ESTRO 36 Abstract Book

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S530 ESTRO 36
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After radiotherapy the level of MEG3 and PANDA
expression increased.
Conclusion
The potential genetic association of the lncRNAs
LINC00336 and PCAT1, and microRNA miR-146a with
radiotherapy-induced late toxicity needs to be confirmed
in larger breast cancer cohorts. The expression of lncRNAs
can be a biomarker of radiotherapy response measurable
in blood.
Funding: This research was supported by a grant [FIS
05/2181] from ‘‘Fondo de Investigación Sanitaria,
Instituto de Salud Carlos III, Ministerio Español de
Economía y Competitividad”.
PO-0959 REQUITE: Radiation Induced Lymphocyte
Apoptosis assay as a predictor for radiotherapy side
effects
C. Talbot1, A. Appanvel2, A. Botma2, T. Rancati3, A.
Webb1, D. Azria4, T. Burr 5, J. Chang-Claude2, C.
Herskind6, D. De Ruysscher 7, R. Elliott8, S. Gutiérrez
Enríquez9, P. Lambin7 , B. Rosenstein10, T. Rattay11, A.
Vega 12, F. Wenz6, R. Valdagni3, C. West8
1 University of Leicester, Department of Genetics,
Leicester, United Kingdom
2 German Cancer Research Centre DKFZ, Genetic
Epidemiology Unit, Heidelberg, Germany
3 Fondazione IRCCS Istituto Nazionale dei Tumori,
Prostate Cancer Program, Milan, Italy
4 University of Montpellier, Institut du cancer de
Montpellier, Montpellier, France
5 Source Bioscience, R&D, Nottingham, United Kingdom
6 Heidelberg University, Department of Radiation
Oncology, Mannheim, Germany
7 Maastricht University Medical Center, Department of
Radiation Oncology MAASTRO clinic, Maastricht, The
Netherlands
8 University of Manchester, Institute of Cancer Sciences,
Manchester, United Kingdom
9 Vall d’Hebron Institute of Oncology-VHIO, Radiation
Oncology Department, Barcelona, Spain
10 Mount Sinai School of Medicine, Department of
Radiation Oncology, New York, USA
11 University of Leicester, Department of Cancer Studies,
Leicester, United Kingdom
12 Universidade de Santiago de Compostela, Centro de
Investigación Biomédica en Red de Enfermedades Raras
CIBERER, Santiago de Compostela, Spain
Purpose or Objective
Recently the first replicated genetic associations for
radiotherapy-induced adverse reactions were reported.
The European Union funded REQUITE consortium aims to
validate known predictors of adverse reactions to develop
clinically useful tools. One such predictor is low levels of
radiation induced lymphocyte apoptosis which has
previously been found in patients experiencing increased
rates of late radiation induced toxicity.
Material and Methods
REQUITE is a multi-centre, observational study. Enrolment
was open for two and a half years in nine centres (eight in
Europe and one in the United States), with another two
years of follow-up still ongoing. The primary endpoints are
change in breast appearance at two years (breast), rectal
bleeding at two years (prostate) and breathlessness at 12
months (lung). Work Package 4 involves validation of
biomarkers. This includes genetic polymorphisms and the
radiation induced lymphocyte apoptosis assay (RILA). The
RILA was carried out in three of the European centres using
a standardised protocol which had been verified with inter
lab testing; it assesses percentage radiation induced
apoptosis in lymphocytes, detected by flow cytometry, 48
hours after ex-vivo irradiation of whole blood.
Results
More than 4300 patients have been enrolled in REQUITE.
1322 samples have been analysed using the apoptosis
assay. The levels of apoptosis 48 hours after ex-vivo
irradiation increase over baseline in a range from 2.4% to
62.4%, confirming large inter-patient variability. In the
Leicester cohort mean RILA is higher in the prostate
patients compared to the breast patients (24.9% vs 20.3%;
p=0.004). Analysis of predictive value for acute toxicity is
being carried out.
Conclusion
Variation in percentage of lymphocyte apoptosis is in
keeping with previous studies. This large scale prospective
observational study will be the largest to date to assess
the use of predictive biomarkers for assessing
radiotherapy related toxicity.
Poster: Radiobiology track: Radiobiology of proton and
heavy ions
PO-0960 Radiobiological effectiveness and its role in
modelling secondary cancer risk for proton therapy
A. Madkhali1,2, C. Timlin 1, M. Partridge1
1University of Oxford, Oncology, Oxford, United Kingdom
2King Saud University, Medicine, Riyadh, Saudi Arabia
Purpose or Objective
In proton therapy, a radiobiological effectiveness ratio
(RBE) of 1.1 (RBE1.1) is often used. In reality, RBE depends
on dose, linear energy transfer (LET), biological end point,
and tissue type. Using a value of RBE that may be not
accurate may affect dose calculation and hence,
outcome.
Material and Methods
We used an in-house built code for modelling malignant
induction probability (MIP) from voxel-by-voxel dose map
(Timlin 2014) and implement a published model to
calculate structure-specific RBE, recalculate dose and
MIP, and compare the outcomes with initial calculations
using RBE 1.1. MIP was calculated using linear quadratic
(LQ), linear (LIN), and linear-no-threshold (LNT) models
for proton therapy plans for an adult and a teenage
patient diagnosed with medulloblastoma (MB). The MIP
was then re-calculated using the RBE model by Dale and
Jones which is a function of dose (d), α and β and RBEmin
and RBEmax:
Results
Results are shown in Table 1. The difference in MIP by
using RBE1.1 and RBEMinMax is ~2-3%. The effect on mean
dose varies between different organs and is between 6%
and 8%. Clinical implications due to difference in RBE
depend on beam characteristics, dose, structures
concerned, and the volume irradiated.