ESTRO 36 Abstract Book

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S318 ESTRO 36 2017
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PO-0616 HPV, CSC marker expression and tumor
hypoxia as prognosticators for LRC in patients with
HNSCC
A. Linge1,2,3,4, S. Löck2,3, C. Krenn2, S. Appold1,3, F.
Lohaus 1,2,3,4, M. Schneider2,5,6, A. Nowak3,6, V. Gudziol3,5,
G.B. Baretton3,4,7, F. Buchholz4,8, M. Baumann1,2,3,4,9, M.
Krause 1,2,3,4,9
1 Department of Radiation Oncology, TU Dresden- Med.
Faculty Carl Gustav Carus, Dresden, Germany
2 OncoRay - National Institute for Radiation Research in
Oncology, TU Dresden- Med. Faculty Carl Gustav Carus,
Dresden, Germany
3 National Center for Tumor Diseases NCT, partner site
Dresden, Dresden, Germany
4 German Cancer Research Center- Heidelberg, DKTK
partner site Dresden, Dresden, Germany
5 Department of Otorhinolaryngology, TU Dresden- Med.
Faculty Carl Gustav Carus, Dresden, Germany
6 Department of Oral and Maxillofacial Surgery, TU
Dresden- Med. Faculty Carl Gustav Carus, Dresden,
Germany
7 Institute of Pathology, TU Dresden- Med. Faculty Carl
Gustav Carus, Dresden, Germany
8 University Cancer Center- Medical Systems Biology, TU
Dresden- Med. Faculty Carl Gustav Carus, Dresden,
Germany
9 Helmholtz-Zentrum Dresden - Rossendorf, Institute of
Radiooncology, Dresden, Germany
Purpose or Objective
To validate the prognostic impact of HPV status, cancer
stem cell (CSC) expression and tumour hypoxia in patients
with locally advanced head and neck squamous cell
carcinoma (HNSCC), who received postoperative
radiotherapy. The impact of these biomarkers has been
previously reported in an explorative multicentre,
retrospective study.
Material and Methods
In this monocentric validation study, 152 patients with
squamous cell carcinoma of the oral cavity, oropharynx,
hypopharynx and larynx were included. Out of them, 40
patients received postoperative radiochemotherapy and
112 patients received radiotherapy only. All patients were
treated between 1999 and 2006. Identical methods for
biomarker analysis were applied compared to the previous
study. HPV DNA status was investigated by PCR-array
based genotyping. Gene expression analysis was
performed for hypoxia-associated genes and the potential
CSC markers CD44, SLC3A2 and MET using nanoString
technology. Cox models presented in the previous study
were validated using the concordance index as a
performance measure. Primary endpoint was loco-regional
control. Results were compared to those previously
reported.
Results
Loco-regional control and overall survival were lower as in
the cohort reported previously. Despite of this, the
prognostic value of the combination of HPV status, CSC
marker expression (SLC3A2) and tumour hypoxia status
could be validated in univariate analyses using this
independent validation cohort. For multivariate models,
the concordance index was between 0.58 and 0.69 in
validation, which indicates a good prognostic performance
of the models. The inclusion of the CSC marker CD44 and
the 15-gene hypoxia signature improved the performance
of the model, when compared to a baseline model without
any CSC markers or hypoxia classifiers.
Conclusion
The HPV status, CSC marker expression of CD44 and
SLC3A2 as well as hypoxia status are potential prognostic
biomarkers for patients with locally advanced HNSCC
treated by postoperative radiotherapy. While a lower
performance of the prognostic models was expected due
to the older validation dataset, the significant validation
results indicate the robustness of these markers. A
currently recruiting prospective clinical trial will allow
further validation of these results and may help to stratify
patients for individualized treatment strategies. In
addition, these biomarkers are currently being further
explored in patients with early-stage HNSCC, who received
surgery only and first results will also be presented.
PO-0617 Functional Brain Abnormalities in NPC
Patients After Radiotherapy
W. Ren1, J. Dai1, Y. Li1, L. Gao1, C. Sun2
1Cancer Hosp.- Chinese Academy of Med.Sciences,
Department of Radiation Oncology, Beijing, China
2Cancer Hosp.- Chinese Academy of Med.Sciences,
Department of Nuclear Medicine, Beijing, China
Purpose or Objective
Studies have consistently demonstrated the
neurocognitive complications emerge in the survivors of
NPC patients who have received RT and greatly affect
their quality of life. It is still unclear how the brain
functions are affected by radiation and whether these
brain functional alterations are related to the radiation
dose. This pilot study is aimed at exploring the brain
functional alterations by using resting-state functional
MRI.
Material and Methods
20 NPC patients and 18 normal controls were recruited in
this study. All patients were treated with intensity-
modulated RT. Resting-state functional MRI scanning and
neurocognitive tests including Montreal cognitive
assessment (MoCA), Auditory verbal learning test (AVLT),
Self-rating depression scale (SDS) and Self-rating anxiety
scale (SAS) were administered individually during every
patient 1 day before initiation of RT and 1 day after
completion of RT. The normal controls also accepted the
same MRI scanning and the neurocognitive tests.
Amplitude of low-frequency (0.01–0.08 Hz) fluctuations
(ALFF) during resting-state functional studies were
calculated by Data Processing Assistant for Resting-State
fMRI (DPARSF) software package to characterize regional
cerebral functions. Paired T test was used to compare the
cerebral functional alterations before and after treatment
while 2-sample T test was used to compare ALFF values
before and after treatment separately with healthy
controls. Neurocognitive tests comparison of patients
before and after radiotherapy and healthy controls were
adopted ANOVA analysis. Significance was set at P=0.05.
Results
Compared with the patients before and after
radiotherapy, increased ALFF were observed in inferior
temporal gyrus, parahippocampal gyrus, hippocampus;
decreased in occipital gyrus, inferior and middle temporal
gyrus, lingual gyrus, fusiform gyrus, cuneus gyrus,
cingulate gyrus, calcarine. Relative to controls, patients
showed significantly increased ALFF in fusiform gyrus and
inferior temporal gyrus bilaterally, decreased in left
frontal gyrus before radiotherapy. After treatment, ALFF
were still showed significantly changes in these regions
and also in parahippocampal gyrus, hippocampus, superior
and middle frontal gyrus, decreased in lingual gyrus,
cingulate gyrus, calcarine. There were no significant
results of neurocognitive tests scores.
Conclusion
Our findings firstly revealed that radiation treatment in
NPC patients leads to regional synchronous neural activity
changed in a short-term while not only in the regions that
involved in the target radiation fields, but also in other
low dose functional regions of relative neural pathways
which may could explain the cognitive deficits in
morphological normal-appearing brain of NPC patients
after RT. Additionally, the present study offers promising
novel neuroimaging approaches for both investigating
mechanism of radiation therapy and tracking clinical
dosage effects to optimize and individualize patient’s