ESTRO 38 Abstract book

S338 ESTRO 38

In the Stage 1 feasibility study 72% plan selections were guideline compliant. To develop this compliancy the trial’s QA programme was revised. Initial results indicate that guideline compliance has improved as a result; thus, to support RTTs to deliver PoD, pro-active continuous QA is recommended. OC-0635 Targeting TEMPRSS2:ERG fusion to achieve a tumor-specific radiosensitization in prostate cancer S. Köcher 1 , B. Beyer 2 , T. Lange 3 , L. Nordquist 1 , S. Burdak- Rothkamm 1 , T. Schlomm 2 , C. Petersen 4 , K. Rothkamm 1 , W. Mansour 1 1 University Medical Center Hamburg - Eppendorf UKE, Lab of Radiobiology and Experimental Radiation Oncology, Hamburg, Germany ; 2 Prostate Cancer Center- University Medical Hamburg Eppendorf, Martini-Klinik-, Hamburg, Germany; 3 University Medical Center Hamburg-Eppendorf, Institute of Anatomy, Hamburg, Germany ; 4 University Medical Center Hamburg - Eppendorf UKE, Department of Radiotherapy and Radiooncology, Hamburg, Germany Purpose or Objective Radiotherapy (RT) is one of the mainstay treatments for prostate cancer (PCa). Despite all technological advances in RT delivery over the recent years, improvements in molecular characterization of PCa have not changed clinical practice. Decision-making in RT for PCa is still guided by conventional clinical-pathological factors such as PSA-levels and Gleason scores. Local recurrence after RT is thought to occur predominantly in regions bearing higher histological tumor burden. Consequently, PCa is still the third-leading cause of cancer-related death in males. Therefore, there is a great need for development of strategies that improve both local control at the tumor site and eradicate occult metastasis in PCa patients. Material and Methods ERG negative (DU145 and PC3) and positive (VCaP, DU145- ERG) cell lines were used to conduct the in vitro experiments. Plasmid assay was used to monitor a repair switch to PARP1-EJ. Immunofluorescence technique was employed to monitor yH2AX, 53BP1 and RAD51. Ex vivo assay was established to monitor DSB repair in (i) xenografts established from DU145 or PC3 cells and (ii) 100 tumor biopsies freshly collected from 50 PCa patients. FISH was used to analyze ERG status in TMA from PCa patients. Results Cells overexpressing ERG (VCaP or DU145-ERG) show a deregulation in DSB repair with a repair switch to PARP1- EJ. Consequently, PARP inhibition significantly increased the number of residual γH2AX/53BP1 foci after IR exclusively in ERG overexpressing cells. HR defect was excluded by (i) plasmid assay, Rad51 foci formation and sensitivity to PARPi alone. We employed a functional ex- vivo assay, which allows the analysis of DSB repair in fresh tumor tissues. We confirmed the repair switch to PARP1- EJ in xenografts of ERG overexpressing cells as evidenced by elevated residual γH2AX/53BP1 foci after PARP inhibition. We analyzed ERG fusion in (i) 14,000 PCa patients, who underwent radical prostatectomy and (ii) 1.426 PCa patients, who underwent salvage radiotherapy. Multivariable Cox proportional hazards model did not show any statistically significant differences between ERG status and PSA-recurrence free survival in both cohorts (p=0.35 and p=0.24, respectively). Next, tumor tissues from 50 PCa patients were collected, sliced in 100-300µm to prevent hypoxia, treated with or without the PARPi olaparib 2h-pre 2Gy and yH2AX and 53BP1 foci wer monitored. Our data showed no difference in the induction of DSBs but significantly higher number of residual γH2AX/53BP1 foci in ERG-overexpressing patients compared to ERG low expressers. Conclusion

Denmark ; 4 The Royal Marsden, The Royal Marsden, Downs Road- Sutton, United Kingdom

Purpose or Objective RAIDER (CRUK/14/016) is the first international multicentre trial of tumour focused radical bladder radiotherapy delivered with plan of the day (PoD) . A quality assurance (QA) programme, led in the UK by the National Radiotherapy Trials Quality Assurance (RTTQA) Group, was implemented to support participating centres. The pre-trial questionnaire identified only a third (11/33) UK centres had prior PoD experience. Therefore the QA programme initially included pre-trial education and assessment for Therapeutic Radiographers (RTTs) and on- trial retrospective feedback. Here we report initial findings on guideline compliance with respect to agreement of RTT led online plan selection with the offline plan selection of RTTQA reviewers. The strategy adopted to sustain compliance is outlined. Material and Methods RAIDER is a two-stage phase II clinical trial randomising bladder cancer patients undergoing 20 fraction (f) or 32f radiotherapy to standard planning versus tumour focused PoD. Plan selections (small, medium, large) for 36 patients treated with PoD in Stage 1 (technical feasibility) were reviewed remotely offline by a single blinded observer from RTTQA. Plan selections were categorised, as per guidelines, using a traffic light approach: Green = Acceptable Amber = Acceptable variation Red = Unacceptable variation Green and amber cases were defined as guideline compliant. The proportion of compliant plans was compared between groups by chi-squared tests. Deviations from guidelines were assessed and plan selection guidance reviewed. Following updated guidance, online plan selections have so far been assessed for 17 Stage 2 patients. Results 439 CBCTs were reviewed from 19 centres. 318/439 (72%) plan selections by RTTs were guideline compliant. In the non-guideline compliant cases, the plan selections by RTTQA were smaller (87%), and larger (3%) and in 10% of cases the action taken would have been different e.g. remove the patient from treatment couch. 13% (n=16) of the non-compliant cases were deemed to require real- time active intervention by RTTQA. Compliance was greater in the 32f cohort, in centres with no previous PoD experience, in centres which previously employed weekly CBCTs for bladder patients, and for plan selections made in 2017, Table 1.

Based on these Stage 1 results the QA programme was revised to include: 1.Updated trial documentation detailing plan selection steps

2.Formal PoD reports for all centres 3.An interactive workshop with RTTs 4.A plan selection presentation 5.One-to-one training sessions

Since the implementation of these revisions for Stage 2, 102 CBCTs have been reviewed, from 16 centres. 98/102 (96%) plan selections were guideline compliant. Conclusion