ESTRO 36 Abstract Book

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S541 ESTRO 36
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with pCR. This effect was most pronounced for the PC lipid
species (Fig. 1). Furthermore, preliminary results
identified changes in plasma lipid species during CRT. A
steeper increase in lipogenicity (PC, PE, Cer) was observed
during CRT (time point 1 to 3) for patients achieving pCR
in comparison to patients without pCR. Statistical analyses
on the complete patient group are ongoing in order to
validate our findings and to develop a discriminative
marker panel with the most promising lipid markers.
Conclusion
Plasma lipidomics is a novel field for biomarker
development. Preliminary analyses show the potential of
lipid profiling to discriminate rectal cancer patients with
heterogeneous responses, treated with standard CRT.
Further work will lead to the development of a predictive
lipid plasma marker panel. Such a predictive panel might
be used to stratify patients for an individualized
treatment, thereby improving the quality of li fe for these
patients.
PO-0978 Potential predictive biomarkers to
chemoradiotherapy response in rectal cancer: a
lipidomic study.
F. Perrotti1, P. Del Boccio2, D. Pieragostino2, L.
Caravatta1, M. Di Tommaso1, C. Rosa1, M. Di Perna1, P.
Sacchetta2, D. Genovesi1
1 "SS Annunziata" Hospital, Radiotherapy, Chieti, Italy
2 "G. D'Annunzio" University, Medical Oral and
Biotechnological Sciences, Chieti, Italy
Purpose or Objective
To highlight the lipid signature able to predict the tumor
response to chemoradiotherapy (CRT), in patients with
advanced rectal cancer (LARC), by using a Lipidomics
approach.
Material and Methods
Between March 2013 and September 2014, 18 patients
with LARC were treated with preoperative CRT at the
Radiation Oncology Unit of SS Annunziata Hospital in
Chieti – Italy. Sera were prospectively collected during
routine chemistry tests before treatment (T0) and at day
14° (T14) and 28° (T28) of CRT. An open Liquid
Chromatography tandem Mass Spectrometry (LC-MS/MS)
analysis was performed to characterize lipid expression at
T0. Differential lipids were validated by an independent
targeted approach and studied during treatment.
Results
Sixty-five lipids significantly differentiated responder (RP)
vs no-responder (NRP) patients; five lipids were validated
as predictive of response to CRT: Sphingomyelin (SM,
d18:2/18:1), Lysophosphatidylcholine (LPC, 16:0/0:0),
Lysophosphatidylcholine (LPC, 15:1(9z)/0:0),
Lysophosphatidylethanolamine (LPE, 22:5/0:0) and
Phosphatidylcholine (PC, 40:2). Receiver Operator
Characteristic curve (ROC curve), generated combining
the pattern of the 5 validated lipids, showed an AUC of
0.95.
Conclusion
The prediction of response to neoadjuvant CRT in LARC
allows to personalize treatments and to improve response
rate and survival outcomes. In this study we focused on
serum lipids to define a differential profile able to predict
response. Our results showed a pattern of 5 lipids that
differentiated RP and NRP before treatment. The ongoing
confirmation of these results could provide a new insight
on lipid metabolism in modulation of CRT response in
LARC, in effort to personalize treatments.
Poster: Radiobiology track: Radiobiology of cancer
(others)
PO-0979 Differential response of glioma cell lines to
microbeam versus conventional radiotherapy
L. Smyth1,2, P. Rogers1, J. Crosbie3, J. Donoghue 1,4
1The University of Melbourne, Department of Obstetrics
& Gynaecology, Parkville, Australia
2Epworth HealthCare, Radiation Oncology, East
Melbourne, Australia
3RMIT University, School of Science, Melbourne,
Australia
4Hudson Institute of Medical Research, Centre for Cancer
Research, Clayton, Australia
Purpose or Objective
Synchrotron microbeam radiotherapy (MRT) has been
proposed as an alternative treatment for Diffuse Intrinsic
Pontine Glioma (DIPG). The aim of this study was to
compare the cellular response of two human DIPG cell
lines to MRT and conventional broad-beam radiotherapy
(CRT). We hypothesised that MRT would elicit a different
cellular response to CRT, and that different DIPG cell lines
would have different intrinsic radio-sensitivities.
Material and Methods
Two human DIPG cell lines, SF7761 and JHH-1, were
exposed to MRT (112 to 560 Gy) or CRT (2 to 8 Gy) in vitro
to produce clonogenic cell-survival curves which were fit
to the linear-quadratic model. Equivalent CRT doses were
interpolated for each MRT dose. Apoptosis induction and
cell-cycle response assays were performed five days after
irradiation via flow cytometry to assess differences in
cellular response between the cell lines and radiotherapy
modalities at equivalent doses.
Results
Equivalent CRT and MRT doses for each cell line are
summarised in Table 1. The SF7761 cell line, which
originated from a six year old female patient with no
prior history of radiation treatment, was significantly
more radiosensitive to both CRT and MRT compared to
the JHH-1 cell line, which originated from a six year old
male who had previously undergone combined
chemotherapy and radiotherapy (Figure 1). JHH-1 formed
polyploid cells and exhibited delayed G2/M arrest
following both CRT and MRT. Furthermore, apoptosis and
cell cycle assays demonstrated that at equivalent doses,
MRT induced more unrepaired DNA damage that was
detrimental to the cell-cycle and cell viability for both
cell lines five days following irradiation.