Development of a Glucocorticoid Toxicity Index (GTI) using multicriteria decision analysis.

OBJECTIVES: To develop a Glucocorticoid Toxicity Index (GTI) to assess glucocorticoid (GC)-related morbidity and GC-sparing ability of other therapies. METHODS: Nineteen experts on GC use and outcome measures from 11 subspecialties participated. Ten experts were from the USA; nine from Canada, Europe or Australia. Group consensus methods and multicriteria decision analysis (MCDA) were used. A Composite GTI and Specific List comprise the overall GTI. The Composite GTI reflects toxicity likely to change during a clinical trial. The Composite GTI toxicities occur commonly, vary with GC exposure, and are weighted and scored. Relative weights for items in the Composite GTI were derived by group consensus and MCDA. The Specific List is designed to capture GC toxicity not included in the Composite GTI. The Composite GTI was evaluated by application to paper cases by the investigators and an external group of 17 subspecialists. RESULTS: Thirty-one toxicity items were included in the Composite GTI and 23 in the Specific List. Composite GTI evaluation showed high inter-rater agreement (investigators κ 0.88, external raters κ 0.90). To assess the degree to which the Composite GTI corresponds to expert clinical judgement, participants ranked 15 cases by clinical judgement in order of highest to lowest GC toxicity. Expert rankings were then compared with case ranking by the Composite GTI, yielding excellent agreement (investigators weighted κ 0.87, external raters weighted κ 0.77). CONCLUSIONS: We describe the development and initial evaluation of a comprehensive instrument for the assessment of GC toxicity.

Combining Computed Tomography-Based Bone Density Assessment with FRAX Screening in Men with Prostate Cancer.

To investigate the addition of a computed tomography (CT)-based method of osteoporosis screening to FRAX without bone mineral density (BMD) fracture risk assessment in men undergoing radiotherapy for prostate cancer, we reviewed the records of all patients with localized prostate cancer treated with external beam radiotherapy at our institution between 2001 and 2012. The 10-yr probability of hip fracture was calculated using the FRAX algorithm without BMD. The CT attenuation of the L5 trabecular bone (L5CT) was assessed by contouring the trabecular bone on a single CT slice at the level of the midvertebral body and by averaging the Hounsfield units (HU) of all included voxels. L5CT values of 105 and 130 HU were used as screening thresholds. The clinical characteristics of additional patients identified by each L5CT screening threshold value were compared to patients whose estimated 10-yr risk of hip fracture was 3% or greater by FRAX without BMD. A total of 609 patients treated between 2001 and 2012 had CT scans available for review and complete clinical information allowing for FRAX without BMD risk calculation. Seventy-four (12.2%) patients had an estimated 10-yr risk of hip fracture of 3% or greater. An additional 22 (3.6%) and 71 (11.6%) patients were identified by CT screening when thresholds L5CT = 105 HU and L5CT = 130 HU were used, respectively. Compared to the group of patients identified by FRAX without BMD, the additional patients identified by CT screening at each L5CT threshold level tended to be younger and heavier, and were more likely to be African-American or treated without androgen deprivation therapy. These results suggest that the addition of CT-based screening to FRAX without BMD risk assessment identifies additional men with different underlying clinical characteristics who may be at risk for osteoporosis and may benefit from pharmacological therapy to increase BMD and reduce fracture risk.