Residual γH2AX foci after ex vivo irradiation of patient samples with known tumour-type specific differences in radio-responsiveness

Purpose: To apply our previously published residual ex vivo gamma H2AX foci method to patient-derived tumour specimens covering a spectrum of tumour-types with known differences in radiation response. In addition, the data were used to simulate different experimental scenarios to simplify the method. Materials and methods: Evaluation of residual gamma H2AX foci in well-oxygenated tumour areas of ex vivo irradiated patient-derived tumour specimens with graded single doses was performed. Immediately after surgical resection, the samples were cultivated for 24 h in culture medium prior to irradiation and fixed 24 h post-irradiation for gamma H2AX foci evaluation. Specimens from a total of 25 patients (including 7 previously published) with 10 different tumour types were included. Results: Linear dose response of residual gamma H2AX foci was observed in all specimens with highly variable slopes among different tumour types ranging from 0.69 (95% CI: 1.14-0.24) to 3.26 (95% Cl: 4.13-2.62) for chondrosarcomas (radioresistant) and classical seminomas (radiosensitive) respectively. Simulations suggest that omitting dose levels might simplify the assay without compromising robustness. Conclusion: Here we confirm clinical feasibility of the assay. The slopes of the residual foci number are well in line with the expected differences in radio-responsiveness of different tumour types implying that intrinsic radiation sensitivity contributes to tumour radiation response. Thus, this assay has a promising potential for individualized radiation therapy and prospective validation is warranted. (C) 2015 Elsevier Ireland Ltd. All rights reserved.