CyberKnife frameless stereotactic radiosurgery for spinal lesions: clinical experience in 125 cases.

OBJECTIVE: The role of stereotactic radiosurgery for the treatment of intracranial lesions is well established. Its use for the treatment of spinal lesions has been limited by the availability of effective target-immobilizing devices. Conventional external beam radiotherapy lacks the precision to allow delivery of large doses of radiation near radiosensitive structures such as the spinal cord. The CyberKnife (Accuray, Inc., Sunnyvale, CA) is an image-guided frameless stereotactic radiosurgery system that allows for the radiosurgical treatment of spinal lesions. This study evaluated the feasibility and effectiveness of the treatment of spinal lesions with a single-fraction radiosurgical technique using the CyberKnife. METHODS: The CyberKnife system uses the coupling of an orthogonal pair of x-ray cameras to a dynamically manipulated robot-mounted linear accelerator with six degrees of freedom that guides the therapy beam to the intended target without the use of frame-based fixation. Real-time imaging allows the tracking of patient movement. Cervical spine lesions were located and tracked relative to cranial bony landmarks; lower spinal lesions were tracked relative to fiducial bone markers. In this prospective cohort evaluation of a spine radiosurgery technique, 125 spinal lesions in 115 consecutive patients were treated with a single-fraction radiosurgery technique (45 cervical, 30 thoracic, 36 lumbar, and 14 sacral). There were 17 benign tumors and 108 metastatic lesions. All dose plans were calculated on the basis of computed tomographic images acquired from 1.25-mm slices with an inverse treatment planning technique. Radiosurgical circular cones ranging in diameter from 5 to 40 mm were used. RESULTS: Tumor volume ranged from 0.3 to 232 cm(3) (mean, 27.8 cm(3)). Seventy-eight lesions had received external beam irradiation previously. Tumor dose was maintained at 12 to 20 Gy to the 80% isodose line (mean, 14 Gy); canal volume receiving more than 8 Gy ranged from 0.0 to 1.7 cm(3) (mean, 0.2 cm(3)). No acute radiation toxicity or new neurological deficits occurred during the follow-up period (range, 9-30 mo; median, 18 mo). Axial and radicular pain improved in 74 of 79 patients who were symptomatic before treatment. CONCLUSION: This is the first large prospective evaluation of this frameless image-guided spinal radiosurgery system. The CyberKnife system was found to be feasible, safe, and effective. The major potential benefits of radiosurgical ablation of spinal lesions are short treatment time in an outpatient setting with rapid recovery and symptomatic response. This technique offers a successful therapeutic modality for the treatment of a variety of spinal lesions as a primary treatment or for lesions not amenable to open surgical techniques, in medically inoperable patients, in lesions located in previously irradiated sites, or as an adjunct to surgery.

CyberKnife frameless single-fraction stereotactic radiosurgery for tumors of the sacrum.

OBJECT: The role of stereotactic radiosurgery for the treatment of intracranial lesions is well established. The experience with radiosurgery for the treatment of spinal and sacral lesions is more limited. Sacral lesions should be amenable to radiosurgical treatment similar to that used for their intracranial counterparts. The authors evaluated a single- fraction radiosurgical technique performed using the CyberKnife Real-Time Image-Guided Radiosurgery System for the treatment of the sacral lesion. METHODS: The CyberKnife is a frameless radiosurgery system based on the coupling of an orthogonal pair of x-ray cameras to a dynamically manipulated robot-mounted linear accelerator possessing six degrees of freedom, which guides the therapy beam to the intended target without the need for frame-based fixation. All sacral lesions were located and tracked for radiation delivery relative to fiducial bone markers placed percutaneously. Eighteen patients were treated with single-fraction radiosurgery. Tumor histology included one benign and 17 malignant tumors. Dose plans were calculated based on computerized tomography scans acquired using 1.25-mm slices. Planning treatment volume was defined as the radiographically documented tumor volume with no margin. Tumor dose was maintained at 12 to 20 Gy to the 80% isodose line (mean 15 Gy). Tumor volume ranged from 23.6 to 187.4 ml (mean 90 ml). The volume of the cauda equina receiving greater than 8 Gy ranged from 0 to 1 ml (mean 0.1 ml). All patients underwent the procedure in an outpatient setting. No acute radiation toxicity or new neurological deficits occurred during the mean follow-up period of 6 months. Pain improved in all 13 patients who were symptomatic prior to treatment. No tumor progression has been documented on follow-up imaging. CONCLUSIONS: Stereotactic radiosurgery was found to be feasible, safe, and effective for the treatment of both benign and malignant sacral lesions. The major potential benefits of radiosurgical ablation of sacral lesions are relatively short treatment time in an outpatient setting and minimal or no side effects. This new technique offers a new and important therapeutic modality for the primary treatment of a variety of sacral tumors or for lesions not amenable to open surgical techniques.

CyberKnife frameless single-fraction stereotactic radiosurgery for benign tumors of the spine.

OBJECT: The role of stereotactic radiosurgery in the treatment of benign intracranial lesions is well established. Its role in the treatment of benign spinal lesions is more limited. Benign spinal lesions should be amenable to radiosurgical treatment similar to their intracranial counterparts. In this study the authors evaluated the effectiveness of the CyberKnife for benign spinal lesions involving a single-fraction radiosurgical technique. METHODS: The CyberKnife is a frameless radiosurgery system in which an orthogonal pair of x-ray cameras is coupled to a dynamically manipulated robot-mounted linear accelerator possessing six degrees of freedom, whereby the therapy beam is guided to the intended target without the use of frame-based fixation. Cervical spine lesions were located and tracked relative to skull osseous landmarks; lower spinal lesions were tracked relative to percutaneously placed fiducial bone markers. Fifteen patients underwent single-fraction radiosurgery (12 cervical, one thoracic, and two lumbar). Histological types included neurofibroma (five cases), paraganglioma (three cases), schwannoma (two cases), meningioma (two cases), spinal chordoma (two cases), and hemangioma (one case). Radiation dose plans were calculated based on computerized tomography scans acquired using 1.25-mm slices. Planning treatment volume was defined as the radiographic tumor volume with no margin. The tumor dose was maintained at 12 to 20 Gy to the 80% isodose line (mean 16 Gy). Tumor volume ranged from 0.3 to 29.3 ml (mean 6.4 ml). Spinal canal volume receiving more than 8 Gy ranged from 0.0 to 0.9 ml (mean 0.2 ml). All patients tolerated the procedure in an outpatient setting. No acute radiation-induced toxicity or new neurological deficits occurred during the follow-up period. Pain improved in all patients who were symptomatic prior to treatment. No tumor progression has been documented on follow-up imaging (mean 12 months). CONCLUSIONS: Spinal stereotactic radiosurgery was found to be feasible, safe, and effective for the treatment of benign spinal lesions. Its major potential benefits are the relatively short treatment time in an outpatient setting and the minimal risk of side effects. This new technique offers an alternative therapeutic modality for the treatment of a variety of benign spinal neoplasms in cases in which surgery cannot be performed, in cases with previously irradiated sites, and in cases involving lesions not amenable to open surgical techniques or as an adjunct to surgery.

Safety and immunogenicity of a modified process hepatitis B vaccine in healthy neonates.

BACKGROUND: A manufacturing process using a modified adjuvant was developed to optimize the consistency and immunogenicity for recombinant hepatitis B vaccine (control: RECOMBIVAX-HB™). This modified process hepatitis B vaccine (mpHBV), which was previously shown to have an acceptable safety and immunogenicity profile in young adults, has now been studied in newborn infants. METHODS: Healthy 1-10-day-old neonates (N=566) received 3 intramuscular doses (5µg hepatitis B surface antigen [HBsAg] per dose) of either mpHBV or control at Day 1, and Months 1 and 6. Serum antibody to HBsAg (anti-HBs) was assayed at Month 7 (1 month Postdose 3). Anti-HBs geometric mean titers (GMTs) and seroprotection rates (SPRs) (% of subjects with an anti-HBs titer ≥10mIU/mL) were compared at Month 7. After each dose, injection-site adverse experiences (AEs) and axillary temperatures were recorded for 5 days; systemic AEs were recorded for Days 1-14. RESULTS: Month 7 SPR was 97.9% for the mpHBV group and 98.9% for the control. The GMT was 843.7mIU/mL for the mpHBV group and 670.1mIU/mL for the control. The GMT ratio (mpHBV/control) was 1.26 (95% confidence interval [CI]: 0.94, 1.69), meeting the prespecified non-inferiority criteria. The percentages of subjects reporting any AE, injection-site AEs, or systemic AEs were similar across the 2 vaccination groups. There were no serious AEs. CONCLUSIONS: The safety profile of mpHBV was comparable to that of the control vaccine. The geometric mean antibody titer for mpHBV was higher than control vaccine in this infant population, but the difference did not meet the predefined statistical criterion for superiority.

Phase I trial of oral vorinostat (suberoylanilide hydroxamic acid, SAHA) in patients with advanced multiple myeloma.

A Phase I trial (NCT00109109) of oral vorinostat 200, 250 or 300 mg twice daily for 5 days/week/4-week cycle or 200, 300, or 400 mg twice daily for 14 days/3-week cycle until progressive disease or intolerable toxicity was conducted. Patients with measurable, relapsed/refractory multiple myeloma were eligible. The objectives were to determine maximum tolerated doses (MTDs) and assess activity and safety. Thirteen patients (median age, 63 years; median prior therapies, 3) were enrolled. MTDs were not determined due to early study termination by sponsor decision. One patient (250 mg twice daily 5 days/week) developed dose-limiting toxicity (DLT; grade 3 fatigue). There were no other DLTs and the maximum administered doses were 250 mg twice daily for 5 days/week/4-week cycle and 200 mg twice daily for 14 days/3-week cycle. Drug-related adverse experiences included fatigue, anorexia, dehydration, diarrhea, and nausea and were mostly grade

Evaluation of CyberKnife frameless real-time image-guided stereotactic radiosurgery for spinal lesions.

BACKGROUND: This study evaluated the CyberKnife frameless image-guided radiosurgery system for the treatment of spinal lesions. METHODS: This system utilizes the coupling of an orthogonal pair of X-ray cameras to a dynamically manipulated robot-mounted linear accelerator that guides the therapy beam to the intended target without the use of frame-based fixation. Cervical spine lesions are located and tracked relative to skull bony landmarks; lower spinal lesions are tracked relative to fiducial markers. 125 spinal lesions in 115 consecutive patients were treated with a single-fraction radiosurgery technique. RESULTS: Tumor volume ranged from 0.3 to 232 ml (mean 27.8 ml). Tumor radiation dose was maintained at 12-20 Gy to the 80% isodose line (mean 14 Gy); the spinal cord or canal volume receiving greater than 8 Gy ranged from 0.0 to 1.7 ml (mean 0.2 ml). No acute radiation toxicity or new neurological deficits occurred during the follow-up period (3-24 months). CONCLUSIONS: The CyberKnife system was found to be feasible, safe and effective. The major potential benefits of radiosurgical ablation of spinal lesions are short treatment time in an outpatient setting with rapid recovery and good response.