Media literacy programs combined with an interactive, student-centered framework may potentially be a safe and effective way of reducing risk factors for eating disorders. The impact of teaching style needs to be further evaluated in prevention research.
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 ...
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.
The aim of the study was to evaluate VEGF expression in tumour biopsies as a prognostic factor for radiotherapy outcome in advanced carcinoma of the cervix. A retrospective study was carried out on 100 patients. Pre-treatment tumour VEGF expression was examined immunohistochemically in formalin-fixed, paraffin-embedded biopsies using a widely available commercial antibody. A semi-quantitative analysis was made using a scoring system of 0, 1, 2, and 3, for increasing intensity of staining. High VEGF expression was associated with a poor prognosis. A univariate log rank analysis found a significant relationship with overall survival (P = 0.0008) and metastasis-free survival (P = 0.0062), but not local control (P = 0.23). There was no correlation between VEGF expression and disease stage, tumour differentiation, patient age, or tumour radiosensitivity (SF2). In a Cox multivariate analysis of survival VEGF expression was the most significant independent prognostic factor (P = 0.001). After allowing for VEGF only SF2 was a significant prognostic factor (P = 0.003). In conclusion, immunohistochemical analysis of VEGF expression is a highly significant and independent prognostic indicator of overall and metastasis-free survival for patients treated with radiotherapy for advanced carcinoma of the cervix. It is also a rapid and easy method that could be used in the clinical setting, to identify patients at high risk of failure with conventional radiotherapy who may benefit from novel approaches or chemoradiotherapy. © 2000 Cancer Research Campaign
Summary A study was made of the relatonship between the intrinsic radiosensifivity of human cervical tumours and the expression of the DNA repair enzyme human apurnic/apyrmidinic endonuclease (HAP1). The radiosensitivity of clonogenic cells in tumour biopsies was measured as surviving fraction at 2 Gy (SF2) using a soft agar assay. HAP1 expression levels were determined after staining of formalin-fixed paraffin-embedded tumour sections with a rabbit antiserum raised against recombinant HAP1. Both measurements were obtained on pretreatment biopsy material. All 25 tumours examined showed positive staining for HAP1, but there was heterogeneity in the level of expression both within and between tumours. The average coefficients of variation for intra-and intertumour heterogeneity were 620o and 82% respectively. There was a moderate but significant positive correlation between the levels of HAP1 expression and SF2 (r= 0.60, P = 0.002). Hence, this study shows that there is some relationship between intrinsic radiosensitivity and expression of a DNA repair enzyme in cervical carcinomas. The resutts suggest that this type of approach may be useful in the development of rapid predictive tests of tumour radiosensitivity.
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