To compare the efficacy and safety of induction FOLFOX followed by PET-directed neoadjuvant chemoradiation therapy (nCRT), induction carboplatin plus paclitaxel (CP) followed by PET-directed nCRT, and nCRT with CP alone in patients with esophageal adenocarcinoma (EAC).

nCRT with CP is a standard treatment for locally advanced EAC. The results of Cancer and Leukemia Group B 80803 support the use of induction chemotherapy followed by PET-directed chemoradiation therapy.

We retrospectively identified all patients with EAC who underwent the treatments above followed by esophagectomy. We assessed incidences of pathologic complete response (pCR), near-pCR (ypN0 with ≥90% response), and surgical complications between treatment groups using Fisher's exact test and logistic regression; disease-free survival (DFS) and overall survival (OS) were estimated by the Kaplan-Meier method and evaluated using the log-rank test and extended Cox regression.

In total, 451 patients were included: 309 (69%) received induction chemotherapy before nCRT (FOLFOX, n=70; CP, n=239); 142 (31%) received nCRT with CP. Rates of pCR (33% vs 16%, P=0.004), near-pCR (57% vs 33%, P<0.001), and 2-year DFS (68% vs 50%, P=0.01) were higher in the induction FOLFOX group than in the induction CP group. Similarly, the rate of near-pCR (57% vs 42%, P=0.04) and 2-year DFS (68% vs 44%, P<0.001) were significantly higher in the FOLFOX group than in the no-induction group.

Induction FOLFOX followed by PET-directed nCRT may result in better histopathologic response rates and DFS than either induction CP plus PET-directed nCRT or nCRT with CP alone.