Changes in the tumor glucose-uptake measured by 18F-FDG PET with two weeks of single-agent cetuximab in localized squamous cell carcinoma of the esophagus.

Abstract

e15042 Background: Cetuximab (CET), an antibody directed against epidermal growth factor receptor (EGFR) has proved efficacy in squamous cell cancer (SCC) of the head and neck in vitro and in vivo by enhancing the activity of chemo- and radiotherapy. The aim was to investigate the early metabolic response in esophageal SCC induced by single agent CET. Methods: Patients with cT3 Nx esophageal SCC received single agent CET for two weeks (400mg/m2 i. v. d -15 followed by 250mg/m2 d -8) before entering a neoadjuvant dose escalation protocol of weekly cetuximab plus weekly oxaliplatin (starting dose level 45mg/m²; d1,8,15,22,29), plus 5-FU cont. i.v. (starting dose level 180mg/m²/d; d1-5, 8-12, 15-19, 22-26, 29-33) and radiotherapy (45Gy cumulative dose; 1.8Gy/d). Surgery was scheduled 4-6 weeks after chemoradiation (CRT). Tumor FDG uptake was assessed by PET at baseline, two weeks after start of CET and two weeks after start of CRT. Standard uptake values (SUV) of the two response PETs were compared with SUVs measured at baseline and correlated with the histopathological response data. Results: 11 patients are assessable for metabolic and histopathological response. Decreases in the SUVs two weeks after the start of CET compared with baseline SUV ranged from -16% to -70% (median -24%) and from 0% to -72% (median -39%) two weeks after start of CRT. Three patients were classified as complete histopathological responders. One patient had a subtotal (<10% residual tumor) and three patients a moderate response (10-50% residual tumor). No histopathological response was seen in 4 patients. We found an association between FDG uptake decreases both after single agent CET and after two weeks of CRT and a favourable histopathological response with no statistical significance due to the low number of cases. Conclusions: This study shows that single agent CET can lead to a marked and early decrease in tumor glucose uptake. Our findings suggest that there may be an association between the early decrease in FDG uptake during CET monotherapy, indicating a growth dependency of some tumors from the EGFR signal pathway. These preliminary observations require confirmation in a larger patient cohort. Clinical trial information: 2006-001097-24.