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S296
ESTRO 36
_______________________________________________________________________________________________
Amsterdam, The Netherlands
3
Radboud University Medical Center, Radiation Oncology,
Nijmegen, The Netherlands
4
Leiden University Medical Center, Radiation Oncology,
Leiden, The Netherlands
Purpose or Objective
In the Dutch phase III HYPRO trial (39x 2 Gy vs. 19x 3.4
Gy), the postulated non-inferiority of the
hypofractionation arm with respect to the incidence of
grade ≥2 late urinary toxicity was not shown. Moreover, a
significant increase in grade ≥3 urinary toxicity was
observed. In the current analysis we evaluated patient-
reported urinary symptoms and possible relationships with
hypofractionation and hospital of treatment.
Material and Methods
Patients with intermediate or high-risk prostate cancer
from four hospitals applying image-guided IMRT protocols
and recruiting >70 patients were analyzed, excluding
patients with a baseline catheter. Long-term hormonal
treatment (36 months) was prescribed to high-risk
patients in hospital A-C but not in hospital D. A total of
561 patients (n=275 for standard fractionation (SF),
hypofractionation (HF) n=296) with ≥1 follow-up symptom
questionnaire were eligible (n=2355 total questionnaires).
Treatment arm was balanced within hospitals. Local
guidelines were applied for dose (in)homogeneity, margins
(5-8 mm), and optimization. One hospital used MRI for
prostate delineation (hospital A) and another hospital
applied a rectal balloon (D). Hospital B and C varied in the
applied safety margins of 5-6mm and 8mm, respectively.
The study protocol did not provide dose constraints for the
bladder; bladder delineation was done retrospectively.
We calculated bladder and urethra dose (EQD2) with α/β
ratios of 3 Gy and 5 Gy, and analyzed incidences of urinary
symptoms between 6 months and 5 year. The impact of
treatment arm and hospital on late urinary toxicity
endpoints was calculated in a multivariate model
including time and hormonal therapy.
Results
Dose to structures within the target volume (urethra, base
of trigone area) was 78 Gy for SF vs 82.7 Gy for HF with
α/β=3 Gy, and 78 Gy for both schedules with α/β=5.
Average mean bladder dose was 29.2 Gy (SF) vs 29.9 Gy
(HF) for α/β=3, (p=0.4), and 30.2 Gy vs 29.1 Gy (α/β=5,
p=0.2), for SF vs. HF, respectively. Planned dose to the
bladder varied significantly (p<0.05) between hospitals
and was relatively low for hospital A and D (≈25 Gy vs. ≈33
Gy for hospital B and C, based on α/β=3 Gy). Symptoms of
incontinence, straining, and weak stream were on average
significantly more reported in the HF arm during follow-
up (
FIG 1A-C
) and varied significantly between hospitals
(
FIG 2A-C)
. Hormonal treatment was not predictive in the
current models. We established that baseline levels of
urinary complaints were considerable as well (
FIG 1
).
Conclusion