ESTRO 36 Abstract Book

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S544 ESTRO 36 2017
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surface molecules CD14, CD83, CD80, CD86 and HLA-DR via
flow cytometry. Functional analysis of irradiated DCs was
performed through FITC-labelled phagocytosis assay.
Results
No major significant changes in the immune profile during
differentiation of monocytes (CD14high, CD83low, CD86low,
CD80low, HLA-DRhigh) into iDCs (CD83low, CD86low,
CD80 medium, HLA-DRmedium) and mDCs (CD83 high, CD86high,
CD80 high, HLA-DRhigh) were seen after treatment with
different radiation doses (1x15 Gy, 5x2 Gy, 1x0.5 Gy)
compared to the untreated control group. Functional
analysis showed no difference in the phagocytotic capacity
of irradiated iDCs and macs compared to the control
group.
Conclusion
Our experiments reveal that after irradiation with
different fractionations and doses maturation of DCs was
unchanged compared to the control group. The capability
for phagocytosis was unaffected after irradiation of DCs,
indicating persistent functionality of the immune system.
Additional RT-induced effects on the immunogenic
potential of DCs will be investigated by using further
functional assays (migration assay, mixed lymphocyte
reaction assay). To investigate the effect of particle
therapy, DCs will be irradiated with protons and carbon
ions (C12) in future experiments.
PO-0994 Integrin antagonistic drugs reveal different
effectiveness in 2D monolayer vs. 3D spheroid culture
V. Kopatz1,2, E. Selzer1, W. Dörr 1,2
1 Medical University of Vienna, Department for Radiation
Oncology, Vienna, Austria
2 Medical University of Vienna, Christian Doppler Lab for
Medical Radiation Research for Radiooncology, Vienna,
Austria
Purpose or Objective
Preclinical evaluation of novel therapeutic substances, as
well as the assessment of radiation effects, is frequently
performed under standard 2D cell culture conditions.
However, such monolayer cultures may fail with regard to
representation of morphological in vivo conditions and
their (radio)biological consequences. An alternative, in
the latter aspect is the use of 3D in vitro models - like
tumor spheroid culture - which are of intermediate
complexity between standard in vitro monolayer cultures
and in vivo tumor models. In spheroid culture, tumor cells
grow in 3D aggregates that display greater similarity to in
vivo tumor architecture and growth conditions, such as the
presence of oxygen and nutrient gradients as well as more
complex cellular interactions or 'in vivo-like” gene
expression profiles. Depending on their size, multicellular
spheroids may also display central hypoxic and/or necrotic
areas and show quiescent and proliferating
compartments. Thus spheroids often depict different
behavior and sensitivity towards certain drugs or
radiotherapeutic treatment as cells cultured as 2D
monolayers. Especially for the study of surface receptors
like integrins the 3D structure and environment is a critical
aspect as these receptors transduce signals from the
extracellular space to the inside, thus influencing
different cell signaling pathways like cell survival,
proliferation and invasion.
Material and Methods
Therefore in addition two standard 2D cell culture, 3D
spheroid models were established with 518A2 and other
melanoma cell lines for evaluation of their response to two
different integrin antagonists, cilengitide and a novel
integrin antagonist (NIA), as well as for the
characterization of the effects of radiation treatment
alone or in combination with the drugs.
Results
While in 2D cultures of 518A2 melanoma cells, the
comparator substance cilengitide showed to be more
efficient than our novel compound NIA (IC50 value of
0,65µM), it had no inhibitory effect in 3D spheroid culture
up to 50µM. Comparatively NIA revealed to have similar
effectiveness in 2D as well as 3D cultures, both in the low
micromolar range. During monitoring of spheroid growth,
NIA treated spheroids initially depicted a growth
retardation, before cells started to disintegrate and die.
The radiosensitivity of 518A2 melanoma cells was found to
be similar in both culture conditions.
Conclusion
Similar differences in drug response and efficacy between
2D and 3D cell culture environments have been reported
for various anti-cancer substances as well as for some
radiation exposure endpoints. However, other endpoints
may - in a treatment-related manner - be depending on
the culture system used. We thus plan to perform further
comparative studies on survival-dependent aspects
(apoptosis, intracellular signaling, and others) with
integrin antagonists alone as well as in combination with
irradiation in 2D cell culture versus 3D spheroids.
PO-0995 Estimation of radiobiology parameters of
infiltrative low-grade gliomas WHO Grade II.
S. Milyukov 1, Y. Lysak2, G. Panshin2, N. Kharchenko1, Z.
Tsallagova2, T. Izmailov2
1Peoples’ Friendship University of Russia, Department of
oncology and roentgenoradiology, Moscow, Russian
Federation
2Russian Scientific Center of Roentgenoradiology of
Russia, Research department of innovative technologies
of radiotherapy and chemoradiation treatment of
malignant tumors, Moscow, Russian Federation
Purpose or Objective
Determine the value of radiobiological parameters of
infiltrative low-grade gliomas WHO Grade II
Material and Methods
In total (the data from) 5 clinical studies: EORTC 22844
(Karim AB et al., 1996.), EORTC 22845 (van den Bent MJ
et al., 2005), NCCTG 86-72-51 (Shaw E et al., 2002), the
RTOG 9802 (Shaw EG et. al., 2012), the study on the
hyperfractionated radiotherapy (Jeremic B et. al., 1998),
and selected data from our database were used for the
calculation radiobiological parameters of LGG. In total,
our study included 870 patients. All patients received
surgery (1-phase treatment) and radiotherapy (2-phase
treatment). Following radiobiological parameters of
radiotherapy were used for the calculation: dose per
fraction, total dose of radiotherapy, total number of
treatment days, 5-year progression-free survival.
Results
Following radiobiological parameters of infiltrative low-
grade gliomas WHO Grade II were calculated: α, β, α/β,
Td, D prolif, Tk, N clonogens. Following values were
calculated (95% Cl): α (Gr – 1) = 0,096 (0,08–0,11), β (Gr –2 )
= 0,014 (0,012-0,018), α/β (Gr) = 6,8 (4,3-9,2), Td (days) =
21,3 (18,3-26,4), Dprolif (Gr) = 0,27 (0,21-0,35), Tk (days) =
44 (34-55), N clonogens = 2,18·103 (1,2-5,3) ·103 .
Conclusion
The calculated values of radiobiological parameters give a
better idea of the biological properties of the low-grade
gliomas and estimate as accurately as possible of the total
dose of radiotherapy using a linear-quadratic model.
Poster: RTT track: Patient preparation, positioning and
immobilisation
PO-0996 Accuracy of an optical surface monitoring
device to reduce daily imaging of breast cancer
patients
J. Sharpe1, A. Tini1, A. Moreira1, I. Pytko1, C. Winter1, M.
Guckenberger 1, C. Linsenmeier 1
1University Hospital of Zurich, Radiation Oncology Clinic,
Zurich, Switzerland