How low is the alpha/beta ratio for prostate cancer?

It has been suggested recently that the alpha/beta ratio for human prostate cancer is low (around 1.5 Gy), and much debate on the evidence for such a low value is ongoing. Analyses reported so far ignored the contribution of tumor repopulation. Extremely low alpha values and unrealistic cell numbers of tumor clonogens are found in these studies. In this paper, we present a comprehensive analysis of the updated clinical data to derive a self-consistent set of parameters for the linear-quadratic (LQ) model.

The generalized LQ model, considering the effects of dose rate, sublethal damage repair, and clonogenic proliferation, was used to analyze the recently reported clinical data for prostate cancer using either external-beam radiotherapy or brachytherapy. Three LQ parameters, alpha, alpha/beta, and the repair time, were determined based on the clinical finding that the external-beam radiotherapy and the 125I and (103)Pd permanent implants are biologically equivalent. The tumor control probability model was used also to analyze the clinical data to obtain an independent relationship of alpha/beta vs. alpha and to estimate clonogenic cell numbers for patients in different risk groups.

Based on the analysis of clinical data and a consideration of repopulation effect, we have derived a self-consistent set of LQ parameters for prostate cancer: alpha = 0.15 +/- 0.04 Gy(-1), alpha/beta = 3.1 +/- 0.5 Gy. Our analysis indicates the half-time of sublethal damage repair to be in the range from 0 to 90 min with a best estimate of 16 min. The best estimate of clonogenic cell numbers in prostate tumors is found to range from 10(6) to 10(7) according to the patient risk level. These values are more realistic than those derived previously (only 10-100).

The effect of tumor repopulation is not negligible in determining the LQ parameters for prostate cancer, especially for the low-dose-rate permanent implants. Analysis of clinical data for prostate cancer with corrections for damage repair and repopulation effects results in a low alpha/beta ratio of 3.1 Gy. Unrealistic clonogenic cell numbers and extremely small values of alpha reported in the literature can be resolved by correcting for repopulation effect. The LQ parameters derived presently from the clinical data are consistent with reports of intrinsic radiosensitivity in vitro.