P20 Prognostic and predictive biomarkers related to p53 pathway and clinical outcome in platinum-treated locally advanced head and neck cancer – A revision after >10 years of a monocentric patient’s population

Introduction Chemo-radiotherapy (CRT) with cisplatin-based regimen is curative in a subset of patients with locally advanced head and neck squamous carcinomas (LAHNSCC), but causes considerable toxicity. Thus, additional biomarkers are required to optimise therapy, personalising treatments selecting from surgery, radiation or a growing number of CRT options. p53 mutations are associated to decreased overall survival (OS) and the disruptive mutations to the group of patients with the poorest survival. We already described polymorphisms SNP72 in TP53 and SNP309 in MDM2 genes, correlating them to clinical prognosis. We now reconsider a group of 66 well characterised LAHNSCC patients with a median follow-up of 4.3 (0.1–16.8) years, under the light of the new available prognostic markers. Patients and methods We updated the follow up (toxicity, PFS and OS) of 61 LAHNSCC patients described >10 years ago for p53 SNP72 and somatic mutations. We analysed P16 and EGFR expression by immunohistochemistry and MDM2 SNP by direct sequencing. p53, EGFR, p16 and MDM2 are analysed using the Kaplan–Meier method and the log-rank test to evaluate significance. Results Clinical outcome in our cohort of LAHNSCC is influenced by p53 SNP72. Mutations occurring in the 72R form predict worse survival. Survival curves for all 66 patients split by presence or absence of mutations (log rank p  = 0.91), and whether the mutation occurred in the 72R or 72P allele (log rank p  = 0.005). In wild-type p53, OS is longer in 72RR and 72RP (median OS = 72.3 and 65.0 months respectively) compared with 72PP (median OS = 7.2 months, p  = 0.005) carriers. Median OS is significantly shorter in patients with MDM2 SNP309 genotypes GG or GT, compared to TT (26.9 vs 97 months; p  = 0.002). p16 and EGFR curves do not discriminate statistically. Conclusion The predictive utility of the SNP72 in TP53 may be of value in the selection of LAHNSCC patients for radical CRT. However its validity in clinical practise has to be related with p53 mutational status. Thus the analysis of SNP309 in MDM2 gene in peripheral blood has to be favoured as clinical biomarker in this subset of patients.