Category: Oncology

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Congress of Neurological Surgeons Systematic Review and Evidence-Based Guidelines on the Management of Progressive Glioblastoma in Adults: Update of the 2014 Guidelines

Neurosurgery 90:E112–E115, 2022

The Institute of Medicine best practice recommendation to review guidelines every 5 years is followed by the Congress of Neurological Surgeons Guidelines Committee. The aim of this work was to provide an updated literature review and evidence-based recommendations on the topic of diagnosis and treatment of patients with progressive glioblastoma (pGBM).

OBJECTIVE: To review the literature published since the last guidelines on pGBM dated 2014, with literature search ending in June 2012.

METHODS: PubMed, Embase, and Cochrane were searched for the period July 1, 2012, to March 31, 2019, using search terms and search strategies to identify pertinent abstracts. These were then screened using published exclusion/inclusion criteria to identify full-text review articles. Evidence tables were constructed using data derived from full-text reviews and recommendations made from the evidence derived.

RESULTS: From the total 8786 abstracts identified by the search, 237 full-text articles met inclusion/exclusion criteria and were included in this update. Two new level II recommendations derived from this work. For the diagnosis of patients with GBM, the use of diffusion-weighted images is recommended to be included in the magnetic resonance images with and without contrast used for surveillance to detect pGBM. For the treatment of patients with pGBM, repeat cytoreductive surgery is recommended to improve overall survival. An additional 21 level III recommendations were provided.

CONCLUSION: Recent published literature provides new recommendations for the diagnosis and treatment of pGBM. The Central Nervous System Guidelines Committee will continue to pursue timely updates to further improve the care of patients with diagnosis. https://www.cns.org/guidelines/browse-guidelines-detail/guidelines-management-ofprogressive-glioblastoma.

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Supraorbital and mini-pterional keyhole craniotomies for brain tumors

J Neurosurg 136:1314–1324, 2022

The authors’ objective was to compare the indications, outcomes, and anatomical limits of supraorbital (SO) and mini-pterional (MP) craniotomies in patients with intra- and extraaxial brain tumors, and to assess approach selection, utility of endoscopy, and surgical field overlap.

METHODS A retrospective analysis was conducted of all brain tumor patients who underwent an SO or MP approach. The analyzed characteristics included pathology, endoscopy use, extent of resection, length of stay (LOS), and complications. On the basis of preoperative MRI data, tumor heatmaps were constructed to compare surgical access provided by both routes, including coronal projection heatmaps for parasellar tumors.

RESULTS From 2007 to 2020, 158 patients underwent 173 (84.8%) SO craniotomies and 30 patients underwent 31 (15.2%) MP craniotomies; 71 (34.8%) procedures were reoperations. Of these 204 operations, 110 (63.6%) SO and 21 (67.7%) MP approaches were for extraaxial tumors (meningiomas in 65% and 76.2%, respectively). Gliomas and metastases together represented 84.1% and 70% of intraaxial tumors accessed with SO and MP approaches, respectively. Overall, 56.1% of tumors accessed with the SO approach and 41.9% of those accessed with the MP approach were in the parasellar region. Axial projection heatmaps showed that SO access extended along the entire ipsilateral and medial contralateral anterior cranial fossa, parasellar region, ipsilateral sylvian fissure, medial middle cranial fossa, and anterior midbrain, whereas MP access was limited to the ipsilateral middle cranial fossa, sylvian fissure, lateral parasellar region, and posterior aspect of anterior cranial fossa. Coronal projection heatmaps showed that parasellar access extended further superiorly with the SO approach compared with that of the MP approach. Endoscopy was utilized in 98 (56.6%) SO craniotomies and 7 (22.6%) MP craniotomies, with further tumor resection in 48 (49%) and 5 (71.4%) cases, respectively. Endoscope-assisted tumor removal was clustered in areas that were generally at farther distances from the craniotomy or in angled locations such as the cribriform plate region where microscopic visualization is limited. Gross-total or neartotal resection was achieved in 120/173 (69%) SO approaches and 21/31 (68%) MP approaches. Major complications occurred in 11 (6.4%) SO approaches and 1 (3.2%) MP approach (p = 0.49). The median LOS decreased to 2 days in the last 2 years of the study.

CONCLUSIONS This clinical experience suggests the SO and MP craniotomies are versatile, safe, and complementary approaches for tumors located in the anterior and middle cranial fossae and perisylvian and parasellar regions. The SO route, used in 85% of cases, achieved greater overall reach than the MP route. Both approaches may benefit from expanded visualization with endoscopy.

 

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Risk of tract recurrence with stereotactic biopsy of brain metastases

J Neurosurg 136:1045–1051, 2022

Stereotactic biopsy is increasingly performed on brain metastases (BrMs) as improving cancer outcomes drive aggressive multimodality treatment, including laser interstitial thermal therapy (LITT). However, the tract recurrence (TR) risk is poorly defined in an era defined by focused-irradiation paradigms. As such, the authors aimed to define indications and adjuvant therapies for this procedure and evaluate the BrM-biopsy TR rate.

METHODS In a single-center retrospective review, the authors identified stereotactic BrM biopsies performed from 2002 to 2020. Surgical indications, radiographic characteristics, stereotactic planning, dosimetry, pre- and postoperative CNS-directed and systemic treatments, and clinical courses were collected. Recurrence was evaluated using RANO-BM (Response Assessment in Neuro-Oncology Brain Metastases) criteria.

RESULTS In total, 499 patients underwent stereotactic intracranial biopsy for any diagnosis, of whom 25 patients (5.0%) underwent biopsy for pathologically confirmed viable BrM, a proportion that increased over the time period studied. Twelve of the 25 BrM patients had ≥ 3 months of radiographic follow-up, of whom 6 patients (50%) developed new metastatic growth along the tract at a median of 5.0 months post-biopsy (range 2.3–17.1 months). All of the TR cases had undergone pre- or early post-biopsy stereotactic radiosurgery (SRS), and 3 had also undergone LITT at the time of initial biopsy. TRs were treated with resection, reirradiation, or observation/systemic therapy.

CONCLUSIONS In this study the authors identified a nontrivial, higher than previously described rate of BrM-biopsy tract recurrence, which often required additional surgery or radiation and justified close radiographic surveillance. As BrMs are commonly treated with SRS limited to enhancing tumor margins, consideration should be made, in cases lacking CNS-active systemic treatments, to include biopsy tracts in adjuvant radiation plans where feasible.

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The Evolution of 5-Aminolevulinic Acid Fluorescence Visualization: Time for a Headlamp/Loupe Combination

The use of 5-aminolevulinic acid (5-ALA) for intraoperative protoporphyrin IX fluorescent imaging in the resection of malignant gliomas has been demonstrated to improve tumor visualization, increase the extent of resection, and extend progression-free survival. The current technique for visualization of 5-ALA consists of excitation and emission filters built into the operating microscope. However, there are notable limitations to this process, including low quantum yield, expense, and masking of surrounding anatomy.

METHODS: We present 3 cases in which 3 separate methods were employed for visualizing fluorescence. The devices reported are 1) a low-cost blue light flashlight, 2) a low-cost headlamp, and 3) the first reported case of the new Designs for Vision REVEAL Fluorescence-Guided Surgery (FGS) 5-ALA fluorescent headlight and loupes. The aim of the study is to provide confirmation that tumor fluorescence can be observed using commercially available products other than the microscope.

RESULTS: We demonstrate through 3 intraoperative cases that a variety of devices can produce visible fluorescence of the high-grade tumor and allow for simultaneous real-time visualization of the adjacent brain parenchyma and vasculature. The REVEAL FGS system appears to offer increased fluorescence emission compared with all other methods, including the microscope. –

CONCLUSIONS: Our study demonstrates the feasibility of using blue/ultraviolet light supplied by a commercially available, inexpensive flashlight or headlamp to visualize 5-ALA fluorescence in high-grade gliomas. We also provide the first documentation of the intraoperative use of the new Designs for Vision REVEAL FGS 5-ALA fluorescent headlight and loupes and report on the experience. Lack of an operative microscope capable of fluorescent illumination should not be a limiting factor in performing fluorescent guided glioma resection

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Severity, timeline, and management of complications after stereotactic brain biopsy

J Neurosurg 136:867–876, 2022

The literature shows discrepancies in stereotactic brain biopsy complication rates, severities, and outcomes. Little is known about the timeline of postbiopsy complications. This study aimed to analyze 1) complications following brain biopsies, using a graded severity scale, and 2) a timeline of complication occurrence. The secondary objectives were to determine factors associated with an increased risk of complications and to assess complication related management and extra costs.

METHODS The authors retrospectively examined 1500 consecutive stereotactic brain biopsies performed in adult patients at their tertiary medical center between April 2009 and April 2019.

RESULTS Three hundred eighty-one biopsies (25.4%) were followed by a complication, including 88.2% of asymptomatic hemorrhages. Symptomatic complications involved 3.0% of the biopsies, and 0.8% of the biopsies were fatal. The severity grading scale had a 97.6% interobserver reproducibility. Twenty-three (51.1%) of the 45 symptomatic complications occurred within the 1st hour following the biopsy, while 75.6% occurred within the first 6 hours. Age ≥ 65 years, second biopsy procedures, gadolinium-enhanced lesions, glioblastomas, and lymphomas were predictors of biopsy-related complications. Brainstem biopsy-targeted lesions and cerebral toxoplasmosis were predictive of mortality. Asymptomatic hemorrhage was associated with delayed (> 6 hours) symptomatic complications. Symptomatic complications led to extended hospitalization in 86.7% of patients. The average extra cost for management of a patient with postbiopsy symptomatic complication was $35,702.

CONCLUSIONS Symptomatic complications from brain biopsies are infrequent but associated with substantial adverse effects and cost implications for the healthcare system. The use of a severity grading scale, as the authors propose in this article, helps to classify complications according to the therapeutic consequences and the patient’s outcome. Because this study indicates that most complications occur within the first few hours following the biopsy, postbiopsy monitoring can be tailored accordingly. The authors therefore recommend systematic monitoring for 2 hours in the recovery unit and a CT scan 2 hours after the end of the biopsy procedure. In addition, they propose a modern algorithm for optimal postoperative management of patients undergoing stereotactic biopsy.

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Pretreatment patient‐reported cognitive function in patients with diffuse glioma

Acta Neurochirurgica (2022) 164:703–711

Cognitive function is frequently assessed with objective neuropsychological tests, but patient-reported cognitive function is less explored. We aimed to investigate the preoperative prevalence of patient-reported cognitive impairment in patients with diffuse glioma compared to a matched reference group and explore associated factors.

Methods We included 237 patients with diffuse glioma and 474 age- and gender-matched controls from the general population. Patient-reported cognitive function was measured using the cognitive function subscale in the European Organisation for Research and Treatment of Cancer QLQ-C30 questionnaire. The transformed scale score (0–100) was dichotomized, with a score of ≤ 75 indicating clinically important patient-reported cognitive impairment. Factors associated with preoperative patient-reported cognitive impairment were explored in a multivariable regression analysis.

Results Cognitive impairment was reported by 49.8% of the diffuse glioma patients and by 23.4% in the age- and gendermatched reference group (p < 0.001). Patients with diffuse glioma had 3.2 times higher odds (95% CI 2.29, 4.58, p < 0.001) for patient-reported cognitive impairment compared to the matched reference group. In the multivariable analysis, large tumor volume, left tumor lateralization, and low Karnofsky Performance Status score were found to be independent predictors for preoperative patient-reported cognitive impairment.

Conclusions Our findings demonstrate that patient-reported cognitive impairment is a common symptom in patients with diffuse glioma pretreatment, especially in patients with large tumor volumes, left tumor lateralization, and low functional levels. Patient-reported cognitive function may provide important information about patients’ subjective cognitive health and disease status and may serve as a complement to or as a screening variable for subsequent objective testing.

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Fluorescein-guided resection of cerebral metastases is associated with greater tumor resection

Acta Neurochirurgica (2022) 164:451–457

Sodium fluorescein (fluorescein) crosses a disrupted blood-brain barrier similarly to gadolinium contrast in contrast-enhancing cerebral tumors. When exposed to light with 560 nm wavelength during surgery, fluorescein emits a yellow-green fluorescent light that can be visualized through an operating microscope equipped with an appropriate emission filter. The distribution of the fluorescence correlates with the contrast on a gadolinium contrast-enhanced MRI.

Objective The objective of this single-center retrospective study was to investigate if the use of fluorescein would increase the extent of resection and to examine if fluorescein guided resection influences postoperative neurological status.

Methods During the study period from August 2014 to August 2018, 117 patients were operated for cerebral metastases. Of these, 56 operations were guided by fluorescein and 61 by traditional white light. All patients had an early postoperative MRI within 72 h after surgery.

Results The use of fluorescein increased the extent of resection in patients with cerebral metastases. The use of fluorescein was not associated with increased postoperative sequelae or neurological damage regardless of underlying primary cancer.

Conclusion Fluorescein is a helpful supplement in the neurosurgical treatment of cerebral metastases.

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Outcome of glioblastoma resection in patients 80 years of age and older

Acta Neurochirurgica (2022) 164:373–383

Objective To evaluate the role and possible complications of tumor resection in the management of glioblastoma (GBM) in a series of patients 80 years of age and older with review of literature.

Methods The authors retrospectively analyzed cases involving patients 80 years or older who underwent biopsy or initial resection of GBM at their hospital between 2007 and 2018. A total of 117 patients (mean age 82 years) met the inclusion criteria; 57 had resection (group A) and 60 had biopsy (group B). Functional outcomes and survival at follow-up were analyzed.

Results Group A differed significantly from group B at baseline in having betterWHO performance status, better ASA scores, more right-sided tumors, and no basal ganglia or “butterfly” gliomas. Nevertheless, 56% of group A patients had an ASA score of 3. Median survival was 9.5 months (95% CI 8–17 months) in group A, 4 months (95% CI 3.5–6 months) in group B, and 17.5 months (95% CI 12–24 months) in the 56% of group A patients treated with resection and Stupp protocol. Rates of postoperative neurologic and medical complications were almost identical in the 2 groups, but the rate of surgical site complications was substantially greater in group A (12% vs 5%). There was no significant difference in mean preoperative and postoperative KPS scores (group A).

Conclusions In selected patients 80 years or older, radical removal of GBM was associated with acceptable survival and a low perioperative complication rate which is comparable to that of a biopsy. Although the median survival of the whole group was lower than reported for younger patients, a subgroup amenable to radical surgery and Stupp protocol achieved a median survival of 17.5 months.

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Adult Posterior Fossa Anaplastic Ependymoma

World Neurosurg. (2022) 158:205-209

Ependymomas are rare central nervous system tumors. The current treatment strategy is gross total tumor removal. Whether adjuvant therapy will be beneficial is controversial. We retrospectively analyzed 3 cases of World Health Organization (WHO) grade III posterior fossa anaplastic ependymomas treated with different treatment modalities. We aimed to identify possible treatment options for infratentorial WHO grade III anaplastic ependymoma in adults.

METHODS: We performed a retrospective analysis of 3 patients diagnosed with infratentorial anaplastic ependymomas in our institution from 2016 to 2020. The demographic data were documented. This case series of 3 patients does not meet the Department of Health and Human Services definition of research and does not need Institutional Review Board approval. All patients’ informed consents have been obtained.

RESULTS: One patient underwent subtotal tumor resection combined with adjuvant radiotherapy and Gamma Knife radiosurgery while the other 2 patients underwent gross total tumor removal combined with Gamma Knife radiosurgery or adjuvant radiotherapy. Tumors recurred in the first patient 20 months later, while the other 2 patents did not develop recurrence. The modified Rankin scale scores of these patients were 1, 0, and 0. All patients are followed up with regular magnetic resonance imaging at our facility.

CONCLUSIONS: The strategy for treating WHO grade III anaplastic ependymomas is controversial, but gross total tumor resection remains the key element. Adjuvant stereotactic radiosurgery after tumor removal might be considered if radiotherapy is not an option. The role of chemotherapy is unclear, and the use of chemotherapy should be tailored to individual patients

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The immunology of low-grade gliomas

Neurosurg Focus 52 (2):E2, 2022

Low-grade gliomas (LGGs), which harbor an isocitrate dehydrogenase (IDH) mutation, have a better prognosis than their high-grade counterparts; nonetheless, they remain incurable and impart significant negative impacts on patients’ quality of life.

Although immunotherapies represent a novel avenue of treatment for patients with LGGs, they have not yet been successful. Accurately selecting and evaluating immunotherapies requires a detailed understanding of LGG tumor immunology and the underlying tumor immune phenotype.

A growing body of literature suggests that LGGs significantly differ in their immunology from high-grade gliomas, highlighting the importance of investigation into LGG immunology specifically.

In this review, the authors aimed to discuss relevant research surrounding the LGG tumor immune microenvironment, including immune cell infiltration, tumor immunogenicity, checkpoint molecule expression, the impact of an IDH mutation, and implications for immunotherapies, while also briefly touching on current immunotherapy trials and future directions for LGG immunology research.

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Racial and Socioeconomic Disparities in Patients With Meningioma: A Retrospective Cohort Study

Neurosurgery 90:114–123, 2022

Meningiomas are the most common intracranial neoplasms. Although genomic analysis has helped elucidate differences in survival, there is evidence that racial disparities may influence outcomes. African Americans have a higher incidence of meningiomas and poorer survival outcomes. The etiology of these disparities remains unclear, but may include a combination of pathophysiology and other factors.

OBJECTIVE: To determine factors that contribute to different clinical outcomes in racial populations.

METHODS: We retrospectively reviewed 305 patients who underwent resection for meningiomas at a single tertiary care facility. We used descriptive statistics and univariate, multivariable, and Kaplan-Meier analyses to study clinical, radiographical, and histopathological differences.

RESULTS: Minority patients were more likely to present through the emergency department than an outpatient clinic (P < .0001). They were more likely to present with more advanced clinical symptoms with lower Karnofsky Performance scores, more frequently had peritumoral edema (P = .0031), and experienced longer postoperative stays in the hospital (P = .0053), and African-American patients had higher hospitalization costs (P = .046) and were more likely to be publicly insured. Extent of resection was an independent predictor of recurrence freedom (P = .039). Presentation in clinic setting trended toward an association with recurrence-free survival (P = .055). We observed no significant difference in gross total resection rates, postoperative recurrence, or recurrence-free survival.

CONCLUSION: Minority patients are more likely to present with severe symptoms, require longer perioperative hospitalization, and generate higher hospitalization costs. This may be due to socioeconomic factors that affect access to health care. Targeting barriers to access, especially to subspecialty care, may facilitate more appropriate and timely diagnosis, thereby improving patient care and outcomes.

 

 

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Proposal of a new grading system for meningioma resection: the Copenhagen Protocol

Acta Neurochirurgica (2022) 164:229–238

The extent of meningioma resection is the most fundamental risk factor for recurrence, and exact knowledge of extent of resection is necessary for prognostication and for planning of adjuvant treatment. Currently used classifications are the EANO-grading and the Simpson grading. The former comprises radiological imaging with contrast-enhanced MRI and differentiation between “gross total removal” and “subtotal removal,” while the latter comprises a five-tiered differentiation of the surgeon’s impression of the extent of resection. The extent of resection of tumors is usually defined via analyses of resection margins but has until now not been implemented for meningiomas. PET/MRI imaging with 68Ga-DOTATOC allows more sensitive and specific imaging than MRI following surgery of meningiomas.

Objective To develop an objective grading system based on microscopic analyses of resection margins and sensitive radiological analyses to improve management of follow-up, adjuvant therapy, and prognostication of meningiomas. Based on the rationale of resection-margin analyses as gold standard and superior imaging performance of 68Ga DOTATOC PET, we propose “Copenhagen Grading” for meningiomas.

Results Copenhagen Grading was described for six pilot patients with examples of positive and negative findings on histopathology and DOTATOC PET scanning. The grading could be traceably implemented and parameters of grading appeared complementary. Copenhagen Grading is prospectively implemented as a clinical standard at Rigshospitalet, Copenhagen.

Conclusion Copenhagen Grading provided a comprehensive, logical, and reproducible definition of the extent of resection. It offers promise to be the most sensitive and specific imaging modality available for meningiomas. Clinical and cost-efficacy remain to be established during prospective implementation.

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Fluorescence real-time kinetics of protoporphyrin IX after 5-ALA administration in low-grade glioma

J Neurosurg 136:9–15, 2022

5-Aminolevulinic acid (5-ALA) induces fluorescence in high-grade glioma (HGG), which is used for resection. However, the value of 5-ALA–induced fluorescence in low-grade glioma (LGG) is unclear. Time dependency and time kinetics have not yet been investigated. The purpose of this study was to investigate real-time kinetics of protoporphyrin IX (PpIX) in LGG based on hyperspectral fluorescence-based measurements and identify factors that predict fluorescence.

METHODS Patients with grade II gliomas and imaging from which HGGs could not be completely ruled out received 5-ALA at 20 mg/kg body weight 4 hours prior to surgery. Fluorescence intensity (FI) and PpIX concentration (CPpIX) were measured in tumor tissue utilizing a hyperspectral camera. Apparent diffusion coefficient (ADC)–based tumor cell density, Ki-67/MIB-1 index, chromosomal 1p/19q codeletion, and 18 F-fluoroethyl-l-tyrosine ( 18 F-FET) PET values and their role for predicting fluorescence were evaluated.

RESULTS Eighty-one biopsies from 25 patients were included. Tissues with fluorescence demonstrated FI and CPpIX maxima between 7 and 8 hours after administration. When visible fluorescence was observed, peaks of FI and CPpIX were observed within this 7- to 8-hour time frame, regardless of any MRI gadolinium contrast enhancement. Gadolinium enhancement (p = 0.008), Ki-67/MIB-1 index (p < 0.001), 18 F-FET PET uptake ratio (p = 0.004), and ADC-based tumor cellularity (p = 0.017) significantly differed between fluorescing and nonfluorescing tissue, but not 1p/19q codeletions. Logistic regression demonstrated that 18 F-FET PET uptake and Ki-67/MIB-1 index were independently related to fluorescence.

CONCLUSIONS This study reports a fluorescence-based assessment of CPpIX in human LGG tissues related to 18 F-FET PET uptake and Ki-67/MIB-1. As in HGGs, fluorescence in LGGs peaked between 7 and 8 hours after 5-ALA application, which has consequences for the timing of administration.

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Influence of supramarginal resection on survival outcomes after gross-total resection of IDH–wild-type glioblastoma

J Neurosurg 136:1–8, 2022

The authors’ goal was to use a multicenter, observational cohort study to determine whether supramarginal resection (SMR) of FLAIR-hyperintense tumor beyond the contrast-enhanced (CE) area influences the overall survival (OS) of patients with isocitrate dehydrogenase–wild-type (IDH-wt) glioblastoma after gross-total resection (GTR).

METHODS The medical records of 888 patients aged ≥ 18 years who underwent resection of GBM between January 2011 and December 2017 were reviewed. Volumetric measurements of the CE tumor and surrounding FLAIR-hyperintense tumor were performed, clinical variables were obtained, and associations with OS were analyzed.

RESULTS In total, 101 patients with newly diagnosed IDH-wt GBM who underwent GTR of the CE tumor met the inclusion criteria. In multivariate analysis, age ≥ 65 years (HR 1.97; 95% CI 1.01–2.56; p < 0.001) and contact with the lateral ventricles (HR 1.59; 95% CI 1.13–1.78; p = 0.025) were associated with shorter OS, but preoperative Karnofsky Performance Status ≥ 70 (HR 0.47; 95% CI 0.27–0.89; p = 0.006), MGMT promotor methylation (HR 0.63; 95% CI 0.52–0.99; p = 0.044), and increased percentage of SMR (HR 0.99; 95% CI 0.98–0.99; p = 0.02) were associated with longer OS. Finally, 20% SMR was the minimum percentage associated with beneficial OS (HR 0.56; 95% CI 0.35–0.89; p = 0.01), but > 60% SMR had no significant influence (HR 0.74; 95% CI 0.45–1.21; p = 0.234).

CONCLUSIONS SMR is associated with improved OS in patients with IDH-wt GBM who undergo GTR of CE tumor. At least 20% SMR of the CE tumor was associated with beneficial OS, but greater than 60% SMR had no significant influence on OS.

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Tumor location and reduction in functional MRI estimates of language laterality

J Neurosurg 135:1674–1684, 2021

Brain tumors located close to the language cortex may distort functional MRI (fMRI)–based estimates of language dominance. The nature of this distortion, and whether this is an artifact of numerous confounders, remains unknown. The authors hypothesized tumor bias based on laterality estimates independent of confounders and that the effects are the greatest for tumors proximal to Broca’s area.

METHODS To answer this question, the authors reviewed more than 1113 patients who underwent preoperative fMRI to match samples on 11 known confounders (tumor location, size, type, and grade; seizure history; prior neurosurgery; aphasia presence and severity; and patient age, sex, and handedness). The samples included 30 patients with left hemisphere tumors (15 anterior and 15 posterior) and 30 with right hemisphere tumors (15 anterior and 15 posterior), thus totaling 60 patients (25 women; 18 left-handed and 4 ambidextrous; mean age 47 [SD 14.1] years). Importantly, the authors matched not only patients with left and right hemisphere tumors but also those with anterior and posterior tumors. Standard fMRI laterality indices (LIs) were calculated using whole-brain and region of interest (ROI) approaches (Broca’s and Wernicke’s areas).

RESULTS Tumors close to Broca’s area in the left hemisphere decreased LIs independently of known confounders. At the whole-brain level, this appeared to reflect a decrease in LI values in patients with left anterior tumors compared with patients with right anterior tumors. ROI analysis replicated these findings. Broca’s area LIs were significantly lower (p = 0.02) in patients with left anterior tumors (mean LI 0.28) when compared with patients with right anterior tumors (mean LI 0.70). Changes in Wernicke’s area–based LIs did not differ as a function of the tumor hemisphere. Therefore, in patients with left anterior tumors, it is essential to assess language laterality using left posterior ROIs. In all remaining tumor groups (left posterior tumors and right hemisphere tumors), language laterality derived from the anterior language ROI was the most robust measure of language dominance.

CONCLUSIONS Patients with tumors close to Broca’s area showed more bilateral fMRI language maps independent of known confounders. The authors caution against the assumption that this reduced language laterality suggests no or little risk to language function following tumor resection in the left inferior frontal gyrus. Their results address how to interpret fMRI data for neurosurgical purposes, along with theoretical questions of contralesional functional compensation and disinhibition.

 

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Is There a Role for Surgical Resection of Multifocal Glioblastoma? A Retrospective Analysis of 100 Patients

Neurosurgery 89:1042–1051, 2021

Glioblastoma with multiple localizations (mGBMs) can be defined as multifocal, where enhancing lesions present a connection visible on magnetic resonance imaging fluid-attenuated inversion recovery imaging, or multicentric, in the absence of a clear dissemination pathway.

OBJECTIVE: To evaluate the role of the extent of resection (EOR) in the treatment of mGBMs and its correlation with overall survival (OS) and progression free survival (PFS).

METHODS: One hundred patients with mGBMs were treated at our Institution between 2009 and 2019. Clinical, radiological, and follow-up datawere collected. EOR of the contrastenhancing part of lesions was classified as gross total resection (GTR, absence of tumor remnant), subtotal resection (STR, residual tumor < 30% of the initial mass), partial resection (PR, residual tumor>30% of the initialmass), and needle or open biopsy (residual tumor > 75% of the initial mass).

RESULTS: Approximately 15% of patients underwent GTR, 14% STR, 32% PR, and 39% biopsy. Median OS was 17 mo for GTR, 11 mo for STR, 7 mo for PR, and 5 mo for biopsy. Greater EOR was associated with a significantly longer OS than biopsy. GTR and STR were associated with a longer PFS in Kaplan-Meier survival analyses. After adjusting for age, Karnofsky performance status (KPS), number of lesions, and adjunctive therapy in multivariable Cox regression analyses, GTR, STR, and PR were still associated with OS, but only GTR remained associated with PFS.

CONCLUSION: Our study suggests that EOR may positively influence survival of patients with mGBM. Surgical resection can be a reasonable option when performance and access to adjuvant treatment can be preserved.

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Central Nervous System Plasticity Influences Language and Cognitive Recovery in Adult Glioma

Neurosurgery 89:539–548, 2021

Gliomas exist within the framework of complex neuronal circuitry in which network dynamics influence both tumor biology and cognition. The generalized impairment of cognition or loss of language function is a common occurrence for glioma patients.

The interface between intrinsic brain tumors such as gliomas and functional cognitive networks are poorly understood. The ability to communicate effectively is critically important for receiving oncological therapies and maintaining a high quality of life.

Although the propensity of gliomas to infiltrate cortical and subcortical structures and disrupt key anatomic language pathways is well documented, there is new evidence offering insight into the network and cellular mechanisms underpinning glioma-related aphasia and aphasia recovery.

In this review, we will outline the current understanding of the mechanisms of cognitive dysfunction and recovery, using aphasia as an illustrative model.

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Tumor Growth Rate as a New Predictor of Progression-Free Survival After Chordoma Surgery

Neurosurgery 89:291–299, 2021

Currently, different postoperative predictors of chordoma recurrence have been identified. Tumor growth rate (TGR) is an image-based calculation that provides quantitative information of tumor’s volume changing over time and has been shown to predict progression-free survival (PFS) in other tumor types.

OBJECTIVE: To explore the usefulness of TGR as a new preoperative radiological marker for chordoma recurrence.

METHODS: A retrospective single-institution study was carried out including patients reflecting these criteria: confirmed diagnosis of chordoma on pathological analysis, no history of previous radiation, and at least 2 preoperative thin-slice magnetic resonance images available to measure TGR. TGR was calculated for all patients, showing the percentage change in tumor size over 1 mo.

RESULTS: A total of 32 patients were retained for analysis. Patients with a TGR ≥ 10.12%/m had a statistically significantly lower mean PFS (P<.0001). TGR≥10.12%/m (odds ratio=26, P=.001) was observed more frequently in recurrent chordoma. In a subgroup analysis, we found that the association of Ki-67 labeling index≥6% and TGR≥10.12%/m was correlated with recurrence (P = .0008).

CONCLUSION: TGR may be considered as a preoperative radiological indicator of tumor proliferation and seems to preoperatively identify more aggressive tumors with a higher tendency to recur. Our findings suggest that the therapeutic strategy and clinical radiological follow-up of patients with chordoma can be adapted also according to this new parameter.

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Intracranial Meningiomas Decrease in Volume on Magnetic Resonance Imaging After Discontinuing Progestin

Neurosurgery 89:308–314, 2021

The behavior of meningiomas under influence of progestin therapy remains unclear.

OBJECTIVE: To investigate the relationship between growth kinetics of intracranial meningiomas and usage of the progestin cyproterone acetate (PCA).

METHODS: This study prospectively followed 108 women with 262 intracranial meningiomas and documented PCA use. A per-meningioma analysis was conducted. Changes in meningioma volumes over time, and meningioma growth velocities, were measured on magnetic resonance imaging (MRI) after stopping PCA treatment.

RESULTS: Mean follow-up time was 30 (standard deviation [SD] 29) mo. Ten (4%) meningiomas were treated surgically at presentation. The other 252 meningiomas were followed after stopping PCA treatment. Overall, followedmeningiomas decreased their volumes by 33% on average (SD 28%). A total of 188 (72%) meningiomas decreased, 51 (19%) meningiomas remained stable, and 13 (5%) increased in volume of which 3 (1%) were surgically treated because of radiological progression during follow-up after PCA withdrawal. In total, 239 of 262 (91%) meningiomas regressed or stabilized during follow-up. Subgroup analysis in 7 women with 19 meningiomas with follow-up before and after PCA withdrawal demonstrated that meningioma growth velocity changed statistically significantly (P = .02). Meningiomas grew (average velocity of 0.25mm3/day) while patients were using PCA and shrank (average velocity of −0.54 mm3/day) after discontinuation of PCA.

CONCLUSION: Ninety-one percent of intracranial meningiomas in female patients with long-term PCA use decrease or stabilize on MRI after stopping PCA treatment. Meningioma growth kinetics change significantly from growth during PCA usage to shrinkage after PCA withdrawal.

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Machine Learning for the Prediction of Molecular Markers in Glioma on Magnetic Resonance Imaging: A Systematic Review and Meta-Analysis

Neurosurgery 89:31–44, 2021

Molecular characterization of glioma has implications for prognosis, treatment planning, and prediction of treatment response. Current histopathology is limited by intratumoral heterogeneity and variability in detection methods. Advances in computational techniques have led to interest in mining quantitative imaging features to noninvasively detect genetic mutations.

OBJECTIVE: To evaluate the diagnostic accuracy of machine learning (ML) models in molecular subtyping gliomas on preoperative magnetic resonance imaging (MRI).

METHODS: A systematic search was performed following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines to identify studies up to April 1, 2020. Methodological quality of studies was assessed using the Quality Assessment for Diagnostic Accuracy Studies (QUADAS)-2. Diagnostic performance estimates were obtained using a bivariate model and heterogeneity was explored using metaregression.

RESULTS: Forty-four original articles were included. The pooled sensitivity and specificity for predicting isocitrate dehydrogenase (IDH) mutation in training datasets were 0.88 (95% CI 0.83-0.91) and 0.86 (95% CI 0.79-0.91), respectively, and 0.83 to 0.85 in validation sets. Use of data augmentation and MRI sequence type were weakly associated with heterogeneity. Both O6-methylguanine-DNA methyltransferase (MGMT) gene promoter methylation and 1p/19q codeletion could be predicted with a pooled sensitivity and specificity between 0.76 and 0.83 in training datasets.

CONCLUSION: ML application to preoperative MRI demonstrated promising results for predicting IDHmutation, MGMT methylation, and 1p/19q codeletion in glioma. Optimized ML models could lead to a noninvasive, objective tool that captures molecular information important for clinical decisionmaking. Future studies should use multicenter data, external validation and investigate clinical feasibility of ML models.

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