Intrinsic radiosensitivity and prediction of patient response to radiotherapy for carcinoma of the cervix

Abstract

Summary The intrinsic radiosensitivity of cervical carcinoma has been measured using a soft agar clonogenic assay. All patients received radical radiotherapy alone with a minimum of 2 years post-treatment follow-up. Only women with stage I, II and III disease were included in the analysis. Values for cell surviving fraction at 2 Gy (SF2) were obtained for 88 tumours with an assay success rate of 73%. The 53 patients alive and well at the time of analysis had tumours with a mean SF2 that was significantly lower than the value from the 22 patients with locoregional failure (P < 0.01). Patients with radioresistant tumours (SF2> 0.40, the median) had a significantly lower 3 year survival level than those with sensitive tumours (SF2 < 0.40) (P = 0.002). Also the frequency of local recurrence was higher (P = 0.001) whether these were central (P = 0.009) or peripheral (P = 0.046). Cell surviving fraction at 3.5 Gy was obtained for 46 tumours and the 3 year patient survival rate was significantly higher for those with SF3.5 values less than the median (P = 0.043). There was, however, no difference in the level of local recurrence (P = 0.24). The ability to grow in culture was not associated with significantly poorer patient survival (P = 0.56) or failure to control the primary disease (P = 0.17). While high colony forming efficiencies were associated with an increased rate of local recurrence (P = 0.029) they did not predict for overall patient survival (P = 0.32). These data suggest that, for cervical carcinoma treated with radical radiotherapy, intrinsic radiosensitivity is important in determining treatment outcome.

In vitro radiosensitivity of tumour cells and fibroblasts derived from head and neck carcinomas: mutual relationship and correlation with clinical data

“…The success rate for measuring tumour cell radiosensitivity was 68%. Furthermore, the plating efficiency and the overall SF 2 values measured in this study fell within the same range as in similar studies on in vitro radiosensitivity (Brock et al, 1989;West et al, 1989West et al, , 1993Girinski et al, 1994;KocagšncŸ et al, 1994;West, 1995).…”

“…To judge the representativeness of these findings, it is of interest to compare our assay with reports in the literature. The assay used in the current study was similar to the often used modified CourtenayÐMills soft agar clonogenic assay (West et al, 1989(West et al, , 1993, except for the addition of an immunocytochemical analysis for staining colonies from soft agar (Stausb¿l-Gr¿n et al, 1995). The 73% overall success rate in this study is consistent with the overall success rate in previous studies on cellular in vitro radiosensitivity of different tumour types using either CAM assays or soft agar clonogenic assays (Brock et al, 1990;Girinski and Fertil, 1993;KocagšncŸ et al, 1994;West, 1995).…”

Radiosensitivity of human tumour cells is correlated with the induction but not with the repair of DNA double-strand breaks

“…This 'intrinsic' radiosensitivity differs largely between tumour types and is at least partly due to the different sensitivity of the respective tumour cells Deacon et al, 1984;Fertil and Malaise, 1985). It was further shown that within one type of tumours, the outcome of the individual patients after radiotherapy was reflected by the in vitro radiosensitivity (SF2) of their tumour cells (West et al, 1993(West et al, , 1995Stausbol-Gron and Overgaard, 1999;Björk-Eriksson et al, 2000).…”

Differential level of DSB repair fidelity effected by nuclear protein extracts derived from radiosensitive and radioresistant human tumour cells

“…Furthermore, there is no obvious relationship between the level (XRCC5, XRCC6 and XRCC7) or activity (XRCC7) of DSB repair proteins in human tumour cell lines exhibiting a range of radioresistance (Allalunis-Turner et al, 1995) that impacts on patient radioresponsiveness (West et al, 1993).…”