Biomarkers for cetuximab-based neoadjuvant radiochemotherapy in locally advanced XXXX .

@entity1 @entity11833 @entity7 @entity5 @entity470 @entity984 @entity319 @entity8554 @entity6758 @entity817
PURPOSE: Phase II trials in locally advanced @entity5 have shown that cetuximab-based neoadjuvant radiochemotherapy is feasible but without an improvement in complete pathologic response rates. Our goal was to identify @entity1 who would benefit from cetuximab-based neoadjuvant chemoradiation measuring gene expression levels of proteins involved in @entity5 growth [ @entity470 ( @entity470 )], angiogenesis [ @entity7 ( @entity6758 , @entity319 )], DNA repair [ @entity11833 ( @entity11833 )], and drug metabolism [thymidylate synthetase (TS)]. We also determined mutation status of @entity984 and @entity817 . EXPERIMENTAL DESIGN: This study was carried out on 130 @entity1 with locally advanced @entity5 who were enrolled in 4 different phase II clinical trials, using cetuximab-based chemoradiation. Tumor tissues were obtained before neoadjuvant and at surgical therapy. After microdissection, intratumoral gene expression levels and @entity984 / @entity817 mutation status were analyzed. RESULTS: A significant decrease of TS, @entity6758 , and @entity319 gene expression was seen following neoadjuvant therapy (P < 0.03). High pretreatment @entity7 gene expression levels were associated with nonresponse (P = 0.070). @entity984 mutations were found in 42% and mutant @entity984 ( @entity984 mt) was significantly associated with pathologic nonresponse (P = 0.037). In @entity1 with wild-type @entity984 ( @entity984 wt), low @entity470 was significantly associated with higher nonresponse and @entity7 mRNA expressions were associated with complete pathologic response (P = 0.012; P = 0.06). @entity984 transversion ( @entity984 tv) was associated with @entity5 regression: nonresponse was more common in @entity1 with @entity984 tv than with @entity984 wt (P = 0.007). @entity817 @entity8554 mutations were not detected in any of the @entity1 . CONCLUSION: This study suggests that pretreatment intratumoral @entity470 and @entity7 mRNA expression levels as well as @entity984 mutation status are predictive markers of pathologic response to neoadjuvant cetuximab-based chemoradiation in locally advanced @entity5 .
