Category: Oncology

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Is there a risk of seizures in “preventive” awake surgery for incidental diffuse low-grade gliomas?

Is there a risk of seizures in “preventive” awake surgery for incidental diffuse low-grade gliomas?

J Neurosurg 122:1397–1405, 2015

Although a large amount of data supports resection for symptomatic diffuse low-grade glioma (LGG), the therapeutic strategy regarding incidental LGG (ILGG) is still a matter of debate. Indeed, early “preventive” surgery has recently been proposed in asymptomatic patients with LGG, after showing that the extent of resection was larger than in symptomatic patients with LGG. However, the quality of life should be preserved by avoiding both neurological deficit and epilepsy. The aim of this study was to determine the risk of seizures related to such a prophylactic surgical treatment in ILGG.

Methods The authors report a prospective series of 21 patients with ILGG who underwent awake surgery with a minimum follow-up of 20 months following resection. Data regarding clinicoradiological features, surgical procedures, and outcomes were collected and analyzed. In particular, the eventual occurrence and type of seizures in the intra- and postoperative periods were studied, as follows: early (< 3 months) and long-term (until last follow-up) periods.

Results There were no intraoperative seizures in this series. During the early postoperative period, the authors observed only a single episode of partial seizures in a patient with no antiepileptic drug (AED) prophylaxis—all other patients were given antiepileptic treatment following resection. The AEDs were discontinued in all cases, with a mean delay of 8 months after surgery (range 3–24 months). No patient had permanent neurological deficits. All 21 patients returned to an active familial, social, and professional life (working full time in all cases). Total or even “supratotal” resection (the latter meaning that a margin around the tumor visible on FLAIR-weighted MRI was removed) was achieved in 14 cases (67%). In 7 patients (33%) subtotal resection was performed, with a mean residual tumor volume of 1.5 ml (range 1–7 ml). No oncological treatment was administered in the postsurgical period. The mean follow-up after surgery was 49 months (range 20–181 months). Only 2 patients had seizures during the long-term follow-up. Indeed, due to tumor progression after incomplete resection, seizures occurred in 2 cases, 39 and 78 months postsurgery, leading to administration of AEDs and adjuvant treatment. So far, all patients are still alive and enjoy a normal life.

Conclusions: The risk of inducing seizures is very low in ILGG, and it does not represent an argument against early surgery. These data strongly support the proposal of a screening policy for LGG that will evolve toward a preventive treatment in a more systematic manner.

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Agreement in the assessment of metastatic spine disease using scoring systems

metastatic spine disease

Radiotherapy and Oncology 115 (2015) 135–140

To assess variability in the use of Tomita and modified Bauer scores in spine metastases.

Materials and methods: Clinical data and imaging from 90 patients with biopsy-proven spinal metastases, were provided to 83 specialists from 44 hospitals. Spinal levels involved and the Tomita and modified Bauer scores for each case were determined twice by each clinician, with a minimum of 6-week interval. Clinicians were blinded to every evaluation. Kappa statistic was used to assess intra and inter-observer agreement. Subgroup analyses were performed according to clinicians’ specialty (medical oncology, neurosurgery, radiology, orthopedic surgery and radiation oncology), years of experience (<7, 8–13, ≥14), and type of hospital (four levels).

Results: For metastases identification, intra-observer agreement was ‘‘substantial’’ (0.60 < k < 0.80) at sacrum, and ‘‘almost perfect’’ (k > 0.80) at the other levels. Inter-observer agreement was ‘‘almost perfect’’ at lumbar spine, and ‘‘substantial’’ at the other levels. Intra-observer agreement for the Tomita and Bauer scores was almost perfect. Inter-observer agreement was almost perfect for the Tomita score and substantial for the Bauer one. Results were similar across specialties, years of experience and type of hospital.

Conclusion: Agreement in the assessment of metastatic spine disease is high. These scoring systems can improve communication among clinicians involved in oncology care.

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Birth desires and intentions of women diagnosed with a meningioma

Petroclival meningioma outcomes

J Neurosurg 122:1151–1156, 2015

To the authors’ knowledge, no previous study has examined the impact of meningioma diagnosis on women’s birth desires and intentions. In an exploratory study, the authors surveyed women affected by meningioma to determine their attitudes toward childbearing and the influences, including physician recommendations, on this major life decision and compared their responses to those of women in the general population.

Methods Meningioma survivors from the Meningioma Mommas online support group participated in an online survey that included questions on their birth desires and intentions, whether the risk of disease recurrence influenced their reproductive decisions, and risks communicated to them by their physicians. Using chi-square and rank-sum tests, the authors compared the survey participants’ responses with those of the general population as assessed by the 2006– 2010 National Survey of Family Growth. Logistic regression was used to adjust for differences in age, race, ethnicity, education, parity, pregnancy status, and infertility status in these populations.

Results Respondents with meningioma were more likely than those in the general population to report wanting a baby (70% vs 54%, respectively), intending to have a baby (27% vs 12%, respectively), and being very sure about this intention (10% vs 2%, respectively). More than half (32 of 61) of the women of childbearing age reported being advised by a physician about potential risk factors for recurrence of the meningioma, and pregnancy was the most commonly cited risk factor (26 of 61). The most common factor influencing birth desires and intentions was risk of the meningioma returning and requiring more treatment, which was reported by nearly two-thirds of the women in their childbearing years.

Conclusions A majority of the meningioma survivors of childbearing age who completed the survey reported a desire for children, although concern about the risk of meningioma recurrence was an important factor for these women when making reproductive decisions. Physicians are in a position to educate their patients on potential risk factors for recurrence and to provide contact information for services such as counseling and family planning.

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A Pilot Cost-Effectiveness Analysis of Treatments in Newly Diagnosed High-Grade Gliomas: The Example of 5-Aminolevulinic Acid Compared With White-Light Surgery

5-ALA-induced fluorescence behavior of reactive tissue changes following glioblastoma treatment with radiation and chemotherapy

Neurosurgery 76:552–562, 2015

High-grade gliomas are aggressive, incurable tumors characterized by extensive diffuse invasion of the normal brain parenchyma. Novel therapies at best prolong survival; their costs are formidable and benefit is marginal. Economic restrictions thus require knowledge of the cost-effectiveness of treatments. Here, we show the cost-effectiveness of enhanced resections in malignant glioma surgery using a well-characterized tool for intraoperative tumor visualization, 5-aminolevulinic acid (5-ALA).

OBJECTIVE: To evaluate the cost-effectiveness of 5-ALA fluorescence-guided neurosurgery compared with white-light surgery in adult patients with newly diagnosed high-grade glioma, adopting the perspective of the Portuguese National Health Service.

METHODS: We used a Markov model (cohort simulation). Transition probabilities were estimated with the use of data from 1 randomized clinical trial and 1 noninterventional prospective study. Utility values and resource use were obtained from published literature and expert opinion. Unit costs were taken from official Portuguese reimbursement lists (2012 values). The health outcomes considered were quality-adjusted life-years, lifeyears, and progression-free life-years. Extensive 1-way and probabilistic sensitivity analyses were performed.

RESULTS: The incremental cost-effectiveness ratios are below €10 000 in all evaluated outcomes, being around €9100 per quality-adjusted life-year gained, €6700 per life-year gained, and €8800 per progression-free life-year gained. The probability of 5-ALA fluorescence-guided surgery cost-effectiveness at a threshold of €20000 is 96.0% for quality-adjusted life-year, 99.6% for life-year, and 98.8% for progression-free life-year.

CONCLUSION: 5-ALA fluorescence-guided surgery appears to be cost-effective in newly diagnosed high-grade gliomas compared with white-light surgery. This example demonstrates cost-effectiveness analyses for malignant glioma surgery to be feasible on the basis of existing data.

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Impact of intraoperative magnetic resonance imaging and functional neuronavigation on surgical outcome in patients with gliomas involving language areas

Impact of intraoperative magnetic resonance imaging and functional neuronavigation on surgical outcome in patients with gliomas involving language areas

Neurosurg Rev (2015) 38:319–330

Balancing the benefit of extensive tumor resection with the consequence of potential postoperative language deficits remains a challenge in glioma surgery involving language areas. This study is designed to evaluate the impact of intraoperative magnetic resonance imaging (iMRI) and functional neuronavigation on surgical outcome in patients with gliomas involving language areas.

Two hundred seventeen patients were prospectively enrolled, 124 in the study group underwent iMRI and functional neuronavigationguided microsurgery and 93 in the control group underwent conventional navigation-guided microsurgery. Extent of tumor volume resection (EoR) and rate of gross total resection (rGTR) were calculated perioperatively. Aphasia quotient (AQ) was assessed to evaluate the change of language function perioperatively and at 6-month follow-up. Survival outcome for glioblastoma, including progression-free survival (PFS) and overall survival (OS), were recorded.

In 198 glioma patients (112 in the study group and 86 in the control group), EoR (95.50 versus 89.85 %, p<0.001) and rGTR (69.60 versus 47.70 %, p=0.002) were significantly higher in the study group, and language functions were also better at 6-month follow-up in the study group (87.47 versus 78.73, p=0.001). Furthermore, postoperative new aphasia occurred in 34.8 % of the control group, whereas it occurred only in 2.3 % of the study group (p<0.001). In addition, PFS (12.5 versus 6.6 m, p=0.003) and OS (19.6 versus 13.0 m, p<0.001) for patients with glioblastomas were dramatically prolonged in the study group than in the control group.

These results indicated that iMRI and functional neuronavigation may help maximize tumor resection, minimize language deficits in patients with gliomas involving language areas, and improve survival time for patients with glioblastomas.

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Subcortical language and non-language mapping in awake brain surgery: the use of multimodal tests

Subcortical language and non-language mapping in awake brain surgery- the use of multimodal tests

Acta Neurochir (2015) 157:577–588

Awake craniotomy is currently considered the gold standard to maximise the extent of resection and to minimise postoperative deficits in patients with supratentorial tumours near eloquent areas. In addition to direct electrical stimulation (DES) of the cortex, intraoperative subcortical mapping is increasingly used as it optimises the benefit-to-risk ratio by decreasing (permanent) postoperative neurological deficits. However, only little attention has been paid to subcortical mapping procedures and especially the tasks to be used.

Methods In this article, language and non-language testing at the subcortical level is described and discussed by means of three right-handed cases with a glioma in the left hemisphere. To assess subcortical functions, a multimodal test named the Quick Mixed Test was developed (QMT). Pre-, intra- and postoperative test results are described and discussed in detail.

Results Based on the analysis of these preliminary observations, a number of clinical recommendations for intraoperative subcortical mapping may be made: (1) the selection of a set of language and non-language tests needs to be tailored according to the functional corticosubcortical regions affected by the tumoral lesion and the patient’s characteristics (job/hobby/daily life activities); (2) language and non-language tests should be presented in a multimodal and alternating way during subcortical stimulation since this approach enables screening various functions simultaneously or in a very short period of time and (3) spontaneous speech is a useful adjunct to standardised tests since it most resembles daily life conversation.

Conclusion Administration of multimodal tests during subcortical DES such as the experimental QMT may facilitate identification of eloquent pathways leading to avoidance of permanent neurological impairments.

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New concepts in the management of diffuse low-grade glioma: Proposal of a multistage and individualized therapeutic approach

New concepts in the management of diffuse low-grade glioma- Proposal of a multistage and individualized therapeutic approach

Neuro-Oncology 17(3), 332–342, 2015

Diffuse low-grade glioma grows, migrates along white matter tracts, and progresses to high-grade glioma. Rather than a “wait and see” policy, an aggressive attitude is now recommended, with early surgery as the first therapy. Intraoperative mapping, with maximal resection according to functional boundaries, is associated with a longer overall survival (OS) while minimizing morbidity.

However, most studies have investigated the role of only one specific treatment (surgery, radiotherapy, chemotherapy) without taking a global view of managing the cumulative time while preserving quality of life (QoL) versus time to anaplastic transformation.

Our aim is to switch towards a more holistic concept based upon the anticipation of a personalized and long-term multistage therapeutic approach, with online adaptation of the strategy over the years using feedback from clinical, radiological, and histomolecular monitoring.

This dynamic strategy challenges the traditional approach by proposing earlier therapy, by repeating treatments, and by reversing the classical order of therapies (eg, neoadjuvant chemotherapy when maximal resection is impossible, no early radiotherapy) to improve OS and QoL.

New individualized management strategies should deal with the interactions between the course of this chronic disease, reaction brain remapping, and oncofunctional modulation elicited by serial treatments. This philosophy supports a personalized, functional, and preventive neuro-oncology.

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Convection-enhanced delivery to the central nervous system

Convection-enhanced delivery to the central nervous system

J Neurosurg 122:697–706, 2015

Convection-enhanced delivery (CED) is a bulk flow–driven process. Its properties permit direct, homogeneous, targeted perfusion of CNS regions with putative therapeutics while bypassing the blood-brain barrier. Development of surrogate imaging tracers that are co-infused during drug delivery now permit accurate, noninvasive real-time tracking of convective infusate flow in nervous system tissues.

The potential advantages of CED in the CNS over other currently available drug delivery techniques, including systemic delivery, intrathecal and/or intraventricular distribution, and polymer implantation, have led to its application in research studies and clinical trials.

The authors review the biophysical principles of convective flow and the technology, properties, and clinical applications of convective delivery in the CNS.

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An evidence-based treatment algorithm for the management of WHO Grade II and III meningiomas

Management of WHO Grade II and III meningiomas

Neurosurg Focus 38 (3):E3, 2015

The management of WHO Grade II “atypical” meningiomas (AMs) and Grade III “malignant” meningiomas (MMs) remains controversial and under-investigated in prospective studies. The roles of surgery, radiation therapy, radiosurgery, and chemotherapy have been incompletely delineated. This has left physicians to decipher how they should treat patients on a case-by-case basis.

In this study, the authors review the English-language literature on the management and clinical outcomes associated with AMs and MMs diagnosed using the WHO 2000/2007 grading criteria. Twenty-two studies for AMs and 7 studies for MMs were examined in detail. The authors examined clinical decision points using the literature and concepts from evidence-based medicine.

Acknowledging the retrospective nature of the studies concerning AM and MM, the authors did find evidence for the following clinical strategies: 1) maximal safe resection of AM and MM; 2) active surveillance after gross-total resection of AM; 3) adjuvant radiation therapy after subtotal resection of AM, especially in the absence of putative radioresistant features; and 4) adjuvant radiation therapy after resection of MM.

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Anatomic features of glioblastoma and their potential impact on survival

Anatomic features of glioblastoma and their potential impact on survival

Acta Neurochir (2015) 157:179–186

Many reports on glioblastoma multiforme discuss the prognostic impact of anatomical features such as cysts, necrotic changes, extent of edema or subependymal spread of tumor cells. In the present study, we examined different growth patterns and their possible relations to patient survival.

Methods To analyze whether anatomical characteristics are related to prognosis, we reviewed the prospectively collected pre- and postoperative MRIs of 83 patients in the 5-ALA study, provided by the 5-ALA Glioma Study Group. Following a standardized analytic work flow, the tumor volume and site, presence of necrosis or cysts, and perifocal edema were assessed preoperatively. In the same way, postoperative MRI and the MRI at first recurrence were analyzed. In addition, survival time of the patients was documented.

Results Median survival time of all 83 patients was 15.1 months (range 1.5 to 70.1, mean 18). The site or volume of glioblastoma, as well as the presence of intratumoral necrosis or cysts, did not exert a significant effect on survival time; 96.4 % of recurrences occurred within the former resection margin. Tumors with initial contact with the subependymal zone had multifocal or ventricular recurrences significantly more often. In patients with residual tumor on early postoperative MRI, the follow-up images displayed enlargement of the remnants in 91.9 % of these cases.

Conclusions A merely anatomical analysis of the glioblastoma growth pattern cannot reliably provide prognostic information. The occurrence of most recurrences next to the resection margin and the high percentage of growing residual tumors underline the importance of complete resections.

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Combined use of 18 F-FDG PET and corticosteroid for diagnosis of deep-seated primary central nervous system lymphoma without histopathological confirmation

Combined use of 18 F-FDG PET and corticosteroid for diagnosis of deep-seated primary central nervous system lymphoma without histopathological confirmation

Acta Neurochir (2015) 157:187–194

Although histological diagnosis is indispensable in treating primary central nervous system lymphoma (PCNSL), we sometimes face an intractable situation in which tissue can be obtained only from a deep-seated brain lesion. In place of a histological diagnosis, the diagnostic adequacy of the combined use of 18 F-FDG PET and corticosteroid administration for PCNSL located in a deep-seated brain structure is reported.

Methods Patients with a deep-seated tumor were treated as having PCNSL without histological confirmation, based on the following criteria: (1) there was no evidence of systemic malignancy; (2) the tumor showed an extremely high FDG uptake relative to normal gray matter on pretreatment 18 FFDG PET;

(3) the tumor decreased in size 1 week after diagnostic therapy by corticosteroid administration on contrast-enhanced T1-weighted magnetic resonance imaging (MRI). FDG uptake of the lesion was evaluated by the maximum of standardized uptake values (SUVmax) and tumor-tonormal ratio of the SUV (T/N ratio). The extent of the tumor reduction was calculated by volumetric analysis for the treatment response to corticosteroid administration.

Results Ten patients (4 males and 6 females) matched these criteria. On pretreatment 18 F-FDG PET, mean SUVmax in the tumor was 24.8 (8.75–60.75), and mean T/N ratio was 3.24 (2.17–5.12). The extent of tumor volume reduction was shown to be 21 to 68 % 1 week after diagnostic therapy by corticosteroids. Mean total dose and duration of corticosteroids were 719 mg as prednisolone and 6.5 days, respectively. Nine patients achieved complete response and one patient achieved partial response on MRI after standard treatment for PCNSL with high-dose methotrexate and/or whole-brain irradiation.

Conclusion Although the value of biopsy is universal, combining 18 F-FDG PET and corticosteroid administration is an important alternative method that may lead to the diagnosis of deep-seated PCNSLs in cases with intractable histopathological confirmations.

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Fluorescent Cancer-Selective Alkylphosphocholine Analogs for Intraoperative Glioma Detection

Fluorescent_Cancer_Selective_Alkylphosphocholine

Neurosurgery 76:115–124, 2015

5-Aminolevulinic acid (5-ALA)-induced tumor fluorescence aids brain tumor resections but is not approved for routine use in the United States. We developed and describe testing of 2 novel fluorescent, cancer-selective alkylphosphocholine analogs, CLR1501 (green) and CLR1502 (near infrared), in a proof-of-principle study for fluorescence-guided glioma surgery.

OBJECTIVE: To demonstrate that CLR1501 and CLR1502 are cancer cell-selective fluorescence agents in glioblastoma models and to compare tumor-to-normal brain (T:N) fluorescence ratios with 5-ALA.

METHODS: CLR1501, CLR1502, and 5-ALA were administered to mice with magnetic resonance imaging-verified orthotopic U251 glioblastoma multiforme- and glioblastoma stem cell-derived xenografts. Harvested brains were imaged with confocal microscopy (CLR1501), the IVIS Spectrum imaging system (CLR1501, CLR1502, and 5-ALA), or the Fluobeam near-infrared fluorescence imaging system (CLR1502). Imaging and quantitative analysis of T:N fluorescence ratios were performed.

RESULTS: Excitation/emission peaks are 500/517 nm for CLR1501 and 760/778 nm for CLR1502. The observed T:N ratio for CLR1502 (9.28 6 1.08) was significantly higher (P , .01) than for CLR1501 (3.51 6 0.44 on confocal imaging; 7.23 6 1.63 on IVIS imaging) and 5-ALA (4.81 6 0.92). Near-infrared Fluobeam CLR1502 imaging in a mouse xenograft model demonstrated high- contrast tumor visualization compatible with surgical applications.

CONCLUSION: CLR1501 (green) and CLR1502 (near infrared) are novel tumor-selective fluorescent agents for discriminating tumor from normal brain. CLR1501 exhibits a tumor-to-brain fluorescence ratio similar to that of 5-ALA, whereas CLR1502 has a superior tumor-to-brain fluorescence ratio. This study demonstrates the potential use of CLR1501 and CLR1502 in fluorescence-guided tumor surgery.

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True aqueductal tumors: a unique entity

True aqueductal tumors-a unique entity

Acta Neurochir (2015) 157:169–177

Pure aqueductal tumors (ATs) differ from pineal region and tectal/tegmental tumors in that they are epicentered within the aqueduct. Nevertheless, these tumors are rarely described as a separate type of tumor, and are often grouped with other lesions located in the same vicinity. The present multicenter study focuses on our experience treating patients with pure ATs.

Methods Data from three large tertiary centers was collected retrospectively, including presenting symptoms, treatment paradigm, surgical approaches, pathology, and outcome.

Results Between 1999 and 2013, 16 patients with AT were diagnosed and treated at the three tertiary centers. Ages at presentation ranged from 5.5 to 57 years. Thirteen patients presented with hydrocephalus-related symptoms, and two were identified incidentally. Thirteen patients underwent an endoscopic third ventriculostomy, and two of these underwent a simultaneous endoscopic biopsy (one grade II ependymoma, one non-specified low-grade glioma). Two others underwent shunt placement. Three patients underwent resection due to tumor progression. Pathologies included glioblastoma multiforme, glioneural tumor, and ependymoma grade II. All non-resected tumors remained stable or grew only minimally.

Conclusions ATs are a rare entities that usually present with obstructive hydrocephalus. Treatment includes primarily cerebrospinal fluid drainage (preferably via an endoscopic third ventriculostomy). Simultaneous endoscopic biopsy may be done in selected cases. Tumor resection should be reserved for growing tumors; the trans-fourth ventricular or transchoroidal approaches are probably safer than other approaches used to reach the tectal region.

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Mapping p53 Mutations in Low-Grade Glioma: A Voxel-Based Neuroimaging Analysis

Mapping p53 Mutations in Low-Grade Glioma

AJNR Am J Neuroradiol 36:70–76

Brain tumor location has proved to be a prognostic factor that may be associated with features of neoplastic origin. Mutation of p53 is an atypical genetic change that occurs during tumorigenesis. Thus, a potential correlation may exist between tumor location and p53 status. The purpose of the current study was to identify anatomic characteristics of mutant p53 expression by using quantitative neuroimaging analyses.

MATERIALS AND METHODS: Preoperative MR images from 182 patients with histologically confirmed low-grade gliomas were retrospectively analyzed. All tumors were manually marked and registered to the standard space. Using a voxel-based lesion-symptom mapping analysis, we located brain regions associated with a high occurrence of p53 mutation and corrected them by using a permutation test. The acquired clusters were further included as a factor in survival analyses.

RESULTS: Statistical analysis demonstrated that the left medial temporal lobe and right anterior temporal lobe were specifically associated with high expression of mutant p53. Kaplan-Meier curves showed that tumors located in these regions were associated with significantly worse progression-free survival compared with tumors occurring elsewhere.

CONCLUSIONS: Our voxel-level imaging analysis provides new evidence that genetic changes during cancer may have anatomic specificity. Additionally, the current study suggests that tumor location identified on structural MR images could potentially be used for customized presurgical outcome prediction.

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The role of cancer stem cells in glioblastoma

The role of cancer stem cells in glioblastoma

Neurosurg Focus 37 (6):E6, 2014

Recurrence in glioblastoma is nearly universal, and its prognosis remains dismal despite significant advances in treatment over the past decade. Glioblastoma demonstrates considerable intratumoral phenotypic and molecular heterogeneity and contains a population of cancer stem cells that contributes to tumor propagation, maintenance, and treatment resistance. Cancer stem cells are functionally defined by their ability to self-renew and to differentiate, and they constitute the diverse hierarchy of cells composing a tumor. When xenografted into an appropriate host, they are capable of tumorigenesis.

Given the critical role of cancer stem cells in the pathogenesis of glioblastoma, research into their molecular and phenotypic characteristics is a therapeutic priority.

In this review, the authors discuss the evolution of the cancer stem cell model of tumorigenesis and describe the specific role of cancer stem cells in the pathogenesis of glioblastoma and their molecular and microenvironmental characteristics. They also discuss recent clinical investigations into targeted therapies against cancer stem cells in the treatment of glioblastoma.

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Surgery of Intradural Extramedullary Tumors: Retrospective Analysis of 107 Cases

Intradural extramedullary tumors

Neurosurgery 75:509–514, 2014

Intradural extramedullary tumors (IDEMTs) are uncommon lesions that cause pain and neurological deficits.

OBJECTIVE: To evaluate the effects of surgery for IDEMTs.

METHODS: This cohort study recruited all patients operated on for IDEMTs at the Department of Neurology and Psychiatry of Sapienza University of Rome from January 2003 to January 2013. The analysis was conducted on clinical records evaluation over a 1-year follow-up. The Graphic Rating Scale was used to assess pain. Neurological deficits were detected through neurological examination. Quality of life was evaluated with the EuroQol (EQ-5D). Statistical interpretation of the data was performed with SPSS version 19 software.

RESULTS: One hundred seven patients were recruited. Three were lost to follow-up. Patients reported lower level of pain 1 year after surgery (before surgery, 6.05; after surgery, 3.65). Mean comparison showed a significant decrease of 22.400 (P , .001). Ninety-two patients (88.5%) were neurologically asymptomatic 1 year after surgery. Only 12 patients (11.5%) presented with a deficit, with a global decrease of 39% (x2 = 27.6; P, .005). The quality of life in patients was middle to high (mean rating of EQ-5D visual analog score, 61.78%). The lowest levels of quality of life were found in patients with sphincter dysfunctions (mean, 33.4).

CONCLUSION: Surgery for IDEMTs has a good outcome. Patients reported lower levels of pain and a drastic reduction in neurological symptoms 1 year after surgery. The quality of life is middle to high. It is influenced mainly by the neurological outcome.

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Practical surgical indicators to identify candidates for radical resection of insulo-opercular gliomas

Surgical indicators insular gliomas

J Neurosurg 121:1124–1132, 2014

Maximum resection of gliomas with minimum surgical complications usually leads to optimum outcomes for patients. Radical resection of insulo-opercular gliomas is still challenging, and selection of ideal patients can reduce risk and obtain better outcomes.

Methods. This retrospective study included 83 consecutively treated patients with newly diagnosed gliomas located at the insulo-opercular region and extending to the sylvian fissure around the primary motor and somatosensory cortices. The authors selected 4 characteristics as surgical indicators: clear tumor boundaries, negative enhancement, intact lenticulostriate arteries, and intact superior extremity of the central insular sulcus.

Results. Univariate analysis showed that tumors with clear boundaries were associated with higher rates of gross-total resection than were tumors with ambiguous boundaries (75.7% vs 19.6%). Tumors with negative enhancement compared with enhanced tumors were associated with lower frequency of tumor progression (32.0% vs 81.8%, respectively) and lower rates of surgical complications (14.0% vs 45.5%, respectively). Tumors with intact lenticulostriate arteries were associated with higher rates of gross-total resection than were tumors with involved lenticulostriate arteries (67.3% vs 11.8%, respectively). Tumors with intact superior extremity of the central insular sulcus were associated with higher rates of gross-total resection (57.4% vs 20.7%, respectively) and lower rates of surgical complications (18.5% vs 41.4%, respectively) than were tumors with involved anatomical structures. Multivariate analysis showed that clear tumor boundaries were independently associated with gross-total resection (p < 0.001). Negative enhancement was found to be independently associated with surgical complications (p = 0.005), overall survival times (p < 0.001), and progression-free survival times (p = 0.004). Independent associations were also found between intact lenticulostriate arteries and gross-total resection (p < 0.001), between intact lenticulostriate arteries and progression-free survival times (p = 0.026), and between intact superior extremity of the central insular sulcus and gross-total resection (p = 0.043). Among patients in whom all 4 indicators were present, prognosis was good (5- year survival rate 93.3%), resection rate was maximal (gross-total resection 100%), and surgical complication rate was minimal (6.7%). Also among these patients, overall rates of survival (p = 0.003) and progression-free survival (p = 0.005) were significantly higher than among patients in whom fewer indicators were present.

Conclusions. The authors propose 4 simple indicators that can be used to identify ideal candidates for radical resection of insulo-opercular gliomas, improve the outcomes, and promote maximum resection without introducing neurological complications. The indicators are clear tumor boundaries, negative enhancement, intact lenticulostriate arteries, and intact superior extremity of the central insular sulcus.

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Management of Atypical Cranial Meningiomas, Part 2: Predictors of Progression and the Role of Adjuvant Radiation After Subtotal Resection

Meningioma_-_brain_invasion_-_high_mag

Neurosurgery 75:356–363, 2014

The efficacies of adjuvant stereotactic radiosurgery (SRS) and external beam radiation therapy (EBRT) for atypical meningiomas (AMs) after subtotal resection (STR) remain unclear.

OBJECTIVE: To analyze the clinical, histopathological, and radiographic features associated with progression in AM patients after STR.

METHODS: Fifty-nine primary AMs after STR were examined for predictors of progression, including the impact of SRS and EBRT, in a retrospective cohort study.

RESULTS: Twenty-seven patients (46%) progressed after STR (median, 30 months). On univariate analysis, spontaneous necrosis positively (hazard ratio = 5.2; P = .006) and adjuvant radiation negatively (hazard ratio = 0.3; P = .009) correlated with progression; on multivariate analysis, only adjuvant radiation remained independently significant (hazard ratio = 0.3; P = .006). SRS and EBRT were associated with greater local control (LC; P = .02) and progression-free survival (P = .007). The 2-, 5-, and 10-year actuarial LC rates after STR vs STR/EBRT were 60%, 34%, and 34% vs 96%, 65%, and 45%. The 2-, 5-, and 10-year actuarial progression-free survival rates after STR vs STR/EBRT were 60%, 30%, and 26% vs 96%, 65%, and 45%. Compared with STR alone, adjuvant radiation therapy significantly improved LC in AMs that lack spontaneous necrosis (P = .003) but did not improve LC in AMs with spontaneous necrosis (P = .6).

CONCLUSION: Adjuvant SRS or EBRT improved LC of AMs after STR but only for tumors without spontaneous necrosis. Spontaneous necrosis may aid in decisions to administer adjuvant SRS or EBRT after STR of AMs.

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Effect of neoadjuvant temozolomide upon volume reduction and resection of diffuse low-grade glioma

Effect of neoadjuvant temozolomide upon volume reduction and resection of diffuse low-grade glioma

J Neurooncol (2014) 120:155–161

Maximal safe resection is associated with prolonged survival in patients with low-grade glioma (LGG). It has been suggested that neoadjuvant temozolomide may provide sufficient tumor shrinkage to facilitate aggressive surgical debulking. We examined the impact of temozolomide upon volume reduction and resectability of LGG.

We retrospectively identified 20 adult patients with biopsy proven, deemed not totally resectable LGGs, treated initially with temozolomide. Volumetric 3D (calculated from serial FLAIR images) and 2D tumor measurements were obtained prior to treatment and at 3 months post-treatment. The anticipated extent of resection (EOR) at the 2 time points was measured based on anatomical limitations, calculated as: [(total tumor volume – unresectable tumor volume)/total tumor volume] x 100. Eloquent cortex, deep structures and corpus callosum were considered unresectable.

Mean tumor volume was 68.4 cm3 pre-treatment and 49.5 cm3 at 3 months post-treatment. The mean change from baseline to 3 months after treatment was -32.5 % (p\0.001). Mean 2D pre-treatment area was 28.6 and 23.3 cm2 at 3 months post-treatment. The 2D change was also significant, with mean change of -17 % (p\0.001). 5 % had partial response; 40 % minor response; 45 % stable disease; and 10 % progressive disease by RANO criteria. Mean pretreatment anticipated EOR was 67.2 and 71.5 %at 3 months post-treatment. The mean change from baseline was 4.3 % (p = 0.10).

Our findings demonstrate significant volumetric and 2D reduction of LGG with temozolomide. Although this tumor shrinkage might facilitate radical surgical resection in some cases, our data failed to show statistically significant improvement in anticipated EOR.

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Aneurysmal bone cysts of the spine: treatment options and considerations

ABC

J Neurooncol (2014) 120:171–178

Aneurysmal bone cysts (ABCs) are benign bone lesions with annual incidences ranging from 1.4 to 3.2 cases per million people. Approximately, 10–30 % of ABCs are found in the spine. Such lesions are traditionally treated with curettage or other intralesional techniques.

Because ABCs can be locally aggressive, intralesional resection can be incomplete and result in recurrence. This has led to increased use of novel techniques, including selective arterial embolization (SAE).

This study aims to: (1) compare outcomes based on extent of surgical resection, and (2) compare the efficacy of SAE versus surgical resection.

Clinical data pertaining to 71 cases of spinal ABCs were ambispectively collected from nine institutions in Europe, North America, and Australia. Twenty-two spinal ABCs were treated with surgery, 32 received preoperative embolization and surgery, and 17 were treated with SAE.

Most tumors were classified as Enneking stage 2 (n = 29, 41 %) and stage 3 (n = 29, 41 %). Local recurrence and survival were investigated and a significant difference was not observed between treatment groups. However, all three local recurrences occurred following surgical resection. Surgical resection was further categorized based on Enneking appropriateness. Recurrences only occurred following intralesional Enneking inappropriate (EI) resections (P = 0.10), a classification that characterized 47 % of all surgical resections. Furthermore, 56 % of intralesional resections were EI, compared to only 10 % of en bloc resections (P = 0.01). Although SAE treatment did not result in any local recurrences, 35 % involved more than five embolization procedures.

Spinal ABCs can be effectively treated with intralesional resection, en bloc resection, or SAE. Preoperative embolization should be considered before intralesional resection to limit intraoperative bleeding. Treatment plans must be guided by lesion characteristics and clinical presentation.

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