Editorial Comment: Ultra-hypofractionated versus conventionally fractionated radiotherapy for prostate cancer: 5-year outcomes of the HYPO-RT-PC randomised, non-inferiority, phase 3 trial
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Abstract
Anders Widmark 1, Adalsteinn Gunnlaugsson 2, Lars Beckman 3, Camilla Thellenberg-Karlsson
4, Morten Hoyer 5, Magnus Lagerlund 6, et al.
1 Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden; 2 Department
of Hematology, Oncology and Radiation Physics, Skåne University Hospital, Lund University,
Lund, Sweden; 3 Department of Oncology, Sundsvall Hospital, Sundsvall, Sweden; 4 Department
of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden; 5 Department of Oncology
and Danish Centre for Particle Therapy, Aarhus University Hospital, Aarhus, Denmark;
6 Department of Oncology, Kalmar Hospital, Kalmar, Sweden
Lancet. 2019 Aug 3;394(10196):385-395.
DOI: 10.1016/S0140-6736(19)31131-6 | ACCESS: 10.1016/S0140-6736(19)31131-6
COMMENT
Due the low alpha/beta ratio, the hypofractionation of the external radiotherapy treatment
of prostate cancer can increase the therapeutic ratio and reduce the health-care cost
and improve the patient comfort. It can be done by moderate hypofractionation (using
2.4 – 3.4 Gy) or by ultra-hypofractionation (at least 5 Gy per fraction) ( 1 - 3 ).
This phase 3 non-inferiority randomized trial is the first to report on the efficacy
and side-effects on ultra-fractionation compared with conventional and has the PSA
relapse and clinical failure as primary endpoint. The most relevant secondary endpoints
were the overall survival and prostate cancer-specific survival and the median follow-up
time was 5yr.
The ultra-hypofractionation was non-inferior to the conventional fractionation (HR
1.002) and no significant differences were found in terms of relevant urinary or gastrointestinal
toxicity.
To determine the dose response parameters and the fractionation sensitivity of prostate tumours from clinical results of patients treated with external beam radiotherapy. The study was based on five-year biochemical results from 14 168 patients treated with external beam radiotherapy. Treatment data from 11 330 patients treated with conventional fractionation have been corrected for overall treatment time and fitted with a logit equation. The results have been used to determine the optimum α/β values that minimise differences in predictions from 2838 patients treated with hypofractionated schedules. Conventional fractionation data yielded logit dose response parameters for all risk groups and for all definitions of biochemical failures. The analysis of hypofractionation data led to very low α/β values (1-1.7 Gy) in all mentioned cases. Neglecting the correction for overall treatment time has little impact on the derivation of α/β values for prostate cancers. These results indicate that the high fractionation sensitivity is an intrinsic property of prostate carcinomas and they support the use of hypofractionation to increase the therapeutic gain for these tumours.
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