Hypofractionated Radiotherapy as Primary Therapy for Prostate Cancer
Condition: Prostate Cancer
MeSH terms: Prostatic Neoplasms
Study type: Interventional
Phase: Phase 2

Summary: 
      External beam radiotherapy (RT) is one of the standard curative treatment options for
      patients with prostate cancer (PC). Several randomised trials have shown excellent long-term
      biochemical outcome with higher radiation doses. Nowadays, RT for PC commonly consists of
      delivering 74-80 Gy in 2 Gy fractions, resulting in an overall treatment time of 7-8 weeks.
      The sensitivity of different tissues to fractionation changes can be quantified through the
      α/β ratio in the linear-quadratic model. Dose-response analysis of PC patients treated with
      both external beam RT and brachytherapy has led to the hypothesis that the α/β ratio of PC is
      lower than for most other tumors and approaches a value characteristic of late responding
      tissues. Values between 1.2 and 3.9 Gy have been calculated. If the α/β ratio of PC is indeed
      low, then hypofractionating RT treatments can theoretically maintain high bioequivalent tumor
      doses, shorten overall treatment time and decrease late toxicities.The advantages in terms of
      patient convenience and treatment cost are obvious. There is level I evidence that shows that
      hypofractionated radiotherapy schedules have at least equivalent biochemical outcome with
      only a small increase in acute but not late toxicity when compared to conventional
      fractionation RT schedules.

      Results on different hypofractionation schedules have been reported, however the optimal
      hypofractionation is not clear so far. In this randomised trial we would like to compare 2
      different radiotherapyschedules: 16 fractions à rato of 4 fractions a week versus 25
      fractions à rato of 5 fractions a week. The incidence on acute toxicity and early late
      toxicity (i.e. within 2 year post radiotherapy) and the impact on quality of life will be
      registrated and compared. The study will be performed in 2 stages. For stage 1, sample size
      was calculated to rule out an upper limit of 40% of patients with RTOG grade 2 or worse bowel
      (GI) complications with an expected rate of 25%, based on a one-stage Fleming-A'Hern design.
      A power of 83.0% (alpha level 0.038 one-sided) was obtained when including 72 patients per
      group (144 patients in total). If 22 or more patients out of 72 had grade 2 or worse GI
      complications, then the study arm was to be rejected. To allow for a dropout of 10%, 160
      patients were included in stage 1. Sample size for stage 2 was calculated analogously
      allowing ruling out an upper limit of 35% of patients with RTOG grade 2 or worse GI
      complications with an expected rate of 25%. When including 155 patients per group (310 in
      total) a power of 85.7% (alpha level 0.049 one-sided) was obtained. If 45 or more patients
      out of 155 had grade 2 or worse GI complications, then the study arm was to be rejected. The
      sample size for stage 1 and stage 2 combined was set at 346 (173 per group), with a 10%
      allowance for dropout.
    


Intervention name(s): hypofractionation
Intervention type(s): Radiation
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment