ESTRO 36 Abstract Book

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S978 ESTRO 36 2017
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generated using two, three or four non-coplanar arcs for
tumors originated in the skull base and coplanar
arrangements for all other locations. Daily IGRT was
performed using Exactrac X-ray 6D system and ConeBeam-
CT. The gross target volume (GTV) was defined in imaging
studies and a GTVpet was automatically created using a
gradient method (42% SUVmax) and registered in planning
CT. Diffusion MRI, contrast T1 and T2 were used to create
a GTVmri. The clinical target volume (CTV) included all
potential areas at risk for microscopic tumor spread, local
and regional. PTVs were created adding a margin around
GTVs and CTVs of 3-5mm. The average prescription dose
to the GTVs was 70Gy and 54-60Gy for the CTVs. All
treatment plans were planned with simultaneous
integrated boost. Adaptative radiotherapy was used when
necessary (17 cases).
Results
Mean age of the population was 60 years (24-83). Median
follow-up was 30 months (range 12 to 48 months). The 3-
year loco-regional control (LRC rates) was 97%. 9 patients
died of distant disease progression. The dose delivered
was 70Gy, 66Gy, 60Gy and 54Gy to the GTVprimary and
positive nodes, GTVsuspicious nodes, CTVhigh risk, and
CTVlow risk, respectively. Only 2% of the GTVs and 5% of
CTVs received less than 95% of the prescribed dose. Only
one patient with a larynx carcinoma (T3N2b) failed in a
grossly positive node after definitive chemoradiotherapy.
The remaining 37 patients experienced a complete
response. No marginal failures have been observed to
date. GTV targets delineated in the PET and MRI are
different and complementary to each other and relative
to the CT contrast, providing safer treatments while
preserving the critical organs.
Conclusion
Accurate dose delivery is imperative in the setting of
intensity modulated radiation therapy because of the
sharp dose gradients generated. The proximity of tumors
to critical organs requires advanced immobilization
devices and the reduction of positional uncertainties. Our
multidisciplinary approach in target volume definition and
imaged guided radiotherapy resulted in excellent LRC and
no marginal failures. The use of PETscan and MRI also
demonstrated an improvement in target delineation.
Electronic Poster: Radiobiology track: Normal tissue
biology of the heart
EP-1807 Reducing Heart Toxicity In Medulloblastoma
Using Proton Therapy
A. Madkhali1,2, M. Partridge 1
1 University of Oxford, Oncology, OXFORD, United
Kingdom
2 King Saud University, Medicine, Riyadh, Saudi Arabia
Purpose or Objective
Radiation therapy is known to cause acute and long term
side effects. Some of those side effects are a major reason
of mortality in cancer survivors. Heart disease after
radiotherapy for Hodgkin and breast cancer patients is a
major cause for mortality that it is offsetting the benefits
of treatment (EBCTCG, 2016). In this work, potential
benefits of using proton therapy in treatment of
medulloblastoma to reduce heart toxicity is discussed and
compared with benefit gained in reduction of secondary
cancer.
Material and Methods
Increase in risk for rate of major coronary events for
3DCRT and proton plans for a patient with
medulloblastoma (MB) was calculated using published
model (Darby et al,2014), the NTCP for cardiac perfusion
deficits was modelled using LKB model and relevant
parameters (Das et al, 2005), and finally, the mortality
risk from ischemic heart disease (IHD) was modelled using
relative seriality model and relevant parameters (Kallman
et al,1992, Eriksson et al,2000). Risk of mortality from
radiotherapy-induced secondary cancer (SC) was modelled
as well using voxel-by-voxel dose maps and models that
includes cell-kill components, linear quadratic (LQ) and
linear model (LIN) (Timlin et al,2015).
Results
The heart mean dose in 3DCRT was 16.1 Gy, and 0.1 Gy in
the proton plan. Risk of major coronary events were 119%
(3DCRT ), 0.7% (proton). NTCP was 34.5%(3DCRT),
0.8%(proton). Risk of mortality from IHD was
1.61%(3DCRT) and 0.01%(proton), while mortality from SC
was for 3DCRT: 1.08%(LQ), 0.10%(LIN) and for proton:
0.32%(LQ) and 0.03%(LIN)
Conclusion
Proton therapy for MB is expected to decreases risk of
major cardiac events, mortality due to IHD and mortality
from RT-induced secondary cancer significantly, when
compared to 3DCRT. With cardiac late side effects being
a major and important clinical burden post-RT, and some
would say more than secondary cancer risk, these results
strengthen the argument to use proton therapy.
Electronic Poster: Radiobiology track: Normal tissue
radiobiology (others)
EP-1808 The response of human induced pluripotent
stem cell- derived chondrocytes to ionizing radiation
E. Augustyniak1,2, W.M. Suchorska1,3
1Greater Poland Cancer Centre, Radiobiology Lab,
Poznan, Poland
2Medical University of Warsaw, The Postgraduate School
of Molecular Medicine, Warsaw, Poland
3Poznan University of Medical Sciences, Department of
Electroradiology, Poznan, Poland
Purpose or Objective
The response of stem-derived cells to treatment with
ionizing radiation (IR) is a questionable issue. It is worth
mentioning that un- and differentiated cells possess
different radiosensitivity. It is also unknown, whether the
DDR mechanisms of stem-derived cells are more similar to
those from 'parental” stem cells (SCs) or perhaps those
from completely differentiated cells. Herein, we assume
that differentiation process leading to obtaining of
specialized cells have a significant effect on mechanisms
activated in cells exposed to anticancer agents. We
believe that it has a great impact on genetic stability of
cells derived from SCs, what has a direct reflection in
safety of application of these cells in clinical practice. The
main goal of this study was to investigate the DDR of
human induced pluripotent (hiPSC)-derived chondrocytes
treated with IR.
Material and Methods
In the experiment three types of cell lines were used:
hiPSCs, human articular chondrocytes and chondrocyte-
like cells differentiated from hiPSCs. The investigated
cells were treated with IR (0; 1; 2; 5 Gy) and collected 1,
5, 9 and 24 h after IR. Finally, the analyses of γH2AX, and
PARP by flow cytometry were performed. Moreover, we
investigated the level of senescence in cells treated with
IR.
Results
These findings show that kinetics of DSBs significantly
differ in hiPSCs, chondrocytes, and chondrocyte-like cells
differentiated from hiPSCs. Nevertheless, the formation of
DSBs in hiPSC-derived chondrocytes is similar to processes
occurring in hiPSCs rather than in human articular
chondrocytes. The hiPSCs and hiPSC-derived chondrocytes
are very prone to DNA damage in comparison with fully
mature chondrocytes. However, it is important to point
out that hiPSC-derived chondrocytes possess more
efficient DNA repair mechanisms resulting in the lower
level of DSBs after 24h, in contrast to hiPSCs.