ESTRO 2022 - Abstract Book

S373

Abstract book

ESTRO 2022

These data indicate two mechanisms of ER independent cellular adaptations underlying tamoxifen induced radioresistance. We report an increased glycolytic capacity in tamoxifen resistant cells, which is generally associated with radioresistance. Additionally, increased metabolism of ROS and higher expression of antioxidants serve to protect cells from DNA damage and death related to irradiation induced ROS as we show that tamoxifen resistant cells regain their sensitivity to ROS when NRF2 is inhibited which expectedly increases sensitivity to irradiation.

OC-0430 Multi-candidate immunohistochemical assessment of prognostic biomarkers in the CHHiP prostate trial.

A. Wilkins 1

1 Institute of Cancer Research, Radiotherapy and Imaging, London, United Kingdom

Purpose or Objective Background: Protein markers of hypoxia, apoptosis, cell proliferation, cell cycle checkpoints, and growth factor signalling have shown prognostic ability in previous randomised trials of radiotherapy for prostate cancer; such markers may help select patients with localised prostate cancer for treatment intensification/de-escalation. Trans-CHHiP (CRUK A12518) was a translational substudy within the CHHiP (CRUK/06/016) trial of prostate radiotherapy fractionation. The study aimed to validate whether protein markers of the above biological pathways could improve prediction of prognosis following radiotherapy. Materials and Methods Methods: A matched case:control study was used in which patients with biochemical or clinical failure after radiotherapy (BCR) were matched to patients without recurrence according to established prognostic factors (Gleason score, presenting PSA, tumour-stage and fractionation schedule). Immunohistochemical (IHC) staining of diagnostic biopsy sections was carried out for markers of hypoxia (HIF1 α ), apoptosis (Bcl-2), cell proliferation (Ki67 and Geminin), cell cycle checkpoints (p16, p53 and p-chk1) and PTEN (growth factor signalling). Two independent investigators scored the staining for each marker. Conditional logistic regression models were fitted using the case:control study samples to estimate the prognostic value of each IHC biomarker separately and then in a multivariable model including all markers identified as significant. All models were adjusted for age at randomisation and stratified by matching strata. Results Results: IHC results were available for up to 164 cases matched to 164 controls for the individual biomarker analyses. PTEN, Geminin and mean Ki67 were prognostic after adjusting for multiple comparisons at 10% false discovery rate and were fitted in a multivariable model (table 1). To maintain the 1:1 matching, 106 matched pairs had data available for all biomarkers for the multivariable analysis where PTEN and Geminin showed significant prediction of prognosis.

Conclusion Conclusion: Geminin and PTEN were prognostic for BCR independently of established clinical prognostic factors.

Proffered Papers: Head & neck

OC-0431 Tumour volume in oropharyngeal cancers – more important than ever!

G. Adrian 1 , H. Carlsson 1 , E. Kjellén 1 , J. Sjövall 1 , B. Zackrisson 2 , P. Nilsson 1 , M. Gebre-Medhin 1

1 Lund University, Skåne University Hospital, Lund, Sweden; 2 Umeå University, Radiation Sciences - Oncology, Umeå, Sweden

Purpose or Objective