Diminishing returns from ultra-hypofractionated radiation therapy for prostate cancer
Abstract
Introduction: More than a decade of randomized controlled trials in prostate cancer have established a positive radiation dose response at moderate doses and a consistently low α/β ratio in the linear quadratic model for moderate hypofractionation. The recently published large randomized trial of ultra-hypofractionated prostate cancer radiotherapy adds substantially to our current knowledge of dose-response and fractionation sensitivity. Methods and Materials: Randomized trials of dose-escalation and hypofractionation of radiotherapy are meta-analyzed to yield the overall best estimate of the α/β ratio. Additionally, a putative saturation of dose effect previously reported at approximately 80 Gy EQD2 is investigated by mapping the relative effectiveness assessed at five years onto a single reference dose-response curve. Results: Meta-analysis of 14 randomized trials including 13,384 patients yields a best estimate of α/β=1.6 Gy [95% CI: 1.3 to 2.0 Gy], but with highly significant heterogeneity (I2=70%, P=0.0005). Further analysis indicates an association between increasing dose per fraction in the experimental arm and increasing α/β ratio (slope: 0.6 Gy increase in α/β per Gy increase in fraction size, p=0.017). This deviation from the linear quadratic model could, however, also be explained by biochemical control maxing out at doses above approximately 80 Gy. Conclusions: Biochemical control data from randomized controlled trials of dose-per-fraction escalation in prostate…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design. Reported size: 13,384 participants or records.
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