Day: 04/01/2012

Use of 11C-methionine PET parametric response map for monitoring WT1 immunotherapy response in recurrent malignant glioma.

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Immunotherapy targeting the Wilms tumor 1 (WT1) gene product is a promising treatment modality for patients with malignant gliomas, and there have been reports of encouraging results. It has become clear, however, that Gd-enhanced MR imaging does not reflect prognosis, thereby necessitating a more robust imaging evaluation system for monitoring response to WT1 immunotherapy. To meet this demand, the authors performed a voxel-wise parametric response map (PRM) analysis of 11C-methionine PET (MET-PET) in WT1 immunotherapy and compared the data with the overall survival after initiation of WT1 immunotherapy (OSWT1).

Methods

Fourteen patients with recurrent malignant glioma were included in the study, and OSWT1 was compared with: 1) volume and length change in the contrast area of the tumor on Gd-enhanced MR images; 2) change in maximum uptake of 11C-methionine; and 3) a more detailed voxel-wise PRM analysis of MET-PET pre- and post-WT1 immunotherapy.

Results

The PRM analysis was able to identify the following 3 areas within the tumor core: 1) area with no change in 11C-methionine uptake pre- and posttreatment; 2) area with increased 11C-methionine uptake posttreatment (PRM+MET); and 3) area with decreased 11C-methionine uptake posttreatment. While the results of Gd-enhanced MR imaging volumetric and conventional MET-PET analysis did not correlate with OSWT1 (p = 0.270 for Gd-enhanced MR imaging length, p = 0.960 for Gd-enhanced MR imaging volume, and p = 0.110 for MET-PET), the percentage of PRM+MET area showed excellent correlation (p = 0.008) with OSWT1.

Conclusions

This study describes the limited value of Gd-enhanced MR imaging and highlights the potential of voxel-wise PRM analysis of MET-PET for monitoring treatment response in immunotherapy for malignant gliomas.

Source: Journal of Neurosurgery

 

 

Incidence and causes of perioperative mortality after primary surgery for intracranial tumors.

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Surgical mortality is a frequent outcome measure in studies of volume-outcome relationships, and the Agency for Healthcare Research and Quality has endorsed surgical mortality after craniotomies as an Inpatient Quality Indicator. Still, the frequency and causes of 30-day mortality after neurosurgical procedures have not been much explored. The authors sought to study the frequency and possible causes of death following primary intracranial tumor operations. They also sought to explore a possible predictive value of perioperative mortality rates from neurosurgical centers in relation to long-term survival.

Methods

Using population-based data from the Norwegian cancer registry, the authors identified 15,918 primary operations for primary CNS tumors treated in Norway in the period from August 1955 through December 2008. Patients were followed up until death, emigration, or September 2009. Causes of mortality as indicated on death certificates were studied. Factors associated with an increased risk of perioperative death were identified.

Results

The overall risk of perioperative death after first-time surgery for primary intracranial tumors is currently 2.2% and has decreased over the last decades. An age ≥ 70 years and histopathological entities with poor long-term prognoses are risk factors. Overlapping lesions are also associated with excess risk, indicating that lesion size or multifocality may matter. The overall risk of perioperative death is also higher in biopsy cases than in resection cases. Perioperative mortality rates of the 4 Norwegian neurosurgical centers were not predictive of their respective long-term survival rates.

Conclusions

Although considered surgically related if they occur within the first 30 days of surgery, most early postoperative deaths can happen independent of the handiwork of the operating surgeon or anesthesiologist. Overall prognosis of the disease seems to be a strong predictor of perioperative death—perhaps not surprisingly since the 30-day mortality rate is merely the intonation of the Kaplan-Meier curve. Both referral and treatment policies at a neurosurgical center will therefore markedly affect such early outcomes, but early deaths may not necessarily reflect overall quality of care or long-term results. The low incidence of perioperative death in intracranial tumor surgery also greatly limits the statistical power in comparative analyses, such as between published patient series or between centers and certainly between surgeons. Therefore the authors question the value of perioperative mortality rates as a quality indicator in modern neurosurgery for tumors.

Source: Journal of Neurosurgery

 

 

Establishment and characterization of a primary human chordoma xenograft model.

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Chordomas are rare tumors arising from remnants of the notochord. Because of the challenges in achieving a complete resection, the radioresistant nature of these tumors, and the lack of effective chemotherapeutics, the median survival for patients with chordomas is approximately 6 years. Reproducible preclinical model systems that closely mimic the original patient’s tumor are essential for the development and evaluation of effective therapeutics. Currently, there are only a few established chordoma cell lines and no primary xenograft model. In this study, the authors aimed to develop a primary chordoma xenograft model.

Methods

The authors implanted independent tumor samples from 2 patients into athymic nude mice. The resulting xenograft line was characterized by histopathological analysis and immunohistochemical staining. The patient’s tumor and serial passages of the xenograft were genomically analyzed using a 660,000 single-nucleotide polymorphism array.

Results

A serially transplantable xenograft was established from one of the 2 patient samples. Histopathological analysis and immunohistochemical staining for S100 protein, epithelial membrane antigen, and cytokeratin AE1/AE3 of the primary patient sample and the xenografts confirmed that the xenografts were identical to the original chordoma obtained from the patient. Immunohistochemical staining and western blot analysis confirmed the presence of brachyury, a recently described marker of chordomas, in the tumor from the patient and each of the xenografts. Genome-wide variation was assessed between the patient’s tumor and the xenografts and was found to be more than 99.9% concordant.

Conclusions

To the best of their knowledge, the authors have established the first primary chordoma xenograft that will provide a useful preclinical model for this disease and a platform for therapeutic development.

Source: Journal of Neurosurgery

 

Long-term outcome of endovascular reconstruction with the Pipeline embolization device in the management of unruptured dissecting aneurysms of the intracranial vertebral artery.

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Use of a flow-diverting device has shown promising short-term results in the management of vertebral artery (VA) dissecting aneurysms, but there is still uncertainty regarding its long-term efficacy and safety. The authors report their initial experience with respect to the potential utility and long-term clinical outcomes of using a flow-diverting device in the treatment of unruptured dissecting VA aneurysms.

Methods

The authors conducted a retrospective review of all cases of unruptured intracranial VA dissecting aneurysms treated at their institution (Tuen Mun Hospital) with a flow-diverting device. They describe the clinical presentations and angiographic features of the cases and report the clinical outcome (with modified Rankin Scale [mRS] scores) at most recent follow-up, as well as results of the latest angiographic assessment, with particular focus on in-stent patency and side-branch occlusion.

Results

A total of 4 aneurysms were successfully obliterated by using flow-diverting devices alone. Two devices were deployed in a telescoping fashion in each of 2 aneurysms, whereas only 1 device was inserted in each of the other 2 aneurysms. No periprocedural complication was encountered. No patient showed any angiographic evidence of recurrence, in-stent thrombosis, or side-branch occlusion in angiographic reassessment at a mean of 22 months after treatment (range 18–24 months). As of the most recent clinical follow-up (mean 30 months after treatment, range 24–37 months), all patients had favorable outcomes (mRS Score 0).

Conclusions

Reconstruction using a flow-diverting device is an attractive alternative in definitive treatment of dissecting VA aneurysms, demonstrating favorable long-term clinical and angiographic outcomes and the ability to maintain parent artery and side-branch patency. It is particularly useful in cases with eloquent side-branch or dominant VA involvement.

Source: Journal of Neurosurgery

 

 

Gamma Knife surgery for basal ganglia and thalamic arteriovenous malformations.

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Gamma Knife surgery (GKS) has emerged as the treatment of choice for small- to medium-sized cerebral arteriovenous malformations (AVMs) in deep locations. The present study aims to investigate the outcomes of GKS for AVMs in the basal ganglia and thalamus.

Methods

Between 1989 and 2007, 85 patients with AVMs in the basal ganglia and 97 in the thalamus underwent GKS and were followed up for more than 2 years. The nidus volumes ranged from 0.1 to 29.4 cm3 (mean 3.4 cm3). The mean margin dose at the initial GKS was 21.3 Gy (range 10–28 Gy). Thirty-six patients underwent repeat GKS for residual AVMs at a median 4 years after initial GKS. The mean margin dose at repeat GKS was 21.1 Gy (range 7.5–27 Gy).

Results

Following a single GKS, total obliteration of the nidus was confirmed on angiograms in 91 patients (50%). In 12 patients (6.6%) a subtotal obliteration was achieved. No flow voids were observed on MR imaging in 14 patients (7.7%). Following single or repeat GKS, total obliteration was angiographically confirmed in 106 patients (58.2%) and subtotal obliteration in 8 patients (4.4%). No flow voids on MR imaging were observed in 18 patients (9.9%). The overall obliteration rates following one or multiple GKSs based on MR imaging or angiography was 68%. A small nidus volume, high margin dose, low number of isocenters, and no history of embolization were significantly associated with an increased rate of obliteration. Twenty-one patients experienced 25 episodes of hemorrhage in 850 risk-years following GKS, yielding an annual hemorrhage rate of 2.9%. Four patients died in this series: 2 due to complications of hemorrhage and 2 due to unrelated diseases. Permanent neurological deficits caused by radiation were noted in 9 patients (4.9%).

Conclusions

Gamma Knife surgery offers a reasonable chance of obliterating basal ganglia and thalamic AVMs and does so with a low risk of complications. It is an optimal treatment option in patients for whom the anticipated risk of microsurgery is too high.

Source: Journal of Neurosurgery

 

 

Endoscopic endonasal approach to cholesterol granulomas of the petrous apex: a series of 17 patients

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The aim of this study was to report the results in a consecutive series of patients who had undergone an endoscopic endonasal approach (EEA) for drainage of a petrous apex cholesterol granuloma (CG).

Methods

Seventeen cases with a confirmed diagnosis of petrous apex CG were identified from a database of more than 1600 patients who had undergone an EEA to skull base lesions at the authors’ institution in the period from 1998 to 2011. Clinical outcomes were reviewed and compared with those in previous studies of open approaches.

Results

Nine patients underwent a transclival approach and 8 patients underwent a combined transclival and infrapetrous approach. A Silastic stent was used in 11 patients (65%), a miniflap in 4 (24%), and a simple marsupialization of the cyst in 3 (18%). All symptomatic patients had partial or complete improvement of their symptoms postoperatively and at the follow-up (mean follow-up 20 months, range 3–67 months). Complications developed in 3 patients (18%) including epistaxis, chronic serous otitis media, eye dryness, and a transient sixth cranial nerve palsy. Two patients (12%) had a symptomatic recurrence of the cyst requiring repeat endoscopic endonasal drainage. There were no instances of internal carotid artery injuries, CSF leaks, or new hearing loss. The mean postoperative hospital stay was 2 days (range 0.7–4.6 days). These results were comparable with those in previous studies of open approaches to petrous apex CGs.

There was a strong correlation between the size of the cyst and the type of approach chosen (Rpb [point biserial correlation coefficient] = +0.67, p = 0.003359) and a very strong correlation between the degree of medial extension (defined by the V-angle) and the choice of approach (Rpb = +0.81, p < 0.0001). Based on these observations, the authors developed an algorithm for guiding the choice of the most appropriate route of drainage.

Conclusions

The EEA is a safe and effective alternative to traditional open approaches to petrous apex CGs.

Source: Journal of Neurosurgery

 

 

 

Growth of untreated vestibular schwannoma: a prospective study.

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Small vestibular schwannomas (VSs) are often conservatively managed and treated only upon growth. Growth is usually reported in mm/year, but describing the growth of a 3D structure by a single diameter has been questioned. As a result, VS growth dynamics should be further investigated. In addition, baseline clinical parameters that could predict growth would be helpful. In this prospective study the authors aimed to describe growth dynamics in a cohort of conservatively managed VSs. They also compared different growth models and evaluated the ability of baseline parameters to predict future growth.

Methods

Between 2000 and 2006, 178 consecutive patients with unilateral de novo small-sized VSs identified among the Norwegian population of 4.8 million persons were referred to a tertiary care center and were included in a study protocol of conservative management. Tumor size was defined by MR imaging–based volume estimates and was recorded along with clinical data at regular visits. Mixed-effects models were used to analyze the relationships between observations. Three growth models were compared using statistical diagnostic tests: a mm/year–based model, a cm3/year–based model, and a volume doubling time (VDT)-based model. A receiver operating characteristic curve analysis was used to determine a cutoff for the VDT-based model for distinguishing growing and nongrowing tumors.

Results

A mean growth rate corresponding to a VDT of 4.40 years (95% CI 3.49–5.95) was found. Other growth models in this study revealed mean growth rates of 0.66 mm/year (95% CI 0.47–0.86) and 0.19 cm3/year (95% CI 0.12–0.26). Volume doubling time was found to be the most realistic growth model. All baseline variables had p values > 0.09 for predicting growth.

Conclusions

Based on the actual measurements, VDT was the most correct way to describe VS growth. The authors found that a cutoff of 5.22 years provided the best value to distinguish growing from nongrowing tumors. None of the investigated baseline predictors were usable as predictors of growth.

Source: Journal of Neurosurgery

 

 

Use of the histological pseudocapsule in surgery for Cushing disease: rapid postoperative cortisol decline predicting complete tumor resection.

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Subnormal postoperative serum cortisol levels indicate successful surgery and predict long-term remission of Cushing disease. Given the short serum half-lives of adrenocorticotropic hormone (ACTH) and cortisol, it is unclear why the decline in cortisol postoperatively is delayed for 18–36 hours. Furthermore, the relevance of the rate of cortisol drop immediately after surgery has not been investigated.

Methods

Patient data were analyzed from a prospectively accrued database. After surgery, cortisol replacement was withheld and serum cortisol measurements were obtained every 6 hours until values of 1.0–2.0 μg/dl or less were reached. The authors selected patients in whom serum cortisol dropped to 2 μg/dl or less after surgery (101 patients). Tumor resection was categorized as follows: 1) complete resection using the histological pseudocapsule as a surgical capsule, 2) complete piecemeal resection), 3) known incomplete resection, and 4) total hypophysectomy.

Results

The median time to reach a cortisol level of less than or equal to 2.0 μg/dl was 9.9, 19.4, 25.3, and 29.5 hours with hypophysectomy, pseudocapsule, incomplete resection, and piecemeal techniques, respectively. Pseudocapsule resection produced a faster decline in cortisol than piecemeal techniques (p = 0.0001), but not as rapid a decline as hypophysectomy (p = 0.033).

Conclusions

Complete resection by other techniques is associated with delayed cortisol decline compared with pseudocapsule surgery, which may represent the product of residual tumor cells and therefore may explain the higher rate of recurrent disease associated with piecemeal techniques. The prompt drop in cortisol after hypophysectomy compared with patients with pseudocapsule surgery suggests that the corticotrophs of the normal gland can secrete ACTH for 10–36 hours after surgery despite prolonged and severe hypercortisolism.

Source: Journal of Neurosurgery

 

Surgical treatment of patients with vestibular schwannomas after failed previous radiosurgery.

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An increasing number of patients with vestibular schwannomas (VSs) are being treated with radiosurgery. Treatment failure or secondary regrowth after radiosurgery, however, has been observed in 2%–9% of patients. In large tumors that compress the brainstem and in patients who experience rapid neurological deterioration, surgical removal is the only reasonable management option.

Methods

The authors evaluated the relevance of previous radiosurgery for the outcome of surgery in a series of 28 patients with VS. The cohort was further subdivided into Group A (radiosurgery prior to surgery) and Group B (partial tumor removal followed by radiosurgery prior to current surgery). The functional and general outcomes in these 2 groups were compared with those in a control group (no previous treatment, matched characteristics).

Results

There were 15 patients in Group A, 13 in Group B, and 30 in the control group. The indications for surgery were sustained tumor enlargement and progression of neurological symptoms in 12 patients, sustained tumor enlargement in 15 patients, and worsening of neurological symptoms without evidence of tumor growth in 1 patient. Total tumor removal was achieved in all patients in Groups A and B and in 96.7% of those in the control group. There were no deaths in any group. Although no significant differences in the neurological morbidity or complication rates after surgery were noted, the risk of new cranial nerve deficits and CSF leakage was highest in patients in Group B. Patients who underwent previous radiosurgical treatment (Groups A and B) tended to be at higher risk of developing postoperative hematomas in the tumor bed or cerebellum. The rate of facial nerve anatomical preservation was highest in those patients who were not treated previously (93.3%) and decreased to 86.7% in the patients in Group A and to 61.5% in those in Group B. Facial nerve function at follow-up was found to correlate to the previous treatment; excellent or good function was seen in 87% of the patients from the control group, 78% of those in Group A, and 68% of those in Group B.

Conclusions

Complete microsurgical removal of VSs after failed radiosurgery is possible with an acceptable morbidity rate. The functional outcome, however, tends to be worse than in nontreated patients. Surgery after previous partial tumor removal and radiosurgery is most challenging and related to worse outcome.

Source: Journal of Neurosurgery