ESTRO 2020 Abstract book

S658 ESTRO 2020

patients with PCa progression post-RT, and patients with metastatic PCa at presentation Material and Methods 19 patients from the PROMPT research cohort were identified with pre-treatment prostate biopsies suitable for analysis: 6 patients with stable PCa following RT (74Gy in 37 fractions) treatment of localised PCa; 5 patients with PCa progression post-RT; 8 patients with metastatic PCa at presentation. Pathology review of biopsies and tumour outlining enabled macro-dissection of multiple slides pooled to a single sample per patient. RNA samples were processed and sequenced with Quantseq 3' mRNA library kit and Illumina Novaseq platform.12 samples (4 per group with optimal RNA from Nanodrop) were analysed in parallel using NScN analysis. Bioinformatic analysis was performed using R 3.52 packages DESEQ2 and EDGER. nSolver analysis software 4.0 was used for NSnC Results Following 3'RNAseq all samples bar one (5%) were sufficient for downstream analysis. All 12 samples selected for NSnC generated sufficient quality data. Upon bioinformatic analysis, differential gene expression between patients with PCa progression post-RT compared to those with stable PCa revealed >600 genes with significant differential expression (p<0.05) adjusted by Benjamini & Hochberg method (DESeq2). Unsupervised hierarchical clustering of gene expression highlighted commonalities between patients with PCa progression post-RT and those with baseline metastatic PCa (Figure 1). Similar findings were found in a separate analysis (EDGER). Gene expression analysis using NSnC confirmed differential gene expression in multiple gene pathways e.g. chromatin remodelling (Figure 2), between patients with stable PCa post-RT and those with PCa progression.

Radiotherapy (RT) is being used with increased frequency in the management of prostate cancer (PC) following radical prostatectomy. However there is some concern that its use in the form of a hypofractionated regimen may lead to tissue injury when carried out in the postoperative setting. We retrospectively reported on acute and late gastrointestinal (GI) and genitourinary (GU) toxicities in a series of patients who received a course of moderately hypofractionated RT post-prostatectomy. Material and Methods Fifty patients with adverse pathologic features or biochemical failure following radical prostatectomy were enrolled between 2013 and 2018. Median age was 70 [47- 80] years. Median pre-treatment PSA was 0.4 ng/ml. Thirty-seven (74%) patients had ISUP grade ≥ 3, 35 (70%) had pT3 disease and 36 (72%) had positive margins. All patients were treated with Volumetric Modulated Arc Therapy (VMAT), and Simultaneous integrated boost (SIB) in 28 fractions for a total dose of 66,64 Gy to the prostate bed and 53,2 Gy to the pelvic drainages, respectively. Androgen deprivation therapy (ADT) was administered to 76% of patients. After completion of RT, follow up was scheduled at 3 months and every 6-12 months thereafter. Acute and Late toxicities were assessed using Common Terminology Criteria for Adverse Events v4. 2-year biochemical disease-free survival (bDFS) was also evaluated. Univariate analysis examining potential relationships between bladder/rectal dosimetric parameters and GU/GI toxicities was performed. Results With a median follow-up of 22 months (range: 5 to 57 months), none of the patients experienced grade ≥3 late GI or GU toxicities and no instances of grade ≥3 acute GI toxicities were recorded. Only one patient experienced G3 acute GU toxicity. Cumulative acute Grade 2 GU and GI toxicity was 6%. The same feature for late Grade 2 GU and GI toxicity was 8%. The median dose received by bladder and rectum was 44.52 Gy [25.34-53.75] and 44.68 Gy [17.43-48.86], respectively. No statistically significant association was found between toxicities and rectal/bladder dosimetric values (P>0.05). 2-year bDFS was 88%. No treatment interruptions > 5 days occurred. Conclusion Moderately hypofractionated RT for PC by means of VMAT and SIB technique resulted in an excellent toxicity profile when applied postoperatively. No dosimetric factors was found predictive of both acute and late toxicity. Long term follow-up is needed to account for toxicities that might occur at later time points. PO-1160 A pilot dual-platform transcriptomic analysis of diagnostic prostate biopsies & radical RT response P. Charlton 1 , D. O'Reilly 1 , Y. Philippou 2 , S. Rao 2 , A. Lamb 2 , G. Higgins 2 , F. Hamdy 2 , C. Verrill 2 , R. Bryant 2 , F. Buffa 1 1 Oxford Institute for Radiation Oncology- University of Oxford, Oncology Department, Oxford, United Kingdom ; 2 Nuffield Department of Surgical Sciences- University of Oxford, Medical Sciences Division, Oxford, United Kingdom Purpose or Objective The use of formalin fixed paraffin embedded (FFPE) diagnostic prostate cancer (PCa) biopsy samples for gene expression analysis is challenging due to small samples with poor quality RNA. Previous studies have demonstrated some potential for transcriptional analysis using microarray techniques. We undertook a feasibility study to explore the potential for multi-modal transcriptional analysis from pre-treatment FFPE PCa biopsies using newer methods of mRNA quantification with 3’RNA sequencing (3’RNAseq) and NanoString nCounter (NSnC) technologies. We undertook an exploratory analysis of differential gene expression using these techniques in 3 patient groups: patients with stable PCa post radical radiotherapy (RT),