ESTRO 36 Abstract Book

S540

ESTRO 36 2017

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induce loco-regional recurrence (significant for tumors

collected 4 days after 5x2Gy). Furthermore, based on the

metabolic profile of the primary MDA-MB231 tumors and

OPLS linear regression, mathematical models were

established in the different groups allowing to predict the

metastatic burden (r²=0,80-0,90).

Conclusion

In preclinical models, we show profound modifications of

the primary tumor metabolome following NeoRT through

NMR analyses, offering new opportunities to understand

tumor metabolism adaptation following NeoRT.

Furthermore, others NMR results appear very relevant

when transposed to clinic. Indeed, with mathematical

models, local recurrence and metastatic profiles were

predictable based on the metabolomic profile of the

primary tumor at the time of surgery, which could be

helpful to adapt adjuvant therapies in order to prevent

relapse.

PO-0986 Downregulation of the oncoprotein SET

enhances RT-induced apoptosis in hepatocellular

carcinoma

C.Y. Huang

, M.H. Hung

, C.W. Kuo

, C.T. Shih

, M.H.

Chen

, K.F. Chen

National Taiwan university hospital, Division of

Radiation Oncology- Department of Oncology, Taipei,

Taiwan

Taipei Veterans General Hospital, Division of Medical

Oncology- Department of Oncology, Taipei, Taiwan

Yuanpei University of Medical Technology, Department

of Medical Imaging and Radiological Technology,

Hsinchu, Taiwan

National Yang-Ming University, Institute of

Biopharmaceutical Sciences, Taipei, Taiwan

National Taiwan university hospital, Department of

Medical Research, Taipei, Taiwan

Purpose or Objective

Hepatocellular carcinoma (HCC) is among the most lethal

human malignancies worldwide. Radiotherapy (RT) is not

commonly used to treat HCC with regard to both

suboptimal treatment efficacy and toxicity. The current

project aimed to characterize the role of a novel

oncoprotein SET/ I2PP2A (Inhibitor-2 of protein

phosphatase 2A) in mediating the radio-resistance of HCC

cell and explore the potential on antagonizing SET to

improve the anti-HCC effects of RT.

Material and Methods

The effects of RT in HCC cells with different expression of

SET were assessed by colony formation and sphere

formation assay. We generated a novel SET antagonist,

EMQA

-(3-ethynylphenyl)-6,7-dimethoxy-N

-(4-

phenoxyphenyl) quinazoline-2,4-diamine), to validate the

therapeutic potential of targeting SET. The combination

effects of EMQA and RT were tested in vitro using four

different HCC cell lines, Hep3B, PLC5, HA22T and HA59T,

and a subcutaneous PLC5 xenografted model in vivo. HCC

cells were exposed to 1 fraction of 4-Gy radiation using a

cobalt 60 unit (at a dose rate of 0.5 Gy/min) with the

source-axis-distance set at 80 cm to the bottom of the

dish. After 48 hours, the cells were treated with or

without EMQA.

Results

To explore the roles of SET in affecting the radio-

sensitivity in HCC, we first generated PLC5 and Hep3B

cells with different SET activity, and assessed the effects

of RT on these cells by colony formation and tumor sphere

assay. Comparing to mock-treated cells, HCC cells

transfected with shRNA against SET were shown with

significant reduced viability under the same RT treatment.

Oppositely, cells with ectopic expression of SET were more

resistant to RT. Next, we used EMQA to test whether

antagonizing SET could enhance the effects of RT against

HCC. Using sub-G1 analysis, we showed that adding EMQA

significantly increased RT-induced apoptosis of HCC cells.

The number of tumor colony was also significantly

decreased in HCC cells exposing to EMQA plus RT than

either of the treatment alone. Lastly, using the PLC5

xenografted tumor model, the synergistic effects of SET

antagonist combining RT were also observed.

Conclusion

SET is a novel oncoprotein that affects the radio

sensitivity of HCC cells. A combination therapy with RT

and the SET antagonist, such as EMQA, enhanced RT-

induced apoptosis of HCC cells in vitro and in vivo.

PO-0987 Gemcitabine-based chemoradiotherapy gets

improved with PARP inhibitor in pancreatic cancer cells

W. Waissi

, H. Burckel

, E. Magisson

, G. Larderet

, G.

Noel

CLCC Paul STRAUSS, EA3430- Laboratoire de

Radiobiologie, Strasbourg, France

Purpose or Objective

Pancreatic ductal adenocarcinoma (PDAC) is a devastating

disease with a cumulative 5-year overall survival of less

than 5% for all stages. Thirty percent of patients diagnosed

with pancreatic adenocarcinoma present with a locally

advanced

disease

and

could

benefit

from

chemoradiotherapy with gemcitabine, which is effective

but toxic. Over the past few years, studies have focused

on the development of targeted radiosensitizer such as

poly(ADP-ribose) polymerase (PARP) inhibitor. We

conducted this in vitro study to determine whether PARP

inhibition enhances radiation-induced cytotoxicity of

pancreatic adenocarcinoma.

Material and Methods

Pancreatic carcinoma cells, MIA PaCa-2 (BRCA1/2 wild-

type) , were treated with olaparib and/or gemcitabine

and/or irradiation (2,5 and 10 Gy). In vitro cell viability,

clonogenic assay, cell cycle distribution, γ-H2AX

quantification, apoptosis and autophagy were assessed.

Results

In vitro, treatment with olaparib alone at 1 µM was not

cytotoxic but highly radiosensitized cells (standard

enhancement ratio =1.23+/-0.02) and particularly at high

dose per fraction (10 Gy). After 24 hours, the number of

remaining γ-H2AX stained cells was higher when cells were

treated with a combination of 10 Gy irradiation and

olaparib compared to irradiation or olaparib alone.

Furthermore, combination of olaparib and irradiation

induced a G2/M arrest. In contrast, a non-cytotoxic

concentration of gemcitabine could also radiosensitize

cells, but clearly less than olaparib (SER=1.11+/-0.04).

Radiosenzitization by gemcitabine was associated with

percentage of cells blocked in early S-phase just before

irradiation. Finally, cell death quantification after 24

hours showed that none of the treatments induced

apoptosis, whereas gemcitabine or 10 Gy irradiation alone

induced autophagy.

Conclusion

Our results showed that MIA PaCa-2 cells could be radio

sensitized with low dose of olaparib , through an increase

of unrepaired double-strand breaks and a block in G2

phase. The radiosensitization was higher with high dose

radiation. This may be translated into an enhancement of

local control in vivo and better disease free survival.

Investigations in three other pancreatic cells lines are in

progress.

PO-0988 Following tumour microenvironment after

Neoadjuvant radiotherapy with IVIM perfusion analysis

F. Lallemand

, N. Leroi

, M. Bahri

, E. Balteau

, A. Noël

P. Coucke

, A. Plenevaux

, P. Martinive

C.H.U. - Sart Tilman, Radiothérapie, Liège, Belgium

ULg, Laboratory of Tumor and Development Biology,

Liège, Belgium

ULg, Cyclotron Research Center, Liège, Belgium

Purpose or Objective