Category: Oncology

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Prediction of Quality of Life and Survival After Surgery for Symptomatic Spinal Metastases

spinal metastasis

Neurosurgery 77:698–708, 2015

Surgery for symptomatic spinal metastases aims to improve quality of life, pain, function, and stability. Complications in the postoperative period are not uncommon; therefore, it is important to select appropriate patients who are likely to benefit the greatest from surgery. Previous studies have focused on predicting survival rather than quality of life after surgery.

OBJECTIVE: To determine preoperative patient characteristics that predict postoperative quality of life and survival in patients who undergo surgery for spinal metastases.

METHODS: In a prospective cohort study of 922 patients with spinal metastases who underwent surgery, we performed preoperative and postoperative assessment of EuroQol EQ-5D quality of life, visual analog score for pain, Karnofsky physical functioning score, complication rates, and survival.

RESULTS: The primary tumor type, number of spinal metastases, and presence of visceral metastases were independent predictors of survival. Predictors of quality of life after surgery included preoperative EQ-5D (P = .002), Frankel score (P , .001), and Karnofsky Performance Status (P , .001).

CONCLUSION: Data from the largest prospective surgical series of patients with symptomatic spinal metastases revealed that tumor type, the number of spinal metastases, and the presence of visceral metastases are the most useful predictors of survival and that quality of life is best predicted by preoperative Karnofsky, Frankel, and EQ-5D scores. The Karnofsky score predicts quality of life and survival and is easy to determine at the bedside, unlike the EQ-5D index. Karnofsky score, tumor type, and spinal and visceral metastases should be considered the 4 most important prognostic variables that influence patient management.

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The Neurological Compromised Spine Due to Ewing Sarcoma. What First: Surgery or Chemotherapy?

The Neurological Compromised Spine Due to Ewing Sarcoma

Neurosurgery 77:718–725, 2015

The vertebral column is an infrequent site of primary involvement in Ewing sarcoma. Yet when Ewing sarcoma is found in the spine, the urge for decompression is high because of the often symptomatic compression of neural structures. It is unclear in alleviating a neurological deficit whether chemotherapy is preferred over decompressive laminectomy.

OBJECTIVE: To underline, in this case series, the efficiency of initial chemotherapy before upfront surgery in the setting of high-grade spinal cord or cauda equina compression of primary Ewing sarcoma.

METHODS: Fifteen patients with Ewing sarcoma primarily located in the spine were treated at our institution between 1983 and 2015. Localization, neurological deficit expressed as Frankel grade, and outcome expressed as Rankin scale before and after initial chemotherapy, the recurrence rate, and overall survival were evaluated. The multidisciplinary approach of 1 case will be discussed in detail.

RESULTS: Nine patients (60%) were female. The age at presentation was 15.0 ± 5.5 years (range: 0.9-22.8 years). Ten patients (67%) were initially treated with chemotherapy, and 1 patient (7%) was treated primarily with radiotherapy followed by chemotherapy. The remaining 4 patients (27%) were initially treated with decompressive surgery. All patients treated primarily nonsurgically improved neurologically at followup, showing the importance of chemotherapy as an effective initial treatment option.

CONCLUSION: Adequate and quick decompression of neural structures with similar results can be achieved by chemotherapy and radiotherapy, avoiding the local spill of malignant cells.

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Subcortical anatomy as an anatomical and functional landmark in insulo-opercular gliomas

Subcortical anatomy as an anatomical and functional landmark in insulo-opercular gliomas

J Neurosurg 123:1081–1092, 2015

Little attention has been given to the functional challenges of the insular approach to the resection of gliomas, despite the potential damage of essential neural networks that underlie the insula. The object of this study is to analyze the subcortical anatomy of the insular region when infiltrated by gliomas, and compare it with the normal anatomy in nontumoral hemispheres.

Methods Ten postmortem human hemispheres were dissected, with isolation of the inferior fronto-occipital fasciculus (IFOF) and the uncinate fasciculus. Probabilistic diffusion tensor imaging (DTI) tractography was used to analyze the subcortical anatomy of the insular region in 10 healthy volunteers and in 22 patients with insular Grade II and Grade III gliomas. The subcortical anatomy of the insular region in these 22 insular gliomas was compared with the normal anatomy in 20 nontumoral hemispheres.

Results In tumoral hemispheres, the distances between the peri-insular sulci and the lateral surface of the IFOF and uncinate fasciculus were enlarged (p < 0.05). Also in tumoral hemispheres, the IFOF was identified in 10 (90.9%) of 11 patients with an extent of resection less than 80%, and in 4 (36.4%) of 11 patients with an extent of resection equal to or greater than 80% (multivariate analysis: p = 0.03).

Conclusions Insular gliomas grow in the space between the lateral surface of the IFOF and uncinate fasciculus and the insular surface, displacing and compressing the tracts medially. Moreover, these tracts may be completely infiltrated by the tumor, with a total disruption of the bundles. In the current study, the identification of the IFOF with DTI tractography was significantly associated with the extent of tumor resection. If the IFOF is not identified preoperatively, there is a high probability of achieving a resection greater than 80%.

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Awake craniotomy to maximize glioma resection: methods and technical nuances over a 27-year period

awake craniotomy

J Neurosurg 123:325–339, 2015

Awake craniotomy is currently a useful surgical approach to help identify and preserve functional areas during cortical and subcortical tumor resections. Methodologies have evolved over time to maximize patient safety and minimize morbidity using this technique. The goal of this study is to analyze a single surgeon’s experience and the evolving methodology of awake language and sensorimotor mapping for glioma surgery.

Methods The authors retrospectively studied patients undergoing awake brain tumor surgery between 1986 and 2014. Operations for the initial 248 patients (1986–1997) were completed at the University of Washington, and the subsequent surgeries in 611 patients (1997–2014) were completed at the University of California, San Francisco. Perioperative risk factors and complications were assessed using the latter 611 cases.

Results The median patient age was 42 years (range 13–84 years). Sixty percent of patients had Karnofsky Performance Status (KPS) scores of 90–100, and 40% had KPS scores less than 80. Fifty-five percent of patients underwent surgery for high-grade gliomas, 42% for low-grade gliomas, 1% for metastatic lesions, and 2% for other lesions (cortical dysplasia, encephalitis, necrosis, abscess, and hemangioma). The majority of patients were in American Society of Anesthesiologists (ASA) Class 1 or 2 (mild systemic disease); however, patients with severe systemic disease were not excluded from awake brain tumor surgery and represented 15% of study participants. Laryngeal mask airway was used in 8 patients (1%) and was most commonly used for large vascular tumors with more than 2 cm of mass effect. The most common sedation regimen was propofol plus remifentanil (54%); however, 42% of patients required an adjustment to the initial sedation regimen before skin incision due to patient intolerance. Mannitol was used in 54% of cases. Twelve percent of patients were active smokers at the time of surgery, which did not impact completion of the intraoperative mapping procedure. Stimulation-induced seizures occurred in 3% of patients and were rapidly terminated with ice-cold Ringer’s solution. Preoperative seizure history and tumor location were associated with an increased incidence of stimulation- induced seizures. Mapping was aborted in 3 cases (0.5%) due to intraoperative seizures (2 cases) and patient emotional intolerance (1 case). The overall perioperative complication rate was 10%.

Conclusions Based on the current best practice described here and developed from multiple regimens used over a 27-year period, it is concluded that awake brain tumor surgery can be safely performed with extremely low complication and failure rates regardless of ASA classification; body mass index; smoking status; psychiatric or emotional history; seizure frequency and duration; and tumor site, size, and pathology.

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The Effect of Timing of Concurrent Chemoradiation in Patients With Newly Diagnosed Glioblastoma

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

Neurosurgery 77:248–253, 2015

The effect of timing of initiation of concurrent radiation and chemotherapy after surgery on outcome of patients with glioblastoma (GBM) remains unclear.

OBJECTIVE: To further explore this issue, we analyzed 4 clinical trials for patients newly diagnosed with GBM receiving concurrent and adjuvant temozolomide.

METHODS: The cohort study included 198 adult patients with newly diagnosed supratentorial GBM who were enrolled from 2004 to 2010 in 4 clinical trials consisting of radiation plus temozolomide and an experimental agent. The interval to initiation of therapy was determined from the time of surgical resection. The partitioning deletion/ substitution/addition algorithm was used to determine the cutoff points for timing of chemoradiation at which there was a significant difference in overall survival (OS) and progression-free survival (PFS).

RESULTS: The median wait time between surgery and initiation of concurrent chemoradiation was 29.5 days (range, 7-56 days). A short delay in chemoradiation administration (at 30-34 days) was predictive of prolonged OS (hazard ratio [HR]: 0.63, P = .03) and prolonged PFS (HR: 0.68, P = .06) compared with early initiation of concurrent chemoradiation (<30 days), after adjusting for protocol and baseline prognostic variables including extent of resection by multivariate analysis. A longer delay to chemoradiation beyond 34 days was not associated with improved OS or PFS compared with early initiation (HR: 0.94, P = .77 and HR: 0.91, P = .63, respectively).

CONCLUSION: A short delay in the start of concurrent chemoradiation is beyond the classic paradigm of 4 weeks post-resection and may be associated with prolonged OS and PFS.

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Adverse radiation effect after stereotactic radiosurgery for brain metastases

Adverse radiation effect after stereotactic radiosurgery for brain metastases- incidence, time course, and risk factors

J Neurosurg 123:373–386, 2015

The authors sought to determine the incidence, time course, and risk factors for overall adverse radiation effect (ARE) and symptomatic ARE after stereotactic radiosurgery (SRS) for brain metastases.

Methods All cases of brain metastases treated from 1998 through 2009 with Gamma Knife SRS at UCSF were considered. Cases with less than 3 months of follow-up imaging, a gap of more than 8 months in imaging during the 1st year, or inadequate imaging availability were excluded. Brain scans and pathology reports were reviewed to ensure consistent scoring of dates of ARE, treatment failure, or both; in case of uncertainty, the cause of lesion worsening was scored as indeterminate. Cumulative incidence of ARE and failure were estimated with the Kaplan-Meier method with censoring at last imaging. Univariate and multivariate Cox proportional hazards analyses were performed.

Results Among 435 patients and 2200 brain metastases evaluable, the median patient survival time was 17.4 months and the median lesion imaging follow-up was 9.9 months. Calculated on the basis of 2200 evaluable lesions, the rates of treatment failure, ARE, concurrent failure and ARE, and lesion worsening with indeterminate cause were 9.2%, 5.4%, 1.4%, and 4.1%, respectively. Among 118 cases of ARE, approximately 60% were symptomatic and 85% occurred 3–18 months after SRS (median 7.2 months). For 99 ARE cases managed without surgery or bevacizumab, the probabilities of improvement observed on imaging were 40%, 57%, and 76% at 6, 12, and 18 months after onset of ARE. The most important risk factors for ARE included prior SRS to the same lesion (with 20% 1-year risk of symptomatic ARE vs 3%, 4%, and 8% for no prior treatment, prior whole brain radiotherapy [WBRT], or concurrent WBRT) and any of these volume parameters: target, prescription isodose, 12-Gy, or 10-Gy volume. Excluding lesions treated with repeat SRS, the 1-year probabilities of ARE were < 1%, 1%, 3%, 10%, and 14% for maximum diameter 0.3–0.6 cm, 0.7–1.0 cm, 1.1–1.5 cm, 1.6–2.0 cm, and 2.1–5.1 cm, respectively. The 1-year probabilities of symptomatic ARE leveled off at 13%–14% for brain metastases maximum diameter > 2.1 cm, target volume > 1.2 cm3, prescription isodose volume > 1.8 cm3, 12-Gy volume > 3.3 cm3, and 10-Gy volume > 4.3 cm3, excluding lesions treated with repeat SRS. On both univariate and multivariate analysis, capecitabine, but not other systemic therapy within 1 month of SRS, appeared to increase ARE risk. For the multivariate analysis considering only metastases with target volume > 1.0 cm3, risk factors for ARE included prior SRS, kidney primary tumor, connective tissue disorder, and capecitabine.

Conclusions Although incidence of ARE after SRS was low overall, risk increased rapidly with size and volume, leveling off at a 1-year cumulative incidence of 13%–14%. This study describes the time course of ARE and provides risk estimates by various lesion characteristics and treatment parameters to aid in decision-making and patient counseling.

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Outcomes in Reoperated Low-Grade Gliomas

OUTCOMES IN REOPERATED LOW-GRADE GLIOMAS

Neurosurgery 77:175–184, 2015

Low-grade gliomas (LGGs) comprise a diverse set of intrinsic brain tumors that correlate strongly with survival. Data on the effect of reoperation are sparse.

OBJECTIVE: To evaluate the effect of reoperation on patients with LGG.

METHODS: Fifty-two consecutive patients with reoperated LGGs treated at the University of Washington between 1986 and 2004 were identified and evaluated in a retrospective analysis.

RESULTS: The average overall survival (OS) for this cohort was 12.95 ± 0.96 years. The overall 10-year survival rate was 57%. The absence of any residual tumor at either the first or second operation was associated with significantly increased OS. Negative prognostic variables for OS included the use of upfront radiation and pathology at recurrence. The average overall progression-free survival to the first recurrence (PFS1) was 6.23 ± 0.51 years. Positive prognostic factors for improved PFS1 included the use of upfront radiation therapy. Variables not associated with differences in PFS1 included the use of upfront chemotherapy, enhancement, pathology, extent of resection, the presence of residual tumor, and Karnofsky Performance Scale score <80. The average overall progression-free survival to the second recurrence was 2.73 ± 0.39 years. Pathology at recurrence was associated with significant differences in progression-free survival to the second recurrence, as was extent of resection at time of first recurrence, and Karnofsky Performance Scale score <80.

CONCLUSION: This is among the largest studies to assess variables associated with outcome in patients with reoperated LGG. Reresection appears to provide significant benefit, and extent of resection remains the strongest predictor of OS.

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Posterior thoracic corpectomy with cage reconstruction for metastatic spinal tumors

mini-open and open transpedicular corpectomy

J Neurosurg Spine 23:217–227, 2015

Spinal metastases most commonly affect the vertebral bodies of the spinal column, and spinal cord compression is an indication for surgery. Commonly, an open posterior approach is employed to perform a transpedicular costotransversectomy or lateral extracavitary corpectomy. Because of the short life expectancies in patients with metastatic spinal disease, decreasing the morbidity of surgical treatment and recovery time is critical. One potential approach to decreasing morbidity is utilizing minimally invasive surgery (MIS). Although significant advances have been made in MIS of the spine, data supporting the utility of MIS are still emerging. This study compared outcomes of patients who underwent mini-open versus traditional open transpedicular corpectomy for spinal metastases in the thoracic spine.

Methods A consecutive cohort from 2006 to 2013 of 49 adult patients who underwent thoracic transpedicular corpectomies for spinal metastases was retrospectively identified. Patients were categorized into one of 2 groups: open surgery and mini-open surgery. Mini-open transpedicular corpectomy was performed with a midline fascial incision over only the corpectomy level of interest and percutaneous instrumentation above and below that level. The open procedure consisted of a traditional posterior transpedicular corpectomy. Chi-square test, 2-tailed t-test, and ANOVA models were employed to compare perioperative and follow-up outcomes between the 2 groups.

Results In the analysis, there were 21 patients who had mini-open surgery and 28 patients who had open surgery. The mean age was 57.9 years, and 59.2% were male. The tumor types encountered were lung (18.3%), renal/bladder (16.3%), breast (14.3%), hematological (14.3%), gastrointestinal tract (10.2%), prostate (8.2%), melanoma (4.1%), and other/unknown (14.3%). There were no significant intergroup differences in demographics, comorbidities, neurological status (American Spinal Injury Association [ASIA] grade), number of corpectomies performed, and number of levels instrumented. The open group had a mean operative time of 413.6 minutes, and the mini-open group had a mean operative time of 452.4 minutes (p = 0.329). Compared with the open group, the mini-open group had significantly less blood loss (917.7 ml vs 1697.3 ml, p = 0.019) and a significantly shorter hospital stay (7.4 days vs 11.4 days, p = 0.001). There was a trend toward a lower perioperative complication rate in the mini-open group (9.5%) compared with the open group (21.4%), but this was not statistically significant (p = 0.265). At follow-up, there were no significant differences in ASIA grade (p = 0.342), complication rate after the 30-day postoperative period (p = 0.999), or need for surgical revision (p = 0.803). The open approach had a higher overall infection rate of 17.9% compared with that in the mini-open approach of 9.5%, but this was not statistically significant (p = 0.409).

Conclusions The mini-open transpedicular corpectomy is associated with less blood loss and shorter hospital stay compared with open transpedicular corpectomy. The mini-open corpectomy also trended toward lower infection and complication rates, but these did not reach statistical significance.

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Survival in patients treated for anaplastic meningioma

Anaplastic meningioma

J Neurosurg 123:23–30, 2015

While most meningiomas are benign, 1%–3% display anaplastic features, with little current understanding regarding the molecular mechanisms underlying their formation. In a large single-center cohort, the authors tested the hypothesis that two distinct subtypes of anaplastic meningiomas, those that arise de novo and those that progress from lower grade tumors, exist and exhibit different clinical behavior.

Methods Pathology reports and clinical data of 37 patients treated between 1999 and 2012 for anaplastic meningioma at Memorial Sloan–Kettering Cancer Center (MSKCC) were retrospectively reviewed. Patients were divided into those whose tumors arose de novo and those whose tumors progressed from previously documented benign or atypical meningiomas.

Results Overall, the median age at diagnosis was 59 years and 57% of patients were female. Most patients (38%) underwent 2 craniotomies (range 1–5 surgeries) aimed at gross-total resection (GTR; 59%), which afforded better survival when compared with subtotal resection according to Kaplan-Meier estimates (median overall survival [OS] 3.2 vs 1.3 years, respectively; p = 0.04, log-rank test). Twenty-three patients (62%) presented with apparently de novo anaplastic meningiomas. Compared with patients whose tumors had progressed from a lower grade, those patients with de novo tumors were significantly more likely to be female (70% vs 36%, respectively; p = 0.04), experience better survival (median OS 3.0 vs 2.4 years, respectively; p = 0.03, log-rank test), and harbor cerebral hemispheric as opposed to skull base tumors (91% vs 43%, respectively; p = 0.002).

Conclusions Based on this single-center experience at MSKCC, anaplastic meningiomas, similar to glial tumors, can arise de novo or progress from lower grade tumors. These tumor groups appear to have distinct clinical behavior. De novo tumors may well be molecularly distinct, which is under further investigation. Aggressive GTR appears to confer an OS advantage in patients with anaplastic meningioma, and this is likely independent of tumor progression status. Similarly, those patients with de novo tumors experience a survival advantage likely independent of extent of resection.

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Magnetic resonance spectroscopy detection of high lipid levels in intraaxial tumors without central necrosis: a characteristic of malignant lymphoma

Magnetic resonance spectroscopy detection of high lipid levels in intraaxial tumors without central necrosis- a characteristic of malignant lymphoma
J Neurosurg 122:1370–1379, 2015

The differentiation of malignant lymphomas from gliomas or malignant gliomas by conventional MRI can be difficult. The authors studied Gd-enhanced MR images to obtain a differential diagnosis between malignant lymphomas and gliomas without central necrosis or cystic changes and investigated the diagnostic value of single-voxel proton MR spectroscopy (1H-MRS) using different parameters, including lipid levels.
Methods This was a retrospective study of patients with primary malignant CNS lymphoma (n = 17) and glioma (n = 122 [Grades I, II, III, and IV in 10, 30, 33, and 49 patients, respectively]) who were treated between 2007 and 2013. The authors focused on 15 patients with homogeneously enhanced primary malignant CNS lymphomas and 7 homogeneously enhanced gliomas. Images of all the included tumors were acquired with 1H-MRS at 3 T, and the diagnoses were histologically confirmed.
Results Using a short echo time 1H-MRS, large lipid peaks were observed in all 17 patients with a malignant lymphoma, in 39 patients (79.6%) with a Grade IV glioma, and in 10 patients (30.3%) with a Grade III glioma. A focus on homogeneously enhanced tumors revealed large lipid peaks in 15 malignant lymphomas that were free of central necrosis on Gd-enhanced T1-weighted images. Conversely, in the 7 homogeneously enhanced gliomas (glioblastoma and anaplastic astrocytoma, n = 2 each; anaplastic oligodendroglioma, diffuse astrocytoma, and pilomyxoid astrocytoma, n = 1 each), lipid peaks were small or absent.
Conclusions Large lipid peaks on 1H-MRS images of tumors without central necrosis were characteristic of malignant lymphomas. Conversely, small or absent lipid peaks in intraaxial tumors without central necrosis were strongly suggestive of glioma.

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Topographical Risk Factor Analysis of New Neurological Deficits Following Precentral Gyrus Resection

Topographical Risk Factor Analysis of New Neurological Deficits Following Precentral Gyrus Resection

Neurosurgery 76:714–720, 2015

Precentral gyrus resections (PGRs) have been regarded as excessively hazardous interventions because of the risk of postoperative major neurological complications.

OBJECTIVE: To evaluate the neurological deterioration that follows PGRs and to assess the topographical risk factors associated with these morbidities.

METHODS: We reviewed 33 consecutive patients who experienced pharmacologically intractable epilepsy and underwent PGR with intraoperative cortical stimulation and mapping while under awake anesthesia. The etiological diagnoses were brain neoplasm in 26 patients (78.8%), cortical lesion in 4 (12.1%), and no lesion in 3 (9.1%). The mean follow-up period was 62.6 months (range, 12-146 months). All topographical analyses of the resected quadrant area were performed based on postoperative magnetic resonance images.

RESULTS: After PGR, 22 patients (66.7%) experienced neurological worsening, including 5 permanent deficits (15.2%) and 17 transient deficits (51.5%). Permanent deficits included 2 instances of weakness, 1 dysarthria, 1 dysesthesia, and 1 fine-movement disturbance of the hand. While the neurological risk for anterior lower quadrant PGR was 20.0% (1/5), the risk for posterior upper quadrant PGR was 100.0% (10/10). The anterior upper and posterior lower quadrant PGR caused neurological deteriorations in 60.0% (6/10) and 62.5% (5/8) of the patients, respectively. In a multivariate analysis, PGR of the posterior and upper quadrant sections were significant risk factors for post-PGR neurological deteriorations (P = .022 and 0.030, respectively).

CONCLUSION: The posterior upper quadrant of the precentral gyrus was vulnerable to post-resective neurological impairment.

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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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