Abstract Book

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ESTRO 37

after brachytherapy is 88%. About 90% of these patients have an unaltered bladder capacity. In conclusion high local control rate can be achieved in selected cases with brachytherapy. Bladder function is preserved in the majority of cases.

genes. The B/T ratios for the gene expression signatures were as follows: 0.79 (Fjeldbo), 0.71 (Halle), 0.69 (Buffa), 0.60 (Eustace), and 0.59 (Winter). Despite being derived in different ways and from different tumor types, the hypoxia gene expression signatures highly correlated with each other, with Spearman correlation coefficients ranging from 0.733 to 0.836. The Spearman coefficients between the hypoxia signature calculated using one biopsy and the same signature calculated using all available biopsies from the same tumor ranged from 0.855 to 0.891. Conclusion Compared with individual genes, hypoxia gene expression signatures are more consistent across multiple biopsies from different areas of an individual tumor and more tolerant of intratumoral heterogeneity. Cervix cancer- specific signatures had the best discriminatory ability in our patient population. In the setting where only a single biopsy is available, a cervix cancer-specific hypoxia gene signature may give a reasonable estimate of global hypoxia level and differentiate cervix cancers based on hypoxia. OC-0150 Assessing the immune contexture of anal squamous cell carcinoma D. Martin 1 , P. Balermpas 1 , R. Winkelmann 2 , U. Wieland 3 , M. Rave-Fränk 4 , C. Helmke 5 , M. Raab 5 , J. Kitz 6 , Y. Matthess 5 , K. Strebhardt 5 , C. Rödel 1 , F. Rödel 1 , E. Fokas 1 1 Klinikum der Johann Wolfgang Goethe Univ, Department of Radiotherapy and Oncology, Frankfurt, Germany 2 Klinikum der Johann Wolfgang Goethe Univ, Senckenberg Institute for Pathology, Frankfurt, Germany 3 University of Cologne, Institute of Virology- National Reference Centre for Papilloma- and Polyomaviruses, Cologne, Germany 4 University Medical Center Göttingen, Department of Radiotherapy and Radiation Oncology, Göttingen, Germany 5 Klinikum der Johann Wolfgang Goethe Univ, Department of Obstetrics and Gynaecology, Frankfurt, Germany 6 University Medical Center Göttingen, Department of Pathology, Göttingen, Germany Purpose or Objective While organ-preserving definitive chemoradiotherapy (CRT) remains standard of care in anal squamous cell carcinomas (ASCC), locoregional persistence or relapse still occurs in up to 30% of all patients. Infection with human-papilloma virus (HPV) is already established as a positive prognostic factor but there exists no clear explanation for this phenomenon. Material and Methods We examined pretreatment samples of patients with ASCC that were treated with chemoradiotherapy for expression of p16 INK4a and measured the HPV16 viral load via PCR. Also, we assessed the prognostic role of immune markers programmed cell death-1 (PD-1) and its ligand (PD-L1), CD8+ tumor-infiltrating lymphocytes (TILs), FOXP3+ Tregs, MPO+ tumor-associated neutrophils (TAN), phosphorylated caspase 8 and polo-like kinase 3, also in conjunction with HPV. Additionally, we assessed pretreatment peripheral white blood cell (WBC) count. Results After a median follow-up of 40 months, the 5-year cumulative incidence of local failure and disease-free survival (DFS) was 19.4% and 67.2%, respectively. A high HPV16 viral load was associated with a favorable local control (LC), disease-free survival (DFS) and overall survival (OS).A strong expression of immune markers was significantly more common in tumors with high HPV16 viral load, except for MPO. In multivariate analysis, high CD8+ and PD-1+ TILs expression predicted for improved LC and DFS. Also, high PD-L1 expression predicted for better LC, whereas high FOXP3+ Tregs expression correlated with superior DFS but not LC. In a separate

SP-0148 Determinants of toxicity in pelvic radiotherapy R. De Crevoisier Centre Eugene Marquis, Rennes, France

Abstract not received

Proffered Papers: RB 2: Biomarkers

OC-0149 Intratumoral heterogeneity and hypoxia gene expression signatures in cervix cancer. J. Lukovic 1 , K. Han 1,2,3 , M. Pintilie 4 , N. Chaudary 5 , R. Hill 1,2,5,6 , A. Fyles 1,2,3 , M. Milosevic 1,2,3 1 Princess Margaret Cancer Centre, Radiation Medicine Program, Toronto, Canada 2 University of Toronto, Department of Radiation Oncology, Toronto, Canada 3 University of Toronto, Institute of Medical Sciences, Toronto, Canada 4 Princess Margaret Cancer Centre, Department of Biostatistics, Toronto, Canada 5 Princess Margaret Research Institute, Princess Margaret Cancer Centre, Toronto, Canada 6 University of Toronto, Department of Medical Biophysics, Toronto, Canada Purpose or Objective In response to hypoxia, cervical cancers modulate gene expression resulting in an aggressive phenotype that is associated with resistance to chemoradiotherapy, increased propensity for metastases, and poor prognosis. Gene expression signatures have been devised to identify hypoxic tumours but the spatial heterogeneity in gene expression within a tumor raises the concern that multiple biopsies may be necessary to correctly identify the global tumor hypoxia status. The objective of this study was to determine if a genetic hypoxia signature is tolerant of intratumoral heterogeneity and whether a single biopsy may be sufficient to obtain a reliable Multiple biopsies (33) were obtained from 11 locally advanced cervical cancer patients prior to chemoradiotherapy. Between two and five different areas of each tumor were sampled. RNA was extracted and hybridized onto the Affymetrix U133 Plus 2.0 oligonucleotide chip. 5 validated hypoxia gene signatures were analyzed: 3 derived from clinical samples from various tumor sites (Winter, Buffa, Eustace) and 2 cervix- cancer specific signatures derived from DCE-MRI (Halle, Fjeldbo). The variance of gene expression within a patient, between patients, and the total variance were calculated. The ratio of between versus total variance (B/T) was calculated for each gene signature; the greater the B/T ratio, the greater the variance between tumors. The Spearman correlation coefficient was used to correlate gene expression signatures to each other and to compare signatures calculated using one biopsy and all the available biopsies. Results Patient and tumor characteristics were representative of typical cervix cancer patients treated with chemoradiotherapy: median age 47 (31-70), FIGO stage IB to IVB, and squamous histology (82%). The 5 hypoxia signatures analyzed were comprised of 6 to 99 genes each. The B/T ratio ranged from 0 to 1 for individual estimate of hypoxia. Material and Methods