Radiology reporting of low-grade glioma growth underestimates tumor expansion.

BACKGROUND: An important aspect in the management of patients with diffuse low-grade gliomas (LGGs) involves monitoring the lesions via serial magnetic resonance imaging (MRI). However, radiological interpretations of LGG interval scans are often qualitative and thus difficult to use clinically. METHODS: To contextualize these assessments, we retrospectively compared radiological interpretations of LGG growth or stability to volume change measured by manual segmentation. Tumor diameter was also measured in one, two, and three dimensions to evaluate reported methods for assessment of glioma progression, including RECIST criteria, Macdonald/RANO criteria, and mean tumor diameter/ellipsoid method. RESULTS: Tumors evaluated as stable by radiologists grew a median volume of 5.1 mL (11.1%) relative to the comparison scan, and those evaluated as having grown had a median volume increase of 13.3 mL (23.7%). Diameter-based measurements corresponded well but tended to overestimate gold standard segmented volumes. In addition, agreement with segmented volume measurements improved from 17.6 ± 8.0 to 4.5 ± 5.8 to 3.9 ± 3.6 mm for diameter and from 104.0 ± 96.6 to 25.3 ± 36.8 to 15.9 ± 21.3 mL for volume with radiological measurements in one, two, and three dimensions, respectively. Measurement overestimation increased with tumor size. CONCLUSIONS: Given accumulating evidence that LGG volume and growth are prognostic factors, there is a need for objective lesion measurement. Current radiological reporting workflows fail to appreciate and communicate the true expansion of LGGs. While volumetric analysis remains the gold standard for assessment of growth, careful diametric measurements in three dimensions may be an acceptable alternative.

Operative Complications with and without Image Guidance: A Systematic Review and Meta-Analysis of the Ommaya Reservoir Literature.

BACKGROUND: The use of image guidance (IG) in neurosurgery is ubiquitous, even though evidence from patient outcome data has remained limited to smaller, mostly observational, studies. Ommaya reservoir insertion (ORI) has been available as a treatment option for targeted intraventricular pharmacotherapy since the 1960s, far preceding the modern neuronavigation era. We conducted a systematic review and meta-analysis investigating the impact of IG on surgical outcome from ORI. METHODS: A systematic database search of MEDLINE and EMBASE was performed to identify studies on operative outcomes from ORI. Only studies reporting patient demographics and perioperative outcomes (hemorrhage, infection, malposition, malfunction, and mortality) were included. Study quality was assessed via MINORS criteria. RESULTS: Of the 3560 records screened, 43 studies met study inclusion criteria, for a total of 1995 ORI procedures. Pooled rates of outcome for IG compared with non-IG were 6.4% versus 14.1% for overall complications; 2.0% compared with 2.8% for catheter malfunction; 2.3% compared with 3.3% for catheter malposition; 0.7% compared with 4.5% for early infection; and 0.6% compared with 1.4% for mortality. Postoperative hemorrhage was increased at 3.4% compared with 2.4%. Subgroup analysis revealed a difference in early infection rate between frameless and frame-based IG at 0.0% versus 1.9%. Meta-regression revealed a relationship between publication date and all operative outcomes except for catheter malposition and hemorrhage. CONCLUSIONS: This study offers a historical context on the evolution of the practice of ORI and comprises the largest observational analysis of operative outcomes providing objective support for the use of IG in neurosurgery.

Impact of Functional Magnetic Resonance Imaging on Clinical Outcomes in a Propensity-Matched Low Grade Glioma Cohort.

BACKGROUND: This study aims to evaluate the impact of preoperative functional magnetic resonance imaging (fMRI) on clinical outcomes in patients with low grade glioma (LGG). METHODS: In a retrospective propensity-matched cohort study, we compared patients with LGG based on whether they underwent fMRI as part of preoperative assessment. Twelve patients with LGG who underwent preoperative fMRI were selected, and a contemporaneous group of 12 control patients with LGG who did not undergo fMRI were matched to the fMRI group based on age, sex, and 1p/19q status. RESULTS: fMRI group subjects tended to have more aggressive surgeries (67% resection, 33% biopsy) than the control group (33% resection, 67% biopsy). There were no significant differences in outcomes between the 2 groups. Time between clinical assessment and surgery tended to be longer in the fMRI group (6.3 ± 4.2 weeks) than in the control group (2.7 ± 2.2 weeks). Extent of resection was similar between the 2 cohorts. fMRI group subjects had lower preoperative functional status and tended to have a greater postoperative functional status improvement than control group subjects. Mean survival was not significantly different (fMRI group 5-year survival: 88.9%, control group 5-year survival: 61.1%). CONCLUSIONS: We evaluated the impact of preoperative fMRI in patients with LGG in this propensity-matched cohort study. This study has not demonstrated any significant difference in outcomes between the fMRI and control groups; however, there were nonsignificant trends for patients who underwent fMRI to undergo more aggressive surgical interventions and have a greater postoperative functional status improvement.

Tumor growth dynamics in serially-imaged low-grade glioma patients.

BACKGROUND: Diffuse low-grade gliomas (LGGs) are infiltrative, slow-growing primary brain tumors that remain relatively asymptomatic for long periods of time before progressing into aggressive and fatal high-grade gliomas. METHODS: We retrospectively identified LGG patients with numerous (≥ 8) serial magnetic resonance imaging (MRI) studies. Tumor volumes were measured by manual segmentation on serial imaging to study the natural history and growth of the lesion. Patient demographic information, tumor characteristics, and histological data were collected from electronic medical records and paper charts. RESULTS: Out of 74 LGG patients, 10 patients (13.5%) were identified to meet the study criteria with number of MRIs acquired ranging from 8 to 18 (median, 11.5) over a median of 79.7 months (range 39.8-113.8 months). Tumor diameter increased at a median of 2.17 mm/year in a linear trajectory. Cox regression analysis revealed that initial tumor volume was an independent predictor of time to clinical intervention, and Mann-Whitney U test found that patients younger than 50 years old had significantly slower-growing tumors. Clinical intervention was more likely for tumors above a volume threshold of 73.6 mL. CONCLUSION: We retrospectively analyzed the natural history of LGGs of patients managed at a single institution with numerous serial MRI scans. Comparisons of our cohort to the literature suggest that this is a subset of particularly slow-growing and low-risk tumors.

Image-guided Ommaya reservoir insertion for intraventricular chemotherapy: a retrospective series.

BACKGROUND: Ayub Ommaya proposed a surgical technique for subcutaneous reservoir and pump placement in 1963 to allow access to intraventricular cerebrospinal fluid (CSF). Currently, the most common indication for Ommaya reservoir insertion (ORI) in adults is for patients with hematologic or leptomeningeal disorders requiring repeated injection of chemotherapy into the CSF space. Historically, the intraventricular catheter has been inserted blindly based on anatomical landmarks. The purpose of this study was to examine short-term complication rates with ORI with image guidance (IG) and without image guidance (non-IG). METHODS: We retrospectively evaluated all operative cases of ORI from 2000 to 2014 by the senior author. Patient demographic data, surgical outcomes, and peri-operative complications were collected. Accurate placement and early (30-day) morbidity or mortality were considered primary outcomes. RESULTS: Fifty-five consecutive patients underwent ORI by the senior author over the study period (43.5 ± 16.6 years; 40.0% female). Indications for placement included acute lymphoblastic leukemia, diffuse large B-cell lymphoma, and leptomeningeal carcinomatosis. There were seven (12.7%) total complications: three (37.5%) with no-IG versus four (8.5%) with IG. Catheter malpositions were significantly higher in the non-IG group at 37.5% compared to 2.1%. Catheters were also more likely to require multiple passes with non-IG at 25% compare to 0% with IG. There were no early infections in either group. CONCLUSIONS: We demonstrate improved accuracy and decreased complications using an image-guided approach compared with a traditional approach. Our results support routine use of intra-operative image guidance for proximal catheter insertion in elective ORI for intraventricular chemotherapy.

Functional Magnetic Resonance Imaging for Preoperative Planning in Brain Tumour Surgery.

BACKGROUND: Functional magnetic resonance imaging (fMRI) is being increasingly used for the preoperative evaluation of patients with brain tumours. METHODS: The study is a retrospective chart review investigating the use of clinical fMRI from 2002 through 2013 in the preoperative evaluation of brain tumour patients. Baseline demographic and clinical data were collected. The specific fMRI protocols used for each patient were recorded. RESULTS: Sixty patients were identified over the 12-year period. The tumour types most commonly investigated were high-grade glioma (World Health Organization grade III or IV), low-grade glioma (World Health Organization grade II), and meningioma. Most common presenting symptoms were seizures (69.6%), language deficits (23.2%), and headache (19.6%). There was a predominance of left hemispheric lesions investigated with fMRI (76.8% vs 23.2% for right). The most commonly involved lobes were frontal (64.3%), temporal (33.9%), parietal (21.4%), and insular (7.1%). The most common fMRI paradigms were language (83.9%), motor (75.0%), sensory (16.1%), and memory (10.7%). The majority of patients ultimately underwent a craniotomy (75.0%), whereas smaller groups underwent stereotactic biopsy (8.9%) and nonsurgical management (16.1%). Time from request for fMRI to actual fMRI acquisition was 3.1±2.3 weeks. Time from fMRI acquisition to intervention was 4.9±5.5 weeks. CONCLUSIONS: We have characterized patient demographics in a retrospective single-surgeon cohort undergoing preoperative clinical fMRI at a Canadian centre. Our experience suggests an acceptable wait time from scan request to scan completion/analysis and from scan to intervention.

Her2neu amplification associates with Co-deletion 1p/14q in recurrent meningiomas.

BACKGROUND: The current methods to predict recurrence and aggressive behaviour of meningiomas rely mainly on histological grading, histological subtype, proliferative index, as well as brain invasion. In many instances, histological grade alone fails to predict recurrence in the grade I and grade II meningiomas. Deletions of 1p and 14q have previously been reported to correlate with poor prognosis in terms of either recurrence or higher histological grades. The Her2neu (ErbB2) amplification has been shown to be a useful predictor of aggressive behaviour in breast and ovarian tumours, but its significance in meningioma is so far uncertain. METHOD: In order to determine the cytogenetic differences between 22 recurrent and 25 non-recurrent meningiomas of all grades, we used fluorescent in situ hybridization (FISH) DNA probes for 1p36, 14q11.2 and 17q11.2-12 (Her2neu) on formalin fixed paraffin embedded (FFPE) tissue from the Brain Tumour Tissue Bank (BTTB), London Health Science Center (LHSC). RESULTS: We showed a positive association for meningioma recurrence correlated with 1p36 deletion plus or minus 14q 11.2 deletions in all grades of meningiomas. The Her2neu amplification was strongly associated with 1p/14q co-deletion in cases of recurrent meningiomas, especially the higher grade tumours. CONCLUSION: These cytogenetic markers can be applied in addition to histological grading for predicting the risk of recurrence and biological behaviour.

Hypofractionated radiotherapy with or without concurrent temozolomide in elderly patients with glioblastoma multiforme: a review of ten-year single institutional experience.

The landmark Stupp study demonstrated a survival advantage with concomitant and adjuvant temozolomide (TMZ) with standard radiotherapy (RT) in glioblastoma multiforme (GBM) patients but excluded those older than 70 years. The prospective Roa study of older GBM patients treated with hypofractionated 3-week course RT demonstrated equivalence to standard 6-week course RT. Taken together, these trials suggest hypofractionated RT with TMZ may be a reasonable treatment option for elderly GBM patients. We conducted a retrospective review of GBM patients (age ≥60 years) treated with hypofractionated RT and temozolomide at our institution between 2000 and 2010. We identified 112 patients who received hypofractionated RT, with 57 receiving concurrent and adjuvant TMZ and 55 without concurrent chemotherapy. Of the 55 patients who received hypofractionated RT alone initially, 24 subsequently received TMZ as salvage treatment at time of progression. Among the concurrent RT + TMZ patients, mean age was 70 years (range 60-86), median KPS was 80 (range 30-100) and 24/57 (42%) received prior debulking surgery. Median overall survival (OS) among the RT + TMZ patients was 6.9 months (95% CI, 4.5-8.6). Patients without concurrent chemotherapy were similar in demographics (age, sex, corticosteroid use, KPS) except 34/55 (62%) were debulked (P-value 0.045.) Median OS was 9.3 months (95% CI, 5.9-11.8) (P-value 0.351). Sub-group analysis revealed patients treated with initial hypofractionated radiation with salvage TMZ had increased median OS of 13.3 months (95% CI, 9.9-19.3) (P-value 0.012). Our results suggest concurrent and adjuvant TMZ does not confer a survival benefit in elderly GBM patients. A sequential approach may be a more effective and efficient strategy by selecting responding patients who may benefit most from subsequent salvage chemotherapy.

Do epileptic seizures predict outcome in patients with oligodendroglioma?

BACKGROUND: Many patients with an oligodendroglioma (OD) experience seizures, some of which become refractory to anti-epileptic drugs (AEDs). This study aims (1) to quantify the rate of seizures and medically refractory epilepsy in patients with ODs; and (2) to determine if there is any association between short-term and long-term survival, and the presence and drug-responsiveness of seizures. METHODS: A retrospective review was conducted of the medical records of patients who had been pathologically identified as having an OD at the London Health Sciences Centre or the London Regional Cancer Program in London, Ontario from January 1996 to July 2008. Deaths were ascertained by reviewing all hospital records. Survival analysis was performed. RESULTS: One-hundred sixty-six patients met inclusion criteria. Epileptic seizures were the presenting feature or occurred as part of the initial manifestation of the OD in 75.3% of patients, with 90.4% (n=150) experiencing at least one seizure and 76.5% developing epilepsy over the course of observation. Of the 150 patients with seizures, 23 experienced a single seizure (13.9% of the 166), whereas 127 patients experienced multiple seizures (76.5%). In those with multiple seizures, the epilepsy was refractory to drug treatment slightly more than half the time (54.3%). Survival analysis demonstrated consistently superior survival among those with a single seizure. Those without seizures had the worst survival rates over the first few years post-diagnosis; but then no further deaths occurred. Survival among those with refractory seizures tended to be better than among those whose seizures were drug responsive, over the first 10 years post-diagnosis. CONCLUSIONS: Seizures are common and may influence survival in patients with oligodendogliomas. Those who experience just one seizure appear to do best.

Suturing technique and the integrity of dural closures: an in vitro study.

OBJECTIVE: The watertight closure of the dura mater is fundamental to intracranial procedures in neurosurgery. Nevertheless, for any given operator and type of suture, it is still not certain which suturing technique affords the most watertight dural closure. We have developed a laboratory model that allows us to compare the pressures at which dural closures leak when different suturing techniques are used. METHODS: Human cadaveric dura was secured to a glass cylinder filled with colored saline. By application of force to a bag of saline attached to the cylinder, the pressure at which sutured dural incisions leak can be recorded. Using this method, we have compared the closure of 2-cm dural incisions with 3-0 silk using the following techniques (10 per group): 1) interrupted simple, 2) running simple, 3) running locked, and 4) interrupted vertical mattress. We have also compared the closure of 1- x 3-cm dural windows with cadaveric dura and 3-0 silk using the same suturing techniques (10 per group). RESULTS: The pressure at which 2-cm linear dural incisions leaked was significantly higher when they were closed with the interrupted simple suturing technique (P < 0.05). There was no significant difference among the different suturing techniques when they were used to close a 1- x 3-cm dural window with a duraplasty. Overall, the pressures at which sutured linear dural incisions leaked were higher than the pressures at which sutured dural windows closed with duraplasties leaked. CONCLUSION: In the experimental model described, an interrupted simple suturing technique affords the most watertight dural closure for linear incisions, whereas no suturing technique proved advantageous for the closure of a duraplasty.