Early prediction of residual disease after neoadjuvant chemoradiotherapy and cetuximab for locally advanced esophageal cancer using 18F-FDG PET-CT imaging: a prospective cohort study

Background: Previous studies in locally advanced esophageal cancer (LAEC) suggested that a change in the tumor's metabolic response, i.e., decrease of its interim 18F-FDG uptake compared with baseline, may predict histopathological response. We evaluated the possible predictive correlation between various PET CT and histopathological parameters following a neoadjuvant biological-containing chemoradiotherapy (CRT) regimen.Methods: Patients with resectable LAEC received neoadjuvant cisplatin/5-fluorouracil-based CRT and cetuximab following one cycle of induction chemotherapy and cetuximab. Changes in maximum and mean standardized uptake values (ASUV-max and ASUV-mean, respectively) and metabolic tumor volume (AMTV), measured by PET-CT at baseline and 2 weeks after the onset of treatment, were compared with histopathological findings at surgery. Histopathological response was defined by tumor regression grade (TRG), pathological complete response (pCR) and microscopic or macroscopic residual disease (RD).Results: Of 18 patients, 13 (72%) with adenocarcinoma (AC) and 5 (28%) with squamous cell carcinoma (SCC), were included. None of the changes in the parameters of PET was associated with pCR; only ASUVmean was associated with TRG in the AC cohort. In contrast, both ASUV-mean% and ASUV-max% were significantly associated with RD, both in the whole cohort and in the AC cohort. Changes in FDGuptake predicted RD2 at surgery: only patients with less than 13% decrease in SUV-mean% or less than 29% decrease in SUV-max% had RD2, while all patients with RD0 or RD1 had greater reductions [100% specificity and 100% positive predictive value (PPV)].Conclusions: Changes in ASUV-max and ASUV-mean after two weeks of onset of cetuximab-based neoadjuvant chemotherapy for LAEC may predict macroscopic RD but not TRG or pCR at surgery.