OverviewIs the α/β Value for Prostate Tumours Low Enough to be Safely Used in Clinical Trials?
Introduction
There is increased interest in the clinically relevant α/β value for prostate tumours in light of the potential advantages of hypofractionated treatments. Such treatment, with a few large radiation fractions, will lead to fewer treatment sessions, which might be convenient from the point of view of both the patient (who will face a shorter treatment) and the economy of the radiotherapy department (which might be able to treat more patients in the same time period and therefore shorten the waiting lists). Furthermore, hypofractionated treatments of prostate carcinomas might also have the potential of an increased therapeutic ratio if it is confirmed that these tumours do have a smaller α/β value than the late responding normal tissues at risk. This paper will critically review the published clinical and experimental data regarding the radiobiological differential that might or might not exist between prostate tumours and the late normal tissues around them. Relevant publications reporting the derivation of the α/β value for prostate tumours or the outcome of radiotherapy in patients with prostate carcinoma were retrieved using standardised queries (e.g. ‘prostate alpha/beta’, ‘prostate radiotherapy’, ‘prostate hypofractionation’, etc.). These were supplemented with references from the relevant papers, as well as by additional papers identified in the personal database of the author.
Section snippets
Radiobiological Analysis of Clinical and Experimental Data
An α/β value as low as 1.5 Gy (95% confidence interval 0.8–2.2 Gy) was first presented in detail by Brenner and Hall [1], based on a review of 367 patients from two centres, some being treated at a low dose rate with I-125 and the others with high dose rate external beams at 1.8 or 2.0 Gy per fraction. This first report was disputed 2, 3 and was the starting point for many discussions about the prospects of hypofractionation for the treatment of prostate tumours 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14
Clinical Studies of Hypofractionated External Beam Radiation Therapy
Hypofractionation has been used for several years, but on a small scale compared with conventional fractionation, due to the risk of an increase rate of unacceptable late effects [41]. This is why there are relatively few studies that have reported clinical results of hypofractionated treatments for prostate carcinoma with external beam irradiation (Table 2).
Highly hypofractionated treatments of the prostate with either 55 Gy in 12 fractions (BED3 = 139 Gy3) or 36 Gy in six fractions (BED3 = 108 Gy3)
Clinical Hypofractionation with High Dose Rate Brachytherapy
Analyses have also been carried out on the results reported from clinical treatments delivering a part or the entire therapeutic dose with high dose rate brachytherapy (Table 3). Borghede et al. [59] presented the results of 50 patients treated with a combination of 50 Gy of external beam radiotherapy and 2 × 10 Gy of brachytherapy (BED3 = 170 Gy3) showing high control rates (84% biochemical and 96% clinical) and minimal toxicity after 4 years. Mate et al. [60] reported on a group of 104 patients
Normal Tissue Radiobiology
Turning from low α/β values in tumours to the relative values for late rectal reactions (usually assumed to be 3 Gy), it seems that almost all the radiobiological aspects that have been taken into consideration point towards an α/β value for prostate tumours that is lower than the α/β value for late rectal complications. Indeed, the review by Fowler et al. [15] suggests α/β values for the rectal response between 4 and 6 Gy (with confidence intervals ranging from 2 to 8 Gy), which are higher than
Discussion
Most of the clinical studies available now seem to support the idea of a low α/β value for the prostate tumours that may favour hypofractionated regimens, which could be beneficial for both the patient and the radiotherapy department. However, such regimens might seem unsettling, especially in light of the many clinical examples of other body sites where the use of a few large fractions has resulted in an unacceptable rate of late effects [41]. The clinical data available now do not justify the
Conclusions
There is now quite a broad range of clinical data, both retrospective analyses and clinical trials, that suggest that the α/β values for prostate carcinomas are small, possibly even lower than the α/β values for the late responding normal tissues at risk. This opens up the prospect of a potential increase in the therapeutic ratio for these cancers through the use of hypofractionated treatments. However, there are many other radiobiological factors that have to be taken carefully into
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