ESTRO 2021 Abstract Book

S668

ESTRO 2021

Conclusion The observed dose-dependent decrease in CG rates combined with the occurrence of large abortive colonies presents a source of systematic error in clonogenicity scoring: slow, exponentially growing colonies are classified as non-clonogenic, while fast, abortive colonies are classified as clonogenic. We have developed an automated time-course image analysis system unveiling these facts by observing growth dynamics in the IVCA. Current data indicates considerable misclassification in the standard readout, motivating the application of this method to additional cell lines and late time points. PD-0832 Revisiting DNA repair biomarkers identification strategy for Head and Neck cancers S. Sauvaigo 1 , G. Muggiolu 1 , S. Libert 1 , B. Treillard 1 , A. Lauret 2 , G. Alfonse 2 , P. Philouze 3 , P. Ceruse 4 , C.A. Righini 5 , C. Rodriguez-Lafrasse 6 1 LXREPAIR, R&D, La Tronche, France; 2 University of Medicine Lyon-Sud, Cellular and Molecular Radiobiology Laboratory, Oullins, France; 3 Head Neck Department, Hospices Civils de Lyon, Lyon, France; 4 Hospices Civils de Lyon, Head Neck Department, Lyon, France; 5 CHU of Grenoble Alpes, Head Neck Surgery Department, Grenoble, France; 6 Lyon-Sud Hospital, Biochemistry and Molecular Biology Department, Pierre-Bénite, France Purpose or Objective Head and neck squamous cell carcinoma (HNSCC) is a highly heterogeneous disease that develops through exposure to tobacco and alcohol carcinogenic action, or via high-risk HPV-infection. Radiotherapy alone or combined with chemotherapy are widely used treatment approaches for HNSCC. Because of the critical role played by DNA repair mechanisms in the etiology and in the response of these tumors to DNA damaging agents, different strategies are developed to 1. identify biomarkers able to predict response to these traditional therapies and 2. improve tumor response by inhibiting specific DNA repair mechanisms, or by potentializing the chemo-radiation treatments. A first requirement however is to have the right tool to accurately characterize and monitor the DNA Damage Response and the different DNA repair pathways. To this end and as a first approach, we conducted a prospective clinical proof-of-concept on 38 patients suffering from HNSCC and enrolled in hospitals in Lyon and Grenoble. Materials and Methods The DNA repair profile of biopsies taken before the start of any treatment was established using multiplexed functional DNA repair assays on biochip. These assays precisely quantify major DNA repair pathways, including double-strand-break (DSB) repair, and excision/synthesis repair mechanisms, using extracts prepared from fresh biopsies and support functionalized by a series of specific DNA lesions substrates. We report here the preliminary analysis conducted 4 months after the beginning of the treatment. Results Life style factors impacted the various DNA repair capacities: Non Homologous End Joining (NHEJ) was significantly decreased in smokers compared to ex-smokers. Alcohol consumption negatively impacted the repair capacity of abasic sites, that involves Ref-1/APE1 enzyme. Both alternative DSB repair pathways were