ESTRO 36 Abstract Book

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S227 ESTRO 36 2017
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represses transcription of genes within its
boundaries. Chromothripsis and kataegis is evident in one
fifth of these tumours and can be associated with more
aggressive disease. Using driver mutations, copy-number
alterations and methylation, we were able to categorize
patients into prognostic categories which has less than 5%
or greater than 50% probability of relapse. The use of
genomic markers as prognostic factors for local failure and
for systemic disease are therefore novel risk-stratification
tools which help to triage patients to existing treatment
options, and potentially identification of molecular
targets for therapy. However, our data also suggest
that novel therapeutic approaches focus on recurrent non-
mutation targets. This new approach could then prevent
castrate-resistance by targeting genetic instability earlier
on the natural history of the disease when fewer driver
events are operational.
OC-0436 Cytokine-dependent regulation of prostate
cancer stem cell maintenance in response to
irradiation
C. Peitzsch1,2, M. Baumbach1, M. Cojoc 1, L. Hein1, I.
Kurth1,2, M. Baumann1,2,3,4,5, M. Krause1,3,4,5, A.
Dubrovska 1,3,4
1 OncoRay - Center for Radiation Research in Oncology,
Faculty of Medicine and University Hospital Carl Gustav
Carus- Technische Universität Dresden, Dresden,
Germany
2 National Center for Tumor Diseases NCT, German
Cancer Research Center DKFZ, Dresden, Germany
3 German Cancer Consortium DKTK, German Cancer
Research Center DKFZ, Dresden, Germany
4 Institute of Radiation Oncology, Helmholtz-Zentrum
Dresden-Rossendorf, Dresden, Germany
5 Department of Radiation Oncology, Faculty of Medicine
and University Hospital Carl Gustav Carus- Technische
Universität Dresden, Dresden, Germany
Purpose or Objective
According to the cancer stem cell hypothesis prostate
cancer is driven by a malignant subpopulation with stem-
like properties. These cancer stem cells (CSC) contribute
to tumor-initiation, metastasis, therapy-resistance and
tumor relapse. In parallel, genetic mutations accumulate
over time and CSC subclones evolve. Therapeutic
interventions like radiotherapy provide selective pressure
for the expansion of resistant subclones with genetic
diversification. We hypothesize that the determination of
CSC-related biomarker in prostate cancer biopsies is
correlating with clinical parameter and can be used for
patient stratification and treatment selection to improve
personalized radiotherapy.
Material and Methods
We generated isogenic radioresistant prostate cancer cell
lines with a high expression of CSC marker, a epithelial-
to-mesenchymal transition (EMT) phenotype, higher self-
renewal properties, higher tumorigenicity and enhanced
DNA repair capacity. We applied comparative genomic,
proteomic, metabolomic, epigenomic and secretome
analysis to identify novel biomarker for prostate cancer
radioresistance and to unravel contributing molecular
mechanisms. Novel biomarkers were validated using the
Cancer Genome Atlas (TCGA) database and correlated
with the tumor-free survival of prostate cancer patients
after anti-cancer therapy including radiotherapy using
SUMO software calculation.
Results
Within our first proof-of-principle study, we could show
that ALDH-positive CSCs are radioresistant and maintained
directly by the Wnt/β-catenin signaling pathway. In
addition, we found that irradiation is inducing CSC marker
and CSC properties in a dose- and time-dependent
manner. This irradiation-induced CSC-plasticity was
attributed to the modulation of the histone methylation
code. Within the present study we analyzed a panel of
secreted cytokines and their corresponding cytokine
receptors in the radioresistant prostate cancer sublines, in
a s.c. xenotransplantation model, in ex vivo irradiated
primary prostate cancer biopsies and in blood samples of
prostate cancer patients during the course of radiotherapy
and found, for example, the CXCR4-CXCL12 signaling to be
involved in the CSC maintenance and the induction of
prostate cancer radioresistance.
Conclusion
Our studies suggest that the combination of irradiation
with cytokine signaling modulation, especially the CXCR4-
CXCL12 signaling, may increase the cytotoxic effects of
irradiation in prostate cancer cells. The expression
profiling of proteins involved in the cytokine signaling can
be used to predict clinical outcome of prostate cancer
patients after radiotherapy.
Proffered Papers: New technologies for imaging and
therapy
OC-0437 Scatter imaging: promising modality for image
guided ablation radiotherapy for lung cancer patients
J. Chu1, G. Redler1, G. Cifter1, K. Jones 1, J. Turian 1
1Rush University Medical Center, Department of Radiation
Oncology, Chicago IL, USA
Purpose or Objective
Early stage lung cancers can be effectively treated by
stereotactic ablation radiation therapy (SABR). Successful
treatment requires hypofractionation and large dose per
fraction (up to 20 Gy) while maintaining a high level of
accuracy (≤1.0mm). By imaging the photons that are
Compton-scattered out of the treatment beam, real-time,
non-invasive monitoring of the tumor location may be
possible. To assess the potential of this modality, we have
obtained scatter images of static and movable tumor
phantoms, and calculated images from CT-based Monte
Carlo simulations.
Material and Methods
Compton scatter is a natural by-product of external beam
radiation therapy. The scattered radiation contains
information about the patient anatomy and the transient
tumor location. An embedded tumor in a Quasar
respiratory motion phantom (Modus Medical Devices Inc.)
was programmed to move linearly over 2.5cm. While
irradiating the embedded tumor using a 6MV Varian
TrueBeam linear accelerator, experimental scatter images
were measured with a Varian PaxScan flat panel detector
and a pinhole collimator. Tumor centroid locations were
then measured from various scatter images and compared
with the expected values. Monte Carlo N-Particle (MCNP)
code was used to simulate scatter images from phantoms
and patient CT images using 10 - 1000MU, or 0.5 – 50
second time scales. The quality of the images was assessed
to determine their potential for tumor localization during
treatment.
Results
The measured tumor centroid locations agreed with the
expected values to within 1mm, which is adequately
accurate for clinical tumor tracking. Lung tumor phantom
images showed excellent signal and contrast. The
contrast-to-noise ratio ranged from 3.4 to 15.1 for scatter
images acquired with 0.5 to 50s. The attached figures
below show CT and simulated scatter images
(corresponding to the red shaded region in CT) for both
inhale and exhale breathing phases. The scatter images
clearly show variation of tumor and diaphragm locations
for two breathing phases. Other pertinent anatomical
structures, such as chest wall, heart, and lung are also
clearly visible.
Conclusion
This study has demonstrated the feasibility of using
scatter imaging to track lung tumor movement during