Utility of ctDNA to support patient selection for early phase clinical trials: the TARGET study.

Next-generation sequencing (NGS) of circulating tumor DNA (ctDNA) supports blood-based genomic profiling but is not yet routinely implemented in the setting of a phase I trials clinic. TARGET is a molecular profiling program with the primary aim to match patients with a broad range of advanced cancers to early phase clinical trials on the basis of analysis of both somatic mutations and copy number alterations (CNA) across a 641 cancer-associated-gene panel in a single ctDNA assay. For the first 100 TARGET patients, ctDNA data showed good concordance with matched tumor and results were turned round within a clinically acceptable timeframe for Molecular Tumor Board (MTB) review. When a 2.5% variant allele frequency (VAF) threshold was applied, actionable mutations were identified in 41 of 100 patients, and 11 of these patients received a matched therapy. These data support the application of ctDNA in this early phase trial setting where broad genomic profiling of contemporaneous tumor material enhances patient stratification to novel therapies and provides a practical template for bringing routinely applied blood-based analyses to the clinic.

Computational Lexical Analysis of the Language Commonly Used to Describe Gout.

OBJECTIVE: To characterize the current language that is used in describing and defining gout, its symptoms, and its treatment by reviewing recent publications in rheumatology and determining how word choice may, or may not, be reflective of recent scientific developments in gout specifically. METHODS: This was a computational linguistics study, using collocations analyses and concordance analyses on a database of scientific literature related to gout. The final data set for analysis included 2,590 articles, all relating to gout and published between May 2003 and May 2013 and amounting to 12,101,036 tokens (sentence segments). Analysis was conducted by a team of linguists and social scientists. RESULTS: Our primary finding is that current disease language in gout is marked by ambiguity and imprecision, as evidenced by numerous terms that have similar but distinct meanings, but are nevertheless used interchangeably, therefore blending the slight but significant distinctions between these words. Whereas treatment language is characterized by a multitude of terms to describe a therapeutic mechanism of action, there is a relative void of terms and phrases used to describe success (treating to target) in gout. CONCLUSION: The data suggest that the language used to describe gout could be improved and updated. A transformation from an antiquated and insufficiently descript terminological set to one that reflects the recent scientific and clinical advancements made in the category would maximize opportunities for patient and physician understanding.