Abstract A34: SNPs as predictors in the tailoring of treatment for HNSCC patients undergoing organ preservation protocols
Authors: Lidia Rebolho Batista M. R. B., Pamela Angelique Kuhlmann, Matias Eliseo Melendez, Ana Carolina Laus, Ana Carolina de Carvalho, Pedro Rafael Martins De Marchi, Adriane Feijó Evangelista, Viana de Souza Luciano, Carvalho Lopes André
Journal: Clinical Cancer Research (2018)

Abstract Background: The treatment of early-stage head and neck squamous cell carcinoma (HNSCC) tumors is conducted through a multimodality approach including surgery, radiation, and chemotherapy, with curative rates of approximately 80-90%. However, only 30-50% of patients with locally advanced disease survive more than five years, despite the advances in surgical techniques and the recognized benefits of chemoradiation. In this scenario, improvement in patients' survival requires both early detection as well as the possibility of predicting, at the moment of diagnosis, which patients will benefit from a specific treatment. Tailoring the treatment is of great importance and may help in the management of treatment planning and follow-up, improving survival rates. Objectives: The aim of the present study was to evaluate SNPs in genes involved in induction chemotherapy with cisplatin and paclitaxel, which are able to predict the response to an organ-preservation protocol based on chemoradiation. Materials and Methods: For this purpose, we assessed the profile of 3.223 SNPs of 59 HNSCC patients with locally advanced and unresectable tumors undergoing treatment using the IonTorrent plataform. Results: From 3,223 SPNs, only 323 were present in the study population and 21 SNPs showed a significant association with response to induction chemotherapy and/or concomitance. Regarding induction chemotherapy response, thirteen polymorphisms were statistically associated. The presence of SNPs rs776746 (CYP3A5 gene) (p=0.03), rs1883322 (PPARD gene) (p=0.03), rs10932374 (ERBB4 gene) (p=0.03), and rs2230806 (ABCA1 gene) (p=0.04) was associated with a favorable treatment response, whereas the remaining polymorphisms with statistical significance were associated with a lack of therapeutic response. It is interesting to note that the presence of three polymorphisms (rs10509681 (p=0.001), rs1058930 (p=0.03), and rs11572080 (p≤0.001)) in the CYP2C8 gene was associated with treatment resistance, showing the importance of these polymorphisms in the process of chemotherapy resistance. Similarly, polymorphisms rs12415607 (p=0.01), rs4353229 (p=0.02), and rs2227310 (p=0.02) in the CASP7 gene were associated with resistance to chemotherapy. Conclusion: The results of this study suggest that the evaluation of SNPs could be an important tool for treatment planning and a prognosis predictor for HNSCC patients undergoing organ preservation protocols. Citation Format: Lidia Rebolho Batista M. R. B., Pamela Angelique Kuhlmann, Matias Eliseo Melendez, Ana Carolina Laus, Ana Carolina de Carvalho, Pedro Rafael Martins De Marchi, Adriane Feijó Evangelista, Viana de Souza Luciano, Carvalho Lopes André. SNPs as predictors in the tailoring of treatment for HNSCC patients undergoing organ preservation protocols [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr A34.