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Nonsurgical treatment with chemoradiation (CRT) alone is less commonly recommended for esophageal adenocarcinoma (EAC) compared to squamous cell carcinoma, due to lower rates of complete response. However, the CALGB 80803 trial indicates that FOLFOX-based CRT can achieve higher rates of pathologic complete response compared to the CROSS-trial regimen of carboplatin/paclitaxel. We reviewed our institutional experience to identify patients who received FOLFOX-RT for localized EAC without surgery, hypothesizing that they may experience relatively favorable survival and local control with CRT alone. A retrospective study was conducted on patients with esophageal or gastroesophageal junction adenocarcinoma who received CRT for Stage I-III disease at our institution. We extrapolated patients who received RT dose ≥41.4Gy with FOLFOX or capecitabine/oxaliplatin chemotherapy prior to or concurrent with RT, and did not undergo post-CRT surgical resection. Overall survival was calculated from the start of RT using Kaplan-Meier method, and local recurrence-free survival (LRFS) was assessed in patients with negative post-CRT endoscopic biopsies. 440 consecutive patients who received CRT between 2016-2021 for esophageal/GEJ adenocarcinoma were reviewed. Excluding patients who did not receive FOLFOX or CAPOX chemotherapy, and/or underwent post-CRT surgery, yielded a total of 50 patients for whom FOLFOX-RT served as definitive treatment. 45 patients received induction chemotherapy prior to CRT. 33 patients underwent post-CRT endoscopic biopsy, of which 22 showed no detectable malignancy. 15 of these patients declined surgery due to the apparent complete response, while the other 7 were medically inoperable. At two years, survival was 100% in biopsy-negative/medically operable patients, 93.8% in all biopsy-negative patients, and 46.7% overall. Median survival was 23.7 months, and 45.0 months in biopsy-negative, medically operable patients. 6 of the 22 patients with negative post-CRT biopsy have experienced local tumor recurrence, and median LRFS in this group was 27.2 months. To our knowledge, this is the first report describing outcomes of non-surgical management in patients receiving FOLFOX-based CRT for esophageal/GEJ adenocarcinoma. Survival outcomes with this approach appear favorable, particularly among patients with negative post-CRT biopsy. This data suggests that patients achieving clinical complete response to FOLFOX-RT can have excellent prognosis even without surgery. FOLFOX-based CRT has promise as a basis for non-operative treatment approaches in esophageal/GEJ adenocarcinoma. [ABSTRACT FROM AUTHOR]