ESTRO 36 Abstract Book

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S277 ESTRO 36 2017
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OC-0529 Circulating exosomal miRNA related to
chemoradiotherapy outcome in locally advanced rectal
cancer
S. Meltzer1,2, L.G. Lyckander3, A.H. Ree 1,2, K.R. Redalen1
1 Akershus University Hospital, Department of Oncology,
Lørenskog, Norway
2 University of Oslo, Institute of Clinical Medicine, Oslo,
Norway
3 Akershus University Hospital, Department of Pathology,
Lørenskog, Norway
Purpose or Objective
Exosomes are extracellular vesicles shown to carry
complex biological information (mRNAs, miRNAs, proteins,
etc.) of their cells of origin, such as tumor cells. Recent
studies have also shown that normoxic and hypoxic cells
produce exosomes with different biological content,
proposing a role of exosomes in the aggravated biology
caused by tumor hypoxia. Further advances in rectal
cancer care require early identification and treatment of
aggressive tumors with poor chemoradiotherapy (CRT)
response and high metastatic propensity. In this context,
we explored associations between plasma exosomal
miRNAs, CRT outcome and survival in locally advanced
rectal cancer (LARC).
Material and Methods
Plasma samples from 20 patients were collected at
baseline. Sixteen patients underwent neoadjuvant long-
course CRT and four patients with synchronous liver
metastasis underwent short-course radiotherapy, followed
by surgery. Exosomes were isolated using the miRCURY ™
isolation kit and analyzed using the miRCURY LNA ™
Universal RT microRNA PCR Human panel I (Exiqon,
Denmark). miRNA expression data was normalized to the
global array mean before miRNA with high differential
expression were determined using the SAM software with
a false recovery rate of 10% and verified by t-tests using
p-values < 0.05 as statistically significant. CRT response
was evaluated by ypTN staging and tumor regression grade
(TRG) (College of American Pathologists system) scoring,
and survival differences assessed by the log-rank test and
visualized using Kaplan-Meier curves. Median follow-up
time was 21 months (range 1-34).
Results
Significant associations between several exosomal miRNAs
to TNM, ypTN, TRG and PFS were detected. For TRG, the
most significant findings were lower expression of miR-
20b-5p and miR-301a-3p in poor responders (TRG2-3 vs
TRG1). Looking at baseline characteristics, patients with
synchronous liver metastasis had higher expression of
several miRNAs, particularly miR-141-3p (p=0.010) (Table
1). Further, for patients without metastasis at baseline,
higher expression of this miRNA was associated with both
metastatic progression to the liver (p=0.020) and thus poor
overall survival (p=0.032) (Figure 1).
Figure 1 hsa-miR-141-3p
Table 1 hsa-miR-141-3p
Differential expression relative to global mean
Conclusion
We identified plasma exosomal miRNAs predicting both
CRT response and survival. Particularly, miR-141-3p was
significantly associated with both synchronous liver
metastasis at time of diagnosis and future progression of
liver metastasis. miR-141-3p has shown to be
overexpressed in colorectal tumour stroma compared to
normal tissue, and was recently associated with radiation
resistance in experimental H&N squamous cell carcinoma
models. The results warrant further investigation into
these miRNAs as potential biomarkers of liver metastasis
and treatment resistance, and if they can be specifically
targeted in LARC treatment. The results are currently
being validated in an independent, larger cohort.
Proffered Papers: Dosimetry and detector development
OC-0530 Equivalent uniform square field sizes of
machine specific reference fields in FFF beams
W. Lechner1, P. Kuess1, D. Georg 1, H. Palmans2,3
1Medizinische Universität Wien Medical University of
Vienna, Department of Radiotherapy and Christian
Doppler Laboratory for Medical Radiation Research for
Radiation Oncology, Vienna, Austria
2EBG MedAustron GmbH, Department of Dosimetry,
Wiener Neustadt, Austria
3National Physical Laboratory, Radiation Dosimetry,
Teddington, United Kingdom
Purpose or Objective
Flattening filter free (FFF) photon beams have been
available in dedicated linear accelerator (LINAC) designs
such as CyberKnife and TomoTherapy for several years.
More recently they were also introduced in clinical
practice at conventional C-arm LINACs. However,
reference dosimetry procedures vary amongst these types
of FFF machines. This work aims to investigate the
concept of equivalent uniform square fields (EQUSFs) of
FFF beams as proposed by the upcoming IAEA/AAPM code
of practice on small field dosimetry.
Material and Methods
In-house determined experimental data as well as
published data [1,2] of the ratio of doses at depths of 20
cm and 10 cm in water (D20,10) was used to characterize
the depth dose in square fields ranging from 2 x 2 cm² to
40 x 40 cm², for 6 and 10 MV flattened (WFF) and FFF
beams. A scatter function (S(x)) that takes the lateral