Rationale, Conduct, and Outcome Using Hypofractionated Radiotherapy in Prostate Cancer
Section snippets
What Is the Fractionation Response of Prostate Cancer?
Conventional fractionation schemes using fraction sizes of 1.8 to 2.0 Gy are based on the premise that tumors typically are less responsive to fraction size than are late-responding normal tissues. The α/β ratio is a measure of fractionation response, with low ratios associated with late-responding normal tissues. A low α/β is consistent with a greater capacity for repair between fractions, with an accompanying greater relative sparing with small fraction sizes, than for tumors with their
The Theoretical Potential for Hypofractionation to Improve Tumor Control
Although conventional fractionation schemes using small fraction sizes of 1.8 to 2.0 Gy are based on the premise that tumors typically have high α/β ratios that make them less responsive to fraction size than are late-responding normal tissues, the situation may well be reversed for prostate cancer, favoring the use of hypofractionation. These relationships, at least over a range of fraction sizes between 1 and 6 Gy, can best be shown through the use of the linear-quadratic equation, which
How Best Can Hypofractionation Be Explored in a Clinical Setting?
Two types of hypofractionation designs could be considered that would exploit the hypothesized radiobiological advantages described earlier: (1) normal tissue de-escalation of total dose while maintaining constant predicted tumor control and (2) tumor biological dose escalation with constant predicted normal tissue late effects. These 2 hypofractionation approaches seek to achieve different desirable objectives.
What Is the Current State of Clinical Experience With Hypofractionation for Prostate Cancer?
Hypofractionated external-beam radiotherapy has actually been used clinically for a number of years, particularly in the United Kingdom.21, 22, 23 Although these treatments were generally well tolerated, overall efficacy is difficult to assess, given that these trials were performed largely in the pre-PSA era. A number of more contemporary hypofractionation trials, either published or currently in progress, are shown in Table 1. The most straightforward and intuitive way of estimating the
Extreme Hypofractionation
Even fewer fractions are beginning to be used in some clinical practices, although not always in the context of prospective trials. Called stereotactic body radiotherapy (SBRT) when only 5 total fractions are used, fraction sizes of between about 5.5 and 7 Gy are typically given, although higher-dose fractions have been used as well. Although this further reduction in fraction number might seem a logical extension of current, more modestly hypofractionated studies, there are numerous reasons
Conclusions
Results from several mostly phase I/II prostate radiotherapy studies have indicated a gain in therapeutic ratio with increases in radiation fraction size beyond the 1.8 to 2 Gy typical of standard practice. However, given that uncertainties exist in extrapolating biological effects to larger fractions and that dose-escalated radiation therapy with standard fractionation is already highly effective, it is imperative that ongoing and future studies of hypofractionation be performed in a
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