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S40

ESTRO 36 2017

_______________________________________________________________________________________________

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. Moussa

1

, P. Weiss

2

, M. Benderitter

1

, C. Demarquay

1

, J.

Guicheux

2

, G. Réthoré

2

, N. Mathieu

1

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. Smyth

1,2

, J. Crosbie

3,4

, J. Ventura

1

, J. Donoghue

1,3

, S.

Senthi

4

, P. Rogers

1

1

University of Melbourne, Obstetrics & Gynaecology,

Melbourne, Australia

2

Epworth HealthCare, Radiation Oncology, Melbourne,

Australia

3

RMIT University, School of Science, Melbourne,

Australia

4

Alfred 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. Deufel

1

, L. McLemore

1

, L. Fong de los Santos

1

, K.

Classic

2

, S. Park

1

, K. Furutani

1

1

Mayo Clinic MN, Radiation Oncology, Rochester, USA

2

Mayo Clinic MN, Radiation Safety, Rochester, USA