In vitro intrinsic radiation sensitivity of glioblastoma multiforme

Glioblastoma multiforme is one of the most resistant of human tumors to radiation whether used alone or in combination with surgery and/or chemotherapy. This resistance may be caused by one or more of several different factors. These include inherent cellular radiation sensitivity, an efficient repair of radiation damage, an increased number of clonogens per unit of volume, a high hypoxic fraction, high [GSH] concentration, and rapid proliferation between fractions. In the present study, we evaluate the intrinsic radiation sensitivity (surviving fraction at 2 Gy or mean inactivation dose) of malignant human glioma cells in vitro. The in vitro radiation sensitivity of 21 malignant glioma cell lines (early and long term passages) has been measured using colony formation as the end-point of cell viability. The survival curve parameters (SF2 measured and calculated, alpha, beta, D0, n and MID) have been determined for single dose irradiations of exponential phase cells (18-24 hr after plating) under aerobic conditions and growing on plastic. The mean SF2 of the 21 cell lines is 0.51 +/- 0.14 (with a range of 0.19 to 0.76). This value may be compared to the mean SF2 of 0.43-0.47 for SCC, 0.43 for melanoma, and 0.52 for glioblastoma as reported from other authors when using colony formation of cells in exponential phase on plastic. Although glioblastoma is almost invariably fatal, our data demonstrate a very wide range of intrinsic radiosensitivities. These broadly overlap the radiation sensitivities of cell lines from tumors that are often treated successfully. We conclude that standard in vitro measurements of cellular radiation sensitivity (SF2) do not yield values that track in a simple manner with local control probability at the clinical level and that, for at least some of the tumors, other parameters and/or physiological factors are more important.