Potential application of the ATP cell viability assay in the measurement of intrinsic radiosensitivity in cervical cancer

Abstract

Background. Intrinsic radiosensitivity using the clonogenic assay and the cell surviving fraction at 2 Gy (SF 2) has been shown to be an independent prognostic factor for patient response to radiotherapy in carcinoma of the cervix. The clonogenic assay has significant shortcomings, making it unsuitable for routine clinical use. The ATP cell viability assay (ATP-CVA) has been shown to have a high tumor evaluability rate, technical simplicity, and reproducibility in chemosensitivity testing. Aims. This study compares the ATP-CVA with the clonogenic assay in the in vitro radiosensitivity testing of cervical cancer cell lines. Correlation of in vitro radiosensitivity and in vivo patient response was also determined. Methods. Five cervical carcinoma cell lines (SiHa, HeLa, Caski, C-33A, and C4-1) were tested using the ATP-CVA and the clonogenic assay. Survival curves were plotted and the mean SF 2 values obtained by the two different assay methods were compared using ANOVA to see if there were significant differences. Mean SF 2 values obtained from 27 cervical cancers were compared with clinical outcomes. Results. The SF 2 values for the cell lines ranged from 0.28 to 0.67 when tested using the ATP-CVA. Using the clonogenic assay, the SF 2 values ranged from 0.27 to 0.70. ANOVA with Bonferroni pairwise multiple comparison showed no significant difference between the mean SF 2 values for the individual cell lines between the two assay methods. Twenty-three cervical cancer samples (85%) were evaluable for SF 2 using ATP-CVA. The mean SF 2 values of patients who had locoregional failure were significantly higher than those who achieved local control (P < 0.01). Conclusions. Testing intrinsic radiosensitivity using the surviving fraction at 2 Gy (SF 2) is comparable using the two assay methods of ATP-CVA and clonogenic assay. The ATP-CVA should be further investigated in the testing of intrinsic radiosensitivity in patients with cervical cancer. © 2004 Elsevier Inc. All rights reserved.