Phase 1/2 trial of single-session stereotactic body radiotherapy for previously unirradiated spinal metastases.

BACKGROUND: In this phase 1/2 study, the authors tested the hypothesis that single-fraction stereotactic body radiotherapy (SBRT) for previously unirradiated spinal metastases is a safe, feasible, and efficacious treatment approach. METHODS: All patients were evaluated by a multidisciplinary team. Spinal magnetic resonance imaging studies were obtained before treatment and at regular intervals to define both target volume and response to treatment. SBRT was delivered to a peripheral dose of 16 to 24 grays in a single fraction while limiting the dose to the spinal cord. Higher doses were used for renal cell histology. The National Cancer Institute Common Toxicity Criteria 2.0 and McCormick neurologic function score were used as toxicity assessment tools. RESULTS: In total, 61 patients who had 63 tumors of the noncervical spine were enrolled and received SBRT between 2005 and 2010 on a prospective, phase 1/2 trial at The University of Texas M. D. Anderson Cancer Center. The mean follow-up was 20 months. The actuarial 18-month imaging local control rate for all patients was 88%, the actuarial 18-month overall survival rate for all patients was 64%, and the median survival for all patients was 30 months. No significant differences in outcomes were noted with respect to tumor histology or SBRT dose. Two patients experienced radiation adverse events (grade 3 or higher). The actuarial rate of 18-month freedom from neurologic deterioration from any cause was 82%. CONCLUSIONS: Data from this phase 1/2 trial supported an expanded indication for SBRT as first-line treatment of spinal metastases in selected patients. The authors concluded that additional studies that can prospectively identify predictive factors for spinal cord toxicity after SBRT are warranted to minimize the incidence of this serious yet rare complication.

Irradiation of spinal metastases: should we continue to include one uninvolved vertebral body above and below in the radiation field?

PURPOSE: Historically, the appropriate target volume to be irradiated for spinal metastases is 1-2 vertebral bodies above and below the level of involvement for three reasons: (1) to avoid missing the correct level in the absence of simulation or (2) to account for the possibility of spread of disease to the adjacent level, and (3) to account for beam penumbra. In this study, we hypothesized that isolated failures occurring in the level adjacent to level treated with stereotactic body radiosurgery (SBRS) were infrequent and that with improved localization techniques with image-guided radiation therapy, treatment of only the involved level of spinal metastases may be more appropriate. METHODS AND MATERIALS: Patients who had received SBRS treatments to only the involved level of the spine as part of a prospective trial for spinal metastases comprised the study population. Follow-up imaging with spine MRI was performed at 3-month intervals following initial treatment. Failures in the adjacent (V±1, V±2) and distant spine were identified and classified accordingly. RESULTS: Fifty-eight patients met inclusion criteria for this study and harbored 65 distinct spinal metastases. At 18-month median follow-up, seven (10.7%) patients failed simultaneously at adjacent levels V±1 and at multiple sites throughout the spine. Only two (3%) patients experienced isolated, solitary adjacent failures at 9 and 11 months, respectively. CONCLUSION: Isolated local failures of the unirradiated adjacent vertebral bodies may occur in <5% of patients with isolated spinal metastasis. On the basis of the data, the current practice of irradiating one vertebral body above and below seems unnecessary and could be revised to irradiate only the involved level(s) of the spine metastasis.

Assessment of potential drug interactions in patients with epilepsy: impact of age and sex.

OBJECTIVES: To understand and quantify the exposure to concomitant medications other than antiepileptic drugs (AEDs) within an age-diverse group of men and women with epilepsy and explore the likelihood of relevant drug interactions as a result. METHODS: The PharMetrics medical and pharmaceutical claims database was used to extract data for commercially insured adult patients with a diagnosis of epilepsy and treated with any AED during the period from July 1, 2001, to December 31, 2004. Data were analyzed for concomitant non-AEDs used after initiating AEDs in six age groups, spanning the ages 18 to 85+ years, in both men and women. RESULTS: Use of concomitant medications occurred in every age group and increased with age for both men and women (mean number of non-AEDs ranging from 2.41 to 7.67 in males aged 18-34 and 85+ years and from 4.04 to 7.05 in females aged 18-34 and 85+ years; p < 0.001 for age trend). beta-Hydroxy-beta-methylglutaryl-coenzyme A reductase inhibitors (statins), calcium channel blockers (CCBs), and selective serotonin reuptake inhibitors (SSRIs) were the most commonly used non-AED medications with the potential for adverse drug interactions. SSRIs use was substantial in all age groups and greater than for statins or CCBs in patients aged 18-54 years. Use of antipsychotics, tricyclic antidepressants, and warfarin was also noted in more than 10% of patients across different age groups. CONCLUSIONS: Polypharmacy with non-antiepileptic drug (AED) medications is common in both men and women, and is not a situation unique to only elderly patients with epilepsy. In particular, use of potentially interacting, enzyme inducing AEDs was common. These findings suggest that clinicians must be mindful of potential AED-non-AED drug interactions, in patients of all age groups.

Economic burden of illness for employees with painful conditions.

OBJECTIVE: We sought to compare the medical services utilization and average annual direct (ie, medical and medication) and indirect (ie, work-loss) costs for employees with painful conditions to a random sample ("average employee"). METHODS: An employer administrative claims database (approximately 600,000 insured lives) was used to identify patients with ICD-9 codes for painful conditions. Direct costs were total employer medical and medication costs and indirect costs were associated with medically related absenteeism days and disability claims. RESULTS: Among employees with painful conditions, total costs were 1.5 to 3.5 times as high (P < 0.01) as those of the average employee (ie, 7088 US dollars to 16,874 US dollars compared with 4,849 US dollars) depending on the painful condition. CONCLUSIONS: Painful conditions are costly to employers, and better management/treatment of such conditions may help reduce the associated employer economic burden.