The independence of intrinsic radiosensitivity as a prognostic factor for patient response to radiotherapy of carcinoma of the cervix

Abstract

Summary A study was made of the prognostic value of pretreatment measurements of tumour radiosensitivity (surviving fraction at 2 Gy, SF2) in 128 patients with stage I-Ill carcinomas of the uterine cervix undergoing radiotherapy. The median follow-up time was 47 months. In a univariate analysis stratifying patients according to the median value, radiosensitivity was a significant prognostic factor for overall survival, local control and metastasis-free survival. The 5-year survival rate for tumours with SF2 values below the median was 81% and was significantly greater than the rate of 51% for those with SF2 values above the median. In bivariate analyses, SF2 was shown to be independent of disease stage, tumour grade, patient age, colony-forming efficiency and tumour diameter. In a multivariate analysis, radiosensitivity was the most important variable and, after allowing for this, only stage was a significant independent predictor of treatment outcome. These data indicate that, in carcinoma of the cervix treated with radiotherapy, pretreatment tumour intrinsic radiosensitivity is an important prognostic parameter and contributes to prognosis independently of other established and putative parameters.Keywords: predictive assay; intrinsic radiosensitivity; SF2; cervix cancer; radiotherapy There are considered to be three important radiobiological factors that determine how well a tumour responds to radiotherapy: intrinsic radiosensitivity, hypoxia and proliferation. The clinical relevance of these parameters is currently receiving considerable attention, and studies have been published suggesting the potential of all three as prognostic factors for radiotherapy (West, 1994).In carcinoma of the cervix, our own studies have indicated that tumour radiosensitivity is an important determinant of treatment outcome (West et al, 1991(West et al, , 1993. In this work, radiosensitivity is measured using a soft agar clonogenic assay as surviving fraction after 2 Gy in vitro irradiation (SF2). Some support for our finding has come from work on head and neck tumours, which has shown that radiosensitivity, measured using a growth assay as the initial slope of radiation survival curves (a), significantly influenced patient outcome when a high (above median) value was used to stratify data (Girinsky et al, 1994). Other smaller studies using a variety of assays have also suggested that radiosensitive tumours are more responsive to therapy (Hinkley and Bosanquet, 1992;Ramsay et al, 1992;Vaughan et al, 1993;Shibamoto et al, 1994). Studies that have shown no relationship between tumour radiosensitivity and treatment outcome either involved the establishment of cell lines before assay (Allalunis-Turner et al, 1992;Schwartz et al, 1992;Taghian et al, 1993) or treatment with surgery plus radiotherapy (Brock et al, 1992), both of which may be confounding influences.This paper forms an update of a previous study (West et al, 1993) Correspondence to: C West 88 patients. In this report, for the first time, a multivariate analysis has been ...

Potential use of the alkaline comet assay as a predictor of bladder tumour response to radiation

“…In this paper, we present data showing that the ACA can be used as a surrogate measure in the prediction of tumour cell radiosensitivity; the results are supported by two further papers (Dunne et al, 2003;Moneef et al, 2003). Prior to using the ACA, we attempted to measure radiosensitivity in 24 primary bladder tumours using the soft agar clonogenic assay of West et al (1997). However, the success rate was very low (8%), this was attributed to the problem of achieving prolonged cell growth in this assay.…”

“…This conclusion also concurs with seminal studies of Malaise et al (1987) and Deacon et al (1984), updated by Steel (1996) in which they provide considerable evidence that the radiosensitivity of tumours is most reliably measured at 2 Gy. The clinical studies of West and colleagues would support this proposition (West et al, 1997;Bjork-Eriksson et al, 2000).…”

“…West and colleagues have shown that biopsies from cervix and head and neck tumours can be used to predict for an individual patient's response to radiotherapy using clonogenic cell survival following exposure to 2 Gy X-irradiation (West et al, 1997;Bjork-Eriksson et al, 2000). The main disadvantages of this assay are that a minimum of 4 weeks is required to obtain a result, and about 30% of excised tumours failed to grow in soft agar; success of this method in other tumour types has been elusive.…”

Expression of DNA damage response proteins and complete remission after radiotherapy of stage IB–IIA of cervical cancer

“…In carcinoma of the cervix, there are indications pointing to intrinsic radiosensitivity of the tumour as a determinant of outcome following RT (West et al, 1997). The possibility to measure radiosensitivity in the primary tumour would be of great importance when deciding optimal treatment regimen for the individual patient.…”

The contribution of women to radiobiology: Marie Curie and beyond

“…The test was suggested as a predictive assay. 40 Her work showed that in vitro measurement of tumor cell radiosensitivity is a highly significant prognostic factor for carcinoma of the cervix treated with radiotherapy 41 (Fig. 6).…”