ESTRO 36 Abstract Book

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S41 ESTRO 36
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experience radiation-induced toxicity due to damage to
normal tissue in the irradiation field. Increasing the
therapeutic window of radiotherapy may be achieved by
using molecularly targeted therapies against pathways
that are altered in cancer. The complement system is an
important pathway in immunity composed of soluble and
cell surface proteins. Several members of this pathway are
upregulated in cancer and complement inhibition is under
investigation as a therapeutic strategy, including in
combination with radiotherapy. Interestingly, our data
suggests that in response to radiotherapy, expression of
complement regulators CD55 and CD59 is decreased in
normal colon. Importantly, these expression changes
correlate with an increase in the C5b-9 complex
(thought to be responsible for cell lysis) in irradiated colon
in vivo. Furthermore, our results suggest that targeting
the complement system (either genetically or
pharmacologically) can result in increased survival of mice
following radiotherapy, through protection of the
gastrointestinal tract from radiation-induced toxicity.
Together, these findings suggest that targeting the
complement system could be a promising approach to
reduced radiation-induced gastrointestinal toxicity
thereby increasing the therapeutic window of
radiotherapy.
SP-0079 Bowel radiation injury: complexity of the
pathophysiology and promises of cell and tissue
engineering
L. Moussa1, P. Weiss2, M. Benderitter1, C. Demarquay1, J.
Guicheux2, G. Réthoré2, N. Mathieu1
1 Institut de Radioprotection et de Sûreté Nucléaire,
SRBE, Fontenay-aux-Roses- Paris, France
2 Institut National de la Santé et de la Recherche
Médicale, LIOAD, Nantes, France
Radiation therapy is crucial in the therapeutic arsenal to
cure cancers; however, normal tissue situated in the
irradiation field can be damaged by ionizing radiation,
leading some specialists to define these specific
gastrointestinal complications as “pelvic radiation
disease”. This is particularly important as the number of
patients suffering from this disease is increasing with
increased life expectancy of patients treated for cancer.
Mesenchymal Stromal Cells (MSCs) represent a promising
strategy to treat radiation-induced intestinal damage.
Indeed, we previously demonstrated in rats, mini-pigs
then patients over-irradiated during radiotherapy for
prostate cancer, that intravenous injection of MSCs
reduces severe colorectal lesions. However, this effect
seems temporary and repeated injections have been
recommended. The beneficial effects of MSCs have been
related to their capacity to engraft, survive and secrete
bioactive factors in the host tissue. We need to optimize
the efficacy of the injected cells, particularly, with regard
to extending their life span in the irradiated tissue. Here,
we propose to use a colonoscope to deliver MSCs
embedded in a biocompatible hydrogel (Si-HPMC) directly
into the colon. We demonstrated in vivo using a rat model
of radiation-induced severe colonic damage that MSC+Si-
HPMC improve colonic epithelial structure and function.
These results could open up new perspectives in
regenerative medicine in particular with the co-
administration of MSC and ex-vivo expended “mini-gut”.
OC-0080 Normal tissue toxicity and in vivo dose-
equivalence of synchroton radiotherapy modalities
L. Smyth1,2, J. Crosbie3,4, J. Ventura1, J. Donoghue 1,3, S.
Senthi4, P. Rogers1
1 University of Melbourne, Obstetrics & Gynaecology,
Melbourne, Australia
2 Epworth HealthCare, Radiation Oncology, Melbourne,
Australia
3 RMIT University, School of Science, Melbourne,
Australia
4Alfred Hospital, William Buckland Radiotherapy Centre,
Melbourne, Australia
Purpose or Objective
Microbeam Radiotherapy (MRT) is a pre-clinical
synchrotron radiotherapy modality characterised by fields
of high intensity, parallel beams which form 25-50 micron
(µm) wide ‘peak dose’ regions spaced by 100 - 400µm
‘valley’ regions. The aim of this study was to assess the
safety profile of MRT compared to high dose-rate broad-
beam radiotherapy based on in vivo normal tissue toxicity.
Material and Methods
A dose-escalation study using MRT and high dose-rate
synchrotron broad-beam radiotherapy (SBBR) was
performed on C57BL/6 mice (male and female, 8-10 weeks
old). Mice received either Total Body Irradiation (TBI) or
Partial Body Irradiation to their entire abdomen (PBI). MRT
was performed at the Australian Synchrotron with an array
of microbeams 50 µm wide and spaced by 400 µm. SBBR
was delivered at the Australian Synchrotron using a dose
rate of 40 Gy/second. For TBI, the broad-beam doses were
4, 6, 8 and 10 Gy and the MRT peak doses were 48, 64, 96
and 144 Gy. For PBI, the broad-beam doses were 6, 9, 12
and 15 Gy and the MRT peak doses were 180, 270, 360 and
450 Gy. Five mice were irradiated per group. Mice were
monitored twice per day for one month following
irradiation for signs of weight loss and other
gastrointestinal toxicities such as diarrhoea, and were
euthanized according to strict intervention criteria.
Results
For TBI, all mice survived with no signs of diarrhoea up to
peak MRT doses of 144 Gy. There was a dose-dependent
increase in the incidence of sustained weight loss, with
four out of five mice in the 144 Gy group showing at least
10% weight loss two weeks following irradiation. All mice
in the 48 Gy and 64 Gy groups returned to within 5% of
their pre-experimental weight eight days following
irradiation. In the SBBR groups, 10 Gy led to irreversible
weight loss and euthanasia for all mice within two weeks
of irradiation. All mice in the 6 and 4 Gy SBBR groups
returned to their pre-experimental weight within nine
days of irradiation. For PBI, all mice in the 450 Gy group
experienced 20% weight loss, severe diarrhoea and
dehydration within six days of irradiation, consistent with
gastrointestinal syndrome, and were euthanized. All mice
in the 360 Gy MRT and 15 Gy SBBR groups also lost 20% of
their pre-experimental body weight, showed signs of
dehydration and were euthanized. All mice in the 270 and
180 Gy MRT groups and the 9 and 6 Gy SBBR groups
survived, experiencing reversible weight loss and showing
no signs of diarrhoea.
Conclusion
These are the first systematic dose-escalation toxicity
data for MRT and high dose-rate SBBR for the
gastrointestinal tract. The threshold for catastrophic
acute gastro-intestinal toxicity lies between 270 and 360
Gy for MRT and between 10 and 15 Gy for high dose-rate
synchrotron broad-beam radiotherapy when irradiating
the entire abdomen. A comparison with toxicity data for
conventional dose-rate broad beam radiotherapy is
required to determine whether ultra-high dose-rates
provide a normal tissue sparing effect.
Proffered Papers: Skin
OC-0081 Patient Safety Is Improved With An Extensive
Incident Learning System—9 Years Of Clinical Evidence
C. Deufel1, L. McLemore1, L. Fong de los Santos1, K.
Classic 2, S. Park1, K. Furutani1
1Mayo Clinic MN, Radiation Oncology, Rochester, USA
2Mayo Clinic MN, Radiation Safety, Rochester, USA