ESTRO 36 Abstract Book

S280 ESTRO 36 _______________________________________________________________________________________________

OC-0529 Circulating exosomal miRNA related to chemoradiotherapy outcome in locally advanced rectal cancer S. Meltzer 1,2 , L.G. Lyckander 3 , A.H. Ree 1,2 , K.R. Redalen 1 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 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). rectal cancer (LARC). Material and Methods

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. OC-0530 Equivalent uniform square field sizes of machine specific reference fields in FFF beams W. Lechner 1 , P. Kuess 1 , D. Georg 1 , H. Palmans 2,3 1 Medizinische Universität Wien Medical University of Vienna, Department of Radiotherapy and Christian Doppler Laboratory for Medical Radiation Research for Radiation Oncology, Vienna, Austria 2 EBG MedAustron GmbH, Department of Dosimetry, Wiener Neustadt, Austria 3 National 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 Proffered Papers: Dosimetry and detector development

Figure 1 hsa-miR-141-3p

Table 1 hsa-miR-141-3p