ESTRO 37 Abstract book

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ESTRO 37

therapeutic image interpretation and how to avoid them taking into consideration multiparametric data will be addressed. Results of combined MR-PET evaluations for the correct staging of recurrent tumors will be presented based on histologically verified data including additional long-term follow-up. Major emphasis will be put recently published research results and on quantitative information that can be easily extracted in clinical routine. The complementarity of apparent diffusion coefficient (ADC) values and of FDG - based standardized uptake values (SUV) will be discussed, as well as the newly proposed multiparametric approach for the assessment of post-radiotherapy necks based on concordant and discordant evaluations with MRI, DWI and FDG-PET. Pitfalls of image interpretation will be addressed and how to avoid them based on complementary multiparametric information. New quantification tools, including histogram based analysis and textural features will be briefly addressed. SP-0548 Genomic biomarkers for selection of patients to hypoxia modification H. Lyng 1 1 Lyng Heidi, Department of Radiation Biology, Oslo, Norway Abstract text Recent advances in the cancer genomic field and understanding of the molecular response to hypoxia, have led to promising biopsy based biomarkers to select patients who are most likely to benefit from hypoxic modifications. A considerable focus has been on gene expression signatures as biomarkers, which measure the transcriptional response of a tumors to its hypoxic environment. In this talk, I will review recent advances in the discovery and validation of such biomarkers. I will further discuss how to translate the biomarkers into clinical practice and face challenges related to tissue sampling and intratumor heterogeneity. SP-0549 Multi-parametric functional imaging for patient stratification and hypoxia modification D. Thorwarth 1 1 University Hospital Tübingen, Section for Biomedical Physics- Department for Radiation Oncology, Tübingen, Germany Abstract text Tumor hypoxia is known to be a major cause for radiation resistance. Several functional imaging methods such as positron emission tomography (PET), magnetic resonance imaging (MRI) or combined PET/MRI have the potential to visualize functional and biological properties of tumor tissue. To discuss the ability of different imaging techniques like [18F]-FMISO, [18F]-FAZA and [18F]-FDG PET, diffusion weighted (DW) or dynamic contrast enhanced (DCE) MRI for patient stratification, methodological aspects as well as results of recent studies will be summarized. Once the prognostic value of an imaging biomarker is proven, it may be used as a basis for hypoxia modification during radiotherapy either by hypoxic sensitizers or by modifying the radiation dose instructed by imaging. As an example for the latter scenario, results of a randomized trial investigating the effectiveness of hypoxia dose painting in head-and-neck cancer based on [18F]-FMISO PET will be presented. Recent studies have shown that multi-parametric functional imaging in terms of hypoxia PET and DW or DCE MRI allow the stratification of patients according to Symposium: Biomarker driven hypoxic modification

RT outcome. Thus, these imaging modalities allow the measurement of three-dimensional resistance maps, which may in the future serve as a basis for hypoxia modifying RT SP-0550 Clinical trials J. Alsner 1 1 Aarhus University Hospital, Department of Experimental Clinical Oncology, Aarhus C, Denmark Abstract text A number of different clinical trials have investigated the possibility of improving outcome of radiotherapy by hypoxic modification. The methods have include increasing oxygen availability, using hypoxic cell radiation sensitizers (such as nimorazole and hyperthermia), using hypoxic cell cytotoxins (such as tirapazamine, targeting tumour vasculature, and increasing radiation dose to resistant tumours or sub- populations within a tumour. Hypoxia displays a large degree of inter-patient and intra-tumour heterogeneity and there is a great need for predictive biomarkers, that can be used for individualized treatment protocols, or PRO (precision radiation oncology). Data from some of the previous trials on hypoxic modification have been used retrospectively to develop and validate such predictive biomarkers for future trials. One class of biomarkers is based on gene expression signatures that measure various genes upregulated by hypoxia in pre-treatment biopsies. Different signatures have been applied successfully to previous trials in head and neck cancer on the radiosensitizer nimorazole, DAHANCA 5 [1] and IAEA-HypoX [2], and a trial on accelerated radiotherapy with carbogen and nicotinamide, ARCON [3]. A similar approach has been successful in a bladder cancer trial on radiotherapy, carbogen, and nicotinamide, BCON [4]. Other classes of biomarkers successfully applied retrospectively to clinical trials include the circulating protein osteopontin, DAHANCA 5 [5]. In the ARCON trial, epidermal growth factor receptor (EGFR) expression [6], the pattern of carbonic anhydrase 9 (CAIX) expression [7], and expression of the proliferation marker Ki-67 [8] have been successfully applied. In a head and neck cancer trial on the hypoxic cytotoxin tirapazamine (TROG 02.02), combinations of circulating levels of interleukin 8 (IL-8) and hepatocyte growth factor (HGF) [9], and expression of the flavoprotein P450 (cytochrome) oxidoreductase (POR) [10] have been successfully applied. In the BCON trial, presence of necrosis has also been applied successfully [11]. Recently, a number of clinical trials on hypoxic modifications have been initiated which integrate genomic or imaging biomarkers. The NIMRAD study (ClinicalTrials.gov ID: NCT01950689) is placebo-controlled randomized trial of nimorazole vs radiotherapy alone in locally advanced head and neck cancer not suitable for chemotherapy or cetuximab, and will retrospectively analyse for two gene expression signatures [1,3]. In two other head and neck cancer trials on nimorazole, a gene expression signature is being measured prospectively during the trials. The randomized multicentre study EORTC-1219-ROG-HNCG/DAHANCA-29 (NCT01880359) has two primary aims, to test chemo-radiotherapy with or without nimorazole, and to test a 15-gene signature. In this trial, the signature is evaluated before randomization and included as parameter for stratification. DAHANCA 30 (NCT02661152) is a randomized non-inferiority trial testing chemo-radiotherapy with or without nimorazole in patients identified as less hypoxic by the 15-gene signature. Finally, DAHANCA 33 (NCT02976051) is a trial on image guided dose-escalated radiotherapy to patients

with hypoxic tumours, based on FAZA-PET. [1] Toustrup. Cancer Res 2011;71:5923–31. [2] Metwally. Radiother Oncol 2015;116:15–20.