Abstract 1145: Molecular markers of neoadjuvant chemotherapy and combined chemoradiotherapy response in patients with oropharynx squamous cell carcinoma

Abstract

The treatment currently considered standard for advanced oropharyngeal tumors involves concomitant chemo- and radiotherapy or surgery followed by adjuvant chemo- and radiotherapy. However, only 30 to 50% of patients with locally advanced disease survive more than three years, even with the advances in surgical techniques and the recognized benefits of therapy combined with radio- and chemotherapy. Treatment with induction TPF (docetaxel plus cisplatin and fluorouracil) chemotherapy followed by chemoradiotherapy was associated with a trend toward improved survival (Posner et al., 2007. N Engl J Med. 357:1705). The aim of this study was to investigate biological markers as potential predictors of response to chemotherapy and/or radiotherapy according to HPV infection in oropharyngeal carcinomas (OC). Thirty-two OC were evaluated by array CGH (4x180k, Agilent). A total of 35% of cases were HPV positives; HPV16 subtype was the most frequently detected (8/37), followed by subtype 18 (2/37). In general, HPV- cases showed a large number of copy number alterations (117 CNAs) in comparison with HPV+ samples. Losses on 7q22.1 and 14q12 were found exclusively in HPV+ tumors (p=0.044). Comparative analysis of genomic alterations among the patients which received combined chemoradiotherapy (22 cases) was done aiming to identify molecular markers that could predict the complete response (CR), partial response (PR) to treatment or progressive disease (PD). Tumors with CR showed a lower number of genomic alterations (90 CNAs versus 110 per cases in PR and PD). Losses at 1p21.3-p21.1 and gains on 10p13-p12.33 and 10p12.31-p12.1(p≤0.017) were exclusively found in patients with PD and PR. Overall survival (OS) analysis between HPV- and HPV+ cases demonstrated no significant differences (p>0.05). HPV- tumors showed more complexity and genomic instability than HPV+ tumors. Genomic losses or gains at different loci have been reported in HPV- compared to few or no alterations in HPV+ cases. In this study, it was detected specific chromosomal imbalances associated with therapy response and consequently, putative candidates to be validated in a large series of cases. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1145. doi:1538-7445.AM2012-1145