ESTRO 36 Abstract Book

S294 ESTRO 36 2017 _______________________________________________________________________________________________

TUESDAY, 9 MAY 2017

Teaching Lecture: New radiotherapeutic horizons in soft tissue sarcoma treatment

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.

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. 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 for hypofractionation in prostate cancer what is the optimum? Lecture: Clinical evidence

Teaching Lecture: Extracellular vesicles in radiation oncology