ESTRO 2023 - Abstract Book

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ESTRO 2023

Though PSMA7 is part of the proteasome, it has proteasome-independent protein-protein interactions that are potentially targetable for improving response of GBM to the current standard of care.

PO-2219 Radiosensitivity Index as potential marker of biological sex differences to radiation response

L. Marignol 1 , D.R. Grimes 2

1 Trinity College Dublin , Radiation Therapy, Dublin , Ireland; 2 Trinity College Dublin, Radiation Therapy, Dublin , Ireland

Purpose or Objective Sex is a biological variable increasingly reported to impact cancer treatment outcomes. The purpose of this in silico study was to investigate whether biological sex is associated with differences in genomic scores defining radiosensitivity; and test the hypothesis that the associated genomic-adjusted radiation dose will reveal inter-sex differences. Materials and Methods Freely available, raw RNA-Seq and gene chip data were accessed from the Cancer Gene Atlas for the 10 Radiosensitivity Index (RSI) genes (AR, cJun [JUN], STAT1, PKC- β [PRKCB], RelA [RELA], cABL [ABL], SUMO1, PAK2, HDAC1, and IRF1) across 4 main cancer sites: head and neck (N= 364 male, N=133 female), bladder (N= 291 male, N=106 female), rectum (N= 90 male, N=75 female) and lung (N=1014 male, N=707 female). The RSI was calculated using the published equations for each patient. The RSI value was subsequently used to derive the Genomically adjusted radiation dose (GARD) score for each patient. To test differences between the sexes, two tailed independent student t-tests were used. Results In male cohorts, the mean ± SD RSI values were 0.33±0.17 (lung). 0.45± 0.21 (head and neck), 0.5±0.19 (rectal) and 0.14±0.21 (bladder). In female cohorts, the mean ± SD RSI values were 0.36±0.17 (lung). 0.43± 0.18 (head and neck), 0.53±0.18 (rectal) and 0.12±0.22 (bladder). The difference in the mean RSI values between male and female patient cohorts was statistically significant in lung cancer only (p=0.0001). A large heterogeneity in GARD values were obtained across both female and male patient population, in all 4 cancer sites. The standard deviation of GARD values in male and female cohorts ranged from 0.51 (female head and neck) to 0.84 (male bladder). Mean GARD values were significantly different between the sexes in lung cancer only (p=0.0001). Conclusion Significantly higher GARD values in this cohort of female lung cancer patients supports reports that female sex is associated with a better outcome for this disease. This small in silico study suggests that further investigation of the impact of sex on radiation responses is warranted. M. Or 1 , P. Sundaresan 1,2 , J. Lai 3 , B. Gloss 4 , H. Shen 5,6 , A. Sharma 7 , H. Mahajan 5,8,9 , N. Pathma-Nathan 5,10,11 , T. El-Khoury 10,11,12 , J. Toh 5,10,11 , J. Jayamohan 13,5 , M. Wong 5,14 , A. Nagrial 5,14 , E. Hau 13,5,15 1 Westmead Hospital, Sydney, Australia, Radiation Oncology, Westmead, Australia; 2 The University of Sydney, Sydney Medical School, Sydney, NSW, Australia; 3 Westmead Institute of Medical Research, Genomics Facility, Westmead, Australia; 4 Westmead Institute of Medical Research, Bioinformatics and Data Analysis, Westmead, Australia; 5 The University of Sydney, Sydney Medical School, Sydney, Australia; 6 Westmead Institute of Medical Research, Radiation Oncology, Westmead, Australia; 7 Harry Perkins Institute of Medical Research, Single Cell Genomics, Perth, Australia; 8 NSW health Pathology, Tissue pathology ICPMR Westmead hospital, Sydney, Australia; 9 Western Sydney University, School of Medicine, Sydney, Australia; 10 Westmead Institute of Medical Research, Surgery, Sydney, Australia; 11 Westmead Hospital, Colorectal Surgery, Sydney, Australia; 12 University of Notre Dame, School of Medicine, Sydney, Australia; 13 Westmead Hospital, Radiation Oncology, Sydney, Australia; 14 Westmead Hospital, Medical Oncology, Sydney, Australia; 15 Westmead Institute of Medical Research, Radiation Oncology, Sydney, Australia Purpose or Objective Curative management of locally advanced rectal cancer (LARC) involves neoadjuvant chemoradiation therapy (nCRT) followed by radical surgery. Pathological complete response (pCR) is seen in 15-27% of patients. The genomic basis of chemoradiation resistance in LARC patients remains poorly understood. Intra-tumoural genetic heterogeneity (ITH) is the proposed mechanism underlying disease progression and treatment failure. Single cell transcriptomics is a revolutionary approach for the in-depth exploration of ITH. We aim to ensure technical feasibility of single RNA sequencing in LARC patients before and after nCRT. Materials and Methods LARC patients undergoing nCRT followed by surgery provided peripheral blood and tissue samples prior to chemoradiation and following surgery. We plan to recruit total of 12 patients. Tissue samples were collected and banked from examination under anaesthesia and prior to treatment and at time of surgery for single RNA sequencing. Clinicopathological information were obtained. The biopsies specimen underwent sample preparation and dissociation, single cell isolation (cell sorting and dividing cell suspension with CD45 positive and negative in 50:50 ratio) and library preparation and single cell RNA sequencing. The first 2 patients will be analysed for feasibility prior to completion of recruitment. Results We successfully processed tumour tissue for single cell RNA sequencing in the 2 recruited patients using our methods with good sequencing and cell quality. The samples did not undergo preservation and all samples were processed fresh. There PO-2220 Single cell sequencing is feasible in delineating chemoradiation resistance in rectal cancer