2029 - Single-Center Experience of Neoadjuvant CROSS or FOLFOX for Esophageal Adenocarcinoma

Purpose/Objective(s): Recent trials challenging the role of preoperative radiation in esophageal adenocarcinoma have evaluated CROSS (carboplatin/paclitaxel), but many centers prefer FOLFOX (oxaliplatin/fluorouracil). We compared downstaging and long-term outcomes at a single tertiary care center treating esophageal adenocarcinoma with preoperative chemoradiation CROSS or FOLFOX.

Materials/Methods: Adult patients who underwent esophagectomy after neoadjuvant CROSS or FOLFOX chemoradiotherapy for esophageal adenocarcinoma between 2010 and 2024 were included. CROSS was generally used with higher radiation doses than in the CROSS trial. Overall and recurrence-free survival were assessed by the Kaplan-Meier method at 3 and 5 years from time of surgery. Cox proportional hazards models were adjusted for year of diagnosis, demographics, insurance, Charlson-Deyo score, tumor grade, and clinical summary stage (forward-staged to AJCC 8^th Edition).

Results: Overall, 103 patients were treated with neoadjuvant CROSS while 104 received neoadjuvant FOLFOX with radiation. The cohort was predominantly male (86.0%) with a median age of 64 years (IQR: 59-71). Comorbidity burden was high (54.4% Charlson-Deyo =3 in FOLFOX patients vs. 54.4% of CROSS patients, p=0.99) and tumors were advanced (88.5% clinical stage III+ in FOLFOX patients, vs. 79.7% CROSS, p=0.35). Median total radiation dose was 50 Gy (IQR 50-50) for both groups (p=0.59). Pathologic complete response (pCR) was higher after FOLFOX (46.2% vs. 23.3%, p=0.001), while 90-day mortality was comparable (2.9% vs 2.9%, p=0.99). Median follow-up was 32.3 months (20.4-60) for FOLFOX and 35.8 months (19.5-60) for CROSS. Overall survival was higher for FOLFOX (73.6% vs. 62.9% at 3 years [p=0.36], 68.4% vs. 50.3% at 5 years [p=0.046]). Recurrence-free survival exhibited similar trends at 3 years (66.7% vs. 55.0%, p=0.11) and 5 years (61.0% vs. 42.7%, p=0.04). In Cox models, the higher hazard ratios of FOLFOX as compared to CROSS were significant for recurrence-free (HR 1.64, 95% CI 1.05-2.56, p=0.03) but not overall 5-year survival (HR 1.52, 95% CI 0.93-2.50, p=0.10).

Conclusion: Neoadjuvant chemoradiation with FOLFOX was associated with a significantly higher pCR rate than CROSS and higher 5-year recurrence-free and overall survival on unadjusted analyses, although failed to reach statistical significance in multivariable models of overall survival. Additional follow-up is needed as the field moves away from radiation based on comparison to the CROSS regimen, and there may be a subset of adenocarcinoma patients that benefit from combining radiation with FOLFOX.