Matched Targeted Therapy for Pediatric Patients with Relapsed, Refractory, or High-Risk Leukemias: A Report from the LEAP Consortium

Despite a remarkable increase in the genomic profiling of cancer, integration of genomic discoveries into clinical care has lagged behind. We report the feasibility of rapid identification of targetable mutations in 153 pediatric patients with relapsed/refractory or high-risk leukemias enrolled on a prospective clinical trial conducted by the LEAP Consortium. Eighteen percent of patients had a high confidence Tier 1 or 2 recommendation. We describe clinical responses in the 14% of patients with relapsed/refractory leukemia who received the matched targeted therapy. Further, in order to inform future targeted therapy for patients, we validated variants of uncertain significance, performed ex vivo drug-sensitivity testing in patient leukemia samples, and identified new combinations of targeted therapies in cell lines and patient-derived xenograft models. These data and our collaborative approach should inform the design of future precision medicine trials

Matched Targeted Therapy for Pediatric Patients with Relapsed, Refractory or High-risk Leukemias: A Report from the LEAP Consortium.

Despite a remarkable increase in the genomic profiling of cancer, integration of genomic discoveries into clinical care has lagged behind. We report the feasibility of rapid identification of targetable mutations in 153 pediatric patients with relapsed/refractory or high-risk leukemias enrolled on a prospective clinical trial conducted by the LEAP Consortium. Eighteen percent of patients had a high confidence, Tier 1 or 2, recommendation. We describe clinical responses in the 14% of patients with relapsed/refractory leukemia who received the matched targeted therapy. Further, in order to inform future targeted therapy for patients, we validated variants of uncertain significance (VUS), performed ex vivo drug sensitivity testing in patient leukemia samples, and identified new combinations of targeted therapies in cell lines and patient-derived xenograft models. These data and our collaborative approach should inform the design of future precision medicine trials

Laser-Induced surface acoustic waves for material testing

Surface acoustic waves are elastic vibrations which propagate along the surface of the material. They are very sensitive to films and surface treatments, since the wave energy is concentrated near the surface. Therefore, there is a growing interest in using this acoustic wave mode for nondestructive testing. Whereas the wave velocity is constant for homogenous materials, the velocity c depends on frequency f for coated and surface-modified materials. This phenomenon, termed dispersion, can be used to determine important film parameters such as Young’s modulus, density, or film thickness. Especially, Young’s modulus is an interesting parameter for nondestructive characterization of film materials, since it depends on the bonding conditions and the microstructure. In order to determine the parameters of the film material, the dispersion curve c(f) is measured and fitted by a theoretical curve. Many experimental setups use pulse lasers to create surface acoustic waves. Short laser pulses can create wideband acoustic impulses. The laser is a non-contact acoustic source that can precisely be positioned on the material surface, which enables an accurate measurement of the dispersion. Five examples of application are presented which demonstrate that surface acoustic waves can be used for very different problems of surface characterization: diamond-like carbon films (ta-C) with thickness down to few nanometers, porous metal films of titanium with a thickness in the micrometer range, thermal-sprayed ceramic coatings with a thickness of some hundreds of micrometers, laser-hardened steels up to the depth of one millimeter, and subsurface damage in semiconductor materials