692P Copy Number Alterations and Response to Radiotherapy + Cisplatin Vs Radiotherapy + Cetuximab after Docetaxel-Cisplatin-fluorouracil Induction Chemotherapy in Patients with Locally Advanced Unresectable Head and Neck Cancer

Chemoradiotherapy is the standard treatment for patients with unresectable, locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN). This randomized, open-label, phase 3 trial studied patients with unresectable LA-SCCHN who received 3 cycles of ICT (concomitant docetaxel, cisplatin, and 5-fluorouracil; TPF) followed by cisplatin plus radiotherapy (cis+RT) or cetuximab plus radiotherapy (cet+RT) and aimed of this research is to identify genomic alterations and associate them with clinical data and response to treatment. 177 patients were recruited and started ICT; 142 patients received post-ICT treatment (cis+RT, n=72; cet+RT, n=70). All diagnostic samples belong to the clinical trial TTCC-2007-01 (NCT0071639122). DNA samples were processed and analyzed with the Affymetrix OncoScan platform (Santa Clara, CA, United States) to assess CNAs and loss of heterozygosity. Mutational status was determined by targeted massive sequencing. CNA score showed that altered genome fraction by Broad CNA events was 11(1-34),133 (15-1045) for FCS and GCS – 2,430 median per sample. Tumor localization Oropharynx showed lower FCS score (103 median per case 16-398) p<0.05. In SD/PD gained region was 3q28 and 11q13.2 (79%) and loss at 9p21.3 (56%). Gains on 3q28, 8q23.3, 8q24 (84%), 8q (68%) and 3p12.3, 3p12.1 and 4p15.32 (89%), were the most frequent changes in cases with Toxicity to ICT. Regards to response Cis +RT, gains on 15q22.31 was associated with CR/PR cases. Changes on 3p, 14q- and del 8p11.2 were most frequent in cases with SD/PD (p<0.05). Gains on 5p13.1 were associates with SD/PD to Cet+ RT (p<0.05). Most cases with BCS score >34, response to Cis+RT as a Cet+RT. Overall survival was associated with BCS score > 11 and GCS score >-0.3. This study identified several genomic regions of interest associated with response to treatment in HNSCC. Our results suggest that genomic alterations could be used as biomarkers for therapeutic optimisation. New studies will be needed to validate these conclusions.