Recent developments in radiosensitization.

Radiation therapy is essential for local tumor control for many types of cancer histologies. Technological advancements in recent years have allowed for precise irradiation of target tissues while minimizing the dose to non-target tissues. To enhance radiation damage to cancer cells and further limit the radiation effects on normal tissue, researchers have explored compounds that specifically target cancer cells and make them more sensitive to ionizing radiation. Recent radiosensitization research has focused on promising compounds that alter hypoxia, inhibit topoisomerases, interfere with microtubules, and activate caspases, among other mechanisms. Many such compounds have shown impressive results in pre-clinical trials against a variety of cell types, but their safety, efficacy and practicability in clinical trials remains to be demonstrated. This review seeks to provide an overview of recent research in radiosensitization, detailing some of the more successful compounds, and illustrating avenues for future research.

Triiodothyronine Supplementation in Infants and Children Undergoing Cardiopulmonary Bypass (TRICC): a multicenter placebo-controlled randomized trial: age analysis.

BACKGROUND: Triiodothyronine levels decrease in infants and children after cardiopulmonary bypass. We tested the primary hypothesis that triiodothyronine (T3) repletion is safe in this population and produces improvements in postoperative clinical outcome. METHODS AND RESULTS: The TRICC study was a prospective, multicenter, double-blind, randomized, placebo-controlled trial in children younger than 2 years old undergoing heart surgery with cardiopulmonary bypass. Enrollment was stratified by surgical diagnosis. Time to extubation (TTE) was the primary outcome. Patients received intravenous T3 as Triostat (n=98) or placebo (n=95), and data were analyzed using Cox proportional hazards. Overall, TTE was similar between groups. There were no differences in adverse event rates, including arrhythmia. Prespecified analyses showed a significant interaction between age and treatment (P=0.0012). For patients younger than 5 months, the hazard ratio (chance of extubation) for Triostat was 1.72. (P=0.0216). Placebo median TTE was 98 hours with 95% confidence interval (CI) of 71 to 142 compared to Triostat TTE at 55 hours with CI of 44 to 92. TTE shortening corresponded to a reduction in inotropic agent use and improvement in cardiac function. For children 5 months of age, or older, Triostat produced a significant delay in median TTE: 16 hours (CI, 7-22) for placebo and 20 hours (CI, 16-45) for Triostat and (hazard ratio, 0.60; P=0.0220). CONCLUSIONS: T3 supplementation is safe. Analyses using age stratification indicate that T3 supplementation provides clinical advantages in patients younger than 5 months and no benefit for those older than 5 months. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00027417.