ESTRO 37 Abstract book

ESTRO 37

S591

FaDu, Cal33, SAS) that were irradiated with more than 20 fractions of 4 Gy. Results We could previously show by functional analysis of the surviving cell populations that they are enriched for cells expressing CSC markers. These cells show enhanced sphere-forming potential, increased migratory potential and higher tumorigenicity. We observed that HNSCC cell populations undergo a phenotypic switch with regards to CSC-marker expression depending on the time point after irradiation, suggesting a dynamic nature of the radioresistant properties. We also found that the aldehyde dehydrogenase + (ALDH) cell population, in contrast to the ALDH- cells, maintains its tumorigenic properties in vivo after irradiation and, therefore, may provide tumor regrowth after radiotherapy. Further investigations revealed that ALDH activity is indicative for HNSCC cells with an accelerated DNA damage response and high radioresistance. Conclusion The constitutive expression of the different fluorescence in distinct CSC clones can be used to track single CSC populations as for example ALDH+ cells in vitro and in vivo at any timepoint. The visualization of cellular phenotypes with the help of fluorescence markers can be used to observe the immediate cellular reaction of a specific defined tumor cell population to ionizing irradiation. This method can be used to prove the predictive potential of biomarkers for radioresistance. PO-1051 Comparative genomic analysis of oral versus laryngeal and pharyngeal cancer D. Vossen 1 , C. Verhagen 1 , M. Verheij 2 , L. Wessels 3 , C. Vens 1 , M. Van den Brekel 4 1 Netherlands Cancer Institute, Cell Biology, Amsterdam, The Netherlands 2 Netherlands Cancer Institute, Radiation Oncology, Amsterdam, The Netherlands 3 Netherlands Cancer Institute, Molecular Carcinogenesis, Amsterdam, The Netherlands 4 Netherlands Cancer Institute, Head and Neck Oncology and Surgery, Amsterdam, The Netherlands Purpose or Objective Oral squamous cell carcinomas (OSCC) appear to respond differently to definitive chemoradiotherapy than laryngeal and pharyngeal squamous cell carcinoma (L/P- SCC). Definitive chemoradiotherapy (CRT) results in similar or improved outcomes in L/P-SCC with regards to control, survival and organ preservation. However, in OSCC, CRT is associated with worse survival compared to surgery followed by postoperative radiotherapy. Recognizing the potential impact of tumor mutations in chemoradiotherapy response, this prompted us to compare the genetic profiles of OSCC with L/P-SCC. Material and Methods Target capture DNA sequencing was performed on 55 OSCC (HPV-negative) and 56 HPV-negative L/P-SCC tumor samples from an in-house patient cohort. We expanded our analysis on somatic mutation and CNA data from 276 HPV-negative OSCC and 134 HPV-negative L/P-SCC samples from The Cancer Genome Atlas (TCGA dataset). Somatic mutations and copy number aberrations (CNAs) were identified and compared in the L/P-SCC and OSCC. Results Overall, the spectrum of somatic mutations was similar in both HNSCC sites. However, significant differences were found for some important and commonly mutated genes. OSCC was enriched for CASP8 mutations (15% vs 0%, Q <

0.1; TCGA: 17% vs 2%, Q < 0.001) and HRAS mutations (TCGA: 10% vs 1%, Q < 0.01). L/P-SCC was enriched for LAMA2 mutations (TCGA: 5% vs 19%, Q < 0.01) and NSD1 mutations containing tumors (TCGA: 7% vs 25%, Q < 0.001, Figure 1A). Notably, OSCC had fewer CNAs in individual genes (P < 0.001) and regions of frequent CNA (P < 0.001), suggesting less pronounced genomic and chromosomal instability features than L/P-SCC. DNA repair defects can drive such instability features in tumor cells. We therefore tested genomic scar signatures that depict BRCA1/2 (and BRCA1/2-like) mutations in breast and ovarian cancer or alterations in homologous recombination repair (HRD, NtAI, LST in Figure 1B). Consistent with the overall CNA data, L/P-SCC scored significantly higher than OSCC on those three genomic scar signatures associated with homologous recombination (HR) deficiency. Conclusion Even though largely similar, there are characteristic genetic differences between OSCC and L/P-SCC, both in terms of somatic mutations and CNAs. Our results also indicate that repair defects may occur less frequently in OSCC. This could explain a different chemo-radiotherapy responsiveness.

Poster: Radiobiology track: Radiobiology of prostate cancer

PO-1052 In vivo radiobiological analysis of prostate carcinoma treated with 12 Gy single-shot IORT C. Pisani 1 , F. Boccafoschi 2 , R. Boldorini 3 , M. Krengli 1 1 University Hospital Maggiore della Carità, Radiotherapy, Novara, Italy 2 University of Piemonte Orientale, Health Medicine, Novara, Italy 3 University of Piemonte Orientale, Translational Medicine, Novara, Italy Purpose or Objective To evaluate apoptotic pathways in prostate cancer treated with intraoperative radiotherapy (IORT), studying the effects on cancer cells, prostatic intraepithelial neoplasia (PIN) and healthy cells. We evaluated correlations between p53, Bcl-2 and ki-67, pathological staging and local control