M. Baumann

Ex vivo γH2AX radiation sensitivity assay in prostate cancer: Inter-patient and intra-patient heterogeneity

INTRODUCTIONnThe aim of the study is to assess inter-patient and intra-patient heterogeneity in tumour cell radiosensitivity using the ex vivo γH2AX assay in prostate cancer specimens.nnnMETHODSnExcised specimens from untreated prostate cancer patients were cultivated 24h in media, irradiated ex vivo and fixed after 24h. Residual γH2AX foci were counted and the slope of the dose response was calculated. Intra-patient heterogeneity was studied from three to seven different biopsies.nnnRESULTSnIn pathology-confirmed tumour samples from 21 patients the slope of residual γH2AX foci and radiation dose showed a substantial heterogeneity ranging from 0.82 to 3.17 foci/Gy. No correlation was observed between the slope values and the Gleason score (p=0.37), prostate specific antigen (p=0.48) and tumour stage (p=0.89). ANOVA indicated that only in 1 out of 9 patients, biopsies from different tumour locations yielded statistically significant differences. Variance component analysis indicated higher inter-patient than intra-patient variability. Bootstrap simulation study demonstrated that one biopsy is sufficient to estimate the mean value of residual γH2AX per dose level and account for intra-patient heterogeneity.nnnCONCLUSIONSnIn prostate cancer inter-patient heterogeneity in tumour cell radiation sensitivity is pronounced and higher than intra-patient heterogeneity supporting the further development of the γH2AX ex vivo assay as a biomarker for individualized treatment.

EP-2040: Can pimonidazole be used to detect cycling hypoxia in tumours?

S963 ________________________________________________________________________________ for early breast cancer includes a wide local excision with adjuvant radiotherapy. Clinical data suggest, that perturbations induced by surgery and the subsequent wound fluids, which are rich in cytokines and growth factors, may stimulate residual disease. Numerous studies demonstrate, that 90% of the local recurrence after surgery occur in the same quadrant as the primary cancer. It has been proposed, that cancer cells displaying the stem-like phenotype play a critical role in local recurrence, invasion and metastasis. One of the new possibilities in conservative cancer treatment is intraoperative radiotherapy (IORT). IORT delivers high dose of radiation as one single fraction at the time of surgery. It was previously reported, that IORT alters the microenvironment through the modulation of wound healing response. Thus we wondered, whether wound fluids can induce the enrichment of breast cancer stem cells phenotype in breast cancer cell lines and whether IORT plays inhibitory role in this process.