ESTRO 36 Abstract Book

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S847 ESTRO 36 2017
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was 23.4 Gy(RBE) given by 13 fractions. The plan was
optimized using a fixed RBE value of 1.1. The IMPT plans
were imported into the FLUKA Monte Carlo code where
dose and dose-average LET distributions (LETD) were
calculated. Subsequently, a published LET-based RBE
model for proton therapy was applied to these
distributions to quantify the biological doses for the heart,
lungs and the PTV.
Results
The Monte Carlo simulations revealed elevated
LETD values both in the PTV, heart and lung and
correspondingly higher biological doses as compared to
the doses obtained with an RBE of 1.1 (Figure 1). The dose
volume histograms revealed small elevation in mean dose
to the lungs (from 2.0 to 2.4 Gy) and the heart (from 0.7
to 1.0 Gy). However, the variable RBE model calculated a
significantly higher max dose in both organs, with a shift
from 21.8 Gy to 27.2 Gy for the lungs and 17.2 Gy to 21.2
Gy for the heart.
Conclusion
Including LET and biological dose models revealed an
increased dose to heart and lung compared to doses
calculated with RBE of 1.1, mainly due to the enlarged LET
values at the distal dose falloff of the beam. The
reproducibility of these results in a larger cohort of
patients will be investigated.
Electronic Poster: Physics track: (Radio)biological
modelling
EP-1593 Accuracy of TCP model for nasopharyngeal
cancer after more than five years average follow-up
M. Avanzo 1, J. Stancanello2, G. Franchin3, S. Barbiero4, R.
Jena5, G. Sartor1, E. Capra1
1 Centro di Riferimento Oncologico, Medical Physics,
Aviano, Italy
2 Oncoradiomics, Mastricht, The Netherlands
3 Centro di Riferimento Oncologico, Radiation Oncology
Department, Aviano, Italy
4 Casa di Cura S. Rossore, Radio-oncology, Pisa, Italy
5 University of Cambridge, Department of Oncology,
Cambridge, United Kingdom
Purpose or Objective
A model for radiation therapy (RT) based tumor control
probability (TCP) of nasopharyngeal carcinoma (NPC)
which includes the effects of hypoxia and
chemoradiotherapy was previously developed by fitting
TCP to clinical local control data from published
randomized studies and tested in a patient dataset with
limited follow-up time.
The purpose of this work was to validate the model by
comparison of estimated TCP and average overall local
control rate in a cohort of patients with long follow-up
time.
Material and Methods
96 patients treated with intensity modulated RT delivered
by LINAC or Helical Tomotherapy and neoadjuvant
chemotherapy for histologically proven nasopharyngeal
carcinoma were followed for an average time of 5.5 years.
TCP was calculated from individual GTV dose-volume
histograms, fractionation and overall treatment duration
data using a previously established model (Ref. 1) based
on the linear-quadratic model and Poisson statistics
modified to account for repopulation, chemotherapy,
heterogeneity of dose to the tumor, and hypoxia. The
model parameters were: α/β of 10 Gy, α of 0.396 Gy−1 with
σα of 0.07 Gy−1, density of clonogens 107 cc-1, fraction of
patients showing hypoxia 22%, oxygen enhancement ratio
(OER) of 1.417, chemotherapy enhancement factor 1.64,
Tpot of 3 days and Tk of 28 days.
The average TCP was compared to the local control rate
(LCR), defined as the absence of clinical and radiological
evidence of disease residuum in the GTV at the last follow-
up visit.
Results
The average calculated TCP in patients treated at our
institution was 86.9% with 95% confidence intervals (95%
CIs) of 74%–95.0%. At a mean follow-up time of 5.5 years,
15 patients developed local failure in the nasopharynx and
three had distant and local recurrences. Three patients
developed recurrence outside the treated volume. Local
control was therefore obtained in 81% (95% CI: 72-87.8%)
patients, and was in agreement with calculated TCP.
Conclusion
The TCP model shows was in agreement with LCR in
patients treated at our institution after a long follow-up
time.
References:
1. Avanzo et al. Med. Phys. 37 (4) 1533-1544, April 2010
EP-1594 Development of multivariable models for
acute toxicities in nasopharyngeal cancer radiotherapy
A. Cavallo1, T. Rancati2, A. Cicchetti2, N.A. Iacovelli3, F.
Palorini2, C. Fallai3, E. Orlandi3, E. Pignoli 1
1Fondazione IRCCS Istituto Nazionale dei Tumori, Medical
Physics Unit, Milan, Italy
2Fondazione IRCCS Istituto Nazionale dei Tumori,
Prostate Cancer Program, Milan, Italy
3Fondazione IRCCS Istituto Nazionale dei Tumori,
Radiation Oncology 2, Milan, Italy
Purpose or Objective
To investigate the dose-response relationship for acute
toxicities in nasopharyngeal cancer (NPC) RT and to build
multivariable models aiming at the inclusion of other non-
dosimetric factors.
Material and Methods
A series of consecutive NPC patients (pts) treated
curatively with IMRT/VMAT + chemotherapy at 70 Gy (35-
33 fr, 2-2.12 Gy/fr) was considered. Clinical- tumor- and
treatment-related data were retrospectively collected:
age, gender, BMI, smoking history, histology, staging,
comorbidities, RT technique, overall treatment time.
Organs-at-risk (OAR) volumes and dose distribution for
each pt were also considered. Acute toxicities were
assessed according to CTCAE v4.0 at baseline and weekly
during RT. Four endpoints were considered: mean grade
(G) ≥1.5 and G≥3 oral mucositis (OM), G3 dysphagia and
G≥2 salivary dysfunction (SD). The selected OARs were:
oral cavity (OC) and parotid glands (PG) considered as a
single organ for OM and SD; OC, pharyngeal constrictor
muscles (PCM), supraglottic and glottic larynx (GL) for
dysphagia. DVHs were reduced to Equivalent Uniform Dose
(EUD): for each OAR the best volume parameter n was
determined through numerical optimization. When this
procedure did not converge, we chose to evaluate DVH
cutpoint through t-test. EUD was inserted into a
multivariable logistic (ML) model together with
clinical/treatment features; variables selection was
guided by LASSO. Goodness of fit was evaluated with
Hosmer-Lemeshow test and calibration plot.
Results
Data were collected for 132 pts. MeanG≥1.5 and G≥3 OM
were reported in 40 pts (30%), G3 dysphagia in 50 (38%)
and G≥2 SD in 90 (68%). ML models (figures 1-2) consisted
in: a single variable for meanG≥1.5 OM, i.e. OC EUD with
n=1 (mean dose) (OR=1.07); 3 variables for G≥3 OM
including OC EUD with n=0.05 (OR=1.02), PG EUD with n=1
(OR=1.06), BMI≥30 (OR=3.8, obese pts); 3 variables for
dysphagia including PCM V50Gy (OR=1.02), GL and OC EUD
with n=0.35 and 0.15 respectively (OR=1.02 and 1.04); 4
variables for SD including PG D98% (OR=1.04), OC EUD with
n=0.05 (OR=1.11), age (OR=1.08, 5-year intervals), smoke
(OR=1.37, yes vs no). Calibration was good in all cases.