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ESTRO 36 2017
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TUESDAY, 9 MAY 2017
Teaching Lecture: New radiotherapeutic horizons in
soft tissue sarcoma treatment
SP-0555 New radiotherapeutic horizons in soft tissue
sarcoma treatment
R. Haas
1,2
1
Netherlands Cancer Institute Antoni van Leeuwenhoek
Hospital, Radiotherapy, Amsterdam, The Netherlands
2
Leiden University Medical Center, Radiotherapy,
Leiden, The Netherlands
The field of radiotherapeutic indications and techniques
is evolving. In this teaching lecture several aspects will
be highlighted:
- The NCIC-SR2 trial and its implication for current daily
practice.
- Balancing wound complications versus late morbidity
and local relapse.
- The consequences of refraining from radiotherapy.
- Alternatives in fraction size and total dose as compared
to conventional fractionation to 50 Gy.
- Combined modality regimens with conventional
chemotherapy and modern targeted agents.
- The evidence for centralization of sarcoma care.
Teaching
Lecture:
Clinical
evidence
for
hypofractionation in prostate cancer what is the
optimum?
SP-0556 Clinical evidence for hypofractionation in
prostate cancer what is the optimum?
P. Blanchard
1
1
Institut Gustave Roussy, Villejuif, France
Technological improvements in treatment planning and
delivery allow to safely deliver high radiation doses in
small volumes over a short period of time with high
conformality. Hence, the pendulum of radiotherapy
fractionation is moving back toward a small number of
fractions. This is true for most cancer types where large
prophylactic fields are not required, and especially for
prostate cancer. The justification is that prostate cancer
cells might be more sensitive to large doses per fraction
than surrounding normal tissues, as demonstrated by their
estimated low alpha/beta ratio. Multiple clinical
randomized trials have evaluated the safety and efficacy
of moderate hypofractionation for prostate cancer, which
is now widely considered a viable alternative to
conventional fractionation regardless of cancer risk group.
More extreme forms of hypofractionation, such as high
dose rate brachytherapy or stereotactic body radiotherapy
(SBRT) are rapidly emerging as a novel treatment modality
for this disease. Obviously, patient convenience and costs,
which are improved with these treatments, are important
aspects to take into consideration prior to administering a
treatment, but efficacy and safety should always be
demonstrated first. So far, clinical data for prostate SBRT
suggest good short-term outcomes but follow-up remains
short for a disease where patients have an extended
survival after their treatment. Data on brachytherapy
have more follow-up, but are limited to selected tertiary
institutions. The goal of this presentation is to review the
current clinical evidence for hypofractionation in prostate
cancer, and to discuss appropriate regimens for routine
clinical use according to patient risk group, as well as
future areas of research and development.
Teaching Lecture: Extracellular vesicles in radiation
oncology
SP-0557 Extracellular vesicles in radiation oncology
K. Røe Redalen
1
1
Norwegian University of Science and Technology,
Department of Physics, Trondheim, Norway
Extracellular vesicles (EVs), once considered as cellular
“garbage dumpsters”, are now recognised as important
mediators of intercellular communication and key players
in the transmission of signals regulating a diverse range of
biological processes. Additionally, recent knowledge on
the pathophysiologic roles of EVs in cancer progression
highlights their potential in biomarker development as
well as targets for therapeutic intervention.
As determined by their biogenesis, there are three main
classes of EVs: exosomes, microvesicles and apoptotic
bodies. The lecture will focus on exosomes, which are the
smallest EVs, ranging between 30 – 100 mm. Unlike
microvesicles, which are generated by outward budding of
the plasma membrane, exosomes are derived from inward
budding of late endosomes released into the extracellular
environment upon fusion with the plasma membrane.
Several cell types can produce exosomes, including
dendritic cells, B cells, T cells, mast cells, epithelial cells,
and tumour cells. Although initially considered as
byproducts of a pathway releasing unwanted material
from cells, exosomes are now believed to perform a
variety of extracellular functions involving interactions
with the cellular microenvironment. For instance, it is
shown that exosomes are capable of mediating matrix
remodelling, and triggering tumour progression and
angiogenesis via induction of proliferation and
communication with the surrounding stromal tissue, as
well as promoting immune escape by modulating T cell
activity and horizontal transfer of genetic material (1).
Importantly, several studies have also implicated
exosomes as key components in the formation of pre-
metastatic niches. Hence, exosomes have emerged as
important constituents of the tumour microenvironment
and main contributors to tumour progression and
development of metastasis.
It has been shown that the exosome cargo comprises
complex biological information (mRNAs, microRNAs
(miRNAs), proteins, etc.) from their cells of origin (i.e.,
tumour cells), which is then transferred to recipient cells
(2). These constituents are remarkably stable when
enclosed in exosomes (3). They remain intact during
sample preparation and following freezing and thawing,
altogether additional reasons for why development of
novel, circulating, tumour-originating cell biopsies based
on exosomes isolated from biofluids, such as blood and
urine, has become attractive.
With regards to their relevance in radiation oncology,
recent studies have revealed that hypoxic cancer cells
produce higher amounts of exosomes than their normoxic
counterparts (4), and that more than half of the secreted
proteome from hypoxic tumour cells are associated with
exosomes (5). Furthermore, the biological content in
normoxic and hypoxic cells differs, and recent evidence
supports a central role for exosomes in the aggravated
biology elicited by tumour hypoxia and metastasis (6). In
glioblastoma multiforme, cell-derived hypoxic exosomes
were found to induce angiogenesis through phenotypic
modulation of endothelial cells (7). Together, these
findings indicate that tumour-derived exosomes may, at
least in part, mediate the hypoxic evolution of the cancer
microenvironment through their transported genetic
cargo. Relevant to these investigations, our research
group has identified exosomal miRNAs from plasma
sampled from rectal cancer patients, which at baseline
were predictive of both chemoradiotherapy response and
clinical outcome. The majority of the implicated miRNAs
were found to be involved in angiogenic processes, and in
particular the PI3K-Akt signalling pathway.