Perioperative FLOT versus Definitive 50.4 Gy Chemoradiotherapy in Siewert II Esophagogastric Junction Adenocarcinoma: A Multicenter Retrospective Cohort Study

Sermin Dinc Sonusen,1 Zehra Sucuoglu Isleyen,1 Okan Aydin,1 Mert Erciyestepe,1 Abdullah Sakin,1 Necla Gurdal,2 Muslih Urun,3 Berrak Mermit Ercek,3 Mehmet Bilici,4 Halide Sena Gurbuz,4 Senar Gunenc,5 Resit Akyel,6 Emir Celik,1 Kayhan Erturk,1 Muhammed Mustafa Atci1 1Department of Medical Oncology, Prof. Dr. Cemil Tascioglu City Hospital, Istanbul, Turkey; 2Department of Radiation Oncology, Prof. Dr. Cemil Tascioglu City Hospital, Istanbul, Turkey; 3Department of Medical Oncology, Van Yuzuncu Yil University Faculty of Medicine, Van, Turkey; 4Department of Medical Oncology, Ataturk University Faculty of Medicine, Erzurum, Turkey; 5Department of Radiation Oncology, Yedikule Chest Diseases and Chest Surgery Training and Research Hospital, Istanbul, Turkey; 6Department of Nuclear Medicine, Yedikule Chest Diseases and Chest Surgery Training and Research Hospital, Istanbul, TurkeyCorrespondence: Sermin Dinc Sonusen, Department of Medical Oncology, Prof. Dr. Cemil Tascioglu City Hospital, Darulaceze Cd. No: 27, Sisli, Istanbul, 34384, Turkey, Tel +90 212 314 55 55, Email [email protected]: Optimal multimodal treatment for esophagogastric junction adenocarcinoma remains debated. While the ESOPEC trial supports perioperative FLOT, real-world evidence is limited, particularly for Siewert type II tumors.Aim: To compare survival and treatment outcomes of perioperative FLOT versus definitive-dose chemoradiotherapy in non-metastatic Siewert II esophagogastric junction adenocarcinoma.Methods: Siewert type II esophagogastric junction adenocarcinoma was defined as tumors with an epicenter located between 1 cm above and 2 cm below the esophagogastric junction. We retrospectively identified patients with non-metastatic Siewert type II esophagogastric junction adenocarcinoma treated between January 2015 and December 2024 at three tertiary cancer centers. Patients received either perioperative FLOT chemotherapy or concurrent chemoradiotherapy with weekly carboplatin–paclitaxel and 50.4 Gy radiotherapy, delivered as definitive therapy or neoadjuvantly prior to planned surgery. Clinical characteristics, treatment delivery, pathological response, survival outcomes, and treatment-related toxicities were analyzed.Results: Seventy patients were included (FLOT, n=50; concurrent chemoradiotherapy, n=20). Surgery was performed in 45/50 (90%) FLOT patients and 7/20 (35%) concurrent chemoradiotherapy patients, representing a major difference between treatment groups. Median follow-up was 53.7 months. Median overall survival was 43.0 months in the FLOT group and 48.6 months in the concurrent chemoradiotherapy group (p=0.498). Median event-free survival was 34.2 months and 35.0 months, respectively (p=0.548). No pathological complete response occurred in the FLOT group; one patient (14.3%) in the concurrent chemoradiotherapy group achieved pathological complete response. Grade 3– 4 toxicities were more frequent with FLOT (26% vs. 5%). Distant relapse was the predominant recurrence pattern in both groups.Conclusion: Despite a substantial difference in surgical resection rates between groups, perioperative FLOT and concurrent chemoradiotherapy showed comparable survival outcomes in this real-world cohort of patients with Siewert type II EGJ adenocarcinoma. These findings should be interpreted with caution, as treatment selection and baseline differences may have influenced outcomes. Treatment decisions should be individualized based on patient characteristics and clinical context.Plain Language Summary: Siewert type II esophagogastric junction adenocarcinoma is a challenging disease with limited real-world comparative data. In this multicenter study, we compared two common treatment approaches: perioperative FLOT chemotherapy and chemoradiotherapy using a standard, full-course radiation treatment (50.4 Gy). Despite higher surgical rates in the FLOT group, survival outcomes were comparable between the two strategies. Pathological complete response was rare, and distant metastasis was the most common pattern of recurrence. FLOT was associated with higher grade 3– 4 toxicities. These findings suggest that treatment should be individualized, and that organ-preserving approaches such as chemoradiotherapy may be a reasonable option for selected patients with Siewert type II EGJ adenocarcinoma in clinical practice.Keywords: esophagogastric junction, siewert type II, FLOT, chemoradiotherapy, adenocarcinoma