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Endometrial adenocarcinoma. Radiation sensitivity and sensitivity to platinum analogs in vitro

Endometrial adenocarcinoma is mostly diagnosed in its early stages and is usually successfully cured by surgery. However, surgical staging has revealed unexpected metastases in pelvic and paraaortic lymph nodes in high risk patients. Radiotherapy and chemotherapy with platinum analogs are widely used in the treatment of recurrent and metastased endometrial carcinoma, as well as in advanced primary tumors. To improve the outcome of patients in these groups, novel radiotherapy methods, including new fractionation schemes and combined techniques, need to be evaluated. This study was undertaken to determine the variability of the intrinsic radiosensitivity and capacity of sublethal damage repair (SLDR) of endometrial adenocarcinoma cell lines. Furthermore, the sensitivity of endometrial carcinoma cell lines to the platinum analogs cisplatin and carboplatin was determined and compared to the intrinsic radiosensitivity. The radiosensitizing effect of cisplatin was studied using cell lines having dissimilar sensitivity to radiation and cisplatin. To provide low-passage cells, new endometrial carcinoma cell lines were established during the study. The recently introduced 96-well plate clonogenic assay was tested as a method to study the ratioand chemosensitivity of adenocarcinoma cell lines. All data was fitted to the linear-quadratic model. The intrinsic radiosensitivity was expressed as D value, corresponding to mean inactivation dose, obtained by calculating area under the radiation survival curve. Chemosensitivities were compared using ICso values indicating the druj, concentration causing 50% inhibition of clonogenic survival. The plating efficiencies (PE) obtained were well comparable to values obtained with1 other assays. The assay gave similar results in repeated experiments in spite of varying PEs. After modifying the assay it could be used to test the effects of radiation fractionation and simultaneous use of cytotoxic drugs and radiation. The two modifications of the 96-well plate assay gave identical results in testing the intrinsic radiosensitivity.