ESTRO 2021 Abstract Book
S300
ESTRO 2021
were identified. The genes showed enrichment in biological processes related to extracellular matrix organization, focal adhesion and PI3K/AKT-signalling. MiR-200a-/b/-429 overexpression decreased cell survival in vitro and increased tumor growth delay in xenografts after radiation. Conclusion Expression of the miR-200 family on 1q may serve as predictive biomarkers of central pelvic recurrence and tumor radioresistance in cervical cancer. In vitro - and xenograft studies show that overexpression of these miRNAs decreases radioresistance OC-0404 Role of single nucleotide polymorphisms (SNPs) in high-grade gliomas treated with concomitant RTCT A. Gonnelli 1 , F. Pasqualetti 2 , A. Molinari 3 , G. Gadducci 1 , N. Giannini 1 , G. Malfatti 1 , P. Fabiola 1 1 AOUP-Azienda Ospedaliera Universitaria Pisana, Radiation Oncology, Pisa, Italy; 2 AOUP-Azienda Ospedaliera Universitaria Pisana, Radiation Oncology, Pisa, Italy; 3 Eco-Medica, Radiation Oncology, Empoli, Italy Purpose or Objective XRCC3 is a member of the RecA/Rad51-related protein family that participates in homologous recombination DNA repair (HRR), maintaining chromosome stability and participating in DNA repair. Through these activities, XRCC3 proteins play a role in resistance to RTCT in several solid tumors. With these basis, the aim of the present study was to evaluate the impact of XRCC3 -SNPs on HGG patients treated with up front RTCT. Materials and Methods This analysis is an mono-institutional, prospective pharmacogenetic study approved by the CEAVNO , Pisa, Italy. From October 2010 to August 2019, 75 pts with proven diagnosis of HGG (7 anaplastic astrocytoma and 68 glioblastoma), IDH 1/2 wild type, ECOG PS 0-2, age>18 years were recruited. All patients were treated with post-operative RTCT and sequential chemotherapy with TMZ. All genetic evaluations were performed simultaneously by histological examination. Polymerase chain reaction amplification was performed using AmpliTaq Gold DNA polymersare. Kaplan Meier curves were performed for statistical association with genotypes. Results In May 2020, at the data analysis, median progression-free survival (PFS) and overall survival (OS) were 11 and 18 months, respectively. A statistically significant association with PFS in univariate and multivariate COX regression analysis was found with XRCC3 rs1799794 polymorphism (p = 0.013 and p = 0.037 on univariate and multivariate analyses, respectively). The median time of PFS of XRCC3 rs1799794 AG versus AA + GG genotypes was 20 months (CI95%: 13-27 months) and 9 months (CI95%: 6-12 months), respectively. A statistically significant association with OS in univariate and a trend in multivariate COX regression analyses was found with the same polymorphism (p = 0.012 and p = 0.068 on univariate and multivariate analyses, respectively ). T he median time of OS of XRCC3 rs1799794 AG versus AA + GG genotypes was 27 months (CI95%: 21-33 months) and 16 months (CI95%: 12-20 months), respectively. Conclusion The present pharmacogenetic study describes for the first time a significant association between XRCC3 rs1799794 and PFS and OS in HGG patients treated with upfront RT-CT with TMZ. We demonstrated that the XRCC3 rs1799794 AG genotype was a predictive marker for longer PFS and better OS in patients with HGG treated with RTCT. The present, pilot study may represent the stimulus to prospectively investigate the role of XRCC3 rs1799794 polymorphisms as a target for new drug therapies for GBM patients. OC-0405 Development and internal validation of an RPA-based pre-treatment decision tool for spinal SBRT R. Kowalchuk 1 , T. Mullikin 1 , W. Harmsen 2 , P. Rose 3 , B. Siontis 4 , D. Kim 5 , B. Costello 4 , J. Morris 5 , J. Marion 5 , B. Johnson-Tesch 5 , R. Gao 1 , S. Shiraishi 6 , J. Lucido 6 , D. Trifiletti 1 , K. Olivier 1 , D. Owen 1 , B. Stish 1 , M. Waddle 1 , N. Laack 1 , S. Park 1 , P. Brown 1 , K. Merrell 1 1 Mayo Clinic, Radiation Oncology, Rochester, USA; 2 Mayo Clinic, Statistics, Rochester, USA; 3 Mayo Clinic, Orthopedic Surgery, Rochester, USA; 4 Mayo Clinic, Medical Oncology, Rochester, USA; 5 Mayo Clinic, Radiology, Rochester, USA; 6 Mayo Clinic, Medical Physics, Rochester, USA Purpose or Objective Despite studies suggesting superior outcomes for select patients who receive metastasis-directed therapy, such as spine-SBRT, limited data is available to optimize patient selection. Such therapies must optimize both patient outcomes and costs, so further guidance is needed. We sought to develop a pre-treatment tool for spine SBRT identifying patients with favorable overall survival (OS) and subsequently analyze predictors for local control (LC) among these patients. Materials and Methods 680 spine SBRT treatments for metastatic disease were performed in 469 patients from December 2007 - October 2019. After exclusion of particle therapy, benign histology, and missing data, 424 patients were included in the OS analysis. Exclusion of treatments without imaging follow-up left 368 patients for the LC analysis. OS data was split using a random number generator into training (70%, n=297) and internal validation sets (30%, n=127). Associations between variables were assessed with a correlation heatmap. Recursive partitioning analysis was conducted using decision-tree analysis, with the log-rank test used as the criterion for node splitting and model accuracy assessed via the concordance index. Feature selection consisted of variables used in the highest-fidelity RPA models. Cumulative incidence curves demonstrated the risk of local failure, with death as a competing risk. Results Patient characteristics were similar in both sets. The final model consisted of the following variables and Proffered papers: Proffered papers 24: Palliation
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