ESTRO 36 Abstract Book

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S534 ESTRO 36
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IX was significantly correlated with overall stage (p=0.03)
and N classification (p=0.04). There was a significant
inverse correlation between MVD and CA-IX expression (r=-
0.22, p = 0.03). Multivariate analysis showed that low MVD
combined with high CA IX-expression was a significant
independent prognostic factor for worse loco-regional
control (HR=2.6, 95%CI 1.1-5.0, p = 0.02) in the whole
population. However, in the p16-positive subgroup, the
difference was not significant (85.7% vs. 89.7%, p=0.73).
Patients treated with CRT had a better LRC than those
with BRT independent of MVD or CA-IX expression.
Conclusion
The combination of MVD and CA-IX status might give
additional prognostic information in HNSCC patients with
known HPV status.
PO-0967 Analysis of tumour microenvironment using
multi-parametric PET/MR imaging in HNSCC xenograft
models
S. Boeke1, R. Winter2, A. Menegakis1, P. Mena-Romano 2,3,
M. Krueger4, E.C. Sezgin1 , G. Reischl4, B. Pichler4, D.
Zips 1, D. Thorwarth2
1 University Hospital Tübingen, University Department of
Radiation Oncology, Tübingen, Germany
2 University Hospital Tübingen, University Department of
Radiation Oncology - Section for Biomedical Physics,
Tübingen, Germany
3 Pontificia Universidad Católica de Chile, Institute of
Physics, Santiago, Chile
4 Werner Siemens Imaging Center, Department of
Preclinical Imaging and Radiopharmacy, Tübingen,
Germany
Purpose or Objective
Hypoxia is a major determinant of outcome in
radiotherapy (RT) especially in head and neck squamous
cell carcinoma (HNSCC). Non-invasive imaging of tumour
microenvironment with multi-parametric PET/MRI, using
e.g. hypoxia specific tracers, is a potentially powerful
technology for personalisation of RT. The aim of this study
is to investigate simultaneously fMRI and hypoxia PET in
HNSCC xenografts during the course of fractionated RT.
Material and Methods
FaDu tumours (n=7) were xenografted on the right hind leg
of immunodeficient nude mice. After a growth period of
4-6 weeks multi-parametric FMISO-PET/MRI (7T, Bruker)
was performed before and after RT (10 x 2 Gy in two
weeks, small animal image guided RT platform, SAIGRT,
Dresden, Germany). Following the second imaging,
tumours were excised after injection of Pimonidazole and
Hoechst for further histological analysis. The imaging
protocol included a 80-90 min dynamic FMISO-PET
acquisition, anatomical T2w and diffusion-weighted MRI
(DWI, 9 b-values from 0 to 800 s/mm²) as well as DCE MRI.
T2w anatomical MRI data was used for precise manual
segmentation of the actual tumour region of interest
(ROI). Within each tumour ROI, mean and maximum
tumour-to-muscle ratios (TMR, TMRmax) as well as mean
ADC values were analysed prior and post fractionated RT
treatment.
Results
Two animals presented with very small tumor volume (<
10 mm³) which did not allow for ROI-based analysis before
(n=1) or after (n=1) RT, respectively. The mean (SD)
volume was 479.3 (651.7) and 808.0 mm³ (1146.3), mean
ADC was 760.0 (138.3) and 950.0 10-³mm²/sec (176.9),
mean TMR at 80 min post injection (pi) was 1.42 (0.27) and
0.98 (0.17) and mean TMRmax at 80 min pi was 2.47 (0.18)
and 1.75 (0.75) before and after 2 weeks of RT
respectively (cf. figure 1). Mean changes (SD) during the
two weeks of irradiation were 25.0% (71.64%), 19.7%
(24.0%), -31.7% (10.5%), -21.5 % (86.9%) for tumour
volume, ADC, TMR and TMR max, respectively.
Fig. 1: Tumour volume, TMRmax and mean ADC before and
after 10 fractions of RT. Red dashed-line depicts the
mean, black the median, lower and upper hinges the 25
and 75 percentile, respectively.
Conclusion
Intra- and intertumoural heterogeneity in hypoxia
distribution and fMRI parameters were observed. FMISO
uptake after irradiation decreased and ADC-value
increased during radiotherapy as a surrogate for
reoxygenation and lower cell density or increasing
necrotic areas, respectively. Our data will be extended
with various tumour models and will form the preclinical
data base for the development of an integrated
multiparametric prediction model for personalised RT in
HNSCC.
PO-0968 The Role of epithelial to mesenchymal
transition (EMT) as Biomarker for Radioresistance in
HNSCC
I. Kurth1,2, D. Digomann2, L. Hein 2, A. Linge1,2,3,4, L. Koi5,
S. Loeck2, K. Maebert2, H. Stephan2, C. Peitzsch1, M.
Krause 1,2,3,4,5, M. Baumann 2,3,4,5,6, A. Dubrovska2,5
1NCT Partnerstandort Dresden, Translationale Onkologie,
Dresden, Germany
2OncoRay-National Center for Radiation Research in
Oncology, Faculty of Medicine and University Hospital
Carl Gustav Carus, Dresden, Germany
3Department of Radiation Oncology, Faculty of Medicine
and University Hospital Carl Gustav Carus, Dresden,
Germany
4German Cancer Consortium DKTK Dresden, German
Cancer Research Center DKFZ, Dresden, Germany
5Helmholtz-Zentrum Dresden-Rossendorf, Institute of
Radiation Oncology, Dresden, Germany
6Deutsches Krebsforschungszentrum DKFZ, Heidelberg,
Germany
Purpose or Objective
It is described that epithelial-to-mesenchymal transition
(EMT) plays an important role in head and neck squamous
carcinomas (HNSCC) progression and resistance to therapy
[1]. Recent studies suggest that for instance the expression
of EMT related microRNAs may cause intrinsic
radioresistance in HNSCC [2]. During the process of EMT
epithelial cancer cells obtain a more mesenchymal-like
motile and invasive phenotype, which has been argued to
sustain survival and therapy resistance of those tumor
cells and facilitate cancer progression. Radiotherapy is
one of the main approaches to treat HNSCC. However,
tumor radioresistance often impedes the success of
radiotherapy and has been found to drive tumor
aggressiveness and expansion. In this study we asked the
question, if radioresistant HNSCC populations display EMT
features on a molecular as well as on a functional level
and whether we can correlate those characteristics to
treatment outcome.
Material and Methods
We used multiple irradiated HNSCC lines (IR) as an
established model to investigate the traits of
radioresistance [3]. Global gene expression, protein