Association of germ-line single nucleotide polymorphisms (SNPs) with pathologic response to neoadjuvant cisplatin-based chemotherapy in patients with resectable non-small cell lung cancers.

Abstract

7558 Background: Pathologic response to neoadjuvant chemotherapy correlates with survival in resected lung cancers. Predictive biomarkers of response are needed. Tumor-specific biomarkers have been hindered by reproducibility and specimen adequacy. Genome-wide association studies (most in SE Asia) have identified candidate SNPs that correlate with clinical outcomes after cisplatin-based chemotherapy. We evaluated whether these candidate SNPs are predictive of pathologic response to neoadjuvant chemotherapy in a US population. Methods: We aimed to correlate SNPs with near complete PR (ncPR) to neoadjuvant cisplatin + docetaxel in patients with resectable lung cancers. ncPR was defined as 90% necrosis, inflammation and fibrosis across serial 1cm sections of the resected tumor. Germline DNA was extracted and 50 candidate SNPs were genotyped by Sequenom Mass ARRAY iPLEX. SNPs were analyzed for correlation with ncPR using recessive (aa vs AA/aA) , dominant (AA vs aa/aA) and log-additive (linear increase in risk with each additional allele) genetic models. In this exploratory dataset, a p-value <0.1 was considered worthy of further study. Results: 60 patients were treated and had sufficient DNA for analysis. Nine patients had a ncPR. 7 of 50 SNPs (table) correlated with pathologic response in one of the three models. Conclusions: Of the candidate SNPs identified from the literature, 7 showed a promising correlation to ncPR to neoadjuvant chemotherapy. This expands upon the experience evaluating SNPs and chemotherapy sensitivity into a North American population. Study of these 7 SNPs is ongoing in our current multimodality trial as a validation cohort. This study was funded by the Lung Cancer Research Foundation. [Table: see text]