Category: Oncology

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Stereotactic biopsies of brainstem lesions: which approach?

Acta Neurochirurgica (2021) 163:1957–1964

Stereotactic biopsies for brainstem lesions are frequently performed to yield an accurate diagnosis and help guide subsequent management. In this study, we summarize our experience with different stereotactic approaches to brainstem lesions of different locations and discuss possible implications for safety and diagnostic yield.

Methods We retrospectively analyzed 23 adult patients who underwent a stereotactic biopsy for brainstem lesions between October 2011 and December 2019. Depending on the location supra- or infratentorial, trajectories were planned. We assessed the postoperative complications during the hospital stay as well as the diagnostic yield.

Results A supratentorial transfrontal approach was used in 16 (70%) cases, predominantly for lesions in the midbrain, upper pons, and medulla oblongata. An infratentorial, transcerebellar-transpeduncular approach was used in 7 (30%) cases mainly for lesions within the lower pons. All biopsies were confirmed to represent pathological tissue and a definitive diagnosis was achieved in 21 cases (91%). Three patients (13%) had transient weakness in the contralateral part of the body in the immediate postoperative period, which improved spontaneously. There was no permanent morbidity or mortality in this series of patients.

Conclusion Lesions of various locations within the brainstem can be successfully targeted via either a supratentorial transfrontal or an infratentorial transcerebellar transpeduncular approach. Our high diagnostic yield of over 90% and the low rate of complications underlines the diagnostic importance of this procedure in order to guide the medical management of these patients.

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A Neurosurgeon’s Guide to Cognitive Dysfunction in Adult Glioma

Neurosurgery 89:1–10, 2021

Cognitive decline is common among patients with low- and high-grade glioma and can significantly impact quality of life. Although cognitive outcomes have been studied after therapeutic interventions such as surgery and radiation, it is important to understand the impact of the disease process itself prior to any interventions.

Neurocognitive domains of interest in this disease context include intellectual function and premorbid ability, executive function, learning and memory, attention, language function, processing speed, visuospatial function, motor function, and emotional function.

Here, we review oncologic factors associated with more neurocognitive impairment, key neurocognitive tasks relevant to glioma patient assessment, as well as the relevance of the human neural connectome in understanding cognitive dysfunction in glioma patients.

A contextual understanding of glioma-functional network disruption and its impact on cognition is critical in the surgical management of eloquent area tumors.

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Improved outcomes associated with maximal extent of resection for butterfly glioblastoma

Acta Neurochirurgica (2021) 163:1883–1894

Butterfly glioblastomas (bGBMs) are grade IV gliomas that infiltrate the corpus callosum and spread to bilateral cerebral hemispheres. Due to the rarity of cases, there is a dearth of information in existing literature. Herein, we evaluate clinical and genetic characteristics, associated predictors, and survival outcomes in an institutional series and compare them to a national cohort.

Methods We identified all adult patients with bGBM treated at Brigham & Women’s Hospital (2008–2018). The National Cancer Database (NCDB) was also queried for bGBM patients. Survival was analyzed with Kaplan–Meier methods, and Cox models were built to assess for predictive factors.

Results Of 993 glioblastoma patients, 62 cases (6.2%) of bGBM were identified. Craniotomy for resection was attempted in 26 patients (41.9%), with a median volumetric extent of resection (vEOR) of 72.3% (95% confidence interval [95%CI] 58.3–82.1). The IDH1 R132H mutation was detected in two patients (3.2%), and MGMT promoter was methylated in 55.5% of the assessed cases. In multivariable regression, factors predictive of longer OS were increased vEOR, MGMT promoter methylation, and receipt of adjuvant therapy. Median OS for the resected cases was 11.5 months (95%CI 7.7–18.8) vs. 6.3 (95%CI 5.1–8.9) for the biopsied. Of 21,353 GBMs, 719 (3.37%) bGBM patients were identified in the NCDB. Resection was more likely to be pursued in recent years, and GTR was independently associated with prolonged OS (p < 0.01).

Conclusion Surgical resection followed by adjuvant chemoradiation is associated with significant survival gains and should be pursued in carefully selected bGBM patients.

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The Validity of the Koos Classification System With Respect to Facial Nerve Function

Neurosurgery 88:E523–E528, 2021

The Koos classification of vestibular schwannomas is designed to stratify tumors based on extrameatal extension and compression of the brainstem. Our prior study demonstrated excellent reliability. No study has yet assessed its validity.

OBJECTIVE: To present a retrospective study designed to assess the validity of the Koos grading system with respect to facial nerve function following treatment of 81 acoustic schwannomas.

METHODS: We collected data retrospectively from 81 patients with acoustic schwannomas of various Koos grades who were treated with microsurgical resection or stereotactic radiosurgery. House-Brackmann (HB) scores were used to assess facial nerve function and obtained at various time points following treatment. We generated Spearman’s rho and Kendall’s tau correlation coefficients along with a logistic regression curve.

RESULTS: We found no significant difference in the presence or absence of facial dysfunction by Koos classification when looking at all patients. There was a positive but fairly weak correlation between HB score and Koos classification, which was only significant at the first postoperative clinic appointment. There was a statistically significant difference in the presence or absence of facial dysfunction between patients treated with surgery vs radiation, which we expected. We found no statistically significant difference when comparing surgical approaches. Logistic regression modeling demonstrated a poor ability of the Koos grading system to predict facial nerve dysfunction following treatment.

CONCLUSION: The Koos grading system did not predict the presence of absence of facial nerve dysfunction in our study population. There were trends within subgroups that require further exploration.

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Adjuvant Radiotherapy Versus Watchful Waiting for World Health Organization Grade II Atypical Meningioma

Neurosurgery 88:E435–E442, 2021

Atypical meningiomas (AMs) are meningiomas that have a higher rate of recurrence than grade Imeningioma. Due to the higher risk of recurrence, adjuvant radiotherapy (RT) after resection of AM has been employed. At our institution, some neurosurgeons employ adjuvant RT on all primarily resected AMs, while others employ watchful waiting with serial imaging.

OBJECTIVE: To study the effect of adjuvant RT on newly resected AMs.

METHODS: A retrospective review of all AMs primarily resected at our institution from 1996 to 2018 was completed. Data on patient demographics, radiographic findings, use of adjuvant RT, time of follow-up, and recurrences were collected. Adjuvant RT was defined as RT that occurred within 6 mo of initial resection.

RESULTS: A total of 162 patients met the inclusion criteria. Gross total resection was achieved in 73% of cases. Average time until recurrence in the cohort was 37mo. A total of 108 patients had adjuvant RT, while 54 patients did not. On multivariate survival analysis, sex, Simpson grade resection, and use of adjuvant RT were independent predictors of recurrence. Mean time to recurrence in patients who received adjuvant RT was 43.7 mo versus 34.7 mo for those who did not receive adjuvant RT.

CONCLUSION: This study includes the largest retrospective cohort of patients who have received adjuvant RT after primary resection of AM. Our results suggest that the use of adjuvant RT is independently associated with a lower chance of recurrence. These data suggest that practitioners can consider the use of adjuvant RT for newly resected AMs, regardless of Simpson grade resection.

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Predictors of visual functional outcome following treatment for cavernous sinus meningioma

J Neurosurg 134:1435–1446, 2021

Cavernous sinus meningioma (CSM) can affect visual function and require expeditious treatment to prevent permanent visual loss. Authors of this retrospective study sought to determine the factors associated with visual functional outcomes in CSM patients treated with surgery, stereotactic radiosurgery (SRS), or stereotactic radiation therapy (SRT), alone or in combination.

METHODS Consecutive patients with CSM who had presented at an academic tertiary care hospital from 2000 to 2018 were identified through retrospective chart review. Visual function—visual eye deficit (VED), optic disc (OD) appearance, intraocular pressure (IOP), and extraocular movement (EOM)—was assessed before and after treatment for CSM. VED with visual acuity (VA) ≤ 20/200 and visual field defect ≥ −11 dB, pale OD appearance in the ipsilateral or contralateral eye, increased ipsilateral IOP, and/or EOM restriction were defined as a poor visual functional outcome. Multivariable logistic regression was used to evaluate the associations between pretreatment visual functional assessment and posttreatment visual outcomes.

RESULTS The study cohort included 44 patients (73% female; median age 55 years), with a median clinical follow-up of 14 months. Ipsilateral VED improved, remained stable, or worsened, respectively, in 0%, 33.4%, and 66.6% of the patients after subtotal resection (STR) alone; in 52.6%, 31.6%, and 15.8% after STR plus radiation treatment; in 28.5%, 43.0%, and 28.5% after gross-total resection (GTR) alone; and in 56.3%, 43.7%, and 0% after radiation treatment (SRS or SRT) alone. Contralateral VED remained intact in all the patients after STR alone and those with radiation treatment (SRS or SRT) alone; however, it improved, remained stable, or worsened in 10.5%, 84.2%, and 5.3% after STR plus radiation treatment and in 43.0%, 28.5%, and 28.5% after GTR alone. EOM remained intact, fully recovered, remained stable, and worsened, respectively, in 0%, 50%, 50%, and 0% of the patients after STR alone; in 36.8%, 47.4%, 15.8%, and 0% of the patients after STR with radiation treatment; in 57.1%, 0%, 28.6%, and 14.3% of the patients after GTR alone; and in 56.2%, 37.5%, 6.3%, and 0% of the patients after radiation treatment (SRS or SRT) alone. In multivariable analyses adjusted for age, tumor volume, and treatment modality, initial ipsilateral poor VED (OR 10.1, 95% CI 1.05–97.2, p = 0.04) and initial ipsilateral pale OD appearance (OR 21.1, 95% CI 1.6–270.5, p = 0.02) were associated with poor ipsilateral VED posttreatment. Similarly, an initial pale OD appearance (OR 15.7, 95% CI 1.3–199.0, p = 0.03), initial poor VED (OR 21.7, 95% CI 1.2–398.6, p = 0.03), and a higher IOP in the ipsilateral eye (OR 55.3, 95% CI 1.7–173.9, p = 0.02) were associated with an ipsilateral pale OD appearance posttreatment. Furthermore, a higher initial ipsilateral IOP (OR 35.9, 95% CI 3.3–400.5, p = 0.004) was indicative of a higher IOP in the ipsilateral eye posttreatment. Finally, initial restricted EOM was indicative of restricted EOM posttreatment (OR 20.6, 95% CI 18.7–77.0, p = 0.02).

CONCLUSIONS Pretreatment visual functional assessment predicts visual outcomes in patients with CSM and can be used to identify patients at greater risk for vision loss.

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Altered corticospinal microstructure and motor cortex excitability in gliomas

J Neurosurg 134:1368–1376, 2021

This prospective case-control study was conducted to examine whether spherical deconvolution (SD) can unveil microstructural abnormalities in the corticospinal tract (CST) caused by IDH-mutant gliomas. To determine the significance of abnormal microstructure, the authors investigated the correlation between diffusion parameters and neurophysiological data collected with navigated transcranial magnetic stimulation (nTMS).

METHODS Twenty participants (10 patients and 10 healthy controls) were recruited. Diffusion-weighted images were acquired on a 3-T MRI scanner using a cardiac-gated single-shot spin echo echo-planar imaging multiband sequence (TE 80 msec, TR 4000 msec) along 90 diffusion directions with a b-value of 2500 sec/mm2 (FOV 256 × 256 mm). Diffusion tensor imaging tractography and SD tractography were performed with deterministic tracking. The anterior portion of the ipsilateral superior peduncle and the precentral gyrus were used as regions of interest to delineate the CST. Diffusion indices were extracted and analyzed for significant differences between hemispheres in patients and between patient and control groups. A navigated brain stimulation system was used to deliver TMS pulses at hotspots at which motor evoked potentials (MEPs) for the abductor pollicis brevis, first digital interosseous, and abductor digiti minimi muscles are best elicited in patients and healthy controls. Functional measurements such as resting motor threshold (rMT), amplitude of MEPs, and latency of MEPs were noted. Significant differences between hemispheres in patients and between patients and controls were statistically analyzed. The Spearman rank correlation was used to investigate correlations between diffusion indices and functional measurements.

RESULTS The hindrance modulated orientational anisotropy (HMOA), measured with SD tractography, is lower in the hemisphere ipsilateral to glioma (p = 0.028). The rMT in the hemisphere ipsilateral to a glioma is significantly greater than that in the contralateral hemisphere (p = 0.038). All measurements contralateral to the glioma, except for the mean amplitude of MEPs (p = 0.001), are similar to those of healthy controls. Mean diffusivity and axial diffusivity from SD tractography are positively correlated with rMT in the hemisphere ipsilateral to glioma (p = 0.02 and 0.006, respectively). The interhemispheric difference in HMOA and rMT is correlated in glioma patients (p = 0.007).

CONCLUSIONS SD tractography can demonstrate microstructural abnormality within the CST of patients with IDH1- mutant gliomas that correlates to the functional abnormality measured with nTMS.

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Mapping and anatomo-surgical techniques for SMA-cingulum-corpus callosum gliomas

Acta Neurochirurgica (2021) 163:1239–1246

Awake brain mapping paradigms are variable, particularly in SMA, and not personalised to each patient. In addition, subpial resections do not offer full protection to vascular injury, as the pia can be easily violated.

Methods Mapping paradigms developed by a multidisciplinary brain mapping team. During resection, a combined subpial/ interhemispheric approach allowed early identification and arterial skeletonization. Precise anatomo-surgical dissection of the affected cingulum and corpus callosum was achieved.

Conclusions In SMA-cingulum-CC tumours, a combined subpial/interhemispheric approach reduces risk of vascular injury allowing precise anatomo-surgical dissections. Knowledge of cognitive functions of affected parcels is likely to offer best outcomes.

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How safe are elective craniotomies in elderly patients in neurosurgery today?

J Neurosurg 134:1113–1121, 2021

With global aging, elective craniotomies are increasingly being performed in elderly patients. There is a paucity of prospective studies evaluating the impact of these procedures on the geriatric population. The goal of this study was to assess the safety of elective craniotomies for elderly patients in modern neurosurgery.

METHODS For this cohort study, adult patients, who underwent elective craniotomies between November 1, 2011, and October 31, 2018, were allocated to 3 age groups (group 1, < 65 years [n = 1008], group 2, ≥ 65 to < 75 [n = 315], and group 3, ≥ 75 [n = 129]). Primary outcome was the 30-day mortality after craniotomy. Secondary outcomes included rate of delayed extubation (> 1 hour), need for emergency head CT scan and reoperation within 48 hours after surgery, length of postoperative intensive or intermediate care unit stay, hospital length of stay (LOS), and rate of discharge to home. Adjustment for American Society of Anesthesiologists Physical Status (ASA PS) class, estimated blood loss, and duration of surgery were analyzed as a comparison using multiple logistic regression. For significant differences a post hoc analysis was performed.

RESULTS In total, 1452 patients (mean age 55.4 ± 14.7 years) were included. The overall mortality rate was 0.55% (n = 8), with no significant differences between groups (group 1: 0.5% [95% binominal CI 0.2%, 1.2%]; group 2: 0.3% [95% binominal CI 0.0%, 1.7%]; group 3: 1.6% [95% binominal CI 0.2%, 5.5%]). Deceased patients had a significantly higher ASA PS class (2.88 ± 0.35 vs 2.42 ± 0.62; difference 0.46 [95% CI 0.03, 0.89]; p = 0.036) and increased estimated blood loss (1444 ± 1973 ml vs 436 ± 545 ml [95% CI 618, 1398]; p <0.001). Significant differences were found in the rate of postoperative head CT scans (group 1: 6.65% [n = 67], group 2: 7.30% [n = 23], group 3: 15.50% [n = 20]; p = 0.006), LOS (group 1: median 5 days [IQR 4; 7 days], group 2: 5 days [IQR 4; 7 days], and group 3: 7 days [5; 9 days]; p = 0.001), and rate of discharge to home (group 1: 79.0% [n = 796], group 2: 72.0% [n = 227], and group 3: 44.2% [n = 57]; p < 0.001).

CONCLUSIONS Mortality following elective craniotomy was low in all age groups. Today, elective craniotomy for well selected patients is safe, and for elderly patients, too. Elderly patients are more dependent on discharge to other hospitals and postacute care facilities after elective craniotomy. Clinical trial registration no.: NCT01987648 (clinicaltrials.gov).

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MGMT-Positive vs MGMT-Negative PatientsWith Glioblastoma: Identification of Prognostic Factors and Resection Threshold

Neurosurgery 88:E323–E329, 2021

The importance of the O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status as a predictive factor for the response to chemotherapy with temozolomide is well established. Its significance though at stratifying glioblastoma (GBM) patients in regard to their prognostic factors and the impact of surgical approach on them has not been identified.

OBJECTIVE: To reveal possible differences in the prognostic factors and the impact of surgery between GBM patients stratified according to their MGMT status.

METHODS: The authors retrospectively analyzed 186 patients with a newly diagnosed primary supratentorial GBM treated with surgical resection followed by standard radiation and chemotherapy. A prospective quantitative volumetric analysis of tumor characteristics identified on magnetic resonance imaging was performed.

RESULTS: For the 109 patients with unmethylated MGMT promoter, extent of resection (EOR) represented independent predictor of survival, whereas residual tumor volume (RTV), Karnofsky Performance Score, and age were found to be independent prognostic factors of survival for the 77 patients with methylated MGMT promoter. For the group of patients with unmethylated and the group with methylated MGMT promoter, an EOR threshold of 70% and 98% and an RTV threshold of 1.5 and 1 cm3 were identified, respectively.

CONCLUSION: The selection of patients according to the MGMT promoter methylation status resulted in different prognostic factors and different resection thresholds for each patient population. A survival benefit seen from 70% EOR threshold in patients with MGMT unmethylated GBM supports the doctrine of maximum safe resection rather than the “all or- nothing” approach.

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Brain connectomics applied to oncological neuroscience: from a traditional surgical strategy focusing on glioma topography to a meta-network approach

Acta Neurochirurgica (2021) 163:905–917

The classical way for surgical selection and planning in cerebral glioma mainly focused on tumor topography. The emerging science of connectomics, which aims of mapping brain connectivity, resulted in a paradigmatic shift from a modular account of cerebral organization to a meta-network perspective. Adaptive behavior is actually mediated by constant changes in interactions within and across large-scale delocalized neural systems underlying conation, cognition, and emotion.

Here, to optimize the onco-functional balance of glioma surgery, the purpose is to switch toward a connectome-based resection taking account of both relationships between the tumor and critical distributed circuits (especially subcortical pathways) as well as the perpetual instability of the meta-network. Such dynamic in the neural spatiotemporal integration permits functional reallocation leading to neurological recovery after massive resection in structures traditionally thought as “inoperable.” This better understanding of connectome increases benefit/risk ratio of surgery (i) by selecting resection in areas deemed “eloquent” according to a localizationist dogma; (ii), conversely, by refining intraoperative awake cognitive mapping and monitoring in so-called non-eloquent areas; (iii) by improving preoperative information, enabling an optimal selection of intrasurgical tasks tailored to the patient’s wishes; (iv) by developing an “oncological disconnection surgery”; (v) by defining a personalized multistep surgical strategy adapted to individual brain reshaping potential; and (vi) ultimately by preserving environmentally and socially appropriate behavior, including return to work, while increasing the extent of (possibly repeated) resection(s).

Such a holistic vision of neural processing can enhance reliability of connectomal surgery in oncological neuroscience and may also be applied to restorative neurosurgery.

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Spinal laser interstitial thermal therapy: single-center experience and outcomes in the first 120 cases

J Neurosurg Spine 34:354–363, 2021

The objective of this study was to present the results of a consecutive series of 120 cases treated with spinal laser interstitial thermal therapy (sLITT) to manage epidural spinal cord compression (ESCC) from metastatic tumors.

METHODS The electronic records of patients treated from 2013 to 2019 were analyzed retrospectively. Data collected included demographic, pathology, clinical, operative, and imaging findings; degree of epidural compression before and after sLITT; length of hospital stay; complications; and duration before subsequent oncological treatment. Independent-sample t-tests were used to compare means between pre- and post-sLITT treatments. Survival was estimated by the Kaplan-Meier method. Multivariate logistic regression was used to analyze predictive factors for local recurrence and neurological complications.

RESULTS There were 110 patients who underwent 120 sLITT procedures. Spinal levels treated included 5 cervical, 8 lumbar, and 107 thoracic. The pre-sLITT Frankel grades were E (91.7%), D (6.7%), and C (1.7%). The preoperative ESCC grade was 1c or higher in 92% of cases. Metastases were most common from renal cell carcinoma (39%), followed by non–small cell lung carcinoma (10.8%) and other tumors (35%). The most common location of ESCC was in the vertebral body (88.3%), followed by paraspinal/foraminal (7.5%) and posterior elements (4.2%). Adjuvant radiotherapy (spinal stereotactic radiosurgery or conventional external beam radiation therapy) was performed in 87 cases (72.5%), whereas 33 procedures (27.5%) were performed as salvage after radiotherapy options were exhausted. sLITT was performed without need for spinal stabilization in 87 cases (72.5%). Post-sLITT Frankel grades were E (85%), D (10%), C (4.2%), and B (0.8%); treatment was associated with a median decrease of 2 ESCC grades. The local control rate at 1 year was 81.7%. Local control failure occurred in 25 cases (20.8%). The median progression-free survival was not reached, and overall survival was 14 months. Tumor location in the paraspinal region and salvage treatment were independent predictors of local recurrence, with hazard ratios of 6.3 and 3.3, respectively (p = 0.01). Complications were observed in 22 cases (18.3%). sLITT procedures performed in the lumbar and cervical spine had hazard ratios for neurological complications of 15.4 and 17.1 (p < 0.01), respectively, relative to the thoracic spine.

CONCLUSIONS sLITT is safe and provides effective local control for high-grade ESCC from vertebral metastases in the thoracic spine, particularly when combined with adjuvant radiotherapy. The authors propose considering sLITT as an alternative to open surgery in selected patients with spinal metastases.

 

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“Zooming in” on Glioblastoma: Understanding Tumor Heterogeneity and its Clinical Implications in the Era of Single-Cell Ribonucleic Acid Sequencing

Neurosurgery 88:477–486, 2021

Glioblastoma (GBM) is the most common primary brain malignancy in adults and one of the most aggressive of all human cancers. It is highly recurrent and treatment-resistant, in large part due to its infiltrative nature and inter- and intratumoral heterogeneity. This heterogeneity entails varying genomic landscapes and cell types within and between tumors and the tumor microenvironment (TME). In GBM, heterogeneity is a driver of treatment resistance, recurrence, and poor prognosis, representing a substantial impediment to personalized medicine.

Over the last decade, sequencing technologies have facilitated deeper understanding of GBM heterogeneity by “zooming in” progressively further on tumor genomics and transcriptomics. Initial efforts employed bulk ribonucleic acid (RNA) sequencing, which examines composite gene expression of whole tumor specimens. While groundbreaking at the time, this bulk RNAseq masks the crucial contributions of distinct tumor subpopulations to overall gene expression. This work progressed to the use of bulk RNA sequencing in anatomically and spatially distinct tumor subsections, which demonstrated previously underappreciated genomic complexity of GBM.

A revolutionary next step forward has been the advent of single-cell RNA sequencing (scRNAseq), which examines gene expression at the single-cell level. scRNAseq has enabled us to understand GBM heterogeneity in unprecedented detail.

We review seminal studies in our progression of understanding GBM heterogeneity, with a focus on scRNAseq and the insights that it has provided into understanding the GBM tumor mass, peritumoral space, and TME. We highlight preclinical and clinical implications of this work and consider its potential to impact neuro-oncology and to improve patient outcomes via personalized medicine.

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Predicting the Extent of Resection in Low-Grade Glioma by Using Intratumoral Tractography to Detect Eloquent FasciclesWithin the Tumor

Neurosurgery 88(2) 2021: E190–E202

An early maximal safe surgical resection is the current treatment paradigm for low-grade glioma (LGG). Nevertheless, there are no reliable methods to accurately predict the axonal intratumoral eloquent areas and, consequently, to predict the extent of resection.

OBJECTIVE: To describe the functional predictive value of eloquent white matter tracts within the tumor by using a pre- and postoperative intratumoral diffusion tensor imaging (DTI) tractography protocol in patients with LGG.

METHODS: A preoperative intratumoral DTI-based tractography protocol, using the tumor segmented volume as the only seed region, was used to assess the tracts within the tumor boundaries in 22 consecutive patients with LGG. The reconstructed tracts were correlated with intraoperative electrical stimulation (IES)-based language and motor subcortical mapping findings and the extent of resection was assessed by tumor volumetrics.

RESULTS: Identification of intratumoral language and motor tracts significantly predicted eloquent areas within the tumor during the IES mapping: the positive predictive value for the pyramidal tract, the inferior fronto-occipital fasciculus, the arcuate fasciculus and the inferior longitudinal fasciculus positive was 100%, 100%, 33%, and 80%, respectively, whereas negative predictive value was 100% for all of them. The reconstruction of at least one of these tracts within the tumor was significantly associated with a lower extent of resection (67%) as opposed to the extent of resection in the cases with a negative intratumoral tractography (100%) (P< .0001).

CONCLUSION: Intratumoral DTI-based tractography is a simple and reliable method, useful in assessing glioma resectability based on the analysis of intratumoral eloquent areas associated with motor and language tracts within the tumor.

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Altered Motor Excitability in Patients With Diffuse Gliomas Involving Motor Eloquent Areas: The Impact of Tumor Grading

Neurosurgery 88( 1) 2021: 183–192

Diffuse gliomas have an increased biological aggressiveness across the World Health Organization (WHO) grading system. The implications of glioma grading on the primary motor cortex (M1)-corticospinal tract (CST) excitability is unknown.

OBJECTIVE: To assess the excitability of the motor pathway with navigated transcranial magnetic stimulation (nTMS).

METHODS: Retrospective cohort study of patients admitted for surgery with diffuse gliomas within motor eloquent areas. Demographic, clinical, and nTMS-related variables were collected. The Cortical Excitability Score (CES 0 to 2 according to the number of abnormal interhemispheric resting motor threshold (RMT) ratios) was calculated for patients where bilateral upper and lower limb mapping was performed.

RESULTS: A total of 45 patients were included: 9 patients had a low-grade glioma and 36 patients had a high-grade glioma. The unadjusted analysis revealed an increase in the latency of the motor evoked potential of the lower limb with an increase of theWHOgrade (P = .038). The adjusted analysis confirmed this finding (P = .013) and showed a relation between the increase in the WHO and a decreased RMT (P = .037) of the motor evoked responses in the lower limb.When CES was calculated, an increase in the score was related with an increase in the WHO grade (unadjusted analysis—P = .0001; adjusted analysis— P = .001) and in isocitrate dehydrogenase (IDH) wild-type tumors (unadjusted analysis— P = .020).

CONCLUSION: An increase in the WHO grading system and IDH wild-type tumors are associated with an abnormal excitability of the motor eloquent areas in patients with diffuse gliomas.

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Impact of Intraoperative Magnetic Resonance Imaging and Other Factors on Surgical Outcomes for Newly Diagnosed Grade II Astrocytomas and Oligodendrogliomas: A Multicenter Study

Neurosurgery 88 (1) 2021: 63–73,

Few studies use large, multi-institutional patient cohorts to examine the role of intraoperative magnetic resonance imaging (iMRI) in the resection of grade II gliomas.

OBJECTIVE: To assess the impact of iMRI and other factors on overall survival (OS) and progression-free survival (PFS) for newly diagnosed grade II astrocytomas and oligodendrogliomas.

METHODS: Retrospective analyses of a multicenter database assessed the impact of patient-, treatment-, and tumor-related factors on OS and PFS.

RESULTS: A total of 232 resections (112 astrocytomas and 120 oligodendrogliomas) were analyzed. Oligodendrogliomas had longer OS (P < .001) and PFS (P = .01) than astrocytomas. Multivariate analyses demonstrated improved OS for gross total resection (GTR) vs subtotal resection (STR; P = .006, hazard ratio [HR]: .23) and near total resection (NTR; P = .02, HR: .64). GTR vs STR (P = .02, HR: .54), GTR vs NTR (P = .04, HR: .49), and iMRI use (P = .02, HR: .54) were associated with longer PFS. Frontal (P = .048, HR: 2.11) and occipital/parietal (P = .003, HR: 3.59) locations were associated with shorter PFS (vs temporal). Kaplan-Meier analyses showed longer OS with increasing extent of surgical resection (EOR) (P=.03) and 1p/19q gene deletions (P=.02). PFS improved with increasing EOR (P = .01), GTR vs NTR (P = .02), and resections above STR (P = .04). Factors influencing adjuvant treatment (35.3% of patients) included age (P=.002, odds ratio [OR]: 1.04) and EOR (P=.003,OR: .39) but not glioma subtype or location. Additional tumor resection after iMRI was performed in 105/159 (66%) iMRI cases, yielding GTR in 54.5% of these instances.

CONCLUSION: EOR is a major determinant of OS and PFS for patients with grade II astrocytomas and oligodendrogliomas. Intraoperative MRI may improve EOR and was associated with increased PFS.

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Vertebral body fracture rates after stereotactic body radiation therapy compared with external-beam radiation therapy for metastatic spine tumors

J Neurosurg Spine 33:870–876, 2020

Stereotactic body radiation therapy (SBRT) is utilized to deliver highly conformal, dose-escalated radiation to a target while sparing surrounding normal structures. Spinal SBRT can allow for durable local control and palliation of disease while minimizing the risk of damage to the spinal cord; however, spinal SBRT has been associated with an increased risk of vertebral body fractures. This study sought to compare the fracture rates between SBRT and conventionally fractionated external-beam radiation therapy (EBRT) in patients with metastatic spine tumors.

METHODS Records from patients treated at the University of California, San Francisco, with radiation therapy for metastatic spine tumors were retrospectively reviewed. Vertebral body fracture and local control rates were compared between SBRT and EBRT. Ninety-six and 213 patients were identified in the SBRT and EBRT groups, respectively. Multivariate analysis identified the need to control for primary tumor histology (p = 0.003 for prostate cancer, p = 0.0496 for renal cell carcinoma). The patient-matched EBRT comparison group was created by matching SBRT cases using propensity scores for potential confounders, including the Spinal Instability Neoplastic Score (SINS), the number and location of spine levels treated, sex, age at treatment, duration of follow-up (in months) after treatment, and primary tumor histology. Covariate balance following group matching was confirmed using the Student t-test for unequal variance. Statistical analysis, including propensity score matching and multivariate analysis, was performed using R software and related packages.

RESULTS A total of 90 patients met inclusion criteria, with 45 SBRT and 45 EBRT matched cases. Balance of the covariates, SINS, age, follow-up time, and primary tumor histology after the matching process was confirmed between groups (p = 0.062, p = 0.174, and 0.991, respectively, along with matched tumor histology). The SBRT group had a higher 5-year rate of vertebral body fracture at 22.22% (n = 10) compared with 6.67% (n = 3) in the EBRT group (p = 0.044). Survival analysis was used to adjust for uneven follow-up time and showed a significant difference in fracture rates between the two groups (p = 0.044). SBRT also was associated with a higher rate of local control (86.67% vs 77.78%).

CONCLUSIONS Patients with metastatic cancer undergoing SBRT had higher rates of vertebral body fractures compared with patients undergoing EBRT, and this difference held up after survival analysis. SBRT also had higher rates of initial local control than EBRT but this difference did not hold up after survival analysis, most likely because of a high percentage of radiosensitive tumors in the EBRT cohort.

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Cognitive functioning in patients with low-grade glioma: effects of hemispheric tumor location and surgical procedure

J Neurosurg 133:1671–1682, 2020

The authors evaluated the cognitive performance of patients with low-grade glioma (LGG) before and after surgery, and specifically investigated 1) the effects of hemispheric tumor location and 2) the type of surgery (either with or without intraoperative stimulation mapping [ISM]).

METHODS Patients underwent neuropsychological assessment 1 day before (T0) and 3 months after (T3) surgery. ISM targeted motor and/or language functions, but no other cognitive functions. Using 2-way mixed ANOVAs, differences between groups (i.e., for patients with right- vs left-sided lesions and normative controls [NCs], and also for patients operated on with vs without ISM and NCs), effects over time (T0–T3), and interaction effects in cognitive functioning were explored. Individual changes over time were assessed with reliable change indices for each neuropsychological test.

RESULTS In total, 77 patients with LGG were included (38 and 39 patients with right- and left-sided lesions, respectively; and 42 patients with and 35 patients without ISM). The majority of patients who were operated on with ISM had left-sided lesions. Patients with right- and left-sided lesions scored significantly lower on 6 and 3 out of 8 tests, respectively, compared to NCs. No significant differences between hemispheric groups were found at T0 or at T3. Patients with left-sided lesions showed significant deterioration of performance on verbal memory and sustained attention over time. Patients who underwent operation with versus without ISM scored significantly lower on 6 and 3 out of 8 tests, respectively, compared to NCs. Patients in the ISM group scored significantly lower on the Stroop test, shifting attention test, and verbal fluency test than patients without ISM. Also, the ISM group showed a significant decline in mean cognitive flexibility and sustained attention performance over time.

CONCLUSIONS Cognitive impairments were found in patients irrespective of hemispheric tumor location, whereby patients who were operated on with ISM performed slightly worse after surgery than patients without ISM. The authors conclude that there is room for improvement of cognitive functioning in surgically treated patients with LGG. The use of specific tests for higher cognitive functions during surgery may potentially improve functional outcome, but that is to be determined in future studies and balanced against oncological outcome. Implementation of neuropsychological assessments into the clinical management of patients with LGG should be encouraged, to inform and alert patients and clinicians on the status of cognitive functioning.

 

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The Glioma-Network Interface: A Review of the Relationship Between Glioma Molecular Subtype and Intratumoral Function

 

Neurosurgery 87:1078–1084, 2020

Gliomas are a major cause of morbidity. Direct cortical stimulation mapping offers the ability to identify functional areas within the broader neural network both cortically and subcortically. Since the World Health Organization (WHO) 2016 classification categorized gliomas into molecular subgroups with varied molecular signatures and clinical behavior, it is possible that gliomas may demonstrate rates of functional network integration.

We therefore retrospectively reviewed a data registry of 181 patients with dominant hemisphere frontal, parietal, insular, or temporal gliomas. Our goal was to test the hypothesis that WHO glioma histopathology and molecular subtype influences functional language or motor sites identified within the tumor.

Intratumoral function as determined by direct cortical and subcortical stimulation mapping was identified at the highest rate in isocitrate dehydrogenase mutant astrocytomas and oligodendrogliomas. Finally, we reviewed the emerging literature exploring the interface between functional neural networks and gliomas. These data shed light on glioma molecular and histological characteristics most commonly associated within intratumoral function.

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Impact of facility type and volume in low-grade glioma outcomes

J Neurosurg 133:1313–1323, 2020

The object of this study was to investigate the impact of facility type (academic center [AC] vs non-AC) and facility volume (high-volume facility [HVF] vs low-volume facility [LVF]) on low-grade glioma (LGG) outcomes.

METHODS This retrospective cohort study included 5539 LGG patients (2004–2014) from the National Cancer Database. Patients were categorized by facility type and volume (non-AC vs AC, HVF vs LVF). An HVF was defined as the top 1% of facilities according to the number of annual cases. Outcomes included overall survival, treatment receipt, and postoperative outcomes. Kaplan-Meier and Cox proportional-hazards models were applied. The Heller explained relative risk was computed to assess the relative importance of each survival predictor.

RESULTS Significant survival advantages were observed at HVFs (HR 0.67, 95% CI 0.55–0.82, p < 0.001) and ACs (HR 0.84, 95% CI 0.73–0.97, p = 0.015), both prior to and after adjusting for all covariates. Tumor resection was 41% and 26% more likely to be performed at HVFs vs LVFs and ACs vs non-ACs, respectively. Chemotherapy was 40% and 88% more frequently to be utilized at HVFs vs LVFs and ACs vs non-ACs, respectively. Prolonged length of stay (LOS) was decreased by 42% and 24% at HVFs and ACs, respectively. After tumor histology, tumor pattern, and codeletion of 1p19q, facility type and surgical procedure were the most important contributors to survival variance. The main findings remained consistent using propensity score matching and multiple imputation.

CONCLUSIONS This study provides evidence of survival benefits among LGG patients treated at HVFs and ACs. An increased likelihood of undergoing resections, receiving adjuvant therapies, having shorter LOSs, and the multidisciplinary environment typically found at ACs and HVFs are important contributors to the authors’ finding.

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