PURPOSE: Temozolomide is a novel oral alkylating agent with demonstrated efficacy as second-line therapy for patients with recurrent anaplastic astrocytoma and glioblastoma multiforme (GBM). This phase II study was performed to determine the safety, tolerability, and efficacy of concomitant radiation plus temozolomide therapy followed by adjuvant temozolomide therapy in patients with newly diagnosed GBM. PATIENTS AND METHODS: Sixty-four patients were enrolled onto this open-label, phase II trial. Temozolomide (75 mg/m 2 /d × 7 d/wk for 6 weeks) was administered orally concomitant with fractionated radiotherapy (60 Gy total dose: 2 Gy × 5 d/wk for 6 weeks) followed by temozolomide monotherapy (200 mg/m 2 /d × 5 days, every 28 days for six cycles). The primary end points were safety and tolerability, and the secondary end point was overall survival. RESULTS: Concomitant radiation plus temozolomide therapy was safe and well tolerated. Nonhematologic toxicities were rare and mild to moderate in severity. During the concomitant treatment phase, grade 3 or 4 neutropenia, thrombocytopenia, or both were observed in 6% of patients, including two severe infections with Pneumocystis carinii. During adjuvant temozolomide, 2% and 6% of cycles were associated with grade 3 and 4 neutropenia or thrombocytopenia, respectively. Median survival was 16 months, and the 1- and 2-year survival rates were 58% and 31%, respectively. Patients younger than 50 years old and patients who underwent debulking surgery had the best survival outcome. CONCLUSION: Continuous daily temozolomide and concomitant radiation is safe. This regimen of concomitant chemoradiotherapy followed by adjuvant chemotherapy may prolong the survival of patients with glioblastoma. Further investigation is warranted, and a randomized trial is ongoing.
Lumbar spinal stenosis is the most frequent reason for spinal surgery in elderly people. For patients with moderate or severe symptoms different conservative and surgical treatment modalities are recommended, but knowledge about the effectiveness, in particular of the conservative treatments, is scarce. There is some evidence that surgery improves outcome in about two thirds of the patients. The aims of this study are to derive and validate a prognostic prediction aid to estimate the probability of clinically relevant improvement after surgery and to gain more knowledge about the future course of patients treated by conservative treatment modalities. This is a prospective, multi-centre cohort study within four hospitals of Zurich, Switzerland. We will enroll patients with neurogenic claudication and lumbar spinal stenosis verified by Computer Tomography or Magnetic Resonance Imaging. Participating in the study will have no influence on treatment modality. Clinical data, including relevant prognostic data, will be collected at baseline and the Swiss Spinal Stenosis Questionnaire will be used to quantify severity of symptoms, physical function characteristics, and patient's satisfaction after treatment (primary outcome). Data on outcome will be collected 6 weeks, and 6, 12, 24 and 36 months after inclusion in the study. Applying multivariable statistical methods, a prediction rule to estimate the course after surgery will be derived. The ultimate goal of the study is to facilitate optimal, knowledge based and individualized treatment recommendations for patients with symptomatic lumbar spinal stenosis.
Study Design: This is prospective multicenter cohort study. Objective: To assess whether patients with confirmed multisegmental lumbar spinal stenosis benefit more from a single-level or a multilevel decompression. Summary of Background Data: In multisegmental lumbar spinal stenotic cases, the decision as to how many levels of stenosis need to be operated to achieve the best possible clinical outcome is still unknown and remains a controversy between spine surgeons. Materials and Methods: Patients of the Swiss Lumbar Stenosis Outcome Study (LSOS) with confirmed multisegmental LSS undergoing first-time decompression without fusion were enrolled in this study. The main outcomes of this study were Spinal Stenosis Measure (SSM) symptoms and function over time, measured at baseline, 6, 12, and 24 months follow-up. Further outcomes of interest were changes in SSM, numeric rating scale, feeling thermometer, the EQ-5D-EL, and the Roland and Morris disability questionnaire from baseline to 6, 12, and 24 months. Results: After 12 months, a total of 141 patients met the inclusion criteria; of these, 33 (23%) underwent a single-level and 108 (77%) a multilevel decompression. Multilevel decompression was associated with a significantly less favorable SSM symptoms and function score, respectively, as compared with single-level decompression. In all further outcomes of interest single-level as well as multilevel patients improved over time. Conclusions: Our study showed that in multisegmental stenotic cases a single-level decompression was associated with a significantly more favorable SSM symptoms and function score, respectively, as compared with multilevel decompression. This study provides evidence that in multisegmental stenotic cases a single-level decompression might be sufficient to improve patient’s symptoms and function.
In a prospective multicenter studYI 20 patients underwent re-operation for recurrent radiculopathy after lumbo-sacral discectomYI and were treated with AOCONê-L (Adhesion Control in a Barrier Gel) to inhibit epidural fibrosis following secondary surgery. Outcomes after re-operation were assessed at six and 12 months using: Visual Analog Scales to measure radicular and back painl straight leg raising examsl and selfassessment of activity-related radicular pain. Each parameter was compared to baseline valuesl obtained immediately prior to the re-operation. The long term clinical results at 12 months after re-operation (summarized below) demonstrate a significant improvement of all clinical parametersl and correlated with the results seen at six months. Radicular painl measured when most severel was reduced from an average pre-operative score of 8.1-3.7 (p < 0.005). The straight leg raising angle increased from an average preoperative value of 41°-67° (p < 0.005). Activity-related pain mean score was 4.61 VS. 17.0 pre-operatively (p < 0.005). Low back painl measured when most severel was reduced from an average pre-operative score of 6.1 to 3.1 (p < 0.012). These clinical findings compare very favorably with data reported in the literature. There were no adverse events or complications related to the use of AOCONê-L. [Neural Res 1999; 21 Suppl 1: S51-S60]
In Brief Study Design. Prospective, controlled, observational outcome study using clinical, radiographic, and patient/physician-based questionnaire data, with patient outcomes at 12 months follow-up. Objective. To validate appropriateness criteria for low back surgery. Summary of Background Data. Most surgical treatment failures are attributed to poor patient selection, but no widely accepted consensus exists on detailed indications for appropriate surgery. Methods. Appropriateness criteria for low back surgery have been developed by a multispecialty panel using the RAND appropriateness method. Based on panel criteria, a prospective study compared outcomes of patients appropriately and inappropriately treated at a single institution with 12 months follow-up assessment. Included were patients with low back pain and/or sciatica referred to the neurosurgical department. Information about symptoms, neurologic signs, the health-related quality of life (SF-36), disability status (Roland-Morris), and pain intensity (VAS) was assessed at baseline, at 6 months, and at 12 months follow-up. The appropriateness criteria were administered prospectively to each clinical situation and outside of the clinical setting, with the surgeon and patients blinded to the results of the panel decision. The patients were further stratified into 2 groups: appropriate treatment group (ATG) and inappropriate treatment group (ITG). Results. Overall, 398 patients completed all forms at 12 months. Treatment was considered appropriate for 365 participants and inappropriate for 33 participants. The mean improvement in the SF-36 physical component score at 12 months was significantly higher in the ATG (mean: 12.3 points) than in the ITG (mean: 6.8 points) (P = 0.01), as well as the mean improvement in the SF-36 mental component score (ATG mean: 5.0 points; ITG mean: −0.5 points) (P = 0.02). Improvement was also significantly higher in the ATG for the mean VAS back pain (ATG mean: 2.3 points; ITG mean: 0.8 points; P = 0.02) and Roland-Morris disability score (ATG mean: 7.7 points; ITG mean: 4.2 points; P = 0.004). The ATG also had a higher improvement in mean VAS for sciatica (4.0 points) than the ITG (2.8 points), but the difference was not significant (P = 0.08). The SF-36 General Health score declined in both groups after 12 months, however, the decline was worse in the ITG (mean decline: 8.2 points) than in the ATG (mean decline: 1.2 points) (P = 0.04). Overall, in comparison to ITG patients, ATG patients had significantly higher improvement at 12 months, both statistically and clinically. Conclusion. In comparison to previously reported literature, our study is the first to assess the utility of appropriateness criteria for low back surgery at 1-year follow-up with multiple outcome dimensions. Our results confirm the hypothesis that application of appropriateness criteria can significantly improve patient outcomes. In this prospective, controlled study of surgery for patients with low back pain and/or sciatica, patients appropriately treated according to criteria developed by a multispecialty panel using the RAND method had a significantly higher improvement at 12 months than inappropriately treated patients. These findings suggest that application of appropriateness criteria can improve outcome.
The gene therapy approach presented in this protocol employs a polymer encapsulated, xenogenic, transfected cell line to release human ciliary neurotrophic factor (hCNTF) for the treatment of Amyotrophic Lateral Sclerosis (ALS). A tethered device, containing around 106 genetically modified cells surrounded by a semipermeable membrane, is implanted intrathecally; it provides for slow continuous release of hCNTF at a rate of 0.25 to 1.0 μg/24 hours. The semipermeable membrane prevents immunologic rejection of the cells and interposes a physical, virally impermeable barrier between cells and host. Moreover, the device and the cells it contains may be retrieved in the event of side effects. A vector containing the human CNTF gene was transfected into a line of baby hamster kidney cells (BHK) with calcium phosphate using a dihydrofolate reductase-based selection vector with a SV40 promoter and containing a HSV-tk killer gene. hCNTF is a potent neurotrophic factor which may have utility for the treatment of ALS. Systemic delivery of hCNTF in humans has been frustrated by peripheral side effects, the molecule's short half life, and its inability to cross the blood-brain barrier. The gene therapy approach described in this protocol is expected to mitigate such difficulties by local intrathecal delivery of a known quantity of continuously-synthesized hCNTF from a retrievable implant.
Lumbar spinal stenosis is the most common reason for spinal surgery in elderly patients. However, the surgical management of spinal stenosis is controversial. The aim of this review was to list aspects a surgeon considers when choosing a specific type of treatment. Appraisal of arguments reported in randomized controlled trials (RCTs) included in systematic reviews published or indexed in the Cochrane library studying surgical treatments in patients with spinal stenosis. Eight out of nine RCTs listed arguments for the choice of their treatments under investigation. The argument for decompression alone was the high success rate, the argument against was a potential increase in vertebral instability. The argument for decompression and fusion without instrumentation was that it is a well-established technique with a high fusion success rate, the argument against it was that the indication for fusion in spinal stenosis has remained unclear. The argument for decompression and fusion with instrumentation was an increased fusion rate compared to decompression and fusion without instrumentation, the argument against this was that the invasive procedure is associated with more complications. The main argument identified in this appraisal for and against decompression alone in patient with lumbar spinal stenosis was whether or not instability should be treated with (instrumented) fusion procedures. However, there is disagreement on how instability should be defined. In a first step it is important that researchers and clinicians agree on definitions for important key concepts such as instability and reoperations.
