Residual γH2AX foci after ex vivo irradiation of patient samples with known tumour-type specific differences in radio-responsiveness
Residual γH2AX foci after ex vivo irradiation of patient samples with known tumour-type specific differences in radio-responsiveness
Menegakis, A.; de Colle, C.; Yaromina, A.; Hennenlotter, J.; Stenzl, A.; Scharpf, M.; Fend, F.; Noell, S.; Tatagiba, M.; Brucker, S.; Wallwiener, D.; Boeke, S.; Ricardi, U.; Baumann, M.; Zips, D.
PURPOSE:
To apply our previously published residual ex vivo γH2AX 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 γH2AX 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 24h in culture medium prior to irradiation and fixed 24h post-irradiation for γH2AX 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 γH2AX 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% CI: 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.
Keywords: DNA repair; Intrinsic radiation sensitivity; Personalized radiation oncology; Radiotherapy; Tumour specimens; γH2AX foci
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Radiotherapy and Oncology 116(2015)3, 480-485
DOI: 10.1016/j.radonc.2015.08.006
Cited 33 times in Scopus
Permalink: https://www.hzdr.de/publications/Publ-22707