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within a 200 times iterated 5-fold cross-validation
approach. One additional analysis was performed with the
lowest MIO over the three follow-up times as response
variable (referred to as “3-12 months”; observed at the
3/6 months follow-ups in 60% of the cases). Candidate
predictors from UVA,
i.e.
with a median two-sided p-
value≤0.05 over all iterations, qualified for multivariate
linear regression analysis (MVA) applying the same cross-
validation approach. Predictability was assessed using
coefficient of determination (r
2
), and Spearman’s rank
correlation coefficient (Rs); both given as the median over
all iterations.
Results
Of 5-12 variables that presented with p≤0.20 on UVA
(
Table
), trismus status pre-RT was an independent
predictor for post-RT trismus (p=0.01-0.02 for all response
variables) as was the mean dose to the ipsilateral masseter
(p=0.05 at 3, 6, and 3-12 months). The combination of
these two candidate predictors generated MVA models
with increased predictability compared to the
corresponding UVA models (r
2
=0.35-0.40 vs. 0.20-0.32;
Rs=0.59-0.63 vs. 0.44-0.57), and consequently steeper
response curves with 11-13 mm and 15-16 mm MIO
difference between the least and the most risky quintile
for the UVA and MVA models, respectively (
Figure
). A
tendency of trismus recovery was noted for longer follow-
up with a lower pre-RT normalized MIO difference at 12
months compared to that of the two earlier assessments;
median (range): 0.14 (-0.67, 0.62) vs. 0.17 (-1.07, 0.66) at
3 months, and 0.16 (-1.33, 0.64) at 6 months.
Conclusion
A temporally robust dose-response relationship for
radiation-induced trismus, quantified as a millimeter
mouth-opening decrease, could be observed within the
first year after completed radiotherapy. Our results
suggest that the dose-response for trismus within this
period relies on the mean dose to the ipsilateral masseter,
as well as the underlying pre-treatment mouth-opening
ability. Up to ten additional variables presented with p-
values in the interval p=0.06-0.19 and may prove to be of
importance if investigated in larger/pooled cohorts with
diversified treatment approaches where potential effects
can be thoroughly investigated.
PO-0855 Use of the LKB model to fit urethral
strictures for prostate patients treated with HDRB
V. Panettieri
1
, E. Onjukka
2
, T. Rancati
3
, R. Smith
1
, J.
Millar
1
1
Alfred Hospital, Alfred Health Radiation Oncology,
Melbourne, Australia
2
Karolinska University Hospital, Dept of Hospital Physics,
Stockholm, Sweden
3
Fondazione IRCCS- Istituto Nazionale dei Tumori,
Prostate Cancer Program, Milan, Italy
Purpose or Objective
High-Dose-Rate brachytherapy (HDRB) is widely used in
combination with external beam radiotherapy in the
treatment of prostate cancer. Despite providing
biochemical control similar to other techniques, due to
the variety of fractionation regimes used there is no clear
consensus on the dose limits for the organs-at-risk, in
particular the urethra.
The aim of the work has been to fit the Lyman-Kutcher-
Burman (LKB) Normal Tissue Complication Probability
model to clinical outcome on urethral strictures data
collected at a single institution.
Material and Methods
Dose-volume histograms and clinical records of 262
patients were retrospectively analysed. The patients had
follow-up 6, 12, 18, 24 months and then every year until
10 years after the treatment. Clinical and toxicity data
were collected prospectively. The end-point was the time
of the first urethrotomy, a follow-up cut-off time of 4
years was chosen and the average stricture rate was about
12.6%. The LKB NTCP model was fitted using the maximum
likelihood method and used simulated annealing to find a
stable solution. Since the patients were treated with 3
different fractionation regimes (18 Gy in 3, 19 Gy in 2 and
18 Gy in 2 fractions) doses were converted into EQD2 with
α/β = 5 Gy.
Results
For this cohort of patients the risk of urethral stricture
could be modelled by means of a smooth function of EUD
(see Fig 1). Using the LKB model the risk of complication
could be represented by a TD50 of 220 Gy, a steepness
parameter m of 0.55 and a volume-effect parameter n of
2.7. The fitted model showed good correlation with the
observed toxicity rates with the largest deviation shown
at higher doses. The large value of n could suggest a
parallel behaviour of the urethra, however further
validation is required with an independent dataset.
Conclusion
In this work we have fitted the LKB model to clinical
outcome on urethral strictures data for patients treated
with HDRB collected at a single institution. The results
show that the fitted model provides a good representation
of the observed data, however further analysis and
independent validation are necessary to confirm its
behaviour and parameters.
Poster: Physics track: Intra-fraction motion
management