A Comparative Analysis of the Usefulness of Survival Prediction Models for Patients with Glioblastoma in the Temozolomide Era: The Importance of Methylguanine Methyltransferase Promoter Methylation, Extent of Resection, and Subventricular Zone Location.

OBJECTIVE: Several survival prediction models for patients with glioblastoma have been proposed, but none is widely used. This study aims to identify the predictors of overall survival (OS) and to conduct an independent comparative analysis of 5 prediction models. METHODS: Multi-institutional data from 159 patients with newly diagnosed glioblastoma who received adjuvant temozolomide concomitant chemoradiotherapy (CCRT) were collected. OS was assessed by Cox proportional hazards regression and adjusted for known prognostic factors. An independent CCRT patient cohort was used to externally validate the 1) RTOG (Radiation Therapy Oncology Group) recursive partitioning analysis (RPA) model, 2) Yang RPA model, and 3) Wee RPA model, Chaichana model, and the RTOG nomogram model. The predictive accuracy for each model at 12-month survival was determined by concordance indices. Calibration plots were performed to ascertain model prediction precision. RESULTS: The median OS for patients who received CCRT was 19.0 months compared with 12.7 months for those who did not (P < 0.001). Independent predictors were: 1) subventricular zone II tumors (hazard ratio [HR], 1.6; 95% confidence interval [CI], 1.0-2.5); 2) methylguanine methyltransferase promoter methylation (HR, 0.36; 95% CI, 0.2-0.6); and 3) extent of resection of >85% (HR, 0.59; 95% CI, 0.4-0.9). For 12-month OS prediction, the RTOG nomogram model was superior to the RPA models with a c-index of 0.70. Calibration plots for 12-month survival showed that none of the models was precise, but the RTOG nomogram performed relatively better. CONCLUSIONS: The RTOG nomogram best predicted 12-month OS. Methylguanine methyltransferase promoter methylation status, subventricular zone tumor location, and volumetric extent of resection should be considered when constructing prediction models.

Moving the goalposts: A comparison of different definitions for primary external ventricular drain infection and its risk factors: A multi-center study of 2575 patients.

External ventricular drainage is the most common procedure performed in daily neurosurgical practice. One devastating complication is ventriculostomy-associated infection, but the establishment of evidence-based management guidelines has been hindered by the lack of an universal definition. There is also limited data with regard to the utility of comorbidity health indices and surgery-related factors in predicting infection. This study aims to compare the incidence of infection according to five commonly used definitions and to identify risk factors for this complication. 2575 patients from seven neurosurgical centers in Hong Kong underwent primary external ventricular drainage. The frequency of infection according to Gozal was 2.2% (n=57), 4.7% (Chi), 0.6% (Lozier), 0.8% (Lyke) and 2.8% (Scheithauer). The commonest pathogen was coagulase negative staphylococcus (39%) and 49% of all microbial isolates were multiple-drug resistant. The mean Charlson comorbidity index was 0.5±1.1. Using Gozal's definition as the primary endpoint, the index was not predictive of infection and no surgical risk factors were identified. The only significant risk factor was the performance of two or more additional neurosurgical procedures within 30days of catheterization (OR: 2.1, 95% CI 1.1-4.5). The rate of infection is relatively low, but considerable disparity exists depending on the definition used. Our data implies that patient factors, in particular the Charlson comorbidity index, and variations in surgical practice are less influential than the strict observance of infection control measures. The high incidence of antibiotic-resistant bacteria is concerning and the routine of exchange of catheters within 30days should be discouraged.

Risk factors for seizures and antiepileptic drug-associated adverse effects in high-grade glioma patients: A multicentre, retrospective study in Hong Kong.

AIM: The aim of this present study was to determine the frequency, as well as risk factors, for seizures and antiepileptic drug (AED)-associated adverse effects among high-grade glioma (HGG) patients. PATIENTS AND METHODS: A multicentre, retrospective study of adult Chinese Hong Kong patients from three neurosurgical centres diagnosed with supratentorial HGG between 1 January 2001 and 31 December 2010 was performed. RESULTS: A total of 198 patients, with a mean age of 55 years (range: 18-88) and a mean follow up of 15 months, was recruited. Most suffered from glioblastoma multiforme (GBM) (63 per cent) followed by anaplastic astrocytoma (25 per cent). Median overall survival for patients with GBM was 8 months, and 11 months for those with grade III gliomas. Prophylactic AED was prescribed in 165 patients (83 per cent), and 64 per cent of patients were continued until end of life or last follow up. A total of 112 patients (57 per cent) experienced seizures at a mean duration of 8 months postoperatively (range: 1 day-75 months). Independent predictors for seizures were a diagnosis of GBM [adjusted odds ratio (OR): 2.33, 95 per cent confidence interval (CI): 1.21-4.52] and adjuvant radiotherapy (adjusted OR: 2.97, 95 per cent CI: 1.49-6.62). One-fifth of patients (21 per cent) experienced AED adverse effects, with idiosyncratic cutaneous reactions and hepatotoxicity most frequently observed. An independent predictor for adverse effects was exposure to aromatic AED, such as phenytoin, carbamazepine and phenobarbital (adjusted OR: 3.32, 95 per cent CI: 1.32-8.40). CONCLUSIONS: Antiepileptic drug prescription for primary seizure prophylaxis is both pervasive and prolonged for HGG patients. Seizures occur frequently, but most were delayed and none were life threatening. Judicious prescription of AED is required, especially when a significant proportion of patients experience adverse effects. Patients with a diagnosis of GBM and exposure to radiotherapy are at risk. We suggest, contrary to present practice, that primary seizure prophylaxis be given only during the perioperative period and resumed when they occur. We also recommend avoidance of aromatic AED due to their association with idiosyncratic adverse effects.