Category: Oncology

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Volumetric growth rates of meningioma and its correlation with histological diagnosis and clinical outcome

Acta Neurochir (2017) 159:435–445

Tumour growth has been used to successfully predict progression-free survival in low-grade glioma. This systematic review sought to establish the evidence base regarding the correlation of volumetric growth rates with histological diagnosis and potential to predict clinical outcome in patients with meningioma.

Methods This systematic review was conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Databases were searched for full text English articles analysing volumetric growth rates in patients with a meningioma.

Results Four retrospective cohort studies were accepted, demonstrating limited evidence of significantly different tumour doubling rates and shapes of growth curves between benign and atypical meningiomas. Heterogeneity of patient characteristics and timing of volumetric assessment, both pre- and post-operatively, limited pooled analysis of the data. No studies performed statistical analysis to demonstrate the clinical utility of growth rates in predicting clinical outcome.

Conclusion This systematic review provides limited evidence in support of the use of volumetric growth rates in meningioma to predict histological diagnosis and clinical outcome to guide future monitoring and treatment.

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Surgical treatment of brain metastases in the central region

J Neurosurg 126:698–707, 2017

Brain metastases are the most frequent intracranial malignant tumor in adults. Surgical intervention for metastases in eloquent areas remains controversial and challenging. Even when metastases are not in ltrating intra- parenchymal tumors, eloquent areas can be affected. Therefore, this study aimed to describe the role of a functional guided approach for the resection of brain metastases in the central region.

METHODS Thirty-three patients (19 men and 14 women) with perirolandic metastases who were treated at the authors’ institution were reviewed. All participants underwent resection using a functional guided approach, which consisted of using intraoperative brain mapping and/or neurophysiological monitoring to aid in the resection, depending on the functionality of the brain parenchyma surrounding each metastasis. Motor and sensory functions were monitored in all patients, and supplementary motor and language area functions were assessed in 5 and 4 patients, respectively. Clinical data were analyzed at presentation, discharge, and the 6-month follow-up.

RESULTS The most frequent presenting symptom was seizure, followed by paresis. Gross-total removal of the metastasis was achieved in 31 patients (93.9%). There were 6 deaths during the follow-up period. After the removal of the metastasis, 6 patients (18.2%) presented with transient neurological worsening, of whom 4 had worsening of motor function impairment and 2 had acquired new sensory disturbances. Total recovery was achieved before the 3rd month of follow-up in all cases. Excluding those patients who died due to the progression of systemic illness, 88.9% of patients had a Karnofsky Performance Scale score greater than 80% at the 6-month follow-up. The mean survival time was 24.4 months after surgery.

CONCLUSIONS The implementation of intraoperative electrical brain stimulation techniques in the resection of central region metastases may improve surgical planning and resection and may spare eloquent areas. This approach also facilitates maximal resection in these and other critical functional areas, thereby helping to avoid new postoperative neurological deficits. Avoiding permanent neurological de cits is critical for a good quality of life, especially in patients with a life expectancy of over a year.

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Foramen magnum meningiomas: surgical results and risks predicting poor outcomes based on a modified classification

J Neurosurg 126:661–676, 2017

This study aimed to evaluate neurological function and progression/recurrence (P/R) outcome of foramen magnum meningioma (FMM) based on a modified classification.

METHODS This study included 185 consecutive patients harboring FMMs (mean age 49.4 years; 124 females). The authors classified the FMMs into 4 types according to the previous classification of Bruneau and George as follows: Type A (n = 49, 26.5%), the dural attachment of the lesion grows below the vertebral artery (VA); Type B (n = 39, 21.1%), the dural attachment of the lesion grows above the VA; Type C1 (n = 84, 45.4%), the VA courses across the lesion with or without VA encasement or large lesions grow both above and below the bilateral VA; and Type C2 (n = 13, 7.0%), Type C1 plus partial/total encasement of the VA and extradural growth.

RESULTS The median preoperative Karnofsky Performance Scale (KPS) score was 80. Gross-total resection (GTR) was achieved in 154 patients (83.2%). Lower cranial nerve morbidity was lowest in Type A lesions (16.3%). Type C2 lesions were inherently larger (p = 0.001), had a greater percentage of ventrolateral location (p = 0.009) and VA encase-ment (p < 0.001), lower GTR rate (p < 0.001), longer surgical duration (p = 0.015), higher morbidity (38.5%), higher P/R rate (30.8%, p = 0.009), and poorer recent KPS score compared with other types. After a mean follow-up duration of 110.3 months, the most recent follow-up data were obtained in 163 patients (88.1%). P/R was observed in 13 patients (7.2%). The median follow-up KPS score was 90. Compared with preoperative status, recent neurological status was improved in 91 (49.2%), stabilized in 76 (41.1%), and worsened in 18 (9.7%) patients. The multivariate Cox proportional hazard regression model demonstrated Type C2 (HR 3.94, 95% CI 1.04–15.0, p = 0.044), nontotal resection (HR 6.30, 95% CI 1.91–20.8, p = 0.003), and pathological mitosis (HR 7.11, 95% CI 1.96–25.8, p = 0.003) as independent adverse predictors for tumor P/R. Multivariate logistic regression analysis identified nontotal resection (OR 4.06, 95% CI 1.16–14.2, p = 0.029) and pathological mitosis (OR 6.29, 95% CI 1.47–27.0, p = 0.013) as independent risks for poor outcome (KPS score < 80).

CONCLUSIONS The modified classification helped to predict surgical outcome and P/R in addition to the position of the lower cranial nerves. Preoperative imaging studies and neurological function should be reviewed carefully to establish an individualized management strategy to improve long-term outcome.

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The new WHO 2016 classification of brain tumors

Acta Neurochir (2017) 159:403–418

The understanding of molecular alterations of tumors has severely changed the concept of classification in all fields of pathology. The availability of high-throughput technologies such as next-generation sequencing allows for a much more precise definition of tumor entities. Also in the field of brain tumors a dramatic increase of knowledge has occurred over the last years partially calling into question the purely morphologically based concepts that were used as exclusive defining criteria in the WHO 2007 classification.

Methods Review of the WHO 2016 classification of brain tumors as well as a search and review of publications in the liter- ature relevant for brain tumor classification from 2007 up to now.

Results The idea of incorporating the molecular features in classifying tumors of the central nervous system led the authors of the new WHO 2016 classification to encounter inevitable conceptual problems, particularly with respect to linking morphology to molecular alterations. As a solution they introduced the concept of a “layered diagnosis” to the classification of brain tumors that still allows at a lower level a purely morphologically based diagnosis while partially forcing the incorporation of molecular characteristics for an “integrated diagnosis” at the highest diagnostic level. In this context the broad availability of molecular assays was debated. On the one hand molecular antibodies specifically targeting mutated proteins should be available in nearly all neuropathological laboratories. On the other hand, different high-throughput assays are
accessible only in few first-world neuropathological institutions. As examples oligodendrogliomas are now primarily defined by molecular characteristics since the required assays are generally established, whereas molecular grouping of ependymomas, found to clearly outperform morphologically based tumor interpretation, was rejected from inclusion in the WHO 2016 classification because the required assays are currently only established in a small number of institutions.

Conclusion In summary, while neuropathologists have now encountered various challenges in the transitional phase from the previous WHO 2007 version to the new WHO 2016 clas- sification of brain tumors, clinical neurooncologists now face many new diagnoses allowing a clearly improved understand- ing that could offer them more effective therapeutic opportu- nities in neurooncological treatment. The new WHO 2016 classification presumably presents the highest number of modifications since the initial WHO classification of 1979 and there- by forces all professionals in the field of neurooncology to intensively understand the new concepts. This review article aims to present the basic concepts of the new WHO 2016 brain tumor classification for neurosurgeons with a focus on neurooncology.

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The Impact of Intracranial Tumor Proximity to White Matter Tracts on Morbidity and Mortality

Neurosurgery 80:193–200, 2017

Using difusion tensor imaging (DTI) in neurosurgical planning allows identification of white matter tracts and has been associated with a reduction in postoperative functional deficits.
OBJECTIVE: This study explores the relationship between the lesion-to-tract distance (LTD) and postoperative morbidity and mortality in patients with brain tumors in order to evaluate the role of DTI in predicting postoperative outcomes.

METHODS: Adult patients with brain tumors (n = 60) underwent preoperative DTI. Three major white matter pathways (superior longitudinal fasciculi [SLF], cingulum, and corticospinal tract) were identified using DTI images, and the shortest LTD was measured for each tract. Postoperative morbidity and mortality information was collected from electronic medical records.

RESULTS: The ipsilesional corticospinal tract LTD and left SLF LTD were significantly associated with the occurrence rate of total postoperative motor (P = .018) and language (P < .001) deficits, respectively. The left SLF LTD was also significantly associated with the occurrence rate of new postoperative language deficits (P = .003), and the LTD threshold that best predicted this occurrence was 1 cm (P < .001). Kaplan–Meier log-rank survival analyses in patients having high-grade tumors demonstrated a significantly higher mortality for patients with a left SLF LTD <1 cm (P = .01).

CONCLUSION: Measuring tumor proximity to major white matter tracts using DTI can inform clinicians of the likelihood of postoperative functional deficits. A distance of 1 cm or less from eloquent white matter structures most significantly predicts the occurrence of new deficits with current surgical and imaging techniques.

 

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The Fluoropen: a simple low-cost device to detect intraoperative fluorescein fluorescence in stereotactic needle biopsy of brain tumors

Acta Neurochir (2017) 159:371–375

The use of fluorescein fluorescence-guided stereotactic needle biopsy has been shown to improve diagnostic accuracy and to expedite operative procedure in the stereotactic needle biopsy of high-grade gliomas. We developed a device (Fluoropen) for detecting fluorescence in brain tumor tissues obtained by fluorescein fluorescence-guided stereotactic needle biopsy.

Methods: The Fluoropen is a device consisting of a light source fitted with color filters to create the required emission and visualization wavelengths. The proof-of-concept study consisted of four consecutive patients who underwent fluorescein fluorescence-guided frameless stereotactic biopsy of brain tumor. Each sample was examined for the presence of fluorescence using the Fluoropen and compared with a microscope with fluorescence visualization capability.

Results: A total of six samples were obtained from four stereotactic needle biopsy procedures. Four out of five samples (80%) taken from the contrast-enhancing part of the tumors were shown to be fluorescent under the microscope fitted with fluorescence module and the Fluoropen. One non-contrast enhancing lesion was non-fluorescent using both the microscope fitted with fluorescence module and the Fluoropen. The Fluoropen was shown to have 100% concordance with the microscope fitted with fluorescence module.

Conclusions: The Fluoropen is a low-cost and simple standalone device for the detection of fluorescein fluorescence that can expedite stereotactic needle biopsy by providing instant confirmation of the diagnostic sample and therefore avoid the need for an intraoperative frozen section. In patients with non-contrast enhancing tumors and those who were pre-treated with dexamethasone prior to surgery, fluorescein fluorescence-guided stereotactic needle biopsy will need to be used with caution.

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Fluorescein sodium-guided resection of cerebral metastases

Acta Neurochir (2017) 159:363–367

Cerebral metastasis (CM) is the most common malignancy affecting the brain. In patients eligible for surgery, complete tumor removal is the most important predictor of overall survival and neurological outcome. The emergence of surgical microscopes fitted with a fluorescein-specific filter have facilitated fluorescein-guided microsurgery and identifi- cation of tumor tissue. In 2012, we started evaluating fluores- cein (FL) with the dedicated microscope filter in cerebral me- tastases (CM). After describing the treatment results of our first 30 patients, we now retrospectively report on 95 patients.

Methods: Ninety-five patients with CM of different primary cancers were included (47 women, 48 men, mean age, 60 years, range, 25–85 years); 5 mg/kg bodyweight of FL was intrave- nously injected at induction of anesthesia. A YELLOW 560-nm filter (Pentero 900, ZEISS Meditec, Germany) was used for microsurgical tumor resection and resection control. The extent of resection (EOR) was assessed by means of early postoperative contrast-enhanced MRI and the grade of fluorescent staining as described in the surgical reports. Furthermore, we evaluated information on neurological outcome and surgical complications as well as any adverse events.

Results: Ninety patients (95%) showed bright fluorescent staining that markedly enhanced tumor visibility. Five patients (5%); three with adenocarcinoma of the lung, one with melanoma of the skin, and one with renal cell carcinoma) showed insufficient FL stain- ing. Thirteen patients (14%) showed residual tumor tissue on the postoperative MRI. Additionally, the MRI of three patients did not confirm complete resection beyond doubt. Thus, gross-total resection had been achieved in 83% (n = 79) of patients. No adverse events were registered during the postoperative course.

Conclusions: FL and the YELLOW 560-nm filter are safe and feasible tools for increasing the EOR in patients with CM. Further prospective evaluation of the FL-guided technique in CM-surgery is in planning.

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Cushing’s disease: pathobiology, diagnosis, and management

J Neurosurg 126:404–417, 2017

Cushing’s disease (CD) is the result of excess secretion of adrenocorticotropic hormone (ACTH) by a benign monoclonal pituitary adenoma. The excessive secretion of ACTH stimulates secretion of cortisol by the adrenal glands, resulting in supraphysiological levels of circulating cortisol.
The pathophysiological levels of cortisol are associated with hypertension, diabetes, obesity, and early death. Successful resection of the CD-associated ACTH-secreting pituitary adenoma is the treatment of choice and results in immediate biochemical remission with preservation of pituitary function.
Accurate and early identification of CD is critical for effective surgical management and optimal prognosis. The authors review the current pathophysiological principles, diagnostic methods, and management of CD.
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Efficacy of the transtemporal approach with awake brain mapping to reach the dominant posteromedial temporal lesions

Acta Neurochir (2017) 159: 177

Surgeries for lesions in the dominant hippocampal and parahippocampal gyrus involving the posteromedial temporal regions are challenging to perform because they are located close to Wernicke’s area; white matter fibers related with language; the optic radiations; and critical neurovascular structures. We performed a transtemporal approach with awake functional mapping for lesions affecting the dominant posteromedial temporal regions. The aim of this study was to assess the feasibility, safety, and efficacy of awake craniotomy for these lesions.

Methods: We retrospectively reviewed four consecutive patients with tumors or cavernous angiomas located in the left hippocampal and parahippocampal gyrus, which further extended to the posteromedial temporal regions, who underwent awake surgery between December 2014 and January 2016.

Results: Four patients with lesions associated with the left hippocampal and parahippocampal gyrus, including the posteromedial temporal area, who underwent awake surgery were registered in the study. In all four patients, cortical and subcortical eloquent areas were identified via direct electrical stimulation. This allowed determination of the optimal surgical route to the angioma or tumor, even in the language-dominant hippocampal and parahippocampal gyrus. In particular, this approach enabled access to the upper part of posteromedial temporal lesions, while protecting the subcortical language-related fibers, such as the superior longitudinal fasciculus.

Conclusions: This study revealed that awake brain mapping can enable the safe resection of dominant posteromedial temporal lesions, while protecting cortical and subcortical eloquent areas. Furthermore, our experience with four patients demonstrates the feasibility, safety, and efficacy of awake surgery for these lesions.

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Perioperative Outcomes in Intracranial Pleomorphic Xanthoastrocytoma

Neurosurgery 80:105–111, 2017

Patients with pleomorphic xanthoastrocytoma (PXA) routinely undergo multiple procedures to ensure recurrence-free survival and are resultantly at increased risk of experiencing perioperative complications (regional, medical, and/or neurological), a combination of which has not been recorded in previous studies.

OBJECTIVE: To determine perioperative outcomes in a cohort of patients (adult and pediatric) with intracranial PXA.

METHODS: We retrospectively identified 39 patients who underwent surgery at our insti- tution for intracranial PXA between 1994 and 2011. Demographic factors were recorded along with Karnofsky Performance Status (KPS), complications, and mortality.

RESULTS: Mean patient age was 31 years at the most recent surgery. A majority of patients (24; 62%) had multiple surgeries with a mean of 2 operations per patient. Eleven PXAs (28%) were malignant (grade III or IV). Perioperative complications included permanent neurological worsening in 4 patients (10%), regional complications in 4 (10%), and medical complications in 3 (8%). Preoperative KPS was ≥70 in 34 of 38 patients (89%). Long- term postoperative KPS was ≥70 in 36 of 37 patients (97%), suggesting good functional outcomes. There was no perioperative mortality, but 7 patients (18%) died of tumor progression. Patients with malignant PXAs trended toward higher risk of regional compli- cations (3 of 11 patients [27%]; P = .06), received adjuvant therapy more often (10 of 11 patients [91%]; P < .001), had higher mortality from tumor progression (7 of 11 patients [64%]; P < .001), and were significantly larger (mean, 6.05 ± 0.73 cm standard error of the mean; n = 7; P < .01).

CONCLUSION: Both pediatric and adult PXAs may be resected with good functional outcomes. Perioperative neurological complications are relatively common, but do not affect long-term functional outcome or mortality. Malignant PXAs are higher risk for perioperative complications and, ultimately, death from tumor progression, despite increased use of adjuvant radiation and chemotherapy.

 

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Passive language mapping combining real-time oscillation analysis with cortico-cortical evoked potentials for awake craniotomy

J Neurosurg 125:1580–1588, 2016

Electrocortical stimulation (ECS) is the gold standard for functional brain mapping; however, precise functional mapping is still difficult in patients with language deficits. High gamma activity (HGA) between 80 and 140 Hz on electrocorticography is assumed to reflect localized cortical processing, whereas the cortico-cortical evoked potential (CCEP) can reflect bidirectional responses evoked by monophasic pulse stimuli to the language cortices when there is no patient cooperation. The authors propose the use of “passive” mapping by combining HGA mapping and CCEP recording without active tasks during conscious resections of brain tumors.

Methods Five patients, each with an intraaxial tumor in their dominant hemisphere, underwent conscious resection of their lesion with passive mapping. The authors performed functional localization for the receptive language area, using real-time HGA mapping, by listening passively to linguistic sounds. Furthermore, single electrical pulses were delivered to the identified receptive temporal language area to detect CCEPs in the frontal lobe. All mapping results were validated by ECS, and the sensitivity and specificity were evaluated.

Results Linguistic HGA mapping quickly identified the language area in the temporal lobe. Electrical stimulation by linguistic HGA mapping to the identified temporal receptive language area evoked CCEPs on the frontal lobe. The combination of linguistic HGA and frontal CCEPs needed no patient cooperation or effort. In this small case series, the sensitivity and specificity were 93.8% and 89%, respectively.

Conclusions The described technique allows for simple and quick functional brain mapping with higher sensitivity and specificity than ECS mapping. The authors believe that this could improve the reliability of functional brain mapping and facilitate rational and objective operations. Passive mapping also sheds light on the underlying physiological mechanisms of language in the human brain.

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Comparison between electric-field-navigated and line-navigated TMS for cortical motor mapping in patients with brain tumors

Acta Neurochir (2016) 158:2277–2289

For the navigation of transcranial magnetic stimulation (TMS), various techniques are available. Yet, there are two basic principles underlying them all: electric-fieldnavigated transcranial magnetic stimulation (En-TMS) and line-navigated transcranial magnetic stimulation (Ln-TMS). The current study was designed to compare both methods.

Methods To explore whether there is a difference in clinical applicability, workflow, and mapping results of both techniques, we systematically compared motor mapping via EnTMS and Ln-TMS in 12 patients suffering from brain tumors.

Results The number of motor-positive stimulation spots and the ratio of positive spots per overall stimulation numbers were significantly higher for En-TMS (motor-positive spots: EnTMS vs. Ln-TMS: 128.3 ± 35.0 vs. 41.3 ± 26.8, p < 0.0001; ratio of motor-positive spots per number of stimulations: EnTMS vs. Ln-TMS: 38.0 ± 9.2 % vs. 20.0 ± 14.4 %, p = 0.0031). Distances between the En-TMS and Ln-TMS motor hotspots were 8.3 ± 4.4 mm on the ipsilesional and 8.6 ± 4.5 mm on the contralesional hemisphere (p = 0.9124).

Conclusions The present study compares En-TMS and LnTMS motor mapping in the neurosurgical context for the first time. Although both TMS systems tested in the present study are explicitly designed for application during motor mapping in patients with brain lesions, there are differences in applicability, workflow, and results between En-TMS and Ln-TMS, which should be distinctly considered during clinical use of the technique. However, to draw final conclusions about accuracy, confirmation of motor-positive Ln-TMS spots by intraoperative stimulation is crucial within the scope of upcoming investigations.

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Analysis of the surgical benefits of 5-ALA–induced fluorescence in intracranial meningiomas

J Neurosurg 125:1408–1419, 2016

One of the most important causes for recurrence of intracranial meningiomas is residual tumor tissue that remains despite assumed complete resection. Recently, intraoperative visualization of meningioma tissue by 5-aminolevulinic acid (5-ALA)–induced protoporphyrin IX (PpIX) fluorescence was reported. The aim of this study was to investigate the possible surgical benefits of PpIX fluorescence for detection of meningioma tissue.

Methods 5-ALA was administered preoperatively to 190 patients undergoing resection of 204 intracranial meningiomas. The meningiomas’ PpIX fluorescence status, fluorescence quality (strong or vague), and intratumoral fluorescence homogeneity were investigated during surgery. Additionally, specific sites, including the dural tail, tumor-infiltrated bone flap, adjacent cortex, and potential satellite lesions, were analyzed for PpIX fluorescence in selected cases.

Results PpIX fluorescence was observed in 185 (91%) of 204 meningiomas. In the subgroup of sphenoorbital meningiomas (12 of 204 cases), the dural part showed visible PpIX fluorescence in 9 cases (75%), whereas the bony part did not show any PpIX fluorescence in 10 cases (83%). Of all fluorescing meningiomas, 168 (91%) showed strong PpIX fluorescence. Typically, most meningiomas demonstrated homogeneous fluorescence (75% of cases). No PpIX fluorescence was observed in any of the investigated 89 dural tails. In contrast, satellite lesions could be identified through PpIX fluorescence in 7 cases. Furthermore, tumor-infiltrated bone flaps could be visualized by PpIX fluorescence in all 13 cases. Notably, PpIX fluorescence was also present in the adjacent cortex in 20 (25%) of 80 analyzed cases.

Conclusions The authors’ data from this largest patient cohort to date indicate that PpIX fluorescence enables intraoperatively visualization of most intracranial meningiomas and allows identification of residual tumor tissue at specific sites. Thus, intraoperative detection of residual meningioma tissue by PpIX fluorescence might in future reduce the risk of recurrence.

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Intraoperative Near-Infrared Optical Imaging Can Localize Gadolinium-Enhancing Gliomas During Surgery

Neurosurgery 79:856–871, 2016

Although real-time localization of gliomas has improved with intraoperative image guidance systems, these tools are limited by brain shift, surgical cavity deformation, and expense.

OBJECTIVE: To propose a novel method to perform near-infrared (NIR) imaging during glioma resections based on preclinical and clinical investigations, in order to localize tumors and to potentially identify residual disease.

METHODS: Fifteen patients were identified and administered a Food and Drug Administration-approved, NIR contrast agent (Second Window indocyanine green [ICG], 5 mg/kg) before surgical resection. An NIR camera was utilized to localize the tumor before resection and to visualize surgical margins following resection. Neuropathology and magnetic resonance imaging data were used to assess the accuracy and precision of NIR fluorescence in identifying tumor tissue.

RESULTS: NIR visualization of 15 gliomas (10 glioblastoma multiforme, 1 anaplastic astrocytoma, 2 low-grade astrocytoma, 1 juvenile pilocytic astrocytoma, and 1 ganglioglioma) was performed 22.7 hours (mean) after intravenous injection of ICG. During surgery, 12 of 15 tumors were visualized with the NIR camera. The mean signal-tobackground ratio was 9.5 6 0.8 and fluorescence was noted through the dura to a maximum parenchymal depth of 13 mm. The best predictor of positive fluorescence was enhancement on T1-weighted imaging; this correlated with signal-to-background ratio (P = .03). Nonenhancing tumors did not demonstrate NIR fluorescence. Using pathology as the gold standard, the technique demonstrated a sensitivity of 98% and specificity of 45% to identify tumor in gadolinium-enhancing specimens (n = 71).

CONCLUSION: With the use of Second Window ICG, gadolinium-enhancing tumors can be localized through brain parenchyma intraoperatively. Its utility for margin detection is promising but limited by lower specificity.

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Maximizing safe resection of low- and high-grade glioma

dti-gliomas

J Neurooncol (2016) 130:269–282

Surgical resection plays a central role in the management of gliomas. In this study, we review the evidence in support of extent of resection to improve survival, symptom management, and time to malignant transformation in low- and high-grade gliomas, and summarize the findings from our literature search regarding the role of extent of resection and intraoperative practices to maximize safety.

There is a growing body of evidence supporting improved overall survival, improved progression-free survival, and superior quality of life with greater extent of resection.

Additionally, a better understanding of central nervous system plasticity allows for a staged approach to the surgical management of low- and intermediate-grade gliomas.

A number of intraoperative techniques have been utilized to offer safer glioma surgery with greater extent of resection. Approaches such as awake brain tumor surgery can be safely performed with low failure rates and excellent long-term functional outcomes.

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Reoperation for Recurrent Glioblastoma and Its Association With Survival Benefit

multifocal glioblastoma

Neurosurgery 79:678–689, 2016

Glioblastoma is the most common and aggressive primary brain tumor. Despite current treatment, recurrence is inevitable. There are no clear guidelines for treatment of recurrent glioblastoma.

OBJECTIVE: To investigate factors at initial surgery predictive of reoperation, and the prognostic variables associated with survival, including reoperation for recurrence.

METHODS: A retrospective cohort study was performed, including adult patients diagnosed with glioblastoma between January 2010 and December 2013. Student t test and Fisher exact test compared continuous and categorical variables between reoperation and nonreoperation groups. Univariable and Cox regression multivariable analysis was performed.

RESULTS: In a cohort of 204 patients with de novo glioblastoma, 49 (24%) received reoperation at recurrence. The median overall survival in the reoperation group was 20.1 months compared with 9.0 months in the nonreoperation group (P = .001). Reoperation was associated with longer overall survival in our total population (hazard ratio, 0.646; 95% confidence interval, 0.543-0.922; P = .016) but subject to selection bias. Subgroup analyses excluding patients unlikely to be considered for reoperation suggested a much less significant effect of reoperation on survival, which warrants further study with larger cohorts. Factors at initial surgery predictive for reoperation were younger age, smaller tumor size, initial extent of resection $50%, shorter inpatient stay, and maximal initial adjuvant therapy. When unfavorable patient characteristics are excluded, reoperation is not an independent predictor of survival.

CONCLUSION: Patients undergoing reoperation have favorable prognostic characteristics, which may be responsible for the survival difference observed. We recommend that a large clinical registry be developed to better aid consistent and homogenous data collection.

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Surgery of insular and paralimbic diffuse low-grade gliomas: technical considerations

insular-lgg-2

J Neurooncol (2016) 130:289–298

Once considered a ‘‘no man’s land’’ especially when invaded by a diffuse low grade glioma (DLGG), the insula remains to this day a surgical challenge. Surgery for insular DLGG involves consideration of its hidden location under the potentially eloquent operculae, the proximity to vascular tree and high density of functions not only in the insular cortex but also in the white fiber pathways passing under the insular lobe. The natural history of DLGG and the potential benefits and consequences of the surgical approach also need a close look.

In the last decade, a better knowledge of the functional anatomy and connectivity of this region, as well as an improvement in surgical techniques as direct stimulation mapping, combined with an increasing literature showing a favorable impact of maximal resection for DLGG, were deciding factors in the paradigmatic shift from expectative treatment to early surgical management.

Here, our goal is to discuss the structural and functional aspects of the insula, the specificities of insular and paralimbic DLGG by emphasizing the technical considerations of surgery in this region, as well as its oncological and functional outcomes. In summary, this new strategy based upon early maximal safe surgical resection showed both oncological benefit and preservation of quality of life—or even an improvement thanks to epilepsy relief.

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Laser interstitial thermal therapy followed by minimal-access transsulcal resection for the treatment of large and dif cult to access brain tumors

litt

Neurosurg Focus 41 (4):E14, 2016

Laser interstitial thermal therapy (LITT), sometimes referred to as “stereotactic laser ablation,” has demonstrated utility in a subset of high-risk surgical patients with dificult to access (DTA) intracranial neoplasms. However, the treatment of tumors larger than 10 cm3 is associated with suboptimal outcomes and morbidity. This may limit the utility of LITT in dealing with precisely those large or deep tumors that are most dif cult to treat with conventional approaches. Recently, several groups have reported on minimally invasive transsulcal approaches utilizing tubular retracting systems. However, these approaches have been primarily used for intraventricular or paraventricular lesions, and subtotal resections have been reported for intraparenchymal lesions. Here, the authors describe a combined approach of LITT followed by minimally invasive transsulcal resection for large and DTA tumors.

Methoss The authors retrospectively reviewed the results of LITT immediately followed by minimally invasive, trans-sulcal, transportal resection in 10 consecutive patients with unilateral, DTA malignant tumors > 10 cm3. The patients, 5 males and 5 females, had a median age of 65 years. Eight patients had glioblastoma multiforme (GBM), 1 had a previously treated GBM with radiation necrosis, and 1 had a melanoma brain metastasis. The median tumor volume treated was 38.0 cm3.

Results The median tumor volume treated to the yellow thermal dose threshold (TDT) line was 83% (range 76%– 92%), the median tumor volume treated to the blue TDT line was 73% (range 60%–87%), and the median extent of resection was 93% (range 84%–100%). Two patients suffered mild postoperative neurological de cits, one transiently. Four patients have died since this analysis and 6 remain alive. Median progression-free survival was 280 days, and median overall survival was 482 days.

Conclusions Laser interstitial thermal therapy followed by minimally invasive transsulcal resection, reported here for the first time, is a novel option for patients with large, DTA, malignant brain neoplasms. There were no unexpected neurological complications in this series, and operative characteristics improved as surgeon experience increased. Further studies are needed to elucidate any differences in survival or quality of life metrics.

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Accurate Delineation of Glioma Infiltration by Advanced PET/MR Neuro-Imaging (FRONTIER Study)

f1-largeNeurosurgery 79:535–540, 2016

Glioma imaging, used for diagnostics, treatment planning, and followup, is currently based on standard magnetic resonance imaging (MRI) modalities (T1 contrast-enhancement for gadolinium-enhancing gliomas and T2 fluid-attenuated inversion recovery hyperintensity for nonenhancing gliomas). The diagnostic accuracy of these techniques for the delineation of gliomas is suboptimal.

OBJECTIVE: To assess the diagnostic accuracy of advanced neuroimaging compared with standard MRI modalities for the detection of diffuse glioma infiltration within the brain.

METHODS: A monocenter, prospective, diagnostic observational study in adult patients with a newly diagnosed, diffuse infiltrative glioma undergoing resective glioma surgery. Forty patients will be recruited in 3 years. Advanced neuroimaging will be added to the standard preoperative MRI. Serial neuronavigated biopsies in and around the glioma boundaries, obtained immediately preceding resective surgery, will provide histopathologic and molecular characteristics of the regions of interest, enabling comparison with quantitative measurements in the imaging modalities at the same biopsy sites.

DISCUSSION: In this clinical study, we determine the diagnostic accuracy of advanced imaging in addition to standard MRI to delineate glioma. The results of our study can be valuable for the development of an improved standard imaging protocol for glioma treatment.

EXPECTED OUTCOME: We hypothesize that a combination of positron emission tomography, MR spectroscopy, and standard MRI will have a superior accuracy for glioma delineation compared with standard MRI alone. In addition, we anticipate that advanced imaging will correlate with the histopathologic and molecular characteristics of glioma.

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The impact of MGMT methylation and IDH-1 mutation on long-term outcome for glioblastoma treated with chemoradiotherapy

Relationship of glioblastoma multiforme to the subventricular zone is associated with survival

Acta Neurochir (2016) 158:1943–1953

Increasingly, biomarkers have been identified that correlate with improved overall and progression-free survival (OS and PFS) in glioblastoma, including MGMT methylation status and mutations in the IDH1 gene. In this study, we investigated the clinical and biological factors associated with long-term survival in glioblastoma patients treated with chemoradiotherapy.

Method Demographic and clinical data were collected for all patients with glioblastoma diagnosed between May 2004 and September 2007, treated with chemoradiotherapy and with associated tissue samples available for biomarker analysis. MGMT methylation was determined by pyrosequencing. IDH1 mutation was identified by R132H immunohistochemistry. Univariate Cox regression analysis of factors associated with survival and Kaplan-Meier survival analysis was performed using the SPSS statistics package.

Results One hundred patients were included in the study. Median follow-up was 12.2 months (range 1.6–102.4). Median OS was 12.1 months (95 % CI: 10.8–13.3) and median PFS was 8.2 months (95%CI: 6.8–9.5). The 2-, 3- and 5- year survival was 18, 9 and 6 % respectively. Three patients are still alive at 7.4, 8.3 and 8.5 years after diagnosis. Cox proportional-hazards regression identified independent prognostic factors for OS, female (p = 0.019), MGMT methylation (p < 0.0001) and IDH1 mutation (p = 0.023), and for PFS, MGMT methylation (p = 0.001) and IDH1 mutation (p = 0.018). Kaplan-Meier survival analysis showed that MGMTmethylated/ IDH1+ve was associated with a significantly longer OS 66.8 months (95 % CI: 0.0–167.8) and PFS 16.9 months (95 % CI: 11.1–22.7) when compared with MGMTmethylated/ IDH1-ve OS 15.5 months (95 % CI: 11.6–19.4) and PFS 9.4 months (95 % CI: 8–10.8) (log-rank, P = 0.000) and MGMTunmethylated/IDH1-ve OS 11.1 months (95 % CI: 8.5– 13.7) and PFS 6.3 months (95 % CI: 4.4–8.3) (log-rank, p=0.000).

Conclusions While the importance of MGMT methylation is well established, we demonstrate that the combination of MGMTmethylated/IDH1+ve is associated with considerably longer OS and PFS in this series of chemoradiotherapy-treated glioblastoma tumours. The long-term cognitive function and quality of life in these long-term survivors warrant investigation.

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