## 4 The Importance of Biomarkers in Monitoring RT Toxicity
### Cell-Intrinsic Radiosensitivity Biomarkers
#### 4.1.1 Cytogenetic Markers
& No correlation between the number of \(\gamma\)H2 AX foci and radiotoxicity at the level of PBMCs. & [44] \\ \hline \multirow{6}{*}{\(\gamma\)H2 AX FCM assay} & Cancer patient lymphocyte cells were isolated from individuals who did and did not have a severe reaction to RT. & No detectable differences were found between the control group and the RS group by following & [59] \\  & PBLs isolated from 12 patients who had experienced severe atypical NTT (Normal Tissue Toxicity) as a consequence of earlier RT were identified. Patients (10) who had experienced little or no NTT acted as one control group, and 7 healthy, non-cancer individuals comprised a second control group. & [60] \\ \hline \multirow{6}{*}{\(\gamma\)H2 AX/53 BP1 IF assay} & Blood lymphocytes of BC patients who had undergone surgical excision of the primary tumor and postoperative RT to the whole breast. Two groups of patients were identified indicating severely marked radiation-induced change (cases) or very little/no change (controls) in the breast. & Higher levels of residual DSBs and deletion-type aberrations in ex vivo irradiated blood lymphocytes from clinically radiosensitive BC patients provide a suggestion for DSB repair in the development of radiation-induced late normal tissue damage. & [42] \\ \hline \multirow{6}{*}{\(\gamma\)H2 AX/53 BP1 IF assay} & PBMCs were isolated from a group of unselected BC patients who received RT treatment and a group of apparently healthy donors. The early skin reaction to RT developing in the skin within the radiation field of the breast was controlled at the end of RT and used as an indicator of clinical radiosensitivity & A minor group of retrospectively identified BC patients with an adverse skin reaction to RT showed differences by the \(\gamma\)H2 AX assay with respect to healthy individuals. The 53 BP1 assay was less sensitive than that for histone \(\gamma\)H2 AX in the case of endogenous (0 Gy) and induced (0.5 Gy, 30 min) foci. & [61] \\ \hline \multirow{6}{*}{\(\gamma\)H2 AX/53 BP1 co-localization IF assay} & Peripheral blood samples from 26 patients who were treated with RT were collected from the BC patients two days before the RT. The acute adverse reactions of all patients are classified according to the Radiation Therapy Oncology Group (RTOG)/European Organization for Research and Treatment of Cancer (EORTC) side effects. & [62] \\  & PBL from 16 patients who developed severe late radiation toxicity following radiotherapy. & Support for the hypothesis that the RS phenotype is associated with compromised DNA repair. & [63] \\ \hline \multirow{6}{*}{\(\gamma\)H2 AX/53 BP1 co-localization IF assay} & Peripheral venous blood was collected from 14 healthy control subjects, 15 patients with benign prostatic hyperplasia (BPH), and 17 patients with prostate cancer. & Enhanced G2 chromosomal radiosensitivity in prostate cancer and BPH patients compared with normal controls. & [40] \\  & Blood samples were then obtained from 27 breast cancer patients with severe side effects (S) and 25 patients without severe side effects (0) after radiotherapy as well as from 23 healthy male age-matched donors. & A significant proportion of breast cancer patients exhibit elevated G2 chromosomal radiosensitivity in contrast to random controls. & [41] \\ \hline \multirow{6}{*}{G2 chromosomal radiosensitivity assay} & Blood lymphocytes of BC patients who had undergone surgical excision of the primary tumor and postoperative RT to the whole breast. & Significantly higher levels of chromosomal aberrations in blood lymphocyte metaphases among women presenting with marked late radiotherapy changes. & [42] \\  & Blood samples were obtained from 25 prostate cancer patients with severe side effects (S) and 25 patients without severe side effects (0) after radiotherapy as well as from 23 healthy male age-matched donors. & The obtained success rate is not sufficient to validate the G2 assay as a good tool for the identification of prostate cancer patients with a high risk for the development of severe clinical side effects.