Value of functional in-vivo endpoints in preclinical radiation research.

Abstract

Cancer research faces the problem of high rates of clinical failure of new treatment approaches after positive preclinical data. We hypothesize that a major confounding factor to this problem in radiooncology is the choice of the preclinical endpoint. We present a comprehensive re-evaluation of large-scale preclinical in-vivo data on fractionated irradiation alone or simultaneously with Epidermal Growth Factor Receptor inhibition. Taking the permanent local tumour control assay as a gold standard, we evaluated different tumour volume dependent endpoints that are widely used for preclinical experiments. The analysis showed the highest correlations between volume related and local tumour control endpoints after irradiation alone. For combined treatments, wide inter-tumoural variations were observed with reduced correlation between the endpoints. Evaluation of growth delay per Gray (GD/Gy) based on two or more dose levels showed closest correlation with local tumour control dose 50% (TCD₅₀). GD/Gy with at least two dose groups correlates with TCD₅₀, but cannot replace the latter as the goldstandard.