial temporal gliomas present identical invasion patterns, resulting in unique radiological features that are strongly affected by the parietooccipital fissure. The parietooccipital fissure is a key anatomical landmark for understanding the complex infiltrating architecture of posterior medial temporal gliomas.

 

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The impact of multiple lesions on progression-free survival of meningiomas: a 10-year multicenter experience

J Neurosurg 137:9–17, 2022

Multiple meningiomas (MMs) occur in as many as 18% of patients with meningioma, and data on progression- free survival (PFS) are scarce. The objective of this study was to explore the influence of the number of lesions and clinical characteristics on PFS in patients with WHO grade I meningiomas.

METHODS The authors retrospectively reviewed the records of all adults diagnosed with a meningioma at their three main sites from January 2009 to May 2020. Progression was considered the time from diagnosis until radiographic growth of the originally resected meningioma. A secondary analysis was performed to evaluate the time of diagnosis until the time to second intervention (TTSI). Univariable and multivariable analyses were conducted to assess whether the number of lesions or any associated variables (age, sex, race, radiation treatment, tumor location, and extent of resection) had a significant impact on PFS and TTSI.

RESULTS Eight hundred thirty-eight patients were included. Use of a log-rank test to evaluate PFS and TTSI between a single and multiple lesions showed a significantly shorter progression for MM (p < 0.001 and p < 0.001, respectively). Multivariable Cox regression analysis showed significantly inferior PFS on MM compared to a single lesion (hazard ratio [HR] 2.262, 95% confidence interval [CI] 1.392–3.677, p = 0.001) and a significantly inferior TTSI for patients with MM when compared to patients with a single meningioma (HR 2.377, 95% CI 1.617–3.494, p = 0.001). By testing the number of meningiomas as a continuous variable, PFS was significantly inferior for each additional meningioma (HR 1.350, 95% CI 1.074–1.698, p = 0.010) and TTSI was significantly inferior as well (HR 1.428, 95% CI 1.189–1.716, p < 0.001). African American patients had an inferior PFS when compared to non-Hispanic White patients (HR 3.472, 95% CI 1.083–11.129, p = 0.036).

CONCLUSIONS The PFS of meningiomas appears to be influenced by the number of lesions present. Patients with MM also appear to be more prone to undergoing a second intervention for progressive disease. Hence, a closer follow-up may be warranted in patients who present with multiple lesions. These results show a decreased PFS for each additional lesion present, as well as a shorter PFS for MM compared to a single lesion. When assessing associated risk factors, African American patients showed an inferior PFS, whereas older age and adjuvant therapy with radiation showed an improved PFS.

 

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Solid vs. cystic predominance in posterior fossa hemangioblastomas: implications for cerebrovascular risks and patient outcome

Acta Neurochirurgica (2022) 164:1357–1364

Hemangioblastomas (HGBs) are highly vascular benign tumors, commonly located in the posterior fossa, and 80% of them are sporadic. Patients usually present with features of raised intracranial pressure and cerebellar symptoms. HGB can be classified as either mostly cystic or solids. Although the solid component is highly vascularized, aneurysm or hemorrhagic presentation is rarely described, having catastrophic results.

Methods We identified 32 consecutive patients with posterior fossa HBG who underwent surgery from 2008 through 2020 at our medical center. Tumors were classified as predominantly cystic or solid according to radiological features. Resection was defined as gross total (GTR) or subtotal (STR).

Results During the study period, 32 posterior fossa HGBs were resected. There were 26 cerebellar lesions and 4 medullar lesions, and in 2 patients, both structures were affected. Predominant cystic tumors were seen in 15 patients and solids in 17. Preoperative digital subtraction angiography (DSA) was performed in 8 patients with solid tumors, and 4 showed tumor-related aneurysms. Embolization of the tumors was performed in 6 patients, including the four tumor-related aneurysms. GTR was achieved in 29 tumors (91%), and subtotal resection in 3 (9%). Three patients had postoperative lower cranial nerve palsy. Functional status was stable in 5 patients (16%), improved in 24 (75%), and 3 patients (9%) deteriorated. One patient died 2 months after the surgery. Two tumors recurred and underwent a second surgery achieving GTR. The mean follow-up was 42.7 months (SD ± 51.0 months).

Conclusions Predominant cystic HGB is usually easily treated as the surgery is straightforward. Those with a solid predominance present a more complex challenge sharing features similar to arteriovenous malformations. Given the important vascular association of solid predominance HGB with these added risk factors, the preoperative assessment should include DSA, as in arteriovenous malformations, and endovascular intervention should be considered before surgery.

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