Abstract
4123 Background: Neoadjuvant therapy has been introduced to improve survival in patients with localized esophageal adenocarcinoma (EA). Yet, the benefit of neoadjuvant for patients with EA is still under debate as only about one third of treated patients respond. The identification of molecular markers that predict response to neoadjuvant therapy will be critical to tailor the appropriate therapy for these patients. Methods: We investigated tissue samples from 104 patients (94 males and 10 females with a median age of 60 years [range: 29-86]) with localized esophageal adenocarcinoma treated with 5-FU based neoadjuvant therapy at USC. A panel of ten genes involved in DNA repairs and 5-FU metabolism were selected. DNA was isolated from formalin-fixed paraffin-embedded normal esophageal tissue samples and germline polymorphisms were analyzed using PCR-RFLP and 5′-end [γ-33P] ATP-labeled PCR methods. Fisher's exact test was used to examine the associations between polymorphism and complete pathological response. Kaplan-Meier curves, log-rank test and Cox proportional hazards model were used for their associations with overall survival. Results: 31 out of 104 patients (30%) had complete pathological response. The median overall survival was 18.5 months (95% CI: 13.5-25.7). Single nucleotide polymorphism ERCC1 118T CC (p-value = 0.031, Fisher's exact test) was identified as an adverse prognostic marker for response in univariate analysis. None of 11 carriers showed evidence of response. In Cox regression analysis adjusting for TNM category, patients carrying XPD 156 A/A (p = 0.01) and XRCC 1 399 G/G (p = 0.03) had shorter survival compared to patients with XPD 156 C/C or C/A and XRCC 1 399 G/A or A/A, respectively. Conclusions: This data supports the role of functional ERCC 1 polymorphism as a predictive marker for response and may therefore be applied as a marker for tailored therapy. Further, XPD 156 and XRCC1 399 were identified as independent prognostic markers in localized EA treated with neoadjuvant therapy. No significant financial relationships to disclose.
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